Hydrogen Cyanide1

HCN

[74-90-8]  · CHN  · Hydrogen Cyanide  · (MW 27.03)

(useful C1 synthon)

Alternate Names: hydrocyanic acid; prussic acid.

Physical Data: mp -13.4 °C; bp 25.6 °C; d (gas) 0.941 g cm-3; d (liquid) 0.687 g cm-3.

Solubility: slightly sol ether; miscible with water and alcohol.

Form Supplied in: colorless gas at rt, or bluish-white when liquefied, with a characteristic odor resembling bitter almonds.

Preparative Methods: anhydrous HCN is prepared on a large scale by the catalytic oxidation of ammonia-methane mixtures (Andrussow process).1c In the laboratory it can conveniently be prepared by acidifying NaCN or potassium hexacyanoferrate, K4[Fe(CN)6].3

HCN oligomers:4 the HCN dimer (HN=CHCN) is too reactive to be isolated. Under acidic conditions the reaction proceeds to the trimer s-triazine5 and under basic conditions to the tetramer Diaminomaleonitrile6 via the trimer intermediate 2-aminomalononitrile.

Handling, Storage, and Precautions: Intensely poisonous. Avoid skin contact and inhalation. Must be handled by specially trained experts. Use in a fume hood. Flash point -17.8 °C (closed cup); explosion limits: upper 40%, lower 5.6% by vol in air; when not pure or stabilized, can polymerize explosively. The principal routes of occupational HCN exposure are inhalation and absorption through the skin. Inhalation of large amounts of cyanide causes immediate unconsciousness, convulsions, and death from respiratory arrest within 1-15 min. TLV ceiling of 10 ppm has been recommended since 1980.2

Electrophilic Aromatic Substitution.

The preparation of aldehydes from phenols or phenol ethers by treatment of the aromatic substrate with HCN and Hydrogen Chloride in the presence of Lewis acid catalysts is known as the Gattermann aldehyde synthesis (eq 1).7 The first stage consists of protonation of the nitrile to give a nitrilium ion or nitrile-Lewis acid complex, regarded as the electrophilic species attacking the substrates.8

Nucleophilic Substitution.

Chlorotrimethylsilane is converted into Cyanotrimethylsilane (eq 2),9 which is also a versatile cyanidation agent,10 whereas carbonocyanidic acid methyl ester [17640-15-2] and ethyl ester [623-49-4], introduced by Mander as selective C-acylation agents,11 are made from the corresponding chloroformates (eq 3).12

Epoxide Opening.

Addition of HCN to epichlorohydrin gives an intermediate, which on quaternization with Trimethylamine and subsequent hydrolysis of the nitrile gives carnitine (eq 4).13

Additions to Alkenes, Dienes, and Alkynes.

These occur in the presence of Ni0, Pd0, or cobalt carbonyl complexes.14,15 The use of Lewis acids as cocatalysts generally improves the activity and lifetime of the catalyst.16 Ethylene is hydrocyanated to propionitrile in the presence of Octacarbonyldicobalt or [M(P(OR)3)4] (M = Ni, Pd; R = alkyl, aryl); with unsymmetrical higher alkenes, the cobalt catalyst gives exclusively the product from Markovnikov addition (e.g. propene gives 2-cyanopropane in 75% yield),14 while the nickel and palladium phosphite systems give product mixtures.17

In the case of conjugated dienes, nickel catalysts are preferred; the mechanism involves a p-allyl intermediate. Both 1,4- and 1,2-addition occur, although the regiochemistry seems to be controlled by the thermodynamic stability of the intermediate allyl species, e.g. 1,3-pentadiene gives exclusively the branched nitrile (eqs 5 and 6).18

In the presence of these catalysts, unconjugated dienes rearrange to conjugated dienes prior to the addition of HCN.

Addition to alkynes is best catalyzed by nickel complexes with syn stereochemistry. The regioselectivity is influenced by both steric and electronic effects.19 The reactions with alkynols show evidence for some chelation between the oxygen and nickel in the transition state (eq 7).20

Hydrolysis and cyclization of some cyanoalkenes containing methoxymethyl ethers gives a-alkylidene-g-lactones (eq 8).21

The asymmetric Markovnikov addition of HCN to vinylarenes in the presence of Ni0 complexes of 1,2-diolphosphinites derived from sugars gives 2-aryl-2-propionitriles in high yield and enantioselectivity (eq 9).22

Asymmetric Hydrocyanation.

Asymmetric hydrocyanation of aldehydes to chiral cyanohydrins is a convenient route to chiral a-hydroxy carboxylic acids and chiral 1-amino-2-alkanols; catalysts are often used, e.g. the cyclic dipeptide cyclo((S)-phenylalanyl-(S)-histidyl) (eq 10)23 or the enzyme (R)-oxynitrilase (eq 11).24 This reaction proceeds normally in aqueous solutions with NaCN; however, the noncatalyzed reaction leading to racemic product can be efficiently suppressed by the use of anhydrous HCN in organic solvents.

Enantioselective addition of HCN to ketones in organic solvents catalyzed by (R)-oxynitrilase proceeds similarly.25


1. (a) Jenks, W. R. In Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed.; Wiley: New York, 1979; Vol. 7, pp 307-319. (b) Klink, H.; Griffiths, A.; Huthmacher, K.; Ittzel, H.; Knorre, H.; Voigt, C.; Weitburg, O. In Ullmann's Encyclopedia of Industrial Chemistry, 5th ed.; VCH: Weinheim, 1978; Vol. A8, pp 159-165. (c) The Merck Index, 11th ed.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 760.
2. Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th ed.; American Conference of Governmental Industrial Hygienists: Cincinnati, 1991; Vol. III, p 775.
3. Glemser, O. In Handbook of Preparative Inorganic Chemistry, 2nd ed.; Brauer, G., Ed.; Academic: New York, 1963; Vol. 1, pp 658-660.
4. Donald, D. S.; Webster, O. W. In Advances in Heterocyclic Chemistry; Academic: New York, 1987; Vol. 41, pp 1-36.
5. Grundmann, C. AG(E) 1963, 2, 309.
6. Okada, T.; Asai, N. Ger. Patent, 2 022 243, 1970 (CA 1971, 74, 22 456h).
7. Baltazzi, E.; Krimen, L. I. CRV 1963, 63, 526.
8. Amer, M. I.; Booth, B. L.; Noori, G. F. M.; Proenca, M. F. JCS(P1) 1983, 1075.
9. Uznanski, B.; Stec, W. J. S 1978, 154.
10. Rasmussen, J. K.; Heilmann, S. M.; Krepski, L. R. In Advances in Silicon Chemistry; Larson, G. L., Ed.; JAI: Greenwich CT, 1991; Vol. 1, pp 65-187.
11. Mander, L. N.; Sethi, S. P. TL 1983, 24, 5425.
12. Lonza A. G. Swiss Patent 675 875, 1990 (CA 1991, 115, 279 444j).
13. Yamaguchi, H. Jpn. Patent 139 559, 1989 (CA 1990, 112, 7049n).
14. Arthur, P.; England, D. C.; Pratt, B. C.; Whitman, G. M. JACS 1954, 76, 5364.
15. Jackson, W. R.; Lovel, C. G. TL 1982, 23, 1621.
16. Druliner, J. D. OM 1984, 205.
17. Brown, E. S. In Organic Syntheses via Metal Carbonyls; Wender, I.; Pino, P., Eds.; Wiley: New York, 1977; Vol. 2, pp 655-672.
18. Keim, W.; Behr, A.; Lühr, H. O.; Weisser, J. J. Catal. 1982, 78, 209.
19. Jackson, W. R.; Lovel, C. G. AJC 1983, 36, 1975.
20. Jackson, W. R.; Lovel, C. G. AJC 1988, 41, 1099.
21. Jackson, W. R.; Perlmutter, P.; Smallridge, A. J. AJC 1988, 41, 251.
22. RajanBabu, T. V.; Casalnuovo, A. L. JACS 1992, 114, 6265.
23. Tanaka, K.; Mori, A.; Inoue, S. JOC 1990, 55, 181.
24. Ziegler, T.; Hörsch, B.; Effenberger, F. S 1990, 575 (CA 1990, 113, 190 847d).
25. Effenberger, F.; Hörsch, B.; Weingart, F.; Ziegler, T.; Kühner, S. TL 1991, 32, 2605.

Gérard Romeder

Lonza, Basel, Switzerland



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