Aromatic acyl cyanides

Wilkinson s catalyst has also been reported to decarbonylate aromatic acyl halides at 180°C (ArCOX ArX). This reaction has been carried out with acyl iodides, bromides, and chlorides. Aliphatic acyl halides that lack an a hydrogen also give this reaction, but if an a hydrogen is present, elimination takes place instead (17-16). Aromatic acyl cyanides give aryl cyanides (ArCOCN—> ArCN). Aromatic acyl chlorides and cyanides can also be decarbonylated with palladium catalysts. °... 

This borane reduces an acyl cyanide to a cyanohydrin-9-BBN adduct, but this intermediate undergoes ready elimination. The desired (3-amino alcohols can be obtained in 75-85% yield by reduction of the cyanohydrin intermediate with NaBH4 and CoCl2. In the case of chiral aromatic acyl cyanides the optical yields are 92-98%. One aliphatic acyl cyanide is reduced in 84% ee.2... 

Decarbonylation of acyl cyanides.9 Aromatic acyl cyanides, which are easily obtained by oxidation of cyanohydrins with /-butyl hydroperoxide catalyzed by RuC12[P(C6H5)3]3, undergo decarbonylation to nitriles in high yield when heated in the presence of Pd(0). 

DBU catalyses cyanoacylation of ketones, R OR2, with aromatic acyl cyanides giving O-acyl cyanohydrin adducts, ArOCO-C(CN)R1R2, in fair to good yields in 2 h at ambient temperature.256... 

The organoindium reagent, prepared from indium metal and bromoacetonitrile, reacts with carbonyl compounds in the presence of chlorotrimethylsilane to give /3-hydroxy nitriles (Scheme 93),336 337 Similarly, indium-mediated coupling of bromoacetonitrile or 2-bromopropionitrile with a variety of aromatic acyl cyanides affords the corresponding aromatic a-cyanoketones in moderate to good yields under mild and neutral conditions (Equation (86)).338 Carbonyl compounds are efficiently transformed into 2,2-dichloro-3-hydroxynitriles by the action of trichloroaceto-nitrile and indium(i) bromide (Scheme 94).339 Bromocyanomethylation of carbonyl compounds is also achieved by the reaction of dibromoacetonitrile and indium(i) bromide.340... 

The recent application of sonochemistry to the reaction of aroyl chlorides with KCN in acetonitrile is very interesting. Aromatic acyl cyanides could also be prepared by reaction of aroyl chlorides with KCN impregnated onto XAD resins. A number of patents describe the results of the two-phase interactions of alkali metal cyanides with a solution of acyl halides or anhydrides in aprotic organic solvents, which in general run in the presence of Cu salts. ... 

Due to the sensitivity of acyl cyanides towards excess cyanide ions it is in general advisable not to use alkali metal cyanides as reagents unless special conditions are secured. Therefore, in most cases cyanides of heavy metals (low concentration of free cyanide) have been applied. These transformations require rather drastic conditions, which restricts the application mainly to the preparation of aromatic acyl cyanides. The latter can be obtained in good yield if copper(I) cyanide is heated with acid chlorides in aromatic solvents for several hours at temperatures of 160 More recent developments are based on the same strategy, but allow the application of milder conditions. In most cases acid chlorides are converted to acyl cyanides. Some reagents and the reaction conditions for their application according to equation (42) are collected in Table 12. 

The palladium-catalyzed decarbonylation of aromatic acyl cyanides proceeds at 120 °C to give the corresponding nitriles in excellent yield. Since acyl cyanides are readily prepared by the ruthenium-catalyzed oxidation of cyanohydrins with BuKDOH this represents a good method for the conversion of aldehydes to nitriles under mild conditions (Scheme 29). 

Radspieler and Liebscher prepared several 4-chloro-2,5-disubstituted oxazoles 1520 from aromatic acyl cyanides 1519. These oxazoles are the first examples in which the 2-substitutent was not derived from an aromatic aldehyde. They extended this methodology to prepare suitably functionalized dichloro indole bis-oxazole C-D-E fragments. Their approach is noteworthy as the first synthesis of such fragments that does not involve chlorination of an intact oxazole ring. 

This method is particularly suitable for the synthesis of a-ethylenic and aromatic acyl cyanides but it also provides a valuable method of preparing certain aliphatic acyl cyanides (Table 6.6). The reaction fails with acryloyl chloride, sulphonyl chlorides, ethyl chloroformate and oxalyl chloride. 

Acyl cyanides.2 Aromatic and a, 3-unsaturated cyanohydrins are oxidized efficiently to acyl cyanides by t-butyl hydroperoxide in benzene in the presence of RuC12[P(QH5)3]3. 

Conjugated—a,/)-unsaturated or aromatic—aldehydes are oxidized by manganese dioxide in the presence of one equivalent of sodium cyanide to give an acyl cyanide (Formula C in Figure 17.18) via an intermediate cyanohydrin (B in Figure 17.18), which is also either an allylic or a benzylic alcohol. Alcohols of this kind can be oxidized by a relatively weak oxi-... 

The conversion of aliphatic and aromatic acyl halides to a keto nitriles has been effected by heating the halides with dry metallic cyanides, of which cuprous cyanide has given the most satisfactory results (60-87%). The acyl bromides rather than the chlorides ate preferred, at least in the formation of aliphatic compounds. Thus, pyruvonitrile is prepared in 77% yield from acetyl bromide and cuprous cyanide whereas no product is obtained if acetyl chloride is employed. Benzoyl cyanide is made in 65% yield by heating the corresponding acyl chloride with cuprous cyanide. "... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

Compared to the older procedures the use of acid iodides in acetonitrile or dichloromethane as solvent constituted a remarkable improvement. Aromatic and aliphatic acyl cyanides are accessible by this route. For example acyl cyanides of cinnamic acid and phenylacetic acid could be obtained in 33% and 49% yields. Copper(I) cyanide in diethyl ether in the presence of lithium iodide gave a-cyano ketones in 50-70%. The reaction can be carried out at room temperature in diethyl ether or slightly above or at 80 C in acetonitrile. It is not possible to obtain the acyl cyanide from acryloyl chloride, chloroformate or oxalyl chloride by this approach. 

Thallium(I) cyanide was introduced by Taylor and McKillop as a reagent. Aromatic and heteroaromatic acyl cyanides are produced in go yield, whereas aliphatic acid halides lead under these conditions mainly to dimerization products. 18-Crown-6 is a good catalyst for the preparation of cyanoformate in methylene chloride with potassium cyanide and chloroformates. Similarly, tetraethylammonium cyanide gives cyanoformates in high yield under very mild conditions. Aroyl cyanides are generated easily by phase transfer catalysis with tetra-n-butylammonium bromide. Tri- -butyltin cyanide proved successful only with aromatic acid halides, leading to dimerization products with aliphatic compounds. ... 

Aromatic and Vinyl Nitriles. Aromatic haUdes (Br, I) have been converted into nitriles in excellent yields by Pd(Ph3P)4 catalysis in the presence of Sodium Cyanide Alumina,Potassium Cyanide, or Cyanotrimethykilane (eq 24). While the latter two procedures require the use of Arl as substrates, a more extensive range of substituents are tolerated than the alternative method employing ArBr. A Pd(Ph3P)4-catalyzed extrasion of CO from aromatic and heteroaromatic acyl cyanides (readily available from cyanohydrins) at 120 °C provides aryl nitriles in excellent yields (eq 25). ... 

The first organocatalytic asymmetric three-component Strecker reaction was reported by List and Pan using Jacobsen s thiourea catalyst 75. Diverse a-aminonitriles 76 and 77 were formed in excellent yields and enantioselectivities from aliphatic and aromatic aldehydes, different amines, and acyl cyanides by using 5mol% of catalyst 75 (Scheme 10.33) [97]. 

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