sign in sign up
<<
Home , Methyl anthranilate, Selenol, Tellurol

3,123,631 United States Patent Office Patented Mar. 3, 1964 raroa

2 ceeds to produce a high yield of an anthranilate. Simi 3,123,631 larly, reaction 1 predominates with reactants having the PRO{CESS FOR PRESPARNG ESERS OF generic formula R-TH, where T is a non-metallic ele ANHRANLECACD ment from the sixth group of the periodic system having Roger P. Staiger, Collegeville, Pa., and George F. an atomic number from 8 through 52, inclusive (i.e., Schaudecker and Enaery B. Miser, Toledo, Ohio, OXygen, sulfur, or ), and R is an or assignors to Maumee Chemical Company, Toledo, ganic group, and preferably, is aryl, or a radical having (Oiaid, a corporation of 60hio the formula -CH-R in which R' is hydrogen, or an No Drawing. Filed Sept. 9, 1957, Ser. No. 682,630 organic group, and preferably is hydrogen, , aryl, 6 Cairns. (C. 260-471) O alkenyl, alkynyl, or acyl. This invention relates to isatoic anhydride reaction When the reactant other than isatoic anhydride is a products, and to a method for reacting isatoic anhydride tertiary , reaction 2 proceeds to produce a high with various hydroxyl-containing, -containing, and yield of an alkyl of N-carboxyl similar inorganic and organic compounds. (isatoic acid) in which the carboxyl that is attached di 5 rectly to the ring is not esterified. isatoic anhydride has been known for some time (see it has been found that both reaction 1 and reaction 2 German Patents 110,577 and 112,976), but neither it proceed when the reactants are isatoic anhydride and a nor any compound produced from it has found any com Secondary alcohol, such as isopropanol. merical use. It is convenient to conduct a reaction until all isatoic The present invention is based upon the discovery of 20 anhydride which is only sparingly soluble in most solvents, an improved method for producing certain reaction prod has been consumed. The anhydride, therefore, is prefer lucts from isatoic anhydride, and of useful isatoic anhy ably used in not more than stoichiometric amounts, al dride reaction products. though, if desired, a substantial excess of either reactant It is, therefore, an object of the invention to provide can be employed. It is usually advantageous to warm an improved method for producing certain reaction prod 25 the reaction mix slightly, for example to a temperature ucts of isatoic anhydride. from about 45° C. to the boiling temperature of the mix, It is a further object of the invention to provide use and to maintain a temperature within such range until ful isatoic anhydride reaction products. reaction has proceeded to a desired extent, for example Other objects and advantages will be apparent from for from 30 minutes to several hours. the description which follows, which is intended only 30 A base is employed in only a catalytic quantity in pro to illustrate and disclose, but in no way to limit, the in ducing an anthranilic acid ester according to the method vention. of the invention. For example, as little as about 1 percent According to one aspect of the invention, an improved of a base has been found to be effective, and, in ordinary method for producing an ester, a , a seleno ester practice, it has usually been preferred to use from about or a telluro ester from isatoic anhydride is provided. In 35 2 percent to about 10 percent of a base. Greater amounts some cases the may be anthranilates, while in other can be employed, if desired, but there appears to be no instances, the reaction product is an ester of N-carboxy advantage, unless a salt of the final reaction product is anthranilic acid (isatoic acid) in which the carboxyl at desired, in which case the stoichiometric amount of the tached directly to the benzene ring is not esterified. The base for production of such salt, plus a small excess two reactions are represented, respectively, in Equations 40 should be employed. 1 and 2, below, wherein R represents, for example, an The terms "percent' and “parts' are used herein and alkyl radical: in the appended claims to refer to percent and parts by EQUATION 1 weight, unless otherwise indicated. In general, any base can be employed in carrying 45 out a reaction with isatoic anhydride in accordance with the invention. It is usually preferred, however, to use a strong base, usually a strong inorganic base, and, most desirably, an alkali metal hydroxide. Excellent results have been obtained when the base has been sodium hy 50 droxide. The invention has been defined, in Equations 1 and 2, O above, in connection with the reaction of isatoic anhy. -C- dride with various . It will be appreciated that -- O R other hydroxyl-containing organic materials, as well as N- N-C-OR 55 various thiol-compounds, -compounds, and II || El O O compounds, can be similarly reacted. Such organic com pounds can be represented by the generic formula RTH, wherein T is a non-metallic element from the sixth group Such reactions proceed between solutions comprising of the periodic system haiving an atomic number from isatoic anhydride and an organic hydroxyl-containing 60 8 through 52, inclusive, and R is an organic radical. In compound in the presence of small amounts of a base. a preferred class of such organic compounds, R is a It has been found that, in many instances, reaction 1 or member of the group consisting of aryl, and those hav reaction 2 proceeds, virtually to the exclusion of the ing the formula -CH2-R' in which R" is a member of other, and that in such instances, the nature of the hy the group consisting of hydrogen, alkyl, aryl, alkenyl, -droxyl-containing compound principally determines which 65 of the two reaction types takes place. When such reactant alkynyl, and acyl. Another preferred class of such is a primary aliphatic alcohol or a phenoi, reaction 1 pro organic compounds can be represented by the generic

3 4. formula reaction product is a modified polyvinyl alcohol or poly R ester containing functional groups which were not pre IO-C-R sent in the starting material. Such additional functional kn groups, or new functional groups, enabie reactions of wherein R' has the meaning previously set fort, R'' and 5 which the original starting materials were incapable. For R' have the same meanings as R' and not more than example, such reaction product from a polyvinyl alcohol one of the symbois R', R'' and R' represents hydrogen. could be reacted with a polyhydroxy organic compound, Most desirably, none of the symbois R', R'' and R' rep for example a glycol, in order further to increase its resents hydrogen. molecular weight at a desired stage in processing. By 0 using glycerol, pentaeryl thritol or other cross-linking agent In addition to the preferred classes of hydroxyl-, thiol-, having three or more hydroxyl groups, the possibility selenol-, and tellurol-organic compounds identitfied in the would exist of producing a modified polyvinyl alcohol preceding paragraph, it will be appreciated that various having a cross-linked molecular structure, which would other thiol or hydroxyl compounds can be so reacted. be expected to be thermosetting. As a specific example of another such reactant, mention It will also be noted from Equation 1, above, that may be made of cellulose, which is believed to have a carbon dioxide can be evolved during the course of a molecular structure made up of an undetermined num reaction in accordance with the invention. In some ber of repeating cellobiose units, hydroxyl-containing instances, the evolved carbon dioxide can be utilized as polyester materials and polyvinyl alcohol, which is chemi a blowing agent in the production of foamed or cellular cally somewhat similar to cellulose. 20 materials. As is indicated above, certain new compositions of The following examples are presented solely for the matter are provided according to the invention. One purpose of further illustrating and disclosing the inven class of such new compounds is characterized by the tion and are in no way to be construed as limitations presence in its molecular structure of the group thereon. O 25 Example 1 -C-T- Isatoic anhydride was reacted with various organic compounds having the generic formula R-TH to pro duce corresponding anthranilates according to the follow wherein T' is a non-metallic element from the sixth group 30 ing procedure. of the periodic system having an atomic number from A large glass test tube was charged with a 3-milliliter 16 thorugh 52, inclusive (i.e., sulfur, selenium or tel portion of absolute methyl alcohol, 2 grams of isatoic lurium). Such new compositions of matter can be acids, anhydride, and one pellet (approximately A0 gram) of acid salts, or esters. The acids can be represented by sodium hydroxide. The resulting reaction mixture was the generic formula then warmed over a steam bath. After a short period O of heating, gas evolution was noted; heating was con --T-H tinued until gas evolution ceased. Most of the sodium hydroxide pellet remained intact in the reaction mixture, and was removed after heating was discontinued. A 30 4th milliliter portion of cold distilled water was added with wherein T' has the meaning previously stated. The salts swirling to dilute the mixture. Methyl anthranilate at can be formed by reaction of any metal hydroxide with this point was present in the test tube below the aqueous any of the acids. The esters have the generic formula phase, and was separated from the water. A 1.74-gram portion (94 percent of theory) of almost colorless methyl g 45 anthranilate, having a crystal point of 24° C. without -C-E-R. purification, was recovered. Methyl anthranilate hydrochloride was produced by -NiI2 dissolving a /2 milliliter portion of the methyl anthranilate in absolute diethyl , and adding to the resulting wherein T' has the meaning previously stated, and R is 50 solution a sufficient quantity of concentrated hydrochloric an organic radical. As is indicated above, a preferred acid for complete reaction with the ester. A voluminous ciass of esters is one wherein R is aryl, or has the formula precipitate of fine white needles formed immediately, and -CH-R' where R' is hydrogen, alkyl, aryl, alkenyl, was separated from the liquid by vacuum filtration, and alkynyi, or acyl. washed twice with cold diethyl ether. The resulting In some instances, products of reaction of isatoic an methyl anthranilate hydrcchloride had a melting point hydride and an organic hydroxyl compound produced ac of 180° C. cording to the method of the invention are useful per Se The picric acid salt of methyl anthraniiate was pro or as organic intermediates. For example, Some of the duced by mixing two solutions, one of which was a satu esters of anthranilic acid produced by the reaction rep rated solution of picric acid in 5 milliliters of methanol, resented by Equation 1, above, are directly useful as and the other of which contained /2 milliliter of methyl erfume essences. In other instances, such reaction prod anthranilate dissolved in methanol, adding a few drops ucts are, as a practical matter, modified materials of of distilled water until the combined solution appeared known utility, which have increased utility by virtue of murky, warming the combined solution until the murki the modification. For example, cellulose modified by ness disappeared, and then cooling the cleared solution reaction with isatoic anhydride in accordance with the 65 in an ice bath, with stirring, until the picric acid salt invention would have at least one which crystallized as bright yellow needles. The yellow needles was not present in the original cellulose, and may have were separated from the mother liquor by vacuum filtra two such functional groups. in either case, an amino tion, and washed sparingly, with cold methanol. After group would have been added to the cellulose molecule, drying, the picric acid salt of methyl anthranilate had a so that the chemical composition would resemble wool in 70 melting point of 103 C. some respects, and it is likely that the modified cellulose Various other anthranilates have been produced in could be dyed directly, for example with an acid reacting accordance with the invention. The starting materials, wooi dye. Faithermore, when a polyvinyl alcohol or amounts, products, properties and derivatives produced a hydroxyl-containing polyester material is reacted with are given in Table I, below, solely for the purpose of isatoic anhydride in accordance with the invention, the 75 illustrating further reactions of isatoic anhydride:

3,123,631 s 5 TABLE I

R-TH Compound Base Solvent GranasIsatoic Grams - Reaction Product Melting Anhy- Unless Iden- Milli- Temper- Point, dride Identity Other- tity Gram Identity liters ature o C. wise in dicated

2.0------95% ------5 ml. NaOH %6- none added------ethyl anthranilate------cogsCul 2. cinuanyl alcohol.------2. NaOH % dioxane----- 5 80 cinnamyl anthranilate------61-65. 2.88------do------2.82 NaO. 46 acetoe- 5 ----- do------61-6.5 2 beta-phenethyl alcohol------2.05 NaOH Mol dioxane----- 5 70 beta-phenethyl anthranilate--- colorlessO. 2. allyl alcohol------3ml. NaOH. 46 none added------50-55 allyl anthranilate------oil. 2. cyclohexanol- 5 m. NaOH 85 cyclohexyl anthranilate.------oil. 1. linalool------0.86 NaO. 95 linallyl anthranilate------yellowOil

2.0------ glycol------4 in. NaOH 46 none added.------45 babydroxyethyl3.0. anthrani- Sweet oil 1. phonol------1.13 NaOH 16 dioxane.----- 4 45 phenyl anthranilate------70. 2. resorcinol- 1.35 NaOE 3.16----- do------5 ------3-hydroxyphenyl anthranilate- about 30. 2. isopropyl alcohol 5 in. NaOH % none added.------75-95 isopropyl anthranilate------2. vanillin------1.88 NaOH 31 dioxane----- 5 80-85 2-methoxy-4-formlyphenylanthranilate. 84-86. 2.53------methyl Salicylate------2.36 NaOH 5 80-90 o-carbomethoxyphenylanthranilate. 70-71. 2. E.A.R. 1.77 NaO 5 55 alpha naphthyl anthranilate-86-87. 2. beta, naphtho 1.77 NaOH 10 55 beta naphthyl anthranilate i8. 2. thymol------1.84 NaO 5 75 thymyl anthranilate. 3. in-butyl alcoh 63 NaOH 5 80 n-butyl anthranilate------coli(u0. 5.0------methanethiol------8.0 NaOH 10 60 methylthio-anthranilate------"Ea1Cli(1. 1.6------benzenethiol.------1. NaO. 5 70 phenylthio-anthranilate------103-05. 40------hydrogen ------excess NaCH O 75 thioanthranilic acid------1855, stage).Ot Na2S-9H2O------3.54 O 60 Sodium thioanthranilate------Na2S.9H2O- 1.66 20 75 ----- do------ethanethiol------1, 5 10 60 ethylthio-anthranilate 1.------yellowO. d-glucose------1.0 10 83 glucose ester of anthranilic 112-14 acid. stage).(hot 2-mercaptoethanol------1.0 NaOH 5 67 beta-hydroxyethylthranilate. thioan- yellowoil. geraniol------1.7 NaOH 10 80 geranyl anthranilate------Do. p-aminophenol- 2.68 NaOI 10 60 p-aminophenyl anthranilate--- 160. - - - - - do------2.68 NaOH 10 60 0.yiamide. en z-p-hydroxyphen- 198. ethylene glycol------0 NaOH 10 75-90 ethylene glycoidianthranilate 8125-126. furfuryl alcohol. 2.0 NaOH 10 80 furfuryl anthranilate------Inercaptoacetic ac 1.3 : NaOH 5 88 capaymethylate. thioanthrani- 18-120. beta-hydroxyethylthioanthra- 2.8 NaOH 5 00 o-aminobenzoyloxyethylthio- 97-101. nilate anthranilate.4 dichlorophene------2.7 NaOE 5 64 dichlorophene monoanthran- 199 ilate. stage).(hot 2-butyne-1,4-diol------11 NaOH 5 100 2-lyneilate. 1,4-diolmonoanthran- 100-103. 3.86------methallyl alcohol------i.5 NaOH. O 00 methalyl anthranilate------'Squid. 1.63------pentaerythrity tetrathiol------0.5 NaOE 5 75 pentaerythrityltetrathiolrathioanthranilate. tet- 210.

1 Boiling point at i5 mm. of Jig pressure=172 C.; refractive index in D25=1.6340; density = 1.1659 grams per cc. at 23° C. 2 This product was strongly fluorescent under ultra violet light, and might be used as a “whitener' for washed clothing. 3 Compounds of this type might be used as hardeners for epoxy resins. 4 Compounds of this type might be used as hardeners for epoxy resins.

Oerivatives HC Picric Acid 1,3,5-Trinitrobenzene Product, Color Melting Melting Melting Point, C. Color Point, C. Color Egg,

Ethyl anthranilate------white.-- 169 ------(5) -red------70.5 Cinnainyl anthranilate------do----- 156-157 103-109 golden yellow--- 129 Beta-phenethyl anthranilate.-- 14-148 ------. 94-95 AllylBeta-naphthyl anthranilate------anthranilate- 184-8520-125 ------71-73 36-3769 n-ButylThynly anthrapilate------anthranilate------130-135127-128 ------yellow 118. 0-118.583-85 Orange------. 61-6221 Methyl thioanthranilate. 185-187 ---- do--- 99 yellow-orange--- 126 Phenylthioanthranilate. 172-174 orange-red 88-89 orange--- 122 Thioanthranilic acid------indefinite yellow- indefinite 186 Ethylthioanthranilate------white--- 145-150 --- do... 7-72 66 Beta-hydroxyethyl anthranilate do 163-165 golden yellow 99-00 84-85 Geranyl anthranilate------yellow---- 117-119 ------(hot stage) EthyleneFurfuryl anthranilate------glycol dianthranilate------do-----white--- 128-135205 ------151 8052 2-butyne-1,4-diol monoanthranilate------tan------145-160 134 23 Methallyl anthranilate------white--- 2S-30 128-130 Orange------63 5 The melting point of the benzene sulfonyl chloride derivative was 92.5°C. 3,123,631 7 8 Example 2 What we claim is: have also been produced according to the 1. A method for producing an anthranilic acid ester se method of the invention. Typical preparations thereof lected from the group consisting of phenyl anthranilate, n are reported below: alkyl anthianilates, methailyl anthranilate, beta phenethyl A large test tube was charged with 2 grams of isatoic anthranilate, and 2-butyne-1,4-diol monoanthranilate, anhydride, 4 grams of tertiary butyl alcohol, and two which method comprises effecting contact between sodium crushed pellets (approximately 0.2 gram) of sodium hy hydroxide and a solution comprising approximately equi droxide, and the resulting mixture was heated to about rolecular proportions of isatoic anhydride and an alcohol 70 C. A 5-milliliter portion of dioxane was then added selected from the group consisting of phenol, a primary to the reaction mixture, and reaction was continued, with O in alkyl alcohol having from 1 to 4 carbon atoms, methall agitation, at 70 to 85 C. for a period of 1/2 hours. yl alcohol, beta phenethyl alcohol, and 2-butyne-1, 4 Heating was then discontinued, and a mixture of chipped diol, respectively; warning the resulting mixture to a ice and water was added to the test tube. A sweet grape temperature of at least about 45 C., but not higher than odor was noted, indicating that some tertiary butyl about 100° C.; and thereafter separating the anthranilic anthranilate had been produced, but no separate oil phase 5 acid ester from the reaction mixture. - was observed. A sample of the resulting reaction mix 2. A method for producing phenyl anthranilate which ture was acidified, whereupon a heavy voluminous slightly comprises effecting contact between sodium hydroxide and yellow precipitate of t-butyl N-o-carboxyphenyl a solution comprising approximately equimolecular pro formed, and was recovered. This product had a hot portions of isatoic anhydride and of phenol, warming the stage melting point of 165-167 C. 20 resulting reaction mixture to a temperature of about 45° Isopropyl N-o-carboxyphenyl carbamate has also been C., and thereafter separating phenyl anthranilate from produced, using a reaction mixture of 2.0 grams of isatoic the reaction mixture. anhydride, 10-milliliters of isopropyl alcohol, and 0.5 3. A method for producing an alkyl anthranilate which gram of sodium hydroxide as the starting materials, and comprises effecting contact between sodium hydroxide and generally the reaction conditions and procedure described 25 a solution comprising approximately equimolecular pro in the preceding paragraph. The product, after recrystal portions of isatoic anhydride and of a primary alkyl ai lization, had a hot stage melting point of 160 C. cohol having from 1 to 4 carbon atoms, warming the re it has been found to be essential that at least a part of suiting reaction mixture to a temperature of at least about the isatoic anhydride reactant dissolve in the reaction 45 C., but not higher than about 80° C., and thereafter mixture. When the other reactant is a solvent type ma 30 separating the alkyl anthranilate from the reaction mix terial, such as methyl alcohol, ethyl alcohol, alyl alcohol, ture. ethylene glycol or the like (see Example 1), an excess of 4. A method for producing beta phenethylanthranilate such reactant can be employed to act as a solvent for which comprises effecting contact between sodium hy the isatoic anhydride. In other instances, a solvent can droxide and a solution comprising approximately equi be added as such; the specific identity of the solvent, in 35 molecular proportions of isatoic anhydride and of beta such case, is unimportant, provided that it itself does phenethyl alcohol, warming the resulting reaction mix not react with isatoic anhydride, unless a mixture of reac ture to a temperature of at least about 45° C., but not tion products is desired. For example, in producing a higher than about 70° C., and thereafter separating beta perfume essence, it might be desired to produce a mix phenethylanthranilate from the reaction mixture. ture of methyl-, ethyl-, and n-butyl-anthranilates. In 40 5. A method for producing methallyl anthranilate such case, a mixture of the corresponding alcohols, in which comprises effecting contact between sodium hy desired proportions, could be employed as the alcohol droxide and a solution comprising approximately equi reactant and as the solvent. molecular proportions of isatoic anhydride and of meth In many cases, the desired anthranilate or carbamate ailyl alcohol, warming the resulting reaction mixture to a reaction product is contaminated with unreacted isatoic temperature of at least about 45° C., but not higher than anhydride. When this is the situation, an easy expedient about 100° C., and thereafter separating methallyl an for purifying the crude reaction product involves merely thranilate from the reaction mixture. washing the same with ammonium hydroxide. Isatoic 6. A method for producing 2-butyne-1,4-diol mono anhydride reacts readily with the ammonium hydroxide, anthranilate which comprises effecting contact between but both carbamates and anthranilates are substantially Sodium hydroxide and a solution comprising approxi inert thereto and insoluble therein. The anthranilamide mately equimolecular proportions of isatoic anhydride produced from the residual isatoic anhydride is fairly and of 2-butyne-1,4-diol, warming the resulting reaction soluble in water, and collects in a water phase, while mixture to a temperature of at least about 45° C., but the desired carbamate or anthranilate remains in a sep not higher than about 100° C., and thereafter separating arate phase. 5 5 2-butyne-1,4-diol monoanthranilate from the reaction mix While isatoic anhydride is capable of reaction with ture. water to preduce anthranilic acid, it has been found that this reaction proceeds at Such a low rate, compared to References Cited in the file of this patent the rate at which desired anthranilates and carbamates 60 UNITED STATES PATENTS are produced, that it is not necessary to establish anhy 2,030,093 Bousquiet et al. ------Feb. 11, 1936 drous reaction conditions. Water can be added to the 2,602,789 Schwartz et al. ------July 8, 1952 reaction mixture to act as a diluent, or solvents contain 2,706,202 Bavley et al. ------Apr. 12, 1955 ing appreciable amounts of dissolved water can be used, 2,716,659 Kreysa et al. ------Aug. 30, 1955 without serious interference with the desired reaction. 2,802,838 Deutschman et al. ------Aug. 13, 1957 It is probable that some anthranilic acid is produced, but 2,806,051 Brockway ------Sept. 10, 1957 in such small proportions as not materially to affect the course of the desired reaction. OTHER REFERENCES it will be apparent that various changes and modifica Koibe: J. Prakt, Chena. 30, 469, 474 (1884). tions can be made from the specific details disclosed Meyer et al.: J. Prakt. Chem. 33, 22-3 (1886). herein without departing from the spirit and scope of the 70 Schmidt: J. Prakt. Chem. 36, 370-1, 376-8 (1887). attached claims,