ANALYST, JANUARY 1991, VOL. 116 39 Ion-selective Electrodes in Organic Analysis: Determination of Alkyl Halides via ln Situ Generation of S-Alkylisothiouronium Salts Wing Hong Chan,* Albert Wai Ming Lee* and Yu Man Cheung Department of Chemistry, Hong Kong Baptist College, 224 Waterloo Road, Kowloon, Hong Kong Low relative molecular mass alkyl halides, after in situ derivatization to the corresponding S-alkyl- isothiouronium salts in the presence of an excess of thiourea, were determined with a poly(viny1 chloride) membrane S-alkylisothiouronium-selective electrode based on S-butylisothiouronium tetraphenylborate. This membrane electrode exhibited Nernstian response in the range 1.0 x 10-1-1.6 x 10-4 mol dm-3with an average cationic (positive) slope of 58.8 mV per concentration decade at 25 "C.The electrode had a reasonably wide working pH range (6.5-8.5), fast dynamic response time (30 s-2 min), stable response for at least 2 months and high selectivity for the S-alkylisothiouronium ion in the presence of many inorganic and organic ions. The electrode functioned satisfactorily for the determination of primary and secondary alkyl halides, excluding alkyl fluorides. Keywords: Alkyl halide determination; ion-selective electrode; organic analysis; in situ S-alkyl- is0 th io u ro n iu m salt genera ti on Organohalides are essential industrial chemicals. They are important intermediates in many chemical reactions and are used extensively as solvents. Other significant uses of this class of compound are as anaesthetics, refrigerants, and grain and fruit fumigants.1 There is a wide range of published methods for the determination of organohalides. The basic approach involves the decomposition of an organohalide sample to halide ions. After decomposition, the liberated halide ions are determined by using a halide ion-selective electrode,2 grav- imetry or visual titrimetry.3 For compounds containing a tightly bound halogen atom such as alkyl halides, the oxygen flask combustion technique is used.3 All of these methods require either a fairly tedious sample preparation procedure or a large sample size. In order to increase the use of ion-selective electrodes (ISEs) in organic analysis, a new strategy has been proposed for converting a covalent organic compound into a water- soluble ionic derivative which is amenable to potential measurement.Many important organic functional groups such as esters, alcohols, aldehydes and amines, after derivatization to ionic species, can be subjected to selective electrode measurement.4 However, a general method for the determi- nation of alkyl halides using an ISE has not yet been developed. The aim of this investigation was to devclop a poly(viny1 chloride) (PVC) membrane S-alkylisothiouronium- selective electrode for the determination of alkyl halides via in situ generation of the corresponding S-alkylisothiouronium salts in 95% ethanol by means of a bimolecular nucleophilic substitution reaction,s viz., + S NH2 X- II 95 % II RX + H2N-C-NH2 - R-S-C-NH? ethanol where X is Br or I. For the less reactive alkyl halides, such as primary alkyl chlorides and secondary alkyl bromides, it was first necessary to convert these compounds into the corresponding alkyl iodides by refluxing overnight with an excess of sodium iodide in 95% ethanol.h The crude iodo compound, without purifica- tion, was then converted into the S-alkylisothiouronium salt by treatment with an excess of thiourea.* To whom correspondence should be addressed. Experimental Apparatus Potentiometric measurements were made at a constant temperature in the range 20-25 "C with an Orion digital pH/ion meter (Model SA720). A platinized platinum elec- trode (Model 3401) from Yellow Springs Instruments was used as an internal reference electrode. A saturated calomel electrode (SCE) from Orion (Model 9006) was used as an external reference electrode. For pH measurements, a Sen- sonex combined pH electrode (Model 5200C) was used. The nuclear magnetic resonance (NMR) spectra were recorded with a Jeol NMR spectrometer (60 MHz) (Model PMX 60SI).Reagents All solutions were prepared with analytical-reagent grade reagents in distilled, de-ionized water unless stated other- wise. The organic solvents and reagents were also of ana- lytical-reagent grade. Tetrahydrofuran (THF) was distilled over sodium under nitrogen before being used. High relative molecular mass PVC was obtained from Aldrich. Sodium tetraphenylborate and bis(2-ethylhexyl) phthalate (DEHP) were obtained from Fluka. The Britton-Robinson buffer of pH 7.5 consisted of 57.5 ml of 0.2 mol dm-3 sodium hydroxide and 100 ml of a stock solution containing 0.04 mol dm-3 acetic acid, 0.04 mol dm-3 orthophosphoric acid and 0.04 mol dm-3 boric acid.S-Butylisothiouronium Tetraphenylborate-PVC Matrix Membrane Electrode Preparation of the sensing material S-Butylisothiouronium bromide (0.01 mol) was dissolved in 20 ml of distilled, de-ionized water. An equimolar amount of sodium tetraphenylborate was dissolved in another 20 ml of distilled, de-ionized water. The solutions were mixed and stirred for 10 min. The white precipitate of S-butyl- isothiouronium tetraphenylborate was filtered off by suction filtration, washed with distilled, de-ionized water, air-dried for 24 h and ground to a fine powder. Preparation of the sensing membrane A mixture of S-butylisothiouronium tetraphenylborate (0.04 g), PVC powder (0.26 g) and plasticizer (DEHP) (0.10 g) was dissolved in 20 ml of distilled THF.The solution was poured into a 75 mm i.d. Petri dish and covered with a piece of40 Internal reference electrode (Pt-Pt) ANALYST, JANUARY 1991, VOL. 116 Internal PVC matrix reference membrane with solution, S-butylisothio- 0.01 mol dm-3 uronium SBB at pH 7.5 tetraphenylborate filter-paper. After all the THF had evaporated, an S-butyliso- thiouronium tetraphenylborate-PVC matrix membrane sheet was obtained. Standard solution at pH 7.5 Assembly of the electrode A portion of the sensor membrane (diameter, 1 cm) was cut and fitted into a screw-cap adaptor with an O-ring placed above the membrane as the electrode body.7 A solution of 1.00 x 10-2 mol dm-3 S-butylisothiouronium bromide at pH 7.5 was used as the internal reference solution and a platinized platinum electrode was used as an internal reference elec- trode.Saturated KC1 solution Conditioning and storage procedure The assembled electrode was conditioned by soaking it in 1 x 10-2 mol dm-3 S-butylisothiouronium bromide solution at pH 7.5 for 1 d before use; the electrode was also stored in the same solution when not in use. Construction of the ISE system The assembled electrode was immersed in an S-butyl- isothiouronium bromide (SBB) solution and acted as a half-cell. The other half of the cell was formed by inserting an SCE into a saturated KC1 solution. The ISE system was completed by connecting the two half-cells by a KC1 salt- I (ion pair) External reference electrode W E ) In Situ Derivatization of Alkyl Halides In the bimolecular nucleophilic substitution reaction, the order of reactivity follows the sequence RI > RBr > RC1 (R = alkyl).For a given halide, the reactivity decreases in the order primary > secondary > tertiary. Based on the difference in reactivity, alkyl halides can be grouped into two classes in the in situ derivatization reaction. Class 1. Halides with higher reactivity, i.e., alkyl iodides and The alkyl halide (about 0.5 g) was weighed accurately in a 100 ml round-bottomed flask and 1.2 equiv. of thiourea were added. The mixture was dissolved in 30 ml of 95% ethanol and the solution was refluxed for a certain period of time (90-150 min). After refluxing, the solvent was removed under reduced pressure to leave a colourless oily liquid, which was dissolved in a pH 7.5 buffer solution which consisted of boric acid, acetic acid, orthophosphoric acid and sodium hydroxide.The resulting solution was diluted to the mark with the buffer in a 100 ml calibrated flask and then potential measurements were performed. primary alkyl bromides Class 2. Halides with lower reactivity, i .e., alkyl chlorides and The alkyl halide (about 0.5 g) was accurately weighed into a 100 ml round-bottomed flask and 3 equiv. of sodium iodide were added. The mixture was dissolved in 40 ml of 95% ethanol and the solution was refluxed overnight. Thiourea secondary alkyl bromides (1.5 equiv.) was then added to the cool solution and the mixture was refluxed for 150 min. After removal of the solvent in vacuo, the oily residue was dissolved in pH 7.5 buffer and diluted to the mark with the same buffer in a 100 ml calibrated flask.The solution was then ready for potential measurement. Calibration The butyl bromide sample, after the aforementioned in situ derivatization, was used to prepare a series of standard solutions in the concentration range 1 X 10-1-1 x 10-5 mol dm-3. Aliquots (80 ml) of the standard solutions were used for the ISE measurements. The potentials of the stirred solutions were recorded when they became stable and were plotted as a function of the logarithm of the butyl bromide concentration. The graph was used for subsequent determina- tion of alkyl halides. Results and Discussion Nature and Composition of the Membrane S-Butylisothiouronium bromide reacts readily with sodium tetraphenylborate to form a stable, crystalline 1 : 1 ion-pair complex whose composition was unambiguously verified by proton NMR spectroscopy.The integration ratio and the multiplicity of the various proton signals of the NMR spectrum agree well with the proposed structure (Fig. 1). The response characteristics of the PVC membrane doped with various amounts of S-butylisothiouronium tetraphenylborate were systematically investigated. The suitability and sensitivity of the membrane, based on both the slope of the calibration graph and the limit of detection, were studied. The calibra- tions were performed in Britton-Robinson buffer (pH 7 . 9 , in which all of the S-butylisothiouronium ions are in the univalent form.As shown in Table 1, the response was dependent on the proportion of active compound contained in the membrane formulation. For optimum performance, 9-12% m/m of the sensor in the membrane formulation was required. When less carrier was used, the response deviated considerably from the Nernst equation. In the fabrication of the PVC sensing membrane, about 25% m/m of plasticizer (DEHP) was added to improve the plasticity of the membrane. In Situ Derivatization Reaction In the presence of an excess of thiourea, the water-soluble ionic S-alkylisothiouronium salts can be prepared quan- titatively from alkyl halides by heating under reflux. For compounds containing a tightly bound halogen atom, the alkyl halides are first converted into the corresponding alkyl iodides by refluxing overnight with 3 equiv.of sodium iodide in 95% ethanol. For quantitative work, it is essential that the extent of S-alkylisothiouronium salt formation is reproducible under a given set of conditions. In order to ensure this and to determine the time required for quantitative conversion of the alkyl halide into the S-alkylisothiouronium salt, the reaction was monitored by potentiometric measurement using the selective electrode. The measured potential readings were plotted as a function of reaction time (Fig. 2). It was found that quantitative (or constant) conversion of butyl bromide into S-butylisothiouronium bromide was obtained when the 6 2.50(s) + / 6 1.38(m) 6 3.15(t) NH2 \ \ I/ C H3-C H 2-C H2-C H 2-S-C-N H 2 B-( CeH 5 / I \ 6 0.89(t) 6 1.58(m) b 2.50(s) 6 6.7&7.18(m) Fig.1 Assignment of the proton NMR data for the sensor (in CDC13)ANALYST, JANUARY 1991, VOL. 116 41 Table 1 Response characteristics of a PVC membrane doped with various amounts of S-butylisothiouronium tetraphenylborate (sensor) Total mass Slope/mV Detection Sensor (PVC + DEHP + per concentration limit/ Correlation (% m/m) sensor)/g Sample decade 10-4 mol dm-3 coefficient 2.5 6.6 9.5 12.3 24.8 0.4091 0.4112 0.4075 0.4105 0.4048 1 2 1 2 1 2 1 2 1 2 38.4 37.2 51.5 52.7 58.0 57.7 57.4 57.6 53.7 52.4 3.2 3.5 2.3 2.0 2.2 2.0 2.0 1.6 1.3 1.6 0.9989 0.9985 0.9990 0.9985 0.9986 0.9983 0.9990 0.9988 0.9931 0.9970 Table 2 Conditions for the in situ derivatization of different alkyl halide samples Primary alkyl iodide 1-Iodobutane Primary alkyl bromide 1-Bromobutane Primary alkyl chloride 1-Chlorobutane Secondary alkyl bromide 2-Bromobutane 1 -Bromopropane Reflux with excess of thiourea in 30 ml of 95% ethanol for 90 min Reflux with excess of thiourea in 30 ml of 95% ethanol for 150 min Reflux with 3 equiv.of NaI in 40 ml of 95% ethanol for 24 h, then reflux with excess of thiourea for 150 min &I -80 0 v) v) I? E ki 2 -100 > -120 I I i 50 100 150 200 250 300 Time/min Fig. 2 Time required for the quantitative conversion of butyl bromide into the S-butylisothiouronium salt (monitored with the ISE) -50 1 w .u 3 ; -100 2 -150 2 B L a -200 / I -Detection limit I -250 -6 -5 - 4 -3 -2 -1 Log of concentration Response of the electrode to the concentration of butyl Fig. 3 bromide in Britton-Robinson buffer of pH 7.5 former was refluxed with an excess of thiourea in 95% ethanol for 150 min.Similarly, the reaction conditions required for quantitative conversion of other alkyl halides into the corre- sponding S-alkylisothiouronium salts were determined and these are given in Table 2. The results obtained are consistent with the relative reactivities of alkyl halides in nucleophilic substitution reactions. Characteristics of the Electrodes As shown in Fig. 3, the PVC membrane electrode exhibited an average Nernstian slope of 58.8 mV per concentration decade 0 - 50 Lu u v) 9 2 -100 2 > E -150 3 5 7 9 11 PH Fig. 4 Effect of pH on the potential of the S-butylisothiouronium tetraphenylborate-PVC matrix membrane electrode. A, 5 X B, 5 x 10-3; and C, 5 x 10-4 mol dm-3 butyl bromide over five determinations (standard deviation = 1.17 mV) with good linearity (correlation coefficient = 0.9991) from 1.0 X 10-1 to 1.6 x 10-4 mol dm-3 butyl bromide.Both the slope of the calibration graph and the correlation coefficient demon- strate the suitability and sensitivity of this membrane for the determination of alkyl halides. Effect of pH The influence of pH on the response of the S-butylisothiouronium tetraphenylborate-PVC matrix membrane electrode was evaluated by performing the potential measurements on the derivatization product of butyl bromide at different pH values. The electrode showed stable and constant readings (+1 mV) in the pH range 6.5-8.5 for various concentrations of butyl bromide (Fig. 4). The S-butylisothiouronium ion can be protonated in a strongly acidic medium to give a divalent cation, whereas it is readily hydrolysed to butanethiol in a strongly alkaline medium +NH2 +NH2 11 + H+ 11 high C4HgS-C-NH3 C4HgS-C-NH2 0 PH C4HgSH + NH2-C-NH2 I142 ANALYST, JANUARY 1991.VOL. 116 Therefore, subsequent potential measurements were made at pH 7.5, at which nearly all of the S-butylisothiouronium ions are in the univalent form. Response Time and Stability of the Electrode The S-butylisothiouronium tetraphenylborane-PVC matrix membrane electrode has a rapid response time. The response time of the standard solutions was recorded in increased order of their concentration. The results indicated that the average dynamic response time was 30 s and 2 min for a concentrated (>1 X 10-3 rnol dm-3) and dilute (<1 X 10-3 rnol dm-3) solution, respectively (Fig.5 ) . On the other hand, ageing of the membrane was not a serious problem. The performance of the electrode in terms of linearity and Nernstian response was reproducible over a period of 2 months, after repeated measurements. Effect of Interfering Ions The response of the electrode to S-alkylisothiouronium ion in the presence of various foreign ions was examined. The 8 -50 B In- C r -100 > -200 0 100 200 300 Ti me/s Fig. 5 Response time of the membrane electrode for different concentrations of butyl bromide in Britton-Robinson buffer of pH 7.5 (stable reading indicated by the arrow). A, 1 X 10-1; B, 1 X 10-2; C, 1 X 10-3; and D, 1 x rnol dm-3 butyl bromide Table 3 Selectivity coefficients ( k r ; ) for the S-butylisothiouronium tetraphenylborate-PVC matrix membrane electrode.Concentration of each foreign ion, 1.0 x 10-2 mol dm-3 kpot Interfering compound (B) S.B Thiourea O* Urea 0* Tetrabutylammonium hydrogen sulphate 0.5 Ammonium chloride 0" * Identical calibration graphs were obtained both in the presence and absence of the foreign ion. potential given by solutions each containing 1 x 10-2 rnol dm-3 of the foreign compound and various S-butylisothio- uronium concentrations in the range 1 x 10-1-1 x 10-5 rnol dm-3 was measured. The selectivity coefficients were calculated by using the fixed interference method.* The results obtained (Table 3) demonstrated that no significant effect was caused by organic compounds such as thiourea and urea, and by inorganic ions such as ammonium and chloride.As an excess of thiourea was used in the derivatization of the alkyl halides, it was fortuitous that thiourea did not interfere with the determination. The tetrabutylammonium ion interfered only when present at concentration levels at least several times greater than that of the S-butylisothiouronium ion. In addition, the calibrations were carried out in Britton- Robinson buffer solution which consisted of boric acid, acetic acid, orthophosphoric acid and sodium hydroxide; none of these inorganic components of the buffer solution caused any interference. Determination of Alkyl Halides At the onset of this investigation, it was expected that the sensing material of the electrode could be used to detect both primary and secondary aliphatic alkyl halides.S- Alkyliso- thiouronium solutions in the concentration range 1 x 10-1- 5 X 10-4 rnol dm-3 were prepared from the corresponding alkyl halides and determined by using the S-butyliso- thiouronium tetraphenylborate-PVC matrix membrane elec- trode. The potentials given by these solutions were compared with the calibration graph prepared from the butyl bromide derivatization product in order to assess the accuracy and reproducibility of the method. The results obtained for five samples (Table 4), each analysed in triplicate, showed that l-iodobutane and l-bromobutane could be quantitatively converted into the S-butylisothiouronium salts and deter- mined with the membrane electrode. The average recovery was 98.1% with a mean standard deviation of 0.88%.The lower recovery of l-bromopropane (Table 4), which is a reactive alkyl halide, may be due to its greater volatility. For the less reactive alkyl halides, l-chlorobutane, and 2-bromo- butane, the two-step derivatization reaction is more prone to side-reactions, such as an elimination reaction. The recovery of these two halides was 86.6 and 61.3%, respectively. However, the excellent precision observed for this electrode method rendered the determination of these less reactive halides equally feasible. The determination of primary chloro- alkanes and secondary bromoalkanes, using the same calibra- tion graph, adjusting the amount of the less reactive halides found with the electrode by a factor of 0.87 and 0.61, respectively, will give the equivalent amount of the halide in the sample.Moreover, the absolute potentials recorded by the electrode for various alkyl halides at the same concentration level were very similar. Therefore, the electrode can be used Table 4 Determination of alkyl halides using the S-butylisothiouronium tetraphenylborate-PVC matrix membrane electrode Sample Trial 1 -1odobutane l-Bromobutane 3 2 3 l-Chlorobutane 1 2 3 2-Bromobutane 1 2 3 l-Bromopropane 1 Mass used1 g 0.9228 0.3809 0.3123 0.6906 0.5571 0.2503 0.1682 0.5369 0.5893 0.4317 0.1079 0.4662 0.6063 0.6790 0.1516 Mass measured by ISEIg 0.8933 0.3790 0.3067 0.6726 0.5460 0.2473 0.1600 0.5235 0.5592 0.3708 0.0940 0.4042 0.3771 0.4094 0.0934 Standard Recovery Mean (Yo) (Yo) deviation (%) 96.8 99.5 98.2 1.35 98.2 97.4 98.0 98.1 0.70 98.8 95.1 97.5 95.8 1.45 94.9 85.9 87.1 86.6 0.61 86.7 62.2 60.3 61.3 0.97 61.6ANALYST, JANUARY 1991, VOL.116 43 either to determine the concentration of an individual alkyl halide or to measure the total concentration of a mixture of alkyl halides. Conclusion An indirect ISE system for the determination of alkyl halides has been described. The in situ generation of the ionic S-alkylisothiouronium salt from the corresponding covalent alkyl halide in the presence of an excess of thiourea is the key factor in the viability of the method. This highly selective electrochemical method has been shown to be applicable to the determination of low relative molecular mass primary and secondary alkyl halides, excluding alkyl fluorides. References 1 Gessner, G. N., The Condensed Chemical Dictionary, Van Nostrand Reinhold, New York, 8th edn., 1971, p. 359. 2 Ma, T. S., and Hassan, S. S. M., Organic Analysis Using Ion Selective Electrodes, Academic Press, London, 1982, vol. 2, p. 14. 3 Ma, T. S., and Robert, C. R., Modern Organic Elemental Analysis, Marcel Dekker, New York, 1979, pp. 1.58-206. 4 Chan, W. H., Lee, A. W. M., and Chan, L. K., Analyst, 1990, 115,201, and references cited therein. .5 Vogel, A. I., Qualitative Organic Analysis, Longman, London, 2nd edn., 1966, p. 98. 6 Fieser, L. F., and Fieser, M . , Reagents for Organic Synthesis, Wiley, New York, 1967, vol. 1, p. 1087. 7 Chan, W. H., Wong, M. S., and Yip, C. W., J . Chem., Educ., 1986, 63, 91.5. 8 Guilbault, G. G., Ion-Sel. Electrode Rev., 1979, 1, 139. Paper 01031 081 Received July 1 Oth, 1990 Accepted August 17th, I990