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Semimicrodetermination of carboxylic acids in the presence of large amounts of acyl chlorides
MICROCHEMICAL
JOURNAL
16, 38.5-390
Semimicrodetermination of Large
(197 1)
of Carboxylic Amounts WALTER
Lawrence
Radiation
Laboratory,
in the
Chlorides
Presence
1
SELIG
University
Received
Acids
of Acyl
of
February
California,
Livermore,
California
5, 1971
INTRODUCTION
The determination of small amounts of carboxylic acid was required at Lawrence Radiation Laboratory as a quality control measure in the production of 4,4-dinitropimeloyl chloride, C10C(CH2),C(N0,),(CH,),COC1. It was also desirable to determine the total acyl chloride (plus hydrogen chloride) content. The analysis of mixtures of acid chlorides, carboxylic acids, and hydrogen chloride has been described by several authors (I, 4-7). Markevich’s method (4) requires three separate titrations: one for the determination of mineral acid plus acyl chloride, another for the mineral acid plus organic acid, and a third for mineral acid plus organic acid plus acyl chloride. Patchornik and Rogozinski (5) present methods for the determination of milligram amounts of the various components of complex mixtures of organic and inorganic acids, acyl halides, anhydrides, and alkyl halides. To determine carboxylic acid by their method requires two separate titrations: one for the determination of total acid and another for mineral acid only. Stahl and Siggia (6, 7) have determined acyl chloride and free carboxylic acid in a single potentiometric titration after reaction with m-chloroaniline. Although Burger and Schulek (I ) consider their procedure cumbersome and often difficult to apply, we considered their method the simplest to meet our requirements. This paper describes improvements and modifications in the procedure of Stahl and Siggia (6, 7) to make it applicable to the semimicrodetermination of carboxylic acids in the presence of a large excess of acyl chloride, with possible adaptation to the microscale. 1 Work performed under the auspices of the U.S. Atomic Energy Commission.
385
386
SELIG MATERIALS
AND
METHODS
Equipment and Reagents
A pH meter, Corning Model 10 or similar instrument, glass-calomel electrode system (miniature combination electrode, Sargent S-30070-1 0 or equivalent). Magnetic stirrer with cooling plate. Buret, lo-ml, graduated in 0.05ml divisions. Sodium hydroxide, aqueous, 0.5, 0.1, and 0.05 N standard solutions. m-Chloroaniline, freshly distilled (may be used for two months). 1,4-Dioxane, analytical reagent. Procedure
For samples containing more than 3% RCOOH use up to 1 mM of -I- RCOOH and titrate with 0.1 N sodium hydroxide, or use up to 0.5 mM and titrate with 0.05 N sodium hydroxide. For samples containing less than 3 % RCOOH, the sample size may be increased up to 3 mM of RCOCI -I- RCOOH. These samples are titrated with 0.5 N sodium hydroxide to pH4 and finished by titrating with 0.05 N sodium hydroxide. Weigh the samples by difference from a glass-stoppered weighing bottle or weighing buret into a 150-ml beaker containing 40 ml of p-dioxane plus 1 ml of m-chloroaniline. Add 5 to 10 ml of distilled water and stir the mixture to dissolve the amine hydrochloride. Titrate potentiometrically with sodium hydroxide of the required normality (see above paragraph) using a pH meter. The end points may be determined from a titration curve or by calculation (3). For the latter method it is expedient to add the titrant in O.lO-ml increments in the end point regions. The neutralization of the amine hydrochloride occurs between pH 4 and 6, and of the carboxylic acid between pH 8 and 12. Run a reagent blank (omitting the sample) and apply the appropriate correction to the second (carboxylic acid) end point. If the amount of free hydrochloric acid is required it can be determined on a separate sample by the method used by Stahl and Siggia (6, 7). RCOCI
RESULTS
AND
DISCUSSION
Stahl and Siggia’s (6, 7) sequential titration method for the determination of acyl chloride (plus HCl) and carboxylic acid is based on the amidation of the acyl chloride with m-chloroaniline: RCOCl + 2ClC,,H,NH, + RCONHC,,H,CI t ClC,;H,NH, . HCl,
( 1)
where R = aliphatic or aromatic. Stahl and Siggia suggest a 5-minute period prior to titration to ensure complete reaction, but we found the amidation reaction to be instantaneous. Since the amine hydrochloride
DETERMINATION
OF ACIDS
387
formed is only slightly soluble in organic solvents, a small amount of water (lo-20%) must be added to ensure its solution. Our attempts to duplicate Stahl and Siggia’s results using mixtures of benzoyl chloride and benzoic acid produced poorly defined end points for the neutralization of the amine hydrochloride while acceptable end points were obtained for the neutralization of the acid. This is due to the high dielectric constant of their titration medium, acetone. According to Huber (2), the sharpness of the first potentionmetric break increases with decreasing dielectric constant of the solvent mixture, since the acid is the positively charged chloroanilinium ion. We have, therefore, used a medium consisting of 80-90% p-dioxane. A typical titration curve obtained during the analysis of a mixture of benzoyl chloride and benzoic acid is shown in Fig. 1. Neutralization of the amine hydrochloride
FIG. 1. Titration 80% p-dioxane.
of 0.425 mM benzoyl chloride and 0.22 mM benzoic acid in
388
SELJG
produced by the reaction with m-chloroaniline (Eq. 1) occurs between pH 4 and 6. The acid is neutralized between pH 8 and 12. The potentiometric break for the neutralization of the amine hydrochloride is suppressedin the presence of more than 20% water. As the amount of carboxylic acid in the sample decreases so, of course, does the separatio’n between the potentiometric breaks. This separation should be at least 0.2 ml of titrant for quantitation of the carboxylic acid. Therefore, the minimum amount of acid which can be determined with 0.1 N sodium hydroxide is 0.02 mA4, while 0.01 mM of carboxylic acid can be determined with 0.05 N titrant. To determine even smaller amounts of acid (less than 0.3%) one must, therefore, increase the sample size. In order to obtain satisfactory potentiometric breaks for the amine hydrochloride the total titration should not exceed 10 ml. This is readily achieved by using two titrants, 0.5 and 0.05 N TABLE ANALYSIS
OF SYNTHETIC
Added (7;)
MIXTURES
1
OF BENZOYL
CHLORIDE
AND BENZOIC
ACID
Q
Found (r/;,)
RCOCI
RCOOH
RCOCI
RCOOH
Error (‘A)
61.70 69.05 86.65 89.81 92.40 94.38 97.11
38.30 30.95 13.35 10.19 7.60 5.62 2.89
61.60 68.85 86.72 89.83 92.64 94.44 96.66
38.40 31.15 13.28 10.17 7.36 5.56 3.34
0.10 0.20 0.07 0.02 0.24 0.06 0.45
67.37 89.12 94.22 96.47 97.46
32.63 10.88 5.78 3.53 2.54
66.97 88.92 94.11 96.43 97.17
33.03 11.08 5.89 3.57 2.83
0.40 0.20 0.11 0.04 0.29
98.39 98.44 99.28 99.62 99.66
1.61 1.56 0.72 0.38 0.34
98.26 98.26 99.18 99.57 99.62
1.74 1.74 0.82 0.43 0.38
0.13 0.18 0.10 0.05 0.04
Titrant
0.1 N sodium hydroxide
Mean error = 0.16
0.05 N sodium hydroxide Mean error = 0.21 0.5 N and 0.05 N sodium hydroxide Mean error = 0.10
a mA4 Benzoyl chloride is equivalent to mM m-chloroaniline hydrochloride titrated. A sample calculation is given for the first set of data: mA4 benzoyl chloride found: 0.26546; mg benzoyl chloride found: 37.32; mA4 benzoic acid found: 0.19046; mg benzoic acid found: 23.26; and mg total found: 60.58. Hence, percentage of benzoyl chloride found: 61.60; percentage of benzoic acid found: 38.40.
DETERMINATION
389
OF ACIDS
sodium hydroxide. By this method, we have determined as little as 0.3 %of carboxylic acid in the presence of 99.7% acyl chloride. These results are shown in Table 1 for mixtures of benzoic acid and benzoyl chloride. Our procedure can probably be adapted to the microscale, using 0.5 and 0.01 N sodium hydroxide. With these titrants it should be possible ‘to determine 0.002 mM of carboxylic acid (0.06%) in a sample of 3 mM of RCOCl f RCOOH. Results for the analysis of various samples of 4,4-dinitropimeloyl chloride are presented in Table 2, and the analysis of a commercial sample of 3,5-dinitrobenzoyl chloride in Table 3. Preliminary experiments have shown that the following alternate approach to the determination of carboxylic acids plus acyl chlorides may be used: After reaction of the acyl chloride with m-chloroaniline (Eq. 1) the amine hydrochloride is titrated in 80% acetone with silver nitrate: ClC,,H,NH, * HCl + AgNO,, + AgCl + ClC,H,NH,
l
HNO,.
(2)
The mixture, containing the acid and nitrate salt, is then titrated with standard sodium hydroxide to yield m-chloroaniline and the sodium salt of the carboxylic acid according to Eq. (3) ClC,H,NH,
l
HNO:, t RCOOH + 2NaOH + RCOONa + ClC,H,NH, + NaNO, + 2H,O,
(3)
and the carboxylic acid is calculated by the difference.
TABLE 2 ANALYSIS OF +I-DINITROPIMELOYL
CHLORIDE
Sample -
No.
RCOCI (7;)
RCOOH ($;)
Remarks
1
94.65 95.16 95.19 95.00 82.6 84.4 82.4 84.6 84.1 83.6 94.63 95.00 95.16 94.93
2.43 2.34 2.50 2.42 12.25 11.00 12.55 11.19 11.00 11.60 3.93 3.64 3.49 3.69
Titrated with 0.05 N NaOH, sample size 60-85 mg.
z 2
x 3 x
Titrated with 0.05 N NaOH, sample size 50-90 mg. Lumps present in sample; hence probably nonhomogeneous.
Titrated to pH 4 with 0.5 N NaOH, then with 0.05 N NaOH. Sample size 200300 mg.
390
SELIG TABLE 3 ANALYSIS
x
OF 3,5-DINITROBENZOYL
RCOCl (%)
RCOOH (yO)
95.52
2.41
94.86 95.43 95.27
3.01 2.61 2.68
CHLORIDE
(EASTMAN)
Titrated to pH 4 with 0.5 N NaOH, followed by titration with 0.05 N NaOH.
SUMMARY A procedure for the semimicrodetermination of carboxylic acids in the presence of a large excess of acyl chloride is described. Acyl chloride is first reacted with n-chloroaniline. The m-chloroaniline hydrochloride and carboxylic acid are then determined sequentially by potentiometric titration with sodium hydroxide. Titrations are performed in 80-90% p-dioxane to enhance the potentiometric breaks. With 0.05 N sodium hydroxide, as little as 0.01 mM of carboxylic acid can be determined. ACKNOWLEDGMENT The writer is indebted to Professor Sidney Siggia of the University of Connecticut for helpful suggestions. REFERENCES 1. Burger, K., and Schulek, E., Determination of the actual content of acid chloride in the chlorides of carboxylic acids. Tulanta 4, 120-125 (1960). 2. Huber, ‘W., “Titrations in Nonaqueous Solvents,” p. 202. Academic Press, New York, 1967. Chemistry,” 2nd ed., p. 91. Interscience, 3. Lingane, J. J., “Electroanalytical New York, 1958. 4. Markevich, V. S., Analysis of mixtures of aliphatic acid chlorides, organic acids, and free mineral acid. Zavod. Lab. 34, 1064-1065 (1968). 5. Patchornik, A., and Rogozinski, S. E., Nonaqueous titration of organic acids, anhydrides, acyl halides, strong inorganic acids, and reactive alkyl halides in various mixtures. Anal. Chem. 31, 985-989 (1959). 6. Siggia, S., “Quantitative Organic Analysis via Functional Groups,” 3rd ed., pp. 179-187. Wiley, New York, 1967. 7. Stahl, C. R., and Siggia, S., Analysis of acid chlorides containing free carboxylic acid and hydrogen chloride. Anal. Chem. 28, 1971-1973 (1956).
JOURNAL
16, 38.5-390
Semimicrodetermination of Large
(197 1)
of Carboxylic Amounts WALTER
Lawrence
Radiation
Laboratory,
in the
Chlorides
Presence
1
SELIG
University
Received
Acids
of Acyl
of
February
California,
Livermore,
California
5, 1971
INTRODUCTION
The determination of small amounts of carboxylic acid was required at Lawrence Radiation Laboratory as a quality control measure in the production of 4,4-dinitropimeloyl chloride, C10C(CH2),C(N0,),(CH,),COC1. It was also desirable to determine the total acyl chloride (plus hydrogen chloride) content. The analysis of mixtures of acid chlorides, carboxylic acids, and hydrogen chloride has been described by several authors (I, 4-7). Markevich’s method (4) requires three separate titrations: one for the determination of mineral acid plus acyl chloride, another for the mineral acid plus organic acid, and a third for mineral acid plus organic acid plus acyl chloride. Patchornik and Rogozinski (5) present methods for the determination of milligram amounts of the various components of complex mixtures of organic and inorganic acids, acyl halides, anhydrides, and alkyl halides. To determine carboxylic acid by their method requires two separate titrations: one for the determination of total acid and another for mineral acid only. Stahl and Siggia (6, 7) have determined acyl chloride and free carboxylic acid in a single potentiometric titration after reaction with m-chloroaniline. Although Burger and Schulek (I ) consider their procedure cumbersome and often difficult to apply, we considered their method the simplest to meet our requirements. This paper describes improvements and modifications in the procedure of Stahl and Siggia (6, 7) to make it applicable to the semimicrodetermination of carboxylic acids in the presence of a large excess of acyl chloride, with possible adaptation to the microscale. 1 Work performed under the auspices of the U.S. Atomic Energy Commission.
385
386
SELIG MATERIALS
AND
METHODS
Equipment and Reagents
A pH meter, Corning Model 10 or similar instrument, glass-calomel electrode system (miniature combination electrode, Sargent S-30070-1 0 or equivalent). Magnetic stirrer with cooling plate. Buret, lo-ml, graduated in 0.05ml divisions. Sodium hydroxide, aqueous, 0.5, 0.1, and 0.05 N standard solutions. m-Chloroaniline, freshly distilled (may be used for two months). 1,4-Dioxane, analytical reagent. Procedure
For samples containing more than 3% RCOOH use up to 1 mM of -I- RCOOH and titrate with 0.1 N sodium hydroxide, or use up to 0.5 mM and titrate with 0.05 N sodium hydroxide. For samples containing less than 3 % RCOOH, the sample size may be increased up to 3 mM of RCOCI -I- RCOOH. These samples are titrated with 0.5 N sodium hydroxide to pH4 and finished by titrating with 0.05 N sodium hydroxide. Weigh the samples by difference from a glass-stoppered weighing bottle or weighing buret into a 150-ml beaker containing 40 ml of p-dioxane plus 1 ml of m-chloroaniline. Add 5 to 10 ml of distilled water and stir the mixture to dissolve the amine hydrochloride. Titrate potentiometrically with sodium hydroxide of the required normality (see above paragraph) using a pH meter. The end points may be determined from a titration curve or by calculation (3). For the latter method it is expedient to add the titrant in O.lO-ml increments in the end point regions. The neutralization of the amine hydrochloride occurs between pH 4 and 6, and of the carboxylic acid between pH 8 and 12. Run a reagent blank (omitting the sample) and apply the appropriate correction to the second (carboxylic acid) end point. If the amount of free hydrochloric acid is required it can be determined on a separate sample by the method used by Stahl and Siggia (6, 7). RCOCI
RESULTS
AND
DISCUSSION
Stahl and Siggia’s (6, 7) sequential titration method for the determination of acyl chloride (plus HCl) and carboxylic acid is based on the amidation of the acyl chloride with m-chloroaniline: RCOCl + 2ClC,,H,NH, + RCONHC,,H,CI t ClC,;H,NH, . HCl,
( 1)
where R = aliphatic or aromatic. Stahl and Siggia suggest a 5-minute period prior to titration to ensure complete reaction, but we found the amidation reaction to be instantaneous. Since the amine hydrochloride
DETERMINATION
OF ACIDS
387
formed is only slightly soluble in organic solvents, a small amount of water (lo-20%) must be added to ensure its solution. Our attempts to duplicate Stahl and Siggia’s results using mixtures of benzoyl chloride and benzoic acid produced poorly defined end points for the neutralization of the amine hydrochloride while acceptable end points were obtained for the neutralization of the acid. This is due to the high dielectric constant of their titration medium, acetone. According to Huber (2), the sharpness of the first potentionmetric break increases with decreasing dielectric constant of the solvent mixture, since the acid is the positively charged chloroanilinium ion. We have, therefore, used a medium consisting of 80-90% p-dioxane. A typical titration curve obtained during the analysis of a mixture of benzoyl chloride and benzoic acid is shown in Fig. 1. Neutralization of the amine hydrochloride
FIG. 1. Titration 80% p-dioxane.
of 0.425 mM benzoyl chloride and 0.22 mM benzoic acid in
388
SELJG
produced by the reaction with m-chloroaniline (Eq. 1) occurs between pH 4 and 6. The acid is neutralized between pH 8 and 12. The potentiometric break for the neutralization of the amine hydrochloride is suppressedin the presence of more than 20% water. As the amount of carboxylic acid in the sample decreases so, of course, does the separatio’n between the potentiometric breaks. This separation should be at least 0.2 ml of titrant for quantitation of the carboxylic acid. Therefore, the minimum amount of acid which can be determined with 0.1 N sodium hydroxide is 0.02 mA4, while 0.01 mM of carboxylic acid can be determined with 0.05 N titrant. To determine even smaller amounts of acid (less than 0.3%) one must, therefore, increase the sample size. In order to obtain satisfactory potentiometric breaks for the amine hydrochloride the total titration should not exceed 10 ml. This is readily achieved by using two titrants, 0.5 and 0.05 N TABLE ANALYSIS
OF SYNTHETIC
Added (7;)
MIXTURES
1
OF BENZOYL
CHLORIDE
AND BENZOIC
ACID
Q
Found (r/;,)
RCOCI
RCOOH
RCOCI
RCOOH
Error (‘A)
61.70 69.05 86.65 89.81 92.40 94.38 97.11
38.30 30.95 13.35 10.19 7.60 5.62 2.89
61.60 68.85 86.72 89.83 92.64 94.44 96.66
38.40 31.15 13.28 10.17 7.36 5.56 3.34
0.10 0.20 0.07 0.02 0.24 0.06 0.45
67.37 89.12 94.22 96.47 97.46
32.63 10.88 5.78 3.53 2.54
66.97 88.92 94.11 96.43 97.17
33.03 11.08 5.89 3.57 2.83
0.40 0.20 0.11 0.04 0.29
98.39 98.44 99.28 99.62 99.66
1.61 1.56 0.72 0.38 0.34
98.26 98.26 99.18 99.57 99.62
1.74 1.74 0.82 0.43 0.38
0.13 0.18 0.10 0.05 0.04
Titrant
0.1 N sodium hydroxide
Mean error = 0.16
0.05 N sodium hydroxide Mean error = 0.21 0.5 N and 0.05 N sodium hydroxide Mean error = 0.10
a mA4 Benzoyl chloride is equivalent to mM m-chloroaniline hydrochloride titrated. A sample calculation is given for the first set of data: mA4 benzoyl chloride found: 0.26546; mg benzoyl chloride found: 37.32; mA4 benzoic acid found: 0.19046; mg benzoic acid found: 23.26; and mg total found: 60.58. Hence, percentage of benzoyl chloride found: 61.60; percentage of benzoic acid found: 38.40.
DETERMINATION
389
OF ACIDS
sodium hydroxide. By this method, we have determined as little as 0.3 %of carboxylic acid in the presence of 99.7% acyl chloride. These results are shown in Table 1 for mixtures of benzoic acid and benzoyl chloride. Our procedure can probably be adapted to the microscale, using 0.5 and 0.01 N sodium hydroxide. With these titrants it should be possible ‘to determine 0.002 mM of carboxylic acid (0.06%) in a sample of 3 mM of RCOCl f RCOOH. Results for the analysis of various samples of 4,4-dinitropimeloyl chloride are presented in Table 2, and the analysis of a commercial sample of 3,5-dinitrobenzoyl chloride in Table 3. Preliminary experiments have shown that the following alternate approach to the determination of carboxylic acids plus acyl chlorides may be used: After reaction of the acyl chloride with m-chloroaniline (Eq. 1) the amine hydrochloride is titrated in 80% acetone with silver nitrate: ClC,,H,NH, * HCl + AgNO,, + AgCl + ClC,H,NH,
l
HNO,.
(2)
The mixture, containing the acid and nitrate salt, is then titrated with standard sodium hydroxide to yield m-chloroaniline and the sodium salt of the carboxylic acid according to Eq. (3) ClC,H,NH,
l
HNO:, t RCOOH + 2NaOH + RCOONa + ClC,H,NH, + NaNO, + 2H,O,
(3)
and the carboxylic acid is calculated by the difference.
TABLE 2 ANALYSIS OF +I-DINITROPIMELOYL
CHLORIDE
Sample -
No.
RCOCI (7;)
RCOOH ($;)
Remarks
1
94.65 95.16 95.19 95.00 82.6 84.4 82.4 84.6 84.1 83.6 94.63 95.00 95.16 94.93
2.43 2.34 2.50 2.42 12.25 11.00 12.55 11.19 11.00 11.60 3.93 3.64 3.49 3.69
Titrated with 0.05 N NaOH, sample size 60-85 mg.
z 2
x 3 x
Titrated with 0.05 N NaOH, sample size 50-90 mg. Lumps present in sample; hence probably nonhomogeneous.
Titrated to pH 4 with 0.5 N NaOH, then with 0.05 N NaOH. Sample size 200300 mg.
390
SELIG TABLE 3 ANALYSIS
x
OF 3,5-DINITROBENZOYL
RCOCl (%)
RCOOH (yO)
95.52
2.41
94.86 95.43 95.27
3.01 2.61 2.68
CHLORIDE
(EASTMAN)
Titrated to pH 4 with 0.5 N NaOH, followed by titration with 0.05 N NaOH.
SUMMARY A procedure for the semimicrodetermination of carboxylic acids in the presence of a large excess of acyl chloride is described. Acyl chloride is first reacted with n-chloroaniline. The m-chloroaniline hydrochloride and carboxylic acid are then determined sequentially by potentiometric titration with sodium hydroxide. Titrations are performed in 80-90% p-dioxane to enhance the potentiometric breaks. With 0.05 N sodium hydroxide, as little as 0.01 mM of carboxylic acid can be determined. ACKNOWLEDGMENT The writer is indebted to Professor Sidney Siggia of the University of Connecticut for helpful suggestions. REFERENCES 1. Burger, K., and Schulek, E., Determination of the actual content of acid chloride in the chlorides of carboxylic acids. Tulanta 4, 120-125 (1960). 2. Huber, ‘W., “Titrations in Nonaqueous Solvents,” p. 202. Academic Press, New York, 1967. Chemistry,” 2nd ed., p. 91. Interscience, 3. Lingane, J. J., “Electroanalytical New York, 1958. 4. Markevich, V. S., Analysis of mixtures of aliphatic acid chlorides, organic acids, and free mineral acid. Zavod. Lab. 34, 1064-1065 (1968). 5. Patchornik, A., and Rogozinski, S. E., Nonaqueous titration of organic acids, anhydrides, acyl halides, strong inorganic acids, and reactive alkyl halides in various mixtures. Anal. Chem. 31, 985-989 (1959). 6. Siggia, S., “Quantitative Organic Analysis via Functional Groups,” 3rd ed., pp. 179-187. Wiley, New York, 1967. 7. Stahl, C. R., and Siggia, S., Analysis of acid chlorides containing free carboxylic acid and hydrogen chloride. Anal. Chem. 28, 1971-1973 (1956).