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Synthesis 2002(3): 0365-0370
DOI: 10.1055/s-2002-20036
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Application of Novel Glyoxylate-derived Chloroformates

Mark J. Mulvihill*, James Gallagher*, Brian S. MacDougall, Damian G. Weaver, Duyan V. Nguyen, KiHo Chung, William Mathis
Rohm and Haas Company, 727 Norristown Road, Spring House, Pennsylvania, 19477, USA
Fax: +1(914)3453565; e-Mail: mark.mulvihill@osip.com;
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Publikationsverlauf

Received 20 October 2001
Publikationsdatum:
28. Juli 2004 (online)

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Abstract

A convenient process for the synthesis of glyoxylate-derived chloroformates has been developed. The approach involves the reaction of glyoxylate esters with triphosgene and pyridine in various solvent systems. These novel glyoxylate-derived chloroformates are multifunctional, possessing a chloroformate, ester, and haloalkyl moiety. Further elaboration via a thiocarbonate route afforded highly functionalized carboxylic acid-derived alkoxycarbonyl-chlorocarbonyloxy-methyl esters. Application of a benzyl glyoxylate-derived chloroformate to halofenozide was also accomplished, affording halofenozide-N-carbonyloxy-chloro/iodoacetic acid benzyl ester derivatives, which were further derivatized to carboxylic acid-derived (halofenozide-N-carbonyloxy)-benzyloxycarbonyl-methyl esters. The trifunctional nature of the glyoxylate moiety was demonstrated through conversion of the benzyloxycarbonyl moiety of a carboxylic acid-derived (halofenozide-N-carbonyloxy)-benzyloxycarbonyl-methyl ester to its respective diethyl-amide.

Key words

glyoxylate esters - chloroformates - alkyl halide - carboxylic acids - aldehydes

    References

  • 1a Mulvihill MJ. MacDougall B. Ajello C. Martinez-Teipel B. Joseph R. Nguyen DV. Weaver DG. Chung K. Gusev A. Wierenga JM. Mathis WD. Synthesis  2002,  53 
    Thieme Connect
  • Thieme Connect
  • Thieme Connect
  • 2a Mulvihill MJ. Nguyen DV. MacDougall B. Martinez-Teipel B. Joseph R. Gallagher J. Weaver D. Gusev A. Chung K. Mathis W. Tetrahedron Lett.  2001,  42:  7751 
    CrossrefSuche in Google Scholar
  • Crossref
  • 3 Silverman RB. The Organic Chemistry of Drug Design and Drug Action   Academic Press; San Diego: 1992.  p.362-363  
  • 4 King FD. Medicinal Chemistry: Principles and Practice   The Royal Society of Chemistry; Carmbridge: 1994.  p.216-227  
  • 5a Sun X. Zeckner DJ. Current WL. Boyer R. McMillian C. Yumibe N. Chen SH. Bioorg. Med. Chem. Lett.  2001,  11:  1875 
    Suche in Google Scholar
  • 5b Omar FA. Farag HH. Bodor N. J. Drug Target.  1994,  2:  309 
    Suche in Google Scholar
  • 6 Gogate US. Repta AJ. Alexander J. Int. J. Pharm.  1987,  40:  235 
    CrossrefSuche in Google Scholar
  • 7 Gogate US. Repta AJ. Int. J. Pharm.  1987,  40:  249 
    CrossrefSuche in Google Scholar
  • 8 Coghlan MJ. Caley BA. Tetrahedron Lett.  1989,  30:  2033 
    CrossrefSuche in Google Scholar
  • 9 Barcelo G. Senet JP. Sennyey G. Synthesis  1986,  627 
    Thieme Connect
  • 10 Folkmann M. Lund FJ. Synthesis  1990,  1159 
    Thieme Connect
  • 11a Finkelstein H. Ber.  1910,  43:  1528 
    Suche in Google Scholar
  • 11b Ingold CK. Structure and Mechanism in Organic Chemistry   2nd ed.:  Cornell Univ. Press; London: 1969.  p.435 
    Suche in Google Scholar
  • 12 James WN, and Aller HE. inventors; U.S.  5358966.  ;Chem. Abstr. 1994, 122, 3593
  • 14 Tomlin CDS. The Pesticide Manual   11th ed.:  British Crop Protection Council; Farnham Surrey GU9 7PH UK: 1997.  p.388-389  
    Suche in Google Scholar
13

The Presidential Green Chemistry Award for Rohm and Haas diacyl hydrazines can be found on the following web pages: http://www.turfnet.com/news/rohm_haas.asp and http://www.epa.gov/greenchemistry/past.htm.

15

One could imagine the attack of the free carboxylate at the Z1/Z2 ester or the carbamate moiety therefore forming a mixed anhydride, which would rapidly degrade to the aldehyde, CO2, and the parent biologically active molecule (in our case, halofenozide 17). Also, a simple hydrogen bonding effect from the free carboxylic acid to the ester or carbamate moiety under aqueous conditions could afford activation of the system and subsequent degradation.