Synthesis of Acyl Cyanides

Some of the starting compounds were commercially available only as acids or anhydride. The respective acyl chlorides were obtained according to the thionyl chloride method of Smith et al. (1991). Reactions with cyanotrimethylsilane were completed under water-free conditions and in an argon atmosphere (Hiinig and Schaller, 1982). Glassware was dried in an oven directly before use. 

0 equivalent of acyl chloride, 1.0-1.4 equivalents of cyanotrimethylsilane were added by syringe under stirring in an ice bath. After 15 min the ice bath was removed and the stirring was continued at room temperature for 2-A h. 

Vacuum distillation with the microdistiUation equipment was used to purify the acyl cyanides. 

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Oxidation of a cyanohydrin derived from a conjugated aldehyde (as the 0-TMS derivative) using py-ridinium dichromate (PE)C) in DMF gave an a,3-unsaturated lactone (5 -butenolide) as the major product (equation 12). Simple nonconjugated cyanohydrins are not satisfactory substrates for the synthesis of acyl cyanides using PDC, because they seem to add to the initially formed acyl cyanides, leading ultimately to cyanohydrin esters. Oxidation of cyanohydrin to acyl cyanides can be carried out either by means of manganese dioxide, ruthenium-catdyzed oxidation with t-butyl hydroperoxide or NBS. ... 

Nagra, B.S., Shaw, G., and Robinson, D.H., A novel synthesis of acyl cyanides from diethyl phosphorocyanidate and some 1-substituted imidazole carboxylic acids including a D-ribofuranoside, J. Chem. Soc., Chem. Commun., 459, 1985. 

Nucleophilic additions of inorganic anions to carbonyl groups or Michael acceptors also proceed efficiently under PTC conditions. Synthesis of acyl cyanides and the Reissert compounds belong to this category (eqs. 149-151). 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

Borch, R. F. Levitan, S. R. Van-Catledge, F. A. The reaction of acyl cyanides with Grignard reagents. J. Org. Chem. 1972, 37, 726—729. Gallina, C. Giordano, C. Selected methods for the oxidation of l,l,l-trichloro-2-alkanols. An efficient modification using chromic acid. Synthesis 1989, 466-468. 

Reaction of acyl cyanides with amidrazones or guanidin-2-amine has been used for the synthesis of l,2,4-triazin-5-amines 11,172 or l,2,4-triazine-3,5-diamines 12. The reaction proceeds via 4-amino-2,3-diazabutadiene-l-carbonitriles.333- 336... 

Reactions of acyl cyanides with aldehydes and HCl afforded 4-chlorooxazole derivatives, potential building blocks for natural product synthesis <01S745>. 

The low ionic character of the aluminium-silicon bond has been cleverly utilized to develop a very mild, general and effective synthesis of acyl silanes, successful for aliphatic, aromatic, heteroaromatic, a-aUcoxy, a-amino and even a-chiral and a-cyclopropyl acyl sUanes. Acyl chlorides are treated with lithium tetrakis(trimethylsilyl)aluminium or lithium methyl tris(trimethylsilyl) aluminium in the presence of copper(I) cyanide as catalyst to give the acyl silanes in excellent yields after work-up. Later improvements include the use of 2-pyridinethiolesters in place of acyl halides, allowing preparation of acyl silanes in just a few minutes in very high yields indeed (Scheme 9) °, and the use of bis(dimethylphenylsilyl) copper lithium and a dimethylphenylsilyl zinc cuprate species as nucleophiles. 

General Synthesis and Reactions.—Linear primary alcohols with at least seven carbon atoms are transformed into esters in high yield using copper oxide at temperatures above 170 C in the liquid phase. RusfCO) catalyses the conversion of an aldehyde, or an alcohol with the same number of carbon atoms, into an ester in the presence of diphenylacetylene. " The carbonylation of organic halides in the presence of cyclic ethers is catalysed by PhPdI(PPh3)2 , it provides a synthesis of halohydrin esters in reasonable yield. Cyanohydrin esters have been synthesized by the sodium borohydride reduction of acyl cyanides in the presence of tetra-n-butylammonium bromide. ... 

Synthesis of Derivatives of Carboxylic Acids.—Dicarboxylic acid di-iodides are prepared (in 37 to 94% yield) from the corresponding diacid chlorides and sodium iodide. Carboxylic acid bromides are prepared under neutral conditions by the reaction of the corresponding acid with dibromotriphenylphosphorane. Radicals generated from cyclohexylmercuric acetate and NaBH4 react with maleic anhydride and related compounds to give cyclic derivatives of maleic acid in 55 to 98% yield. The chemistry of acyl cyanides has been reviewed. ... 

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

To form the stereocenter at C-3 a direct reduction-alkynylation sequence was applied, that provided the diastereomeric homopropargylic alcohols 83 in a ratio of syn anti=76l2A, The major isomer syn-S3 was isolated in 55% yield. The key step of the synthesis was an intramolecular imidotitanium-al-kyne [2+2] cycloaddition/acyl cyanide condensation. With this sequence the pyrrolidine ring was formed and all the carbon atoms of the alkyl side chain were established in acrylonitrile 84. The reduction of the imine double bond proceeded stereoselectively and the nitrile group was removed reductively en route to the target compound. 

Formylfuran reacts with potassium cyanide in alcohol solution to give a product containing two furan nuclei. What is this product and how does it form Can you suggest an alternative synthesis of the compound from 2-formylfuran using propane-1,3-dithiol as one reagent Hint consider an acyl anion equivalent approach). 

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). 

Reaction XLVm. (a) Action of Alkali Cyanides on Alkyl and Acyl Halides. (Bl., [2], 50, 214.)—This reaction is capable of very wide application, all the simple alkyl halogen compounds, the acyl halides, and the halogen fatty acids come within its scope. The nitriles so formed yield acids by hydrolysis, so it is frequently the first step in the synthesis of an acid—the preparation and hydrolysis of the nitrile are often combined. The preparations of malonic, succinic, tricarballylic and other acids (Preparations 60, 61, 62) illustrate this. The extension of this reaction to acyl halides is important, and should be referred to, as should the interaction of silver cyanide, and alkyl iodides, to give isonitriles. Mercuric and silver cyanides, it may be noted, give with acyl chlorides and bromides better yields of normal acyl nitriles than do the alkali cyanides. 

A Japanese group have been investigating the use of readily accessible dihydrocinnoline derivatives of the type 1 (R = alkyl, aryl, styryl, ethoxy X = H or methoxy) as novel precursors for the synthesis of other types of heterocycles. The following synthesis of 2-acetyl-3-cyanoindole is representative of a new general method (22-88% for 10 examples) for the preparation of 2-acyl- and 2-ethoxycarbonyl-3-cyanoindoles from 1 a mixture of 1 (R = Me, X = H 1 eq.) and powdered potassium cyanide (2 eq.) was stirred overnight in aqueous DMF at room temperature. Addition of water to the reaction mixture precipitated 2-acetyl-3-cyanoindoIe, which was obtained in 54% yield after recrystallisation. 

Vitamin B12, the coenzyme, is sometimes called cyanocobalamine, and is contained in the liver in ppm level. It is comprised of Co2+, porphyrine, cyanide, and porphyrine-side chained nucleoside, and is a complicated complex, as can be seen in Figure 11.1. It is well known that the first total synthesis of vitamin B12 was carried out by Woodward. Vitamin B12 plays a variety of important roles such as rearrangement of C-C bonds (1,2-acyl transfer) and rearrangement of C-N bonds, through radical species. Eq. 11.1 shows a typical acyl-transfer between glutamic acid and... 

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