阅读说明：本技术 一种苄基醚类化合物及其合成方法 (Benzyl ether compound and synthesis method thereof ) 是由 刘石惠 周伟 李子瑜 吕晓庆 高金来 于 2021-09-07 设计创作，主要内容包括：本发明公开了一种苄基醚类化合物及其合成方法,包括下列步骤：将苄基化合物、醇类、金属催化剂、光催化剂、氧化剂和有机溶剂混合,获得反应体系；在隔绝氧气的条件下,以可见光为驱动力,照射所述反应体系；反应结束后,纯化,获得苄基醚类化合物。该合成方法具有绿色高效、原子经济性高、选择性高、副产物少、反应底物范围广泛、成本低的优势,能够在有机合成、药物、农药、材料、染料、洗涤剂等领域推广应用。(The invention discloses a benzyl ether compound and a synthesis method thereof, comprising the following steps: mixing a benzyl compound, alcohols, a metal catalyst, a photocatalyst, an oxidant and an organic solvent to obtain a reaction system; irradiating the reaction system by using visible light as a driving force under the condition of isolating oxygen; after the reaction is finished, purifying to obtain the benzyl ether compound. The synthesis method has the advantages of greenness, high efficiency, high atom economy, high selectivity, few byproducts, wide range of reaction substrates and low cost, and can be popularized and applied in the fields of organic synthesis, medicines, pesticides, materials, dyes, detergents and the like.)

1. The synthesis method of the benzyl ether compound is characterized by comprising the following steps:

mixing a benzyl compound, alcohols, a metal catalyst, a photocatalyst, an oxidant and an organic solvent to obtain a reaction system;

irradiating the reaction system by using visible light as a driving force under the condition of isolating oxygen;

after the reaction is finished, purifying to obtain the benzyl ether compound.

2. The synthesis method of claim 1, wherein the metal catalyst is a nickel-based catalyst.

3. The synthesis method of claim 2, wherein the nickel-based catalyst is selected from one of nickel acetylacetonate, nickel chloride, nickel bromide and nickel acetate.

4. The method of claim 1, wherein the photocatalyst is selected from the group consisting of Ru (bpy)₃Cl₂·6H₂O、Ir(ppy)₃、[Ir{dF(CF₃)ppy}₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆4CzIPN, benzaldehyde, benzophenone, 9-fluorenone, rose bengal, acid red, rhodamine and riboflavin.

5. The method of claim 1, wherein the oxidizing agent is selected from the group consisting of ammonium persulfate, sodium persulfate, potassium persulfate, fluorine, N-fluorobisbenzenesulfonamide, [ bis (acetoxy) iodo ] benzene, [ bis (trifluoroacetyloxy) iodo ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide, t-butyl hydroperoxide;

the organic solvent is one or a mixture of any two of acetonitrile, ethyl acetate, dichloromethane, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 2-dichloroethane, hexafluoroisopropanol and N-methylpyrrolidone.

6. The synthesis method according to claim 1, wherein the metal catalyst is used in an amount of 0.1 to 20% by mol.

7. The synthesis method according to claim 1, wherein the photocatalyst is used in an amount of 0.1 to 20% mol; the amount of the oxidant is 100-500% mol.

8. The synthesis method of claim 1, wherein the light irradiation time of the reaction system is 2-48h, and the reaction temperature is-20-80 ℃.

9. The synthetic method of claim 1 wherein the purification is by column chromatography.

10. A benzyl ether compound obtained by the synthesis method according to any one of claims 1 to 9.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a benzyl ether compound, and the benzyl ether compound prepared by the synthesis method.

Background

Benzyl ether compounds are compounds with important biological activity, and widely exist in drug molecules, natural products and organisms, and the synthesis of the compounds is always concerned by chemists. The existing nucleophilic substitution synthesis method (Williamson ether forming reaction) usually uses strong base and high temperature reaction conditions, the reaction conditions of the methods are not mild enough, the total yield is low, the substrate range is also limited, and the synthesis of the ether compound with large steric hindrance is usually difficult.

At present, a visible light/transition metal co-catalysis free radical coupling reaction strategy has become to construct C (sp)³) Emphasis on the study of the X bond. For example, the Micmelan topic group of Princeton university (Nature,2020, 580,220) reports visible light/copper co-catalyzed C (sp)³) -N bond construction. But this strategy is still lacking for C (sp)³) Method for constructing-O, not applicable to benzyl ethersIn the synthesis of the compounds. In addition, in the prior art, a method for obtaining a benzyl ether compound by reacting a benzyl silane compound with an alcohol is available, but the benzyl silane compound adopted in the technical scheme has no commercial source and is difficult to synthesize, and an alcohol substrate needs to be used as a solvent, so that only the synthesis of the benzyl ether compound with a simple structure can be realized, and the method cannot be applied to the synthesis of the benzyl ether compound with a complex structure. . In the technical scheme, a copper-catalyzed synthesis method of benzyl ether is also disclosed, wherein a high-oxidative divalent copper catalyst is adopted, so that a large amount of ketone byproducts which are excessively oxidized are usually generated, the range of reaction substrates is also influenced, and the copper-catalyzed synthesis method is also difficult to be applied to the synthesis of benzyl ether compounds with complex structures.

Disclosure of Invention

In view of the above, the present invention needs to provide a method for synthesizing benzyl ether compounds, which uses unmodified alcohols and benzyl compounds as starting materials, and uses visible light as a driving force under the conditions of a metal catalyst, a photocatalyst and an oxidant to prepare the benzyl ether compounds. The synthesis method has the advantages of greenness, high efficiency, high atom economy, high selectivity, few byproducts, wide range of reaction substrates and low cost.

In order to achieve the purpose, the invention adopts the following technical scheme:

the invention provides a synthesis method of a benzyl ether compound, which comprises the following steps:

mixing a benzyl compound, alcohols, a metal catalyst, a photocatalyst, an oxidant and an organic solvent to obtain a reaction system;

irradiating the reaction system by using visible light as a driving force under the condition of isolating oxygen;

after the reaction is finished, purifying to obtain the benzyl ether compound.

Further, the metal catalyst is a nickel-based catalyst.

Further, the nickel catalyst is selected from one of nickel acetylacetonate, nickel chloride, nickel bromide and nickel acetate.

Further, the photocatalyst is selected from Ru (bpy)₃Cl₂·6H₂O、Ir(ppy)₃、[Ir{dF(CF₃)ppy}₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆4CzIPN, benzaldehyde, benzophenone, 9-fluorenone, rose bengal, acid red, rhodamine and riboflavin.

Further, the oxidant is selected from one of ammonium persulfate, sodium persulfate, potassium persulfate, fluorine, N-fluoro-diphenyl sulfonamide, [ bis (acetoxy) iodine ] benzene, [ bis (trifluoroacetoxy) iodine ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide and tert-butyl hydroperoxide;

the organic solvent is one or a mixture of any two of acetonitrile, ethyl acetate, dichloromethane, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 2-dichloroethane, hexafluoroisopropanol and N-methylpyrrolidone.

Further, the amount of the metal catalyst is 0.1 to 20% by mol.

Further, the dosage of the photocatalyst is 0.1-20% mol; the amount of the oxidant is 100-500% mol.

Further, the light irradiation time of the reaction system is 2-48h, and the reaction temperature is-20-80 ℃.

Further, the purification adopts a column chromatography mode to purify the product.

The invention also provides a benzyl ether compound which is obtained by adopting the synthesis method of any one of the preceding methods.

Compared with the prior art, the invention has the following beneficial effects:

on the basis of transition metal co-catalysis free radical coupling reaction, the invention develops that unmodified alcohols and benzyl compounds are used as reaction substrates, the benzyl ether compounds are directly obtained by one-step reaction under mild conditions, the reaction substrates are cheap and wide in range, and the synthetic method is simple to operate, high in yield, good in selectivity, few in by-products, economical and efficient.

The synthesis method is beneficial to industrial production, has wide application prospect, and can be popularized and applied in the fields of organic synthesis, medicines, pesticides, materials, dyes, detergents and the like.

Detailed Description

In order that the invention may be more fully understood, reference will now be made to the specific embodiments illustrated. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

Main terms in this text

As used herein, "benzyl compound" refers to any organic compound containing a benzyl functionality, and which has not been modified, and has the general structural formula:

wherein Ar is selected from-Ph, 4MeO Ph, 3MeO Ph, 2MeO Ph, 4Br Ph, 4Cl Ph, 4Ac Ph, 4CN Ph, 4COOCH₃ Ph、4CH₂CH₂COOCH₃Any one of Ph, 4PhO Ph, 4BzO Ph, 4Ph Ph, 1-naphthalene, 2-thiophene, 2-furan, 2-pyridine and 2-pyridine;

R₂selected from H, CH₃、ⁿBu、ⁱPr、Ph、4-MeO-Ph、4-Cl-Ph、CN、COOMe、CH₂CH₂Br、CH₂CH₂Cl、CH₂CH₂OBz、CH₂CH₂Any one of OAcs.

As used herein, "alcohols" refer to compounds containing a hydroxyl group in the molecule bound to a carbon in a side chain of a hydrocarbon group or benzene ring, and having the general structural formula:

R₁-OH

wherein R1 is selected from CH₃、Et、CD₃、ⁿPr、ⁱPr、ⁿBu、^tBu、-Cy、CH₂Ph、CH₂CF₃、CH₂COOMe、CH₂CH₂OCH₃、CH₂CH₂OPh、CH₂CH₂OH、(CH₂CH₂)_nOH、(CH₂CH₂O)_nH、CH₂CH₂NHBoc, -2-methylethylrafuran, -3-tetrahydrofuran, -2-methylethylrafuran-2H-pyran, -4-tetrahedron-2H-pyran, -glucose, -mannose, -ribose, -deoxyribose, -rhamnose, -nucleotide, -carbohydrates.

By "metal catalyst" is herein understood a halide, organic or inorganic salt of a transition metal, especially a copper-based or nickel-based catalyst.

By "photocatalyst" is herein understood a class of metal complexes or organic compounds that absorb visible light and convert light energy into chemical energy.

An "oxidizing agent" is herein understood to be a substance that, in a chemical reaction, acquires electrons, having oxidizing properties.

Technical scheme of the invention

The invention discloses a synthesis method of a benzyl ether compound, which comprises the following steps:

mixing a benzyl compound, alcohols, a metal catalyst, a photocatalyst, an oxidant and an organic solvent to obtain a reaction system;

irradiating the reaction system by using visible light as a driving force under the condition of isolating oxygen;

after the reaction is finished, purifying to obtain the benzyl ether compound.

The invention takes visible light/transition metal co-catalysis free radical coupling reaction as the basis, takes unmodified benzyl compound and alcohol as reaction substrates, and directly obtains benzyl ether compound by one-step reaction under mild conditions, wherein the reaction process is as follows:

the synthesis method adopts unmodified benzyl compounds and alcohols as substrates, and is not only suitable for synthesizing simple benzyl ether compounds, but also suitable for synthesizing various complex benzyl ether compounds. The adopted raw materials are cheap and easy to obtain, the process steps are simple, the product yield is high, and the selectivity is good. The method for isolating oxygen is not particularly limited, and inert gas or nitrogen is generally introduced into the reaction system to remove air from the reaction system. The progress of the reaction can be monitored by means conventional in the art, such as by tracking the progress of the reaction by TLC in one or more embodiments of the invention.

In one or more embodiments of the present invention, preferably, the metal catalyst is a nickel catalyst, and a visible light + nickel catalytic system with weaker oxidation capability and more efficient reaction is adopted, so that generation of ketone byproducts is avoided, and the reaction is efficient, high yield and few byproducts are generated.

Further, the nickel-based catalyst in the present invention is not particularly limited, and any one of halides, inorganic or organic salts of metallic nickel that is conventional in the art may be used, and specific examples include, but are not limited to, nickel acetylacetonate, nickel chloride, nickel bromide, and nickel acetate, and preferably, one of nickel acetylacetonate and nickel bromide.

Further, the photocatalyst described in the present invention is not particularly limited and may be conventionally selected in the art, and specific examples thereof include, but are not limited to, Ru (bpy)₃Cl₂·6H₂O、Ir(ppy)₃、[Ir{dF(CF₃)ppy}₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆One of 4CZIPN, benzaldehyde, benzophenone, 9-fluorenone, rose bengal, acid red, rhodamine and riboflavin, preferably [ Ir { dF (CF) ()₃)ppy}₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆And riboflavin.

Further, the oxidizing agent used in the present invention may be conventionally selected in the art, and specific examples include, but are not limited to, one of ammonium persulfate, sodium persulfate, potassium persulfate, selective fluorine, N-fluorobisbenzenesulfonamide, [ bis (acetoxy) iodine ] benzene, [ bis (trifluoroacetoxy) iodine ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide, t-butyl hydroperoxide, preferably one of N-fluorobisbenzenesulfonamide, ammonium persulfate, and selective fluorine.

Further, the organic solvent is selected from one or a mixture of any two of acetonitrile, ethyl acetate, dichloromethane, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 2-dichloroethane, hexafluoroisopropanol and N-methylpyrrolidone, and preferably is acetonitrile, dichloromethane or dichloromethane/hexafluoroisopropanol (4:1, v/v).

Further, the amounts of the metal catalyst, the photocatalyst and the oxidizing agent used in the present invention may be adjusted as needed, and in one or more embodiments of the present invention, the amount of the metal catalyst is 0.1 to 20% by mol, preferably 5 to 20% by mol, with respect to the benzyl compound.

The amount of the photocatalyst is 0.1-20% mol, preferably 1-2% mol.

The amount of the oxidant is 100-500% mol, preferably 200-400% mol.

In a further scheme, the light irradiation time can be adjusted according to the reaction progress, based on the complete reaction, in one or more embodiments of the invention, the light irradiation time of the reaction system is 2-48h, the reaction temperature is-20-80 ℃, and the preferable temperature is 25-40 ℃.

In some specific embodiments of the present invention, the obtained reaction solution is post-treated, specifically, the reaction solution is extracted with ethyl acetate, the organic phase is distilled to remove the solvent, the organic phase is taken out, the solvent is removed, the residue is separated by 200300 mesh silica gel column chromatography, and the volume ratio of ethyl acetate to petroleum ether is 1: 1-1: and (5) performing gradient elution by using the mixed solution of 100 as an eluent, evaporating the solvent of the eluent, and drying. Obtaining the benzyl ether compound.

The second aspect of the invention discloses a benzyl ether compound, which is obtained by the synthesis method according to the first aspect of the invention. The benzyl ether compound has high yield and good purity.

In a third aspect, the present invention discloses the use of the benzyl ether compound according to the second aspect in organic synthesis, medicine, pesticide, material, dye or detergent.

The technical solution of the present invention will be further described below by way of specific examples.

Example 1

0.5mmol of 1-ethylnaphthalene and 2.5mmol of deuterated methanol were placed in 2.5mL of acetonitrile, and then 0.05mmol of the metal catalyst nickel acetylacetonate and 0.005mmol of the photocatalyst [ Ir { dF (CF) ]₃)ppy}₂(dtbbpy)]PF₆And 1.0mmol of oxidant N-fluoro-bis-benzenesulfonamide, filling inert gas into the reaction device to replace the air in the device;

reacting for 24 hours at 40 ℃ by taking visible light as a driving force; after the reaction is finished, extracting an organic phase from the obtained reaction liquid by using ethyl acetate, distilling to remove the solvent, carrying out column chromatography separation on the residue by using 200-mesh silica gel of 300 meshes, carrying out gradient elution by using a mixed solution of the ethyl acetate and petroleum ether with the volume ratio of 1: 50 as an eluent, evaporating to remove the solvent from the eluent, and drying to obtain the product 1- (1- (deuterated methoxy) ethyl) naphthalene, wherein the yield is 84%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.09(d,J＝7.7Hz,1H),7.80(dd,J＝7.1,2.2Hz,1H),7.70(d,J＝8.1Hz,1H),7.49(d,J＝6.9Hz,1H),7.46-7.37(m,3H),4.99(q,J＝6.5Hz,1H),1.53(d,J＝6.6Hz,3H).¹³C NMR(150MHz,CDCl₃)δ139.1,133.9,130.8,128.9,127.78,125.8,125.5,125.4,123.3,123.2,77.2,55.7(quin,J＝21.0Hz),23.2.HRMS(ESI)Calcd.for C₁₃H₁₂D₃O[(M+H)⁺]190.1311,found 190.1315。

example 2

The present example uses the same embodiment as example 1, except that: the photocatalyst adopted is [ Ir (ppy)₂(dtbbpy)]PF₆The yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 66%.

Example 3

The present example uses the same embodiment as example 1, except that: the adopted photocatalyst is Ru (bpy)₃Cl₂.6H₂O, product 1- (1- (deuterated methoxy) ethyl) naphthalene in 55% yield.

Example 4

The present example uses the same embodiment as example 1, except that: the photocatalyst adopted is Ir (ppy)₃The yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 34%.

Example 5

The present example uses the same embodiment as example 1, except that: the photocatalyst used was 4CzIPN, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 47%.

Example 6

The present example uses the same embodiment as example 1, except that: the adopted photocatalyst is benzaldehyde as the photocatalyst, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 36 percent.

Example 7

The present example uses the same embodiment as example 1, except that: the photocatalyst adopted is acid red, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 45 percent.

Example 8

The present example uses the same embodiment as example 1, except that: the photocatalyst used was riboflavin, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 53%.

Example 9

The present example uses the same embodiment as example 1, except that: the amount of the photocatalyst used was 0.0025mmol, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 65%.

Example 10

The present example uses the same embodiment as example 1, except that: the amount of the photocatalyst used was 0.01mmol, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 84%.

Example 11

The present example uses the same embodiment as example 1, except that: the metal catalyst used was nickel chloride and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 75%.

Example 12

The present example uses the same embodiment as example 1, except that: the metal catalyst adopted is nickel acetate, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 77%.

Example 13

The present example uses the same embodiment as example 1, except that: the metal catalyst used was nickel bromide, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 80%.

Example 14

The present example uses the same embodiment as example 1, except that: the metal catalyst used was nickel nitrate and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 70%.

Example 15

The present example uses the same embodiment as example 1, except that: the adopted metal catalyst is cuprous chloride, the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 60 percent, and the yield of the byproduct 1-acetylnaphthalene is 22 percent.

Example 16

The present example uses the same embodiment as example 1, except that: the adopted metal catalyst is copper trifluoroacetate, the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 50 percent, and the yield of the byproduct 1-acetylnaphthalene is 32 percent.

Example 17

The present example uses the same embodiment as example 1, except that: the adopted metal catalyst is copper trifluoromethanesulfonate, the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 34%, and the yield of the byproduct 1-acetylnaphthalene is 42%.

Example 18

The present example uses the same embodiment as example 1, except that: the amount of the metal catalyst used was 0.025mmol, and the yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 80%.

Example 19

The present example uses the same embodiment as example 1, except that: the amount of the metal catalyst used was 0.1mmol, and the yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 83%.

Example 20

The present example uses the same embodiment as example 1, except that: the oxidant used was ammonium persulfate and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 68%.

Example 21

The present example uses the same embodiment as example 1, except that: the oxidant used was sodium persulfate, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 60%.

Example 22

The present example uses the same embodiment as example 1, except that: the oxidant used was selective fluorine and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 57%.

Example 23

The present example uses the same embodiment as example 1, except that: the oxidant used was [ bis (acetoxy) iodo ] benzene, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 45%.

Example 24

The present example uses the same embodiment as example 1, except that: the oxidant used was 2-iodoxybenzoic acid and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 46%.

Example 25

The present example uses the same embodiment as example 1, except that: the oxidant used was m-chloroperoxybenzoic acid and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 37%.

Example 26

The present example uses the same embodiment as example 1, except that: the oxidant used was t-butyl hydroperoxide and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 23%.

Example 27

The present example uses the same embodiment as example 1, except that: the amount of the oxidizing agent used was 0.5mmol, and the yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 56%.

Example 28

The present example uses the same embodiment as example 1, except that: the amount of the oxidizing agent used was 2.0mmol, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 78%.

Example 29

The present example uses the same embodiment as example 1, except that: the solvent used was dichloromethane and the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was obtained in 67% yield.

Example 30

The present example uses the same embodiment as example 1, except that: the solvent used was dimethyl sulfoxide and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 45%.

Example 31

The present example uses the same embodiment as example 1, except that: the solvent used was N, N-dimethylformamide and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 27%.

Example 32

The present example uses the same embodiment as example 1, except that: the solvent used was hexafluoroisopropanol and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 12%.

Example 33

The present example uses the same embodiment as example 1, except that: the solvent used was dichloromethane/hexafluoroisopropanol (4:1, v/v) and the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was obtained in 79% yield.

Example 34

The present example uses the same embodiment as example 1, except that: the amount of the solvent used was 1.25mL, and the yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 70%.

Example 35

The present example uses the same embodiment as example 1, except that: the amount of the solvent used was 5.0mL, and the yield of the product, 1- (1- (deuterated methoxy) ethyl) naphthalene, was 82%.

Example 36

The present example uses the same embodiment as example 1, except that: the reaction temperature employed was-20 ℃ and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 32%.

Example 36

The present example uses the same embodiment as example 1, except that: the reaction temperature employed was 25 ℃ and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 82%.

Example 36

The present example uses the same embodiment as example 1, except that: the reaction temperature employed was 80 ℃ and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 72%.

Example 37

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 4-ethyl-1, 1' -biphenyl. The obtained product was 4- (1- (deuterated methoxy) ethyl) -1,1' -biphenyl in 82% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.57-7.46(m,4H),7.35(t,J＝7.6Hz,2H),7.32-7.22(m,3H),4.26(q,J＝6.5Hz,1H),1.39(d,J＝6.5Hz,3H).¹³C NMR(150MHz,CDCl₃)δ142.6,140.9,140.4,128.7,127.2,127.0,126.6,79.2,55.6(quin,J＝21.5Hz),23.8.HRMS(ESI)Calcd.for C₁₅H₁₄D₃O[(M+H)⁺]216.1468,found 216.1473。

example 38

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 1-ethyl-4-methoxybenzene. The product obtained was 1-methoxy-4- (1- (deuterated methoxy) ethyl) benzene with a yield of 75%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.16(d,J＝8.4Hz,2H),6.82(d,J＝8.4Hz,2H),4.18(q,J＝6.4Hz,1H),3.74(s,3H),1.35(d,J＝6.4Hz,3H).¹³C NMR(150MHz,CDCl₃)δ159.0,135.6,127.4,113.8,79.0,55.3,23.8.HRMS(ESI)Calcd.for C₁₀H₁₂D₃O₂[(M+H)⁺]170.1260,found 170.1265。

example 39

The present example uses the same embodiment as example 1, except that: the benzyl substrate employed was hexylbenzene. The product obtained was (1- (deuterated methoxy) hexyl) benzene with a yield of 72%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.33-7.24(m,2H),7.21(d,J＝7.1Hz,3H),4.00(t,J＝6.6Hz,1H),1.80-1.66(m,1H),1.59-1.52(m,1H),1.37-1.28(m,1H),1.25-1.13(m,6H),0.78(t,J＝6.1Hz,3H).¹³C NMR(150MHz,CDCl₃)δ142.6,128.3,127.4,126.7,84.0,55.7(quin,J＝21.3Hz),38.2,31.8,25.5,22.6,14.0.HRMS(ESI)Calcd.for C₁₃H₁₈D₃O[(M+H)⁺]196.1781,found 196.1790。

example 40

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was (3-bromopropyl) benzene. The obtained product was (3-bromo-1- (deuterated methoxy) propyl) benzene with a yield of 56%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.34-7.27(m,2H),7.26-7.20(m,3H),4.28(dd,J＝8.2,4.9Hz,1H),3.49(dd,J＝15.4,8.5Hz,1H),3.37-3.23(m,1H),2.30-2.19(m,1H),2.08-1.97(m,1H).¹³C NMR(150MHz,CDCl₃)δ141.1,128.6,127.9,126.6 81.3,56.0(quin,J＝21.5Hz),41.1 30.3.HRMS(ESI)Calcd.for C₁₀H₁₁D₃BrO[(M+H)⁺]232.0416,found 232.0424。

EXAMPLE 41

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 1,2,3, 4-tetrahydronaphthalene. The obtained product was 1- (deuterated methoxy) -1,2,3, 4-tetrahydronaphthalene in a yield of 70%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.32-7.24(m,1H),7.15-7.06(m,2H),7.06-6.98(m,1H),4.24(t,J＝4.6Hz,1H),2.80-2.70(m,1H),2.70-2.57(m,1H),2.00-1.87(m,2H),1.86-1.74(m,1H),1.73-1.58(m,1H).¹³C NMR(100MHz,CDCl₃)δ137.5,136.6,129.3,129.0,127.5,125.7,29.1,27.4,18.7.HRMS(ESI)Calcd.for C₁₁H₁₂D₃O[(M+H)⁺]166.1311,found 166.1317。

example 42

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 2- (4-methoxyphenyl) acetonitrile. The obtained product was 2- (deuterated methoxy) -2- (4-methoxyphenyl) acetonitrile, which was obtained in 82% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.41(d,J＝8.7Hz,2H),6.94(d,J＝8.7Hz,2H),5.14(s,1H),3.83(s,3H).¹³C NMR(100MHz,CDCl₃)δ160.8,128.9,125.4,117.2,114.4,71.8,55.4.HRMS(ESI)Calcd.for C₁₀H₉D₃NO₂[(M+H)⁺]181.1056,found 181.1063。

example 43

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was diphenylmethane. The obtained product was ((deuterated methoxy) methylene) diphenyl, and the yield thereof was 84%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.25(q,J＝7.7Hz,8H),7.16(t,J＝6.7Hz,2H),5.16(s,1H).¹³C NMR(150MHz,CDCl₃)δ142.1,128.4,127.5,126.9,85.4,56.2(quin,J＝21.3Hz).HRMS(ESI)Calcd.for C₁₄H₁₂D₃O[(M+H)⁺]202.1311,found 202.1317。

example 44

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 2-hexylthiophene. The product obtained was 2- (1- (deuterated methoxy) hexyl) thiophene, the yield of which was 71%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.20(d,J＝5.1Hz,1H),6.89(d,J＝4.9Hz,2H),4.28(t,J＝6.8Hz,1H),1.84(dd,J＝18.4,10.8Hz,1H),1.67(dd,J＝12.3,6.1Hz,1H),1.39-1.29(m,1H),1.21(s,7H),0.80(t,J＝5.7Hz,3H).¹³C NMR(150MHz,CDCl₃)δ146.4,126.3,125.2,124.8,79.4,55.7(quin,J＝21.1Hz),38.3,31.6,25.5,22.6,14.1.HRMS(ESI)Calcd.for C₁₁H₁₆D₃OS[(M+H)⁺]202.1345,found 202.1348。

example 45

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was ibuprofen methyl ester. The obtained product was methyl 2- (4- (1- (deuterated methoxy) -2-methylpropyl) phenyl) propionate in a yield of 70%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.19(d,J＝7.9Hz,2H),7.12(d,J＝8.0Hz,2H),3.66(dd,J＝6.7,4.7Hz,2H),3.60(s,3H),1.87-1.76(m,1H),1.43(d,J＝7.2Hz,3H),0.90(d,J＝6.6Hz,3H),0.66(d,J＝6.8Hz,3H).¹³C NMR(150MHz,CDCl₃)δ175.2,140.0,139.4,127.7,127.1,89.3,56.2(quin,J＝21.2Hz),52.0,45.1,34.7,19.0,18.9,18.6.HRMS(ESI)Calcd.for C₁₅H₂₀D₃O₃[(M+H)⁺]254.1835,found 254.1837。

example 46

The present example uses the same embodiment as example 1, except that: the benzyl substrate used was 2- (5-bromo-2-methylbenzyl) -5- (4-fluorophenyl) thiophene. The product obtained was 2- ((5-bromo-2-methylphenyl) (deuterated methoxy) methyl) -5- (4-fluorophenyl) thiophene in 92% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ7.65(d,J＝1.9Hz,1H),7.47-7.39(m,2H),7.28(dd,J＝8.1,2.1Hz,1H),6.96(dd,J＝9.4,7.6Hz,4H),6.68(d,J＝3.2Hz,1H),5.45(s,1H),2.17(s,3H).¹³C NMR(150MHz,CDCl₃)δ163.1,161.5,143.8,143.7,141.2,134.5,132.2,130.8,130.53,129.1,128.9,128.4,127.4,127.3,126.9,126.0,122.3,120.1,115.0,115.7,77.8,56.3(quin,J＝21.4Hz),18.7.HRMS(ESI)Calcd.for C₁₉H₁₄D₃BrFOS[(M+H)⁺]394.0356,found 394.0359。

example 47

The present example uses the same embodiment as example 1, except that: the alcohol substrate used is ethanol. The product obtained was 1- (1-ethoxyethyl) naphthalene in 75% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.19(d,J＝7.7Hz,1H),7.91-7.84(m,1H),7.76(d,J＝8.1Hz,1H),7.58(d,J＝6.9Hz,1H),7.52-7.41(m,3H),5.16(q,J＝6.5Hz,1H),3.44(q,J＝7.0Hz,2H),1.61(d,J＝6.5Hz,3H),1.23(t,J＝7.0Hz,3H).¹³C NMR(100MHz,CDCl₃)δ139.8,134.0,130.9,128.9,127.7,125.8,125.6,125.4,123.4,123.2,75.5,64.1,23.6,15.6.HRMS(ESI)Calcd.for C₁₄H₁₇O[(M+H)⁺]201.1279,found 201.1283。

example 48

The present example uses the same embodiment as example 1, except that: the alcohol substrate used was tert-butanol. The product obtained was 1- (1- (tert-butyl) ethyl) naphthalene in 68% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.13(d,J＝8.1Hz,1H),7.88-7.82(m,1H),7.72(t,J＝8.5Hz,2H),7.54-7.42(m,3H),5.38(q,J＝6.5Hz,1H),1.51(d,J＝6.5Hz,3H),1.18(s,9H).¹³C NMR(100MHz,CDCl₃)δ143.3,133.7,129.8,128.9,126.89,125.6,125.1,123.3,123.1,74.3,67.0,28.4,26.0.HRMS(ESI)Calcd.for C₁₆H₂₁O[(M+H)⁺]229.1592,found 229.1601。

example 49

The present example uses the same embodiment as example 1, except that: the alcohol substrate used was cyclohexanol. The product obtained was 1- (1- (cyclohexyloxyethyl) naphthalene in a yield of 60%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.19(d,J＝7.7Hz,1H),7.90-7.83(m,1H),7.76(d,J＝8.2Hz,1H),7.63(d,J＝7.0Hz,1H),7.48(dt,J＝11.8,4.8Hz,3H),5.34(q,J＝6.5Hz,1H),3.26-3.17(m,1H),2.03(d,J＝10.3Hz,1H),1.80(d,J＝10.3Hz,1H),1.74-1.62(m,2H),1.58(d,J＝6.6Hz,3H),1.48(dd,J＝10.9,4.8Hz,1H),1.41-1.31(m,2H),1.17-1.05(m,3H).¹³C NMR(100MHz,CDCl₃)δ140.7,133.9,130.79,128.9,127.45,125.7,125.6,125.3,123.4,75.1,71.8,33.5,31.8,25.8,24.4,24.3,24.2.HRMS(ESI)Calcd.for C₁₈H₂₃O[(M+H)⁺]255.1749,found 255.1753。

example 50

The present example uses the same embodiment as example 1, except that: the adopted alcohol substrate is 2,2, 2-trifluoroethane-1-alcohol. The product obtained was 1- (1- (2,2, 2-trifluoroethoxy) ethyl) naphthalene in 65% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.14(d,J＝7.6Hz,1H),7.89(dd,J＝6.9,2.4Hz,1H),7.82(d,J＝8.1Hz,1H),7.61-7.42(m,4H),5.33(q,J＝6.5Hz,1H),3.86-3.60(m,2H),1.69(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ137.3,130.6,129.0,128.5,126.3,125.7,125.5,123.7,123.0,77.6,66.1,65.8,29.7,23.2.HRMS(ESI)Calcd.for C₁₄H₁₄F₃O[(M+H)⁺]255.0997,found 255.1003。

example 51

The present example uses the same embodiment as example 1, except that: the alcohol substrate used was tert-butyl (2-hydroxyethyl) carbamate. The product obtained was tert-butyl (2- (1- (naphthalen-1-yl) ethoxy) ethyl) carbamate in 77% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.17(d,J＝7.9Hz,1H),7.91-7.84(m,1H),7.77(d,J＝8.1Hz,1H),7.56-7.42(m,4H),5.14(q,J＝6.5Hz,1H),4.93(s,1H),3.43(dd,J＝11.4,6.6Hz,2H),3.33-3.23(m,2H),1.62(d,J＝6.5Hz,3H),1.43(s,9H).¹³C NMR(100MHz,CDCl₃)δ155.9,138.9,133.9,130.7,128.9,128.0,125.9,125.5,125.4,123.5,123.3,76.1,67.7,28.4,27.5.HRMS(ESI)Calcd.for C₁₉H₂₆NO₃[(M+H)⁺]316.1913,found 316.1917。

example 52

The present example uses the same embodiment as example 1, except that: the alcohol substrate used was ethylene glycol. The product obtained was 2- (1- (naphthalen-1-yl) ethoxy) ethan-1-ol in 88% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.17(d,J＝7.9Hz,1H),7.92-7.83(m,1H),7.78(d,J＝8.1Hz,1H),7.56(d,J＝6.9Hz,1H),7.53-7.41(m,3H),5.20(q,J＝6.5Hz,1H),3.78-3.68(m,2H),3.55-3.46(m,2H),2.13(br,1H),1.65(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ138.9,133.9,130.7,128.9,128.0,125.9,125.5,123.4,123.2,76.2,69.8,62.1,23.2.HRMS(ESI)Calcd.for C₁₄H₁₇O₂[(M+H)⁺]217.1229,found 217.1240。

example 53

The present example uses the same embodiment as example 1, except that: the alcohol substrate used is tetrahydrofurfuryl alcohol. The product obtained was 2- ((1- (naphthalen-1-yl) ethoxy) methylene) tetrahydrofuran in 85% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.27-8.13(m,1H),7.91-7.83(m,1H),7.76(d,J＝8.1Hz,1H),7.59(dd,J＝12.8,7.0Hz,1H),7.55-7.41(m,3H),5.26-5.15(m,1H),4.14-4.04(m,1H),3.92-3.82(m,1H),3.77(dd,J＝14.8,6.9Hz,1H),3.46-3.32(m,2H),1.96-1.77(m,3H),1.63(t,J＝6.4Hz,3H).¹³C NMR(100MHz,CDCl₃)δ139.4,139.3,133.9,130.8,128.8,127.75,127.7,125.8,125.5,125.4,123.6,123.5,123.3,78.2,77.8,76.5,76.0,71.7,71.3,68.3,28.3,28.0,25.6,25.5,23.5.HRMS(ESI)Calcd.for C₁₇H₂₁O₂[(M+H)⁺]257.1542,found 257.1549。

example 54

The present example uses the same embodiment as example 1, except that: the adopted alcohol substrate is tetrahydropyran-4-ol. The product obtained was 4- (1- (naphthalen-1-yl) ethoxy) tetrahydro-2H-pyran in a yield of 70%.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.22-8.17(m,1H),7.86(dd,J＝7.0,2.4Hz,1H),7.76(d,J＝8.2Hz,1H),7.60(d,J＝6.9Hz,1H),7.54-7.42(m,3H),5.33(q,J＝6.5Hz,1H),3.97-3.91(m,1H),3.90-3.84(m,1H),3.50-3.41(m,1H),3.36-3.22(m,2H),2.00-1.91(m,1H),1.79-1.62(m,3H),1.60(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ140.0,133.9,130.6,128.9 127.7,125.8 125.5,125.4,123.5,123.3,72.1,71.5,65.9,65.7,33.5,32.0,24.1.HRMS(ESI)Calcd.for C₁₇H₂₁O₂[(M+H)⁺]257.1542,found 257.1544。

example 55

The present example uses the same embodiment as example 1, except that: the alcohol substrate used was ((3aR, 5R, 5aS, 8aS, 8bR) -2,2,7, 7-tetramethyltetrahydro-5H-bis ([1,3] dioxine) [4,5-b:4', 5' -d ] pyran-5-yl) methanol. The product obtained was (3aR, 5R, 5aS, 8bR) -2,2,7, 7-tetramethyl-5- ((1- (naphthalen-1-yl) ethoxy) methyl) tetrahydro-5H-bis ([1,3] dioxanyl) [4,5-b:4', 5' -d ] pyran in 82% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ8.22-8.17(m,1H),7.86-7.84(m,1H),7.76-7.74(m,1H),7.59-7.57(m,1H),7.51-7.37(m,3H),5.56-5.49(m,1H),5.30-5.20(m,1H),4.60-4.54(m,1H),4.35-4.16(m,2H),4.03-3.96(m,1H),3.60-3.59(d,J＝6.7Hz,2H),1.64-1.62(m,3H),1.58(1.49)(s,3H),1.40(1.37)(s,3H),1.34-1.27(m,6H).¹³C NMR(100MHz,CDCl₃)δ139.1,133.9,130.8,128.8,128.7,127.8,125.7,125.5,125.4,125.3,123.6,123.5,123.4,109.1,108.5,108.4,96.3,76.3,75.9,71.1,71.0,70.7,70.6,67.5,67.3,67.0,66.5,26.1,26.0,24.9,24.4,24.3,23.13.HRMS(ESI)Calcd.for C₂₄H₃₁O₆[(M+H)⁺]415.2121,found 415.2125。

example 56

The present example uses the same embodiment as example 1, except that: the adopted alcohol substrate is 1- ((3aR, 4R, 6R, 6aR) -6- (hydroxymethyl) -2, 2-dimethyltetrahydrofuran [3,4-d ] [1,3] dioxyl-4-yl) pyrimidine-2, 4(1H, 3H) -diketone. The product obtained was 1- ((3aR, 4R, 6aR) -2, 2-dimethyl-6- ((1- (naphthalen-1-yl) ethoxy) methyl) tetrahydrofuran [3,4-d ] [1,3] dioxy-4-yl) pyrimidine-2, 4(1H, 3H) -dione in 73% yield.

The nuclear magnetic resonance results are as follows:¹H NMR(400MHz,CDCl₃)δ9.26(9.11)(s,1H),8.22-8.03(m,1H),7.92-7.83(m,1H),7.81-7.77(m,1H),7.73-7.39(m,5H),5.94(5.90)(d,J＝2.6Hz,1H),5.71-5.68(5.27-5.23)(m,1H),5.20-5.10(m,1H),4.87-4.68(m,2H),4.43-4.34(m,1H),3.81-3.48(m,2H),1.67-1.63(m,3H),1.58(1.57)(s,3H),1.35(1.32)(s,3H).¹³C NMR(100MHz,CDCl₃)δ163.3,163.1,150.1,150.0,141.1,140.8,138.1,137.9,134.0,133.9,130.5,129.1,128.4,128.3,126.1,125.9,125.7,125.4,125.3,123.9,123.3,123.2,123.0,114.3,114.0,102.0,93.1,92.0,85.9,85.6,85.2,84.8,81.1,80.8,77.2,76.3,68.9,68.5,27.2,25.4,25.3,22.9,22.1.HRMS(ESI)Calcd.for C₂₄H₂₇N₂O₆[(M+H)⁺]439.1869,found 439.1877。

the technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.