Conversion of nucleophilic halides to electrophilic halides: Efficient and selective halogenation of azinones, amides, and carbonyl compounds using metal halide/lead tetraacetate

Article abstract of DOI:10.1055/s-2006-926224

AlCl₃/Pb(OAc)₄ and ZnBr₂/Pb(OAc) ₄ are efficient electrophilic N- and α-C-halogenating agents. A variety of azinones, amides and carbonyl compounds were chemoselectively and regioselectively N-, or α-C-halogenated in good to excellent yield using AlCl₃/Pb(OAc)₄ and ZnBr₂/Pb(OAc)₄ in acetonitrile. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926224

1
94
LETTER
Conversion of Nucleophilic Halides to Electrophilic Halides: Efficient and
Selective Halogenation of Azinones, Amides, and Carbonyl Compounds Using
Metal Halide/Lead Tetraacetate
a
a
a
a
b
a
C
J
onversio
e
n of
N
ucleo
u
philic Halid
m
e
s
to Electrophilic
H
-
alides Jong Kim, Deok-Heon Kweon, Su-Dong Cho,* Ho-Kyun Kim, Sang-Gyeong Lee, Yong-Jin Yoon*
a
Department of Chemistry & Environmental Biotechnology National Core Research Center, Gyeongsang National University,
Chinju 660-701, Korea
Fax +82(55)7610244; E-mail: yjyoon@gsnu.ac.kr
b
Department of Chemistry & Research Institute of Life Science Gyeongsang National University, Chinju 660-701, Korea
Received 18 October 2005
benzene system,27 we had found that a combination of
metal chloride and lead tetraacetate (LTA) chlorinates py-
ridazin-3(2H)-ones to the corresponding N-chloro deriva-
Abstract: AlCl /Pb(OAc) and ZnBr /Pb(OAc) are efficient elec-
trophilic N- and a-C-halogenating agents. A variety of azinones,
amides and carbonyl compounds were chemoselectively and regio-
3
4
2
4
selectively N-, or a-C-halogenated in good to excellent yield using tives. This is an evidence of conversion of nucleophilic
AlCl /Pb(OAc) and ZnBr /Pb(OAc) in acetonitrile.
chlorine, metal chloride, to electrophilic chlorine such as
3
4
2
4
+
AcOCl (Cl equivalent). Therefore, we anticipated this
Key words: N-halogenation,, a-C-halogenation, electrophilic halo-
genation, selective halogenation, metal halide/lead tetraacetate
reaction to go through the following mechanism:
Pb(OAc) + MXn → Pb(OAc) + MX (OAc) + AcOX
4
2
n-1
AcOX + NuH → NuX + AcOH
In this study, we examined the N-chlorination of 4,5-
a-Halocarbonyl compounds1–3 and N-halonitrogen
4
,5
heterocycles are among the most versatile intermediates
in organic synthesis. Direct selective halogenation of car-
bonyl compounds and nitrogen heterocycles is also a very
important synthetic transformation technique. Electro-
philic halogenating agents are useful for halogenating
these carbonyl compounds and nitrogen heterocycles. In
general, direct conversion of carbonyl compounds such as
ketones to a-halocarbonyl compounds can be achieved by6
using halogenating agents such as copper(II) halides,
dichloropyridazin-3(2H)-one (1a) with ZnCl /Pb(OAc)4
2
in refluxing organic solvents such as dichloromethane,
dimethylformamide, acetonitrile, n-hexane and tetrahy-
drofuran (entries 1–5 in Table 1). Using acetonitrile as
solvent, 2-chloro derivative 2a was obtained exclusively
in 78% yield (entry 2 in Table 1). Subsequently, the chlo-
rination of 1a was evaluated in acetonitrile using various
MX /Pb(OAc) systems (entries 6–18 in Table 1). Using
n
4
FeCl (1 equiv) and AlCl (1 equiv), 2a was obtained ex-
7
8
3
3
sulfuryl chloride, p-toluenesulfonyl chloride, N-halo-
clusively in excellent yields (entries 6 and 10 in Table 1).
On the other hand, chlorination of 1a with SnCl4/
9
succinimide/p-toluenesulfonic acid, Koser’s reagent/
1
0
11
magnesium halides, tetraalkylammonium trihalides
Pb(OAc) (1:1 equiv) in refluxing dichloromethane gave
1
2
4
and bromine. Recently, much effort has been made to
2
a in 85% yield (entry 15 in Table 1), whereas 2a was not
develop new efficient methods for a-halogenation of 1,3-
formed at room temperature. Reaction of 1a with SnCl4/
1
3
dicarbonyl compounds.
Pb(OAc) (1:1 equiv) in refluxing acetonitrile for four
4
Also N-halo derivatives have been found to be useful and hours gave 2a in low yield although the reaction did not
4
,5,14–22
valuable compounds in organic synthesis.
For N- proceed completely (entry 16 in Table 1). Although the
halogenation of nitrogen heterocycles, and amides, a treatment of 1a with AlBr /Pb(OAc) in acetonitrile did
3
4
relatively few reagents for N-halogenation have been not yield 2-bromo derivative 2b, the compound 1a, when
described, including among others, tert-butyl hypo- reacted with ZnBr /Pb(OAc) in acetonitrile at room tem-
2
4
1
4–16
23
24
chlorite,
hypochlorite,
chlorine, sodium hypochlorite, calcium perature, gave 2b in excellent yield (entry 18 in Table 1).
9 ®25
1
Oxone
and trichloroisocyanuric However, treatment of 1a with AlI /Pb(OAc) or ZnI /
3 4 2
2
6
acids. However, these methods suffer from such draw- Pb(OAc) in acetonitrile did not give products. Neither
4
backs as long reaction times, cumbersome work-up proce- did the reaction of 1a with zinc chloride and other metal
dures, short shelf lifetime and emission of active oxygen. acetates such as Zn(OAc) , Cu(OAc) , Hg(OAc) ,
2
2
2
Here, we report a more convenient and effective method Sn(OAc) , Pd(OAc) and Tl(OAc) occur.
4
2
3
for the N- or a-C-halogenation of azinones, amides, and
carbonyl compounds.
On the other hand, the chlorination of benzene derivatives
with elemental chlorine has been reported to have yielded
In our previous work on phenylation of 4,5-dichloro- from SnCl /Pb(OAc)4 (2:1 equiv).28 However, when
4
pyridazin-3(2H)-one using lead tetraacetate/zinc chloride/ Pb(OAc) /AlCl (1:2 equiv; entry 11 in Table 1) or
4
3
Pb(OAc) /AlCl (0.5:1 equiv; entry 12 in Table 1) were
4
3
SYNLETT 2006, No. 2, pp 0194–0200
Advanced online publication: 24.01.2006
DOI: 10.1055/s-2006-926224; Art ID: U29005ST
0
1.
0
2.
2
0
0
6
used, the reactions did not occur. Consequently, the
mechanism of our system is different from the pathway
described in the literature28 although small amounts of
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Conversion of Nucleophilic Halides to Electrophilic Halides
195
Table 1 Reaction of 4,5-Dichloropyridazin-3(2H)-ones (1a) with Pb(OAc) /MX
4
n
Cl
Cl
Cl
Cl
Pb(OAc)4/MXn
solvent, reflux
N
N
O
N
H
O
N
X
1a
2a: X= Cl
b: X= Br
2
Entry
Pb(OAc) (equiv)
MX (equiv)
Solvent
CH Cl
Conditionsa
Product (%)b
4
n
2
a
2b
–
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
0.5
1
1
1
1
1
1
ZnCl (1)
20 h, r.t.
60c
2
2
2
ZnCl (1)
MeCN
DMF
1.5 h, reflux
4 h, reflux
4 h, reflux
4 h, reflux
1.5 h, reflux
4 h, reflux
5 h, reflux
7 h, reflux
1.1 h, reflux
1.1 h, reflux
1.1 h, reflux
1.1 h, reflux
3.7 h, reflux
12 h, reflux
4 h, reflux
10 min, r.t.
5 min, r.t.
78
–
2
ZnCl (1)
–d
–
2
ZnCl (1)
n-hexane
THF
No reaction
2
ZnCl (1)
No reaction
2
FeCl (1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
91
–
3
TiCl (1)
No reaction
4
CuCl (1)
30c
–
–
–
–
CuCl (1)
50c
2
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
AlCl (1)
93
3
AlCl (1)
92
3
AlCl (1)
No reaction
3
AlCl (2)
No reaction
3
AlCl (0.5)
48c
85
30c
–e
–
3
SnCl (1)
–
4
SnCl (1)
–
4
AlBr (1)
–
3
ZnBr (1)
–
95
2
a
b
c
d
e
Isolated yield.
Unreacted 1a was isolated.
N-Methyl-N-(6-oxo-6H-pyridazin-1-ylmethyl)formamide was isolated in good yield.
The unknown product was detected on TLC.
AlBr was reacted explosively with 1a under this condition to some unknown products.
3
chlorine or bromine were detected at the initial step. be formed by the reaction of lead tetraacetate with X , two
2
Based on the experiments for five different mole ratios of equivalents of lead tetraacetate would be required. How-
Pb(OAc) /AlCl (entries 10–14 in Table 1), the optimum ever, when one equivalent of Pb(OAc) (entry 10 in
4
3
4
molar ratio is 1:1 equivalent of Pb(OAc) /AlCl (entry 10 Table 1) was used, the N-halogenation proceeded com-
4
3
in Table 1). However, treatment of 1a with zinc chloride pletely. On the other hand, when excess AlCl was used
3
or chlorine in the absence of lead tetraacetate in acetoni- (entries 12, 13 in Table 1), no reaction occurred.
trile did not give trichloro compound 2a. Neither did the
For detailed comparison with a panel of representative
reaction of 1a with Zn(OAc) /Br occur. These results are
2
2
azinones and amides, two reaction systems, i.e., AlCl3/
Pb(OAc) /MeCN and ZnBr /Pb(OAc) /MeCN were
strongly suggestive of the conversion of nucleophilic
chloride such as zinc chloride to an electrophilic chloride
4
2
4
selected. N-Chlorination of benzotriazole, nicotinamide,
+
of AcOCl (Cl equivalent) in our system. Lead tetra-
isoindole-1,3-dione and saccharin with AlCl /Pb(OAc)4
3
2
9
acetate is a good acetoxylation agent. Reaction of lead
(
1:1 equiv) in acetonitrile gave the corresponding N-
3
0
tetraacetate with iodide affords AcOI. If AcOX were to
monochlorides in good to excellent yields, respectively
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York

1
96
J.-J. Kim et al.
LETTER
3
1
(
entries 1, 3, 7, 11, 15 and 17 in Table 2), whereas 2-py- indole-1,3-dione, 2,3-dihydrophthalzine-1,4-dione, sac-
ridone was found to be unreactive under the identical con- charin, pyrrolidine-2,5-dione and azepan-2-one with
dition. The reaction of toluene-4-sulfonamide and 2,3- ZnBr /Pb(OAc) in MeCN gave the corresponding N-
2
4
3
2
dihydrophthalzine-1,4-dione with AlCl /Pb(OAc) (2:2 bromo derivatives (entries 8, 12, 16 and 18 in Table 2)
3
4
equiv) in acetonitrile gave the corresponding N,N-dichlo- and N,N-dibromo derivative (entries 10 in Table 2).32
rides in 88% and 94% yields, respectively (entries 5 and 9
in Table 2). On the other hand, N-bromination of iso-
a
Table 2 N-Chlorination of Azaheterocycles and Amides Using Pb(OAc) /MX in Acetonitrile
4
n
RHN NHR'
or
X X
X2-NR or RN NR
Pb(OAc)4/MXn
MeCN
X-NRR'(H)
or
RNHR'(H)
X = Cl, Br
Time
1 h
Entry
1
MXn
Method b
A
Product
Yield (%)c
96
AlCl3
N
N
N
Cl
2
3
ZnBr2
AlCl3
1.1 h
1 h
A
A
N
No reaction
86
N
N
Br
O
NHCl
N
N
4
ZnBr2
1.3 h
A
O
No reaction
NHBr
5
6
7
AlCl3
ZnBr2
AlCl3
6 h
B
B
A
SO NCl
88
2
2
50 min
3 h
SO NBr
No reaction
88
2
2
O
NCl
O
8
9
ZnBr2
AlCl3
5 min
A
B
O
86
94
NBr
O
45 min
O
NCl
NCl
O
O
1
0
ZnBr2
1 h
B
41
NBr
NBr
O
S
1
1
1
2
AlCl3
ZnBr2
30 min
55 min
A
A
O
91
82
NCl
O2
O
NBr
S
O2
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York

LETTER
Conversion of Nucleophilic Halides to Electrophilic Halides
197
a
Table 2 N-Chlorination of Azaheterocycles and Amides Using Pb(OAc) /MX in Acetonitrile (continued)
4
n
RHN NHR'
or
X X
X2-NR or RN NR
Pb(OAc)4/MXn
MeCN
X-NRR'(H)
or
RNHR'(H)
X = Cl, Br
Time
7 h
Entry
MXn
Method b
A
Product
Yield (%)c
1
1
1
3
4
5
AlCl3
No reaction
O
N
Cl
ZnBr2
AlCl3
3 h
A
A
Unknown product
95
O
N
Br
1.3 h
O
NCl
O
O
1
6
ZnBr2
1 h
A
93
NBr
O
1
1
1
7
8
9
AlCl3
ZnBr2
AlCl3
45 min
1 h
A
B
B
O
90
84
97
NCl
O
NBr
15 mind
O
Cl
NH
Cl
Br
O
N
H
O
2
0
ZnBr2
20 min
B
O
94
Br
NH
O
N
H
O
2
2
1
2
AlCl3
ZnBr2
55 mind
15 min
B
B
O
O
95
85
H2N
NH2
NH2
Cl
Cl
O
O
H2N
Br
Br
a
b
c
d
Reaction temperature: at reflux temperature for the chlorination; at room temperature for the bromination.
Method A: MXn/ Pb(OAc) = 1:1 equiv. Method B: MXn/Pb(OAc) = 2:2 equiv.
Isolated yield.
4
4
Reflux temperature.
31
Furthermore, a-chlorination of 2-acetyl-3,4-dihydro-2H- respectively (entries 1, 6 and 9 in Table 3). Bromination
naphthalen-1-one and 2-benzylmalonic acid diethyl ester of 1-phenylbutane-1,3-dione, 2-acetyl-3,4-dihydro-2H-
with AlCl /Pb(OAc) (1:1 equiv) in acetonitrile gave ex- naphthalen-1-one and 2-benzylmalonic acid diethyl ester
3
4
clusively the corresponding a-monochlorides in excellent with ZnBr /Pb(OAc) (1:1 equiv) in MeCN furnished the
2
4
yields (entries 4 and 11 in Table 3), whereas malonic acid corresponding a-monobromides in good to excellent
diethyl ester was reacted under identical condition to yields, respectively (entries 2, 5 and 12 in Table 3).32 In
afford 2-chloro (60%) and 2,2-dichloro derivative (24%, addition, reaction of 1-phenylbutane-1,3-dione, indan-
3
1
entry 8 in Table 3). Treatment of 1-phenylbutane-1,3-di- 1,3-dione and malonic acid diethyl ester with ZnBr2/
one, indan-1,3-dione, and malonic acid diethyl ester with Pb(OAc) (2:2 equiv) in MeCN afforded the correspond-
4
AlCl /Pb(OAc) (2:2 equiv) in acetonitrile afforded the ing a,a-dibromides in good yields, respectively (entries 3,
3
4
corresponding a,a-dichlorides in good to excellent yields, 7 and 10 in Table 3).32
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York

1
98
J.-J. Kim et al.
LETTER
Table 3 a-Chlorination of Carbonyl Compounds 7 with MX /Pb(OAc) (1:1 equiv) in Acetonitrile at Room Temperature
n
4
O
O
MXn/
Pb(OAc)4
O
O
O
O
R
R'
R
R' or
R
R'
MeCN, r.t.
X
X
X
Entry
1
MXn
AlCl3
Time
Methoda
B
Product
Yield (%)b
6 h
O
O
97
Cl
O
Cl
O
2
3
4
5
6
ZnBr2
ZnBr2
AlCl3
ZnBr2
AlCl3
20 min
5.3 h
A
B
A
A
B
75
85
97
97
88
Br
O
O
Br
O
Br
O
5 min
10 min
3 h
Cl
O
O
Br
O
Cl
Cl
O
O
7
ZnBr2
AlCl3
30 min
2 h
B
A
86
Br
Br
O
8
9
O
O
O
O
O
60/24
EtO
OEt EtO
OEt
Cl
Cl
Cl
AlCl3
ZnBr2
AlCl3
15 min
3.5 h
7 h
B
B
A
O
88
86
98
EtO
EtO
EtO
OEt
OEt
OEt
Cl
Cl
O
1
1
0
1
O
Br
Br
O
O
Cl
Ph
O
1
2
ZnBr2
18 h
A
O
80
EtO
OEt
Br
Ph
a
Method A: molar ratio of azinone/MXn/Pb(OAc) = 1:1:1 equiv. Method B: molar ratio of azinone/MXn/Pb(OAc) = 1:2:2 equiv.
Isolated yield.
4
4
b
On the other hand, halogenation of barbituric acid or In summary, metal halide/lead tetraacetate [MXn/
malonamide using AlCl /Pb(OAc) (2:2 equiv) and Pb(OAc) ] is proven to be a good system for converting of
3
4
4
–
+
ZnBr /Pb(OAc) (2:2 equiv) in MeCN gave the corre- nucleophilic halogen (X ) to electrophilic halogen (X
2
4
sponding C ,C -dihalo derivatives chemoselectively in equivalent). The systems AlCl /Pb(OAc) and ZnBr /
a
a
3
4
2
excellent yields, respectively (entries 19–22 in Table 2).
Pb(OAc) are efficient electrophilic halogenating agents
4
for azinones, amides, and 1,3-dicarbonyl compounds. A
variety of azinones and amides were chemoselectively
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York

LETTER
Conversion of Nucleophilic Halides to Electrophilic Halides
199
N-halogenated in good to excellent yield using AlCl3/
Pb(OAc) and ZnBr /Pb(OAc) in acetonitrile. In addi-
(14) Poisel, H.; Schmidt, U. Angew. Chem., Int. Ed. Engl. 1976,
5, 294.
1
4
2
4
(
(
(
15) Kolar, A. J.; Olsen, R. K. Synthesis 1977, 457.
16) Daoust, B.; Lessard, J. Tetrahedron 1999, 55, 3495.
tion, a-halogenation of some 1,3-dicarbonyl compound
with AlCl /Pb(OAc) and ZnBr /Pb(OAc) in acetonitrile
3
4
2
4
17) Miosses, B.; Danion-Bougot, R.; Danion, D. Synthesis 1994,
171.
afforded a-monohalides or a,a-dihalides selectively in
good to excellent yields. The halogenation of barbituric
acid or malonamide involving 1,3-dicarbonyl and amide
NH chemoselectively afforded the corresponding C ,C -
1
(
18) de Souza, S. P. L.; da Silva, J. F. M.; de Mattos, M. C. S.
Synth. Commun. 2003, 33, 935.
(19) Freeman, J. P. Org, Synth. Coll. Vol. VII; John Wiley and
Sons: New York, 1993, 167.
a
a
dihalo derivatives in excellent yields. We believe that
these systems will also be applicable particularly to halo-
genation of various nitrogen heterocycles, amides, and ac-
tive methylene/methyne compounds.
(
(
(
(
(
(
(
20) Larionov, O. V.; Kozhushkov, S. I.; de Meijere, A. Synthesis
003, 1916.
21) Park, Y. D.; Kim, J. J.; Lee, S. G.; Falck, J. R.; Yoon, Y. J.
Synthesis 2005, 1136.
22) Marigo, M.; Kumaragurubaran, N.; Jorgensen, K. A. Chem.
Eur. J. 2004, 10, 2133.
23) Drago, R. S.; Wenz, D. A.; Carlson, R. J. J. Am. Chem. Soc.
2
Acknowledgment
1962, 84, 1106.
This work was supported by a grant from the Korea Science and
Engineering Foundation (KOSEF) to the Environmental Biotechno-
logy National Core Research Center (grant #: R15-2003-012-
24) Bachand, C.; Driguez, H.; Paton, J. M.; Touchard, D.;
Lessard, J. J. Org. Chem. 1974, 39, 3136.
25) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.;
Tsadjout, A. Synlett 2000, 813.
0
2001-0).
26) Luca, L. D.; Giacomelli, G.; Nieddu, G. Synlett 2005, 223.
References and Notes
(27) Kim, J. J.; Park, Y. D.; Cho, S. D.; Kim, H. K.; Chung, H.
A.; Lee, S. G.; Falck, J. R.; Yoon, Y. J. Tetrahedron Lett.
(
1) (a) De Kimpe, N.; Verhe, R. In The Chemistry of a-
Haloketones, a-Haloaldehydes and a-Haloimines; Patai, S.;
Rappoport, Z., Eds.; John Wiley: Chichester, UK, 1988, 1–
2004, 45, 8781.
(
(
28) Muathen, H. A. Tetrahedron 1996, 52, 8863.
29) Bulter, R. N. Synthetic Reagents; Pizey, J. S., Ed.; Ellis
Horwood Ltd: New York, 1977, 277.
119. (b) Smith, M. B.; March, J. In March’s Advanced
Organic Chemistry, 5th ed.; John Wiley and Sons, Inc.: New
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March’s Advanced Organic Chemistry, 5th ed.; John Wiley
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B.; March, J. In March’s Advanced Organic Chemistry, 5th
ed.; John Wiley and Sons, Inc.: New York, 2001, 1403–
(
(
30) Kalvoda, J.; Heusler, K. Synthesis 1971, 501.
31) Typical N-Chlorination of Azinones, Amides and
Carbonyl Compounds.
Pb(OAc) (2.0 or 4.0 mmol) was dissolved in MeCN (20
4
mL). AlCl or ZnCl (2.0 or 4.0 mmol) was added to the
3
2
MeCN solution, and the mixture was stirred for 5 min at r.t.
After adding the nitrogen heterocycle (2 mmol) or carbonyl
compound (2 mmol) to the above solution, the resulting
mixture was refluxed until nitrogen heterocycle or carbonyl
compound was disappeared. After evaporating the solvent
under reduced pressure, the resulting residue was applied to
the top of an open-bed silica gel column (3.0 × 7 cm). The
column was eluted with CH Cl or CH Cl –n-hexane (1:1).
1
405.
2) Larock, R. C. Comprehensive Organic Transformations,
nd ed.; VCH Publishers Inc.: New York, 1999, 715–719.
3) For examples of a-bromo 1,3-dicarbonyl compounds in
organic transformations, see: (a) Misa, A. P.; Raj, K.;
Bhaduri, A. P. Synth. Commun. 1999, 29, 3227. (b) Coats,
S. J.; Wasserman, H. H. Tetrahedron Lett. 1995, 36, 7735.
(
(
2
2
2
2
2
(
(
c) Endo, M.; Droghini, R. Can. J. Chem. 1988, 66, 1400.
d) Hlavka, J.; Bitha, P.; Lin, Y.; Srohmeyer, T. J.
Fractions containing the product were combined and
evaporated under reduced pressure to give monochlorides
and/or dichlorides.
Heterocycl. Chem. 1985, 22, 1317.
(
(
4) Fieser, M.; Fieser, L. F. Reagents for Organic Synthesis;
John Wiley and Sons: New York, 1967, 78.
5) Barton, D. R. H.; Ollis, W. D. In Comprehensive Organic
Chemistry, Vol. 2; Trost, B. M.; Fleming, I., Eds.; Pergamon
Press: Oxford, 1979, 1030.
Selected Analytical Data.
2
,4,5-Trichloropyridazin-3(2H)-one: colorless crystals
21
(CH Cl ); mp 146–147 °C (lit. 146–147 °C). TLC
2 2
(
1
1
CH Cl ): R = 0.5. IR (KBr): 3100, 1700, 1600, 1580, 1360,
2 2 f
–1
1
260, 1180, 1160, 960 cm . H NMR (CDCl ): d = 7.76 (s,
3
(
6) (a) Kosower, E. M.; Cole, W. J.; Wu, G. S.; Cardy, D. E.;
Meisters, G. J. Org. Chem. 1963, 28, 630. (b) King, L. C.;
Ostrum, G. K. J. Org. Chem. 1964, 29, 3459.
13
H) ppm. C NMR (CDCl ): d = 134.8, 137.0, 137.5, 153.8
3
ppm. Anal. Calcd for C HCl N O: C, 24.09; H, 0.51; N,
4
3
2
14.05. Found: C, 24.10; H, 0.53; N, 14.07.
(
(
(
7) Warnhoff, E. W.; Martin, D. G.; Johnson, W. S. Org. Synth.,
Coll. Vol. IV; J. Wiley and Sons: New York, 1963, 162.
8) Brummond, K. M.; Gesenberg, K. D. Tetrahedron Lett.
N-Chloroisoindole-1,3-dione: colorless crystals (CH Cl );
2
2
mp 184–185 °C. TLC (CH Cl ): R = 0.73. IR (KBr): 3070,
2
2
f
2
1
7
1
5
950, 2880, 1750, 1720, 1620, 1510, 1470, 1360, 1310,
1
999, 40, 2231.
9) Lee, J. C.; Bae, Y. H.; Chang, S. K. Bull. Korean Chem. Soc.
003, 24, 407.
–1 1
080, 860 cm . H NMR (CDCl ): d = 7.82–7.84 (m, 2 H),
3
13
.89–7.93 (m, 2 H) ppm. C NMR (CDCl ): d = 123.9,
3
2
31.0, 134.7, 163.3 ppm. Anal. Calcd for C H ClNO : C,
8
4
2
(10) Lee, J. C.; Park, J. Y.; Yoon, S. Y.; Bae, Y. H.; Lee, S. J.
Tetrahedron Lett. 2004, 45, 191.
2.92; H, 2.22; N, 7.71. Found: C, 52.98; H, 2.24; N, 7.79.
N,N-Dichlorotoluene-4-sulfonamide: colorless crystals
(
11) (a) Schlama, T.; Gabriel, K.; Gouverneur, V.; Mioskowski,
C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2342.
(
CH Cl ); mp 130–131 °C. TLC (CH Cl ): R = 0.57. IR
2 2 2 2 f
(
KBr): 3100, 3070, 1860, 1770, 1600, 1470, 1360, 1250,
(
b) Kajigaeshi, S.; Kakinami, T.; Okamoto, T.; Fujisaki, S.
–1 1
1
8
1
3
100, 910 cm . H NMR (CDCl ): d = 7.91–7.95 (m, 2 H),
3
Bull. Chem. Soc. Jpn. 1987, 60, 1159.
13
.02–8.06 (m, 2 H) ppm. C NMR (CDCl ): d = 125.7,
3
(
12) Pearson, D. I.; Poper, H. W.; Hargrove, W. E. Org. Synth.,
Coll. Vol. V; J. Wiley and Sons: New York, 1973, 117.
13) Yang, D.; Yan, Y.-L.; Lui, B. J. Org. Chem. 2002, 67, 7429.
31.3, 136.1, 162.8 ppm. Anal. Calcd for C H Br N O : C,
8
4
2
2
2
0.03; H, 1.26; N, 8.76. Found: C, 30.11; H, 1.30; N, 8.82.
(
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York

2
00
J.-J. Kim et al.
LETTER
combined and evaporated under reduced pressure to give
2
-Acetyl-2-chloro-3,4-dihydro-2H-naphthalen-1-one:
colorless crystals (CH Cl –n-hexane = 1:1); mp 49–50 °C
monobromides or dibromides.
Selected Analytical Data.
2
2
21
(
lit. mp 48–50 °C). TLC (CH Cl –n-hexane = 1:1):
2
2
R = 0.51. IR (KBr): 2950, 1720, 1680, 1600, 1460, 1420,
2-Bromo-3,4-dichloropyridazin-3(2H)-one: colorless
crystals (CH Cl ); mp 169 °C. IR (KBr): 3100, 1690, 1600,
f
–
1 1
1360, 1300, 1240, 1200, 900, 850, 750, 720 cm . H NMR
2
2
–
1 1
(
1
2
CDCl ): d = 2.42 (s, 3 H), 2.45–2.51 (m, 1 H), 2.90–2.99 (m,
1460, 1400, 1300, 1260, 1120, 960 cm . H NMR (CDCl ):
3
3
1
3
H), 3.05–3.08 (m, 1 H), 3.12–3.16 (m, 1 H), 7.41–7.46 (m,
H), 7.63–7.69 (m, 1 H), 7.95 (d, 1 H, J = 7.8 Hz) ppm. 13
d = 7.50 (s, 1 H) ppm. C NMR (CDCl ): d = 132.3, 136.2,
154.7, 168.0 ppm. Anal. Calcd for C HBrCl N O: C, 19.70;
3
C
4
2
2
NMR (CDCl ): d = 25.0, 26.6, 30.0, 75.9, 127.3, 127.7,
H, 0.41; N, 11.49. Found: C, 19.76; H, 0.43; N, 11.51.
3
1
29.2, 129.5, 134.7, 142.9, 189.3, 201.0 ppm. Anal. Calcd
N-Bromoisoindole-1,3-dione: colorless crystals (CH Cl );
2
2
3
3
for C H ClO : C, 64.73; H, 4.98. Found: C, 64.75; H, 4.99.
mp 199–200 °C (lit. mp 198–202 °C). TLC (CH Cl ):
1
2
11
2
2
2
2
,2-Dichloro-1-phenylbutane-1,3-dione: colorless crystals
R = 0.76. IR (KBr): 3090, 3050, 1775, 1730, 1690, 1610,
1460, 1350, 1290, 1100, 1070, 860, 800, 700 cm . H NMR
f
2
1
–1 1
(CH Cl –n-hexane = 1:2); mp 75–76 °C (lit. mp 75–
2
2
7
3
1
6 °C). TLC (CH Cl –n-hexane = 1:2): R = 0.50. IR (KBr):
(CDCl ): d = 7.73–7.77 (m, 2 H), 7.88–7.91 (m, 2 H) ppm.
2
2
f
3
1
3
070, 2930, 2880, 1760, 1730, 1710, 1680, 1600, 1580,
510, 1450, 1360, 1250, 1230, 840, 780, 690, 660, 580
C NMR (CDCl ): d = 123.8, 131.9, 134.3, 165.0 ppm.
3
Anal. Calcd for C H BrNO : C, 42.51; H, 1.78; N, 6.20.
8
4
2
–
1 1
cm . H NMR (CDCl ): d = 2.47 (s, 3 H), 7.46–7.54 (m, 2
H), 7.61–7.67 (m, 1 H), 8.06–8.10 (m, 2 H) ppm. C NMR
Found: C, 42.59; H, 1.84; N, 6.27.
3
13
2,3-Dibromophthalazine-1,4-dione: colorless crystals
(CH Cl ); mp 130–131 °C. TLC (CH Cl ): R = 0.57. IR
(
1
CDCl ): d = 24.9, 86.5, 128.7, 130.6, 130.9, 134.5, 185.9,
3
2
2
2
2
f
92.2 ppm. Anal. Calcd for C H Cl O : C, 51.98; H, 3.49.
(KBr): 3100, 3070, 1860, 1770, 1600, 1470, 1360, 1250,
1
0
8
2
2
–
1 1
Found: C, 51.99; H, 3.52.
1100, 910 cm . H NMR (CDCl ): d = 7.91–7.95 (m, 2 H),
3
1
3
2,2-Dichloroindan-1,3-dione: colorless crystals (CH Cl –
8.02–8.06 (m, 2 H) ppm. C NMR (CDCl ): d = 125.7,
131.3, 136.1, 162.8 ppm. Anal. Calcd for C H Br N O : C,
2
2
3
n-hexane = 1:1); mp 125–126 °C. TLC (CH Cl –n-hexane =
2
2
8
4
2
2
2
1
:1): R = 0.63. IR (KBr): 3100, 3060, 2930, 2880, 1780,
30.03; H, 1.26; N, 8.76. Found: C, 30.11; H, 1.30; N, 8.86.
2-Bromo-1-phenylbutane-1,3-dione: colorless oil. TLC
(CH Cl ): R = 0.52. IR (KBr): 3080, 2970, 2940, 1720,
f
–
1 1
1740, 1600, 1260, 1160, 870, 810, 780, 650 cm . H NMR
(
CDCl ): d = 8.07–8.11 (m, 2 H), 8.13–8.17 (m, 2 H) ppm.
3
2
2
f
1
3
C NMR (CDCl ): d = 72.8, 125.8, 137.0, 138.1, 186.4 ppm.
1680, 1600, 1450, 1360, 1300, 1230, 1190, 1000, 760, 690,
3
–
1 1
Anal. Calcd for C H Cl O : C, 50.27; H, 1.87. Found: C,
550 cm . H NMR (CDCl ): d = 2.44 (s, 3 H), 5.67 (s, 1 H),
8
4
2
2
3
50.29; H, 1.91.
7.46–7.52 (dd, 2 H, J = 7.87, 7.41 Hz), 7.50–7.65 (m, 1 H),
1
3
(
32) Typical N-Bromination of Azinones, Amides and
7.95–7.98 (m, 2 H) ppm. C NMR (CDCl ): d = 27.2, 53.0,
128.6, 129.0, 129.2, 134.5, 190.0, 198.1 ppm. Anal. Calcd
for C H BrO : C, 49.82; H, 3.76. Found: C, 49.84; H, 3.80.
3
Carbonyl Compounds.
Pb(OAc) (2.0 or 4.0 mmol) was dissolved in MeCN (20
4
10
8
2
mL). ZnBr (2.0 or 4.0 mmol) was added to the MeCN
2,2-Dibromomalonic Acid Diethyl Ester: colorless oil.
TLC (CH Cl –n-hexane = 1:1): R = 0.50. IR (KBr): 2980,
2
solution, and the mixture was stirred for 5 min at r.t. The
nitrogen heterocycle (2 mmol) or carbonyl compound (2
mmol) was added to the resulting solution. The resulting
mixture was stirred at r.t. until nitrogen heterocycle or
carbonyl compound disappeared. After evaporating the
solvent under reduced pressure, the resulting residue was
applied to the top of an open-bed silica gel column (3.0 × 7
cm). The column was eluted with CH Cl or CH Cl –n-
2
2
f
2930, 2890, 1760, 1740, 1465, 1445, 1390, 1365, 1290,
–
1 1
1240, 1200 cm . H NMR (CDCl ): d = 1.32–1.37 (t, 6 H,
3
1
3
J = 7.13 Hz), 4.33–4.41 (q, 4 H, J = 7.13 Hz) ppm. C NMR
(CDCl ): d = 13.7, 50.7, 64.7, 163.1 ppm. Anal. Calcd for
3
C H Br O : C, 26.44; H, 3.17. Found: C, 26.50; H, 3.20.
7
10
2
4
(33) Day, J. C.; Govindaraj, N.; McBain, D. S.; Skell, P. S.;
Tanko, J. M. J. Org. Chem. 1986, 51, 4959.
2
2
2
2
hexane (1:1). Fractions containing the product were
Synlett 2006, No. 2, 194–200 © Thieme Stuttgart · New York