Nitrile reduction

In nitrile reduction a nitrile is reduced to either an amine or an aldehyde with a suitable chemical reagent.[1][2]

Catalytic hydrogenation

The catalytic hydrogenation of nitriles is often the most economical route available for the production of primary amines.[3] Catalysts for the reaction often include group 10 metals such as Raney nickel,[4][5][6] palladium black, or platinum dioxide.[1] However, other catalysts, such as cobalt boride, also can be regioselective for primary amine production:

R-C≡N + 2 H2 → R-CH2NH2

A commercial application of this technology includes the production of hexamethylenediamine from adiponitrile, a precursor to Nylon 66.[7]

Depending on reaction conditions, reactive intermediate imines can also undergo attack by amine products to afford secondary and tertiary amines:

2 R-C≡N + 4 H2 → (R-CH2)2NH + NH3
3 R-C≡N + 6 H2 → (R-CH2)3N + 2 NH3

Such reactions proceed via enamine intermediates.[8] The most important reaction condition for selective primary amine production is catalyst choice.[1] Other important factors include solvent choice, solution pH, steric effects, temperature, and the pressure of hydrogen.

Stoichiometric reductions

To amines

Reducing agents for the non-catalytic conversion to amines include lithium aluminium hydride, lithium borohydride,[9] diborane,[10] or elemental sodium in alcohol solvents.[11]

To aldehydes

Nitriles can also be converted to aldehydes by reduction and hydrolysis. The Stephen aldehyde synthesis uses Tin(II) chloride and hydrochloric acid to yield an aldehyde via the hydrolysis of a resulting iminium salt. Aldehydes can also form using a hydrogen donor followed by in-situ hydrolysis of an imine. Useful reagents for this reaction include formic acid with a hydrogenation catalysis[12] or metal hydrides, which are used to add one mol of hydrogen to the nitrile. For example, sodium borohydride reduces nitriles in alcoholic solvents with a CoCl2 catalyst or Raney nickel.[13]

With diisobutylaluminium hydride

The mechanism for the reduction of a nitrile to an aldehyde with DIBAL-H.

The hydride reagent Diisobutylaluminium hydride, or DIBAL-H, is commonly used to convert nitriles to the aldehyde.[14] Regarding the proposed mechanism, DIBAL forms a Lewis acid-base adduct with the nitrile by formation of an N-Al bond. The hydride is then transferred to the carbon of the nitrile. Aqueous workup produce the desired aldehyde and ammonia.[15]

Electrochemical methods

Benzyl nitriles can also be reduced electrochemically.[16][17]

See also

References

  1. ^ a b c Nishimura, Shigeo (2001). Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis (1st ed.). New York: Wiley-Interscience. pp. 254–277. ISBN 9780471396987.
  2. ^ March, Jerry (1985). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.). New York: Wiley. ISBN 9780471854722. OCLC 642506595.
  3. ^ Karsten, Eller; Henkes, Erhard; Rossbacher, Roland; Höke, Hartmut (2000). "Amines, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a02_001. ISBN 3527306730.
  4. ^ Biggs, B. S.; Bishop, W. S. (1947). "Decamethylenediamine". Organic Syntheses. 29: 18. doi:10.15227/orgsyn.027.0018.
  5. ^ Allen, C. F. H.; Wilson, C. V. (1947). "2,4-Diphenylpyrrole". Organic Syntheses. 27: 33. doi:10.15227/orgsyn.027.0033.
  6. ^ Robinson, John C.; Snyder, H. R. (1943). "β-Phenylethylamine". Organic Syntheses. 23: 71. doi:10.15227/orgsyn.023.0071.
  7. ^ Musser, Michael Tuttle (2000). "Adipic Acid". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a01_269. ISBN 3527306730.
  8. ^ Barrault, J. (1997). "Synthesis of fatty amines. Selectivity control in presence of multifunctional catalysts". Catalysis Today. 37 (2): 137–153. doi:10.1016/S0920-5861(97)00006-0.
  9. ^ Ookawa, Atsuhiro; Soai, Kenso (1986). "Mixed solvents containing methanol as useful reaction media for unique chemoselective reductions within lithium borohydride". The Journal of Organic Chemistry. 51 (21): 4000–4005. doi:10.1021/jo00371a017.
  10. ^ Hutchins, R. O.; Maryanoff, B. E. (1973). "2-tert-Butyl-1,3-diaminoproane". Organic Syntheses. 53: 21. doi:10.15227/orgsyn.053.0021.
  11. ^ Suter, C. M.; Moffett, Eugene W. (1934). "The Reduction of Aliphatic Cyanides and Oximes with Sodium and n-Butyl Alcohol". Journal of the American Chemical Society. 56 (2): 487. doi:10.1021/ja01317a502.
  12. ^ van Es, T.; Staskun, B. (1971). "4-Formylbenzenesulfonamide". Organic Syntheses. 51: 20. doi:10.15227/orgsyn.051.0020.
  13. ^ Smith, Michael; March, Jerry (October 2001). March's advanced organic chemistry : reactions, mechanisms, and structure (5th ed.). New York: Wiley. ISBN 9780471585893. OCLC 43936853.
  14. ^ Carey, F. A.; Sundberg, R. J.; Advanced Organic Chemistry, Part B: Reactions and Synthesis
  15. ^ Solomons, T W. G, Craig B. Fryhle, and S A. Snyder. Organic Chemistry. , 2014. Print.
  16. ^ V. Krishnan; A. Muthukumaran; H. V. K. Udupa (1979). "The electroreduction of benzyl cyanide on iron and cobalt cathodes". Journal of Applied Electrochemistry. 9 (5): 657–659. doi:10.1007/BF00610957. S2CID 96102382.
  17. ^ V. Krishnan; A. Muthukumaran; H. V. K. Udupa (1983). Process for Electrochemical Preparation of beta phenylethylamine using cobalt black cathode (PDF). Calcutta: India Patent Office.