Aryl nitrile, preparation

Nitriles contain the —C=N functional group We have already discussed the two mam procedures by which they are prepared namely the nucleophilic substitution of alkyl halides by cyanide and the conversion of aldehydes and ketones to cyanohydrins Table 20 6 reviews aspects of these reactions Neither of the reactions m Table 20 6 is suitable for aryl nitriles (ArC=N) these compounds are readily prepared by a reaction to be dis cussed m Chapter 22... 

Because cyano groups may be hydrolyzed to carboxylic acids (Section 20 19) the Sand meyer preparation of aryl nitriles is a key step m the conversion of arylammes to sub stituted benzoic acids In the example just cited the o methylbenzomtnle that was formed was subsequently subiected to acid catalyzed hydrolysis and gave o methylbenzoic acid in 80-89% yield... 

Preparation of aryl nitriles Cop-per(l) cyanide converts aryl diazonium salts to aryl nitriles. 

As noted in Section 11.2.2, nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides can be catalyzed by the presence of copper metal or copper salts.137 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reactions are usually carried out at elevated temperature in DMF or a similar solvent. 

NUCLEOPHILIC AROMATIC SUBSTITUTION OF ARYL FLUORIDES BY SECONDARY NITRILES PREPARATION OF 2-(2-METHOXYPHENYL)-2-METHYLPROPIONITRILE... 

Reaction of the 5-substituted aminothiadiazole (88 R = Bu ) with aryl nitriles produced amidines (89) in yields dependent on the reactivity of the nitriles (Scheme 14). Decreasing the electron density of the cyano group by such electron-withdrawing groups as p-nitrophenyl-, and 2- and 4-cyanopyridyl, led to higher yields as compared to unsubstituted benzonitrile. A bis thiadiazole (92 R = Bu ) was prepared by reacting the sodium salt of (88) with 2-methanesulfonyl-5-(-butyl-1,3,4-thiadiazole (91) <84JHC1377>. 

The microwave-assisted preparation of aryl tetrazoles 179 was reported using the intermolecular 1,3-dipolar cycloaddition of aryl nitriles 178 with sodium azide (38) (Scheme 9.38). 

The lithium derivatives of 1-substituted pyrroles and indoles provide another general route of access to 2-acyl pyrroles and indoles. The ketones can be obtained directly by reaction with aryl nitriles or acid halides but, at least for 1-benzenesulfonylindole, a two-step procedure involving reaction with an aldehyde followed by oxidation of the carbinol to the ketone is frequently more convenient (equation 179) (73JOC3324, 75JOC2613). This method is probably the most general route to 2-acylindoles, although many have also been prepared by direct Fischer cyclization (see Section 3.06.3.4.2). 

Kurabayashi and Grundmann have reported the preparation of the 1,2,4-oxadiazoles (34) from 1,3,5-triazine and aryl nitrile oxides in the presence of boron trifluoride. The mechanism has not been fully elucidated, but it is most likely that the initial stage is the formation of the complex (33) (78BCJ1484). 

Dicyandiamide (116) reacts with a variety of two-atom components to form 2,4-diamino-1,3,5-triazines. The route, which bears some resemblance to the syntheses from biguanides (see Section 2.20.4.2.1), was discovered by Ostrogovich (11MI22000). He found that 1,3,5-triazines were prepared efficiently on heating alkyl or aryl nitriles with dicyandiamide (equation 59). 

This valuable method for the preparation of aryl nitriles via the diazonium salt is discussed in Section 6.7.1, p. 922, and offers one of the most convenient routes for obtaining this class of compound. Experimental procedures are described in Expt 6.76. 

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

Aryl nitriles can be prepared by the cyanation of aryl halides with an excess of copper(I) cyanide in a polar high-boiling solvent such as DMF, nitrobenzene, or pyridine at reflux temperature. 

Various 3,5-disubstituted 1,2,4-triazoles 593 have been prepared in good yields by the reaction of nitriles 591 with acylhydrazides 592 in the presence of catalytic potassium carbonate under microwave heating (Scheme 266) <2005TL3429, CHEC-III(5.02.9.2)182>. Likewise, alkyl and aryl nitriles 594 react with thiosemicarbazide 595 under acidic conditions to give 1,3,4-thiadiazoles 596 (Scheme 267) <1995BML1995, CHEC-III(5.10.9.2.2)595>. 

Compound CuClPhNC is also known. By contrast, similar acetonitrile complexes are easily air oxidized, but they can be prepared by reducing CuXg (X = Cl, Br) with copper in MeCN (230) several alkyl or aryl nitriles complex with CuCl (290). 

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