PAPER
Halogenation of Aromatic Compounds and Epoxide Ring Opening to Halohydrins
2343
Acetone 2,4,6-Tribromophenylhydrazone
GC/MS: tR 20.4 min.
References
(1) Since citation of more than 50 papers in this short article is
not appropriate, we are ready to send a copy of a text file
with the citations to interested readers.
(2) Sharghi, H.; Eskandari, M. M. Synthesis 2002, 1519.
(3) For concluding that the phenylhydrazine is a catalyst, it is
necessary to find it, or better to isolate it, or much better to
use it again, after reaction.
MS (EI, 70 eV): m/z (%) = 367 (10), 369 (18), 371 (20), 373 (7)
[C8H6Br3N2, M – CH3], 352 (33), 354 (100), 356 (82), 358 (28)
[C7H3Br3N2, M – 2 CH3],
232 (8), 234 (18), 236 (9) [C6H2Br2], 153 (18), 155 (16) [C6H2Br],
74 (32) [C6H2] (no molecular ion at 382/384/386/388).
The collected filtrates were evaporated to leave an oily dark residue
(2.5 g), which was analyzed by means of NMR and GC/MS. No
phenylhydrazine was found. The oil is a mixture of more than 12
compounds, mainly brominated phenylhydrazines and products,
which could be derived from brominated phenyldiazonium salts,
such as brominated benzenes and brominated phenylazophenylhy-
drazines.4,5
(4) There are two possibilities: electrophilic halogenation of
phenylhydrazine, and the oxidation of phenylhydrazine by
halogen. Both reactions give hydrogen halogenide as a side
product. Therefore, the reaction of arylhydrazines with
chlorine or bromine gave a mixture of chlorination/
bromination and oxidation products, mainly aryldiazonium
salts, and the products thereof. We found some precedents in
the literature. For examples, see: (a) Chattaway, F. D.;
Hodgson, G. D. J. Chem. Soc. 1916, 583. (b) Chattaway, F.
D. J. Chem. Soc. 1908, 852. (c) Chattaway, F. D. J. Chem.
Soc. 1909, 862. (d) Michaelis, L. Ber. Dtsch. Chem. Ges.
1893, 26, 2190. (e) Vaubel, W. J. Prakt. Chem. 1894, 49,
540.
(5) The oxidation of arylhydrazines to diazonium salts by
bromine were exploited as a preparative way for substitution
of the NHNH2 moiety by bromine. For examples, see:
(a) Callander, D. D.; Coe, P. L.; Tatlow, J. C. Tetrahedron
1966, 22, 419. (b) Field, L. D.; Hambley, T. W.; Pierens, G.
K. Tetrahedron 1990, 46, 7069. (c) Joshi, S. S.; Deorha, D.
S. J. Chem. Soc. 1957, 2414.
NMR (CDCl3): there are more than 20 signals in the NMR spec-
trum, the most intense in the aromatic region are: d = 7.18 (s), 6.82
(d), 7.37 (d), 7.42 (s) and 7.63 (s), but there are no peaks of phenyl-
hydrazine at d = 7.21 (t), 6.76 (d + t).
GC/MS: there are more than 20 peaks. However, there are no peaks
from phenylhydrazine. Since most of the MS spectra show no signal
of molecular ions, we were not able to find the exact structures, so
we present only the most representative fragments derived from the
highest peaks on the total ion chromatogram.
GC/MS (EI, 70 eV) (tR 13.8 min): m/z (%) = 197 (8), 199 (7)
[C6H4BrN3], 169 (25), 171 (24) [C6H4BrN], 90 (100) [C6H4N] (no
molecular ion).
GC/MS (EI, 70 eV) (tR 20.9 min): m/z (%) = 292 (6), 294 (9), 296
(4) [C6H6Br2N4], 172 (100), 174 (96) [C6H7BrN] (no molecular
ion).
(6) The substitution of the NHNH2 moiety by iodine was
described by Joshi,5c as well as by: (a) Brady, O. L.;
Bowman, J. H. J. Chem. Soc. 1921, 119, 896. (b) Meyer, E.
J. Prakt. Chem. 1887, 36, 115.
2,4,6-Tribromophenylhydrazine
(7) Also, the application of halogens for the oxidation of N,N¢-
disubstituted hydrazines to azo compounds is a well-
documented fact. See for example: (a) Overberger, C. G.;
Pao-Tung, H.; Berenbaum, M. B. Org. Synth. Coll. Vol. IV;
Wiley: London, 1966, 66. (b) Rabjohn, N. Org. Synth. Coll.
Vol. III; Wiley: London, 1966, 375.
GC/MS (EI, 70 eV) (tR 22.6 min): m/z (%) = 327 (35), 329 (100),
331 (98), 333 (32) [C6H4Br3N, M – NH], 248 (17), 250 (30), 252
(16) [C6H4Br2N, M – NH – Br], 168 (34), 170 (34) [C6H4BrN, M –
NH – 2 Br], 90 (46) [C6H4N, M – NH – 3 Br] (no molecular ion).
GC/MS (EI, 70 eV) (tR 28.3 min): m/z (%) = 445 (3), 447 (9), 449
(13), 451 (9), 453 (2) [C6HBr4N2], 352 (40), 354 (100), 356 (92),
358 (29) [C6HBr3N3] (no molecular ion).
(8) Sharghi and Eskandari2 concluded that 10 mol% of
phenylhydrazine is enough to obtain optimum yields of
halohydrins. This is inconsistent with the stoichiometry of
the total possible bromination and oxidation of
All fragments of mass spectra clearly indicate the presence of bro-
minated compounds.
phenylhydrazine which could give only eight HBr molecules
(PhNHNH2 + 7 Br2 = C6Br6 + N2 + 8 HBr). However, we did
not observe more than tetrabrominated products in the
reaction mixture. Since the main product is 2,4,6-
tribromophenylhydrazine, the proper stoichiometry should
be at least one mole of phenylhydrazine per three moles of
bromine (and respectively 3 mol of epoxide).
Tandem Halogenation and Epoxide Ring Opening; General
Procedure
To a stirred solution of epoxide (0.10 mol) and aromatic compound
(0.10 mol) in CH2Cl2 (25 mL), a solution of bromine (16.0 g, 0.10
mol) in CH2Cl2 (25 mL) was added dropwise (about 30 min) at
10 °C (ice–H2O bath was necessary since the reaction was exother-
mic). The reaction mixture was stirred to reach a temperature of
about 25 °C, then kept for a further 1 h the same temperature. The
solvent was evaporated, then the products were distilled off or frac-
tionated under reduced pressure. All compounds prepared accord-
ing to this procedure are known and were identified by means of
NMR.
(9) If our conclusion is correct, Sharghi and Eskandari2 should
observe the same or similar regioselectivity in their reaction
as in a common ring opening by hydrogen halogenides.
However, some of the results described in Table 2 of ref.2 are
hard to understand, since in many cases the regioselectivities
recorded are opposite to those indicated by the mechanism of
the ring opening reaction of epoxides and, therefore, should
be re-analysed.
(10) There are many examples of using epoxides as hydrogen
halogenide scavengers or a specific kind of ‘terminating’
base. The side products of those reactions are usually
halohydrins. For example, epoxides were extensively used
for the precipitation of amino acids from their
In the case of chlorination, an analogous procedure was applied ex-
cept that gaseous chlorine was bubbled through a cooled and stirred
solution of the epoxide (0.10 mol) and aromatic compound (0.10
mol) in CH2Cl2 (50 mL).
hydrochlorides or hydrobromides, see: (a) Gmeiner, P.;
Feldman, P. L.; Chu-Moyer, M. Y.; Rapoport, H. J. Org.
Chem. 1990, 55, 3068. (b) Jackson, R. F. W.; Turner, D.;
Synthesis 2003, No. 15, 2341–2344 © Thieme Stuttgart · New York