14
Preparation of Chlorodibenzo-p-dioxins for Toxicological Evaluation
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ORM ANILINE Organic Chemicals Production Research Laboratory, The Dow Chemical Co., Midland, Mich. 48640
Chlorinated
dibenzo-p-dioxins
were prepared on the gram
scale for use as toxicological benzo-p-dioxin
was prepared
standards.
potassium 2-bromo-4-chlorophenate condensation
of the potassium
hydroxydiphenyl fractional
in 70% yield. Thermal
salt of 2,4,4'-trichloro-2'-
ether gave a mixture
2,7-dichlorodibenzo-p-dioxins
2,7-Dichlorodi-
by catalytic condensation of
which
recrystallization.
of the 2,8- and
were
separated
by
2,3,7,8-Tetrachlorodibenzo-p
-dioxin of 99.9+% purity was prepared by catalytic condensation
of potassium
2,4,5-trichlorophenate.
mixture of hexachlorodibenzo-p-dioxins pyrolytic condensation of sodium Chlorination
of
benzo-p-dioxin to produce
(containing
in trichlorobenzene
in 80%
yield
heptachlorodibenzo-p-dioxin.
isomeric by
2,3,4,6-tetrachlorophenate.
pentachlorophenol
tetrachlorophenol)
An
was prepared
gave
contaminated
-dioxin. Purified 2,4,5-trichlorophenol (50 grams, 0.26 mole) was converted to its potassium salt and dissolved in 100 m l of b E E E . After addition of the copper catalyst and ethylene diacetate, the mixture was transferred to the bottom of a 300-ml sublimer with chloroform. Sublimation (200°C/2 mm) yielded 14 grams (39% yield) of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mass spectral analysis revealed trace quantities of pentachlorodibenzo-p-dioxin, tetrachlorodibenzofuran, and several unidentified substances of similar molecular weight. The combined impurity peaks were estimated to be < 1 % of the total integrated G L C area. The product was further purified by recrystallizations from o-dichlorobenzene and anisole. The final product had an estimated 260 p p m of trichlorodibenzo-p-dioxin as the only detected impurity. Hexachlorodibenzo-£-dioxin. 2,3,4,6-Tetrachlorophenol was purified by distillation and recrystallization to yield a product containing < 0 . 1 % trichlorophenol impurity. The phenol was dissolved i n toluene and mixed with an equimolar amount of aqueous caustic. Water was azeotropically Table III.
G L C and Mass Spectrometry Analysis
GLC Peak Area, %
Observed Parent Ion m/e
80
252
253
15
288
289.5
Structure
Molecular Weight
H
5
162
OH
In Chlorodioxins—Origin and Fate; Blair, E.; Advances in Chemistry; American Chemical Society: Washington, DC, 1973.
163
Downloaded by UNIV OF ARIZONA on January 10, 2013 | http://pubs.acs.org Publication Date: March 1, 1973 | doi: 10.1021/ba-1973-0120.ch014
134
CHLORODIOXINS
ORIGIN A N D F A T E
distilled. After trituration of the sodium 2,3,4,6-tetrachlorophenate with toluene, the salt was ground to a powder. As i n a typical pyrolytic preparation, powdered sodium tetrachlorophenate ( 30 grams ) was placed evenly on the bottom of a 300-cc Nester-Faust sublimer. The salt was covered with 20 grams of C a O and a glass wool pad. The vessel was immersed i n a sand bath and heated at 350°C under reduced pressure. Temperatures over 380°C induced localized hot spots which caused smoking or bumping. Product crystals began to form on the sublimer walls after 2 hours of heating. Several product samples were isolated from their reaction mixtures by extraction with o-dichlorobenzene. The o-dichlorobenzene extracts were combined and analyzed by G L C . Four peaks were observed under standard G L C conditions in the 10 to 15 min retention time range which is characteristic of hexachlorodibenzo-p-dioxins (sample 1 in Table I V ) . The mixture was fractionally sublimed (120° to 175°C/1 m m ) . The major crop was harvested at 175 °C and recrystallized from anisole. Analysis of this material by G L C indicated that two isomeric hexachlorodibenzo-p-dioxins were present (sample 2). Overall yield (1.5 grams) of the product was 1 - 3 % at 9 9 + % purity, as determined by G L C and mass spectrometry. Table IV.
G L C Analysis of o-Dichlorobenzene Extracts
Sample
Description
Peak
GLC Retention Time, min
% of Total
1
o-dichlorobenzene extract
A Β C D
10.8 12.4 13.4 14.0
16 65 10 9
2
sublimed and recrystallized
Β C
12.0 13.5
55 45
Octachlorodibenzo-^-dioxin. Pentachlorophenol was purified by sublimation and recrystallization to yield a product with the following composition: trichlorophenol, 0.04%; tetrachlorophenol, 0.07%; and pen tachlorophenol, 100.4 ± 1 % . Pentachlorophenol (300 grams, 1.13 mole) was dissolved in 900 m l of trichlorobenzene and chlorinated anhydrously for 18 hours at reflux. Chlorine addition was stopped and the mixture was heated for 28 more hours at reflux. The crystalline product was washed with 2-liter portions of chloroform, I N N a O H , methanol, and water. Analysis by G L C suggested the presence of 5-15% heptachlorodibenzo-p-dioxin. The mixture was carefully added to a cleaning solution of 200 m l water, 3.5 liters sulfuric acid, and 125 grams sodium dichromate. The mixture was heated at 150 °C for six hours. The product was recrystallized from hot o-dichlorobenzene and then from anisole. The purified product (160 grams, mp 329.8° ± 0.5°C) contained
