US 2002O128522A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0128522 A1 Te0doro et al. (43) Pub. Date: Sep. 12, 2002 (54) PROCESS FOR THE PREPARATION OF 4.4 (30) Foreign Application Priority Data -DHALOGEN-O-HYDROXYDIPHENYL COMPOUNDS Oct. 6, 1998 (EP)........................................ 988 11 OO2.9 Publication Classification (76) Inventors: Armando Di Teodoro, Rheinfelden (51) Int. Cl." ..................................................... C07C 43/20 (DE); Werner Holzl, Eschentzwiller (52) U.S. Cl. .............................................................. 568/637 (FR); Dieter Reinehr, Kandern (DE); Rudolf Zink, Therwil (CH) (57) ABSTRACT Disclosed is a four-step proceSS for the preparation of Correspondence Address: 4,4'-dihalogen-O-hydroxydiphenyl compounds of formula CBA SPECIALTY CHEMICALS CORPORATION (1) PATENT DEPARTMENT OH 540 WHITE PLAINS RD PO BOX 2005 TARRYTOWN, NY 10591-9005 (US) Hal Hall, (21) Appl. No.: 10/137,791 (22) Filed: May 2, 2002 by halogenation of a diphenyl compound (step 1a) or by the reaction of p-halophenol and p-dihalobenzene (step 1b), Related U.S. Application Data acylation of the dihalogen compound in a Friedel-Crafts (63) Continuation of application No. 09/806,359, filed on reaction (2"step), oxidation of the acyl compound (3"step) Mar. 29, 2001, now abandoned, filed as 371 of and hydrolysis (4" step). international application No. PCT/EP99/07158, filed The compounds of formula (1) are used for protecting on Sep. 27, 1999. organic materials and objects from microorganisms. US 2002/O128522 A1 Sep. 12, 2002 PROCESS FOR THE PREPARATION OF 4.4 -DHALOGEN-O-HYDROXYDIPHENYL -continued COMPOUNDS 0001. The present invention relates to a process for the OH preparation of 4,4'-dihalogen-O-hydroxy-diphenyl com pounds of formula (1) OH Cl C O (3) Hal Hall, 0006) However, the yield obtained by this method of 0002 wherein preparation is unsatisfactory as different chemical reactions 0003 Hal is a halogen atom, may take place concurrently. 0004 and to the use of these compounds for pro 0007 Accordingly, this invention has for its object to tecting organic materials and objects from micro organisms. provide an economic proceSS for the preparation of 4,4'- dihalogen-O-hydroxydiphenyl compounds in which undesir 0005 The preparation of 4,4'-dihalogen-o-hydroxydiphe able concurrent reactions are Suppressed. nyl compounds is usually carried out by diazotisation and Subsequent hydrolysis of 2-amino-4,4'-dichlorodiphenyl 0008. This object is achieved in accordance with this ether (compound of formula (2)): invention by a four-step reaction, where in the first Step a diphenyl compound is halogenised or p-halophenol is reacted with p-dihalophenol in the presence of copper and/or copper Salts, in the Second Step the dihalogen compound is acylated in a Friedel-Crafts reaction; in a third Step the acyl C Cl compound is oxidised, and in a fourth Step the oxidised (2) compound is hydrolysed, corresponding to the following reaction Scheme: O 1a. chlorination Hal Hal (6) Hal Hal 1b. Cu-cat. (4a) O + (4b) O NaOHAKOH OH Hal 2. Friedel-Crafts acylation R NY R O O 3. O Oxidation O a- (7) Hal Hall Hal Hal 4. hydrolysis US 2002/O128522 A1 Sep. 12, 2002 -continued OH (1) Hal Hal 0009) In the above Scheme: 0021 Further details on the reaction step 1b are to be found in DE-OS-2.242.519. 0010 R is C-C alkyl which is unsubstituted or substituted by 1 to 3 halogen atoms or hydroxy; 0022. The acylation reaction (2" step) is usually carried unsubstituted C-Caryl; or C-Caryl which is out in the presence of a Lewis acid, Such as aluminium Substituted by 1 to 3 halogen atoms, C1-C5alkyl or chloride. The Lewis acid is used in this case in 1 to 3, C-Calkoxy, or their combinations, and preferably 1.25 to 2, molar amount, based on the haloge nated acyl compound of formula (5). A Suitable acylation 0011 Hal is a halogen atom; reagent for this reaction is an acyl halide, preferably acetyl 0012 C-Calkyl is branched or unbranched alkyl, for chloride. Other suitable acylation example methyl, ethyl, propyl, isopropyl, n-butyl, Sec-butyl, 0023 agents are, for example, isobutyl, t-butyl, 2-ethylbutyl, n-pentyl, isopentyl, 1-meth ylpentyl, 1,3-di-methylbutyl, n-hexyl, 1 -methylhexyl, n-heptyl, isoheptyl, 1,1,3,3-tetramethylbutyl, 1-methyl-hep O tyl, 3-methylheptyl, 2-ethylhexyl or n octyl. 0013 C-C Alkoxy is straight-chain or branched radi HC-Cf C-C-Cf tic-(O cals, for example methoxy, ethoxy, propoxy, butoxy, penty W | \ loxy, hexyloxy, heptyloxy or octyloxy. O, H O, HC O 0.014 Halogen is fluoro, bromo or, preferably, chloro. C Cl 0015. In formulae (6) and (7) of the above reaction O c--o Scheme, R is C-C alkyl and, preferably, methyl. | \ Cl O. 0016. If halogen is preferably chlorine, the chlorination agent used for reaction Step 1a is, for example, Sulfuryl chloride or, preferably, gaseous chlorine. The reaction is 0024. In this instance, Lewis acid and acylation reagent preferably carried out in the presence of a catalyst, Such as are preferably used in equimolar amounts. The reaction is dibenzothiophene, methyl Sulfide, propyl Sulfide, phenyl carried out in the solvents conventionally used for Friedel Sulfide, a Lewis acid, Such as aluminium chloride, or mix Crafts reactions, Such as halogenated Solvents, preferably tures of these compounds. Aparticularly Suitable catalyst for methylene chloride or ethylene chloride. the novel chlorination reaction is a mixture of propyl Sulfide 0025. In a special embodiment of this invention, the and an equimolar amount of aluminium chloride. acylation reaction is carried out in the presence of acetyl 0.017. The temperature for the reaction of the first step chloride and aluminium chloride, which are used in equimo can be chosen from within a wide range, for example from lar amounts. -10 to 50° C. The reaction is preferably carried out at a 0026. The reaction time is of Subordinate importance for temperature from 0 to 40 C. this reaction Step and may vary within a wide range, for 0.018. The reaction times are also within a wide range. example from 1 to 18 hours. The reaction is normally carried out over 1 to 48 hours, 0027. The halogenation reaction (first step) and the acy preferably over 2.5 to 10 hours. lation reaction (Second step) as well as the optionally 0019. The reaction of step 1b is usually carried out at repeated chlorination reaction are preferably carried out in temperatures from 120 to 200, preferably from 130 to 170° the same reaction vessel and are thus one-pot reactions. C, it being necessary for the phenol compound of formula (4a) and the dihalogen compound of formula (4b) to be 0028. The oxidation of the acyl compound of formula (6) present in a Stoichiometric ratio, and the alkali hydroxide to the compound of formula (7) (Baeyer-Villiger oxidation) must be present in less than equivalent amount (20 to 80% can be carried out with different oxidants. Suitable oxidants of theory). are for example: 0020. The copper catalysts used are preferably the copper 0029 equimolar mixture of dilute peracetic acid and Salts conventionally used for the Ullmann Synthesis, for acetic anhydride in the presence of a catalytic example copper(II) oxide, copper(I) oxide, copper carbon amount of perchloric acid; ate, basic copper carbonate, copper(I) chloride, copper(II) excess of 3-chloro-perbenzoic acid in water; chloride, copper(I) bromide, copper(II) bromide or copper 0030) Sulfate. 0.031) di-peroxydodecane diacid (DPDDA); US 2002/O128522 A1 Sep. 12, 2002 0032 mixture of dilute peracetic acid and acetic and/or unsaturated fatty acids), lotions and creams, deodor anhydride and Sulfuric acid; ants, other aqueous or alcoholic Solutions, for example cleansing Solutions for the skin, moist cleansing tissues, oils 0033 persulfuric acid; or powders. 0034 mixture of concentrated Sulfuric acid, anhy 0052 Accordingly, this invention also relates to body drous acetic acid and hydrogen peroxide; care products containing at least one compound of formula 0035 mixture of m-chloroperbenzoic acid (1) and to cosmetically compatible carriers or auxiliaries. (MCPBA), trifluoroacetic acid and dichloromethane; 0053. The novel body-care product comprises 0.01 to 0036) mixture of sodium perborate and trifluoroace 15% by weight, preferably 0.5 to 10% by weight, based on tic acid; the total weight of the composition, of the compound of 0037 mixture of formic acid, hydrogen peroxide, formula (1) as well as cosmetically compatible auxiliaries. acetic anhydride, phosphoropentoxide and acetic 0054 Depending on the body-care product’s form of acid; presentation, it contains other components besides the com 0038 mixture of acetic acid, hydrogen peroxide, pound of formula (1), for example sequestrants, colourants, acetic anhydride and phosphoropentoxide; perfume oils, thickenerS or consistency regulators, emol lients, UV absorbers, Skin protectives, antioxidants, addi 0039 mixture of KSOs, sulfuric acid and a 1:1 tives for improving the mechanical properties, Such as -water/methanol mixture; dicarboxylic acids and/or the Al, Zn, Ca, Mg Salts of 0040 mixture of acetic acid and the potassium salt C-Cfatty acids, and, optionally, additional antimicrobial of monoperoxomaleic acid; active Substances. 0041 mixture of trichloromethylene, the potassium 0055. The novel body-are product may be formulated as Salt of monoperoXomaleic acid and Sodium hydrogen water-in-oil or oil-in-water emulsion, as alcoholic or alco Sulfate; hol-containing formulation, as vesicular dispersion of a ionic or non-ionic amphiphilic lipid, as gel, Solid Stick or as 0042 mixture of maleic anhydride, acetic anhy aeroSol formulation. dride, hydrogen peroxide and trichloromethane, 0056. A water-in-oil or oil-in-water emulsion comprising 0043 mixture of maleic anhydride, a urea-hydrogen the compound of formula (1) contains as cosmetically peroxide complex and acetic acid; compatible auxiliaries preferably 5 to 50% of an oil phase, 0044) Mg-monoperphthalate.