TECHNICAL FIELD

The invention relates to the technical field of organic compounds, and particularly relates to a β-amino phosphonic acid derivative and a preparation method therefore.

BACKGROUND TECHNIQUE

β-Aminophosphonic acid derivatives have a wide range of physiological activities, such as antibacterial, nerve stimulation, affecting cell growth and metabolism, analgesia, regulating blood pressure, regulating plant growth, etc., so they can be used as medicine, pesticides, antagonists, anthocyanins Synthetic inhibitors, fructose diphosphatase inhibitors, etc. (see Maier, L. Phosphorus Sulfur 1983, 14, 295; Abbenante, Giovanni;Australian J. Chem.,1997, 50, 523-527).

In the prior art, the synthesis methods of β-amino phosphonic acid derivatives are mainly as follows:



However, the prior art has the following problems: equivalent metal lithium reagent and sodium borohydride reducing agent are required, the reaction conditions are harsh, and the reaction steps are many; the raw materials are difficult to obtain, the reaction steps are many, and the yield is low; the expensive cyanoborohydride is needed, sodium has lower yield.

In summary, it is important to develop a method for preparing β-aminophosphonic acid derivatives with mild reaction conditions, wide application range, few reaction steps, high yield, low cost, and meeting the requirements of green chemistry.

Technical Problems

The object of the present invention is to provide a β-aminophosphonic acid derivative and a preparation method thereof.

Technical Solutions

In order to achieve the above-mentioned object of the invention, the technical solution adopted by the present invention is:

A method for preparing the β-amino phosphonic acid derivative includes the following steps: dissolving an N-(arylvinyl)benzamide derivative, a dialkyl phosphite, manganese acetate, and potassium carbonate in a solvent and reacting at room temperature to obtain a (2-benzamido-1-arylvinyl)dialkylphosphonate derivative; reducing the (2-benzamido-1-arylvinyl) dialkylphosphonate derivative to obtain a (2-benzamido-1-arylethyl) dialkylphosphonate derivative; hydrolyzing the (2-benzamido-1-arylethyl) dialkylphosphonate derivative to obtain β-amino phosphonic acid derivative.

The structural formula of N-(arylvinyl) benzamide derivative is shown as follow:



R is hydrogen, methyl, methoxy, fluorine, chlorine, or bromine.

The structural formula of dialkyl phosphite is shown as follow:



R1is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl.

A method for preparing a (2-benzamido-1-arylethyl) dialkylphosphonate derivative includes the following steps: dissolving an N-(arylvinyl)benzamide derivative, a dialkyl phosphite, manganese acetate, and potassium carbonate in a solvent and reacting at room temperature to obtain a (2-benzamido-1-arylvinyl) dialkylphosphonate derivative; reducing the (2-benzamido-1-arylvinyl) dialkylphosphonate derivative to obtain the (2-benzamido-1-arylethyl)dialkylphosphonate derivative.

The structural formula of N-(arylvinyl)benzamide derivative is shown as follow:



R is hydrogen, methyl, methoxy, fluorine, chlorine, or bromine.

The structural formula of dialkyl phosphite is shown as follow:



R1is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl.

The invention also discloses that application of N-(arylvinyl)benzamide and dialkyl phosphite as substrates in the preparation of β-aminophosphonic acid derivative or (2-benzamido-1-arylethyl) dialkylphosphine. Preferably, the preparation is performed in the presence of manganese acetate and potassium carbonate in the solvent, and at room temperature.

In the present invention, the dialkyl phosphite is selected from the group consisting of dimethyl phosphite, diethyl phosphite, and diisopropyl phosphate; the solvent is selected from the group consisting of methanol, ethanol, acetone, and acetonitrile; the N-(arylvinyl)benzamide derivative is selected from the group consisting of N-(styryl)benzamide, 2-methyl-N-(styryl)benzamide, 2-methoxy-N-(styryl)-benzamide, 2-chloro-N-(styryl)benzamide, 2-fluoro-N-(styryl)benzamide, 2-bromo-N-(styryl)benzamide, 3-methyl-N-(styryl)benzamide, 3-methoxy-N-(styryl)benzamide, 3-chloro-N-(styryl)benzamide, 3-fluoro-N-(styryl)benzamide, 3 bromo-N-(styryl)benzamide, 4-methyl-N-(styryl)benzamide, 4-methoxy-N-(styryl)benzamide, 4-chloro-N-(styryl)benzamide, 4-fluoro-N-(styryl)benzamide, and 4-bromo-N-(styryl)benzamide.

In the present invention, the reaction is tracked to completion by a thin layer chromatography and the reaction is performed at room temperature.

In the present invention, a molar ratio of the N-(arylvinyl)benzamide derivative:dialkyl phosphite:manganeseacetate:potassium carbonate is 1:2:2.5:2.

In the present invention, the (2-benzamido-1-arylvinyl)dialkylphosphonate derivative is reduced with Raney-Ni/H2. Preferably, a molar ratio of the Raney-Ni is 20% of (2-benzamido-1-arylvinyl)dialkylphosphonate derivative.

(2-Benzamido-1-arylethyl) dialkylphosphonate derivatives are hydrolyzed with hydrochloric acid, which is also as the solvent.

In the present invention, the chemical structural formula of the (2-benzamido-1-arylvinyl)dialkylphosphonate derivative is as follow:



The chemical structural formula of β-amino phosphonic acid derivative is as follows:



The chemical structural formula of (2-benzamido-1-arylethyl)dialkylphosphonate derivative is as follows:



The reaction process of the above technical solution can be expressed as:



Beneficial Effects

Due to the application of the above technical solutions, the present invention has the following advantages over the prior art:

1. In the present invention, N-(arylvinyl)benzamide derivatives are used as starting materials, and the raw materials are readily available; by using the method of the present invention, a new type of β-aminophosphonic acid derivatives can be obtained.

2. The invention has mild reaction conditions, few steps, simple reaction operation and post-treatment process, high yield, and is suitable for large-scale production.

