JV-nitroso compounds and

In general, most types of C-nitroso compounds appear to be reactive heterodienophiles. On the other hand, JV-nitroso compounds and nitrosyl chloride do not usually undergo [4 + 2] cycloadditions.1 Much of the early work in this area can be found in the Hamer and Kresze reviews, which cover the literature through 1967.,a b This chapter will emphasize newer aspects of [4 + 2] cycloadditions involving nitroso dienophiles. 

Typical primary amines which undergo such nitrosation are m-toluidine, p-xylidine, m-anisidine, 2-amino-4-methoxytoluene, 3-amino-4-methoxy-toluene, m-aminophenol, a-naphthylamine, l-naphthylamine-2-, -6-, -7-, and -8-monosulfonic acids, and l-naphthylamine-4-monosulfonic acid (which reacts with displacement of the sulfonic acid group). The secondary amines derived from these primary amines also can be nitrosated directly (i.e., without the intermediate formation of an JV-nitroso compound which needs to be subjected to the Fischer-Hepp rearrangement). The entering nitroso group appears to substitute exclusively in the para position. 

Treatment of the JV-nitrosocyanides (283)198 or the W-nitrosoguanyl-hydrazines (284)199 with hydrogen chloride yielded the 1,2,3,4-oxatriazolium chlorides (285, X = Cl), which with aqueous sodium bicarbonate gave the meso-ionic l,2,3,4-oxatriazol-5-imines (277, R2 = H).198 Nitrosation of these compounds (277, R2 = H) gave the interesting JV-nitroso compounds (277, R2 = NO), and acylation gave the JV-acyl derivatives (277, R2 = RCO).198... 

Oxazolidinones react with nitrous acid, the resulting jV-nitroso compounds being decomposed by alkali to yield a variety of products alkynes, aldehydes and vinyl ethers. These transformations are rationalized by postulating the intermediacy of transient alkenediazonium ions (Scheme 27) (79CB2120). 

The following paragraphs describe the methods of forming azo compounds in which an N-N bond is created (for preparation by coupling see the Section on Preparation of the C-N bond by replacement .) These methods can be classified as (a) oxidative junction of amines (b) oxidation of hydrazo compounds (c) disproportionation of hydrazo compounds (d) action of hypochlorite on iV,jV -diarylsulfamides (e) condensation of nitroso compounds with amines (f) reaction of nitro compounds with amines (g) reduction of nitro and nitroso compounds and (h) reaction of JV-arylhydroxylamines with sulfinylimines. 

Nitrates and nitrites can give rise to other effects. They are, for example, able to decompose carotene. Nitrates affect the activity of the thyroid gland, which plays an important role in the conversion of carotene to vitamin A. The interactions of nitrites with amines are, however, much more dangerous, since they result in the production of jV-nitroso compounds. Many of these compounds damage the liver and exhibit teratogenic and carcinogenic effects [5, 15]. 

G. Neurath and M. Duenger, JV-Nitroso compounds from tobacco alkaloids. Beitr. Tabakforsch. 3, 339 (1966) CA 67, 64605 (1967). 

Castegnaro, M., Michelon, J., Walker, E. A. Some detoxifications methods for nitrosamine contaminated wastes, in JV-Nitroso Compounds Occurrence and Biological Effects (lARC Scientific Publications No. 41), (eds.) Bartsch, H., O Neill, I. K., Castegnaro, M., Okada, M., p. 151, Lyon, International Agency for Research on Cancer, 1982... 

Once again, biological interest in JV-nitroso-compounds has stimulated new syntheses of JV-nitrosoamines " and N-nitrosoureas. ... 

As indicated above, tertiary aromatic amines are directly C-nitrosated. The usual reagents are sodium nitrite and dilute hydrochloric acid, sodium nitrite and glacial acetic acid containing concentrated hydrochloric acid, and nitrite esters with hydrochloric acid [21a, 27]. While tertiary amines with such complex alkyl groups as found in A,A-di(3,5,5-trimethylhexyl)aniline are readily nitrosated [25], of the four A-butyl-A-methylaniline isomers, JV-r-butyl-A-methylaniline does not undergo the reaction, and even the nitroso compounds which did form were only unstable oils [27]. 

Broadly, NOC are divided into two groups (a) /V-nitrosamines and (b) N-nitrosamides. In jV-nitrosamines, the two remaining substituent groups on the >N—N=0 atom can be either alkyl or aryl, or they can form the part of a heterocyclic ring (as in N-nitrosopyrrolidine). On the other hand, in N-nitrosamides, more correctly called N-acyl-N-nitroso compounds, one of these... 

The jV-nitrosamines (and some C-nitroso compounds that yield nitrous acid when treated with concentrated sulphuric acid) may be detected by Lieber-mann s reaction (p. 1216). 

Oxaziranes are rapidly decomposed by the further action of peracids. As shpwn by Emmons24 and Krimm25 the oxazirane is converted into a carbonyl compound and a nitroso compound dimer. The reaction can be formulated via an oxazirane JV-oxide intermediate [Eq. (30)]. 

Not only simple iV-alkyl-iV-nitr osoanilines 303,308 undergo this reaction, but also ring-substituted aniline derivatives with a free />ara-position, such as iV-ethyl-jV-nitroso-n-toluidine,303 m-chloro- and m-bromo-iV-methyl-jV-nitro-soaniline,310 and iV-methyl-JV-nitrosoanthranilic acid 301,311 the C-nitroso derivative obtained from the last-mentioned compound can be hydrolysed to nitrosalicylic acid.312 Rearrangements of the derivatives of 1- and 2-naph-thylamine have been reported by several authors.305,308,309,313... 

Sulfonation of nitroso compounds by sodium hydrogen sulfite leads to amino sulfonic acids by simultaneous reduction.1240 194 When aromatic nitro compounds are subjected to this reaction, sulfonation in the ring is accompanied by formation of arylamine-JV-sulfonic acids (arylsulfamic acids), which on acid fission also give amino sulfonic acids this reaction, known in the literature as the Piria reaction, has been reviewed in papers by Hunter and his co-workers.195... 

Some of the most volatile priority pollutants that have been quantitated by HPLC are the JV-nitrosoamines. The dimethyl- to dibutyl-, piperidyl-, and pyrrolidyl-substituted A-nitroso compounds were well resolved as their 4-(2-phthalimidyl)ben-... 

The condensation of A(-alkyl- and JV-arylhydroxylamines with nitroso compounds leads ta the formation of azoxy compounds (equation 25). 

The amino groups of free amino acids and JV-terminal amino groups of proteins also react with free fatty acids and triacylglyc-erols, yielding the corresponding fatty acid amides. These may be precursors of non-volatile nitroso compounds (nitrosamides) classified as food contaminants (see Section 12.2.7.1). 

Vol. 28, p. 226, ref. 44 for related work). Similar cycloadditions of dienyl pyrrolidinones [le. AT-(peiita-l,3-dienyl)- or -(buta-l,3-dienyl)-pyrolidin-2-one] with the in situ generated acyl nitroso compound derived from benzyl-JV-hydroxy-carbamate with periodate have led to the preparations of racemic pyroUidines 56 and 57 (R = H or Me). The latter compound is thought to exist as a dimer. An asymmetric synthesis of l,S,6-trideoxy-l,5-imino-D-altritol in which the piperidine ring is formed from a pyiidinium ring bearing Seebach s oxazolidinone chiral auxiliary has also been described. ... 

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