Nitrothiophenes as electrophiles in polar Diels-Alder reactions . Solvent effect and microwave irradiation

In this work the electrophilic behaviour of nitrothiophenes in polar Diels-Alder toward dienes of different nucleophilicity is studied. In thermal conditions the reactions were developed in molecular solvents and in protic ionic liquids trying to compare the solvent effects on this class of reactions. In the presence of these solvents the reaction system was exposed to microwave irradiation as a complement of reaction conditions.


Introduction
The Diels-Alder (DA) reaction is one of the most useful processes in preparative organic chemistry.Its potential in heterocyclic chemistry and natural products synthesis is very well known.It provides the chemist with one of his best tools for the preparation of cyclic compounds having a six-membered ring.The process is in one step inter or intramolecular from a diene and a dienophile bearing an almost unlimited number of variants.It is worth noting that these variants exist not only in the substitution of the reaction component but also in the electronic nature of these dienes and dienophiles.
Benzothiophenes are an important class of heterocycles used as starting materials for the synthesis of bioactive structures and are present in a variety of pharmaceuticals substances Consequently, a considerable effort has been devoted to the development of efficient methods for the construction of these ring system 1,2,3 .
In the 1980s, studies of aromatic heterocycles such as indoles, benzofurans, pyrroles, furans, and thiophenes part of DA reactions demonstrate the viability of these systems as dienophiles. 4 recently we have confirmed that aromatic nitroheterocyclic act as electrophiles in DA reactions. 5,6,7,8rein we report our findings electrophilic behaviour of nitrothiophenes when they were exposed to different dienes strongly, moderately and poorly activated, under thermal conditions, using molecular solvents and ionic liquids and in some experiences combining it with microwave irradiation.
In contrast to these results, the combination between microwave irradiation with ionic liquids (30 minutes, 180 ºC) in both cases afforded the same product 5 with better yield hetero DA product (Scheme 2, Table 1, entry 6 and 7).It is necessary taken into account that the normal temperature used in the experiences with MW is 170-180 ºC due to the irradiation of the reaction system need.Moreover, the influence of the microwave irradiation was analyzed in the presence of a molecular solvent (benzene) for the reaction of 2-nitrothiophene with isoprene.Again the reaction yielded the N-thiophenpyrrol 5 as the principal product.(Scheme 2, Table 1, entry 9).

Conclusion
In thermal conditions the reactions proceeded in a similar way that when nitrothiophenes are the electrophiles.
On the other hand it was noted that the presence of microwave irradiation in combination with any class of solvent (molecular solvent or protic ILs) improved the yield of the reactions.This reaction processes should be applicable for the preparation of many biologically interesting molecules.

Table 1
Reactions were carried out for 72 h, benzene as solvent.Reactions were carried out for 30 minutes and Microwave b d

Diels-Alder reactions of 1 with different dienes
Similar case was observed to make the experience with the same diene-dienophile system, solvent free and microwave irradiation, where product 5 is obtained in low yield.(Scheme 2,