PAPER
Parallel Synthesis of a Library of Acylsemicarbazides
2391
4-Benzyl-4-methyl-1-(5-chlorothiophene-2-carbonyl)thiosemi-
carbazide (6f)
Yield: 84%; beige solid; Rf 0.30 (hexane–EtOAc, 7:3).
1H NMR (CD3OD): d = 7.66 (d, J = 4.0 Hz, 1 H), 7.26–7.34 (m, 5
H), 7.06 (d, J = 4.0 Hz, 1 H), 5.15 (s, 2 H), 3.14 (s, 3 H).
Mathis, W. D. Synthesis 2002, 53.
(5) Wang, Q.; Huang, R. Tetrahedron Lett. 2001, 42, 8881.
(6) For reviews on solid-phase organic synthesis, see:
(a) Krchnák, V.; Holladay, M. W. Chem. Rev. 2002, 102,
61. (b) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99,
1549. (c) Kobayashi, S. Chem. Soc. Rev. 1999, 28, 1.
(d) Brown, A. R.; Hermkens, P. H. H.; Ottenheijm, H. C. J.;
Rees, D. C. Synlett 1998, 817. (e) Brown, R. C. D. J. Chem.
Soc., Perkin Trans. 1 1998, 3293. (f) Nefzi, A.; Ostresh, J.
M.; Houghten, R. A. Chem. Rev. 1997, 97, 449.
4-Phenyl-4-methyl-1-(5-chlorothiophene-2-carbonyl)thiosemi-
carbazide (6g)
Yield: 22%; yellow solid; mp 200–203 °C; Rf 0.30 (hexane–EtOAc,
7:3).
(g) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96,
555.
IR (thin film): 3095, 1612, 1515, 1502, 1427, 1341, 1278, 1172,
1027 cm–1.
1H NMR (CD3OD): d = 7.59 (d, J = 4.0 Hz, 1 H), 7.34–7.48 (m, 5
H), 7.01 (d, J = 4.0 Hz, 1 H), 3.61 (s, 3 H).
13C NMR (CD3OD): d = 184.4, 161.5, 143.7, 135.8, 135.7, 130.2,
129.3, 128.3, 127.5, 126.7, 43.5.
MS (EI): m/z (%) = 325 (16) [M+], 291 (43), 218 (100), 158 (57),
106 (75).
HRMS (EI): m/z [M+] calcd for C13H12ClN3OS2: 325.0110; found:
325.0108.
(7) For reviews on liquid-phase organic synthesis, see: (a) Sun,
C.-M. Comb. Chem. High Throughput Screening 1999, 2,
299. (b) Wentworth, P. Jr. Trends Biotechnol. 1999, 17,
448. (c) Wentworth, P. Jr.; Janda, K. D. Chem. Commun.
1999, 1917. (d) Gravert, D. J.; Janda, K. D. Chem. Rev.
1997, 97, 489.
(8) For reviews on solution-phase organic synthesis, see:
(a) An, H.; Cook, P. D. Chem. Rev. 2000, 100, 3311.
(b) Merritt, A. T. Comb. Chem. High Throughput Screening
1998, 1, 57. (c) Boger, D. L.; Goldberg, J. J. Comb. Chem.
2000, 303. (d) Coe, D. M.; Storer, R. Mol. Diversity 1999, 4,
31.
4,4-Diallyl-1-(5-chlorothiophene-2-carbonyl)thiosemicarb-
azide (6h)
Yield: 63%; white solid; mp 116–118 °C; Rf 0.55 (hexane–EtOAc,
1:1).
(9) (a) Peng, S. X.; Henson, C.; Strojnowski, M. J.;
Golebiowski, A.; Klopfenstein, S. R. Anal. Chem. 2000, 72,
261. (b) Chen, Y.; Bilban, M.; Foster, C. A.; Boger, D. L. J.
Am. Chem. Soc. 2002, 124, 5431.
IR (thin film): 3228, 1644, 1513, 1424, 1326, 1236, 928 cm–1.
(10) (a) Curran, D. P. Angew. Chem. Int. Ed. Engl. 1998, 37,
1174. (b) Curran, D. P.; Hadida, S. J. Am. Chem. Soc. 1996,
118, 2531. (c) Curran, D. P.; Hoshino, M. J. Org. Chem.
1996, 61, 6480. (d) Studer, A.; Curran, D. P. Tetrahedron
1997, 53, 6681. (e) Studer, A.; Jeger, P.; Wipf, P.; Curran,
D. P. J. Org. Chem. 1997, 62, 2917. (f) Curran, D. P.;
Hadida, S.; He, M. J. Org. Chem. 1997, 62, 6714.
(11) (a) Parlow, J. J.; Devraj, R. V.; South, M. S. Curr. Opin.
Chem. Biol. 1999, 3, 320. (b) Song, C. E.; Le, S.-G. Chem.
Rev. 2002, 102, 3495. (c) Ley, S. V.; Baxendale, I. R.;
Brusotti, G.; Caldarelli, M.; Massi, A.; Nesi, M. Il Farmaco
2002, 57, 321. (d) Ley, S. V.; Baxendale, I. R.; Bream, R.
N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi,
M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc.,
Perkin Trans. 1 2000, 3815. (e) Booth, R. J.; Hodges, J. C.
Acc. Chem. Res. 1999, 32, 18. (f) Weller, H. N. Mol.
Diversity 1999, 4, 47.
(12) (a) Shuttleworth, S. J.; Quimpére, M.; Lee, N.; DeLuca, J.
Mol. Diversity 1998, 4, 183. (b) Kang, K. H.; Pae, A. N.;
Choi, K. I.; Cho, Y. S.; Chung, B. Y.; Lee, J. E.; Jung, S. H.;
Koh, H. Y.; Lee, H.-Y. Tetrahedron Lett. 2001, 42, 1057.
(c) Tietze, L. F.; Evers, H.; Töpken, E. Helv. Chim. Acta
2002, 85, 4200. (d) Tietze, L. F.; Evers, H.; Töpken, E.
Angew. Chem. Int. Ed. 2001, 40, 903. (e) Beaulieu, P. L.;
Haché, B.; von Moos, E. Synthesis 2003, 1683. (f) Lee, H.-
K.; Chui, W.-K. Bioorg. Med. Chem. 1999, 7, 1255.
(g) Pirrung, M. C.; Sarma, K. D. J. Am. Chem. Soc. 2004,
126, 444.
1H NMR (CD3OD): d = 7.63 (d, J = 4.0 Hz, 1 H), 7.05 (d, J = 4.0
Hz, 1 H), 5.82–5.95 (m, 2 H), 5.19–5.25 (m, 4 H), 4.34 (d, J = 5.0
Hz, 4 H).
13C NMR (CD3OD): d = 184.1, 161.6, 135.8, 135.7, 131.9, 129.3,
127.6, 116.7, 52.9.
MS (EI): m/z (%) = 315 (23) [M+], 274 (27), 218 (71), 155 (85), 145
(100).
HRMS (EI): m/z [M+] calcd for C12H14ClN3OS2: 315.0267; found:
315.0270.
Acknowledgment
We thank Crompton Co., the Natural Sciences and Engineering Re-
search Council of Canada (NSERC), the Ontario Research and De-
velopment Challenge Fund, and the Environmental Science and
Technology Alliance of Canada for financial support. We thank
Crompton Co. for running the biological assays. We would also like
to thank Dr. Ming Shen for initial work with carbamoylimidazolium
salts and hydrazides. We thank Dr. A.B. Young for mass spectro-
metric analysis.
References
(1) (a) Gante, J. Synthesis 1989, 405. (b) Gibson, C.; Goodman,
S. L.; Hahn, D.; Hölzemann, G.; Kessler, H. J. Org. Chem.
1999, 64, 7388. (c) Weber, D.; Berger, C.; Eickelmann, P.;
Antel, J.; Kessler, H. J. Med. Chem. 2003, 46, 1918.
(2) Andurkar, S. V.; Béguin, C.; Stables, J. P.; Kohn, H. J. Med.
Chem. 2001, 44, 1475.
(3) (a) Wing, K. D. Science 1988, 241, 467. (b) Wing, K. D.;
Slawecki, R. A.; Carlson, G. R. Science 1988, 241, 470.
(4) (a) Nakagawa, Y.; Smagghe, G.; Kugimiya, S.; Hattori, K.;
Ueno, T.; Tirry, L.; Fujita, T. Pestic. Sci. 1999, 55, 909.
(b) Mulvihill, M. J.; Shaber, S. H.; MacDougall, B. S.;
Ajello, C.; Martinez-Teipel, B.; Joseph, R.; Nguyen, D. V.;
Weaver, D. G.; Chung, K.-H.; Gusev, A.; Wierenga, J. M.;
(13) (a) Honigfort, M. E.; Brittain, W. J.; Bosanac, T.; Wilcox, C.
S. Macromolecules 2002, 35, 4849. (b) Bosanac, T.;
Wilcox, C. S. J. Am. Chem. Soc. 2002, 124, 4194.
(c) Bosanac, T.; Yang, J.; Wilcox, C. S. Angew. Chem. Int.
Ed. 2001, 40, 1875.
(14) (a) Ahn, J.-M.; Wentworth, P. Jr.; Janda, K. D. Chem.
Commun. 2003, 480. (b) Sieber, F.; Wentworth, P. Jr.;
Janda, K. D. J. Comb. Chem. 1999, 1, 540. (c) Zhao, X.-Y.;
Metz, W. A.; Sieber, F.; Janda, K. D. Tetrahedron Lett.
1998, 39, 8433. (d) Huang, K.-T.; Sun, C.-M. Bioorg. Med.
Chem. Lett. 2002, 12, 1001. (e) Huang, K.-T.; Sun, C.-M.
Synthesis 2005, No. 14, 2384–2392 © Thieme Stuttgart · New York