Nitrile From alcohol, with inversion

Inter and intramolecular nucleophilic displacement of alcohols with inversion by means of diethyl azodicarboxylate (DEAD)-triphenylphosphine and a nucleophile. Also dehydration, esterification of alcohols or alkylation of phenols and one step synthesis of nitriles from alcohols (see 1 st edition). 

Benzylic carbocations are also stabilized by complexation to chromium and a number of interesting reactions have been reported. Again, reaction of the carbocations with nucleophiles occurs from the exo face of the complex, relative to the metal. Carbocations are readily formed by treatment of benzylic alcohols with a strong acid, such as sulfuric acid, tetrafluoroboric acid, or borontrifluoride etherate. The cation can be trapped with water, alcohols, nitriles, and mono-or disubstituted amines to form alcohols, ethers, amides, and di- or trisubstituted amines respectively. Scheme 96 illustrates the formation of a benzylic carbocation followed by intramolecular trapping, resulting in a net inversion of stereochemistry. Benzylic acetates react with trimethyl aluminium introducing a methyl group from the opposite face of the metal. 

A popular reaction type in recent years has been the conversion of alcohols into other compounds by use of an organophosphorus compound in the presence of a source of a nucleophile [reaction (8)]. PhsP plus diethyl azodicarboxylate has been a particularly popular form of organophosphorus reagent, and the product is formed with inversion of configuration. In 1977 there appeared a number of variations on this general theme, for the synthesis of halides, thiocyanates, thio-ethers, azides, and esters from alcohols.Similar systems have been used to convert amides and thioamides into nitriles. ... 

The absolute reaction rate of methyl acrylate and the nitrile ylide derived from 2,3-diphenyl-2/f-azirine at 25°C has been estimated as 7.6 X 10 AT sec. Inductive effects exerted by substituents on the nitrile ylide also have an important effect on the regioselectivity of the cycloaddition. Benzonitrilio-hexafluoro-2-propanide (44) and methyl acrylate yield products with inverse regioselectivity as compared with the reactions of the related benzonitrilo-2-propanide 47. The difference in regioselectivity has been attributed to the larger coefficient at the trisubstituted carbon atom of the gem-trifluoromethyl substituted nitrile ylide 44. This result parallels the different mode of addition of alcohols to nitrile ylides 44 and 47. 

The cyanide ion is a source of nucleophilic carbon and is only weakly basic. It is thus available as a salt that can be used in water solution. It can be alkylated most readily by nucleophilic substitution under phase-transfer conditions using a quaternary ammonium catalyst (Eq. 7.14, Section 9.6.1) [26]. The alkylations also proceed well under homogeneous conditions in DMSO. Trimethylsilyl ethers may serve as electrophiles and can be prepared in situ from alcohols. Heating an alcohol at 65 °C with sodium cyanide, trimethylchlorosilane, and a catalytic amount of sodium iodide in acetonitrile and DMF gives the nitriles in a single operation [27]. Good yields are obtained with primary, secondary, and tertiary alcohols, and inversion of configuration has been demonstrated in a secondary case. 

---