Patented Nov. 5, 1946 . ZiAlJiZ UNITED STATES PATENT OFFIQE 2,410,772 PREPARATION OF NEW SULPHONAMIDE DERIVATIVES Gordon 'Cecil Butler, Ottawa, Ontario, Ezra Lozinski, Westmount, Quebec, and Arthur Duston Odell, Su?ield, Alberta, Canada No Drawing. Original application January 12, I 1942, Serial No. 426,470. Divided and this ap- ’ plication April 7,1945, Serial No. 587,202. In Canada December 24, 1941 2 Claims. (or. 260-397.?) 1 . This invention relates to sulphonamide derivatives and has for its object the preparation of new therapeutically useful para-amino-benzene sul phonamide derivatives of substituted naphthols by reacting is preferably carried out in an atmosphere of para-acylaminobenzenesulphonyl benzenesulphonyl chlorides with the requisite amino-naphthalene derivatives followed by hy '- IITH-C—CH3 l. n + (‘>11 . —CH;—CH=OH2 a 0:‘ =0 , NH: 1 (II) (III) _ NH-o-cm on 1 The invention is further illustrated by the fol lowing examples of procedures which may be fol lowed in the preparation of N-(para-amino-ben —CH2—OH=CH1 1| zene-sulphonylyl) - 2 - a1ly1-4-amino-l-naphthol, and N-(para-amino-ber1zene-su1ph0nylyl) -l-hy 20 derstood, however, that the invention is not lim ited to the exact details given in these examples: , - n ‘(130,7 .7 The solution is cooled and the crystals are then ?ltered off and washed thoroughly on the ?lter with alcohol. By this procedure there results Example 1 50 grams of 2-a11y1-‘l-amino-1-naphtho1hydro chloride (Formula I) (prepared according to Fieser, Campbell and Fry, J. A. C. S. 61, 2213, ing the water. to boiling temperature. l 0=s=o droxy-_4-amino-2-naphthoic acid. It is to be un 1939) are dissolved in one litre of water by bring 2 nitrogen chlorides with the amino group of 4-amino-naph thols containing an organic substituent attached to the nucleus at position 2. This application is a division of parent appli cation Serial No. 426,470, ?led January 12, 1942. 10 The new compounds contemplated by this in vention are prepared by reacting para-acylamino drolysis of the acyl group. ' cedure, as represented by the following reaction, N ~(para - acetamino - benzene - sulphonylyl) - 2 allyl-‘l-amino-l-naphthol (Formula IV), which melts at 240° C. with decomposition. In order to achieve the hydrolysis of the acetyl 30 group of this compound (Formula IV), 60 grams of it are re?uxed for two hours with four litres of alcohol and 300 cc. of concentrated aqueous hydrochloric acid, as represented by the following 35 reaction: ‘u’ NH2.H G1 NH-C-C‘Ha OH (I) 60 grams of sodium acetate (3H2O) are then 40 added to the solution to precipitate free amine, the reactions involved being substantially as rep resented by the following equation: OH OH | I CHrCH=CH2 '‘ 45 2% (IV) -CH2—CH=CH1 -—-> + NaCl + CHa-COONa NHgHCl , + CHa-CO OH NHa '50 (II) on ' Q @GHPOH=CH2 3 addition of ‘700 cc. of lA-dioxane and 49 grams mula III) are then added during a ?ve minute 11TH: 0:8 _--—NH The amine (Formula II) is re-dissolved by the of p-acetamino-benzene-sulphonyl chloride (For _ 55 (V) When the alcohol is removed by distillation and the residue is crystallized from 50% aqueous al period With continual stirring. Stirring is con tinued for a further ?fteen minute period, during c'ohol there is obtained a product which, on fur which time a large amount of crystalline product ther recrystallization from 50% aqueous alcohol separates from the reaction mixture. This pro 60 yields N -(para - amino - benzene-sulphonylyl) -2 v. 4 3 allyl-4-amino-l-naphthol (V). This compound trated hydrochloric acid. After 2 hours re?ux ing, charcoal is added to the solution, boiling con melts with decomposition at 195° C. Example 2 _ tinued for 5 minutes and the solution is ?ltered ' . hot. The ?ltrate is reduced to about one-quarter of its original volume and chilled. The N -(para 10 grams of 1-hydroxy-4-aminoé2-naphthoic' acid (VI) is dissolved in 1 litre of water con taining 4.15 grams of sodium bicarbonate. After solution has been effected 6.7 grams of sodium acetate (31-120) are added followed by 500 cc. di oxane. amino-benzene-sulphonylyl)-1-hydroxy-4 - ami no-2-naphthoic acid hydrochloride (VIII) sepa rates as colourless needles which are ?ltered o? and washed with alcohol. After drying the crys tals do not melt but decompose slowly between 240 and 250° C. The free amine prepared from 11.5 grams p-acetamino benzene sul phonyl chloride (I11) are added in small portions to the above solution over 15 minutes with con the above hydrochloride (VIII), after crystallisa tion from alcohol, melts at 225° C. with decompo sition. tinuous stirring and warming to 50° C. Stirring is continued another 15 minutes to complete the reaction; the solution is. then cooled and made slightly acid by the addition of hydrochloric acid when the N-(para-acetamino-benzene-sulphon ylyl)-1-hydroxy-4-amino-2-naphthoic acid (VII) separates in the form of ?ne needles. This is ?l tered off and washed thoroughly on the ?lter, with 20 water and alcohol. Further puri?cation is achieved by digesting the crystals with hot alco hol, cooling, ?ltering and Washing with alcohol. After drying, the product melts at 240° C. with decomposition. We claim: 7 I 1. A process for the preparation of N-(para amino - benzene-sulphonylyl)-1-hydroxy-4-ami 30 no-2-naphthoic acid by the interaction of para- acetamino-benzene-sulphonyl chloride and l-hy droxy-4-amino-2-naphthoic acid followed by hy drolysis of the acylamino group in the resultant 35 (v1) ' ivii) For hydrolysis of the acetyl group 20 grams of the N- (para-acetamino-benzene-sulphonylyl) ~1 hydroxy-li-amino-2-naphthoic acid (VII) are re ?uxed with 2 litres alcohol and 100 cc. concen 40 product. ' 1 > 2. The new compound N-(para-amino-ben zene - sulphonylyl) -1-hydroxy-4-amino-2-naph thoic acid. . - GORDON CECIL BUTLER. EZRA LOZINSKI. ARTHUR DUSTON ODELL.