Aryl halides nitrile synthesis

Diazonium salts are valuable reagents for the synthesis of aryl halides, nitriles, phenols, hydrazines and azo compounds. 

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... 

Th synthesis of the acid from the nitrile thus becomes in reality a synthesis from sulphonic acids. An exactly analogous reaction takes place when an aryl halide, with the halogen in the side chain, is distilled with potassium cyanide, as discussed later (p. 678). 

Luminescence spectra of a series of Ce(III) compounds containing halide, alkyl, aryl, ether, nitrile, and cyclic aromatic hydrocarbon ligands have been recorded under a range of conditions auid a matrix isolation UV study of the direct synthesis of (C2H4>f Eu using europium atoms has been reported. ... 

An intramolecular alkylation of a-thionitrile (58) leads to a macrocycle, an intermediate for the synthesis of the sesquiterpene (-)-dihydrogermacrene D (Scheme 29). Alkylation of an a-cyanosulfone followed by reduction gave a-substituted acetonitriles. Cyclization of a 1,3-dibromoalkane with (methylthio)acetonitrile yields a l-cyano-l-(methylthio)cyclobutane, a precursor for the synthesis of cyclopentanones. Reaction of a-(arylthio)nitriles with aryl halides in the presence of LDA and BusP at -78 C affords cyanostilbenes. ... 

The PTC synthesis of aryl nitriles by the reaction of aryl halides with NaCN is effectively catalyzed by a Ni° complex [188]. 

Special solvent. Newman - recommends N-methyl-2-pyrrolidone as solvent for the reaction of an aryl halide with cuprous cyanide to produce the corresponding nitrile. Dimethylformamide (b.p. 153°) has been suggested as a better solvent than originally used pyridine (b.p. 115°), but l-methyl-2-pyrrolidone has an even higher boiling point and seems still more satisfactory. An example is the synthesis of... 

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

The most important member of the group is an effective synthesis of aryl nitriles that involves heating the aryl halide with cuprous cyanide. Some examples of the reaction are given in Scheme 7.9. 

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... 

Due to their synthetic utility and pharmaceutical applications, a number of synthetic routes to a,P-unsatuiated nitriles have been developed. Classical methods include dehydration of amides [15] or aldoximes [16], Wittig- [17] and Peterson-type [18, 19] olefination processes, ammoxidation of alkenes [20], and carbocyanation of alkynes [21], These approaches suffer variously from high waste generation, low yields and poor stereoselectivity. As such the transition metal-catalysed cyanation of vinyl halides is an attractive route for the synthesis of alkaiyl nitriles. Whilst several instances of such transformations have been reported in the literature, the area remains underdeveloped, particularly in comparison to analagous cyanations of aryl halides. 

The well known palladium-catalysed insertion of carbon monoxide into substituted aryl halides has been elaborated to provide a useful synthesis of benzo-diazepinones, and the reaction of 1,2-diamines with allenic nitriles has been... 

The synthesis of a-aryl activated derivatives has been approached via a Pd-catalyzed reaction. The enolate form of the activated nucleophile may act as a transmetallating agent, which may, therefore, react with a Pd intermediate resulting from the oxidative addition of aryl halides. Arylation of di-teri-butyl malonate was described in the presence of Pd(dba)2 catalyst the reaction also was possible with dimer 1 (eq 86). Aryl bromides and ethyl cyanoacetate also can participate in such reactions. Other ligands than P(f-Bu)3 were efficient for these couplings. The bicyclic triaminophosphine, P(i-BuNCH2CH2)3N, served as a versatile ligand for the Pd-catalyzed a-arylation of nitriles with aryl bromides. 

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. 

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

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

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],... 

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