2-Chloro-1,3-dimethylimidazolinium chloride. 1. A powerful dehydrating equivalent to DCC

Journal of Organic Chemistry

Volumn 64, Issue 19, 1999, Pages 6984-6988

  Isobe, Toshio ^a   Ishikawa, Tsutomu ^b  

^a Shiratori Pharmaceutical Co Ltd   (Japan)

^b CHIBA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 1,3 DIMETHYLIMIDAZOLINIUM CHLORIDE; ACID ANHYDRIDE; CYCLOARTENOL; DESICCANT; DICYCLOHEXYLCARBODIIMIDE; ESTER DERIVATIVE; IMIDAZOLINE DERIVATIVE; KETONE DERIVATIVE; OXIME DERIVATIVE; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; CHEMICAL STRUCTURE; COMPARATIVE STUDY; DESICCATION; ESTERIFICATION; REACTION ANALYSIS;

EID: 0033578942     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo990210y     Document Type: Article

References (66)

1. For example, see: (a) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; John-Wiley and Sons: New York, 1967; Vol. 1, pp 231-236.
2. (b) March, J. Advanced Organic Chemistry, 3rd ed.; Wiley-Interscience: New York, 1985; pp 349-350.
3. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; John-Wiley and Sons: New York, 1967; Vol. 1, p 274.
4. The price of EDCI is ¥16500/25 g (Nacalai Tesque, Inc., Japan). This corresponds to $137.5/25 g, based on the exchange rate of ¥120/$ of Japanese yen to U.S. dollars.
5. Fujisawa, T. Mori, T.; Fukumoto, K.; Sato, T. Chem. Lett. 1982, 1891.
6. The CAS No is 37091-73-9. In the 9th Collective Index of Chemical Abstracts an alternative nomenclature of 2-chloro-4, 5-dihydro-1, 3-dimethyl-1H-imidazolium chloride has been adopted. The name of DMC is derived from the chloro derivative of 1, 3-dimethyl-2-imidazolidinone (DMI) (4).
7. Fujisawa, T.; Tajima, K.; Sato, T. Bull. Chem. Soc. Jpn. 1983, 56, 3529.
8. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
9. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
10. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
11. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
12. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
13. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
14. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
15. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
16. Substitution reactions of 3 acting as an electrophile have been reported: Kessler, H.; Kalinowski, H.-O. Leigibs Ann. Chem. 1971, 743, 1. Kalinowski, H.-O.; Kessler, H.; Walter, A. Tetrahedron 1974, 30, 1137. Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979, 18, 873. Isolated examples of the use of 3 as a dehydrating agent can also be found in recent literature. For example, see: Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 81. Hirose, M.; Kawai, R.; Hayakawa, Y. Synlett 1997, 495. Iwata, S.; Matsuoka, H.; Tanaka, K. J. Chem. Soc., Perkin Trans. 1 1997, 1357. Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Kodera, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143. Node, M.; Fujiwara, T.; Ichihashi, S.; Nishide, K. Tetrahedron Lett. 1998, 39, 6331. Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998, 1185.
17. 3
18. 50) of DMI (4) in mouse has been reported as 2, 840 mg/kg [Lien, E. J.; Kumler, W. D. J. Med. Chem. 1968, 11, 214]. This suggests that 3 is basically nontoxic because of easy decomposition of 3 into 4. On the other hand, cytotoxicity of N,N,N′,N′-tetramethylurea, a synthetic precursor for a linear-type chloroamidinium salt, has been reported [Chen, S.; Xu, J. Tetrahedron Lett. 1992, 33, 647].
19. 50) of DMI (4) in mouse has been reported as 2, 840 mg/kg [Lien, E. J.; Kumler, W. D. J. Med. Chem. 1968, 11, 214]. This suggests that 3 is basically nontoxic because of easy decomposition of 3 into 4. On the other hand, cytotoxicity of N,N,N′,N′-tetramethylurea, a synthetic precursor for a linear-type chloroamidinium salt, has been reported [Chen, S.; Xu, J. Tetrahedron Lett. 1992, 33, 647].
20. Koenig, H.-B.; Wilfried S.; Cologne, H. D.; Metzger, K. G. Ger. Offen. DE 2104579, 1972; Chem. Abstr. 1972, 77, 140048. Koenig, H.-B.; Schroeck, W.; Disselnkoetter, H.; Metzger, K. G. US 3959258, 1976; Chem. Abstr. 1976, 85, 160079.
21. Koenig, H.-B.; Wilfried S.; Cologne, H. D.; Metzger, K. G. Ger. Offen. DE 2104579, 1972; Chem. Abstr. 1972, 77, 140048. Koenig, H.-B.; Schroeck, W.; Disselnkoetter, H.; Metzger, K. G. US 3959258, 1976; Chem. Abstr. 1976, 85, 160079.
22. Koenig, H.-B.; Wilfried S.; Cologne, H. D.; Metzger, K. G. Ger. Offen. DE 2104579, 1972; Chem. Abstr. 1972, 77, 140048. Koenig, H.-B.; Schroeck, W.; Disselnkoetter, H.; Metzger, K. G. US 3959258, 1976; Chem. Abstr. 1976, 85, 160079.
23. Koenig, H.-B.; Wilfried S.; Cologne, H. D.; Metzger, K. G. Ger. Offen. DE 2104579, 1972; Chem. Abstr. 1972, 77, 140048. Koenig, H.-B.; Schroeck, W.; Disselnkoetter, H.; Metzger, K. G. US 3959258, 1976; Chem. Abstr. 1976, 85, 160079.
24. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 025375, 1984; Chem. Abstr. 1984, 101, 151844. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 039851, 1984; Chem. Abstr. 1984, 101, 130410. Kiso and co-workers also reported the preparation of 3 according to our method (Kiso, Y.; Fujiwara, Y.; Kimura, T.; Nishitani, A.; Akaji, K. Int. J. Peptide Protein Res. 1992, 40, 308).
25. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 025375, 1984; Chem. Abstr. 1984, 101, 151844. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 039851, 1984; Chem. Abstr. 1984, 101, 130410. Kiso and co-workers also reported the preparation of 3 according to our method (Kiso, Y.; Fujiwara, Y.; Kimura, T.; Nishitani, A.; Akaji, K. Int. J. Peptide Protein Res. 1992, 40, 308).
26. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 025375, 1984; Chem. Abstr. 1984, 101, 151844. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 039851, 1984; Chem. Abstr. 1984, 101, 130410. Kiso and co-workers also reported the preparation of 3 according to our method (Kiso, Y.; Fujiwara, Y.; Kimura, T.; Nishitani, A.; Akaji, K. Int. J. Peptide Protein Res. 1992, 40, 308).
27. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 025375, 1984; Chem. Abstr. 1984, 101, 151844. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 039851, 1984; Chem. Abstr. 1984, 101, 130410. Kiso and co-workers also reported the preparation of 3 according to our method (Kiso, Y.; Fujiwara, Y.; Kimura, T.; Nishitani, A.; Akaji, K. Int. J. Peptide Protein Res. 1992, 40, 308).
28. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 025375, 1984; Chem. Abstr. 1984, 101, 151844. Mukaiyama, T.; Isobe, T.; Kato, M.; Miyagaki, M.; Kogo, S. Jpn. Kokai Tokkyo Koho, JP 59 039851, 1984; Chem. Abstr. 1984, 101, 130410. Kiso and co-workers also reported the preparation of 3 according to our method (Kiso, Y.; Fujiwara, Y.; Kimura, T.; Nishitani, A.; Akaji, K. Int. J. Peptide Protein Res. 1992, 40, 308).
29. 2O (76% and 100% decomposition after 10 nun and 3 h, respectively).
30. References to the products in Table 2 are as follows: (a) Run 1: Korte, W. D. J. Chromatogr. 1981, 214, 131.
31. (b) Run 3: Muramatsu, M.; Shiraishi, S.; Fujii, S. Biochim. Biophys. Acta 1972, 285, 224.
32. Run 4: ref 4.
33. Run 5: Ono, N.; Yamada, T.; Saito, T.; Tanaka, K.; Kaji, A. Bull. Chem. Soc. Jpn. 1978, 51, 2401.
34. (e) Runs 6 and 7: Takahashi, S.; Cohen, L. A.; Miller, H. K.; Peake, E. G. J. Org. Chem. 1971, 36, 1205.
35. References to the products in Table 3 are as follows; (a) runs 1-3: Isobe, T.; Imai, Y.; Saito, M.; Murata, S.; Nagao, T.; Tsurumi, C. Jpn. Kokai Tokkyo Koho, JP 05 239088, 1993; Chem. Abstr. 1994, 120, 134934.
36. References to the products in Table 3 are as follows; (a) runs 1-3: Isobe, T.; Imai, Y.; Saito, M.; Murata, S.; Nagao, T.; Tsurumi, C. Jpn. Kokai Tokkyo Koho, JP 05 239088, 1993; Chem. Abstr. 1994, 120, 134934.
37. (b) Run 4: Kimura, G.; Hirose, Y.; Yoshida, K.; Kuzuya, F.; Fujita, K. Eur. Patent EP 166542, 1986; Chem. Abstr. 1987, 106, 18881.
38. (b) Run 4: Kimura, G.; Hirose, Y.; Yoshida, K.; Kuzuya, F.; Fujita, K. Eur. Patent EP 166542, 1986; Chem. Abstr. 1987, 106, 18881.
39. References of the products in Table 4 are as follows, (a) Run 1: Yamada, S. J. Org. Chem. 1992, 57, 1591.
40. (b) Run 2: Izawa, T.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1979, 53, 555.
41. Run 3: Isobe, T. Jpn. Kokai Tokkyo Koho, JP 07 010853, 1995; Chem. Abstr. 1995, 123, 33057.
42. Run 3: Isobe, T. Jpn. Kokai Tokkyo Koho, JP 07 010853, 1995; Chem. Abstr. 1995, 123, 33057.
43. Run 4: Nagao, Y.; Seno, K.; Kawabata, K.; Miyasaka, T.; Takao, S.; Fujita, E. Chem. Pharm. Bull. 1984, 32, 2687.
44. References to the products in Table 5 are as follows, (a) Run 2: Gerrard, W.; Thrush, A. M. J. Chem. Soc. 1953, 2117.
45. (b) Run 3: ref 6.
46. Run 4: Isobe, T.; Saito, M. Jpn. Kokai Tokkyo Koho, JP 05 025155, 1993; Chem. Abstr. 1993, 119, 48943.
47. Run 4: Isobe, T.; Saito, M. Jpn. Kokai Tokkyo Koho, JP 05 025155, 1993; Chem. Abstr. 1993, 119, 48943.
48. Run 6: Mestres, R.; Palomo, C. Synthesis 1981, 218.
49. (e) Run 7: Miyoshi, M. Bull. Chem. Soc. Jpn. 1970, 43, 3321.
50. (f) Run 8: Patel, K. M.; Morrisett, J. D.; Sparrow, J. T. J. Lipid Res. 1979, 20, 674.
51. References to the products in Table 6 are as follows, (a) Runs 1 and 4: Isobe, T. Jpn. Kokai Tokkyo Koho, JP 07 285913, 1995; Chem. Abstr. 1996, 124, 201688.
52. References to the products in Table 6 are as follows, (a) Runs 1 and 4: Isobe, T. Jpn. Kokai Tokkyo Koho, JP 07 285913, 1995; Chem. Abstr. 1996, 124, 201688.
53. (b) Run 2: Goldblum, A.; Mechoulam, R. J. Chem. Soc., Perkin Trans. 1 1977, 1889.
54. Run 3: Anderson, R. J.; Grina, J.; Kuhnen, F.; Lee, S. F.; Luehr, G. W.; Schneider, H.; Seckinger, K. Ger. Offen. DE 3902818, 1989; Chem. Abstr. 1990, 112, 215765.
55. Run 3: Anderson, R. J.; Grina, J.; Kuhnen, F.; Lee, S. F.; Luehr, G. W.; Schneider, H.; Seckinger, K. Ger. Offen. DE 3902818, 1989; Chem. Abstr. 1990, 112, 215765.
56. Tabuchi, H.; Hamamoto, T.; Ichihara, A. Synlett 1993, 651.
57. Reference to the product in run 6 in Table 8 is as follows; Lucier, J. J.; Tuazon, E. C.; Bentley, F. F. Spectrochim. Acta, Part A 1968, 24, 771; Chem. Abstr. 1968, 69, 14319.
58. Reference to the product in run 6 in Table 8 is as follows; Lucier, J. J.; Tuazon, E. C.; Bentley, F. F. Spectrochim. Acta, Part A 1968, 24, 771; Chem. Abstr. 1968, 69, 14319.
59. Reference of the product in run 5 in Table 9 is as follows. Mueller, E.; Huber, H. Chem. Ber. 1963, 96, 670.
60. Reference to the products in runs 1 and 3 in Table 10 is as follows. Johnson, H. W., Jr.; Krutzsch, H. J. Org. Chem. 1967, 32, 1939.
61. References to the products in Table 12 are as follows, (a) Run 1: Huenig, S.; Lehman, H.; Grimmer, G. Leibigs Ann. Chem. 1953, 579, 77.
62. (b) Run 2: Fell, J. B.; Coppola, G. M. Synth. Commun. 1995, 25, 43.
63. Run 3: Petersen, H. J. Ger. Offen. DE 2557438, 1976; Chem. Abstr. 1976, 85, 142993.
64. Run 3: Petersen, H. J. Ger. Offen. DE 2557438, 1976; Chem. Abstr. 1976, 85, 142993.
65. Run 4: Anglada, J. M.; Campos, T.; Campos, F.; Moreto, J. M.; Pages, L. I. J. Heterocycl. Chem. 1996, 33, 1259.
66. 12 Thus, one can use a pre-prepared solution of 3 in dichloromethane in place of 3 itself as a more convenient method of handling this moisture-sensitive reagent.