Formaldehyde cyanohydrin

A solution of 32.5 g. (0.5 mole) of potassium cyanide in 100 ml. of water is cooled to 0-5° while 15 g. (0.5 mole of monomer) of paraformaldehyde is added in small portions at this temperature. The clear solution is allowed to stand for 1 hour. To the solution is added slowly, at 0-5°, 50 g. of 20% aqueous sulfuric acid solution. (Hood.) The resulting solution is just neutralized with sodium carbonate solution and filtered from the precipitated potassium sulfate. The filtrate is extracted with ether in an apparatus for continuous liquid-liquid extraction [Org. Syntheses, 23, 49 (1943)], and the resulting ethereal solution is dried over sodium sulfate and distilled. There is obtained 29 g. (100%) of formaldehyde cyanohydrin boiling at 102o/14 mm. 

---

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

Formaldehyde Cyanohydrin. This cyanohydrin, also known as glycolonitrile [107-16-4], is a colorless Hquid with a cyanide odor. It is soluble in water, alcohol, and diethyl ether. Equimolar amounts of 37% formaldehyde and aqueous hydrogen cyanide mixed with a sodium hydroxide catalyst at 2°C for one hour give formaldehyde cyanohydrin in 79.5% yield (22). 

Although usually handled as an aqueous solution, formaldehyde cyanohydrin can be isolated in the anhydrous form by ether extraction, followed by drying and vacuum distillation (23). Pure formaldehyde cyanohydrin tends to be unstable especially at high pH. Small amounts of phosphoric acid or monochloroacetic acid are usually added as a stabiLher. Monochloroacetic acid is especially suited to this purpose because it codistiHs with formaldehyde cyanohydrin (24). Properly purified formaldehyde cyanohydrin has excellent stability (25). 

Direct reaction of formaldehyde cyanohydrin and ethylenediamine in the presence of a sulfuric acid catalyst gives ethylenediarninetetraacetonitrile [5766-67-6], hydrolysis of which leads to ethylenediarninetetraacetic acid [60-00-4] (EDTA), a widely used sequestering agent (26). 

Nitrilotriacetonitrile [628-87-5], N(CH2CN)2, a precursor to nitrilotriacetic acid [139-13-9], N(CH2COOH)2, can be prepared from the reaction of formaldehyde cyanohydrin with ammonia (26). Formaldehyde cyanohydrin is also used as an intermediate in pharmaceutical production. Commercial formaldehyde cyanohydrin is available as a 70% aqueous solution stabiLhed by phosphoric acid. 

Formaldehyde cyanohydrin was detected in Halley s comet by the Vega I space probe (27). 

Methyliminodiacetic acid has been prepared by the action of methylamine on formaldehyde cyanohydrin, subsequent hydrolysis of the dinitrile with barium hydroxide, and regeneration from the barium salt with sulfuric acid.1 This method was found by the submitter to be much less satisfactory than the procedure given above. 

Let us consider the decomposition of formaldehyde cyanohydrin (2-hydroxyacetonitrile) into formaldehyde and hydrogen cyanide which is equivalent to the retrosynthetic analysis. The corresponding BE-matrices and the R-matrix are ... 

Ethyl tert-butvl ether. Ethylene dibromide, Ethyl ether, Ethvl sulfide. 2-Heptanone, Methanol, 2-Methyl-1,3-butadiene, 2-Methvl-2-butene. Methyl chloride, Methylene chloride, Methyl iodide. Methyl mercaptan, 2-Methylphenol, Methyl sulfide. Monuron. Nitromethane, 2-Nitropropane, A-Nitrosodimethylamine, 1-Octene, 2-Pentanone, Propylene oxide, Styrene, Thiram, Toluene, Vinyl chloride, o-Xylene, tn-Xylene Formaldehyde cyanohydrin, see Acetontrile,... 

---