Reactions of organic anions. 161. Dihalomethylation of nitroarenes via vicarious nucleophilic substitution of hydrogen with trihalomethyl carbanions

Makosza, M.; Owczarczyk, Zbyslaw R.

doi:10.1021/jo00282a025

Cited by 84 publications

(51 citation statements)

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“…1-Nitronaphthalene and 2-nitrothiophene are dichloromethylated exclusively in the ortho position. 24 These and many other observations show that factors which favor fast b-elimination, such as the presence of efficient or more than one leaving group in the nucleophile and a high concentration of a strong base, favor ortho orientation of VNS. The tendency for ortho orientation is enhanced at low temperature when all reactions, but particularly dissociation of the ' H -adducts, and thus equilibration, are decelerated.…”

Section: Orientation Of the Vns Reactionmentioning

confidence: 84%

“…24 These anions can form ' H -adducts to nitroarenes provided that the addition proceeds faster than their dissociation into dihalocarbenes. Since all substituents at the carbanion center are good leaving groups, the belimination of the HX from these ' H adducts should be a particularly facile and rapid process.…”

Section: Effect Of Electrophilicity Of Arenes On the Vns Reactionmentioning

confidence: 99%

“…24 Some selected results of VNS in 4-substituted nitrobenzenes are shown in Scheme 5. Although they confirm the expected effects of substituents para to the nitro group on the electrophilic reactivity of the ring, the lower reactivity of derivatives in which lone electron pairs of the heteroatoms can be conjugated with the nitro group of the substrate such as 4-OMe and 4-F is noteworthy.…”

Section: Effect Of Electrophilicity Of Arenes On the Vns Reactionmentioning

confidence: 99%

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Vicarious nucleophilic substitution of hydrogen. Mechanism and orientation

Mąkosza

Kwast

1998

J. Phys. Org. Chem.

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Hydrogens located at activated positions in electrophilic arenes, e.g. ortho and para hydrogens in nitrobenzenes, can be replaced with a nucleophile moiety provided there is at least one nucleofuge X connected to the nucleophilic centre. As the group really leaving in this hydrogen substitution process is not the hydride anion but X, the reaction has been named vicarious nucleophilic substitution of hydrogen (VNS). The concepts on the mechanism of the reaction and their experimental background are presented. Reactivity and orientation-the fundamental questions concerning synthetical applications of VNS-are discussed in light of the supposed mechanistic picture.

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Section: Orientation Of the Vns Reactionmentioning

confidence: 84%

Section: Effect Of Electrophilicity Of Arenes On the Vns Reactionmentioning

confidence: 99%

Section: Effect Of Electrophilicity Of Arenes On the Vns Reactionmentioning

confidence: 99%

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Vicarious nucleophilic substitution of hydrogen. Mechanism and orientation

Mąkosza

Kwast

1998

J. Phys. Org. Chem.

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“…5,33 Compounds 1a, 1c-e, 7a-d, 9f-g, 13a-d and 14a-d were identified comparing their spectral data with the literature reported. 5,7,[34][35][36][37][38][39][40] Spectroscopic data are given only for compounds never previously described. 5-Iodo-2-methylbenzonitrile (9f).…”

Section: Methodsmentioning

confidence: 99%

Reaction of benzal bromides in water/dioxane system for easy access to benzaldehydes and 2-formylbenzonitriles (2-cyanobenzaldehydes)

Mola¹,

Caruso²,

Caprariis³

et al. 2016

Arkivoc

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ARKAT-USA, Inc.However, 2-formylbenzonitriles are not cheap compounds and to our knowledge relatively few methodologies which describe their synthesis have been reported (Figure 2). 2,[5][6][7][15][16][17] In addition, many of the existing synthetic methods suffer from certain limitations with respect to yield, reaction conditions and toxicity. In particular, the formylations of 6, performed under strongly basic conditions, usually lead to 1 in rather low yields. 2,18 Similar disappointing results are obtained in the reaction of 8 with the toxic CuCN. 2,19 On the other hand, the transformation of gem-dihalo compounds (benzal halides) into benzaldehydes is quite a common method. [20][21][22][23][24][25][26][27][28][29][30] In this case solvolytic displacement of halogen with successive replacement by hydroxyl followed by formal loss of HBr to generate the corresponding aldehyde, is favored by resonance stabilization offered by the aromatic ring. 29 Figure 2. Common approaches to 2-formylbenzonitriles.Hydrolysis of the benzal halides to the corresponding aldehydes is often conducted in the presence of strong acids (e.g., 95% H2SO4) or strong bases (aq. NaOH) at high temperatures, [25][26] conditions too harsh for the synthesis of 2-formylbenzonitriles, Therefore, the transformation of benzal halides 7 into 2-formylbenzonitriles have been reported under milder conditions only in the presence of the rather expensive AgNO3, used in large excess (> 3 eq.), 5-7 with severe limitations concerning the scale of the synthetic procedure, the necessity of additional tedious purification operations and eventual metal contamination. In our ongoing project on large-scale reaction of 2-formylbenzonitriles, we came across these problems and we realized that not much attention has been devoted to the development of simple and effective methods for the synthesis of these valuable aldehydes. Thus, in this article, we have reconsidered the reactivity of benzal bromides 7, developing a convenient approach to 2-formylbenzonitriles, and then we have extended the method to the synthesis of other model benzaldehydes.

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“…In this methodology, the appropriate nitroaromatic compounds were transformed into the desired ortho-substituted derivatives, and the crucial step of these syntheses was realized by Vicarious Nucleophilic Substitution of Hydrogen (VNS) [4]. Hence, the use of VNS reaction has been found to be an excellent tool for introduction of the dihalomethyl group [5] and isocyanomethyl group [3,6] in the ortho position of aromatic or heteroaromatic nitrocompounds, which thus giving an opportunity for further transformations leading to cyclizable intermediates.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of N-7-Substituted Purines from Imidazole Precursors

Ostrowski

1999

Molecules

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Synthesis of purines and purine mono-1-oxides from the respective 5-substituted 4-nitroimidazole derivatives is described. The commercially available 4-nitroimidazole, in a few simple steps (including Vicarious Nucleophilic Substitution of Hydrogen), was transformed into: 4-aminoimidazoyl-5-carboximes, N-[1-(4-amino-1H-imidazol-5-yl)methylidene]-N-(aryl)amine derivatives or into 4-amino-5-aminomethyl-imidazole. These intermediates were cyclized to the final products.

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Reactions of organic anions. 161. Dihalomethylation of nitroarenes via vicarious nucleophilic substitution of hydrogen with trihalomethyl carbanions

Cited by 84 publications

References 0 publications

Vicarious nucleophilic substitution of hydrogen. Mechanism and orientation

Vicarious nucleophilic substitution of hydrogen. Mechanism and orientation

Reaction of benzal bromides in water/dioxane system for easy access to benzaldehydes and 2-formylbenzonitriles (2-cyanobenzaldehydes)

Synthesis of N-7-Substituted Purines from Imidazole Precursors

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