Formaldehyde → 2-(Hydroxymethyl)octadecanoic acid

Participants

Reaction Conditions

Reaction Steps

Anhydrous THF (327 ml) and 19.7 g (0.195 mole) of diisopropylamine are added to a dry three-neck flask purged with nitrogen and maintained under a nitrogen atmosphere. After cooling the mixture to -20° C., 123 ml of n-butyllithium in hexane (1.6 M) (0.195 mole) is added slowly to prevent the temperature from exceeding 0° C. and then 32.2 ml of anhydrous HMPA (0.18 mole) is added. A solution of 23.0 g of stearic acid (0.081 mole) in 165 ml of THF is added dropwise with stirring while maintaining the reaction temperature below 0° C. A milky white suspension results after the addition of stearic acid. The reaction mixture is brought to about 40° C. by using a warm water bath. The suspension changed to a clear solution as the temperature gradually reaches 40° C. This system is then connected to a formaldehyde generating system. Paraformaldehyde (16.4 g) is heated in a three-neck flask at 180°-200° C. to generate formaldehyde and the formaldehyde vapors are carried by a stream of nitrogen over the surface of the stirred solution of α-lithiated lithium stearate prepared previously. The reaction is terminated after complete depolymerization of paraformaldehyde (2 to 21/2 hrs.). The reaction solution is cooled in an ice bath and neutralized with hydrochloric acid until acidic. The organic layer is separated and then concentrated under reduced pressure to remove most of the THF solvent. The resulting oily residue is dissolved in 2 liters of ether and washed three times with 10% hydrochloric acid and then twice with water. The ether layer is dried over Na2SO4 and the solvents removed under reduced pressure to give 22.4 g (92%) of crude product which is recrystallized once from acetone to give 17.3 g (71% yield) of α-hydroxymethylstearic acid, m.p. 62°-67° C. This material is used for the next reaction withouth further purification.

Provenance & Evidence