Multistep synthesis of polyheterocyclic systems

The purpose of this section is to highlight the applications of microwave irradiation to multistep synthesis of polyheterocyclic systems with potent pharmaceutical value. When conventional thermal procedures (metal or oil bath) fail, and irrespective of the conditions needed in the homogeneous phase, microwave irradiation can be used as an alternative to classical methods enabling development of easy and rapid access to new heterocycles. 

Step Starting material Product Conventional heating Microwave irradiation 

Reaction time Yield (%) Reaction time Yield (%) 

Noticeable improvements were achieved for steps (i) and (iv) when the experimental conditions were realized under the action of microwave irradiation with the same concentration of starting material and volume of dimethylformamide. Product 35a (R = Me, X = H) was obtained in 91% yield after 5 min under the action of micro-wave irradiation at 150 W conventional heating in oil bath resulted in only 65% yield of 35a after 180 min (DMF, reflux). For step (iv), transposition of the conventional heating conditions for reaction of 38a (40% yield, 60 min, reflux) to micro-wave irradiation of solutions gave the desired compound 38a in better yield (60%) and reduced reaction time (5 min, 80 °C, 150 W). 

The authors showed that it was possible to perform this reaction in a multimode microwave oven [19] in a few minutes on a large scale in water containing a slight excess of potassium hydroxide but without cosolvent. Under the action of classical heating the major problem with these syntheses is the instability of the thiophene o-amino acids, which readily decarboxylate at room temperature to give aminothio-phenes which are themselves unstable [20 a] and have to be used as soon as they are prepared. With large quantities of reactants, moreover, the hydrolysis step is not easy to perform because of the low reactivity of thiophene carboxylates 39 and 42 [20 b]. 

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