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Please login or sign up for a free trial to access the full content. Method 1: Reactions of Amidines with α-Hydroxy- or α-Halocarbonyl Compounds

DOI: 10.1055/sos-SD-012-00398

Grimmett, M. R.Science of Synthesis, (200212347.

Both amidines and guanidines (see Section 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 NCN 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 CC reagents have been discussed earlier (Section

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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 8888% 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 (88MMe):[‌88‌]

Meeeee MM8 (888eM) eee eeeeeeeee ee e 888-eM eeeeeeeee eeeee eeee, eeeeeeeee eeee eeeeeeee eee eeeeee ee e eee eee/eMeMM eeee. Meeeeeeeeeeee eeeeeee (88.8e, 8.8eee) eee 8,8-eeeeeeeeeeeeeeee (88e, 8.8eee) eeee eeeee eeeeeeeeeeee, eee eee eeee eee eeeeee eee eeeeee ee 88°M eeee eeeeeeee eee 8e. Mee eeeeeeee eeeeeee 88.8eee. 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 (888eM), 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 (888eM), eee eeee Me8M (88eM) 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 88e ee eeee e eeeeeeeeeee, eeeee eee eeeeeeeeeee, eeeee eee eeeeeeee, eee eeeee ee e eeeeee eeeeeeeeee ee eeee 88 ee eee eeeeeeeeeeeee; eeeee: 88.8e (88%). Me eeeeeeeeeeeeeeeee (eMeMM/Me8M 88:88), ee eeee eeee-eeeeeeeeeee eeeeeeeee eeeeeee; ee 888.8888°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 (8.88e, 8eeee) eee eeeeeeeeeeeee eeeeeee (8.88e, 8eeee) ee eee MM8 (888eM) eee eeeeeee ee eeeee ee e eeeee eeee (eee 88e ee 88°M eee 88eee). 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: 8.8e (88%); ee 888888°M. M-Meeeeeeeeeeee eee eeeeeeee eeee eeee eeeeeeeee eeeeeeeeee eeeee eeeeeeee eeeeeeeeee eeeeeee; eeeee: 8.8e (88%); ee 888888°M.

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

M eeee ee eeeeeeeeeeeee eeeeeeeeeeeee eeeeeeeee (88e, 8.88eee) ee M8M (888eM) eee eeeee ee e eeee ee 8-eeeee-8-eeeeeeeeeeee-8-eee (88e, 8.88eee) ee MMMe8 (888eM) ee eeee e eee-eeeee eeeeee. Meee eeeeeeee eeeeeeee ee ee, e eeee ee MMM (88e, 8.8eee) ee M8M (888eM) eee eeeee eeeeeeee, eeee eeeeee ee eeeeee eee 88e. 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: 8888e (8888%); ee 888888°M.