Reaction of p-toluenesulfonyl Isocyanate with Polymers Having Amide Moieties and Hydrolysis of the Obtained Polymers

Transcription

1 Reaction of p-toluenesulfonyl Isocyanate with Polymers Having Amide Moieties and Hydrolysis of the Obtained Polymers TAKERU IWAMURA, 1 IKUYOSHI TOMITA, 2 MASATO SUZUKI, 3 TAKESHI ENDO 1, * 1 Research Laboratory of Resources Utilization, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama , Japan 2 Department of Electronic Chemistry, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama , Japan 3 Department of Organic and Polymeric Materials, Graduate School of Science and Engineering, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo , Japan Received 3 August 1999; accepted 3 July 2000 ABSTRACT: The chemical modification of polymers having amide moieties was carried out with p-toluenesulfonyl isocyanate. The resulting polymers revealed high hydrolytic character. For example, poly(acrylamide) was refluxed with an excess amount of p- toluenesulfonyl isocyanate in THF for 50 h to obtain a structurally modified polymer in 76% yield, whose sulfonylurea functionality was 100%. The resulting polymer was subjected to hydrolysis in a 1 M NaOH solution at 50 C to convert 90% of the sulfonylurea in the side chain to the carboxylic acid moieties John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: , 2000 Keywords: sulfonyl isocyanate; poly(acrylamide) derivatives; polymer reaction; hydrolysis; chemical modification INTRODUCTION Activated isocyanates such as acyl isocyanate and sulfonyl isocyanate are known to be much more reactive than common isocyanates toward nucleophiles. For example, sulfonyl isocyanates readily react with various nucleophiles such as amides under mild conditions without any catalysts, to afford the corresponding adducts. 1 3 Modification of monomers carrying active hydrogens with the activated isocyanates is expected to provide new * Present address: Department of Polymer Science and Engineering, Faculty of Engineering, Yamagata University, Jonan, Yonezawa, Yamagata , Japan Correspondence to: T. Endo ( tendo@poly.yz. yamagata-u.ac.jp) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 38, (2000) 2000 John Wiley & Sons, Inc. monomers and consequently new polymers having unique functions. Previously, we reported the chemical modification of vinyl monomers possessing active hydrogens using acyl or sulfonyl isocyanates. 4,5 For instance, N-acryloyl-N -p-toluenesulfonylurea was prepared by the reaction of acrylamide with p-toluenesulfonyl isocyanate and subjected to the radical polymerization to yield the polymer having sulfonylurea moieties. The resulting polymer was found to be hydrolyzed readily in a1mnaoh aqueous solution to afford poly(acrylic acid) in a good yield with releasing a sulfonylurea derivative. These results have brought the following idea to us: structural modification of polymers having amide moieties might also be attainable and hydrolysis of the resulting polymers might provide polymers bearing carboxylic acids. The two-step process would be of im- 3440

2 REACTION OF P-TOLUENESULFONYL ISOCYANATE WITH POLYMERS HAVING AMIDE MOIETIES 3441 portance in that they enable the hydrolysis of amide moieties under mild conditions. Herein, we describe the model studies on the synthesis and hydrolytic properties of acylsulfonylurea derivatives using low-molar-mass amides, which are advanced further to modification of polymers having amide moieties with p-toluenesulfonyl isocyanate and the subsequent hydrolysis of the obtained polymers as a new method of hydrolysis of amide functions on the polymers. EXPERIMENTAL Materials Acrylamide and methacrylamide were recrystallized from benzene. Methanol was distilled from magnesium methoxide under nitrogen atmosphere. Acetonitrile was dried over CaH 2, distilled, and stored under nitrogen. Other commercially available reagents were used without further purification. N-n-Butyl-propionamide 6 was prepared by the reaction of n-butylamine with propionyl chloride. Measurements IR spectra were measured on a JASCO FT/IR spectrometer. 1 H NMR and 13 C NMR spectra were recorded on a JEOL JNM-EX90 ( 1 H NMR: 90 MHz and 13 C NMR: 22.4 MHz) or a JEOL JNM-EX400 ( 1 H NMR: 400 MHz and 13 C NMR: 100 MHz) spectrometer. Products obtained by hydrolysis were purified by a Japan Analytical Industry recycling preparative HPLC system equipped with polystyrene gel columns (JAI- GEL-1H and JAIGEL-2H) using chloroform as eluent. Fast atom bombardment mass spectra (FAB/MS) were recorded by using a JEOL JMS- 700 spectrometer, whereby a mixture of a sample and m-nitrobenzyl alcohol on a standard FAB target was subjected to a beam of xenon atoms produced at 6 kev, 2 ma. Reaction of p-toluenesulfonyl Isocyanate with Amides The following acylsulfonylureas (1a 1c) were prepared by the reaction of p-toluenesulfonyl isocyanate with corresponding amides, which was referred to a literature procedure. 7 N-Propionyl-N -p-toluenesulfonylurea (1a) Yield 91%; mp 123 C; R f 0.73 (chloroform/ methanol 4/1 v/v); IR (KBr) 3420 (NH), 3250 (NH), 2982, 2942 (CH 3, OCH 2 O), 1746 (CAO), 1696 (CAO), 1370 (OSO 2 O), 1161 (OSO 2 O), 554 (NOCAO) cm 1 ; 1 H NMR (DMSO-d 6,90MHz) 1.00 (t, J 7.74 Hz, 3H, CH 3 CH 2 O), (m, 2H, CH 3 CH 2 O), 2.41 (s, 3H, CH 3 OC 6 H 4 O), 7.44 (d, J 8.64 Hz, 2H, OC 6 H 4 O), 7.89 (d, J 8.64 Hz, 2H, OC 6 H 4 O), (bs, 1H, OCON- HCOO), (bs, 1H, OCONHSO 2 O) ppm; 13 C NMR (DMSO-d 6, 22.4 MHz) , 29.06, , , , , , ppm; FAB/MS m/z 271 [M H]. N-n-Octanoyl-N -p-toluenesulfonylurea (1b) Yield 95%; mp 112 C; R f 0.50 (chloroform/ methanol 9/1 v/v); IR (KBr) 3439 (NH), 3248 (NH), 2959, 2926, 2857 (CH 3, OCH 2 O), 1746 (CAO), 1688 (CAO), 1370 (OSO 2 O), 1159 (OSO 2 O), 554 (NOCAO) cm 1 ; 1 H NMR (CDCl 3, 400 MHz) 0.89 (t, J 6.80 Hz, 3H, CH 3 CH 2 O), (m, 8H, OCH 2 O), (m, 2H, OCH 2 OCH 2 OCOO), 2.30 (t, J 7.20 Hz, 2H, OCH 2 OCOO), 2.43 (s, 3H, CH 3 OC 6 H 4 O), 7.31 (d, J 8.40 Hz, 2H, OC 6 H 4 O), 7.92 (d, J 8.40 Hz, 2H, OC 6 H 4 O), 9.14 (bs, 1H, OCONHCOO), (bs, 1H, OCONHSO 2 O) ppm; 13 C NMR (CDCl 3, 100 MHz) 14.06, 21.71, 22.59, 24.45, 28.93, 28.97, 31.62, 36.92, , , , , , ppm; FAB/MS m/z 341 [M H]. N-Propionyl-N-n-butyl-N -p-toluenesulfonylurea (1c) Yield 100%; R f 0.68 (chloroform/methanol 9/1 v/v); IR (neat) 3412 (NH), 2963, 2934, 2875 (CH 3, OCH 2 O), 1723 (CAO), 1672 (CAO), 1354 (OSO 2 O), 1169 (OSO 2 O), 548 (NOCAO) cm 1 ; 1 H NMR (CDCl 3, 400 MHz) (m, 3H, CH 3 CH 2 CH 2 O), (m, 3H, CH 3 CH 2 COO), (m, 2H, CH 3 CH 2 CH 2 CH 2 O), (m, 2H, CH 3 CH 2 CH 2 CH 2 O), (m, 3H, CH 3 CH 4 O), (m, 2H, ONOCH 2 O), (m, 2H, OCOOCH 2 O), (m, 2H, OC 6 H 4 O), (m, 2H, OC 6 H 4 O), (bs, 1H, OCONHSO 2 O) ppm; 13 C NMR (CDCl 3, 100 MHz) 8.64, 13.50, 19.91, 20.99, 29.40, 31.08, 44.21, , , , , , ppm; FAB/MS m/z 327 [M H]. Hydrolysis of p-toluenesulfonylurea Derivatives (1a 1c) A p-toluenesulfonylurea derivative (1a 1c) (2.0 mmol) was dissolved in a1mnaoh aqueous (or

3 3442 IWAMURA ET AL. methanol) solution (3 ml). After the reaction, the mixture was slightly acidified by the addition of a 1 M HCl aqueous solution. The resulting mixture was evaporated to dryness and chloroform was added to the residue. Insoluble inorganic salts were removed by filtration and the filtrate was evaporated to dryness. The residue was subjected to chromatography on a silica gel column with chloroform as eluent to isolate hydrolyzed products that were identified by 1 H NMR spectra, TLC analyses, and FAB/MS spectra by comparison against those of authentic samples. Authentic Samples p-toluenesulfonylurea p-toluenesulfonylurea was prepared by the reaction of the NH 3 gas with p-toluenesulfonyl isocyanate according to the literature procedure. 1 Yield 80% (2.36 g, 11.0 mmol), mp C, R f 0.38 (chloroform/methanol 9/1 v/v). IR (KBr) 3331 (NH), 3206 (NH), 1655 (CAO), 1375 (OSO 2 O), 1169 (OSO 2 O) cm 1. 1 H NMR (DMSO-d 6,90MHz) 2.39 (s, 3H, CH 3 C 6 H 4 O), 6.33 (bs, 2H, OCOONH 2 ), 7.40 (d, J 8.01 Hz, 2H, OC 6 H 4 O), 7.78 (d, J 8.01 Hz, 2H, OC 6 H 4 O), (bs, 1H, OCONHSO 2 O) ppm. 13 C NMR (DMSO-d 6, 22.4 MHz) 22.40, , , , , ppm; FAB/MS m/z 215 [M H]. p-toluenesulfonamide This compound is commercially available. mp C, R f 0.55 (chloroform/methanol 9/1 v/v), IR (KBr) 3329 (NH), 3243 (NH), 1327 (OSO 2 O), 1152 (OSO 2 O) cm 1. 1 H NMR (DMSO-d 6,90MHz) 2.38 (s, 3H, CH 3 C 6 H 4 O), 7.24 (bs, 2H, OSO 2 ONH 2 ), 7.35 (d, J 8.06 Hz, 2H, OC 6 H 4 O), 7.72 (d, J 8.06 Hz, 2H, OC 6 H 4 O) ppm. 13 C NMR (DMSO-d 6, 22.4 MHz) 20.82, , , , ppm; FAB/MS m/z 172 [M H]. N-n-Butyl-N -p-toluenesulfonylurea To a 50-mL round-bottomed flask containing a benzene (20 ml) solution of p-toluenesulfonyl isocyanate (1.33 g, 6.72 mmol) was added n-butylamine (1.0 ml, 18.5 mol) at 0 C under nitrogen. After stirring at room temperature for 1 h, the reaction mixture was washed with water, a 10% citric acid aqueous solution, and a saturated NaHCO 3 aqueous solution. The organic layer was dried over MgSO 4 and evaporated to dryness. The obtained white solid was recrystallized from a mixture of H 2 O and methanol. Yield 62% (1.12 g, 4.15 mmol), mp 109 C, R f 0.70 (chloroform/methanol 9/1 v/v). IR (KBr) 3339 (NH), 3171 (NH), 1661 (CAO), 1346 (OSO 2 O), 1165 (OSO 2 O)cm 1. 1 H NMR (CDCl 3, 90 MHz) 0.95 (t, J 6.48 Hz, 3H, CH 3 CH 2 O), (m, 4H, CH 3 CH 2 CH 2 CH 2 O), 2.49 (s, 3H, CH 3 C 6 H 4 O), 3.28 (dt, J 6.66 Hz, 2H, OCH 2 ONHCOO), 6.60 (t, J 6.66 Hz, 1H, OCH 2 ONHCOO), 7.36 (d, J 8.37 Hz, 2H, OC 6 H 4 O), 7.83 (d, J 8.37 Hz, 2H, OC 6 H 4 O), 8.75 (bs, 1H, OSO 2 ONHOCOO) ppm. 13 CNMR (CDCl 3, 22.4 MHz) 13.60, 19.77, 21.55, 31.50, 39.97, , , , , ppm; FAB/MS m/z 271 [M H]. Radical Polymerization of Acrylamide, Methacrylamide, and N-n-Butylacrylamide The monomer (acrylamide, methacrylamide, or N-n-butylacrylamide) (1.0 M), 2,2 -azobisisobutyronitrile (AIBN, 3 mol %), and 1-dodecanethiol (34, 10, or 32 mol %, respectively) were dissolved in methanol in a round-bottomed flask, which was then degassed in vacuo. After the reaction at 60 C for 5, 12, or 24 h, respectively, under nitrogen, the reaction mixture was poured into diethyl ether (in the case of acrylamide or methacrylamide) or water (in the case of N-n-butylacrylamide) and the precipitated polymer was dried in vacuo. Poly(acrylamide) (5a) Yield 45%; P n 5.22; IR (KBr) 3374 (NH), 3200 (NH), 2922, 2853 (CH 3 O, OCH 2 O), 1661 (CAO) cm 1. 1 H NMR (DMSO-d 6, 400 MHz) 0.86 (t, J 6.80 Hz, 3H 0.19, CH 3 OCH 2 O), (m, 20H 0.19, O(CH 2 ) 10 O), (m, 2H, OCH 2 OCHO), (m, 1H, OCH 2 OCHO), (m, 2H 0.19, OSOCH 2 O), (m, 2H, NH 2 ) ppm. 13 C NMR (DMSO-d 6, 100 MHz), 13.95, 22.11, 26.95, 28.25, 28.64, 28.71, 29.02, 29.09, 31.05, 31.05, 31.31, 35.62, , , ppm. Poly(methacrylamide) (5b) Yield 47%; P n 4.11; IR (KBr) 3418 (NH), 3214 (NH), 2924, 2855 (CH 3 O, OCH 2 O), 1663 (CAO) cm 1. 1 H NMR (DMSO-d 6, 400 MHz) 0.86 (t, J 6.80 Hz, 3H 0.24, CH 3 OCH 2 O), (m, 3H, OCH 2 OC(CH 3 )O), (m, 20H 0.24, O(CH 2 ) 10 O), (m, 2H,

4 REACTION OF P-TOLUENESULFONYL ISOCYANATE WITH POLYMERS HAVING AMIDE MOIETIES 3443 OCH 2 OC(CH 3 )O), (m, 2H 0.24, OSOCH 2 O), (m, 2H, NH 2 ) ppm. 13 C NMR (DMSO-d 6, 100 MHz) 13.95, 17.88, 18.43, 20.85, 22.11, 28.25, 28.71, 28.88, 29.02, 29.41, 31.31, 33.14, 35.22, 35.62, 41.31, 44.60, 44.86, 45.21, 45.50, 45.70, 45.88, 46.07, 46.40, , , , , , , , ppm. Poly(N-n-butylacrylamide) (5c) Yield 99%; P n 2.96; IR (KBr) 3436 (NH), 3293 (NH), 2957, 2924, 2853 (CH 3 O, OCH 2 O), 1645 (CAO) cm 1. 1 H NMR (DMSO-d 6, 400 MHz) (m, 3H 0.34, CH 3 O(CH 2 ) 11 SO, 3H, CH 3 O(CH 2 ) 3 ONO), (m, 20H 0.34, O(CH 2 ) 10 O, 4H, CH 3 O(CH 2 ) 2 OCH 2 ONO, and 2H, OCH 2 OCHO), (m, 1H, OCH 2 OCHO), (m, 2H 0.34, OSOCH 2 O), (m, 2H, CONHOCH 2 O), (m, 1H, NH) ppm. 13 C NMR (DMSOd 6, 100 MHz) 13.60, 13.88, 19.53, 19.64, 22.07, 24.41, 27.17, 28.22, 28.60, 28.69, 28.98, 31.00, 31.22, 31.27, 33.10, 33.70, 35.92, 38.11, 45.70, , , , , , , ppm. Reaction of p-toluenesulfonyl Isocyanate with Polymers Having Amide Moieties To a 50-mL round-bottomed flask containing a THF solution of polyacrylamide derivatives (5a: 4.24 mm, 5b: 18.4 mm, or 5c: 17.6 mm, respectively) was added a large excess of p-toluenesulfonyl isocyanate under nitrogen. The mixture was refluxed for 50 h (5a) or96h(5b, 5c). After the reaction, the mixture was treated with methanol and evaporated to dryness. The residue was dissolved in methanol and the resulting solution was poured into hexane-diethyl ether (1/1 v/v), methanol-water (1/4 v/v), or water, respectively. The precipitated polymer was filtered and dried in vacuo. Poly(N-acryloyl-N -p-toluenesulfonylurea) (6a) Yield 77%; IR (KBr) 3455 (NH), 3177 (NH), 2926, 2855 (CH 3, OCH 2 O), 1736 (CAO), 1699 (CAO), 1358 (OSO 2 O), 1159 (OSO 2 O), 548 (NOCAO) cm 1. 1 H NMR (CDCl 3 /TFA 4/1 v/v, 400 MHz) 0.88 (t, J 6.40 Hz, 3H 0.19, CH 3 OCH 2 O), (m, 20H 0.19, O(CH 2 ) 10 O), (m, 2H, OCH 2 OCHO), (m, 1H, OCH 2 OCHO), 2.45 (s, 3H, CH 3 OC 6 H 4 O), (m, 2H 0.19, OSOCH 2 O), (m, 2H, OC 6 H 4 O), (m, 2H, OC 6 H 4 O), (m, 1H, OCONHCOO) ppm C NMR (DMSO-d 6, 100 MHz) 13.92, 21.07, 22.05, 28.14, 28.55, 28.67, 28.97, 31.27, 32.81, 41.31, , , , , , , , , , ppm. Poly(N-methacryloyl-N -p-toluenesulfonylurea) (6b) Yield 58%; IR (KBr) 3449 (NH), 3246 (NH), 2926, 2855 (CH 3, OCH 2 O), 1720 (CAO), 1698 (CAO), 1358 (OSO 2 O), 1163 (OSO 2 O), 550 (NOCAO) cm 1. 1 H NMR (CDCl 3 /TFA 4/1 v/v, 400 MHz) (m, 3H 0.24, CH 3 OCH 2 O), (m, 3H, OCH 2 OC(CH 3 )O, 20H 0.24, O(CH 2 ) 10 O, 2H, OCH 2 OC(CH 3 )O, and 2H 0.24, OSOCH 2 O), 2.49 (s, 3H, CH 3 OC 6 H 4 O), (m, 2H, OC 6 H 4 O), (m, 2H, OC 6 H 4 O), (m, 1H, OCONHCOO) ppm. 813 C NMR (DMSO-d 6, 100 MHz) 13.88, 21.05, 22.05, 23.21, 28.03, 28.33, 28.51, 28.66, 28.70, 29.22, 31.25, 34.32, 36.30, 38.05, 41.23, 52.80, , , , , , , , , , , , , , , , , , , ppm. Scheme 1

5 3444 IWAMURA ET AL. Table I. Model Reactions of Low-Molar-Mass Amides with p-toluenesulfonyl Isocyanate Run R 1 R 2 Solvent Temperature Time (h) Product Yield (%) 1 Et H THF reflux 2 1a 91 2 CH 3 (CH 2 ) 6 H THF reflux 6 1b 95 3 Et n-bu Benzene RT a 36 1c 100 a RT, room temperature. Poly(N-acryloyl-N-n-butyl-N -ptoluenesulfonylurea) (6c) Yield 82%; IR (neat) 3322 (NH), 2957, 2927, 2855 (CH 3, OCH 2 O), 1752 (CAO), 1651 (CAO), 1352 (OSO 2 O), 1163 (OSO 2 O)cm 1. 1 H NMR (CDCl 3 / TFA 4/1 v/v, 400 MHz) (m, 3H 0.34, CH 3 O(CH 2 ) 11 SO,3H,CH 3 O(CH 2 ) 3 ONO), (m, 20H 0.34, O(CH 2 ) 10 O, 4H, CH 3 O(CH 2 ) 2 OCH 2 ONO, 2H,OCH 2 OCHO, 1H, OCH 2 OCHO), (m, 3H, CH 3 OC 6 H 4 O) (m, 2H 0.34, OSvCH 2 O), (m, 2H, CONOCH 2 O), (m, 2H, OC 6 H 4 O), (m, 2H, OC 6 H 4 O) ppm. 13 C NMR (CDCl 3, 100 MHz) 13.63, 14.07, 22.63, 28.11, 29.31, 29.60, 31.87, 39.46, 41.81, , , , , , , , , , , , , , , , ppm. Hydrolysis of 6a (or 6b) The polymer [6a (or 6b)] (100 mg) was dissolved ina1mnaohaqueous solution (10 ml) in a round-bottomed flask. After the reaction at room temperature for 48 h, at 50 C for 24 h, at 50 C for 52 h, or at 50 C for 52 h, respectively, the mixture was slightly acidified by a1mhclaque- ous solution and evaporated to dryness. DMF (2 ml) was added to the residue and the insoluble salt was filtrated off. The filtrate was poured into hexane-diethyl ether (6/4 v/v, ca. 100 ml) and the precipitated polymer [7a (or 7b)] was dried in vacuo. Polymer 7a Obtained from 6a at Room Temperature Yield 100%; IR (KBr) 3491 (OH), 3238 (NH), 2926, 2855 (CH 3, OOCH 2 O), 1719 (CAO), 1638 (CAO), 1163 (OSO 2 O)cm 1. 1 H NMR (DMSOd 6, 400 MHz) 0.88 (t, J 6.40 Hz, 3H 0.19, CH 3 OCH 2 O), (m, 20H 0.19, O(CH 2 ) 10 O), (m, 2H, OCH 2 OCHO), (m, 1H, OCH 2 OCHO), 2.45 (s, 3H 0.5, CH 3 OC 6 H 4 O), (m, 2H 0.19, OSOCH 2 O), (m, 2H 0.5, OC 6 H 4 O), (m, 2H 0.5, OC 6 H 4 O) ppm. Polymer 7a Obtained from 6a at 50 C Yield 94%; IR (KBr) 3449 (OH), 2928, 2855 (CH 3, OCH 2 O), 1718 (CAO), 1638 (CAO) cm 1. 1 H NMR (DMSO-d 6, 400 MHz) 0.86 (t, J 6.40 Hz, 3H 0.19, CH 3 OCH 2 O), (m, 20H 0.19, O(CH 2 ) 10 O), (m, 2H, OCH 2 OCHO), (m, 1H, OCH 2 OCHO), 2.45 (s, 3H 0.1, CH 3 OC 6 H 4 O), (m, 2H 0.19, OSOCH 2 O), (m, 2H 0.1, OC 6 H 4 O), (m, 2H 0.1, OC 6 H 4 O) ppm. 13 C NMR (DMSO-d 6, 100 MHz) 13.95, 20.88, 22.07, 27.52, 28.14, 28.69, 29.00, 31.27, 34.69, 41.66, 51.30, , , , , , , , , , , ppm. Polymer 7b Obtained from 6b at 50 C Yield 83%; IR (KBr) 3449 (NH, OH), 3246 (NH), 2998, 2928, 2855 (CH 3, OCH 2 O), 1701 (CAO), 1663 (CAO), 548 (NOCAO) cm 1. 1 H NMR (DMSO-d 6, 400 MHz) (m, 3H 0.24, CH 3 OCH 2 O, 3H, OCH 2 OC(CH 3 )O, 20H 0.24, O(CH 2 ) 10 O, and 2H, OCH 2 OC(CH 3 )O), (m, 2H 0.24, OSOCH 2 O), (m, 3H 0.18, CH 3 OC 6 H 4 O), (m, 2H 0.18, OC 6 H 4 O), (m, 2H 0.18, OC 6 H 4 O), (bs, 1H 0.82, OCOOH) ppm. 13 C NMR (DMSO-d 6, 100 MHz) 13.99, 16.42, Scheme 2

6 REACTION OF P-TOLUENESULFONYL ISOCYANATE WITH POLYMERS HAVING AMIDE MOIETIES 3445 Table II. Hydrolysis of 1 under Basic Conditions Hydrolytic Product (Yield %) Run Substrate R 1 R 2 Solvent Temperature Time (h) a Et H H 2 O RT a b 2 1b CH 3 (CH 2 ) 6 H MeOH reflux c Et n-bu MeOH RT b 4 1c Et n-bu MeOH reflux b a RT, room temperature. b Not determined , 17.85, 18.21, 20.28, 20.94, 22.11, 28.14, 28.71, 28.84, 29.02, 29.30, 31.31, 34.86, 44.20, 44.46, 54.09,125.66, , , , , , , , , , , , ppm. Hydrolysis of 6c at 50 C Polymer 6c (191.5 mg, mmol) was dissolved in a 1 M NaOH methanol solution (19 ml) in a 100-mL round-bottomed flask. After stirring at 50 Cfor72h, a1mhclaqueous solution (ca. 19 ml) was added and the mixture was evaporated to dryness. To the residue was added chloroform (50 ml) and the resulting suspension was filtered. The filtrate was evaporated to dryness. The resulting mixture was purified by recycling preparative HPLC (eluent: chloroform) to afford 82 mg of 7c (78%, mmol) and 28 mg of p- toluenesulfonamide (99%, mmol). Polymer 7c Obtained from 6c at 50 C IR (KBr) 3436 (NH), 3299 (NH), 2959, 2924, 2855 (CH 3 O, OCH 2 O), 1645 (CAO) cm 1. 1 HNMR (CDCl 3, 400 MHz) (m, 3H 0.34, CH 3 O(CH 2 ) 11 SO, 3H, CH 3 O(CH 2 ) 3 ONO), (m, 20H 0.34, O(CH 2 ) 10 O, 4H, CH 3 O(CH 2 ) 2 OCH 2 ONO, 2H, OCH 2 OCHO, and 1H, OCH 2 OCHO), (m, 3H 0.1, CH 3 OC 6 H 4 O), (m, 2H 0.34, OSOCH 2 O), (m, 2H, CONOCH 2 O), (m, 2H 0.1, OC 6 H 4 O), (m, 2H 0.1, OC 6 H 4 O), 9.13 (bs, 1H 0.9, ONH) ppm. 13 C NMR (CDCl 3, 100 MHz) 13.58, 13.93, 19.94, 21.44, 22.52, 26.54, 26.84, 27.26, 27.81, 28.37, 28.70, 28.83, 29.07, 29.18, 29.52, 29.98, 30.16, 31.34, 31.43, 31.76, 32.05, 32.58, 32.76, 33.27, 33.57, 34.06, 34.61, 34.96, 39.78, 51.56, , , , , , ppm. RESULTS AND DISCUSSION Model Reactions As reported by King, 7 the addition of p-toluenesulfonyl isocyanate to propionamide and octanamide took place readily to give crystalline products of N-acyl-N -p-toluenesulfonylureas (1a and 1b, respectively) in high yields (91 and 95%, respectively) (Scheme 1 and Table I, runs 1 and 2). Although the reaction of p-toluenesulfonyl isocyanate with N-alkylamides has been reported to give complicated products, 7 N-butylpropionamide was found to react with p-toluenesulfonyl isocyanate at ambient temperature to form 1c in a quantitative yield (run 3). Scheme 3

7 3446 IWAMURA ET AL. Table III. Reactions of p-toluenesulfonyl Isocyanate with Polymers Having Amide Moieties Run Amide R 1 R 2 P n Time (h) Adduct Yield (%) 1 5a H H a b Me H b c H n-bu c 96 The obtained N-acyl-N -p-toluenesulfonylureas (1a 1c) were subjected to hydrolysis under various conditions. When N-propionyl-N -p-toluenesulfonylurea (1a) was hydrolyzed in a 1 M NaOH aqueous solution at room temperature for 16 h, p-toluenesulfonylurea, which was identified by comparing its R f value and 1 H NMR spectrum with those of an authentic sample, 5 was isolated in 83% yield (Scheme 2 and Table II, run 1). In this case, however, propionic acid as another hydrolyzed component was not detected, probably because of its low boiling point. Instead, hydrolysis of N-n-octanoyl-N -p-toluenesulfonylurea (1b) in refluxing methanol solution of NaOH (1 M) gave octanoic acid in 80% yield (run 2), where p-toluenesulfonylurea and p-toluenesulfonamide also were obtained in 9 and 76% yields, respectively. The lower yield of p-toluenesulfonylurea and, alternatively, the higher yield of p-toluenesulfonamide are ascribable to the forced reaction conditions. In our previous work, 89% of p-toluenesulfonylurea was found to be hydrolyzed to p-toluenesulfonamide by using aqueous NaOH at 50 C for 24 h. 5 Therefore, p-toluenesulfonylurea initially formed by hydrolysis of 1b might be hydrolyzed to p-toluenesulfonamide under the examined conditions. The hydrolysis of N-propionyl- N-n-butyl-N -p-toluenesulfonylurea (1c) at room temperature for 168 h produced N-n-butyl-N -ptoluenesulfonylurea in 83% isolate yield, whose R f value and 1 H NMR spectrum were also consistent with those of an authentic sample (run 3). N-n-Butyl-N -p-toluenesulfonylurea was also produced in 84% yield by refluxing 1c for9hina1m NaOH methanol solution (run 4). As mentioned earlier, N-acyl-N -p-toluenesulfonylurea derivatives (1a 1c) were found to be readily hydrolyzed by the chemoselective nucleophilic attack to the amide-carbonyl group. This high hydrolytic character and selectivity might be originated from the intramolecular-hydrogen bonding between the NOH adjacent to the sulfonyl group and the oxygen of the amide-carbonyl group. As a result of the increase in character of the amide-carbonyl group, N-acyl-N -p-toluenesulfonylurea derivatives might be easily attacked by the hydroxide anion chemoselectively at this position (Scheme 3). From the above-noted results on the model studies, it is expected that polymer reactions starting from poly(acrylamide) and its derivatives proceed effectively and that the resulting polymers reveal high hydrolytic character. Reaction of p-toluenesulfonyl Isocyanate with Polymers Having Amide Moieties Although we tried to modify commercially available poly(acrylamide) with p-toluenesulfonyl isocyanate, the reaction did not proceed under the examined conditions because of its insolubility. Accordingly, we prepared the oligomers of acrylamide derivatives (5a 5c) by the radical polymerization of acrylamide, methacrylamide, and N- butylacrylamide using AIBN (3 mol %) as an initiator and 1-dodecanethiol as a chain-transfer agent. 9 Table III summarizes the results of the reaction of p-toluenesulfonyl isocyanate with 5a 5c (Scheme 4). When a THF solution of poly- (acrylamide) (5a, P n 5.22) with an excess of p-toluenesulfonyl isocyanate were refluxed for 50 h, poly(n-acryloyl-n -p-toluenesulfonylurea) (6a) was obtained in 76% yield. Figure 1 shows the 1 H NMR spectra of 5a and 6a, which indi- Scheme 4

8 REACTION OF P-TOLUENESULFONYL ISOCYANATE WITH POLYMERS HAVING AMIDE MOIETIES 3447 Figure 1. 1 H NMR spectra of 5a in DMSO-d 6 (a), 6a in CDCl 3 /CF 3 COOH (v/v 4/1) (b), and 7a in DMSO-d 6 (c). cated that the polymer reaction with p-toluenesulfonyl isocyanate proceeded quantitatively. In similar manner, the sulfonylurea moieties were quantitatively introduced into the side chains of 5b and 5c. Hydrolysis of Polymers Having Sulfonylurea Moieties Hydrolysis of 6a 6c was carried out with a1m NaOH solution under several conditions (Scheme 5 and Table IV). By hydrolysis of 6a at room temperature for 48 h, 7a was obtained quantitatively, which was composed of both the unreacted sulfonylurea unit (x unit, 50%) and the carboxylic unit (y unit, 50%) (run 1). When 6a was hydrolyzed at 50 C for 24 h, the remaining sulfonylurea moieties in 7a decreased to 10% (run 2). To obtain the polymer solely having the carboxylic acid unit, the hydrolysis was carried out for 52 h (run 3), which, however, brought about no significant change in the degree of hydrolysis. In the 1 H NMR spectrum of 6a (Fig. 1b), signals resulting from the aromatic and the methyl protons in the tosyl group are observed at (g, h) and 2.45 (i) ppm, respectively. These signals become very small in that of the polymer after the hydrolysis 7a (Fig. 1c, run 2). The formation of the carboxylic acid moieties could be supported by the absorption band at 1719 cm 1 in the IR spectrum of 7a (Fig. 2). In good accordance with our previous report on the production and the hydrolysis of the polymer analogous to 6a, 5 the hydrolyzed polymer revealed the almost identical IR spectrum. Generally, hydrolysis of poly(acrylamide) requires much higher temperature; for instance, a maximum degree of hydrolysis reached only to 63% by the treatment with a 0.5 M NaOH aque- Scheme 5

9 3448 IWAMURA ET AL. Table IV. Hydrolysis of Polymers Having Sulfonylurea Moieties by Using a 1 M NaOH Solution Run Substrate R 1 R 2 Solvent Temperature ( C) Time (h) Hydrolytic Product Yield (%) x/y/z ( 1 H NMR) 1 6a H H H 2 O RT a 48 7a /50/0 2 6a H H H 2 O a 84 10/90/0 3 6a H H H 2 O a 90 10/90/0 4 6b Me H H 2 O b 80 18/82/0 5 6c H n-bu MeOH c 78 10/0/90 a RT, room temperature. ous solution at 100 C. 10 Notably, the high hydrolytic character of N-acyl-N -p-toluenesulfonylurea is potentially applicable as an effective method to convert poly(acrylamide) to poly(carboxylic acid). Likewise, 6b was subjected to hydrolysis at 50 C for 52 h in a 1 M NaOH aqueous solution to afford 7b, which contained 82% of the carboxylic acid moieties (run 4). In the case of 6c, the hydrolysis at 50 C for 72 h in a1mnaoh methanol solution produced 7c and p-toluenesulfonamide, which were isolated by recycling preparative HPLC. In the 1 H NMR spectrum, 7c was found to have 90% of the amide moiety (the z unit) along with 10% of the unreacted urea moiety (the x unit) and no carboxylic acid moiety (the y unit). The results of the hydrolysis of 6a and 6b coincided with those of the model reactions in which the N-acyl-N -p-toluenesulfonylurea moiety was chemoselectively hydrolyzed to the carboxylic acid moieties, whereas 6c was found to undergo hydrolysis at the different position, that is, at the carbonyl group adjacent to the TsNH group. Steric hindrance and/or hydrophobicity of the butyl group and the polymer main chain might prevent the nucleophilic attack to the amide-carbonyl group. Figure 2. IR spectrum of 7a (KBr disk). In summary, the reaction of poly(acrylamide) derivatives 5a 5c with p-toluenesulfonyl isocyanate gave polymers 6a 6c with quantitative sulfonylurea functionality. Polymers 6a and 6b undertook hydrolysis with a 1 M NaOH solution to provide polymers containing 82 to 90% of the carboxylic acid moieties. Although the present study has dealt with hydrolysis of the oligomeric poly- (acrylamide) derivatives resulting from the low solubility of the high polymer in organic solvents such as THF, we believe that this method is potentially applicable to copolymers having amide moieties. By modification of the conditions for the reaction of polymers with the sulfonyl isocyanate, it might also be possible to obtain poly(n-acryloyl- N -p-toluenesulfonylurea) suitable for the hydrolysis step. In the synthetic point of view, p-toluenesulfonyl isocyanate might act as a useful reagent to promote base-catalyzed hydrolysis of primary amide groups under milder conditions via the urea intermediates. REFERENCES AND NOTES 1. (a) Billeter, O. C. Ber Dtsch Chem Ges 1904, 36, 690; (b) idem ibid. 1905, 37, (a) Logemann, W.; Artini, D.; Tosolini, G.; Piccini, F. Ber Dtsch Chem Ges 1957, 90, 2527; (b) idem ibid. 1958, 91, 951, Ulrich, H. Chem Rev 1965, 65, Kanamaru, M.; Takata, T.; Endo, T. J Polym Sci Part A: Polym Chem 1995, 33, Iwamura, T.; Tomita, I; Suzuki, M.; Endo, T. J Polym Sci Part A: Polym Chem 1998, 36, IR (neat) 3299 (NH) 2963, 2934, 2876 (CH 3, OCH 2 O), 1647 (CAO) cm 1. 1 H NMR (CDCl 3, 400 MHz) 0.92 (t, J 7.20 Hz, 3H, CH 3 CH 2 CH 2 CH 2 O), 1.15 (t, J 7.60 Hz, 3H, CH 3 CH 2 COO), 1.35 (tq, J 7.20 Hz, 2H, CH 3 CH 2 CH 2 CH 2 O), 1.48 (tt, J 7.20 Hz, 2H,

10 REACTION OF P-TOLUENESULFONYL ISOCYANATE WITH POLYMERS HAVING AMIDE MOIETIES 3449 CH 3 CH 2 CH 2 CH 2 O), 2.21 (dt, J 7.20 Hz, 2H, ONOCH 2 O), 3.24 (q, J 7.60 Hz, 2H, OCOOCH 2 O), 6.02 (bs, 1H, ONHO) ppm. 13 C NMR (CDCl 3, 100 MHz) 10.02, 13.79, 20.12, 29.74, 31.77, 39.25, ppm; FAB/MS m/z 130 [M H]. 7. King, C. J Org Chem 1960, 25, In the present system; the peak resulting from the NOH group adjacent to the sulfonyl group could not be separated from that of trifluoroacetic acid ( ppm). The same polymer obtained from N-acryloyl-N -p-toluenesulfonylurea showed the NOH peak at ppm (see Ref. 5). 9. (a) Cellard, B.; Pichot, C.; Revillon, A. Makromol Chem 1982, 183, 1935; (b) idem ibid. 1982, 183, 1949; (c) Pichot, C.; Pellicer, R.; Grossetete, P.; Guillot, J. ibid. 1984, 185, It is reported that 47% of the amide moieties in poly(acrylamide) (0.025 M) was hydrolyzed to the carboxylic acid moieties by the reaction at 50 C for 410 min in a 0.25 M NaOH aqueous solution. (See Higuchi, M.; Senju, R. Polym J 1972, 3, 370.) Under the same reaction conditions, hydrolysis of poly(nacryloyl-n -p-toluenesulfonylurea) prepared by the radical polymerization of the corresponding monomer (in Ref. 5) was found to proceed in 76%.