[CONTRIBUTION FROM THE CHEMICAL LABORATORY, HARVARD UNIVERSITY~

THE DETERMINATION OF COMPOSITION OF MIXTURES OF

ACIDS

ARTHUR MICHAEL AND HOWARD 8. MASON",*

Received December 7. 19@

CY-BROMO-CY-METHYL- AND a-BROMO-,%METHYL-SUCCINIC

In the course of a study of the addition of hydrogen bromide to substituted a,@-unsaturated acids, a method for the determination of composition of a-bromo-a-methyl- and a-bromo-@-methyl-succinic acids was required. While i t m-as found possible to effect qualitative separation of these isomeric compounds by differential adsorption upon activated charcoal, and by systematic crystalliza- tion, the quantitative analysis of their mixtures proved more difficult. The ultraviolet absorption spectra of these substances provided no basis for differen- tiation (Figure 1) nor did the behavior of their salts in neutral solutions or in buffered solutions of low alkalinity under many conditions. However, the rates of hydrolysis of t,he secondary and tertiary bromo acids in unbuffered alkali were suffxiently different so that under rigidly controlled conditions significant and constant differences in pH a t t,he end of a fixed period could be observed potentiometrically. Composition-pH curves constructed from these d a h (Figure 2) were found accurate to about &2.5a/,.

ESPERIIMENTAL

Melting, points and boiling poiuts are corrected values. u-BromtT-a-methylsuccinic acid. Citraconic acid was prepared by the method of Shriner,

Ford, and Roll (1). The product melted a t 92", comparing favorably with the reported melting point 92-93'. By the addition of hydrogen bromide t o this substance according t o the diractions of Autenrieth and Pretzel1 (2) a-bromo-a-methylsuccinic acid was ob- tained; i t melted a t 145.5-149.2' with decomposition. Lutz (3) reports the value 149'.

a-Bromo-6-niethylsuccinic acid was synthesized from propane-1 , 1 ,2-tricarboxylic acid and aqueous bromine according t o the directions of 13ischoff and Gutzeit (4 ) . The steps leading to the tricarboxylic acid started with propionic acid and proceeded by D series of standard Itechniques for bromination, esterification, malonation, and hydrolysis. The product melted a t 203-204", comparing favorably with the melting point 203.5' reported by Bischoff and Gutzeit. Repeated attempts t o isolate the unknown diastereomer from the products of this synthesis were unsuccessful, as Mere those attempts with the hydrogen broinide adducts of citraconic acid.

The determination of the composition of mixtures of a-bromo-a-methylsuccinic and a-bromo-6-methylsuccinic acids depended upon the difference in the rates of reaction of the isomers wiith alkali. In order to obtain optimal accuracy, the following procedure was used. Ex:tctly 0.100 gram of the bromo acids was weighed out (in duplicate) and dissolved in 113 cc. of distilled water, previously boiled. Into this was run 9.70 cc. of 0.1060 N sodium hydroxide froni a microburette supplied from an alkali-stable stock bottle suitably pro-

1 Present address: The National Institute of Health, Bethesda, Maryland. 2 This research was initiated by the late Professor Arthur Michael. The statement>s

contained in this report, and the responsibility for them, are t,hose of the junior author. 393

I I I I I I I 'i" I

A

\

\ \

~ \

9400 2500 2600 2700 2:OO 2900 3000 3100 32 WAVE LENGTH IN ANGSTROM UNITS

.O I

FIGURE 1. ABSORPTION SPECTRA OF ~-BROMO-~-METHYLSUCCINIC ACID (DOTTED LINE) AND ~-BROMO-~-METHYLSUCCINIC ACID (SOLID LINE), 0.01 N SOLUTION IN 0.01 N AQUEOUS

HYDROCHLORIC ACID

11.0

10.0

v) W

2 5

:: f i

k. 9.0 0

z W

c 4

I

n

P

8.0

7.0 I I 50 60 70 80 90 I O 0

I 0 I O 20 30 40

PERCENT 4-BROM-.(- METHYLSVCCINIC ACID

FIGURE 2. THE RELATIONSHIP BETWEEN THE COMPOSITION OF MIXTURES OF U-BROMO-a-METHYL- AND U-BROMO-8-METHYL-SUCCINIC ACIDS AND THE pH

394 O F THEIR ALKALINE SOLUTIONS AT THE END O F FORTY MINUTES

DETERMINATION OF BROMOMETHYLSUCCINIC ACIDS 395

tected. The rate of decrease of pH of the resulting solution a t 27" was measured; timing commenced when 8.94 cc. of alkali had been added, and the final reading taken a t 40minutes. All i3olutions were kept in the thermostat previous t o use. The pH was followed by a glass electrode (:Coleman Electric Co., model 3D) ; the calomel half-cell was also thermostatted a t 27", connected to the reaction vessel through a sintered-glass potassium chloride bridge which was flushed from a stock bottle after each determination.

SUMMARY

A method for the determination of composition of a-bromo-a-methyl- and a-bromo-6-methyl-succinic acids has been developed and found accurate to about 3~2.5%.

CAMBBII)GE, MASEL

REFERENCES (1) SHRINZB, FORD, AND ROLL, Org. Syntheses, 11, 28 (1931). (2) AUTEXRIETH AND PRETZELL, Ber., 36, 1271 (1903). (3) LUTZ, Ber., 36, 4370 (1902). (4) BISCHOFF AND GUTZEIT, Ber . , 14,616 (1881); 23, 1928 (1890).