Anal. Chem. 1998, 70, 3548-3552
A New Method of Determining Chlorine Kinetic Isotope Effects K. C. Westaway,*,† T. Koerner,† Y.-R. Fang,† J. Rudzin˜ski,‡ and P. Paneth*,‡
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6, and Institute of Applied Radiation Chemistry, Technical University of Ło´ dz´ , Wro´ blewskiego 15, 90-924 Ło´ dz´ , Poland
Two methods have been used to measure the chlorine leaving group kinetic isotope effect for the SN2 reduction of benzyl chloride to toluene by sodium borohydride in DMSO at 30.000 °C. The reaction was monitored by titrating the unreacted borohydride ion. One method involved determining the chlorine isotope effect using the classical IRMS method, which requires the conversion of the chloride ions into gaseous methyl chloride that is analyzed in an isotope ratio mass spectrometric analyses (Hill, J. W.; Fry, A. J. Am. Chem. Soc. 1962, 84, 2763. Taylor, J. W.; Grimsrud, E. P. Anal. Chem. 1969, 41, 805.). Two different measurements using this method yielded isotope effects of k35/k37 ) 1.007 19 ( 0.000 19 and 1.007 64 ( 0.000 19. The second method was a new technique where the ratio of the chlorine isotopes was obtained by fast atom bombardment mass spectrometry on the silver chloride recovered from the reaction, i.e., from the first step in the classical procedure. Therefore, the new method is much simpler and avoids the timeconsuming preparation, purification, and recovery of the gaseous methyl chloride. Although the experimental error is larger (k35/k37 ) 1.008 03 ( 0.00 10 and 1.008 02 ( 0.000 65) when the new technique is used to analyze the silver chloride samples from the same set of experiments that were used to measure the isotope effect by the classical method, the chlorine isotope effect found by the two methods is identical within experimental error. This large chlorine kinetic isotope effect indicates there is considerable Cr-Cl bond rupture in the SN2 transition state. Chlorine kinetic isotope effects are a sensitive tool for distinguishing between alternative mechanisms.1 Although the magnitude of these isotope effects is small (large chlorine kinetic isotope effects are close to 1%),2 they can be used to indicate whether a bond to a chlorine atom is broken or weakened in the transition state.1,3 Chlorine has two stable isotopes in a proportion
suitable for direct measurement of their isotopic ratio,4 so determining a chlorine isotope effect is both feasible and attractive.5,6 However, determining chlorine isotope effects is impeded by the tedious procedure required for the conversion of chlorine atoms into the gaseous methyl chloride that is required for determining the 35Cl/37Cl isotopic ratio by isotope ratio mass spectrometry (IRMS).1,5-7 This obstacle could be avoided if the isotopic composition of a reactant could be determined by direct analysis. In fact, this can be accomplished by determining the 35Cl/37Cl isotopic ratio of silver chloride samples by fast atom bombardment-isotope ratio mass spectrometry (FAB-IRMS). A comparison of the classical conversion (IRMS) and a newly developed FAB-IRMS method for measuring chlorine isotope effects is presented. The dehalogenation of benzyl chloride by borohydride ion
C6H5CH2-Cl + BH4- f C6H5CH2-H + Cl- + BH3
(1)
was used as a model reaction for comparing the old and new methods of measuring a chlorine isotope effect. The results also provide information about the amount of CR-Cl bond rupture in the transition state of this SN2 reaction.1,8 EXPERIMENTAL SECTION Reagents. The isotope effect was measured with the same batch of a distilled in glass grade dry DMSO [67-68-5] from Caledon Laboratories Ltd. The sodium borohydride [16940-662] (Aldrich), which was stored in a vacuum desiccator once it had been opened, was used as purchased. The benzyl chloride [100-44-7] (Aldrich) was purified by vacuum distillation. The bp was 49-50 °C at 3 mmHg; lit.9 bp 51-52 °C at 4 mmHg. Kinetic Measurements. All the glassware, the solvent, a Mettler AE 160 semimicrobalance, and the reagents were placed in an Instruments for Research and Industry model X-37-37 glovebag which was sealed, evacuated, and partially filled with extra-dry nitrogen (Praxair) five times. All the solutions used to monitor the reaction were standardized the day they were used. Sodium borohydride and benzyl chloride stock solutions were prepared by diluting approximately 0.16 g (0.0042 mol) of NaBH4
†
Laurentian University. Technical University Ło´dz´. (1) Shiner, V. J., Jr.; Wilgis, F. P. In Isotopes in organic chemistry; Buncel, E., Saunders: W. H., Jr., Eds.; Elsevier: Amsterdam, 1992; Vol. 8, pp 272288. (2) Maccoll, A. Ann. Rep. A, Chem. Soc. 1974, 71, 77. (3) Sims, L. B.; Fry, A.; Netherton, L. T.; Wilson, J. C.; Reppond, K. D.; Crook, S. W. J. Am. Chem. Soc. 1972, 94, 1364. ‡
3548 Analytical Chemistry, Vol. 70, No. 17, September 1, 1998
(4) Weast, R. C., Ed. CRC handbook chemistry and physics, 61st ed.; CRC Press: Boca Raton, FL, 1980; p B-263. (5) Hill, J. W.; Fry, A. J. Am. Chem. Soc. 1962, 84, 2763. (6) Taylor, J. W.; Grimsrud, E. P. Anal. Chem. 1969, 41, 805. (7) McLennan, D. J.; Stein, A. R.; Dobson, B. Can. J. Chem. 1986, 64, 1201. (8) Koerner, T. MSc. Dissertation, Laurentian University, Sudbury, ON, 1996. (9) Willi, A. V.; Ho, C.-K.; Ghanbarpour, A. J. Org. Chem. 1972, 37, 1185. S0003-2700(97)01235-3 CCC: $15.00
© 1998 American Chemical Society Published on Web 07/23/1998
and 0.95 g (0.0075 mol) of benzyl chloride (accurately weighed) to 100 and 250 mL, respectively, with DMSO in volumetric flasks. The substrate stock solution was transferred into a 250-mL roundbottom flask fitted with a serum cap greased on the ground glass joint, sealed with Parafilm and a wire. A 25-mL aliquot of the NaBH4 stock solution was pipetted into three different 100-mL Erlenmeyer flasks fitted with greased serum caps and sealed with Parafilm. Then, the flasks were removed from the glovebag and temperature equilibrated at 30.000 ( 0.002 °C for at least 1 h. The reaction was started by transferring 25 mL of the benzyl chloride stock solution with a 25-mL Hamilton gastight syringe into the reaction vessel containing the borohydride ion stock solution. At predetermined times, between 10 and 90% of completion, a 1-mL aliquot of the reaction mixture was withdrawn with a 1-mL Hamilton gastight syringe and diluted with 25.00 mL of double-distilled water; the borohydride ion was titrated immediately to a methyl red end point with 0.004 821 M HCl.10 The second-order rate constant was determined using the integrated form of a second-order rate expression that was first order in both the nucleophile and the substrate.11 All the second-order kinetic plots were linear up to 90% of completion and more than 90% of the plots had correlation coefficients greater than 0.999. Determining the Chlorine (Leaving Group) Kinetic Isotope Effect. The chlorine isotope effect was determined for the SN2 reaction between sodium borohydride and benzyl chloride in DMSO at 30.000 ( 0.002 °C. Six reactions were done at the same time. One reaction was taken to 100% of completion. Three different analyses (vide infra) indicated the complete reactions in trials 1 and 2 had gone to 100.2 ( 0.65 and 99.73 ( 0.11% of completion, respectively. The other five reactions were used to obtain the 35Cl/37Cl ratio in the product after different fractions of reaction. A sodium borohydride stock solution was prepared under a nitrogen atmosphere in a glovebag by diluting ∼1.65 g (0.044 mol) of sodium borohydride to 1 L in a volumetric flask with DMSO. Then, 150 mL of this solution was pipetted into five different 500mL round-bottom flasks. These solutions were used for the partial reactions. Another sodium borohydride solution was prepared by dissolving ∼0.49 g (0.013 mol) of NaBH4 in 150.0 mL of DMSO. This solution was used for the complete reaction. A benzyl chloride stock solution was prepared by pipeting 75 mL of DMSO onto ∼9.0 g (0.071 mol) of benzyl chloride in a 100-mL Erlenmeyer flask. All of the flasks were fitted with greased serum caps, sealed with Parafilm and copper wire, and temperature equilibrated for at least 1 h. The reactions were started by injecting 5 mL of the benzyl chloride stock solution with a Hamilton gastight syringe into the reaction flask containing 150 mL of the sodium borohydride stock solution. At predetermined times between 8 and 25% of completion (see Kinetic Measurements), a reaction vessel was removed from the bath, 100 mL of cold double-distilled water was added, and the reaction mixture was titrated to a methyl red end point immediately with standard 0.3086 M nitric acid.10 The solution from the titration was transferred to a 500-mL separatory funnel and extracted once with 100 mL of heptane. The aqueous layer was put aside and the heptane layer was extracted with 25 mL of double-distilled water. The aqueous layers were combined (10) Davis, W. D.; Mason, L. S.; Stegeman, G. J. Am. Chem. Soc. 1949, 71, 2775. (11) Laidler, K. Chemical kinetics, 2nd ed.; McGraw-Hill: New York, 1965; p 8.
and extracted with 100 mL of heptane. Then, the 100-mL heptane layer was extracted with 25 mL of double-distilled water. All the aqueous layers were made slightly basic with NaOH12 and reduced to ∼100 mL on the rotary evaporator. The ionic strength of this solution was increased by adding 10.0 g of KNO313 [7757-79-1] (BDH) and the pH was reduced to below 2.0 with 1 M HNO3.15 The reaction mixture was then titrated in the dark under photographic safety lamps to a potentiometric end point with a standard AgNO3 solution16 and a silver electrode.17 A reference saturated calomel electrode connected to the solution through an agar- KNO3 salt bridge18 and the silver indicating electrode were attached to a Fisher Scientific, model 50, pH meter set in the mV mode. A Teflon stirring bar hit the silver electrode during the titration.19 Then, the mixture was warmed and left in a dark cupboard overnight so the colloidal AgCl precipitate would form larger crystals.13 The AgCl precipitate was collected on a preweighed sintered glass filter, washed with dilute HNO3, dried in the dark at 110 °C overnight, and cooled in a desiccator in a dark cupboard. Finally, the filter and AgCl precipitate were weighed and the weight of AgCl calculated. The nitric acid titration, the chloride ion titration, and the weight of silver chloride gave three independent estimates of the f value that is used to calculate the isotope effect (Table 1). Because all of the errors in f are e1.0%, the value of f is known very accurately. Determining the Chlorine Isotope Effect Using the IRMS Method. The silver chloride recovered from the reaction was converted to methyl chloride using the procedure developed partly by Hill and Fry5 and partly by Taylor and Grimsrud.6 Approximately 10 mg of AgCl was put into the reaction vessel (Figure 1), which was wrapped in foil to reduce photodecomposition, and the vessel was connected to the vacuum line at cup seal C. The vacuum line, with valves 12, 1, 11, 10, 9, and 7 open and valves 2, 8, and 5 closed, was evacuated to
