Cyanogen Bromide

X-C&tbond;N
(1; X = Br)

[506-68-3]  · CBrN  · Cyanogen Bromide  · (MW 105.92) (2; X = Cl)

[506-77-4]  · CClN  · Cyanogen Chloride  · (MW 61.47) (3; X = I)

[506-78-5]  · CIN  · Cyanogen Iodide  · (MW 152.92) (4; X = Ts)

[19158-51-1]  · C8H7NO2S  · p-Toluenesulfonyl Cyanide  · (MW 181.21) (5; X = OPh)

[1122-85-6]  · C7H5NO  · Phenyl Cyanate  · (MW 119.12)

(counter-attack reagent useful for the cleavage of carbon-heteroatom bonds,1 cyanation,2 and synthesis of heterocycles3)

Physical Data: (1) bp 61.4 °C; mp 52 °C; d 2.015 g cm-3; (2) bp 12.7 °C; mp -6 °C; d 1.186 g cm-3; (3) sublimes at 45 °C; mp 146.7 °C; d 2.84 g cm-3; (4) mp 49 °C; (5) bp 77 °C/13 mmHg; d 1.096 g cm-3.

Preparative Methods: p-toluenesulfonyl cyanide (TsCN) is prepared from the reaction of sodium p-toluenesulfinate with ClCN.4 Phenyl cyanate (PhOCN) is available from the reaction of phenol with BrCN.5a,b

Handling, Storage, and Precautions: BrCN and its analogs are highly toxic. These reagents should be handled in a fume hood.

Counter-Attack Reagent.

Cyanogen halides are representative of a class of counter-attack reagents6 which are useful for the cleavage of carbon-heteroatom bonds. The classic Von Braun reaction1 with BrCN provides a convenient method for the demethylation of tertiary methyl amines (eq 1).7 The products of this reaction are a dialkyl-substituted cyanamide and an alkyl bromide, with bromide attack occurring at the more electrophilic8a or sterically accessible site. Similar methodology with BrCN has been utilized to induce ring opening8b as well as ring expansion8c,d of N-heterocycles (eq 2).

Cleavage of thioethers is also accomplished with cyanogen halides. The selective reaction of BrCN with methionine in peptide chains (eq 3)9a has been applied to the removal of peptide chains from the resin after solid phase synthesis.9b In a related sequence, treatment of dithioacetals with ICN affords the a-thionitrile.10 The synthesis of symmetrical11a and mixed11b disulfides and the intramolecular formation of disulfide bonds in peptides11c have been accomplished with BrCN and ICN, respectively. Another example of the counter-attack properties of BrCN and ICN is shown by their reaction with dialkylvinylboranes to produce trans-alkenes (eq 4).12 In addition, vinyl bromides are available from the treatment of disubstituted vinylsilanes with BrCN and Aluminum Chloride.13

Cyanation.

The synthesis of unsaturated nitriles is accomplished by treatment of vinyl cuprates with ClCN or TsCN14 or more conveniently from the reaction of vinyllithium reagents with PhOCN (eq 5).5a Cyanation of lithium ketone enolates with TsCN proceeds in good yield (eq 6).2 In addition, enamines react readily with ClCN to provide the a-cyanoketone.15a The use of BrCN in the latter reaction affords the corresponding a-bromo ketone.15b Alkylation of an N-alkylimidazole to its 2-cyano derivative proceeds through an intermediate imidazolium ylide (eq 7).16

Heterocycle Synthesis.

Cyanogen halides are useful for the synthesis of N-heterocycles via double attack by nitrogen and/or sulfur nucleophiles.3 In addition, the cyano group of TsCN participates in a Diels-Alder reaction with selected dienophiles (eq 8).17


1. Hageman, H. A. OR 1953, 7, 198.
2. Kahne, D.; Collum, D. B. TL 1981, 5011.
3. (a) Leonard, N. J.; Curtin, D. Y.; Beck, K. M. JACS 1947, 69, 2459. (b) Richardson, Jr., A. JOC 1963, 28, 2581. (c) Basu, N. K.; Rose, F. L. JCS 1963, 5660. (d) Potts, K. T.; Huseby, R. M. JOC 1966, 31, 3528.
4. Cox, J. M.; Ghosh, R. TL 1969, 3351.
5. (a) Murray, R. E.; Zweifel, G. S 1980, 150. (b) Martin, D.; Bauer, M. OS 1983, 61, 35.
6. Hwu, J. R.; Gilbert, B. A. T 1989, 45, 1233.
7. (a) Rapoport, H.; Lovell, C. H.; Reist, H. R.; Warren, Jr., M. E. JACS 1967, 89, 1942. (b) Werner, G.; Schickfluss, R. LA 1969, 729, 152.
8. (a) Fitt, J. J.; Gschwend, H. W. JOC 1981, 46, 3349. (b) Verboom, W.; Visser, G. W.; Reinhoudt, D. N. T 1982, 38, 1831. (c) Bremner, J. B.; Browne, E. J.; Chohan, V.; Yates, B. F. AJC 1984, 37, 1043. (d) Bremner, J. B.; Thirasasana, N. AJC 1982, 35, 2307.
9. (a) Gross, E. Methods Enzymol. 1967, 11, 238. (b) Hancock, W. S.; Marshall, G. R. JACS 1975, 97, 7488.
10. Pochat, F.; Levas, E. TL 1976, 1491.
11. (a) Ho, T. L.; Wong, C. M. SC 1973, 3, 317. (b) Abe, O.; Lukacovic, M. F.; Ressler, C. JOC 1974, 39, 253. (c) Bishop, P.; Chmielewski, J. TL 1992, 33, 6263.
12. Zweifel, G.; Fisher, R. P.; Snow, J. T.; Whitney, C. C. JACS 1972, 94, 6560.
13. Chan, T. H.; Lau, P. W. K.; Mychajlowskij, W. TL 1977, 3317.
14. Westmijze, H.; Vermeer, P. S 1977, 784.
15. (a) Kuehne, M. E. JACS 1959, 81, 5400. (b) Fusco, R.; Rossi, S.; Bianchetti, G. G 1961, 91, 841.
16. McCarthy, J. R.; Matthews, D. P.; Whitten, J. P. TL 1985, 26, 6273.
17. (a) Jagt, J. C.; van Leusen, A. M. JOC 1974, 39, 564. (b) Jagt, J. C.; van Leusen, A. M. RTC 1977, 96, 145.

Joel Morris

The Upjohn Company, Kalamazoo, MI, USA



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