Pyrrolidine, 2- -1-nitroso

V-Nitrosopyrrolidine. Pyrrolidine, 1-nitroso- (8,9) (930-55-2) Ethyl nitrite Nitrous acid, ethyl ester (8,9) (109-95-5)... 

Pyrrolidine, 2.5-dimethyl-, 1-nitroso-Pyrrolidine, 1-nitroso- NPYR ... 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

Barriers to rotation of nitrosamines in which the amino part is embedded in a cyclic system seem generally to be smaller. However, Harris and associates (82) reported that the barrier of /V-nitroso-2,2,5,5-tetramethylpyrrolidine (43) was over 22.6 kcal/mol. This must be higher than the barrier required for isolation of rotamers at room temperature, and is even higher than that in /V-nitroso-2,2,6,6-tetramethylpiperidine (44). Harris and Pryce-Jones attribute the high barrier of 43 relative to 44 to the more stable ground state of the former. If the pyrrolidine derivative is properly substituted, the atropisomers are expected to be isolable at room temperature. 

Of about 300 NNCs tested, some 90% have been found in animal experiments to be eareinogenic. iV-nitroso-dimethylamine is among the most carcinogenic NNCs, while the activity of N-nitroso-pyrrolidine is about 100 times lower. 

The nitrosation of 2,5-diphenylpyrrolidine in an ice-cold solution of ethanol and hydrochloric acid with sodium nitrite produced the expected iV-nitroso-2,5-diphenylpyrrolidine. The product could be separated into trans and cis isomers by fractional crystallization using acetone-water mixtures. The ratio of trans to cis isomer was found to be 2.5 1. When the nitrosation was carried out in an acetic acid solution, the ratio of trans to cis isomer remained the same although the yield of the identified products was somewhat lower (71 vs 56 %) [29]. The ratio of the isomers of the starting pyrrolidine was not reported. 

Quinoxaline derivatives (36), and not the expected sydnones, were obtained from the Af-nitroso derivatives of 3-arylamino-l-aryl-pyrrolidine-2,5-diones (35). The precise nature of this rearrangement has not so far been determined.40 The derived quinoxaline-2,3-dicarboxylic acid mono-jV-arylamides (37) were obtained in 40-60% yield. The latter compounds were also made by the conventional reaction of quinoxaline 2,3-dicarboxylic anhydride and an amine.40... 

Pyrrolidine readily forms an IV-nitroso derivative. This can be lithiated in the 2-position, and subsequent reaction with electrophiles and deprotection yields 2-substituted pyrrolidines (780S(58)l 13), as illustrated in Scheme 54. The transformation of tetrahydrothiophene 1,1-dioxide (238) into its 2-bromo derivative (239) is similar in principle. This involves deprotonation with ethylmagnesium bromide followed by electrophilic attack by bromine. Sodium ethoxide treatment of (239) gives buta-1,3-diene in 74% yield (80LA1540). 

Functionalization of the carbon radical resulting from cyclization of an aminium radical is an important step for synthetic chemists in order to obtain the desired product directly or to provide a handle for further transformations. Radical reactions of A-chloroalkenylamines (Section III,B) lead to /3-chloro pyrrolidines, which are prone to rearrangement to give piperidines. Reactions of N-nitroso alkenylamines lead to 8-nitroso pyrrolidines and, if an a-hydrogen is present, ultimately to oximes of aldehydes or ketones. Advantages of the latter transformation are the formation of stable substituted pyrrolidines and the utility of the oxime moiety in regard to further transformations. 

Mirvish (15) showed that weak bases are more easily N-nitrosated than strong bases under mildly acidic conditions. Since the secondary amine nitrogen on the 1,3-thiazolidine ring is much less basic (pKa 6.3) than in the pyrrolidine ring (pKfl 11.3), the formation of N-nitroso-l,3-thiazoline should be favorable and hence would be predicted to occur in products such as bacon where N nitrosopyrrolidine is of major concern. 

N-Nitroso pyrrolidine 92 can be lithiated just with LDA. Double benzylation gives principally the trans isomer of 93 after reduction.61... 

The venom of the fire ant, Solenopsis punctaticeps, contains several 2,5-dialkyl-pyrrolidines and -pyrrolines their structures have been settled by combined g.c-m.s., and confirmed by syntheses employing the Hofmann-Loffler reaction on the corresponding primary amines.7 A new synthesis of 2,5-dialkyl-pyrrolidines via lithiated iV-nitrosopyrrolidine and two stages of alkylation, followed by removal of the nitroso-group, should be applicable to the synthesis of the venom components. The major products are trans in stereochemistry.8... 

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