8
Tetrahedron
ACCEPTED MAN
To
U
SC
a
so
R
lut
I
ion of 1-tetradecene (7a, 408 mg, 2.08 mmol) in
P
T
CH Cl (4 mL) was added 3a (990 mg, 2.11 mmol), and the
2
2
mixture was stirred at 20 °C for 1 h. The reaction mixture was
then diluted with hexane (50 mL) and washed with water (20 mL
×
2). The organic layer was dried over Na SO (15 g) and
2 4
concentrated in vacuo. The crude residue (690 mg) was purified
using silica gel column chromatography (eluent: hexane) to
afford 1,2-dibromotetradecane (8a, 683 mg, 92 %) [23] as a
1
colourless liquid; H NMR (400 MHz, CDCl ) δ 0.88 (t, J = 6.9
3
Hz, 3H), 1.27–1.45 (m, 20H), 1.73–1.82 (m, 1H), 2.10-2.18 (m,
1
H), 3.62 (dd, J = 9.7 Hz, J = 10.1 Hz, 1H), 3.84 (dd, J = 4.1 Hz,
Scheme 13. Evaluation of the Hofmann rearrangement of
benzamide with 3a.
J = 10.1 Hz, 1H), 4.17 (ddt, J = 9.7 Hz, J = 4.1 Hz, J = 5.5 Hz,
1H); C NMR (100 MHz, CDCl ) δ 14.21, 22.78, 26.82, 28.91,
13
3
2
9.45, 29.49, 29.63, 29.74 (3C), 32.01, 36.07, 36.32, 53.09.
3
. Conclusion
4.3. Typical procedure for the α-bromination of carbonyl
compounds with 3a (Table 6, 10a)
We developed bis(1,3-dimethyl-2-imidazolidinone) hydro-
To a solution of propiophenone (9a, 285 mg, 2.15 mmol) in
tribromide (DITB, 3a) as novel bromine alternative. In addition,
a novel procedure for the preparation of HBr complexes was
established. Our procedure is significant since it uses lower
amounts of reagents and provides higher yields of products than
previous methods. Specifically, since Br also produces HBr, no
HBr source is required in this new method. The physical
properties of 3a reveal that this complex is robust in air. In
addition, 3a is more soluble in a variety of organic solvents than
MPHT (3b) and TBATB (1c). X-ray crystallography revealed
that the Br3 unit is surrounded by four DMI units, which
indicates that Br3 is highly stable within the crystal. Olefins,
carbonyl compounds, and aromatics were brominated with 3a,
which also facilitated the Hofmann rearrangement, providing the
desired products in good-to-excellent yields. To evaluate the
reactivity of 3a, the above four reactions were also carried out
with 3b, 1c, and DDB (1a). The reactivity of 3a was observed to
be almost identical to that of alternatives 3b, 1a, and 1c during
the bromination of olefins and in the Hofmann rearrangement.
On the other hand, the use of 3a for the α-bromination of
carbonyl compounds yielded the desired products in much higher
yields than 3b owing to its superior solubility. Similarly, when
CH Cl (4 mL) was added 3a (1.23 g, 2.62 mmol), and the
2
2
3
mixture was stirred at 20 °C for 1 h. The reaction mixture was
quenched with saturated NaHCO aqueous solution and then
3
extracted with diethyl ether (15 mL × 3). The combined organic
layers were washed with water (20 mL × 2), dried over Na SO
and concentrated in vacuo. The resulting crude residue was
purified using silica gel column chromatography (eluent:
2
2
4
hexane/chloroform = 1:2) to afford bromide 10a (433 mg, 94 %)
1
-
[24] as a white crystalline solid; H NMR (400 MHz, CDCl )
3
-
δ 1.90 (d, J = 6.7 Hz, 3H), 5.30 (q, J = 6.7 Hz, 1H), 7.48 (t, J =
8
.1 Hz, 2H), 7.59 (t, J = 8.1 Hz, 1H), 8.02 (d, J = 8.1 Hz, 2H);
1
3
C NMR (100 MHz, CDCl ) δ 20.25, 41.60, 128.87, 129.04,
3
1
4
33.81, 134.14, 193.46.
.4. Typical procedure for the bromination of aromatic
compounds with 3a (Table 7, 13a)
To a mixture of 1,4-dimethoxybenzene (12a, 277 mg, 2.01
mmol) in acetic acid (4 mL), was added 3a (1.02 g, 2.17 mmol)
and the mixture was stirred at 50 °C for 6 h. The reaction mixture
was quenched with saturated NaHCO aqueous solution and then
3
brominating
aromatics,
1c
afforded
2-bromo-1,4-
extracted with diethyl ether (15 mL × 3). The combined organic
layers were washed with water (20 mL × 2), dried over Na SO
and concentrated in vacuo. The resulting crude residue was
purified using silica gel column chromatography (eluent:
dimethoxybenzene in moderate yield due to its poor solubility in
acetic acid, while 3a provided the product in higher yield. In
conclusion, DITB (3a) is a simple to prepare, air stable, and
convenient alternative to molecular bromine in many
bromination reactions.
2
4
hexane/benzene = 1:1) to afford bromide 13a (310 mg, 71%) [25]
1
as a pale brown crystalline solid; H NMR (400 MHz, CDCl ) δ
3
3
1
1
.72 (s, 3H), 3.81 (s, 3H), 6.77–6.82 (m, 2H), 7.10 (d, J = 2.3 Hz,
13
H); C NMR (100 MHz, CDCl ) δ 55.81, 56.74, 111.84,
3
12.98, 113.53, 118.96, 150.19, 153.95.
4
. Experimental section
4
.5. Typical procedure for the Hofmann rearrangement with 3a
4
.1. Preparation of Bis (1,3-dimethyl-2-imidazolidinone)
(Table 8, 15c)
hydrotribromide (DITB, 3a)
To a mixture of benzamide (14c, 244 mg, 2.01 mmol) in
To a 50 mL round-bottom-flask equipped with a drying tube
containing calcium chloride, was added 1,3-dimethyl-2-
imidazolidinone (2.54 g, 22.2 mmol) in diethyl ether (20 mL) at 0
methanol (2 mL), was added NaOMe (498 mg, 9.21 mmol) in
methanol (6 mL) and the mixture was stirred at 20 °C for 15 min.
Complex 3a (1.18 g, 2.52 mmol) and methanol (2 mL) were
added to the mixture and stirred at reflux for 4 h. The reaction
mixture was then cooled to room temperature, diluted with
°
C. Molecular bromine (809 mg, 5.06 mmol) was slowly added
to the flask at the temperature, and the mixture was stirred at 0 °C
for 1 h. Diethyl ether (30 mL) was added to the mixture,
separating an orange precipitation, which was then filtered and
washed with ether (10 mL × 3) to afford an orange crystalline
diethyl ether (20 mL) and quenched with a saturated NH Cl
4
aqueous solution (40 mL). After separation of the organic layer,
the aqueous layer was further extracted with diethyl ether (15 mL
3). The combined organic layers were washed with water (20
−1 1
solid (1.41 g, 89%). Mp: 117-118 °C; νmax (KBr) 1625 cm ; H
NMR (400 MHz, CDCl ) δ 2.98 (s, 12H, NCH ), 3.63 (s, 8H,
×
3
3
13
mL × 2), dried over Na SO , and concentrated in vacuo. The
2
4
CH ), 10.5 (bs, 1H, HBr); C NMR (100 MHz, CDCl ) δ 32.15,
2
3
resulting crude residue was purified using silica gel column
chromatography (eluent: hexane/chloroform = 1:1) to afford
4
6.30, 161.76. Found: C, 25.58; H, 4.50; N, 11.99; Br, 51.13.
C H N O Br requires C, 25.61; H, 4.51; N, 11.95, Br, 51.11%.
10
21
2
3
3
methyl phenylcarbamate (15c, 289 mg, 95 %) [26] as a white
1
4
.2 Typical procedure for the bromination of olefins with 3a
crystalline solid; H NMR (400 MHz, CDCl ) δ 3.77 (s, 3H),
3
(Table 5, 8a)