In the Laboratory edited by
The Microscale Laboratory
Arden P. Zipp SUNY-Cortland Cortland, NY 13045
A Microscale Synthesis of the Diastereomers of 2,3-Dibromosuccinic Acid John Tomsho, James McKee, and Murray Zanger Department of Chemistry and Biochemistry, University of the Sciences in Philadelphia, 600 South 43rd St., Philadelphia, PA 19104-4495
The experiment described below is a microscale adaptation of a popular synthesis for the undergraduate laboratory which illustrates both bromination of a double bond and diastereoisomerism. The stereospecific (trans) addition of halogens to alkenes is one of the benchmark reactions in organic chemistry and is discussed in all major organic texts. A typical example used in several lab manuals (1) involves the addition of bromine to maleic and fumaric acids (eqs 1, 2). The diastereomeric products formed are remarkable in that their melting points differ by some 90 °C. Their solubilities are also totally different: the racemic isomer is very soluble in cold water, whereas the meso form can be recrystallized from water. H C H
Br
COOH +
C COOH
H
COOH
H
COOH
Br2 Br
racemic-dibromosuccinic acid
maleic acid
Br
HOOC C H
(1)
H
HOOC +
H
Br2 H
C
COOH
(2)
Br
COOH
fumaric acid
meso-dibromosuccinic acid
meso -2,3-Dibromosuccinic Acid (2) Procedure A stock solution of bromine (7.75 g) and potassium bromide (6.25 g) in 10 mL of water is prepared in a 25-mL volumetric flask and diluted to the mark with water. CAUTION: Bromine is moderately toxic by vapor inhalation and poisonous by ingestion. Its vapor is extremely corrosive. It should be used in a good fume hood and protective gloves should be worn when handling it (3a). Fumaric acid (200 mg) is weighed into a 25-mL Erlenmeyer flask and 2.5 mL of the stock bromine solution1 is added. CAUTION: Fumaric acid is mildly toxic by ingestion and is a skin and eye irritant (3b). The contents of the flask are mixed and the flask is placed in a boiling water bath. Within a minute some bromine vapor is expelled and a clear orange solution forms. After 6-10 minutes a white precipitate forms and the solution color fades to a light yellow. Heating is continued for a total of 10-12 minutes. If the solution becomes colorless, a few drops of the stock solution are added and the heating is continued for several more minutes. The flask is removed from the bath and
cooled in an ice-water bath. The mixture is vacuum filtered and the product is washed with ice water and then dried in an oven at 100 °C. If desired, the product can be recrystallized from water. Without recrystallization, the meso-2,3dibromosuccinic acid weighed between 280 and 360 mg (51– 62% yield) and had a melting point of 261–266 °C (lit. 255– 256 °C; c.a. 280 °C). The IR spectrum should match that of an authentic sample of meso-2,3-dibromosuccinic acid.
racemic-2,3-Dibromosuccinic Acid (4 ) Procedure CAUTION: All equipment and reagents must be dry! 2 Maleic acid (200 mg) is weighed into a test tube and 2 mL of anhydrous ether is added. CAUTION: Maleic acid is moderately toxic by ingestion and can be absorbed through the skin. It is a severe skin and eye irritant. It should be handled carefully avoiding skin contact or inhalation (3c). Ethyl ether is moderately toxic by ingestion and mildly toxic by inhalation. It is a very dangerous fire and explosion hazard. It forms explosive peroxides when exposed to air. All possible sources of ignition should be removed from the area where ether is being used (3d). On a balance, 310 mg of bromine3 is added dropwise to the test tube and the contents are mixed thoroughly. A small exotherm will result, and as the ether gently boils the solid will slowly dissolve. If any solid either remains or forms, it indicates that the reaction mixture was contaminated with water. Should this occur, it is usually best to abort the reaction, dispose of the reactants properly, and redo the experiment. If no precipitate forms, the solution is allowed to sit for 10– 15 minutes; the deep orange color should fade to pale orange or yellow. The ether is removed by placing the test tube in a beaker of warm water in a good fume hood, leaving a pale orange or yellow solid. The test tube is cooled in an ice-water bath for a few minutes, petroleum ether is added, and a glass rod is used to break up the solid. The solid is vacuum filtered, rinsed with a few milliliters of petroleum ether, and dried in air. Yields of racemic-2,3-dibromosuccinic acid range from 440 to 450 mg (95–96%), with a melting point of 168–170 °C (lit. 166-167 °C). Notes 1. The synthesis of meso-2,3-dibromosuccinic acid by adding bromine to a suspension of fumaric acid in boiling water (2) gives very poor yields on the microscale level. The yield is raised by adding KBr to complex the bromine.
JChemEd.chem.wisc.edu • Vol. 76 No. 1 January 1999 • Journal of Chemical Education
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In the Laboratory 2. Contamination of the reactants by water produces hydrogen bromide, which rapidly isomerizes the maleic acid to the less reactive and less soluble fumaric acid. The product isolated in these cases consists of mixtures of the product (racemic-dibromosuccinic acid) and fumaric acid. 3. Pyridinium hydrobromide perbromide (5) as a safer and more conveniently handled alternative to liquid bromine is also cited as possessing greater stereospecificity than bromine. For these reactions, however, the products are contaminated with pyridine hydrobromide and are not stereochemically pure. The racemic isomer especially (from maleic acid) contains at least 50% of the meso product.
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Literature Cited 1. Zanger, M.; McKee, J. R. Small Scale Synthesis: A Laboratory Textbook of Organic Chemistry; W. C. Brown: Dubuque, IA, 1995; pp 113–118. 2. Organic Synthesis, Coll. Vol. II; Wiley: New York, 1967; pp 177–179. 3. Sax’s Dangerous Properties of Industrial Materials, 9th ed.; Lewis, R. J., Sr., Ed.; Van Nostrand Reinhold: New York, 1996: (a) Vol. II, p 506; (b) Vol. II, p 1701; (c) Vol. III, p 2084; (d) Vol. II, p 1557. 4. McKenzie, A. J. Chem. Soc. 1912, 101, 1196–1205. 5. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley: New York, 1967; pp 967–968.
Journal of Chemical Education • Vol. 76 No. 1 January 1999 • JChemEd.chem.wisc.edu
