N-Tosyl-3-nitroindole reacts with moderate and strong nucleophilic dienes in a polar Diels-Alder reaction using protic ionic liquid (PIL) [HMIM][BF4] as reaction media. In the cases in which the diene has oxygenated substituents, the PIL favors the aromatization of the formal [4+2] cycloadducts. Although the presence of the PIL in the reactions of Ntosyl- 3-nitroindole as electrophile shows a clear tendency to the aromatization of the [4+2] cycloadducts, we observed that the neoteric solvent did not increase the yields in relation to a molecular solvent. Part of this work is specifically concerned with theoretical studies using DFT reactivity indices. The global and local electrophilicity and nucleophilicity indices were calculated for N-tosyl-3-nitroindole, and the dienes used in this study. For the studied reactions, the regioselectivity involved in the polar Diels-Alder reaction is well predicted.

The reactions between 1-nitronaphthalene 1 and two nucleophilic dienes, Danishefskýs diene 2 and 1-trimethylsilyloxy-1,3-butadiene 3, to yield phenanthrenols 7 and 8 developed in protic and aprotic ionic liquids (ILs) with an imidazolium cation base permit to conclude that the reactions occur in better experimental conditions than in molecular solvents. The yields obtained with protic ILs are better than those observed with aprotic ILs. In this sense, the higher yields obtained with aprotic ILs, (working at 60 °C, 48 h) are comparable with the lower yields observed in protic ILs (60 °C, 24 h). DFT calculations for the reaction of 1-nitronaphthalene 1 with diene 3, in the absence and in the presence of tetrafluoroborate of 1-metilimidazolium [HMIM][BF₄] as protic ILs, indicate that this reaction is a domino process that comprises two consecutive processes: i) a polar Diels–Alder (P-DA) reaction between 1 and 3, and ii) an elimination of nitroso acid 5 to yield dihydrophenanthrene 11. Thermodynamic calculations indicate that while the first reaction is the rate-determining step of this domino process, the nitroso acid elimination is the driving force responsible for the formation of dihydrophenanthrene 11. Implicit and explicit solvent effects indicate that while the hydrogen bond formation between HMIM and one oxygen atom of the nitro groups favour the two reactions, implicit solvent effects modelled by PCM decelerate the P-DA reaction by a large solvation of reagents. Finally, DFT analysis of reagents offers an explanation of the catalytic role of protic ILs in these P-DA reactions.

Background: The behavior of N-tosylnitroindoles acting as electrophilic dienophiles in polar Diels-Alder reactions joint to different dienes was analyzed. Reactions were developed under microwave irradiation using toluene or protic ionic liquids as solvents under solvent-free conditions. Good yields in short reaction times were observed. Solvent-free conditions and protic ionic liquids as solvents offered similar results. However, solvent-free conditions favor environmental sustainability. The processes between N-substituted nitroindoles and isoprene were selected for a theoretical study. Method: The reactions between the different electrophile-nucleophile pairs were developed under two conditions: (A) reactants and solvents (PILs) were heated in a closed ampoule under conventional thermal conditions, 60°C-48h, except for those developed in toluene that react at 180°-72h; (B) under the effect of MW irradiation in a MW apparatus at 180°C-0.5h. In both the cases, the solvents used were toluene and PILs. All calculations were carried out within the DFT framework using the Gaussian 09 suite of programs. For this purpose, the hybrid functional B3LYP was used together with the 6-31G(d) basis set. Results: Experiments were carried out with P-DA process using microwave irradiation instead of conventional heating. Cycloaddition reactions of nitro substituted indoles with different dienes were particularly analyzed using this methodology in the presence of PILs as solvent and under solvent-free conditions. Good yields were obtained in short reaction times. The yields observed in this thermal reaction are lower than those obtained under MW irradiation. This can be explained considering the type of heating produced by MW irradiation. Nitro indoles substituted in the heterocyclic ring and in the benzene moiety were used to compare the behaviors. In both cases, yields and reactivity were similar. A theoretical analysis was performed using Density Functional Theory, which explained the experimental data. Conclusion: The N-tosyl-nitroindoles explored in this work reacted as dienophilic electrophiles with dienes of different nucleophilicity. Reactions with different diene/dienophile pairs offered similar products under conventional heating or microwave irradiation. However, under the latter experimental condition, reaction times were significantly short with similar yields. Solvent-free conditions constitute a frequently used tool in microwave systems due to simpler manipulation, low cost, good product separation and for being environmentally friendly. Concerning the DFT study, the theoretically explored system shows that the TSs are unique and asynchronous. Theoretical calculations coincide with the experimental results. Under MW irradiation, in the presence of a PIL, the charge transfer is higher than solvent-free conditions.