脲的合成汇总

脲是有机合成中非常重要的一类中间体，下面对其合成方法进行汇总，点击标题查看详细内容。本文大部分内容非原创，如涉及版权问题请联系本号删除。

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苯胺在Boc2O/TEA/DMAP条件下很难制备得到Boc保护产物，大概率会生成脲。

（氰酸有两种指代，有对正氰酸和异氰酸的混合物的指代或者对这两种酸类别上得总称，也有单独对正氰酸的默认指代。氰酸的游离酸是正氰酸与异氰酸二者的混合物，未曾分离开，但其酯类则有两种形式。）

六、生成异氰酸酯的重排反应，加入胺可到脲

由羰基化合物、氰化钾(KCN)和碳酸铵[(NH4)2CO3]或者氰醇和碳酸铵制备乙内酰脲的反应被称为Bucherer–Bergs反应。

七、芳胺在常见的上Boc条件，TEA/DMAP条件下通常会生成二芳基脲，有时甚至没有Boc保护产物，主要产物为二芳基脲。

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通过硫脲合成脲

有时候我们也会通过各种氧化方法由硫脲合成脲，如双氧水，NaIO4，HgO，乙酸汞，氯乙酸等。

实例：由硫脲合成脲

Sulfonythiourea(470 mg, 1 mmol) was dissolved in 1 N NaOH (3 mL) and hydrogen peroxide (0.6 mL, 30%) was added. After 1 h stirring at room temperature the mixture was acidified with 2 N HCl and the precipitate filtered off and dried to give thetile compound (420 mg, 92% yield) as colorless solid.

【Heinrich C. Englertetc J. Med. Chem.2001, 44, 1085-1098】

1,3-二烷基硫脲在醋酸汞作用下生成1,3-二烷基-O-乙酰基异硫脲中间体，然后生成1,3-二烷基脲。

【J. Org. Chem.,2005, 70, 6362】

通过直接加热或铜催化对伯胺进行转酰胺基合成脲

在有些情况下，我们也会通过伯脲与胺在加热下进行胺交换来合成需要的脲。当然有时也可利用铜催化对伯胺进行转酰胺基合成脲，能有效地提高反应的收率。

实例一：通过伯脲与胺反应合成脲

The primary amide species (2 mmol) was added to an oven-dried Radleys carousel tube followed by toluene (2 mL) and the amine species (2 mmol). Hydroxylamine hydrochloride was then added and the carousel tube was sealed before the reaction mixture was heated at 105 oC. After being allowed to cool to room temperature, the solvent was removed in vacuo on a rotary evaporator and 20 mL dichloromethane added. The reaction mixture was then washed with water (2 x 30 mL) to remove the hydroxylamine hydrochloride, and the resulting organic layer was dried over MgSO4. The solution was concentrated in vacuo to give product.

【C. Liana Allen,* Benjamin N. Atkinson, Angewandte Chemie, International Edition,2012, 51(6), 1383-1386】

实例二：铜催化合成脲

Cu(OAc)2 (18 mg, 0.1 mmol), 1(135 mg, 1 mmol), aniline (121 mg, 1.3 mmol), and tert-amyl alcohol (2 mL) were added successively to a Schlenk tube (25 mL) equipped with a magnetic stirrerbar. The Schlenk tube was then closed and the resulting mixture was stirred at 140 oC for 14 h under an argon atmosphere. The accumulated ammonia gas in the pressure tube was then released under argon protection, and the reaction mixture was stirred at 140 oC for another 2 h. After cooling down to room temperature, the reaction solvent was removed under vacuum. The residue was directly purified by flash chromatography on silica gel eluting with heptane/ethanol (25:1) to give the desired compound as a white solid (165mg, 78% yield).

【Min Zhang，Angewandte Chemie,International Edition,51(16), 3905-3909, 2012】

转自：公众号“Labnetwork”