Ethyl cyanoacetate

Ethyl cyanoacetate may be prepared in various ways: • Kolbe nitrile synthesis using ethyl chloroacetate and sodium cyanide. • Fischer esterification of cyanoacetic acid with ethanol in the presence of a strong mineral acids (e.g. concentrated sulfuric acid). The cyanoacetic acid can be prepared via Kolbe nitrile synthesis using sodium chloroacetate and sodium cyanide. • Oxidation of 3-ethoxypropionitrile, an ether, with oxygen under pressure in the presence of cobalt(II) acetate tetrahydrate as catalyst and N-hydroxyphthalimide as a radical generator. ==Properties==

Physical properties The vapor pressure follows the Antoine equation log10(P) = A−(B/(T+C)) (P in bar, T in K) with A = 7.46724, B = 3693.663 and C = 16.138 in the temperature range from 341 to 479 K Two polymorphic forms occur. Below −111 °C, the crystal form II is dominant. The heat capacity at 25 °C is 220.22 J K−1 mol−1. ==Use==

Due to its functionality cyanoacetate reacts: • 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 (see below) 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 Ethyl cyanoacetate is a building block for the synthesis of heterocycles which are used for example as drugs: • 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. Also many other functional heterocycles are in good yields accessible from ethyl cyanoacetate, such as 3-substituted coumarin derivatives. Non-cyclic products from this starting material include: • The anticonvulsant valproic acid • Ethyl cyanoacrylate, used as superglue, via reaction with formaldehyde Ethyl cyanoacetate is also used to prepare 3,3-diphenylpropan-1-amine, which is the precursor used in the synthesis of prenylamine and droprenilamine. ==Safety==

Ethylcyanoacetate has an of 2820 mg/kg (oral, rat). ==References==