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Synlett 2006(2): 194-200  
DOI: 10.1055/s-2006-926224
LETTER
© Georg Thieme Verlag Stuttgart · New York

Conversion of Nucleophilic Halides to Electrophilic Halides: Efficient and Selective Halogenation of Azinones, Amides, and Carbonyl Compounds Using Metal Halide/Lead Tetraacetate

Jeum-Jong Kima, Deok-Heon Kweona, Su-Dong Cho*a, Ho-Kyun Kima, Sang-Gyeong Leeb, Yong-Jin Yoon*a
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
Further Information

Publication History

Received 18 October 2005
Publication Date:
24 January 2006 (online)

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Abstract

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.

Key words

N-halogenation, - α-C-halogenation - electrophilic halogenation - selective halogenation - metal halide/lead tetraacetate

31

Typical N-Chlorination of Azinones, Amides and Carbonyl Compounds.
Pb(OAc)4 (2.0 or 4.0 mmol) was dissolved in MeCN (20 mL). AlCl3 or ZnCl2 (2.0 or 4.0 mmol) was added to the 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 CH2Cl2 or CH2Cl2-n-hexane (1:1). Fractions containing the product were combined and evaporated under reduced pressure to give monochlorides and/or dichlorides.
Selected Analytical Data.2,4,5-Trichloropyridazin-3(2 H )-one: colorless crystals (CH2Cl2); mp 146-147 °C (lit. [21] 146-147 °C). TLC (CH2Cl2): R f = 0.5. IR (KBr): 3100, 1700, 1600, 1580, 1360, 1260, 1180, 1160, 960 cm-1. 1H NMR (CDCl3): δ = 7.76 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 134.8, 137.0, 137.5, 153.8 ppm. Anal. Calcd for C4HCl3N2O: C, 24.09; H, 0.51; N, 14.05. Found: C, 24.10; H, 0.53; N, 14.07.
N -Chloroisoindole-1,3-dione: colorless crystals (CH2Cl2); mp 184-185 °C. TLC (CH2Cl2): R f = 0.73. IR (KBr): 3070, 2950, 2880, 1750, 1720, 1620, 1510, 1470, 1360, 1310, 1080, 860 cm-1. 1H NMR (CDCl3): δ = 7.82-7.84 (m, 2 H), 7.89-7.93 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 123.9, 131.0, 134.7, 163.3 ppm. Anal. Calcd for C8H4ClNO2: C, 52.92; H, 2.22; N, 7.71. Found: C, 52.98; H, 2.24; N, 7.79.
N , N -Dichlorotoluene-4-sulfonamide: colorless crystals (CH2Cl2); mp 130-131 °C. TLC (CH2Cl2): R f = 0.57. IR (KBr): 3100, 3070, 1860, 1770, 1600, 1470, 1360, 1250, 1100, 910 cm-1. 1H NMR (CDCl3): δ = 7.91-7.95 (m, 2 H), 8.02-8.06 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 125.7, 131.3, 136.1, 162.8 ppm. Anal. Calcd for C8H4Br2N2O2: C, 30.03; H, 1.26; N, 8.76. Found: C, 30.11; H, 1.30; N, 8.82.
2-Acetyl-2-chloro-3,4-dihydro-2 H -naphthalen-1-one: colorless crystals (CH2Cl2-n-hexane = 1:1); mp 49-50 °C (lit. [21] mp 48-50 °C). TLC (CH2Cl2-n-hexane = 1:1): R f = 0.51. IR (KBr): 2950, 1720, 1680, 1600, 1460, 1420, 1360, 1300, 1240, 1200, 900, 850, 750, 720 cm-1. 1H NMR (CDCl3): δ = 2.42 (s, 3 H), 2.45-2.51 (m, 1 H), 2.90-2.99 (m, 1 H), 3.05-3.08 (m, 1 H), 3.12-3.16 (m, 1 H), 7.41-7.46 (m, 2 H), 7.63-7.69 (m, 1 H), 7.95 (d, 1 H, J = 7.8 Hz) ppm. 13C NMR (CDCl3): δ = 25.0, 26.6, 30.0, 75.9, 127.3, 127.7, 129.2, 129.5, 134.7, 142.9, 189.3, 201.0 ppm. Anal. Calcd for C12H11ClO2: C, 64.73; H, 4.98. Found: C, 64.75; H, 4.99.
2,2-Dichloro-1-phenylbutane-1,3-dione: colorless crystals (CH2Cl2-n-hexane = 1:2); mp 75-76 °C (lit. [21] mp 75-76 °C). TLC (CH2Cl2-n-hexane = 1:2): R f = 0.50. IR (KBr): 3070, 2930, 2880, 1760, 1730, 1710, 1680, 1600, 1580, 1510, 1450, 1360, 1250, 1230, 840, 780, 690, 660, 580 cm-1. 1H NMR (CDCl3): δ = 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. 13C NMR (CDCl3): δ = 24.9, 86.5, 128.7, 130.6, 130.9, 134.5, 185.9, 192.2 ppm. Anal. Calcd for C10H8Cl2O2: C, 51.98; H, 3.49. Found: C, 51.99; H, 3.52.
2,2-Dichloroindan-1,3-dione: colorless crystals (CH2Cl2-n-hexane = 1:1); mp 125-126 °C. TLC (CH2Cl2-n-hexane = 1:1): R f = 0.63. IR (KBr): 3100, 3060, 2930, 2880, 1780, 1740, 1600, 1260, 1160, 870, 810, 780, 650 cm-1. 1H NMR (CDCl3): δ = 8.07-8.11 (m, 2 H), 8.13-8.17 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 72.8, 125.8, 137.0, 138.1, 186.4 ppm. Anal. Calcd for C8H4Cl2O2: C, 50.27; H, 1.87. Found: C, 50.29; H, 1.91.

32

Typical N-Bromination of Azinones, Amides and Carbonyl Compounds.
Pb(OAc)4 (2.0 or 4.0 mmol) was dissolved in MeCN (20 mL). ZnBr2 (2.0 or 4.0 mmol) was added to the MeCN 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 CH2Cl2 or CH2Cl2-n-hexane (1:1). Fractions containing the product were combined and evaporated under reduced pressure to give monobromides or dibromides. Selected Analytical Data.
2-Bromo-3,4-dichloropyridazin-3(2 H )-one: colorless crystals (CH2Cl2); mp 169 °C. IR (KBr): 3100, 1690, 1600, 1460, 1400, 1300, 1260, 1120, 960 cm-1. 1H NMR (CDCl3): δ = 7.50 (s, 1 H) ppm. 13C NMR (CDCl3): δ = 132.3, 136.2, 154.7, 168.0 ppm. Anal. Calcd for C4HBrCl2N2O: C, 19.70; H, 0.41; N, 11.49. Found: C, 19.76; H, 0.43; N, 11.51.
N -Bromoisoindole-1,3-dione: colorless crystals (CH2Cl2); mp 199-200 °C (lit. [33] mp 198-202 °C). TLC (CH2Cl2): R f = 0.76. IR (KBr): 3090, 3050, 1775, 1730, 1690, 1610, 1460, 1350, 1290, 1100, 1070, 860, 800, 700 cm-1. 1H NMR (CDCl3): δ = 7.73-7.77 (m, 2 H), 7.88-7.91 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 123.8, 131.9, 134.3, 165.0 ppm. Anal. Calcd for C8H4BrNO2: C, 42.51; H, 1.78; N, 6.20. Found: C, 42.59; H, 1.84; N, 6.27.
2,3-Dibromophthalazine-1,4-dione: colorless crystals (CH2Cl2); mp 130-131 °C. TLC (CH2Cl2): R f = 0.57. IR (KBr): 3100, 3070, 1860, 1770, 1600, 1470, 1360, 1250, 1100, 910 cm-1. 1H NMR (CDCl3): δ = 7.91-7.95 (m, 2 H), 8.02-8.06 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 125.7, 131.3, 136.1, 162.8 ppm. Anal. Calcd for C8H4Br2N2O2: C, 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 (CH2Cl2): R f = 0.52. IR (KBr): 3080, 2970, 2940, 1720, 1680, 1600, 1450, 1360, 1300, 1230, 1190, 1000, 760, 690, 550 cm-1. 1H NMR (CDCl3): δ = 2.44 (s, 3 H), 5.67 (s, 1 H), 7.46-7.52 (dd, 2 H, J = 7.87, 7.41 Hz), 7.50-7.65 (m, 1 H), 7.95-7.98 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 27.2, 53.0, 128.6, 129.0, 129.2, 134.5, 190.0, 198.1 ppm. Anal. Calcd for C10H8BrO2: C, 49.82; H, 3.76. Found: C, 49.84; H, 3.80.
2,2-Dibromomalonic Acid Diethyl Ester: colorless oil. TLC (CH2Cl2-n-hexane = 1:1): R f = 0.50. IR (KBr): 2980, 2930, 2890, 1760, 1740, 1465, 1445, 1390, 1365, 1290, 1240, 1200 cm-1. 1H NMR (CDCl3): δ = 1.32-1.37 (t, 6 H, J = 7.13 Hz), 4.33-4.41 (q, 4 H, J = 7.13 Hz) ppm. 13C NMR (CDCl3): δ = 13.7, 50.7, 64.7, 163.1 ppm. Anal. Calcd for C7H10Br2O4: C, 26.44; H, 3.17. Found: C, 26.50; H, 3.20.