Nitrile reduction explained

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

Catalytic hydrogenation

The catalytic hydrogenation of nitriles is often the most economical route available for the production of primary amines.^[2] Catalysts for the reaction often include group 10 metals such as Raney nickel,^{[3] [4] [5]} palladium black, or platinum dioxide. 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.^[6]

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.^[7] 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,^[8] diborane,^[9] or elemental sodium in alcohol solvents.^[10]

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^[11] 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.^[12]

With diisobutylaluminium hydride

The hydride reagent Diisobutylaluminium hydride, or DIBAL-H, is commonly used to convert nitriles to the aldehyde.^[13] 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.^[14]

Electrochemical methods

Benzyl nitriles can also be reduced electrochemically.^{[15] [16]}

See also

• Urushibara cobalt
• Imine

Notes and References

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