A mild and simple method for the preparation of isocyanates from aliphatic amines using trichloromethyl chloroformate. Synthesis of an isocyanate containing an activated disulfide
A mild and simple method for the preparation of isocyanates from aliphatic amines using trichloromethyl chloroformate. Synthesis of an isocyanate containing an activated disulfide
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DOI：
10.1021/jo9521920
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发表时间：
1996-05-31
影响因子：
3.6
通讯作者：
Eckstein, F
中科院分区：
文献类型：
--
作者：
Sigurdsson, ST;Seeger, B;Eckstein, F
最近，我们开发了一种用于探测RNA三级结构的交联法，并用它来评估两种不同的锤头状核酶三维模型的催化活性。1在我们为揭开复杂核酸结构中的三级相互作用而不断努力的过程中，我们对制备异氰酸酯1感兴趣，该异氰酸酯1用于将活化的硫醇特定地掺入到寡核苷酸中。我们决定从相应的胺中制备1，2，6-二甲基-4-甲氧基丙烷，这种胺可以一步从市场上获得的原料中获得。2使用各种方法3-5合成1，3-5的初步尝试都不成功，主要是导致产物的复杂混合物。结果表明，吡啶二硫基官能团与反应条件不相容，因此选择了一种较温和的方法来制备1，2，4-三氯氯甲酸三氯甲酯(双光气)，用于从相应的胺盐酸盐制备芳香族异氰酸酯。6然而，这种方法不能推广到脂肪胺，因为它们未能成功地将1，6-二氨基己烷盐酸盐转化为相应的二异氰酸酯。6我们现在已经确定，脂肪胺与双光气在非亲核碱1，8-二(二甲氨基)-萘存在下，在0℃下反应，以很好到很好的产率生成异氰酸酯(方案1)。此外，只需对反应混合物进行萃取处理，即可获得纯度大于95%的产品，无需进一步提纯。这与大多数其他报道的异氰酸酯制备方法形成对比，这些方法依赖于蒸馏来提纯产品。7-9因此，该方法能够制备热敏性和/或非挥发性异氰酸酯。此外，这项技术将在合成
Recently we developed a cross-linking methodology for probing the tertiary structure of RNA and used it to assess the catalytic competence of two different threedimensional models of the hammerhead ribozyme. 1 During our continued effort toward unravelling tertiary interactions within complex nucleic acid structures, we were interested in the preparation of isocyanate 1 for the site-specific incorporation of an activated thiol into oligonucleotides. We decided to prepare 1 from the corresponding amine, which was readily available in one step from commercially available materials. 2 Preliminary attempts to synthesize 1 using a variety of methods3-5 were not successful, primarily resulting in complex mixtures of products. It was concluded that the pyridyl disulfide functionality was incompatible with the reaction conditions and a milder method for the preparation of 1 was sought.Trichloromethyl chloroformate (diphosgene) has been used for the preparation of aromatic isocyanates from the corresponding amine hydrochlorides. 6 However, this method could not be extended to aliphatic amines, as illustrated by their lack of success in converting 1, 6-diaminohexane hydrochloride to its corresponding diisocyanate. 6 We have now established that the reaction of aliphatic amines with diphosgene at 0 C, in the presence of the non-nucleophilic base 1, 8-bis (dimethylamino)-naphthalene, affords isocyanates in good to excellent yields (Scheme 1). Furthermore, the products can be obtained in greater than 95% purity by mere extractive workup of the reaction mixtures, making further purification unnecessary. This is in contrast to most other reported procedures for the preparation of isocyanates which rely on distillation for the purification of products. 7-9 Thus, this procedure enables the preparation of heatsensitive and/or nonvolatile isocyanates. Additionally, this technique would be useful in the synthesis of