United States Patent (19) [11] 3,897,453 Gante et al. (45) July 29, 1975

54 DBENZOFURAN AND Routier, CA 51:5076-5077 (1957). DBENZOTHIOPHENE ACETIC ACID Chatterjea, CA 52:3759-3761 (1958). DERVATIVES Gilman, II, CA 41:752-753 (1947). 75 Inventors: Joachim Gante; Werner Mehrhof; Hogg, CA 40:4716-4717 (1946). Albrecht Wild, all of Darmstadt, Gilman, III, CA 34:2366-2367 (1940). Germany Burger, CA 34:1654-1655 (1940). 73) Assignee: Merck Patent Gesellschaft mit beschrankter Haftung, Darmstadt, Gilman, IV, CA 33:579-581 (1939). Germany Primary Examiner-John M. Ford 22 Filed: May 10, 1973 Assistant Examiner-C. M. S. Jaisle 21 Appl. No. 358,872 Attorney, Agent, or Firm-Millen, Raptes & White 30 Foreign Application. Priority Data (57) ABSTRACT

May 13, 1972 Germany...... ------2223391 Dibenzofuran and dibenzothiophene derivatives of the Dec. 16, 1972 Germany...... 2261745 formula (52) U.S. Cl. ... 260/329.3; 260/243 B; 260/247. 1 P; CHR, R2 260/247.2 B; 260/247.2 R; 260/268 TR; R 2N-1N1: 260/293.57; 260/293.58; 260/326.34; 260/327 M; 260/338; 260/340.7; 260/340.9; 3 St n Y C 260/346.2 M; 424/246; 424/248; 424/250; 424/267; 424/274; 424/275; 424/278 (S1) int. Cl...... C07d 63/24 wherein R is COOH, CHO, or CHOH, R is H or 58) Field of Search...... 260/329.3, 346.2 M alkyl of 1-4 carbon atoms, Ra is H, alkyl, alkoxy, al kanoyl, monoalkylamino, dialkylamino, or acylamino 56) References Cited of up to 4 carbon atoms, F, Cl, Br, I, OH, NH, NO, UNITED STATES PATENTS CN, or CF; and Y is O or S, with the proviso that at 3,506,688 4/1970 Wang...... 260/346.2 least one of R2 and Ra is other than H, and the physio 3,567,742 3/1971 Cavalleri...... 260/346.2 logically acceptable salts thereof, possess antiinflam 3,655,697 4/1972 Shen...... 260/346.2 matory activity. OTHER PUBLICATIONS 27 Claims, No Drawings Gilman, I, CA 49:6218 (1955). 3,897,453 1. 2 DIBENZOFURAN AND DIBENZOTHOPHENE Ar is aryl of a total of 6-10 carbon atoms, optionally ACETIC ACID DERVATIVES substituted, e.g., by Rs: Ib R1 is COOR, CONHR, CONCA), CHO, or BACKGROUND OF THE INVENTION CHOH, wherein This invention relates to novel dibenzofuran and 5 Rs is H or an alkyl, cycloalkyl, cycloalkylalkyl, aryl, dibenzothiophene derivatives similar to the known 2 or aralkyl, respecively up to 20 carbon atoms dibenzofurylacetic acid (cf. J. Amer. Chem. Soc., 68. which optionally can contain 1 or 2 C-C multiple 2104-05 (1946)). bonds and/or whose carbon chain can be inter rupted once or several times by Q and/or can be SUMMARY OF THE INVENTION 10 branched and/or can be mono- or poly-substituted The novel compounds of this invention are diben by Cl, OH, SH, and/or NH, zofuran and dibenzothiophene derivatives of the gen Q being O, S, NH, or optionally OH-substituted N eral Formula I Z-CHRR (I) alkyl or 1-6 carbon atoms, N-Ar, or N-aralkyl of 15 7-10 carbon atoms; in which Z is Ic R1 is COORs. CHO, or CHOH, wherein 1 N Rs is H, A, or dialkylaminoalkyl of up to 10 carbon atoms, t-GN1 a y 1 Id R is COOH, COOCH, or COOCHs; wherein R is COOH, CHO, or CHOH including func 20 e Rais CH3 or CH, especially those of Ia - Id; tional derivatives thereof; R2 is H or alkyl of 1-4 carbon If R is CH, especially those of Ia - Id; atoms; Ra is H, alkyl, alkoxy, alkanoyl, monoalk Ig Ra is H, CH, CH, CHO, CH3CO, F, Cl, Br, I, ylamino, dialkylamino or acylamino, each of up to 4 OH, NH, or NO, especially those of Ia - Id; carbon atoms, F, Cl, Br, I, OH, NH2, NO, CN or CFs; Ih Rs is H, especially those of Ia - Id; and Y is O or S; with the proviso that at least one of R2 25 Ii R is COOH, COOA, CHO, or CHOH, and R is other than H; and the physiologically accept R2 is CH3, and able salts thereof. Rs is H, CH5, F, Cl, Br, or I; I R is COOH, COOA, CHO, or CHOH, DETAILED DISCUSSION R2 is CH3, and Compounds of Formula I possess, with good compat 30 R is H or F; ibility, excellent antiphlogistic activity. In particular, Ik R is COOH or COOA, they exert a favorable influence on chronically progres R is CH3, and sive inflammation diseases involving the joints. They R is H or 7-F. also possess analgesic and antipyretic activity. There Included in the compounds of Formula I and Ia are fore, the compounds of Formula I can be employed as 35 functional derivatives of aldehydes (R1 = functionally drugs, especially for producing antiphlogistic, i.e., anti modified CHO-group) derived from the enol form inflammatory, effects in living beings. They are also thereof and accordingly exhibiting an additional double useful as intermediates for the preparation of other bond, thus having the formula Z-CR-R1, for exam medicines. In its composition aspect, this invention re ple, the enol ethers (R1 = -CHOA or -CHOAr, respec lates to pharmaceutical compositions comprising a 40 tively) and the enol esters (RF=CHOAc). compound of Formula I in admixture with a pharma Ra is preferably at the 3-, 7-, or 8-position. However, ceutically acceptable carrier. In its method of use as this group can also be at the 1-, 4-, 6-, or 9-position. pect, this invention relates to the treatment of inflam (The numbering of the individual positions is in accor matory conditions with a compound of Formula I. 45 dance with the disclosure in "The Ring Index,' Second In its preferred aspects, this invention relates to the Edition, 1960, No. 301 1.) compounds of Formulae Ia-Ik below, and pharmaceu Examples of compounds of Ia wherein R is an esteri tical compositions comprising them wherein any fied carboxyl group are those wherein the esterifying groups not otherwise defined have the values given in group is hydrocarbon including alkyl, arylalkyi, e.g., Formula I. 50 benzyl, p-methylbenzyl, phenethyl, aryl, e.g., phenyl; Ia R is a free or esterified carboxyl group of 1-20 and wherein R1 is mono- or disubstituted CONH2 are carbon atoms, optionally mono- or disubstituted CONHA and CONA wherein A is as defined above, or CONH group, CN, or R, wherein cycloalkyl or cycloalkyl alkyl of 3-7 rings and a total R is -CHO, -CHOH-SOM, -CHOH-OA, -CH(OA), -CH(OAc), -CHOH-SA, -CH of 3-12 carbon atoms, e.g., cyclopentyl, e.g., cyclo (SA), -CH=NOH, -CHOH, -CH2OAc, -CH 55 hexyl, cyclopentylmethyl, -ethyl and -propyl, aryl, e.g., OA, or =CHOA, =CHOAc or =CHOAr, carbocyclic containing 1-3 separate or fused rings, and M is an equivalent of an alkali or alkaline earth the corresponding aralkyl wherein the aryl portion is as metal, defined herein and the alkyl portion contains 1-4 car A is alkyl of 1-8, preferably 1-4 carbon atoms, e.g., bon atoms. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, oc 60 Aryl preferably in each instance is of 6-10 ring car tyl, or, when two A groups are present, collectively bon atoms and more preferably is carbocyclic, e.g., alkylene of 2-5 carbon atoms, optionally inter phenyl, biphenyl and naphthyl, optionally substituted rupted by O, e.g., ethylene, propylene, trimethy by R3. lene, ethyleneoxyethylene; In its process aspect, this invention relates to a pro Ac is acyl of 1-18, preferably alkanoyl of 2-10, alkyl 65 cess for the preparation of compounds of general For sulfonyl of 1-6, arylsulfonyl of 6-10, or aroyl of mula I, which comprises converting, in a compound of 7-10 carbon atoms, and general Formula II 3,897,453 3 4 R1 is not critical, so long as it is removable under physi ological conditions to the free acid, aldehyde or alcohol (II) and is physiologically acceptable. Of course, it is also wherein X is a group convertible into the group possible to modify the physiological effects obtained -CHR R2 and Z, R1, R2, R3, and Y have the values in with the free forms by a suitable selection of the func dicated in Formula I, X into the group -CHRR, or tional group, for example, depot effects can be treating a compound of general Formula III achieved by the use of long-chain or difficult-to saponify alcohol groups or acyl groups in esters. Im 1N1 CHR, R2 provements in solubility can be acheived by the incor an 10 poration of polar groups (O-atoms, N-atoms) into such - N2 functionally modified R groups. S-N E For example, R can be COOR or COORs, as de (III) fined above, preferably COOH, COOCH or COOCHs. wherein one of the two groups E is the group E and the 15 Rs is preferably hydrogen; alkyl of 1-20, preferably other is the group Y-E2, wherein E is a group which 1-8, more preferably 1-4, carbon atoms, e.g., methyl, can be split off with E. as EE, and E2 is H or an equiv ethyl, n-proply, isopropyl, n-butyl, isobutyl, sec.-butyl, alent of an alkali or alkaline earth metal, one of the two tert.-butyl, n-pentyl, isoamyl, n-hexyl, n-heptyl, n-octyl, benzene rings is substituted by Ra, and R, R2, R3, and 2-ethylhexyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, Y have the values given in Formula I, with an agent 20 n-tridecyl, n-tetradecyl; alkenyl of 2-8, preferably 2-4, splitting off E - E2; or by treating a compound of gen carbon atoms, e.g., vinyl, allyl, crotyl; alkinyl of 2-8, eral Formula IV preferably 2-4-carbon atoms, e.g., propargyl; hydroxy alkyl of 2-8, preferably 2-4, carbon atoms, wherein the hydroxy group is preferably 3 or o, e.g., 2 1n 1 CHRR2 25 hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl; alk (IV) oxyalkyl, wherein the alkoxy group is of 1-8, preferably 1-4, carbon atoms and alkyl is as defined above, e.g., (SJ U 2-methoxyethyl, 2-ethoxyethyl; 3-oxa-5- hydroxypentyl, 3-oxa-5-methoxypentyl, 3-oxa-5- wherein one of the two benzene rings is substituted by 30 butoxyphenyl, 3,6-dioxa-8-hydroxyoctyl, 3,6-dioxa-8- Ra and R, R2, and Rs have the values given in Formula methoxyoctyl, 3,6-dioxa-8-ethoxyoctyl, 3-oxa-5- I, with sulfur in the presence of a catalyst; or by ther ethoxypentyl; aminoalkyl, alkylaminoalkyl and dialkyl mally cyclizing a compound of general Formula V aminoalkyl wherein alkyl, in each instance contains up to 8, preferably up to 4 carbon atoms, e.g., 2 35 aminoethyl, 3-aminopropyl, 2-dimethylaminoethyl, 2 G G \ CHR, R2 diethylaminoethyl, 2-di-n-propylaminoethyl, 3 dimethylaminopropyl, 3-diethylaminopropyl, 2 methyl-3-diethylaminopropyl; 4-dimethylaminobutyl, OC 4-diethylaminobutyl; cycloalkyl, preferably containing N y 40 5-8 ring carbon atoms, and 1-3 rings, e.g., cyclopentyl, (W) cyclohexyl, cycloalkylalkyl, wherein cycloalkyl and alkyl are as defined above, e.g., 2-cyclohexylethyl, 3 wherein one of the two G groups is OH or a diazonium cyclohexylpropyl; azacycloalkyl, C-9., N salt group, and the other is H, and one of the two ben methylpiperidyl(4); azacycloalkylalkyl and related cy zene rings is substituted by Ra, and R, R2, R3, and Y 45 cloamino groups, e.g., containing in a total of 5-7 ring have the values given in Formula I; and optionally atoms and a ring N, O, or Satom g- to the amino group, thereafter converting, in a thus-obtained product of e.g., (N-methylpiperidyl-3)-methyl, 2-(N-methylpiperi Formula I, in one or several stages, one or both of the dyl-2)-ethyl, 2-pyrrolidinoethyl, 2-piperidinoethyl, 2 R1 and/or R3 groups into one or two other R1 and/or R3 homopiperidinoethyl, 2-morpholinoethyl, 2-thiomor groups having a different value. 50 pholinoethyl, 2-(N-methylpiperazino)-ethyl, 2-(N- In all of the above formulae, R preferably is a free ethylpiperazino)-ethyl, 2-(N-phenylpiperazino)-ethyl, -COOH, CHO or CH-OH group. However, such 2-(N-2-hydroxyethylpiperazino)-ethyl, 2-(N- groups can also be a functionally modified group. The methylhomopiperazino)-ethyl, 2-(N- term "functionally modified group' as used herein benzylpiperazino)-ethyl, 2-pyrrolidinopropyl, 3 means a group that can be removed in vivo to regener 55 pyrrolidinopropyl, 2-piperidinopropyl, 3 ate the free group. Examples are esterified COOH piperidinopropyl, 2-(N-methylpiperazino)-propyl, 3 groups, wherein the alcohol portion is preferably of (N-methylpiperazino)-propyl, 3-(N-ethylpiperazino)- 1-14 carbon atoms, a free or acetalyzed CHO group or propyl, 3-(N-phenylpiperazino)-propyl, 2 a free or esterified CH-OH group, e.g., as defined in Ia. morpholinopropyl, 3-morpholinopropyl, 3-thiomor Because the free carboxylic acids, aldehydes, and alco 60 pholinopropyl, 2-methyl-3-pyrrolidinopropyl, hols, of Formula I (R = COOH, CHO and/or CHOH) 2-methyl-3-piperidinopropyl, 2-methyl-3- are physiologically active compounds, it will be obvious morpholinopropyl; mercaptoalkyl, e.g., 2-mercapto that functional derivatives thereof which can be con ethyl; alkylmercaptoalkyl, e.g., 2-methylmercapto verted, e.g., hydrolyzed, thereto under physiological, 65 ethyl, 2-ethylmercaptoethyl, 3-methylmercaptopropyl, i.e., in vivo, conditions, preferably at a pH of between 3-ethylmercaptopropyl; aryl as defined above, e.g., 1 and 8, are the functional equivalents thereof. There phenyl, o-tolyl, m-tolyl, p-tolyl, p-ethylphenyl, 1 fore, the type of functional modification of the group naphthyl, 2-naphthyl; aralkyl, e.g., benzyl, p 3,897,453 S 6 methylbenzyl, l-phenylethyl, 2-phenylethyl. Rs can or unsaturated aliphatic, cycloaliphatic, aromatic, or also be Z-CHR2-CH2-, wherein Z is as defined heterocyclic substituted or unsubstituted carboxylic above. acid or sulfonic acid. Preferred carboxylic acids are R can also represent other functionally modified fatty acids of 1-18, preferably 1-6, carbon atoms, e.g., carboxyl groups. Examples are acid halogenides (R1 = 5 formic acid, acetic acid, propionic acid, butyric acid, COF, COCl, COBr); ortho esters (R1 = C(OA)); acid isobutyric acid, valeric acid, isovaleric acid, caproic anhydrides (R = COOAcyl, wherein Acyl is the acyl acid, isocaproic acid, enanthic acid, caprylic acid, pe group of a carboxylic acid of up to 28 carbon atoms, largonic acid, capric acid, lauric acid, myristic acid, e.g., as defined herein above, preferably the residue palmitic acid, stearic acid. Others are crotonic acid, Z-CHR-CO-); nitriles (R = CN); acid amides (R1 10 oleic acid, cyclohexanecarboxylic acid, cyclohexyla = CONH, CONHA, CONCA), or CONHAr); hydrox cetic and -propionic acid, benzoic acid, phenylacetic amic acids (R = CONHOH); acid hydrazides (R. and -propionic acid, picolinic acid, nicotinic acid, CONHNH or CONHNHA); acid azides (R = CON); isonicotinic acid and furan-2-carboxylic acid. Of spe imino ethers (R = C(OA)=NH); acid amidines (R cial importance are those esters which contain a group C(=NH)NH); acid hydrazidines (R = C(NH2)=NNH 15 rendering the compound water-soluble, e.g., a car or C(NHNH)=NH); thio acids (R = CSOH or boxyl, hydroxyl, or amino group, since they can be used COSH); thio acid esters (R1 = CSOA or COSA); and -- particularly in the form of their ester salts -- of the thio acid amides (R = CSHN, CSNHA, or CSN (A)), preparation of aqueous solutions. The thus-obtainable wherein the A groups, which can be the same or differ monoesters and/or dydroxy or amino esters are de ent when more than one is present, have the values 20 rived, for example, from dicarboxylic acids, e.g., oxalic, given above. malonic, succinic, maleic, glutaric, dimethylglutaric, Examples of the preferred substituted amides groups adipic, pimelic, acetonedicarboxylic, phthalic, tetrahy are N-monoalkylamides, -dibenzofuryl)-propionamide drophthalic, hexahydrophthalic, or diglycolic acid, hy methylamides, ethylamides, n-propylamides, iso droxycarboxylic acids, such as glycolic acid, or amino propylamides, n-butylamides, isobutylamides; N,N- 25 carboxylic acids, such as diethylaminoacetic acid or as dialkylamides, e.g., dimethylamides, methylethyla partic acid. Preferred sulfonic acid esters are those de mides, diethylamides, di-n-propylamides, diisopropyla rived from alkylsulfonic acids of 1-6 carbon atoms, mides, di-n-butylamides, disobutylamides; N e.g., methane- and ethanesulfonic acid and arylsulfonic monoaryl- and N-monoaralkylamides, e.g., anilides, N acids of 6-10 carbon atoms, e.g., benzene-, p-toluene benzylamides; N-hydroxyalkylamides, e.g., N-2- 30 and 1- and 2-naphthalenesulfonic acids. The OH-group hydroxyethylamides; N,N-bis-hydroxyalkyl-amides, in Formula I (R = CHOH) can also be esterified with e.g., N,N-bis-2-hydroxyethylamides; heterocyclic am an inorganic acid, such as sulfuric acid or phosphoric ides, e.g., pyrrolidides, piperidides, morpholides, thi acid, and can also represent an ester salt (e.g., sodium omorpholides, piperazides, N'-alkyl-piperazides, e.g., salt) group derived from such an ester. N'-methylpiperazides, N'-ethylpiperazides, 35 R can also represent an etherified CH-OH-group, N'-hydroxyalkyl-piperizides, e.g., N'-2-hydroxyethyl preferably alkoxy of 1-12, preferably 1-4 carbon piperazides. atoms, e.g., methoxy, ethoxy, propoxy, isopropoxy, n The compounds of Formula I include aldehydes of butoxy, isobutoxy, sec.-butoxy, or tert.-butoxy, as well the formula Z-CHR-CHO, and also derived there as amyloxy, isoamyloxy, n-heptyloxy, n-hexyloxy, n from, the metal, particularly the alkali metal and/or al 40 octyloxy, n-decyloxy, n-dodecyloxy. Examples of other kaline earth metal bisulfite, especially sodium bisulfite, etherified groups are alkenyloxy or alkinyloxy of pref addition compounds of the formula Z-CHR2-- erably up to 12, especially up to 4 carbon atoms, e.g., CHOH-SOM, hemiacetals of the formula Z-CH vinyloxy, allyloxy, propargyloxy, or butenyloxy, aryl R-CHOH-OA, acetals of the formula Z-CH oxy of preferably 6-12 carbon atoms, e.g., phenoxy, o-, R-CH(OA), acylates of the formula Z-CHR2-CH 45 m- or p-tolyloxy, 1- and 2-maphthyloxy, and aralkoxy of (OAc), hemimercaptals of the formula Z-CHR.-- preferably 7-12 carbon atoms, e.g., benzyloxy, p CHOA-SA, mercaptals of the formula Z-CH methylbenzyloxy, 1- and 2-phenylethoxy and 1- and 2 R-CH(SA), oximes of the formula Z-CHR2-CH naphthylmethoxy. These alkoxy, alkenyloxy, al =NOH, enol ethers of the formula Z-CRFCHOA or kinyloxy, aryloxy and aralkoxy groups can be unsubsti Z-CR=CHOAr, enol esters of the formula 50 tuted or mono- or polysubstituted, especially by hy Z-CR=CHOAc, and Schiff bases of the formula Z-CH-droxy, lower alkoxy of 1-4-carbon atoms, e.g., methoxy, R-CH=NAr, hydrazones of the formula Z-CH ethoxy or n-butoxy, halogen, e.g., F, Cl, Br or I, amino, R-CH=N-NH-R' wherein R' preferably is H, Ar, substituted amino, e.g., monoalkylamino or dialkyl CONH, CONHAr, COOA, CSNH or the residue of a amino, wherein the alkyl groups contain preferably 1-4 Girard reagent) and azines of the formula Z-CH 55 carbon atoms, heterocyclic groups, e.g., pyrrolidino, R-CH=N-N=CH-CHR-Z, wherein in each in piperidino, homopiperidino, morpholino, thiomor stance Z,M1, A, Ac, Ar and R2 have the values given pholino, N-alkylpiperazino, wherein the alkyl group above. contains 1-4 carbon atoms, N-phenylpiperazino, These functional derivatives, among which the bisul N-(hydroxyalkyl)-piperazino, mercapto and alkylmer fite compounds and the acetals are preferred, are nor 60 capto of 1-4 carbon atoms. mally more stable than the free aldehydes, which are in A preferably is methyl or ethyl but can also be, for most cases very reactive, and thus can be more readily example, propyl, isopropyl, n-butyl, sec.-butyl, isobu processed into stable pharmaceutical preparations than tyl, tert-butyl, n-amyl, isoamyl, hexyl, isohexyl, heptyl, the free aldehydes. 65 isoheptyl, octyl and isooctyl. Among the compounds of Formula I are those In the acetals, hemi-mercaptals, mercaptals, acid am wherein R is CHOH. Here, also the OH-group can be ides and thio acid amides of Formula I, in which two A functionally modified, e.g., esterified with a saturated groups are present in the formula, the two A groups can 3,897,453 7 8 )-CH(CH collectively be, for example, -CH2-, -CHRR2, and preferably is a group otherwise corre -(CH2)3-, -(CH2)4-, -(CH2)5- or -CH2C sponding to -CHRR, but which contains in place of H-O-CH2CH2-, and, less preferably Ri a group oxidizable to R1, with a dehydrogenating -CH2CH(CH3)-, -CH(CH3)-CH(CH3)- and and/or oxidizing agent; or -CH2CH (C2H5)-. c. treating a compound of the Formula IIc (II, X = In the compounds described above having an Ac Xa) wherein X3 is a group reducible to the group group, Ac preferably is acetyl, or less preferably propi -CHR, R2, and preferably is a group otherwise corre onyl, butyryl or isobutyryl. Ac can also be, for example, sponding to -CHRR2 but additionally contains at formyl, valleryl, isovaleryl, caproyl, trimethylacetyl, least one reducible group and/or multiple bond, with a heptanoyl, octanoyl, decanoyl, methanesulfonyl, hex 10 reducing agent; or anesulfonyl, benzenesulfonyl, p-toluenesulfonyl, 1- or d. treating a compound of the Formula lid (II, X = 2-naphthalenesulfonyl, benzoyl, toluyl and 1- or 2 X) wherein X4 otherwise corresponds to the group naphthoyl. -CHRR, but additionally contains a group removable Ar is preferably phenyl, but can also be phenyl substi by thermolysis or solvolysis, with a thermolyzing or sol tuted by 1-3 substituents, e.g., methyl, ethyl, methoxy, 15 volyzing agent; or ethoxy, F, Cl, Br, for example o-, m- and especially p e. reacting a compound of the Formula IIe (II, X = tolyl, o-, m- and p-ethylphenyl, o-, m- and p CHRX), or a des-HX derivative thereof, with CO methoxyphenyl, o-, m- and p-ethoxyphenyl, o-, m- and and/or a metal carbonly, optionally in the presence of p-fluorophenyl, o-, m- and p-chlorophenyl, o-, m- and a reducing agent and/or a reaction catalyst; or p-bromophenyl and l- and 2-naphthyl. 20 f. treating a halogenide of the Formula IIf (II, X = M preferably is Na, but can also be, for example, K CO-CHRHal) with a strong base; or or an equivalent of Ca or Mg. g. rearranging a compound of the Formula Ilg (II, X R. preferably contains 1-3 carbon atoms and, in par -CHR2-Xs) wherein Xs is -CO-Rs or -C(- ticular, is CH and CH5, and when R3 is other than H, =NOH)-Rs, with HN or an acidic catalyst, respec also H. 25 tively; or Ra preferably is H or F and can also be, for example, h. catalytically or thermally splitting an epoxide of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, the Formula IIh sec.-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, iso propoxy, n-butoxy, isobutoxy, sec.-butoxy, tert.- (II, X = -CR-CHR or -CR -2Rs-COOH) butoxy, formyl, acetyl, butyryl, isobutyryl, me 30 (7"'s thylamino, ethylamino, n-propylamino, iso O V/ propylamino, n-butylamino, isobutylamino, sec.- butylamino, tert.-butylamino, dimethylamino, methyle wherein s thylamino, diethylamino, formamido, acetamido, pro one of R and Rs is R and the other is H; or pionamido, butyramido, isobutyramido, Cl, Br, I, OH, 35 i. treating a compound of the Formula IIi (II, X = NH, NO, CN and CF. R3 preferably a 7- or 8-position -CRX-CHRs-ORs) wherein Rg is H, A, or Ac, substituent. with an agent which splits off HX, or The dibenzofuran and dibenzothiophene derivatives j. reacting a compound of the Formula IIj (II, X = of Formulae I and Ia-Ik can be produced by: -CO-R) with a compound of the Formula VII a. i. reacting a compound of the Formula IIaa (II, 40 ArP=CH-OR 1 (VII) Rio is A or Ar; or X = H or M), wherein M is MgHal or an equivalent of k. reacting a compound of the Formula IIk (II, X = a metallic atom or an organometallic group and Hal is -CHR2-CH2Xs) wherein Xs is Hal or a diazonium Cl, Br, or I, with a compound of Formula Vla. group, with a compound of the Formula ROH and/or ArCH or with a metallic derivative of such a com X-CHRR2 45 pound; or Via 1. reacting a compound of the Formula III (II, X = wherein X is Hal or an hydroxy or amino group, which -COCH3) with ammonium polysulfide or with a pri optionally can be in reactively functionally modified mary or secondary amine in the presence of sulfur. form, or with a des-HX derivative thereof, or The above-mentioned Formulae IIaa-IIaf, as well as ii. reacting a compound of the Formula IIab (II, X = 50 IIb - III, all correspond to Formula II, except X in each X) with a compound of the formula M-CHRR2 case has the values given for the individual formula. (VIb), or In the aforementioned compounds, in addition to iii. reacting a compound of the Formula IIac (II, X MgCl, MgBr, or Mg, M can especially be an equivalent CHRM) with a compound of the formula XR2 (VIc) 55 of an alkali metal atom (e.g., Li, Na, K), an alkaline or with a des-HX derivative thereof, or earth metal atom (e.g., Mg, Ca), or a Cu, Cd or Zn iv. reacting a compound of the Formula Ilad (II, X = atom, or an organometallic radical, e.g., Mg-Z, Cd-Z, -CHRX) or a des-HX derivative thereof with a or Zn-Z. The term “organometallic residue' includes compound of the formula M-R2 (VId), or organoboron groups, for example, 9 -borabicy v. reacting a compound of the Formula IIae (II, X = 60 clo[3,3, nonyl-(9). When X1 optionally is a hydroxy -CHRM) with a compound of the formula XR or amino group in reactively functionally modified (VIe) or with a des-HX derivative thereof, or form, included especially are those groups which can vi. reacting a compound of the Formula IIaf (II, X = be split off, under the selected reaction conditions, in -CHRX) or a des-HX derivative thereof with a a manner analogously to Cl, Br, or I, as Hx, for exam compound of the formula M-R (VIf), under condi 65 ple NH2, NHA, NHAr, OH, ASO)- (e.g., methanesul tions wherein HX and/or MX are split off; or fonyloxy), ArSOO- (e.g., benzenesulfonyloxy, p b. treating a compound of the Formula IIb (II, X = toluenesulfonyloxy, 1- or 2-naphthalenesulfonyloxy), X2) wherein X2 is a group oxidizable to the group AcO (e.g., acetoxy, benzoyloxy), or an etherified OH 3,897,453 10 group of preferably 1-7 carbon atoms (e.g., methoxy, dibenzothienylacetaldehyde, OT 2-(2- benzyloxy). dibenzothienyl)-ethanol and/or the functional de The individual variants of the process are more spe rivatives thereof, cifically described as follows: Z-CHRX (Illad): derivatives of the above-named a. Compounds of Formula I can be obtained, for ex 5 compounds halogenated in the o-position, e.g., 2 ample, by the reaction of dibenzofurans and/or -thio dibenzofurylchloro-, -bromo-, or -iodoacetic acid, phenes (II, X = H), optionally substituted in the 2 2-dibenzothienylchloro-, -bromo-, and -iodoacetic position, with compounds (VIa) wherein X preferably acid, and the functional derivatives thereof, and is Cl or Br, under Friedel-Crafts alkylation conditions. derivatives of 2-dibenzofurylbromoethanol and of Especially suitable as the starting compounds are, on 10 2-dibenzothienylbromoethanol, 2-(2- the one hand, dibenzofuran, dibenzothiophene, 2 dibenzofuryl)-2-bromoethanol and 2-(2- alkyldibenzofurans, such as 2-methyldibenzofuran, dibenzothienyl)-2-bromoethanol and the ethers 2-alkyl-dibenzothiophenes, e.g., 2-methyldibenzothio and esters thereof; phene, 2-alkoxy-dibenzofurans, C.g., 2 Z-CHRM (IIae): 1-(2-dibenzofuryl)-ethyllithium, methoxydibenzofuran, 2-alkoxy-dibenzothiophenes, 15 -magnesium chloride or -magnesium bromide, 1 e.g., 2-methoxydibenzothiophene and, on the other (2-dibenzothienyl)-ethyllithium, -magnesium chlo hand, 2-halocarboxylic acids of the formula R2-CHHal ride, and -magnesium bromide; COOH, e.g., 2-chloro and 2-bromopropionic acid and Z-CHRX (Ilaf): 2-(1-chloroethyl)-dibenzofuran, the functional derivatives thereof, e.g., the correspond 2-(1-bromoethyl)-dibenzofuran, 2-(1-hydroxye ing esters, nitriles and amides, and also 2-haloalcohols 20 thyl)-dibenzofuran, 2-vinyldibenzofuran, 2-(1- of the formula R2-CHHal-CH2OH, e.g., 2-chloro-and chloroethyl)-dibenzothiophene, 2-(1-bromoethyl)- by 2-bromopropanol and/or esters and ethers thereof. dibenzothiophene, 2-(1-hydroxyethyl)-dibenzothi Also suitable are the des-HX derivatives of the com ophene, 2-vinyldibenzothiophene; pounds of Formula Vla, for example, the correspond X-CHRR (VIa): 2-halocarboxylic acids, 2 ing unsaturated compounds, e.g., allyl alcohol and/or 25 haloalkanals, 2-haloalkanols and the functional de esters and ethers thereof, or epoxides, e.g., propylene rivatives thereof, preferably the bromine and io oxide. The reaction takes place generally according to dine compounds, e.g., 2-chloropropionic acid, 2 procedures disclosed in the literature. Examples of suit bromopropionic acid ethyl ester, 2 able catalysts are Lewis acids, e.g., AlCl3, AlBrs, BFs, bromopropionitrile, 2-bromopropionaldehyde die and the etherate of the latter, BCl, BBra, ZnCl2, ZnBir, 30 thylacetal, 2-chloropropanol, 2 FeCl, SbCls, a mineral acid, C-8, HF, H2SO4. HPO, bromopropylmethyl ether, and the des-HX deriva or an anhydride thereof, e.g., POs. Preferably, an inert tives of these compounds, e.g., propylene oxide, solvent is employed, e.g., hexane, 1,2-dichloroethane, allyl alcohol; 1,1,2-trichloroethane, trichloroethylene, CS, or nitro M-CHRR (Vib): the Grignard compounds and or benzene. Normally, the reaction is first conducted with 35 ganolithium compounds derived from 2 cooling and terminated at a temperature of about 0 to halocarboxylic acids and/or the salts and functional 100 C., suitably at room temperature. Reaction times derivatives thereof, from 2-haloaldehyde deriva of about 1 hour to 100 hours are usually required. tives, or from 2-haloalcohol derivatives, e.g., the A variant of this method comprises heating a com lithium salt of 2-lithiumpropionic acid; pound of Formula II (X = H) with a halofatty acid to 40 XR2 (VIc): alkyl halides, e.g., methyl chloride, bro a temperature of about 100-250° C., in the presence mide, or iodide, ethyl chloride, bromide or iodide, of a heavy metal oxide, e.g., Fe2O3, and a metallic hal n-propyl chloride, bromide or iodide, n-butyl chlo ide, e.g., KBr. ride, bromide or iodide, and also the corresponding Compounds of Formula I can also be obtained by the alcohols and the reactive esters thereof, e.g., the reaction of an organometallic compound of Formula 45 sulfuric acid and sulfonic acid esters, e.g., the p-tol IIaa (X = M), VIb, IIac, VId, IIae or VIf, respectively, uenesulfonates, e.g., dimethyl sulfate and p-tol with a halogen compound or an analog thereof of For uenesulfonic acid ethyl ester; mula Vla, IIab, VIc, Ilad, VIe or Ilaf, respectively, or MR2 (VId): the Grignard and organolithium com with the corresponding des-HX derivative, especially pounds derived from the aforementioned halides the dehydrohalogen derivative thereof, under condi 50 Vic, e.g., methyllithium, methylmagnesium chlo tions wherein MX is split off and which correspond to ride, bromide or iodide, butyllithium; the conditions for organometallic syntheses known in XR1 (VIe): carbonic acid derivatives, e.g., orthocar the literature. bonic acid tetraethyl ester, CO, diethyl carbonate, Starting compounds for this reaction are, for exam ethyl chloroformate; formic acid derivatives, e.g., ple: 55 ethyl formate, ethyl orthoformate; derivatives of Z-M (IIaa, X = M): 2-dibenzofuryllithium, 2-diben formaldehyde, e.g., methylal, chloromethyl methyl zofurylmagnesium chloride, bromide and iodide, ether; bromomethyl benzyl ether; bis(2-dibenzofuryl)cadmium, 2-dibenzothienylli MR1 (VIf): salts of hydrocyanic acid, e.g., NaCN, thium, 2-dibenzothienylmagnesium chloride, bro KCN; Cu2(CN). mide and iodide, bis(2-dibenzothienyl)cadmium; 60 These starting compounds for the most part are Z-X (IIab): 2-chloro-, 2-bromo- and 2 known or can be prepared in a conventional manner. hydroxydibenzofuran; Thus, the halogen compounds are obtained, for exam Z-CHRM (IIac): derivatives metallized in the ple, by the direct halogenation of the halogen-free cy-position, for example, by Na or an Mgxi group, is basic members, or by reacting the corresponding hy of 2-dibenzofurylacetic acid, 2 droxy compounds with SOCl, HBr or PBra. The iodine dibenzofurylacetaldehyde, 2-(2-dibenzofuryl)- compounds can also be produced, for example, by re ethanol, 2-dibenzothienylacetic acid, 2 action of the bromine compounds with KI. The organo 3,897,453 11 12 metallic compounds can be obtained, for example, by with equimolar amounts of reactants. First, the reac metallizing the corresponding hydrogen or halogen tion mixture is allowed to react for several hours under compounds, e.g., with metallic Na, Li, or Mg, NaH, cold conditions and then the mixture is heated to NaNH2, alkyllithium or aryllithium compounds, e.g., 50-80 C., optionally while replacing a low-boiling butyllithium or phenyllithium. inert solvent, e.g., ether, by a higher-boiling solvent, Suitable solvents for these reactions are, for example, e.g., benzene. ethers, e.g., diethyl ether, diisopropyl ether, 1,2- Schiff bases of the formula Z-CHR-CH=NAr are dimethoxyethane, tetrahydrofuran (THF), dioxane and obtained by reacting the organometallic reagents IIae mixtures thereof with each other or with hydrocarbons, with N-(alkoxymethylene)-arylamines of the formula e.g., hexane, benzene, toluene or xylene, amides, e.g., 10 AO-CH=NAr, e.g., ethoxymethylene aniline. This re dimethylformamide (DMF), hexamethylphosphoric action takes place under very gentle conditions and is acid triamide, sulfoxides, e.g., dimethyl sulfoxide usually terminated after boiling the components for (DMSO). The reaction temperatures are normally one-half hour in an ether solution. By decomposing the about -20° to 180°C., preferably 0° to 70° C. The reac reaction mixture with ice and hydrochloric acid, the al tion times usually range from 0.5 to 72 hours. It is pos 15 dehydes (Z-CHR-CHO) are directly obtained. sible to add a Lewis acid to the reaction mixtures, e.g., Also, substituted formamides, usually formyl mo AlCl3, FeCl3, ZnCl2. Furthermore, the reaction can be noalkylanilines of the formula CHO-NAAr or formyl started in a low-boiling solvent, e.g., diethyl ether, and diarylamines of the formula CHO-NArt, can be re this solvent then replaced by a higher boiling one, e.g., acted with organometallic reagents of the Formula IIae. benzene, and the reaction can then be terminated in 20 Ordinarily, the reaction is conducted at room tempera the latter solvent, for example by refluxing. ture. The formamides are employed in excess and the Several variants of these organometallic reactions are aldehyde ammonias formed as an intermediate are de specifically: composed by working up the reaction mixture in an Carboxylic acids of Formula I (R = COOH) are ob acidic medium, with the formation of the desired alde tained by reacting a compound IIae with CO2. For this 25 hydes. Preferred formamides are N-methylformanilide purpose, a dry stream of CO, can be introduced into and N-phenylformanilide. the cooled solution of the organometallic compound, b. To produce the compounds of Formula I, it is also or this solution can be poured onto solid CO2. Prefera possible to treat compounds of the formula Z-X (IIb) bly, Grignard compounds of the formula Z-CH with a dehydrogenating and/or oxidizing agent. R-MgHal are employed, which can be produced with 30 a large excess of a mixture of magnesium filings and Suitable starting compounds of Formula IIb are, for pulverized magnesium, and a vigorous steam of CO2 is example, those wherein X2 is -CHR-CH=CHR, passed through the reaction mixture during the Grig -CHR-CHOH-CHOH-R, -CHR-- nardization. CHOH-CO-R, -CHR-CHOH-COOR, In addition to employing an organometallic com 35 -CHR-CHOH-CHNHR, -CHR-C- pound of Formula IIaa, there can also be employed C-R1, -CHR2-CO-R1, wherein R11 is H or any compounds of Formulae VIb, Ilac, VId, IIae and/or Vif, desired organic radical, preferably A, Ar, CN or wherein M is an organoboron residue, particularly 9 COOH, since the part of the molecule carrying the R borabicyclo[3,3,1)nonyl-(9). These starting com group is removed by oxidation so that the exact nature pounds can be obtained, for example, by reacting the 40 of the R11 group is not critical, -CHR2-CH-R, corresponding organolithium compounds with 9 wherein R12 is a hydroboron, boroalkyl, or aluminum borabicyclo3,3, nonane in an ether at a temperature alkyl group, an alkali metal or an alkaline earth metal of about -10° to +20° C. and subsequent acidification. halide group, or -CRFR, wherein R is =CH2. (OH, They normally are not isolated. The actual reaction of CH3), or the group -O-CH2-. these organoboron compounds with the compounds of 45 According to the oxidation conditions described in Formula VIa or of Formulae IIab, VIc, Iad, VIe and/or the literature, suitable oxidizing agents are, for exam IIaf, takes place suitably with the addition of a lower ple, air or oxygen, preferably with the addition of a cat tert.-alkanol and an excess of a lower alkali metal tert.- alyst, e.g., Mn, Co, Fe, Agor VOs; silver oxide, option alkoxide, preferably potassium tert.-butylate or -penty ally also together with copper oxide; HO, preferably late, at a temperature of about -10° to +20 C. 50 in the presence of an alkaline agent; organic peracids, Aldehydes and/or the derivatives thereof of Formula e.g., peracetic acid, perbenzoic acid, perphthalic acid; I (R optionally functionally modified aldehyde potassium permanganate in an aqueous or acetonic so group) can be obtained by reacting the organometallic lution and/or an acidic, neutral, or alkaline medium, optionally with the addition of MgSO; chromic acid or compounds of Formula IIae with formic acid deriva 55 tives. CrO3, e.g., in acetic acid or acetone, or in an aqueous The reaction of compounds IIae with formic acid es acetonic solution in the presence of sulfuric acid; ters of the formula HCOOA leads directly to aldehydes HNO, and the salts thereof, HNOa and the salts thereof, of the formula Z-CHR2-CHO. However, since the for example 2-68% strength nitric acid, optionally reaction readily goes beyond the aldehyde stage, it is under pressure (up to 100 atmospheres); nitrogen ox advantageous to work with an excess of the ester and 60 ides; HClO or the salts thereof, e.g., NaClO, MnO, at a temperature, e.g., -100° to -50° C. e.g., in dilute sulfuric acid or in a suspension in inertor Orthoformic acid esters of the formula HC(OA) ganic solvents, for example petroleum ether; PbO, react with the compounds IIae with the formation of lead tetraacetate, e.g., in acetic acid or benzene, op acetals of the formula Z-CHR2-CH(OA). By work 65 tionally with the addition of some pyridine; SeO; N ing up the reaction mixture in an acidic medium, the haloamides, e.g., N-bromo-succinimide, for example in free aldehydes of the formula Z-CHR2-CHO are ob acetic acid/sodium acetate or in pyridine; m-nitroben tained. The reaction is most advantageously effected Zenesulfonic acid; HsOs and the salts thereof; ozone; 3,897,453 13 14 NaBiO3, and a mixture of sulfur and an anhydrous pri pounds required as the starting materials in the pure mary or secondary amine, e.g., morpholine. form. Instead, they can be oxidized directly in the reac Examples of suitable solvents for these oxidations are tion mixture in which they were produced. water or aqueous alkali solutions; carboxylic acids, e.g., In one mode of operation of this reaction, an ethyl acetic acid; alcohols, e.g., methanol, ethanol, isopropa ene derivative of the formula Z-CRFCH is first re nol, or tert-butanol; ethers, e.g., diethyl ether, THF, acted with diborane. For this purpose, a BH-solution dioxane, ketones, e.g., acetone; hydrocarbons, e.g., or a complex boron hydride, e.g., NaBH4, and a Lewis benzene; amides, e.g., DMF or hexamethylphosphoric acid, e.g., BFetherate, are added, for example, to a triamide; and sulfoxides, e.g., DMSO. Also suitable are solution of the olefin in, e.g., THF or di- or triethylene mixtures of these solvents, especially mixtures of water 10 with an organic solvent. The temperatures during the glycol dimethyl ether at a temperature from about oxidation step range from -30° to 300 C., depending -80°C. to the boiling point of the solvent, and the thus on the method employed. produced trisubstituted borane is then oxidized, op Characteristic oxidation methods are, for example: tionally after decomposing the excess complex hydride 2-Oxocarboxylic acids of the formula Z-CH 15 with water. Depending on the oxidation agent em R-CO-COOH can be decarbonylated by oxidation, ployed and the oxidation conditions, various products for example with aqueous-alkaline H2O2, to carboxylic of Formula I can be obtained. For example, by oxidiz acids of the formula Z-CHR-COOH. A decarbony ing with H2O, with the addition of a base, e.g., NaOH, lation is likewise possible in a sulfuric acid or hydro preferably at a temperature of from 20' to 60°C., alco chloric acid solution in the presence of an oxidation 20 hols (I, R = CHOH) are produced, whereas oxidation agent. In an alkaline solution, the reaction is advanta with an excess of CrO3, preferably in aqueous acetic geously conducted at a temperature from 0 to 25 C. acid at about 0-40 C., and after a reaction time of The 2-oxocarboxylic acids are obtainable, for example, about 1-48 hours, leads to the carboxylic acids (I, R by the reaction of 2-acyldibenzofurans and/or - diben = COOH). Alkylaluminum compounds can be used in zothiophenes of the formual Z-CO-R2 with acetylg 25 place of the diborane, which former compounds can be lycine to the corresponding azlactone and alkaline hy added and split by oxidation in an analogous manner. drolysis. Furthermore, the dibenzofuryl- or dibenzo Unsaturated compounds of the formula Z-CH thienylethyl metal and metal halide compounds of the R-CH=CH-R, e.g., wherein R1 = CN, which are formula Z-CHR2-CH2M, obtainable from the halo obtainable by reacting a carbonyl compound Z-- 30 genides of the formula Z-CHR2-CH2-Hal with al CO-R with acrylonitrile in the presence of triphenyl kali metals, preferably Li, or alkaline earth metals, phosphine in cyclohexanol, and/or of the formula preferably Mg, can be treated with an oxidation agent Z-CHR -C=CR11 can be converted, for example. for conversion into compounds of Formula I (R = op by oxidation into aldehydes of the formula Z tionally functionally modified CH-OH-group). In a pre CHR - CHO or into carboxylic acids of the formula 35 ferred embodiment of this method, oxygen is passed Z-CHR -COOH, depending on the choice of the through a solution of the corresponding Grignard com oxidation agent and the conditions. An oxidation with pound of the formula Z-CHR2-CH2-MgHal in an KMnO, or OsO4 leads, first of all, to the 1,2-glycols inert solvent, e.g., ether, THF, or dioxane, at a temper Z-CHR-CHOH-CHOH-R which can be 40 ature of about 40' to 100° C. After the usual working split, for example with HIOs, to form the correspond up procedure, alcohols of the formula Z-CHR-CH ing aldehydes. OH are obtained. An oxidation of the olefinic double bond with ozone, e.g., in CHCl, or ethyl acetate, leads to ozonides which In a modification of this variant of the process, a can be split reductively by means of zinc in acetic acid, compound of the formula Z-CR-Ra is treated with or by catalytic hydrogenation on palladium/calcium 45 sulfur and an anhydrous amine at an elevated tempera carbonate to aldehydes (I, R = CHO). On the other ture, preferably at at least 100° C., until a thioamide hand, they can be converted, with stronger oxidation has been formed. The reaction mixture should contain agents, into carboxylic acids (I, R1 = COOH). at least 2, preferably at least 3 molar equivalents of sul Compounds of Formula IIc carrying groups with fur in finely divided form. At least 2 molar equivalents functional groups on adjacent carbon atoms, e.g., 1,2- 50 of amine should be employed. Any primary or secon diols, 1,2-ketols, 2-hydroxy-carboxylic acids, or 1,2- dary aliphatic or alicyclic amine can be used in this re hydroxy-amines can be split, for example, with lead action, e.g., primary or secondary hydrocarbon amines of up to 12 carbon atoms, e.g., methylamine, dimethyl tetraacetate, with NaBiO3, or with HsOs between the amine, ethylamine, diethylamine, n-butylamine, n carbon atoms carrying the functional groups, to form 55 an aldehyde function. The lead tetraacetate oxidation hexylamine, n-octylamine, etc. Also suitable are cyclic is suitably accomplished with the stoichiometric amines, which can be substituted by alkyl groups and amount of oxidation agent in an inert solvent, such as can contain oxygen in the ring structure, e.g., piperi acetic acid, chloroform, tetrachloroethane, benzene, or dine, morpholine, etc. Morpholine is preferred, since nitrobenzene at temperatures of between 0 and 60 C. 60 this compound makes possible conducting the reaction When conducting the oxidation with periodic acid, at ambient pressure. No solvent is necessary in the re an aqueous medium is suitably utilized. Advantageous action mixture. However, if desired, pyridine or an ex solubilizers for the glycol are emulsifiers, dioxane, cess amine, DMF, etc., can be used. The reaction time acetic acid or tert.butanol. The reaction temperature depends primarily on the reaction temperature; ordi ranges suitably from 0 to 15 C. 65 narily, 4-48 hours are sufficient. The thus-obtained thi Compounds of the formula Z-CHR2-CH2-R12 can oamide of the formula Z-CHR-CSNR, wherein be converted into the corresponding compounds of the R14N group corresponds to the starting amine Formula I by oxidation. For this purpose, it is unneces R14NH, can optionally be hydrolyzed to the corre sary to isolate the organoboron or organometallic con sponding carboxylic acid (I; R = COOH). It is not nec 3,897,453 15 16 essary to isolate the thioamide from the reaction mix Advantageous acids are, for example, hydrochloric ture. acid or acetic acid. A mixture of zinc with acetic acid, c. Compounds of Formula I can also be obtained by for example, can be advantageously employed for the the reduction of compounds of Formula IIc. reduction of ozonides IIcb Typical compounds of the Formula IIc are those of O Formula IIca, Icb or IIcc, for example: (R16 = H, c 1 N. CHR) Z-CR FR1s. No-o-1 IIca to aldehydes (I, R = CHO). Also suitable for the wherein Rus is an alkylidene of up to 4 carbon atoms, 10 production of the nascent hydrogen is sodium or an corresponding to R2, other alkali metal in a lower alcohol, e.g., ethanol, iso propanol, n-butanol, amyl alcohol and isoamyl alcohol, Z-CRFR18 or in phenol. An aluminum-nickel alloy in an alkaline Icb aqueous solution, optionally with the addition of meth wherein R is FCHR, 15 anol, can likewise be used for this purpose. Sodium or aluminum amalgam in an aqueous-alcoholic or aque O ous solution can also be employed for producing the (H, -CH 1N CHR ll. nascent hydrogen. The reaction can also be effected in a heterogeneous phase, wherein an aqueous phase and 20 a benzene or toluene phase are advantageously utilized. or -O-CH2-and R1 is an esterified or etherified In this reducing method, temperatures of about 0 to OH-group; about 150° C., preferably 20° C. to the boiling point of the solvent employed, are employed. Z-CRR2-Rs Other suitable reducing agents are metal hydrides, IIcc 25 particularly complex metal hydrides. This is especially wherein R1s is a group removable by hydrogenolysis, advantageous when it is desired to simultaneously a re especially OH, OAc, Hal, SH, NH, aralkyloxy or aralk duction of the group R1 to the aldehyde or alcohol ylamino, each of up to 10 carbon atoms. stage. Suitable hydrides of this type are, for example, The reduction of these starting substances can be lithium aluminum hydride, sodium borohydride, e.g., in suitably effected by catalytic hydrogenation or by 30 the presence of aluminum chloride or lithium bromide, chemical methods. calcium borohydride, magnesium borohydride, sodium The starting materials can be treated with hydrogen, aluminum hydride, lithium and sodium alkox for example in the presence of a catalyst, at pressures yaluminum hydrides, e.g., LiAl(OC2H5)2H2, LiAl of about 1 to about 200 atmospheres and at tempera (OCH)H, LiAl(0-tert.-CHg)H, NaAl(OCH3)H tures of about -80° to 200° C., preferably 20 to 100 35 and sodium trialkoxy borohydrides, e.g., sodium trime C. The hydrogenation is advantageously accomplished thoxyborohydride. Additionally suitable reducing in the presence of an inert solvent, e.g., water, acqueous agents are dialkylaluminum hydrides, e.g., sodium hydroxide solution, lower alcohols, e.g., metha disobutylaluminum hydride. These reductions are ad nol, ethanol, isopropanol, n-butanol, esters, e.g., ethyl vantageously conducted in the presence of an inert sol acetate, ethers, e.g., THF or dioxane or carboxylic 40 vent, for example, an ether, e.g., diethyl ether, THF, acids, e.g., acetic or propionic acid. It is also possible dioxane, 1,2-dimethoxyethane, or diglyme. Sodium to utilize solvent mixtures. For the hydrogenation, the borohydride can also be used in an aqueous or aque free compounds IIc can be employed, or also the corre ous-alcoholic solution. The reaction takes place prefer sponding salts, e.g., the hydrochlorides or sodium salts. ably at temperatures of from -80 to +100° C., espe Suitable catalysts are, for example, noble metal, nickel 45 cially from 20°C. to the boiling point of the solvent em and cobalt catalysts. The noble metal catalysts can be ployed. An inert gas atmosphere, e.g., N2 or argon, can provided on supports, e.g., on charcoal, calcium car be used in this reaction. The thus-formed metal com bonate, or strontium carbonate, as oxide catalysts, or plexes can also be decomposed in the usual manner, as finely divided metallic catalysts, e.g., platinum and e.g., with moist ether or with an aqueous ammonium palladium, which are preferred, and ruthenium or rho 50 chloride solution. As is known in the art, depending on dium. Nickel and cobalt catalysts are suitably em the conditions employed, reduction of unsaturated es ployed as Raney metals. Nickel can also be used on kie ters of the type Z-C(=Rs)-COOA with LiAlH re selguhr or pumice as the support. Another suitable cat sults in various products, for example, in aldehydes (I, alyst is copper-chromium oxide. With this catalyst, it is R = CHO) or alcohols (I, R = CHOH). simultaneously possible to effect a reduction of any 55 Another preferred reducing agent especially suitable ester groups present in the molecule to alcohols. for the removal of a tertiary OH-group in a starting Preferably, normal pressure is utilized during the hy compound of the formula Z-CRR2-OH is tin(II) drogenation of multiple bonds, and the reaction is car chloride, which is preferably utilized in the form of the ried out so that the hydrogenation is terminated after dihydrate thereof in an aqueous, aqueous-alcoholic, or absorption of the stoichiometric amount of hydrogen. 60 aqueous-acidic solution, e.g., in the presence of acetic It is basically possible to operate in an acidic, neutral acid and/or hydrochloric acid. This reagent is suitably or basic range. used at temperatures of between about 0° and 120° C. Also suitable as a reducing method for the com This reagent is usable as a reducing agent in the pre pounds of Formula IIc is the reaction with nascent hy 65 ferred method of synthesizing the acids and esters of drogen. The latter can be produced, for example, by Formula I described below. treating metals with acids or bases, e.g., the systems A dibenzofuran or dibenzothiophene of the formula zincfacid, zincfalkaline solution, iron/acid and tin/acid. Z-H is reacted, in a Friedel-Crafts reaction, with 3,897,453 17 18 ethoxalyl chloride to the corresponding 2-(2- Thus, for example, one obtains 2-(7-ethyl-2-diben dibenzofuryl)- or 2-(2-dibenzothienyl)glyoxylic acid zofuryl) valeric acid from 2-(7-acetyl-2-dibenzofuryl)- ethyl ester, respectively, which are converted, with an 4-oxopentanoic acid, according to Wolff-Kishner or organometallic compound of the formula R2M, into the Clemmensen, or 2-(7-amino-2-dibenzofuryl)-propionic corresponding tertiary hydroxy ester of the formula 5 acid from 2-(7-nitro-2-dibenzofuryl)-2-hydroxypro Z-CR(OH)-COOC2H5, which can be reduced, with pionic acid by reaction with SnCl2. tin(II) chloride, to the desired ester Z-CH d. Compounds of Formula I can also be produced R-COOCHs. When operation under hydrolyzing from compounds of Formula IId by thermolysis or sol conditions, carboxylic acids of the formula Z-CH volysis. R-COOH are obtained. 10 Additional functional groups in the X4 groups which Another reducing agent is hydriodic acid, optionally can be removed by thermolysis or solvolysis are, for ex with the addition of phosphorus and/or solvents, e.g., ample, carboxyl groups, which can be removed by de acetic acid, preferably at a temperature of from 100 C. carboxylation. to the boiling temperature. Oxo groups, in particular, Acyl groups, particularly acetyl groups, can be split 15 off by treatment with a strong alkali (acid cleavage). It can thus be reduced to CH2-groups. is also possible, for example, to remove the oxo group Additional suitable reducing agents are, for example, of 2-oxocarboxylic acids in the form of carbon monox sodium dithionite in an alkaline or ammoniacal solu ide or to split off CO, from these acids with the forma tion; iron(II) hydroxide; hydrogen sulfide and the de tion of the basic aldehyde and/or aldehyde derivative. rivatives thereof, especially metal hydrogen sulfides, 20 Starting compounds suitable for the decarboxylation metal sulfides and polysulfides; SO, and the derivatives are, for example, compounds of the formula Z-CR thereof, e.g., bisulfites and sulfites. R-COOH wherein R preferably is an optionally It is also possible to reduce, in compounds of the For functionally modified COOH-group. Such malonic acid mula IIc, one or more carbonyl groups to CH2-groups derivatives can be obtained, for example, by the con in accordance with the methods of Clemmensen or 25 densation of a 2-dibenzofuryl- or 2-dibenzothienyla Wolff-Kishner known in the literature. cetic acid ester of the formula Z-CH-COOA with The Clemmensen reduction can be conducted, for an oxalic acid dialkyl ester to the corresponding 2-(2- example, by treating the carbonyl compound with a dibenzofuryl)- or 2-(2-dibenzothienyl)-3-oxosuccinic mixture of zinc and hydrochloric acid, amalgamated acid diester. The decarbonylation of these compounds zinc and hydrochloric acid, or tin and hydrochloric 30 results in 2-(2-dibenzofuryl)- or 2-dibenzothienyl)- acid. This reaction is conducted, for example, either in malonic esters which, in the form of their sodium deriv an aqueous-alcoholic solution or in a heterogeneous atives, can be alkylated with a compound of the for phase with a mixture of water and benzene or toluene. mula Ra-Hall. The thus-produced diesters of the for The reaction is preferably effected at a temperature of mula Z-CRCCOOA), can subsequently be saponi from 20° to 130° C., especially at the boiling tempera 35 fied, optionally partially. ture of the reaction mixture. The metal can either be A decarboxylation of these starting substances can, supplied first and the acid added thereto dropwise, or as described in the literature, be accomplished, for ex conversely, the acid can be supplied first and the metal ample, by dry heating or by warming in a solvent, e.g., can be added in batches. water, ethanol, dioxane or xylene, to a temperature of The Wolff-Kishner reduction is accomplished, for ex 40 from 50 to 300° C. Suitably, the reaction mixture is ample, by treatment of the carbonyl compounds with heated until the evolution of CO, has stopped. It is pos hydrazine in an autoclave and/or in a bomb tube at re sible to conduct the reaction under reduced pressure. action temperatures of from 100 to 250 C. An advan CO2 can also be split off by heating with acids, e.g., a tageous catalyst in this reaction is sodium alcoholate. mixture of aqueous hydrochloric acid and acetic acid. The reduction can also be modified by using hydrazine 45 This reaction can be conducted under an inert gas, e.g., hydrate as the reducing agent and executing the reac nitrogen. tion in an alcohol or in a high-boiling water-miscible For acid cleavage, especially suitable are keto esters solvent, e.g., diethylene glycol or triethylene glycol of the formula Z-CR-Ac-COOA, wherein Ac pref and/or in the presence of a strong base, e.g., NaOH, erably is acetyl or benzoyl. These keto esters can be ob KOH, or K-tert.butylate. The reaction mixture is nor 50 tained, for example, by the condensation of esters of mally refluxed for about 3-4 hours. Thereafter, the the formula AcOA, especially alkyl esters of acetic water is distilled off and the residue heated for a period and/or benzoic acid, with esters of the formula Z-CH of time to a temperature of up to about 200 C. During 2-COOA and/or with cyanides of the formula this step, the formed hydrazone is decomposed and the Z-CH2CN. The thus-produced keto esters or ketoni CO-group is converted into a CH2-group. 55 triles of the formulae Z-CH(COOA)-Ac and It is also possible to replace Hall-atoms by hydrogen Z-CH(CN)-Ac, respectively, can thereafter be al by converting the corresponding Hal-compounds into kylated as described above, thus obtaining compounds the associated organometal, e.g., Grignard, com of the formulae Z-CRCCOOA)-Ac and Z-CR(C- pounds, and hydrolyzing the latter with water or dilute 60 N)-Ac, respectively. If desired, additional functional acids. modifications can be effected on the ester or nitrile By the above-described methods, it is possible to re groups. The acid cleavage of the thus produced com duce several reducible groups in a given starting com pounds of the formula Z-CRR-Ac takes place nor pound, wherein the compounds of Formula IIC are mally by treatment with a strong base, e.g., NaOH, passed through an intermediate stages of the reaction, 65 KOH, or Ca(OH)2, in a solvent, e.g., water, lower alco but need not be isolated. Furthermore, an R and/or Rs hols, e.g., methanol or ethanol, ethers, e.g., diethyl group in the starting compound can be reduced to an ether, THF, dioxane, hydrocarbons, e.g., benzene and other group R and/or Rs. mixtures thereof. The reaction temperatures range 3,897,453 19 20 from about -10 to 200 C. If it is intended to obtain alkali metal tert.-alcoholate is added as the catalyst and the free carboxylic acids of Formula I (R1 = COOH), a lower tert.-alkanol is used as the solvent. At least one the reaction mixture is preferably heated for several and preferably 3-20 molar equivalents of the heavy hours to a temperature of about 60 to 100 C., option metal carbonyl are employed. Preferred solvents in this ally under an inert gas, e.g., nitrogen. 5 reaction are, for example, tert-butanol, tert-pentanol, It is furthermore possible to produce compounds of 2-methyl-2pentanol and 3-methyl-3-pentanol. Espe Formula I by the decarbonylation of correspondingly cially suitable alkali metal alcoholates are the sodium, substituted 2-oxocarboxylic acids of the formula potassium and lithium derivatives of the aforemen Z-CHR-CO-COOH, which can be obtained by tioned tert.-alkanols, e.g., sodium, potassium and lith treating glycidic esters of the formula 10 ium tert.-butylate. The reaction mixture should contain at least one and preferably 2-5 molar equivalients of the alkali metal alcoholate. Reaction temperatures can range from about 0 to about 120° C., preferably be N/ tween 30 and 100° C. Reaction times of one hour up O 15 to about 4 days are required for the reaction. Under with Lewis acids, e.g., BFs, followed by saponification. these conditions, the tert.-alkyl esters of the corre Thus, it is possible, for example to decarbonylate such sponding carboxylic acids of Formula I (R = COOH) a 2-oxo acid to an acid of the Formula I (R1 = COOH, are obtained, which need not be isolated, but instead by heating in concentrated sulfuric acid. can be saponified in situ to the free acids. The 2-oxocarboxylic acids split off CO2 at tempera 20 In another embodiment, a compound of the Formula tures of from 100 to 300° C., with the formation of an IIe, preferably Z-CH=Rs or Z-CHROH, is reacted aldehyde. The decarboxylation is enhanced by the ad with the heavy metal carbonyl, preferably nickel car dition of an amine. Colloidal platinum, osmium and ru bonyl, suitably in an inert solvent, such as THF, diox thenium likewise catalyzes the dissociation. Thus, the ane, acetone, in the presence of water. An inorganic decarboxylation can be conducted in the presence of a 25 acid, e.g., HCl, HSO, HBr, HI, HPO, can be present primary, secondary, or tertiary base, normally at the in the reaction mixture. The reaction temperatures boiling point thereof. When a primary amine, e.g., ani range, for example, from about 20 to about 100° C. line, is employed, a Schiff base of the aldehyde is pro The reaction can be accelerated by irradiation, for ex duced with splitting off of H2O and CO2. When the re ample, with a mercury-vapor lamp. Depending on the action mixture is worked up in an acidic fashion, the 30 conditions, the reaction usually requires about 2 hours aldehyde is then liberated. In another embodiment, the to 2 days to go to completion. bisulfite compounds of the 2-oxocarboxylic acids When using formic acid-fsulfuric acid as the cabony Z-CHR-CO-COOH can be decarboxylated at lation reagent, suitable starting compounds are the 2 temperatures of about 100 to 300 C., thus obtaining vinyldibenzofurans or -dibenzothiophenes and the car a bisulfite of the corresponding aldehyde. 35 binols of the formula Z-CHR-OH. The starting e. Compounds of Formula I are also produced by the compounds are reacted, for example, at temperatures carbonylation of compounds of the Formula IIe or the of about 0-40 C., with a mixture of formic acid and des-HX derivatives thereof, optionally in the presence a concentrated sulfuric acid, which can contain 0-50% of a reducing agent and/or a catalyst. acetic acid or trifluoroacetic acid. Ordinarily, reaction Suitable starting compounds for the carbonylation 40 times of about one minute to 4 hours are required. The are, for example, compounds of the formulae Z-CH reaction mixture should contain at least 2 and prefera R-Cl, Z-CHR-Br, Z-CHR-I, Z-CHR-OH, bly 5-20 molar equivalents of formic acid. as well as Z-CR-CH2, e.g., 1-(2-dibenzofuryl)-ethyl Carbonylation with gaseous CO is advantageously chloride, bromide O iodide; 1-(2- conducted under a pressure of 100-700 atmospheres in dibenzofuryl)ethanol; 2-vinyldibenzofuran; 1-(2- 45 an inert solvent, suitably a lower alcohol, e.g., metha dibenzothienyl)-ethyl chloride, bromide or iodide; nol, ethanol, propanol, isopropanol, n-butanol, n 1-(2-dibenzothienyl)-ethanol; and 2-vinyldibenzothio pentanol, n-hexanol or a cycloalkanol, e.g., cyclohexa phene. nol. Examples of suitable catalysts are nickel or cobalt The carbonylation can be effected, as described in carbonyls or halogenides, palladium dichloride, rho the literature, by treatment with gaseous CO, prefera 50 dium trichloride (preferably in the form of the trihy bly under a pressure of up to 700 atmospheres and at drate), or a compound of the formula (R)P2PdCl, a temperature of up to 300+ C., with the addition of a wherein R19 is an alkyl, cycloalkyl, aryl or aralkyl heavy metal catalyst. It is also possible to contact the group, preferably of up to 10 carbon atoms, e.g., (bis starting compound of Formula IIe to CO in the form of (triphenylphosphine)palladium dichloride. During this a heavy metal carbonyl. The CO required for the car 55 reaction, up to 10% by weight of an organic or inor bonylation can also be produced directly in situ from ganic, preferably strong, acid can be present, e.g., HCl, a mixture of formic acid and a mineral acid, preferably HBr, H2SO4, p-toluenesulfonic acid and methanesul concentrated sulfuric acid. When operating in the pres fonic acid. ence of a reducing agent, e.g., gaseous hydrogen, alde 60 It is also possible to react compounds of Formula IIe, hydes of Formula I (R = CHO) are obtained. especially unsaturated compounds of the type Several typical variants of the carbonylation process Z-CH-Rs, and halogenides of the formula Z-CH are the following: R2-Hal, with a mixture of CO and H, in the presence Compounds of the formulae Z-CHR2-Hal, of a heavy metal catalyst, especially a cobalt catalyst, ZCHR - OHor Z-CH=Rs can be reacted with a e.g., cobalt(II) acetate, pulverized cobalt, or prefera heavy metal carbonyl, e.g., nickel carbonyl. One em 65 bly dicobalt octacarbonyl, to obtain aldehydes of For bodiment advantageously uses the halogen derivatives mula I (RFCHO). In this reaction, pressures of about z-CHR2-Hal as the starting compounds, wherein an 10 to about 250 atmospheres and temperatures of 3,897,453 21 22 about 0 to 200 C., and optionally an inert solvent, for ratus. In this connection, the glass surface of the appa example, an ether, e.g., diethyl ether, THF, 1,2- ratus can function as the catalyst. The rearrangement dimethoxyethane and/or a ketone, e.g., acetone, are can also be accelerated by adding small amounts of a employed. catalyst, e.g., ZnCl2. For the rearrangement of the ep f. Haloketones of the formula Z-CO-CHRHal, 5 oxides, it is also possible to employ solid catalysts, e.g., obtainable by the halogenation of ketones of the for copper, copper bromide, magnesium silicates, alumi mula Z-CO-CH2R, or from diazoketones of the for num oxides and chromium oxide - tungsten oxide mula Z-CO-CRN by reaction with hydrogen halide contact catalysts. In these reactions, temperatures of in ether or by a Friedel-Crafts acylation of dibenzofu from 100 to 300° C. and pressures between reduced rans or dibezothiophenes of the formula Z-H, respec O pressure and 200 atmospheres are employed. The car tively, with haloacyl halides CHRHal-COHal, e.g., boxylic acids IIhc and IIhd, respectively, are suitably 2-chloropropionyl chloride, can be rearranged into split thermally under reduced pressure with the addi acids of the formula Z-CHR-COOH in accordance tion of copper or copper bromide as catalyst. The rear with the Faworskii method described in the literature, rangement can be conducted in the gaseous or liquid 15 phase, depending on the stability of the epoxide and the for example, in boiling toluene or xylene in the pres type of catalyst. A brief heating of the epoxides with ence of a strong base, e.g., NaOH, or by heating in an concentrated NaHSOs solution yields directly the cor aqueous-ethanolic silver nitrate solution. responding sodium bisulfite addition compounds of g. Amides of Formula I (R = CONHRs) can be ob Formula I (R = CHOH-SONa). tained by subjecting a carbonyl compound of Formula 20 Ig (Xs = CORs) to a Schmidt degradation according to The epoxides of Formula IIha or IIhb can be obtained methods disclosed in the literature with HN3, prefera for example, by reacting ketones of the formula Z-- bly in an inert solvent, e.g., benzene or chloroform, and CO-R, with alkyl-magnesium halides, hydrolysis to in the presence of an acidic catalyst, e.g., concentrated the carbinols, dehydration to ethylene derivatives of sulfuric acid, at a temperature of about -40 to +100 25 the formula Z-CRFCHRs, and epoxidation with per C. acids, e.g., perbenzoic acids. The epoxides can also be Amides of Formula I can also be produced by sub produced from the chlorohydrins of the formula Z jecting an oxime of the Formula Ilg (Xs = C(=NOH -CR (OH)-CHRs-Cl by treatment with a base, thus )-Rs) to a Beckmann rearrangement, as described in splitting off HCl. These chlorohydrins can be obtained, detail in the literature, with an acidic agent, e.g., con 30 in turn, from chloroketones of the formula Z-- centrated sulfuric acid, polyphosphoric acid, phospho CO-CH2-Cl by reaction with methyl- or ethylmag rus pentachloride, or benzenesulfochloride, preferably nesium iodide, or by reduction. It is also possible to at a temperature of from 80° to 180° C. react chloromethyl ketones of the formula R-- h. The conversion of epoxides of Formula IIh, espe COCH2Cl with organometallic compounds Z-M, with cially those of formulae Ilha - IIhd: 35 the epoxide not normally being isolated. Thus, 2-(2- ZCR-CH ZCH-CR \-/ 2 V o/ 2 Zeyti-cool/ ha IIhb IIhc into compounds of Formula I (R = CHO) can be ac dibenzofuryl)-butanal is produced from 2-diben complished basically according to the rearrangement zofurylmagnesium bromide by reaction with chloro reactions described in the literature under catalytic or methyl ethyl ketone. In other cases, the isolation of the thermal conditions, thus splitting off CO2 from the car epoxides IIh often is unnecessary. Thus, for example, boxylic acids IIhc or IIhd, respectively. For catalytically 45 the corresponding epoxide can be prepared from 2 controlled rearrangements, the epoxide is caused to chloro-2-(2-dibenzofuryl)-propanol by treatment with react with the catalyst in a suitable solvent. Suitable a base, and this epoxide is rearranged in situ without solvents for the rearrangement reactions are inert sol isolation into 2-(2-dibenzofuryl)-propanal by treat vents, e.g., benzene, toluene, xylene, CCl4, acetonitrile, ment with an acid. ether, THF, dioxane, alcohols, e.g., ethanol, propanol, 50 The epoxy acids Iihc and IIhd are advantageously ob butanol or acids, e.g., formic acid, acetic acid, both as tained by condensation of ketones of the formula Z-- anhydrous solvents and in mixture with water. The re CO-R, with ethyl chloroformate and subsequent alka arrangement can also be effected on the interphase of line saponification. It is advantageous not to isolate two solvents immiscible with each other, wherein one 55 these epoxy acids but instead the alkaline saponifi phase contains the catalyst and the other the com cation mixture is adidified and heated until termination pound to be rearranged. Preferred catalysts are mineral of the decarboxylation, thus obtaining the desired alde acids, e.g., HSO, HCl, HBr, HF, HClO; organic acids, hydes (I, R = CHO). The epoxy acids, and/or the es e.g., formic acid, acetic acid, oxalic acid, p-toluenesul ters thereof, can also be prepared by expoxidation of fonic acid; Lewis acids, e.g., BF3, AlCl3, ZnCl2, MgBr, 60 the acrylic acids Z-CRFCH-COOH and/or the esters FeCls and SnCl2. The rearrangement can be accom thereof. plished, for example, by heating a solution of the epox i. Aldehydes of Formula I (R1 = CHO) can be pro ide in THF with 25% strength sulfuric acid or with BFs, duced by splitting off HX from compounds of the For p-toluenesulfonic acid, or ZnCl2 as the catalyst in anhy mula Ili, especially by dehydrating glycols of the for drous benzene. The rearrangement can also be con 65 mula Z-CR(OH)-CHRs-OH, preferably Z-CR ducted with the aid of agents which split off water, e.g., (OH)-CH2OH, but also Z-CHOH-CHR-OH, polyphosphoric acid, which can simultaneously serve which process takes place by a rearrangement which is as the reaction solvent. catalyzed by acids, metal halides, Lewis acids or solid The epoxides can also be thermally rearranged, for catalysts. Advantageous acids are HCl, HBr, HSO, example, by distillation or by heating in a sealed appa HPO, HSO, HClO, HCOOH, CHCOOH, oxalic 3,897,453 23 24 acid and p-toluenesulfonic acid. Suitable Lewis acids iline, tetraethylammonium chloride, 1,4- are, for example, ZnCl2 BCls, BF3, AlCls and SnCl2 and diazabicyclo[2.2.2]octane, DMF, potassium tert.- solid catalysts are, for example, activated alumina, lith butylate in DMSO, NaHCO3, Li,CO3, LiBr, LiCl, ium phosphates, chromium oxide catalysts and chro MgBr, NaI, KOH, NaOH, NaNH2, AgO, CH3COONa, mium oxide-tungsten oxide contact catalysts. In place C2H5Na and AlOa. A suitable solvent is either an ex of acids, acidic ion exchange resins can likewise be uti cess of the selected base, if liquid, or a solvent de lized, wherein the rearrangement reaction can be ac scribed in the literature for dehydrohalogenation reac complished on the surface thereof. The removal of tions, e.g., DMSO, acetone; ether, e.g., diethyl ether, water from the molecule can be effected with or with THF, dioxane; acetonitrile; alcohols, e.g., methanol, out an inert solvent. It is also feasible to employ an ex 10 ethanol or tert.-butanol; water; or mixtures of the cess of the acid as the solvent, e.g., formic acid, acetic above-mentioned solvents. Thus, for example, 2-(2- acid, trifluoroacetic acid, sulfuric acid, or polyphos dibenzofuryl)-propanal is obtained from 2-(2- phoric acid. Additional suitable solvents are, e.g., hy dibenzofuryl)-2-chloro-1-propanol by treatment with drocarbons, e.g., toluene, benzene, xylene, tetrahydro pyridine or 1,5-diazabicyclo[3,4,0nonene-(5) under naphthalene, decahydronaphthalene; halogenated hy 15 heating, or from 2-(2-dibenzofuryl)-2-bromo-1- drocarbons, e.g., chlorobenzene; ethers, e.g., anisole, propanol by treatment with dimethylaniline. As by THF, dioxane, diethyl ether, diisopropyl ether, 1,2- products, the corresponding epoxides are partially ob dimethoxyethane, diethylene glycol dimethyl ether; al tained, which can be converted into the aldehydes by cohols, e.g., ethanol, propanol, butanol; also DMF, di treatment with an acid, as described above. methylsulfone, DMSO, hexamethylphosphoric triam 20 j. Compounds of Formula I can also be obtained by ide; N-ethylmorpholine, water and mixtures thereof. reacting ketones of Formula IIj with triphenylphos The reaction can be accomplished in anhydrous sol phine alkoxymethylenes of the formula ArP=CH vents or in the presence of water. In some cases, the ad OA, which can be produced, normally in situ, from dition of water is advantageous in order to dissolve the a triphenylphosphine and alkyl- or aryl-halogen catalyst. When anhydrous conditions are employed, the 25 methyl ethers by the addition of a base thereto. In water produced during the reaction can be bound by this reaction, the product is not isolated. Instead, suitable additives, e.g., molecular sieves (such as sur the reaction mixture is directly reacted with the ke face-active aluminum silicates), or it can be removed, tones Ilj. Inert anhydrous solvents are suitably em for example, by a water trap when using toluene as the ployed, e.g., ether, THF, dioxane, benzene. Strong solvent. Preferably, the reaction is carried out in a tem 30 bases, such as organometals and alkali metal alkox perature range of from -10° to 200 C., especially ad ides, e.g., C6HsLi, n-C4H9Li, K-tert-butylate, vantageously at the boiling point of the selected sol NaOC2H5, are advantageously used for liberating vent. In addition to the desired aldehyde, the rear the triphenylphosphine alkoxy- or aryloxymethy rangement can also yield the corresponding isomeric lenes. The reaction is conducted at temperatures of ketone as a by-product. No difficulties are encountered 35 between about -60 and 100 C. Thus, for exam in the separation of the aldehyde, which can be ef ple, 1-methoxy-2-(2-dibenzofuryl)-propene is pro fected, for example, via the bisulfite compound. duced from 2-acetyl-dibenzofuran by reaction with In addition to the glycols of Formula IIi (X = OH, Rg triphenylphosphine methoxymethylene. = H), the monoesters or monoethers of the Formula IIi k. Compounds of Formula I (R = optionally func (X = OH, Rg = Ac and A, respectively) thereof can 40 tionally modified CH2OH-group) can also be obtained likewise be converted into the corresponding aldehydes by subjecting a halogen compound of the formula (I, R = CHO) by an acid-catalyzed rearrangement. Z-CHR2-CH2Hal (IIk, Xs = Hal) to hydrolysis, alco The monoethers can readily be obtained from the ke holysis or acidolysis, or by reaction with a metallic salt tones of the formula Z-CO-R2 by Grignard synthesis and/or metallic alcoholate of the formula ROM. with chloromethyl alkyl ethers of the formula 45 Thus, for example, alcohols of Formula I (R CICH-O-A. Thus, for example, 2-(2-dibenzofuryl)- CH2OH) are produced by saponifying a halogen com propanal is produced from 2-methoxy-1-methyl-1-(2- pound of the formula Z-CHR-CHHal in an aque dibenzofuryl)-ethanol by refluxing with formic acid or ous or aqueous-alcoholic solution or suspension, op anhydrous oxalic acid. The conversion of the esters or tionally with the addition of a solubilizer, e.g., an alco ethers IIi (X = OH, R = Ac and A, respectively) into 50 hol, glycol or polyglycol ether. Preferred saponifying the aldehydes I (R = CHO) can basically be conducted agents are alkalis, e.g., NaOH and KOH, but slurries of in accordance with the methods described for the diols Ca(OH)2, Pb(OH)2 and AgOH can also be employed. IIi (X = OH, R = H). The saponification is normally effected at an elevated Enol ethers of the formula Z-CR-CHOA can be temperature, e.g., at the boiling temperature of the sol produced by splitting off water from the compounds of 55 vent. The halogenide IIk can, however, also be reacted the formula Z-CR(OH)-CHOA. The dehydration in a non-aqueous medium, by agitating the solution is accomplished, for example, with POs in pyridine, thereof in an inert solvent, e.g., acetone, ether, THF, with polyphosphoric acid, molecular sieves, dehydrat acetonitrile, or benzene, with suspended AgOH or ing oxides, or by azeotropic dehydration. Pb(OH)2 under boiling. Also, compounds of the general Formula IIi (X 60 Ethers of Formula I (R = etherified CHOH-group) Hal) can be converted into compounds of the general are obtained by reacting a compound of the formula Formula I by dehydrohalogenation. Suitable reagents Z-CHR2-CH2Hal with an alkali metal alcoholate or splitting off hydrogen halide or organic or inorganic phenolate. Advantageously, the sodium alcoholate is bases, which are generally employed for this purpose, produced by dissolving the required amount of sodium e.g., triethylamine, tributylamine, pyridine, lutidine, 65 in the respective alcohol, using an excess thereofas the quinoline, N-methylpiperidine, tert.-butylamine, colli Solvent. When using the less reactive chlorides or bro dine, 1,5-diazabicyclo[3,4,0) nonene-(5), dimethylan mides of Formula IIk (Xs = Cl or Br), a small amount 3,897,453 25 26 of KI can be added thereto. The reaction mixture is or thiophenolate), preferably in the form of a sodium then suitable refluxed until it has become neutral, Aryl salt. The other of the two E groups can be identical to ethers are obtained, for example, by mixing an alco the first or can be, e.g., a halogen atom, preferably Cl holic alkali metal alcoholate solution with an equiva or Br, an amino group or a functionalized, e.g., etheri lent of the respective phenol, and further processing 5 fied or esterified, OH- or SH-group. The E-E com the mixture as described for the alkyl ethers. In the pro pound to be split off accordingly depends on the nature duction of the aryl ethers, water or aqueous alcohols of the E group and can be, for example, water, ammo are additionally suitable as the solvents. The alkali nia, hydrogen halide, e.g., HCl or HBr or hydrogen sul metal alcoholates or phenolates can also be reacted in fide. The various reagents employed as the media for a suspension with halogen compounds of the formula 10 splitting off E-E will depend on the nature of the Z-CHR-CH2-Hal, in which case an inert solvent is starting compound, as will be apparent to those skilled employed, e.g., ether, THF, acetone or benzene. in the art. For example, if water is to be split off, duita Esters of Formula I (R = esterified CH-OH-group) ble dehydration agents are, e.g., ZnCl2, POs and poly are obtained in an analogous manner by refluxing a phosphoric acid. compound of Formula IIk in an aqueous, aqueous 15 Hydrogen halide is suitably split off employing a alcoholic, or alcoholic solution with an alkali metal salt base, e.g., NaOH, KOH, or Ca(OH), optionally in the of the carboxylic acid or sulfonic acid to be esterified. presence of a catalyst, e.g., a heavy metal, e.g., copper, The addition of triethylamine accelerates the reaction. preferably in pulverized form. The splitting-off step can A preferred method for obtaining acetates of the for be accomplished in the presence of an additional inert, mula Z-CHR-CHOCOCH resides in refluxing a 20 preferably high-boiling solvent, e.g., in the presence of halogenide of the formula Z-CHRa-CHHal with an xylene or "Tetralin' (tetrahydronaphthalene). How hydrous sodium acetate in acetic acid. For the prepara ever, the reaction is preferably conducted in the ab tion of esters of Formula I (R = esterified CHOH sence of a solvent. The reaction temperatures range group), it is also possible to reflux a halogen compound from about 0° to about 250° C. preferably from 80° to of the formula Z-CHR-CH2Hal in an inert solvent, 25 220° C. e.g., ether, acetone, chloroform, THF or benzene, with It is also possible to proceed in such a manner that a suspension of the silver salt or lead salt of the acid to the starting material (III) is not isolated but rather is be esterified. Diazonium compounds of Formula IIk formed in situ in the reaction mixture. Thus, a com (Xs = a diazonium group) are produced when treating pound can be the starting substance, for example, amines of the formula Z-CHR2-CH2NH2 with nitrous 30 which otherwise corresponds to Formula III, but acid or the derivatives thereof, such as, for example, wherein both groups E represent amino groups which alkyl nitrites and NOCl. They are split in the presence are thereafter diazotized and decomposed by boiling. of water in accordance with methods known in the lit As the intermediate product, which is not isolated, a erature, to alcohols of the Formula I (R1 = CHOH). In diphenyl is produced (III, both groups E = OH), which this case, the reaction is conducted especially advanta 35 is dehydrated by heating in an acidic solution. It is also geously by combining an aqueous solution of NaNO, possible, for example, to heat pyrocatechol together with a mineral acid or acetic acid solution of the amine with a p-hydroxyphenyl-fatty acid or a p-mercaptophe at a temperature of 0-100° C., and terminating the re nyl-fatty acid, wherein, as the intermediate product, action by heating. The amines are reacted with alkyl the aforementioned diphenol or the corresponding nitrites preferably in an inert solvent, e.g., ether, ben 40 2-hydroxy-2'-mercaptodiphenyl derivative, or a com zene, THF, an absolute alcohol, e.g., methanol or etha pound V (one of the groups G = OH; see below) is most nol, or in a water-alcohol mixtures. When using alco likely formed. hols, ethers, of the Formula I (R = etherified OH The dibenzothiophenes (I, Y = S) are also obtained group) can also be produced. When conducting the re by treating corresponding diphenyl derivatives (IV) action in the presence of an acid, e.g., acetic acid, the 45 with sulfur in the presence of a catalyst. Especially suit reaction product is also an ester of Formula I (R1 = es able catalysts are Lewis acid, e.g., AlCla. The reaction terified OH-group). takes place suitably at higher temperatures, especially 1. In accordance with the methods of the Willgerodt from 100 to 250 C. reaction described in the literature, ketones of Formula Compounds of Formula I are also obtained by heat IIl can be converted into amides of the formula Z-CH 50 ing a hydroxy or diazonium compound (V), thus clos -CONH, with ammonium polysulfides, which can ing the five-membered ring with liberation of nitrogen. also be formed in situ in an aqueous solution from am Advantageously, the acidic, e.g., hydrochloric or sulfu monia and hydrogen sulfide and/or sulfur. During the ric, solution in which the diazonium salt is produced is reaction of the ketones IIl with a primary or secondary heated to a temperature of from 80° to 150° C. A hy amine (preferably morpholine) in the presence of sul 55 droxy compound (V, wherein one group G = OH) can fur, the corresponding substituted thioamides (prefera also be produced as an intermediate product in the re bly thiomorpholides) are produced. Suitably, an ex action of 4-Ra-pyrocatechol with a p-HY-phenyl-fatty cess, e.g., up to 1 mole, of sulfur and amines is utilized. acid, e.g., in the reaction of pyrocatechol with In these reactions, an inert solvent can be added, e.g., 60 2-(p-hydroxyphenyl)-propionic acid. dioxane or THF. The preferred reaction temperatures Optionally, one or both of the R and Ra groups in a range from 100 to 200° C., especially from 120° to thus-obtained product of Formula I, can be converted 160° C. When using volatile solvents, the reaction is ad into other R1 and Ra groups. vantageously carried out under pressure. For example, an R group can be converted into an The compounds of Formula I can also be obtained by 65 other R1 group by treating the product with a solvolyz splitting E-E, from a compound (III) wherein one of ing, thermolyzing, esterifying, interesterifying, amidat the two E groups is a phenolic hydroxy or a mercapto ing, dehydrating, acetalizing, acylating, etherifying, re group or a metallic salt derived therefrom (A phenolate ducing, oxidizing, or salt-forming agent. 3,897,453 27 28 Functional derivatives of the carboxylic acids of the Thus, the free aldehydes can be obtained from hemi Formula I (R = COOH) and functional derivatives of acetals or acetals by means of hydrolysis. The hemiace the alcohols of the Formula I (R1 = CHOH), especially tals, e.g., those of the formula Z-CHR2-CHOH-OA, the esters of these compounds (R1 esterified and acetals, e.g., those of the formula Z-CHR2-CH COOH- or CHOH-group, especially R = COOA or 5 (OA), are normally hydrolyzed very easily with water CHOAc), can be solvolyzed, particularly hydrolyzed in the presence of an acid. For the cleavage step, dilute or thermolyzed, to the free carboxylic acids or the free or concentrated mineral acid generally is used, e.g., sul alcohols, respectively, according to methods described furic acid, hydrochloric acid, phosphoric acid, or an or in the literature. Hydrolysis can be conducted in an ganic acid, e.g., oxalic acid, tartaric acid, citric acid. acidic or alkaline medium at temperatures of about 10 The cleavage can be accomplished at temperatures of -20 to about 200° C., preferably about room tempera about -20° to +100° C., preferably --20 to +80° C., in ture to the boiling temperature of the selected solvent. the absence or presence of an additional solvent. Thus, Examples of suitable acidic catalysts are hydrochloric, the acetals can be dissolved by adding acetone, etha sulfuric, phosphoric or hydrobromic acid. Suitable nol, THF or acetic acid, before they are split. The ace 15 tals can also be reacted with acids in the presence of basic catalysts are, for example, sodium, potassium and anhydrides. Suitable acid anhydrides, which are em calcium hydroxide and sodium and potassium carbon ployed preferably in an equivalent molar ratio, are, for ate. Water is preferably the solvent. Other advanta example, acetic anhydride, benzoic acid anhydride, geous solvents are lower alcohols; ethers, e.g., THF, di and phthalic acid anhydride. It is also possible to utilize oxane, amides, e.g., DMF; sulfones, e.g., tetramethy 20 acetyl bromide. The hydrolysis of the acetals with an lenesulfone; and mixtures thereof, especially mixtures aqueous NaHSOs solution results, by way of the alde containing water. For saponification purposes, the es hydes, in the bisulfite addition compounds thereof, ters are treated preferably for about 1-48 hours with Z-CHR-CHOH-SONa. K2CO3 in methanol, ethanol or isopropanol attempera Aldehydes of Formula I (R1 = CHO) can also be pro tures of about 20° to 80° C. If the saponification is ef 25 duced by splitting a hemi-thioacetal thereof, e.g., those fected in an acidic medium, acetic acid can also be of the formula Z-CHR2-CHOA-SA, or thioacetal used as the solvent. The acid or alcohol derivatives can thereof, i.e., mercaptals, e.g., those of the formula also be converted into carboxylic acids or alcohols of Z-CHR2-CH(SA). The hemi-thioacetals are Formula I (R = COOH or CHOH), for example, in cleaved, for example, with Raney nickel, and the mer ether or benzene with the addition of a strong base, 30 captals are split with HgCl2 in acetone, THF or diox e.g., potassium carbonate, or in the absence of solvent ane. It is also possible to employ mixtures of HgCl2 and by melting together with an alkali, e.g., KOH and/or CdCO3 or HgCl2 and HgC for splitting purposes. NaOH or alkaline earths, or by heating with water Schiff bases, e.g., those of the formula Z-CH under pressure to temperatures of 150-200° C. R2-CH=NAr can be split by brief heating with dilute A further embodiment of this invention resides in the 35 acids, e.g., the above-mentioned mineral acids or oxalic saponification of amides of Formula I (R1 = CONH2, acid, optionally with the addition of a solvent, e.g., eth CONHA or CONCA)) and thioamides of Formula I anol or acetic acid. The Schiff bases can also be split (R = CSN (A)2). The thioamides or amides are prefer with NaHSO and the thus-formed amine (ArNH) re ably hydrolyzed by heating with an aqueous mineral moved by distillation or extraction and the aldehyde acid, e.g., hydrochloric acid or with an alcoholic alkali. 40 isolated as the bisulfite addition compound or liberated A partial hydrolysis of the thioamides, for example by from the latter as described below. The aldehydes can heating with a mixture of a lower alcohol and water, re also be liberated by hydrolysis, e.g., by treatment with sults in the production of the corresponding amide. For an acid, of the condensation products thereof with the synthesis of 2-dibenzofurylacetic acids, it is pre compounds of the acid amide type, e.g., carboxylic acid ferred to hydrolyze the thiomorpholides, which can be 45 amides, sulfonic acid amides, urethanes, urea deriva obtained by the Willgerodt-Kindler method. tives. By dry heating of especially tertiary alkyl esters of Aldehydes of Formula I (R = CHO) can also be ob Formula I (R1 = COO-tert.-alkyl) to temperatures of tained by the hydrolysis of hydrazones of the formula between about 50 and 350° C., acids of Formula I (R Z-CHR2-CH=N-NHR' or azines of the formula = COOH) are produced. The thermolysis can also be 50 (Z-CHR2-CH-N)2. In general, the splitting of these conducted in an inert solvent, e.g., benzene, water, derivatives is preferably accomplished by acid hydroly DMF, ethylene glycol, glycerin, DMSO, cyclohexanol, sis. For decomposition purposes, a dilute solution of preferably with the addition of a catalytic amount of an oxalic acid or phthalic acid can be employed. It is also acid, e.g., p-toluenesulfonic acid. possible to employ sulfurous acid with heating for split Another embodiment of the invention is the hydroly 55 ting the oximes. Also suitable for the splitting reaction sis of nitriles of Formula I (R = CN), which can be ef. are aqueous mineral acids. In this procedure, the com fected in an acidic medium, e.g., HCl or H2SO4 in wa pounds to be cleaved are dissolved by the addition of ter, a lower alcohol, aqueous dioxane or acetic acid, or ethanol, THF, acetic acid, or dioxane. Hydrazones can in an alkaline medium, e.g., KOH in an aqueous lower also be split by treating them with other carbonyl com alcohol or in cyclohexanol. Partial hydrolysis of the ni 60 pounds, C.g., p-nitrobenzaldehyde, 2,4- triles, for example treating same with concentrated sul dinitrobenzaldehyde, or pyruvic acid. In the thus furic acid at room temperature or with H2O, in an alka produced equilibrium mixture, the aldehyde is liber line solution, results in the production of an amide of ated, while the corresponding derivative of the added Formula I (R = CONH2). 65 carbonyl compound is formed, which is normally of In a compound of Formula I wherein R is a function lower solubility. The process is suitably conducted so ally modified aldehyde group, the aldehyde group can that the hydrazone and the carbonyl compound are be liberated by treatment with a solvolyzing agent. heated under reflux in an aqueous suspension or in an 3,897,453 29 30 alcoholic-aqueous solution. If the aldehydes are pres chloroform or 1,2-dichloroethane, is added thereto. ent in the form of their Girard derivatives T or P, they The esterification takes place under gentle conditions can be liberated by cleavage with hydrochloric acid or if the water of reaction is bound chemically by the addi sulfuric acid attemperatures of 0°C. to the boiling tem tion of a carbodiimide, e.g., N,N'-dicyclohexylcar perature of the solvent employed, e.g., water, option bodiimide. In this reaction, an inert solvent is used, e.g., ally in mixture with methanol or ethanol. The thus ether, dioxane, 1,2-dimethoxyethane, benzene, CH,Cl formed aldehyde is extracted from the aqueous phase or CHCl3. A base, e.g., pyridine, can also be added. The with a suitable organic solvent, e.g., CHCls. methyl, ethyl or benzyl esters can also be produced by Oximes of the formula Z-CHR2-CH=NOH can reacting the free acids with diazomethane, diazoethane also be split by oxidation, which is done by treatment 10 or phenyldiazomethane, respectively, in an inert sol with nitrous acid and/or amyl nitrite or FeCl3 in the vent, e.g., ether, benzene or methanol. Esters of For presence of an acid. mula I (R = esterified COOH-group) can also be ob Bisulfite addition compounds of the formula Z-CH tained by the chemical addition of the carboxylic acids R-CHOH-SOM can be split by treatment with a (I, R = COOH) to an olefin, e.g., isobutylene, cyclo base or acid, thus liberating the corresponding alde 15 hexene, or to an acetylene, preferably in the presence hyde. The cleavage reaction can take place merely by of a catalyst, e.g., ZnCl2, BF, HSO4, arylsulfonic acids, heating an aqueous solution thereof. More advanta pyrophosphoric acid, boric acid, oxalic acid, attemper geously, the reaction mixture is heated in the presence atures of about 0° to about 200° C., pressures of 1 to of dilute aqueous acid, e.g., HCl or H2SO4, of a bicar 300 atmospheres, and in an inert solvent, e.g., ether, bonate, e.g., NaHCO3, of a carbonate, e.g., Na2CO3, or 20 THF, dioxane, benzene, toluene and xylene. of an alkali, e.g., NaOH. The splitting step can also be Esters of Formula I (R1 = esterified COOH-group) achieved by adding another carbonyl compound having can also be produced by reacting metallic salts of the a greater affinity to bisulfite, e.g., formaldehyde. carboxylic acids of Formula I (R = COOH), preferably Aldehydes of Formula I (R1 = CHO) can also be ob the alkali metal, lead or silver salts, with an alkyl halo tained by splitting enol ethers of the formula 25 genide, e.g., those of the formula R5Cl or RCI, option Z-CR-CHOA or Z-CR-CHOAr. These enol ethers canally in an inert solvent, e.g., ether, benzene, DMF or be cleaved, for example, with diulte mineral acids, e.g., petroleum ether, or with an alkyl chlorosulfite, e.g., HCl or HSO4. those of the formula A-OSOCl, and subsequent ther The splitting step can also be effected with acetic molysis of the thus-obtained adducts. acid or NaHCO3. In the case of sensitive enol ethers, 30 It is likewise possible to convert acid halogenides, an heating in water to 100° C. under evaporated pressure hydrides and nitriles of Formula I (R = COCl, COBr, is sufficient. The cleavage can also be accomplished COOAc, CO-O-CO-CHR-Z and CN) into esters with hydroxylamine hydrochloride or semi-carbazide of Formula I (R = esterified COOH) by reaction with hydrochloride, in which case the aldehydes are isolated an alcohol, e.g., an alcohol of the formula ROH or in the form of the oximes or semi-carbazones. 35 ROH, if desired in the presence of an acidic catalyst Ethers of Formula I (R = CHOA or CHOAr) can or a base, e.g., NaOH, KOH, Na2CO3, KCOs or pyri be converted into alcohols of Formula I (R1 = CHOH) dine. Preferably, an excess of the respective alcohol is in accordance with the ether splitting methods known utilized and the reaction is conducted at temperatures in the literature. For example, the ethers can be split by of about 0°C. to the boiling temperature of the mix treatment with hydrogen bromide or hydrogen iodide 40 ture. tert.-Alkyl esters are obtainable, for example, in an aqueous or acetic solution, by heating with a from the corresponding acid chlorides and potassium Lewis acid, e.g., AlCls or boron trihalide, or by melting tert.-alcoholates in the presence of an inert solvent. Al with a pyridine hydrohalide or aniline hydrohalide at cohols of Formula I (R1 = CHOH) and the alkali metal about 200 C. alcoholates thereof can be reacted with the halogenides From other compounds of Formula I, esters of For 45 or anhydrides of the acids to be esterified, without or mula I (R = esterified COOH- or CH2OH-group) with the addition of an acid-neutralizing agent, e.g., so can be prepared according to methods disclosed in the dium hydroxide or potassium hydroxide, sodium car literature. Thus, it is possible, for example, to react an bonate or potassium carbonate or pyridine. Suitable acid of Formula I (R = COOH) with the respective al solvents are inert organic solvents, e.g., ether, THF or cohol, or an alcohol of Formula I (R1 = CH2OH) with 50 benzene. It is also possible to employ an excess of the the respective acid, especially a carboxylic acid, in the halogenide or anhydride as a solvent. In a preferred presence of an inorganic or organic acid, e.g., HCl, mode of operation, the selected alcohol of Formula I HBr, HI, HSO, HPO, trifluoroacetic acid, a sulfonic (R1 = CH2)H) in a pyridine solution is combined with acid, e.g., benzenesulfonic acid or p-toluenesulfonic the halogenide and/or anhydride of the acid to be ester acid, or an acidic ion exchanger, optionally in the pres 55 ified. ence of an inert solvent, e.g., benzene, toluene or xy It is also possible to esterify alcohols of Formula I (R lene, at temperatures of about 0°C. to preferably the = CHOH) with ketenes. This reaction is preferably boiling temperature of the reaction mixture. Either the conducted in an inert solvent, e.g., ether, benzene or alcohol or the carboxylic acid is preferably employed 60 toluene, and in the presence of an acidic catalyst, e.g., in excess. Preferred alcohols are those of the formulae sulfuric acid or p-toluenesulfonic acid. Thus, 2-(2- ROH and ROH wherein Rs and Rs have the values dibenzofuryl)-propyl acetate can be produced, for ex given above except H. It is also possible to conduct the ample, from 2-(2-dibenzofuryl)-propanol and ketene. reaction in the presence of a water-binding agent, e.g., Esters of Formula I (R1 = esterified COOH-group) an anhydrous heavy metal sulfate or molecular sieve. It 65 can also be prepared by the transesterification of an is also possible to remove the water of reaction azeo other ester of Formula I (R = COOR wherein R = tropically, wherein advantageously a hydrocarbon, e.g., any desired organic residue, preferably A) with an ex benzene or toluene, or chlorinate hydrocarbon, e.g., cess of the respective alcohol, or by reacting a carbox 3,897,453 31 32 ylic acid of Formula I (R = COOH) with any desired dimethylamine, methylethylamine, diethylamine, di-n- other ester of the selected alcohol, which is preferably propylamine, diisopropylamine, di-n-butylamine, employed in an excess. Analogously, the esters of For diisobutylamine; and also aryl- and aralkylamines, e.g., mula I (R = esterififed CH-OH-group) can be obtained aniline, benzylamine; hydroxyalkylamines, e.g., etha by the transesterification of alcohols of Formula I (R1 nolamine, diethanolamine; cyclic amines, e.g., pyrroli = CHOH) with an excess of a lower alkyl ester, e.g., dine, piperidine, morpholine, thiomorpholine, pipera of the formula AcOA, or by the transesterification of zine; N-alkyl-piperazines, e.g., N-methyl- or N-ethyl other esters of Formula I (R = esterified CH2OH piperazine; N-hydroxyalkylpiperazines, C3, group, preferably esterified with a lower carboxylic N-2-hydroxyethylpiperazine. It is possible, but not re acid) with an excess of the carboxylic acid to be esteri 10 quired to add an inert solvent during the production of fied. The reaction is conducted in accordance with the the amides, e.g., an alcohol, e.g., methanol or ethanol transesterification methods described in the literature, or a chlorinated hydrocarbon, e.g., CHCla. It is likewise especially in the presence of a basic or acidic catalyst, possible, but not required, to employ pressure, e.g., up e.g., sodium ethylate or sulfuric acid, at temperatures to about 200 atmospheres. The reaction temperatures of about 0°C. to the boiling temperature. Preferably, 15 range from about -20° to +150° C., prefereably 0° to the reaction is carried out so that after the equilibrium 100° C. One variant of the amidation resides in con has been established, one reactant is withdrawn from verting an acid of formula I (R = COOH) first with a the equilibrium mixture by distillation. Thus, 2-(2- chloroformic acid ester of the formula C1COOA in the dibenzofuryl)-propanol can be converted into 2-(2- presence of a base, e.g., triethylamine, into the mixed dibenzofuryl)-propylbutyrate with the methyl ester of 20 anhydride of the formula Z-- butyric acid by distilling off the methanol. CHR-2-CO-O-CO-OA, and then further react Among the esters of Formula I (R esterified ing the latter with the amine. COOH), of particular interest are those which are Amides of Formula I (R = CONH2) can optionally readily cleavable under physiological conditions, for be dehydrated to the nitriles of Formula I (R = CN), example the vinyl, tert-butyl, tetrahydro-2-furyl, and 25 for example with a dehydration agent, e.g., P.O.s, tetrahydro-2-pyranyl esters, obtainable for example by POCl3, p-toluenesulfochloride/pyridine, at tempera reacting the free carboxylic acids with acetylene, isobu tures of about 0° to 200° C., preferably 20° to 100° C. tylene, 2,3-dihydrofuran and 2,3-dihydropyran, prefer Heating of the carboxylic acids of Formula I (R ably in the presence of a catalyst, e.g., ZnCl2, BFs, COOH) with lower alkanoic acid anhydrides produce H2SO4, aryl-sulfonic acids, pyrophosphoric acid, boric 30 the acid anhydrides of Formula I (R = -CO-O-- acid and oxalic acid, at about 0-120° C. in an inert sol CO-CHR-Z). vent, e.g., ether, THF, dioxane, benzene and xylene. Aldehydes of Formula I (R1 = CHO) optionally can Esters of Formula I (R = esterified COOH) can also be converted into hemiacetals, e.g., those of the for be obtained by solvolyzing compounds of Formula I mula Z-CHR-CHCH-OA, or acetals, e.g., those of wherein R is a thioester, imino ether, oximino ether, 35 the formula Z-CHOH-2-CH(OA), by treatment hydrazone ether, thioamide, amidine, amidoxime or with an acetalizing agent, e.g., an alcohol. For example, amide hydrazone group, with water or dilute aqueous the aldehyde is reacted with an alcohol of the formula base or acid, e.g., ammonia, NaOH, KOH, Na2CO3, A-OH, e.g., methanol, ethanol, n-propanol, isopropa KCO, HCl, HSO4, with the addition of the respective nol, n-butanol, isobtuanol, or with a glycol of the for alcohol and splitting off, respectively, of hydrogen sul 40 mula HO-CnH2n-OH wherein m = 2, 3 or 4 e.g., eth fide, ammonia, amines, hydrazine derivatives and hy ylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2- droxylamine. Although most of the imino ether hydro butanediol, 2,3-butanediol, 1,4-butanediol, or with a chlorides are usually immediately split into the esters phenol of the formula Air-OH, with the addition of a and ammonium chloride in an aqueous solution at reaction catalyst. The condensation of the aldehydes room temperature, the solvolysis of other derivatives, 45 with polyhydric alcohols or phenols produces cyclic ac e.g., the amidoximes or thioamides, takes place only at etals. For example, with 1,2-glycols, derivatives of 1,3- higher temperatures, e.g., up to 100 C. dioxolane are obtained and with 1,3-glycols, deriva Acids of Formula I (R = COOH) can be converted tives of 1,3-dioxane are produced. Suitable catalysts into the corresponding acid halogenides of Formula I are acids, e.g., mineral acids, e.g., HC1, HSO, HPO, (R = e.g., COCl or COBr) in the presence or absence 50 sulfonic acids, e.g., p-toluene-sulfonic acid Also suit of an inert solvent by treatment with an inorganic acid able, for example, are NaHCOs, POs, CaCl, FeCls, halogenide, e.g., SOCl2 or SOBr. Hydrochlorides of ZnCl2, iodine, anhydrous CuSO and cation exchang the imino ethers of Formula I (R = C(=NH)OA) can ers. The water of reaction advantageously is removed be obtained from the nitriles of Formula I (R = CN) by azeotropic distillation using an entraining agent, with an alcohol of the formula A-OH in ether, in the e.g., benzene, toluene, pertroleum ether. An advanta presence of HCl. geous mode of operation for producing the dimethyl It is also possible to convert the acids of Formula I or diethylacetals is introducing gaseous hydrogen chlo (R COOH) and/or the functional derivatives ride (approximately up to 1%) into the methanolic or thereof, preferably the halogenides and esters thereof 60 ethanolic solution of the aldehyde. of Formula I (R = COCl, COBr, and/or esterified Acetals of the formula Z-CHR2-CH(OA) can also COOH-group) into the corresponding amides (or hy be produced by reacting the aldehydes with orthofor droxamic acids) by treatment with an amidating agent, mic acid esters of the formula HC(OA) in the pre e.g., ammonia or an amine of the formulae A-NH2 or Snece of an acidic catalyst. In general, these substances (A)NH, respectively, or with hydroxylamine. Exam are permitted to react in the corresponding alcohol of ples of suitable amines are monoalkylamines, e.g., me 65 the formula A-OH. The catalysts are suitably small thylamine, ethylamine, n-propylamine, isopropyla amounts of a mineral acid, aromatic sulfonic acid, mine, n-butylamine, isobutylamine; dialkylamines, e.g., FeCls, NHCl, NHNO3, KHSO, or a hydrochloride of 3,897,453 33 34 a base, e.g., pyridine hydrochloride. Advantageously, the formula Z-CHR-CH(OAc), by treatment with the reaction mixture is briefly heated and then allowed an acylating agent, e.g., an acid anhydride. At an ele to stand for some time at room temperature. In place vated temperature and in the presence of an acidic cat of the orthoformic acid esters, it is also possible to em alyst, one molar equivalent of H-OAc can be elimi ploy formimido ester salts, e.g., formimido ester hydro nated from the acylates, with the formation of the cor chlorides. The reaction of the aldehydes with orthosil responding enol acylates, e.g., of the formula Z-CR icic acid esters of the formula Si(OA) in an alcoholic =CH-OAc, solution in the presence of acids or acidreacting sub The free aldehydes of Formula I (R = CHO) can also stances likewise results in the desired acetals. Further be converted, by reaction with a metal bisulfite solu more, a combination of an alcohol of the formula 10 tion, into stable, often crystalline addition compounds A-OH with dimethylsulfite in the presence of an acidic of the formula Z-CHR-CHOH-SOM (M prefer catalyst can likewise be used for the acetalization. Dur ably F Na). In general, this reaction is carried out by ing the reaction, SO2 is liberated so that the progression dissolving the free aldehyde in ether and treating the of the reaction can be followed by observing the gas solution with a concentrated aqueous NaHSOs solu evolution. 15 tion. It is sometimes advantageous to employ an alco A further method for the production of acetals is the hol, e.g., methanol or ethanol, as an additional solvent, trans-acetalization of a lower acetal, e.g., dimethyl- or or to add this alcohol to achieve quantitative precipita diethylacetal, in the presence of an acidic catalyst and tion toward the end of the reaction. The bisulfite solu a higherboiling alcohol, e.g., a glycol of the formula tion can be freshly prepared by combining 1 mole of HO-CnH2n-OH, wherein m is an integer from 2 to 20 Na2SOs and 1 mole of acetic acid. Another mode of op 6. The thus-obtained equilibrium can be shifted by re eration is to combine the aldehyde and an aqueous Na2 moving the lower alcohol in favor of the acetal of the SOa solution, introduce SO2 and continuously neutral higher-boiling alcohol. For accomplishing the reaction, ize the thus-liberated sodium hydroxide solution. Also, it is sufficient to reflux the lower acetal for some time SO, can convert aqueous aldehyde solutions or suspen with an excess of the higher-boiling alcohol with the ad 25 sions into bisulfite compounds by the continuous addi dition of an acidic catalyst, e.g., HCl, H2SO4, p-toluene tion of NaOH. The bisulfite compounds are, in most sulfonic acid, FeCls, or BF3. Dihydric and polyhydric cases, difficult to dissolve in excess NaHSO solution. alcohols react particularly smoothly with lower acetals, They can therefore be easily separated therefrom and so that this process is especially well suitable for the can normally be purified by recrystallization from preparation of cyclic acetals. It is also possible to com 30 aqueous ethanol. bine the production of the acetal with orthoformic acid The aldehydes of Formula I (R1 = CHO) can also be esters and the trans-acetalization into one operation. converted into other functional derivatives in accor Under the conditions of trans-acetalization, an ex dance with methods described in the literature, e.g., ox change of the carbonyl compounds can likewise occur. imes, semicarbazones, phenylhydrazones and substi Thus, an aldehyde of Formula I (R1 = CHO) can be 35 tuted phenylhydrazones. converted, e.g., with acetone dimethyl ketal or buta Ethers of Formula I (R = etherified CHOH-group, none ethylene ketal, in the presence of p-toluenesul preferably CHOA) are obtained from alcohols of For fonic acid, into the corresponding dimethyl- or mula I (RF CHOH) by reacting the corresponding al ethyleneacetal. The thus-liberated acetone or buta kali metal alcoholates with an alkyl halogenide, alkyl none, respectively, is removed from the equilibrium. 40 methanesulfonate or alkyl p-toluenesulfonate. The al Hemithioacetals, e.g., those of the formula Z-CH kali metal alcoholates are obtained by agitating the al R-CHOA-SA, or thioacetals, e.g., those of the for cohol of Formula I (R1 = CHOH) in an inert solvent, mula Z-CHR-CH(SA), are obtained by reacting e.g., ether, THF, dioxane, or benzene, with finely di the aldehydes of Formula I (R1 = CHO) with mercap vided Na, NaNH, or NaH until the evolution of hydro toalkanols, e.g., those of the formula HS-CnH2n-OH 45 gen or ammonia, respectively, is terminated. Thereaf wherein m has the values given above, preferably ter, the alkyl halogenide, most advantageously the re 2-mercaptoethanol, mercaptans, e.g., those of the for spective alkyl iodide, is added thereto and the mixture mula A-SH, preferably methyl- or ethylmercaptan, or refluxed for several hours. N-propyl-, isopropyl-, n-butyl-, isobutyl-, n-amyl-, n Ethers of Formula I (R = etherified CHO,-group) hexyl-, n-heptyl, n-octylmercaptan, or dithiols, e.g., 50 are also produced by reacting alcohols of Formula I (R those of the formula HS-CnH2n-SH wherein m has F CH-OH) in an inert solvent, e.g., ether, benzene or the values given above, preferably ethane-1,2-dithiol, toluene, with a diazoalkane, by the addition of catalytic or propane-1,2,-dithiol, propane-1,3,-dithiol, butane amounts of a Lewis acid, e.g., AlCl, BF3 or FeCls. The 1,2-dithiol, butane-2,3-dithiol, butane-1,4-dithiol. In amount of catalyst added is normally dependent on the the foregoing description and in the following descrip 55 reaction velocity, i.e., reactions which are slowing tion, the mercaptoalkanols, mercaptans, and dithiols down can be accelerated by the addition of further are included within the term acetalizing agents. The amounts of the catalyst. condensation of the aldehydes with these substances Finally, alcohols of Formula I (R = CHOH) can also takes place rapidly at room temperature. In general, a 60 be converted into the corresponding ethers by adding temperature of -70° to +200° C. is suitable for the re these alcohols to olefins. Preferred olefins are those hy action. The reaction can be conducted, especially with drocarbons produced by splitting off water from a ter low-boiling mercaptans, in the presence of an inert sol tiary alcohol. The addition step is executed in the pres vent, e.g., a hydrocarbon, e.g., benzene, toluene or xy ence of an acidic catalyst, e.g., mineral acids, tetra lene. A preferred catalyst is boron trifluoride etherate, 65 fluoroboric acid, perchloric acid, or BFs. In some cases, with or without the addition of acetic acid. basic catalysts are also suitable, e.g., alkali metal al Aldehydes of Formula I (R1 = CHO) can also be con coholates. An excess of the olefin is a suitable solvent verted into the corresponding acylates, e.g., those of but normally inert solvents are employed, e.g., THF, 3,897,453 35 36 dioxane, benzene or toluene. The preferred reaction agents of all kinds, e.g., pulverized iron in aqueous temperature is the boiling temperature of the selected acetic acid, LiAlla, NaBH4, aluminum alcoholates, solvent. Thus, for example, it is possible to obtain the such as aluminum isopropylate, according to the 2-(2-dibenzofuryl)-propyl-tert.-amyl ether from 2-(2- method of Meerwein-Ponndorf, e.g., in benzene or tol dibenzofuryl)-propanol and trimethylethylene. 5 uene at temperatures of between about 20 and about Functional derivatives of compounds of Formula I 1 iO C.; from acid azides of the formula Z-CH (e.g., R = functionally modified COOH- or CH2OH Re-CON by reaction with NaBH4, from acid chlo group) can be converted, by further modifications, into rides of the formula Z-CHR-COCl by reaction with other functional derivatives of the same type. For ex NaAlH4 or LiAlH4; from acid amides of the formula ample, esters containing additional reactive groups in 10 Z-CHR-CONH2 by reaction with alkali metals in the alcohol portion can be converted into other esters. lower alcohols, e.g., Na in ethanol; and from mixed car For example, haloalkyl esters (e.g., 2-chloroethyl es bonic acid esters of the formula Z-CHR ters) of acids of Formula I (R = COOH) can be re CO-O-CO-OA by reaction with LiAlH4. acted with sodium alcoholates to alkoxyalkyl esters or Ethers of the fomula Z-CHR2-CHOA are obtain with dialkylamines to dialkylaminoalkyl esters, suitably 15 able, for example, by reduction of the corresponding in the presence of an inert solvent, e.g., benzene or esters of the formula Z-CHR-CO-OA with dibo chloroform, attemperatures of from 0 to 150°C., pref rane, which can be produced in situ from NaBH4/BFa erably 20 and 100° C., optionally also under elevated Or LiAlH4/BF. pressure. Further details of the reducing methods are de It is also possible to convert, in a thus-obtained prod- 20 scribed above, e.g., paragraph (c). uct of Formula I, an R group, preferably an optionally Ethers or esters of the formula Z-CHR2-CH2OR2 functionally modified COOH- or CHO-group, by wherein R2 is a group which can be split off by hydro treatment with reducing agents, into another R group, genolysis, e.g., benzyl, diphenylmethyl, triphenyl preferably an optionally functionally modified CHO methyl, p-methylbenzyl, 2-picolyl or carbobenzoxy, or CH2OH-group. 25 can be split reductively, thus forming alcohols of For Suitable for such reductions are, e.g., compounds of mula I (R = CHOH). A preferred hydrogenolysis is Formula I wherein R is -COOH, -COCl, -CN, conducted with hydrogen in the presence of a Pd cata -COOA, -CO-SA, -CONCA), -CHO, -COHall, lyst, e.g., Pd on charcoal. Thus 2-(2-dibenzofuryl)- -CO-O-Ac, -CO-O-CO-CHR2-Z, -CON propanol is obtained, for example, from 2-(2- or -CH(OA). 30 dibenzofuryl)-propylbenzyl ether. For example, aldehydes of the formula Z-CHR2-- Conversely, it is also possible, in a thus-obtained CHO are obtainable from acid chlorides Z-CH compound of Formula I, to oxidize an R group, espe R-COCl by catalytic hydrogenation according to the cially a CH-OH- or CHO-group, to another R group, Rosenmund method (suitably under normal pressure using a Pd/BasO4 catalyst in benzene, toluene or xylene 35 especially a CHO- or COOH- group. as the solvent; or by reaction with quinoline and NaCN Alcohols of the formula Z-CHR-CHOH and al according to the Reissert method; or by reaction with dehydes of the formula Z-CHR2-CHO can readily be a lithium tri-tert.-alkoxyaluminum hydride, e.g., lith converted into the corresponding carboxylic acids of ium tri-tert.-butoxyaluminum hydride; or from nitriles the formula Z-CHR2-COOH with a plurality of oxi Z-CHR-CN by reduction with SnCl2/HCl according 40 dizing agents. These oxidizing agents include chromic to the Stephen method; or reduction with a dialkylalu acid and/or the salts thereof, e.g., sodium dichromate, minum hydride, e.g., diisobutylaluminum hydride. preferably in an aqueous-sulfuric acid medium and/or These aldehydes are also obtainable from esters of the with the addition of acetone, acetic acid and/or ben formula Z-CHR-COOA by reaction with dialkylal Zene as the solvent; silver oxide, which can suitably be muminum hydrides or lithium tri-tert.-alkoxyaluminum 45 prepared in situ from silver nitrate and NaOH, prefera hydrides; and from unsaturated esters of the type Z bly in an aqueousalkaline medium; KMnO, for exam C(=Rs)-COOA, e.g., 2-(2-dibenzofuryl)-acrylic acid ple, in pyridine; NiO2, for example, in THF in the pres ence of a base, e.g., Na2CO3. ethyl ester; or from acid imidazolides or 3,5- An oxidation of alcohols of the formula Z-CH dimethylpyrazolides or carbazolides, e.g., N-(2-(2- 50 R2-CH2OH to the corresponding aldehydes is likewise dibenzofuryl)-propionyl)-imidazole O as 3,5- possible, which can be accomplished according to dimethylpyrazole or -carbazole, or from acid aziridides methods described in detail in the literature. For exam of the formula ple, these alcohols can be dehydrogenated catalytically CH with hydrogen being split off, or with the aid of oxida 1 2 55 tion agents. Z-CHR-CON The catalytic dehydrogenation is suitably effected under reduced pressure in the vapor phase. Suitable N CH2 catalysts are primarily copper, silver and zinc com 60 pounds. The reaction temperature is normally between by reaction with LiAlH4, or from phenylimide chlorides i00 and 450° C. The dehydrogenation can also be con of the formula Z-CHR2-CCl =N-CHs by reaction ducted in the presence of hydrogen acceptors. Suitable with tetrachlorotin(II) acid. as such acceptors are, above all, aromatic nitro com Alcohols of the formula Z-CHR-CHOH are ob pounds, e.g., nitrobenzene or m-dinitrobenzene. A suit tained, for example, from acids of the formula Z-CH- 65 able catalyst is pulverized copper, for example. The re R-COOH or esters of the formula Z-CHR-COOA action is conducted by heating the reactants in an inert by reaction with LiAlH4; from aldehydes of the formula solvent, e.g., xylene, while passing air through the reac Z-CHR-CHO by reaction with a number of reducing tion mixture. 3,897,453 37 38 The oxidation can furthermore be conducted, for ex rine in an inert solvent, such as water, aqueous sodium ample, with chromic acid. The reaction can be effected hydroxide solution, ether, tetrachloromethane, acetic in an aqueous solution or another inert solvent at a acid, without or with the addition of specific catalysts, temperature of from 0 to 100° C. Also the chromic such as, for example, FeCla, AlCl3, SbCls, or SnCl4, acid-pyridine complex is suitable as an oxidation agent. preferably between -10° and 100° C., or by reaction in Nitrogen or carbon dioxide can be introduced into the a strongly hydrochloric solution with H2O, or with Na reaction mixture in order to suppress the further oxida ClOoa, wherein the chlorination is effected by the chlo tion of the thus-formed aldehyde. A variant of the CrO3 rine produced in the nascent state, or by reaction with oxidation is the dehydrogenation with tert.-butyl chro SOCl in an inert solvent, such as chlorobenzene, in mate which is conducted in excess tert-butanol or in an 10 the presence of radical-forming catalysts, e.g., perox inert diluent, e.g., petroleum ether, benzene or CCls. ides, at preferably 80°-180° C. Further oxidation agents for the oxidation of the al b. Bromine: cohols of Formula I (R = CHOH) to the aldehydes of Formula I (R = CHO) are MaC), which is used in di For example, by direct reaction with elemental bro lute sulfuric acid but can also be employed suspended 15 mine in an inert solvent, such as water, aqueous sodium in inert organic solvents, e.g., petroleum ether or aceto hydroxide solution, carbon disulfide, acetic acid, chlo nitrile; PbO2, lead tetraacetate, which is used in acetic roform, tetrachloromethane, or dioxane, especially acid or also in benzene, optionally with the addition of with the addition of catalysts effective as bromine some pyridine; SeC), N2O4, most advantageously in transfer agents, such as iron filings, AlCla, AlBra, FeCia, CHCla Or CCl; N-haloamides, C.S., N 20 iodine, or pyridine, preferably between -30° and 90° bromosuccinimide, which compounds can be em C., or by reaction with hypobromous acid, acylhypo ployed in acetic acid/sodium acetate or in pyridine; bromites, N-bromoimides, such aS N. concentrated HNO3 or m-nitrobenzenesulfonic acid; or bromosuccinimide, N-bromophthalimde, or other bro 1-chlorobenzotriazole. mine-yielding agents, such as 1,3-dibromo-5,5- With the use of very low-volatile carbonyl com 25 dimethylhydantoin, in inert solvents, such as nitroben pounds as hydrogen acceptors, e.g., diphenylcarbalde zene or carbon disulfide, preferably at -10° to 150° C. hyde, benzoquinone or phenanthrenequinone, it is also c. Iodine: possible to convert alcohols of the formula Z-CH R-CHOH into the aldehydes according to the Op For example, by direct reaction with elemental io penauer method. In this reaction, the alcohol is first dine, especially in the presence of nitric acid in chloro converted into the alcoholate with the stoichiometric form or of HgC) in an inert solvent, such as alcohol, amount of aluminum isopropylate or aluminum phen acetic acid, or benzene, preferably at temperatures of oxide, and then mixed with an excess of the high between 0 and 120° C., or by reaction with iodine - al boiling hydrogen acceptor. The thus-formed aldehyde kali metal iodide solutions in the presence of carbon can be distilled from the redox equilibrium, for exam 35 ates, acetates, alkali metal hydroxide solutions, ammo ple, under reduced pressure. nia, or amines, or by reaction of mixtures of alkali Anodic oxidation can likewise be utilized for the de metal iodides and oxidation agents, such as alkali metal hydrogenation of alcohols of Formula I (R = CHOH). iodates, alkali metal nitrates, or H2O, in inert solvents, A preferred oxidation method resides in converting such as water, acetic acid, or ethanol, wherein the thus alcohols of the formula Z-CHR-CHOH into the al 40 liberated iodine reacts in the nascent state, or by reac dehydes of Formula I (R = CHO) with dimethyl sul tion with Cll in dilute acetic acid, preferably at 50 - foxide (DMSO). This reaction is advantageously car 100° C., or after mercuration, for example in an aque ried out in the presence of an agent splitting off water, ous or acetic medium with mercury(II) acetate to the e.g., acetic anhydride or, in an even gentler manner, in Hg-O-COCHs compound and exchange of the orga the presence of dicyclohexylcarbodiimide with the ad 45 nometallic residue against iodine, for example by reac dition of a suitable acid, e.g., trifluoroacetic acid or tion with iodine or iodine - alkali metal hydroxide solu HPO, by allowing the components to react with each tions. other at temperatures of from 0 to 50 C., preferably d. Nitro: at about room temperature, for about 0.5 - 24 hours. In a thus-obtained product of Formula I, an Ra group For example, with the aid of the following agents: a can be converted into another Ra group by substitution mixture of anhydrous nitric acid with BF; metal ni reactions and/or further conversions of the introduced trates, such as Cu, Fe, Mn, Co, Ni nitrate, in a mixture or already present substituents. with acetic acid or acetic anhydride; metal nitrates, For example, it is possible to introduce, by halogena such as Ag, Ba, Na, K, NH, or Pb nitrate, in a mixture tion, alkylation, nitration, etc., a halogen atom, an al 55 with Friedel–Crafts catalysts, such as AiCl3, FeCl, BF, kyl, alkanoyl, monoalkylamino, dialkylamino, acyl or SiCla; alkyl nitrates, such as ethyl nitrate, in a mix amino, amino, or nitro group into the dibenzofuran ture with concentrated sulfuric acid, HBF, or Lewis and/or the dibenzothiophene ring. An amino group can acids, such as BCl3, SnCl4, PCl3, AlCls, SiCl, SbCl, or be diazotized and the thus-obtained diazonium residue 60 FeCl3, nitryl fluoride, chloride, bromide, perchlorate, can be further converted into other functional groups. or tetrafluoroborate, preferably in the presence of Frie Thus, according to methods described in the litera del-Crafts catalysts, such as AlCls, FeCls, ZrCl, or ture, one of the following substituents can be intro AlBra, in solvents such as carbon disulfide, n-pentane, duced into the dibenzofuran or dibenzothiophene ring, or CHCls, nitrogen oxides, such as N,0s, N0s, in the respectively: presence of concentrated HSO, HF, or Friedel–Crafts 65 catalysts, such as BF3, AlCl3, or FeCls, optionally in sol a. Chlorine: vents, such as tetramethylenesulfone or acetic acid; For example, by direct reaction with elemental chlo concentrated nitric acid mixtures of concentrated sul

3,897,453 39 40 furic acid with concentrated and/or anhydrous nitric be alkylated to corresponding alkoxy, monoalk acid; alkali metal nitrates, such as sodium or potassium ylamino, or dialkylamino compounds, or acylated to nitrate, in a mixture with concentrated sulfuric acid; the corresponding acylamino compounds. The alkyla mixtures of concentrated nitric acid with pyrosulfuric tion can be accomplished according to methods de acid, oleum, acetic acid and/or acetic anhydride; mix scribed in the literature by treatment with an alkylating tures of nitric acid, sulfuric acid, and acetic acid; acetyl agent. For the O-alkylation, the starting substances are or benzoyl nitrate; nitrosulfonic acid, producible by in suitably first converted into the corresponding pheno troducing SO, into fuming HNO3, nitrosylsulfuric acid; lates by the addition of a base, e.g., NaOH or KCOa. nitroguanidine; highly concentrated nitric acid in the Suitable alkylating agents are, for example, alkyl halo presence of dehydrating agents, such as P20s or anhy O genides, such as methyl chloride, bromide, or iodide; drous hydrofluoric acid, optionally in solvents, such as ethyl chloride, bromide, or iodide; n-propyl chloride, nitrobenzene or polychloroethanes. A special nitration bromide, or iodide; isopropyl chloride, bromide, or io reaction resides in dissolving the substance to be ni dide; n-butyl chloride, bromide, or iodide, or the corre trated in a solvent, such as CHCla, CH2Cl2, or CCl4, sponding dialkylsulfuric acid or alkylsulfonic acid es forming a bottom layer of concentrated sulfuric acid 5 ters, e.g., dimethyl sulfate, diethyl sulfate, the methyl thereunder, and then adding anhydrous nitric acid in ester of p-toluenesulfonic acid. Also diazo compounds, CHCl, CHCl2 or CCl. In general, the temperatures such as diazomethane, can be used for the O employed in this reaction are not too high, in order to alkylation. Amino compounds can also be alkylated avoid side reactions; they are normally between -20° with the corresponding alcohols, e.g., methanol or eth and +100° C., preferably between -10° and +80° C. 20 anol, in the presence of Raney nickel, or reductively with formaldehyde or acetaldehyde in the presence of e. Alkyl, alkanoyl, amino, alkyl- or dialkylamino, or hydrogen or formic acid. When conducting the reac acylamino: tion in the presence of hydrogen, it is advantageous to For example, by reaction with the corresponding have one of the abovementioned catalysts present. chlorine, bromine, iodine, hydroxy, or acyloxy com 25 Examples of suitable solvents are water or aqueous pounds of the type R-X1, such as, for example, methyl sodium hydroxide solution; alcohols, such as methanol, chloride, ethyl iodide, n-propyl bromide, n-butanol, ethanol, n-butanol; hydrocarbons, such as benzene, xy ethyl acetate, acetyl chloride or bromide, acetic anhy lene; ethers, such as THF, amides, such as DMF, or dride, hydroxylamine, chloramine, diethyl chloramine, mixtures thereof. The alkylations are advantageously or acethydroxamic acid, in accordance with the condi 30 conducted at temperatures of between about -10 and tions of a Friedel-Crafts reaction as described in about --150° C., especially between room and boiling greater detail in the literature. Suitable catalysts are temperature. In case starting substances are employed Lewis acids, such as AlCl3, AlBra, SnCl4, ZnCl2, FeCls, having a free carboxyl group (R = COOH), this group SbCs, HF, or polyphosphoric acid, and suitable solvents can simultaneously be esterified, unless the reaction are n-hexane, 1,2-dichloroethane, carbon disulfide, ni 35 mixture is kept at a strongly alkaline level. trobenzene, tetramethylenesulfone, or nitroethane. An acylation is suitably accomplished with carbox The reaction is advantageously conducted at between ylic acids or carboxylic acid derivatives. Suitable as the 0 and 200° C. In place of the compounds R-X, it is latter are, for example, carboxylic acid esters, anhy also possible to use the corresponding des-HX deriva drides (e.g., acetic anhydride), or halogenides, such as tives, e.g., olefins, ketene. 40 chlorides, bromides, or iodides (e.g., acetyl chloride, In thus-obtained compounds of Formula I containing bromide, or iodide). An excess of the carboxylic acid reducible substsituents Rs (e.g., nitro, alkanoyi, or acyl derivative can be used as the solvent; or the reaction is amino groups, or Hal atoms), the latter can be reduced carried out in the presence of an inert solvent such as to other substituents (e.g., amino, alkyl, or alkylamino benzene, toluene, THF, dioxane, or chloroform. Dur groups, or H) in accordance with methods described in 45 ing the acylation, a base is preferably added, such as the literature. It is possible to hydrogenate the reduc NaOH, KOH, sodium carbonate or potassium carbon ible groups catalytically, or to reduce them chemically, ate, pyridine, triethylamine. wherein suitably one of the above-described methods In compounds of Formula I containing one or more (paragraph c) is employed. diazonium groupings, these can be exchanged for fluo In addition to the catalytic hydrogenation, further 50 rine, chlorine, bromine, iodine, NO, OH, alkoxy, or more suitable as a way of reducing NO2-groups to NH2 cyano in accordance with methods disclosed in the lit groups are especially metals (e.g., iron, zinc) with acids erature. The diazonium compounds are obtainable ac (e.g., HC1, CH3COOH) or SnCl2. Alkanoyl groups can cording to methods described in the literature by the be reduced to the corresponding alkyl groups by cata diazotization of corresponding amino compounds, e.g., lytic hydrogenation or according to the methods of 55 in a hydrochloric or hydrobromic aqueous solution by Wolff-Kishner or Clemmensen. When treating acyl adding the stoichiometric amount of an inorganic ni amino compounds with LiAlH4, for example in boiling trite, preferably NaNO, or KNO, at temperatures of THF, the corresponding alkylamino compounds are between about -20° and +10 C., or in inert organic produced. solvents, such as diethyl ether, diisopropyl ether, THF, It is furthermore possible to replace chlorine, bro 60 dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, di mine, or iodine atoms contained in the residue Rs by glyme, or diethylene glycol diethyl ether, by adding an hydrogen; this is done by converting the corresponding organic nitrite, such as n-butyl nitrite, n-amyl nitrite, or halogen compounds into the associated organome isoamyl nitrite, at temperatures of between -20° and tallic, e.g., Grignard, compounds and hydrolyzing same 65 --5° C. with water or dilute acids. In order to introduce a fluorine atom, the compounds Compounds of Formula I containing a free hydroxy, are diazotized, for example, in anhydrous hydrofluoric amino, or monoalkylamino group in the residue Rs can acid and then heated; or the diazonium salts are re 3,897,453 41 42 acted with HBF4 to the sparingly soluble diazonium tet R3 = CN) with the aid of metal cyanides, such as rafluoroborates which can be isolated and thermally NaCN, KCN, or preferably CuCN. This reaction is ad converted into the desired fluorine compounds, for ex vantageously conducted in an inert solvent, such as ample by heating in an inert solvent. DMF, N-methylpyrrolidone, or pyridine at tempera The diazonium group is exchanged against chlorine 5 tures of between 140 and 220 C. or in the absence of preferably in a hot acqueous solution in the presence of a solvent at temperatures of between 150 and 260° C. CuCl in accordance with the Sandmeyer method. The Halogen compounds of Formula I (R3 = Hal) can be exchange against bromine can be effected, for exam converted into the corresponding alkoxy compounds ple, in an aqueous solution in the presence of Cu2Bre (I, R = alkoxy) by reaction with alkali metal or magne according to Sandmeyer, or by reaction with bromine O sium alcoholates in the presence of a copper(I) halide, to the diazonium perbromide and subsequent refluxing such as Cu2Cl2, Cu2Brz, or Cu22 in a heterocyclic basic in solvents, such as water or lower alcohols. It is also solvent, such as pyridine, collidine, lutidines, such as possible to convert the diazonium bromides with HgBr 2,6-lutidine, quinoline, isoquinoline, picolines, at tem into the diazonium mercury bromides, and to decom peratures of preferably 1 10-220 C. in 0.5 to 24 hours. pose them thermally to the desired bromine com 5 A basic compound of Formula I (for example a com pounds. pound substituted by at least one amino group) can be The exchange of a diazonium iodide group against converted into the associated acid addition salt by iodine can readily be accomplished by gently heating. means of an acid. Suitable for this reaction are those It is also possible to add catalysts, such as Cul, Cubr, acids yielding physiologically acceptable salts. Thus, or CuCl in order to accelerate the reaction (as de 20 suitable are organic and inorganic acids, such as, e.g., scribed in the literature). aliphatic, alicyclic, araliphatic, aromatic, or heterocy Furthermore, the diazonium salt grouping can be ex clic mono- or polybasic carboxylic or sulfonic acids, changed against the corresponding alkoxy group, for such as formic acid, acetic acid, propionic acid, pivalic example, by heating in an aqueous-alcoholic solution. acid, diethylacetic acid, oxalic acid, malonic acid, suc Also, by heating, if necessary by refluxing, the aque 25 cinic acid, pimelic acid, fumaric acid, maleic acid, lac ous solutions of the diazonium salts can also be hydro tic acid, tartaric acid, malic acid, aminocarboxylic lyzed to the corresponding phenols. acids, sulfamic acid, benzoic acid, salicyclic acid, phen With the aid of CuCN or complex nickel cyanides, ylpropionic acid, citric acid, gluconic acid, ascorbic the diazonium group can be replaced by a cyano group. acid, nicotinic acid, isonicotinic acid, methanesulfonic For purposes of this reaction, the reactant is suitably 30 acid, ethanedisulfonic acid, S-hydroxyethanesulfonic produced in situ from CuCl2 and/or fromm Ni(NO3)2 acid, p-toluenesulfonic acid, naphthalene-mono- and and an alkali metal cyanide. It is advantageous to add -disulfonic acids, sulfuric acid, nitric acid, hydrohalic the neutral diazonium salt solution dropwise to the cya acids, such as hydrochloric acid or hydrobromic acid, nide solution at about 0°-5 C.; additionally, an inert, or phosphoric acids, such as orthophosphoric acid. water-immiscible solvent, such as benzene, can be 35 On the other hand, the free carboxylic acids of For added thereto, and the reaction mixture is then heated mula I (R = COOH) can be converted into one of the for some time (up to about 50° C.). physiologically acceptable metal or ammonium salts It is furthermore possible to hydrolyze acylamino thereof by reaction with a base. Suitable salts are espe compounds of Formula I (R3 = acylamino) to the basic cially the sodium, potassium, magnesium, calcium, and amino compounds (I, Ra = NH2) under the conditions 40 ammonium salts, furthermore substituted ammonium set forth above for the hydrolysis of acid amides, for ex salts, such as, for example, the dimethyl- and die ample by heating with a strong acid, such as HCl. thylammonium, monoethanol-, diethanol-, and trie In halogen compounds of Formula I (R3 = Cl, Br, or thanolammonium, cyclohexylammonium, dicyclohex I), the halogen atom can be exchanged against other ylammonium, and dibenzylethylenediammonium salts. substituents Ra in accordance with various methods. 45 Conversely, basic and/or acidic compounds of For Thus, for example, such compounds (preferably I, R3 mula I can be liberated from the acid addition salts = Br) can be treated with ammonia (e.g., aqueous am thereof by treatment with strong bases, such as sodium monia) or substances yielding ammonia (e.g., ammo or potassium hydroxide, sodium or potassium carbon nium carbonate), preferably under pressure (10-70 at ate; and from the metal and ammonium salts thereof by mospheres) at elevated temperatures (about 150° to 50 treatment with acids, especially mineral acids such as 250° C.) and in the presence of heavy metal salts, espe hydrochloric or sulfuric acid. cially copper salts, such as CuCl2. During this reaction, If the compounds of Formula I contain a center of the halogen atom is replaced by an amino group. Anal asymmetry, they are ordinarily present in the racemic ogously, it is possible to substitute the halogen atom by form. an alkylamino or dialkylamino group, respectively, by 55 The racemates can be separated into the optical an treatment with alkyl- or dialkylamines, respectively, tipodes thereof in accordance with a large number of wherein the alkyl groups contain in each case 1-4 car conventional methods, as described in the literature. bon atoms. The method of chemical separation is preferred. Ac Furthermore, halogen compounds (I, R3 = preferably 60 cording to this method, diastereomers are formed from I) can be converted into the corresponding trifluoro the racemic mixture by reaction with an optically ac methyl compounds (I, Ra = CFs) by reaction with ICF tive auxiliary agent. Thus, an optically active base can in the presence of copper powder. This reaction is ac be optionally reacted with the carboxyl group, or an complished, for example, in solvents, such as DMF or optically active acid can be reacted with the amino hexamethylphosphoric triamide at temperatures of be 65 group of a compound of Formula I. For example, it is tween OO and 200° C. possible to form diastereomeric salts of the compounds Further, halogen compounds (I, R3 = Hal) can be of Formula I (R1 = COOH) with optically active converted into the corresponding cyano compounds (I, amines, such as quinine, cinchonidine, brucine, cincho 3,897,453 43 44 nine, hydroxyhydrindamine, morphine, 1 chloropropionic acid, 0.015 g. of Fe2O3, and 0.07 g. of phenylethylamine, 1-naphthylethylamine, KBr is heated to 200 for 15 hours. The reaction prod phenyloxynaphthylmethylamine, quinidine, strychnine, uct is taken up in ether, extracted with sodium hydrox basic amino acids, such as lysine, arginine, amino acid ide solution, and finally precipitated from the aqueous esters; or diastereomeric salts of basic compounds of 5 phase with hydrochloric acid. After working up as Formula I can be formed with optically active acids, usual, 2-(2-dibenzofuryl)-propionic acid is obtained, such as (--)- and (-)-tartaric acid, dibenzoyl-(-)- and m.p. 139-140°. -(-)-tartaric acid, diacetyl-(+)- and -(-)-tartaric acid, Instead of 2-chloropropionic acid, it is also possible camphoric acid, (3-camphorsulfonic acid, (+)- and (-)-. to employ equivalent amounts of 2-bromo- or 2 mandelic acid, (+)- and (-)-malic acid, (-)- and (-)- 10 iodopropionic acid. 2-phenylbutyric acid, (+)- and (-)-dinitrodiphenic Analogously, the corresponding 2-(2-dibenzofuryl)- acid, or (--)- and (-)-lactic acid. In a similar manner, propionic acids, e.g. 2-(8-methyl-2-dibenzofuryl)- ester diastereomers can be produced by the esterifi propionic acid, are obtained with 2chloropropionic cation of compounds of Formula I (R = COOH) with acid from 2-methyldibenzofuran, 2-ethyldibenzofuran, optically active alcohols, such as borneol, menthol, 2 15 2-n-propyldibenzofuran, 2-isopropyldibenzofuran, 2-n- octanol. The thus-obtained mixtures of diastereomeric butyldibenzofuran, 2-isobutyldibenzofuran, 2-sec.- salts or esters can be separated by selective crystalliza butyldibenzofuran, 2-tert-butyldibenzofuran, 2 tion. By the hydrolytic dissociation of the isolated dias methoxydibenzofuran, 2-ethoxydibenzofuran, 2-n- tereomeric compound, the desired optically active propoxydibenzofuran, 2-isopropoxydibenzofuran, 2-n- compounds of Formula I are obtained. 20 butoxydibenzofuran, 2-isobutoxydibenzofuran, 2-sec.- Furthermore, it is, of course, possible to obtain opti butoxydibenzofuran, and 2-tert.-butoxydibenzofuran. cally active compounds according to the above From dibenzothiophene, 2-(2-dibenzothienyl)- described methods by using starting substances which propionic acid is obtained, m.p. 182-184. are already optically active. EXAMPLE 2 The compounds of Formula I and/or optionally the 25 physiologically acceptable salts thereof can be em (a) A solution of 16.8 g. of dibenzofuran in 300 ml. ployed in a mixture with solid, liquid and/or semiliquid of nitrobenzene is agitated with 18.1 g of the ethyl excipients as medicines in the human or veterinary ester of 2-bromopropionic acid and 26.7 g. of AlCl3 for medicine. Suitable vehicles are those organic or inor 24 hours at 25. The reaction mixture is poured on ice, ganic substances suitable for parenteral, enteral, or 30 worked up as usual, and the product thus obtained is topical application, and which do not react with the the ethyl ester of 2-(2-dibenzofuryl)-propionic acid, novel compounds, such as, for example, water, vegeta b.p. 173°-177/0.2 mm. ble oils, benzyl alcohols, polyethylene glycols, gelatin, In place of AlCl3, it is also possible to use equivalent lactose, amylose, magnesium stearate, talc, vaseline, amounts of AlBra, BF or the etherate thereof, BCl, cholesterol. Especially suitable for parenteral applica 35 BBra, ZnCl2, or ZnBr2, and in place of the ethyl ester tion are solutions, preferably oily or aqueous solutions, of 2-bromopropionic acid, it is also possible to employ as well as suspensions, emulsions, or implants. Suitable equivalent amounts of the ethyl ester of 2-chloro-, 2 for enteral application are tablets, dragees, capsules, iodo-, 2-hydroxy-, or 2-acetoxypropionic acid. syrups, elixirs, or suppositories, and for topical applica Analogously, the corresponding esters of 2-(2-diben tion salves, creams or powders. The above-mentioned 40 zofuryl)-propionic acid are produced from dibenzofu preparations can optionally be sterilized or can contain ran with the following esters of 2-bromopropionic acid: auxiliary substances, such as lubricants, preservatives, methyl ester stabilizers, or wetting agents, emulsifiers, salts for influ isobutyl ester n-propyl ester encing the osmotic pressure, buffers, coloring flavoring 45 and/or aromatous substances. n-pentyl ester The substances are preferably administered in dos isopropyl ester ages of between l and 500 mg. per dosage unit. n-hexyl ester The temperatures herein are set forth in degrees Cel n-butyl ester sius. "Working up as usual' means the following: b. At -70, 13.4 g. of the ethyl ester of 2-(2-diben Water is added, if necessary; the reaction mixture is ex 50 zofuryl)-propionic acid is added dropwise to a solution tracted with ethyl acetate, ether, or chloroform; sepa of 7.3 g of diisobutylaluminum hydride in 150 ml. of rated; and the organic extract is washed with water, absolute hexane within 1 hour. The reaction mixture is dried over sodium sulfate, filtered; the solvent is dis agitated for one hour at -70, decomposed with aque tilled off; and the residue is distilled and/or crystallized 55 ous NHCl solution, the hexane phase is separated, and from the solvent indicated in parentheses. DMF = di the aqueous phase is extracted with ether. The etherf methylformamide DMSO = dimethyl sulfoxide, THF = hexane solution is dried and concentrated by evapora tetrahydrofuran. tion. The residue is chromatographed on silica gel with Without further elaboration, it is believed that one benzene/hexane (9 : 1), thus obtaining 2-(2- skilled in the art can, using the preceding description, 60 dibenzofuryl)-propanal, m.p. 52-54. utilize the present invention to its fullest extent. The following prferred specific embodiments are, therefore, EXAMPLE 3 to be construed as merely illustrative, and not limitative a. 14 g. of pulverized anhydrous AlCl3 is added to a solution of 16.8 g. of dibenzofuran in 200 ml. of nitro of the remainder of the disclosure in any way whatso benzene; then, 10 g. of 2-chloropropanol is added ever. 65 dropwise at 20-25. The mixture is stirred overnight at EXAMPLE 1. 20, then heated for 3 hours on a steam bath, decom A mixture of 10 g. of dibenzofuran, 1.5 g. of 2 posed by adding ice thereto, and the nitrobenzene is 3,897,453 45 46 driven off with steam. After the usual working-up pro cedure, 2-(2-dibenzofuryl)-propanol is obtained, m.p. EXAMPLE 6 48-50, a. A solution of 18.1 g of the ethyl ester of 2 Analogously, the corresponding 2-(8-halo-2- bromopropionic acid in 20 ml. of THF is added at 20 dibenzofuryl)-propanols are obtained, e.g. 2-(8-bromo to a bis-(2-dibenzofuryl)-cadmium solution (obtained 2-dibenzofuryl)-propanol, from 2-fluoro-, 2-chloro-, by adding 24.7 g of 2-bromodibenzofuran in 300 ml. 2-bromo-, or 2-iododibenzofuran, respectively. of THF dropwise to 2.5 g. of Mg filings in 100 ml. of b. 2.26 g. of 2-(2-dibenzofuryl)-propanol is agitated THF under agitation and refluxing, adding 20 g. of cad in 150 ml. of acetonitrile together with 10 g. of active mium chloride thereto, and refluxing for 10 minutes); manganese dioxide for 30 hours at 25. The reaction 10 the reaction mixture is allowed to stand for 24 hours at mixture is filtered and worked up as usual, thus obtain 20. After working up as usual, 2-(2-dibenzofuryl)- ing 2-(2-dibenzofuryl)-propanal, m.p. 52-54. propionic acid ethyl ester is thus obtained, b.p. c. 22.6 g. of 2-(2-dibenzofuryl)-propanol is allowed 73-77/0.2 mm. to stand in 200 ml. of DMSO and 200 ml. of benzene Analogously, the corresponding esters, e.g., the ethyl 15 ester of 2-(2-dibenzothienyl)-propionic acid (b.p. together with 24.8 g. of dicyclohexylcarbodiimide, 6.4 179-183/0.05 mm.) or the ethyl ester of 2-(8-methyl g. of pyridine, and 3.1 ml. of trifluoroacetic acid for 4 2-dibenzofuryl)-propionic acid are obtained via the hours at 25. The mixture is then diluted with benzene, corresponding Grignard and organocadmium com the precipitated dicyclohexylurea is filtered off, and the pounds, starting with filtrate is washed repeatedly with water, evaporated, 2-bromodibenzothiophene, and the product is 2-(2-dibenzofuryl)-propanal, m.p. 2-bromo-8-methyldibenzofuran, 52-54°. 2-bromo-8-ethyldibenzofuran, d. Under the exclusion of moisture, a solution of 9. 2-bromo-8-n-propyldibenzofuran, g. of CrO3, 13.5 g. of tert.-butanol, and 15.1 g of 2-bromo-8-isopropyldibenzofuran, CH3COOH in 150 ml. of absolute CCI is gradually 25 2-bromo-8-n-butyldibenzofuran, added dropwise to a solution of 22.6 of 2-(2- 2-bromo-8-isobutylidibenzofuran, dibenzofuryl)-propanol in 200 ml. of absolute CCI at 2-bromo-8-sec.-butyldibenzofuran, 0. The reaction mixture, after the tert.-butyl chromate 2-bromo-8-tert.-butyldibenzofuran, solution has been added thereto dropwise, is allowed to 2-bromo-8-methoxydibenzofuran, stand for 24 hours at 25°. After working up as usual, 2 30 2-bromo-8-ethoxydibenzofuran, (2-dibenzofuryl)-propanol is obtained, m.p. 52-54. 2-bromo-8-n-propoxydibenzofuran, 2-bromo-8-isopropoxydibenzofuran, EXAMPLE 4 2-bromo-8-n-butoxydibenzofuran, a. 14.g. of powdered anhydrous AlCl3 is added to a 2-bromo-8-isobutoxydibenzofuran, solution of 16.8 g. of dibenzofuran in 150 ml. of trichlo 35 2-bromo-8-sec.-butoxydibenzofuran, or roethylene; at 0-5, a solution of 8 g. of propylene 2-bromo-8-tert-butoxydibenzofuran. oxide in 50 ml. of trichloroethylene is added dropwise b. At 20-25, a solution of 6.8 g. of 2-(2-diben to thhs mixture. The latter is agitated for 12 hours at zofuryl)-propionic acid ethyl ester in 10 ml. of 1,2- -10°, then decomposed by adding ice, worked up as dichloroethane is added dropwise to a mixture of 2.43 usual, and the thus-obtained product is 2-(2- 40 g. of acetyl chloride, 6.7 g of aluminum chloride, and dibenzofuryl)-propanol, m.p. 48-50. 40 ml. of 1,2-dichloroethane. After agitating the mix b. 5.3.g. of 2-(2-dibenzofuryl)-propanol is agitated in ture for 3 hours at room temperature, it is poured onto 40 ml. of 10% strength HSO4 with 2.5 g. of sodium di ice water and worked up in the usual manner, thus pro chromate dihydrate for 2 hours at 60°. The reaction ducing the ethyl ester of 2-(8-acetyl-2-dibenzofuryl)- mixture is then cooled, worked up as usual, and chro 45 propionic acid. matographic purification on silica gel yields Analogously, the following compounds are produced 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140. with propionyl chloride, butyryl chloride, and isobuty c. Silver oxide, freshly prepared from 6.4 g. of ryl chloride, respectively: AgNO, and 1.6 g. of NaOH in 50 ml. of water is added the ethyl ester of 2-(8-propionyl-2-dibenzofuryl)- to a mixture of 4.5 g. of 2-(2-dibenzofuryl)-propanol 50 propionic acid and 4 g. of NaOH in 40 ml. of water. The mixture is re the ethyl ester of 2-(8-butyryl-2-dibenzofuryl)- fluxed for two hours, the thus-precipitated silver is fil propionic acid tered off, the filtrate is worked up as usual, and the the ethyl ester of 2-(8-isobutyryl-2-dibenzofuryl)- product is 2-(2-dibenzofuryl)-propionic acid, m.p. propionic acid 55 and the following compounds are prepared from 2 139-140°. (2-dibenzofuryl)-propanol and from the ethyl ester of EXAMPLE 5 2-dibenzothienylpropionic acid: 14 g. of pulverized anhydrous AlCl3 is added to a so 2-(8-acetyl-2-dibenzofuryl)-propanol lution of 16.6 g. of dibenzofuran in 200 ml. of trichloro 2-(8-propionyl-2-dibenzofuryl)-propanol ethylene; under cooling to below +5, 7 g. of allyl alco 60 2-(8-butyryl-2-dibenzofuryl)-propanol hol in 20 ml. of trichloroethylene is added dropwise to 2-(8-isobutyryl-2-dibenzofuryl)-propanol the mixture. The latter is allowed to reach room tem the ethyl ester of 2-(8-acetyl-2-dibenzothienyl)- perature, agitated for 12 hours, decomposed by adding propionic acid ice thereto, and worked up as usual, thus obtaining 2 the ethyl ester of 2-(8-propionyl-2-dibenzothienyl)- (2-dibenzofuryl)-propanol, m.p. 48-50. 65 propionic acid With 2-buten-1-ol, 2-(2-dibenzofuryl)-1-butanol is the ethyl ester of 2-(8-butyryl-2-dibenzothienyl)- obtained. propionic acid 3,897,453 47 48 the ethyl ester of 2-(8-isobutyryl-2-dibenzothienyl)- mixture is stirred for 30 minutes at 20, filtered, propionic acid. evaporated, and worked up as usual, thus obtaining c. From the above-mentioned esters, the following the tert.-butyl ester of 2-(2-dibenzofuryl)- compounds are produced by refluxing with KOH in propionic acid. ethanol for several hours: 5 e. A solution of 1 g of 2-(2-dibenzofuryl)-propionyl 2-(8-acetyl-2-dibenzofuryl)-propionic acid chloride in 10 ml. of THF is added dropwise under 2-(8-propionyl-2-dibenzofuryl)-propionic acid cooling to 15 ml. of concentrated aqueous NH3 so 2-(8-butyryl-2-dibenzofuryl)-propionic acid lution. The mixture is agitated for 2 hours, evapo 2-(8-isobutyryl-2-dibenzofuryl)-propionic acid rated, and worked up as usual, thus producing 2 2-(8-acetyl-2-dibenzothienyl)-propionic acid 10 (2-dibenzofuryl)-propionamide, m.p. 180°-182. 2-(8-propionyl-2-dibenzothienyl)-propylonic acid f. A suspension of 2.39 g, of 2-(2-dibenzofuryl)- 2-(8-butyryl-2-dibenzothienyl)-propionic acid propionic acid amide in 40 ml. of pyridine is mixed at 2-(8-isobutyryl-2-dibenzothienyl)-propionic acid. room temperature with 2.85g. of p-toluenesulfonic d. A mixture of 10 g. of 2-(8-acetyl-2-dibenzofuryl)- acid chloride and then stirred for 45 hours at 60. The propionic acid, 15 ml. of 60% hydrazine hydrate, 6.5 g. 15 mixture is poured onto water, extracted with ethyl ace of pulverized KOH, and 100 ml. of ethylene glycol is tate, and worked up as usual, thus producing 2-(2- refluxed on a water trap for 6 hours. Then, the mixture dibenzofuryl)-propionitrile, m.p. 58-61. is dissolved in water, acidified with hydrochloric acid, g. At 0, 60 ml. of a 1.1-molar ether LiAlH4 solution and worked up as usual, thus obtaining 2-(8-ethyl-2- is added dropwise during 20 minutes to a solution of dibenzofuryl)-propionic acid, m.p. 89-91. 20 26.5 g. of 2-(2-dibenzofuryl)-propionyl aziridine (ob Analogously, the following compounds are produced tainable by reacting 2-(2-dibenzofuryl)-propionyl chlo by reducing the corresponding 2-(8-alkanoyl-2-diben ride with ethylenimine) in 800 ml. of absolute ether. zofuryl)-propionic acids or -propanols or the 2-(8- The reaction mixture is agitated for 1.5 hours at 0, alkanoyl-2-dibenzothienyl)-propionic acids: then hydrolyzed by adding dilute sulfuric acid, worked 2-(8-n-propyl-2-dibenzofuryl)-propionic acid 25 up as usual, the product being 2-(2-dibenzofuryl)- 2-(8-n-butyl-2-dibenzofuryl)-propionic acid propanal, m.p. 52-54. 2-(8-isobutyl-2-dibenzofuryl)-propionic acid h. At -70 to -80, a solution of 25.5 g. of lithium 2-(8-ethyl-2-dibenzofuryl)-propanol aluminum tri-tert-butoxyhydride in 150 ml, of absolute 2-(8-n-propyl-2-dibenzofuryl)-propanol diglyme is added dropwise within 1 hour to a solution 2-(8-n-butyl-2-dibenzofuryl)-propanol 30 of 25.85g. of 2-(2-dibenzofuryl)-propionyl chloride in 2-(8-isobutyl-2-dibenzofuryl)-propanol 100 ml. of absolute diglyme under agitation and intro 2-(8-ethyl-2-benzothienyl)-propionic acid duction of dry nitrogen. The temperature of the mix 2-(8-n-propyl-2-benzothienyl)-propionic acid ture is allowed to rise to 20 within 1 hour. The mixture 2-(8-n-butyl-2-benzothienyl)-propionic acid is then poured onto ice and worked up as usual, thus 2-(8-isobutyl-2-benzothienyl)-propionic acid. 35 obtaining 2-(2-dibenzofuryl)-propanal, m.p. 52-54. i. 25.85g. of 2-(2-dibenzofuryl)-propionyl chloride is EXAMPLE 7 hydrogenated on 7 g. of 2% Pd-BasO, catalyst in 500 a. A solution of 2-dibenzofuryllithium (obtained ml. of toluene until the stoichiometric amount of hy from 24.7 g. of 2-bromodibenzofuran and 1.4g. of lith drogen has been absorbed. The reaction mixture is ium in 300 ml. of ether) is added to a solution of 12.2 40 worked up as usual, thus obtaining 2-(2-dibenzofuryl)- g. of 9-borabicyclo[3,3,1) nonane in 100 ml. of THF at propanal, m.p. 52-54. 0. The reaction mixture is agitated for 1 hour at 0, 9.5 j. 12.9 g, of 2-(2-dibenzofuryl)-propionyl chloride is g. of methanesulfonic acid is added thereto, the mix dissolved in 150 ml. of ether and gradually added drop ture is stirred for another hour, and thereafter a solu wise to a suspension of 2 g. of LiAlH4 in 100 ml. of tion of 18 g. of the ethyl ester of 2-bromopropionic acid 45 ether. The mixture is agitated for 4 hours at 25, de (or 22.8 g. of the ethyl ester of 2-iodopropionic acid) composed with methanol, and then with 15% aqueous in 50 ml. of ether is added thereto, and subsequently a Sodium hydroxide solution, worked up as usual, and the suspension of 25 g. of potassium tert-butylate in 100 product is 2-(2-dibenzofuryl)-propanol, m.p. 48°-50°. ml. of tert.-butanol is furthermore added to this reac tion mixture. The latter is maintained at 10 for 24 50 EXAMPLE 8 hours, acidified with 500 ml. of 6N hydrochloric acid, a. 2.47 g. of 2-bromodibenzofuran is allowed to react refluxed for 6 hours, cooled, and worked up as usual, with 0.5 g. of magnesium filings in 60 ml. of absolute thus producing 2-(2-dibenzofuryl)-propionic acid, m.p. THF, heating and adding a trace of iodine; 10 g. of po 139-140°. tassium 2-iodopropionate is added thereto in incremen (b) 6 g. of thionyl chloride and 11 g of 2-(2-diben 55 tal portions, and the mixture is refluxed for 20 hours zofuryl)-propionic acid are allowed to stand in 80 ml. under agitation. Thereafter, the mixture is evaporated of benzene for 24 hours at 25. The mixture is then to dryness, worked up as usual, and 2-(2-dibenzofuryl)- evaporated under reduced pressure; the thus-obtained propionic acid is thus obtained, m.p. 139°-140°. residue is 2-(2-dibenzofuryl)-propionyl chloride. b. 9.6 g of 2-(2-dibenzofuryl)-propionic acid is dis c. One gram of crude 2-(2-dibenzofuryl)-propionyl 60 solved in 75 ml, of absolute THF and mixed with 3.5 chloride is heated with 10 ml. of n-propanol for 3 ml. of triethylamine. At -10, a solution of 2.4 ml of hours to 95. The mixture is evaporated, worked up ethyl chloroformate in 16 ml. of THF is added dropwise as usual, and the product is the n-propyl ester of within 15 minutes; the mixture is stirred for 30 minutes 2-(2-dibenzofuryl)-propionic acid. at 10, and 1.9 g of NaBH4 is introduced into the so d. 2.6 g. of crude 2-(2-dibenzofuryl)-propionyl chlo 65 lution containing the mixed anhydride of of monoethyl ride is dissolved in 30 ml. of absolute THF and carbonate and the aforementioned acid, 2-(2- mixed with 1.12 g of potassium tert-butylate. The dibenzofuryl)-4,6-dioxaoctane-3,5-dione. The mixture 3,897,453 49 50 is thereafter agitated for 90 minutes at 25, 40 ml. of EXAMPLE 1.4 water is added, the mixture is extracted with ether, evaporated, and the thus-obtained remainder is re 25g. of methyl iodide is added to a mixture of 24 g. fluxed for 30 minutes with a solution of 1 g of KOH in of the methyl ester of 2-dibenzofurylacetic acid and 2.5 30 ml. of ethanol. After distilling off the ethanol, work 5 g. of NaH in 150 ml. of 1,2-dimethoxyethane after 15 ing up the reaction mixture as usual, and chromatogra minutes of agitation at 20°. The reaction mixture is al phy on AlO3, 2-(2-dibenzofuryl)-propanol, m.p. lowed to stand for several hours and worked up as 48-50, is obtained. usual, thus obtaining the methyl ester of 2-(2-diben zofuryl)-propionic acid. EXAMPLE 9 10 A solution of 22 g. of 2-chloropropylmethyl ether in EXAMPLE 1.5 80 ml. of absolute benzene is added to a solution pre a. Under a nitrogen atmosphere, a solution of 20.7 g. pared from 2.6 of magnesium filings and 24.7 g. of 2 of 2-dibenzofurylacetonitrile in 40 ml. of DMSO is bromodibenzofuran in 120 ml. of absolute ether; the added dropwise under agitation and cooling to 2.6 g. of ether is evaporated, and the residue is refluxed for 12 15 NaH in 20 ml. of DMSO. The mixture is stirred for 1 hours. After decomposition with aqueous NHCl solu hour at 25, 14.6 g. of methyl iodide in 20 ml. of DMSO tion and working up as usual, 2-(2-dibenzofuryl)- is added dropwise under agitation at the same tempera propylmethyl ether is obtained. ture, the reaction mixture is stirred overnight at 25, mixed with dilute acetic acid, and worked up as usual, EXAMPLE 10 20 thus obtaining 2-(2-dibenzofuryl)-propionitrile, m.p. Under agitation and cooling to 0-5, a solution of 58-61°, 5.8 g. of propylene oxide in 10 ml. of absolute ether is b. 22.1 g of 2-(2-dibenzofuryl)-propionitrile and 4.6 added to a solution obtained from 2.6 g. of magnesium g. of absolute ethanol are dissolved in 300 ml. of abso filings and 24.7 g of 2-bromodibenzofuran in 120 ml. lute ether and saturated with gaseous HCl at 0°. The of absolute ether; the reaction mixture is allowed to 25 2-(2-dibenzofuryl)-propionic acid iminoethyl ether hy stand overnight. Then, 80 ml. of benzene is added drochloride, separated after standing for 8 days at 0, thereto, the ether is distilled off, and the benzenic solu is filtered off. tion is refluxed for one hour. After decomposition with c. One gram of 2-(2-dibenzofuryl)-propionic acid aqueous NHCl solution and the usual working-up op iminoethyl ether hydrochloride is refluxed with 25 ml. eration, 2-(2-dibenzofuryl)propanol is produced, m.p. 30 of water for one hour. After working up as usual, the 48-50, ethyl ester of 2-(2-dibenzofuryl)-propionic acid is ob tained, b.p. 173-177/0.2 mm. EXAMPLE 11 Under agitation, 25 g. of potassium iodopropionate EXAMPLE 16 is reacted with 0.85g. of magnesium filings, while add 35 a. A solution of 1 g of CHLi in 40 ml. of absolute ing traces of iodine, by refluxing for 6 hours in 350 ml. THF is added dropwise to a solution of 2.86 g. of 2 of absolute THF; 5g of 2-bromodibenzofuran is added dibenzofuryl bromoacetonitrile (obtainable by the bro thereto, and the mixture is refluxed for another 24 mination of 2-dibenzofurylacetonitrile) in 40 ml. of ab hours. After evaporation to dryness, the product is solute THF. Thereafter, the reaction mixture is re worked up as usual, thus obtaining 2-(2-dibenzofuryl)- 40 fluxed for 1 hour, cooled, decomposed with saturated NHCl solution, and extracted with ethyl acetate. After propionic acid, m.p. 139-140. working up as usual, 2-(2-dibenzofuryl)-propionitrile is EXAMPLE 12 produced, m.p. 58-61. A solution of 22.6 g. of 2-dibenzofurylacetic acid in b. One gram of 2-(2-dibenzofuryl)-propionitrile is re 250 ml. of hexamethylphosphoric triamide is treated 45 fluxed in 15 ml. of ethanol and 2 ml. of water with 2 g. with 50 ml. of a 4N solution of propylmagnesium bro of KOH for 40 hours. The mixture is evaporated and mide in ether and then with 30 g. of methyl iodide. The the residue worked up as usual, thus producing mixture is heated for 5 minutes to 65, poured into di 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140. lute hydrochloric acid, extracted with hexane, and the c. One gram of 2-(2-dibenzofuryl)-propionitrile is re extract is evaporated to dryness. The residue is refluxed 50 fluxed with 6 ml. of acetic acid and 6 ml. of concen with 20 g. of NaOH in 75 ml. of water for 1 hour, then trated hydrochloric acid for 2 hours under a nitrogen acidified with HCl, filtered off, and the product thus atmosphere. The reaction mixture is evaporated, the produced is 2-(2-dibenzofuryl)-propionic acid, m.p. residue is dissolved in dilute NaOH, washed with ether, and worked up as usual, thus obtaining 2-(2-diben 139°-140°. 55 zofuryl)-propionic acid, m.p. 139-140°. EXAMPLE 13 d. One gram of 2-(2-dibenzofuryl)-propionitrile is re 1.5 g. of methyl iodide is added to a mixture of 2.8 fluxed for 48 hours with 3 ml. of n-hexanol and 0.1 g. g. of the tert-butyl ester of 2-dibenzofurylacetic acid of concentrated HSO4. To this mixture is added 3 ml. (obtainable by reacting the acid chloride with potas of water, the mixture is refluxed for another 48 hours, sium tert.-butylate), 0.3 g of NaH, and 20 ml. of 1,2- 60 and worked up as usual, thus producing 2-(2-diben dimethoxyethane, agitated for 15 minutes at 20; this zofuryl)-propionic acid, m.p. 139-140°. mixture is then stirred for 12 hours at 20, diluted with ether, worked up as usual, and the product is the tert.- EXAMPLE 1 7 butyl ester of 2-(2-dibenzofuryl)-propionic acid. The 65 a. At -20, a dry stream of CO, is introduced into a thus-obtained crude product is heated for 30 minutes solution of 1-(2-dibenzofuryl)-ethyllithium (obtainable to 260, thus producing 2-(2-dibenzofuryl)-propionic by adding dropwise 35 ml. of a 20% solution of n acid, m.p. 139-140. butyllithium in hexane to a solution of 27.5 g. of 3,897,453 5. 52 2-(1-bromoethyl)-dibenzofuran in 300 ml. of absolute under agitation to a mixture of 2.6 g. of pulverized ether under cooling to -60 and agitating the mixture magnesium and 200 ml, of THF at 45. The mixture is for one-half hour at -60). After 2 hours, the mixture stirred for 15 minutes, filtered, and the solution is is poured into water, acidified, and worked up as usual, poured on 1 kg. of solid carbon dioxide, allowed to yielding 2-(2-dibenzofuryl)-propionic acid, m.p. warm up to 20, the solvent is removed, and the mix 139-140°. ture is worked up as usual, thus producing 2-(2-diben 2-(1-Bromoethyl)-dibenzofuran is obtainable by the zofuryl)-propionic acid, m.p. 139-140°. reduction of 2-acetylidibenzofuran with NaBH4 to 2-(1- As the starting material, it is also possible to employ hydroxyethyl)dibenzofuran and subsequent reaction equivalent amounts of with aqueous HBr solution. O 1-(2-dibenzofuryl)-1-ethylmagnesium iodide Analogously, the corresponding carboxylic acids, for 1-(2-dibenzofuryl)-1-ethylmagnesium chloride example 2-(8-methyl-2-dibenzofuryl)-propionic acid, 1-(2-dibenzofuryl)-1-ethyllithium are obtained via the corresponding lithium compounds 1-(2-dibenzofuryl)-1-ethylzinc from the following starting substances: 1-(2-dibenzofuryl)-1-ethylcadmium 2-(1-bromoethyl)-dibenzothiophene 15 1-(2-dibenzofuryl)-1-ethylsodium 2-(1-bromoethyl)-8-methyldibenzofuran 1-(2-dibenzofuryl)-1-ethylpotassium. 2-(1-bromoethyl)-8-ethyldibenzofuran b. 24 g. of 2-(2-dibenzofuryl)-propionic acid is dis 2-(1-bromoethyl)-8-n-propyldibenzofuran solved with 14 ml. of triethylamine in 260 ml. of chlo 2-(1-bromoethyl)-8-isopropyldibenzofuran roform and cooled to -10'. Within 15 minutes, a solu 2-(1-bromoethyl)-8-n-butyldibenzofuran 20 tion of 9.5 ml. of ethyl chloroformate in 60 ml. of chlo 2-(1-bromoethyl)-8-isobutyldibenzofuran roform is added dropwise, and the reaction mixture is 2-(1-bromoethyl)-8-sec.-butyldibenzofuran stirred for 30 minutes at -10 to -15, with ammonia 2-(1-bromoethyl)-8-tert.-butyldibenzofuran being introduced until saturation. After 1 hour of agita 2-(1-bromoethyl)-8-methoxydibenzofuran tion at 0 to -10, the solvent is removed by evapora 2-(1-bromoethyl)-8-ethoxydibenzofuran 25 2-(1-bromoethyl)-8-n-propoxydibenzofuran tion; the residue is mixed with water and worked up as 2-(1-bromoethyl)-8-isopropoxydibenzofuran usual, thus obtaining 2-(2-dibenzofuryl)- 2-(1-bromoethyl)-8-n-butoxydibenzofuran propionamide, m.p. 180°-182. 2-(1-bromoethyl)-8-isobutoxydibenzofuran Analogously, the corresponding amides are obtained 30 from the corresponding acids of Formula I (R = 2-(1-bromoethyl)-8-sec.-butoxydibenzofuran COOH) by successive reaction with ethyl chlorofor 2-(1-bromoethyl)-8-tert.-butoxydibenzofuran mate and ammonia, methylamine, ethylamine, n 2-(1-bromopropyl)-dibenzofuran propylamine, n-butylamine, ethanolamine, cyclohexyl 2-(1-bromobutyl)-dibenzofuran amine, pyrrolidine, piperidine, and morpholine, respec 2-(1-bromo-2-methylpropyl)-dibenzofuran tively; for example: 2-(1-bromopentyl)-dibenzofuran 35 2-(2-dibenzofuryl)-propionic acid methylamide 2-(1-bromo-3-methylbutyl)-dibenzofuran. 2-(2-dibenzofuryl)-propionic acid ethylamide b. 24 g. of 2-(2-dibenzofuryl)-propionic acid is 2-(2-dibenzofuryl)-propionic acid n-propylamide heated in 250 ml. of absolute benzene with 15 g. of POCla for 15 minutes on a steam bath. After cooling, 2-(2-dibenzofuryl)-propionic acid n-butylamide the reaction mixture is mixed with 120 ml. of concen 40 2-(2-dibenzofuryl)-propionate acid (2- trated aqueous NH3. The benzene solution is separated hydroxyethylamide) and concentrated, thus obtaining 2-(2-dibenzofuryl)- 2-(2-dibenzofuryl)-propionic acid cyclohexylamide propionamide, m.p. 180°-182. 2-(2-dibenzofuryl)-propionic acid pyrrolidide Analogously, by reacting the acids of Formula I (R 2-(2-dibenzofuryl)-propionic acid piperidide = COOH) with POCl and subsequent reaction with 45 2-(2-dibenzofuryl)-propionic acid morpholide. methylamine, benzylamine and/or aniline, the corre c. 30 g. of the (2-chloroethyl ester) of 2-(2-diben sponding amides are produced, for example zofuryl)-propionic acid (obtainable by dissolving 2-(2- 2-(2-dibenzofuryl)-propionic acid methylamide dibenzofuryl)propionamide in 2-chloroethanol and in 2-(2dibenzofuryl)-propionic acid benzylamide troducing gaseous HCl for 5 hours at 100) is heated 2-(2-dibenzofuryl)-propionic acid anilide. 50 with 15 g. of diethylamine in 120 ml. of absolute ben Zene in a tube to 100 for 10 hours. The thus EXAMPLE 18 precipitated diethylamine hydrochloride is filtered, and 1.2 g of magnesium filings and 1.2 g of powdered the filtrate is evaporated, thus obtaining the (2- magnesium are heated under agitation in 60 ml. of ab diethylaminoethyl ester) of 2-(2-dibenzofuryl)- solute ether, a moderate stream of dry CO2 is intro 55 propionic acid, b.p. 180°-183/0.1 mm. duced, a granule of iodine is added thereto, and a solu tion of 2.3 g of 2-(1-chloroethyl)-dibenzofuran (ob EXAMPLE 2.0 tainable from 2-(1-hydroxyethyl)-dibenzofuran and 20 g. of the tetraethyl ester of orthocarbonic acid is SOCl) in 20 ml. of absolute ether is added dropwise 60 added to a solution of 1-(2-dibenzofuryl)-1- thereto. The reaction mixture is refluxed for 20 min ethylmagnesium bromide (produced from 27.5 g. of 2 utes, cooled, filtered, evaporated, water is added, and (1-bromoethyl)-dibenzofuran) in 300 ml. of THF, and the mixture is worked up as usual, thus obtaining the mixture is stirred for 4 hours at 25. An excess of 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140. semiconcentrated hydrochloride acid is gradually added thereto, the mixture is refluxed for 24 hours, al EXAMPLE 1.9 65 lowed to cool, worked up as usual, and the product thus a. A solution of 27.5 g. of 2-(1-bromoethyl)- obtained is 2-(2-dibenzofuryl)propionic acid, m.p. dibenzofuran in 200 ml. of THF is gradually added 139°-140°. 3,897,453 53 54 yielding 2-(2-dibenzofuryl)-propionic acid, m.p. EXAMPLE 21 139-140°. A Grignard solution produced from 27.5 g, of e. Under N, at 25, 22.1 g of 2-(2-dibenzofuryl)pro 2-(4-bromoethyl)-dibenzofuran in 200 ml. of THF is pionitrile in 350 ml. of absolute ether is added dropwise added gradually to a solution of 12 g. of ethyl chloro within 1 hour to a solution of 16.5 g. of diisobutylalumi formate in 200 ml. of THF. To this mixture is added num hydride in 350 ml. of absolute ether. The reaction 150 ml. of concentrated hydrochloric acid; the reaction mixture is agitated for 2 hours at 25, decomposed with mixture is refluxed for 24 hours, worked up as usual, aqueous NHCl solution, and worked up as usual, yield and the product thus obtained is 2-(2-dibenzofuryl)- ing 2-(2-dibenzofuryl)-propanal, m.p. 52-54. propionic acid, m.p. 139-140°. 10 EXAMPLE 26 EXAMPLE 22 28.2g. of 2-oxo-3-(2-dibenzofuryl)-butyric acid (ob A Grignard solution, prepared from 23 g. of 2-(i- tainable by condensation of 2-acetyldibenzofuran with chloroethyl)-dibenzofuran in 500 ml. of absolute ether acetylglycine to 2-methyl-4-1-(2-dibenzofuryl)- is added dropwise to a solution of 16 g. of N 5 ethylidene)-5-oxazolone and alkaline hydrolysis) is dis ethoxymethylene aniline in 100 ml. of absolute ether. solved in 280 ml. of 5% sodium hydroxide solution. The The reaction mixture is then refluxed for one-half hour, mixture is cooled to 0, and a solution of 150 ml. of the ether is removed by evaporation, the residue is de 10% H2O, is added dropwise thereto under agitation at composed with ice and hydrochloric acid, and worked 5-10. The mixture is agitated for 2 hours at 5° and for up as usual, yielding 2-(2-dibenzofuryl)-propanal, m.p. 20 24 hours at 20' and worked up as usual, producing 52°-54°, 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140'. EXAMPLE 23 EXAMPLE 27 27.5 g. of 2-(1-bromoethyl)-dibenzofuran is con a. A mixture of 22.6 g. of 2-(2-dibenzofuryl)-2- verted into the Grignard compound with 2.6 g. of mag 25 propanol (obtainable from 2-acetyldibenzofuran and nesium filings in 400 ml. of ether. Within 15 minutes, CHaMg with subsequent hydrolysis), 10 g. of sulfur, 15 g, of triethyl orthoformate is added dropwise to the and 17.4 g of morpholine is refluxed for 18 hours. The Grignard compound, the the mixture is agitated for 10 excess morpholine is removed under reduced pressure, hours at 25°. The ether is replaced by benzene, and the and the residue is refluxed with 100 ml. of concen mixture is heated for 3 hours at 75. After decomposi 30 trated hydrochloric acid and 100 ml. of acetic acid for tion with NHCl solution and the usual working-up 4 hours. The mixture is then poured into water and step, 2-(2-dibenzofuryl)-propanal diethylacetal is ob worked up as usual, thus obtaining 2-(2-dibenzofuryl)- propionic acid, m.p. 139-140°. tained. Equivalent amounts of 2-(2-propenyl)-dibenzofuran EXAMPLE 24 35 or 2-(2-dibenzofuryl)-1,2-propylene oxide can also be 27.5 g. of 2-(1-bromoethyl)-dibenzofuran is reacted employed as the starting substance. in 200 m. of absolute ether together with 2.6 g. of mag Analogously, with the use of 2-(8-methyl-2- nesium filings. A solution of 8 g. of chloromethyl dibenzofuryl)-2-propanol, 2-(8-ethyl-2-dibenzofuryl)- methyl ether in 100 ml. of absolute ether is gradually 2-propanol, and 2-(2-dibenzofuryl)-2-butanol, respec added dropwise to the thus-obtained Grignard solution. 40 tively, the following final products are obtained: The mixture is refluxed for 2 hours, aqueous NHCl so 2-(8-methyl-2-dibenzofuryl)-propionic acid, lution is added thereto, and the mixture is worked up 2-(8-ethyl-2-dibenzofuryl)-propionic acid, and as usual, thus producing 2-(2-dibenzofuryl)- 2-(2-dibenzofuryl)-butyric acid, respectively. propylmethyl ether. b. 24 g. of 2-(2-dibenzofuryl)-propionic acid is dis 45 solved in a mixture of 100 ml. of dioxane, 5.6 g. of EXAMPLE 25 KOH, and 40 ml. of water and then mixed dropwise and a. 27.5 g. of 2-(1-bromoethyl)-dibenzofuran is added under agitation at 5-7 with a solution of 16 g. of bro within 15 minutes at 60 and under agitation to a mix mine in 160 ml. of dioxane (duration about 2 hours). ture of 5.5 g. of NaCN and 40 ml. of DMSO. The mix The mixture is evaporated, the residue is dissolved in ture is heated for 6 hours to 70' and worked up as 50 150 ml. of water and worked up as usual, yielding 2-(8- usual, yielding 2-(2-dibenzofuryl)-propionitrile, m.p. bromo-2-dibenzofuryl)-propionic acid, m.p. 58-61. 1749-176°. b. 2.21 g of 2-(2-dibenzofuryl)-propionitrile is dis Analogously, the corresponding bromine compounds solved in 15 ml. of sulfuric acid and allowed to stand of Formula I are obtained from the corresponding un overnight at 25°. The mixture is then poured on ice wa 55 substituted compounds by bromination, for example: ter, sodium hydroxide solution is added to a pH of 8, 2-(8-bromo-2-dibenzofuryl)-butyric acid. and the product is 2-(2-dibenzofuryl)-propionamide, c. A solution of 2.4 g of 2-(2-dibenzofuryl)- m.p. 180°-182. propionic acid in the minimum amount of ether is c. 2.4 g of 2-(2-dibenzofuryl)-propionamide and 5 g. 60 treated with dry chlorine; the progression of the chlori of KOH are refluxed in 100 ml. of ethanol under N for nation is controlled by means of thin-layer chromatog 3 hours. The mixture is concentrated by evaporation raphy. After termination of the reaction, the mixture is and worked up as usual, producing 2-(2-dibenzofuryl)- filtered, the filtrate is evaporated, and the residue is propionic acid, m.p. 139-140. chromatographed on silica gel, thus producing 2-(8- d. A mixture of 1 g of 2-(2-dibenzofuryl)- chloro-2-dibenzofuryl)-propionic acid. propionamide, 2 ml. of concentrated hydrochloride 65 Analogously, the chlorine compounds of Formula I acid, and 2 ml. of acetic acid is refluxed for 48 hours are obtained by the chlorination of the corresponding and, after adding water thereto, worked up as usual, unsubstituted compounds. 3,897,453 SS 56 d. A solution of 5 g. of 2-(2-dibenzofuryl)-propionic 14 ml. of a 3N NaOH solution as well as 14 ml, of 30% acid in 120 ml. of acetic acid is treated with 0.745 g. H2O, are thereafter added dropwise at 80-100. The of chlorine at 25-30. After working up the mixture as mixture is cooled, mixed with ice water, and worked up usual, 2-(8-chloro-2-dibenzofuryl)-priopionic acid is as usual, thus producing 2-(2-dibenzofuryl)-propanol, produced. m.p. 48-50. e. A mixture of 2.75 g. of 2-(8-chloro-2-diben zofuryl)-propionic acid, 3 g of sodium methylate, 1 g. EXAMPLE 30 of Cu22, and 30 ml. of collidine is refluxed for 6 hours, 2.89 g. of 2-(1-bromo-2-propyl)-dibenzofuran is re acidified with hydrochloric acid, and worked up as acted with 0.26 g. of magnesium filings in 100 ml. of usual, yielding 2-(8-methoxy-2-dibenzofuryl)- 10 ether. The mixture is cooled to -5, oxygen is intro propionic acid. duced for 4 hours, and the mixture is combined with Analogously, the corresponding 2-(8-alkoxy-2- aqueous NHCl solution. The usual working-up step dibenzofuryl)-propionic acids are obtained with so yields 2-(2-dibenzofuryl)-propanol, m.p. 48-50. dium ethylate, propylate, isopropylate, n-butylate, or isobutylate. 15 EXAMPLE 31 f. 1.4 ml. of 100% nitric acid is added to a mixture of 26.6 g. of 4-(2-dibenzofuryl)-2-pentenic acid (ob 4.8 g. of 2-(2-dibenzofuryl)-propionic acid, 2.5 g. of tainable by reacting 2-acetyldibenzofuran with acrylo iodine, and 40 ml. of chloroform; the mixture is re nitrile in the presence of triphenylphosphine and subse fluxed for 4 hours and worked up as usual, producing quent saponification of the thus-produced 2-(8-iodo-2-dibenzofuryl)-propionic acid, m.p. 20 4-(2-dibenzofuryl)-2-pentenic acid nitrile) is dissolved 168-170 (ethyl acetate/hexane). in 300 ml. of absolute CHCl. At -70, a 3% g. 3.19 g. of 2-(8-bromo-2-dibenzofuryl)-propionic ozone/oxygen mixture is introduced until a dilute bro acid, 3 g. of CuCl2, and 50 ml. of 25% strength aque mine solution is no longer decolorized by the reaction ous NH3 solution are heated in an autoclave under agi solution. The reaction mixture is gently evaporated, the tation to 200-210 for 10 hours and then worked up 25 residue is stirred into 200 ml. of acetic acid with 10 g. as usual, obtaining 2-(8-amino-2-dibenzofuryl)- of zinc dust and agitated for 4 hours at 25, then fil propionic acid. tered, and the filtrate is worked up as usual, thus ob h. A mixture of 3.66 g. of 2-(8-iodo-2-dibenzofuryl)- taining 2-(2-dibenzofuryl)-propanal, m.p. 52-54. propionic acid, 15 g. of iodotrifluoromethane, 5 g. of copper powder, and 5 ml. of DMF is heated in an auto 30 EXAMPLE 32 clave under agitation to 120°-130' for 15 hours and a. One gram of crude 2-(2-dibenzofuryl)-acrylic acid then worked up, yielding 2-(8-trifluoromethyl-2-diben (obtainable by refluxing the ethyl ester thereof with zofuryl)-propionic acid. aqueous ethanolic KOH), is dissolved in 25 ml. of diox i. A mixture of 3.19 g. of 2-(8-bromo-2-diben ane, mixed with 0.1 g of PtC), and hydrogenated at 20 zofuryl)-propionic acid, 1.2 g of CuCN, and 2 ml. of 35 and under normal pressure until the absorption of hy pyridine is heated for 15 hours to 220. After working drogen is terminated. The reaction product is filtered, the mixture up as usual, 2-(8-cyano-2-dibenzofuryl)- evaporated, and 2-(2-dibenzofuryl)-propionic acid is propionic acid is obtained. thus obtained, m.p. 139-140' (ethyl acetate/hexane). Sodium salt (obtainable by dissolving molar amounts of EXAMPLE 28 40 the acid and NaOH in ethanol and evaporation), m.p. A solution of 20.8 g. of 2-(2-propenyl)-dibenzofuran 277-280°. (obtainable by reacting 2-acetyldibenzofuran with In place of the dioxane, it is also possible to use ethyl CHMg1, hydrolysis, and splitting off water) in 200 ml. acetate, and in place of PtC), 5% Pd/C can also be em of ether is treated with a solution of diborane in THF ployed. until analysis by thin-layer chromatography indicates 45 Analogously, the corresponding acids of Formula I the end of the reaction. The mixture is then treated at (R1 = COOH) are obtained by the hydrogenation of 0 with 20 g. of CrO3 in 100 ml. of water, and 20 ml. 2-(2-dibenzothienyl)-acrylic acid of acetic acid is added in incremental portions within 2-(8-methyl-2-dibenzofuryl)-acrylic acid 30 minutes. After 2 hours of agitation at 20, the mix 2-(8-ethyl-2-dibenzofuryl)-acrylic acid ture is diluted with water and worked up as usual, yield 50 2-(8-n-propyl-2-dibenzofuryl)-acrylic acid ing 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140. 2-(8-isopropyl-2-dibenzofuryl)-acrylic acid Analogously, 2-(8-n-butyl-2-dibenzofuryl)-acrylic acid 2-(8-methyl-2-dibenzofuryl)-propionic acid and isobutyl-2-dibenzofuryl)-acrylic acid 2-(2-dibenzofuryl)-butyric acid, m.p. 140-143, 2-(8-sec.-butyl-2-dibenzofuryl)-acrylic acid respectively, 55 2-(8-tert-butyl-2-dibenzofuryl)-acrylic acid ac obtained from 2-(2-propenyl)-8- 2-(8-methoxy-2-dibenzofuryl)-acrylic acid methyldibenzofuran and 2-(1-buten-2-yl)- 2-(8-ethoxy-2-dibenzofuryl)-acrylic acid dibenzofuran, respectively. 2-(8-n-propoxy-2-dibenzofuryl)-acrylic acid 2-(8-isopropoxy-2-dibenzofuryl)-acrylic acid EXAMPLE 29 60 2-(8-n-butoxy-2-dibenzofuryl)-acrylic acid 20.8 g. of 2-(2-propenyl)-dibenzofuran is dissolved in 2-(8-isobutoxy-2-dibenzofuryl)-acrylic acid 50 ml. of diglyme and mixed with 30 ml. of a 1-molar 2-(8-sec.-butoxy-2-dibenzofuryl)-acrylic acid solution of NaBH4 in diglyme. Under agitation and 2-(8-tert-butoxy-2-dibenzofuryl)-acrylic acid while introducing N2, a solution of 5.6 g. of freshly dis 2-(8-fluoro-2-dibenzofuryl)-acrylic acid tilled BFs etherate in 12 ml. of diglyme is gradually 65 2-(8-chloro-2-dibenzofuryl)-acrylic acid added dropwise to this solution within 30 minutes. The 2-(8-bromo-2-dibenzofuryl)-acrylic acid reaction mixture is then mixed with 7 ml. of water, and 2-(8-iodo-2-dibenzofuryl)-acrylic acid 3,897,453 57 58 2-(8-hydroxy-2-dibenzofuryl)-acrylic acid d, 2.4 g of 2-(2-dibenzofuryl)-propionic acid and 2-(2-dibenzofuryl)-2-butenic acid 0.86 g. of cyclopentanol are dissolved in 15 ml, of abso 2-(2-dibenzofuryl)-2-pentenic acid lute THF and mixed with 2.06 g, of dicyclohex 2-(2-dibenzofuryl)-3-methyl-2-butenic acid ylcarbodiimide. The mixture is allowed to stand for 24 2-(2-dibenzofuryl)-2-hexenic acid hours at 25, filtered, the filtrate evaporated, and the 2-(2-dibenzofuryl)-4-methyl-2-pentenic acid. thus-obtained product is the cyclopentyl ester of b. One gram of 2-(2-dibenzofuryl)-propionic acid is 2-(2-dibenzofuryl)-propionic acid. allowed to stand in 15 ml. of methanolic hydrochloric Analogously, the cyclohexyl ester of 2-(2-diben acid for 24 hours at room temperature. The reaction zofuryl)propionic acid is produced with cyclohexanol. 10 e. 2.4 g. of 2-(2-dibenzofuryl)-propionic acid and 0.1 mixture is evaporated, worked up as usual, and the g. of anhydrous ZnCl2 are agitated in 5 ml. of 2,3- product is the methyl ester of 2-(2-dibenzofuryl)- dihydropyran for 12 hours at 50. The mixture is di propionic acid, luted with ether, washed with sodium bicarbonate solu Analogously (reaction times of up to 3 days), the tion and water, the ether solution is dried and evapo products set forth below are obtained from the corre 15 rated. The residue is filtered in benzenefacetone 1:1 sponding acids by reaction with HCl in methanol, etha over silica gel, and the eluate is evaporated, thus ob nol, n-propanol, iso-propanol, n-butanol, isobutanol, taining the (2-tetrahydropyranyl ester) of 2-(2-diben sec.-butanol, n-pentanol, iso-pentanol, n-hexanol, n zofuryl)-propionic acid. heptanol, n-octanol, 2-ethylhexanol, n-nonanol, n Analogously, the (2-tetrahydrofuryl ester) of decanol, and n-dodecanol, respectively: 20 2-(2-dibenzofuryl)-propionic acid is produced with the corresponding methyl, ethyl, n-propyl, isopropyl, 2,3-dihydrofuran. n-butyl, isobutyl, sec.-butyl, n-pentyl, isopentyl, n f. 12 g. of the n-butyl ester of 2-(2-dibenzofuryl)- hexyl, n-heptyl, n-octyl, 2-ethylhexyl, n-nonyl, n-decyl, propionic acid is dissolved in a mixture of 100 ml. of and n-dodecyl esters, respectively, for example THF and 50 ml. of diglyme and added dropwise to a so the following esters of 2-(2-dibenzofuryl)-propionic 25 lution, cooled to 0, of 3.8 g. of NaBH and 14 g. of acid: boron trifluoride etherate in 100 ml. of THF/diglyme ethyl ester, b.p. 173-177/0.2 mm., (2:1). The mixture is stirred for one hour at 0, heated n-propyl ester, to 60 for 45 minutes, mixed with water, and worked up isopropyl ester, as usual, yielding 2-(2-dibenzofuryl)-propylbutyl ether. n-butyl ester, 30 Analogously, isobutyl ester, 2-(2-dibenzofuryl)-propylethyl ether and sec.-butyl ester, 2-(2-dibenzofuryl)-propylisopropyl ether n-pentyl ester, are obtained by reduction of the corresponding ethyl isopentyl ester, ester and isopropyl ester, respectively. n-hexyl ester, 35 n-heptyl ester, EXAMPLE 33 n-octyl ester, a. 28.2 g of 2-(2-dibenzofuryl)-2-hydroxypropionic 2-ethylhexyl ester, acid ethyl ester (b.p. 195-200/0.2 mm.; obtainable by n-nonyl ester, reacting dibenzofuran with ethoxalyl chloride in 1,2- n-decyl ester, and 40 dichloroethane in the presence of AlCls at 10-20 and n-dodecyl ester, as well as by reaction of the thus-obtained ethyl ester of 2 the following esters of 2-(2-dibenzothienyl)-propionic dibenzofurylglyoxylic acid (b.p. 196-200/0.3 mm.) acid: with CHMg in ether) is dissolved in 500 ml. of xylene; n-propyl ester, 1 gram of p-toluenesulfonic acid is added thereto, and isopropyl ester, 45 the mixture is refluxed for 3% hours with the use of a n-butyl ester, water trap. After cooling, the mixture is washed with isobutyl ester, sodium bicarbonate solution and water, separated, sec.-butyl ester, dried over sodium sulfate, and evaporated. The thus n-pentyl ester, produced oily ethyl ester of 2-(2-dibenzofuryl)-acrylic isopentyl ester, 50 acid is dissolved in 270 ml. of ethanol and hydroge n-hexyl ester, nated on 8 g. of 5% palladium charcoal at 50 and n-heptyl ester, under 6 atmospheres until the absorption of hydrogen n-octyl ester, is terminated (3 hours). The reaction product is fil 2-ethylhexyl ester, tered, evaporated, and the final product is the ethyl n-nonyl ester, 55 ester of 2-(2-dibenzofuryl)-propionic acid, b.p. n-decyl ester, and 173-177/0.2 mm. f n-dodecyl ester. Analogously, with the use of the starting compounds With 2-(2-dibenzofuryl)-propanol in ether/HCl, the set forth below: 2-(2-dibenzofuryl)-propyl ester) of 2-(2-diben ethyl ester of 2-(2-dibenzothienyl)-acrylic acid ob zofuryl)-propionic acid is analogously obtained. 60 tainable from dibenzothiophene via the ethyl ester c. 12 g. of 2-(2-dibenzofuryl)-propionic acid is re of 2-dibenzothienylglyoxylic acid (m.p. 85) and fluxed with 3 ml. of concentrated HSO4 and 100 ml. the ethyl ester of 2-(2-dibenzothienyl)-2-hydroxy of n-butanol for 7 hours. The mixture is concentrated propionic acid (b.p. 198-201/0.05 mm.) by evaporation, taken up in chloroform, washed with ethyl ester of 2-(8-methyl-2-dibenzofuryl)-acrylic NaHCO solution, dried, and evaporated, thus obtain 65 acid ing the n-butyl ester of 2-(2-dibenzofuryl)-propionic ethyl ester of 2-(8-ethyl-2-dibenzofuryl)-acrylic acid acid. obtainable from 8-ethyldibenzofuran (b.p. 3,897,453 59 60 112/0.1 mm.) via the ethyl ester of 8-ethyl-2- 2-(8-n-propyl-2-dibenzofuryl)-propionic acid dibenzofurylglyoxylic acid (b. p. 180°-184/0.1 2-(8-isopropyl-2-dibenzofuryl)-propionic acid mm.) and the ethyl ester of 2-(8-ethyl-2- 2-(8-n-butyl-2-dibenzofuryl)-propionic acid dibenzofuryl)-2-hydroxypropionic acid) 2-(8-isobutyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(8-n-propyl-2-dibenzofuryl)-acrylic 2-(8-sec.-butyl-2-dibenzofuryl)-propionic acid 2-(8-tert.-butyl-2-dibenzofuryl)-propionic acid ester of 2-(8-isopropyl-2-dibenzofuryl)-acrylic 2-(8-methoxy-2-dibenzofuryl)-propionic acid 2-(8-ethoxy-2-dibenzofuryl)-propionic acid es ester of 2-(8-n-butyl-2-dibenzofuryl)-acrylic 2-(8-n-propoxy-2-dibenzofuryl)-propionic acid 10 2-(8-isopropoxy-2-dibenzofuryl)-propionic acid elsette of 2-(8-isobutyl-2-dibenzofuryl)-acrylic 2-(8-n-butoxy-2-dibenzofuryl)-propionic acid 2-(8-isobutoxy-2-dibenzofuryl)propionic acid ester of 2-(8-sec.-butyl-2-dibenzofuryl)-acrylic 2-(8-sec.-butoxy-2-dibenzofuryl)-propionic acid 2-(8-tert.-butoxy-2-dibenzofuryl)-propionic acid ester of 2-(8-tert-butyl-2-dibenzofuryl)-acrylic 15 2-(8-fluoro-2-dibenzofuryl)-propionic acid 2-(8-chloro-2-dibenzofuryl)-propionic acid ester of 2-(8-methoxy-2-dibenzofuryl)-acrylic 2-(8-bromo-2-dibenzofuryl)-propionic acid, b.p. of the ethyl ester: 203-206/0.1 mm. es ester of 2-(8-ethoxy-2-dibenzofuryl)-acrylic 2-(8-iodo-2-dibenzofuryl)-propionic acid 20 2-(8-hydroxy-2-dibenzofuryl)-propionic acid ester of 2-(8-n-propoxy-2-dibenzofuryl)-acrylic 2-(2-dibenzofuryl)-butyric acid 2-(2-dibenzofuryl)-valeric acid es ester of 2-(8-isopropoxy-2-dibenzofuryl)- 2-(2-dibenzofuryl)-isovaleric acid acrylic acid 2-(2-dibenzofuryl)-caproic acid ethyl ester of 2-(8-n-butoxy-2-dibenzofuryl)-acrylic 25 2-(2-dibenzofuryl)-isocaproic acid acid 2-(2-dibenzothienyl)-butyric acid ethyl ester of 2-(8-isobutoxy-2-dibenzofuryl)-acrylic 2-(2-dibenzothienyl)-valeric acid acid 2-(2-dibenzothienyl)-isovaleric acid ethyl ester of 2-(8-sec.-butoxy-2-dibenzofuryl)- 2-(2-dibenzothienyl)-caproic acid acrylic acid 30 2-(2-dibenzothienyl)-isocaproic acid. ethyl ester of 2-(8-tert-butoxy-2-dibenzofuryl)- b. 171 g. of the ethyl ester of 2-(2-dibenzofuryl)pro acrylic acid pionic acid is refluxed with 53 g. of KOH in 1,350 ml. ethyl ester of 2-(8-fluoro-2-dibenzofuryl)-acrylic of ethanol for 2 hours. The reaction mixture is concen acid 35 trated by evaporation, the residue is dissolved in water, ethyl ester of 2-(8-chloro-2-dibenzofuryl)-acrylic washed with ether, acidified to pH 3 with hydrochloric acid acid, worked up as usual, and the product thus ob ethyl ester of 2-(8-bromo-2-dibenzofuryl)-acrylic tained is 2-(2-dibenzofuryl)propionic acid, m.p. acid obtainable from 2-bromodibenzofuran via 139-140 (diisopropyl ether). 4-Carbethoxycyclohex the ethyl ester of 8-bromo-2-dibenzofurylglyoxylic 40 ylammonium salt, melting point 159-166. acid (m.p. 108-111) and the ethyl ester of 2-(8- In place of KOH, it is also possible to utilize equiva bromo-2-dibenzofuryl)-2-hydroxypropionic acid lent amounts of NaOH, Na2CO3, or K2CO3. (m.p. 80-82) Analogously, the following final products are ob ethyl ester of 2-(8-iodo-2-dibenzofuryl)-acrylic acid tained by saponification of the corresponding esters: ethyl ester of 2-(8-hydroxy-2-dibenzofuryl)-acrylic 45 acid 2-(2-dibenzothienyl)-propionic acid, m.p. 182-184 ethyl ester of 2-(2-dibenzofuryl)-crotonic acid 2-(8-methyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzofuryl)-2-pentenic acid 2-(8-ethyl-2-dibenzofuryl)-propionic acid, ethyl ester of 2-(2-dibenzofuryl)-3-methyl-2-butenic 899-91 acid 2-(8-n-propyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzofuryl)-2-hexenic acid 50 2-(8-isopropyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzofuryl)-4-methyl-2- 2-(8-n-butyl-2-dibenzofuryl)-propionic acid pentenic acid 2-(8-isobutyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzothienyl)-crotonic acid 2-(8-sec.-butyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzothienyl)-2-pentenic acid 2-(8-tert-butyl-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzothienyl)-3-methyl-2- 55 2-(8-methoxy-2-dibenzofuryl)-propionic acid butenic acid 2-(8-ethoxy-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzothienyl)-2-hexenic acid 2-(8-propoxy-2-dibenzofuryl)-propionic acid ethyl ester of 2-(2-dibenzothienyl)-4-methyl-2- 2-(8-isopropoxy-2-dibenzofuryl)-propionic acid pentenic acid 60 2-(8-n-butoxy-2-dibenzofuryl)-propionic acid the following final products can be obtained by hydro 2-(8-isobutoxy-2-dibenzofuryl)-propionic acid genation: 2-(8-sec.-butoxy-2-dibenzofuryl)-propionic acid the ethyl ester of each of the following acids: 2-(8-tert-butoxy-2-dibenzofuryl)-propionic acid 2-(2-dibenzothienyl)-propionic acid, b.p. of the ethyl 2-(8-fluoro-2-dibenzofuryl)-propionic acid, m.p. ester: 179-183/0.5 mm. 118-120° 2-(8-methyl-2-dibenzofuryl)-propionic acid 65 2-(8-chloro-2-dibenzofuryl)-propionic acid 2-(8-ethyl-2-dibenzofuryl)-propionic acid, b.p. of the 2-(8-bromo-2-dibenzofuryl)-propionic acid, m.p. ethyl ester: 170°-174/0.5 mm. 1749-176° 3,897,453 61 62 2-(8-iodo-2-dibenzofuryl)-propionic acid, m.p. methyl ester of 2-(8-amino-2-dibenzofuryl)- 168-170° propionic acid 2-(8-hydroxy-2-dibenzofuryl)-propionic acid ethyl ester of 2-(8-amino-2-dibenzofuryl)-propionic 2-(2-dibenzofuryl)-butyric acid, m.p. 140-143 acid 2-(2-dibenzofuryl)-valeric acid n-butyl ester of 2-(8-amino-2-dibenzofuryl)- 2-(2-dibenzofuryl)-isovaleric acid propionic acid 2-(2-dibenzofuryl)-caproic acid 2-(8-amino-2-dibenzofuryl)-butyric acid 2-(2-dibenzofuryl)-isocaproic acid 2-(8-amino-2-dibenzofuryl)-valeric acid 2-(2-dibenzothienyl)-butyric acid 2-(8-amino-2-dibenzofuryl)-isovaleric acid 2-(2-dibenzothienyl)-valeric acid 10 2-(8-amino-2-dibenzofuryl)-caproic acid 2-(2-dibenzothienyl)-isovaleric acid 2-(8-amino-2-dibenzofuryl)-isocaproic acid 2-(2-dibenzothienyl)-caproic acid h. 90 g. SnCl2 2H2O is dissolved in 225 ml. of con 2-(2-dibenzothienyl)-isocaproic acid. centrated hydrochloric acid; 21 g of 2-(8-nitro-2- c. 2.68 g. of the ethyl ester of 2-(2-dibenzofuryl)pro dibenzofuryl)-propionic acid is added thereto, and the pionic acid is refluxed for 90 minutes in a mixture of 25 15 mixture is stirred for a short time and then allowed to ml. of acetic acid and 25 ml. of 25% hydrochloric acid. stand for 24 hours at 25'. Thereafter, the mixture is fil After working the reaction mixture up as usual, tered; the still moist residue is introduced into 300 ml. 2-(2-dibenzofuryl)-propionic acid is obtained, m.p. of water, neutralized with aqueous ammonia solution, 139-140 (ethyl acetate/hexane). and agitated for 2 hours at 25°. The residue is filtered Analogously, the remaining esters of Formula I (R 20 off, washed with water, dried, and extracted in an ex = esterified carboxyl group) can be saponified to the traction apparatus with ethyl acetate. From the extract, corresponding acids. 2-(8-amino-2-dibenzofuryl)-propionic acid is obtained. d. A mixture of 1 g. of the ethyl ester of 2-(2-diben i. Under agitation, a solution of 10.4 ml. of concen zofuryl)-propionic acid and 100 ml. of water is heated trated hydrochloric acid in 50 ml. of 50% strength etha in an autoclave for 24 hours to 180°. The mixture is 25 nol is added dropwise at 80 to a mixture of 28.5 g. of then cooled, worked up as usual, and the product is 2-(8-nitro-2-dibenzofuryl)-propionic acid and 255 g. of 2-(2-dibenzofuryl)propionic acid, m.p. 139-140°. iron powder in 300 ml. of 50% strength ethanol. The e. 2 g of 2-(2-dibenzofuryl)-propionic acid is intro mixture is then refluxed for 2 hours, filtered, washed duced at 0° to +5 into 10 ml. of fuming HNO3 in incre with ethanol, the filtrate evaporated, and the thus mental portions. The reaction mixture is stirred for 15 30 obtained product is 2-(8-amino-2-dibenzofuryl)- minutes at 0 to +5, and then poured into ice water propionic acid hydrochloride. and filtered. The residue is washed with water, dried, j. A solution of 6.9 g. of NaNO in 20 ml. of water is purified by chromatography on silica gel (benzene : added dropwise at 0 to a solution of 25.5 g. of 2-(8- methanol 8:2), and the thus-obtained product is 2-(8- amino-2-dibenzofuryl)-propionic acid in 250 ml. of nitro-2-dibenzofuryl)-propionic acid. 35 15% hydrochloric acid. Thereafter, 12 ml. of a 40% By nitration of the corresponding compounds (I, R8 HBF solution is added dropwise to the reaction mix = H), the following final products are obtained in an ture; the latter is buffered to pH 5-6, the thus analogous manner: precipitated diazonium tetrafluoroborate is filtered off, 2-(8-nitro-2-dibenzothienyl)-propionic acid washed with water, dried, and introduced in batches the methyl ester of 2-(8-nitro-2-dibenzofuryl)- 40 into 200 ml. of boiling xylene. After the decomposition propionic acid process is terminated, the reaction mixture is evapo the ethyl ester of 2-(8-nitro-2-dibenzofuryl)- rated and worked up as usual, yielding 2-(8-fluoro-2- propionic acid dibenzofuryl)-propionic acid, m.p. 118-120°. the n-butyl ester of 2-(8-nitro-2-dibenzofuryl)- Analogously, the following products are obtained propionic acid 45 from the corresponding amino compounds: 2-(8-nitro-2-dibenzofuryl)-butryic acid 2-(8-fluoro-2-dibenzothienyl)-propionic acid 2-(8-nitro-2-dibenzofuryl)-valeric acid 2-(8-fluoro-2-dibenzofuryl)-butyric acid 2-(8-nitro-2-dibenzofuryl)-isovaleric acid 2-(8-fluoro-2-dibenzofuryl)-valeric acid 2-(8-nitro-2-dibenzofuryl)-caproic acid 2-(8-fluoro-2-dibenzofuryl)-isovaleric acid 2-(8-nitro-2-dibenzofuryl)-isocaproic acid. 50 2-(8-fluoro-2-dibenzofuryl)-caproic acid f. Under agitation, 9.4 ml. of 65% strength nitric acid 2-(8-fluoro-2-dibenzofuryl)-isocaproic acid. is added dropwise within 15 minutes to a suspension, k. 25.5 g. of 2-(8-amino-2-dibenzofuryl)-propionic heated to 50, of 9.5 g. of 2-(2-dibenzofuryl)-propionic acid is dissolved in 200 ml. of water and 70 ml. of con acid in 40 ml. of acetic acid. Thereafter, the mixture is 55 centrated hydrochloric acid, mixed at 0°-5 with 6.9 g. heated for 1 hour to 80 and worked up as usual, ob of NaNO, in 20 ml. of water, gradually added dropwise taining 2-(8-nitro-2-dibenzofuryl)-propionic acid. to a hot CuCl2 solution (obtained by reducing 21 g. of g. 28.5 g. of 2-(8-nitro-2-dibenzofuryl)-propionic CuSO4 with SO, in 130 ml. of water in the presence of acid is dissolved in 300 ml. of absolute ethanol and hy 26 g. of NaCl), heated another 30 minutes to 90°-95, drogenated on 2 g. of 10% Pd/C until the hydrogen ab 60 cooled, saturated with H2S, and filtered. The filtrate is sorption is terminated; this reaction is carried out at worked up as usual, thus producing 2-(8-chloro-2- 25. The catalyst is filtered off and the solvent is evapo dibenzofuryl)-propionic acid. rated, thus obtaining 2-(8-amino-2-dibenzofuryl)- Analogously, the following final products are ob propionic acid. tained from the corresponding amino compounds: Analogously, the final products set forth below are 65 2-(8-chloro-2-dibenzothienyl)-propionic acid obtained by reduction of the corresponding nitro com 2-(8-chloro-2-dibenzofuryl)-butyric acid pounds: 2-(8-chloro-2-dibenzofuryl)-valeric acid 2-(8-amino-2-dibenzothienyl)-propionic acid 2-(8-chloro-2-dibenzofuryl)-isovaleric acid 3,897,453 63 64 2-(8-chloro-2-dibenzofuryl)-caproic acid Analogousiy, the corresponding alkoxy compounds 2-(8-chloro-2-dibenzofuryl)-isocaproic acid. of Formula I are obtained from the corresponding hy 1. 25.5 g. of 2-(8-amino-2-dibenzofuryl)-propionic droxy compounds by reaction with dimethyl sulfate, di acid is dissolved in 120 ml. of water and 12 ml. of con ethyl sulfate, di-n-propyl sulfate, and isopropyl bro centrated HSO4, mixed dropwise at 0-5 with a solu mide, for example: tion of 6.9 g of NaNO, is 20 ml. of water, added drop 2-(8-ethoxy-2-dibenzofuryl)-propionic acid wise to a boiling solution of 6.6 g. CuSO4 5H2O, 15.4 2-(8-n-propoxy-2-dibenzofuryl)-propionic acid g. of NaBr, and 2 g of copper powder (previously re 2-(8-isopropoxy-2-dibenzofuryl)-propionic acid fluxed for 4 hours and then mixed with 0.25 g. of Na2 2-(8-methoxy-2-dibenzothienyl)-propionic acid SO), heated for 30 minutes to 95, cooled, saturated 10 2-(8-ethoxy-2-dibenzothienyl)-propionic acid with HS, filtered, and the filtrate worked up as usual, 2-(8-n-propoxy-2-dibenzothienyl)-propionic acid yileding 2-(8-bromo-2-dibenzofuryl)-propionic acid, 2-(8-isopropoxy-2-dibenzothienyl)-propionic acid m.p. 174°-176. 2-(8-methoxy-2-dibenzofuryl)-butyric acid Analogously, the following final products are ob 2-(8-methoxy-2-dibenzofuryl)-valeric acid tained from the corresponding amino compounds: 15 2-(8-methoxy-2-dibenzofuryl)-isovaleric acid 2-(8-bromo-2-dibenzothienyl)-propionic acid 2-(8-methoxy-2-dibenzofuryl)-caproic acid 2-(8-bromo-2-dibenzofuryl)-butyric acid 2-(8-methoxy-2-dibenzofuryl)-isocaproic acid. 2-(8-bromo-2-dibenzofuryl)-valeric acid p. One gram of crude 2-(8-hydroxy-2-dibenzofuryl)- 2-(8-bromo-2-dibenzofuryl)-isovaleric acid propionic acid is agitated with 10 ml. of DMF, 0.5 g. of 2-(8-bromo-2-dibenzofuryl)-caproic acid 20 KCO, and 10 ml. of CHI for 24 hours at about 20. 2-(8-bromo-2-dibenzofuryl)-isocaproic acid. The reaction mixture is then poured into water, worked m. 25.5 g. of 2-(8-amino-2-dibenzofuryl)-propionic up as usual, and the product is the methyl ester of 2-(8- acid is dissolved in 120 ml. of 18% sulfuric acid and di methoxy-2-dibenzofuryl)-propionic acid. azotized at 0–5 with 6.9 g of NaNO in 15 ml. of wa 25 q. At 20-25, 26.9 g of the methyl ester of 2-(8- ter. This solution is introduced under agitation into a amino-2-dibenzofuryl)-propionic acid is added to a mixture of 25 g. of KI in 50 ml. of 1N HSO4. The mix mixture of 10.6 g. of 30% formaldehyde and 0.1 g of ture is stirred overnight, heated for 30 minutes on a triethylamine; the mixture is stirred for 10 minutes, the steam bath, decolorized with carbon, and worked up as organic phase is separated, decomposed with 20 ml. of usual, yielding 2-(8-iodo-2-dibenzofuryl)-propionic 30 methanol, and 1 ml. of triethylamine is added thereto. acid, m.p. 168-170. This mixture is hydrogenated on nickel-kieselguhr at Analogously, the following final compounds are pro 70-80 and 10 atmospheres hydrogen pressure. After duced from the corresponding amino compounds: 1.5 hours, the catalyst is filtered off, the filtrate is 2-(8-iodo-2-dibenzothienyl)-propionic acid evapaorated, and the methyl ester of 2-(8- 2-(8-iodo-2-dibenzofuryl)-butyric acid 35 methylamino-2-dibenzofuryl)-propionic acid is thus 2-(8-iodo-2-dibenzofuryl)-valeric acid obtained. 2-(8-iodo-2-dibenzofuryl)-isovaleric acid Analogously, the following final products are ob 2-(8-iodo-2-dibenzofuryl)-caproic acid tained from the corresponding amino compounds: 2-(8-iodo-2dibenzofuryl)-isocaproic acid. the methyl ester of each of the following acids: n. 25.5 g. of 2-(8-amino-2-dibenzofuryl)-propionic 40 2-(8-methylamino-2-dibenzothienyl)-propionic acid acid is dissolved in 100 ml. of 10% strength sulfuric 2-(8-methylamino-2-dibenzofuryl)-butyric acid acid and diazotized at 0°-5' by adding 6.9 g, of NaNO, 2-(8-methylamino-2-dibenzofuryl)-valeric acid in 20 ml. of water. The diazonium salt solution is intro 2-(8-methylamino-2-dibenzofuryl)-isovaleric acid duced under agitation into 250 ml. of boiling water. 2-(8-methylamino-2-dibenzofuryl)-caproic acid Thereafter, the reaction mixture is refluxed for 30 min 45 2-(8-methylamino-2-dibenzofuryl)-isocaproic acid. utes, cooled, and acidified, thus obtaining 2-(8- r. 2.55 g. of 2-(8-amino-2-dibenzofuryl)-propionic hydroxy-2-dibenzofuryl)-propionic acid. acid is dissolved in 50 ml. of 1N sodium hydroxide solu From the corresponding amino compounds, the foll tion and mixed dropwise, under vigorous agitation and lowing final products are analogously obtained: cooling, with 3 g. of acetic anhydride. The mixture is 2-(8-hydroxy-2-dibenzothienyl)-propionic acid 50 allowed to stand overnight at 25, hydrochloric acid is 2-(8-hydroxy-2-dibenzofuryl)-butyric acid added to pH 3-6, the reaction mixture is separated 2-(8-hydroxy-2-dibenzofuryl)-valeric acid from the precipitate, and 2-(8-acetamido-2-diben 2-(8-hydroxy-2-dibenzofuryl)-isovaleric acid zofuryl)-propionic acid is thus produced. 2-(8-hydroxy-2-dibenzofuryl)-caproic acid Analogously, the corresponding acylamino com 2-(8-hydroxy-2-dibenzofuryl)-isocaproic acid. 55 pounds of Formula I are obtained by the acylation of o. The crude 2-(8-hydroxy-2-dibenzofuryl)- the corresponding amino compounds with acetic anhy propionic acid obtained according to (n) is dissolved, dride or propionic acid, butyric acid, or isobutyric acid under a nitrogen atmosphere, in 250 ml. of 1N sodium anhydride, for example: hydroxide solution and is then mixed batchwise under 2-(8-propionamido-2-dibenzofuryl)-propionic acid agitation with 26 g. of dimethyl sulfate. The methyl 60 2-(8-butyramido-2-dibenzofuryl)-propionic acid ester of 2-(8-methoxy-2-dibenzofuryl)-propionic acid 2-(8-isobutyramido-2dibenzofuryl)-propionic acid. thus produced is gradually separated in an oily form. s. 2.9 g, of 2-(8-amino-2-dibenzofuryl)-propionic After agitating the reaction mixture for one-half, 100 acid hydrochloride is mixed in 50 ml. of pyridine under ml. of 2N sodium hydroxide solution is added, the mix 65 agitation and ice cooling with 3.5 g. of acetyl chloride. ture is refluxed under stirring for one-half hour, cooled After 2 hours, 50 ml. of water is added thereto; the mix to 0, and acidified, thus producing 2-(8-methoxy-2- ture is allowed to stand overnight, mixed with another dibenzofuryl)-propionic acid. 200 ml. of water, and acidified with hydrochloric acid, 3,897,453 65 66 thus obtaining 2-(8-acetamido-2-dibenzofuryl)- W. A cold diazonium salt solution, obtained from propionic acid. 2.55 g. of 2-(*-amino-2-dibenzofuryl)-propionic acid, Analogously, the corresponding acylamino com 3 ml. of concentrated hydrochloric acid, 0.7 g. of pounds of Formula I are produced by acylation of the NaNO, and 10 ml, of water is added dropwise to a corresponding amino compounds with acetyl, priopio- 5 CuCN solution (produced by heating 2.5 g. of copper nyl, butyryl, or isobutyryl chloride, respectively; for ex sulfate in 10 ml. of water with 2.8 g. of KCN), heated ample: to 60-70. The mixture is heated for another 20 min 2-(8-acetamido-2-dibenzothienyl)-propionic acid utes on a steam bath, cooled, worked up as usual, and 2C8-propionamido-2-dibenzothienyl)-propionic acid the product thus obtained is 2-(8-cyano-2-diben 2-(8-butyramido-2-dibenzothienyl)-propionic acid 10 zofuryl)-propionic acid. 2-(8-isobutyramido-2-dibenzothienyl)-propionic EXAMPLE 34 acid 2-(8-acetamido-2-dibenzofuryl)-butyric acid a. 26.6 g. of the ethyl ester of 2-(2-dibenzofuryl)- 2-(8-acetamido-2-dibenzofuryl)-valeric acid acrylic acid is refluxed in 140 ml. of 1N sodium hydrox 2-(8-acetamido-2-dibenzofuryl)-isovaleric acid 15 ide solution and 300 ml. of ethanol for 3 hours. To this 2-(8-acetamido-2-dibenzofuryl)-caproic acid mixture is added 400 ml. of water and then 550 g. of 2-(8-acetamido-2-dibenzofuryl)-isocaproic acid. 2.5% sodium amalgam is added in incremental portions t. 29.7 g. of 2-(8-acetamido-2-dibenzofuryl)- at 25' under agitation and in the course of 5 hours; the propionic acid is dissolved in 200 ml. of absolute THF mixture is vigorously stirred for another 5 hours, and added dropwide to a suspension of 8 g. of LiAlH4 20 heated on a water bath, decanted from the mercury, in 160 mi. of absolute THF. The reaction mixture is re and the alcohol is distilled off. The mixture is worked fluxed for 12 hours, cooled, 20 ml. of 20% NaOH solu up as usual, thus producing 2-(2-dibenzofuryl)- tion is added, and, after working up the reaction mix propionic acid, m.p. 139-140. ture as usual, 2-(8-ethylamino-2-dibenzofuryl)- For the reduction, it is also possible to use the equiva propanol is obtained. 25 lent amount of the free acid in place of the ester, with Analogously, the following products are obtained by the same result. reduction of the corresponding 2-(8-acylamino-2- b. 2.4 g. of 2-(2-dibenzofuryl)-propionic acid and dibenzofuryl-and-dibenzothienyl)-propionic acids, re 1.72 g. of 2-diethylaminoethyl chloride hydrochloride spectively: are refluxed in a solution prepared from 0.46 g. of Na 2-(8-ethylamino-2-dibenzothienyl)-propanol 30 and 30 ml. of isopropanol for 8 hours. The mixture is 2-(8-n-propylamino-2-dibenzofuryl)-propanol then concentrated by evaporation and worked up as 2-(8-n-butylamino-2-dibenzofuryl)-propanol usual, yielding the (2-diethylaminoethyl ester) of 2-(8-isobutylamino-2-dibenzofuryl)-propanol. 2-(2-dibenzofuryl)-propionic acid, b.p. 180°-183/0.1 u. 2.83 g. of the ethyl ester of 2-(8-amino-2-diben . zofuryl)-propionic acid is heated with 3 g. of 90% for Analogously, the (2-diethylaminoethyl ester) of 2-(2- mic acid and 2 g of 39% formaldehyde solution for 10 dibenzothienyl)-propionic acid, b.p. 202-206/0.1 hours to 90-95. The mixture is then diluted with wa mm., is obtained from 2-(2-dibenzothienyl)-propionic ter, made alkaline with sodium hydroxide solution, and acid. worked up at once as usual, thus obtaining the ethyl In an analogous manner, using the hydrochlorides of ester of 2-(8-dimethylamino-2-dibenzofuryl)-propionic 2-dimethylaminoethyl chloride, acid. 2-pyrrolidinoethyl chloride, v. 2.55 g. of 2-(8-amino-2-dibenzofuryl)-propionic 2-piperidinoethyl chloride, acid is refluxed for 2 hours in 20 ml. of n-butanol to 2-morpholinoethyl chloride, gether with 4 g. of CHI and 3 g of powdered K2CO3. 3-dimethylaminopropyl chloride, The mixture is combined with a solution of 0.5 g. of 45 3-diethylaminopropyl chloride, KOH in 100 ml. of water, refluxed for 2 hours, cooled, 3-pyrrolidinopropyl chloride, acidified with hydrochloric acid, and worked up as 3-piperidinopropyl chloride, and usual, obtaining 2-(8-dimethylamino-2-dibenzofuryl)- 3-morpholinopropyl chloride, respectively, propionic acid. the following esters of 2-(2-dibenzofuryl)-propionic Analogously, the following compounds are produced acid are obtained: from the corresponding amino compounds: the (2-dimethylaminoethyl ester), 2-(8-dimethylamino-2-dibenzothienyl)-propionic the (2-pyrrolidonoethyl ester), acid the (2-piperidinoethyl ester), 2-(8-dimethylamino-2-dibenzofuryl)-butyrid acid the (2-morpholinoethyl ester), 2-(8-dimethylamino-2-dibenzofuryl)-valeric acid the (3-dimethylaminopropyl ester), 2-(8-dimethylamino-2-dibenzofuryl)-isovaleric acid the (3-diethylaminopropyl ester), 2-(8-dimethylamin-2-dibenzofuryl)-caproic acid the (3-pyrrolidinopropyl ester), 2-(8-dimethylamino-2-dibenzofuryl)-isocaproic acid. the (3-piperidinopropyl ester), and With the use of CHI in place of CHI, the following the (3-morpholinopropyl ester). products are obtained: c. 2.7 g of CHONa is suspended in 100 ml. of DMF; 2-(8-diethylamino-2-dibenzothienyl)-propionic acid 8.6 g. of 2-diethylaminoethyl chloride hydrochloride is 2-(8-diethylamino-2-dibenzofuryl)-propionic acid added thereto, and the mixture is agitated for 30 min 2-(8-diethylamino-2-dibenzofuryl)-butyric acid utes at 20. Then, 11.3 g of the sodium salt of 2-(8-diethylamino-2-dibenzofuryl)-valeric acid 65 2-(2-dibenzofuryl)-propionic acid is introduced into 2-(8-diethylamino-2-dibenzofuryl)-isovaleric acid this reaction mixture. Under agitation, the mixture is 2-(8-diethylamino-2-dibenzofuryl)-caproic acid heated for 10 hours to 80, poured onto water, and 2-(8-diethylamino-2-dibenzofuryl)-isocaproic acid. worked up as usual, thus producing the (2- 3,897,453 67 68 diethylaminoethyl ester) of 2-(2-dibenzofuryl)- 2-(1-fluoro-2-dibenzofuryl)- propionic acid. 2-(3-fluoro-2-dibenzofuryl)- 2-(4-fluoro-2-dibenzofuryl)- EXAMPLE 35 2-(6-fluoro-2-dibenzofuryl)- a. A solution of 2.1 g of 2-(2-dibenzofuryl)-2- 2-(9-fluoro-2-dibenzofuryl)- hydroxy-propionic acid (obtainable by reacting 2 2-(1-chloro-2-dibenzofuryl)- acetyldibenzofuran with sodium cyanide and benzoyl 2-(3-chloro-2-dibenzofuryl)- chloride in THF to 2-(2-dibenzofuryl)-2-(benzoyloxy 2-(4-chloro-2dibenzofuryl)- propionitrile and hydrolysis thereof with HCl/acetic 2-(6-chloro-2-dibenzofuryl)- acid) in 30 ml. of acetic acid is hydrogenated on 0.2g. O 2-(7-chloro-2-dibenzofuryl)- of 10% Pd/C in the presence of 0.01 ml. of HClO4 at 2-(9-chloro-2-dibenzofuryl)- 20 and under normal pressure. The reaction mixture 2-(1-bromo-2-dibenzofuryl)- is filtered, diluted with water, and the thus-obtained 2-(3-bromo-2-dibenzofuryl)- product is 2-(2-dibenzofuryl)-propionic acid, m.p. 2-(4-bromo-2-dibenzofuryl 139-140°. 15 2-(6-bromo-2-dibenzofuryl)- With the same success, it is also possible to use the 2-(7-bromo-2-dibenzofuryl)- following starting substances: 2-(9-bromo-2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-acetoxypropionic acid, 2-(1-iodo-2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-chloropropionic acid, 2-(3-iodo-2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-bromopropionic acid, 20 2-(4-iodo-2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-iodopropionic acid, or 2-(6-iodo-2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-methoxypropionic acid. 2-(7-iodo-2-dibenzofuryl)- b. One gram of 2-(2-dibenzofuryl)-propionic acid is 2-(9-iodo-2-dibenzofuryl)- dissolved in 10 ml. of THF and, under agitation, such 2-(1-methyl-2-dibenzofuryl)- an amount of ethereal diazomethane solution in added 25 2-(3-methyl-2-dibenzofuryl)- dropwise thereto that the evolution of nitrogen can no 2-(4-methyl-2-dibenzofuryl)- longer be observed. After 20 minutes, the reaction mix 2-(6-methyl-2-dibenzofuryl)- ture is evaporated, thus obtaining the methyl ester of 2-(7-methyl-2-dibenzofuryl)- 2-(2-dibenzofuryl)-propionic acid. 2-(9-methyl-2-dibenzofuryl)- Analogously, with the use of the corresponding acids 30 2-(1-ethyl-2-dibenzofuryl)- of Formula I (R1 = COOH), the corresponding methyl 2-(3-ethyl-2-dibenzofuryl)- esters (I, R =COOCH3) are obtained, e.g. the methyl 2-(4-ethyl-2-dibenzofuryl)- ester of 2-(2-dibenzothienyl)-propionic acid; the 2-(6-ethyl-2-dibenzofuryl)- methyl ester of 2-(7-fluoro-2-dibenzofuryl)-propionic 2-(7-ethyl-2-dibenzofuryl)- acid; and the methyl ester of 2-(7-chloro-2-diben 35 2-(9-ethyl-2-dibenzofuryl)- zofuryl)-propionic acid. 2-(1-methoxy-2-dibenzofuryl)- c. A solution of 0.5 g. of sodium in 10 ml. of absolute 2-(3-methoxy-2-dibenzofuryl)- ethanol is added dropwise to a solution of 1.4g. of hy 2-(4-methoxy-2-dibenzofuryl)- droxylamine hydrochloride in 35 ml. of absolute etha 2-(6-methoxy-2-dibenzofuryl)- nol. The thus-precipitated sodium chloride is filtered 40 2-(7-methoxy-2-dibenzofuryl)- off; the filtrate is mixed with 5 g. of the methyl ester of 2-(9-methoxy-2-dibenzofuryl)- 2-(2-dibenzofuryl)-propionic acid and thereafter with 2-(1-hydroxy-2-dibenzofuryl)- a solution of 0.5g. of sodium in 10 ml. of absolute etha 2-(3-hydroxy-2-dibenzofuryl)- nol. After allowing the mixture to stand overnight at 2-(4-hydroxy-2-dibenzofuryl)- 25, the alcohol is distilled off, the residue is dissolved 45 2-(6-hydroxy-2-dibenzofuryl)- in water, and the mixture is worked up as usual, yield 2-(7-hydroxy-2-dibenzofuryl)- ing 2-(2-dibenzofuryl)-propionehydroxamic acid. 2-(9-hydroxy-2-dibenzofuryl)- Analogously, the corresponding hydroxamic acids 2-(1-amino-2-dibenzofuryl)- are obtained from the esters, e.g. the methyl or ethyl 2-(3-amino-2-dibenzofuryl)- esters, of Formula I (R = esterified COOH-group) by 50 2-(4-amino-2-dibenzofuryl)- reaction with hydroxylamine. 2-(6-amino-2-dibenzofuryl)- 2-(7-amino-2-dibenzofuryl)- EXAMPLE 35a 2-(9-amino-2-dibenzofuryl)- a. A mixture of 30.2 g of the ethyl ester of 2-(7- 2-(1-trifluoromethyl-2-dibenzofuryl)- fluoro-2-dibenzofuryl)-2-hydroxypropionic acid (oil; 55 2-(3-trifluoromethyl-2-dibenzofuryl)- obtainable by reacting 3-fluorodibenzofuran with 2-(4-trifluoromethyl-2-dibenzofuryl)- ethoxalyl chloride in 1,2-dichloroethane in the pres 2-(6-trifluoromethyl-2-dibenzofuryl)- ence of AlCls at 10-20 and by reacting the thus 2-(7-trifluoromethyl-2-dibenzofuryl)- obtained ethyl ester of 7-fluoro-2-dibenzofuryl 2-(8-trifluoromethyl-2-dibenzofuryl)- glyoxylic acid (m.p. 90–92) with CHaMg in ether), 60 2-(9-trifluoromethyl-2-dibenzofuryl)-2-hydroxypro 8.65 g. of KI, 5.07 g. of red phosphorus, 41 ml. of 85% pionic acid, phosphoric acid, and 16.5 ml. of water is heated for 16 the following final products are obtained by reduction hours to 130-140. After working the mixture up as with KI/red phosphorus/HPO: usual, the ethyl ester of 2-(7-fluoro-2-dibenzofuryl)- the ethyl ester of each of the following acids: propionic acid is produced, b.p. 177-182/0.15 mm. 65 2-(1-fluoro-2-dibenzofuryl)-propionic acid Analogously, from the following starting compounds: 2-(3-fluoro-2-dibenzofuryl)-propionic acid the ethyl ester of each of the following acids: 2-(4-fluoro-2-dibenzofuryl)-propionic acid

3,897,453 71. 72 mixture is refluxed for 3 hours; the solution is buffered 2-(2-dibenzofuryl)-2-hydroxyvaleric acid with dilute sodium hydroxide solution to pH 2, and hy 2-(2-dibenzofuryl)-2-hydroxyisovaleric acid drogen sulfide is introduced until the precipitation of 2-(2-dibenzofuryl)-2-hydroxycaproic acid SnS has stopped; the mixture is then filtered and dibenzofuryl)-2-hydroxyisocaproic acid, worked up as usual, yielding 2-(2-dibenzofuryl)- 5 the corresponding des-hydroxy esters are produced by propionic acid, m.p. 139-140. reduction with SnCl2, for example: b. 5 g. of 2-(2-dibenzofuryl)-propionic acid is re the ethyl ester of 2-(2-dibenzothienyl)-propionic fluxed for 10 hours with 30 ml. of acetic anhydride. acid, b.p. 179-183/0.05 mm., After the acetic acid and the excess acetic anhydride the ethyl ester of 2-(8-ethyl-2-dibenzofuryl)pro have been distilled off, 2-(2-dibenzofuryl)-propionic O pionic acid, b.p. 170°-174/0.05 mm., and acid anhydride is obtained. a. 140 g. of SnCl2. 2H2O is the ethyl ester of 2-(8-bromo-2-dibenzofuryl)- dissolved in 650 ml. of 96% ethanol; HCl gas is intro propionic acid, b.p. 203-206/0.1 mm. duced into the solution until saturation, and 69g. of the b. 2.68 g. of the ethyl ester of 2-(2-dibenzofuryl)- ethyl ester of 2-(2-dibenzofuryl)-2-hydroxypropionic propionic acid is dissolved in 20 g. of 2 acid is added thereto. The reaction mixture is allowed 15 diethylaminoethanol and heated for 20 hours to 165. to stand for 18 hours at room temperature, then poured The excess alcohol is distilled off, the residue is mixed onto water, extracted with ether, and the aqueous with water and ether and worked up as usual, thus ob phase is washed with dilute sodium hydroxide solution taining the (2-diethylaminoethyl ester) of 2-(2-diben and water, dried, and evaporated, thus producing the zofuryl)-propionic acid. c. 2.5 g. of the ethyl ester of ethyl ester of 2-(2-dibenzofuryl)-propionic acid, b.p. 20 2-(2-dibenzofuryl)-propionic acid is heated in a sealed 173-177/0.2 mm. tube with 30 ml. of saturated ethanolic NH for 16 Analogously, by using as the starting compounds the hours to 100. The reaction mixture is then concen ethyl esters of each of the following acids: trated by evaporation, the residue is triturated with di 2-(2-dibenzothienyl)-2-hydroxypropionic acid isopropyl ether, and the product is 2-(2-dibenzofuryl)- 2-(8-methyl-2-dibenzofuryl)-2-hydroxypropionic 25 propionamide, m.p. 180°-182. acid Analogously, the corresponding amides are obtained 2-(8-ethyl-2-dibenzofuryl)-2-hydroxypropionic acid from the corresponding esters of Formula I (R = ester 2-(8-n-propyl-2-dibenzofuryl)-2-hydroxypropionic ified COOH-group) by reaction with alcoholic NH, for example: 2-topropyl-2-dientour)-2-hydropropicnic 30 2-(2-dibenzothienyl)-propionamide 2-(8-methyl-2-dibenzofuryl)-propionamide 2-butyl-2-dibenzofury )-2-hydroxypropionic 2-(8-ethyl-2-dibenzofuryl)-propionamide 2-(8-n-propyl-2-dibenzofuryl)-propionamide 2. butyl-2-dibenzofuryl)-2-hydroxypropionic 2-(8-isopropyl-2-dibenzofuryl)-propionamide 35 2-(8-n-butyl-2-dibenzofuryl)-propionamide 2 re-butyl-2-dibenofuji )-2-hydroxypropionic 2-(8-isobutyl-2-dibenzofuryl)-propionamide 2-(8-sec.-butyl-2-dibenzofuryl)-propionamide 2rt-butyl-2-dientouri)-2-hydroxyproponic 2-(8-tert-butyl-2-dibenzofuryl)-propionamide 40 2-(8-methoxy-2-dibenzofuryl)-propionamide 2-tiethoty 2-dibeniour).2-hydroxypropicnic 2-(8-ethoxy-2-dibenzofuryl)-propionamide 2-(8-n-propoxy-2-dibenzofuryl)-propionamide 2 hog 2-dibenzofuryl)-2-hydroxyproponic 2-(8-isopropoxy-2-dibenzofuryl)-propionamide 2-(8-sec.-butoxy-2-dibenzofuryl)-propionamide 2. propoy-2 dibenous )-2-hydroxypropionic 45 aC 2-(8-tert-butoxy-2-dibenzofuryl)-propionamide 2-(8-isopropoxy-2-dibenzofuryl)-2-hydroxypro 2-(8-fluoro-2-dibenzofuryl)-propionamide pionic acid 2-(8-chloro-2-dibenzofuryl)-propionamide 2-(8-n-butoxy-2-dibenzofuryl)-2-hydroxypropionic 2-(8-bromo-2-dibenzofuryl)-propionamide acid 2-(8-iodo-2-dibenzofuryl)-propionamide 2-(8-isobutoxy-2-dibenzofuryl)-2-hydroxypropionic 50 2-(8-hydroxy-2-dibenzofuryl)-propionamide acid 2-(7-fluoro-2-dibenzofuryl)-propionamide 2-(8-sec.-butoxy-2-dibenzofuryl)-2-hydroxypro 2-(7-chloro-2-dibenzofuryl)-propionamide pionic acid 2-(2-dibenzofuryl)-butyramide 2-(8-tert.-butoxy-2-dibenzofuryl)-2-hydroxypro 2-(2-dibenzofuryl)-valeric acid amide pionic acid 55 2-(2-dibenzofuryl)-isovaleric acid amide 2-(8-fluoro-2-dibenzofuryl)-2-hydroxypropionic acid 2-(2-dibenzofuryl)-caproic acid amide 2-(8-chloro-2-dibenzofuryl)-2-hydroxypropionic 2-(2-dibenzofuryl)-isocaproic acid amide. acid d. A solution of 40.3 g of the ethyl ester of 2-(8-bromo-2-dibenzofuryl)-2-hydroxypropionic 2-(2-dibenzofuryl)-propionic acid in 250 ml. of abso acid (m.p. of this ethyl ester 80-82; obtainable lute THF is added dropwise to a suspension of 5.7 g of from 8-bromodibenzofuran via the ethyl ester of LiAlH4 in 250 ml. of THF. The solution is stirred for 30 8-bromo-2-dibenzofurylglyoxylic acid (m.p. minutes, and then a mixture of 20 ml. of THF, 5 ml. of 108°-111) water, and 15 ml. of 32% strength sodium hydroxide 2-(8-iodo-2-dibenzofuryl)-2-hydroxypropionic acid solution is added dropwise thereto under ice cooling; 2-(8-hydroxy-2-dibenzofuryl)-2-hydroxypropionic 65 the reaction mixture is filtered over kieselguhr, dried, acid and evaporated, thus producing 2-(2-dibenzofuryl)- 2-(2-dibenzofuryl)-2-hydroxybutyric acid propanol, m.p. 48-50. 3,897,453 73 74. In an analogous manner, the following final products ture is extracted with ether. The ether phase is ex are obtained by the reduction of the corresponding es tracted with 4% NaOH, and the alkaline extracts are ters with LiAlH: worked up as usual, thus obtaining 2-(2-dibenzofuryl)- 2-(2-dibenzothienyl)-propanol, b.p. 173-177/0.2 propionic acid, m.p. 139-140°. . 5 c. A mixtue of 2.24 g. of 2-(2-dibenzofuryl)- 2-(8-methyl-2-dibenzofuryl)-propanol propanal, 4 g. of pulverized KMnO, and 50 ml. of pyri 2-(8-ethyl-2-dibenzofuryl)-propanol dine is agitated for 24 hours, filtered, diluted with 2N 2-(8-n-propyl-2-dibenzofuryl)-propanol H2SO4, and worked up as usual, thus producing 2-(8-isopropyl-2-dibenzofuryl)-propanol 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140'. 2-(8-n-butyl-2-dibenzofuryl)-propanol 10 d. A solution of 4.48 g of 2-(2-dibenzofuryl)- 2-(8-sec.butyl-2-dibenzofuryl)-propanol propanal in 110 ml. of methanol is added to a solution 2-(8-tert.-butyl-2-dibenzofuryl)-propanol of 6.7 g. of AgNO3 in 12 ml. of water. Within 2 hours, 2-(8-methoxy-2-dibenzofuryl)-propanol 120 ml. of 0.5NNaOH is added dropwise thereto under 2-(8-ethoxy-2-dibenzofuryl)-propanol agitation and at 20; the mixture is then filtered, diluted 2-(8-n-propoxy-2-dibenzofuryl)-propanol 15 with water, and worked up as usual, yielding 2-(8-isopropoxy-2-dibenzofuryl)-propanol 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140. 2-(8-n-butoxy-2-dibenzofuryl)-propanol e. A solution of 2.24 g. of 2-(2-dibenzofuryl)- 2-(8-isobutoxy-2-dibenzofuryl)-propanol propanal in 50 ml. of THF is mixed with 4.5 g. of nickel 2-(8-sec.-butoxy-2-dibenzofuryl)-propanol peroxide and 6 ml. of aqueous 10% NaCOs solution. 2-(8-tert-butoxy-2-dibenzofuryl)-propanol 20 The mixture is stirred for 24 hours, acidified with 2-(8-fluoro-2-dibenzofuryl)-propanol H2SO4, and worked up as usual, thus obtaining 2-(8-chloro-2-dibenzofuryl)-propanol 2-(2-dibenzofuryl)-propionic acid, m.p. 139-140°. 2-(8-bromo-2-dibenzofuryl)-propanol 2-(8-iodo-2-dibenzofuryl)-propanol EXAMPLE 40 2-(8-hydroxy-2-dibenzofuryl)-propanol 25 a. 13.2 g of the ethyl ester of 2-(2-dibenzofuryl)- 2-(7-fluoro-2-dibenzofuryl)-propanol, b.p. acrylic acid is refluxed for 15 hours together with 2 g. 67-169/0.1 mm. of LiAlH4 in 200 ml. of absolute THF. Then, the mix 2-(7-chloro-2-dibenzofuryl)-propanol ture is combined with 20 ml. of 25% NaOH solution, 2-(2-dibenzofuryl)-1-butanol the THF phase is decanted off, the residue is washed 2-(2-dibenzofuryl)-1-pentanol 30 twice with ether, the combined organic phases are 2-(2-dibenzofuryl)-3-methyl-1-butanol dried, and evaporated. The residue is dissolved in 200 2-(2-dibenzofuryl)-1-hexanol ml. of absolute THF, 2 g. of LiAlH4 is added thereto, and the mixture is again refluxed for 8 hours. The usual 2-(2-dibenzofuryl)-4-methyl-1-pentanol. working-up operation yields 2-(2-dibenzofuryl)- EXAMPLE 38 35 propanol, m.p. 48-50. 15.7 g of the ethyl ester of 2-(8-ethyl-2- Analogously, the other alcohols of Formula I (R = dibenzofuryl)-2-hydroxypropionic acid is dissolved in CHOH) are obtained by reducing the corresponding 50 ml. of dichloromethane, saturated with dry gaseous esters. HCl, and mixed with 5 ml. of SOCl. The reaction mix b. One gram of 2-(2-dibenzofuryl)-propanol is al ture is heated to 50 for 2 hours and the solvent is then 40 lowed to stand in 5 ml. of pyridine and 5 ml. of acetic removed. The residue consisting of the ethyl ester of anhydride for 24 hours. The mixture is then concen 2-(8-ethyl-2-dibenzofuryl)-2-chloropropionic acid is trated, worked up as usual, and the product is 2-(2- dissolved in 500 ml. of methanol and hydrogenated on dibenzofuryl)-propyl acetate. 5 g. of platinum oxide under normal pressure and at Analogously, the following final products are ob 25°. The catalyst is filtered off, the filtrate is mixed with 45 tained from the following corresponding alcohols: a solution of 2.2 g of NaOH in 5 ml. of water, the mix 2-(2-dibenzothienyl)-propyl acetate ture is refluxed for 2 hours, evaporated to dryness, and 2-(8-methyl-2-dibenzofuryl)-propyl acetate the residue is dissolved in water and worked up as 2-(8-ethyl-2-dibenzofuryl)-propyl acetate usual, thus producing 2-(8-ethyl-2-dibenzofuryl)- 2-(8-n-propyl-2-dibenzofuryl)-propyl acetate 50 2-(8-n-butyl-2-dibenzofuryl)-propyl acetate propionic acid, m.p. 89-91. 2-(8-isobutyl-2-dibenzofuryl)-propyl acetate . EXAMPLE 39 2-(8-sec.-butyl-2-dibenzofuryl)-propyl acetate a. A solution of 8 g. of the ethyl ester of 2-(2- 2-(8-tert-butyl-2-dibenzofuryl)-propyl acetate dibenzofuryl)-acrylic acid is gradually added dropwise 55 2-(8-methoxy-2-dibenzofuryl)-propyl acetate at 20° to 1.1 g of LiAlH4 in 100 ml. of absolute THF. 2-(8-ethoxy-2-dibenzofuryl)-propyl acetate The mixture is then refluxed for 18 hours, the excess 2-(8-n-propoxy-2-dibenzofuryl)-propyl acetate LiAlH4 is destroyed with ethyl acetate, and the reaction 2-(8-isopropoxy-2-dibenzofuryl)-propyl acetate mixture is mixed with 20% NaOH solution. After work 2-(8-n-butoxy-2-dibenzofuryl)-propyl acetate ing up the reaction mixture as usual, 2-(2- 60 2-(8-isobutoxy-2-dibenzofuryl)-propyl acetate dibenzofuryl)-propanol is obtained, m.p. 52-54. 2-(8-sec.-butoxy-2-dibenzofuryl)-propyl acetate b. 0.9 g of 2-(2-dibenzofuryl)-propanal is cooled in 2-(8-tert-butoxy-2-dibenzofuryl)-propyl acetate a mixture of 20 ml. of acetic acid and 20 ml. of benzene 2-(7-fluoro-2-dibenzofuryl)-propyl acetate, b.p. to 0° and mixed, under agitation and within 10 minutes, 162-163/0.1 mm. with a solution of 0.25 g. of CrO3 in 1 ml. of water and 65 2-(8-fluoro-2-dibenzofuryl)-propyl acetate 20 ml. of acetic acid. After agitating the mixture for 2-(8-chloro-2-dibenzofuryl)-propyl acetate one hour at 25, 10 ml. of methanol is added thereto, 2-(8-bromo-2-dibenzofuryl)-propyl acetate then water is added for dilution purposes, and the mix 2-(8-iodo-2-dibenzofuryl)-propyl acetate 3,897,453 75 76 2-(2-dibenzofuryl)-1-butyl acetate 2-(8-nitro-2-dibenzofuryl)-propanal 2-(2-dibenzofuryl)-1-pentyl acetate 2-(8-amino-2-dibenzofuryl)-propanal 2-(2-dibenzofuryl)-3-methyl-l-butyl acetate 2-(8-hydroxy-2-dibenzofuryl)-propanal 2-(2-dibenzofuryl)-1-hexyl acetate 2-(8-methylamino-2-dibenzofuryl)-propanal 2-(2-dibenzofuryl)-4-methyl-1-pentyl acetate. 2-(8-acetamido-2-dibenzofuryl)-propanal c. At 0, 4.6 g. of 2-(2-dibenzofuryl)-propanol in 20 2-(8-propionamido-2-dibenzofuryl)-propanal ml. of DMF is gradually added dropwise under agita 2-(8-butyramido-2-dibenzofuryl)-propanal tion to a suspension of 4.8 g. of NaH in 50 ml. of DMF. 2-(8-isobutyramido-2-dibenzofuryl)-propanal The reaction mixture is stirred for 20 minutes, and then 2-(8-dimethylamino-2-dibenzofuryl)-propanal 4.2 g of CH in 10 ml. of DMF is added dropwise 10 2-(8-diethylamino-2-dibenzofuryl)-propanal thereto. The mixture is agitated overnight at 20 and 2-(8-ethylamino-2-dibenzofuryl)-propanai worked up as usual, yielding 2-(2-dibenzofuryl)propyl 2-(8-n-propylamino-2-dibenzofuryl)-propanal methyl ether. 2-(8-n-butylamino-2-dibenzofuryl)-propanal Analogously, the following final products are ob 2-(8-isobutylamino-2-dibenzofuryl)-propanal. tained from the corresponding alcohols with methyl io 15 EXAMPLE 4 dide: 2-(2-dibenzothienyl)-propylmethyl ether One gram of 2-(2-dibenzofuryl)-3-methoxy-1- 2-(8-methyl-2-dibenzofuryl)-propylmethyl ether propene (obtainable by reacting 2-acetyldibenzofuran 2-(8-ethyl-2-dibenzofuryl)-propylmethyl ether with CHMgBr and then splitting off water with poly 2-(8-n-propyl-2-dibenzofuryl)-propylmethyl ether 20 phosphoric acid, or by reaction of 2-methoxyacetyl 2-(8-methoxy-2-dibenzofuryl)-propylmethyl ether dibenzofuran with triphenylmethylphosphonium bro 2-(8-ethoxy-2-dibenzofuryl)-propylmethyl ether mide) is dissolved in 15 ml. of ethanol and hydroge 2-(8-fluoro-2-dibenzofuryl)-propylmethyl ether nated on 100 mg. of 5% Pd/C at 20 and under normal 2-(8-chloro-2-dibenzofuryl)-propylmethyl ether pressure until the hydrogen absorption is terminated. 2-(2-dibenzofuryl)-1-butylmethyl ether. 25 The reaction product is then filtered and concentrated d. 4.5 g. of 2-(2-dibenzofuryl)-propanol is dissolved by evaporation, yielding 2-(2-dibenzofuryl)propyl in 30 ml. of pyridine. At 0, a solution of 3.8 g. of p methyl ether. toluenesulfonyl chloride in 10 ml. of pyridine is gradu Analogously, by hydrogenating ally added to the reaction mixture, the latter is stirred 2-(2-dibenzofuryl)-2-propen-1-ol for 3 hours at 20, and worked up as usual, yielding 30 2-(2-dibenzofuryl)-2-buten-1-ol, 2-(2-dibenzofuryl)-propyl p-toluenesulfonate. the corresponding alcohols of Formula I (R = CHOH) Analogously, 2-(2-dibenzofuryl)-propyl methanesul are produced, and by the hydrogenation of fonate is obtained by reaction with methanesulfonyl 2-(2-dibenzofuryl)-1-ethoxy-2-propene chloride. 2-(2-dibenzofuryl)-1-methoxy-2-butene, e. The nitration of 2-(2-dibenzofuryl)-propyl acetate 35 the corresponding ethers of Formula I (R e CHOCH analogously to Example 33(f) yields 2-(8-nitro-2- or CH2 OCHs) are obtained. dibenzofuryl)propyl acetate which is saponified, analo gously to Example 33(b), to 2-(8-nitro-2- EXAMPLE 42 dibenzofuryl)-propanol. One gram of 1-methoxy-2-(2-dibenzofuryl)-1- The reduction of these substances analogously to Ex 40 propene (obtainable from 2-acetyldibenzofuran and ample 33(g) yields: methoxymethyltriphenylphosphonium chloride) is dis 2-(8-amino-2-dibenzofuryl)-propyl acetate or solved in 20 ml. of methanol and hydrogenated on 5% 2-(8-amino-2-dibenzofuryl)-propanol. Pd/C until the hydrogen absorption is ended. The cata From these compounds the following final products lyst is filtered off, and the reaction product is concen can be produced analogously to: 45 trated by evaporation, thus obtaining 2-(2-diben Example 33(n): 2-(8-hydroxy-2-dibenzofuryl)- zofuryl)-propylmethyl ether. propanol Example 33(q): 2-(8-methylamino-2-dibenzofuryl)- EXAMPLE 43 propanol a. 26.6 g. of 2-(2-dibenzofuryl)-acroleinethylene ace Example 33(r): 2-(8-acetamido-2-dibenzofuryl)- 50 tal (obtainable by oxidizing 2-(2-dibenzofuryl)-2- propanol propen-1-ol to the aldehyde and acetalization with eth 2-(8-propionamido-2-dibenzofuryl)-propanol ylene glycol) is hydrogenated in 200 ml. of absolute 2-(8-butyramido-2-dibenzofuryl)-propanol methanol with 7 g. of 5% Pd/C until the absorption of 2-(8-isobutyramido-2-dibenzofuryl)-propanol hydrogen is terminated. The reaction product is evapo Example 33(v): 2-(8-dimethylamino-2- 55 rated after removing the catalyst by filtration, thus ob dibenzofuryl)-propanol taining 2-(2-dibenzofuryl)-propanal ethylene acetal. 2-(8diethylamino-2-dibenzofuryl)-propanol. b. One gram of 2-(2-dibenzofuryl)-propanal ethylene Reduction of the aforementioned 2-(8-acylamino-2- acetal is heated for 30 minutes to 60 with 5 ml. of 10% dibenzofuryl)-propanols analogously to Example 33(t) 60 hydrochloric acid in 15 ml. of THF. After the usual results in: working-up operation, 2-(2-dibenzofuryl)-propanal is 2-(8-ethylamino-2-dibenzofuryl)-propanol obtained, m.p. 52-54. 2-(8-n-propylamino-2-dibenzofuryl)-propanol 2-(8-n-butylamino-2-dibenzofuryl)-propanol EXAMPLE 44 2-(8-isobutylamino-2-dibenzofuryl)-propanol. 65 7.6 g. of the ethyl ester of 2-chloro-2-(2-diben f. The oxidation of the aforementioned alcohols in zofuryl)propionic acid is dissolved in 70 ml. of absolute accordance with the method described in Example ether and gradually added dropwise to a suspension of 3(c) yields: 2.2g. of LiAlH4 in 100 ml. of ether. The mixture is re 3,897,453 77 78 fluxed for several hours; methanol is added thereto, b. 4.8 g. of 2-(2-dibenzofuryl)-propionic acid and 15 and the mixture is worked up as usual, thus obtaining g. of vinyl acetate are shaken with 0.15g. of mercury 2-(2-dibenzofuryl)-propanol, m.p. 48-50. acetate for 40 minutes. Then, the mixture is heated to the boiling point, 1 drop of H2SO4 is added thereto, the EXAMPLE 45 5 mixture is refluxed for 8 hours, and 200 mg. of sodium 18 ml. of a l-molar ether LiAlH4 solution is added to acetate is then added. The reaction mixture is concen a suspension of 10.7 g. of anhydrous AlCls in 50 ml. of trated by evaporation and worked up as usual, yielding absolute ether. Within one hour, a solution of 4.46 g. the vinyl ester of 2-(2-dibenzofuryl)-propionic acid. of 1-methyl-1-(2-dibenzofuryl)-ethylene oxide (obtain c. 1.5 g. of NaH is added to a solution of 4.8 g. of able by reacting 2-isopropenyldibenzofuran with N 10 2-(2-dibenzofuryl)-propionic acid in 100 ml. of abso bromosuccinimide in the aqueous phase to the corre lute THF. The mixture is agitated for 30 minutes at 25, sponding bromohydrin and splitting off HBr witih solu cooled off, and at 5° a solution of 3.6 g. of allyl bromide tion of sodium hydroxide) in 70 ml. of absolute ether in 25 ml. of absolute THF is added thereto and the mix is added dropwise to the reaction mixture within 1 ture is again stirred for 24 hours at 25. After evapora hour. The mixture is refluxed for 2 hours, hydrolyzed 15 tion and working up as usual, the allyl ester of by adding 10 ml. of water and 100 ml. of 10% sulfuric 2-(2-dibenzofuryl)-propionic acid is obtained. acid, and worked up as usual, yielding 2-(2- dibenzofuryl)-propanol, m.p. 48-50. EXAMPLE 50 One gram of the monoethyl ester of 2-(2- EXAMPLE 46 20 dibenzofuryl)-2-methylmalonic acid (obtainable by Under agitation, 25.65 g. of 2-(2-dibenzofuryl)- partial saponification of the diethyl ester with 1 mole acryloyl chloride (obtainable from the acid with SOCl, of KOH in ethanol, and acidification) is gradually in benzene) is added dropwise at 20 to a suspension of heated under 18 torr (mm. Hg) to 100°-130 until the 4 g. of LiAlH4 in 300 ml. of ether. The mixture is stirred 25 evolution of CO, has ceased, thus obtaining the ethyl for 3 hours at 20; methanol is added thereto, and the ester of 2-(2-dibenzofuryl)-propionic acid, b.p. reaction mixture is worked up as usual, thus producing 173-177/0.2 mm. 2-(2-dibenzofuryl)-propanol, m.p. 48-50. EXAMPLE 51 EXAMPLE 47 30 One gram of the ethyl ester of 2-(2-dibenzofuryl)-2- 24.2 g. of 2-(2-dibenzofuryl)-propane-1,2-diol (ob methylbutan-3-onic acid (obtainable by condensation tainable by the reduction of the ethyl ester of 2 of the ethyl ester of 2-dibenzofurylacetic acid with hydroxy-2-(2-dibenzofuryl)-propionic acid with ethyl acetate to the ethyl ester of 2-(2-dibenzofuryl)- LiAlH4) is hydrogenated in 500 ml. of methanol on 2 butan-3-onic methylation and emethylation with g. of CuCrO catalyst at 100 atmospheres and 140. 35 methyl iodide) is agitated with 15 ml. of 50% KOH for The reaction mixture is cooled, filtered, and evapo 45 minutes at 90 under N. The reaction mixture is rated, yielding 2-(2-dibenzofuryl)-propanol, m.p. cooled, water and HCl are added to pH 10, the mixture 48°-50°. is washed with ether, and worked up as usual, thus pro ducing 2-(2-dibenzofuryl)-propionic acid, m.p. EXAMPLE 48 40 1399-140°. 20 g. of the diethyl ester of 2-(2-dibenzofuryl)-2- methylmalonic acid (obtainable by reacting the ethyl EXAMPLE 52 ester of 2-dibenzofurylacetic acid with the diethyl ester 2.68 g. of 2-oxo-3-(2-dibenzofuryl)-butyric acid is of oxalic acid to the diethyl ester of 2-(2-dibenzofuryl)- heated in 10 ml. of aniline to 140 until the liberation 3-oxosuccinic acid, decarbonylation to the diethyl ester 45 of CO2 has ended. After cooling, the reaction mixture of 2-dibenzofurylmalonic acid, and methylation with is combined with 30 ml. of water, acidified with hydro methyl iodide) is refluxed for 3 hours with 300 ml. of chloric acid, and heated on a water bath for 10 minutes 10% ethanolic KOH solution. The ethanol is distilled in order to split the anil which was formed as an inter off, the residue is introduced into 600 ml. of water and mediate. The reaction mixture is then extracted with acidified to pH 4 with hydrochloric acid. The thus 50 ether and worked up as usual, yielding 2-(2- precipitated 2-(2-dibenzofuryl)-2-methylmalonic acid dibenzofuryl)-propanal, m.p. 52-54. is filtered off, dried, dissolved in acetone, and the solu tion is filtered and evaporated. The residue is heated to EXAMPLE 53 100-120/20 mm. until the end of the liberation of a. A mixture of 27.5 g. of 2-(1-bromoethyl)- CO, thus obtaining 2-(2-dibenzofuryl)-propionic acid, 55 dibenzofuran, 400 ml. of tert.-butanol, 23 g. of potas m.p. 139-140°. sium tert-butylate, and 100 g. of nickel carbonyl is heated for 24 hours to 50 and then evaporated to dry EXAMPLE 49 ness. To this mixture is added 400 ml. of 6N hydrochlo a. A solution of crude 2-(2-dibenzofuryl)-2- ric acid, the mixture is refluxed for 12 hours, and methylmalonic acid (obtainable by the saponification 60 worked up as usual, thus obtaining 2-(2-dibenzofuryl)- of 20 g. of the diethyl ester of 2-(2-dibenzofuryl)-2- propionic acid, m.p. 139-140'. methylmalonic acid with ethanolic KOH under N2) in 24 g. of 2-(2-dibenzofuryl)-propionic acid is heated 200 ml. of acetic acid and 200 ml. of 15% HCl is re for 1.5 hours to 170 with 75 g. of acethydroxamic acid fluxed under a nitrogen atmosphere until the evolution 65 in 300 ml. of polyphosphoric acid. Thereafter, the reac of CO has ceased. After cooling the reaction mixture tion mixture is poured into water and worked up as and working up as usual, 2-(2-dibenzofuryl)-propionic usual, producing 2-(8-acetamido-2-dibenzofuryl)- acid is obtained, m.p. 139-140'. propionic acid. 3,897,453 79 80 c. One gram of 2-(8-acetamido-2-dibenzofuryl)- worked up as usual, thus obtaining 2-(2-dibenzofuryl)- propionic acid is refluxed with 10 ml. of 25% hydro propionic acid, m.p. 139-140°. chloric acid for 1 hour under agitation. A portion of the b. A solution of 12 g of 2-(2-dibenzofuryl-propionic hydrochloric acid is distilled off, the mixture is neutral acid in 80 ml. of absolute THF is added dropwise to a ized with sodium hydroxide solution and worked up as mixture of 2.84 g. of LiAlH4 in 100 ml. of absolute usual, yoekding 2-(8-amino-2-dibenzofuryl)propionic THF. The mixture is refluxed for 8 hours, 10 ml. of acid. water in 15 ml, of THF and 20 ml, of 25% sodium hy droxide solution are added thereto, the mixture is de EXAMPLE 54 canted, and the residue is wahsed with ether. After dry With 20 minutes, 4 ml. of formic acid is added to a 10 ing, filtration, and evaporation of the combined organic solution of 1.94 g. of 2-vinyldibenzofuran (obtainable phases, 2-(2-dibenzofuryl)-propanol is produced, m.p. by splitting off water from 2-(1-hydroxyethyl)- 48°-50°. dibenzofuran with polyphosphoric acid) in a mixture of Analogously, the corresponding alcohols (I, R 12 ml. of sulfuric acid and 8 ml. of trifluoroacetic acid. CHOH) are obrained by reduction of the correspond After another 20 minutes, the mixture is poured into 15 ing acids (I, R = COOH) with LiAlH4. water, thus obtaining 2-(2-dibenzofuryl)propionic acid, m.p. 139-140°. EXAMPLE 59 25.3 g of 3-(2-dibenzofuryl)-2-butanone oxime (ob EXAMPLE 55 tainable by reacting 2-(2-dibenzofuryl-propionitrile 21.2 g of 2-(1-hydroxyethyl)-dibenzofuran (or 19.4 20 with CHMg to 3-(2-dibenzofuryl)-2-butanone and ox g. of 2-vinyldibenzofuran) is dissolved in 100 ml. of 3% imation) is introduced into 600 g. of polyphosphoric ethanolic hydrochloric acid; 0.2 g of (C6H5)3P2PdCl2 acid. The reaction mixture is heated under agitation to is added thereto and the mixture is heated under CO at 130' for 25 minutes, poured into water, and worked up 500 atmospheres in an autoclave for 5 hours to 85. 25 as usual. Chromatograpy on silica gel yields 2-(2-diben After cooling and working up the reaction mixture as zofuryl)-propionic acid N-methylamide. usual, the ethyl ester of 2-(2-dibenzofuryl)propionic acid is obtained, b.p. 173-177/0.2 mm. EXAMPLE 60 EXAMPLE 56 A solution of 23.8 g. of 3-(2-dibenzofuryl)-2- 30 butanone and 5 g. of HNs in 200 ml. of benzene is aded A mixture of 19.4 g. of 2-vinyldibenzofuran (or 21.2 dropwise under agitation and cooling to a mixture of 25 g. of 2-(1-hydroxyethyl)-dibenzofuran), 20 ml. of ml. of H2SO4 and 50 ml. of benzene. Thereafter, the nickel carbonyl, 20 ml. of concentrated hydrochloric mixture is agitated for 30 minutes, crushed ice is added acid, and 200 ml. of acetone is heated for 12 hours to thereto, and the mixture is worked up as usual. Chro 50 under irradiation by a mercury vapor lamp. The 35 matography on silica gel yields 2-(2-dibenzofuryl)pro mixture is evaporated to dryness, the residue is ex pionic acid N-methylamide. tracted with ether and worked up as usual, and the product is 2-(2-dibenzofuryl)-propionic acid, m.p. EXAMPLE 61 139-140°. 22.4 g of 2-(2-dibenzofuryl)-2-methylethylene oxide 40 EXAMPLE 57 (Obtainable by reacting 2-isopropenyldibenzofuran a. A mixture of 19.4 g of 2-vinyldibenzofuran and 15 with m-chloroperbenzoic acid) is heated with 100 ml. g. of dicobalt octacarbonyl in 250 ml. of ether is shaken of THF and 300 ml. of 10% hydrochloric acid for 1 in an autoclave with a mixture of carbon monoxide and hour to 50. After the usual workingup operation, 2-(2- hydrogen (1:1) at 140 atmospheres and 120 for 8 45 dibenzofuryl)-propanal is produced, m.p. 52-54. hours. After cooling, filtration, and evaporation, 2-(2- EXAMPLE 62 dibenzofuryl)-propanal is obtained, m.p. 52-54. b. 11.2 g of 2-(2-dibenzofuryl)-propanal is dissolved a. 22.4 g of 2-(2-dibenzofuryl)-2-methylethylene in 50 ml. of ethanol and added dropwise to a solution oxide is heated with 50 ml. of THF and 100 ml. of satu of 3 g of NaBH4 in 75 ml. of ethanol. The mixture is 50 rated aqueous NaHSO solution for 1 hour to 100 agitated for 2 hours at 20 and worked up as usual, ob under agitation. Water is then added to the mixture, the taining 2-(2-dibenzofuryl)propanol, m.p. 48-50. latter is filtered, and the bisulfite compound of 2-(2- c. A solution of 2.24 g. of 2-(2-dibenzofuryl)- dibenzofuryl)-propanal is thus obtained. propanal in 20 ml. of anhydrous THF is treated at -75 b. 8 g. of the sodium bisulfite addition product of with a solution of 0.6 g. of LiAlH4 in 20 ml. of anhy 55 2-(2-dibenzofuryl)-propanal is suspended in 150 ml. of drous THF. The mixture is allowed to warm up to 20, 1N hydrochloric acid and heated on a water bath for 30 decomposed with ethyl acetate, and worked up as minutes. After working up the mixture as usual, 2-(2- usual, thus producing 2-(2-dibenzofuryl)-propanol, dibenzofuryl)-propanal is obtained, m.p. 52°-54°. Analogously, the remaining sodium bisulfite addition m.p. 48-50. 60 products of Formula I (R = CHOH-SONa) can be EXAMPLE 58 converted into the free aldehydes (I, R = CHO). a. A mixture of 25.85g. of 2-(2-chloropropionyl)- c. 5.5 g. of 2-(2-dibenzofuryl)-propanal is heated on dibenzofuran (obtainable by reacting dibenzofuran with a water bath for 1.5 hours in 20 ml. of ethanol together 2-chloropropionyl chloride in the presence of AlCla), 65 with 1.75 g. of hydroxylamine hydrochloride and 2.1 g. 8 g. of extremely finely pulverized NaOH, and 500 ml. of anhydrous sodium acetate. After removing the etha of toluene is refluxed under agitation for 30 hours. The nol and working up the mixture as usual, 2-(2- mixture is then cooled, water is added, and the mixture dibenzofuryl)-propanal oxime is obtained. 3,897,453 81 82 2-(8-ethyl-2-dibenzofuryl)-propanal EXAMPLE 63 2-(8-n-propyl-2-dibenzofuryl)-propanal 2.5 g. of sodium is dissolved in 75 ml, of absolute eth 2-(8-isopropyl-2-dibenzofuryl)-propanal anol; under agitation and under a nitrogem atmo 2-(8-n-butyl-2-dibenzofuryl)-propanal sphere, at 20-25, 29.6 g of the ethyl ester of 2,3- 2-(8-isobutyl-2-dibenzofuryl)-propanal epoxy-3-(2-dibenzofuryl)-butyric acid (obtainable by 2-(8-sec.-butyl-2-dibenzofuryl)-propanal reacting 2-acetyldibenzofuran with ethyl chlorofor 2-(8-tert-butyl-2-dibenzofuryl)-propanal mate in tert.-butanol in the presence of potassium tert.- 2-(8-methoxy-2-dibenzofuryl)-propanal butylate at 10-15) is gradually added thereto. The re 2-(8-ethoxy-2-dibenzofuryl)-propanal action mixture is cooled in an ice bath. After adding 2 10 2-(8-n-propoxy-2-dibenzofuryl)-propanal ml. of water dropwise to the mixture, the latter is al 2-(8-isopropoxy-2-dibenzofuryl)-propanal lowed to stand overnight, then filtered, washed with 2-(8-n-butoxy-2-dibenzofuryl)-propanal ether dissolved in 60 ml. of water and 10 ml. of concen 2-(8-isobutoxy-2-dibenzofuryl)-propanal trated HCl, and gently heated on a steam bath until the 2-(8-sec.-butoxy-2-dibenzofuryl)-propanal evolution of CO2 is terminated. The usual working-up 15 2-(8-tert-butoxy-2-dibenzofuryl)-propanal steps yield 2-(2-dibenzofuryl)-propanal, m.p. 52-54. 2-(8-fluoro-2-dibenzofuryl)-propanal 2-(8-chloro-2-dibenzofuryl)-propanal EXAMPLE 64 2-(8-bromo-2-dibenzofuryl)-propanal a. 18.2 g of 2-(2-dibenzofuryl)-propane-1,2-diol 2-(8-iodo-2-dibenzofuryl)-propanal (m.p. 95-97; obtainable by refluxing the ethyl ester 20 2-(8-hydroxy-2-dibenzofuryl)-propanal of 2-hydroxy-2-(2-dibenzofuryl)-propionic acid for 2 2-(7-fluoro-2-dibenzofuryl)-propanal hours with LiAlH4 in absolute THF and subsequent de 2-(7-chloro-2-dibenzofuryl)-propanal composition with sodium hydroxide solution) is dis 2-(2-dibenzofuryl)-butanal solved in 400 ml. of toluene and refluxed with the use 2-(2-dibenzofuryl)-pentanal of a water trap for 30 minutes in the presence of 0.9 g. 25 2-(2-dibenzofuryl)-3-methylbutanal of p-toluenesulfonic acid. The mixture is then cooled, 2-(2-dibenzofuryl)-hexanal washed with sodium bicarbonate solution, dried, and 2-(2-dibenzofuryl)-3-methylpentanal. evaporated, thus obtaining 2-(2-dibenzofuryl)- b. 4.48 g. of 2-(2-dibenzofuryl)-propanal is refluxed propanal, m.p. 52-54. with the use of a water trap with 100 ml. of absolute In place of p-toluenesulfonic acid, it is also possible 30 benzene, 2.5 g, of ethylene glycol, and 0.2 g of p-tol to employ benzenesulfonic acid, sulfuric acid, or phos uenesulfonic acid for 6 hours. After cooling the ben phoric acid. zene phase is washed neutral with 1N sodium hydrox Analogously, by using the following starting com ide solution and water, dried, and evaporated. The resi pounds: due is chromatographed on silica gel with benzene/pe 2-(2-dibenzothienyl)-propane-1,2-diol 35 troleum ether 9:1. The first fractions are concentrated 2-(8-methyl-2-dibenzofuryl)-propane-1,2-diol by evaporation. The thus-obtained product is 2-(2- 2-(8-ethyl-2-dibenzofuryl)-propane-1,2-diol dibenzofuryl)-propanal ethylene acetal. 2-(8-n-propyl-2-dibenzofuryl)-propane-1,2-diol Analogously, the corresponding ethylene acetals are 2-(8-isopropyl-2-dibenzofuryl)-propane-1,2-diol produced from the corresponding aldehydes, e.g. the 2-(8-n-butyl-2-dibenzofuryl)-propane-1,2-diol 40 above-mentioned aldehydes, by acetalization with eth 2-(8-isobutyl-2-dibenzofuryl)-propane-1,2-diol ylene glycol, for example: 2-(8-sec.-butyl-2-dibenzofuryl)-propane-1,2-diol 2-(2-dibenzothienyl)-propanal ethylene acetal, 2-(8-tert-butyl-2-dibenzofuryl)-propane-1,2-diol 2-(8-methyl-2-dibenzofuryl)-propanal ethylene ace 2-(8-methoxy-2-dibenzofuryl)-propane-1,2-diol tal, etc. 2-(8-ethoxy-2-dibenzofuryl)-propane-1,2-diol 45 c. 8.96 g. of 2-(2-dibenzofuryl)-propanal is dissolved 2-(8-n-propoxy-2-dibenzofuryl)-propane-1,2-diol in a mixture of 150 ml. of absolute benzene and 150 ml. 2-(8-isopropoxy-2-dibenzofuryl)-propane-1,2-diol of methanol together with 500 mg. of p-toluenesulfonic 2-(8-n-butoxy-2-dibenzofuryl)-propane-1,2-diol acid and refluxed with the use of a water trap for 10 2-(8-isobutoxy-2-dibenzofuryl)-propane-1,2-diol hours, thus separating a mixture of water/methanol? 2-(8-sec.-butoxy-2-dibenzofuryl)-propane-1,2-diol 50 benzene. The amount of benzene/methanol withdrawn 2-(8-tert-butoxy-2-dibenzofuryl)-propane-1,2-diol from the water trap is replaced by equal amounts of an 2-(8-fluoro-2-dibenzofuryl)-propane-1,2-diol absolute solvent mixture. The usual working-up opera 2-(8-chloro-2-dibenzofuryl)-propane-1,2-diol tion yields 2-(2-dibenzofuryl)-propanal dimethylacetal. 2-(8-bromo-2-dibenzofuryl)-propane-1,2-diol Analogously, the corresponding dimethylacetals are 2-(8-iodo-2-dibenzofuryl)-propane-1,2-diol 55 obtained from the corresponding aldehydes, e.g. the 2-(8-hydroxy-2-dibenzofuryl)-propane-1,2-diol aldehydes mentioned above, by acetalization with 2-(7-fluoro-2-dibenzofuryl)-propane-1,2-diol methanol, for example: 2-(7-chloro-2-dibenzofuryl)-propane-1,2-diol 2-(8-methyl-2-dibenzofuryl)-propanal dimethylac 2-(2-dibenzofuryl)-butane-1,2-diol etal, etc. 2-(2-dibenzofuryl)-pentane-1,2-diol 60 d. 13.5g. of 2-(2-dibenzofuryl)-propanal dimethylac 2-(2-dibenzofuryl)-2-methylbutane-1,2-diol etal is refluxed together with 6.2 g of ethylene glycol 2-(2-dibenzofuryl)-hexane-1,2-diol and 1.g. of p-toluenesulfonic acid in 150 ml. of absolute 2-(2-dibenzofuryl)-4-methylpentane-1,2-diol, the toluene. During this step, a portion of the toluene is dis following final products are obtained by treatment 65 tilled off together with the methanol produced during with p-toluenesulfonic acid: the trans-acetalization; the amount of toluene removed 2-(2-dibenzothienyl)-propanal by distillation is replaced by absolute toluene. As soon 2-(8-methyl-2-dibenzofuryl)-propanal as the distilled-off toluene contains no methanol any 3,897,453 83 84 more, the mixture is worked up as usual, thus produc Analogously, the corresponding aldehydes are pro ing 2-(2-dibenzofuryl)-propanal ethylene acetal. duced by the acid treatment of: e. 11.2 g of 2-(2-dibenzofuryl)-propanal is refluxed 1-ethoxy-2-(8-methyl-2-dibenzofuryl)-propan-2-ol in 200 ml. of acetone dimethyl ketal with 2g. of p-tol 1-ethoxy-2-(8-ethyl-2-dibenzofuryl)-propan-2-ol uenesulfonic acid for 8 hours; the thus-liberated ace 5 1-ethoxy-2-(8-methoxy-2-dibenzofuryl)-propan-2-ol tone is removed from the reaction mixture by way of a 1-ethoxy-2-(8-hydroxy-2-dibenzofuryl)-propan-2-ol column. After the usual working-up operation, 2-(2- 1-ethoxy-2-(2-dibenzofuryl)-butan-2-ol. dibenzofuryl)-propanal dimethylacetal is obtained. In place of the ethoxy compounds, other lower alkyl f. 22.4 g. of 2-(2-dibenzofuryl)-propanal is refluxed ethers can also be employed, such as the methyl ethers; 10 for example, 1-methoxy-2-(2-dibenzofuryl)-propan-2- together with 25 g. of triethyl orthoformate, 1 g of am ol can be used as the starting compound. b. 22.4 g. of monium nitrate, and 10 ml. of absolute ethanol for 20 2-(2-dibenzofuryl)-propanal is heated on a water bath minutes. The reaction mixture is cooled, filtered, di for 1 hour with 50 ml. of acetic anhydride and 4 g. of luted with ether, washed with dilute aqueous ammonia anhydrous sodium acetate, and then allowed to stand solution, dried, and evaporated, thus obtaining 2-(2- 15 for 24 hours at 25. The reaction mixture is then mixed dibenzofuryl)-propanal diethylacetal. with benzene, washed twice with water, dried, and the Analogously, the corresponding diethylacetals are residue is evaporated twice with respectively 150 ml. of obtained from the corresponding aldehydes, e.g. those absolute benzene and under reduced pressure, in order mentioned above, by reaction with triethyl orthofor to remove the excess acetic anhydride. From the resi mate, for example: 20 due, 2-(2-dibenzofuryl)-propanal diacetate is obtained. 2-(8-methyl-2-dibenzofuryl)-propanal diethylacetal, Analogously, the corresponding diacetates are ob etc. g. 22.4 g. of 2-(2-dibenzofuryl)-propanal is refluxed tained by the acylation of the corresponding aldehydes, with a water trap in 300 ml. of absolute benzene to e.g. those set forth above. gether with 14 g. of 1,2-ethanedithiol and 2 g. of p-tol 25 EXAMPLE 67 uenesulfonic acid for 12 hours. After cooling and work a. 2.68 g. of 1-ethoxy-2-(2-dibenzofuryl)-propan-2-ol ing up the mixture as usual, 2-(2-dibenzofuryl)- is refluxed for 1.5 hours after being dissolved in 30 ml. propanal ethylenethioacetal is produced. of absolute toluene and after the addition of 100 mg. In an aldehydes, manner, the corresponding thioacet of p-toluene-sulfonic acid. The mixture is then cooled, als are obtained from the corresponding aldehyddes, 30 washed with aqueous NaHCOs solution, dried, evapo e.g. those set forth above, by reaction with 1,2- rated, and the product thus obtained is 1-ethoxy-2-(2- ethanedithiol, 1,3-propanedithiol, methylmercaptan, dibenzofuryl)-propene (the ethylenol ether of 2-(2- or ethylmercaptan, for example: dibenzofuryl)-propanal). 2-(2-dibenzofuryl)-propanal 1,3-propylenethioacetal b. One gram of 1-ethoxy-2-(2-dibenzofuryl)-propene 2-(2-dibenzofuryl)-propanal dimethylmercaptal, 35 is refluxed for 2 hours with 10 ml. of 10% aqueous hy 2-(2-dibenzofuryl)-propanal diethylmercaptal, etc. drochloric acid and 10 of ethanol. After working up the h. 22.4 g. of 2-(2-dibenzofuryl)-propanal is shaken in mixture as usual, 2-(2-dibenzofuryl)-propanal is ob 200 ml. of 5% aqueous sulfurous acid for 30 minutes. tained, m.p. 52-54. Thereafter, the solution is neutralized by adding 240 ml. of IN NaOH solution, and the thus-formed bisulfite 40 EXAMPLE 68 compound is precipitated by the addition of a small 2.98 g. of 1,2-diethoxy-2-(2-dibenzofuryl)-propane amount of ethanol. The mixture is allowed to stand (obtainable by reacting 2-dibenzofurylmagnesium bro overnight, thus obtaining the sodium bisulfite com mide with ethoxyacetone diethylacetal) is refluxed for pound of 2-(2-dibenzofuryl)-propanal. 3 hours in 50 ml. of THF and 10 ml. of 15% HSO. The Analogously, the bisulfite compounds of the corre 45 reaction mixture is worked up as usual, yielding 2-(2- sponding aldehydes, e.g. those mentioned above, are dibenzofuryl)-propanal, m.p. 52-54. produced. EXAMPLE 69 EXAMPLE 65 8 g. of 1-ethoxy-2-bromo-2-(2-dibenzofuryl)- 24.2 g of 2-(2-dibenzofuryl)-propane-1,2-diol is dis 50 propane (obtainable by reacting dibenzofuran with solved in 200 ml. of formic acid and agitated for 30 ethoxyacetyl chloride in the presence of AlCls, reacting minutes at 25. The formic acid is distilled off, the resi the thus-obtained 2-ethoxyacetyldibenzofuran with due is mixed with 300 ml. of water and 30 ml. of con methylmagnesium iodide, and reacting the thuspro centrated H2SO4, agitated for 1 hour at 25, and duced 1-ethoxy-2-(2-dibenzofuryl)-propan-2-ol with worked up as usual, yielding 2-(2-dibenzofuryl)- 55 PBr3 in ether) is dissolved in 100 ml. of absolute ben propanal, m.p. 52-54. Zene and mixed dropwise with 12.4 g. of 1,5-diazabicy clo3,40) nonene-(5) at 0-5. Thereafter, the mixture EXAMPLE 66 is heated for 30 minutes to 60, poured on ice, and (a) 26.8 g. of crude 1-ethoxy-2-(2-dibenzofuryl)- worked up as usual, thus producing 1-ethoxy-2-(2- propan-2-ol (obtainable by reacting 2 60 dibenzofuryl)-propene. acetyldibenzofuran with ethoxymethylmagnesium chloride in THF and subsequent hydrolysis) is refluxed EXAMPLE 70 for 1 hour with 400 ml. of formic acid. After cooling, a. A solution of 0.1 mole of phenyllithium in 200 ml. the mixture is combined with 250 ml. of 15% sulfuric 65 of absolute ether is gradually added to a suspension of acid, agitated for 3 hours at 50, and worked up as 34.25 g. of methoxymethyltriphenylphosphonium chlo usual, thus obtaining 2-(2-dibenzofuryl)-propanal, m.p. ride in 500 ml. of absolute ether. After 15 minutes, a 52°-54°, Solution of 21 g. of 2-acetyldibenzofuran in 240 ml. of 3,897,453 85 86 absolute ether is added dropwise under stirring to the then, the mixture is refluxed for 12 hours and cooled. reaction mixture. The latter is agitated for 2 hours at After the usual working-up operation, 7-fluoro-2- 25, filtered off, the ether solution is washed with wa dibenzofurylthioacetomorpholide is produced, m.p. ter, dried, and evaporated, thus obtaining 1-methoxy-2- 150-154. (2-dibenzofuryl)-propene. 5 Analogously, with the use of the following starting Analogously, 1-p-tolyloxy-2-(2-dibenzofuryl)- compounds: propene is obtained with triphenylphosphine p 1-, 3-, 4-, 6-, 3-, or 9-fluoro-2-acetyldibenzofuran, tolyloxymethylene (obtainable in situ from triphenyl 1-, 3-, 4-, 6-, 7-, 3-, or 9-chloro-2-acetyldibenzofuran, phosphine and p-tolyloxymethyl chloride). 1-, 3-, 4-, 6-, 7-, 3-, or 9-bromo-2- In an analogous manner, using the following starting 10 acetyldibenzofuran, compounds: 1-, 3-, 4-, 6-, 7-, 8-, or 9-iodo-2-acetyldibenzofuran, 2-acetyldibenzothiophene 1-, 31, 4-, 6-, 7-, 8-, or 9-methyl-2- 2-acetyl-8-methyldibenzofuran acetyldibenzofuran, 2-acetyl-8-ethyldibenzofuran 1-, 3-, 4-, 6-, 7-, 8-, or 9-ethyl-2-acetyldibenzofuran, 2-acetyl-8-methoxydibenzofuran 15 1-, 3-, 4-, 6-, 7-, 8-, or 9-methoxy-2- 2-propionyldibenzofuran acetylidibenzofuran, 2-butyryldibenzofuran 1-, 3-, 4-, 6-, 7-, 8-, or 9-hydroxy-2- the following final products are obtained with triphen acetylidibenzofuran, ylphosphine methyxomethylene: 1-, 3-, 4-, 6-, 7-, 8-, or 9-amino-2-acetyldibenzofuran, 1-methoxy-2-(2-dibenzothienyl)-propene 20 1-, 3-, 4-, 6-, 7-, 8-, or 9-trifluoromethyl-2- i-methoxy-2-(8-methyl-2-dibenzofuryl)-propene acetyldibenzofuran, i-methoxy-2-(8-ethyl-2-dibenzofuryl)-propene the following final products are obtained with mor 1-methoxy-2-(8-methoxy-2-dibenzofuryl)-propene pholine/sulfur: 1-methoxy-2-(2-dibenzofuryl)-1-butene 1-fluoro-2-dibenzofurylthioacetomorpholide l-methoxy-2-(2-dibenzofuryl)-1-pentene. 25 3-fluoro-2-dibenzofurylthioacetomorpholide b. 2.38 g. of 1-methoxy-2-(2-dibenzofuryl)-propene 4-fluoro-2-dibenzofurylthioacetomorpholide is heated in 30 ml. of acetic acid and 10 ml. of 10% 6-fluoro-2-dibenzofurylthioacetomorpholide HSO4 for 10 hours to 80°. The usual working-up oper 8-fluoro-2-dibenzofurylthioacetomorpholide ation yields 2-(2-dibenzofuryl)-propanol, m.p. 52-54. 9-fluoro-2-dibenzofurylthioacetomorpholide 30 1-chloro-2-dibenzofurylthioacetomorpholide EXAMPLE 71 3-chloro-2-dibenzofurylthioacetomorpholide 2.25 g. of 2-(2-dibenzofuryl)-propylamine (obtain 4-chloro-2-dibenzofurylthioacetomorpholide able from 2-(2-dibenzofuryl)-propionamide with 6-chloro-2-dibenzofurylthioacetomorpholide LiAlH4) is dissolved in 50 ml. of 15% aqueous acetic 7-chloro-2-dibenzofurylthioacetomorpholide acid and mixed, under ice cooling, with a solution of 1 35 8-chloro-2-dibenzofurylthioacetomorpholide g of NaNO, in 5 ml. of water. The mixture is heated for 9-chloro-2-dibenzofurylthioacetomorpholide 1 hour to 80, and worked up as usual. After purifica 1-bromo-2-dibenzofurylthioacetomorpholide tion by chromatography on silica gel, 2-(2- 3-bromo-2-dibenzofurylthioacetomorpholide dibenzofuryl)-propanol is produced, m.p. 48-50. 4-bromo-2-dibenzofurylthioacetomorpholide 40 6-bromo-2-dibenzofurylthioacetomorpholide EXAMPLE 72 7-bromo-2-dibenzofurylthioacetomorpholide 2.89 g. of 1-bromo-(2-dibenzofuryl)-propane is dis 8-bromo-2-dibenzofurylthioacetomorpholide solved in 20 ml. of DMF, mixed with 3 g. of anhydrous 9-bromo-2-dibenzofurylthioacetomorpholide potassium acetate, and agitated for 3 hours at 60°. The 1-iodo-2-dibenzofurylthioacetomorpholide mixture is worked up as usual, thus obtaining 2-(2- 45 3-iodo-2-dibenzofurylthioacetomorpholide dibenzofuryl)-propyl acetate. In addition, a small 4-iodo-2-dibenzofurylthioacetomorpholide amount of 2-(2-dibenzofuryl)-propene is produced. 6-iodo-2-dibenzofurylthioacetomorpholide 7-iodo-2-dibenzofurylthioacetomorpholide EXAMPLE 73 8-iodo-2-dibenzofurylthioacetomorpholide a. A solution of 2.89 g. of 1-bromo-2-(2- 50 9-iodo-2-dibenzofurylthioacetomorpholide dibenzofuryl)-propane in 10 ml. of DMF is added drop 1-methyl-2-dibenzofurylthioacetomorpholide wise to a suspension of 0.4 g of NaH and 2 g of benzyl 3-methyl-2-dibenzofurylthioacetomorpholide alcohol in 5 ml. of DMF at 0 under agitation. The mix 4-methyl-2-dibenzofurylthioacetomorpholide ture is stirred for 24 hours at 20 and then worked up 6-methyl-2-dibenzofurylthioacetomorpholide as usual, yielding 2-(2-dibenzofuryl)-propylbenzyl 55 7-methyl-2-dibenzofurylthioacetomorpholide ether. 8-methyl-2-dibenzofurylthioacetomorpholide b. 2 g. of 2-(2-dibenzofuryl)-propylbenzyl ether is 9-methyl-2-dibenzofurylthioacetomorpholide dissolved in 25 ml. of methanol and hydrogenated on 1-ethyl-2-dibenzofurylthioacetomorpholide 0.2 g of 5% Pd/C catalyst at 20 until the hydrogen ab 3-ethyl-2-dibenzofurylthioacetomorpholide sorption has ceased. The reaction mixture is filtered 60 4-ethyl-2-dibenzofurylthioacetomorpholide off, evaporated, and the product thus obtained is 2-(2- 6-ethyl-2-dibenzofurylthioacetomorpholide dibenzofuryl-propanol, m.p. 48-50. 7-ethyl-2-dibenzofurylthioacetomorpholide 8-ethyl-2-dibenzofurylthioacetomorpholide EXAMPLE 74 9-ethyl-2-dibenzofurylthioacetomorpholide a. A mixture of 22.8 g. of 2-acetyl-7- 65 1-methoxy-2-dibenzofurylthioacetomorpholide fluorodibenzofuran, 5 g. of sulfur, and 13.g. of morpho 3-methoxy-2-dibenzofurylthioacetomorpholide line is heated until the evolution of H2S has ended; 4-methoxy-2-dibenzofurylthioacetomorpholide 3,897,453 87 88 6-methoxy-2-dibenzofurylthioacetomorpholide 1-methyl-4-dibenzofurylacetic acid 7-methoxy-2-dibenzofurylthioacetomorpholide 3-methyl-2-dibenzofurylacetic acid 8-methoxy-2-dibenzofurylthioacetomorpholide 4-methyl-2-dibenzofurylacetic acid 9-methoxy-2-dibenzofurylthioacetomorpholide 6-methyl-2-dibenzofurylacetic acid 1-hydroxy-2-dibenzofurylthioacetomorpholide 7-methyl-2-dibenzofurylacetic acid 3-hydroxy-2-dibenzofurylthioacetomorpholide 8-methyl-2-dibenzofurylacetic acid 4-hydroxy-2-dibenzofurylthioacetomorpholide 9-methyl-2-dibenzofurylacetic acid 6-hydroxy-2-dibenzofurylthioacetomorpholide 1-ethyl-2-dibenzofurylacetic acid 7-hydroxy-2-dibenzofurylthioacetomorpholide 3-ethyl-2-dibenzofurylacetic acid 8-hydroxy-2-dibenzofurylthioacetomorpholide 10 4-ethyl-2-dibenzofurylacetic acid 9-hydroxy-2-dibenzofurylthioacetomorpholide 6-ethyl-2-dibenzofurylacetic acid 1-amino-2-dibenzofurylthioacetomorpholide 7-ethyl-2-dibenzofurylacetic acid 3-amino-2-dibenzofurylthioacetomorpholide 8-ethyl-2-dibenzofurylacetic acid 4-amino-2-dibenzofurylthioacetomorpholide 9-ethyl-2-dibenzofurylacetic acid 6-amino-2-dibenzofurylthioacetomorpholide 15 1-methoxy-2-dibenzofurylacetic acid 7-amino-2-dibenzofurylthioacetomorpholide 3-methoxy-2-dibenzofurylacetic acid 8-amino-2-dibenzofurylthioacetomorpholide 4-methoxy-2-dibenzofurylacetic acid 9-amino-2-dibenzofurylthioacetomorpholide 6-methoxy-2-dibenzofurylacetic acid 1-trifluoromethyl-2-dibenzofurylthioacetomorpho 7-methoxy-2-dibenzofurylacetic acid lide 20 8-methoxy-2-dibenzofurylacetic acid 3-trifluoromethyl-2-dibenzofurylthioacetomorpho 9-methoxy-2-dibenzofurylacetic acid lide 1-hydroxy-2-dibenzofurylacetic acid 4-trifluoromethyl-2-dibenzofurylthioacetomorpho 3-hydroxy-2-dibenzofurylacetic acid lide 4-hydroxy-2-dibenzofurylacetic acid 6-trifluoromethyl-2-dibenzofurylthioacetomorpho- 25 6-hydroxy-2-dibenzofurylacetic acid lide 7-hydroxy-2-dibenzofurylacetic acid 7-trifluoromethyl-2-dibenzofurylthioacetomorpho 8-hydroxy-2-dibenzofurylacetic acid lide 9-hydroxy-2-dibenzofurylacetic acid 8-trifluoromethyl-2-dibenzofurylthioacetomorpho 1-amino-2-dibenzofurylacetic acid lide 30 3-amino-2-dibenzofurylacetic acid 9-trifluoromethyl-2-dibenzofurylthioacetomorpho 4-amino-2-dibenzofurylacetic acid lide. 6-amino-2-dibenzofurylacetic acid b. One gram of 7-fluoro-2-dibenzofurylthi 7-amino-2-dibenzofurylacetic acid oacetomorpholide is refluxed for 4 hours with 0.3 g of 8-amino-2-dibenzofurylacetic acid KOH in 15 ml. of ethanol. After working up the mix 9-amino-2-dibenzofurylacetic acid ture is usual, 7-fluoro-2-dibenzofurylacetic acid is ob 1-trifluoromethyl-2-dibenzofurylacetic acid tained, m.p. 160-162. 3-trifluoromethyl-2-dibenzofurylacetic acid Analogously, the following compounds are produced 4-trifluoromethyl-2-dibenzofurylacetic acid by hydrolysis of the corresponding thioacetomorpho 40 6-trifluoromethyl-2-dibenzofurylacetic acid lides: 1-fluoro-2-dibenzofurylacetic acid 7-trifluoromethyl-2-dibenzofurylacetic acid 3-fluoro-2-dibenzofurylacetic acid 8-trifluoromethyl-2-dibenzofurylacetic acid 4-fluoro-2-dibenzofurylacetic acid 9-trifluoromethyl-2-dibenzofurylacetic acid. 6-fluoro-2-dibenzofurylacetic acid c. The procedure of paragraph (a) is followed, with 8-fluoro-2-dibenzofurylacetic acid 45 the exception that, after cooling, 130 ml. of concen 9-fluoro-2-dibenzofurylacetic acid trated hydrochloric acid and 100 ml. of water are 1-chloro-2-dibenzofurylacetic acid added to the reaction mixture, and the latter is again 3-chloro-2-dibenzofurylacetic acid refluxed for 24 hours, cooled, and worked up as usual, 4-chloro-2-dibenzofurylacetic acid thus obtaining 7-fluoro-2-dibenzofurylacetic acid. 6-chloro-2-dibenzofurylacetic acid 50 Analogously, the further 2-dibenzofurylacetic acids set 7-chloro-2-dibenzofurylacetic acid forth under (b) are produced. 8-chloro-2-dibenzofurylacetic acid d. The acetylation of the amino acids obtained ac 9-chloro-2-dibenzofurylacetic acid cording to (b) in analogy to Example 33(r) or 33(s) re 1-bromo-2-dibenzofurylacetic acid sults in: 3-bromo-2-dibenzofurylacetic acid 55 1-acetamido-2-dibenzofurylacetic acid 4-bromo-2-dibenzofurylacetic acid 3-acetamido-2-dibenzofurylacetic acid 6-bromo-2-dibenzofurylacetic acid 4-acetamido-2-dibenzofurylacetic acid 7-bromo-2-dibenzofurylacetic acid 6-acetamido-2-dibenzofurylacetic acid 8-bromo-2-dibenzofurylacetic acid 7-acetamido-2-dibenzofurylacetic acid 9-bromo-2-dibenzofurylacetic acid 60 8-acetamido-2-dibenzofurylacetic acid 1-iodo-2-dibenzofurylacetic acid 9-acetamido-2-dibenzofurylacetic acid. 3-iodo--2-dibenzofurylacetic acid 4-iodo-2-dibenzofurylacetic acid EXAMPLE 75 6-iodo-2-dibenzofurylacetic acid 2.86 g. of the ethyl ester of 2-3-(o-hydroxyphenyl)- 7-iodo-2-dibenzofurylacetic acid 65 4-hydroxyphenyl-propionic acid is heated with 0.7 g. 8-iodo-2-dibenzofurylacetic acid of ZnCl2 for 2 hours to 170. After working up the reac 9-iodo-2-dibenzofurylacetic acid tion mixture as usual, the ethyl ester of 2-(2-diben 3,897,453 89 90 zofuryl)-propionic acid is obtained, b.p. 173-177/0.2 From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this m. invention, and without departing from the spirit and EXAMPLE 76 scope thereof, can make various changes and modifica 2.56 g. of 2-3-(o-aminophenyl)-4-aminophenyl)- tions of the invention to adapt it to various usages and propionic acid is diazotized in dilute hydrochloric acid conditions. with 1.4 g of NaNO2. The mixture is allowed to stand What is claimed is: for 15 minutes and then heated on a water bath until 1. A compound of the formula the evolution of nitrogen has ceased. As an intermedi ate product, 2-3-(o-hydroxyphenyl)-4-hydroxy 10 phenyl)-propionic acid is obtained, which is not iso s CHR, R2 lated. Working up as usual yields 2-(2-dibenzofuryl)- 2 i . . . !. NY propionic acid, m.p. 139-140'. N-N y 1S2 EXAMPLE 77 15 A mixture of 3 g of pyrocatechol and 4 g. of substituted in the 1-, 3-, 4-, 6-, 7-, 8-, or 9-position by 2-(p-hydroxyphenyl)-propionic acid is heated in a R wherein R is COOR in which R5 is hydrogen, alkyl bomb tube for 30 hours to 220. As an intermediate of 1 to 20 carbon atoms or aminoalkyl, alkylamino product, 2-3-(o-hydroxyphenyl)-4-hydroxyphenyl)- alkyl, or dialkylaminoalkyl wherein alkyl in each in propionic acid or 2-[4-(2-hydroxyphenoxy-phenyl)- 20 stance is of up to 8 carbon atoms; R is H or alkyl of 1-4 propionic acid is probably produced. After cooling and carbon atoms; R is H, alkyl, alkoxy, alkanoyl, mo working up the mixture as usual, 2-(2-dibenzofuryl)- noalkylamino, dialkylamino, or alkanoylamino, each of propionic acid is obtained, m.p. 139-140. up to 4 carbon atoms, F, Cl, Br, I, OH, NH, NO, CN, or CF; and Y is O or S; with the proviso that at least EXAMPLE 78 25 one of R and Ra are other than H; and the physiolog A mixture of 27.65 g. of 2-3-(o-hydroxyphenyl)-4- ically acceptable salts thereof. chlorophenyl)-propionic acid, 5.6 g. of KOH, and 1 g. 2. A compound of claim 1, wherein R is COOR in of powdered Cu is heated for 5 hours to 190. After which Rs is H, alkyl of 1-8 carbon atoms or dialkylami cooling and working up as usual, 2-(2-dibenzofuryl)- 30 noalkyl of up to 10 carbon atoms. propionic acid is produced, m.p. 139-140'. 3. A compound of claim 1, wherein R is COOH, Analogously, 2-3-(o-chlorophenyl)-4-hydroxy COOCH or COOCHs. phenyl-propionic acid can be employed to achieve the 4. A compound of claim 1, wherein R is CH or same result. CHs. 35 5. A compound of claim 4, wherein R2 is CH3. EXAMPLE 79 6. A compound of claim 1, wherein Ra is H, CH, A mixture of 22.6 g. of 2-(3-diphenylyl)-propionic CH, CHO, CHCO, F, Cl, Br, I, OH, NH or NO. acid (3-(1-carboxyethyl)-diphenyl), 6.4 g of sulfur, 7. A compound of claim 6, wherein R3 is H. and 1.2 g of AlCl is heated for 10 hours to 200. After 8. A compound of claim 1, wherein R is COOH or the mixture has been worked up as usual, 2-(2-dibenzo 40 COOAlkyl wherein alkyl is of 1-8 carbon atoms, R is thienyl)-propionic acid is obtained, m.p. 182-184. CH3 and R3 is H, CH5, F, Cl, Br or I. 9. A compound of claim 8, wherein Ra is H or F. EXAMPLE 80 10. A compound of claim 8, wherein R3 is H or 7-F. 15.3 g. of 2-4-(2-aminophenoxy-phenyl)-propionic 11. A compound of claim 1, 2-(2-dibenzofuryl)- acid is dissolved in 120 ml. of water and 40 ml. of con 45 propionic acid. centrated hydrochloric acid and diazotized at 0-5 and 12. A compound of claim 1, the ethyl ester of 4.2 g of NaNO, in 15 ml. of water. The thus-obtained 2-(2-dibenzofuryl)-propionic acid. diazonium salt solution is poured into 200 ml. of hot 13. A compound of claim 1, the 2-diethylaminoethyl 50% HSO, and the mixture is further heated until the ester of 2-(2-dibenzofuryl)-propionic acid. liberation of nitrogen has ceased. After the usual work 50 14. A compound of claim 1, the 2-(2-dibenzofuryl)- ing-up operation, 2-(2-dibenzofuryl)-propionic acid is butyric acid. obtained, m.p. 139-140. 15. A compound of claim 1, the 2-(2-dibenzo thienyl)-propionic acid. EXAMPLE 81 16. A compound of claim 1, the ethyl ester of 2-(2- A solution of 2.3 9. of 2-4-(2- 55 dibenzothienyl)-propionic acid. aminophenylmercapto)-phenyl)-propionic acid in 25 17. A compound of claim 1, the 2-diethylaminoethyl ml. of hot 2N HSO4 is rapidly cooled. The sulfate, pre ester of 2-(2-dibenzothienyl)-propionic acid. cipitated in finely divided form, is diazotized at 0 with 18. A compound of claim 1, the 2-(8-ethyl-2-diben a solution of 0.65 g. of NaNO, in 5 ml. of water, and zofuryl)-propionic acid. the mixture is stirred for 2 hours. Thereafter, the mix 60 19. A compound of claim 1, the ethyl ester of 2-(8- ture is poured into 120 ml. of 50% H2SO4, refluxed for ethyl-2-dibenzofuryl)-propionic acid. 6 hours, worked up as usual, the product being 2-(2- 20. A compound of claim 1, the 2-(7-fluoro-2-diben dibenzothienyl)-propionic acid, m.p. 182-184. zofuryl)-propionic acid. The preceding examples can be repeated with similar 21. A compound of claim 1, the ethyl ester of 2-(7- success by substituting the generically and specifically 65 fluoro-2-dibenzofuryl)-propionic acid. described reactants and/or operating conditions of this 22. A compound of claim 1, the 2-(8-fluoro-2-diben invention for those used in the preceding examples. zofuryl)-propionic acid. 3,897,453 91 92 23. A compound of claim 1, the 2-(7-chloro-2-diben- 26. A compound of claim 1, the 2-(8-iodo-2-diben zofuryl)-propionic acid. zofuryl)-propionic acid. 24. A compound of claim 1, the 2-(8-bromo-2-diben- 27. A compound of claim 1, the 4-carbethoxycy zofuryl)-propionic acid. clohexyl-ammonium salt of 2-(2-dibenzofuryl)- 25. A compound of claim 1, the ethyl ester of 2-(8- 5 propionic acid. bromo-2-dibenzofuryl)-propionic acid. *k k k is sk

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