Cyanoacetic Acid

[372-09-8]  · C3H3NO2  · Cyanoacetic Acid  · (MW 85.06)

(active methylene compound for preparing a,b-unsaturated nitriles and esters, for carbolactonization of alkenes to a-cyano g-lactones, and for converting trans-1,2-bromohydrins to cis-1,2-diols)

Physical Data: mp 70-71 °C.

Solubility: sol H2O, ethanol, ether.

Form Supplied in: hygroscopic crystals; widely available.

Analysis of Reagent Purity: gas chromatography; titration.

Handling, Storage, and Precautions: keep container well closed. Inhalation or skin contact should be avoided. Hydrogen cyanide may be liberated in the event of overheating. This reagent should be handled in a fume hood.

Condensation with Carbonyl Compounds.

Ammonium acetate,1 IR-4B,2 Dowex-3,2 pyridine,3 and potassium hydroxide4 are effective catalysts for the condensation of cyanoacetic acid with aldehydes and ketones to form a,b-unsaturated nitriles. Cyclohexanone reacts with cyanoacetic acid to yield cyclohexylidenecyanoacetic acid, which can be hydrolyzed to 1-cyclohexenylacetonitrile.1 Furfural reacts with cyanoacetic acid to afford 3-(2-furyl)acrylonitrile in good yield (eq 1).3 2,5-Dihydroxy-3,4,6-trimethylbenzaldehyde condenses with cyanoacetic acid to form a coumarin derivative (eq 2).4

Carbolactonization of Alkenes to a-Substituted g-Lactones.

Cyanoacetic acid and malonic acid react with alkenes in the presence of Manganese(III) Acetate to form a-substituted g-lactones.5 In this procedure, cyclohexene is converted to the a-cyano-g-lactone (2) (eq 3).

Conversion of trans-1,2-Bromohydrins into cis-1,2-Diols.

Esterification of cyanoacetic acid with trans-2-bromocyclohexanol forms the cyanoacetate ester (2). The ester (2) is converted into the ketene acetal (3), which is hydrolyzed to the monocyanoacetate of cis-cyclohexane-1,2-diol (4) (eq 4).6 Hydrolysis of (4) with Potassium Carbonate in methanol affords the cis-cyclohexane-1,2-diol (95%). Similarly, the trans-1,2-bromohydrin (5) is converted to the cis-1,2-diol (6) through the cyano ester (eq 5). Attempted dihydroxylation of the alkene precursor to (5) with Osmium Tetroxide led to a 1:1 mixture of the 2a,3a-diol and the 2b,3b-diol.

Other Applications.

Cyanoacetic acid is converted to cyanoacetyl chloride which is esterified with t-butanol to afford t-butyl cyanoacetate,7 N-Bromosuccinimide converts cyanoacetic acid to dibromoacetonitrile.8 A key step in the synthesis of 3-vinylbenzofuran was the alkylation of 3-(pyrrolidin-1-yl)benzofuran to (3-benzofuranyl)cyanoacetic acid with cyanoacetic acid.9 Cyanoacetic acid serves as an a-ketoacetyl anion equivalent in the diastereoselective synthesis of a highly functionalized decalin fragment of the natural product insecticide azadirachtein.10

Related Reagents.

Acetonitrile; (Diethoxyphosphoryl)acetonitrile Oxide; Ethyl Cyanoacetate; Lithioacetonitrile; Malononitrile; Trimethylsilylacetonitrile.

1. Cope, A. C.; D'Addieco, A. A.; Whyte, D. E.; Glickman, S. A. OSC 1963, 4, 234.
2. Hein, R. W.; Astle, M. J.; Shelton, J. R. JOC 1961, 26, 632.
3. Patterson, J. M. OSC 1973, 5, 585.
4. Hann, R. A. JCS(P1) 1974, 1379.
5. Corey, E. J.; Gross, A. W. TL 1985, 26, 4291.
6. Corey, E. J.; Das, J. TL 1982, 23, 4217.
7. Ireland, R. E.; Chaykovsky, M. OSC 1973, 5, 171.
8. Wilt, J. W.; Diebold, J. L. OSC 1963, 4, 254.
9. Pearson, J. R.; Porter, Q. N.; AJC 1991, 44, 907.
10. Kolb, H. C.; Ley, S. V.; Slawin, A. M. Z.; Williams, D. J. JCS(P1) 1992, 2735.

Fillmore Freeman

University of California, Irvine, CA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.