通過磺酰氯制備磺酸酯

磺酰氯具有較高的反應(yīng)活性，在堿性條件下，與醇反應(yīng)生成磺酸酯[1]，所用堿通常為三乙胺，吡啶和DMAP。

實例：

To a suspension of p-TsCl (14.3 g, 75.0 mmol) in pyridine (60 mL) was added slowly 3-methyl-3-oxetanemethanol (5.11 g,50.0 mmol) at 0 °C, and the mixture was stirred under nitrogen atmosphere at 0 °C for 4 h. The mixture was added to ice water and stirred for 1 h. The precipitate was collected by ?ltration, washed with cold water, and dried to give the target (8.97 g, 70%) as colorless crystals. (Negoro,N et al. J. Med. Chem. 2012, 55,3960.)

當?shù)孜锿瑫r含有伯羥基和仲羥基時，通過控制磺酰氯的當量，可以選擇性地在伯羥基上引入磺?；鵞2]。

實例：

To a solution of cis-tert-butyl 1-[4-(hydroxymethyl)piperidin-3-ol-1-yl]carboxylate  (760 mg, 3.28 mmol), Et3N (540 mL, 3.6mmol) and catalytic amount of 4-dimethyl aminopyridine in CH2Cl2(24 mL), was added portionwise 4-nitrobenzene sulfonylchloride (797 mg, 3.6mmol) at -50 oC under nitrogen atmosphere. After 3h, the reaction mixture was warmed up to room temperature and was stirred further overnight. Then, the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (310 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The puri?cation by silica gel chromatography(CH2Cl2:MeOH = 99:1) led to the target as a yellow solid (1.26 g,93%). (Koudih, R et al. Eur. J. Med. Chem. 2012, 53, 408.)

通過磺酰氯制備磺酰胺

磺酰氯與胺在堿性條件下反應(yīng)生成磺酰胺。所用堿包括三乙胺，吡啶，DMAP等。反應(yīng)通常以二氯甲烷為溶劑，在0 oC至室溫進行。也可以直接以吡啶做堿和溶劑，高產(chǎn)率得到磺酰胺[3]。

實例：

A mixture of amine A (0.84 g, 4 mmol) and methanesulfonyl chloride (0.69 g, 6 mmol) in pyridine (10 mL) was stirredat 0 oC for 10 min. After aqueous workup, the residue was puri?ed by ?ash column chromatography on silica gel using EtOAc:hexanes (1:2) as eluant togive the desired product (1.05 g,91%) as a white solid. (Kim, Y et al. Bioorg.Med. Chem. 2012, 20, 215.)

對于某些活性較差的底物，如帶有吸電子的芳胺或者含氮雜環(huán)化合物，其與磺酰氯反應(yīng)制備磺酰胺時通常需要較強的堿，包括KOH[4]，t-BuOK[5]和NaH[6]等。

實例：

Methyl indole-2-carboxylate (1.86 g,10.6 mmol) was dissolved in a ?ask by distilled DMF. NaH (0.50 g, 1.1 equiv) and PhSO2Cl(1.6 mL, 1.2 equiv) were slowly added to the ?ask on a pre-cooled bath of ice. The mixture was stirred overnight at room temperature.The crude product was extracted with ethyl ether/puri?ed water (320 mL), the organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to obtain the desired product(3.3 g, 99%) as a white solid. (Oikawa, M et al. Eur. J. Org. Chem. 2011, 24, 4654.)

【參考文獻】

[1] Negoro, N et al. J. Med. Chem. 2012, 55, 3960.

[2] Koudih, R et al. Eur. J. Med. Chem. 2012, 53, 408.

[3] Kim, Y et al. Bioorg. Med. Chem. 2012, 20, 215.

[4] Lai, Met et al. J. Med. Chem. 2012, 55, 3777.

[5] Lai, Metet al. J. Med. Chem. 2012, 55, 3777.

[6] Oikawa,M et al. Eur.J. Org. Chem. 2011, 24, 4654.