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Synlett 2008(16): 2437-2442  
DOI: 10.1055/s-2008-1078171
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis and Reactivity of Novel α,α,β- and α,α,δ-Trichlorinated Imines

Matthias D’hooghe, Bruno De Meulenaer, Norbert De Kimpe*
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
e-Mail: norbert.dekimpe@UGent.be;
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Publikationsverlauf

Received 21 May 2008
Publikationsdatum:
10. September 2008 (online)

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Abstract

A variety of different N-(2,2,3-trichloropropyli­dene)amines, N-(2,2,3-trichlorobutylidene)amines, and N-(2,2,5-trichloropentylidene)amines were synthesized for the first time, and their reactivity with regard to hydride reagents was investigated. In this way, N-(2,2,5-trichloropentylidene)amines were evaluated as substrates for the synthesis of piperidines, and N-(2,2,3-trichloropropylidene)amines and N-(2,2,3-trichlorobutylidene)amines were reduced efficiently into the corresponding novel β,β,γ-trichloro-amines by means of sodium cyanoborohydride in methanol in the presence of acetic acid. Furthermore, N-(2,2,3-trichloropropyli­dene)amines were transformed into 2-(chloromethyl)aziridines by lithium aluminium hydride in Et2O, and N-(2,2,5-trichloropentylidene)acetamide was used for the first time as a suitable substrate for the addition of oxygen, nitrogen, and sulfur nucleophiles in good yields.

Key words

trichlorinated imines - hydride reagents - trichloro­amines - 2-(chloromethyl)aziridines

    References and Notes

  • 1 Duhamel L. Duhamel P. Valnot JY. C. R. Hebd. Seances Acad. Sci, Ser. C  1970,  271:  1471 
    Google Scholar
  • 2 Duhamel L. Valnot JY. Tetrahedron Lett.  1974,  3167 
    CrossrefGoogle Scholar
  • 3 De Kimpe N. Verhé R. De Buyck L. Schamp N. Declercq JP. Germain G. Van Meersche M. J. Org. Chem.  1977,  42:  3704 
    Google Scholar
  • 4 De Kimpe N. Verhe R. De Buyck L. Hasma H. Schamp N. Tetrahedron  1976,  32:  3063 
    CrossrefGoogle Scholar
  • 5 De Kimpe N. Verhe R. De Buyck L. Schamp N. Bull. Soc. Chim. Belg.  1977,  86:  663 
    Google Scholar
  • 6 De Kimpe N. Stanoeva E. Verhe R. Schamp N. Synthesis  1988,  587 
    Artikel in Thieme ConnectGoogle Scholar
  • 7 De Kimpe N. Yao Z. Boeykens M. Nagy M. Tetrahedron Lett.  1990,  31:  2771 
    CrossrefGoogle Scholar
  • 8 De Kimpe N. Stevens C. Virag M. Tetrahedron  1996,  52:  3303 
    CrossrefGoogle Scholar
  • 9 Van Brabandt W. Dejaegher Y. De Kimpe N. Pure Appl. Chem.  2005,  77:  2061 
    Google Scholar
  • 10a Bellesia F. De Buyck L. Ghelfi F. Synlett  2000,  146 
    Google Scholar
  • 10b Bellesia F. De Buyck L. Ghelfi F. Libertini E. Pagnoni UM. Roncaglia F. Tetrahedron  2000,  56:  7507 
    Google Scholar
  • 10c Bellesia F. De Buyck L. Ghelfi F. Pagnoni UM. Parsons AF. Pinetti A. Synthesis  2003,  2173 
    Google Scholar
  • 11a De Kimpe N. Verhe R. De Buyck L. Schamp N. Synth. Commun.  1975,  5:  269 
    Google Scholar
  • 11b Verhé R. De Kimpe N. De Buyck L. Tilley M. Schamp N. Tetrahedron  1980,  36:  131 
    Google Scholar
  • 11c De Kimpe N. Stevens C. Tetrahedron  1991,  47:  3407 
    Google Scholar
  • 12 Stas S. Abbaspour Tehrani K. Tetrahedron  2007,  63:  8921 
    CrossrefGoogle Scholar
  • 13 De Buyck L. Vanhulle P. Bull. Soc. Chim. Belg.  1992,  101:  329 
    Google Scholar
  • 15 Sulmon P. De Kimpe N. Schamp N. Synthesis  1989,  8 
    Artikel in Thieme ConnectGoogle Scholar
  • 16a Higasio YS. Shoji T. Appl. Catal., A  2001,  221:  197 
    Google Scholar
  • 16b Felpin F.-X. Lebreton J. Eur. J. Org. Chem.  2003,  3693 
    Google Scholar
  • 16c Källström S. Leino R. Bioorg. Med. Chem.  2008,  16:  601 
    Google Scholar
  • 17a Hammer CF. Heller SR. Craig JH. Tetrahedron  1972,  28:  239 
    Google Scholar
  • 17b Alabugin IV. Manoharan M. Zeidan TA. J. Am. Chem. Soc.  2003,  125:  14014 
    Google Scholar
  • 18a Ulrich H. Tucker B. Sayigh AAR. J. Org. Chem.  1968,  33:  2887 
    Google Scholar
  • 18b Zinner H. Siems WE. Erfurt G. J. Prakt. Chem.  1974,  316:  63 
    Google Scholar
  • 18c De Kimpe N. Verhé R. De Buyck L. Dejonghe W. Schamp N. Bull. Soc. Chim. Belg.  1976,  85:  763 
    Google Scholar
  • 19a Akiyama Y, Nakao M, Nagahara N, and Nara E. inventors; JP 09104640  A.  ; Chem. Abstr. 1997, 127, 44971
  • 19b Kundu M, Narayana L, Kotame PM, Khairatkar-Joshi N, and Karnik P. inventors; WO 2007086080  A2.  ; Chem. Abstr. 2007, 147, 235166
  • 21a Shin C.-G. Sato Y. Yoshimura J. Bull. Chem. Soc. Jpn.  1976,  49:  1909 
    Google Scholar
  • 21b Koeppen J. Matthies D. Schweim H. Liebigs Ann. Chem.  1985,  2383 
    Google Scholar
  • 21c Sicker D. Hartenstein H. Z. Chem.  1989,  29:  169 
    Google Scholar
  • 21d Zabirov NG. Galyautdinov NI. Shcherbakova VA. Cherkasov RA. Zh. Obshch. Khim.  1990,  60:  1247 ; Chem. Abstr. 1991, 114, 6634
    Google Scholar
  • 21e Zabirov NG. Cherkasov RA. Zh. Obshch. Khim.  1990,  60:  1251 ; Chem. Abstr. 1990, 113, 231520
    Google Scholar
  • 21f Booth BL. Cabral IM. Dias AM. Freitas AP. Matos Beja AM. Proença MF. Ramos Silva M. J. Chem. Soc., Perkin Trans. 1  2001,  1241 
    Google Scholar
  • 21g Sokolov VB. Aksinenko AY. Epishina TA. Goreva TV. Martynov IV. Russ. Chem. Bull.  2005,  54:  472 
    Google Scholar
  • 22 De Buyck L. Verhe R. De Kimpe N. Courtheyn D. Schamp N. Bull. Soc. Chim. Belg.  1980,  89:  441 
    Google Scholar
  • 24a Zinner H. Siems WE. Erfurt G. J. Prakt. Chem.  1974,  316:  443 
    Google Scholar
  • 24b Zinner H. Siems WE. Erfurt G. J. Prakt. Chem.  1974,  316:  491 
    Google Scholar
  • 24c Zinner H. Siems WE. Erfurt G. J. Prakt. Chem.  1974,  316:  698 
    Google Scholar
  • 24d Fisera L. Science of Synthesis   Vol. 27:  Thieme; Stuttgart: 2004.  p.349-373  
    Google Scholar
  • 26 Singh GS. D’hooghe M. De Kimpe N. Chem. Rev.  2007,  107:  2080 
    CrossrefPubMedGoogle Scholar
  • 27a D’hooghe M. Van Brabandt W. De Kimpe N. J. Org. Chem.  2004,  69:  2703 
    Google Scholar
  • 27b D’hooghe M. Waterinckx A. De Kimpe N. J. Org. Chem.  2005,  70:  227 
    Google Scholar
  • 27c D’hooghe M. Waterinckx A. Vanlangendonck T. De Kimpe N. Tetrahedron  2006,  62:  2295 
    Google Scholar
  • 27d D’hooghe M. Vanlangendonck T. Törnroos KW. De Kimpe N. J. Org. Chem.  2006,  71:  4678 
    Google Scholar
  • 27e D’hooghe M. De Kimpe N. Synlett  2006,  2089 
    Google Scholar
  • 27f D’hooghe M. De Kimpe N. Chem. Commun.  2007,  1275 
    Google Scholar
  • 27g D’hooghe M. Vervisch K. De Kimpe N. J. Org. Chem.  2007,  72:  7329 
    Google Scholar
  • 27h D’hooghe M. De Kimpe N. Arkivoc  2008,  (ix):  6 
    Google Scholar
  • 28 De Kimpe N. Jolie R. De Smaele D. J. Chem. Soc., Chem. Commun.  1994,  1221 
    Google Scholar
  • 29 Gaertner VR. J. Org. Chem.  1970,  35:  3952 
    CrossrefGoogle Scholar
  • 31 D’hooghe M. De Kimpe N. Tetrahedron  2008,  64:  3275 
    CrossrefGoogle Scholar
  • 33 Atsumi K. Katano K. Nishihata K. Kai F. Akita E. Niida T. Tetrahedron Lett.  1982,  23:  2977 
    CrossrefGoogle Scholar
  • 34 Drach BS. Mis’kevich GN. Zh. Org. Khim.  1975,  11:  316 ; Chem. Abstr. 1975, 82, 125017
    Google Scholar
14

N -(2,2,5-Trichloropentylidene)isopropylamine (3a)Bp 41-42 ˚C (0.10 Torr). ¹H NMR (270 MHz, CDCl3): δ = 1.19 (6 H, d, J = 6.3 Hz), 2.18-2.22 (2 H, m), 2.57-2.62 (2 H, m), 3.49 (1 H, septd, J = 6.3, 0.7 Hz), 3.64 (2 H, t, J = 5.9 Hz), 7.75 (1 H, d, J = 0.7 Hz). ¹³C NMR (68 MHz, CDCl3): δ = 23.5, 28.4, 40.9, 44.2, 59.8, 88.5, 157.1. IR (NaCl): ν = 1667 (C=N) cm-¹. MS (70 eV): m/z (%) = 229/231/233/235 (0.3) [M+], 194/196/198(16), 70(100); for chlorine isotopes, the reported relative intensity (%) represents the largest peak.

20

N -(2,2,5-Trichloro-1-phenoxypentyl)acetamide (9a)
Mp 130 ˚C. ¹H NMR (270 MHz, CDCl3): δ = 2.07 (3 H, s), 2.10-2.60 (4 H, m), 3.59 (2 H, t, J = 6.3 Hz), 6.18 (1 H, d, J = 10.1 Hz), 6.47 (1 H, d, J = 10.1 Hz), 7.01-7.06 (3 H, m), 7.26-7.34 (2 H, m). ¹³C NMR (68 MHz, CDCl3): δ = 23.3, 27.9, 41.4, 44.0, 81.3, 93.7, 115.9, 122.8, 129.9, 155.5, 170.2. IR (NaCl): ν = 3270 (NH), 1660 (C=O) cm-¹. MS (70 eV): m/z (%), no [M+] = 149 (19), 112 (18), 110 (20), 77 (100), 49 (22); for chlorine isotopes, the reported relative intensity (%) represents the largest peak. Anal. Calcd for C13H16Cl3NO2: C, 48.10; H, 4.97; N, 4.31. Found: C, 48.33; H, 5.20; N, 4.15.

23

N -(2,2,3-Trichloropropylidene)isopropylamine (14a)
Bp 24-26 ˚C (0.01 Torr). ¹H NMR (270 MHz, CDCl3): δ = 1.19 (6 H, d, J = 6.3 Hz), 3.52 (1 H, sept, J = 6.3 Hz), 4.26 (2 H, s), 7.77 (1 H, s). ¹³C NMR (68 MHz, CDCl3): δ = 23.3, 51.8, 59.8, 85.0, 155.3. IR (NaCl): ν = 1667 (C=N) cm-¹. MS (70 eV): m/z (%) = 201/203/205/207 (1) [M+], 186/188/190/192 (9), 124/126/128 (20), 116/118 (10), 111 (17), 96/98 (12), 70 (42), 63 (16), for chlorine isotopes, the reported relative intensity (%) represents the largest peak.

25

2-Chloromethyl-1-isopropylaziridine (15a)
Bp 40-43 ˚C (15 Torr). Purity: 90% (based on GC). ¹H NMR (270 MHz, CDCl3): δ = 1.12 (3 H, d, J = 6.3 Hz), 1.18 (3 H, d, J = 6.3 Hz), 1.40-1.46 (1 H, m), 1.73-1.75 (1 H, m), 1.46 (1 H, sept, J = 6.3 Hz), 1.68-1.74 (1 H, m), 3.31 (1 H, dd, J = 11.2, 7.6 Hz), 3.58 (1 H, dd, J = 11.2, 4.5 Hz). ¹³C NMR (68 MHz, CDCl3): δ = 21.8, 22.3, 33.3, 39.6, 47.2, 60.7. MS (70 eV): m/z (%) = 133/135 (3) [M+], 118/120 (10), 99 (15), 98 (69), 90/92 (15), 56 (100), 55 (10); for chlorine isotopes, the reported relative intensity (%) represents the largest peak.

30

N -(2,2,3-Trichloropropyl)isopropylamine (18a)
Bp 28.5 ˚C (0.2 Torr). ¹H NMR (270 MHz, CDCl3): δ = 1.07 (6 H, d, J = 6.3 Hz), 1.10-1.30 (1 H, m), 2.90 (1 H, sept, J = 6.3 Hz), 3.29 (2 H, s), 4.14 (2 H, s). ¹³C NMR (68 MHz, CDCl3): δ = 23.2, 48.8, 50.9, 56.6, 90.7. IR (NaCl): ν = 3330 (NH) cm-¹. MS (70 eV): m/z (%) = 203/205/207/209 (1) [M+], 188/190/192/194 (23), 72 (100). Anal. Calcd for C6H12Cl3N: C, 35.23; H, 5.91; N, 6.85. Found: C, 35.11; H, 6.09; N, 6.74; for chlorine isotopes, the reported relative intensity (%) represents the largest peak.

32

N -(2,2,3-Trichlorobutylidene)isopropylamine (21a)
¹H NMR (270 MHz, CDCl3): δ = 1.21 (6 H, d, J = 6.3 Hz), 1.78 (3 H, d, J = 6.5 Hz), 3.55 (1 H, sept, J = 6.3 Hz), 4.69 (1 H, q, J = 6.5 Hz), 7.78 (1 H, s). ¹³C NMR (68 MHz, CDCl3): δ = 20.5, 23.3, 23.4, 60.2, 62.3, 89.8, 156.6. IR (NaCl): ν = 1663 (C=N) cm-¹. MS (70 eV): m/z (%) = 215/217/219/221 (2) [M+], 57 (100), 56 (3); for chlorine isotopes, the reported relative intensity (%) represents the largest peak.

35

N -(2,2,3-Trichlorobutyl)- tert -butylamine (22a)
¹H NMR (270 MHz, CDCl3): δ = 1.11 (9 H, s), 1.55 (1 H, br s), 1.76 (3 H, d, J = 6.5 Hz), 3.26 and 3.44 (2 × 1 H, 2 d, J = 13.2 Hz), 4.75 (1 H, q, J = 6.5 Hz). ¹³C NMR (68 MHz, CDCl3): δ = 20.2, 29.3, 50.6, 55.1, 60.5, 96.4. IR (NaCl): ν = 3330 (NH) cm-¹. MS (70 eV): m/z (%), no [M+] = 216/218/220/222 (61), 181/183/185 (15), 140/142/144 (11), 118/120 (17), 87 (13), 86 (100), 70 (14), 58 (45), 57 (45), 53 (11). Anal. Calcd for C8H16Cl3N: C, 41.31; H, 6.93; N, 6.02. Found: C, 41.47; H, 7.13; N, 5.92; for chlorine isotopes, the reported relative intensity (%) represents the largest peak.