Synthesis 2003(12): 1916-1919
DOI: 10.1055/s-2003-41037
PSP
© Georg Thieme Verlag Stuttgart · New York

New Protocol for Efficient N-Chlorinations of Amides and Carbamates [1]

Oleg V. Larionov, Sergei I. Kozhushkov, Armin de Meijere*
Institut für Organische Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
Fax: +49(551)399475; e-Mail: [email protected];
Further Information

Publication History

Received 12 May 2003
Publication Date:
25 August 2003 (online)

Abstract

N-Chlorination of various amides, carbamates and lactams with inexpensive and stable calcium hypochlorite on moist alumina proceeds smoothly and efficiently, e.g. the technically important 1-chlorohexahydroazepin-2-one (3-Cl) and 1-chloropyrrolidin-2-one (7-Cl) were obtained in 95% and 98% yield, respectively. Excellent results were also observed for the N-chlorination of protected amino acid esters with a cyclopropane moiety to give derivatives such as methyl (tert-butoxycarbonylchloroamino)cyclopropylacetate (1-Cl), methyl (benzyloxycarbonylchloroamino)cyclopropylacetate (2-Cl), methyl 1-(tert-butoxycarbonylchloroamino)cyclopropanecarboxylate (5-Cl) and methyl trans-2-(tert-butoxycarbonylchloroamino)cyclopropanecarboxylate (6-Cl) in 99%, 96%, 90% and 97% yield, respectively.

    References

  • 1a

    Part 95 in the series ‘Cyclopropyl Building Blocks in Organic Synthesis’. For Part 94 see: Gensini, M.; de Meijere, A. Chem.-Eur. J. 2003, 9, in press

  • 1b Part 93: Kozhushkov SI. Leonov A. de Meijere A. Synthesis  2003,  956 
  • 2 Fieser M. Fieser LF. Reagents for Organic Synthesis   John Wiley and Sons; New York: 1967.  p.78 
  • 3 Barton DRH. Ollis WD. In Comprehensive Organic Chemistry   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1979.  p.1030 
  • 4a Poisel H. Schmidt U. Angew. Chem., Int. Ed. Engl.  1976,  15:  294 
  • 4b Poisel H. Chem. Ber.  1977,  110:  948 
  • 4c Kolar AJ. Olsen RK. Synthesis  1977,  457 
  • 5 Daoust B. Lessard J. Tetrahedron  1999,  55:  3495 
  • 6a Kawaya M. Neogi P. Khattri PS. Butsugan Y. Chem. Lett.  1990,  577 
  • 6b Miosses B. Danion-Bougot R. Danion D. Synthesis  1994,  1171 
  • 7a Caprara G. Lemetre G. Vercellone A. Ann. Chim. (Rome)  1959,  49:  1167 
  • 7b Drago RS. Wenz DA. Carlson RJ. J. Am. Chem. Soc.  1962,  84:  1106 
  • 8 Bachand C. Driguez H. Paton JM. Touchard D. Lessard J. J. Org. Chem.  1974,  39:  3136 
  • 9 Zimmer H. Audrieth LF. J. Am. Chem. Soc.  1954,  76:  3856 
  • 10 Curini M. Epifano F. Marcotullio MC. Rosati O. Tsadjout A. Synlett  2000,  813 
  • 11a Hirano M. Yakabe S. Fukami M. Morimoto T. Synth. Commun.  1997,  27:  2783 
  • 11b Hirano M. Yakabe S. Uraoka N. Morimoto T. Org. Prep. Proced. Int.  1998,  30:  360 
  • 12 Hirano M. Yakabe S. Itoh S. Clark JH. Morimoto T. Synthesis  1997,  1161 
  • 15a Moist alumina was prepared according to the published procedure: Greenhalgh RP. Synlett  1992,  235 
  • 15b For a recent review on reactions carried out on alumina see: Kabalka GW. Pagni RM. Tetrahedron  1997,  53:  7999 
  • 17 Biagini SCG. Gibson SE. Keen SP. J. Chem. Soc., Perkin Trans. 1  1998,  2485 
  • 18 Kordes M. Winsel H. de Meijere A. Eur. J. Org. Chem.  2000,  3235 
  • 19 Csuk R. von Scholz Y. Tetrahedron  1994,  50:  10431 
  • 20 This compound was prepared by a standard sequence of esterification (MeOH/SOCl2) and N-Boc-protection (Boc2O/ Et3N in CH2Cl2) of the previously described 3-(trans-2-nitrocyclopropyl)alanine: Larionov OV. Savel’eva TF. Kochetkov KA. Ikonnikov NS. Kozhushkov SI. Yufit DS. Howard JAK. Khrustalev VN. Belokon YuN. de Meijere A. Eur. J. Org. Chem.  2003,  5:  869 
  • 21 Yokoyama Y. Hikawa H. Murakami Y. J. Chem. Soc., Perkin Trans. 1  2001,  1431 
  • 22a Phan XT. Shannon PJ. J. Org. Chem.  1983,  48:  5164 
  • 22b Beyer H. Korosi J. Chem. Ber.  1961,  94:  480 
  • For the preparation and application of this compound in chemical industry see:
  • 23a Walles WE. inventors; US Patent  3591601.  1971; Chem. Abstr. 1971, 75, 88620
  • 23b Choi SK. inventors; US Patent  3875147.  1975; Chem. Abstr. 1975, 83, 79999
  • 23c Walles WE. inventors; US Patent  3850920.  1974; Chem. Abstr. 1975, 82, 125410
  • For the preparation and application of this compound in chemical industry see:
  • 24a Lessard J. Couture Y. Mondon M. Touchard D. Can. J. Chem.  1984,  62:  105 
  • 24b Phan XT. Shannon PJ. J. Org. Chem.  1983,  48:  5164 
  • (c) See ref. 23a,c.

13

Larionov, O. V.; de Meijere, A. manuscript in preparation.

14

N-chlorination of the cyclopropyl-containing amino acid derivatives 1-H and 2-H with any of the other known reagents was to a greater extent hampered by some side-processes furnishing the products 1-Cl and 2-Cl respectively in low yields and purities.

16

Larionov, O. V. Part of a forthcoming Dissertation, University of Göttingen 2004.