Zinc Cyanide1


[557-21-1]  · C2N2Zn  · Zinc Cyanide  · (MW 117.43)

(mild Lewis acid used as an alternative to HCN in Gattermann formylation reactions, in the synthesis of a-cyanoenamines, and in the cyanosilylation of carbonyl compounds)

Physical Data: mp 800 °C (dec).

Solubility: practically insol water, alcohols; sol aq solutions of alkali cyanides.

Form Supplied in: white crystalline powder, with alkali metal chlorides as possible impurities. Drying: one of the cyanides most stable to heat, it volatilizes only to a small extent on strong heating.2

Preparative Methods: can be made by the action of cyanogen on the metal at 300 °C, by dissolving Zinc Oxide in Hydrogen Cyanide, or by a metathetical reaction (see below).

Handling, Storage, and Precautions: as required by national poisons rules; extremely toxic by ingestion, inhalation, and skin contact. Irritating to the eyes. All work must be carried out in an efficient fume hood.

Gattermann Reactions.

In the classical Gattermann aldehyde synthesis, hydrogen cyanide and Hydrogen Chloride are used together with a Lewis acid such as Aluminum Chloride or Zinc Chloride. In the Adams modification,3 zinc cyanide is used together with hydrogen chloride as a more convenient reagent system, effectively generating hydrogen cyanide and zinc chloride. Any phenol that can be formylated using the classical Gattermann reaction conditions can be converted equally well into a hydroxy aldehyde by the Adams method. Pure zinc cyanide is said to be ineffective but may be activated by the addition of potassium chloride.4

Although the mechanism of the Gattermann reaction has not been investigated in detail, it is known that an initial nitrogen-containing product is hydrolyzed to the aldehyde (eq 1). It has been suggested that the electrophile may be a protonated dimer of HCN.5 In some cases the hydrocyanic acidium ion may be involved; in others, a Lewis acid complex could be formed between hydrogen cyanide and, for example, zinc chloride or aluminum chloride. In this connection, a very high acidity is required for reaction to occur with benzene; evidence has been presented in favor of a diprotonated HCN in that case.6 In reactions involving the system Zn(CN)2-HCl-AlCl3, a relative rate for the formylation of toluene versus benzene (KT/KB) of 128 was obtained.7

Early examples showed that both a- and b-naphthol could be formylated in good yields, in the absence of a Lewis acid other than the zinc chloride, as indicated (eq 2).3a Anisole (eq 3) and resorcinol dimethyl ether are converted in good yields into the expected aldehydes in the presence of added aluminum chloride.3b Another improvement in the experimental procedures involves the use of tetrachloroethane as the solvent; this method has been used in the formylation of hindered systems such as 1,3,5-triisopropylbenzene.8 A detailed and checked method for the preparation of mesitaldehyde is available.9 The first stage in the synthesis of a number of fungal metabolites involves the formylation of orcinol at the 4-position.10 Another recent example is shown in eq 4,11 and others are known.12 As with Friedel-Crafts alkylation and acylation reactions of alkylarenes, it is not unusual to observe rearrangement of the substrate in the presence of aluminum chloride. Thus, although 2,3-dimethylnaphthalene was formylated to give the expected product at 55 °C, at temperatures in excess of 65 °C 1-formyl-2,4-dimethylnaphthalene was formed in good yield (eq 5).13

Electron-rich heterocycles are formylated particularly easily; the product shown in eq 6 was obtained in a quantitative yield.14

The reaction of a suitably activated phenylacetonitrile can lead to the formation of isoquinoline derivatives. The method can be regarded as a modification of the Gattermann reactions of 3,5-dihydroxybenzyl ketones, which lead to the corresponding 3-alkyl-6,8-dihydroxyisoquinolines. The cyclization of the intermediate imine was assumed to occur during the workup.15 In the reaction of 3,5-dimethoxyphenylacetonitrile using zinc cyanide and either Hydrogen Bromide or hydrogen chloride (eq 7), 15N-labeling showed that the nitrogen in the product came from the zinc cyanide.16 It is noteworthy that two activating substituents are required; an attempted reaction was unsuccessful using 3,4-dimethoxyphenylacetonitrile. b-Oxoaldimines are formed when ketones such as deoxybenzoin are reacted under Gattermann conditions.17 Hydrolysis of the products leads to b-keto aldehydes and so, with a suitable phenol, a one-step synthesis of an isoflavone can be accomplished.18 This method is exemplified in the synthesis of pseudobaptigenin (eq 8).19

Cyanoenamine Formation.

A number of methods are available for the conversion of a-chloroenamines into a-cyanoenamines. The a-chloroenamines, which can function as keteniminium chlorides, are able to undergo nucleophilic substitution with cyanide ion. Substrates such as 1,2-dichloro-N,N-dimethylpropenylamine (eq 9) require a Lewis acid catalyst, and zinc cyanide in chloroform was found to be satisfactory.20

Cyanosilylation of Carbonyl Compounds.

A development from an in situ procedure, in which Chlorotrimethylsilane and a cyanide are used to replace Cyanotrimethylsilane,21 uses zinc cyanide to obtain cyanohydrin trimethylsilyl ethers (eq 10)22 in good yields.23 Other silylated cyanohydrins have been prepared by a development of the in situ method.24 For example, 1-benzenesulfonyl-2-formylpyrrole was converted into its cyanohydrin t-butyldimethylsilyl ether, and piperonal into the t-butyldiphenylsilyl and triisopropylsilyl analogs in very high yields by using Potassium Cyanide, Zinc Iodide, and the appropriate chlorosilane.

1. (a) Truce, W. E. OR 1957, 9, 37. (b) Bayer, O. MOC 1954, 7/1, 20.
2. Truthe, W. Z. Anorg. Chem. 1912, 76, 129.
3. (a) Adams, R.; Levine, I. JACS 1923, 45, 2373. (b) Adams, R.; Montgomery, E. JACS 1924, 46, 1518.
4. Arnold, R. T.; Sprung, J. JACS 1938, 60, 1699.
5. Hinkel, L. E.; Watkins, T. I.; Jones, K. M. JCS 1944, 647.
6. Yato, M.; Ohwada, T.; Shudo, K. JACS 1991, 113, 691.
7. (a) Olah, G. A.; Pelizza, F.; Kobayashi, S.; Olah, J. A. JACS 1976, 98, 296. (b) Olah, G. A.; Ohannesian, L.; Arvanaghi, M. CRV 1987, 87, 671.
8. Fuson, R. C.; Horning, E. C.; Ward, M. L.; Rowland, S. P.; Marsh, J. L. JACS 1942, 64, 30.
9. Fuson, R. C.; Horning, E. C.; Rowland, S. P.; Ward, M. L. OSC 1955, 3, 549.
10. (a) Chen, K.-M.; Joullié, M. M. TL 1982, 23, 4567. (b) Chen, K.-M.; Semple, J. E.; Joullié, M. M. JOC 1985, 50, 3997.
11. Chen, K.-M.; Joullié, M. M. OPP 1986, 18, 109.
12. (a) Hicks, M. G.; Jones, G.; Sheikh, H. JCS(P1) 1984, 2297. (b) Pert, D. J.; Ridley, D. D. AJC 1989, 42, 405. (c) Vela, M. A.; Fronczek, F. R.; Horn, G. W.; McLaughlin, M. L. JOC 1990, 55, 2913. (d) Yang, Z.; Hon, P. M.; Chui, K. Y.; Xu, Z. L.; Chang, H. M.; Lee, C. M.; Cui, Y. X.; Wong, H. N. C.; Poon, C. D.; Fung, B. M. TL 1991, 32, 2061. (e) Yang, Z.; Liu, H. B.; Lee, C. M.; Chang, H. M.; Wong, H. N. C. JOC 1992, 57, 7248. (f) Wong, H. N. C.; Niu, C. R.; Yang, Z.; Hon, P. M.; Chang, H. M.; Lee, C. M. T 1992, 48, 10 339. (g) Miknis, G. F.; Williams, R. M. JACS 1993, 115, 536.
13. Aslam, F. M.; Gore, P. H.; Jehangir, M. JCS(P1) 1972, 892.
14. Nicolaus, R. A.; Mangoni, L.; Caglioti, L. AC(R) 1956, 46, 793.
15. Birchall, G. R.; Galbraith, M. N.; Whalley, W. B. CC 1966, 474.
16. White, J. D.; Straus, D. S. JOC 1967, 32, 2689.
17. Farkas, L. CI(L) 1957, 1212.
18. Farkas, L. CB 1957, 90, 2940.
19. Farkas, L.; Major, A.; Pallos, L.; Várady, J. CB 1958, 91, 2858.
20. Toye, J.; Ghosez, L. JACS 1975, 97, 2276.
21. Rasmussen, J. K.; Heilmann, S. M. S 1978, 219.
22. Rasmussen, J. K.; Heilmann, S. M. OSC 1990, 7, 521.
23. Witiak, D. T.; Tehim, A. K. JOC 1990, 55, 1112.
24. Rawal, V. H.; Rao, J. A.; Cava, M. P. TL 1985, 26, 4275.

Harry Heaney

Loughborough University of Technology, UK

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