Nitrous acid reaction with hydrazine

The tetrazoloquinoline such as 789 are readily prepared by reaction of 2-hydrazinocinconic acid 788 with nitrous acid (91KG1227). Reaction of 790 with hydrazine introduces hydrazine residues at positions 2, 6 and 7 whose reaction with nitrous acid gave 791 (90M1017) (Scheme 139). 

Monosubstituted hydrazines treated with nitrous acid give azides in a reaction exactly analogous to the formation of aliphatic diazo compounds mentioned in 12-47. Among other reagents used for this conversion have been N204 ° and nitrosyl tetrafluoroborate (NOBp4). ... 

The main starting compound is the labeled nitroguanidine 257 obtained from guanidine with isotope-labeled potassium nitrate. Reduction of 257 to hydrazine carboximidamide 258 was carried out with zinc and, then, ring closure to 3-amino[l,2,4]triazole 259 was carried out using formic acid. Finally, the ring closure to form the [l,2,4]triazine ring - similar to other procedures presented in Scheme 54 - was perfected by reaction with nitrous acid followed by treatment with ethyl nitroacetate to 260. 

Recently a novel member of the meso-ionic class of l,2,4-triazole-3-thiones (227) has been described. Heating the sodium salt, Ph-CO-NPh-NH-CS—S-CHj—COjNa, with hydrazine gave the compound 227, R = R = Ph, R = NHj, which was characterized as a monobenzylidene derivative. The meso-ionic hydrazine derivative 227, R = R = Ph, R = NHj, undergoes an interesting reaction with nitrous acid, yielding the l,2,4-triazoline-3-thione (239). ... 

Amino-5-aryl-l,3,4-oxadiazoles form stable N-nitrosamines (71c) which are converted into hydrazines (7ld) with zinc in acetic acid. Treatment of the hydrazine (71d) with nitrous acid yields the corresponding azide and with benzaldehyde a hydrazone is formed (B-61MI42300). On heating in benzene or in nitrobenzene, the nitrosamine (71c) undergoes the Gomberg-Bachmann reaction to yield 2,5-diaryl-l,3,4-oxadiazoles (73JCS(P1)1357). 

Diphenylhydrazine is oxidized to diphenylnitrosamine (50%) by potassium superoxide. The same reagent also oxidizes 1-methyl-1-phenylhydrazine, but here the nitrosamine is a minor product the major reaction is deamination. A better meAod of oxidative deamination of some 1,1-disubstituted hydrazines and hydrazinium salts is reaction with nitrous acid. Thus, several hydrazinium salts MezRN NHi X were deaminated to the tertiary amine by treatment with nitrous acid. The method has also been used to deaminate IV-aminoheterocyclic compounds for example, some 1,2,3-triazoles are conveniently prepared by deamination of the corresponding 1-aminotriazoles with nitrous acid. °... 

Preparation. Hiis stable, crystalline white solid is readily prepared as shown, starting with the condensation of benzhydrol and methyl chlorothiolcarbonate to produce the ester (1). The crude ester is treated in ether with hydrazine in methanol to form the hydrazide (2) and this is converted into the azide (3) by reaction with nitrous acid. 

The racemic acid (78) was converted into the acid chloride (80) by reaction of its sodium salt with oxalyl chloride in benzene. Compound (80) was treated with anhydrous hydrazine to afford the hydrazide (81). Reaction with nitrous acid followed by photolysis of the resulting azide (82) gave the desired 5-lactam (83). 

Asymmetrically substituted hydrazines can be converted to N-nitro-soamines by reaction with nitrous acid. They can be detected by using the Liebermann reaction (p. 195). 

Treatment of piperidine with nitrous acid affords the N-nitroso derivative (190) reduction gives the corresponding hydrazine (191). Condensation of this intermediate with the carbamate (192) obtained from p-toluenesulfonamide leads to the oral hypoglycemic agent tolazemide (193). In a similar vein, reaction of the hydrazine obtained by the same sequence from azepine (194) with the carbamate, 188, gives azepinamide (195). ... 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Fused ring tetrazoles such as 96 are obtained from the reaction of nitrous acid with heterocyclic hydrazines (95) (Eq. 19).159 160 This method is also suitable for the preparation of fused ring ditetrazoles such as... 

Tricyclic antihistamines as a rule carry aliphatic nitrogen as a substituent on a side chain attached to the central ring the side chain nitrogen may be part of a heteroaromatic ring. Conjugate addition of p-chloroaniline (49) to the substituted vinylpyridine 50 gives the alkylated aniline 51. Treatment of that intermediate with nitrous acid leads to N-nitroso intermediate 52 which is then reduced to the hydrazine (53). Reaction of 53 with N-methyl-4-piperidone... 

Sugar lactones react readily with hydrazine to give crystalline derivatives useful for isolation and identification (127). Thus, addition of hydrazine to a reaction mixture containing an aldonolactone facilitates isolation of the product. The lactone may be regenerated from the hydrazide by treatment with nitrous acid (128). The phenylhydrazides obtained on treatment of aldonolactones with phenylhydrazine are also useful for characterization (129,130). 

C. Reaction of Hydrazine and Derivatives with Nitrous Acid to Give Azides 280... 

Hydrazine substituents attached to triazolopyridines undergo normal reactions (for oxidative removal see Section IV, A,3). Treatment with nitrous acid gives an azide216 except in the case of compound 303 when cyclization occurs.16 ... 

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