同一般的酰基氨基酸比较，Pht-氨基酸在接肽时不易消旋，但它对碱不稳定，在碱皂化的条件下发生邻苯二甲酰亚胺环的开环生成邻羧基苯甲酰基衍生物。因此，当选用Pht作氨基保护基时，肽链的羧基末端则不能用甲酯（或乙酯）保护，而只能用苄酯或叔丁酯保护，以避免将来用皂化去酯的步骤。Pht对催化氢解、HBr/HOAc处理以及Na/NH₃（液）还原（后处理的碱性条件需要避免）等均稳定，但很容易用肼处理脱去。

邻苯二甲酰基的引入

最先导入Pht基的方法是将邻苯二甲酸酐同氨基酸在145-150℃进行熔融反应，但这个方法对有的氨基酸会引起部分消旋作用，因而后来又进行了一些改进，如邻苯二甲酸酐/CHCl₃/70℃下反应。然而最成功的是Nefkens提出的用N-乙氧羰基邻苯二甲酰亚胺为试剂的方法（见下式），即N-乙氧羰基邻苯二甲酰亚胺与氨基酸在Na₂CO₃水溶液仲于25℃反应10-15分钟，就可以得到85-95%的Pht-氨基衍生物。这个试剂可在仲胺的存在的情况下选择性地保护伯胺。

一、邻苯二甲酸酐引入邻苯二甲酰基示例

P. Meffre, P. Durand.,Org. Syn., 76, 123

Into a 2-L, round-bottomed flask fitted with a Dean-Stark apparatus,reflux condenser, and drying tube containing calcium chloride are placedL-methionine methyl ester hydrochloride (50.0 g, 0.25 mol),phthalic anhydride (37.1 g, 0.25 mol), triethylamine (100 mL, 0.72 mol),and toluene (1 L). The mixture is magneticallystirred and heated under reflux for 4.5 hr at which point approximately 4.5 mLof water has separated. The reaction mixture is allowed to cool to roomtemperature and the precipitated triethylaminehydrochloride (34 g) is collected by suction filtration. Thefiltrate is washed with four 300-mL portions of 1 Naqueous hydrochloric acidfollowed by three 300-mL portions of water. The organiclayer is dried over magnesium sulfate, filtered, and the filtrate is concentrated underreduced pressure using a rotary evaporator. Theresidual oil is placed under reduced pressure for 12 hr at 0.1-0.5 mm, followed by trituration with 200 mL of pentaneto give 59 g (80%) ofproduct as a white solid after collection and drying at room temperature underreduced pressure (mp 37-40°C). mp 37-40°C,; [α]²⁰_D−41.6° (CHCl₃, c 1.49).

二、邻苯二甲酸单乙酯引入邻苯二甲酰基示例

N. Aguilar; A.Moyano et al., J. Org. Chem., 1998, 11, 3560

To a suspension of PyBOP (2.84 g, 5.46 mmol, 1.1 equiv) in dry THF (10mL) was added a solution of 2-ethoxycarbonylbenzoic acid(1.08 g, 5.46 mmol, 1.1 equiv) in THF (10 mL)and i-Pr₂NEt (1.27 mL, 7.44 mmol, 1.5 equiv), and the resulting mixture was stirredfor 30-40 min at rt. Afterwards, this solution was added to a suspension of 7(0.898 g) inTHF (10 mL) at 0 °C, and themixture was stirred at rt for 3 h. The solvent was eliminated in vacuo, and theresidue was heated at 85 °Covernight. The reaction mixture was then dissolved in 250 mL of dichloromethaneand washed with saturated NaHCO₃solution (2 x100 mL) and with brine (100 mL). The organic layer was dried (Na₂SO₄) andevaporated to give a crude product which was purified by column chromatography toyield 1.28 g of (2S,3S)-4-phenyl-3-phthalimidobutane-1,2-diol (8) (83%) as a white solid: mp 91-93 °C.

三、N-乙氧羰基邻苯二甲酰胺引入邻苯二甲酰基示例:

Worster, Paul M; Leznoff, Clifford C etal., J. Org. Chem., 1980, 45(1), 174-175

Ethyl chloroformate (115 mL, 1.29mol) was added dropwise over a period of 90 min to a stirred solution of phthalimide(149.9 g, 1.02 mol) andtriethylamine (160 mL, 1.15 mol) in dimethylformamide (500 mL) at 0-5°Cunder argon. The reaction mixture was allowed to warm to room temperature andstand for 4 h. It then was slowly added to an agitated mixture of ice and water(3 L). The solid product wascollected and extracted with two portions of chloroform (450 mL and then 50mL). The extract was dried (Na₂SO₄), cooled overnight inthe refrigerator, and filtered to remove phthalimide (mp 238°C).The chloroform solution was concentrated to about 350 mL, diluted withpetroleum ether (bp 60-80 °C;350 mL) and allowed to stand at room temperature to give N-(ethoxycarbony1)phthalimide(179 g, followed by two additional crops for a total of212 g, 95% yield): mp 83°C.

W. Shijun; Y.Zhujun et al., Org. Lett., 2004, 16, 2721

The solution of compound 1 (150.2 mg, 1.05 mmol) in THF (4 mL) was treated with N-(ethoxycarbonyl)-phthalimide(230 mg, 1.05 mmol), and NaHCO₃(88 mg, 1.05 mmol) at 0°C.The reaction was stirred for 7 h at rt, and separated. The aqueous layer wasextracted with EtOAc (4 x 5 mL). The combined organic extracts were washed withsaturated aqueous NH₄Cl (3x 3 mL) and brine (3 mL), dried (Na₂SO₄),and concentrated in vacuo. Chromatography (hexane/EtOAc = 5/1) provided 9as an oil (215 mg, 75%). 

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