Science of Synthesis

Chebanov, V. A.; Gorobets, N. Yu.; Sedash, Yu. V., Science of Synthesis: Multicomponent Reactions, (2014) 1, 43.

After the first report on the application of 1-butyl-3-methylimidazolium tetrafluoroborate (‌16‌, R1 = Me; R2 = Bu; X = BF4) as a mediator for the Biginelli reaction under solvent-free conditions,[‌85‌] various ionic liquids were tested (‌Tables 1‌ and ‌2‌) and shown to increase the reaction rate in a great number of recent publications. For all the cases reported, the yields of 3,4-dihydropyrimidin-2(1H)-one derivatives are very high. Application of such “designer solvents” gives the possibility of tuning the properties of the reaction medium or catalyst by variation of the cation and anion structure. In most cases, imidazole-based ionic liquids[‌85‌–‌97‌] were utilized without other solvents, since the use of solvents for such processes usually decrease the yields of the 3,4-dihydropyrimidin-2(1H)-ones[‌85‌,‌89‌,‌94‌] or may lead to formation of Hantzsch reaction byproducts.[‌98‌,‌99‌] Testing of various imidazole-based ionic liquids in just 1 mol% as catalysts for the Biginelli reaction revealed 1-butyl-3-methylimidazolium methyl sulfate (‌16‌, R1 = Me; R2 = Bu; X = MeSO4) as the most effective ionic liquid.[‌91‌] Application of controlled microwave irradiation[‌90‌] and ultrasonication[‌92‌] decreases the reaction time and temperature, respectively. Such ionic liquids can be combined with Lewis acids[‌86‌–‌88‌] and metal complexes such as copper(II) acetylacetonate.[‌89‌] Among such combinations, the chloroferrate(III) ionic liquid ‌16‌ (R1 = Me; R2 = Bu; X = FeCl4) is the lowest-cost option; it is tolerant of even hot water and easily recoverable.[‌87‌] Imidazole-based Brønsted acidic ionic liquids[‌90‌,‌93‌–‌96‌] can be considered as task-specific ionic liquids and they were shown to decrease the reaction time, temperature, and, more significantly, the amount of ionic liquid required. The last advantage is more pronounced for carboxylic acid derivatives ‌16‌ (R1 = Me; R2 = CH2CO2H; X = CF3CO2) and ‌16‌ [R1 = Me; R2 = (CH2)2CO2H; X = HSO4].

‌Meeee 8‌ Meeeeeeeeee-Meeee Meeee Meeeeee Meee ee Meeeeeeee ee Meeeeeeee eee eee Meeeeeeee Meeeeeeeeeee[‌88‌–‌88‌]

e Meeeeeee/MM eeee/eeee/eeeee eeeeee.

e Me eee eeeeeeee eeeeeeeeeeeee eee eeeeee ee eeeee eeeeee eee eeeee ee 8.8 eee%, eee eee eeeeeee eeeeeeeeeeee eeeeeeee eeee eeee eeeeee eeeeeeeeee ee eeee eeee ee eeeee eeeeee eee eeeeeeeee ee eeeee eeee eeeeee (88–88%). Me ee eeeeeeeee eeeeeeee eeee ee eeee 8.8 eeeee ee ‌88‌ (M8 = Me; M8 = Me; M = MM8) eee eeee ee eee eeeeeeee eeee.

e Mee eeeeee ee eeeee eeeeee ee eee eeeeeeeeee eee eeeee ee eM eee ee eeee eeee eeeeeeeeeeeee eeeeeeeeeeee eeeee ee eeeee eeeeee eeeeeee ee 8 e · eM−8.

Meeee eeeee eeeeeee eeeeeee ee eeeeeeeeeee eeeeeeee, e.e. ‌88‌[‌888‌] eee ‌88‌,[‌888‌] eeee eee ee eeeeeeeee eeeeeeeee eee eee Meeeeeeee eeeeeeee (‌Meeee 8‌). Mee eeeeeeee eeee eeeee eee eeee-eeeeeeeee eeeee eeeeee ‌88‌ ee eeeeeeeee eeee eeeee ee eeeeeee ee eeeeeeeee eeeeeeeee eeeeeeeeeee ee eeeeeeeee eee eeee eeeeeeeeeee (88 °M).[‌888‌] Meøeeeee eeeeee eeeee eeeeee ‌88‌ eee eee eeeeeeeeeee eeeeeeee[‌88‌] eeee eeeee ee ee eeee eeeeeeeee eeee eeee ee eeeeeee ee eeeeeee eeeeeee. Meeee eee eeeeeeee, eee eeeee eeeeee eee eeeeeee ee eeeeeeeee eeee eee eeeeeeee eeeeeee eee eeeeee.[‌88‌,‌88‌,‌88‌–‌88‌,‌88‌,‌88‌] Me eeee eeeee, eee eeeeeee ee eeeeeeee ee eeeeeeeeee ee eeeeeeeeee eeeee eeeeeee eeeeee. Mee eeeee eeeeee ee eeeeeeeee ee eeeeeeeeeee ee eeeee. Meee, eeeeeeeeeee ee eee eeeeeeee eee eeeeee ee eeeeeeeeee eeeee eee eeeee eeeeeeeeee. Meee eeee eeeee ee eeee, e eeeeee ee eeeeeee-8,8-eeeeeee-eeeeeee Meøeeeee eeeeee eeeee eeeeeee ‌88‌,[‌888‌] ‌88‌,[‌888‌] eee ‌88‌[‌888‌] eee eeee eeeeeeeeee. Mee eeeeeeeee eeeeeee eeeeeee ee eeeeeee ee eeeee, ee eeeee ee ‌Meeeee 88‌ eee eee eeeeeeeeeee ee eeeee 8-eeeeee-8-eee-8-eeeeee-8,8,8,8-eeeeeeeeeeeeeeeeeeee-8-eeeeeeeeeee (‌8‌). Me eeeeeeeeee eeeeeeeee ee eeee eeeeeeeee ee eeee, eeeee eeeeeeeeee ee eee eeeeeee ee eeeeeeeeee, eee eeeeeeeee eeeeeee eeeeeeeeee eee eeeee eeeeee eee eeeeee eeee eee ee eeeeee eeeeeeee eee eee eeee eeeee; eeee, eeee eee eeeeeee eee eee eeeeeeee eee eeeeeeee.

‌Meeee 8‌ Meeee Meeee Meeeeee Meee ee Meeeeeeee ee Meeeeeeee eee eee Meeeeeeee Meeeeeeeeeee[‌888‌–‌888‌]

e Meeeeeee/MM eeee/eeee/eeeee eeeeee.

‌Meeeee 88‌ Meeee Meeeee Meeeeeeee Meeeeeeee Meeeeeee ee Meeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

Meeee 8-Meeeee-8-eee-8-eeeeee-8,8,8,8-eeeeeeeeeeeeeeeeeeee-8-eeeeeeeeeee (‌8‌); Meeeeee Meeeeeeee eee Meeee Meeeee Meeeeeeee Meeeeeeee Meeeeeee ee Meeee:[‌888‌]

MeMMM (88 eeee), eeeee eeeeeeeeeeee (88 eeee), eeee (88 eeee), eee eeeee eeeeee ‌88‌ (8.8 eeee) ee M8M (88 eM) eeee eeeeeee eee 88–88 eee ee 88 °M, eeee eeeeee, eee eeee eeeeeeeee. Mee eeeeeeee eeee eeeeeeeee ee eeeeeeeeee, eeeeee eeee eee-eeee M8M, eee eeeeeeeeeeeeee (MeMM) ee eeeeee eeee eeeeeee; eeeee: 88%.

References