Nitrile From aryl halide

Rosenmund—von Braun synthesis. Formation of aromatic nitriles from aryl halides and cuprous cyanide. 

Leadbeater NE, Torenius HM, Tye H (2003) Ionic liquids as reagents and solvents in conjunction with microwave heating rapid synthesis of alkyl halides from alcohols and nitriles from aryl halides. Tetrahedron 59 2253-2258... 

Scheme 4.18 Synthesis of aryl nitriles from aryl halides...

Very recently, arylboronic esters have been directly obtained from aryl halides via the cross-coupling reaction of (tetraalkoxy)diboron (Scheme 2-7) [28]. The reaction tolerates various functional groups such as ester, nitrile, nitro, and acyl groups. 

Nitriles are versatile and important components of a range of dyes, natural products, and pharmaceuticals. Aryl nitriles can be synthesized from aryl halides by direct reaction between aryl halides and copper cyanide, known as the Rosemund von Braun reaction [36]. These cyanation reactions can have several disadvantages, in particular the long reaction times required. Ren and coworkers showed that 1,3-dialkylimidazolium halide-based ionic liquids can be used as solvents in the Rosemund von Braun reaction [37]. Complete conversion, based on GC-MS analysis, was achieved after 24 h at 90 °C. When using microwave irradiation and ionic liquid as a solvent, Leadbeater and coworkers showed the reaction times could be reduced to between 3 and 10 min [38]. Under the optimized reaction conditions, 2 equiv. CuCN and 1 equiv. aryl halide were rapidly heated to 200 °C in [i-PrMIM]Br as solvent. Representative results are collected in Table 7.3. The microwave method works as well as the conventional method for a range of aryl iodide and aryl bro-... 

Another important class of reactions involves the introduction of a cyano group by substitution in an Ar-Z precursor. In fact, novel pathways leading to aromatic nitriles-for example, photosubstitution reactions-are desirable in view of the many applications of aryl cyanides as agrochemicals and pharmaceuticals. Today, the classical copper(l)-mediated Rosenmund-von Braun and Sandmeyer reactions, from aryl halides and aryldiazonium salts respectively, have been supplanted by reactions which employ palladium- or copper-catalysis [57]. The rather common use of excess cyanide anion may lead to a deactivation of the catalyst, and affect to a remarkable extent each of the key steps of the catalytic cycle [58aj. Although the use of complex iron cyanide has been shown to offer an effective solution to this limitation [58b,c], photocyanation provides an equally useful alternative [10],... 

The Rosenmund-von Braun synthesis of aryl nitriles (40) from aryl halides (38) also shares some commonality with the Castro-Stephens reaction. This transformation was discovered nearly a century ago, and was mentioned in the initial Castro-Stephens publication where the authors noted potential mechanistic similarity. 

Alonso, R.A., Austin, E., and Rossi, R.A., Photostimulated reaction of carbanions from a, P unsaturated nitriles with aryl halides by the Sj l mechanism, /. Org. Chem., 53,6065, 1988. 

By the hydrolysis of nitriles. The nitriles may be easily prepared either from amines by the Sandmeyer reaction (Section IV,66) or by the action of cuprous cyanide upon aryl halides (compare Section IV,163). Benzyl cyanide... 

The synthesis of (hetero)aryl cyanides from (hetero)aryl halides via transition-metal catalysis is a very valuable reaction since a nitrile can be easily transformed into several other functional groups. Not until 2000 were the first examples on microwave-assisted cyanation reported in the literature. Alter-man and Hallberg found that 3-bromopyridine and 3-bromothiophene were... 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

A single-mode microwave procedure has been reported for the palladium-catalyzed preparation of both aryl and vinyl nitriles from the corresponding bromides. The reaction times were short and full conversions were achieved in just a few minutes (Eq. 11.33) [50], The cycloadditions to yield the tetrazoles needed slightly longer reaction times, from 10 to 25 min, but only 20 W of power was required as a temperature of 220 °C was reached after 10 min heating. The yields in this step ranged from 36% to 96%. This method for transforming halides into tetrazoles has been used for the synthesis of a novel HIV-protease inhibitor [50],... 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

Alterman, M. and Hallberg, A., Fast microwave-assisted preparation of aryl and vinyl nitriles and the corresponding tetrazoles from organo-halides, /. Org. Chem., 2000, 65, 7984-7989. 

The hydrocyanation of alkenes [1] has great potential in catalytic carbon-carbon bond-formation because the nitriles obtained can be converted into a variety of products [2]. Although the cyanation of aryl halides [3] and carbon-hetero double bonds (aldehydes, ketones, and imines) [4] is well studied, the hydrocyanation of alkenes has mainly focused on the DuPont adiponitrile process [5]. Adiponitrile is produced from butadiene in a three-step process via hydrocyanation, isomerization, and a second hydrocyanation step, as displayed in Figure 1. This process was developed in the 1970s with a monodentate phosphite-based zerovalent nickel catalyst [6],... 

By far one of the most important reactions through the S l mechanism is formation of a C—C bond by the reaction of aryl halides with carbanions derived from hydrocarbons, ketones, esters, amides, nitriles and even, with some limitations, from aldehydes. The reactions of cyanide ions and carbonyl complexes of Co and Fe also form a new C—C bond. 

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