Industrially, hydrocyanation is commonly performed on alkenes catalyzed by nickel complexes of phosphite ligands. A general reaction is shown: The reaction proceeds via the oxidative addition of HCN to Ni to give a hydridonickel cyanide complex, abbreviated NiL2. Subsequent binding of the alkene gives the intermediate NiL, which then undergoes migratory insertion to give an alkylnickel cyanide NiL2. The cycle is completed by the reductive elimination of the nitrile. Lewis acids, such as B3, can increase hydrocyanation rates and allow for lower operating temperatures. Triphenylboron may derive this ability induce reductive elimination of the nitrile product. Rates can also be amplified with electron-withdrawing groups OR, C on the phosphite ligands, because they stabilize Ni.
Catalyst deactivation
Catalyst deactivation involves formation of dicyanonickel species, which are unreactive toward alkenes. The dicyanide arises via two pathways :
Most alkenes are prochiral, meaning in this context that their hydrocyanation generates chiral nitriles. Conventional hydrocyanation catalysts, e.g. Ni4, catalyse the formation of racemic mixtures, consisting of equal amounts of the two enantiomeric nitriles. When however the supporting ligands are chiral, the hydrocyanation can be highly enantioselective. For asymmetric hydrocyanation, popular chiral ligands are chelatingaryl diphosphite complexes.
Transhydrocyanation
In transhydrocyanation, an equivalent of HCN is transferred from a cyanohydrin, e.g. acetone cyanohydrin, to another HCN acceptor. The transfer is an equilibrium process, initiated by base. The reaction can be driven by trapping reactions or by the use of a superior HCN acceptor, such as an aldehyde.
Applications
Hydrocyanation is important due to the versatility of alkyl nitriles, which are important intermediates for the syntheses of amides, amines, carboxylic acids and esters. The most important industrial application is the nickel-catalyzed synthesis of adiponitrile synthesis from buta-1,3-diene. Adiponitrile is a precursor to hexamethylenediamine, which is used for the production of certain kinds of Nylon. The DuPont ADN process to give adiponitrile is shown below: This process consists of three steps: hydrocyanation of butadiene to a mixture of 2-methyl-butene-3-nitrile and pentene-3-nitrile, an isomerization step from 2M3BM to 3PN and a second hydrocyanation to adiponitrile.
Asymmetric hydrocyanation
, an anti-inflammatory drug, is prepared via an asymmetric hydrocyanation of a vinylnaphthalene utilizing a phosphinite ligand, L. The enantioselectivity of this reaction is important because only the S enantiomer is medicinally desirable, whereas the R enantiomer produces harmful health effects. This reaction can produce the S enantiomer with >90% stereoselectivity. Upon recrystallization of the crude product, the optically pure nitrile can be obtained.
History
Hydrocyanation was first reported by Arthur and Pratt in 1954, when they homogeneously catalyzed the hydrocyanation of linear alkenes. The industrial process for catalytic hydrocyanation of butadiene to adiponitrile was invented by William C. Drinkard.
