Synthesis of naphthothiophene derivatives through polar Diels-Alder reactions employing 5-nitrobenzothiophene as electrophile . Microwave irradiation vs classical thermal conditions

Herein we report a simple, economical and efficient one-step procedure to synthesize the naphtho[2,1-b]thiophene ring system in good to excellent yield through the polar Diels-Alder reactions of 5-nitro-3-acetylbenzothiophene and dienes of different nucleophilicity. In thermal conditions the reactions were developed in molecular solvents; moreover the reaction system was exposed to microwave irradiation as a complement of reaction conditions.


Introduction
Naphthothiophene has been reported as a promising p-type semiconductor.The development of high-performance n-type semiconductors is highly desirable. 1n the other hand, in the hierarchy of carbon-carbon bond constructions, the Diels-Alder (DA) reaction has attained a preminent position.Its potential in heterocyclic chemistry synthesis is very well known.This process is in one step inter or intramolecular from aspects diene and dienophile bearin an almost unlimited number of variants. 2,3ecently we have reported a simple scheme to synthesize the dibenzothiophene ring system in good yield through the DA reaction of 2-and 3-nitrobenzothiophenes and different dienes. 4erein we report a simple, economical and efficient one-step procedure to synthesize the naphtho [2,1-b]thiophene ring system in good yield through the polar DA reactions of 5-nitrobenzothiophene and electron-rich (ER) dienes.A very strong EW group, such as nitro group, push the nucleophilic character of these heterocyclic compounds and owing to this substituent is easily extruded under thermal conditions make this reaction sequence a simple method of organic compound's families with heteroatom rings preparation.

Figure 1
When 5-nitro-3-acetylbenzothiophene 1a reacted with Danishefsky´s diene 2 in a sealed ampoule at 150 ºC and 120 ºC for 72 h using benzene as solvent the reaction proceeded to produce hidroxylated naphthothiophene 5 with acceptable yield and complete regioselectivity (Scheme 1, Table 1).These results indicate a properly substituted benzothiophene functions as a normal dienophile with an activated 1,3-butadiene.

Conclusions
The reactions between 5-nitro-3-acetylbenzothiopheno 1a and different dienes, developed in benzene as solvent to yield naphthothiophenes derivatives permit to conclude that a properly substituted benzothiophene functions as a normal dienophile with an activated 1,3-butadiene.With microwave irradiation and benzene as reaction media, 1a react with 2, 3 and 4, respectively, to yield the same products than before.Reaction of dienes 2 and 3 with 5nitrobenzothiophenes 1a under microwave irradiation in solvent-free condition give good yields of the aromatic naphthothiophenes through elimination of the nitro group and subsequent aromatization.The use of MW irradiation decreases the time of reaction for similar yields.5-The temperature, the length of the reaction, and the diene/dienophile ratio were dependent on the starting material and are indicated in Table 1.An ampule containing a solution of 1.0 mmol of the dienophile and the required amount of diene in 1 ml of dry benzene was cooled in liquid nitrogen, sealed (under nitrogen atmosphere), and then heated with stir in a bath.After the reaction time was completed, it was cooled once more in liquid nitrogen and opened.The solution was evaporated and the residue purified by column chromatography on silica gel or alumina using hexane/ethyl acetate mixtures as eluent.
6-Microwave irradiation was performed in a Anton Parr Monowave 300, microwave reactor in standard closed vessels.The temperature, the length of the reaction, and the diene/dienophile ratio were dependent on the starting material and are indicated in Table 2.After the reaction time was completed, the solution was evaporated and the residue purified by column chromatography on silica gel or alumina using hexane/ethyl acetate mixtures as eluent.

Table 1 .
Thermal reactions of nitrobenzothiophenes with dienes a Reaction time 72 h; reaction media: benzene anh.bBased on consumed nitrobenzothiophene.

Table 2 .
Diels-Alder reactions of nitrobenzothiophenes with different dienes employing microwave irradiation.
a Reaction time 60 min.b Based on consumed nitrobenzothiophene.