Benzonitrile acylation

Oxathiane 101 is readily deprotonated using s-BuLi, and the resulting anion reacts with alkyl halides, ketones, and benzonitrile (85JOC657). The majority of work in this area, however, is due to Eliel and coworkers and has involved chiral 1,3-oxathianes as asymmetric acyl anion equivalents. In the earliest work it was demonstrated that the oxathianes 102 and 103, obtained in enantiomeri-cally pure form by a sequence involving resolution, could be deprotonated with butyllithium and added to benzaldehyde. The products were formed with poor selectivity at the new stereocenter, however, and oxidation followed by addition... 

It has been found that 3-azapyrylium salts 57 and 58 are obtained in reactions of pinacolone as well as vinyl chlorides 59 with N-acylnitrilium salt 56 (91ZOR2479 92ZOR2577). The acylation of vinyl chlorides 59 in benzonitrile also leads to salts 60 (91ZOR1986). The same salts 55 are formed as intermediates by acylation of acetylenes in the presence of nitriles (88ZOR1605). Vinyl chlorides and acetylenes are both direct derivatives of carbonyl compounds with the same oxidation level (72MI2 85KGS1443). 

When acrylamides are used as dipolarophUes, FMO theory predicts that the 4-amido isomer should be preferred, which is contrary to the results found with tertiary amides (129). Semiempirical, ab initio, and density functional theory (DFT) calculations were applied to the regioisomeric transition state stmctures of benzonitrile oxide cycloadditions (129-131). The results suggest that there is an unfavorable steric repulsion between the phenyl ring of the nitrile oxide and the methyl group of the ester (or amide) functionalities of the dipolarophile in the transition state leading to the 4-acyl regioisomer (Scheme 6.17). 

N-Alkylnitrilium salts, prepared from benzonitriles and SbQs, acylate activated aromatic compounds under mild conditions. The resulting benzophenone imines can be cyclised and hydrolysed providing a good route to substituted xanthones (Scheme 34) <99 JOC4050>. 

Much the same activity is retained when the nitrogen atoms in the heterocyclic nucleus are shifted around. The convergent scheme to this related compound starts with the acylation of alanine (35-1) with butyryl chloride (35-2). The thus-produced amide (35-3) is then again acylated, this time with the half-acid chloride from ethyl oxalate in the presence of DMAP and pyridine to afford the intermediate (35-4). In the second arm of the scheme, the benzonitrile (35-5) is reacted with the aluminate (35-6), itself prepared from trimethyl aluminum and ammonium chloride, to form the imidate (35-7). Treatment of this intermediate with hydrazine leads to the replacement of one of the imidate nitrogen atoms by the reagent by an addition-elimination sequence to form (35-8). Condensation of this product with (35-4) leads to the formation of the triazine (35-9). Phosphorus oxychloride then closes the second ring... 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

Alkyl aryl ketones 191 react with benzonitrile in the presence of a perchloric acid/acetic anhydride mixture to yield the 3-azapyrylium salts 194113. The structure of 194 indicates the intermediate formation of A-acylenamines 192 which are acylated at the carbon to 193, the precursor to 194 (equation 61). 

The same authors116 showed that 1,3-diketones 198 react easily with benzonitrile in the presence of a HC104-Ac20 mixture to form 3-azapyrylium perchlorates 199 (equation 63). This reaction did not occur without acetic anhydride, which is a catalyst since the acylium ions are not included in the end products. The application of the C-acylated ketones 198 leads to 3-azapyrylium salts 199 which are isomeric to those mentioned above (194), i.e. products 199 have an inverted orientation of heteroatoms comparatively to the three-carbon fragment of the cycle116. The azapyrylium salts 199 can be hydrolyzed to the enamides 200. 

In a recent modification, urea/hydrogen peroxide is used to achieve the cyclization of 2-(acyl-amino)benzonitriles to quinazolin-4(3//)-ones (86-97%). ... 

Acylation of (2) with benzonitrile gives an intermediate which yields acetophenone (52%) on hydrolysis with 3 M HCl. This seems to be the only recorded reaction of a boron-stabilized carbanion with a nitrile. ... 

A rhodium-catalyzed decomposition of a-diazoacetophenones in benzonitrile gives an intermediate acyl-substituted nitrile ylide (157) that cyclizes to the oxazole or may be trapped with DMAD to produce a pyrrole (Scheme 73) <92CL2197>. Ethyl cyanoformate and ethyl 3,3,3 trifluoro-... 

In this respect the acylation of vinyl chlorides 270 in benzonitrile medium turned out to be a very interesting process. The action of acylium salts 271 on the vinyl chlorides is related to three problems, namely (a) the formation of the reactive chlorocarbenium ions 272, (b) the lengthening of the carbon chain as the first step of the future heterocycle construction and (c) the introduction of another functional group which shall have to subsequently ensure the cyclization, The chlorocarbenium ions 272 cannot rearrange, and therefore it is expected that the nitrile will add to ion 272 to form 3-azapyrylium salts of structure 273 (equation 74). However, it has been found unexpectedly that the 3-azapyrylium salts 277 obtained under these conditions have the inverted orientation of the heteroatoms in cycle, i.e. they are the structural isomers of the salts expected. The constitution of products 277 was confirmed by comparison with 3-azapyrylium hexachloroantimonates obtained by other methods. Moreover, they were characterized by IR and NMR spectroscopy as well as by mass-spectral study of ) -acylaminovinyl ketones 278, i.e. the products of opening of 3-azapyrylium cycles,... 

Metallo-l,3-benzothiazole ergeben mit Carbonsaure-Derivaten 2-Acyl-1,3-ben zot hi azole. So erhalt man aus l-Lithio-l,3-benzothiazol (1,1 Aquivalente) mit Bcnzoesaure-ethylester bzw. Benzonitril 76 bzw. 82% 2-Benzoyl-l, 3-benzothiazol 07 ... 

Table 3.2 Acylation of aromatics with anhydrides catalyzed by dichlorobis(benzonitrile)platinum(Il)-silver hexafluoroantimonate mixture...

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