An Efficient Synthesis of Carbamates by Tin-Catalyzed Transcarbamoylation Reactions of Primary and Secondary Alcohols

Abstract

A new approach to the synthesis of carbamates based on a tin-catalyzed transcarbamoylation process has been developed. Reactions of primary and secondary alcohols with phenyl carba­mate in toluene at 90 ˚C proceed smoothly in the presence of tin-catalyst to generate the corresponding carbamates in good yields. This mild method exhibits a broad functional-group tolerance.

transcarbamoylation - carbamates - tin catalyst - phenyl carbamate

References and Notes

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Although phenyl carbamate (2) is commercially available, the cost is unacceptably high for us. As a result, this substance was prepared by treatment of inexpensive phenyl chloroformate with aq NH₃.
Preparation of Phenyl Carbamate (2)
To a biphasic mixture of concd aq NH₃ (15 M, 64 mL, 0.80 mol, 2.5 equiv) and CH₂Cl₂ (120 mL) at 0 ˚C was added a solution of phenyl chloroformate (50 g, 0.32 mol) in CH₂Cl₂ (80 mL) through a dropping funnel, and the dropping funnel was washed with CH₂Cl₂ (50 mL). After vigorous stirring at 0 ˚C for 40 min, the reaction mixture was diluted with H₂O. The separated aqueous layer was extracted with CH₂Cl₂, and the combined organic extracts were dried (Na₂SO₄) and concentrated in vacuo. The crude product was dissolved in warm EtOAc (220 mL). Upon cooling the solution, phenyl carbamate crystallized as white solid, which was separated by filtration (30.6 g). The mother liquors were concentrated and then purified by recrystallization to provide additional product (6.0 g, total yield 84%).

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<A NAME="RU03010ST-17">17</A>

Representative Experimental Procedure
A solution of geraniol (3a, 5.00 g, 32.4 mmol), phenyl carbamate (6.70 g, 48.6 mmol, 1.50 equiv), and dibutyltin maleate (337 mg, 0.97 mmol, 3.0 mol%) in toluene was heated at 90 ˚C for 150 min. The solution was cooled to 0 ˚C, and diluted with 5% aq NaOH (25 mL). After stirring at 0 ˚C for 5 min, CH₂Cl₂ and H₂O was added. The organic layer was separated, washed with 5% aq NaOH, H₂O, and brine, dried over Na₂SO₄, and then concentrated in vacuo. The resulting crude product (7.3 g) was subjected to silica gel chromatography (EtOAc and hexane, stepwise gradient from 1:5 to 1:0) to afford geranyl carbamate (3b, 6.30 g, 98%).

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