Aroyl cyanides

A simple and elegant one-pot synthesis of 3-amino-4-arylfurazans from the corresponding aroyl cyanides was developed by Lakhan and Singh (Scheme 102) [87IJC(B)690]. 

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

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. 

The condensation of an a-diketone or its synthetic equivalent (e.g. aroyl cyanide (87S914)) with a 1,2-diaminoalkane gives 2,3-dihydropyrazines (Scheme 41), which like their 2,5-analogues can be oxidized by air, or better by Mn02 in ethanolic KOH, to pyrazines (78MI21400). 

Olah et al.715,716 have prepared a series of a-cyanodiarylcarbenium ions 283 (R = Ar) under superacidic conditions and have evaluated their mesomeric nitrenium ion character by H, 13C, and 15N NMR spectroscopy. A subsequent one-bond 13C-13C coupling constant measurement717 also indicates significant mesomeric nitrenium ion character of 283 (R = Ar). Protonated aroyl cyanides 284, however, exist predominantly in the carboxonium ion form of 284a over the nitrenium ion form 284b.718... 

Aroylcyanides.2 Aroyl cyanides can be prepared by reaction of an aroyl chloride with KCN in acetonitrile. Addition of a trace of water markedly accelerates the rate and improves the yield (by as much as 100%). No other additives show this effect. 

Aromatization, of cyclohexenones, 35, 197 Aroyl cyanides, 434 Arylacetic acids, 148, 189... 

Because the iron-catalyzed formation of diaryl ketones oftengives low yields, Knochel s group tackled this problem by introducing aroyl cyanides as alternative acylation agents [61]. These types of compounds are more powerful in acylation... 

Scheme 5.19 Ketone synthesis via aroyl cyanides developed by Knochel s group.

Aldonitrones, prepared by the condensation of aromatic aldehydes and phenylhydroxylamine, are converted by the action of aqueous potassium cyanide to substituted anils of aroyl cyanides. ... 

Aroyl cyanides may be obtained from substrates which are not too electron poor on treatment with cyanogen and HF, when the reaction temperature is slowly raised fix)m -30 to 50 °C. Instead of cyanogen, carbonyl cyanide may also be usol, but preparation and handling of this reagent is problematic (equation 24). ... 

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. ... 

Moreover, aryl-oxazoles, -imidazoles [17], or-thiazoles [18], anhydrides [19], and imides [20] are accessible via intramolecular Heck-type carbonylations. In addition to typical acid derivatives, aldehydes [21], ketones [22], aroyl cyanides, aroyl acetylenes, and their derivatives [23] could be synthesized via nucleophilic attack of the acyl metal complex with the corresponding hydrogen or carbon nucleophiles. Even anionic metal complexes like [Co(CO)4] can act as nucleophiles and lead to aroylcobalt complexes as products [24]. 

The formation of acrylonitriles from the reaction of dihalogenomethylene-phosphoranes with aroyl cyanides has now been extended to include the use of aliphatic acyl cyanides, although the conditions need to be closely defined. Perfluoroisocyanates with diphenylmethylenetriphenylphosphorane give the expected keten-imines (28) or their rearrangement products (29). Formylation of both reactive and stable ylides has been achieved using the mixed anhydride of formic and acetic acids. ... 

A new primary synthesis of 2-amino-3-arylpyrazines is accomplished by reaction of aroyl cyanides with 1,2-diaminoethane (Scheme 33). An important synthesis is that of 2-amino-3-cyano-5-sub-stituted pyrazines, which are conveniently synthesized by condensation of aminomalononitrile with a-oximino ketones and then deoxygenation of the resulting pyrazine jV-oxides (Scheme 37). 

In the presence of ai compounds are reduced I Aroyl cyanides under) Allylation of carbon toward aldehydes enable system in ring A. Ally. Mn-MejSiCl in THF. Fluorinated homoally bonyl compounds" or tlx... 

Aroyl cyanides undergo reductive coupling to furnish a-diketones in moderate yields. Allylation of carbonyl compounds. The chemoselectivity of allylindium reagents toward aldehydes enables elaboration of the steroid side chain without affecting the enone system in ring A. Allylation is also viable using a catalytic amount of indium and Mn-MejSiClinTHF. o... 

Benzoins. The cross-coupling of aroyl cyanides with aldehydes by aqueous... 

Several debrominations using triphenylphosphine have been reported. Stilbene dibromides and other vicinal dibromides are debrominated stereospecifically in an fl /i-elimination. 9,9-Dibromofluorene and dibromodiphenylmethane (43) have been converted into the corresponding ethylene, and the compounds (44) gave moderate yields of aroyl cyanides when fused with triphenylphosphine. ... 

Lakhan and Singh ° described the first direct synthesis of 4-amino-2,5-disub-stituted oxazoles 552 from readily available starting materials. They condensed equimolar amounts of an aroyl cyanide 551 and an aldehyde with anhydrous ammonium acetate to afford 552 in 40-65% yield (Scheme 1.151). The reaction works better for aroyl cyanides containing electron-withdrawing groups. The... 

TABLE 1.38 4-AMINO-2,5-DIARYLOXAZOLES AND 2-ALKYL-4-AMINO-5-ARYLOXAZOLES FROM CONDENSATION OF AROYL CYANIDES, ALDEHYDES, AND AMMONIUM... 

The modifications of this reaction include the reaction between aroyl cyanide and aromatic aldehyde in the presence of HCl gas and the reaction of nitrile with aromatic aldehyde, HCl and SOC. ... 

Aroyl cyanides may similarly be prepared from phenacyl bromide, nitrosyl chloride and triphenylphosphine [129], When a P = C bond cannot be formed, for example, in Ph3PCMe2.COPh X , then the phosphonium salt reacts at room temperature with cyanide ion to give an o 0-unsaturated nitrile. MejC = CPh.CN, in 54% yield [130]. The following is another example ... 

Sulphonyl Cyanides.—Arylsulphonyl cyanides are more reactive than aroyl cyanides in cycloaddition reactions, because of delocalization of CN TT-charge density this is illustrated by their cycloaddition to 5,5-dimethoxy-tetrahalogeno-cyclopentadienes. Olefins give jS-cyano-sulphones under irradiation (254 nm), e.g. ArS02CH2 CH(CN) (CHa)3Me from hex-l-ene. ... 

Pd-catalyzed cyanocarbonylation of aryl iodides with potassium cyanide is effected by 1% of PdPdI(PPh3)2 under 20 atm of CO at 100 °C (Scheme 40). The optimum ratio of KCN to Arl differs from aryl iodide to aryl iodide, and the best yield of aroyl cyanides is usually obtained with 0.5-0.3 equiv of KCN. The direct coupling product (arylcyanide) is produced in negligibly small amount (< 2%) except for the reaction of 2-thienyl iodide, which furnishes a mixture of cyano 2-thienyl ketone (45%) and 2-cyanothiophene (22%, under 8 atm CO, 100 °C, 24 h). Aryl bromides do not work well. 

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