Formamide → Formamide, N-(diphenylmethyl)-N-methyl-

Participants

Reaction Steps

15.5 g of p-toluoyl chloride and 13.3 g of aluminum chloride were mixed in 250 ml of dichloroethane in a dropping funnel. The solution was added dropwise to the cooled, stirred suspension of the resin beads over a period of about 40 min., care being taken not to allow the reaction to warm up above 5° C. The stirring was continued for 4 hours at room temperature when the resin was washed sequentially with isopropanol, isopropanol-water (1:1 mixture), isopropanol and dried to give 53.8 g of p-toluoyl resin. This resin was then mixed with 168 g of ammonium formate, 201 ml of formamide, 134 ml of formic acid and 350 ml of nitrobenzene. The mixture was gradually heated up to 165°-170° C. under reflux and maintained for 1 day during which time about 115 ml of the aqueous phase was collected into a Dean-Stark trap. The resin was washed and dried as above to yield 55.5 g of N-formyl methylbenzhydrylamine resin. The product was hydrolyzed in a mixture of 300 ml each of 12N HCl and isopropanol under reflux for 3 hr. Washing and drying the resulting resin provided 54.9 g of the hydrochloride form of methylbenzhydrylamine resin. It showed a very strong positive reaction to ninhydrin reagent and incorporated 0.4 mmol of Boc-Ala-OH when neutralized and coupled with Boc-Ala-OH in the presence of dicyclohexylcarbodiimide.

Provenance & Evidence