Hydrocyanation

Hydrocyanation is, most fundamentally, the process whereby H+ and –CN ions are added to a molecular substrate. Usually the substrate is an alkene and the product is a nitrile. When –CN is a ligand in a transition metal complex, its basicity makes it difficult to dislodge, so, in this respect, hydrocyanation is remarkable. Since cyanide is both a good σ–donor and π–acceptor its presence accelerates the rate of substitution of ligands trans from itself, the trans effect.1 A key step in hydrocyanation is the oxidative addition of hydrogen cyanide to low–valent metal complexes.[1] In hydrocyanation of unsaturated carbonyls addition over the alkene competes with addition over the carbonyl group.

Contents

Inorganic Chemistry

Hydrocyanation is performed on alkenes and alkynes with copper, palladium, and most commonly, nickel catalysts.[1] Industrial hydrocyanation utilizes phosphite (P(OR)3) complexes of nickel. Phosphites give excellent catalysts, whereas the related phosphine (PR3) ligands, which are more basic, are catalytically inactive.[1] Chiral, chelating aryl diphosphite complexes are commonly employed in asymmetric hydrocyanation. An example of a nickel–phosphite catalyzed hydrocyanation of ethene.[1]

Lewis acids, such as B(C6H5)3, can increase hydrocyanation rates and allow for lower operating temperatures.[2] Triphenylboron may derive this ability from sterically protecting the –CN as it is bound to nitrogen.[1] Rates can also be amplified with electron–withdrawing groups (NO2, CF3, CN, C(=O)OR, C(=O)R) on the phosphite ligands, because they stabilize Ni(0).[3] A major problem when using nickel catalysts for hydrocyanation is the production of Ni0(CN)x as a result of excess HCN.3 Bulky ligands impede the formation of these unreactive Ni0(CN)x complexes.[4]

Usage

Hydrocyanation is important due to the versatility of alkyl nitriles (RCN), which are important intermediates for the syntheses of amides, amines, carboxylic acids, and ester compounds.[5] The most popular industrial usage of nickel-catalyzed hydrocyanation is for adiponitrile (NC–(CH2)4–CN) synthesis from 1,3–butadiene (CH2=CH–CH=CH2). Adiponitrile is a precursor to hexamethylenediamine (H2N–(CH2)6–NH2), 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-3-butenenitrile (2M3BM) and 3-pentenenitrile (3PN), an isomerization step from 2M3BM (not desired) to 3PN and a second hydrocyanation (aided by a Lewis acid cocatalyst such as aluminium trichloride or triphenylboron) to adiponitrile.[6]

Naproxen, an anti-inflammatory drug, utilizes an asymmetric enantioselective hydrocyanation of vinylnaphthalene from a phosphinite(OPR2) 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% selectivity. Upon recrystallization of the crude product, the optically pure nitrile can be attained.

History

Hydrocyanation was first reported by Arthur and Pratt in 1954, when they homogeneously catalyzed the hydrocyanation of linear alkenes.[7]

References

  1. ^ a b c d e Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M. Advanced Inorganic Chemistry; John Wiley & Sons: New York, 1999; pp. 244-6, 440, 1247-9.
  2. ^ Baker, M.J.; Pringle, P.G. (1991). "Chiral aryl diphosphites: a new class of ligands for hydrocyanation catalysis". J. Chem. Soc. Chem. Commun. (18): 1292–3. doi:10.1039/c39910001292. 
  3. ^ Goertz, W.; Kramer, P. C. J.; van Leeuwen, P. W. N. M.; Vogt, D. (1997). "Application of chelating diphosphine ligands in the nickel-catalysed hydrocyanation of alk-l-enes and ω-unsaturated fatty acid esters". Chem. Commun. (16): 1521–2. doi:10.1039/a702811c. 
  4. ^ Yan, M.; Xu, Q. Y.; Chan, A. S. C. (2000). "Asymmetric hydrocyanation of olefins catalyzed by chiral diphosphite–nickel complexes". Tetrahedron: Asymmetry 11 (4): 845–9. doi:10.1016/S0957-4166(00)00026-4. 
  5. ^ RajanBabu, T. V.; Casalnuovo, A. L. (1994). "Electronic effects in asymmetric catalysis: Enantioselective carbon-carbon bond forming processes". Pure & Appl. Chem. 66 (7): 1535–42. doi:10.1351/pac199466071535. 
  6. ^ Bini, L.; Muller, C.; Wilting, J.; von Chrzanowski, L.; Spek, A. L.; Vogt, D. (2007). "Highly Selective Hydrocyanation of Butadiene toward 3-Pentenenitrile". J. Am. Chem. Soc. 129 (42): 12622. doi:10.1021/ja074922e. PMID 17902667. 
  7. ^ Arthur Jr., P.; England, D. C.; Pratt, B. C., Whitman, G. M. (1954). J. Am. Chem. Soc. 76 (21): 5364–7. doi:10.1021/ja01650a034.