A-Amino nitrite

Thus the postulate that a-amino nitrite esters could form and fragment to nitrosamines has provided a useful construct for explaining some aspects of the nitrosative dealkylation of tertiary amines and their derivatives. 

These seemingly anomalous results suggest that the formation and fragmentation of a-amino nitrite esters could be playing a central role in the nitrosation of aminopyrine. The characterization of both fast and slow reactions, as well as the identification of two pH optima, imply that more than one kinetically significant pathway is involved in the overall transformation. The mechanism of Fig. 5a could well be the first order component the kinetic studies show to be operative under some conditions. It is noteworthy that this pathway also leads directly in its final step to the keto-enol derivative IV, which Mirvish et al. have identified as a by-product of aminopyrine nitrosation. 

An apparent order in nitrite of 3 or more would also be consistent with a-amino nitrite fragmentation mechanisms if one assumes that nitrite is preferentially consumed in redox or nitrosation reactions elsewhere in the molecule which compete with nitrosation of the dimethylamino group. One such possibility was suggested by Dr. R.N. Loeppky (private communication), as shown in Fig. 6. This mechanism, which postulates the intermediacy of two different o-amino nitrites, le and If, should obey third order kinetics, since dimethylnitrosamine is produced only after aminopyrine reacts with the third mole of nitrite. Moreover, this pathway offers a mechanistic explanation for the direct production of nitrosohydrazide V, which has also been reported to be a product of aminopyrine nitrosation (12.17). 

It is possible that structural analogs of the a-amino nitrite esters might also be intermediates in nitrosamine-forming re-... 

Another possible mechanism for this reaction was suggested by Dr. G.R. Krow (private communication), this one involving a a bona fide a-amino nitrite ester as an intermediate. If the qumone monoxime tautomer of the nitrosophenol were reacting as an electrophilic carbonyl compound with the amine according to Fig. 3, the resulting immonium ion, VII, could attack nitrite to yield the nitrosamine via intermediate Ih with regeneration of the nitrosophenol. This proposal is summarized in Fig. 9. 

Thanks are due to the Editor of this volume for suggesting the similarity of N,N-disubstituted carbamoyl nitrites to the a-amino nitrite esters discussed above. When N,N-diphenyl carbamoyl chloride was refluxed with sodium nitrite in acetonitrile solution for 24 hours, N-nitrosodiphenylamine was produced in quantitative yield (M. Nakajima and J.-P. Anselme, unpublished results). The N,N-dibenzyl derivative underwent a similar reaction with nitrite. The mechanism shown in Fig. 13 was postulated to account for these transformations. 

One obvious reaction that proteins may undergo when exposed to nitrite is with the a-amino group (Van Slyke reaction). 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

Fischer polypeptide synthesis org chem A synthesis of peptides in which a-amino acids or those peptides with a free amino group react with acid halides of a-haloacids, followed by amination with ammonia. fish-ar pal-e pep,tTd. sin tha sas ) Fischer projection orgchem) A method for representing the spatial arrangement of groups around chiral carbon atoms the four bonds to the chiral carbon are represented by a cross, with the assumption that the horizontal bonds project toward the viewer and the vertical bonds away from the viewer fish-ar pra.jek-shon) Fischer s salt See cobalt potassium nitrite. fish-3rz solt)... 

A second order alternative in which the nitrosamine is produced in a Fig. 1 fragmentation of an o-amino nitrite is shown in Fig. 5c. This mechanism differs from the one proposed by Mirvish al. (12, summarized in Fig. 5b) only in involving the 0-nitroso rather than the C-nitroso function in co-elimination with the dimethyl amino group to produce the nitrosamine. 

In fact, even in such a low acidic medium, fluoride is not reactive enough to compete with strong nucleophiles and, for example, a-chloro or a-bromo acids can be obtained by halodediazoniation of a-amino acids with sodium nitrite/potassium chloride (or bromide) in 48% hydrogen fluoride/pyridine mixture.311... 

Human neutrophils use HOC1 formed by myeloperoxidase to oxidize a-amino acids such as tyrosine to reactive aldehydes that form adducts with -SH, -NH2, imidazole, and other nucleophilic groups.560 They also contain NO synthases, which form NO, peroxynitrite (Fig. 18-24), and nitrite.561562... 

An example of fluorodediazoniation of a-amino acids is the preparation of P-fluoroaspartic acid in 25% yield from 0c,P-diaminosuccinic acid and sodium nitrite in anhydrous hydrogen fluoride [4]... 

E. C. C. Baly and co-workers 2 showed that soln. of nitrates and carbonic acid are respectively converted into nitrite and formaldehyde in ultra-violet light, and these products then react to form formhydroxamic acid this acid then combines with more photosynthesized formaldehyde to give a variety of products —e.g. glyoxaline, free and substituted a-amino-acids, and substances of an alkaloidal nature. Methylamine and pyridine are produced by the action of... 

Acylaminomalonic esters and related reagents are widely used for the synthesis of a-amino acids. The method differs from those syntheses already discussed in that the amino group is incorporated into the system from the outset. A popular reagent is diethyl acetamidomalonate (35). The acetamido group can readily be introduced into the reactive methylene position in diethyl malonate by first converting the latter into the hydroxy-imino derivative (33) by reaction with nitrous acid or an alkyl nitrite (cf. Section 4.2.7, p. 413). This derivative is then reduced catalytically to diethyl aminomalonate (34) which is acetylated using acetic anhydride. 

The diazotizatioii/fluorodediazoniation of a-amino acids takes place with retention of configuration. Thus, when (S )-2-amino-3-cyclohexylpropioiiic acid (1) is treated with excess sodium nitrite in hydrogen nuoride/pyridine, (5 )-2-fluoro-3-cyclohcxyipropionic acid (2) is obtained without any racemization. ... 

Amino groups possessing replaceable hydrogen atoms react with nitrous acid. The tertiary amines are not affected, except for the formation of a salt (nitrite). Secondary amines with nitrous acid yield nitrosoamines. The nitrosoamine can be easily reduced back to the secondary amine by zinc and acid. 

Contrary to the case of free a-amino acids, deamination-substitution of esters of a-amino acids generally proceeds with racemization with excess inversion about the a-carbon atom. However, reaction of the ethyl ester of phenylalanine and its derivatives with sodium nitrite in trifluoroacetic acid affords substitution products with retention of configuration and migration products with inversion of configuration. This result may be explained by assuming initial formation of the phenonium intermediate (2 Scheme 6). ... 

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