Cyclization microwave heating

A one-pot synthesis of thiohydantoins has been developed using microwave heating [72]. A small subset of p-substituted benzaldehydes, prepared in situ from p-bromobenzaldehyde by microwave-assisted Suzuki or Negishi reactions, was reacted in one pot by reductive amination followed by cyclization with a thioisocyanate catalyzed by polystyrene-bound dimethyl-aminopyridine (PS-DMAP) or triethylamine, all carried out under microwave irradiation, to give the thiohydantoin products in up to 68% isolated yield (Scheme 16). 

The cyclization of 1,2-dicarbonyl compounds with aldehydes in the presence of NH4OAC to give imidazoles was employed in a combinatorial study that compared conventional and microwave heating in the preparation of a library of sulfanyl-imidazoles (Scheme 15). The study employed an array of expandable reaction vessels that could accommodate a pressure build-up system for heating without loss of volatile solvents or reagents. A 24-membered library of imidazoles (48 and 49) was prepared in 16 min instead of the 12 h required using conventional heating [45]. 

The Jacobs-Gould intramolecular cyclization of diethyl N-(6-methyl-2-pyridyl)amino-methylenemalonate to 3-ethoxycarbonyl-7-methyl-l,8-naphthyrid-4-one is another reaction ideally suited to microwave heating, although conductively heated equipment was employed for laboratory-scale experiments [45]. The product is a key intermediate in the synthesis of nalidixic acid, the first of the quinolone antibacterials. The process usually is conducted at temperatures of 200-250 °C and in high dilution, with heat transfer oils such as the eutectic mixture of diphenyl ether and biphenyl. However, it proceeded rapidly, predictably and controllably under solvent-free conditions. 

Microwave heating was found to improve yields of this process <2004SC315>. A one-pot reaction was also reported where the cyclization was accompanied by introduction of a new cyclic amino substituent on the aromatic ring (Equation 32) <2005S1876>. A similar but metal-catalyzed cycloaddition of a 1,2-benzoquinone monoxime 300 with dimethyl acetylenedicarboxylate (DMAD) gives both 301 and 302 (Equation 33) <1995JCM454, 1995JRM2701>. 

A highly efficient one-pot, two-step microwave procedure has been developed for the synthesis of l-aryl-l/7-indazoles. Microwave heating of 2-halobenzaldehydes or 2-haloacetophenones with phenylhydrazines at 160°C for 10 min quantitatively yielded the arylhydrazones, which were further cyclized to give l-aryl-17/-indazoles via Cul/diamine-catalyzed... 

Abramovitch, R.A. and Bulman, A., Fischer cyclizations by microwave heating, Synlett, 1992, 795. 

The synthesis of the pyrazino[l,2-a]indole nucleus (64)/(65) was attained by intramolecular cyclization of several 2-carbonyl-1-propargylindoles (63) in the presence of ammonia. The reaction conditions were optimized using microwave heating and a... 

The cyclization procedure of imines 56 was developed by using microwave heating in such high boiling solvents as yV-methylpyrrolidin-2-one at 150 °C, or even an ecofriendly solvent-free process in the presence of graphite at the same temperature <2003SC3795>. Yields are moderate (45-52%). 

A library of 2-(arylamino)benzimidazoles was prepared in a microwave-accelerated cyclocondensation of PEG-supported orffto-phcnylenediamines 31 with isothiocyanates, followed by the product cleavage from polymer support [55,56]. The quantitative cyclization required either microwave heating (in an open vessel system) for 10 min or reflux in MeOH for 4 hours (Scheme 20). The use of a soluble PEG matrix substantially simplified the... 

Comment. Although a 20% solution of the nitrohydrazone in polyphosphoric acid could be cyclized by heating,71 (c) the use of polyphosphoric acid is not particularly desirable. The microwave-assisted process could be worthy of development if there was no other, more economical, way of accessing this specific indole derivative—for example, by nitration of the more readily prepared 1,2,3,4-tetrahydro-1 -oxo- (3 -carboline.71 (a)... 

A parallel synthesis method for the synthesis of a dihydropteridine library in five steps was recently published by Zhang. The synthetic route was based on the use of fluorous amino acids, which were prepared from A-Boc-amino acids. The final cyclization was promoted by the use of microwave heating. 

We will encounter more of these fantastic tandem cascade Pd-induced cyclizations in Chapter 3. Using microwave heating, Beccalli and co-workers performed an intramolecular Heck cyclization with pyrrole 211 leading to tricycle 212 in excellent yield [127]. 

Thermal cyclization of 350 produced furo[3,4-d]-pyrimidines 351. Prior treatment of 350 with a variety of primary amines, followed by high-temperature microwave heating led to pyrrolo[3,4-d]-pyrimidine 352. While 350 with hydrazine gave pyrimido[4,5-d]-pyridazines 353 (Scheme 133) (02MI6). 

Bischler-Napieralski cyclization of N -formyl and A/ -acetyltryptamine has been carried out with microwave heating the reactant and POCI3 adsorbed on silica [363]. 

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