Para-Selective Chlorination and Bromination of Phenols
____________________________________________________________________________________________PROCEDURE
Table 4 Comparison of the selectivity of hypochlorites in the reaction with phenol 1
Reagent
ortho-product (%)
para-product (%)
dichloro product (%)
sodium hypochlorite
tert-butyl hypochlorite
tert-butyl hypochlorite/Ti(OiPr)4
tert-butyl hypochlorite/Zr(OtBu)4
77
60
53
49
18
38
46
49
5
2
1
2
tert-butyl hydroperoxide; regioselectivity
References
Bromination of Phenols (General Procedure)
A solution of the phenol (1 mmol) in THF (10 ml) was treated
with TiBr(OiPr)3 (1 ml, 1 mol) and stirred 30 min at room
temperature. A solution of TBHP (0.57 ml, 2 mmol, 3.5mol/l
in CH2Cl2) at –40 °C was then added within 5 min. The
cooling bath was removed after 2 h at –40 °C, and stirring
was continued for 30 min. The orange mixture was quenched
by addition of 10% H2SO4 (10 ml), and the aqueous phase
was extracted twice with CH2Cl2 (each 7.5 ml). The combined
organic phases were extracted three times with 5% NaOH
(each 5 ml), the aqueous phase was acidified to pH 2 with
10% H2SO4 and then extracted three times with CH2Cl2 (each
5 ml). The combined organic phases were dried (MgSO4),
and the solvent was evaporated at reduced pressure. The crude
products were analyzed by GC (see Table 3); the pure
bromides were obtained by filtration through a batch of silica
gel and crystallization. 6: (75%) m.p. 62 °C (Lit. [24] m.p.
66.4 °C); 8: (73%) m.p. 34–35 °C (Lit. [25] m.p. 35–36 °C);
10: (78%) m.p. 61 °C (Lit. [18] m.p. 60–61 °C); 11: (80%)
m.p. 58 °C (Lit. [25] m.p. 61–62 °C).
[1] Part 10: K. Krohn, J. Küpke, Eur. J. Org. Chem. 1997, 679
[2] Selectivity, a Goal for Synthetic Efficiency (Edit.: W. Bart-
mann; B. M. Trost), Verlag Chemie, Weinheim 1983
[3] K. Krohn, Synthesis 1997, 1115
[4] G. K. Chip, J. S. Grossert, Can. J. Chem. 1972, 50, 1233
[5] K. H. Chung, H. J. Kim, H. R. Kim, E. K. Ryu, Synth. Com-
mun. 1990, 20, 2991
[6] Some loss occurred during workup.
[7] M. Hirano, S. Yakabe, H. Monobe, T. Morimoto, Can. J.
Chem. 1997, 75, 1905
[8] G. A. Olah, L. Ohannesian, M, Arvanaghi, Synthesis 1986,
868
[9] J. R. L. Smith, L. C McKeer, J. M. Taylor, J. Chem. Soc.,
Perkin Trans. II 1987, 1533
[10] W. D. Watson, J. Org Chem. 1985, 50, 2145
[11] A. Guy. M. Lemaire, J.-P. Guette, Tetrahedron 1982, 2339
[12] K. Krohn, H. Rieger, K. Khanbabaee, Chem. Ber. 1989, 122,
2323
[13] L. Forlani, Synthesis 1980, 487
[14] S. Kajigaeshi, T. Kakinami, T. Okamoto, H. Nakumura, M,
Fujikawa, Bull. Chem. Soc. Jpn. 1987, 60, 4187
[15] V. A. Mikkhailov, V. A. Savelova, M. Y. Rodygin, Russ. J.
Org. Chem. 1993, 29, 1868
Chlorination of Phenols with Sodium Hypochlorite
[16] S. H. Mashraqui, C. D. Mudaliar, H. Hariharasubrahmanian,
Tretrahedron Lett. 1997, 38, 4865
[17] K. Smith, D. M. James, I. Matthews, M. R. Bye, J. Chem.
Soc., Perkin Trans.1 1992, 1877
[18] R. H. Mitchell, Y.-H. Lai, R. V. Williams, J. Org. Chem. 1979,
44, 4733
[19] B. Fuchs, Y. Belsky, E. Tartakovsky, J. Zizuashvili, S. Wein-
man, J. Chem. Soc., Chem. Commun. 1982, 778
[20] We thank Prof. E. Pritzkow for drawing our attention to that
possibility.
A solution of the phenol (1 mmol) in CH2Cl2 (10 ml) was
treated at 0 °C with an aqueous solution of sodium hypo-
chlorite (5 ml, 11 mmol). The resulting emulsion was stirred
4 h at room temperature. The organic phase was washed twice
with 10% H2SO4 (5 ml), dried (MgSO4 ), and the solvent was
evaporated at reduced pressure. The crude oily residues were
analyzed by GC (comparison with authentic samples; ratio of
ortho- to para products see Table 4).
[21] K. Krohn, A. Michel, U. Flörke, H.-J. Aust, S. Draeger, B.
Schulz, Liebigs Ann. Chem. 1994, 1093
Chlorination of Phenol (1) with tert-Butyl Hypochlorite
[22] G. Norwitz, N. Nataro, P. N. Keliher, Anal. Chem. 1986, 58,
639
[23] M. Fujio, Bull. Chem. Soc. Jpn. 1975, 48, 2127
[24] A. Schoenberg. R. F. Heck, J. Am. Chem. Soc. 1974, 96,
7761
[25] J. Delobelle, M. Fetizon, Bull. Soc. Chem. Fr. 1961, 1900
[26] C. Walling, J. A. McGuinness, J. Am. Chem. Soc. 1969, 91,
2053
A solution of phenol (1) (1 mmol) in CH2Cl2 (10 ml) was
treated at 0 °C with tert-butyl hypochlorite [26] in CH2Cl2
(2 ml, 2.5 ml, 0.8 mol/L). The mixture was allowed to warm
to room temperature and was stirred for 24 h. The solution
was then extracted three times with 10% NaOH (each 5 ml),
acidified to pH 2 and again extracted three times with CH2Cl2
(each 5 ml). The solvent was evaporated at reduced pressure
and the ortho to para ratio analyzed by GC.
Address for correspondence:
Prof. K. Krohn
Fachbereich Chemie und Chemietechnik
der Univ.-GH Paderborn
Warburger Str. 100
D-33098 Paderborn
Chlorination of Phenol (1) with tert-Butyl Hypochlorite
in Presence of Ti(OiPr)4 or Zr(OtBu)4
The phenols were equilibrated for 30 min at room temperature
in CH2Cl2 (10 ml) with 1 mmol with Ti(OiPr)4 or Zr(OtBu)4.
The reactions were then performed as described above and
the ortho to para ratios analyzed by GC (ratio see Table 4).
FAX: internat. code (0) 5251-60-3245
E-mail: kk@chemie.uni-paderborn.de
J. Prakt. Chem. 1999, 341, No. 1
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