PAPER
Catalytic Sandmeyer Bromination
2537
F4BN2
N2BF4
Br
Br
Br
1
0 mol% CuBr/CuBr2/phen, KBr
+
MeCN, 20 °C
dibenzo-18-crown-6
1r
2r
1%
8
13%
Scheme 2
Cu(II)/phen catalytic system. This synthetic protocol er 2 min and a solution of 1a (0.210 g, 1 mmol) in anhyd MeCN (2
mL) was slowly syringed into the mixture.
seems to be highly useful for the preparation of various
aryl bromides and dibromides in excellent yields.
Procedure C: To a stirred suspension of KBr (0.119 g, 1 mmol) in
a solution of dibenzo-18-crown-6 (0.018 g, 0.05 mmol) in anhyd
MeCN (2 mL), was added Cu(I) salt (0.1 mmol, 10 mol%), and the
resulting mixture was stirred at r.t. for 5 min. Copper(II) salt (0.1
mmol, 10 mol%) was pretreated similarly. To the combined solu-
tions, was added 1,10-phenanthroline (0.018g, 0.1 mmol, 10 mol%)
and then, after stirring for 2 min, a solution of 1a (0.210 g, 1 mmol)
in anhyd MeCN (2 mL) was slowly syringed into the mixture.
The reactions were carried out by using standard Schlenk technique
under N with magnetic stirring. MeCN was distilled over CaH . PE
2
2
refers to the petroleum ether fraction with boiling point range of 40–
7
0
0 °C. Column chromatography was performed on silica gel 0.035–
.070 mm. TLC was performed on Fluka silica gel plates and visu-
1
13
alized by UV (254 nm). H and C NMR spectra were recorded in
CDCl on a Bruker AMX400 spectrometer (400.13 and 100.61
3
Aryl Bromides 2a–p; General Procedure
To a stirred suspension of KBr (0.714 g, 6 mmol) in anhyd MeCN
19
MHz, respectively). F NMR spectra were recorded in CDCl on a
3
Bruker Avance 300 spectrometer (282.38 MHz). Chemical shifts
are given in ppm relative to the resonance of the residual protons of
(
6 mL) were added dibenzo-18-crown-6 (0.108 g, 0.3 mmol, 10%
mol), CuBr (0.043 g, 0.3 mmol, 10% mol), and CuBr (0.067 g, 0.3
2
1
19
the solvent ( H: CHCl = 7.25 ppm). F chemical shifts are given
3
mmol, 10% mol). After stirring for 2 min, 1,10-phenanthroline
(0.054 g, 0.3 mmol, 10% mol) was added. A solution of diazonium
salt 1 (3 mmol) in anhyd MeCN (6–12 mL) was added dropwise to
the resulting mixture. The mixture was stirred for 20 min at r.t., di-
relative to PhF. (MeCN) CuBF was prepared by dissolving Cu O
4
4
2
in a boiling mixture of MeCN and 40% HBF (50:1 by volume) and
4
recrystallized from MeCN.
luted with Et O (50 mL) and passed through a layer of Celite to re-
2
Arenediazonium Tetrafluoroborates 1a–r; General Procedure
To a solution of the corresponding amine (0.1 mol) in concd HCl
move inorganic salts. The organic solvents were removed in
vacuum, and the residue, if necessary, was subjected to column
(
30 mL) and H O (30 mL) cooled to 0–5 °C, was slowly added a
1
2
chromatography to give the corresponding aryl bromide. H NMR
cold solution of NaNO (6.9 g, 0.1 mol) in H O (15 mL). The result-
2
2
spectra of 2a–n,p–q were identical with those of the authentic com-
pounds.
ing solution was filtered, cooled, and a solution of NH BF (13.7 g,
4
4
0
0
.13 mol) in H O (50 mL) was added. After stirring for 30 min at
°C, the precipitate formed was filtered, washed with cold 5% so-
2
1
-Bromo-4-chlorobenzene (2b)
lution of NH BF , cold MeOH, and Et O. Diazonium salt was air-
4
4
2
Purified by column chromatography (PE); yield: 0.568 g (99%);
colorless solid; mp 64–65 °C (Lit. mp 64–66 °C).
dried and stored at 0 °C before use. Bisdiazonium salts were pre-
pared analogously from 0.05 mol of the corresponding diamine. The
yields of arenediazonium tetrafluoroborates were 61–97%.
10
1
-Bromo-3-chlorobenzene (2c)
Purified by the column chromatography (PE); yield: 0.568 g (99%);
colorless liquid.
Catalyst Screening
To a stirred suspension of KBr (2 mmol) in a solution of a phase-
transfer catalyst (0.1 mmol, 10 mol%) in anhyd MeCN (2 mL), was
added the appropriate quantities of copper salts (see Table 1) and
4
-Bromoanisole (2e)
Purified by the column chromatography (PE–EtOAc, 99:1); yield:
0
.1 mmol (10 mol%) of a ligand. After stirring for 2 min at r.t., a so-
0
.544 g (97%); colorless liquid.
lution of 1a (0.210 g, 1 mmol) in anhyd MeCN (2 mL) was slowly
syringed into the mixture. When the gas evolution had ceased, 0.4
1
-Bromo-3,5-dichlorobenzene (2k)
1
9
mL of the solution was mixed with 0.2 mL of DMSO-d and
F
10
6
Yield: 0.677 g (99%); white crystals; mp 76–77 °C (EtOH) (Lit.
mp 76–76.5 °C).
NMR spectrum was recorded.
Variations of Catalyst Preparation
1
-Bromo-3,4,5-trichlorobenzene (2l)
Procedure A: To a stirred suspension of KBr (0.238 g, 2 mmol) in a
solution of dibenzo-18-crown-6 (0.036 g, 0.1 mmol, 10 mol%) in
anyhd MeCN (2 mL), were added (MeCN) CuBF (0.031 g, 0.1
Yield: 0.781 g (99%); colorless needles; mp 55–56 °C (EtOH)
11
(
Lit. mp 56 °C).
4
4
mmol, 10 mol%), Cu(BF ) (0.024 g, 0.1 mmol, 10 mol%), and
4
2
4-Bromo-N,N-diethylaniline (2m)
Purified by the column chromatography (PE–EtOAc, 97:3); yield:
1
,10-phenanthroline (0.018 g, 0.1 mmol, 10 mol%). After stirring
for 2 min at r.t., a solution of 1a (0.210 g, 1 mmol) in anhyd MeCN
2 mL) was slowly syringed into the mixture.
12
0
.650 g (95%); colorless solid; mp 33–34 °C (Lit. mp 33 °C).
(
Procedure B: To a stirred suspension of KBr (0.238 g, 2 mmol) in a
solution of dibenzo-18-crown-6 (0.036 g, 0.1 mmol, 10 mol%) in
anhyd MeCN (2 mL), were added (MeCN) CuBF (0.031 g, 0.1
4¢-Bromoacetophenone (2n)
Yield: 0.591 g (99%); colorless crystals; mp 51–52 °C (PE) (Lit.
mp 51–52 °C).
1
3
4
4
mmol, 10 mol%), and Cu(BF ) (0.024 g, 0.1 mmol, 10 mol%). Af-
4
2
1,2-Dibromo-3-chloro-5-methylbenzene (2o)
ter stirring for 2 min at r.t., 1,10-phenanthroline (0.018g, 0.1 mmol,
0 mol%) was added to the mixture. The mixture was stirred anoth-
The synthesis and work-up were carried out as described in the gen-
eral procedure. After column chromatography (PE), 3-bromo-5-
1
Synthesis 2007, No. 16, 2534–2538 © Thieme Stuttgart · New York