Microwave-Assisted Synthesis of Acyclic Imides

Imides are an important class of compounds found in the structure of many biologically active and natural compounds. Imides are also important starting materials used in the synthesis of many heterocyclic compounds. Therefore, the synthesis of these compounds has attracted considerable attention and several innovative methods have been developed. Herein, the synthesis of acyclic imides has been reported from nitriles and carboxylic anhydrides in the presence of catalytic amounts of ptoluenesulfonic acid (PTSA) or H2SO4 under microwave irradiation. The reaction has proceeded in better yields with PTSA. When sulfuric acid was used, the product was obtained in lower yields since the degradation was increased. This new microwave-assisted method is compared with conventional heating, and the other methods, reported in the literature. The main advantages of this procedure are shorter reaction times, easier work-up, and good yields.

Since the first reports in 1986 (Gedey et al., 1986;Giguere et al., 1986) the use of the microwave heating technique has become an essential tool in all areas of organic synthesis. The microwave mediated organic reactions are environmentally friendly, safe, rapid, and high yield compared to conventional methods.
The synthesis of acyclic imides from the reaction of nitriles with acyclic anhydrides, in the presence of, silica sulfuric acid (Habibiet et al., 2007), tungtophosphoric acid under microwave irradiation (Mohammadpoor-Baltork et al., 2011) or p-toluenesulfuric acid by ultrasound-assisted (Nasresfahani et al., 2012) have been reported previously. Herein we report a microwave-assisted method for the synthesis of acyclic imides from nitriles and carboxylic anhydrides by using PTSA or H2SO4 as a catalyst ( Figure 1).

Materials
Melting points were determined in Electrothermal 9100 melting point apparatus and are uncorrected. Infrared spectra were recorded on Spectrum Two (Perkin Elmer, USA) FT-IR spectrometer in ATR and the wave numbers were given in cm -1 . NMR spectra were recorded using 400-MR NMR spectrometer (Agilent Technologies, USA). All of the microwave-assisted reactions was carried out with Discover System 908010 (Cem Corporation) All solvents and reagents were commercially available. Aluminum backed silica gel plates (Merck Kiesgel 60 F-254) were used for thin-layer chromatography (TLC).

Experimental Procedure
A mixture of nitrile (1mmol), carboxylic anhydride (2 mmol) and PTSA (30 mol %, 0.3 mmol) (or concantrared (98%, d=1.84 g/mL) H2SO4, 2 drops) was placed in a sealed tube and heated at 110°C in silicon bath or irradiated under microwave at 100°C (80°C for H2SO4). The reaction was monitored by TLC (ethyl acetate: hexan, 1:3). After the reaction was completed, the reaction mixture was cooled to room temperature. Chloroform was added to the reaction mixture and washed several times with water. The organic phase dried with Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography using ethyl acetate : hexane (1:3 or 1:1) eluent system or crystallized from hexane.
All products were characterized by the comparison of their melting or boiling points, IR, and 1 H NMR spectra with those of authentic samples.

RESULTS AND DISCUSSION
Acyclic imides were prepared by the reaction of aromatic and aliphatic nitriles with carboxylic anhydride in the precense of p-toluenesulphonic acid (PTSA) or H2SO4 under microwave irradiation in good to excellent yields. The reaction of benzonitrile and acetic anhydride was chosen as the model for optimization of the reaction condition. For this purpose, the reaction of benzonitrile (1 eqv.) and acetic anhydride (2 eqv.) was carried out with both H2SO4 and PTSA in different temperatures in solvent-free condition ( Table 1). The reaction was monitored by TLC. The reaction was completed within 5 min. As shown in Table 1, both sulfuric acid and PTSA catalyzed reaction proceeds in good to excellent yields. However, when H2SO4 was used, it was observed that the yield decreased due to increased degradation at high temperatures. Decomposition products have not been determined because the rate of degradation is very low. According to the results, the optimum temperature was determined as 80 °C for H2SO4 and 100 °C for PTSA.  In order to study the generality of this procedure, other aromatic and aliphatic nitriles were reacted with carboxylic anhydrides under optimized conditions (Table 2). Regarding aromatic nitriles, the substituents of benzonitriles did not affect the reactivity of the reaction electronically and sterically. In general, benzonitriles with both electron-donating and electron-withdrawing groups reacted well with acetic anhydride. When PTSA was used as the acid catalyst, imides have been obtained in much better yields in the same conditions. Compared to the method in the literature (Nasr-Esfahani et al.,2012), products were obtained in a shorter time than the ultrasonic-assisted reaction in similar yields.
The reaction was also carried out under conventional heating in the silicone bath, and the results were compared (Table 3). As shown in Table 3, the synthesis of imides under microwave irradiation is more effective than conventional heating. The transformations under conventional heating were completed within 1-2 hours in average yields, while under microwave irradiation were completed within 5 min in good yields.   The synthesized products were purified by colon chromatography or recrystallization and characterized by the comparison of melting points and FTIR and NMR data from the literature. In the FTIR spectra of imide compounds, the characteristic -NH vibration bands were observed in the range of 3070-3300 cm -1 , and the vibration bands of the two C=O bonds were observed in approximately 1650 and 1750 cm -1 . In the 1 H NMR spectra, the NH protons were observed as singlet in the range of 8.5-9.5 ppm as a broad signal. In the 13 C NMR spectra, the carbonyl carbons of imides were observed at about 170 and 175 ppm. Among the synthesized compounds, N-Acetyl-3,4-dimethoxybenzamide (4) is new, and 1 H and 13 C NMR spectra are given in Figure 1. Microwave-Assisted Synthesis of Acyclic Imides

CONCLUSION
As a result, an efficient and rapid synthesis of acyclic imides from the reaction of nitriles and carboxylic anhydrides presence of PTSA or H2SO4 as catalyst under microwave irradiation was reported. It was determined that PTSA is a more suitable catalyst than H2SO4 for this reaction. The products were obtained in a very short time in high yields compared with conventional heating and reported methods in the literature. This method will provide an easier way to synthesize of symmetrical or unsymmetrical acyclic imides from nitriles.