Sulphapyridine

Note that p-acetamidobenzenesulphonyl chloride will similarly react with primary and secondary amines, and the products, after hydrolysis of the acetyl group, may furnish notable drugs e.g., the condensation products with 2-amino-pyridine and 2-aminothiazole, after remo al of the acetyl groups, provide the drugs commonly known as sulphapyridine (M B 693) and sulphathidzole respectively. 

The important drug sulphapyridine (or M. B. 693 or 2-sulphaniIyl-aminopyridine) may be readily synthesised from 2-aminopyridine and p-acet-amidobenzenesulplionyl chloride (Section IX,9) as follows ... 

Sulphapyridine. Dissolve 18-8 g. of 2-aminopyridine in 40 ml. of dry pyridine (Section 11,47,22) in a 250 ml. flask and add 48 0 g. of p-acetamidobenzenesulphonyl chloride (4) the temperature rises to about 70°. Cool, add excess of water, filter the precipitated 2-(p-acet-amidobenzonesulphonamido)p3Tidine (s acetyl-sulphapyridine) at the pump and recrystallise it from 50 per cent, acetic acid. The yield of pm product, m.py. 224°, is 46-5 g. 

Hydrolyse the acetyl-sulphap3Tidine by boiling it with 10 parts of 2N sodium hydroxide for 1 hour, and allow to cool. Precipitate the base by the addition of 50 per cent, acetic acid until the mixture is just acid to litmus (pH about 6 5) avoid a large excess of acid. Filter off the crude sulphapyridine, wash well with water, and dry at 90° to constant weight (about 12 hours any acetate formed will bo decomposed). The yield is 35 g. RecrystaUise from 90 per cent, acetone (5) the recovery of the pure compoimd, m.p. 190-191°, is about 80 per cent. 

An alternative method of purification, well adapted for large scale practice, is as follows. Dissolve the crude sulphapyridine in 1-05 mols of 30 per cent. u>/v sodium hydroxide, salt out the sodium derivative with excess of sodium chloride,... 

The components present in the mixture are as follows a/ sulfaguanidine, b/ sulfanilamide, c/ sulfadiazine, d/ sufathiazole, e/ sulphapyridine, it sulfamerazine, g/ sulfamethazine,... 

Cool and filter. Dissolve in the minimum volume of hot water, treat with about 0-5 per cent, by weight of decolourising carbon, filter, precipitate the base with 50 per cent, acetic acid imtil just acid to litmus (avoid an excess of acid), filter off the sulphapyridine at the pump, wash thoroughly with hot water, and dry to constant weight at 90° (about 12 horirs). Alternatively, the cold solution of the sodium salt may be just acidified with dilute hydrochloric acid with very vigorous stirring the presence of a local excess of acid must be avoided since sulphapyridine is hydrolysed by mineral acids to sulphanilic acid and 2-aminopyridine. 

Kanerud, L., Hafttrom, 1. and Ringertz, B. (1990). Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production role of cytosolic free calcium. Ann. Rheum. Dis. 49, 296-300. 

SOZ Serum-opsonized zymosan SP Sulphapyridine SR Systemic reaction sr Sarcoplasmic reticulum SRBC Sheep red blood cells SRS Slow-reacting substance SRS-A Slow-reacting substance of anaphylaxis STZ Streptozotocin Sub P Substance P... 

Titration with nitrous acid is used in pharmacopoeial assays of the following benzocaine, dapsone, primaquine, procainamide, procaine, sulphacetamide, sulphadoxine, sulphamethizole, sulphapyridine and sulphathiazole. 

Sulphapyridine, 1007, 1008 Sulphides, 496, 497, 498, 500, 1078 Sulphinic acids, 826, 1078 o-Sulphobenzoic acid, acid ammonium salt, 988... 

Sulphapyridine. Dissolve 4.7 g (0.05 mol) of 2-aminopyridine in a mixture of 40 ml of anhydrous acetone and 6 ml of dry pyridine (CAUTION) in a 250-ml flask, and add 11.7 g (0.05 mol) of pure p-acetamidobenzenesulphonyl chloride (4). The reaction mixture is set aside overnight and 5.5 g of the almost pure 2-( p-acetamidobenzenesulphonamido)pyridine (s acetylsulpha-pyridine) is filtered off by diluting the filtrate with water a further crop (4g) is obtained. The total product is recrystallised from acetone to give white needles of pure product, m.p. 224 °C. The yield is 8g (55%). 

The acetylsulphapyridine (7.3 g) is hydrolysed by heating it under reflux with 75 ml of ethanol containing 15 ml of concentrated hydrochloric add for 20 min. The cooled solution is diluted with water and made just alkaline with concentrated ammonia solution (d 0.880). The sulphapyridine is isolated by filtration and recrystallised from ethanol yield 4.9 g (75%), m.p. 190-191 °C. 

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