GB1591874A - N-methoxy-carbonyl-n'-supphonylhydrazines - Google Patents

Description

PATENT SPECIFICATION ( 11) 1 591 874

l ( 21) Application No765/80 ( 22) Filed 18 May 1977 ( 19) ( 62) Divided Out of No 1591872 ( 31) Convention Application No 696263 ( 32) Filed 15 Jun 1976 in o ( 33) United States of America (US) ( 44) Complete Specification Published 1 Jul 1981 ( 51) INT CL 3 C 07 C 143/825 ( 52) Index at Acceptance C 2 C20 Y 220 227 22 Y 30 Y 311 31 Y 385 510 51 Y 524 695 AA SC ( 54) N-METHOXYCARBONYL-N'-SULFONYLHYDRAZINES ( 71) We, PFIZER INC, a Corporation organised under the laws of the State of Delaware, United States of America, of 235 East 42nd Street, New York, State of New York, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be

particularly described in and by the following statement: 5

The invention relates to novel N-methoxycarbonyl-N'-sulfonylhydrazines for use in preparing 3-( 2-quinoxalinylmethylene)carbazate-N 1,N 4-dioxides with useful antibacterial properties and/or with growth promotant properties in animals.

According to our application no 20800/77 (Serial no 1591872) a process for preparing a methyl 3-( 2-quinoxalinylmethylene)carbazate N 1,N 4-dioxide of the formula: 10 W R (I) 15 N Ck I N-NH-COOCH wherein R is hydrogen, alkyl, hydroxyalkyl, alkanoyl, benzoyl or -CONR 1 R 2 wherein R' and R 2 are each hydrogen, alkyl, hydroxyalkyl or aminoalkyl, any such alkyl, hydroxyalkyl 20 or aminoalkyl group containing 1 to 6 carbon atoms and any such alkanoyl group containing 2 to 7 carbon atoms, comprises reacting a compound of the formula:

N R 25 | 1 11 ___ (II) N X X 0 30 wherein R is as defined above and X is chlorine or bromine, with a compound of the formula:

R 3-NH-NH-COOCH 3 (III) 35 wherein R 3 is an aliphatic or aromatic sulphonyl group, in a reactioninert solvent, in the presence of anhydrous potassium carbonate.

Some of the compounds of the formula III are the subject of claims in British Patent No.

1505120.

The present invention provides compounds of the formula III where R 3 is a 40 trifluoromethane or 2,2,2-trifluoroethane sulphonyl group.

The trifluoromethane sulphonyl (CF 3 SO 2) and 2,2,2-trifluoroethane sulphonyl (CF 3 CH 2 SO 2) groups are commonly known as the trifyl and tresyl groups respectively The preferred compound of formula (III) is that in which R 3 is trifyl, i e NmethoxycarbonylN'-trifyl-hydrazine 45 1 591 874 Compounds of formula (I) in which R is hydrogen or alkyl containing 1 to 6 carbon atoms are described and claimed in British Patent Specification No 1058047, while those in which

R is -CONRIR 2 are described and claimed in British Patent Specification No 1365441.

The compounds of formula (III) are prepared by the general procedures described in J.

Org Chem 40, 3450 ( 1975) and United States Patent No 3925270 ( 1975) For example, 5 N-methoxycarbonyl-N'-trifylhydrazine is prepared by adding a solution of triflic anhydride in methylene chloride dropwise to a methylene chloride solution containing an equimolar amount of methyl carbazate and a slight molar excess of triethylamine at 78 C The resulting mixture is allowed to warm to room temperature and stirred for about 16 hours.

The mixture is concentrated under vacuum at room temperature and the residue is then 10 extracted with several portions of ether The ether extract is concentrated under vacuum at room temperature to a waxy solid that is used directly in the subsequent reaction without further purification Alternatively, the omission of triethylamine and the use of two molar equivalents of methyl carbazate yields the crystalline product.

The following examples illustrate the preparation of compounds of formula (III) 15 according to the invention.

EXAMPLE I

N-Methoxycarbonyl-N'-trifylhydrazine (A) Triflic anhydride ( 35 4 mmoles) in methylene chloride ( 40 ml) was added dropwise to 20 a solution of methyl carbazate ( 35 5 mmoles) and triethylamine ( 38 9 mmoles) in methylene chloride ( 200 ml) at -78 C with stirring The resulting mixture was allowed to warm to room temperature and stirred for 16 hours The mixture was concentrated at room temperature under vacuum and the residue was extracted with three 100 ml portions of refluxing ether The combined ether extract was concentrated under vacuum at room 25 temperature to yield a waxy solid ( 5 26 g, ca 67 %) The nmr spectrum of the crude product was consistent with the expected product contaminated with the triethylamine salt of triflic acid The crude material was used directly without further purification for subsequent reactions.

(B) Methyl carbazate ( 336 mmoles) was added over a 20 minute period with stirring to a 30 solution of triflic anhydride ( 178 mmoles) in methylene chloride ( 2000 ml) under a nitrogen atmosphere at -78 C The resulting solution was allowed to warm to room temperature and stirred for 20 hours The resulting thick white suspension was concentrated under vacuum at room temperature to give a white solid This material was triturated with diethyl ether ( 450 ml) and collected to give the methyl carbazate salt of triflic acid The diethyl 35 ether filtrate was concentrated under vacuum at room temperature to give a white solid which was triturated with hexane, collected, washed with hexane and dried to give the product as a white crystalline solid (yield, 84 %) mp 107-109 C.

Analysis 40 Calc'd for C 3 H 504 N 2 F 3 S: C, 16 21; H, 2 25; N, 12 61 % Found: C, 16 24; H, 2 20; N, 12 68 % 45 EXAMPLE II

N-Methoxycarbonyl-N'-tresylhydrazine The method of Example I may be repeated employing tresyl chloride in place of triflic anhydride.

Claims (3)

WIHAT WE CLAIM IS: 50

1 A compound of the formula:

R 3-NH-NH-COOCH 3 (III) wherein R 3 is a trifluoromethane or 2,2,2-trifluoroethane sulphonyl group 55

2 N-Methoxycarbonyl-N'-trifylhydrazine.

3 N-Methoxycarbonyl-N'-tresylhydrazine.

P.C C GRAHAM, Chartered Patent Agent, 60 Agent for the Applicants.

Printed for Her Majesty's Stationery Office by Croydon Printing Company Limited Croydon, Surrey 1981.

Published by The Patent Office, 25 Southampton Buildings London, WC 2 A l AY, from which copies may be obtained.