Method for synthesizing d-biotin

A synthetic method and biotin technology, applied in the direction of organic chemistry, can solve problems such as potential safety hazards, and achieve the effects of increasing yield, improving reaction efficiency, and being environmentally friendly

Active Publication Date: 2014-05-07
ZHEJIANG NHU CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Convert (2S,3S,4S)-5-(3,4-diamino-tetrahydrothiophen-2-yl)pentanoic acid into d-biotin, the ring-closing reagent used is generally phosgene, the publication number is CN Chinese patent application 1374312 A discloses a preparation method of d-biotin, which includes (2S,3S,4S)-5-(3,4-diamino-tetrahydrothiophen-2-yl) The step of ring-closing valeric acid to generate d-biotin, the ring-closing reagent used is trichloromethyl chloroformate (diphosgene) or bis(trichloromethyl)carbonate (triphosgene), the product obtained by this preparation method The yield is relatively high. However, if diphosgene and triphosgene are used as reaction raw materials, the intermediate phosgene will inevitably be produced, which has great potential safety hazards. During the production process, it is necessary to strictly do a good job of sealing the equipment and controlling the tail gas. absorption process

Method used

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  • Method for synthesizing d-biotin
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  • Method for synthesizing d-biotin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] In a 500ml lined polytetrafluoroethylene autoclave, put (2S,3S,4S)-5-(3,4-diamino-tetrahydrothiophen-2-yl)pentanoic acid 30.0g (98.5%, 0.1354mol) , put in 200g of dimethyl carbonate (99.2%, 2.2044mol), and 3.5g of boron trifluoride-ether complex. After the feeding is completed, high-purity nitrogen is introduced into the autoclave to 0.3MPa, and then exhausted to 0.05MPa, and then replaced twice, a total of three replacements, and the last replacement is completed to ensure that the nitrogen residual pressure in the autoclave is about 0.05MPa. After the replacement, turn on the electric heating of the autoclave, and set the heating temperature to 150°C. When the internal temperature reaches 150°C, start timing and carry out the heat preservation reaction. At this time, the pressure is about 0.3-0.6MPa (related to the residual pressure after the last replacement).

[0036]During the reaction, the high-performance liquid chromatograph detects the reaction liquid content ...

Embodiment 2

[0048] In a 500ml lined polytetrafluoroethylene autoclave, put (2S,3S,4S)-5-(3,4-diamino-tetrahydrothiophen-2-yl)pentanoic acid 30.0g (98.5%, 0.1354mol) , put in 300g of diethyl carbonate (99.0%, 2.5169mol), and 2.2g of trisulfomethane (CAS: 54322-33-7). After the feeding is completed, high-purity nitrogen is introduced into the autoclave to 0.3MPa, and then exhausted to 0.05MPa, and then replaced twice, a total of three replacements, and the last replacement is completed to ensure that the nitrogen residual pressure in the autoclave is about 0.05MPa. After the replacement, turn on the electric heating of the autoclave, and set the heating temperature to 170°C. When the internal temperature reaches 120°C, start timing and carry out the heat preservation reaction. The pressure at this time is about 0.4-0.6MPa (related to the residual pressure after the last replacement).

[0049] During the reaction, the high-performance liquid chromatograph detects the reaction liquid content...

Embodiment 3～14

[0054] Examples 3 to 14 were reacted according to the input amount of raw materials in Table 1 and the reaction conditions in Table 2, and the other conditions were the same as in Example 1, and the results obtained were recorded in Table 1.

[0055] Table 1 The raw material input amount of embodiment 3~14

[0056]

[0057] The reaction condition and reaction result of table 2 embodiment 3~14

[0058]

[0059]

[0060] From the results in Table 2, it can be seen that the efficiency of the reaction catalyzed by the Lewis acid is generally higher than that of the protonic acid, and the reaction time is shorter.

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Abstract

The invention discloses a method for synthesizing d-biotin. The method comprises the following steps: carrying out cyclization on (2S, 3S, 4S)-5-(3,4-diamido-thiophane-2-yl) valeric acid and carbonic ester under the effect of an acid catalyst; carrying out post-treatment to obtain the d-biotin after the reaction is ended, wherein the structure of the carbonic ester is shown in the specification; R<1> and R<2> are independently selected from C1-C5 alkyls; the acid catalyst is one or combination of more of a protonic acid and a lewis acid. By adopting the synthetic method, the carbonic ester is adopted as a reagent to replace triphosgene or diphosgene to react, and generation of a virulent phosgene intermediate is avoided, so that the method is friendlier to the environment; meanwhile, the reaction efficiency is improved by selecting a specific catalyst, and the yield of the d-biotin is increased.

Description

technical field [0001] The invention relates to an organic synthesis reaction in the field of chemistry, in particular to a method for forming d-biotin through a ring closure reaction. Background technique [0002] d-biotin is also known as vitamin H and coenzyme R. Its structure is shown in formula (I). It is a water-soluble vitamin and also belongs to the vitamin B group. It is a necessary substance for the synthesis of vitamin C and is indispensable for the normal metabolism of fat and protein. [0003] [0004] At present, d-biotin can be prepared by biosynthesis or chemical synthesis. Due to the large demand for d-biotin, chemical synthesis has more important application significance. [0005] The Chinese patent application with the publication number CN 1145072 A discloses an improved method for preparing d-biotin intermediates. The improved method uses dibenzyl biotin as a raw material to obtain d-biotin under strongly acidic conditions, wherein, The chemical nam...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04
CPCC07D495/04
Inventor 张谦吴英李松松石春晓
Owner ZHEJIANG NHU CO LTD
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