Tetraethylammonium Cyanide

(R = Et)

[13435-20-6]  · C9H20N2  · Tetraethylammonium Cyanide  · (MW 156.31) (R = n-Bu)

[10442-39-4]  · C17H36N2  · Tetrabutylammonium Cyanide  · (MW 268.55)

(nitrile synthesis; asymmetric cyanohydrin synthesis; catalyst)

Physical Data: R = Et, mp 250 °C; R = n-Bu, mp 82-85 °C.

Form Supplied in: white powders, commercially available.

Handling, Storage, and Precautions: highly toxic, irritant solids; very hygroscopic and light sensitive; keep container tightly closed, store in dry and dark area. Use only in chemical fume hood. Incompatible with strong acids and bases. Thermal decomposition may produce hydrogen cyanide.

Nitrile Synthesis.

Primary, secondary, neopentyl, benzylic, and allylic halides are readily converted into the corresponding nitriles by reaction with Et4NCN in polar aprotic solvents (eq 1).1,2 The workup of the reaction is simple, since the solvent is removed, and the nitrile is dissolved in ether and filtered from the quaternary ammonium halide byproduct which precipitates out. The same reaction applies to acyl or thioacyl halides, while dihalides furnish dinitriles (eq 2).1

Aromatic or heteroaromatic halides are less reactive, but their trimethylammonio derivatives react with Et4NCN under very mild conditions yielding nitriles. In this way, chloropyrimidines and chloroquinazolines are converted smoothly into their carbonitriles (eq 3).3 The same conditions are applied for the conversion of 6-chloropurines to 6-cyanopurines.4 Treatment of a-halo ketones with Et4NCN in CH2Cl2 furnishes oxiranecarbonitriles (eq 4)2 which, under more vigorous conditions, especially with the presence of Et4NBr, furnish b-keto nitriles (eq 4).

Both methoxymethyl (MOM) and (2-methoxyethoxy)methyl (MEM) ethers are directly converted into cyanomethyl ethers by sequental treatment with Bromodimethylborane and Bu4NCN in CH2Cl2 at -78 °C (eq 5).5 The reaction conditions are applicable for the preparation of primary, secondary, or tertiary cyanomethyl ethers, which are being used as excellent acyl anion equivalents in intramolecular alkylation reactions.6

Treatment of trans-octahydro-8a-tosyloxymethyl-2(1H)-naphthalenone derivatives with Bu4NCN in THF results in the formation of the nitrile and the simultanous ring closure, yielding the corresponding (4a)-1a-cyano-11-oxatricyclo[]dodecane derivative (eq 6).7

Asymmetric Cyanohydrin Synthesis.

Reaction of racemic or optically active p aldehyde-rhenium Lewis acid complexes [CpRe(NO)(PPh3)(h2-O=CHR)]+ BF4- with Et4NCN in CH2Cl2 at -80 °C gives cyanohydrin alkoxide complexes, which by treatment with MTPA-Cl and DMAP in C6H6 furnish the optically active Mosher esters of the cyanohydrins (eq 7).8 Analogous reactions of racemic s methyl ketone complexes leading to the corresponding optically active cyanohydrins are also reported.8

Use as a Catalyst.

Et4NCN is formed in situ during the phase transfer catalyzed displacement reactions of alkyl halides (or methansulfonates) with cyanide anion (eq 8).9

The complex Bu4NCu(CN)2 (prepared as a colorless solid by treatment of a slurry of Copper(I) Cyanide in MeOH with a solution of 1 equiv of Bu4NCN in MeOH at rt under N2 and evaporation of the resulting solution to dryness) is used as catalyst for the coupling of vinyllithium components with OBO ester iodides (eq 9).10

Benzyltrimethylammonium Cyanide.

This related quaternary ammonium cyanide reagent is prepared by dissolving equimolar amounts of BnNMe3Cl and NaCN in water.11 It is used for the transformation of alkyl halides to nitriles in aqueous solution. The reaction proceeds in the absence of any organic solvent, and the ammonium salt serves not only as a cyanide source, but also as a surface active agent, thus promoting the reaction rate (eq 10).12

Related Reagents.

Acetone Cyanohydrin; t-Butyldimethylsilyl Cyanide; Cyanotrimethylsilane; Diethylaluminum Cyanide; Hydrogen Cyanide; Potassium Cyanide; Sodium Cyanide.

1. Simchen, G.; Kobler, H S 1975, 605.
2. Kobler, H.; Schuster, K-H.; Simchen, G. LA 1978, 1946.
3. Hermann, K.; Simchen, G. LA 1981, 333.
4. Herdewijn, P.; Van Aerschot, A.; Pfleiderer, W. S 1989, 961.
5. Morton, H. E.; Guindon, Y. JOC 1985, 50, 5379.
6. (a) Stork, G.; Maldonado, L. JACS 1971, 93, 5286; (b) JACS 1974, 96, 5272.
7. Dailey, O. D.; Fuchs, P. L. JOC 1980, 45, 216.
8. Dalton, D. M.; Garner, C. M.; Fernández, J. M.; Gladysz, J. A. JOC 1991, 56, 6823.
9. (a) Starks, C. M. JACS 1971, 93, 195; (b) Starks, C. M.; Owens, R. M. JACS 1973, 95, 3613.
10. Corey, E. J.; Kyler, K.; Raju, N. TL 1984, 25, 5115.
11. Fieser, L.; Fieser, M. FF 1967, 1, 53.
12. Sugimoto, N.; Fujita, T.; Shigematsu, N.; Ayada, A. CPB 1962, 10, 427.

Serkos A. Haroutounian

Agricultural University of Athens, Greece

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