制備酰胺的非常規(guī)方法
制備酰胺有很多方法，一種是酸直接和胺縮合，此類方法有：氯甲酸酯類形成活性酯縮合，DCC和EDC之類的碳二酰亞胺類縮合劑，HATU和BOP等鎓鹽類縮合劑，DPP-Cl和DPPA之類的有機磷類縮合劑。第二種是，酰鹵和酸酐和胺反應(yīng)得到酰胺。
除了以上常規(guī)方法下面介紹兩種非常規(guī)方法。
一、酰基疊氮
?；B氮也是一個較為溫和的?；噭捎谠诜磻?yīng)時其不會引起光學(xué)活性物質(zhì)的消旋且對水及其他親核試劑較為穩(wěn)定，因而常用于肽及化合物庫的合成.但?；B氮由于反應(yīng)活性低，對于位阻大且親核性低的胺是不適用的。
?；B氮合成酰胺實例（J. Med. Chem 2004, vol. 47, No. 10 2599-2610）
To a solution of Boc-Tyr-N3(0.65 mmol) in DMF (6 mL) were added 7.3N HCl/dioxane (1.30 mmol) and isopentyl nitite (0.78 mmol) under cooling to –15 oC; The solution was stirred for 10 min at the same temperature, NMM (1.37 mmol) was added to adjust the pH to 8. This solution was added to a cooled solution of 55 (0.26 mmol) and NMM (0.52 mmol) in DMF (6mL). The reaction mixture was stirred for another 24 h under the same conditions and the pH maintained at 8. After removal of DMF, the residue was dissolved in EA and washed with water, 5% NaHCO3, 10% citric acid, and saturated brine. The organic layer was dried over Na2SO4 and evaporated. The product was crystallized from ether, and the crystals were collected by filtration (Yield 53.6%).
二、3-?；?2-硫噻唑啉
3-?；?2-硫噻唑啉也是一個較為溫和的酰化試劑(Tetrahedron lett. 1980,21，841；J Org. Chem. 1994, 3506), 其對各類胺的反應(yīng)選擇性較好，同時反應(yīng)可以用乙醇作溶劑。該反應(yīng)的一個特點是一般3-酰基-2-硫噻唑啉是黃色的，但反應(yīng)完2-硫噻唑啉為無色，因此可以通過黃色是否消失來跟蹤反應(yīng)。
1、 3-酰基-2-硫噻唑啉的合成示例（J. Org. Chem., Vol. 57, No. 15,1992. 4243-4249）
A solution of 2-(benzyloxy)propionic acid (2.16 g, 12 mmol) in CH2Cl2(50 mL) were added thiozolidine-2-thione (1.93 g, 12 mmol), followed by EDC. HCl(2.42 g, 12.6 mmol) and DMAP (50 mg, 0.41 mmol). After being stirred at RT overnight, the reaction mixture was washed with water and brine, dried, evaporated in vacuum to give an oil residue. The residue was purified by silica gel column chromatography (elution 5:1hexane-AcOEt) to give the desired amide 58 (3.32 g, 86%) as yellow oil.
2 、3-酰基-2-硫噻唑啉的合成酰胺示例（Genin, Michael J.; Allwine, Debra A. ect.; J. Med. Chem., 2000, 5, 953-970）
p-Anisidine (920 mg, 7.47 mmol) was added to a solution of 59 (3.0 g, 6.24 mmol) in CH2Cl2(20 mL) and the solution was stirred at RT overnight. Evaporation of the solvent in vacuum followed by purification of the residue on a silical gel column with 5:1 of hexane-AcOEt gave amide 60 (2.76 g, quantitatively yield) as colorless needles.
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