Ring nitrosation

Secondary aromatic amines form /V-nitrosamines and tertiary aromatic amines undergo ring nitrosation to yield C-nitroso products. 

Ring nitrosation with nitrous acid is normally carried out only with active substrates such as amines and phenols. However, primary aromatic amines give diazonium ions (12-47) when treated with nitrous acid, " and secondary amines tend to give N-nitroso rather than C-nitroso compounds (12-49) hence this reaction is normally limited to phenols and tertiary aromatic amines. Nevertheless secondary aromatic amines can be C-nitrosated in two ways. The N-nitroso compound first obtained can be isomerized to a C-nitroso compound (11-32), or it can be treated with another mole of nitrous acid to give an N,C-dinitroso compound. Also, a successful nitrosation of anisole has been reported, where the solvent was CF3COOH—CH2CI2. " ... 

None of the C7H9N isomers in this problem is a tertiary amine hence none will undergo ring nitrosation. 

Ring nitrosation is an electrophilic aromatic substitution reaction, in which the... 

The reasons for this apparent polywalent activity toward nitrosation (N ring reaction, N exocyclic reaction, nitrosation on the 5-position) are not... 

Tertiary alkylamines illustrate no useful chemistry on nitrosation Tertiary aryl-amines undergo nitrosation of the ring by electrophilic aromatic substitution... 

Nitrosation (Section 22 15) The reaction of a substance usu ally an amine with nitrous acid Pnmary amines yield dia zonium 10ns secondary amines yield N nitroso amines Tertiary aromatic amines undergo nitrosation of their aro matic ring... 

Caprolactam was first successfully polymerized to Pedon in 1938 by I. G. Farben and the associated technology was acquired as a part of postwar reparations by the Western AUies and the former USSR (1). By 1965 other countries, eg, Italy and Japan, had developed their own caprolactam processes, each involving nitrosation of an aUphatic ring. 

The nitrosation of pyrroles and indoles is not a simple process. The 3-nitroso derivatives (84) obtained from indoles exist largely in oximino forms (85) (80IJC(B)767). Nitrosation of pyrrole or alkylpyrroles may result in ring opening or oxidation of the ring and removal of the alkyl groups. This is illustrated by the formation of the maleimide (86) from 2,3,4 -trime thylpyrrole. 

In a study of the nitrosation of camphor-3-glyoxylic acid (89), Chorley and Lapworth isolated a compound whose structure (90) has recently been clarified by Hatfield and Huntsman. Decarboxylation and ring expansion occur and the reaction is rationalized in the sequence 89 90. The buttressing effect of a methyl group on... 

A number of benzodiazepines have heterocyclic rings anne-lated to them. One such is the tranquilizer midazol am (94). Nitrosation (HONO) of secondary amine leads to the ] -nitroso analogue Nitrosoamidines, in the presence of carbanions,... 

Nevertheless, the reaction in region B has other unusual features, notably in the pattern of substituent effects for 4-substituents this is the reverse of that observed in region A. From these and other considerations, Ridd s group (Challis and Ridd, 1962 de Fabricio et al., 1966) concluded that the nitrosating agent attacks the pro-tonated amine and is loosely associated with the aromatic ring in the transition state. 

The C-nitrosation of aromatic compounds is characterized by similar reaction conditions and mechanisms to those discussed earlier in this section. The reaction is normally carried out in a strongly acidic solution, and in most cases it is the nitrosyl ion which attacks the aromatic ring in the manner of an electrophilic aromatic substitution, i. e., via a a-complex as steady-state intermediate (see review by Williams, 1988, p. 58). We mention C-nitrosation here because it may interfere with diazotization of strongly basic aromatic amines if the reaction is carried out in concentrated sulfuric acid. Little information on such unwanted C-nitrosations of aromatic amines has been published (Blangey, 1938 see Sec. 2.2). 

The kinetics of aromatic nitrosation at ring carbon have received little attention. The first attempt to determine the nature of the electrophile was made by Ingold et a/.117, who measured the rates of the nitrous acid-catalysed nitration of 4-chloroanisole by nitric acid in acetic acid which proceeds via initial nitrosation of the aromatic ring. Assuming that the electrophiles are the nitrosonium ion and... 

It is claimed that the limiting value of k bs, 2.81 x 10" sec-1, represents the rate coefficient for the rearrangement reaction above (k,). The ring deuterium isotope effect kH kD was re-determined for this individual rate coefficient for rearrangement by finding the limiting value in the presence of added N-methylaniline and was found to be 2.4 at two different acidities, as compared with 1.7 for the ratio of the observed composite rate coefficients, as expected, since no isotope effect would be predicted for the de-nitrosation step. 

Scheme 26, which recalls the classic reactions involved in the synthesis of 50 from small, common molecules, will help in following the methods used for labeling the imidazole ring of AIRs. Nitrosation with (l5N)NaN02 allowed the preparation of AIRs labeled on N-3. When methyl cyanoacetate was prepared with (i5N)KCN, AIRs labeled on the amino nitrogen were obtained. 

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