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DOI: 10.1055/s-2006-941580
Metal-Halogen Exchange Using tri-n-Butyl Lithium Magnesate in the Diazine Series: Diazine 49
Publication History
Publication Date:
12 June 2006 (online)
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Abstract
We report herein the ‘metal-halogen exchange’ reaction in the diazine series with lithium tri-n-tributylmagnesate. The reaction was performed with 2-iodopyrazine, 2-methylsulfanyl-4-iodopyrimidine and 3-iodo-6-phenylpyridazine. Benzophenone, aldehydes and diphenylsulfur were used as electrophiles affording alcohols and phenylsulfanyl derivatives with satisfactory to good yields.
Key words
ate complex - magnesium - diazines - lithium - iodine
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References and Notes
Procedure 1 for 2-Iodopyrazine and 4-Iodo-2-methyl-sulfanylpyrimide.
A solution of n-BuLi (1.6 M in hexane, 0.66 mmol) was added to a cold (-10 °C) stirred solution of n-butyl-magnesium chloride (0.33 mmol) in THF (5 mL). After 1 h at -10 °C a solution of iododiazine (1 mmol) in THF (2 mL) was added at -30 °C and the mixture was stirred at -10 °C for 2.5 h. The electrophile (1.5 mmol) was then added at
-10 °C; the mixture was stirred at this temperature for 1 h and kept at r.t. for 18 h before addition of H2O (1 mL). The reaction mixture was diluted with EtOAc (50 mL). The organic layer was dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel.
Representative Spectroscopic Data2-(1-Hydroxy-4-methoxyphenylmethyl) Pyrazine (
2)
Prepared according to procedure 1. 1H NMR (CDCl3): δ = 8.50 (s, 1 H, H3), 8.36 (d, 1 H, J = 2.5 Hz, H6), 8.31 (d, 1 H, J = 2.5 Hz, H5), 7.18 (d, 2 H, J = 8.7 Hz, HPh2,6), 6.76 (d, 2 H, J = 8.7 Hz, HPh3,5), 5.71 (s, 1 H, CH), 4.74 (m, 1 H, OH), 3.68 (s, 3 H, OCH3). 13C NMR (CDCl3): δ = 159.4 (CPh4), 157.5 (C2), 143.2-143.0 (C3, C5 and C6), 134.2 (CPh1), 128.2 (CPh2,6), 114.2 (CPh3,5), 73.9 (CH), 55.3 (OCH3). IR (KBr): 3352, 2930, 2840, 1613, 1513, 1469, 1403, 1304, 1249, 1149, 1064, 832, 582 cm-1. Anal. Calcd for C12H12N2O2 (216.24): C, 66.65; H, 5.59; N, 12.96. Found: C, 66.90; H, 5.47; N, 12.91.
2-Methylsulfanyl-4-(1-hydroxy-4-methoxyphenyl-methyl) Pyrimidine (
7)
Prepared according to procedure 1. 1H NMR (CDCl3): δ = 8.33 (d, 1 H, J = 5.3 Hz, H6), 7.21 (d, 2 H, J = 8.7 Hz, HPh2,6), 6.81 (d, 2 H, J = 8.7 Hz, HPh3,5), 6.72 (d, 1 H, J = 5.1 Hz, H5), 5.53 (d, 1 H, J = 3.8 Hz, CH), 4.51 (m, 1 H, OH), 3.73 (s, 3 H, OCH3), 2.53 (s, 3 H, SCH3). 13C NMR (CDCl3): δ = 172.2 (C2 and C4), 159.8 (CPh4), 157.3 (C6), 133.6 (CPh1), 129.6 (CPh2,6), 114.5 (CPh3,5), 113.5 (C5), 74.3 (CH), 55.4 (OCH3), 14.3 (SCH3). IR (KBr): 3369, 2929, 2836, 1565, 1513, 1349, 1249, 1174, 1032, 832 cm-1. Anal. Calcd for C13H14N2O2S (262.33): C, 59.52; H, 5.38; N, 10.68. Found: C, 59.34; H, 5.42; N, 10.75.
Procedure 2 for 2-Iodo-6-phenylpyridazine.
A solution of n-BuLi (1.6 M in hexane, 0.66 mmol) was added to a cold (-10 °C) stirred solution of n-butyl-magnesium chloride (0.33 mmol) in THF (5 mL). After 1 h at -10 °C, The solution was added in a solution of 2-iodo-6-phenylpyridazine (1 mmol) in THF (2 mL) at -30 °C and the mixture was stirred at -10 °C for 2.5 h. The electrophile (1.5 mmol) was then added at -10 °C; the mixture was stirred at this temperature for 1 h, then brought to, and kept at, 35 °C for 18 h before addition of H2O (1 mL). The reaction mixture was diluted with EtOAc (50 mL). The organic layer was dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel.
Representative Spectroscopic Data3-(1-Hydroxy-4′-methoxyphenylmethyl)-6-phenyl Pyridazine (
12)
Prepared according to procedure 2. Mp 140 °C. 1H NMR (CDCl3): δ = 8.05 (m, 2 H, HPh2,6), 7.77 (d, 1 H, J = 8.9 Hz, H5), 7.40 (m, 6 H, H4, HPh
′
2,6, HPh3,4,5), 6.88 (d, 2 H, J = 8.7 Hz, HPh
′
3,5), 6.02 (s, 1 H, CH), 5.02 (m, 1 H, OH), 3.78 (s, 3 H, OCH3). 13C NMR (CDCl3): δ = 161.7 (CPh
′
4), 159.6 (C3 and C6), 135.9 (CPh1), 134.1 (CPh
′
1), 130.3-124.9 (C4, C5, CPh2,6, CPh
′
2,6, CPh4, CPh3,5), 114.3 (CPh
′
3,5), 74.4 (CH), 55.4 (OCH3). IR (KBr): 3135, 2999, 2933, 2838, 1611, 1514, 1433, 1251, 1171, 1064, 813, 692 cm-1. Anal. Calcd for C18H16N2O2 (292.34): C, 73.96; H, 5.52; N, 9.58. Found: C, 73.68; H, 5.48; N, 9.32.