Sodium Cyanide1

NaCN

[143-33-9]  · CNNa  · Sodium Cyanide  · (MW 49.01)

(preparation of nitriles,2 cyanohydrins,3 a-amino nitriles,4 methyleneamino acetonitriles;5 catalyst for benzoin condensation6)

Physical Data: mp 563.7 °C; vp1 1.0 mmHg (817 °C).

Solubility: sol water; slightly sol ethanol; the aq soln is strongly alkaline and rapidly decomposes.

Form Supplied in: white powder with chunks; widely available.

Purification: Perrin and Armarego7 for general procedure.

Handling, Storage, and Precautions: highly toxic; severe eye irritant; hygroscopic; readily absorbed through skin. Avoid breathing dust particles. Can be fatal if inhaled, swallowed, or absorbed through skin. Exposure can cause lung irritation and cyanosis (orl-hmn LDLo: 2857 mg kg-1; orl-rat LD50: 6440 mg kg-1). Store in a dry area; use only in a fume hood. Incompatible with acids, strong oxidizing agents, and carbon dioxide. May decompose on exposure to moist air or water. Thermal decomposition produces toxic fumes of hydrogen cyanide, carbon monoxide, carbon dioxide, and nitrogen oxides.

Nitrile Synthesis.

Nitriles can be readily prepared from activated alcohols and halides by treatment with NaCN in an appropriate solvent. The reactivity of NaCN closely parallels Potassium Cyanide and the review of the latter reagent should also be considered for general reaction conditions. A difference in reactivity, however, was observed in the reaction of NaCN with alkyl chlorides in DMSO.8 Increased yields and lower reaction times were seen for NaCN compared to KCN (eq 1). The conversion of alkyl bromides to nitriles using NaCN is accomplished under phase-transfer conditions employing primary, secondary, or tertiary amines as catalysts.9

NaCN has also proved to be the most favorable reagent for the preparation of sodium dicyanocuprate. The cyanocuprate generated in situ reacts readily with vinyl and aryl halides to afford the corresponding nitrile (eq 2).10 Aryl cyanation can also be effected with NaCN in the presence of catalytic Tetrakis(triphenylphosphine)palladium(0).11 This method requires the use of neutral Alumina either as a support for NaCN or as a cocatalyst.

Aldehydes can be converted to nitriles by treating the N-tosyl imines with NaCN in HMPA (eq 3).12 Tetrahydropyranyl ethers have also been shown to react with NaCN in the presence of Triphenylphosphine Dibromide to yield a nitrile (eq 4).13

The reaction of NaCN with aryl nickel compounds also provides a facile route to aromatic nitriles in high yields (eq 5).14

Cyanohydrin Synthesis.

Cyanohydrins are versatile synthetic intermediates which can be prepared by the reaction of NaCN with aldehydes, although benzoin condensations often compete. The reactions of NaCN with ketones,15 acid chlorides,16 and epoxides17 are much more general. A novel preparation of aryl cyanohydrin esters involves treatment of an acid chloride with NaCN, Sodium Borohydride, and catalytic Tetra-n-butylammonium Bromide (eq 6).18 The cyanohydrin anion generated by reduction of the acyl cyanide is immediately captured by any anhydrides or acid chlorides present.

a-Amino Nitriles.

Cyclopropane hemiacetals can undergo a one-pot modified Strecker synthesis under sonication to provide a-amino nitriles (eq 7).19 The reaction is high yielding and does not suffer significant polymerization or ring-opening side reactions. Since the cyanide group is easily hydrolyzed to the acid, this is a convenient method for the preparation of a-amino acids.

Acyl Cyanides.

a-Cyanoalkyl aryl ketones can be obtained from arylhydrazones by heterogeneous reaction with aq NaCN, an inert organic solvent, and acetic acid in the presence of air with catalytic quaternary ammonium salts (eq 8).20 Air oxidation of the initial adduct is followed by alkaline-induced decomposition affording the a-cyanoalkyl ketone.

Ring Opening/Forming.

NaCN in DMSO has been used to nucleophilically open geminally activated cyclopropanes (eq 9).21 Conversely, the reaction of NaCN on a dimethylene heptanedionate yields a cyano-oxobicyclo[3.2.1]octanecarboxylate via a novel double-ring closure (eq 10).22

Reducing Agent.

Deethoxycarbonylation of geminal diesters can be effected with NaCN in DMSO (eq 11).23 The same reaction in HMPA can selectively cleave methyl esters in the presence of ethyl esters.24

The reaction of benzil with NaCN in DMSO has been shown to produce a trans-a,a-stilbenediol dibenzoate (eq 12).25 The proposed mechanism assumes cleavage of the central C-C bond in benzil, generating a resonance stabilized carbanion. In the presence of a proton donor this carbanion is forced to attack a second benzil molecule, forming the stilbene product.

NaCN has also been used in the desulfurization of dialkyl disulfides in DMSO or DMF to give the corresponding monosulfide (eq 13).26 Under similar conditions, thiophenols react with NaCN to afford methyl thioethers (eq 14).

Oxidations.

The oxidation of a,b-unsaturated aldehydes to the corresponding methyl esters can be accomplished with NaCN (eq 15).27 The cyanohydrin generated in situ is susceptible to further oxidation by Manganese Dioxide to an acyl cyanide, leading finally in an alcoholic medium to an ester. Aside from the simplicity and convenience of this procedure, the high yield and lack of cis-trans isomerization of the a,b-alkenic linkage is also noteworthy compared to traditional methods such as Silver(I) Oxide oxidation.


1. Fatiadi, A. J. In The Chemistry of Triple-Bonded Functional Groups; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1983; Part 2, Chapter 26.
2. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel's Textbook of Practical Organic Chemistry, 5th ed.; Wiley: New York, 1989; Chapter 5, p 712.
3. Friedrich, K. In Ref. 1(a), Chapter 28.
4. Williams, R. M. Synthesis of Optically Active a-Amino Acids; Pergamon: New York, 1989; pp 208-229.
5. Adams, R.; Langley, W. D. OSC 1941, 1, 355.
6. Stetter, H. AG(E) 1976, 15, 639.
7. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 369.
8. Friedman, L.; Shechter, H. JOC 1960, 25, 877.
9. Reeves, W. P.; White, M. R. SC 1976, 6, 193.
10. House, H. O.; Fischer, W., Jr. JOC 1969, 35, 3626.
11. Dalton, J. R.; Regen, S. L. JOC 1979, 44, 4443.
12. Glass, R.; Hoy, R. TL 1976, 1781.
13. Sonnet, P. F. SC 1976, 6, 21.
14. Cassar, L. JOM 1973, 54, C57.
15. Swain, C. J.; Kneen, C.; Baker, R. TL 1990, 31, 2445.
16. Koenig, K. E.; Weber, W. P. TL 1974, 2275.
17. Nagata, W.; Yoshioka, M.; Okumura, T. TL 1966, 847.
18. Photis, J. JOC 1981, 46, 182.
19. Fadel, A. T 1991, 47, 6265.
20. Chiba, T.; Okimoto, M. JOC 1991, 56, 6163.
21. Kondo, K.; Takahatake, Y.; Sugimoto, K.; Tunemoto, D. TL 1978, 907.
22. Stetter, H.; Kuhlmann, H. LA 1979, 1122.
23. Krapcho, A. P.; Glynn, G. A.; Grenon, B. J. TL 1967, 215.
24. Muller, P.; Siegfried, B. HCA 1974, 57, 987.
25. Trisler, J.; Frye, J. JOC 1965, 30, 306.
26. Tanaka, K.; Hayami, J.; Kaji, A. BCJ 1972, 45, 536.
27. Corey, E. J.; Gilman, N. W.; Ganem, B. E. JACS 1968, 90, 5616.

Timothy E. Wilson

Emory University, Atlanta, GA, USA

Serkos A. Haroutounian

Agricultural University of Athens, Greece



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