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.

Key words

transcarbamoylation - carbamates - tin catalyst - phenyl carbamate

References and Notes

• 1a Nakatsubo F. Cocuzza AJ. Keeley DE. Kishi Y.
  J. Am. Chem. Soc.  1977,  99:  4835 
• 1b Nakatsubo F. Fukuyama T. Cocuzza AJ. Kishi Y. J. Am. Chem. Soc.  1977,  99:  8115 
• 2 Tanino H. Nakata T. Kaneko Y. Kishi Y. J. Am. Chem. Soc.  1977,  99:  2818 
• 3 Millar A. Kim K.-H. Minster DK. Ohgi T. Hecht SM. J. Org. Chem.  1986,  51:  189 
• 4 Minami N. Ko SS. Kishi Y. J. Am. Chem. Soc.  1982,  104:  1109 
• 5 Hirama M. Shigemoto T. Yamazaki Y. Ito S. J. Am. Chem. Soc.  1985,  107:  1797 
• 6 Donohoe TJ. Johnson PD. Cowley A. Keenan M. J. Am. Chem. Soc.  2002,  124:  12934 
• 7 Espino CG. Du Bois J. Angew. Chem. Int. Ed.  2001,  40:  598 
• 8a Ichikawa Y. Synlett  1991,  238 
• 8b Ichikawa Y. Synlett  2007,  2927 
• 9 Vaterlaus BP. Kiss J. Spiegelberg H. Helv. Chim. Acta  1964,  47:  381 
• 10a Loev B. Kormendy MF. J. Org. Chem.  1963,  28:  3421 
• 10b Loev B. Kormendy MF. Goodman MM. Org. Synth, Coll. Vol. V  1973,  162 
• 11a Graf R. Chem. Ber.  1963,  96:  56 
• 11b Graf R. Angew. Chem., Int. Ed. Engl.  1968,  7:  172 
• 11c Hirama M. Shigemoto T. Ito S. J. Org. Chem.  1987,  52:  3342 
• 11d Hirama M. J. Synth. Org. Chem. Jpn.  1987,  45:  346 
• 12 Hirama M. Uei M. Tetrahedron Lett.  1982,  23:  5307 
• 13 Kocovsky P. Tetrahedron Lett.  1986,  27:  5521 
• 14 Stryer L. Biochemistry   3rd ed.:  Freeman and Company; New York: 1988. 
• 16 Adams P, and Hill M. inventors; US 3,161,  676. 
• 18a Poller RC. Retout SP. J. Organomet. Chem.  1979,  173:  C7 
• 18b Otera J. Dan-oh N. Nozaki H. J. Org. Chem.  1991,  56:  5307 
• 18c Baumhof P. Mazitschek R. Giannis A. Angew. Chem. Int. Ed.  2001,  40:  3672 
• 19 Relative rate data for solvolysis in 50% aq EtOH of allyl chlorides shown below demonstrates the unusual methyl effect. Specifically, 3,3-dimethy allyl chloride is more reactive than the monosubstituted compound by a factor of about 10^³ (Figure 1) This experimental result may explain why derivatives of 3-methyl-2-cyclohexenol, such as 18b, are highly prone to undergo solvolysis reactions. See the reference: Vernon DA. J. Chem. Soc.  1954,  423 

15

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%).

17

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%).