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SYNTHESIS AND CHEMISTRY OF N-NITROSOENAMINES
Abstract
The synthesis of (S)-N-methyl-N-nitroso-2-(tosyloxy)-propylamine (1) was carried out from (S)-ethylacetate. The acetolysis product of (1) was identified as (S)-N-methyl-N-nitroso-2-acetoxypropylamine (2). Thus the acetolysis proceeded with retention of configuration via double displacement at carbon 2, first by the N-nitroso group to form a oxadiazolium ion, (3) and secondly by acetate. N-Nitrosoenamines are formed by potassium hydroxide elimination of (beta)-tosyloxy nitrosamines, by base catalyzed equilibration of allylic isomers, by oxidative elimination of (alpha)-phenylseleno or (alpha)-phenylsulfinyl nitrosamines. Dehydrohalogenation of alkyl((beta)-chloroethyl)nitrosamines resulted in the formation of alkyl-vinylnitrosamines. However, with longer (beta)-chloroalkyl chains the elimination occurred to give the (beta),(gamma)-allylic isomer. Thus, 3-chloro-1-nitrosopiperidine (4) reacted with crown ether/potassium hydroxide to give 1-nitroso-1,2,3,6-tetrahydropyridine (5) while 1-nitroso-3-(tosyloxy)piperidine (6) reacted under the same conditions to yield 1-nitroso-1,2,3,4-tetrahydropyridine (7). The allylic isomer (5) was converted to (7) by heating in methanolic potassium hydroxide. These elimination reactions were leaving group dependent. The tosylate (6) reacted via a classical E,(,1)cB mechanism while the chloride (4), a much poorer leaving group, reacted via a competing irreversible E(,2) process. When a weak base was used, a 2:1 mixture of (7) and (5) was formed. Formation of the (alpha)-carbanion of nitrosamines with LDA, followed by reaction with diphenyldiselenide or disulfide, resulted in the formation of (alpha)-phenylseleno or (alpha)-phenylthio nitrosamines. Oxidation gave the corresponding selenoxides or sulfoxides. The selenoxide spontaneously eliminated to yield N-nitrosoenamines while the sulfoxide required heating. A property of N-nitrosoenamines is that undergo reaction with electrophilic and nucleophilic reagents. As a consequence, Michael-type additions to N-nitrosoenamines proceed in high yields. This is true also of acid catalyzed addition reactions. Examples of these reactions are presented. A nitrosamine route to the mitomycins was studied. It was found that the anion of 1-nitroso-pyrroline (8) reacted with 2',5'-dimethoxy-4'-methylacetophenone (9) to produce 1-{2-(1-nitroso-pyrrolidyl)}-1-(2',5'-dimethoxy-4'-methylphenyl)ethanol (10). Compound (10) was oxidized to the 2,5-quinone (11). Reductive denitrosation of (11), followed by oxidation, resulted in the formation of 7-hydroxy-6,9-dimethylpyrrolo{1,2-a}indole.
Subject Area
Organic chemistry|Food science
Recommended Citation
KUPPER, ROBERT JOE, "SYNTHESIS AND CHEMISTRY OF N-NITROSOENAMINES" (1982). ETD collection for University of Nebraska-Lincoln. AAI8306488.
https://digitalcommons.unl.edu/dissertations/AAI8306488