Acetyl Cyanide1

(R = Me)

[631-57-2]  · C3H3NO  · Acetyl Cyanide  · (MW 69.06) (R = Ph)

[613-90-1]  · C8H5NO  · Benzoyl Cyanide  · (MW 131.13)

(versatile electrophile useful for selective acylation, cyanohydrin synthesis, and cycloaddition reactions)

Alternate Names: 2-oxopropanenitrile; pyruvonitrile.

Physical Data: AcCN: bp 92.3 °C; d 0.9745 g cm-3; BzCN: mp 30-32 °C; bp 206 °C; d 1.106 g cm-3.

Preparative Methods: acyl cyanides are readily prepared from the reaction of acyl halides with Copper(I) Cyanide,2a Sodium Cyanide,2b or Cyanotrimethylsilane2c and via the oxidation of cyanohydrins.2d

Handling, Storage, and Precautions: AcCN and its analogs are highly toxic; use in a fume hood.

Acylation.

Acyl cyanides are useful for the selective acylation of alcohols3 and amines4 (eq 1). This process is utilized in the reaction of AcCN with orthoesters5a,b and amido acetals,5c resulting in the substitution of an alkoxy group with a cyano group (eq 2). In addition, aldehydes are cyanoacylated with benzoyl cyanide (BzCN).1a Lithium ketone enolates react cleanly with acyl cyanides, producing 1,3-diketones uncontaminated by O-acylated or diacylated products (eq 3).6 Other efficiently acylated carbon nucleophiles include Grignard reagents,7 primary nitroalkanes,8 dithianes,9 nitrosoamines,10 and active methylene compounds.11 A one-pot synthesis of pyridines utilizes AcCN as the trapping agent with an intermediate ketone enolate (eq 4).12

Treatment of trimethylsilyl ketene acetals with BzCN in the presence of Titanium(IV) Chloride affords a-benzoylcarboxylates.13 In contrast, attack of the nucleophile at the nitrile carbon of BzCN is observed when the same reaction is performed in the absence of catalyst. Nitrile attack is also the preferred mode in the Nickel(II) Acetylacetonate catalyzed reaction of 1,3-dicarbonyls with BzCN.14

A synthesis of 4-chlorooxazoles from aromatic aldehydes and BzCN formally involves the addition of HCl across the nitrile bond (eq 5).15

Cyanohydrin Synthesis.

The addition of silyl enol ethers to AcCN in the presence of TiCl4 affords the corresponding b-hydroxy ketone which retains the cyano functionality (eq 6).16 Similar results are found with allylsilanes.16 Retention of the cyano group is also accomplished in the Wittig reaction of dihalomethylenephosphorus ylides with BzCN.17 Acidic treatment of phenol and AcCN provides a cyano containing bis-adduct (eq 7).18 Reductive coupling of aldehydes and ketones with BzCN by Titanium(III) Chloride affords an intermediate cyanohydrin diol, which upon base treatment produces the mixed benzoin.19

Cycloadditions.

In the presence of Zinc Chloride, AcCN serves as a dienophile in hetero-Diels-Alder reactions (eq 8).20 Acyl cyanides are also reactive toward photochemically generated o-quinodimethanes21 and act as substrates in the Paterno-Büchi reaction with furan.22 In addition, AcCN is useful for the preparation of optically pure 1-cyanovinyl esters which serve as dienophilic equivalents of Ketene in [4 + 2] cycloadditions.23

Related Reagents.

Acetic Anhydride; Acetyl Bromide; Acetyl Chloride.


1. (a) Thesing, J.; Witzel, D.; Brehm, A. AG 1956, 68 425. (b) Hünig, S.; Schaller, R. AG(E) 1982, 21, 36.
2. (a) Normant, J. F.; Piechucki, C. BSF 1972, 2402. (b) Koenig, K. E.; Weber, W. P. TL 1974, 2275. (c) Herrmann, K.; Simchen, G. S 1979, 204. (d) Murahashi, S-I.; Naota, T.; Nakajima, N. TL 1985, 26, 925.
3. Abbas, S. A.; Haines, A. H. Carbohydr. Res. 1975, 39, 358.
4. Hibbert, F.; Satchell, D. P. N. JCS(B) 1968, 568.
5. (a) Böhme, H.; Neidlein, R. CB 1962, 95, 1859. (b) Babler, J. H.; Marcuccilli, C. J. TL 1987, 28 4657. (c) Bredereck, H.; Simchen, G.; Kantlehner, W. CB 1971, 104, 924.
6. Howard, A. S.; Meerholz, C. A.; Michael, J. P. TL 1979, 1339.
7. Borch, R. F.; Levitan, S. R.; Van-Catledge, F. A. JOC 1972, 37, 726.
8. Bachman, G. B.; Hokama, T. JACS 1959, 81, 4882.
9. Page, P. C. B.; van Niel, M. B.; Westwood, D. JCS(P1) 1988, 269.
10. Renger, B.; Hügel, H. CB 1978, 111, 2630.
11. Dornow, A.; Grabhöfer, H. CB 1958, 91, 1824.
12. Kelly, T. R.; Liu, H. JACS 1985, 107, 4998.
13. Reddy, C. P.; Tanimoto, S. JCS(P1) 1988, 411.
14. (a) Basato, M.; Corain, B.; Cofler, M.; Veronese, A. C.; Zanotti, G. CC 1984, 1593. (b) Basato, M.; Casellato, U.; Graziani, R.; Veronese, A. C. JCS(D) 1992, 1193.
15. Davis, M.; Lakhan, R.; Ternai, B. JHC 1977, 14, 317.
16. Kraus, G. A.; Shimagaki, M. TL 1981, 1171.
17. Raulet, M. C. CRC 1973, 276, 903.
18. Banucci, E. G. S 1973, 671.
19. Clerici, A.; Porta, O. JOC 1993, 58, 2889.
20. Page, P. C. B.; Williams, P. H.; Collington, E. W.; Finch, H. CC 1987, 756.
21. Connors, R.; Durst, T. TL 1992, 33, 7277.
22. Zagar, C.; Scharf, H-D. CB 1991, 124, 967.
23. (a) Reymond, J-L.; Vogel, P. CC 1990, 1070. (b) Reymond, J-L.; Vogel, P. TA 1990, 1, 729.

Joel Morris

The Upjohn Company, Kalamazoo, MI, USA



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