Nitrosopiperazines

Hansen, L. C. Hribar, J. D. Levon, E. F. Shubeck, M. B. Wagner, H. The analysis and source of 1-diphenylmethyl-4-nitrosopiperazine in l-diphenylmethyl-4-[(6-methyl-2-pyridyl) methyleneamino]piperazine A case history. In Walker, E. A. Castegnaro, M. Griciute, L. Lyle, R. E.,... 

The elementary analysis is in agreement with the theoretical values. The starting l-amino-4-cyclopentylpiperazine (b.p. 80°-82°C/0.1 mm Hg) is obtained by alkylating N-nitrosopiperazine with cyclopentyl bromide in ethanol in the presence of NaHC03 and reducing the so-obtained l-nitroso-4-cyclopentylpiperazine with LiAIH4 in ethyl ether. 

There are several preparative routes to N-nitrosopiperazines, illustrated by the following examples ... 

Piperazine (25) gave 1-nitrosopiperazine (26) [substrate, (KS03)2N0, Na2C03, H20—pyridine H2NOH.HCl J, 20°C, 15 min 98% the mechanism appears to involve the unisolated complex (24)].1074... 

Note Although such a procedure was successful in related series, 4-methyl-1-piperazinamine (27) failed to give l-methyl-4-nitrosopiperazine (28) on treatment with tri-tert-butylamine oxide in tetranitromethane.1082... 

A few reactions of A-nitrosopiperazines have been reported recently. At least some such piperazines undergo facile transnitrosation and may be used to nitrosate other secondary bases or the like. For example, 2,6-dimethyl-1,4-dinitrosopiperazine (31) with piperidine (32), at pH 1.7 in the presence of sodium thiocyanate as catalyst, gave 2,6-dimethyl-4-nitrosopiperazine (33) and 1-nitrosopiperidine (34).763,cf-954... 

The reduction of A-nitroso- to A-aminopiperazines is sometimes useful. Thus 1-methyl-4-nitrosopiperazine (35) afforded 4-methyl-l-piperazinamine (36) by refluxing with aluminum hydride in ether for 10 h (88% yield)449 or by treatment with zinc in acetic acid (>30% yield).1016, cf 982... 

SYNS N -METHYL-N-NITROSOPIPERAZINE 1-METHYL-4-NITROSOPIPERAZINE N-NITROSO-N -METHYLPIPERAZIN (GERMAN) O N-NITROSO-N -METHYLPIPERAZINE... 

METHYL-4-NITROSOPIPERAZINE see NKW500 N -METHYL-N-NITROSOPIPERAZINE see NKW500 N-METHYL-N-NTTROSO-1 -PROPANAMINE see MNAOOO... 

The chemical shift of the A -methyl group of various 1,4-dimethyl-piperazinium dichlorides has been examined in the presence of a-substituents and the basicities of nitrogens 1 and 4 and the nitrogen 1 inversion rate, in HjO and DjO at 33°, have been determined by analysis of this signal in the case of 1,4-cis-(2,6)-tetramethylpiperazine (1681). Carbon-13 chemical shifts have been measured for a number of substituted nitrosopiperazines (1682), and the population ratio of the ee and ae + ea conformations in 1,4-dichloropiperazine at — 45°C was determined as 3 1 (AG° = 0.5 kcal/mol) (1683). 

In most patients, piperazine is free of adverse reactions. Mild gastrointestinal disturbances may occur neurotoxicity is rare. Eczematous skin reactions, lacrimation, rhinorrhea, joint pains, productive cough, and bronchos-pasm can develop after sensitization, especially with occupational exposure. Urticaria has also been reported. When hypersensitivity reactions occur it should be withdrawn and not used again in the same patient. Mononitrosylation of piperazine can occur in the stomach, releasing the potential carcinogen A-mono-nitrosopiperazine, but there is no direct proof of risk in human subjects. 

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