Organic Syntheses, Coll. Vol. 3, p.623 (1955); Vol. 26, p.57 (1946).
To the acid chloride, mechanically stirred and heated on the steam bath, is added 2.5 kg. (805 ml., 15.6 moles) of dry bromine (p. 124)
as rapidly as it will react (Note 5)
. The addition requires about 12 hours. The contents of the flask are stirred and heated an additional 2 hours, transferred to a dropping funnel (Note 6)
, and added in a thin stream to 5 l. of absolute ethanol
, which has previously been placed in a 12-l. flask
provided with a stopper carrying an efficient reflux condenser, a separatory funnel
, and a mechanical stirrer. The resulting vigorous reaction is controlled by external cooling. After the dibromoacid chloride
has been added, the reaction mixture is allowed to stand at room temperature overnight and is then poured into 5 l. of cold water. The top ethanolic aqueous layer is decanted and extracted once with 8 l. of ether
. The oily bottom layer is dissolved in the ether
extract and washed first with 1 l. of a 2% sodium bisulfite
solution, then with two 1-l. portions of 3% sodium carbonate
solution, and finally with several portions of water. The ether
solution is dried over 175 g. of potassium carbonate
; the solvent is distilled on the steam bath. The yield of residual ester (Note 7)
amounts to 2260–2400 g.
B. Muconic acid.
To a solution of 3 kg. of potassium hydroxide
and 5 l. of methanol (Note 8)
in a 12-l. flask, equipped as described above, is added in a thin stream from a separatory funnel (Note 6)
, and with stirring, 1130 g. (3.14 moles) of diethyl α,δ-dibromoadipate
. The ester is heated on the steam bath to nearly 100° before it is added. The addition is so regulated as to permit rather vigorous refluxing and requires 45 minutes. Heating on the steam bath and stirring are continued an additional 2 hours. The mixture is allowed to stand at room temperature overnight and is cooled. The potassium muconate
and potassium bromide
are filtered (Note 9)
, washed on the funnel with two 350-ml. portions of methanol
and 400 ml. of ether
, transferred without further drying to an enameled 11- to 12-l. pail, and dissolved in 8 l. of hot water. The aqueous solution, to which is added 30 g. of Norit
, is heated to boiling by introduction of steam, filtered through a Norit filter pad
by suction, and cooled in an ice-salt bath
. The muconic acid
is precipitated by the addition of a large excess (1.5 l.) (sp. gr. 1.18) of concentrated hydrochloric acid
to the cold solution. The acid is added in a thin stream to the well-stirred solution. After 2 hours the muconic acid
is filtered, washed first with two 400-ml. portions of cold water and then with 200 ml. of methanol
, and dried at 85°. The yield of nearly colorless product melting at 296–298°
, with decomposition, amounts to 165–195 g.
Apparatus with ground-glass joints is preferable.
The yield obtained in molar-sized runs is also about 40% of the theoretical.
is added as rapidly as it will react but not so rapidly that loss occurs through the condenser. A photoflood lamp accelerates the rate of bromination.
The dibromoacid chloride
solidifies at room temperature. It is advisable to heat the funnel by means of a coil of copper
tubing through which steam is passed.
Two isomers, a solid and a liquid, are formed during the bromination and subsequent esterification.
A commercial grade of methanol
was used; absolute methanol
did not result in an increased yield.
A pad of Filter-Cel aids in the slow filtration. About 100 g. is needed with a 30-cm. funnel.
has been obtained in a variety of ways. The procedures that seem most important from a preparative point of view are by treatment of ethyl α,δ-dibromoadipate
with ethanolic potassium hydroxide
by condensation of glyoxal
(as the sodium bisulfite
addition product) with malonic acid
by heating ethyl 1-acetoxy-1,4-dihydromuconate
(obtained by condensing ethyl oxalate
and ethyl crotonate
, acetylating, and reducing),5,6
by oxidation of phenol7
with peracetic acid
, and by hydrolysis of the half-ester obtained by the condensation of ethyl fumaraldehydate
with malonic acid
Three steroisomeric muconic acids
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