Cleavage of epoxides into halohydrins with elemental iodine and bromine in the presence of 2,6-bis[2-(o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene (BABMB) as catalyst

Article abstract of DOI:10.1016/S0040-4020(02)01349-2

The ring opening of epoxides with elemental iodine and bromine in the presence of 2,6-bis[2-(o-aminophenoxy)methyl]-4-bromo-1-methoxybenzene as a new catalyst affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs regioselectively under neutral and mild conditions in various aprotic solvents even when sensitive functional groups are present.

Full text of DOI:10.1016/S0040-4020(02)01349-2

Tetrahedron 58 (2002) 10259–10261
Cleavage of epoxides into halohydrins with elemental iodine and
bromine in the presence of 2,6-bis[2-(o-aminophenoxy)methyl]-4-
bromo-1-methoxybenzene (BABMB) as catalyst
*
Khodabakhsh Niknam and Taibeh Nasehi
Department of Chemistry, Faculty of Science, Persian Gulf University, Bushehr 75168, Iran
Received 9 July 2002; revised 23 September 2002; accepted 17 October 2002
Abstract—The ring opening of epoxides with elemental iodine and bromine in the presence of 2,6-bis[2-(o-aminophenoxy)methyl]-4-
bromo-1-methoxybenzene as a new catalyst affords vicinal iodo alcohols and bromo alcohols in high yields. This new procedure occurs
regioselectively under neutral and mild conditions in various aprotic solvents even when sensitive functional groups are present. q 2002
Elsevier Science Ltd. All rights reserved.
There is a continued interest in the regioselective ring
opening of oxiranes to the corresponding vicinal halo-
hydrins. Although a variety of new and mild procedures to
effect this transformation have been reported, most of them
have some limitations.1 The reaction is typically performed
with hydrogen halides, but the harsh reaction conditions and
the low observed regioselectivity in the opening of
unsymmetrical epoxides have prompted a search for more
selective and milder procedures.1b Recently, it has been
found that epoxides can be converted into halohydrins by
means of elemental halogen,2 but this method has
limitations such as low yield, long reaction times, low
regioselectivity and formation of acetonide byproducts in
addition to the expected iodoadduct. Furthermore, iodina-
tion does not occur in aprotic solvents other than acetone.
As shown in Table 1, in each case, cleavage of the epoxide
ring occurs and upon thiosulfate workup, the corresponding
iodohydrins and bromohydrins are obtained. The yields
obtained with this methodology are good to excellent and
the reaction times are very short. The optimum amount of
catalyst was found to be 0.1 mol for 1 mol of epoxide and
halogen. As indicated in entries 9 and 10 in which only the
anti-isomer is obtained, the reactions are completely anti-
stereoselective. As for the regioselectivity, an attack of the
nucleophile preferentially occurs at the less-substituted
oxirane carbon. An anti-Markovnikov-type5,6 regio-
selectivity is generally observed in these reactions. In
many cases, this type of regioselectivity appears to be the
opposite of that observed in ring opening of the same
epoxides with aqueous hydrogen halides under classic
acidic conditions.7
In conjunction with ongoing work in our laboratory on the
synthesis and formation of complex heterocyclic com-
pounds containing donor nitrogen atoms, with neutral
molecules such as iodine and bromine,3 we found out that
2,6-bis[2-(o-aminophenoxy)methyl]-4-bromo-1-methoxy-
benzene (BABMB) efficiently catalyzed the addition of
elemental iodine and bromine to epoxides under mild
reaction conditions with high regioselectivity. Recently, we
prepared4 BABMB and used it as a starting diamine
material for the preparation of corresponding macracyclic
diamides. In this study, we wish to report the results of the
reactions of some epoxides with elemental iodine and
bromine in the presence of a sub-stoichiometric amount of
BABMB (Scheme 1, Table 1).
On the basis of our study on the complexation of BABMB
and other work reported on different ligands8–14 with
elemental halogen, it seems that in these reactions trihalide
ion, X23 , is formed and used as the nucleophile. The
electronic absorption spectra of the related addition of
BABMB to iodine shows a strong band at 364 nm and a
strong band at 272 nm in addition of BABMB to bromine,
presumably due to the complex formation of this ligand with
I2 and Br2. In contrast, none of the initial reactants show any
measurable absorption in these regions. It should be noted
that the bands of 364 and 272 nm are characteristic for the
formation of I23 and Br32 ions, respectively, in the process of
complex formation of different electron pair donor ligands
with iodine10–12 and bromine.13,14 In order to ascertain the
effect of the nature of solvent, the reactions with styrene
oxide in various aprotic solvents were carried out. The
Keywords: epoxide; halohydrin; catalyst.
*
Corresponding author. Tel.: þ98-771-4541494; fax: þ98-771-4545188;
e-mail: kh_niknam@yahoo.com
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01349-2

10260
K. Niknam, T. Nasehi / Tetrahedron 58 (2002) 10259–10261
Scheme 1.
Table 1. Reaction of various epoxides with iodine and bromine in the
presence of BABMB catalyst in CH2Cl2 at room temperature
results are shown in Table 2. The reactions were largely
dependent on the nature of solvent.
Entry Substrate Halogenation
(X2)
Product
Reaction time Yielda
(h)
(%)
In conclusion, this new method appears to be highly
competitive with the other methods reported in the
literature. The reaction occurs in neutral and mild conditions
on the acid-sensitive substrates and vicinal halohydrins
were obtained in high yields and regioselectivity. In
addition, in comparison with our previous methods,3
BABMB is cheaper, less step need for preparation, and
overall yield is higher.
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1c
1c
1d
1d
I2
Br2
I2
Br2
I2
Br2
I2
2a
0.17
0.25
6.5
5.5
6.0
0.67
5.75
1.5
97
95
94
95
93
87
80
85
2g
2b
2h
2c
2i
2d
2j
Br2
9
I2
2.5
90
91
1. General procedure for cleavage of epoxides with
elemental halogens
10
1e
Br2
0.67
Epoxide (1 mmol) in CH2Cl2 (5 mL) was added to a stirred
solution of BABMB catalyst (0.1 mmol) in CH2Cl2 (5 mL)
at room temperature. Next, a solution of elemental halogen
(1 mmol) in CH2Cl2 (5 mL) was added portion-wise
(15 min) to the above mixture. The progress of the reaction
was monitored by GLC and TLC. After complete
disappearance of the starting material, the reaction mixture
was washed with 10% aqueous Na2S2O3 (2£10 mL) and
water (2£10 mL). The aqueous layer was extracted with
CH2Cl2 (2£10 mL).The combined organic layer was dried
over anhydrous MgSO4 and evaporated to give crude
alcohol–catalyst. The crude products were purified on a
column of silica gel. The solvent was evaporated and pure
halohydrin was obtained. The halohydrins obtained
throughout this procedure were identified by comparison,
where possible, with authentic samples prepared in
accordance with literature procedures.2,3,15–18
11
12
1f
1f
I2
Br2
2f
2l
10.0
3.75
82
80
a
Yield of isolated product.
Table 2. Halogenation reaction of styrene oxide in the presence of 0.1 mol
of BABMB in various solvents
Entry
Solvent
Time (h)
Yielda (%)
Bromination Iodination Bromination Iodination
1
2
3
4
5
6
CH2Cl2
CHCl3
C6H6
CH3CN
CH3COCH3
THF
0.33
0.5
1
1
1.5
1.5
0.75
1.5
2
2
3
.95
.95
86
87
77
.95
91
90
85
62
51
3
63
a
GC yield.

K. Niknam, T. Nasehi / Tetrahedron 58 (2002) 10259–10261
10261
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Acknowledgements
We gratefully acknowledge Professor H. Sharghi for his
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