N-Nitrosoamides

Reaction of metal hydride complexes with N-nitrosoamides, e.g. Af-methyl-7V-nitrosourea ... 

N-Substituted amides can be converted to N-nitrosoamides, which are more easily hydrolyzable than the orginal amide. For example, see Rull, M. Serratosa, F. Vilarrasa, J. Tetrahedron Lett., 1977,A5A9. For another method of hydrolyzing N-substituted amides, see Flynn, D.L. Zelle, R.E. Grieco, PA. J. Org. Chem., 1983, 48, 2424. Ladenheim, H. Bender, M.L. J. Am. Chem. Soc., 1960, 82, 1895. 

General Preparation of N-Alkyl-N-nitrosoamides with Sodium Nitrite in Acetic... 

Alkyl Af-nitroso-A -alkylcarbamates, 441 N-Alkyl-N-nitrosoamides, 435 7V-Alkyl-7V-nitroshydroxylamines, 447 l-Alkyl-2-phenylhydrazines, 327 Allene dipropargyl phosphonate, 31 Allenes, 1-40, see also names of specific allenes, 1,2-Dienes... 

The products formed in deamination depend on the lifetimes of the different ion-pair species, which, in turn, depend on the structure of the amine and the nature of the solvent. The counter-ion in such reactions can conveniently be varied by using N-nitrosoamides as starting materials. These compounds react to give diazonium ion-pairs in reactions that closely resemble amine deamination, and the lifetime of the ion-pairs can be studied by using lsO-labelled ni-trosoamides (see Scheme 2, XH = solvent or added nucleophile). 

A similar trend has been observed for the closely related, N-nitrosoamide decomposition see Ref. 23. 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

RCH2NH2 - RCH2OH. One method for this conversion is the thermal rearrangement of N-nitrosoamides derived from RCH2NH2. An improved procedure is based on the observation that the N-nitrosoamides derived from a trihaloacetamide of RCH2NH2 can rearrange at 0° in the presence of HOAc.1... 

Biaryls are produced in low yields by several related coupling reactions. When benzenediazonium chloride is treated with aqueous sodium hydroxide in the presence of benzene, nitrogen is eliminated and biphenyl is formed in 22% yield. Better results are sometimes obtained when the sodium hydroxide is replaced by sodium acetate or when stabilized diazonium salts are employed. In the former modification the aryl-diazoacetate, ArN = NOCOCHj, is an intermediate product. The tautomeric forms of the aryldiazoacetates are N-nitrosoamides, ArN(N0X30CH, which are obtained by the action of nitrous fumes or nitrosyl chloride on... 

The rearrangement of N-alkyl-N-nitrosoamides has contributed much to the delineation of scheme 5. The reaction has been shown to proceed with the formation of a diazoester intermediate which fragments to a diazonium ion pair as shown below (White, 1955 White and Aufder-marsh, 1961b Huisgen and Reimlinger, 1956a and b). 

The results for the two reactions are quite close, and the known formation of carboxylate esters with incompletely equilibrated oxygens in the rearrangement of N-nitrosoamides (White and Aufdermarsh, 1961b) suggests that the small discrepancy may be due to the fact that the rate of equilibration provides too low a measure of the fraction of... 

Amines and their Derivatives.—In continuation of mechanistic studies on deaminations, " the N-nitrosoamides (435 R = Me, 2-naphthyl, or benzyloxy) derived from 3a- and 3) -amino-5a-cholestane have been formed and allowed to decompose in a variety of non-polar solvents. The resulting esters (436) showed predominant retention of configuration, accompanied by appreciable inversion. The outcome of experiments under carefully devised conditions appears to establish an intramolecular mechanism, even when inversion occurs. 4-Aza-cholest-5-en-3-one and its N-methyl derivative reacted with nitrous acid to give complex mixtures of products, derived via nitrosation of the olefinic bond at C-6. ... 

The substituents in I and II are generally alkyl and aryl groups. However, recently imidoyl chlorides having N-carbethoxy and N-cyano groups have been synthesized. Dichlorination of aliphatic isocyanates in the a-position yields N-chlorocarbonyl-substituted imidoyl chlorides, and C-cyano-substituted imidoyl chlorides were found to be intermediates in the 1,2-rearrangement of N-nitrosoamides, using phosphorus pentachloride. 

Other derivatives of amides, such as N-nitrosoamides acylcar-bamates and N-phosphoryl amides (78.ioo,i83-i85 likewise... 

There has been much interest in the synthesis and investigation of N-nitrosoamides, which are known to be potent carcinogens. Nitrosation by the use of NO has been reported [37] ... 

This reaction system can exclude oxygen at least to the order of 1 pi of O in 22.4 ml of NO. The solvent effect was investigated using Ph-C(=0)-NH-CH2Ph as a substrate. The yields of N-nitrosoamides suggest that oxygen-containing solvents (acetone,... 

THF, CHjOH, dimethylformamide (DMF)) are totally ineffective. On the contrary, the use of non-oxygen solvents such as CCl or 1,2-dichloroethane resulted in the formation of N-nitrosoamides in good yields (77-94%). The influence of oxygen was investigated for elucidation of the active species of the reaction (Equation 3.32). The addition of linearly increased the yield of N-nitrosoamides. Thus, it is undeniable that the reaction proceeded by participation of a trace amount of N O. ... 

The readily available /3-lactam amides (36) have not been used very often because of the difficulty of converting the amide into an acid or ester in the presence of the /3-lactam ring. This conversion has now been achieved in moderate yield, in a wide range of examples, by the formation of the corresponding N-nitrosoamides followed by thermal decomposition into esters (Scheme 27). ... 

A new procedure for converting amines and amides to the corresponding azides is exemplified in Scheme 6. It involves controlled reduction of N-alkyl-N-nitrosoamides to hydrazides, e,g., (26),... 

Sather AC, Berryman OB, Ajami D, Rebek J Jr (2011) Reactivity of N-nitrosoamides in confined spaces. Tetrahedron Lett 52(17) 2100-2103... 

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