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
York, 2001, 559–561. (c) Smith, M. B.; March, J. In
March’s Advanced Organic Chemistry, 5th ed.; John Wiley
and Sons, Inc.: New York, 2001, 1212–1213. (d) Smith, M.
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