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gently agitated. Then acetyl chloride (3.2 mL, 3.53 g, 0.045 mol) was added by pipette, leading to
some fuming was noticed. The reaction vessel was immersed into an oil bath preheated to 93 ºC. The
mixture melted and vigorous evolution of gas ensued for about 15 min. The mixture was stirred for
2½ h at 9092 ºC, by which time it had gradually turned brown and TLC (1:6: ethyl acetate/petroleum
ether) showed no starting material and two more slowly moving products. After 3 hr the mixture was
poured with stirring into a mixture of 60 g of ice and 25 mL of 32% HCl. A creamy yellow solid
separated and the liquid phase was yellow. The mixture was extracted with 5 × 25 mL of ethyl ether
and the combined ether phase was washed with 2 × 10 mL H2O, 10 mL of 10% sodium carbonate
solution, 2 × 7 mL H2O and finally 5 mL of saturated NaCl solution; the last washings were neutral.
The yellow-orange organic layer was dried with sodium sulfate and magnesium sulfate, filtered, and
the solvent distilled off to give a brown oil (8.32 g). NMR showed the crude product to be 89% pure
2′,4′-dibromoacetophenone (21), with the remainder being mainly p-bromoacetophenone (22).
Distillation of the crude product at 0.02 Torr yielded a forerun at 7681 ºC, followed by a main
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fraction (5.80 g, 0.0209 mol, 70%) at 8184 ºC/0.02 Torr. H NMR (acetone-d6): 2.60 (s, 3H), 7.55
13
(dd, J = 0.2, 8.4 Hz, 1H), 7.63 (dd, J = 1.8, 8.4 Hz, 1H), 7.83 (dd, J = 0.2, 1.8 Hz, 1H). C NMR
(acetone-d6): 30.06, 119.60, 125.24, 131.16, 131.43, 136.43, 140.76, 199.60. The aforementioned
forerun crystallized partially and proved to be mainly p-bromoacetophenone (22, 0.988 g,
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0.00496 mol). H NMR (CDCl3): 2.59 (s, 3H), 7.61 (m, 2H), 7.82 (m, 2H). When the reaction was
performed on a 3-fold scale of p-dibromobenzene (23.60 g, 0.100 mol scale) at 6575 ºC, the crude
product contained about 80% of 21. Distillation gave a main cut of 20.71 g (74% yield) at
8798.5 ºC/0.07 Torr which contained 12% of impurities as p-bromoacetophenone as determined by
NMR. 1H NMR (CDCl3, 600 MHz): 2.62 (s, 3H), 7.37 (d, J = 8.3 Hz, 1H), 7.52 (dd, J = 1.8, 8.3 Hz,
1H), 7.80 (d, J = 1.8 Hz, 1H). 13C NMR (CDCl3, 600 MHz): 30.20, 119.89, 125.41, 130.21, 130.71,
136.31, 139.96, 200.05. 2D NMR: HMQC correlations: 7.37–130.21; 7.52–130.71; 7.80–136.31.
HMBC correlations: 2.62–30.20, 139.96, 200.05; 7.37–119.89, 125.41, 130.71, 136.41, 200.05;
7.52–119.89, 125.41, 130.21, 136.31, 139.96; 7.80–119.89, 125.41, 130.71, 139.96.
2,4-Dibromobenzoic acid (20) [47]. Distilled 2′,4′-dibromoacetophenone (21, 4.60 g, 0.0166 mol) was
placed in a 500 mL R.B. flask fitted with a magnetic stirrer. A solution of NaOH (1.05 g, 0.0263 mol)
in 10.5 mL H2O was added, followed by a solution potassium permanganate (7.50 g, 0.0475 mol) in
260 mL H2O. The mixture was stirred under reflux using an oil bath heated to 143155 ºC for 5 h, at
which time the permanganate color from the aqueous phase had disappeared. The mixture was allowed
to cool, acidified with a solution of 5 mL of concentrated sulfuric acid in 10 mL H2O, and the black
precipitate of manganese dioxide decomposed with sodium bisulfite (Fluka, 64% SO2, a total of 6.7 g).
The mixture was adjusted to pH 7 by addition of 6 M NaOH followed by 6 M H2SO4 and then
extracted with a total of 190 mL of ethyl ether in 4 portions. The aqueous layer was then acidified by
adding small aliquots of 6 M H2SO4 with stirring, and a thick white precipitate was obtained. This was
filtered off, washed with 2 × 20 mL H2O, and dried in vacuo to give of the desired product (3.35 g)
softening at 145 ºC and melting at 162165 ºC, (lit. [90] 169 ºC). The latter proved by NMR to be
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fairly pure 2,4-dibromobenzoic acid (20) containing a few percent of p-bromobenzoic acid (26). H
NMR (acetone-d6): 7.71 (dd, J = 1.9, 8.3 Hz, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.96 (d, 1.9 Hz, 1H).
From the mother liquors of the aqueous layer an additional 0.49 g of crystalline material was obtained