Reaction SMILES: CCCCNC([NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([CH2:18]O)=[CH:14][CH:13]=1)(=[O:11])=[O:10])=O.CCCCNC(NS(C1C=CC(C)=CC=1)(=O)=O)=O.[C:38]([C:41]1C=CC(S(N)(=O)=O)=CC=1)([OH:40])=[O:39].C(Cl)Cl>C(O)C>[C:38]([CH2:41][CH2:18][C:15]1[CH:14]=[CH:13][C:12]([S:9]([NH2:8])(=[O:10])=[O:11])=[CH:17][CH:16]=1)([OH:40])=[O:39]
Reactant: NS(=O)(=O)c1ccc(C(=O)O)cc1
Reactant: CCCCNC(=O)NS(=O)(=O)c1ccc(CO)cc1
Agent: CCCCNC(=O)NS(=O)(=O)c1ccc(C)cc1
Solvent: CCO
Solvent: ClCCl
Product: NS(=O)(=O)c1ccc(CCC(=O)O)cc1
Yield: 68 %

Procedure:
Hydroxytolbutamide, the product of the oxidation of tolbutamide, was prepared using a procedure revised from earlier (Knodell et al. J. Pharmacol. Exp. Ther. 241:1112-1119, 1987). 4-Carboxybenzenesulfonamide (20 g, 0.10 mol, Aldrich) was dissolved in 300 ml of absolute C2H5OH and the solution was purged with HCl gas. The solution was heated under reflux overnight and then concentrated to dryness in vacuo. The residue was dissolved in water and the solution was made alkaline by the addition of Na2CO3 ; the ethyl ester was extracted into CH2Cl2 (3 times) and the combined extracts were dried over Na2SO4, filtered through paper, and concentrated in vacuo. The product 4-carboxyethylbenzenesulfonamide (15.5 g, 68% yield) crystallized from CH2Cl2 : mp 97°-99° C., fast atom bombardment (+) mass spectrum (glycerol, (CH3)2SO) (relative abundance in parentheses) m/z 230 ([M+H]+, 100), 202 (M-28, 32), 184 (m-46, 84); elemental analysis--cald. for C9H11NO4S: C 47.16%, H 4.80%, N 6.11%; found: C 47.33%, H 5.04%, N 6.06%. A portion of the ethyl ester (12.0 g, 60 mmol) was dissolved in 100 ml of distilled tetrahydrofuran (from LiAlH4) containing NaH (4.8 g of a 60% dispersion in mineral oil, 120 mmol) at -10° C. and butyl isocyanate (6.0 g, 60 mmol) was added dropwise, with stirring, over 30 min. The reaction was allowed to come to room temperature and stirred for 2 h more, after which it was quenched by the addition of solid NH4Cl and then H2O. The solution was added to 200 ml of 0.5N NaOH, which was washed three times with CH2Cl2 (to remove residual butyl isocyanate) and then stirred at room temperature overnight to hydrolyze the ethyl ester. The pH of the solution was adjusted to <2 by the addition of 6N HCl and the resulting white precipitate was collected on a filter and washed with H2O. This product, carboxytolbutamide, was dissolved in absolute C2H5OH to yield 9.5 g of crystals (three crops, 53% yield): mp 216°-218° C., 1H NMR [(C2H3)2SO] δ 0.80 (t, 3H, CH3), 1.43 (m, 2H, --CH2CH3), 1.30 (m, 2H, --CH2CH2CH3), 2.93 (m, 2H, --NHCH2 --), 6.57 (bt, 1H, NHCH2 --) 8.01 (d, 2H, phenyl), 8.14 (d, 2H, phenyl). An aliquot of the carboxytolbutamide (2.0 g, 6.3 mmol) was stirred in 50 ml of distilled tetrahydrofuran under N2 at 0° C. and 50 ml of a 1M solution of BH3 in tetrahydrofuran (Aldrich) was added dropwise over 30 min. The solution was allowed to come to room temperature and stirred for 3 h more. Thin layer chromatography (silica gel G, Whatman LK6DF, CHCl3 --CH3OH--conc NH4OH/80-20-1/v-v-v) indicated that the reaction was essentially complete, as judged by the migration of UV-detectable material near tolbutamide (Rf 0.4). H2O (50 ml) was added slowly to the reaction and the pH was lowered to <2 with 6N HCl. The product, hydroxytolbutamide, was extracted into CH2Cl2 three times. The pooled extracts were dried with Na2SO4, filtered through paper, and concentrated in vacuo and the product was crystallized from C2H5OH/H2O (1.2 g from three crops, 67% yield): mp 104.5°-106° C. [lit 98.5°-100° C. (44) and 101°-102° C. (Knodell et al., 1987)]; UV (CH3OH) ε228 13.0 mM-1 cm-1 and ε267 2.85 mM-1 cm-1 ; fast atom bombardment (+) mass spectrum (glycerol/(CH3)2SO) m/z 287 ([M+H]+, 100); 1H NMR [(C2H3)2SO] δ 0.82 (t, 3H), --CH3), 1.18 (m, 2H, --CH2CH3), 1.30 (m, 2H, --CH2CH2CH3), 2.94 (m, 2H, --NHCH2 --), 4.59 (d, 2H, --CH2OH), 5.44 (t, 1H, --OH), 6.46 (t, 1H, NH--CH2 --), 7.51 (d, 2H, o-phenyl, o to CH2OH), 7.84 (d, 2H, m-phenyl, m to --CH2OH), 10.5 (sb, 1H, --SO2NH--); el. anal., cald. for C12H18N2O4S: C 50.35%, H 6.29%, N 9.79%, found: C 50.45%, H 6.36%, N 9.20%.