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703
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1986, 1171–1179; (b) Grinblat, J.; Ben-Zion, M.; Hoz, S. J. Am. Chem. Soc. 2001,
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4456.
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1999, 40, 1459–1462; (b) Shen, Y.; Yang, B. J. Chem. Soc., Chem. Commun. 1988,
1394–1395.
8. Underwood, G. R.; Dietze, P. E. J. Org. Chem. 1984, 49, 5225–5229.
9. Eberson, L.; Finkelstein, M.; Folkesson, B.; Hutchins, G. A.; Jönsson, L.; Larsson,
R.; Moore, W. M.; Ross, S. D. J. Org. Chem. 1986, 51, 4400–4403.
10. Baranac-Stojanovic´, M.; Tatar, J.; Kleinpeter, E.; Markovic´, R. Synthesis 2008,
2117–2121.
As shown in Scheme 3, the formation of the a-carbonyl- substi-
tuted acetophenones 10a–g is consistent with the stepwise nature
of the reaction of 7a,b with anionic nucleophiles. As a result of the
carbophilic reaction (Scheme 3, step i), the initially formed inter-
mediate in the reactions of 7a,b with a range of nucleophiles is
the
a-bromo-a-substituted species 8, which was not isolated.
Changing the one
a-carbon substituent in 7a,b from Br to an elec-
tron-withdrawing substituent presumably makes the intermediate
8 susceptible to bromophilic attack (step ii), allowing the forma-
tion of the fairly stable carbanion 9, which is subsequently proton-
ated to the corresponding product 10.18
ˇ
11. Markovic´, R.; Dzambaski, Z.; Baranac, M. Tetrahedron 2001, 57, 5833–5841.
In summary, we have found that o-methoxy- and o-hydroxy-
12. For selective mono- and dibromination of o-hydroxy- and o-
methoxyacetophenones, see: (a) Juneja, S. K.; Choudhary, D.; Paul, S.; Gupta,
R. Synth. Commun. 2006, 2877–2881; (b) King, L. C.; Ostrum, G. K. J. Org. Chem.
1964, 29, 3459–3461; (c) Arbuj, S. S.; Waghmode, S. B.; Ramaswamy, A. V.
Tetrahedron Lett. 2007, 48, 1411–1415; (d) Pravst, I.; Zupan, M.; Stavber, S.
Tetrahedron 2008, 64, 5191–5199.
13. For selective dibromination of meta- and para-substituted acetophenones, see:
(a) Kajigaeshi, S.; Kakinami, T.; Tokiyama, H.; Hirakawa, T.; Okamoto, T. Bull.
Chem. Soc. Jpn. 1987, 60, 2667–2668; (b) Paul, S.; Gupta, V.; Gupta, R.; Loupy, A.
Tetrahedron Lett. 2003, 44, 439–442; (c) Diwu, Z.; Beachdel, C.; Kalubert, D. H.
Tetrahedron Lett. 1998, 39, 4987–4990.
a,
a
-dibromoacetophenones react in an unexpected and facile
manner with various soft, moderate, and hard anionic nucleo-
philes, giving rise to -carbonyl-substituted acetophenones. The
a
new type of reactivity of these compounds is attributed to the
ambident nature of the C–Br bonds which undergo stepwise,
nucleophile-induced carbophilic and bromophilic reactions.
Acknowledgment
14. Selected spectroscopic data for 2,2-dibromo-1-(2-methoxyphenyl)ethanone
(7a): Mp 50–51 °C. Yield: 95%; 1H NMR (200 MHz, CDCl3): d = 3.97 (s, 3H,
OCH3), 6.98–7.11 (m, 2H, m-Ph), 7.12 (s, 1H, CHBr2), 7.51–7.60 (m, 1H, p-
Ph), 7.82–7.87 (m, 1H, o-Ph); 13C NMR (50.3 MHz, CDCl3): d = 44.8 (CHBr2),
55.9 (OCH3), 111.7 (m-Ph), 121.4 (m-Ph), 132.6 (p-Ph), 135.2 (o-Ph), 158.2
(OCH3C2-Ph), 187.8 (CO); MS (EI, 70 eV): m/z (rel. intensity): 312 (M++4,
4), 310 (M++2, 8) 308 (M+, 4), 215 (12), 169 (4), 135 (100), 91 (10), 78
(19), 43 (21). Anal. Calcd for C9H8Br2O2: C, 35.10; H, 2.62. Found: C,
35.32; H, 2.78.
This research was partially supported by the Ministry of Science
of the Republic of Serbia, Grant No. 142007 (to R.M.).
References and notes
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17. General experimental procedure: To a stirred solution of 0.32 mmol of
a,a-
dibromoacetophenone 7a,b in 5.5 cm3 of acetone/H2O or DMF/H2O in 10/1 (v/
v) ratio, 0.96 mmol of the corresponding nucleophile was added. The reaction
mixture was stirred at rt for the time specified in Table 2 when TLC indicated
complete consumption of the substrate 7a,b. After extraction of the mixture
with CHCl3, washing with H2O, drying, and evaporation, the crude products
10a–g were purified by column chromatography on silica gel, using petroleum
ether/ethyl acetate gradient 100:0 to 80:20 (v/v).
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18. At the present time it is not possible to rule out that the bromophilic step
precedes the carbophilic step.