360 Analyst, June, 1974, Vol. 99, $$. 360-366 Ionic Polymerisation as a Means of End-point Indication in Non-aqueous Thermometric Titrimetry Part VI.* The Determination of Thiols BY E. J. GREENHOW AND MISS L. H. LOO (Departmeizt of Chemistry, Chelsea College, University of London, Manresa Road, London S . W.3) Alkyl and aryl thiols have been determined in the presence of carboxylic acids and phenols by means of acid - base catalytic thermometric titrimetry. Two titrations are carried out, with acrylonitrile and acetone as the end- point indicators. With the former indicator, thiol groups are not deter- mined, so that the difference between the titration values obtained by using the two methods of end-point indication is a measure of the thiol content. The thiol content of 2-mercaptothiazoline, 4,6-dihydroxypyrimidine-2- thiol (2-thiobarbituric acid), purine-6-thiol and 2-mercaptobenzimidazole can be determined by the same procedure.In the titration of 2-thiohydantoin, 4-hydroxypyrimidine-2-thiol (2-thiouracil), 2-mercaptobenzoxazole and 2-mercaptobenzothiazole, however, both end-point methods give the same titration value. These apparently anomalous results can be explained if it is accepted that the last four heterocyclic thiols exist in the thione tautomeric form in dimethylformamide solution. Some thioamides also titrate as acids, and differences between titration values obtained by using the two methods of end-point indication can again be attributed to thione - thiol tautomerism. Thiols can be determined conveniently in amounts down to 0.01 mequiv, i.e., about 2 mg of dodecane-l-thiol, with 0.1 M titrants. In instances when the acrylonitrile method can be used for the direct determination of the thiol function, 0.001 M titrant can be used and the lower level of determination is then about 0.0001 mequiv.THE determination of the thiol function is important in connection with the refining of petroleum because thiols are an undesirable impurity in distillate fractions. In other industries, certain thiols find use as additives. For example, dodecane-l-thiol is used to control the degree of polymerisation in the manufacture of thermoplastics, while 2-mercapto- benzothiazole is added to rubber formulations as an accelerator for the vulcanisation stage. The performance of such additives is dependent on their thiol content, and determination of the latter can be used as a method of quality control.Thiols differ from hydroxy compounds in their ability to form insoluble copper, silver and mercury derivatives and in the ease with which they undergo oxidation. These reactions form the basis of the preferred chemical methods for the determination of the thiol function in organic compounds.1,2 Thiols are more acidic than the corresponding hydroxy compounds, thus even ethanethiol, with a pK, of 10.5 at 20 "C, can be titrated as a weak acid.2 Acid - base titration is not, however, generally recommended for the selective determination of thiols because other acidic compounds in the sample would interfere. An attempt has been made to determine thiols iodimetrically in non-aqueous solution by use of catalytic thermometric titration with ethyl vinyl ether as an end-point indicator, but the titration values obtained were considerably lower than those required by a 1 : 1 stoicheiometry.3 Apparently, a high proportion of the thiol was converted into an un- reactive, i.e., unoxidisable, sulphide by addition to the indicator monomer during the course of the titration : -SH + C2H,0CH=CH2 -+ C,H,OCH,CH,S- * For Part V of this series, see Analyst, 1974, 99, 82.@ SAC and the authors;GREENHOW AND LOO 361 In the present paper an analytical procedure is reported in which the acid content of a sample is determined by two catalytic thermometric methods, the acrylonitrile method described in Part 114 and the acetone-indicator method of Vaughan and S~ithenbank.~ With acrylonitrile as the end-point indicator thiol groups that undergo rapid addition to acrylonitrile are not determined, and the difference between the titration values obtained by using the two end-point indicators is taken as being a measure of the content of these thiol groups.This procedure offers an alternative to the two preferred methods, noted above, for the selective determination of the thiol group, and it has been evaluated for a range of alkyl, aryl and heterocyclic thiols and for some thioamides. EXPERIMENTAL REAGENTS- Acetone, propan-2-01 and methanol were analytical-reagent grade materials, and acrylonitrile, toluene and dimethylformamide were laboratory-reagent grade materials. All were dried over molecular sieve 4A before use.Other solvents and reagents, including the thiols, were laboratory-reagent grade materials and were used as received. Potassium hydroxide, 1.0 and 0.1 M solutions in propan-2-02-Standardise these solutions against benzoic acid (analytical-reagent grade) in acetone by the thermometric method using acetone as the end-point indicator. Tetra-n-butylammonium hydroxide, 0- 1 M solution in toluene - methanol-Laboratory- reagent grade material was used as received. Prepare 0.01 and 0.001 M solutions by adding appropriate volumes of toluene - propan-2-01 mixture (3 + 1) to the 0.1 M reagent. Standardise the solutions against benzoic acid (analytical-reagent grade) dissolved at 0.1 or 0.01 N concentration in dimethylformamide by the thermometric method with acrylonitrile as the end-point indicator.APPARATUS- ture, and a 10-ml titration flask with a magnetic stirrer, as described in Part 111.6 Use a motor-driven syringe to supply the titrant, a thermistor to measure the tempera- PROCEDURE A. ACETONE-INDICATOR METHOD- Use the procedure described by Vaughan and Swithenbank6 in the following manner. Add potassium hydroxide titrant solution at a rate of 0.1 ml min-l to a mixture of 1 ml of sample solution and 3 ml of acetone in the titration flask; use 1.0 mequiv of sample with the 1.0 M titrant and 0.1 mequiv of sample with the 0.1 M titrant. Record the temperature and titrant volume on a millivolt chart recorder (50 and 20-mV scales with the 1.0 and 0.1 M titrants, respectively) at a chart speed of 600 mm h-l.B. ACRYLONITRILE-INDICATOR METHOD- Use the procedure described in Part IV7 for the titration of acidic functions. Dissolve the sample in 1 ml of dimethylformamide and use 0.1 mequiv of sample with the 0-1 M tetra-n-butylammonium hydroxide titrant or correspondingly smaller amounts with the 0.01 and 0.001 M titrants; 1.0 or 0.1 M potassium hydroxide solution can also be used as a titrant. The end-point of the titration, when either indicator method is used, is located at the point where the tangent to the main heat rise leaves the curve at its lower temperature end.8 RESULTS AND DISCUSSION Table I lists the compounds titrated and the reaction stoicheiometries obtained by using the acetone and acrylonitrile-indicator methods. Some thioamides that can be titrated as acids are included in the table.Titration curves obtained in the determination of some of the thiols and thioamides arc shown in Figs. 1 and 2, respectively. It can be seen from Table I that the monofunctional alkyl and aryl thiols are not deter- mined by the acrylonitrile-indicator method. Thus, the addition of acrylonitrile to these compounds, i.e., cyanoethylation, must have proceeded to completion before the acid - base362 reaction could occur. GREENHOW AND LOO : IONIC POLYMERISATION FOR END-POINT [Analyst, Vol. 99 Cyanoethylation is catalysed by the alkaline titrant : OH- RSH + CH2=CHCN --+ RSCH2CHCN The carboxylic and phenolic groups of 2-mercaptobenzoic acid and salicylideneaminobenzene- 2-thiol are determined, and the difference between the titration value for each compound and the corresponding titration value obtained by using the acetone-indicator method, which determines the thiol function also, is a measure of the thiol content.TABLE I THIOLS AND THIOAMIDES TITRATED WITH 1.0 M POTASSIUM HYDROXIDE AND 0 . 1 M TETRA-n-BUTYLAMMONIUM HYDROXIDE SOLUTIONS WITH ACETONE AND ACRYLONITRILE, RESPECTIVELY, AS END-POINT INDICATORS Conditions: titrate 1 mequiv of thiol in 3 ml of acetone with 1.0 M potassium hydroxide solution by using the acetone-indicator method, and 0.1 mequiv of thiol in a mixture of 1 ml of dimethylformamide and 2 ml of acrylonitrile with 0.1 M tetra-n-butyl- ammonium hydroxide solution by using the acrylonitrile-indicator method Aliphatic thiols- Heptane-l-thiol (1 : 0.9 : 0) ; dodecane-l-thiol (1 : 0.9 : 0) ; 2,3-dimercaptopropan-l-o1 (2 : 1.7 : 0) ; and mercaptosuccinic acid (3 : 2.5 : 1.9) Toluene-1’-thiol (1 : 0.8 : 0) ; toluene-4-thiol (1 : 0.8 : 0) ; 4-aminobenzenethiol (1 : 0.65 : 0) ; 2-mercaptobenzoic acid (2 : 2 : 1) ; salicylideneaminobenzene-2-thiol (2 : 1.9 : 1) ; and pyridine- 2-thiol (1 : 1 : 0.18) 2-Mercaptothiazoline (1 : 1 : 0) ; 2-thiohydantoin (1 : 1 : 1) ; 4-hydroxypyrimidine-2-thiol (2 : 1 : 1) ; 4,6-dihydroxypyrimidine-2-thiol (3 : 2 : 1) ; purine-6-thiol (1 : 1.7 : 0.8) ; 2-mercapto- benzimidazole (1 : 1 : 0.3) ; 2-mercaptobenzoxazole (1 : 1 : 1) ; and 2-mercaptobenzothiazole Aromatic thiols- Heterocylic thioZs- (1: 1: 1) Thioamides- Thioacetamide (1 : 1 : 0.9*) ; thiourea (l(2) : 0.1 : 1*) ; thiocarbanilide (l(2) : 1 : 0.36 or 0.53*) ; dithiooxamide (rubeanic acid) (2 : 2 : 1) ; thiosemicarbazide (l(2) : 1.1 : 0.9) ; and diphenyl- thiocarbazone (dithizone) (l(2) : 1 : 0-8 or 1*) Figures in parentheses following the name of the compound denote the theoretical number of acidic functional groups in the molecule, the number of groups titrated by using the acetone- indicator method and the number of groups titrated by using the acrylonitrile-indicator method, respectively.* Values obtained in the titration of 1 mequiv of sample by using the acrylonitrile-indicator method and 1.0 M potassium hydroxide titrant. The content of thiols in mixtures with carboxylic acids and phenols can also be deter- mined by using the two indicators. In Fig. 3 calibration graphs are shown for mixtures of dodecane-l-thiol with benzoic acid and 3,5-xylenol with 2-mercaptothiazoline.The irregular shape of the calibration graph for the mixture containing dodecane-l-thiol is due to the low reaction stoicheiometry with this compound. It can be seen from Table I that the titration reactions with several of the thiols are sub-stoicheiometric, and it is necessary to use calibration graphs, or to allow for the sub- stoicheiometry in some other way, when determining these thiols by the suggested procedure. The small but finite titration value obtained when pyridine-2-thiol is determined by using the acrylonitrile-indicator method indicates that the rate of cyanoethylation is influ- enced by the heterocyclic ring. The titration values obtained with the other heterocyclic thiols examined have been found to depend on the position of the thiol group in the molecule, or the presence of reactive functional groups in addition to the thiol group, or both.Thus, while 2-mercaptothiazoline behaves on titration in the same way as do simple alkyl and aryl thiols, the corresponding benzo-derivative, 2-mercaptobenzothiazole does not. The thiol group in the latter compound can, apparently, be determined by either of the two catalytic end-point methods. This anomaly can be explained if it is assumed that, in solution in dimethylformamide, 2-mercaptobenzothiazole exists entirely in the thione t automeric form. In this form it is the acidic imido group and not the thiol group that is titrated. The reactionJune, 19741 INDICATION IN NON-AQUEOUS THERMOMETRIC TITRIMETRY. PART VI 363 stoicheiometry of 2-mercaptobenzoxazole can be similarly explained.This proposed reaction path presupposes that the imido group undergoes cyanoethylation more slowly than it undergoes neutralisation by the titrant. In contrast with its sulphur and oxygen analogues, 2-mercaptobenzimidazole was found to give a titration value corresponding to a sub-stoicheiometric reaction when it was deter- mined by using the acrylonitrile-indicator method. This would suggest that the compound is only partly in the thione form when in solution in dimethylformamide. 2-Thiohydantoin and 2-thiouracil (4-hydroxypyrimidine-2-thiol) were also found to be titrated as monobasic acids irrespective of the end-point indicator used in the thermometric titration.With these two compounds, however, there is the possibility that the hydroxyl group in the enolic form of the molecules rather than the imido group, is being titrated. c f 9 h J I I I I Titrant/rnl (1 division=lml) Fig. 1. Thermometric titration curves obtained in the determination of thiols by the acetone and acrylonitrile-indicator methods Compound/mg . . A, 205.5 B, 1.67 C, 105.9 D, 212.5 E, 7.8 F, 3.7 G, 6.4 H, 7.1 Solvent/ml . . K, 2 D, 1 K, 2 K, 1 D, 1 D, 1 D, 1 D, 1 Titrant/M . . P, 1-0 B, 0.01 P, 1.0 P, 1.0 B, 0.1 B, 0.1 B, 0.1 B, 0.1 Indicator method K P K K P P P P Compounds-A, dodecane-l-thiol; B, 2-mcrcaptobenzothiazole; C, 2,3-dimercaptopropan-l- 01 ; D, salicyliderieaminobenzene-2-thiol ; E, 2-thiobarbituric acid ; F, mercaptosuccinic acid; G, 2-thiouracil; and H, 2-thiohydantoin a* b C* d* e f g h Solvents-K, acetone ; and D, dimethylformamide Titrants-P, potassium hydroxide reagent ; and B, tetra-n-butylammonium hydroxide Indicator methods-K, acetone method using 3 ml of acetone; and P, acrylonitrile method * 1 division of temperature scale = 0.5 "C reagent using 2 ml of acrylonitrile Thiobarbituric acid (4,6-dihydroxypyrimidine-Z-thiol), when determined by the thermo- metric titration, functions either as a dibasic or monobasic acid, depending on whether the acetone or acrylonitrile method of end-point indication is used.Barbituric acid (2,4,6- trihydroxypyrimidine), in contrast, behaves as a dibasic acid whichever method of end-point indication is used, thereby supporting the hypothesis that thiol groups cannot be determined in the presence of acrylonitrile.Purine-6-thiol is similar to thiobarbituric acid with respect to the acidity it displays on catalytic thermometric titration, but the corresponding stoicheiometries, 1.7 and 0.8, are less well defined. Although the thioamides are formally classed as thiones, they can undergo tautomeric change to thienols. The stoicheiometries of the neutralisation reactions in which dithio-364 GREENHOW AND LOO : IONIC POLYMERISATION FOR END-POINT [ A ~ ~ d y s t , Vol. 99 oxamide and thiocarbanilide are determined by using the two methods of end-point indi- cation suggest that, in solution in dimethylformamide, the former compound has the structure S: C(NH,).C(SH) : NH, while the latter is partly in the thienolic form, C6H,NH.C(SH) : NH.- Thioacetamide, thiosemicarbazide and diphenylthiocarbazone (dithizone) would appear to retain the thione structure in solution in dimethylformamide, as a stoicheiometry of 1 : 1, or nearly 1 : 1, is obtained when either method of end-point indication is used.Thiourea behaves in an unusual way in the thermometric titration in that, while the simple 1 : 1 stoicheiometry is obtained by using the acrylonitrile indicator, the neutralisation proceeds to only a small extent when acetone is used to mark the end-point. Both thiourea and thioacetamide show an immediate temperature rise when they are titrated in the presence of the acrylonitrile end-point indicator, but the neutralisation then proceeds and an S-shaped titration curve results (Fig.2). The curves are similar in shape to those obtained in the titration of slightly soluble cat echo la mine^^ but, as thiourea and thioacetamide are readily soluble, the shape must be due to some other factor. A possible answer is that the initial addition of titrant causes a rearrangement of either the thioamide or an unstable addition compound of the thioamide and acrylonitrile. It should be noted (Table I) that, for these two amides, 1 . 0 ~ potassium hydroxide solution was used as the titrant instead of 0.1 M tetra-n-butylammonium hydroxide solution. With the latter titrant the titration curves were rounded and the end-point was difficult to assess. C6H5. Tit ran t/m I (1 division= 1 ml) Fig. 2. Thermometric titration curves obtained in the determination of thioamides by the acetone and acrylonitrile-indicator methods Compound/mg .. A,31.0 A,48-4 B,43.5 CJ4.1 C.Fi.96 D,278.0 D,17.2 E,3.2 E,36.8 F,83.7 F,117.4 Solvent/ml . . D , 1 D , 1 D , 1 K , 1 D , 1 K , l D , 1 D , l K , 2 D , 1 D , 2 Indicator method K P P K P K P P K K P carbazide ; and F, diphenylthiocarbazone a* b c d* e f* g h j k* m Titrant/M . . P, 1.0 P, 1.0 P, 1.0 P, 1.0 B, 0.1 P, 1.0 B, 0.1 P, 0.1 P, 1.0 P, 1.0 P, 1.0 Comfiounds-A, thioacetamide ; B, thiourea ; C, dithiooxamide ; D, thiocarbanilide ; E, thiosemi- Solvents-K, acetone ; and D, dimethylformamide Tztrants-P, potassium hydroxide reagent ; and B, tetra-n-butylammonium hydroxide reagent Ilzdicator methods-K, acetone method using 3 ml of acetone; and P, acrylonitrile method using 2 ml * 1 division of temperature scale = 0.5 "C of acrylonitrile When 1.0 M potassium hydroxide titrant was used in conjunction with the acrylonitrile method for the determination of thiocarbanilide and diphenylthiocarbazone, the stoicheio- metries of the neutralisation reactions differed from those obtained when the tetra-n-butyl-June, 19741 INDICATION IN NON-AQUEOUS THERMOMETRIC TITRIMETRY.PART VI 365 ammonium hydroxide reagent was used, and the possibility of steric hindrance influencing the stoicheiometry must be considered. The precision of the method for the determination of thiols in the presence of carboxylic acids and phenols has been determined for mixtures of dodecane-1-thiol and benzoic acid, and 2-mercaptothiazoline and 3,5-xylenol, by carrying out eight titrations on each mixture dissolved in dimethylformamide against 1.0 and 0-1 M potassium hydroxide titrants, respec- tively.The acetone and acrylonitrile-indicator methods were used alternately as the titrations were carried out. 0 50 100 Thiol, mol per cent. Fig. 3. Calibration graphs for the thermo- metric titration of mixtures of dodecane-l- thiol with benzoic acid, and 2-mercapto- thiazoline with 3,5-xylenol. (u), Dodecane-l- thiol plus benzoic acid, 1 mequiv dissolved in 2 ml of dimethylformamide; and (b), 2-mercapto- thiazoline plus 3,5-xylenol, 0.1 mequiv dissolved in 1 ml of dimethylformamide. 1.0 and 0.1 M potassium hydroxide titrants, respectively, were used in the determinations of mixtures (a) and * A and B are the titration values obtained by using the acetone-indicator method with 3 ml of acetone and the acrylonitrile-indicator method with 2 ml of acrylonitrile, respectively (b).Precisions were calculated in two ways: (a), from the differences between pairs of titration values taken in sequence; and (b), from the precisions of the groups of four titration values obtained by each method of end-point indication. In (b) the required coefficient of variation has been calculated as the square root of the sum of the squares of the coefficients of variation of the two groups of four titrations. Details of the experimental results and the calculated values are shown in Table 11. It can be seen that the direct determination of the coefficient of variation from the differences between pairs of titration values leads to lower values than by calculation using method (b) and there is, therefore, apparently some advantage in carrying out the titrations in the sequence proposed. The method is suitable for the determination of thiols in the presence of carboxylic acids and phenols at precisions of about 1 per cent., and in amounts down to 0.01 mequiv when 0.1 M titrants are used, provided that the thiol function is titrated when the acetone-indicator method is used, but is not titrated in the acrylonitrile-indicator method.This procedure requires that two titrations be carried out with each sample but, of course, gives the content of acidic compounds other than thiols as well as the thiol content. Values for the precisions of the titration values obtained in the direct determination of the thiol function in some other compounds are shown in Table 111, and it can be seen that these values are of the same order, Le., 0.32 to 2-2 per cent., as those obtained previously in acid - base titrations in which acrylonitrile was used as the end-point indi~ator.~ When this366 GREENHOW AND LOO TABLE I1 RESULTS FOR PRECISION FROM THE THERMOMETRIC TITRATION OF MIXTURES OF DODECANE-1-THIOL WITH BENZOIC ACID, AND 2-MERCAPTOTHIAZOLINE WITH 3,5-XYLENOL, AGAINST 1.0 AND 0.1 M SOLUTIONS OF POTASSIUM HYDROXIDE Titration resuZts- Method* .. .. .. .. . . A B A B A B A B Compoundslmgt (i) Dodecane-l-thiol, 81.2 Titre/ml 0.683 0.390 0.681 0.391 0.678 0.388 0.678 0.391 plus benzoic acid, 48.2 } A-B/ml 0-293 0.290 0.290 0.287 1.004 0.492 1.012 0.494 1.016 0.500 1.016 0.496 0.512 0.518 0.516 0.520 Coeficients of variation of the differences in titration values obtained by using methods A and B- Indirectly from the individual coefficients of variation of methods A and B, per cent.[method (b)] Directly from the differences in sequential titration values, per cent. [method (a)] Mixture (i) .. 0.99 1-19 Mixture (ii) . . 0.67 0.90 * A, acetone-indicator method ; B, acrylonitrile-indicator method. t Dissolved in 1 ml of dimethylformamide. end-point indicator is suitable for the direct determination, it is possible to useO.001~ titrants and to determine thiols in amounts down to about 0.0001 mequiv, although this is possible only if other acidic functions are absent. TABLE I11 RESULTS FOR PRECISION FROM THE THERMOMETRIC TITRATION OF THIOLS AND THIOAMIDES WITH 1.0 AND 0.1 M POTASSIUM HYDROXIDE AND 0.1 M TETRA-n- BUTYLAMMONIUM HYDROXIDE REAGENTS Amount/ Thiol or thioamide mg 2-Mercaptobenzothiazole 14.8 2-Mercaptobenzothiazole 0.17 2-Thiohydantoin .. . . 7.12 Mercaptosuccinic acid . . 7.40 2-Mercaptobenzoic acid . . 67.5 4-Aminobenzenethiol . . 163.5 Dithiooxamide . . . . 6.0 Titration method* P P P P A A P Titrantt / Mean B, 0.1 3 0.87 B, 0.001 4 1.31 B, 0.1 4 0.58 B, 0.1 3 0.94 K, 1.0 3 0.84 K, 1.0 3 0.88 B, 0.1 3 0.97 M n$ titrelml Standard deviation 0.004 0.029 0.003 0-003 0.007 0.005 0.005 Coefficient of variation, per cent. 0.46 2.20 0.52 0.32 0.83 0.57 0.50 * P, acrylonitrile indicator; A, acetone indicator. t B, tetra-n-butylammonium hydroxide reagent ; K, potassium hydroxide reagent. $ Number of determinations. 1. 2. 3. 4. 5. 6. 7. 8. REFERENCES Ryland, L. B., and Tamele, M. W., in Karchmer, J. H., Editor, “The Analytical Chemistry of Miller, J. W., in Snell, F. D., and Ettre, L. S., Editors, “Encyclopedia of Industrial Chemical Greenhow, E. J., Chem. 6% Ind., 1973, 697. Greenhow, E. J., and Spencer, L. E., Analyst, 1973, 98, 90. Vaughan, G. A., and Swithenbank, J. J. Ibid., 1965, 90, 594. Greenhow, E. J., and Spencer, L. E., Ibid., 1973, 98, 98. -- , Ibid., 1973, 98, 485. Vauihan, G. A., and Swithenbank, J. J., Ibid., 1970, 95, 890. NOTE-References 4, 6 and 7 are to Parts 11, I11 and IV of this series respectively. Sulfur and its Compounds,” Part I, Wiley-Interscience Ltd., London, 1970, p. 465. Analysis,” Volume 15, Interscience Publishers Ltd., London, 1972, p. 551. Received December 4th, 1973 Accepted January 1 lth, 1974