Synthesis method of N-benzyl acetamidine hydrochloride

A technology of benzylacetamidine hydrochloride and a synthesis method is applied in the field of synthesis technology of amidine compounds, can solve problems such as environmental pollution, and achieve the effects of simple post-processing, mild reaction conditions, and good prospects for industrial application.

Active Publication Date: 2020-03-13
苏州诚和医药化学有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] For above-mentioned deficiency, the present invention provides a kind of synthetic method of N-benzylacetamidine hydrochloride, and synthetic route is as follows figure 2 As shown, the environmental pollution problem of the original production process is overcome, and the product yield is high, the purity is good, and there is a good industrialization prospect

Method used

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  • Synthesis method of N-benzyl acetamidine hydrochloride
  • Synthesis method of N-benzyl acetamidine hydrochloride
  • Synthesis method of N-benzyl acetamidine hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0023] The synthesis of N-benzylacetamidine hydrochloride comprises the following steps:

[0024] I: Add 20g (0.125mol) of benzylhydroxylamine hydrochloride and 100ml of toluene into a 250ml reaction flask, stir and cool to 0°C under nitrogen protection for 2 hours, adjust the pH to 9-10 with 2M aqueous sodium hydroxide solution, and let it stand , the lower aqueous layer was removed, the organic layer was dried by adding 5 g of sodium sulfate, filtered, and the filtrate was added to the reaction flask;

[0025] II: Add 10.25 g (0.25 mol) of acetonitrile into the above reaction flask, raise the temperature to 50°C under the protection of nitrogen, keep it warm for 3 hours, and concentrate under negative pressure until no liquid comes out to obtain 17.2 g of intermediate 1 with a yield of 84%. ;

[0026] III: Put 17.2g of intermediate 1, 100ml of ethyl acetate, and 2g of Raney nickel into the autoclave, replace with nitrogen twice, and then pass in hydrogen to 0.6MPa, raise th...

Embodiment 2

[0028] The synthesis of N-benzylacetamidine hydrochloride comprises the following steps:

[0029] I: Add 20g (0.125mol) of benzylhydroxylamine hydrochloride and 100ml of toluene to a 250ml reaction bottle, stir and cool to 5°C under nitrogen protection for 3 hours, adjust the pH to 9-10 with 2M aqueous sodium hydroxide solution, and let it stand , the lower aqueous layer was removed, the organic layer was dried by adding 5 g of sodium sulfate, filtered, and the filtrate was added to the reaction flask;

[0030] II: Add 10.25 g (0.25 mol) of acetonitrile to the above reaction flask, raise the temperature to 70°C under the protection of nitrogen, keep it warm for 5 hours, concentrate under negative pressure until no liquid comes out, and obtain 18.9 g of intermediate 1 with a yield of 92%;

[0031] III: Put 18.9g of intermediate 1, 100ml of ethyl acetate, and 2g of Raney nickel into the autoclave, replace with nitrogen for 3 times, then pass in hydrogen to 0.8MPa, raise the temp...

Embodiment 3

[0033] The synthesis of N-benzylacetamidine hydrochloride comprises the following steps:

[0034] I: Add 20g (0.125mol) of benzylhydroxylamine hydrochloride and 100ml of toluene into a 250ml reaction flask, stir and cool to 5°C for 4 hours under nitrogen protection, adjust the pH to 9-10 with 2M aqueous sodium hydroxide solution, and let it stand , the lower aqueous layer was removed, the organic layer was dried by adding 5 g of sodium sulfate, filtered, and the filtrate was added to the reaction flask;

[0035] II: Add 10.25 g (0.25 mol) of acetonitrile into the above reaction flask, raise the temperature to 80°C under the protection of nitrogen, keep it warm for 8 hours, concentrate under negative pressure until no liquid comes out, and obtain 18.2 g of intermediate 1 with a yield of 88%;

[0036] III: Put 18.2g of intermediate 1, 100ml of ethyl acetate, and 2g of Raney nickel into the autoclave, replace with nitrogen for 3 times, and then pass in hydrogen to 1.0MPa, raise t...

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Abstract

The invention discloses a synthesis method of N-benzyl acetamidine hydrochloride. The synthesis method mainly comprises the following three steps: 1, adding a benzyl hydroxylamine hydrochloride into toluene, adding a sodium hydroxide aqueous solution at a low temperature, and removing a water layer to obtain a benzyl hydroxylamine toluene solution; 2, adding acetonitrile into the benzyl hydroxylamine toluene solution, heating to react, and concentrating to remove the solvent after the reaction is finished, thereby obtaining an intermediate 1; and 3, adding the intermediate 1, ethyl acetate andraney nickel into an autoclave, introducing hydrogen for hydrogenation at a certain temperature, filtering to remove a catalyst, adding a hydrogen chloride methanol solution, cooling and crystallizing to obtain the target product with the purity higher than 95%. The synthetic route is mild in conditions, good in product quality, less in three wastes and simple and convenient in post-treatment, can meet the requirements of current green chemistry, has obvious economic and social benefits, and has a promising industrial application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and relates to a synthesis process of amidine compounds. [0002] technical background [0003] As important intermediates in the application of medicine and pesticides, amidine compounds are widely used in the fields of medicine and chemical industry, and their synthetic methods have always been the focus of attention. Wherein N-benzylacetamidine hydrochloride is an important pharmaceutical intermediate, and its chemical structure is as follows: [0004] [0005] The synthesis route of this intermediate reported in the patent WO2015 / 5615,2015,A1 is shown in Figure 1. The product content of this process is low, and a large amount of hydrogen chloride gas is generated during the production process, which is highly corrosive, is not conducive to industrial production, and produces a large amount of The three wastes cause environmental pollution. Contents of the invention [000...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C257/14
CPCC07C257/14
Inventor 陈晓强方欢
Owner 苏州诚和医药化学有限公司
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