Microwave Irradiation : Polar Diels-Alder Reactions using Nitropyrrole and Nitroindole derivates as Electrophiles .

In this work we studied the influence of the microwave irradiation in polar DielsAlder reactions using nitropyrrole and nitroindole derivatives as electrophiles with dienes of different nucleophilicity. The cycloadditions was performed under two conditions with benzene as the reaction medium and solvent free. The results clearly confirm that the use of microwave irradiation in this type of reactions have advantages in relation to the carried out under classical heating. In general the products obtained are similar, but reaction times are lower and the yields increases.


Introduction
The microwave-assisted controlled heating has become a powerful tool in organic synthesis, being increasingly used to accelerate organic reactions, increase yields and even reach desired products in minutes and further suppressing the formation of byproducts. 1 The conventional synthesis is often difficult and time consuming, this way of heating of a reaction mixture is comparatively slow and energy inefficient, since first the heat energy is transferred from the heat source to the reaction vessel, and then the hot surface heats the content of the reaction vessel, due a this the application of microwaves in organic reactions has become popular over the past few years.In many instances microwave heating results in fast reactions, high yields and lower amount of side products.Microwave heating depends on the microwave power absorbing ability of the molecules present in the reaction mixture.Under microwave irradiation the reaction mixture undergoes dielectric heating, which occurring by two form: dipolar polarization and ionic conduction.In this way polar and ionic compound can absorb microwave energy very efficiently and are heated up fast. 2 The Diels-Alder (DA) reaction is one of the most useful tools in organic synthesis.Its potential in heterocyclic chemistry and natural product synthesis is very well known. 3Due to our interest in the chemistry of cycloaddition of aromatic heterocyclic compounds substituted with electron withdrawing groups, we have reported studies on the dienophilic character of aromatic systems such as naphthalenes, furans, pyrroles, thiophenes, selenophenes and indoles in their reactions with different dienes developed in benzene as the reaction medium and under conventional heating.5][6][7][8] Considering that microwave irradiation (MW) have been used to enhance organic reactions we have realized some experiences with some of these polar process using this methodology.Then, and taken into account the results obtained with the polar Diels-Alder (P-DA) reactions developed in normal thermal conditions, the principal aim of this work is to study the influence of microwave irradiation in the cycloaddition reactions of pyrroles and indoles nitro-substituted, exposed to dienes of different nucleophilicity in the presence of benzene as solvent and complementary in free-solvent conditions.

Figure 1
The treatment of the 1-tosyl-2-nitropyrrole 1a and less reactive isoprene 3 reacted under microwave heating following the optimal experimental conditions in the presence of benzene as solvent and in free-solvent conditions, in both cases was obtained the mixture of indoles 5a and 5b (Table 1, entries 1 and 2).Similarly the reaction between 1b and 3 showed the mixture of isomeric cycloadducts 5a and 5b (Table 1, entries 3 and 4).The reactions carried out in benzene showed lower yield and longer reaction time that the free solvent conditions.
When the 1a y 1b reacted with 4 under the same conditions, afforded the indole 5c (Table 1, entries 5-8), the best results were obtained with free-solvent experience showing high yields.
The reaction in the presence of benzene offered moderate yields.[8] Table 1.P-DA reactions of 1a and 1b with 3 and 4, under microwave irradiation.
a Reaction temperature: 180ºC b Based on consumed dienophile.
In turn, the reaction of 2a with the dienes 3 and 4 using microwave irradiation produce the respective isomeric mixture of carbazoles 6a and 6b for the experience with isoprene and the product 6c was observed when the diene was 1-trimethylsilyloxy-1,3-butadiene.All the products are the result of the nitro group elimination and subsequent aromatization (Table 2, entries 1-4).The reactions of 1-tosyl-3-nitroindole with each diene proceeded similarly to

Conclusions
The use of microwave irradiation in this type of P-DA reactions present advantages in relation with those developed in classic conditions although in general the products obtained are similar.
In this direction is possible to observe lower reaction times and better yields.In the process developed with nitrated nitropyrroles and nitroindoles it was observed that in all cases the nitro group is responsible to orientation and the selectivity observed and the processes showed nitro extrusion as nitrous acid.It is important to note that microwave irradiation in solvent-free conditions yielded the best results.The importance of this type of experience is related to the reduction of the toxicity and cost, and moreover is a too simple methodology.

Table 2 .
P-DA reactions of 2a and 2b with 3 and 4, under microwave irradiation bBased on consumed dienophile