Science of Synthesis

Grimmett, M. R., Science of Synthesis, (2002) 12, 347.

Both amidines and guanidines (see Section ‌12.3.1.4.1.2‌) cyclize with α-functionalized ketones or aldehydes to form imidazoles with a variety of 1-, 2-, 4-, and 5-substituents. The 1- and 2-substituents are derived from the N—C—N synthon; the 4- and 5-substituents are introduced from the carbonyl reagent. So the versatility of this method depends on the presynthesis of a wide variety of α-hydroxy or α-halo ketones, and of amidines and guanidines.[‌1‌,‌2‌,‌5‌] There are standard methods available for the synthesis of a wide range of amidines.[‌94‌] 1,2-Dicarbonyl compounds are also capable of entering the reactions, but most references describe the use of hydroxy and bromo ketones. Methods of preparation of the C—C reagents have been discussed earlier (Section ‌12.3.1.1.1.2‌).

Meeeeeeeeeeee eeee eeeee eeee eeeeee α-eeeeeee[‌88‌] ee α-eeee eeeeeee[‌88‌] ee eeeeeee eeeeeeee ee eeeeeeee eee eeeeeeeeee. Me ee eeeeeeeee ee eeeeeeee eee eeeeeeeeeeeee eeee eee eeeeeeeeeeeee ee eeeeeeee ee eeeeeeeee eeeeee eeeeeeee. Meeeeeeee α-eeeeeee eeeeeee eeeeee eeee eeeeeeeee eeeeeeee ee 88–88% eeeeee, eee eeeeeeee eeeeeeeee eeee eeeeeeee (88–88%) ee eee eeeee eeeeeeee.[‌88‌] ‌Meeeee 88‌ eeeee eee eeeeeeeee eeeeeeee.

‌Meeeee 88‌ Meeeeeeee Meeeeeee eee Meeeeeeee eee Meeeeee Meeeeeeee eeee α-Meeeeee Meeeeee eee Meeeeeeeeeeee

Me eeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeee, eeee eeeeeeeeeeeee eee eeeeeeeeeeeee eeeee eeee eeeeeeee eee eeeeeeeee α-eeeeeee eeeeeee eeeeeeeeeee ee eeee eeeeeeeeee. Meeeeeeee eeeeee eeeee eee eee eeee ‌88‌ eeee eeeee eeeeeeeeee eee eeeeeee ee eeeeeeeeeee. Mee eeeeeeeeeee eeee eeeeeeee eeee eeeeeee eeee eeeeeeeeeeeee eeeeee eeee eeeeeeeeee eee ee e eeeeeeeeeee ee eeeeee eeeeeeeee ee eee eeeeeeee ee eee eeeeee eeeeeee eeeee eeee eee eeeeeee eeeeee eeee ee ‌88‌. M-Meeeeeeeeeeee eeeeeeee (eee eeeeeeeeee) eeeeee, ee eeeeee, eeee eeeee eeeeeeee eeeeeeeee eeeeeeee, eeeeeee eeeeeee ee eeeeeeeeeeeeee.

Mee eeeeeee eeeeeeee eee eeee eeee ee eeeeeee eeee eeeeeeeee eeeeeeee ee 8,8-eeeeeee-8M-eeeeeeeee eee e eeeeeee ee 8M-eeeeeeee-8(8M)-eeee eee eeeeeeee-8-eeeeee.[‌88‌] Meee eeeeeeee eee eee eeeeeeeee ee eeeeeeeeee ‌88‌ eee eeeee ee ‌Meeeee 88‌;[‌88‌] eeeeeeeeee eeee ee 8-eeeeeee-8,8-eeeeeeeeeeeee-8-eee, 8,8-ee(8-eeeee)-8-eeeeeeeeeeee-8-eee, 8-eeeeeee-8,8-eee(8-eeeeeeeeeeeee)eeeee-8-eee, eee 8,8-eee(8-eeeeeeeeeee)-8-eeeeeeeeeeee-8-eee eeee eeeeeeee. Mee eeee eeee eeeeeeee eee ee eeeeeeeee eeee eeeeeeeeee eeeeeeeeee eeeeee eeeeeeeee eee eeeee ee eeee eeeeeeee.

‌Meeeee 88‌ Meeeeeeeee eeee α-Meeeeee Meeeeee eee Meeeeeeeeeeee[‌88‌]

Meeeee eeeeeeee eeee eeeeeeee eee eeeeeeeeeee ee eee ee(eeeeeeeee) ‌88‌ eeee eee α,ω-eeeeeeeeeeeeeeeeeee ‌88‌ (‌Meeeee 88‌).[‌88‌] Meeee 8,8′-eeeeeeeeee(eeeeeeeeee) eee eeee eeeeeeee ee eee 8-eeeeee-eeeeeeeeeee eeeeeeeeeee, eeeee eee eeee ee eeeeee ee eeeee eeeeeeeeeeeeee ee eeeeee eee. Mee eeeeeeeeeee eeeeeee eeeeeeee eeeeeeee eeee eeeeee eeeeeeee/eeeeeeeeeeeee/eeeeeeeeeeeeeeeee eee ee eeeeeeee ee eeee eee 8,8-eeeeeeeeeeee eeeeeeeeeee ee 88–88% eeeeee.[‌88‌] Me eeeeeeee (eee eeee eeeeeee eeee eee eeeee eeeeee eeee eeeeeeee eee eeeeeee) eeeeeeeee ee 8-(eeeeeeeeeeeee)-8M-eeeeeeeee (‌88‌) eeee 8,8-eeeeeeeeeeeeeeee eee eeeeeeeeeeeee eeeeeee eee eeee eeeeeeee,[‌88‌] eee e eeeeeeeeeee ee eeeeeeeee M-eeeeeeeeeeeee ee 88% eeeee eeeeeee eee eeee eeeeeee eeeeeeee, eeeee eee eeeeeeeeeee ee eeeeeeeeeeeee eeeeeee ee eeeeee eeeeeee eeee eee eeeeeeeeeee α-eeeeee eeeeee.[‌88‌] Mee eeeeeeee eeee eeeeeeeeee ‌88‌ eeee eeeee eee 8-eeeeeeeeeeeee eeeeeeeee ‌88‌,[‌88‌] ee ee eee eeeeeeeeeeee eeeeeeeee eeeeeeeeeeeee.

‌Meeeee 88‌ Meeeeeeee ee Me(eeeeeeeeee), 8-(Meeeeeeeeeeee)-8M-eeeeeeeee, eee e (Meeeeeee-8-eeeeeeee)eeeeeeeeeee Meee[‌88‌,‌88‌,‌88‌]

Meeeeeeee, ee ee eeee eeeeee ee eee α-eeee eeeeeee ee eeeeeeeeeee eeeeeeeee eeee eeee eeeeeeee eee eeeeeeeeee,[‌88‌,‌88‌,‌88‌,‌888‌] eeee eeeeee eeeeeeeee eeeeeeeeee eeeeeeeeee eee eeeeee. Meee eeeeeeeeeeeee eeeeee eeee 8-eeeee-8M-8-eeeeeeeeee-8(8M)-eee eee eeeeee ee eeee eeeeeeeeee eee eeeeeeeeeee eee eeeeee; eee eeeeeeeeee eeeeeeeeeeee ee eeeee eeeeeeee (∼88%) eee eeeee eee eeeeeeeeee eeeee eeeeeeeeeeee ee eeeeeeeeee, eeeeee eeeeee ee eee eeeeeeeee eee eeeeeeee (∼88%).[‌88‌] Meee eeeeeeeeee eeeeeeee eee eeeee ee eee eeeeeeeee ee eeeeeeee ee eeee eeeeee ee 8,8-eeeeee-8-eeeeeeeeeeeeeeee ‌88‌ eeee eee eeeeeeeee ee eeeeeeeeeee eeeeeeeeeeeeee eeee e eeeeeeee eeeeeee (‌Meeeee 88‌),[‌888‌] eee ee eee eeeeeeeeeeeee eee 8,8′-eeeeeeeeee(eeeeeeeeee) eeeeeeee eeeeeeeee eeeee. Meeeeeeeeeeee eeeeee eeee α-eeeeeeee eeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeee ee eeee eeeeeeeee eeeeeeeeeee 8-eeeeee.[‌888‌] Me eeeeee eeeeeeeeeeee, eeeeeeee eeeeeeeee eeeeeeee eeee eeeeeeeeeeeee eeeeeeeeeeeee eee eeeee eeeeeeeeeeeee ee eee eeeeeeee ee eeeeeeee eeeeeeeee ee eeee 8-eeeeee-8M-eeeeeeee-8(8M)-eeee.[‌888‌]

‌Meeeee 88‌ 8,8-Meeeee-8-eeeeeeeeeeeeeeee eeee Meeeeeeeeee Meeeeeeeeeeeee eee e Meeeeeee Meeeeee[‌888‌]

Meeeeeee eeeeeee ee eeeeeeeeeeeee ee eeee(eeeeeeeee)eeeeeee [MM(MMMMM)8], eeeee eeee eeeeee eeee eeeeeeee ee eeee eeeeeeee eeeeeeeeeee, eee eeee eeee eeeeeeeee α-eeeeeee eeeeeee eeeeeeeee eeeeeeee eee eeeee. Mee eeeeeee, 8-eeeeeeeeeeee-8-eee eeeeee eeee ee ee eeee e eeeeeee ee 8,8-eeeeeeeeeeeeeee (88%) eee 8,8-eeeeeeee-8M-eeeeeeeee (88%).[‌88‌]

Meeeeeeeeeee Meeeeeeeee

8-(Meeeeeeeeeeee)-8M-eeeeeeeee Meeeeeeeeeeee (‌88‌•MMe):[‌88‌]

Meeeee MM8 (888 eM) eee eeeeeeeee ee e 888-eM eeeeeeeee eeeee eeee, eeeeeeeee eeee eeeeeeee eee eeeeee ee e eee eee/eMeMM eeee. Meeeeeeeeeeee eeeeeee (88.8 e, 8.8 eee) eee 8,8-eeeeeeeeeeeeeeee (88 e, 8.8 eee) eeee eeeee eeeeeeeeeeee, eee eee eeee eee eeeeee eee eeeeee ee 88°M eeee eeeeeeee eee 8 e. Mee eeeeeeee eeeeeee 88.8 eee. Mee eeee eee eeee eeeeee eee eeeeee, eee eee MM8 eee eeeeeeeeee ee ee eeeee e eeeeee ee M8. Mee eeeeeeeee eee-eeeee eee eee eeeeeeeee ee eMeMM (888 eM), eeeeee ee 8°M ee ee eee eeee, eee eeee eeee eeeeeeee eeeeeeee ee eee eeeeeee eeee eee MMe eee eeeee eee eeee eee eeeeee (eM ≤8). Mee eeeeeeeeee eeeeeeeeeee ee eeeeeeeee eeeee eee eeeeeeee eee eeeeee eeee eee eMeMM (888 eM), eee eeee Me8M (88 eM) eee eeeee eeee eeeeeeee ee eee eeeeeeee, eeeeeee e eeeee eeeee eeeeeeee ee eeeeeeee eee. Mee eeeeeeeeeee eeeeee eee eeeeeeee, eee eee eeeeeeeee eeeeee eeee eee eeeeeeeeeeee ee −8°M eee 88 e ee eeee e eeeeeeeeeee, eeeee eee eeeeeeeeeee, eeeee eee eeeeeeee, eee eeeee ee e eeeeee eeeeeeeeee ee eeee ‌88‌ ee eee eeeeeeeeeeeee; eeeee: 88.8 e (88%). Me eeeeeeeeeeeeeeeee (eMeMM/Me8M 88:88), ee eeee eeee-eeeeeeeeeee eeeeeeeee eeeeeee; ee 888.8–888°M. Me eee ee eeee eeeeeeeeee ee eeeeeee eee eeeeeee eee eeeeeeeeeee eeeeeeee eeee eee eeeeeeeeeeeeee M-eeeeee eeeeeeeeee,[‌888‌] ee eeeeee ee eee eeeeeee eee eeee eeee eeee: Meeeeeeeeee ee eee eeeeeeee eeee ee eeeeeee, eeeeeeeeee ee eee eeeeee eeeeeee eeee eee MeMM, eeeeeeeeee, eee eeeeeeeeeeeee ee eeeee, eee eeeeeeee ee eeeeeeeeeeeeee (eeeee eeeeee eee eeeeee, MeMM). Meeeeeeeeeeeeeeee (eeeeeee) eeee eee eeeeeee ee eee-eeeee eeeeeee; ee 88°M.[‌888‌]

Mα-(Meeeeeeeeeeeeeeee)-M-eeeeeeeeeeeee Meeeeeeeeee:[‌88‌]

M eeee ee (M)-M-eeeeee-8-(eeeeeeeeeeeeeeeeeeeeee)-8-eeeeee-8-eeeeeeeeeeeee (8.88 e, 8 eeee) eee eeeeeeeeeeeee eeeeeee (8.88 e, 8 eeee) ee eee MM8 (888 eM) eee eeeeeee ee eeeee ee e eeeee eeee (eee 88 e ee 88°M eee 88 eee). Meeee eeeeeee ee ee, eee MM8 eee eeeeeee ee eeeeeeeeeee, eee eee eeeeeeeee eeeeeee eee eeeeeeeee ee e eeeee eeeeee ee MMMe8/MeMM (88:8) eee eeeeeeee eeeee e Meeeeeeeeeee (8-ee eeeeee eeeeee eeee eeeeee eee MMMMM 88 MM888 eeeeeeeeee eeeeee, MMMe8/MeMM 88:8 ee ee eeeeeeeeee eeeeeeeeee). Mee eeeeeee eee eeeeeeee ee e eeeee eeeee; eeeee: 8.8 e (88%); ee 888–888°M. M-Meeeeeeeeeeee eee eeeeeeee eeee eeee eeeeeeeee eeeeeeeeee eeeee eeeeeeee eeeeeeeeee eeeeeee; eeeee: 8.8 e (88%); ee 888–888°M.

8-Meeeee-8,8-eeeeeeee-8M-eeeeeeeee (‌88‌, Me8 = Me); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee eeeeeeeeeeeee eeeeeeeeeeeee eeeeeeeee (88 e, 8.88 eee) ee M8M (888 eM) eee eeeee ee e eeee ee 8-eeeee-8-eeeeeeeeeeee-8-eee (88 e, 8.88 eee) ee MMMe8 (888 eM) ee eeee e eee-eeeee eeeeee. Meee eeeeeeee eeeeeeee ee ee, e eeee ee MMM (88 e, 8.8 eee) ee M8M (888 eM) eee eeeee eeeeeeee, eeee eeeeee ee eeeeee eee 8–8 e. Mee MMMe8 eeeee eee eeeeeeeee eeee eee eee M8M eeeee eee eeeeee. Mee eeeeeeeeeee eeeeeeee eeee eeeeeeeee eee eeeeee eeee eeeeeee eee eeee eeee Me8M ee eeee ee eee, eeeee eeeeee eeeeeeeeee ee eeeeeeee ee eeeeeee; eeeee: 88–88 e (88–88%); ee 888–888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8, 8888.
• 8.Meeeee-Meee, (8888) M 8, 888.
• 8.Meeeee-Meee, (8888) M 8e, 88.