||||IIIHIIIHIIII USOO5151540A United States Patent (19) 11) Patent Number: 5,151,540 Aslam et al. 45) Date of Patent: Sep. 29, 1992 (54) THIO CARBAMATES AND THEIR Attorney, Agent, or Firm-Marvin Turken; Donald R. DERVATIVES Cassady 75) Inventors: Mohammad Aslam; Kenneth G. (57) ABSTRACT Davenport, both of Corpus Christi, A method is provided for preparing N-acylaminothio Tex. phenols, e.g., N-acetyl-para-aminothiophenol, or 73 Assignee: Hoechst Celanese Corporation, aminothiophenols, e.g., para-aminothiophenol, or N.S.- diacylaminothiophenols, e.g., N.S.-diacetyl-para-amino Somerville, N.J. thiophenol, by reacting any of certain sulfur-containing 21 Appl. No.: 935,461 ketones, viz., an S-(acylary) N,N-di(organo)thiocarba mate, e.g., S-(4'-acetophenyl)-N,N-dimethylthiocarba 22 Filed: Nov. 26, 1986 mate, an acylthiophenol acylate ester, e.g., 4-acetothio 51) Int. Cl. ................... C07C333/00; CO7C 211/00 phenol acetate, or a free acylthiophenol, e.g., 4-aceto 52 U.S. Cl. .................................... 558/232; 558/242; thiophenol with hydroxylamine or a hydroxylamine 558/234; 558/241; 564/428 salt, to form the oxime of the ketone, subjecting the 58 Field of Search ............... 558/242, 232, 234, 241; oxime to a Beckmann rearrangement in the presence of y 564/428 a catalyst to form an S-(N-acyl-aminoaryl) N,N-di(or gano)thiocarbamate, e.g., S-(N-acetyl-para-aminophe 56 References Cited nyl) N,N-dimethylthiocarbamate, an N,S-diacylamino U.S. PATENT DOCUMENTS thiophenol, e.g., N.S.-diacetyl-paraaminothiophenol, or 3,476,791 1 1/1969 Newman et al. .................... 558/234 an N-acyl aminothiophenol, e.g., N-acetyl-para-amino 4,524,217 6/1985 Davenport et al. ................ 564/223 thiophenol, respectively. The S-(N-acyl-aminoaryl) N,N-di(organo)thiocarbamate may be hydrolyzed to OTHER PUBLICATIONS the N-acyl aminothiophenol or aminothiophenol. The Reid, Org. Chen. of BiValent Sulfur, vol. IV, p. 201, S-(acylaryl) N,N-di(organo)thiocarbamate may be pro Chem. Pub. Co., Inc., N.Y., 1962. duced by reacting a hydroxy aromatic ketone, e.g., Chem. Ber., vol. 58, 1925, pp. 36-51. 4-hydroxyacetophenone (4-HAP) with an N,N-di(or Synthetic Communications, 12 (11), 941-944 (1983). gano)thiocarbamoyl halide, e.g., N,N-dimethylthiocar bamoyl chloride (DMTC) to form an O-(acylaryl) N,N- Pearson, et al., J. Am. Chem. Soc., 1953, pp. 5905-5908. di(organo)thiocarbamate, e.g., O-(4'-acetophenyl) N,N- Newman, et al., J. Org. Chemistry, vol. 31, pp. dimethylthiocarbamate, and pyrolytically rearranging 3980-3984 (1966). the latter compound. The acylthiophenol may be pro Kwart, et al., J. Org. Chemistry, vol. 31, pp. 410-413 duced by hydrolyzing the S-(acylaryl) N,N-di(organo)- (1966). thiocarbamate. Primary Examiner-M. Lee Assistant Examiner-Robert C. Whittenbaugh 6 Claims, No Drawings 5,151,540 1. 2 thiophenols and their derivatives, including a somewhat THO CARBAMATES AND THER DERVATIVES different sequence of reactions than that of the instant application. BACKGROUND OF THE INVENTION This invention relates to the production of aminothio 5 SUMMARY OF THE INVENTION phenols, e.g.,para-aminothiophenol, and their deriva In accordance with this invention, aminothiophenols, tives, such as N-acyl-aminothiophenols, e.g., N-acetyl and their derivatives such as N-acyl-aminothio-phenois, para-aminothiophenol. or N.S.-diacylaminothio-phenols, are produced by sub Aminothiophenols and their derivatives have various actual and potential uses in commerce. For example, ojecting any of certain sulfur-containing ketones, viz., an aminothiophenols such as para-aminothiophenol are acylthiophenol, either unmodified, or, preferably with important intermediates for the synthesis of pharmaceu the thiol group masked, i.e., esterified, with a thiocar ticals such as antiarthritics, steroid derivatives, and bamoyl or acyl group, to reaction with hydroxylamine anti-malarials, and are also used as photograph antifog or a hydroxylamine salt, to form the oxime of the ke ging agents. 15 tone, and subjecting the oxime to a Beckmann rear U.S. Pat. No. 4,524,27, issued Jun. 18, 1985 to K. G. rangement in the presence of a catalyst to form the free Davenport and C. B. Hilton, and assigned to the same N-acylaminothiophenol or its corresponding thioester. assignee as this application, teaches the preparation of The latter compounds may be hydrolyzed to obtain an N-acyl-hydroxy aromatic amines, e.g., N-acetyl N-acyl aminothiophenol (in the case of thioesters), or an paraaminophenol (APAP), by reacting a hydroxy aro-20 aminothiophenol. The N-acyl-aminothiophenol may be matic ketone, e.g., 4-hydroxyacetophenone (4-HAP), reacted with an acylating agent to form an N,S- with hydroxylamine or a hydroxylamine salt, to form diacylaminothiophenol, or may be hydrolyzed to the the oxime of the ketone, and subjecting the oxime to a Beckmann rearrangement in the presence of a catalyst aminothiophenol. to form the N-acyl-hydroxy aromatic amine. The patent 25 The reaction of the sulfur-containing ketone with also discloses the preparation of hydroxy aromatic es hydroxylamine added as is or from a hydroxylamine salt ters such as phenyl acetate or the Friedel-Crafts acyla to form the oxime of the ketone proceeds as shown in tion of phenols using hydrogen fluoride as catalyst and equation (I): cites several references disclosing these reactions. The entire disclosure of this patent is incorporated by refer (I) eCe. Auwers et al, Chemische Berichte 58, 36-51 (1925), show the Beckmann rearrangement of a large number of oximes of aromatic ketones, most of which are substi tuted acetophenones. 35 Q-SAr-C=NOH + H2O Ganboa et al, Synthetic Communications 13,941-944 (1983), show the production of acetanilide from aceto where Ar is a divalent aromatic radical, Q is H, phenone by refluxing in a solution of hydroxylamine hydrochloride. None of the three preceding references discloses any method for the preparation of an N-acyl aromatic amine from an aromatic ketone by oxime formation and Beck mann rearrangement, where the aromatic groups have a and R, R" and R'' are monovalent organo radicals as sulfur-containing ring substituent such as mercapto or further defined hereinafter. R, R and R' when used in thiocarbamoyl. 45 the naming of organic compounds herewithin are called Newman et al, Journal of Organic Chemistry 31, "organo'. 3980-3984 (1966), teach the formation of O-aryl dialkyl thiocarbamates by reaction of a phenol with a dialkyl The Beckmann rearrangement of the latter oxime to thiocarbamoyl chloride, and the pyrolytic rearrange form an N-acyl-aminothiophenol or its thioester pro ment of O-aryl dialkylthiocarbamates to S-aryl dialkyl so ceeds as in equation (II): thiocarbamates. Specifically disclosed in Table I is the pyrolytic rearrangement of O-4-acetophenyl to S-4- (II) acetophenyl dimethylthiocarbamate. Newman et al, U.S. Pat. No. 3,476,791, disclose a Q-SAr-t=NOH -catalystse process similar to that disclosed in the article cited in 55 the preceding paragraph and was issued to patentees who are the same as the authors of such article. Exam Q-SAr-N-C=O ple 14 of the patent shows the preparation of p-acetyl phenyl dimethylthiolcarbamate from p-acetylphenyl When Q is dimethylthioncarbamate. 60 Kwart et al, Journal of Organic Chemistry, 31, 40-413 (1966), show the vapor phase pyrolytic rear rangement of various diaryl thioncarbonates to O.S.-dia R"N-CFO, ryl thiolcarbonates and of various O-aryl dialkylthion carbamates to S-aryl dialkylthiolcarbaeates. 65 the hydrolysis of the resulting S-(N-acyl-aminoaryl) Copending application Ser. No. 875,158 filed Jun. 17, N,N-di(organo)thiocarbamate produced as in equation 1986 by Davenport and assigned to the same assignee as (II) forms the N-acyl aminothiophenol as shown in this application discloses a method of producing amino equation (III): 5,151,540 4. The reaction between a hydroxy aromatic ketone and an N,N-di(organo)thiocarbamoyl halide to form an O H R (II) O-(acylaryl) N,N-di(organo)thiocarbamate is as shown R"N-C-SArN-CFO + H2O OH G in equation (VII): H. R. R i (VII) HSArN-C=O -- NHR'. -- CO: Under more stringent hydrolysis conditions, the hy drolysis results in the formation of the free aminothio 10 phenol as shown in equation (IV): O H R (IV) where X is halide, e.g., chloride, bromide, or iodide, and OH G Ar, R and R' are used as in equation (I). 5 The pyrolytic rearrangement of the O-(acylaryl) N,N-di(organo)thiocarbamate to the S-(acylaryl) N,N- HSArNH2 + NHR'2 + CO2 + RCOOH di(organo)thiocarbamate proceeds as in equation The acylation of the thiol group of the N-acyl aminothi (VIII): ophenol proceeds as in equation (V): 20 i R (VIII) H R O (V) O R O H R 25 I R'-a-Ca-SAN-CEO - HY The hydrolysis of an S-(acylaryl) N,N-di(organo)thi ocarbamate to an acylthiophenol proceeds as in equa where Y is the residue of an acylating agent and R' is tion (IX): a monovalent organo radical as more fully defined here 30 inafter. The N-acyl aminothiophenol produced by the Beck O R (IX) mann rearrangement of equation (II) or by hydrolysis as in equation (III) may be further hydrolyzed to the aminothiophenol as shown in equation (VI): 35 R HSAr-CEO + NHR'2 + CO2 H. R. (VI) The acylation of the thiol group of the acylthio HSAN-tso-- Ho HF or Otis HSArNH2 + RCOOH phenol proceeds as in equation (X): The sulfur-containing ketone starting compounds of 40 equation (I) may be produced by any method known in R O (X) the art. It is preferable, however, that an S-(acylaryl) N,N-di(organo)thiocarbamate be initially produced by reacting a hydroxy aromatic ketone, e.g., 4-hydrox 45 O R yacetophenone (4-HAP) with an N,N-di(organo)thi ocarbamoyl halide, e.g., N,N-dimethylthiocarbamoyl R'-C-SAr-C-O - HY chloride (DMTC) to form an O-(acylaryl) N,N-di(or In the foregoing equations Ar is a divalent aromatic gano)thiocarbamate, e.g., O-(4'-acetophenyl) N,N- radical.