Synlett 2002(3): 0447-0450
DOI: 10.1055/s-2002-20462
LETTER
© Georg Thieme Verlag Stuttgart · New York

Palladium-catalyzed 3-Thiomethyltriazine-boronic Acid Cross Coupling: Easy Access to 3-Substituted-1,2,4-triazines

France-Aimée Alphonsea,b, Franck Suzeneta, Anne Keromnesb, Bruno Lebretb, Gérald Guillaumet*a
a Institut de Chimie Organique et Analytique, UMR-CNRS 6005, Université d"Orléans, rue de Chartres, BP 6759, 45067 Orléans cedex 2, France
b Commissariat à l’Energie Atomique, CEA/Le Ripault, B.P.16, 37260 Monts, France
Fax: +33(2)38417078; e-Mail: gerald.guillaumet@univ-orleans.fr;
Further Information

Publication History

Received 18 December 2001
Publication Date:
05 February 2007 (online)

Abstract

The palladium-catalyzed coupling reaction of 3-thiomethyl-1,2,4-triazine 1 with different organoboron compounds in the presence of copper(I) 3-methylsalicylate proceeds to afford the corresponding 3-substituted-1,2,4-triazines in good yield. This approach leads very easily to a large range of C-5 and C-6 unsubstituted as-triazines.

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The related nickel- and palladium-catalyzed cross coupling of Grignard and benzylzinc reagents with methylthio-substituted heterocycles is known. [16]

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Experimental Procedure: The following procedure for the synthesis of 3-(p-methoxyphenyl)-1,2,4-triazine is representative. To a mixture of 3-methylthio-1,2,4-triazine 1 (50 mg, 0.393 mmol, 1.0 equiv), CuMeSal (186 mg, 0.867 mmol, 2.2 equiv), p-methoxyphenylboronic acid (132 mg, 0.867 mmol, 2.2 equiv) in dry THF (3 mL) under argon, was added Pd(PPh3)4 (23 mg, 0.02 mmol, 5% mol). The reaction was stirred for 5 h at 50 °C. The mixture was quenched with a Na2CO3 solution (2 N) and extracted with dichloromethane. The combined organic phases were washed with a Na2CO3 solution (2 N) and water, dried over MgSO4 and concentrated in vacuo. After purification by column chromatography on silica gel (petroleum ether-ethyl acetate, 70:30), the desired 3-(p-methoxyphenyl)-1.2.4-triazine 2 was obtained as yellow powder (63 mg, 85%); mp 90-91 °C; (M + H)+ (IS) 188; 1H NMR (250 MHz, CDCl3) δ 9.08 (d, 1 Htriazine, J = 2.1 Hz); 8.61 (d, 1 Htriazine, J = 2.1 Hz); 8.51 (d, 2 HAr, J = 7 Hz); 7.03 (d, 2 HAr, J = 7Hz); 3.90 (s, 3 HOMe); 13C NMR (62.5 MHz, CDCl3) δ 164.3, 163.1, 149.0, 147.4, 130.0, 127.6, 114.7, 55.8. Spectroscopic data for 3: tan solid; mp 75 °C; (M + H)+ (IS) 148; 1H NMR (250 MHz, CDCl3) δ 9.09 (d, 1 Htriazine, J = 2.5 Hz), 8.62 (d, 1 Htriazine, J = 2.5 Hz), 7.72 (dd, 1 Hfuryl, J = 0.9, 1.6 Hz), 7.54 (dd, 1 Hfuryl, J = 0.9, 3.5 Hz), 6.65 (dd, 1 Hfuryl, J = 1.6, 3.5 Hz); 13C NMR (62.5 MHz, CDCl3) δ 158.1, 149.5, 148.8, 147.2, 146.6, 115.7, 112.3.