Di(4-trifluoromethylbenzyl) azodiformate, intermediate and preparation method of di(4-trifluoromethylbenzyl) azodiformate

A technology of trifluoromethyl benzyl ester and azodicarboxylic acid, applied in the field of organic compound synthesis, can solve the problems of difficult recovery, difficult separation, limited application research and the like, and achieves the effects of strong practicability, environmental friendliness and simple process

Inactive Publication Date: 2015-11-11
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although the Mitsunobu reaction is powerful in organic synthesis, two reagents (an azo reagent and a trivalent phosphine reagent) are required in this redox process, generating stoichiometric hydrazine by-products and penta phosphine oxide by-product
[0003] Diethyl azodicarboxylate (DEAD) and diisopropyl azodicarboxylate (DIAD) are two commonly used azo reagents, which can be purchased conveniently on the market, but they are sensitive to light and heat. During storage, it is easy to be heated and explode and cause danger, so it needs to be stored in a dark and dry place at low temperature
In addition, under the Mitsunobu reaction conditions, the by-products diethyl hydrazine dicarboxylate and diisopropyl hydrazine dicarboxylate generated by DEAD and DIAD are difficult to separate from the product and are not easy to recover. Careful and tedious column chromatography is usually required to separate the product from the product. The unreacted reagents and by-products are separated, and the by-products are difficult to recycle. These shortcomings limit its application research in combinatorial chemistry

Method used

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  • Di(4-trifluoromethylbenzyl) azodiformate, intermediate and preparation method of di(4-trifluoromethylbenzyl) azodiformate
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  • Di(4-trifluoromethylbenzyl) azodiformate, intermediate and preparation method of di(4-trifluoromethylbenzyl) azodiformate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Synthesis of 4-trifluoromethylbenzyl chloroformate

[0042]

[0043] In a 250mL four-necked reaction flask, dissolve triphosgene (14.8g, 50mmol) in 100mL of dichloromethane, and control the temperature below 5°C in an ice bath. 4-Trifluoromethylbenzyl alcohol (8.8 g, 50 mmol) was slowly added dropwise. After the dropwise addition was completed, stirring was continued for 2 h, and then the reaction was continued for 42 h at room temperature. The reaction progress was monitored by TLC. After the reaction is complete, wash with water (100mL×3), the mass fraction is 8% NaHCO 3 Wash with aqueous solution (100mL×2), and finally wash with saturated brine (100mL×1) to obtain a dichloromethane solution of 4-trifluoromethylbenzyl chloroformate, which is directly used in the next reaction.

[0044] Synthesis of Di-4-trifluoromethylbenzyl Hydrazinedicarboxylate

[0045]

[0046] In a 500mL four-necked flask, add the dichloromethane solution of chloroformic acid-4-trifluorom...

Embodiment 2

[0054] Synthesis of 4-trifluoromethylbenzyl chloroformate

[0055] In a 250 mL four-neck reaction flask, dissolve triphosgene (10.4 g, 35 mmol) in 120 mL of chloroform, and control the temperature below 5° C. in an ice bath. 4-Trifluoromethylbenzyl alcohol (8.8 g, 50 mmol) was slowly added dropwise. After the dropwise addition was completed, stirring was continued for 2 h, and then the reaction was continued for 42 h at room temperature. The reaction progress was monitored by TLC. After the reaction is complete, wash with water (100mL×3), the mass fraction is 5% KHCO 3 Wash with aqueous solution (100mL×2), and finally wash with saturated brine (100mL×1) to obtain a chloroform solution of 4-trifluoromethylbenzyl chloroformate, which is directly used in the next reaction.

[0056] Synthesis of Di-4-trifluoromethylbenzyl Hydrazinedicarboxylate

[0057] In the 500mL four-necked flask, add the chloroform solution of 4-trifluoromethylbenzyl chloroformate obtained in the previous s...

Embodiment 3

[0061] Synthesis of 4-trifluoromethylbenzyl chloroformate

[0062] In a 250mL four-necked reaction flask, dissolve triphosgene (13.3g, 45mmol) in 70mL of 1,2-dichloroethane, and control the temperature below 5°C in an ice bath. 4-Trifluoromethylbenzyl alcohol (8.8 g, 50 mmol) was slowly added dropwise. After the dropwise addition was completed, stirring was continued for 2 h, and then the reaction was continued for 42 h at room temperature. The reaction progress was monitored by TLC. After the reaction is complete, wash with water (100mL×3), the mass fraction is 3% KHCO 3 Wash with aqueous solution (100mL×2), and finally wash with saturated brine (100mL×1) to obtain a solution of 4-trifluoromethylbenzyl chloroformate in 1,2-dichloroethane, which is directly used in the next reaction.

[0063] Synthesis of Di-4-trifluoromethylbenzyl Hydrazinedicarboxylate

[0064] In a 500mL four-neck flask, add the 1,2-dichloroethane solution of 4-trifluoromethylbenzyl chloroformate obtained...

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Abstract

The invention discloses a novel azo-type reagent of di(4-trifluoromethylbenzyl) azodiformate, an intermediate, and a preparation method of di(4-trifluoromethylbenzyl) azodiformate. The preparation method comprises the following steps in sequence: taking 4-trifluoromethylbenzyl alcohol and triphosgene as raw materials and taking chloralkane as a solvent; performing reaction in an ice-water bath to produce 4-trifluoromethylbenzyl chloroformate; after washing the reacting liquid with a weakly alkaline solution, slowly adding hydrazine monohydrate drop by drop at a room temperature to obtain di(4-trifluoromethylbenzyl) hydrazinodiformate; and obtaining di(4-trifluoromethylbenzyl) azodiformate from di(4-trifluoromethylbenzyl) hydrazinodiformate through oxidation by an oxidizing agent. According to the invention, the preparation method of di(4-trifluoromethylbenzyl) azodiformate is mild in condition, less in step, simple in operation, and high in yield.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and specifically relates to a bis-4-trifluoromethylbenzyl azodicarboxylate, an intermediate and a preparation method thereof. Background technique [0002] In 1967, Professor Oyo Mitsunobu reported the Mitsunobu reaction for the first time. Due to its mild reaction conditions, wide application range, and high stereoselectivity, it has become a standard method for chiral inversion of chiral secondary alcohols and has been widely used in compound synthesis, heterocyclic chemistry, and medicinal chemistry. , biochemistry and natural product synthesis are widely used. Although the Mitsunobu reaction is powerful in organic synthesis, two reagents (an azo reagent and a trivalent phosphine reagent) are required in this redox process, generating stoichiometric hydrazine by-products and penta valent phosphine oxide by-products. [0003] Diethyl azodicarboxylate (DEAD) and diisopropyl ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C245/04C07C281/02
Inventor 戴立言施秋龙王晓钟张玲玲陈英奇
Owner ZHEJIANG UNIV
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