CN108383876B - A Class of Sulfur-Substituted Quaternary Pentavalent Phosphorus Derivatives, Synthetic Methods and Their Catalytic Applications - Google Patents

Abstract

以一种五烷基丙烯为原料，在路易斯酸的催化下与三价磷反应生成氯磷盐，再与硫羟基化合物发生亲核取代形成磷氧键，从而得到一种硫取代的四元五价磷衍生物。该发明引入了一种硫取代的四元五价磷环结构，可作为一种高效实用的氧磷试剂，且应用范围广，在许多特定的磷参与反应中有着不可替代的作用。本发明合成了一类全新结构的硫取代的四元五价磷衍生物；以及制备这类大张力硫取代的四元五价磷衍生物的全新合成路线，该合成路线为一种步骤少、产率高的新方法；同时，成功取得了该类大张力硫取代的四元五价磷衍生物有效应用，即能有效的催化分子内Wittig反应。The present invention relates to a kind of sulfur-substituted quaternary pentavalent phosphorus derivatives as organic catalysts, and the chemical structural formula of the compound is:

Using a pentaalkyl propylene as a raw material, it reacts with trivalent phosphorus under the catalysis of Lewis acid to generate chlorophosphorus salt, and then undergoes nucleophilic substitution with a thiol compound to form a phosphorus-oxygen bond, thereby obtaining a sulfur-substituted quaternary pentagonal Phosphorus derivatives. The invention introduces a sulfur-substituted quaternary pentavalent phosphorus ring structure, which can be used as an efficient and practical oxonate reagent, has a wide range of applications, and plays an irreplaceable role in many specific phosphorus reactions. The invention synthesizes a new type of sulfur-substituted quaternary pentavalent phosphorus derivatives; and a new synthetic route for preparing this type of large-strain sulfur-substituted quaternary pentavalent phosphorus derivatives. A new method with high yield; at the same time, the effective application of such large-strained sulfur-substituted quaternary pentavalent phosphorus derivatives was successfully obtained, that is, it can effectively catalyze the intramolecular Wittig reaction.

Description

A Class of Sulfur-Substituted Quaternary Pentavalent Phosphorus Derivatives, Synthetic Methods and Their Catalytic Applications

technical field

The invention relates to the technical field of organic chemical industry, in particular to a class of sulfur-substituted quaternary pentavalent phosphorus derivatives, a synthesis method and its catalytic application.

Background technique

Organocatalysis is a very important field in organic chemistry. In the reported reaction examples of organic catalysis, the catalysts are generally nitrogen-containing organic catalysts such as imines and amines, while phosphorus-containing organic catalysts are more commonly reported. It is particularly urgent to develop new organophosphine catalysts with novel structure and excellent performance. Due to the structural characteristics of the four-membered small ring, it has a large ring tension; and the outermost layer of the sulfur atom has two pairs of lone pairs of electrons. When the sulfur atom is connected to the phosphine atom, it will greatly change the electronic structure of the phosphine atom. , the mutual combination of the two points greatly reduces the bond energy of the phosphine-oxygen double bond of the active center phosphine atom. Application of trivalent phosphine and pentavalent catalytic cycle of organophosphine-catalyzed reactions. In this patent, we developed a class of structurally novel high-strain sulfur-substituted quaternary pentavalent phosphorus derivatives. The large-strain sulfur-substituted quaternary pentavalent phosphorus derivative has good catalytic activity. Meanwhile, all the experimental steps for synthesizing the large-strain sulfur-substituted quaternary pentavalent phosphorus derivative are conventional methods, which have high operability and are easy to realize the application of the phosphine catalyst in other fields.

SUMMARY OF THE INVENTION

The main purpose of the present invention is to provide a class of sulfur-substituted quaternary pentavalent phosphorus derivatives, a synthesis method and its catalytic application.

The technical scheme of the present invention is as follows:

A class of quaternary pentavalent phosphorus derivatives substituted by high tension sulfur, the chemical structural formula of the compound is:

Wherein, the substituents R ¹ , R ² , R ⁵ and R ⁶ are any one of hydrogen, alkyl, alkoxy, aryl or other substituents; R ³ and R ⁴ are hydrogen, alkyl or aryl Any one of; R ⁷ is an alkyl group or an aryl group.

The preparation method of the quaternary pentavalent phosphorus derivative substituted by the high tension sulfur, the method comprises the following synthetic routes:

所述方法包括以下步骤：

The method includes the following steps:

(1) Under nitrogen protection, add raw material 1, CH ₂ Cl ₂ , PCl ₃ , and AlCl ₃ in sequence to the reactor, stir to dissolve, cool down to -5℃～5℃ and react for 1-10h to obtain quaternary phosphorus chloride Salt 2 (preferably the reaction temperature is 0°C, and the reaction time is 3h);

(2) continue adding water to the reactor under nitrogen protection for quenching, the water-adding quenching process continues for 15-25 minutes (preferably 20min), then separate the organic phase and dry it with anhydrous sodium sulfate, remove the solvent under reduced pressure to obtain a white crystal 3;

(3) Put the white crystal 3 in the reaction flask and protect it with nitrogen, add toluene, triethylamine and thiol compound dropwise in turn, and continue to react at 30-90°C for 1-24h to obtain a quaternary phosphorus derivative substituted with high tension oxygen Compound 4 (preferably the reaction temperature is 60°C, the reaction time is 12h), monitored by TLC, after the reaction is completed, the temperature is lowered to room temperature, the solids in the reaction system are filtered off with suction, and then sodium bicarbonate solution is added dropwise to quench the organic phase. After extraction with water twice and drying over anhydrous sodium sulfate, the final product 4 was obtained after removing the solvent under reduced pressure.

Completion of the synthesis of quaternary pentavalent phosphorus derivatives substituted with high tension sulfur

In the step (1), the molar ratio of compound 1 to PCl ₃ to AlCl ₃ is 1:0.1-2:0.1-2; the yield of compound 2 will be affected by changing the feeding ratio or the order of feeding.

The step (1) reaction time is 1-10 hours. If the time is too short, the reaction is not complete; the reaction temperature is 0°C, which is conducive to the smooth progress of the reaction and the reduction of by-products.

In the step (2), the molar ratio of compound 2 to H ₂ O is 1:1-10; the yield of compound 3 will be affected by changing the feeding ratio or the order of feeding.

In the step (3), the mass ratio of compound 3 to triethylamine and thiol compound is 1:0.1-6:0.1-2; changing the feeding ratio or the order of feeding will affect the yield of compound 4.

The reaction time of the step (3) is 1-24 hours, and if the time is too short, the reaction is incomplete; the reaction temperature is 30-90°C. At this reaction temperature, the reaction proceeds smoothly and the formation of by-products is reduced.

The beneficial effects of the present invention are as follows:

1. The present invention synthesizes a new type of quaternary pentavalent phosphorus derivatives substituted by high tension sulfur, which can effectively replace common phosphine catalysts, and is widely used in the reaction systems of many catalytic cycles as a new type of organic catalyst, and is relatively great application prospects.

2. The present invention designs a synthetic route of the quaternary pentavalent phosphorus derivatives substituted by high tension sulfur as organic catalysts. This route uses polysubstituted propylene derivatives as raw materials, reacts with trivalent phosphorus under the catalysis of Lewis acid, and then synthesizes a series of quaternary pentavalent phosphorus derivatives substituted by high tension sulfur through substitution. The method has high yield, few by-products and high use value.

3. A new type of high-tension sulfur-substituted quaternary pentavalent phosphorus derivative synthesized in the present invention has good catalytic activity, and exhibits good catalytic performance in the intramolecular Wittig reaction.

Detailed ways

The present invention will be further described below in conjunction with the embodiments, but the claimed scope of the present invention is not limited to the scope expressed by the embodiments.

Instruments and Reagents:

SHZ-E circulating water vacuum pump (Shanghai Rongyasheng Chemical Instrument Factory); DZE-6120 vacuum drying oven (Shanghai Hengtian Scientific Instrument Manufacturing Co., Ltd.); WRS-1A Digital Melting Point Apparatus (Shanghai Suoguang Photoelectric Technology Co., Ltd.) ;EB2005A electronic balance; ZF-I type three-purpose UV analyzer; DE-102J collector type constant temperature heating magnetic stirrer (Gongyi Huafa Chemical Instrument Factory); DFX-5L/30 low temperature constant temperature reaction bath (Wuxi Baichuan Instrument Factory) ); 2YZ-4A rotary vane vacuum pump (Linhai Yonghao Vacuum Equipment Factory). Trimethylpentene (AR), Dichloromethane (AR), Phenol (AR), Triethylamine (AR), Toluene (AR), Phosphorus Trichloride (AR), Petroleum Ether (AR), Ethyl acetate (AR), deionized water (homemade), industrial nitrogen (AR).

Example 1

A method for synthesizing 1-((4-chlorophenyl)thio)-2,2,3,4,4-pentamethylphosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.146g, 1.1 mmol.) and CH ₂ Cl ₂ (10 mL) were successively added to the reactor, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.151 g, 1.1 mmol.), trimethylpentene 1a (0.112 g, 1 mmol.), and reacted at this temperature for 3 h, then added 3 mL of deionized water dropwise with a syringe, and the time for adding water was 20 min. After mixing, separate The organic phase was removed, dried over anhydrous sodium sulfate and spin-dried to give 3a as a white solid (0.135 g, 0.69 mmol, 69%). 3a (0.135g, 0.69mmol) was placed in a reaction flask under nitrogen protection, followed by dropwise addition of toluene (3ml), triethylamine (0.153g, 1.52mmol.) and thiophenol (0.106g, 0.83mmol.) , continue to react at 60 ° C for 12 h to obtain the quaternary pentavalent phosphorus derivative 4a substituted by large tension sulfur, TLC monitoring, after the reaction is completed, cool down to room temperature, add dropwise sodium bicarbonate solution for quenching, and extract the organic phase with water for two The mixture was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the final product 4a (0.13 g, 0.43 mmol, 62%).

Example 2

A method for synthesizing 2,2,3,4,4-pentamethyl-1-((6-methylheptyl)thio)phosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.146g, 1.1 mmol.) and CH ₂ Cl ₂ (10 mL) were successively added to the reactor, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.151 g, 1.1mmol.), trimethylpentene 1a (0.112g, 1mmol.), and react at this temperature for 3h, then dropwise add 3mL of deionized water with a syringe, the time for adding water is 15min, and after mixing evenly, separate The organic phase was removed, dried over anhydrous sodium sulfate and spin-dried to give 3a as a white solid (0.135 g, 0.69 mmol, 69%). 3a (0.135g, 0.69mmol) was placed in a reaction flask with nitrogen protection, and toluene (3ml), triethylamine (0.153g, 1.52mmol.) and isooctanethiol (0.121g, 0.83mmol.) were added dropwise in turn. ), continue to react at 60°C for 12h to obtain the quaternary pentavalent phosphorus derivative 4b substituted with high tension sulfur, monitored by TLC, after the reaction is completed, it is cooled to room temperature, quenched by dropwise addition of sodium bicarbonate solution, and the organic phase is extracted with water Twice and dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure to give the final product 4b (0.173 g, 0.57 mmol, 83%).

Example 3

A method for synthesizing 2,2,3,4,4-pentamethyl-1-((4-(6-methylheptyl)phenyl)thio)phosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.146g, 1.1 mmol.) and CH ₂ Cl ₂ (10 mL) were successively added to the reactor, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.151 g, 1.1mmol.), trimethylpentene 1a (0.112g, 1mmol.), and react at this temperature for 3h, then dropwise add 3mL of deionized water with a syringe, the time for adding water is 25min, after mixing, separate The organic phase was removed, dried over anhydrous sodium sulfate and spin-dried to give 3a as a white solid (0.135 g, 0.69 mmol, 69%). 3a (0.135g, 0.69mmol) was placed in a reaction flask with nitrogen protection, and toluene (3ml), triethylamine (0.153g, 1.52mmol.) and p-isooctylthiophenol (0.184g, 0.83 mmol.), continue to react at 60 ° C for 12 h to obtain the quaternary pentavalent phosphorus derivative 4c substituted by high tension sulfur, TLC monitoring, after the reaction is completed, cool down to room temperature, dropwise add sodium bicarbonate solution for quenching, organic The phase was extracted twice with water and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the final product 4c (0.171 g, 0.45 mmol, 65%).

Example 4

A method for synthesizing 1-((4-chlorophenyl)thio)-2,2,3,4,4-pentamethylphosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (1.46g), CH ₂ Cl ₂ (100 mL) were added to the reactor in sequence, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (1.51 g), trimethyl Pentene 1a (1.12g) was reacted at this temperature for 3h, and then 30mL of deionized water was added dropwise with a syringe for 20min. After mixing uniformly, the organic phase was separated, dried with anhydrous sodium sulfate and Spin dry to give 3a as a white solid. 3a was placed in a reaction flask and protected with nitrogen, and toluene (30ml), triethylamine (1.53g) and thiophenol (1.06g) were added dropwise in turn, and the reaction was continued at 60 ° C for 12h to obtain a large tension sulfur-substituted The quaternary pentavalent phosphorus derivative 4a was monitored by TLC. After the reaction was completed, the temperature was lowered to room temperature, and sodium bicarbonate solution was added dropwise for quenching. The organic phase was extracted twice with water and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain Final product 4a (65%).

Example 5

A method for synthesizing 1-((4-chlorophenyl)thio)-2,2,3,4,4-pentamethylphosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.0146g), CH ₂ Cl ₂ (1mL) were added to the reactor in turn, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.0151g), trimethyl Pentene 1a (0.0112g) was reacted at this temperature for 3h, then 0.3mL of deionized water was added dropwise with a syringe for 20min. After mixing, the organic phase was separated and dried with anhydrous sodium sulfate. and spin-dried to obtain a white solid 3a. 3a was placed in a reaction flask under nitrogen protection, and toluene (0.3ml), triethylamine (0.0153g) and p-thiophenol (0.0106g) were added dropwise in turn, and the reaction was continued at 60°C for 12h to obtain a large tension sulfur substitution. The quaternary pentavalent phosphorus derivative 4a was monitored by TLC. After the reaction was completed, the temperature was lowered to room temperature, and sodium bicarbonate solution was added dropwise for quenching. The organic phase was extracted twice with water and dried with anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The final product 4a was obtained (61%).

Example 6

A method for synthesizing 1-((4-chlorophenyl)thio)-2,2,3,4,4-pentamethylphosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.146g, 1.1 mmol.) and CH ₂ Cl ₂ (10 mL) were successively added to the reactor, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.151 g, 1.1 mmol.), trimethylpentene 1a (0.112 g, 1 mmol.), and react at this temperature for 3 h, after mixing uniformly, separate the organic phase, dry with anhydrous sodium sulfate and spin dry to obtain a solid substance. The solid substance was placed in a reaction flask and protected with nitrogen, and toluene (3ml), triethylamine (0.153g, 1.52mmol.) and thiophenol (0.106g, 0.83mmol.) were added dropwise successively, and the temperature was continued at 60°C. The product was reacted for 12 h to obtain the product, monitored by TLC. After the reaction was completed, the temperature was lowered to room temperature, and sodium bicarbonate solution was added dropwise for quenching. The organic phase was extracted twice with water and dried with anhydrous sodium sulfate. After the solvent was removed under reduced pressure, the final product was not detected. The product is a large-strain sulfur-substituted quaternary pentavalent phosphorus derivative 4a, that is, the yield is 0%.

Example 7

A method for synthesizing 1-((4-chlorophenyl)thio)-2,2,3,4,4-pentamethylphosphetane 1-oxide, comprising the following experimental steps:

Under nitrogen protection, AlCl ₃ (0.146g, 1.1 mmol.) and CH ₂ Cl ₂ (10 mL) were successively added to the reactor, and after stirring to dissolve, the temperature was lowered to 0° C. PCl ₃ (0.151 g, 1.1 mmol.), trimethylpentene 1a (0.112 g, 1 mmol.), and reacted at this temperature for 3 h, then added 3 mL of deionized water dropwise with a syringe, and the time for adding water was 20 min. After mixing, separate The organic phase was removed, dried over anhydrous sodium sulfate and spin-dried to give 3a as a white solid (0.135 g, 0.69 mmol, 69%). 3a (0.135g, 0.69mmol) was placed in a reaction flask under nitrogen protection, toluene (3ml) and thiophenol (0.106g, 0.83mmol.) were added dropwise in turn, and the reaction was continued at 60°C for 12h to obtain the product, TLC monitoring, after the reaction was completed, the temperature was lowered to room temperature, and sodium bicarbonate solution was added dropwise for quenching. The organic phase was extracted twice with water and dried with anhydrous sodium sulfate. The quaternary pentavalent phosphorus derivative 4a, that is, the yield is 0%.

Example 8

Catalytic Activity Experiment (Catalyzing Intramolecular Wittig Reaction)

We tested the catalytic activity of the synthesized new high-strain sulfur-substituted quaternary pentavalent phosphorus derivatives, mainly testing the catalytic activity of our new high-strain sulfur-substituted quaternary pentavalent phosphorus derivatives to catalyze the intramolecular Wittig reaction. active. The test results are as follows:

Reaction conditions: 1 mmol of raw carbonyl bromide, 10 ml of solvent, 3 mmol of TMDS, 0.2 mmol of Ti(i-Pr) ₄ , 0.3 mmol of phosphorus compound, and the reaction time was 12 hours.

This experiment well demonstrates that our prepared novel large-strain sulfur-substituted quaternary pentavalent phosphorus derivatives are effective for catalyzing intramolecular Wittig.

The above-mentioned embodiments are only the preferred technical solutions of the present invention, and should not be regarded as limitations of the present invention. The embodiments and features in the present application may be arbitrarily combined with each other without conflict. The protection scope of the present invention shall take the technical solutions described in the claims, including the equivalent alternatives of the technical features in the technical solutions described in the claims, as the protection scope. That is, equivalent replacements and improvements within this scope are also within the protection scope of the present invention.

Claims (8)

1. the quaternary pentavalent phosphorus derivative that a class of high tension sulfur replaces, is characterized in that, the chemical structural formula of described compound is:

Wherein, the substituents R ¹ , R ² , R ³ , R ⁵ , and R ⁶ are methyl groups; R ⁴ is hydrogen; R ⁷ is isooctyl or p-isooctylphenyl. 2. the method for the quaternary pentavalent phosphorus derivative substituted by the high tension sulfur of claim 1, is characterized in that, described method comprises following synthetic route:

Wherein, the substituents R ¹ , R ² , R ³ , R ⁵ and R ⁶ are methyl groups; R ⁴ is hydrogen; R ⁷ is isooctyl or p-isooctyl phenyl; The method includes the following steps: (1) Under nitrogen protection, add raw material 1, CH ₂ Cl ₂ , PCl ₃ , and AlCl ₃ in sequence to the reactor, stir to dissolve, cool down to -5℃～5℃ and react for 1-10h to obtain quaternary phosphorus chloride salt 2; (2) continue to add water quenching in the reactor under nitrogen protection, add water quenching process and continue for 15-25 minutes, then separate the organic phase and dry with anhydrous sodium sulfate, obtain white crystal 3 after removing the solvent under reduced pressure; (3) Put the white crystal 3 in the reaction flask and protect it with nitrogen, add toluene, triethylamine and thiol compound dropwise in turn, and continue to react at 30-90°C for 1-24h to obtain a quaternary phosphorus derivative substituted with high tension oxygen Compound 4, monitored by TLC, after the reaction was completed, the temperature was lowered to room temperature, and the solid in the reaction system was filtered off with suction, and then sodium bicarbonate solution was added dropwise for quenching. The organic phase was extracted twice with water and dried with anhydrous sodium sulfate. The final product 4 is obtained after removal of the solvent. 3. The method according to claim 2, characterized in that: the molar ratio of raw material 1, PCl ₃ and AlCl ₃ in the step (1) is 1:0.1-2:0.1-2. 4. The method according to claim 2, characterized in that: the molar ratio of the step (2) quaternary phosphorus chloride salt 2 and H ₂ O is 1:1-10. 5. The method according to claim 2, characterized in that: the reaction temperature of the step (1) is 0°C, and the reaction time is 3 hours. 6. The method according to claim 2, characterized in that: in the step (3), the mass ratio of white crystals 3, triethylamine and thiol compound is 1:0.1-6:0.1-2. 7. The method according to claim 2, characterized in that: the reaction temperature of the step (3) is 60° C., the reaction time is 12 hours, and the mass fraction of the sodium bicarbonate solution is 10%. 8. the application of the quaternary pentavalent phosphorus derivative of claim 1 as a catalyzer on the intramolecular Wittig reaction, it is characterized in that, the step of the quaternary pentavalent phosphorus derivative catalyzed intramolecular Wittig reaction that the high tension sulfur replaces for:

Reaction conditions: 1 mmol of raw material carbonyl bromide, 10 ml of solvent, 3 mmol of TMDS, 0.2 mmol of Ti(i-Pr) ₄ , and 0.3 mmol of phosphorus compound, and the reaction time was 12 hours.