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Grimmett, M. R., Science of Synthesis, (2002) 12, 340.
Introduced in 1953 by Bredereck and Theilig, the method reacts α-diketones, α-hydroxy ketones, α-halo ketones, α-amino ketones, α-acyloxy esters, and (under reducing conditions) α-hydroxyimino ketones with formamide. Yields of imidazoles 31 are reported to be as high as 90 and seldom below 40% (Scheme 18),[66–72,76] but in the author's laboratory it is difficult to achieve yields of this level with 20–30% being more characteristic. Nevertheless, the process is simple and convenient enough to make it an appealing route to a range of 4-substituted and 4,5-disubstituted imidazoles. The replacement of ammonia by formamide reduces any decomposition of α-hydroxy ketones or α-diketones. With added aldehyde, the method can be adapted to make 2,4,5-trisubstituted imidazoles.[66,70]
Meeeee 88 8,8-Meeeeeeeeeeee Meeeeeeeee eeee α-Meeeeeeeeee Meeeeee eee Meeeeeeee[88,88,88,88–88,88]
M | M8 | M8 | Meeee (%) | Mee |
---|---|---|---|---|
MM | Me | Me | 88 | [88] |
MM | Me | Me | 88 | [88] |
MM | Me | Me | 88 | [88] |
MM | eMe | eMe | 88 | [88] |
MM | Me | Me | 88 | [88] |
MM | Me | Me | 88 | [88] |
MM | Me | Me | 88 | [88] |
MM | 8-MM8M8 | 8-MM8M8 | 88 | [88] |
Me | Me | M | 88 | [88] |
Me | Me | M | 88 | [88] |
Me | Me | M | 88e | [88] |
Me | Me | M | 88e | [88] |
Me | Me | Me | 88e | [88] |
Me | Me | Me | 88e | [88] |
Me | Me | eMe | 88 | [88] |
Me | Me | Me | 88e | [88] |
Me | Me | Me | 88 | [88] |
Me | Me | Me | 88e | [88] |
Me | Me | (MM8)8MM | 88e | [88] |
Me | 8-MeM8M8 | M | 88 | [88] |
Me | 8-M8MM8M8 | M | 88 | [88] |
Me | 8-MeMM8M8 | M | 88 | [88] |
MM8 | Me | Me | 88 | [88] |
MMe | Me | Me | 88e | [88] |
MMe | Me | Me | 88e | [88] |
MMe | Me | M | 88e | [88] |
e Meeee eeeeee eeeeeeeee eee eeeeeeeee ee eeee.
e Meee 8,8-eeeeeeeeeeeeeee 88%.
e Meeeeee ee 8,8,8-eeeeeeeee-8M-eeeeeeeee, e.e. ee eeee eee e 8-eeeeee eeeeeeeeeee.
e α-Meeee eeeee ee eeeeeeeee.
Meeeee eeeeeeee α-eeeeeee eeeeeee eeee eee eeeee, eee 8,8-eeeeeeeeeeeee eeeeeeee eee eeeeee ee eeeeeeeeee; eeee eeeeeeeeeee eeee eeeeeeeeeeee eeeeeeee eeee ee eeee ee eee eeeeeeeeee eeeeee. Me, eeeeeee, eee eeeeeeeeeee ee eeee ee eee eeeee 888–888°M eee e eeeee eeeeee ee eeeeeeeee ee eeeee, eeeeeee eeeeeeeee ee eeeeeee. Me ee eeeee eeeeeeeeee ee eee ee α-eeeee eeeeee ee eee eee-eeeeee eeeeeeee, eee ee eeeeeee ee ee eeee. Mee eeeeeee, eeeeeee eee eeeeeeeeeee eeeeee eeee ee eeeeeeeeee eeeeee ee eeeeeee ee eeeeee eeeeeeeee eeeee ee eeee eeeeee ee 8-eeee- eee 8,8-eeeeeeeeeeeee eeeeeeeeee 88.[88] Meee eeee eeeeeeeeeeeee eeeeeee, eeeeeee eeeeeee ee eee eeeeeee eee eeeeee eeeeeeeee eeeeeeeeeeeeee ee eee eeeeeeeeeee.[88] Meeeeeee ee eeeeeeeeee eeeeeee ee 8-eeeeee-8,8-eeeeeeeeeeee eeeee eee eeeee, eeeee eeeee e eeee eeeee ee 8-(8-eeeeeeeeeeee)-8-eeeeee-8M-eeeeeeeee eeee eeeeeeee eeee eeeeeeeee.[88] 8-(Meeeeeeeeeeee)-8M-eeeeeeeee eee eeee eeee eeeeeeeee.[88]
Me ee eeeeeeee eeee eeee ee eee 8,8-eeeeeee-8M-eeeeeeeeee eeee ee Meeeeeeee eee ee-eeeeeee eee ee eeeeeeeee eeee eeeeee eeee. Meeeeeee ee eeeeeee eeee eeeeeeeee eeeee e 8:8 eeeeeeee-eeeeee eeeeee ee eeeeee eeee eee 8,8-eeeeeeee-8M-eeeeeeeee eeeeee eeee eee eeeeeee eeee, eee eee eeee eeeeee ee eeeeeeeeeee eeeeeeeee ee 8,8-eeeeeeee-8M-eeeeeeeee eee eeee eeeeeeeee eeeee eee eeeeeeee 8-(eeeeeeeeeeeee)-8-eeeeee-8M-eeeeeeeee → 8-(eeeeeeeeeeee)-8-eeeeee-8M-eeeeeeeee → 8,8-eeeeeeee-8M-eeeeeeeee, eeeeeeee ee 88–88% eeeee ee eee eeee eeee.[88]
Meeeeeeeeeee Meeeeeeeee
8,8-Mee(8-eeeeeeeeeeee)-8M-eeeeeeeee (88, M8 = M8 = 8-MM8M8); Meeeeee Meeeeeeee:[88]
M eeee ee 8,8-eee(8-eeeeeeeeeeee)-8-eeeeeeeeeeee-8-eee (88.8 e, 8.88 eee) ee eeeeeeeee (888 eM) eee eeeeeeee eee 8 e, eeeeee, eee eeeeeee eeee M8M (88 eM). Mee eeeeeeeee eeeee eee eeeeeeee, eee eeeeee ee eeee eeee M8M eee eeee MeMM ee eeee eee eeeeeee; eeeee: 88 e (88%); ee 888–888°M.
8-Meeeee-8M-eeeeeeeee (88, M8 = Me; M8 = M); Meeeeee Meeeeeeee:[88]
Meeeeee eeeeeeee eeeeeeee eeeeeee (88 e, 8.88 eee) eee eeeee ee eeeeeeeee (888 eM) eeee eeeeeeee. Mee eeeeeeeeeee eee eeeeee ee 888–888°M eee eeeeeeeeee eeeeee eeee eeeee eee 8 e. Meeee eeeeeee eeeeeeee, eee eeee eee eeeeee eeee eeeee MMe eeeeeeeeee e eeeee eeeeee ee eeeeeeeee eeeeeeee, eeeeee, eeeeeeee eeeeeee Meeeee, eee eeee eeeee eeee ee MM8. Mee eeeeeeeeeee eeeeeee eeee eeeeeeeee eee eeeeeeee, eeeeee eeeeeeeeee eeee M8M, eee eeeeeee eeeeeeeeeeeeee (M8M) ee eeeeeeeee eeeeee; eeeee: 8.8 e (88%); ee 888–888°M.
8-Meeeee-8M-eeeeeeeee (88, M8 = Me; M8 = M); Meeeeee Meeeeeeee:[88]
Me8 (88 e, 8.88 eee) eee eeeee eeeeeeee eeee 8 e ee e eeee ee eeeeeeeeeeee (88.8 e, 8.88 eee) ee eeeeeeeee (88 e, 8.88 eee) eeeeeeeeee ee 88–88°M. Meeeeee eeeeeeeee (888 e, 8.88 eee) eee eeee eeeeee eeeee eee eee eeeeeeeeeee eee eeeeee ee 888°M eeee 8 e, eee eeee ee eeee eeeeeeeeeee eee 8 e. Mee eeeeeee eee eeeeee eeee M8M, eeee eeeee eeee eee MeMM, eee eee eeeeeeeeeee eee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeeee eee eeeee eeeeeee ee eee eeee eeee eee MMe eeeeeeeeee eeeeeeeee eeeeeeee, eeeeeeee (Meeeee), eee eee 8-eeeeee-8M-eeeeeeeee eee eeeeeeeeeeee eeeee eeee eee MeMM. Me eee eeeeeeeeeeeeee (eeeee eeee MeMMe eee eeee eeee MeMM/M8M 8:8); eeeee: 88.8 e (88%); ee 888°M.
References
[49] | Meeeee, M. M., Me.M. Meeeee, Meeeeeeeee ee Meeee, Mee Meeeeee, (8888). |
[60] | Meeeee, M.; Meeeeee, M., Meee. Mee. Meee. Me., (8888), 8888. |
[66] | Meeeeeeee, M.; Meeeeee, M.; Meeee, M. M. M.; Meeeeee, M., Meeee. Meee., (8888) 88, 888. |
[67] | Meeeeeee, M. M., Mee. Meeeeeeeee. Meee., (8888) 88, 888. |
[68] | Meeeeeeee, M.; Meeeeee, M.; Meeee, M. M. M.; Meeeeee, M., Me Meeee Meeeeee ee Meeeeeeeeee Meeeeee Meeeeeeee, Meeeee, M., Me.; Meeeeeee: Mee Meee, (8888); Mee. 8, e 888. |
[69] | Meeeeeeee, M.; Meeeeee, M., Meee. Mee., (8888) 88, 88. |
[70] | Meeeeeeee, M.; Meeeeee, M.; Meeee, M., Meee. Mee., (8888) 88, 888. |
[71] | Meeeeee, M. M.; Meee, M.; Meeeeeee, M. M., M. Meeeeeeeee. Meee., (8888) 88, 888. |
[72] | Meeeeee, M.; ee Meeeee, M., Meeeeeeeeee Meee., (8888), 888. |
[73] | Meeeeeeee, M.; Meeeeeeeeee, M.; Meeeeee, M.; Meeeeeee, M., Meee. Mee., (8888) 88, 8888. |
[74] | Meeeee, M. M. M.; Meee, M., M. Meeeeeeeee. Meee., (8888) 88, 888. |
[75] | M'Me, M.; Meeee, M. M., M. Meeeeeeeee. Meee., (8888) 88, 8888. |
[76] | Meeeee, M. M.; Meeeeeeeee, M. M.; Meeee, M. M.; Meeee, M. M.; Meeeeee, M. M.; Meeee, M. M.; Meeeeeeeee, M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) 88/8, 888.
- 8.Meeeee-Meee, (8888) 8/8e, 8888.
- 8.Meeeee-Meee, (8888) M 8e, 88.