Solvent-free domino reactions

in the field of organic chemistry, increasing attention is being given to Green Chemistry [19], using environmentally safe reagents and, in particular, solvent-free procedures. Reactions performed without the use of a solvent can indeed 

Entry Product 10-60 R1 R2 Milling time [h] (T [°C]) Yield [%] in solution solid state  

3-Thiazines, a heterocyclic system which is found, for example, in antibiotics of the cephalosporin type, were synthesized using a solvent-free domino procedure by Yadav and coworkers [24]. Hence, reaction of N-acylglycines 10-64, an aromatic 

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Tetrasubstituted pyrroles could be obtained by skeletal rearrangement of 1,3-oxazolidines, a reaction that is substantially accelerated by microwave irradiation. Dielectric heating of a 1,3-oxazolidine 7, absorbed on silica gel (1 g silica gel/mmol) for 5 min in a household MW oven (900 W power) cleanly afforded the 1,2,3,4-tetrasubstituted pyrrole 8 in 78% yield, thus reducing the reaction time from hours to minutes (Scheme 5) [24], 1,3-Oxazolidines are accessible in one-pot, two-step, solvent-free domino processes (see also Sect. 2.6). The first domino process, a multi-component reaction (MCR) between 2 equivalents of alkyl propiolate and 1 equivalent of aldehyde furnished enol ethers 9 (Scheme 5). Subsequent microwave-accelerated solvent-free reactions of enol ethers 9 with primary amines on silica support afforded intermediate 1,3-oxazolidines, which in situ rearranged to the tetrasubstituted pyrroles (2nd domino process). Performed in a one-pot format, these... 

A new synthetic route for functionalized polyhydroxyalkyl-pyrimidines starting from unprotected aldoses and based on montmorillonite K-10 catalysis and solvent-free microwave irradiation conditions, has been reported by Yadav et al,m Thus, reaction of D-glucose and D-xylose with semicarbazide or thiosemicarbazide (186) in the presence of montmorillonite K-10, under microwave irradiation, proceeded via domino cycloisomerization, dehydrazination, and dehydration of the intermediate semi- or thiosemicarbazones (187) to afford l,3-oxazin-2-ones or l,3-oxazine-2-thiones (188) in one single step and in yields between 79% and 85% (Scheme 34). Other mineral catalysts tested, such as silica gel and basic alumina, were far less effective for this transformation and only silica gel was active at all, giving low yields (15-28%) of compounds 188a-d. The l,3-oxazin-2-ones(thiones) thus synthesized were subsequently converted into the target pyrimidines by reaction with aromatic... 

Gerard, EMC, Sahin H, Encinas A, Erase S (2008) Systematic Study of a Solvent-Free Mechanochemically Induced Domino Oxa-Mic/jaeZ-Aldol Reaction in a Eall Mill. Synlett 2702... 

Domino [3+3] heterocyclization reactions have been established for the synthesis of anti-tetrahydropyrimidone derivatives 64 in 70-86% yields (Scheme 12.23) [44]. These reactions were conducted by reacting +aryhdene-2-phenyloxazol-5(4H)-ones 52 with aryl amidines 63 under solvent-free and microwave irradiation conditions within 17-28min. The selective constmction of the anti-tetrahydropyrimidinone skeleton with one amide function was readily achieved under TEA (triethylamine) catalyzed condition by ring-opening of the oxazoles in a one-pot operation. 

Tu and coworkers [56] synthesized new substituted 2,4-diaminopyridine-3,5-dicarbonitriles 92 under microwave irradiation and solvent-free conditions (Scheme 12.35). The multicomponent domino reaction of 2 mol of malononitrile... 

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