CN104804039A - Synthesis method for organic phosphorus based flame retardant metabolite - Google Patents

Abstract

The invention relates to a method for synthesizing metabolites of organophosphorus flame retardants. The present invention greatly improves the purity of the product by improving the synthetic route; and each reaction raw material involved in the present invention: chlorine oxychloride, triethylamine, ROH, etc. are cheap and easy to get, and the synthetic principle of each intermediate compound is simple, and the reaction The conditions are controllable, the yield is stable, and the product has high purity.

Description

Synthetic method of organophosphorus flame retardant metabolites

technical field

The invention relates to a method for synthesizing metabolites of organophosphorus flame retardants. Including bis(butoxyethyl)phosphate (DBEP), a metabolite of synthetic tri(butoxyethyl)phosphate (TBEP); dichloroethylphosphate, a metabolite of trichloroethylphosphate (TCEP) (BCEP); bis(1-chloro-2-propyl) phosphate (BCPP), a metabolite of tris(1-chloro-2-propyl) phosphate (TCPP); phosphoric acid, a metabolite of triphenyl phosphate (TPhP) Diphenyl ester (DPhP); the metabolite of tricresyl phosphate (TCP), dimethyl phenyl phosphate (DCP), etc.

Background technique

Due to the bioaccumulation and potential toxicity of polybrominated diphenyl ethers, the flame retardants of polybrominated diphenyl ethers are gradually banned in the world, so organophosphate flame retardants are widely used, which makes the flame retardants widely exist in environmental media . In 2009, Schindler et al. detected the metabolites of organophosphorus flame retardants for the first time in German urine samples, and confirmed the structure of the metabolites. To further study the biotoxicity of metabolites of organophosphorus flame retardants, a large number of high-purity metabolite standards are needed. The current traditional method of synthesizing this type of compound is to directly hydrolyze the organophosphorus flame retardant, and the reaction is as follows:

The disadvantage of this reaction is that the degree of hydrolysis is difficult to control, and the resulting products are complex, with one, two and three hydroxyl groups, respectively. Due to the lack of UV absorption of these compounds, it is difficult to purify each metabolite by traditional column chromatography. . The standard samples of metabolites of organophosphorus flame retardants currently on the market are all prepared by HPLC method. Therefore, it is difficult to prepare a large amount of metabolites of organophosphorus flame retardants by this synthesis method.

Contents of the invention

The purpose of the present invention is to overcome the difficulty of purification in the existing synthesis method, and provide a new synthesis method of organophosphorus flame retardant metabolites, which can synthesize a relatively large amount of purified target compound.

To achieve the above object, the present invention adopts following reaction mechanism:

According to above-mentioned reaction mechanism, the present invention adopts following technical scheme:

A method for synthesizing metabolites of organophosphorus flame retardants, characterized in that the specific steps of the method are:

a. Dissolve phosphorus oxychloride in dichloromethane, add triethylamine and ROH dropwise at -60~0°C; stir and react at room temperature for 30~150min, remove dichloromethane, and obtain compound 2, which The structural formula is: , described ROH is ethylene glycol butyl ether, 2-chloroethanol, 1-chloro-2-propanol, phenol, p-cresol or m-cresol; described phosphorus oxychloride: triethylamine: ROH The molar ratio range is kept at 1:2:2～1.5:2:2;

b. Dissolve compound 2 obtained in step a in tetrahydrofuran, keep it at -10 ⁰ C ~ 10 ⁰ C, carry out hydrolysis reaction in 1 mol/L NaOH aqueous solution, stir for 40 ~ 150 minutes, adjust the pH value to 1 ~ 4 ; Extract with ethyl acetate, remove organic solvent, separate and purify, obtain organophosphorus flame retardant metabolite, its structural formula: .

¹ H NMR (CDCl ₃ , 500MHz), δ 0.892-0.921 (t, J =14.5Hz, 6H), 1.318-1.393 (m, J =37.5Hz, 4H), 1.535-1.578 (m, J =21.5Hz, 4H), 3.458-3.489 (td, J ₁ =2Hz, J ₂ =2.5Hz, J ₃ =2Hz, 4H), 3.608-3.644 ( m, J =18Hz, 4H), 4.134-4.217 (td, J ₁ =2Hz, J ₂ =3Hz, J ₃ =4.5Hz, 4H), 10.98 (s, 1H).

¹ H NMR (CDCl _{3 ,} 500MHz), δ 3.730-3.750 (t, J ₁ =5Hz, J ₂ =5Hz,4H), 4.295-4.306 (d, J =32.5Hz, 4H), 10.086 (s, 1H).

1 H NMR spectrum of bis(1-chloro-2-propyl)phosphate (BCPP) ¹ H NMR (CDCl ₃ , 500MHz), δ 1.18 (s, 6H) 3.59 (d, J =6Hz, 4H), 3.71 (s, 2H ), 9.97 (s, 1H).

¹ H NMR (CDCl _{3 ,} 500MHz), δ 7.155-7.184 (t, J ₁ =7.5Hz, J ₂ =7Hz,6H), 7.279-7.31 (t, J ₁ =7.5Hz, J ₂ =8Hz, 4H), 9.764 (s, 1H).

¹ H NMR spectrum of m-xylyl phosphate DmCP (CDCl _{3 ,} 500MHz), δ 2.281 (s, 6H), 6.964 (s, 6H), 7.145 (s,2H), 10.04 (s,1H).

¹ H NMR (CDCl _{3 ,} 500MHz), δ 2.3 (s, 6H), 7.025-7.082 (m, 8H), 9.79 (s, 1H) of p-xylyl phosphate DpCP.

Compared with the existing methods, the preparation method of organophosphorus flame retardant metabolites of the present invention has the following advantages:

1. Low production cost. Compared with the existing methods, the price of the synthetic raw materials utilized in the present invention is comparatively low.

2. Easy to purify. The original synthesis method has complex products and is difficult to purify. Utilizing the method of the invention, the number of substituted molecules is controlled through the equivalent ratio, and the product has high purity and is easy to purify.

3. High yield. Through experimental research, the productive rate of product is as high as more than 80%.

4. The experiment is easy to operate. The existing method obtains many by-products, and uses HPLC to purify. The post-treatment method is relatively complicated to operate and has a small amount of preparation. Utilizing the method of the present invention, the operation is relatively simple, and the purification only needs to be purified by conventional column chromatography.

Detailed ways

Specific steps are as follows:

(1) Add (1.53 g, 10 mmol) phosphorus oxychloride to dichloromethane (100 ml) in a 250 ml three-necked flask and place it in a cryogenic instrument at -60~0 °C; triethylamine (2.02 g g, 20 mmol) and compound (1) (10 mmol) were dissolved in dichloromethane (30 ml). Slowly add it dropwise into a three-necked flask with a constant pressure funnel; after the dropwise addition, stir at room temperature for 30-150 min, and after the reaction is complete, rotate under reduced pressure to remove dichloromethane to obtain compound (2).

(2) Dissolve the above product in tetrahydrofuran (10ml); place it in a system at -10~10°C, and gradually add 10ml of 1 mol/L sodium hydroxide aqueous solution dropwise, and stir vigorously under the system for 30 minutes after the addition is completed. After the reaction, hydrochloric acid was added to adjust the pH value to acidic, and then extracted with ethyl acetate, and the aqueous layer was washed three times with ethyl acetate. After the completion, the organic layer is rotary evaporated and purified by a chromatographic column to obtain relatively pure organophosphorus flame retardant metabolites.

Claims (1)

1. a synthetic method for organic phosphorus flame retardant metabolite, is characterized in that the concrete steps of the method are:

A. phosphorus oxychloride is dissolved in methylene dichloride, at-60 ~ 0 DEG C of temperature, is added dropwise to triethylamine and ROH; At room temperature stirring reaction 30 ~ 150min, removing methylene dichloride, obtain compound 2, its structural formula is: , described ROH is butyl glycol ether, ethylene chlorhydrin, 1-chloro-2-propanol, phenol, p-cresol or meta-cresol; The molar ratio range of described phosphorus oxychloride: triethylamine: ROH remains on 1:2:2 ~ 1.5:2:2;

B. step a gained compound 2 is dissolved in tetrahydrofuran (THF), remains on-10 ⁰c ~ 10 ⁰c, be hydrolyzed reaction in the aqueous solution of 1 mol/L NaOH, stirring reaction 40 ~ 150min, adjust ph to 1 ~ 4; Be extracted with ethyl acetate, remove organic solvent, separation and purification, obtains organic phosphorus flame retardant metabolite, its structural formula: .