Allyl cyanide hydrolysis

J,V-Unsaturated carboxylic acids and their derivatives are valuable synthetic intermediates for various natural products. Two typical multi-step processes for the synthesis of p.y-unsaturated acids, Knoevenagel reaction/isomerization with base and allylic cyanide/hydrolysis,3 are those most commonly used. Other new methods have been developed 4-7 however, there is a problem with E/Z stereoselectivity. One straightforward way to obtain p,y-unsaturated acids is by the carboxylation of an allyl metal Intermediate. In the substituted allylic series, the reaction usually occurs at the more sterically hindered terminus. A stereospecific route for the synthesis of homogeranlo acid and homoneric acid by carboxylation of the lithiated allylic sulfone... 

The only practical methods for the preparation of vinylacet.ic acid involve hydrolysis of allyl cyanide 6 carbonation of allylmag-nesium bromide 8 or the malonic acid synthesis.9... 

Allyl cyanides can be added across alkynes in the presence of a nickel catalyst prepared from (COD)2Ni and (4-CF3CeH4)3P in situ to give functionalized di- or tri-substituted acrylonitriles in a highly stereoselective manner, presumably via n-allylnickel intermediates. a-Siloxyallyl cyanides also react at the y -position of a cyano group with both internal and terminal alkynes to give silyl enol ethers, which can be converted into the corresponding aldehydes or ketones upon hydrolysis.70... 

Acid hydrolysis of the simpler olefinic nitriles to olejinic acids occurs without appreciable migration of the double bond. Acrylic acid is made by hydrolysis of acrylonitrile with sulfuric acid (78%). Concentrated hydrochloric acid is used to convert allyl cyanide to vinylacetic acid (75-82%). Similarly, 3"pentenonitrile furnishes a 70% yield of 3-pen-tenoic acid, but the isomeric 2-methyl-3-butenonitrile is not hydrolyzed under the same conditions. The alkaline hydrolysis of higher-molecular-weight branched a, -olefinic nitriles gives mixtures of isomeric and /S,7-olefinic acids. ... 

This is proven by the fact that allyl cyanide on hydrolysis yields crotonic acid in which the double bond is at carbon-2 (p. 173). Of the other cyanogen derivatives of propene the following are known though the position of the double bond is not established in all cases. 

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]. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

If on the other hand the Sn2 reaction with cyanide is favoured, as with allylic 47 or benzylic 50 halides, that method is better.15 Hydrolysis of the nitrile 48 gives the acid 49 but treatment with an alcohol in acidic solution gives the ester 52 directly.16... 

Similarly, Shono studied the diastereoselective introduction of the allyl group into the 5-position of A/ -acylated L-proline derivatives by reaction of the N,0-aceia with allyltrimethylsilane in the presence of titanium tetrachloride [214]. Substitution of the anodically introduced methoxy group by cyanide using trimethylsilyl cyanide [215,216] or an isocyanide [217] as the nucleophile can be used to generate a-amino acids via hydrolysis of the cyano function. Equation (41) shows an example [216]. 

Of the five positional isomers of the four-carbon saccharinic acids theoretically possible, 3-hydroxy-2-(hydroxymethyl)propanoic acid (VI) is the only one that lacks an asymmetric carbon atom and is optically inactive and unresolvable. The first attempt at its synthesis, by Glattfeld and cowork-ers, " was by a direct method. The reaction of 2-chloro-2-deoxyglyceritol (LII) [prepared from allyl alcohol (LI) by reaction with hypochlorous acid] with cyanide ion and subsequent hydrolysis of the anticipated nitrile (LIII) should have produced the desired 3-hydroxy-2-(hydroxymethyl)-... 

Crotonic acid was discovered in croton seeds by Pelletier and Caventou by saponifying the oil, adding tartaric acid, and distilling, but was more definitely characterised by T. Schlippe. Crotonitrile C4H5N, present in crude mustard oil, yields on hydrolysis with alcoholic potash crotonic acid C4He02, and crotonitrile is formed from allyl iodide and potassium cyanide hence the acid was formulated CH2 = CH-CH2 C02H. An isomeric acid was discovered by A. Geuther in the form of an acid chloride in the products of the action of phosphorus pentachloride on acetoacetic ester. 

---