Synlett 2010(12): 1815-1818  
DOI: 10.1055/s-0030-1258102
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Yoshiyasu Ichikawa*, Yukinori Morishita, Shuhei Kusaba, Naoto Sakiyama, Yasunori Matsuda, Keiji Nakano, Hiyoshizo Kotsuki
Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan
e-Mail: ichikawa@kochi-u.ac.jp;
Further Information

Publication History

Received 20 April 2010
Publication Date:
30 June 2010 (online)

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.

    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 10³ (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%).