Benzoyl cyanides

Submitted by T. S. Oakwood and C. A. Weiscf.rber. Checked by R. L. Shriner and Charles R. Russell. 

In a 500-ml. distilling flask (Note 1) fitted with a thermometer extending to within 0.5 in. of the bottom are placed 110 g. (1.2 moles) of cuprous cyanide (Note 2) and 143 g. (118 ml., 1.02 moles) of purified benzoyl chloride (Note 3). The flask is shaken to moisten almost all the cuprous cyanide and is placed in an oil bath (Note 4) which has been previously healed to 145-150°. The temperature of the bath is raised to 220-230° and maintained between these limits for 1.5 hours. During the heating the flask is frequently removed from the bath (about every 15 minutes) and the contents are thoroughly mixed by vigorous shaking (Note 5). At the end of the 1.5 hours the flask 

The crude benzoyl cyanide is purified by fractional distillation through a column (Note 7). The low-boiling material is taken off at a reflux ratio of 25-30 to 1 until the temperature reaches 208° about 15 g. is collected. The benzoyl cyanide is collected at a reflux ratio of 1 to 1 at a temperature of 208-209°/745 mm. (bath temperature 260-280°). The distillate solidifies to colorless crystals which melt at 32-33° the product weighs 80-86 g. (60-65%). 

It is advisable to wrap the neck of the flask with asbestos paper or asbestos tape. 

The commercial grade of benzoyl chloride may be purified as follows 300 ml. (363 g.) of benzoyl chloride in 200 ml. of benzene is washed with two 100-ml. portions of cold 5% sodium bicarbonate solution. The benzene layer is separated, dried over calcium chloride, and distilled. After all the benzene has distilled, pure benzoyl chloride boiling at 196.8° (corr.)/745 mm. is collected. The recovery is 225 g. 

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Formation - benzoyl chloride, benzoic anhydride, benzoyl cyanide (TL 1971, 185), benzoyl tetrazole (TL 1997, 38, 8811)... 

In the presence of KCN, cyanocarbonylation of iodobenzene takes place to form benzoyl cyanide (587)[428]. 

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

Ethyl benzoylformate has been prepared by the direct esterification of the acid 1 and by the action of oxides of nitrogen on an alcoholic suspension of indigo.2 The acid has been prepared by many different reactions but the most practical are the hydrolysis of benzoyl cyanide,3 the oxidation of acetophenone 4 and the oxidation of mandelic acid.5... 

Irradiation of mixtures of 2-methylbenzoyl cyanide and benzoyl cyanide results in the exclusive formation of the mixed cycloadduct, from which elimination of HCN leads to isocoumarins <96CJC221>. 

The question of whether the commercially available benzoyl cyanide (PhCOCN), methyl cyanoformate (MeOCOCN), and R2NCOCN are formed (cf, however. Ref... 

Diazadiphosphetidines (106) or (107) are also produced by the reaction of bis(2,2,3,3-tetrafluoropropyl)phosphoroisocyanatidite (101) with either benzoyl cyanide (102) or chloral (103) respectively52. The mechanism, as shown for the formation of (.106), presumably involves the unstable betaine (104) and the cyclic imino-ylid (105). 

R)-Benzoins and (/ )-2-hydroxypropiophcnonc derivatives are formed on a preparative scale by benzaldehyde lyase (BAL)-catalyzed C-C bond formation from aromatic aldehydes and acetaldehyde in aqueous buffer/DMSO solution with remarkable ease in high chemical yield and high optical purity (Eq. 8.112).303 Less-stable mixed benzoins were also generated via reductive coupling of benzoyl cyanide and carbonyl compounds by aqueous titanium(III) ions.304... 

Benzoyl cyanide can be prepared by the thermal decomposition of cj-isonitrosoacetophenone,5 from silver cyanide and benzoyl chloride,3 from anhydrous hydrogen cyanide and benzoyl chloride in the presence of pyridine,4 and by the thermal decomposition of phenylchloronitrocyanomethane.6 6... 

In a 1-1. flask are placed 50 g. (0.38 mole) of benzoyl cyanide (p. 14) and 500 ml. of concentrated hydrochloric acid (sp. gr. 1.18). The mixture is shaken occasionally until the solid is dissolved completely and is then allowed to stand at room temperature for 5 days (Note 1). At the end of this time the clear yellow... 

Benzotriazole, 20,16 Benzoylacetic ester, 23, 35 Benzoylation of acetoacetic ester by ethyl benzoate, 23, 35 Benzoyl chloride, 24, 14 purification of, 24, 15 Benzoyl Cyanide, 24,14, 16 Benzoyleormic acid, 24,16 Benzoyl-o-toluidines, conversion to indoles, 22, 95... 

With occasional shaking about a day is necessary for complete solution of the solid benzoyl cyanide. A yellow oil separates which dissolves on shaking. At the end of this time some ammonium chloride occasionally separates. 

This class of acylating agents has thus far been but little used in carbohydrate chemistry. However, unimolar benzoylation of methyl 4,6-O-benzylidene-a-D-glucopyranoside, methyl 4,6-O-benzylidene-a-D-altropyranoside, and benzyl 4,6-O-benzylidene-jS-D-galactopy-ranoside with benzoyl cyanide gave good yields of the corre-... 

Dinitrogen tetroxide reacts with phenylethynyltrimethyltin to give benzoyl cyanide, probably by rearrangement of (dimeric) phenyl(nitroso)ethyne (Equation (84)).245... 

Aroyl cyanides, which have low stability in the presence of water, can be prepared under phase-transfer catalytic conditions in yields >60% [24], A major byproduct of the reaction with benzoyl chloride is a,a-dicyanobenzyl benzoate, resulting from reaction of the benzoyl cyanide with the cyanide ion and subsequent esterification. 

Nitriles of keto acids are reduced with lithium aluminum hydride at both functions. Benzoyl cyanide afforded 2-amino-1-phenylethanol in 86% yield... 

Benzoyl cyanide azine (5%) 9,10-dicyano-9,10-dihydrophenanthrene (8%) 9,10-dicyanophenan-threne (11%) and an unidentified product (6%). 

The glyoxime dehydration route is compatible with various substituents including not only alkyl, aryl, and heteroaryl but also acyl, carboxyl, and amino groups for example, 3-amino-4-phenylfurazan is formed on heating a-(hydroxyimino)phenylacetamidoxime with sodium acetate in ethanol, and the same compound also results from treatment of benzoyl cyanide with hydroxylamine and sodium acetate in ethanol <87IJC(B)690>. 

A similar rate-enhancing effect is probably observed with cyano substitution. 2-Cyano-3,3-dimethyl-2-phenyloxetane (22) underwent thermal decomposition at 350 °C to give benzoyl cyanide (68ZOR2055). The regioselectivity in this case would be in accord with cleavage to the intermediate biradical (23), which would have extensive spin stabilization at the cyano-substituted carbon atom and would probably be the most stable of the four possible biradical intermediates. 

Caution. Benzoyl cyanide is extremely toxic and should be handled with suitable precautions to prevent human contact. 

The two-step deoxygenation of benzoyl cyanide to phenylcyanocarbene, which added quickly to alkenes via photolysis of the appropriate 2,2-dihydro-1,3,2,-dioxaphos-pholanes, has been performed70. A homolytic fragmentation mechanism was assumed. When the 1,3,2-dioxaphospholane 36 in trans-butene was irradiated, the range of observed substances included 37 and 38 as the major products, in addition to fluorenone and bifluorenylidene (equation 16)70. 

Stoichiometry (28) is followed under neutral or in alkaline aqueous conditions and (29) in concentrated mineral acids. In acid solution reaction (28) is powerfully inhibited and in the absence of general acids or bases the rate of hydrolysis is a function of pH. At pH >5.0 the reaction is first-order in OH but below this value there is a region where the rate of hydrolysis is largely independent of pH followed by a region where the rate falls as [H30+] increases. The kinetic data at various temperatures both with pure water and buffer solutions, the solvent isotope effect and the rate increase of the 4-chloro derivative ( 2-fold) are compatible with the interpretation of the hydrolysis in terms of two mechanisms. These are a dominant bimolecular reaction between hydroxide ion and acyl cyanide at pH >5.0 and a dominant water reaction at lower pH, the latter susceptible to general base catalysis and inhibition by acids. The data at pH <5.0 can be rationalised by a carbonyl addition intermediate and are compatible with a two-step, but not one-step, cyclic mechanism for hydration. Benzoyl cyanide is more reactive towards water than benzoyl fluoride, but less reactive than benzoyl chloride and anhydride, an unexpected result since HCN has a smaller dissociation constant than HF or RC02H. There are no grounds, however, to suspect that an ionisation mechanism is involved. 

A synthetic route to Elaeocarpus alkaloids has been explored. Acylation of the lithium enolate (197) by the benzoyl cyanide (198) gave the diketone (199), which is the key intermediate in a previously reported synthesis of elaeocarpine (Section 3.08.8.2) (79TL1339). 

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