Ind. Eng. Chem. Res. 2005, 44, 7045-7048
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APPLIED CHEMISTRY Improved Preparation of Macroporous, Chlorosulfonated Poly(styrene-co-divinylbenzene) and Conversion to Sulfonamides and Sulfonylhydrazines David W. Emerson* and Sylvester O. Ifalade Department of Chemistry, The University of Nevada, Las Vegas, P. O. Box 454003, Las Vegas, Nevada 89154-4003
Sulfochlorinated, macroporous poly(styrene-co-divinylbenzene), 1, is a useful intermediate for synthesis of polymers with functional groups such as primary and secondary sulfonamides, sulfonylhydrazine, sulfinic acid, and thiol, all of which can be prepared by reaction of 1 with aqueous reagents. An improved method for preparing 1 consists of using dried, commercially available sulfonic acid cation exchange resins in the hydrogen ion or sodium ion form to react with PCl5 in a suspending medium of POCl3, separating the resin by filtration, and washing the resin with ice-water. The byproducts are POCl3, partially recoverable by atmospheric pressure distillation, small amounts of HCl or NaCl, and H3PO4. No organic solvents are required. Prompt conversion of 1 to the desired final product minimizes hydrolysis of 1. Introduction
Scheme 1. Reactions
Macroporous, chlorosulfonated poly(styrene-co-divinylbenzene), Ps∼SO2Cl, 1, is a useful intermediate for the preparation of various polymer-supported reagents such as sulfonamides,1-3 sulfonylhydrazines,4,5 sulfinic acids,6 and ring-thiolated polystyrene.7-10 Existing methods for preparing 1 include direct chlorosulfonation11 or, often more conveniently, conversion of commercial sulfonic acid ion exchange resins to 1. Preparation methods include use of excess chlorosulfonic acid, which reacts violently with water,1,4 conversion of sulfonic acid groups by use of phosphorus pentachloride in phosphorus oxychloride followed by washing with carbon tetrachloride3 (Scheme 1, reaction 1), and conversion of the sulfonic acid group to the pyridinium salt in ethyl acetate followed by reaction with thionyl chloride.12 These methods entail serious problems for disposing of reaction byproducts and the solvents used to clean up the resins. The methods described below minimize the production of noxious byproducts and do not entail the use of chlorinated or other organic solvents. Materials and Methods Temperatures are uncorrected. Phosphorus oxychloride, 99% [CAS Registry No. 10025-87-3], phosphorus pentachloride, 95% [10026-13-8], Amberlyst-15 [3938920-3], methylamine, 40% [74-89-5], and 1,5-diaminopentane, 95% [462-94-2], were obtained from Aldrich and used without further purification. Ethylenediamine [107-15-3], obtained from an unknown source, was distilled before use. Monosphere Dowex 88 in the sodium ion form [69011-22-9] was obtained from Su* To whom correspondence should be addressed: Tel.: (702) 895-4071. E-mail:
[email protected].
pelco. Cesium carbonate, 99.9% [534-17-8], was obtained from Research Organic/Inorganic Chemical Corp. Hydrazine hydrate, 99% [7803-57-8], was obtained from Alfa Aesar. Amberlyst-15 and Dowex-88 are registered trademarks of the Rohm & Haas and Dow Chemical Companies, respectively. Caution: Both POCl3 and PCl5 react violently and exothermically with water. POCl3 is highly toxic, volatile, and corrosive. PCl5 is corrosive. Skin contact and breathing the fumes of both must be avoided. Characterization of the Resins. Sulfonic acid groups were determined by a strong acid total exchange capacity measurement by displacement of H+ by Na+ followed by titration.13 Small samples were analyzed by converting strong acid groups to the cesium salt with cesium carbonate, drying the resin in a vacuum oven, and calculating the concentration of acid groups from the weight gain of 132 mg/g dry resin resulting from replacement of 1 mmol of H+ by 1 mmol of Cs+. Determination of primary and secondary sulfonamide functional groups was accomplished by chlorinating the resin with household bleach containing 5% glacial acetic
10.1021/ie050371u CCC: $30.25 © 2005 American Chemical Society Published on Web 08/09/2005
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Ind. Eng. Chem. Res., Vol. 44, No. 18, 2005
acid (Scheme 1, reaction 5), rinsing the resin with water, and measuring the volume of N2 produced at standard temperature and pressure (STP) when the fully Nchlorinated resin is treated in a simple gasometer with hydrazine hydrate1 (Scheme 1, reaction 6 or 7). Determination of sulfonylhydrazine functionality was determined by determining the volume of N2 produced when the resin is treated with bleach in the gasometer4 (Scheme 1, reaction 8). The gasometer is easily assembled using a 50 mL buret, a 25 mm × 200 mm sidearm test tube with a glass tube mounted in a stopper and extending to the bottom of the test tube, a suction flask, latex or plastic tubing for connecting the parts, and a syringe with needle to inject the hydrazine hydrate solution (for chlorinated sulfonamides) or household bleach (for sulfonylhydrazines) into the flask containing the sample. A 1.5-2 M NaOAc/HOAc buffer is used with the N-chlorinated sulfonamide samples. Preparation of A15-SO2Cl or D88-SO2Cl, Large Scale (Scheme 1, Reaction 2). The apparatus consisted of a 250 mL, three-neck, round-bottomed flask equipped with a reflux condenser, a football-shaped magnetic stirring bar, a hemispherical heating element, and a stirrer driver under the heater, all mounted in a fume hood. The dried resin in the sodium ion form, 2031 g, was placed in the flask and 40-50 mL of POCl3 was added. Stirring was begun and 6 mmol of PCl5 per gram of the dry resin was added in 10-12 batches, about 2 min apart. After all of the PCl5 was added, the mixture was refluxed for 1 h, allowed to cool, and then cooled to ice temperature in an external ice-water bath to minimize the vapor pressure of POCl3. The resin was then filtered by vacuum on a coarse, rapid-flow, fritted glass funnel. The filter flask was then changed and the resin was washed once with ice-water. The resin was transferred promptly to other flasks containing ice-cold solutions of ammonia, or an amine, or a diamine, or hydrazine hydrate depending on what final product(s) is(are) desired. Precautions: Filter the POCl3/resin mixture into a dry filter flask. After filtration of the POCl3, transfer the filter funnel to a clean, dry filter flask for the washing operation. Use of a water aspirator, protected against water backup, for suction minimizes the escape of HCl. The discharge from the aspirator may be trapped in a bucket for neutralization before disposal if local regulations require. Preparation of A15-1,1 (Scheme 1, Reaction 3, G ) CH3). About three-fourths of a 31 g batch of A15(Na+) converted to A15-SO2Cl was quickly transferred to a flask containing 12 mL of 40% methylamine [139 mmol] and ice, and the mixture was stirred. An additional 18 mL of methylamine [208 mmol] was added along with 12 g [113 mmol] of sodium carbonate. The mixture was allowed to warm overnight while being stirred gently. The mixture was filtered, washed with deionized (DI) water, put in the H+ form, and washed, and the total strong acid exchange capacity was determined to be 20.40 mequiv. The sodium salt form was dried to a constant weight of 21.20 g, or 0.962 mequiv/g basis Na+ form. The H+ form weighed 19.95 g and the total exchange capacity is thus 1.02 mequiv/g basis H+ form. A 1.131 g sample of the Na+ form was chlorinated, washed with 5 × 5 mL of DI water, and subjected to an active Cl analysis by the gasometric method (Scheme 1, reaction 6), which produced 49.50 mL of gas collected
over water at 716 Torr and 21 °C. The volume at STP was 42.15 mL. Thus, 42.15 mL × (2 mmol Cl/mmol N2)/ (22.4 mL N2/mmol N2) × 1/1.131 g ) 3.33 mmol Cl/g, basis Na+ form; 3.39 mmol of sulfonamide/g, basis H+ form. The resin was converted to the H+ form and then to the Cs+ form, which was dried to a constant weight of 1.260 g, leading to an estimate of strong acid exchange capacity of 1.17 mequiv/g. Preparation of A15-SO2NHNH2 (Scheme 1, Reaction 3, G ) NH2). A portion of washed, wet A15-SO2Cl was added to a solution of 6.0 mL [123 mmol] of hydrazine hydrate in ice and water. The pH was checked periodically, and an additional 2.5 mL of hydrazine hydrate [51 mmol] was added in portions. After 2 h the resin was filtered in a conical filter, washed with DI water, and converted to H+ form with 1.2 N HCl. (Hydrazinium sulfate, N4H6SO4, is sparingly soluble in water, so strong sulfuric acid should be avoided. PsSO2NHNH2 decomposes readily in basic solutions to yield short-lived diimine, N2H2. Converting the sulfonic acid groups to the H+ form or an alkali metal salt yields a product that is stable, except to heating.4) The dried product was subjected to gasometric analysis using bleach (Scheme 1, reaction 8); the yield was 2.9 mmol/ g. Preparation and Characterization of A15-0,1 (Scheme 1, Reaction 3, G ) H). Approximately 1.2 g of moist A15-SO2Cl was added to 10 mL of concentrated ammonium hydroxide. After 4 days (a few hours works just as well), more ammonium hydroxide was added and the mixture was brought to a boil and then cooled. The mixture was filtered, washed with water, converted to the H+ form by 10 × 5 mL of 1 N HCl, washed with deionized (DI) water and methanol, and vacuum-dried. A 0.627 g portion of the dry resin was treated with 0.50 g of Cs2CO3 [1.5 mmol] in 10 mL of DI water. After 16 h the resin was filtered on a fritted glass funnel and washed with DI water followed by methanol. It was then dried in the vacuum oven at 30-40 °C,
