A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1954, 34, 82
DOI: 10.15227/orgsyn.034.0082
Submitted by J. C. Bill and D. S. Tarbell1.
Checked by Arthur C. Cope and Harris E. Petree.
1. Procedure
This preparation should be conducted in a hood, and rubber gloves should be worn, to avoid exposure to bromine as well as the by-product o-xylylene dibromide which is a lachrymator and skin irritant.
A. α,α,α',α'-Tetrabromo-o-xylene. In a 2-l. three-necked flask equipped with an oil-lubricated Trubore stirrer, a dropping funnel, a thermometer extending nearly to the bottom of the flask, and a reflux condenser (Note 1) attached to a gas absorption trap2 is placed 117 g. (1.1 moles) of dry o-xylene (Note 2). An ultraviolet lamp such as a General Electric R.S. Reflector Type 275-watt sun lamp is placed about 1 cm. from the flask so as to admit the maximum amount of light. The stirrer is started, and the o-xylene is heated to 120° with an electric heating mantle. A total of 700 g. (4.4 moles) of bromine (N.F. grade) is added in portions from the dropping funnel to the reaction flask at such a rate that the bromine color is removed as fast as it is added. After approximately one-half of the bromine has been added, the temperature is slowly increased to 175° for the remainder of the addition; the mixture becomes very dark toward the end of the reaction. The bromine can be added rapidly at first, but toward the end it must not be added at a rate exceeding 4–5 drops per minute in order to avoid loss of a visible amount of bromine with the evolved hydrogen bromide. After all the bromine has been added (10–14 hours), the mixture is illuminated and stirred at 170° for 1 hour. After removal of the stirrer, etc., the mixture is cooled and allowed to stand overnight to crystallize in the reaction flask exposed to the air.
The dark, solid tetrabromide is dissolved in 2 l. of hot chloroform (Note 3) and treated with 100 g. of 325-mesh Norit. The mixture is filtered with slight suction, the Norit is washed with hot chloroform, and the Norit treatment is repeated. The tancolored filtrate from the second Norit treatment is concentrated to 250–300 ml. by distillation under reduced pressure and chilled to 0°. The solid product is collected on a cold Büchner funnel and washed with a small amount of cold chloroform. The filtrate is concentrated further and cooled to obtain a second crop of crystals, which is purified by recrystallization from chloroform. The yield of the tetrabromide obtained from the first crop (white) and second crop after recrystallization (light tan) is 344–370 g. (74–80%), m.p. 115–116°.
B. o-Phthalaldehyde. The α,α,α',α'-tetrabromo-o-xylene (344–370 g.) obtained as described above, part A, is placed in a 5-l. round-bottomed flask with 4 l. of 50% (by volume) ethanol and 275 g. of potassium oxalate. The mixture is heated under reflux for 50 hours (a clear yellow solution is formed after 25–30 hours). About 1750 ml. of the ethanol is then removed by distillation (which is stopped before the product begins to steam-distil), and 700 g. of disodium monohydrogen phosphate dodecahydrate (Na2HPO4 · 12H2O) is added to the aqueous residue. The mixture is steam-distilled rapidly (Note 4), using an efficient condenser, until 10–12 l. of distillate is collected and the distillate no longer gives a black color test for o-phthalaldehyde3 when a portion is treated with concentrated ammonium hydroxide followed by glacial acetic acid. The distillate is then saturated with sodium sulfate at room temperature and divided into portions of approximately 4 l.; each portion is extracted first with 200 ml. and then with six 100-ml. portions of ethyl acetate. The combined ethyl acetate extracts are dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is crystallized from 90–100° ligroin, and a second crop is obtained by concentration of the mother liquor. The total yield of o-phthalaldehyde, m.p. 55.5–56°, is 87–94 g. (74–80% based on the tetrabromide, or 59–64% based on o-xylene).
2. Notes
1. Best results are obtained if an all-glass apparatus with ground-glass connections is used, as noted by Wawzonek and Karll.4
2. Pure commercial o-xylene (99% or higher purity) is dried by distillation until the distillate shows no further turbidity, and the residue is used.
3. The chloroform is allowed to stand over anhydrous calcium chloride overnight to remove water and ethanol.
4. The submitters state that the steam distillation is much more efficient if superheated (175–180°) steam is used, in which case special care must be taken to condense all the distillate.
3. Discussion
o-Phthalaldehyde has been made by the action of potassium hydroxide on o-(dichloromethyl)benzaldehyde,5 by the hydrolysis of α,α,α',α'-tetrachloro-o-xylene,6 by the hydrolysis of the α,α,α',α'-tetraacetate of o-phthalaldehyde,3 by the oxidation of α,α'-dihydroxy-o-xylene with selenium dioxide7 or N-chlorosuccinimide,8 and by the reduction of phthalic acid N-methylanilide with diisobutylaluminum hydride.9 The present method is essentially that of Thiele and Günther.10,11 Hydrolysis of the tetrabromide may also be carried out by treatment with fuming sulfuric acid followed by water.12 For small-scale preparations of o-phthalaldehyde the reduction of N,N,N',N'-tetramethylphthalamide with lithium aluminum hydride is the method of preference.13

References and Notes
  1. University of Rochester, Rochester, New York.
  2. Org. Syntheses Coll. Vol. 2, 4 (1943).
  3. Thiele and Winter, Ann., 311, 360 (1900).
  4. Wawzonek and Karll, J. Am. Chem. Soc., 70, 1666 (1948).
  5. Chaudhuri, J. Am. Chem. Soc., 64, 315 (1942).
  6. Colson and Gautier, Ann. chim. (Paris), 6, 11, 28 (1887).
  7. Weygand, Kinkal, and Tietjen, Chem. Ber., 83, 394 (1950).
  8. Hebbelynck and Martin, Bull. soc. chim. Belges, 60, 54 (1951) [C. A., 46, 7051 (1952)]; Hebbelynck, Ind. chim. belge, 16, 483 (1951) [C. A., 46, 10127 (1952)].
  9. Zakharkin and Khorlina, Izvest. Akad. Nauk S.S.S.R., Otdel. Khim. Nauk, 1959, 2146 [C. A., 54, 10932 (1960)].
  10. Thiele and Günther, Ann., 347, 107 (1906).
  11. Cope and Fenton, J. Am. Chem. Soc., 73, 1672 (1951).
  12. Weygand, Vogelbach, and Zimmermann, Chem. Ber., 80, 396 (1947).
  13. Weygand and Tietjen, Chem. Ber., 84, 625 (1951).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)



α,α,α',α'-tetraacetate of o-phthalaldehyde

ethanol (64-17-5)

calcium chloride (10043-52-4)

sulfuric acid (7664-93-9)

acetic acid (64-19-7)

ethyl acetate (141-78-6)

chloroform (67-66-3)

hydrogen bromide (10035-10-6)

bromine (7726-95-6)

sodium sulfate (7757-82-6)

Norit (7782-42-5)

selenium dioxide (7446-08-4)

potassium hydroxide (1310-58-3)

ammonium hydroxide (1336-21-6)

N-chlorosuccinimide (128-09-6)

lithium aluminum hydride (16853-85-3)


diisobutylaluminum hydride (1191-15-7)

o-Xylylene dibromide (91-13-4)


potassium oxalate

disodium monohydrogen phosphate dodecahydrate (10039-32-4)

phthalic acid N-methylanilide

α,α'-dihydroxy-o-xylene (612-14-6)

o-Xylene (95-47-6)


α,α,α',α'-tetrabromo-o-xylene (13209-15-9)