a,a“-Dibromo-o-xylene

[91-13-4]  · C8H8Br2  · a,a“-Dibromo-o-xylene  · (MW 263.97)

(a source of o-quinodimethane, a highly reactive diene useful in Diels-Alder reactions;1 an electrophile for the synthesis of carbo- and heterocyclic compounds including macrocycles (cyclophanes, crown ethers, hemispherands, spherands),2 cryptands,3 hemicarcerands,4 vaulted cappedophanes,5 bicyclic compounds,6 spirocyclic compounds;7 a protective group reagent for diols8)

Alternate Name: 1,2-bis(bromomethyl)benzene.

Physical Data: mp 95 °C (CHCl3-EtOH); bp 140 °C/20 mmHg; d 1.960 g cm-3; dipole moment (hexane, 20 °C) 1.98 D.

Solubility: sol ethanol, ether, chloroform; slightly sol petroleum ether.

Form Supplied in: commercially available as a solid.

Purification: recrystallization from 95% ethanol (3 mL g-1), petroleum ether (bp 60-80 °C) (19 mL g-1), chloroform (1 mL g-1). Column chromatography (silica gel, cyclohexane-ethyl acetate).

Handling, Storage, and Precautions: avoid moisture; corrosive (forms HBr on hydrolysis); lachrymator; not mutagenic in Ames test; decontaminate by soaking apparatus, etc. in alcoholic alkali for 24 h or longer.

Precursor of o-Quinodimethane.

A reductive 1,4-elimination1 of two bromide ions generates the reactive diene which can be intercepted by dienophiles and by iron9 or cobalt10 carbonyl reagents to form stable complexes. The elimination may be accomplished by activated Zinc,11 particularly with ultrasonication at rt (eq 1),12 activated Nickel,13 Sodium Iodide14 in DMF, sodium benzenetellurolate,15 Chromium(II) Chloride,16 and elemental Copper17 (as the t-butyl isocyanide complex). The dibromide is a precursor of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide (2)18 and 1,4-dihydro-2,3-benzoxathiin 3-oxide (3),19 which yield o-quinodimethane on thermolysis (eqs 2 and 3).

Cyclization Reactions.

Any reagent capable of functioning as a bis-nucleophile can, in principle, yield a cyclic product with (1). Benzocyclobutene may be formed in reactions yielding o-quinodimethane,18a and fused ring compounds containing five or more atoms in the second ring are available from (1). Examples of various fused ring compounds obtained from (1) are as follows: five-membered (eqs 2 and 4),18b,20 six-membered (eqs 3 and 5),19a,19b,21 seven-membered (eq 6),22 and eight-membered (eq 7).23 The attachment of larger rings is not uncommon, as shown in eq 8 for a macrocycle.2d

Bicyclic ring systems have been obtained by the appropriate choice of nucleophile (e.g. the cryptand shown in eq 9),3a and spirocyclic compounds have been prepared (eq 10).7b Four molecules of (1) were used in a critical step in the construction of a globe-shaped hemicarcerand by uniting two bowl-like units via reaction with eight phenolic hydroxy groups on the rims of the two bowls.4 A monensin ionophore bridged by treatment with (1) shows excellent chiral recognition ability for salts of amino acids and amines.2g

In addition to undergoing cyclizations with nucleophiles, (1) also dimerizes in 65% yield to 1,2;5,6-dibenzocyclooctadiene by treatment with 2 equiv of Ethylenebis(triphenylphosphine)nickel(0) at -20 °C in ether2f and in 80% yield by ultrasonication with Lithium in THF.24

Protective Group Reagent for Diols.

1,2- and 1,3-diols containing primary or secondary alcohol functions, catechols, and ene-1,2-diols are protected by reaction with (1). Deprotection involves hydrogenolysis of the protecting group (eq 11).8

Miscellaneous Uses.

The dichloride rather than dibromide (1) is preferable for synthesis of the bis-Grignard reagent which is obtained in good yield, especially by treatment with Mg(anthracene)(THF)3 in THF, hexane, or toluene under moderately high dilution to forestall Wurtz coupling.25 A 75% yield of o-dibenzylbenzene is obtained by Friedel-Crafts reaction of (1) catalyzed by Aluminum Chloride-Nitromethane.26 Yields are poor if AlCl3 alone is used.

Related Reagents.

1,3-Dihydrobenzo[c]thiophene 2,2-Dioxide.


1. (a) Martin, N.; Seoane, C.; Hanack, M. OPP 1991, 23, 237. (b) Charlton, J. L.; Alauddin, M. M. T 1987, 43, 2873. (c) Ciganek, E. OR 1984, 32, 72. (d) Oppolzer, W. S 1978, 793. (e) Rigby, J. H. COS 1991, 5, 622, 638. (f) Oppolzer, W. COS 1991, 5, 385.
2. (a) Buter, J.; Kellogg, R. M. JOC 1981, 46, 4481. (b) Shatzmiller, S.; Menashe, N.; Shalom, E.; Bahar, E. LA 1991, 1259. (c) Allwood, B. L.; Kohnke, F. H.; Slawin, A. M. Z.; Stoddart, J. F.; Williams, D. J. CC 1985, 311. (d) Murakami, J.; Aoyama, Y.; Kikuchi, J.; Nishida, K. JACS 1982, 104, 5189. (d) Chavez, F.; Sherry, A. D. JOC 1989, 54, 2990. (e) Petti, M. A.; Shepodd, T. J.; Dougherty, D. A. TL 1986, 27, 807. (f) Uhlig, E.; Hipler, B. TL 1984, 25, 5871. (g) Tsukube, H.; Sohmiya, H. TL 1990, 31, 7027. (h) Cram, D. J.; Dicker, I. B.; Lauer, M.; Knobler, C. B.; Trueblood, K. N. JACS 1984, 106, 7150. (i) Tucker, J. A.; Knobler, C. B.; Goldberg, I.; Cram, D. J. JOC 1989, 54, 5460.
3. (a) Bradshaw, J. S.; An, H.; Krakowiak, K. E.; Wang, T.; Zhu, C.; Izatt, R. M. JOC 1992, 57, 6112. (b) Lukyanenko, N. G.; Basok, S. S.; Filonova, L. K. JCS(P1) 1988, 3141.
4. Cram, D. J.; Blanda, M. T.; Paek, K.; Knobler, C. B. JACS 1992, 114, 7765.
5. Vinod, T. K.; Hart, H. JOC 1991, 56, 5630.
6. (a) Bilyard, K. G.; Garratt, P. J.; Underwood, A. J.; Zahler, R. TL 1979, 1815. (b) Baierweck, P.; Hoell, D.; Müllen, K. AG(E) 1985, 24, 972. (c) Mataka, S.; Takahashi, K.; Hirota, T.; Takuma, K.; Kobayashi, H.; Tashiro, M.; Imoda, K.; Kuniyoshi, M. JOC 1986, 51, 4618. (d) Auchter-Krummel, P.; Krummel, G.; Lex, J.; Müllen, K. CB 1991, 124, 2819. (e) Chou, T.; Chang, C.-Y. JOC 1991, 56, 4560.
7. (a) Eck, G.; Julia, M.; Pfeiffer, B.; Rolando, C. TL 1985, 26, 4725. (b) Chen, B.-C.; Lue, P. OPP 1992, 24, 185.
8. Poss, A. J.; Smyth, M. S. SC 1989, 19, 3363.
9. Kerber, R. C.; Ribacove, E. C. OM 1991, 10, 2848.
10. (a) Hersh, W. H.; Hollander, F. J.; Bergman, R. G. JACS 1983, 105, 5834. (b) Hersh, W. H.; Bergman, R. G. JACS 1983, 105, 5846.
11. (a) Ardecky, R. J.; Kerdesky, F. A. J.; Cava, M. P. JOC 1981, 46, 1483. (b) Tamao, K.; Yoshida, J.; Akita, M.; Sugihara, Y.; Iwahara, T.; Kumada, M. BCJ 1982, 55, 255. (c) Alder, K.; Fremery, M. T 1961, 14, 190. (d) Use of Zn-Ag is said to be superior to Zn in reactions of the 3,6-dimethyl derivative: Rubottom, G. M.; Wey, J. E. SC 1984, 14, 507.
12. Han, B. H.; Boudjouk, P. JOC 1982, 47, 751.
13. Inaba, S.; Wehmeyer, R. M.; Forkner, M. W.; Rieke, R. D. JOC 1988, 53, 339.
14. (a) Kametani, T.; Takahashi, T.; Kajiwara, M.; Hirai, Y.; Ohtsuka, C.; Satoh, F.; Fukumoto, K. CPB 1974, 22, 2159. (b) Rak, S. F.; Jozefiak, T. H.; Miller, L. L. JOC 1990, 55, 4794.
15. Kambe, N.; Tsukamoto, T.; Miyoshi, N.; Murai, S.; Sonoda, N. BCJ 1986, 59, 3013. The corresponding bis-phenyl telluride is obtained in the absence of a dienophile: Ferreira, J. T. B.; Oliveira, A. R. M.; Comasseto, J. V. TL 1992, 33, 915.
16. Stephan, D.; Gorgues, A.; LeCoq, A. TL 1984, 25, 5649.
17. Ito, Y.; Yonezawa, K.; Saegusa, T. JOC 1974, 39, 2769.
18. (a) Cava, M. P.; Deana, A. A. JACS 1959, 81, 4266. (b) Eq 2 shows an improved synthesis of the cyclic sulfide: Steliou, K.; Salama, P.; Corriveau, J. JOC 1985, 50, 4969. (c) Use of a phase transfer catalyst also improves the yield of the sulfide from (1) and Na2S: Durst, T.; Lancaster, M.; Smith, D. J. H. JCS(P1) 1981, 1846.
19. (a) Hoey, M. D.; Dittmer, D. C. JOC 1991, 56, 1947. (b) Jarvis, W. F.; Hoey, M. D.; Finocchio, A. L.; Dittmer, D. C. JOC 1988, 53, 5750. (c) Knittel, D.; Kastening, B. B. J. Appl. Electrochem. 1973, 3, 291. (d) Jung, F.; Molin, M.; Van Den Elzen, R.; Durst, T. JACS 1974, 96, 935. (e) Durst, T.; Charlton, J. L.; Mount, D. B. CJC 1986, 64, 246.
20. Carlson, G. L. B.; Quina, F. H.; Zarnegar, B. M.; Whitten, D. G. JACS 1975, 97, 347.
21. Urove, G. A.; Welker, M. E.; Eaton, B. E. JOM 1990, 384, 105.
22. Mataka, S.; Mimura, T.; Lee, S. T.; Kobayashi, H.; Takahashi, K.; Tashiro, M. JOC 1989, 54, 5237.
23. Thummel, R. P.; Goulle, V.; Chen, B. JOC 1989, 54, 3057.
24. Boudjouk, P.; Sooriyakumaran, R.; Han, B.-H. JOC 1986, 51, 2818.
25. Harvey, S.; Junk, P. C.; Raston, C. L.; Salem, G. JOC 1988, 53, 3134.
26. Mataka, S.; Tsuda, Y.; Takahashi, K.; Tashiro, M. OPP 1981, 13, 93.

Donald C. Dittmer

Syracuse University, NY, USA



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