Direct formylation of nitroarenes via vicarious nucleophilic substitution of hydrogen

A new method of synthesis of nitroaromatic aldehydes via vicarious nucleophilic substitution of hydrogen with dichloromethyl group and its hydrolysis is described.     

Synthesis of 5-pentafluorosulfanyl indazoles

An efficient method for the synthesis of 5-SF₅ substituted indazoles from commercially available 4-nitro-(pentafluorosulfanyl)benzene through vicarious nucleophilic substitution of hydrogen (VNS) reaction, reduction of nitro group and cyclization of resulting anilines were described. Transformations of 5-SF₅-indazoles led to a variety of SF₅-substiuted heteroarenes that can serve as a versatile building block for diversity-oriented organic synthesis.     

Synthesis of substituted azaoxindoles for the preparation of aza-tenidap analogs

The preparation of a set of eight azaoxindoles bearing substituents on the aromatic nucleus is outlined. These compounds were required for the preparation of aza-analogs of the anti-inflammatory oxindole tenidap. Two methods of synthesis were used, the first involving the addition of malonate to 2-chloro-3-nitropyridine derivatives followed by nitro group reduction and one-pot cyclization/hydrolysis/decarboxylation. The second method, utilizing the vicarious nucleophilic substitution (VNS) reaction of nitropyridine derivatives (followed by nitro group reduction and one-pot cyclization/hydrolysis), constitutes a novel route to azaoxindoles.     

Chemistry of ethanediyl S,S-acetals 6- An example of vicarious nucleophilic substitution of hydrogen in 1,4-benzodithians

1,4-Benzodithians, when treated with bromine in anhydrous chloroform, undergo very fast monobromination at the aromatic ring. By the use of quantum mechanical semiempirical calculations, the reaction is shown to proceed most likely via a vicarious nucleophilic substitution of hydrogen.     

Rapid Synthesis of New 5‐Nitroimidazoles as Potential Antibacterial Drugs via VNS Procedure

Original 4‐arylsulfonylmethyl‐5‐nitroimidazoles were prepared by reacting four chloromethylaryl sulfones with 5‐nitroimidazole derivatives via a vicarious nucleophilic substitution (VNS) of hydrogen reaction.     

Regioselective functionalisation of nitrobenzene and benzonitrile derivatives via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions

The synthesis of P-benzylic products by reaction of anions stabilised by N-phosphorylphosphazenyl, N-methoxycarbonylphosphazenyl, phosphine borane complex, and phosphine oxide groups by displacement of hydrogen of a variety of electron-deficient benzene derivatives is described. Lithium phosphazenes were the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene and some ortho-, meta-, and para- substituted nitrobenzenes. Lithiated phosphine borane complexes produced efficiently the substitution of the hydrogen at the para position of a cyano group in cyanobenzenes, whereas the anion of ethyldiphenylphosphine oxide lead to complex mixtures with all electrophiles assayed. The method reported here represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilised anions that do not bear a leaving group at the carbanionic centre.     

A three-component coupling process based on vicarious nucleophilic substitution (VNS(AR))-alkylation reactions: an approach to indoprofen and derivatives.

The intermediate anion derived from the vicarious nucleophilic substitution (VNS) of hydrogen reacts with a series of alkyl halides to generate the corresponding alpha-alkylated conventional VNS product in a one-pot process. This one-pot VNS-alkylation reaction offers a convenient route to a range alpha-substituted nitrobenzyl phosphine oxides, sulfones, and esters via a three-component coupling reaction. Reactions of alpha-chloroethyl phenyl sulfone (14) and ethyl 2-chloropropionate (16) with nitrobenzene followed by subsequent addition of an alkylating agent give a series of sulfones and esters bearing an alpha-aryl quaternary center. The VNS-alkylation protocol has been applied to the synthesis of derivatives of Indoprofen from nitrobenzene using readily available inexpensive starting materials. Indoprofen itself was prepared using the conventional VNS reaction in four steps and 24% overall yield from nitrobenzene.     

Reactions of carbanions derived from α-substituted-methyl tolyl sulfones with quinone methides as Michael acceptors

Nucleophilic addition of α-halo-4-tolylsulfonyl methyl anions to quinone methides and subsequent reactions were studied. Three kinds of consecutive reaction products were isolated, depending on the substrate structures and reaction conditions. 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. The mechanism of the reactions is briefly discussed.     

One-pot regioselective synthesis of nitrophenyloxazolinyl styrene oxides by the Darzens reaction of vicarious nucleophilic substitution-formed carbanions of 2-dichloromethyl-4,4-dimethyloxazoline

The vicarious nucleophilic substitution reaction of dichloromethyloxazoline 2 with nitrobenzene has been investigated. Treatment of 2 with t-BuOK followed by the addition of nitrobenzene leads to benzylic carbanions 4 or 9 depending upon the solvent used (DMSO, DMF, or THF). Subsequent treatment of 4 or 9 with aldehydes, in a Darzens-like reaction, furnishes very good yields of nitrophenyl oxazolinyloxiranes 8 and 11. 1,2-Dioxazolinyl-1,2-dinitrophenylethene 7 forms quantitatively when carbanion 4 is allowed to warm to room temperature in the absence of external electrophiles.     

A base-modulated chemoselective synthesis of 3-cyanoindoles or 4-cyanoquinolines using a palladium-catalyzed N-heterocyclization

A selective methodology for the synthesis of either 3-cyanoindoles or 4-cyanoquinolines via a base-modulated palladium-catalyzed reductive N-heterocyclization from a common 1-cyano-1-(2-nitrophenyl)-1-alkene precursor is described. The required starting materials were prepared either by a Kosugi-Migita-Stille coupling of 2-halo-1-nitrobenzenes with a tributyl(1-alkenyl)stannane or by a vicarious nucleophilic substitution (VNS) of nitrobenzenes followed by a Knoevenagel condensation with an aldehyde.     

硝基芳烃直接氨化的新方法

评述了硝基芳烃直接氨化的几种新方法,主要是芳香亲核氢取代(NASH)反应,Vicarious亲核氢取代(VNS)反应以及由羟氨或烷氧基氨引起的直接氨化反应等。对每种反应的机理(或模式)也作了介绍。     

Selective ortho methylation of nitroheteroaryls by vicarious nucleophilic substitution

An efficient and scalable three-step one-pot approach to 6-methyl-5-nitroisoquinoline (1) from inexpensive 5-nitroisoquinoline, utilizing the vicarious nucleophilic substitution (VNS) as a key step, is described. The optimized reaction conditions can be applied to a limited number of other aromatic and heteroaromatic nitro compounds. Attempts to understand the observed selectivity in the VNS step led to the discovery of two new reaction pathways under VNS conditions, one leading to an isoxazole and the other resulting in the formal cyclopropanation of an aromatic nitro compound.     

Vicarious Nucleophilic Substitution of Hydrogen in Nitro-substituted Pyrroles, Azoles, and Benzannelated Systems Based on Them. (Review)

Published data on the participation of nitro-substituted pyrroles, azoles, and their benzannelated derivatives in vicarious nucleophilic substitution are reviewed.     

Tandem Michael Addition-Vicarious Nucleophilic Substitution of Hydrogen. A New Access to Substituted Nitroaromatic Compounds

Michael addition of alkoxides or diethyl methylmalonate to 2-chloroacrylonitrile provides functional carbanions which are able to react with 1,3-dinitrobenzene following a vicarious nucleophilic substitution to give new substituted nitroarenes.     

Vicarious nucleophilic substitution of α-hydrogen of BODIPY and its extension to direct ethenylation

Direct, oxidizer-free substitution of the 3-hydrogen of BODIPY derivatives has been established through a vicarious nucleophilic substitution procedure. This methodology has been combined with a reversible Michael addition on nitrostyrenes to provide a novel, highly efficient entry to the valuable 3-styrylated BODIPY dyes.     

A vicarious approach to porphyrin aldehydes

The novel synthesis of nitro-porphyrin aldehydes via vicarious nucleophilic substitution of hydrogen in the corresponding nitro-meso-tetraphenylphyrinates (Zn^II, Cu^II) with haloform carbanions, followed by hydrolysis of the introduced dihalomethyl groups under mild conditions (H₂O–toluene, AgClO₄, reflux) is described.     

Alkylation and the Knoevenagel Condensation of Nitrobenzylic Sulfones and Nitriles.1

Nitrobenzylic sulfones and nitriles easily available via the vicarious nucleophilic substitution of hydrogen are readily alkylated in the catalytic two-phase systems, the latter enter also the Knoevenagel condensation with aldehydes.     

Free radicals in vicarious C-amination reactions of 1-methyl-4-nitropyrazole

The primary radical anions of substrate in the reactions of vicarious nucleophilic substitution of hydrogen in 1-methyl-4-nitropyrazole with 1,1,1-trimethylhydrazinium iodide and 4-amino-1,2,4-triazole in t-BuOK-DMSO were observed and identified by EPR monitoring. The probable mechanism of the substrate radical anions formation is discussed.     

氨基硝基吡啶及其氮氧化物的亲核取代胺化反应

以盐酸羟胺、1,1,1-三甲基肼碘化物(TMHI)和4-氨基-1,2,4-三唑(ATA)为胺化剂,研究了2-氨基-3,5-二硝基吡啶(1)和2-氨基-3,5-二硝基吡啶-1-氧化物(3)的亲核取代（VNS）胺化反应。 结合VNS胺化反应机理讨论了胺化剂活性、胺化剂和胺化底物的立体、电子效应对产物的组成和收率的影响。 以羟胺为胺化剂时,氨基可被引入到底物的6-位和4-位,胺化产物的收率在64%~89%之间;以TMHI和ATA为胺化剂时,氨基只能被引入到底物的6-位,胺化产物的收率在90%以上;在相同条件下,胺化产物的收率随胺化剂活性的提高而提高;受N+→O-的影响,化合物3的胺化产物收率稍高于化合物1的胺化产物收率。     

Isolation and Characterization of s̀-Adducts upon Attempted Vicarious Nucleophilic Substitution with Cationic Arene-Iron Complexes

Reaction of the carbanions derived from chloromethyl phenyl sulfone or 1 -chloroethyl phenyl sulfone with the cationic [Fe(arene)Cp] complexes 8 or 9 produced isolable c-adducts 10-12 . Attempted base induced elimination of the s?-adducts, which would have led to products of vicarious nucleophilic substitution (VNS reaction), failed. Similarly, no VNS products were obtained, when the (arene)tricarbonylchromium complexes 4 were reacted with the anion of chloromethyl phenyl sulfone.