阅读说明：本技术 一种三氟甲硫基化合物的制备方法 (Preparation method of trifluoromethylthio compound ) 是由 孙东伟 李丽 周永言 唐念 张曼君 于 2020-11-27 设计创作，主要内容包括：本发明涉及有机合成技术领域,尤其涉及一种三氟甲硫基化合物的制备方法。本发明公开了一种三氟甲硫基化合物的制备方法,该制备方法首次以取代的芳基硅烷为原料,使用三氟甲硫基试剂制备得到三氟甲硫基化合物,该制备方法反应效率高、选择性高、合成路线简单,且绿色经济。(The invention relates to the technical field of organic synthesis, in particular to a preparation method of a trifluoromethylthio compound. The invention discloses a preparation method of a trifluoromethylthio compound, which takes substituted aryl silane as a raw material for the first time, and prepares the trifluoromethylthio compound by using a trifluoromethylthio reagent.)

1. A method for preparing trifluoromethylthio compound, which is characterized by comprising the following steps:

in a solvent system, mixing a compound with a structure shown in a formula (II) and a fluorine reagent, and then adding a trifluoromethylthio reagent for reaction to obtain a trifluoromethylthio compound with a structure shown in a formula (I);

wherein R is¹Selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, methyl, methoxy, benzyl or phenyl, [ Si]Selected from SiCH₃(OMe)₂、Si(OMe)₃、Si(Me)₃、SiCH₃(OSiMe₃)₂、Si(OEt)₃Or Si (OSiMe)₃)₃。

2. The method of claim 1, wherein the trifluoromethylthio reagent comprises a compound of the following structure:

wherein R is hydrogen or methyl.

3. The method of claim 1, wherein the fluorine reagent is selected from tetrabutylammonium fluoride, silver fluoride, potassium fluoride, sodium fluoride, and cesium fluoride.

4. The method according to claim 1, wherein the molar ratio of the compound having the structure represented by the formula (II) to the fluorine reagent is 1: (1.5-3.0);

the molar ratio of the compound with the structure shown in the formula (II) to the trifluoromethylthio reagent is 1: (1.2-2.0).

5. The method of claim 1, wherein the solvent system comprises at least one of DCM, toluene, tetrahydrofuran, acetonitrile, DMF, DMA, and DMSO.

6. The method of claim 1, wherein the reaction is carried out at a temperature of 50-80 ℃ for 2-4 hours.

7. The method according to claim 1, further comprising, after the reaction is completed: extraction, drying, filtration, solvent removal and purification.

8. The preparation method according to claim 7, wherein the extraction is specifically: extracting with ethyl ester for three times, mixing organic phases, and extracting with dilute hydrochloric acid, distilled water and saturated salt water once respectively;

the purification specifically comprises the following steps: the volume ratio is 10: the mixture of petroleum ether and ethyl acetate of 1 is purified by silica gel column.

9. The method according to any one of claims 1 to 8, wherein the reaction is carried out under an atmosphere of nitrogen or an inert gas.

10. The method according to any one of claims 1 to 8, wherein the reaction is carried out in an anhydrous and oxygen-free environment.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of a trifluoromethylthio compound.

Background

As is known, fluorine is a very special element, and has not only unique properties due to strong electronegativity, but also respective characteristics of some fluorine-containing groups. Among the various fluorine-containing groups, trifluoromethylthio (SCF)₃) Has strong electron withdrawing property and high lipophilicity (pi R1.44), and is widely used in medicineResearchers have been fascinating for a long time in the fields of pesticides, material science and the like. Over the past, a number of methods have been reported for introducing trifluoromethylthio groups, all of which can be divided into two categories, (1) indirect trifluoromethylthionation for converting other functional groups to trifluoromethylthio groups, which often requires harsh reaction conditions with some by-product formation. (2) Direct trifluoromethylthio methods, i.e., direct introduction of a trifluoromethylthio group onto a precursor substrate using a trifluoromethylthio reagent, have been the focus of recent research.

To date, significant progress has been made in the trifluoromethylmethylation reaction and a series of trifluoromethylthiolation reagents have been developed. Initial highly reactive trifluoromethylsulfenyl Chloride (CF)₃SCl) was used for the direct trifluormethylthionation reaction, but its toxicity and difficulty in storage limited its use. Later with the progress of research, a series of trifluoromethylthio reagents such as Me₄NSCF₃、AgSCF₃And CuSCF₃Have been developed. In recent years, new strategies and new methods are continuously provided, the trifluoromethylthionation reaction achieves great breakthrough, and meanwhile, a plurality of high-efficiency and stable electrophilic trifluoromethylthio reagents are discovered and achieve a plurality of remarkable results in application.

Therefore, the technical problem to be solved in the art is to provide a preparation method of trifluoromethylthio compound diversity by utilizing trifluoromethylthio reagent.

Disclosure of Invention

In view of the above, the invention provides a preparation method of a trifluoromethylthio compound, the preparation method takes substituted aryl silane as a raw material, and uses a trifluoromethylthio reagent to prepare the trifluoromethylthio compound, and the preparation method has the advantages of high reaction efficiency, high selectivity, simple synthetic route, greenness and economy.

The specific technical scheme is as follows:

the invention provides a preparation method of a trifluoromethylthio compound, which comprises the following steps:

in a solvent system, mixing a compound with a structure shown in a formula (II) and a fluorine reagent, and then adding a trifluoromethylthio reagent for reaction to obtain a trifluoromethylthio compound with a structure shown in a formula (I);

wherein R is¹Selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, methyl, methoxy, benzyl or phenyl, [ Si]Selected from SiCH₃(OMe)₂、Si(OMe)₃、Si(Me)₃、SiCH₃(OSiMe₃)₂、Si(OEt)₃Or Si (OSiMe)₃)₃。

The reaction route of the trifluorothio compound of the invention is as follows:

the mechanism of this reaction is: and (3) mixing the compound with the structure shown in the formula (II) with a fluorine reagent to generate aryl negative ions under the action of fluorine negative ions, and reacting the aryl negative ions with trifluoromethylthio positive ions generated by the trifluoromethylthio reagent to directly obtain the trifluoromethylthio compound.

In the preparation method of the trifluoromethylthio compound, the solvent system comprises at least one of DCM, toluene, tetrahydrofuran, acetonitrile, DMF, DMA and DMSO, and tetrahydrofuran is preferred;

firstly, adding the compound with the structure shown in the formula (II) into the solvent system, and then adding a fluorine reagent for mixing preferably under the condition of stirring;

the molar ratio of the compound with the structure shown in the formula (II) to the fluorine reagent is 1: (1.5-3.0), preferably 1: 2;

the fluorine reagent is selected from tetrabutylammonium fluoride, silver fluoride, potassium fluoride, sodium fluoride or cesium fluoride, and is preferably tetrabutylammonium fluoride;

the mixing is preferably carried out under the condition of stirring, the rotating speed of the stirring is 1000-2400 r/min, the time is 0.4-3.0 h, and the preferable time is 0.5 h;

after the mixing is finished, adding a trifluoromethyl reagent for reaction;

the trifluoromethylthio reagent comprises a compound of the following structure:

wherein R is hydrogen or methyl.

The molar ratio of the compound with the structure shown in the formula (II) to the trifluoromethylthio reagent is 1: (1.2-2.0), preferably 1: 1.2;

the reaction is carried out under the atmosphere of nitrogen or inert gas;

the reaction temperature is 50-80 ℃, the reaction time is 2-4h, and the reaction is preferably carried out for 3h at 60 ℃;

after the reaction is finished, the method further comprises the following steps: extracting, drying, filtering, removing solvent and purifying;

the extraction is specifically as follows: extracting with ethyl ester for three times, mixing organic phases, and extracting with dilute hydrochloric acid, distilled water and saturated salt water once respectively;

the drying is carried out by adopting anhydrous magnesium sulfate;

the purification specifically comprises the following steps: the volume ratio is 10: the mixture of petroleum ether and ethyl acetate of 1 is purified by silica gel column.

According to the technical scheme, the invention has the following advantages:

(1) the method takes substituted aryl silane as a raw material for the first time, uses the trifluoromethylthio reagent, directly prepares the trifluoromethylthio compound through one-step reaction, and has the advantages of high reaction efficiency, simple operation, mild condition, novel route, clean reaction system, safety and practicability; in particular, the reaction stability is good, the pollution is small, the selectivity is high, and the applicability is wide.

(2) The trifluoromethylthio compound provided by the invention has short reaction time and synthesis route, simple post-treatment mode and less purification loss, greatly saves manpower, material resources and time, and can meet and meet the requirements of industrial production.

(3) In the preparation method of the trifluoromethylthio compound, severe virulent reagents, high-temperature conditions and expensive metal catalysts are avoided. The method is a green and economic preparation method, can obtain the target product trifluoromethylthio compound with excellent high selectivity and chemical yield, and has wide market prospect.

Detailed Description

In order to make the objects, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it should be apparent that the embodiments described below are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The raw materials and reagents in the examples of the present invention were all commercially available.

Example 1

The invention provides a molecular formula C₇H₅F₃The preparation method comprises the following specific steps:

adding 1.0 equivalent of phenyltrimethoxysilane (79.32mg,0.4mmol) into 1.5mL of tetrahydrofuran at room temperature, slowly adding 2.0 equivalent of fluorine reagent (209.17mg,0.8mmol) during stirring, stirring at 1500r/min for 0.5h after the fluorine reagent is added, adding 1.2 equivalent of trifluoromethylthio reagent N-trifluoromethylthio-saccharin (135.95mg,0.48mmol), and replacing N₂Heating to 60 deg.C for 3 hr, cooling to room temperature after the fluorine spectrum detection reaction, slowly dripping distilled water into the system, extracting with ethyl acetate for three times, mixing organic phases, extracting with dilute hydrochloric acid, distilled water, saturated saline solution once, drying with anhydrous magnesium sulfate, filteringMixing samples, performing rotary steaming, and performing volume ratio of 10: the mixed solution of the petroleum ether and the ethyl acetate of the step 1 is purified by a silica gel column to obtain the product of the trifluoromethyl phenylsulfide. A colorless liquid, in 81% yield,¹⁹F NMR(376MHz,CDCl₃)δ-43.28(s,3F),HRMS:calcd for C₁₆H₉IO₄[M+H]⁺178.0064,found 178.0071。

example 2

This example is trifluoromethylphenylsulfide C₇H₅F₃Preparation of S

This example differs from example 1 in that: the [ Si ] in the step]Replacement is SiCH₃(OMe)₂Tested by C₇H₅F₃The yield of S was 68%.

Example 3

This example is trifluoromethylphenylsulfide C₇H₅F₃Preparation of S

This example differs from example 1 in that: replacing the trifluoromethyl sulfide reagent in step (a)

Confirmation of C by NMR₇H₅F₃S is successfully prepared, C₇H₅F₃The yield of S was 71%.

Example 4

This example differs from example 1 in that: replacing the fluorine reagent in the step with silver fluoride, and confirming C through nuclear magnetic resonance fluorine spectrum and hydrogen spectrum₇H₅F₃S is successfully prepared, C₇H₅F₃The yield of S was 66%.

The above-mentioned embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the same; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.