293 ROYCHOWDHURY et al: SYNTHESIS OF SULPHACETAMIDE SODIUM BY ULTRASONIC IRRADIATION Journal of Scientific & Industrial Research Vol. 69, April 2010, pp. 293-294 *Author for correspondence E-mail: research@eastindiapharma.org Synthesis of sulphacetamide sodium by ultrasonic irradiation Sunanda Roychowdhury, Sanat Kumar Mandal, Sukumar Ghosh and Soumitra Deb* Research & Development, East India Pharmaceutical Works Limited, Kolkata 700061, India Received 16 October 2009; revised 13 January 2010; accepted 18 January 2010 An efficient method for synthesis of sulphacetamide sodium by ultrasonic irradiation at room temperature is described. Quality of product prepared by this method has been found to be comparable with standard methods using refluxing conditions. Keywords: Sulphacetamide sodium, Ultrasonic irradiation Introduction Sulphacetamide sodium 1 (sodium salt of N 1 - acetylsulphanilamide) is a sulphonamide drug used as eye-drops and ointment for ophthalmic infections. Since its use in treatment of corneal ulcers 1 , it is still popular in ophthalmology, particularly for acute conjunctivitis and in prophylaxis of ocular infections after injuries or burns 2 . Several methods, developed for synthesis of this compound, make use of sulphanilamide with acetic anhydride under refluxing conditions 3 . These methods take longer reaction time and tedious work-up procedures. Ultrasonic assisted organic synthesis has attracted attention in recent years 4 , due to enhanced reaction rates, high yields, improved selectivity and ecofriendly reaction conditions. This study presents a mild, rapid and efficient procedure for synthesis of sulphacetamide sodium under ultrasonic irradiation (UI). Materials and Methods Melting points were determined in open capillary method and uncorrected. Progress of reaction was monitored by TLC using butanol-methanol-ammonia (10:5:3). Experiment under UI was carried out in ultrasonic cleaner model UC-55 (Analytical Instruments Consortium, Kolkata, India) having maximum power output of 120W and 30 KHz operating frequency. Synthesis of Sulphacetamide Sodium by Ultrasonic Irradiation (UI) A solution of 0.1 mol sulphanilamide 2 (17.2 g) was prepared in an aqueous sodium hydroxide (NaOH) solution (20% w/w, 14 ml) using UI at room temperature (RT) for 15 min. Then, an aqueous solution of NaOH (30%, 12 ml) and acetic anhydride (18 ml) were added, simultaneously, to reaction mixture under UI and irradiation continued for another 25 min. Finally, an aqueous NaOH solution (30%, 24 ml) was added and reaction mixture subjected to UI till reaction was complete as indicated by TLC (5 min). Contents of flask were poured over crushed ice and acidified with hydrochloric acid (HCl) till pH 8.0. Charcoal (1 g) was added and solution was cooled (15-20°C) and filtered. Filtrate was then acidified with HCl till pH 4.0. Solid thus obtained was filtered and washed with water. Residue was taken in water and NaOH solution added till pH 8.0. Sulphacetamide sodium 1, thus obtained, was filtered and filtrate evaporated to a point of crystallisation by gentle rapid boiling and cooling (yield, 12.7 g; 50%). m.p. 256-258°C (lit 5 . m.p.257°C); IR (KBr): 3472 (NH), 3381 (NH), 1685 (COCH 3 ), 1640 (NH 2 ), 1596, 1505, 1469 and 1417 (C=C, aromatic ring), 1322 (SO 2 ); UV-Vis (H 2 O): 258nm (logε 4.27). Results and Discussion UI of sulphanilamide 2 with acetic anhydride and NaOH solution gives N 1 -acetyl sodium sulphanilamide 3 as major product and two other minor products (N 4 - acetyl sodium sulphanilamide 4 and N 1 , N 4 -diacetyl disodium sulphanilamide 5) (determined by TLC). After acidification with HCl (pH 8.0), N 1 -acetyl sodium sulphanilamide 3 passed into solution while simultaneously formed N 4 -acetyl sulphanilamide and N 1 , N 4 -diacetyl sulphanilamide, from 4 and 5 respectively, remain undissolved. It was filtered and filtrate again