SYNTHESIS OF A MODIFIED 4-AMINOBENZOIC ACID DERIVATIVE UNDER ULTRASOUND CONDITIONS
Authors: Zhakina A.Kh. , Abdrakhmanova D.S. 
Published: April 2020

The search for new effective drugs with biologically active properties is one of the urgent problems. Recently, to intensify the process of their synthesis and increase the efficiency of chemical reactions, wave chemistry has been used. Increased interest of researchers is caused by the synthesis of compounds with biologically active properties using the method of ultrasonic treatment (US). It is known that derivatives of p-aminobenzoic acid and their esters are synthetic analogues of natural compounds, and pyrrolidone derivatives have high hypnotic, anticonvulsant, antiarrhythmic activity, which stimulates the synthesis of new biologically active compounds. In a brief report, the possibility of synthesizing ethyl-4-(2,5-dioxo-2,5-dihydro-1H-pyrrolyl) benzoate from 3-[(4-ethoxycarbonyl) phenylcarbamoyl]-2-propenoic acid using ultrasonic activation through a step is considered disclosure of the furan cycle with further cyclization. Ethyl ester p-aminobenzoic acid and maleic anhydride were used as starting reagents. An ultrasound device IL-100-6/2, equipped with a magnetostrictive transducer, with an operating frequency of 22 kHz, with a maximum power of 1200 W and a cylindrical waveguide, was used as a source of ultrasound. The synthesis of 3-[(4-ethoxycarbonyl) phenylcarbamoyl]-2-propenoic acid was carried out by reacting the starting reagents at equimolar ratios and room temperature. The US time was 10 minutes. The reaction proceeds smoothly. Ultrasound has a significant effect on the rate of chemical reactions and can increase the yield of the final product. Under classical conditions, the synthesis time was 180 minutes; using ultrasound, the synthesis time was reduced by 3 times. The product yield was 92%. The structure and composition of the obtained compound was confirmed by IR- and H1 NMR-spectroscopy. In the IR-spectra of the obtained compound, there are absorption bands of the amide group (NHCO) in the region of 3280, 3190 cm-1, absorption bands of the carbonyl group (C=O), characteristic in the region of 1670 cm-1, absorption band (COC) in the region of 1230 cm-1.
The resulting compound, 3-[(4-Ethoxycarbonyl) phenylcarbamoyl]-2-propenoic acid, made it possible to study the step of opening the furan ring, with further cyclization. Ethyl 4-(2,5-dioxo-2,5-dihydro-1H-pyrrolyl) benzoate was obtained in 89% yield by azeotropic distillation of water in the presence of toluenesulfonic acid in a DMFA-toluene mixture. The resulting product is a light yellow powder with melting point 114-115°C. The structure and composition of the obtained compound was confirmed by IR-and H1 NMR-spectroscopy. In the IR-spectra of the obtained compound, the stretching vibrations of the НС=СН group manifest themselves in the form of a low-intensity but characteristic signal at 3100-3090 cm-1, stretching vibrations of the С=О group as intense bands in the region of 1700-1680 cm-1 and a weak overtone at 3465-3450 cm-1, stretching vibrations of the COC group in the region of 1245 cm-1. When analyzing the Н1 NMR-spectrum of a compound, ethyl 4-(2,5-dioxo-2,5-dihydro-1Н-pyrrolyl) benzoate, the signals of aromatic four protons Н1- Н2 (4Нaryl, 3JНН 8 Hz) are recorded in the field of weak fields: H1 doublet at 7.51 ppm. and a doublet at 8.05 ppm. Signals of the ethyl fragment: (3H, CH3, 3JHH 8 Hz), appear as a singlet at 1.43 ppm. and (2H, CH2, 3JHH 8 Hz) quadruplet at 4.34 ppm. The protons of the CH group of the imide cycle (2H, CH=CH) appear as a singlet at 7.11 ppm.
Keywords: ultrasound, ethyl ether p-aminobenzoic acid, maleic anhydride, cyclization.