Method for dechlorinating and alkylating gem-dichloro compound

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a method for dechlorination alkylation of gem-dichloro compounds. According to the gem-dichloro compound dechlorination alkylation method provided by the invention, the problems of low reaction efficiency and poor selectivity in the prior art are solved, the boron free radical is used as a medium, meanwhile, 4CzIPN and diphenyl disulfide are used as photocatalysts, thermal excitation is not needed, and light initiation is performed, so that the gem-dichloro compound dechlorination alkylation efficiency is greatly improved; the preparation method which is mild in reaction condition, simple and convenient to operate, high in product purity and easy to industrialize is provided, and a new thought and technical support are provided for industrial application of dechlorination alkylation of the gem-dichloro compound.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for dechlorination alkylation of geminal dichloro compounds. Background Art

[0002] Organic molecules containing four alkyl-substituted all-carbon quaternary carbon centers are widely used as drugs and functional materials. They have broad application prospects in the fields of pesticide production, specialty chemical manufacturing, and pharmaceutical synthesis. Especially in the field of environmentally friendly pesticides and new drug intermediates, organic molecules containing four alkyl-substituted all-carbon quaternary carbon centers show great development potential due to their unique chemical properties.

[0003] In recent years, new breakthroughs have been made in the exploration of catalytic systems and reaction conditions. For example, the research team of Xie Jin innovatively applied the excited-state binuclear gold catalysis technology, which enabled a series of geminal dichloroalkanes to exhibit multiple reactivity, and they can be regarded as equivalents of chloroalkyl radicals, alkyl radical cations, and carbenes at the same time. This characteristic gives them the ability to undergo diversified dechlorination and alkylation reactions with a variety of olefins, including hydrochloroalkylation, chloroalkane arylation, formal [4+1] cyclization, and cyclopropanation, all of which can be achieved under controllable conditions. This method not only greatly broadens the application field of the traditional Simmons-Smith cyclopropanation reaction, but also significantly improves the selectivity and efficiency of the reaction, bringing new opportunities to the field of chemical synthesis. The research team of Wang Yifeng cleverly used the three-step continuous reaction strategy of boron radicals to successfully construct a full-carbon quaternary carbon center on the activated trichloromethyl skeleton. However, despite this remarkable progress, they still face a challenge, that is, the effective dechlorination and alkylation process of geminal dichloroalkanes cannot be achieved at present. Summary of the invention

[0004] The present invention aims to solve one of the technical problems in the related art at least to a certain extent. To this end, an object of the present invention is to provide a method for dechlorination alkylation of geminal dichloro compounds, which cleverly uses boron radicals as a medium, and uses 4CzIPN and diphenyl disulfide as photocatalysts, without thermal excitation, and is triggered by light, successfully solving the technical problem that boron radicals are difficult to achieve alkylation in geminal dichloro compounds, and greatly improving the efficiency of dechlorination alkylation of geminal dichloro compounds. At the same time, the reaction process uses light energy as a driving force, which is not only efficient but also extremely environmentally friendly, reflecting the core concept of green chemistry.

[0005] To this end, the first aspect of the present invention provides a method for dechlorination alkylation of a geminal dichloro compound. In some embodiments of the present invention, the method comprises:

[0006] The compound represented by Formula 2 is reacted with the geminal dichloro compound represented by Formula 1 under the catalytic conditions of trimethylamine borane, 4CzIPN and diphenyl disulfide to achieve dechlorination alkylation of the geminal dichloro compound represented by Formula 1 to obtain a dechlorinated product.

[0007] Wherein, the structural formula of the compound shown in Formula 1 is:

[0008]

[0009] The structural formula of the compound shown in Formula 2 is R2-CH=CH2,

[0010] R1 is selected from H, unsubstituted or optionally substituted with at least one R a Substituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0011] The at least one R a Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0012] R2 is selected from H, unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0013] The at least one R b Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl.

[0014] The method for dechlorination and alkylation of geminal dichloro compounds provided by the present invention overcomes the problems of low reaction efficiency and poor selectivity in the prior art, uses boron free radicals as a medium, and uses 4CzIPN and diphenyl disulfide as photocatalysts, and does not require thermal excitation. It is triggered by light, thereby greatly improving the efficiency of dechlorination and alkylation of geminal dichloro compounds. A preparation method with mild reaction conditions, simple operation, high product purity and easy industrialization is provided, which provides new ideas and technical support for the industrial application of dechlorination and alkylation of geminal dichloro compounds.

[0015] In other embodiments of the present invention, in the reaction, the molar ratio of the geminal dichloro compound represented by Formula 1, the compound represented by Formula 2, trimethylamine borane, 4CzIPN and diphenyl disulfide is (0.9-1.1):(3-5):(1.8-2.2):(0.05-0.1):(0.1-0.2).

[0016] In some embodiments of the present invention, the reaction is carried out in the solvent DMSO.

[0017] In some embodiments of the present invention, the reaction temperature of the reaction is 20-30°C.

[0018] In some embodiments of the present invention, the reaction is carried out in a continuous flow microchannel reactor.

[0019] The prior art mainly relies on traditional intermittent reactions, which have problems such as low mass and heat transfer efficiency, slow reaction speed, uneven mixing, difficult temperature control, and low safety during the reaction process, resulting in low reaction efficiency and low product purity. Preferably, the method provided by the present invention is carried out in a continuous flow microchannel reactor, and the specific surface area of ​​the reaction system is increased to hundreds or thousands of times that of the autoclave through the special flow channel design of the microchannel reactor, thereby enhancing the mass and heat transfer efficiency, and having the advantages of fast reaction rate, good selectivity, and safety.

[0020] In some embodiments of the invention, the reaction is carried out under light having a wavelength of 450-460 nm.

[0021] In some embodiments of the present invention, when the reaction is carried out in the continuous flow microchannel reactor, the flow rate of the reactants pumped in is 1-3 ml / h.

[0022] In some embodiments of the present invention, R1 is selected from unsubstituted or optionally substituted with at least one R a Substituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl;

[0023] The at least one Ra Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group;

[0024] R2 is selected from unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl;

[0025] The at least one R b Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group.

[0026] In some embodiments of the present invention, R1 is selected from unsubstituted C6-C 12 Aryl;

[0027] R2 is selected from unsubstituted or b substituted carboxyl groups;

[0028] The R b Selected from C1-C 10 Alkyl, C1-C 10 Alkoxy.

[0029] In some preferred embodiments of the present invention, R1 is a benzene ring; R2 is -C(=O)OC(CH3)3.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] (1) The method provided by the present invention uses a microchannel reactor, which is a continuous flow reaction with a fast reaction speed, thereby improving the reaction rate;

[0032] (ii) In the method provided by the present invention, the material has a short residence time in the reactor, which reduces the occurrence of side reactions and the reaction has excellent selectivity;

[0033] (III) The method provided by the present invention does not require mechanical stirring for the reaction, and the mass transfer and heat transfer effects are 1-3 orders of magnitude higher than those of traditional reactors. The material inventory in the reactor is small, which reduces the possibility of temperature rise, and the production is safe and reliable.

[0034] (IV) The method provided by the present invention cleverly uses boron free radicals as a medium, successfully solving the technical problem that boron free radicals are difficult to achieve alkylation in geminal dichloro compounds, without the need for thermal excitation, and is triggered by light, greatly improving the efficiency of dechlorination and alkylation of geminal dichloro compounds. At the same time, the reaction process uses light energy as a driving force, which is not only efficient but also extremely environmentally friendly, reflecting the core concept of green chemistry.

[0035] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0037] Figure 1 A reaction formula for dechloroalkylation of (4,4-dichloropiperidin-1-yl)(phenyl)methanone according to one embodiment of the present invention is shown;

[0038] Figure 2 A process flow diagram showing the dechlorination alkylation of (4,4-dichloropiperidin-1-yl)(phenyl)methanone according to one embodiment of the present invention is shown;

[0039] Figure 3 The NMR result of the reaction product obtained in Example 2 of the present invention is shown. DETAILED DESCRIPTION

[0040] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0041] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. Further, in the description of the present invention, unless otherwise specified, the meaning of "plurality" is two or more.

[0042] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0043] In order to make the present invention more easily understood, certain technical and scientific terms are specifically defined below. Unless otherwise clearly defined elsewhere in this document, all other technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which the present invention belongs.

[0044] In this document, the terms “include” or “comprising” are open expressions, that is, including the contents specified in the present invention but not excluding other contents.

[0045] As used herein, the terms "optionally", "optional" or "optionally" generally mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0046] In this article, "4CzIPN" is the full name of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, which is a typical "donor-acceptor (DA)" type fluorescent molecule, in which carbazolyl (Cz) acts as an electron donor and dicyanobenzene acts as an electron acceptor. 4CzIPN is an efficient organic photocatalyst that can absorb light energy under illumination and convert it into chemical energy, promoting chemical reactions between organic molecules. Its photocatalytic reaction has the advantages of mild conditions, simple operation, and high product purity.

[0047] According to a specific embodiment of the present invention, the present invention provides a method for dechlorination alkylation of geminal dichloro compounds, comprising:

[0048] The compound represented by Formula 2 is reacted with the geminal dichloro compound represented by Formula 1 under the catalytic conditions of trimethylamine borane, 4CzIPN and diphenyl disulfide to achieve dechlorination alkylation of the geminal dichloro compound represented by Formula 1 to obtain a dechlorinated product.

[0049] Wherein, the structural formula of the compound shown in Formula 1 is:

[0050]

[0051] The structural formula of the compound shown in Formula 2 is R2-CH=CH2,

[0052] R1 is selected from H, unsubstituted or optionally substituted with at least one R aSubstituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0053] The at least one R a Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0054] R2 is selected from H, unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl;

[0055] The at least one R b Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl.

[0056] The method provided by the present invention uses boron free radicals as a medium, and uses 4CzIPN and diphenyl disulfide as catalysts. It does not require thermal excitation, but is initiated by light, which greatly improves the efficiency of dechlorination and alkylation of geminal dichloro compounds. At the same time, the reaction process uses light energy as a driving force, which is not only efficient but also extremely environmentally friendly, reflecting the core concept of green chemistry.

[0057] According to a specific embodiment of the present invention, in the reaction, the molar ratio of the geminal dichloro compound of Formula 1, the compound of Formula 2, trimethylamine borane, 4CzIPN and diphenyl disulfide is (0.9-1.1):(3-5):(1.8-2.2):(0.05-0.1):(0.1-0.2). For example, the molar ratio of the geminal dichloro compound of Formula 1, the compound of Formula 2, trimethylamine borane, 4CzIPN and diphenyl disulfide is 0.9:3:1.8:0.05:0.1, 1.1:5:2.2:0.1:0.2, 1:4:2:0.05:0.1, 1:4:2:0.1:0.1, 1:4:2:0.05:0.2, etc. Preferably, the molar ratio of the geminal dichloro compound represented by Formula 1, the compound represented by Formula 2, trimethylamine borane, 4CzIPN and diphenyl disulfide is 1:4:2:0.05:0.1.

[0058] According to a specific embodiment of the present invention, the reaction is carried out in a solvent DMSO. The reaction in a solvent DMSO is conducive to further improving the product yield.

[0059] According to a specific embodiment of the present invention, the reaction temperature of the reaction is 20-30° C. For example, the reaction temperature is 20° C., 21° C., 22° C., 23° C., 24° C., 25° C., 26° C., 27° C., 28° C., 29° C., 30° C. Preferably, the reaction temperature of the reaction is 25° C.

[0060] According to a preferred embodiment of the present invention, the reaction is carried out in a continuous flow microchannel reactor.

[0061] According to a specific embodiment of the present invention, the reaction is carried out under light with a wavelength of 450-460 nm. For example, the reaction is carried out under light with a wavelength of 456 nm.

[0062] According to a specific embodiment of the present invention, when the reaction is carried out in the continuous flow microchannel reactor, the flow rate of the reactant pumping is 1-3 ml / h. Preferably, when the reaction is carried out in the continuous flow microchannel reactor, the flow rate of the reactant pumping is 2 ml / h.

[0063] According to a preferred embodiment of the present invention, in the compounds represented by Formula 1 and Formula 2,

[0064] R1 is selected from unsubstituted or optionally substituted with at least one R a Substituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl;

[0065] The at least one Ra Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group;

[0066] R2 is selected from unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl;

[0067] The at least one R b Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group.

[0068] According to a preferred embodiment of the present invention, in the compounds represented by Formula 1 and Formula 2,

[0069] R1 is selected from unsubstituted C6-C 12 Aryl;

[0070] R2 is selected from unsubstituted or b substituted carboxyl groups;

[0071] The R b Selected from C1-C 10 Alkyl, C1-C 10 Alkoxy.

[0072] According to a preferred embodiment of the present invention, in the compounds represented by Formula 1 and Formula 2,

[0073] R1 is a benzene ring; R2 is -C(=O)OC(CH3)3.

[0074] The present invention aims to provide a dechlorination alkylation preparation process of geminal dichloro compounds based on a continuous flow method. The process adopts the optimization of the selection of catalysts, the control of reaction conditions and the design of a continuous flow reactor, and finally determines that the optimal process is geminal dichloro compounds under 450-460nm light source irradiation, solvent DMSO, reaction system is trimethylamine borane, 4CZIPN and diphenyl disulfide, preferably in a coil-type microchannel reactor, to achieve efficient and highly selective dechlorination alkylation of geminal dichloro compounds.

[0075] The scheme of the present disclosure will be explained below in conjunction with the examples. Those skilled in the art will appreciate that the following examples are only used to illustrate the present disclosure and should not be considered to limit the scope of the present disclosure. Where specific techniques or conditions are not indicated in the examples, the techniques or conditions described in the literature in this area or the product instructions are used. Where the manufacturers of reagents or instruments are not indicated, they are all conventional products that can be obtained commercially.

[0076] Example 1 Preparation of (4,4-dichloropiperidin-1-yl)(phenyl)methanone

[0077] At -78 ° C, tungsten hexachloride (1.5 equivalents) was slowly added to a CH2Cl2 solution of 1-benzoylpiperidin-4-one (1.0 equivalents). After addition, the mixture was stirred at room temperature until TLC showed that 1-benzoylpiperidin-4-one disappeared. The reaction was then quenched with H2O and extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by silica gel flash column chromatography to obtain the desired product.

[0078] The synthetic route for preparing the geminal dichloro substrate (4,4-dichloropiperidin-1-yl)(phenyl)methanone is:

[0079]

[0080] Example 2

[0081] The present embodiment provides a method for realizing efficient dechlorination and alkylation of geminal dichloro compounds by using a microchannel reactor. The reaction formula is as follows: Figure 1 , process flow such as Figure 2 , including the following steps:

[0082] (1) Connect a single-mouth bottle to the end of the reactor, purge the entire pipeline with nitrogen for 15-30 minutes to ensure that the pipeline is full of nitrogen, and insert a balloon filled with nitrogen on the single-mouth bottle;

[0083] (2) Trimethylamine borane (145.9 mg, 2.0 equiv.), 4CzIPN (39.4 mg, 0.05 equiv.), PhSSPh (21.8 mg, 0.1 equiv.), the geminal dichloro substrate (4,4-dichloropiperidin-1-yl)(phenyl)methanone (257.0 mg, 1.0 equiv.) prepared in Example 1 and DMSO (10 mL) were added to a two-necked bottle dried by a drying gun and blown dry with nitrogen and equipped with a rubber septum, and then tert-butyl acrylate (590 uL, 4.0 equiv.) was added dropwise. The resulting solution was sonicated for 1 minute to ensure sufficient homogeneity. The above solution was drawn up with a 20 mL syringe (diameter 20.00 mm), placed on a syringe pump, and connected to a straight-through mixer. The latter was connected to a coil-type photocatalytic reactor (coil volume 4 mL, light source was Blue (40W×2), reaction was carried out under light with a wavelength of 456 nm), pumped in at a total flow rate of 2.0 ml / L, reacted at room temperature (25° C.) and pressure, and a balloon was tied to a single-mouth bottle at the end of the reactor for collection. The solvent in the reaction mixture was removed under reduced pressure, and the corresponding product was obtained by separation and purification by silica gel column chromatography, with a yield of 76%, which met the requirements. The product is a white solid; mp: 66.3-68.9°C; 1HNMR (500MHz, CDCl3) δ1.44 (9H, s). 1.80 (2H.m), 1.92-2.20 (4H, d, J = 10 Hz), 2.52 (2H.m), 3.12-3.78 (3H, d, J = 10 Hz), 4.61 (1H, d, J = 10 Hz), 7.36 (1 H, dd.J = 10 Hz), 7.38-7.40 (2H, m). 7.41 (1H.d, J = 10 Hz), 7.42 (1H, d, J = 5.0 Hz), 13C NMR (125MHz.CDCl3)δ21.0.31.2.46.9.87.0.116.6.121.9.122.9.127.1.127.9.128.4.129.2.133.5.135.8.136.3.136.7.138.9.148.8.163.6.ESIHRMS:Found:m / 395.0694.Calcd for C19H26ClNO3:(M+Na)+351.8688(NMR results, see Figure 3 ).

[0084] Example 3 Screening of reaction solvents

[0085] The method for efficient dechlorination and alkylation of geminal dichloro compounds provided in this embodiment has the same reaction steps as those in Example 2, except that the solvent is different. After the reaction is completed, the solvent in the reaction mixture is removed under reduced pressure, and the corresponding product is separated and purified by silica gel column chromatography to obtain the corresponding product, which is weighed and the yield is calculated. The reaction equation is as follows:

[0086]

[0087] The reaction results are shown in Table 1 below:

[0088] Table 1

[0089]

[0090]

[0091] Note: [a] Using 1,1,2,2-tetrachloroethane as external standard, the crude 1 The yield was determined by H NMR spectroscopy. [b] Reaction time: 4h, concentration: 0.2M. Trace shows almost no reaction.

[0092] The results in Table 1 show that, when other variables are kept the same, different solvents are tried and DMSO is finally determined to be the best solvent.

[0093] Example 4 Catalyst Screening

[0094] (1) The method for efficient dechlorination and alkylation of geminal dichloro compounds provided in this embodiment is the same as that in Example 2, except that the photocatalyst is different. After the reaction is completed, the solvent in the reaction mixture is removed under reduced pressure, and the corresponding product is obtained by separation and purification by silica gel column chromatography, and the yield is calculated. The reaction equation is as follows:

[0095]

[0096] The reaction results are shown in Table 2 below:

[0097] Table 2

[0098]

[0099] Note: 1,1,2,2-Tetrachloroethane was used as external standard. 1 The yield was determined by H NMR spectroscopy.

[0100] The results in Table 2 show that by comparing the effects of different photocatalysts on product yields, 4CzIPN was ultimately determined to be the best photocatalyst when other variables were kept the same.

[0101] (2) The method for efficient dechlorination and alkylation of geminal dichloro compounds provided in this embodiment is the same as that in Example 2, except that a different borane is used as a catalyst. After the reaction is completed, the solvent in the reaction mixture is removed under reduced pressure, and the corresponding product is obtained by separation and purification by silica gel column chromatography, and the yield is calculated. The reaction equation is as follows:

[0102]

[0103] The reaction results are shown in Table 3 below:

[0104] Table 3

[0105]

[0106] Note: 1,1,2,2-Tetrachloroethane was used as external standard. 1 The yield was determined by H NMR spectroscopy. NR indicates no reaction.

[0107] The results in Table 3 show that, by comparing the effects of different boranes as catalysts on product yields, ammonia borane was ultimately determined to have the best effect, while keeping other variables the same.

[0108] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", "some implementation schemes" or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0109] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A method for dechlorination alkylation of geminal dichloro compounds, characterized in that: include: The compound represented by Formula 2 is reacted with the geminal dichloro compound represented by Formula 1 under the catalytic conditions of trimethylamine borane, 4CzIPN and diphenyl disulfide to achieve dechlorination alkylation of the geminal dichloro compound represented by Formula 1 to obtain a dechlorinated product. Wherein, the structural formula of the compound shown in Formula 1 is: The structural formula of the compound shown in Formula 2 is R2-CH=CH2, R1 is selected from H, unsubstituted or optionally substituted with at least one R a Substituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl; The at least one R a Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl; R2 is selected from H, unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl; The at least one R b Each of the same or different, and each independently selected from -F, -Cl, -Br, -I, -OH, -CN, =O, -NH2, Cl-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl, 5-20 membered heteroaryl.

2. The method according to claim 1, characterized in that In the reaction, the molar ratio of the geminal dichloro compound represented by Formula 1, the compound represented by Formula 2, trimethylamine borane, 4CzIPN and diphenyl disulfide is (0.9-1.1):(3-5):(1.8-2.2):(0.05-0.1):(0.1-0.2).

3. The method according to claim 1, characterized in that: The reaction was carried out in the solvent DMSO.

4. The method according to claim 1, characterized in that The reaction temperature of the reaction is 20-30°C.

5. The method according to claim 1, characterized in that The reaction is carried out in a continuous flow microchannel reactor.

6. The method according to claim 5, characterized in that The reaction is carried out under light with a wavelength of 450-460 nm.

7. The method according to claim 5, characterized in that When the reaction is carried out in the continuous flow microchannel reactor, the flow rate of the reactants pumped in is 1-3 ml / h.

8. The method according to claim 1, characterized in that: R1 is selected from unsubstituted or optionally substituted with at least one R a Substituted with the following groups: C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl; The at least one R a Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group; R2 is selected from unsubstituted or optionally substituted with at least one R b Substituted with the following groups: carboxyl, C1-C 10 Alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group, C6-C 20 Aryl; The at least one R b Each of the same or different, and are independently selected from C1-C 10 Alkyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C3-C 10 Cycloalkyl, 3-10 membered heterocyclic group.

9. The method according to claim 1, characterized in that: R1 is selected from unsubstituted C6-C 12 Aryl; R2 is selected from unsubstituted or b substituted carboxyl groups; The R b Selected from C1-C 10 Alkyl, C1-C 10 Alkoxy.

10. The method according to claim 1, characterized in that R1 is a benzene ring; R2 is -C(=O)OC(CH3)3.

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