Patent GB-782420-A (GB)
Title: New hydrazides
Inventor: ROSE FRANCIS LESLIE
Filed: 1954-08-23
Abstract: The invention comprises hydrazides of the formula A-S-(CH2)n-CO-NR1-NR2R3 wherein A is hydrogen, or a hydrocarbon radical which may be substituted by one or more amino, nitro, methyl, chloro, acetylamino or propionylamino radicals, or A is an acyl radical which may contain a nitro group, or A is the group -(CH2)nCO-NR1-NR2R3 or -S-(CH2)n-CO-NR1-NR2R3, wherein R1 and R2 are hydrogen or alkyl, R3 is hydrogen or an alkyl or acetyl radical and n is 1 or 2, excluding thioglycolic hydrazide.  The hydrazides may be prepared (a) by reacting NHR1-NR2R3 or a salt or hydrate thereof with an acylating derivative, e.g. a halide, amide, ester or anhydride, of the acid A-S-(CH2)n-COOH, preferably by heating in an inert solvent such as water or an alcohol; (b) when R1, R2 and R3 are all alkyl radicals, by reacting ASH with Hal-(CH2)n-CO-NR1-NR2R3 in presence of an acid-binding agent, or by using an alkali metal derivative of ASH in absence of such an agent; (c) for compounds where A is a substituted or unsubstituted hydrocarbon or acyl radical, by reacting HS-(CH2)n-CO-NR1NR2R3 either with DHal (where D is a substituted or unsubstituted hydrocarbon radical) in presence of an acid-binding agent, e.g. Na2CO3 or NaOH, or with an acylating derivative, e.g. a halide or anhydride or the corresponding thioacid E.COSH, of the acid E.COOH (wherein E is a hydrocarbon group which may be substituted by a nitro group); (d) for compounds where A is an acylamino substituted hydrocarbon group and R3 is alkyl or acetyl, by acylation of the corresponding amino substituted compound; (e) when R3 is an acetyl group, by acetylating A-S-(CH2)n-CO-NR1-NHR2 provided A does not contain an amino group; (f) where A is a hydrocarbon radical containing at least one acetylamino group, R1 and R2 are hydrogen and R3 is acetyl, by acetylating B-S-(CH2)n-CO-NH-NH2 (wherein B is a hydrocarbon radical containing at least one amino group).  In examples: (1) to (9) hydrazine or its hydrate and the appropriately substituted ethyl or methyl thioacetate, thiopropionate or thiodiglycollate give 2-(methylthio)-, 2-(ethylthio)-and 2-(allylthio) acethydrazide, the latter as its hydrochloride, b  - mercapto - propionhydrazide hydrochloride, monothiodiglycollic dihydrazide, 2 - (p - chlorophenylthio)-, 2 - (p - nitrophenylthio)-, 2 - (o - nitrophenylthio)-, 2 - (21:41 - dinitrophenylthio)-, 2 - (p - methylphenylthio)-, 2 - (o - methylphenylthio)-, 2 - (21 - methyl - 41 - chlorophenylthio)-, 2 - phenylthio-, 2 - (p-aminophenylthio)-, 2 - (p - acetylaminophenylthio)- and 2 - (p - propionylaminophenylthio)-acethydrazide, and 3-(p-nitrophenylthio) propionhydrazide; (10) 2-(p-acetylaminophenylthio) acethydrazide is acetylated to N-[2-(p-acetylaminophenylthio) acetyl]-N1-acetylhydrazine; (11) to (13) N-acetyl-N1-thioglycollylhydrazine with, respectively, p-chloro-nitrobenzene, benzyl halide, p-nitrobenzoyl chloride and thioacetic acid gives N-acetyl-N1-[2-(p-nitrophenylthio) acetyl] hydrazine, N-acetyl-N1 - [2 - (benzylthio) acetyl] hydrazine, N-acetyl-N1 - [2 - (p - nitrobenzoylthio) acetyl] hydrazine and N - acetyl - N1 - 2 - (acetylthio) - acetyl hydrazine; (14) methyl hydrazine sulphate and methyl 2 - (p - nitrophenylthio) acetate give N - methyl - N1 - 2 - (p - nitrophenylthio) acetyl-hydrazine; (15) and (16) 1 : 1-dimethylhydrazine and trimethylhydrazine give, respectively, with 2 - (p - nitrophenylthio) acetyl chloride, 1 : 1 - dimethyl - 2 - [21 - (p - nitrophenylthio) acetyl] hydrazine and N : N : N1-trimethyl-N1-2 - (p - nitrophenylthioacetyl) hydrazine; (17) chloroacetyltrimethylhydrazine and sodium-p-nitrothiophenate give the product of (16); (18) and (19) thioglycollic hydrazide and, separately, 2 - (p - aminophenylthio) acethydrazide are acetylated to give, respectively, N-acetyl-N1-thioglycollyhydrazine and N-[2-(p-acetylaminophenylthio) acetyl] - N1 - acetylhydrazine; the following are similarly prepared:-N-acetyl-N1-2-(phenylthio) acetylhydrazine, N : N1-diacetyl-monothiodiglycollicdihydrazide, N-acetyl-N1-[2 - (p - nitrophenylthio) acetyl] hydrazine, N - acetyl - [2 - (41 - chloro - 21 - methyl - phenylthio) acetyl] hydrazine and N-acetyl-N1-[2-(p-propionylaminophenylthio) acetyl] hydrazine; (20) diethyl dithiodiglycollate and hydrazine hydrate give dithioglycollic dihydrazide.  In the Provisional Specification the substituents which A may bear are not specifically defined.  Methyl 2-(p-chlorophenylthio) acetate is prepared from methyl chloroacetate and sodium p-chlorothiophenate.  Methyl 2-(p-aminophenylthio) acetate is prepared either by reduction of the corresponding nitro compound or by esterification, and is acetylated to methyl 2-(p-acetylaminophenylthio) acetate.  Chloroacetyltrimethylhydrazine is prepared from trimethylhydrazine and chloroacetyl-chloride.