Ethyl cyanoacetate

Production

• Kolbe nitrile synthesis using ethyl chloroacetate and sodium cyanide.
• Fischer esterification of cyanoacetic acid with ethanol in the presence of a strong mineral acids. The cyanoacetic acid can be prepared via Kolbe nitrile synthesis using sodium chloroacetate and sodium cyanide.
• Reaction of the sodium cyanoacetate with ethyl bromide in an aqueous–organic two-phase system in the presence of a phase transfer catalyst.
• Oxidation of 3-ethoxypropionitrile, an ether, with oxygen under pressure in the presence of cobalt acetate tetrahydrate as catalyst and N-hydroxyphthalimide as a radical generator.

  Properties

Physical properties

Chemical properties

Use

• At the nitrile group in various ways:
• *Hydrogenation leads to the β-amino acid β-alanine
• *Nucleophilic attack at the carbon, as a step in the synthesis of many heterocycles and other products
• *As a safe cyanide-donor reagent
• Nucleophilic attack at the ester group, as part of acyl substitution: reaction with ammonia leads to cyanoacetamide, which can be converted by dehydration with PCl₅ or POCl₃ to malononitrile.
• Via the acidic methylene group as a nucleophile

• Allopurinol, used for the treatment of chronic gout, can be synthesized starting with a Knoevenagel condensation with triethyl orthoformate; the condensation product is cyclized with hydrazine to give a substituted pyrazole and subsequently with formamide to allopurinol, a substituted pyrazolo-pyrimidine.
• The purine derivatives theophylline, caffeine and uric acid are synthetically accessible from ethyl cyanoacetate and N,N'-dimethylurea.
• The pteridine derivative folic acid is assigned to the vitamin B complex; ethyl cyanoacetate and guanidine can be used as starting material in a multi-stage convergent synthesis.
• The pyrrole ethosuximide is used to treat epilepsy, it can be obtained from ethyl cyanoacetate and butanone in a multistep synthesis.
• The pyrimidine derivative trimethoprim is used as co-trimoxazole in fixed combination with sulfamethoxazole used as bacteriostatic agent and is synthesized from ethyl cyanoacetate and 3,4,5-trimethoxybenzaldehyde or its benzyl chloride.

• The anticonvulsant valproic acid
• Ethyl cyanoacrylate, used as superglue, via reaction with formaldehyde

Safety