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ANALYTICAL CHEMISTRY
sulfonamides. The reliability of such potentiometric curves has as yet, however, not been convincingly demonstrated. ACKNOWLEDGMENT
The authors wish t o acknowledge gratefully the assistance of Lewis J. Throop who helped prepare some of the sulfonamides used in this work. They also wish to thank the R. P. Scherer Co., Gelatin Products Division, for supplying some of the sulfa drugs and E. I. du Pont de Nemours & Co., which donated the dimethylformamide used.
LITERATURE CITED
(1) (2) (3) (4) (5) (6)
(7) (8)
(9) (10)
Bell and Roblin, J . Am. Chem. SOC.,64, 2905 (1942). Fritz and Lisicki, ASAL. CHEM.,23, 589’(1951). Ivanova, Farmatsiya, No. 9-10, 28 (1940). Laporta and Mossini, Boll. SOC. ital. biol. sper., 16, 503 (1941). Marshall, J . Bid. Chem., 12, 263 (1937). Moss, Elliott, and Hall, ASAL. CHEM.,20, 784 (1948). Schulek and Rozsa, Z. anal. Chem., 122, 96 (1941). Schurman, J . Assoc. Ofic.A g r . Chemists, 24,810 (1941). Shriner and Fuson, “Systematic Identification of Organic Compounds,” 3rd ed., New York. John Wiley & Co., 1948. Tomicek, Collection Caechoslm. C h m . Communs.. 13, 116 (1948).
RECEIVED January 22, 1961.
Round- Table Discussion
Titrations in Nonaqueous Solutions Moderator: JOHN A. RIDDICK, Commercial Solvents Corp., Terre Haute, Ind. Panel: JAMES S . FRITZ’, Wayne University, Detroit, Mich. MARION MACLEAN DAVIS, National Bureau of Standards, Washington, D. C . E. F. HILLENBRAND, JR., Carbide and Carbon Chemicals Corp., South Charleston, W . V a . P. C . RIARKUNAS*, Commercial Solvents Corp., Terre Haute, Ind.
T
HE round table discussion of titrations in nonaqueous sol-.
vents gave a resume of the present status. The following topics were discussed by the several panel members: solvents and titrants, indicators, applications, accuracy, precision, interference, and limitations. SOLVEhTS AND TITRANTS
The general requirements for solvents to be used for titration in nonaqueous solvents are fairly simple. 1. The first one is fairly obvious: The solvent must be available a t a reasonable price. There are probably many solvents that are superior in certain respects, but they are not available commercially a t a reasonable pricr. 2. A solvent must dissolve the substance being titrated or the substance must dissolve when excess titrant is added. An excess of the titrant may be back-titrated as in aqueous systems. 3. The products of titration preferably should be soluble, and if a precipitate is formed it should be dense and crystalline and not gelatinous. 4. The solvent should not enter into side reactions. 5. The solvent should be such that the titration can be followed otentiometrically. There are no electrode systems available w%ch are satisfactory for following the reaction in solvents that have low dielectric constants. The behavior of the electrodes in nonaqueous systems needs a considerable amount of investigation. The requirements for titrants are about the same as for those in aqueous systems. They should react rapidly and quantitatively, with no side reactions with the substance being analyzed or with the solvent. They should be stable on standing without any appreciable change in the titer or the development of color. There are three types of titrations in aqueous solutions which also can be carried out in nonaqueous solutions. The first general type is the redox reartion. Only a few known redox analytical methods take place in nonaqueous solvents. S o t much 1% ork has been done in this field. The second type is volumetric precipitation and complex-forming reactions. Practically nothing has been done in strictly nonaqueous systems The third general type is acid-base titrations. Today this is the most important field because more work has been done to show the possibilities. If a base such as an aliphatic amine is fairly strong, it can be titrated satisfactorily in aqueous solution. Weaker bases, such as the pyridine type or aromatic amines, will not give a satisfac1 f
Present address, Iowa State College, Ames, Iowa. Present address, R J Reynolds Tobacco Co , Winston-Salem, K. C.
tory end point in water. The bases that are too x-eak to be titrated in water become much stronger bases when dissolved in such solvents as acetic acid. The strong acids in water-hydiochloric, nitric, sulfuric, perchloric, etc.-show decidedly different strengths in nonaqueous solutions. Perchloric acid is the btrongest knoan acid in acetic acid. Many compounds of different chemical t j pes ma>-be titrated in acetic acid using the titrant perchloric acid dissolved in acetic acid. I n some instances, a substance that cannot be titrated satisfactorilv by a titrant dissolved in the same solvent as the sample can be titrated if the titrant is dissolved in a different solvent. For example, hexamethylenetetramine cannot be titrated in acetic acid with perchloric acid dissolved in acetic acid, but if the perchloric acid is dissolved in p-dioxane the titration is satisfactory. The strength of weak acids is increased in solvents $5 hich have almost no acidic character or whose properties are basic. The titrant should be a strong base in the solvent system used. Two solvents have been proposed which exhibit outstanding properties for titration of substances that show extremely weak acidic properties in water, such as phenols: ethylenediamine and dimethylformamide. S o satisfactory indicator has been reported for ethylenediamine. The relative value of some of the titrants that have been proposed was discussed. IhDICATORS
Indicators were defined for this discussion to include electreod systems and organic compounds that change color a t definite acidities or basicities. In geneial, the electrode systems are the same as those used in water. Two years ago it was reportrd that conductometric titrations were superior to potentiometric a t least for fatty acids in soap mixtures. The most common electrode system in use today is the glass-calomel. The glass-antimony electrodes have been found most satisfactory for amine ‘solvents. I t seems likely that high frequency titrations ma\- espand in the field of titration in organic solvents. The organic compounds used as indicators are in general the ones that have been found suitable for use in water. Others have been reported, and there are many that appear to be promising in a group used as biological stains. A large percentage of the indicators that have found use belong to the triphenylmethane group. The remaining ones helong to various group types and do not find
V O L U M E 24, NO. 2, F E B R U A R Y 1 9 5 2
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too wide an application. The remainder of the discussion was very informative and concerned the theory of triphenylmethane indicators and their application to acid-base titrations in the several solvent systems. APPLICATIONS
The applications were limited to acid-base titrations. They are divided into two parts: the determination of substances that behave as bases in acidic solvents, and those that behave as acids in basic solvents. The substances that act as bases in acidic solvents can be divided into three general classes: primary, secondary, and tertiary amines; arnine salts of carboxylic acids; and metallic salts of carboxylic acids. Xadeau and Branchen demonstrated t h r titration of amino acids in acetic acid with 0.1 S perchloric acid in acetic acid. Blumrich and Bandel determined tertiary amines in a mixture of amines by acetylating the primary and secondary amines and titrating the unacetylated tertiary amine in acetic acid. Markunas and Riddick developed a method for the determination of choline salts in aqueous solutions. Pifer and JVollish have made an extensive study of the determination of amine, heterocyclic, and quaternary ammonium salts They have extended the application of titration in nonaqueous solutions to include chlorides of these salts. The fact that amine salts may be titrated in nonaqueous EOIUtions has led to a number of important applications. For instance, acid anhydrides can be determined by reaction with a measured excess of morpholine. Epoxy compounds may be determined in a similar manner by using different solvents and titrants. RIoss, Elliott, and Hall have shown that salicylic acid may be titrated in ethylenediamine. Katz has modified and adapted their method for the determination of acidic products of catalytic reactions, particularly for phenolic-type compounds. This procedure has formed the basis of a method for determining primary amines. The method has not been successfully applied for the determination of aromatic amines or ethanolamines. The combination of direct titration and titration of reaction products has been made the basis for determination of mixture of acetic acid and acetic anhydrides. ACCURACY, PRECISIOY, IYTERFERENCES, A h D LIMITATIONS
The precision, 01 reproducibility of results, and the accuracy are on the same order as for acid-base titrations in aqueous solutions. The accuracy was established by using primary standards such as potassium acid phthalate, sodium carbonate, and diphenylguanidine. A standardization of the titrant by two or more standards can be made as accurately as in aqueous solutions.
The analysis of highly purified substances with a titrant standardized by one of the accepted standards approached 100% within the accuracy of the method. Titrations using the best technique . accuracy and precision have been will agree to r k O . O f ~ ~ ~The demonstrat,ed by several workers in the field. Some of the major limit,ations are large volume changes in the titrant due to temperature changes, insolubility of sample in solvent, lack of variety of indicators, and unpredictable reactions of some samples with the titrant and the solvent. In a survey of the application of titration in acetic acid with perchloric acid in acetic acid as the titrant it was found that about 10% of approximately 600 compounds tested were insoluble in acetic acid. Some methods were prescribed for overcoming the insolubility difficulty. One of the substances causing the most interference is water. The water may be eliminated in most samples by the addition of acetic anhydride. However, some substances react with acetic anhydride, and to date no met,hod has been devised to eliminate the effect of water present in such materials. There have been several anomalous behaviors reported when titrating in nonaqueous solvents. A few of these were cited. REMARKS
I n the discussion following the panel presentation it u'as brought, out that acid-base reactions in nonaqueous solvents are not classified as such in Chemical Abstracts. This makes it difficult to survey the literature on t'he subject. The moderator was requested to confer with E. J. Crane to determine whether or not it would be feasible to have nonaqueous titrations listed separately in the subject index of Chemical Abstracts. Considerable time \vas devoted to the discussion of possible indicators. Davis explained the line of work that she and her coworkers were pursuing a t the National Bureau of Standards. She gave some excellent suggestions for additional investigation on indicators. The application of nonaqueous titrations as a control procedure in plant operation and as a means for analyzing the finished product was discussed. Three companies have adopted the use of titration in nonaqueous solvents and have found that they have been able to analyze certain products much more readilv. In has been greatly reduced. some cast's the cost of anal! ACKNOWLEDGMENT
The moderator wishes to express his appreciation to H. H. JI-iIlard for his assistance and advice in organizing this round table. I t was a pleasure to have S . F. Hall present. RECEIVED December 1 3 , 1931.
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