常用烷基化试剂----Meerwein盐

Meerwein盐也称为Meerwein试剂，是指三甲基氧鎓四氟硼酸盐 (Me3OBF4)或是三乙基氧鎓四氟硼酸盐 (Et3OBF4)。此试剂以其发现者Hans Meerwein的名字命名，此烷氧鎓盐是很强的烷基化试剂，可以对各种杂原子亲核试剂进行烷基化，如酰胺，内酰胺（O-烷基化），胺（可以N-烷基化到季铵盐），α-吡啶酮（N-或O-烷基化），芳香氮杂环（N-烷基化后形成鎓盐），硫代羰基化合物（S-烷基化）。

【 J. Chem. Ber., 1956, 89, 2060； Can. J. Chem. , 1977, 5, 1433 】

在水相中Meerwein 盐能作用于羧酸实现酯化反应，在这一反应条件下，酰胺基团不会发生O-烷基化反应。而在非质子溶剂和不存在碱的条件中，羧酸酰胺化合物只会发生O-烷基化反应。

O -烷基化的酰胺，可以还原制备胺，也可以水解制备酯。

常见的烷基化试剂强弱按照以下顺序排列：

Me2Cl(SbF6) > (MeO)2CHBF4> Me3OBF4> Et3OBF4> MeOTf >MeOSO2F > (MeO)2SO2> MeI

试剂的制备：

【 (a) Meerwein, H. Org. Synth.; Coll. Vol. V 1973, 1080. Triethyloxonium tetrafluoroborate. (b) Curphey, T. J. Org. Synth.; Coll. Vol. VI, 1988, 1019. Trimethyloxonium tetrafluoroborate. 】

反应实例

【 J. Organomet. Chem. 1983 , 247, 187–201 】

【 J. Am. Chem. Soc. , 1993, 115, 30 】

【Tetrahedron Lett. 1996, 37, 5679】

To a stirred mixture of 163 mg 6-nitro-1Hindazole (1 mmol) and 3 mL EtOAc was added 192 mg trimethyloxonium tetraflfluoroborate (1.3 mmol). The mixture was stirred at room temperature for 5 h under nitrogen and then diluted with 20 mL EtOAc and washed with 20 mL saturated NaHCO 3 solution. The organic layer was separated, and the aqueous layer was extracted with EtOAc (20 mL × 2). The combined organic layers were dried over anhydrous MgSO 4 , fifiltered, and evaporated. The residue was purifified by column chromatography (1:1, EtOAc/hexane) to afford 154 mg 2-methyl-6-nitro-2 H - indazole as a yellow solid, in a yield of 87%, mp 158–16 0 ◦ C (EtOAc).

【 J. Org. Chem. , 2003 , 68 , 4093 】

To a solution of 300 mg gluconothiolactam (0.54 mmol) in 13 mL dry CH2Cl2 at 0℃ was added 112 mg triethyloxonium tetraflfluoroborate (0.59 mmol). The mixture was stirred at 0 ℃ for 1.5 h, then the solvent was removed under vacuum to afford 298 mg ethyl 2,3,4,6-tetra- O -benzyl-D-gluconoiminothioether, in a yield of 95%.

【 J. Am. Chem. Soc. , 2004 , 126 , 1971 】

【 J. Fluorine Chem. 2006, 127, 1261–1264 】

【 J. Org. Chem. 2008, 73, 6816–6823. 】

【J. Org. Chem., 2016, 81, 3470-3472】

相关文献

1. (a) Meerwein, H.; Hinz, G.; Hofmann, P.; Kroning, E.; Pfeil, E. J. Prakt. Chem. 1937, 147, 257–285. (b) Meerwein, H.; Bettenberg, E.; Pfeil, E.; Willfang, G. J. Prakt. Chem. 1939, 154, 83–156.

2. (a) Meerwein, H. Org. Synth.; Coll. Vol. V 1973, 1080. Triethyloxonium tetrafluoroborate. (b) Curphey, T. J. Org. Synth.; Coll. Vol. VI, 1988, 1019. Trimethyloxonium tetrafluoroborate.

3. Chen, F. M. F.; Benoiton, N. L. Can. J. Chem. 1977, 55, 1433–1435.

4. Dötz, K. H.; Möhlemeier, J.; Schubert, U.; Orama, O. J. Organomet. Chem. 1983, 247, 187–201.

5. Downie, I. M.; Heaney, H.; Kemp, G.; King, D.; Wosley, M. Tetrahedron 1992, 48, 4005–4016.

6. Kiessling, A. J.; McClure, C. K. Synth. Commun. 1997, 27, 923–937.

7. Pichlmair, S. Synlett 2004, 195-196. (Review).

8. Egashira, M.; Yamamoto, Y.; Fukutake, T.; Yoshimoto, N.; Morita, M. J. Fluorine Chem. 2006, 127, 1261–1264.

9. Delest, B.; Nshimyumukiza, P.; Fasbender, O.; Tinant, B.; Marchand-Brynaert, J.; Darro, F.; Robiette, R. J. Org. Chem. 2008, 73, 6816–6823.

10. Perst, H.; Seapy, D. G. Triethyloxonium Tetrafluoroborate In Encyclopedia of Reagents for Organic Synthesis Wiley: New York, 2008,

11. Hari, D. P., König, B. Angew. Chem. Int. Ed. 2013, 52, 4734–4743. (Review).

参考资料：

一、Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Meerwein’s salt，page 384-385.

二、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，P1877-1879.

三、《现代有机合成试剂——性质、制备和反应》，胡跃飞等编著