Nitrite esters, a-amino

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. 

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solution for 24 hours, N-nitrosodiphenylamine was produced in quantitative yield (M. Nakajima and J.-P. Anselme, unpublished results).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. 

As the proton release is often too slow under the acidic conditions used for the diazotization of aromatic amines, syntheses of aliphatic diazo compounds by this method are carried out without an excess of mineral acid. Usually, equimolar amounts of amine, HCl and NaN02, or amine and NOCl, are used. A better alternative is nitrosation with pentyl nitrite in the presence of up to 30% acetic acid, as found by Takamura et al. (1975). Yields higher than 60% were obtained with a-amino-substituted esters of some aliphatic carboxylic acids. 

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. 

Eow-spin Fe porphyrins continue to be of major interest to many investigators, both because of the large number of different low-spin complexes that can be prepared, and because of the relevance of this spin state to a variety of heme proteins. Ligands that give rise to low-spin complexes of Fe porphyrins include two imidazoles, two imidazolates, two pyridines (for TPPs but not OEP and natural porphyrins for lower-basicity pyridines), " two thioethers, two thiolates, two isocyanides, two phosphines, two anunonia molecules, two primary amines (as amino acid esters), two cyanides, two nitrite ions, two methoxide ions, two alkyl... 

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). ... 

Nitrosation takes place in the benzenoid 5-position in pyrimidines with three strongly electron-donating groups, e.g., 0x0, thioxo, or amino groups. In disubstituted pyrimidines, the relative positions of the substituents are decisive for any reaction 4,6-diamino- and 4,6-dihydroxy-pyrimidines are 5-nitrosated whereas their 2,4-isomers fail to react. Nitrosation is brought about by nitrous acid or by nitrite esters. When the reaction is slow, an alkyl substituent may be nitrosated on the a-carbon the product is an oxime. An extensive review on nitrosopyrimidines is available [Pg.120]

Amino-3-methylisothiazole has been converted, by way of the diazonium salt, into 3-methyl-5-nitroisothiazole. Treatment of 3,5-dichloro-isothiazole-4-carbonitrile with sodium or silver nitrite yields the 5-hydroxy-compound, presumably via an unstable nitrite ester a nitro-compound is not obtained. ... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

The (R)-enantiomer of (242) has also been prepared and used as a chiral auxiliary in an enantioselective aldol synthesis of (+)-(S )-gingerol (79CB3703). (R )-Glutamic acid (246) was thus converted into (i )-pyroglutamic acid by simply heating in water. Conversion of (247) to its methyl ester and LAH reduction delivered alcohol (248). Ethyl nitrite treatment of (248) gave nitrosoamine (249), which was methylated to furnish (250). Exposure of (250) to LAH completed the synthesis of the required chiral auxiliary RAMP [(R)- l-amino-2-(methoxymethyl)pyrrolidine]. The hydrazone (252), derived from RAMP and acetone, was... 

An aqueous solution of sodium nitrite that is treated with HC1 contains nitrosyl cations 0=N . These can react with the enol E of the malonic acid diethyl ester (cf. Figure 12.9, bottom). First, a nitroso compound (F) is formed, which then undergoes acid-catalyzed isomerization to give the oxime A. Usually, the oxime is reduced by zinc, which is dissolved in acetic acid, to yield an amine that normally undergoes in situ acetylation in acetic acid. In this way the (acetamido)malonic acid diethyl ester B is obtained as the reduction/acetylation product, which can be employed, for example, in the synthesis of amino acids (Figure 13.39). 

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