Simple Synthesis of Aryl p‐Nitroarylacetonitriles by Vicarious Nucleophilic Substitution with Carbanions of Protected Cyanohydrins

Abstract

Acetals of the cyanohydrins of aromatic aldehydes were deprotonated to generate carbanions, which were used in the vicarious nucleophilic substitution of the hydrogen atom of aromatic and heteroaromatic nitro compounds to form p‐nitro‐substituted diarylacetonitriles. The reaction selectively occurred para to the nitro group. The anion of the hemiacetal of acetaldehyde was shown to be an efficient leaving group in the base‐induced β‐elimination step.

Introduction of Carbon Substituents into Nitroarenes via Nucleophilic Substitution of Hydrogen: New Developments

“…Scheme 17 Synthesis of (cyanomethyl)anilines via cyanomethylation of nitroarenes with (phenylthio)acetonitrile A much more convenient and simple way of synthesizing nitroaryl(phenyl)acetonitriles consists of the conversion of readily available cyanohydrins of aromatic aldehydes into acetals by reaction with ethyl vinyl ether, followed by VNS reaction of these protected cyanohydrins with nitroarenes (Scheme 18). 50 Due to bulkiness of the carbanions of such nitriles the reaction proceeds selectively in the para position.…”

Simple Synthesis of Dimethyl Nitrobenzhydrylphosphonates and Heteroarylnitroarylacetonitriles via Vicarious Nucleophilic Substitution (VNS) Reaction

“…06,109.61,111.10,115.80,126.39,126.85,128.18,131.10,138.70,144.32,145.31. MS (EI): m/z (%) = 264 (M + + 2, 43), 262 (100), 245 (9), 227 (32), 217 (19), 216 (30), 215 (20), 204 (10), 189 (22), 188 (28), 187 (36), 181 (15), 169 15 IR (film): 3103,2927,2251,1590,1528,1473,1351,1184,11443,1119,1014,892,818, 742 cm -1 . 1 H NMR (500 MHz, CDCl 3 ):  = 5.73 (s, 1 H), 6.39-6.43 (m, 2 H), 7.42 (br s, 1 H), 7.76 (d,J = 8.6 Hz,1 H),8.20 (dd,J = 8.6,2.3 Hz, 1 H), 8.33 (d, J = 2.3 Hz, 1 H).…”

“…5 Recently, we have presented a simple synthesis of p-nitrodiarylacetonitriles via VNS reaction of carbanions generated from readily available cyanohydrins of aromatic aldehydes protected in the form of acetals in the reaction with ethyl vinyl ether. 20 Observation that a hemiacetal group can be eliminated in base-induced -elimination prompted us to attempt VNS reaction in nitroarenes by carbanions of readily available dimethyl -hydroxybenzylphosphonates O-protected in a form of acetals and expand this approach to the synthesis of heteroarylnitroarylacetonitriles.…”

“…31 P NMR (202 MHz, CDCl 3 ):  = 25.10.MS (EI): m/z (%) = 357 (M + + 2, 23), 355 (M + , 38), 325(7), 309(9), 248 (43), 247 (28), 246 (100), 232 (10),230 (25), 200 (33), 199 (26), 181(20), 165 (69), 164(22), 163 (26), 153 (24), 139 (10), 165 (69), 164(22), 163 (27), 153 (24), 139 (10), 115(12), 111(13), 109 (29). HRMS (EI): m/z calcd for C 15 H 15 ClNO 5 P: 355.0376; found: 355.0373.…”

Recent Advances on O-Ethoxycarbonyl and O-Acyl Protected Cyanohydrins

“…Synthetic methodology to prepare cyanohydrins with protecting groups commonly used in organic chemistry, such as tetrahydropyranyl ( I , THP) [ 4 , 5 ], trimethylsilyl ( II , TMS) and 1-ethoxyethyl ( III , EE) [ 6 , 7 , 8 ] have been described ( Scheme 3 ). Such protected cyanohydrins can function as pronucleophiles in nucleophilic substitutions [ 9 ] and nucleophilic additions [ 10 ].…”