VNS, vicarious nucleophilic substitution

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. 

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). 

The 2-alkylene-substituted aromatic nitro compound 1011, which is readily accessible via vicarious nucleophilic substitution (VNS) [88-90] of 4-fluoronitroben-... 

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. 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

Die VN-Substitution (vicarious nucleophilic substitution, VNS) tritt allgemein bei der Um-setzung von Nitro-arenen mit solchen Carbanionen ein, die am Carbanionen-Zentrum zusatz-lich eine Abgangsgruppe tragen ... 

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 theory and practice of vicarious nucleophilic substitution of hydrogen (VNS) were examined in detail mostly by Mqkosza and his co-workers (87ACR282,... 

Selected substituted thiophene derivatives may also react with nucleophiles. Primary and secondary amines react with 2-bromo-3-substituted-5-nitrothiophenes to produce 11 <95T5403>. Vicarious nucleophilic substitution of hydrogen (VNS) works generally for both 2-nitro- and 3-... 

The vicarious nucleophilic substitution (VNS) of hydrogen in nitrothiophenes is of great synthetic potential. Carbanions bearing leaving groups (L) at the carbanion center can initially add to nitrothiophenes forming H adducts subsequent elimination of HL, followed by protonation, leads to products which have formally been obtained by... 

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. 

In many cases, vicarious nucleophilic substitutions (VNS) were observed with activated olefins (Scheme 59). 

Vicarious nucleophilic substitution (3.3.3) permits the introduction of amino groups para (or ortho if para blocked) to nitro groups by reaction with methoxyamine or 1-amino-l,2,4-triazole. In contrast, VNS substitution of 3-nitropyridine with benzyl chloroacetate proceeds at C-4. °... 

As with pyrroles and furans, indoles undergo very few nucleophilic substitution processes. Most of those that are known involve special situations iV-substituted benzene-ring-nitro-indoles undergo vicarious nucleophilic substitutions (VNS) (3.3.3). ° Arelated process involves addition of stabilised enol(ate)s ortho to a 5-sulfoxide, with loss of the oxygen from sulfur. The reaction is highly selective for C-4, even in the presence of 3-substituents. ... 

Various pyridazines, their 3-oxo or 3,6-dioxo analogs, readily undergo vicarious nucleophilic substitution (VNS) with the carbanion of chloromethyl p-tolyl sulfone. 2-Phenyl-3(2//)-pyridazinone, of a higher reactivity as an... 

In a so-called vicarious nucleophilic substitution of hydrogen (= VNS),75 2,3-diphenylpyrido[2,3-/)]pyrazine is alkylated in the 5-position by t(chloromethyl)sulfonyl]benzene. Generally, this proceeds by addition of the carbanion to the electron-deficient ring position of a nitroarene or electrophilic heteroaromatic system, followed by base-induced -elimination of the corresponding hydrogen halide.76,77 As with quinoxalines and naphthyridines, the reaction with pyri-do[2,3-h]pyrazines also affords products bisannulated at the pyrazine or the pyridine moiety, depending on the kind of 2/3-substitution (cf. Section 7.2.3.1.1.5.4.). 

---