Patent GB-794762-A (GB)
Title: Dichloroacetanilide esters and the manufacture thereof
Inventor: OXLEY PETER
IPC: C07F9/12
Filed: 1955-11-03
Abstract: 794,762. Dichloroacetanilide esters. BOOTS PURE DRUG CO., Ltd. Oct. 23, 1956 [Nov. 3, 1955; March 9, 1956], Nos. 31482/55 and 7513/56. Class 2 (3). The invention comprises compounds of the general formula: wherein R is an alkyl radical containing at most 8 carbon atoms and R<SP>1</SP> is HOSO 2 -, (HO) 2 PO-, (R<SP>2</SP> being alkyl, halogenated alkyl, alkenyl, alkoxy, aralkoxy or phenyl) or (X being oxygen or sulphur and R<SP>3</SP> a [dichloracet - N - (alkyl) - amido]phenyl radical), the alkali metal, alkaline earth metal, ammonium and amine salts of the sulphates and phosphates, and the following methods for the preparation of these compounds: (1) for the sulphates and salts thereof, reacting the appropriate N-alkyl dichloracetamidophenol with sulphur trioxide or sulphamic acid in presence of pyridine with subsequent conversion, if desired, of the so-formed pyridine salt to other salts; (2) for the phosphates and salts thereof, reacting the appropriate N-alkyl dichloracetamidophenol with phosphorus oxychloride in presence of pyridine, hydrolysing the chlorophosphate so obtained and, if desired, forming the phosphate salts; (3) for compounds of the above general formula in which R<SP>1</SP> is a: group in which R<SP>2</SP> is alkyl, halogenated alkyl, alkenyl or phenyl, reacting the appropriate N- alkyl dichloracetamidophenol with an acid halide R<SP>2</SP>COY in the presence of an acid-binding agent (or using an alkali metal salt of the phenol in absence of such agent) or with an acid anhydride (R 2 CO) 2 O; or reacting a compound of the formula: with dichloroacetylchloride, preferably in presence of an acid-binding agent; (4) for compounds of the first general formula above wherein R<SP>1</SP> is a: group, reacting the appropriate N-alkyl dichloracetamidophenol with phosgene or thiophosgene; and (5) for compounds wherein R<SP>1</SP> is a: group in which R<SP>2</SP> is alkoxy or aralkoxy, reacting the appropriate N-alkyl dichloracetamido phenol with an alkyl or aralkyl haloformate in presence of an acid-binding agent. In examples: (1) dichloroacet-4-hydroxy-N-methyl anilide (hereinafter called compound A), sulphamic acid and pyridine give a pyridine salt which with piperazine hydrate gives piperazine 4-(dichloroacet - N - methylamido) phenyl sulphate; (2) compound A and crotonyl chloride in presence of dimethylaniline give 4-(dichloroacet- N-methylamido) phenyl crotonate; (3) the corresponding propionate is similarly prepared, pyridine replacing the dimethylaniline of (2); (4) the sodium derivative of compound A and dichloroacetyl chloride give dichloroacet-4- dichloro acetoxy-N-methylanilide; (5) compound A and acetic anhydride in presence of sodium hydroxide give dichloroacet-4-acetoxy- N-methylanilide; (6) compound A and benzoyl chloride in presence of sodium hydroxide give 4- benzoyloxy-N-dichloroacet-N-methylanilide; 7 compound A and chloroacetyl chloride in presence of pyridine give 4-chloroacetoxy-N- dichloroacet - N - methylanilide; 4 - alphachloropropionyloxy - N - dichloracet - N- methylanilide is similarly prepared; (8) compound A and butyric anhydride in presence of pyridine give 4-N-butyryloxy-N-dichloroacet- N-methylanilide; (9) compound A and phosphorus oxychloride in presence of pyridine give 4 - (dichloroacet - N - methylamido) phenyl phosphoric acid; (10) to (17) the product of (9) is converted into its mono and disodium salts, diammonium salt, calcium salt. bisbenzylammonium salt, mono and bis salts with chloroquine, piperazinium salt and anilinium and bisanilinium salts by reaction with sodium hydroxide, ammonium hydroxide, calcium carbonate, benzylamine, 7-chloro-4-(41-diethylamino - 1<SP>1</SP> - methylbutylamino) quinoline, piperazine hexahydrate and aniline respectively; (18) compound A and phosgene in presence of sodium hydroxide and sodium bisulphite give bis - [4 - (dichloroacet - N - methylamido)phenyl] carbonate; the thionocarbonate is prepared similarly from thiophosgene; (19) compound A and ethyl chloroformate in presence of pyridine give 4-(dichloroacet-N-methylamido) phenyl ethyl carbonate; benzyl chloroformate gives the corresponding benzyl carbonate; (20) the product of (6) is obtained from dichloroacetyl chloride and 4-methylaminophenyl benzoate (prepared by refluxing p-methylaminophenol sulphate, formic acid and sodium formate to give formo - 4 - hydroxy N - - methylanilide, reacting this with benzoyl chloride in presence of NaOH to give 4-(formo-N-methylamido) phenyl benzoate and refluxing this with HCl) in presence of sodimn acetate at room temperature; and (21) the product of (6) and (20) is obtained by refluxing 4-methylaminophenyl benzoate with dichloroacetyl chloride. In the Provisional Specification there is no limitation on the number of carbon atoms that R may contain. Specification 767,148 is referred to.