Vicarious nucleophilic substitution reactions

The carbanion of 2,3-dimethylthiazolidine-4-one reacted with nitroarenes to give either a ting opened product (50) via a VNS (vicarious nucleophilic substitution) reaction or a product resulting from oxidative nucleophilic substitution of hydrogen (51). Ring opening VNS reactions with 5-membered 5-heterocycles are limited to those heterocycles which show some conformational flexibility <96TL983>. 

When the attacking atom of the nucleophile carries a leaving group, replacement of hydrogen can take place via the VNS (vicarious nucleophilic substitution) reaction,15 as shown in Scheme 3.16 The key feature of this reaction is the rate-limiting base-induced 3-elimination from the cr-adduct. 

Vicarious nucleophilic substitution reactions of azolopyridazines have been found to be controlled by methyl substituents.35 On treatment with bromomethyl phenyl sulfone in DMSO-r-BuOK, azolopyridazines yield mainly typical reaction products, whereas 7-methylazolopyridazines under the same conditions undergo annulation. These competitive reactions illustrate the role of charge distribution and steric hindrance for the course of the nucleophilic substitution. 

The nitroazoles are widely used in the reaction of vicarious nucleophilic substitution of hydrogen. Vicarious nucleophilic C-amination is, practically, the single method of direct introduction of the amino group into nitro compounds. Using the vicarious nucleophilic substitution reaction we have successfully carried out the C-amination of some representatives of nitrobenzazoles, nitroazoles, and model compounds thereof and studied the structure of aminated products and the C-amination mechanism [673-678],... 

Cyclopropylphosphine oxides (140) react with the sodium salts of amides, presumably via cyclopropane ring-opening and intramolecular olefination, to give dihydropyrrole derivatives in moderate to good yield. Vicarious nucleophilic substitution reactions of a variety of substituted nitrobenzene derivatives with the carbanion of chloromethyldiphenylphosphine oxide to give o-(141) and p-(142)-nitrobenzyldiphenylphosphine oxides have been investigated. ... 

Kozhevnikov et al. (02EJO1412) have investigated the vicarious nucleophilic substitution reactions of l,2,4-triazine-4-oxides 53. They have shown that, although mixtures are often formed, by tuning the conditions the reaction can be biased to favour either the deoxygenated (59) or dehalogenated product (60). For a representative example, see Scheme 20. 

In recent years there has been a proliferation of new reactions and reagents that have been so useful in organic synthesis that often people refer to them by name. Many of these are stereoselective or regioselecth/e methods. While the expert may know exactly what the Makosza vicarious nucleophilic substitution, or the Meyers asymmetric synthesis refers to, many students as well as researchers would appreciate guidance regarding such "Name Reactions". 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

Nucleophilic addition of a-halo-4-tolylsulfonyl methyl anions to quinone methides has been reported to afford three kinds of products as a result of domino reactions. Two of them were identified as rearrangement products and one as the vicarious nucleophilic substitution (VNS) product. An unexpected 1,2-migration of the tosyl group was observed.180... 

The unusual [2,l]oxazine (27) is formed by an interesting variation of vicarious nucleophilic substitution in the reaction of 1 -chloropropyl-/ -tolyl sulfone carbanion with 5-nitroquinoline (Equation (17)) <86LA69>. 

Deoxygenative v.s vicarious nucleophilic substitution of hydrogen in reactions of 1,2,4-triazine-4-oxides with a-halocarbanions has been described <02EJO1412>. Tandem vicarious nucleophilic substitution of hydrogen/intramolecular Diels-Alder reaction of 1,2,4-triazine (19) into functionalized cycloalkenopyridines 21 has been reported <02CPB463>. 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

Carbanions of a-haloalkyl aryl sulfones, sulfonates and sulfonamides react with quinoxalines according to two general pathways vicarious nucleophilic substitution of hydrogen and/or bis-annulation to bis(azirino)quinoxaline derivatives. The charge distribution in the anionic (T-adducts and reaction conditions influence the direction of these reactions. ... 

Reaction of l-methyl-4-nitropyrazole with 1,1,1-trimethylhydrazinium halides in the presence of sodium methoxide or potassium fert-butoxide afforded 5-amino-l-methyl-4-nitropyrazoles <1999CHE1109>. Specifically, the primary radical anions of substrate in the vicarious nucleophilic substitution of hydrogen in 1-methyl-4-nitropyrazole 192 with 1,1,1-trimethylhydrazinium iodide yielded 5-amino-l-methyl-4-nitropyrazole 193, which was studied by electron spin resonance (ESR) (Equation 31) <2005MRC1023>. Reaction of 3,5-dinitropyrazole 194 with trimethylhydrazinium iodide in DMSO afforded 4-amino-3,5-dinitro-l//-pyrazole 195 via another vicarious nucleophilic substitution (Equation 32) <2001JHC1227>. 

---