N-Nitroso amides

Other compounds with nitrogen-nitrogen bonds have been used instead of diazonium salts. Among these are N-nitroso amides [ArN(NO)COR], triazenes, and azo compounds. Still another method involves treatment of an aromatic primary amine directly with an alkyl nitrite in an aromatic substrate as solvent. ... 

The aryl radical thus formed attacks the substrate to give the intermediate 1 (p. 898), from which the radical 26 abstracts hydrogen to give the product. N-Nitroso amides probably rearrange to N-acyloxy compounds, which cleave to give aryl radicals ... 

For a report of formation of about 15% ortho product in the case of N,N-diaryl-N-nitroso amides, sec Titova Arinich Gorelik /. Org. Chem. USSR 1986, 22, 1407. 

Analoge Verfahren existieren fur sek. Amide. Hierzu sind u. a. die Nitrosierung mit Nitro-sylchlorid413 oder Natriumnitrit414 in Acetanhydrid oder Tetrachlormethan zu zahlen. Die primar gebildeten N-Nitroso-amide zerfallen thermisch in die entsprechenden Carbonsauren. 

Bei der Umsetzung von Alkyl(Aryl)amiden mit Natriumnitrit bzw. Distickstofftetroxid entstehen uber die Zwischenstufe der N-Nitroso-amide unter Stickstoff-Abspaltung die entsprechenden Carbonsaure-ester363. 

This problem is not encountered in the thermal rearrangement of N-nitroso amides (7.10, R = alkyl). Aliphatic N-nitroso amides were first studied by von Pechmann (1898 a). The rearrangement was originally investigated and elucidated for aromatic A-nitroso amides by Huisgen and others (see summary by Zollinger, 1994, Sect. 6.7.5). 

N-Nitroso amides can also be used for the formation of alkyldiazenolates (7.9) by bases. Alkyldiazenolates can be isolated from aprotic solvents as alkali metal salts, as found by Hantzsch and Lehmann (1902). More modern procedures have been described by Tandy and Jones (1965) and by Moss (1966). One obtaines the (Z)-diazenolate, as confirmed by X-ray analysis (Muller et al., 1963). From Scheme 7-3, one might assume that the route starting with diazenolates will lead to the same products as the nitrosation of alkylamines because the diazenol is common for both pathways. 

The last-mentioned disadvantage of deaminations of amines with nitrosating compounds in aqueous and other protic solvents is, of course, not present if N-nitroso amides and related compounds discussed earlier (7.10, and footnote on p. 246, concerning White s pioneering work) are used in aprotic solvents. 

In conclusion, we propose a specific research program for deaminations in aqueous systems based on ideas mentioned in this section, namely to investigate (a) deamination kinetics and products of a series of simple aliphatic amines in water with sodium nitrite and perchloric acid at various acidities, (b) decompositions of diazenolates of the same amines in water and (c) decompositions of a standard type of N-nitroso amides, again of the same amines and all in the same aprotic solvent. The reaction conditions should be as similar as possible in the experiments of all three series. The series of amines should include methyl-, ethyl-, 1-methylethyl-, 1-methylpropyl-, and ( cr butyl)amine and [l- H]ethylamine, but not amines with longer aliphatic chains, as the very informative work of Southam and Whiting (1982) demonstrated clearly that, in deaminations of such amines, many mechanistically complex products are formed. In addition, micellar effects increase the complexity of reactions with such amines (see Sect. 7.3). It is obvious from the series of amines that we have proposed that this program is based on the work of Brosch and Kirmse (1991), Hovinen and Fishbein (1992), Hovinen et al. (1992), Finneman et al. (1993), and Ho and Fishbein (1994). Work with chiral 1-methylpropyl- and [l- H]ethyl-amine will provide information on the stereochemistry of these reactions. 

Investigations with N-nitroso amides and related N-nitroso compounds have the advantage that many difficulties with combined nitrosation and dediazoniation processes (as discussed above) can be avoided. Their results cannot, however, always be applied for an understanding and improvement of the most classical deamination method, i. e., the hydroxy-de-amination of an amine in an aqueous nitrosation. 

Carboxylic acids, their esters, and amides are usually resistant to sodium borohydride reduction, whereas carboxylic acid chlorides may be reduced in inert solvents to give alcohols. Where this proves unsatisfactory a new alternative procedure for acid chloride reduction in ether solution involves sodium borohydride adsorbed on alumina. Other recently published borohydride reductions of acid derivatives to primary alcohols include those of the 1-succinimidyl esters (8)" and the N-nitroso-amides (9). 2-Methoxyethoxymethyl (MEM) esters have the possibility of co-ordinating the metal cation of complex hydrides at the MEM group, and hence of activating the carbonyl group towards reduction by intramolecular hydride delivery. The selective reduction of the less hindered ester group in the bis-MEM ester (10) to give (11) illustrates this idea. 

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