Development of Pd/C-Catalyzed Cyanation of Aryl Halides

Abstract

A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C is described. The new method can be applied to a variety of aryl bromide and active aryl chloride substrates to effect efficient conversions. The process features many advantages over existing cyanation conditions and the practical utility of the process has been demonstrated on scale.

Alternative Approach to Synthesis of 3-(4-chloro butyl)-1H-indole-5-carbonitrile: A Key Intermediate of Vilazodone Hydrochloride, an Antidepressant Drug

“…6-Hydoxy hexanal (4b) was prepared by the reduction of E-caprolactone (8) with DIBAL-H [26] (Scheme 4). With aryl hydrazine 3 and aldehyde 4a in hand we explored Fisher indolization under standard reaction conditions such as 4% H 2 SO 4 (aqueous)=DMAc, [27] EtOH=H 2 O in the presence of Na 2 HPO 4 , p-TsOH= toluene, [18] p-TsOH=EtOH, [19] ceric ammonium nitrate (CAN)=MeOH, [28] HCl= AcOH, [29] EtOH=water, [20] dioxane=water, [30] H 2 SO 4 =MeOH, [31] and ZnCl 2 . In most of the cases predominant formation of hydrazone (5a) or its decomposition products was noticed, the amounts of which varied based on the reaction temperature (Table 1, entries 1-11).…”

“…[23] However, both these syntheses involve usage of advanced starting material 1H-indole-5-carbonitrile whose synthesis requires multiple chemical conversions (Scheme 2). [24][25][26][27][28][29][30][31] Interestingly no reports were found for the synthesis of 2a,b through the Fisher indolization approach, which could be an economical and straightforward approach starting from easily accessible raw materials. Herein we report an efficient and alternative synthesis to 3-(4-chloro butyl)-1H-indole-5-carbonitrile (2) by suitably establishing reaction conditions starting from simple starting materials without involvement of protection-deprotection chemistry.…”

Application of biosynthesized palladium nanoparticles (Pd NPs) on Rosa caninafruit extract‐modified graphene oxide as heterogeneous nanocatalyst for cyanation of aryl halides

“…Aryl nitriles are one of the most adaptable organic building blocks. They are available in many natural products, and are utilized in agrochemicals, pharmacologicals and fragrances . Additionally, the nitrile group can be changed to several functional groups like amides, carboxylic acids, aldehydes, ketones or amines.…”

“…Additionally, the nitrile group can be changed to several functional groups like amides, carboxylic acids, aldehydes, ketones or amines. The production of these aryl nitriles needs a stoichiometric quantity of highly toxic cyanating reagents, such as copper cyanide, potassium cyanide, sodium cyanide, zinc cyanide or trimethylsilylcyanide . Moreover, applying relatively less toxic cyanating reagents, such as phenyl cyanates, acetone cyanohydrins and benzyl thiocyanates, is usually expensive and risky.…”

Microwave-enhanced cyanation of aryl halides with a dimeric ortho-palladated complex catalyst

“…A variety of methods for the introduction of the cyanide functional group into aromatic compounds have been described [4]. The Sandmeyer reaction (involving diazonium salts plus copper(I) cyanide) and Rosenmund-Von Braun reaction, in which aryl halides react with stoichiometric amounts of copper(I) cyanide, provide early examples of the conversion of aryl halides to aryl cyanides [5]. Drawbacks of these reactions are the high temperature required (150-250°C) and the use of stoichiometric amounts of copper(I) cyanide, which leads to equimolar amounts of heavy metal waste.…”