In organic chemistry, hydrocyanation is a process for conversion of alkenes to nitriles. The reaction involves the addition of hydrogen cyanide and requires a catalyst if the substrate alkene is unactivated. This conversion is conducted on an industrial scale for the production of precursors to nylon. Direct hydrocyanation is rare in the laboratory because hydrogen cyanide is extremely toxic, but transfer variants can allow other nitrilic compounds to serve as hydrogen cyanide synthons.
Hydrocyanation of unactivated alkenes
Industrially, hydrocyanation is commonly performed on alkenes catalyzed by nickel complexes of phosphite () ligands. A general reaction is shown:
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Mechanism
The reaction proceeds via oxidative addition of HCN to a low-valent metal complex to give a hydrido cyanide complex. Subsequently the alkene binds to the complex. The intermediate then undergoes migratory insertion to give an alkylmetal cyanide. The cycle completes with reductive elimination of the nitrile, which is rate-limiting. Lewis acids, such as triphenylboron (), speed elimination, increasing the overall reaction rate.
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.
With activated alkenes
Carbonyls are well-known to add cyanide, in the cyanohydrin reaction; and several variants on the Michael reaction are formal hydrocyanations. Simple conjugate addition leads to β-cyanoketones; direct addition to form a cyanohydrin sometimes induces a second addition to form β-cyano-cyanohydrins. Reaction conditions allows access to any of these products.
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Generally acidic conditions favor 1,2-adducts, while basic conditions favor 1,4-adducts. Additions of alkali metal cyanides, for instance, lead exclusively to 1,4-addition. In contrast to alkali metal cyanides and cyanoaluminates, Lewis acidic cyanides, such as TMSCN, favor 1,2-addition. Acetylenic substrates undergo the reaction; however the scope of this reaction is limited and yields are often low. nitriles,
Naproxen, 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.
Transfer reactions
In transhydrocyanation, an equivalent of HCN is transferred from a cyanohydrin, e.g. acetone cyanohydrin, to another activated HCN acceptor. The transfer is an equilibrium process, initiated by base. The reaction can be driven by trapping or a superior acceptor, such as an aldehyde.
Some hydrocyanation catalysts generate a reversible equilibrium, and can transfer HCN units between two different alkenes.