A-nitroso compound

A Alkylarylammes resemble secondary alkylammes m that they form A nitroso compounds on reaction with nitrous acid... 

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

There are several useful syntheses which effectively commence with the cycloaddition of oxygen, a nitroso compound, an azo compound or a sulfinylamine to a 1,3-diene leading to the corresponding 1,2-dioxins, 1,2-oxazines, pyridazines or 1,2-thiazines. Examples of the transformation of these adducts into five-membered heterocycles are shown in Scheme 114 together with leading references. 

With a peroxyacid, the reagent used in their preparation, oxaziridines further react to yield aliphatic nitroso compounds. An electrophilic attack to ring nitrogen is plausible, leading to an intermediate oxaziridine N-oxide (81), which immediately decomposes to a nitroso compound and an aldehyde (57JA6522). 

Electrophilic nitrosation of the carbanion generated from the reaction of an organic base with a strong organic acid, such as a-hydrohexafluoroisobutyronitnle [2], a hydrohexafluoroisobutyric acid or its acid chloride [2], or a hydrotetra fluoroethanesulfonyl fluoride [4], yields the corresponding a-nitroso compound as the major product (equations 2 and 3) The a-hydrohexafluoroisobutyric acid or acid chloride reacts with excess trifluoroacetyl nitrite in dimethylformamide to afford the O substituted oxime [3] (equation 4)... 

When primary fflnines are nitrosated, then- A/-nitroso compounds can t be isolated because they react further. 

Scheme 10.1 Thetmal or photochemical generation of a nitroso compound...

A -Nitroso derivatives, prepared from secondary amines and nitrous acid, are cleaved by reduction (H2/Raney Ni, EtOH, 28°, 3.5 h CuCl/concd. HCF). Since many A -nitroso compounds are carcinogens, and because some racemiza-tion and cyclodehydration of A -nitroso derivatives of A -alkyl amino acids occur during peptide syntheses, A -nitroso derivatives are of limited value as protective groups. 

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

In a reaction similar to 12-50, azoxy compounds can be prepared by the condensation of a nitroso compound with a hydroxylamine. The position of the oxygen in the final product is determined by the nature of the R groups, not by which R groups came from which starting compound. Both R and R can be alkyl or aryl, but when two different aryl groups are involved, mixtures of azoxy compounds (ArNONAr, ArNONAr, and Ar NONAr ) are obtained and the unsymmetrical product (ArNONAr ) is likely to be formed in the smallest amount. This behavior is probably caused by an equilibration between the starting compounds prior to the actual reaction (ArNO -I- Ar NHOH Ar NO - - ArNHOH). The mechanism has been investigated in the presence of base. Under these conditions both reactants are converted to radical anions, which couple ... 

These radical anions have been detected by ESR. This mechanism is consistent with the following result when nitrosobenzene and phenylhydroxylamine are coupled, and N labeling show that the two nitrogens and the two oxygens become equivalent. Unsymmetrical azoxy compounds can be prepared by combination of a nitroso compound with an N,N-dibromoamine. Symmetrical and unsymmetrical azo and azoxy compounds are produced when aromatic nitro compounds react with aryliminodimagnesium reagents, ArN(MgBr>2. ... 

Azoxy compounds can be obtained from nitro compounds with certain reducing agents, notably sodium arsenite, sodium ethoxide, NaTeH, NaBH4—PhTeTePh, and glucose. The most probable mechanism with most reagents is that one molecule of nitro compound is reduced to a nitroso compound and another to a hydroxylamine 119-42), and these combine (12-51). The combination step is rapid compared to the reduction process. Nitroso compounds can be reduced to azoxy compounds with triethyl phosphite or triphenylphosphine or with an alkaline aqueous solution of an alcohol. ... 

Rose SL, Jurs PC. Computer-assisted studies of structure-activity relationships of A-nitroso compounds. J Med Chem 1981 25 769-76. 

The joint action of di-/-butyl nitroxide radicals and tetranitromethane on the hydrazine 371 in ether at room temperature yielded 75% of the A-nitroso compound 372, together with 10% of the dinitrohydrazone 373413. 

TABLE 7. A-Nitroso compounds in the diet, carcinogenicity and occurrence"... 

The possible health hazards associated with the smoking of food are caused by carcinogenic compounds from wood smoke that are found in smoked meats, fish, and cheese. These compounds include PAHs, A-nitroso-compounds (NNCs), and HAs. 

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