Preparation method of DCC impurity isocyanate and tricyclohexylguanidine

Abstract

The invention belongs to the technical field of preparation of chemical intermediates, and particularly relates to a preparation method of DCC impurity isocyanate and tricyclohexylguanidin.The preparation method comprises the steps that N, N-dicyclohexylthiourea and DCC (N, N-dicyclohexylcarbodiimide) are added into a four-opening bottle according to a certain proportion, then the temperature is increased to 60-180 DEG C, stirring is conducted for 2-12 h, then central control detection is conducted, and finally the content of the DCC impurity isocyanate and the content of the DCC impurity tricyclohexylguanidinium are detected. According to the method, isocyanate and tricyclohexylguanidine can be respectively obtained, high-purity cyclohexyl isocyanate and tricyclohexylguanidine are obtained through rectification separation, preparation of impurities is realized, and generation reasons of the impurities are determined.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical intermediate preparation, and particularly relates to a method for preparing DCC impurity isocyanate and tricyclohexylguanidine. Background Art

[0002] DCC (N,N-dicyclohexylcarbodiimide) is a widely used dehydrating agent in the fields of chemical industry and pharmaceutical industry. It is widely used in the synthesis of esters and amides. With the improvement of quality awareness in various industries, especially the wide application of DCC in the pharmaceutical field, it is required to determine the source of each impurity in DCC, determine the correct structure and obtain related impurities. The main impurities in DCC are cyclohexyl isocyanate and N,N,N-tricyclohexylguanidine, and their structural formulas are as follows:

[0003] Summary of the invention

[0004] The object of the present invention is to provide a method for preparing DCC impurity isocyanate and tricyclohexylguanidine.

[0005] The technical solution adopted by the present invention to solve the technical problem is: a method for preparing DCC impurity isocyanate and tricyclohexylguanidine, comprising the following steps:

[0006] 1) Add N,N-dicyclohexylthiourea and DCC (N,N-dicyclohexylcarbodiimide) into a four-necked bottle in a certain proportion;

[0007] 2) heating to 60-180° C., stirring for 2-12 hours, and then performing central control testing to obtain isocyanate and tricyclohexylguanidine respectively;

[0008] 3) After distillation and separation, high-purity cyclohexyl isocyanate and tricyclohexylguanidine are obtained.

[0009] Specifically, the molar ratio of the N,N-dicyclohexylthiourea to DCC (N,N-dicyclohexylcarbodiimide) is 1:1 to 1:1.5.

[0010] The invention has the following beneficial effects: according to the invention, N,N-dicyclohexylthiourea and DCC (N,N-dicyclohexylcarbodiimide) are added into a four-necked bottle in a certain ratio, and then the temperature is raised to 60-180°C, and stirred for 2-12 hours, and then central control detection is performed, so that isocyanate and tricyclohexylguanidine can be obtained respectively, and high-purity cyclohexyl isocyanate and tricyclohexylguanidine can be obtained through distillation separation, so that the preparation of impurities is realized, and the cause of the generation of the impurities is determined. DETAILED DESCRIPTION

[0011] The present invention will now be described in further detail.

[0012] A method for preparing DCC impurity isocyanate and tricyclohexylguanidine comprises the following steps:

[0013] Add N,N-dicyclohexylthiourea and DCC (N,N-dicyclohexylcarbodiimide) into a four-necked bottle in a certain proportion, heat to 60-180°C, stir for 2-12 hours, and then perform central control detection to obtain isocyanate and tricyclohexylguanidine respectively. After distillation separation, high-purity cyclohexyl isocyanate and tricyclohexylguanidine are obtained.

[0014] The reaction mechanism is as follows:

[0015]

[0016] The molar ratio of N,N-dicyclohexylthiourea to DCC (N,N-dicyclohexylcarbodiimide) is 1:1-1:1.5, preferably 1:1; the reaction temperature is 60-180°C, preferably 170°C, and the stirring is 8-12h, preferably 10h.

[0017] Example 1

[0018] In a 1000L four-necked bottle, 240g of N,N-dicyclohexylthiourea and 206g of DCC (N,N-dicyclohexylcarbodiimide) were added, the temperature was raised to 170°C, and the mixture was stirred for 10h. After the intermediate control reaction was completed, vacuum distillation was performed to collect about 101g of low-boiling cyclohexyl isothiocyanate with a purity of 99.2% and a conversion rate of 71.6%, and about 223g of tricyclohexylguanidine with a purity of 99.1% and a conversion rate of 73.1% was obtained. DCC impurity cyclohexyl isothiocyanate and tricyclohexylguanidine can be effectively prepared.

[0019] Example 2

[0020] In a 1000L four-necked bottle, 240g of N,N-dicyclohexylthiourea and 309g of DCC (N,N-dicyclohexylcarbodiimide) were added, the temperature was raised to 60°C, and the mixture was stirred for 8h. After the intermediate control reaction was completed, vacuum distillation was performed to collect about 93g of low-boiling cyclohexyl isothiocyanate with a purity of 98.2% and a conversion rate of 65.9%, and about 210g of tricyclohexylguanidine with a purity of 97.1% and a conversion rate of 68.8%. DCC impurity cyclohexyl isothiocyanate and tricyclohexylguanidine can be effectively prepared.

[0021] Example 3

[0022] In a 1000L four-necked bottle, 240g of N,N-dicyclohexylthiourea and 246g of DCC (N,N-dicyclohexylcarbodiimide) were added, the temperature was raised to 150°C, and the mixture was stirred for 9h. After the reaction was completed, the reaction was distilled under reduced pressure to collect about 99.1g of low-boiling cyclohexyl isothiocyanate with a purity of 99.0% and a conversion rate of 70.28%. About 203g of tricyclohexylguanidine was obtained with a purity of 97.9.1% and a conversion rate of 66.5%. DCC impurity cyclohexyl isothiocyanate and tricyclohexylguanidine can be effectively prepared.

[0023] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0024] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing DCC impurity isocyanate and tricyclohexylguanidine, characterized in that: The following steps are involved: 1) Add N,N-dicyclohexylthiourea and DCC (N,N-dicyclohexylcarbodiimide) into a four-necked bottle in a certain proportion; 2) heating to 60-180° C., stirring for 2-12 hours, and then performing central control testing to obtain isocyanate and tricyclohexylguanidine respectively; 3) After distillation and separation, high-purity cyclohexyl isocyanate and tricyclohexylguanidine are obtained.

2. The method for preparing a DCC impurity isocyanate and tricyclohexylguanidine according to claim 1, characterized in that: The molar ratio of the N,N-dicyclohexylthiourea to DCC (N,N-dicyclohexylcarbodiimide) is 1:1 to 1:1.5.

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