CN113717033B - Benzyl ether compound and synthesis method thereof - Google Patents

Benzyl ether compound and synthesis method thereof Download PDF

Info

Publication number
CN113717033B
CN113717033B CN202111040688.2A CN202111040688A CN113717033B CN 113717033 B CN113717033 B CN 113717033B CN 202111040688 A CN202111040688 A CN 202111040688A CN 113717033 B CN113717033 B CN 113717033B
Authority
CN
China
Prior art keywords
yield
nickel
except
reaction
benzyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111040688.2A
Other languages
Chinese (zh)
Other versions
CN113717033A (en
Inventor
刘石惠
周伟
李子瑜
吕晓庆
高金来
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiaxing University
Original Assignee
Jiaxing University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiaxing University filed Critical Jiaxing University
Priority to CN202111040688.2A priority Critical patent/CN113717033B/en
Publication of CN113717033A publication Critical patent/CN113717033A/en
Application granted granted Critical
Publication of CN113717033B publication Critical patent/CN113717033B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/04—Formation or introduction of functional groups containing oxygen of ether, acetal or ketal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
    • C07D493/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a benzyl ether compound and a synthesis method thereof, comprising the following steps: mixing benzyl compound, alcohols, metal catalyst, photocatalyst, oxidant and organic solvent to obtain a reaction system; under the condition of isolating oxygen, using visible light as driving force to irradiate the reaction system; and after the reaction is finished, purifying to obtain the benzyl ether compound. The synthesis method has the advantages of green and 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.

Description

Benzyl ether compound and synthesis method thereof
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of benzyl ether compounds, and also relates to benzyl ether compounds prepared by the synthesis method.
Background
Benzyl ether compounds are compounds with important biological activity, widely exist in drug molecules, natural products and organisms, and the synthesis of the compounds is always widely focused by chemists. Existing nucleophilic substitution synthesis methods (Williamson ether formation reaction) generally use strong alkali and high-temperature reaction conditions, the reaction conditions of the methods are not mild enough, the total yield is low, the substrate range is extremely limited, and the ether compounds with large steric hindrance are generally difficult to synthesize.
At present, visible light/transition metal co-catalytic free radical coupling reaction strategies have become established to build C (sp 3 ) The focus of the study of the X bond. For example, the group of Mimland topics at the university of Prins, nature,2020, 580,220, reported visible light/copper co-catalysis of C (sp 3 ) -new method of N-bond construction. But the strategy still lacks a solution to C (sp 3 ) The construction method of O cannot be used for synthesizing benzyl ether compounds. In addition, in the prior art, there is a method for obtaining benzyl ether compound by reacting benzyl silane compound and alcohol, but the benzyl silane compound adopted in the technical scheme has no commercial source and is difficult to synthesize, and alcohol substrate needs to be used as solvent, so that the synthesis of benzyl ether compound with simple structure can be realized, and the method cannot be applied to the synthesis of benzyl ether compound with complex structure. . Also has the technologyThe scheme discloses a method for synthesizing benzyl ether catalyzed by copper, which generally generates a large amount of ketone byproducts excessively oxidized due to the adoption of a bivalent copper catalyst with high oxidability, and the range of reaction substrates is also influenced, so that the method is difficult to be applied to the synthesis of benzyl ether compounds with complex structures.
Disclosure of Invention
In view of the above, it is necessary to provide a method for synthesizing benzyl ether compounds, which uses unmodified alcohols and benzyl compounds as starting materials and uses visible light as driving force under the conditions of a metal catalyst, a photocatalyst and an oxidant to prepare benzyl ether compounds. The synthesis method has the advantages of green and high efficiency, high atom economy, high selectivity, few byproducts, wide range of reaction substrates and low cost.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the invention provides a method for synthesizing benzyl ether compounds, which comprises the following steps:
mixing benzyl compound, alcohols, metal catalyst, photocatalyst, oxidant and organic solvent to obtain a reaction system;
under the condition of isolating oxygen, using visible light as driving force to irradiate the reaction system;
and after the reaction is finished, purifying to obtain the benzyl ether compound.
Further, the metal catalyst is a nickel-based catalyst.
Further, the nickel-based catalyst is selected from one of nickel acetylacetonate, nickel chloride, nickel bromide and nickel acetate.
Further, the photocatalyst is selected from Ru (bpy) 3 Cl 2 ·6H 2 O、Ir(ppy) 3 、[Ir{dF(CF 3 )ppy} 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 4CzIPN, benzaldehyde, diphenyl ketone, 9-fluorenone, rose bengal, acid red, rhodamine and riboflavin.
Further, the oxidant is selected from one of ammonium persulfate, sodium persulfate, potassium persulfate, selected fluorine, N-fluoro-bis-benzenesulfonamide, [ bis (acetoxy) iodo ] benzene, [ bis (trifluoroacetoxy) iodo ] benzene, 2-iodoacyl benzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide and tert-butyl hydroperoxide;
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.
Further, the metal catalyst is used in an amount of 0.1 to 20% mol.
Further, the photocatalyst is used in an amount of 0.1 to 20% mol; the amount of the oxidizing agent 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 according to any one of the above.
Compared with the prior art, the invention has the following beneficial effects:
on the basis of the transition metal co-catalysis free radical coupling reaction, the invention develops the method which takes the unmodified alcohols and benzyl compounds as reaction substrates, directly obtains the benzyl ether compounds by one-step reaction under mild conditions, has the advantages of cheap reaction substrates, wide range, simple operation, high yield, good selectivity, fewer byproducts, economy and high efficiency.
The synthesis method is favorable for 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 readily understood, a more particular description of the invention will be rendered by reference to specific embodiments that are illustrated below. 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.
The primary terms herein
The term "benzyl compound" as used herein refers to any organic compound containing benzyl functionality, and which has not been modified, and has the general structural formula:
wherein Ar is selected from the group consisting of-Ph, 4MeO Ph, 3MeO Ph, 2MeO Ph, 4Br Ph, 4Cl Ph, 4Ac Ph, 4CN Ph, 4COOCH 3 Ph、4CH 2 CH 2 COOCH 3 Any one of Ph, 4PhO Ph, 4BzO Ph, 4Ph Ph, 1-naphthlene, 2-thiophen, 2-furan, 2-pyridine;
R 2 selected from H, CH 3 、 n Bu、 i Pr、Ph、4-MeO-Ph、4-Cl-Ph、CN、COOMe、CH 2 CH 2 Br、CH 2 CH 2 Cl、CH 2 CH 2 OBz、CH 2 CH 2 OAc, any one of which.
As used herein, "alcohol" refers to a compound having a hydroxyl group bonded to a carbon on a side chain of a hydrocarbon group or benzene ring in the molecule, and has the general structural formula:
R 1 -OH
wherein R1 is selected from CH 3 、Et、CD 3 、 n Pr、 i Pr、 n Bu、 t Bu、-Cy、CH 2 Ph、CH 2 CF 3 、CH 2 COOMe、CH 2 CH 2 OCH 3 、CH 2 CH 2 OPh、CH 2 CH 2 OH、(CH 2 CH 2 ) n OH、(CH 2 CH 2 O) n H、CH 2 CH 2 NHBoc, -2-methylethylethylene-of, -3-tetrahydrof-an, -2-methylethylethylene-2H-pyran, -4-tetrahydroo-2H-pyran, -glucose, -manose, -ribose, -deoxyribose, -rhamnose, -nucleoside, -glycoside.
By "metal catalyst" is herein understood a halide, organic or inorganic salt of a transition metal, in particular copper-based or nickel-based catalysts.
By "photocatalyst" is herein understood a class of metal complexes or organic compounds that can absorb visible light and convert light energy into chemical energy.
Herein, "oxidizing agent" is understood to be a class of substances that gain electrons in a chemical reaction, having oxidizing properties.
The technical proposal of the invention
The invention discloses a method for synthesizing benzyl ether compounds, which comprises the following steps:
mixing benzyl compound, alcohols, metal catalyst, photocatalyst, oxidant and organic solvent to obtain a reaction system;
under the condition of isolating oxygen, using visible light as driving force to irradiate the reaction system;
and after the reaction is finished, purifying to obtain the benzyl ether compound.
The invention is based on visible light/transition metal co-catalytic free radical coupling reaction, and uses unmodified benzyl compound and alcohol as reaction substrates, and the benzyl ether compound is directly obtained by one-step reaction under mild conditions, and 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 mode of oxygen isolation is not particularly limited, and inert gas or nitrogen is generally introduced into the reaction system to discharge air in the reaction system. The progress of the reaction may be monitored by means conventional in the art, such as in one or more embodiments of the invention, by TLC thin layer chromatography.
Further, the metal catalyst in the present invention may be selected from copper-based catalysts or nickel-based catalysts, but the use of copper-based catalysts is easy to generate more ketone byproducts, and in one or more embodiments of the present invention, it is preferable that the metal catalyst is nickel-based catalysts, and a visible light+nickel catalytic system with weaker oxidizing ability and more efficient reaction is used, so that the generation of ketone byproducts is avoided, the reaction is efficient, the yield is high, and the byproducts are few.
Further, the nickel-based catalyst described in the present invention is not particularly limited, and halides, inorganic or organic salts of metallic nickel conventional in the art may be used, and specific examples include, but are not limited to, one of nickel acetylacetonate, nickel chloride, nickel bromide, 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 selected conventionally in the art, and examples specifically mentioned include, but are not limited to, ru (bpy) 3 Cl 2 ·6H 2 O、Ir(ppy) 3 、[Ir{dF(CF 3 )ppy} 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 One of 4CzIPN, benzaldehyde, benzophenone, 9-fluorenone, rose bengal, acid red, rhodamine, and riboflavin, preferably [ Ir { dF (CF) 3 )ppy} 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 One of the riboflavin.
Further, the oxidizing agent described in the present invention may be selected conventionally in the art, and examples specifically mentioned include, but are not limited to, one of ammonium persulfate, sodium persulfate, potassium persulfate, selective fluorine, N-fluoro-bis-benzenesulfonamide, [ bis (acetoxy) iodo ] benzene, [ bis (trifluoroacetoxy) iodo ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide, t-butyl hydroperoxide, preferably one of N-fluoro-bis-benzenesulfonamide, ammonium persulfate, 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, preferably acetonitrile, dichloromethane or dichloromethane/hexafluoroisopropanol (4:1, v/v).
Further, the amounts of the metal catalyst, photocatalyst and oxidant used in the present invention may be adjusted as desired, and in one or more embodiments of the present invention, the metal catalyst is used in an amount of 0.1 to 20% by mol, preferably 5 to 20% by mol, with respect to the benzyl compound.
The photocatalyst is used in an amount of 0.1 to 20% by mol, preferably 1 to 2% by mol.
The amount of the oxidizing agent is 100 to 500% mol, preferably 200 to 400% mol.
Further, the light irradiation time of the present invention may be adjusted according to the reaction progress, so that the reaction is complete, and in one or more embodiments of the present invention, the light irradiation time of the reaction system is 2 to 48 hours, the reaction temperature is-20 to 80 ℃, and preferably 25 to 40 ℃.
Further, the purification purpose of the present invention is to purify the product obtained, the purification mode is not particularly limited, and a purification means conventional in the art may be adopted, or a plurality of purification means may be combined, in some embodiments of the present invention, the purification is performed by using a column chromatography method, generally, after extracting an organic phase, removing a solvent in the extracted organic phase, classifying by using column chromatography, performing gradient elution, finally removing the solvent and drying to obtain a final product, in some specific examples of the present invention, performing post-treatment on the obtained reaction solution, specifically, extracting the reaction solution with ethyl acetate, distilling the organic phase to remove the solvent, separating the residue by using 200 300 mesh silica gel by column chromatography, and using ethyl acetate to obtain a petroleum ether volume ratio of 1:1-1:100 as eluent, evaporating the eluent to remove the solvent and drying. To obtain the benzyl ether compound.
The second aspect of the invention discloses a benzyl ether compound which is obtained by adopting 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 invention discloses the application of the benzyl ether compound in organic synthesis, medicaments, pesticides, materials, dyes or detergents.
The technical scheme of the invention is further described through specific examples.
Example 1
0.5mmol of 1-ethylnaphthalene and 2.5mmol of deuterated methanol are placed in 2.5mL of acetonitrile, followed by the addition of 0.05mmol of the metal catalyst nickel acetylacetonate, 0.005mmol of the photocatalyst [ Ir { dF (CF) 3 )ppy} 2 (dtbbpy)]PF 6 And 1.0mmol of oxidant N-fluoro-bis-benzene sulfonamide, and filling the air in the inert gas substitution device into the reaction device;
taking visible light as driving force, and reacting for 24 hours at 40 ℃; after the reaction is finished, the organic phase is extracted from the obtained reaction liquid by ethyl acetate, the solvent is removed by distillation, the residue is separated by column chromatography by 200-300 meshes of silica gel, the mixed liquid of ethyl acetate and petroleum ether with the volume ratio of 1:50 is used as an eluent for gradient elution, the solvent is distilled off from the eluent, and the eluent is dried, so that the product 1- (1- (deuteromethoxy) ethyl) naphthalene is obtained, and the yield is 84%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 13 H 12 D 3 O[(M+H) + ]190.1311,found 190.1315。
example 2
This example uses the same implementation as example 1, except that: the photocatalyst used was [ Ir (ppy) 2 (dtbbpy)]PF 6 The yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 66%.
Example 3
This example uses the same implementation as example 1, except that: the photocatalyst used was Ru (bpy) 3 Cl 2 .6H 2 O, yield of product 1- (1- (deuterated methoxy) ethyl) naphthalene was 55%.
Example 4
This example uses the same implementation as example 1, except that: the photocatalyst used was Ir (ppy) 3 The yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 34%.
Example 5
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the photocatalyst adopted is benzaldehyde which is used as a photocatalyst, and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene is 36%.
Example 7
This example uses the same implementation as example 1, except that: the photocatalyst used was acid red, and the yield of the product 1- (1- (deuteromethoxy) ethyl) naphthalene was 45%.
Example 8
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the photocatalyst was used in an amount of 0.01mmol and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 84%.
Example 11
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the metal catalyst used was nickel acetate and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 77%.
Example 13
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation 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%, and the yield of the byproduct 1-acetyl naphthalene is 22%.
Example 16
This example uses the same implementation as example 1, except that: the metal catalyst used was copper trifluoroacetate with a yield of 50% of the product 1- (1- (deuterated methoxy) ethyl) naphthalene and a yield of 32% of the byproduct 1-acetylnaphthalene.
Example 17
This example uses the same implementation as example 1, except that: the metal catalyst used was copper triflate with a yield of 34% for the product 1- (1- (deuterated methoxy) ethyl) naphthalene and 42% for the by-product 1-acetylnaphthalene.
Example 18
This example uses the same implementation as example 1, except that: the amount of metal catalyst used was 0.025mmol and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 80%.
Example 19
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the oxidant used was selected to be fluoro and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 57%.
Example 23
This example uses the same implementation as example 1, except that: the oxidant used was [ bis (acetoxy) iodo ] benzene and the yield of 1- (1- (deuterated methoxy) ethyl) naphthalene was 45%.
Example 24
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the oxidant used was m-chloroperoxybenzoic acid with a yield of 37% of the product 1- (1- (deuterated methoxy) ethyl) naphthalene.
Example 26
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the amount of oxidant used was 0.5mmol and the yield of product 1- (1- (deuterated methoxy) ethyl) naphthalene was 56%.
Example 28
This example uses the same implementation as example 1, except that: the amount of oxidant used was 2.0mmol and the yield of product 1- (1- (deuterated methoxy) ethyl) naphthalene was 78%.
Example 29
This example uses the same implementation as example 1, except that: the solvent used was dichloromethane and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 67%.
Example 30
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation 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
This example uses the same implementation as example 1, except that: the solvent used was dichloromethane/hexafluoroisopropanol (4:1, v/v) and the yield of product 1- (1- (deuterated methoxy) ethyl) naphthalene was 79%.
Example 34
This example uses the same implementation as example 1, except that: the amount of solvent used was 1.25mL and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 70%.
Example 35
This example uses the same implementation as example 1, except that: the amount of solvent used was 5.0mL and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 82%.
Example 36
This example uses the same implementation as example 1, except that: the reaction temperature used was-20℃and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 32%.
Example 36
This example uses the same implementation as example 1, except that: the reaction temperature used was 25℃and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 82%.
Example 36
This example uses the same implementation as example 1, except that: the reaction temperature used was 80℃and the yield of the product 1- (1- (deuterated methoxy) ethyl) naphthalene was 72%.
Example 37
This example uses the same implementation as example 1, except that: the benzyl substrate used was 4-ethyl-1, 1' -biphenyl. The product obtained was 4- (1- (deuterated methoxy) ethyl) -1,1' -biphenyl in 82% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 15 H 14 D 3 O[(M+H) + ]216.1468,found 216.1473。
example 38
This example uses the same implementation 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 in 75% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )δ159.0,135.6,127.4,113.8,79.0,55.3,23.8.HRMS(ESI)Calcd.for C 10 H 12 D 3 O 2 [(M+H) + ]170.1260,found 170.1265。
example 39
This example uses the same implementation as example 1, except that: the benzyl substrate used was hexylbenzene. The product obtained was (1- (deuterated methoxy) hexyl) benzene in a yield of 72%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 13 H 18 D 3 O[(M+H) + ]196.1781,found 196.1790。
example 40
This example uses the same implementation as example 1, except that: the benzyl substrate used was (3-bromopropyl) benzene. The product obtained was (3-bromo-1- (deuterated methoxy) propyl) benzene in a yield of 56%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )δ141.1,128.6,127.9,126.6 81.3,56.0(quin,J＝21.5Hz),41.1 30.3.HRMS(ESI)Calcd.for C 10 H 11 D 3 BrO[(M+H) + ]232.0416,found 232.0424。
example 41
This example uses the same implementation as example 1, except that: the benzyl substrate used was 1,2,3, 4-tetrahydronaphthalene. The product obtained was 1- (deuterated methoxy) -1,2,3, 4-tetrahydronaphthalene in a yield of 70%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )δ137.5,136.6,129.3,129.0,127.5,125.7,29.1,27.4,18.7.HRMS(ESI)Calcd.for C 11 H 12 D 3 O[(M+H) + ]166.1311,found 166.1317。
example 42
This example uses the same implementation as example 1, except that: the benzyl substrate employed was 2- (4-methoxyphenyl) acetonitrile. The product obtained was 2- (deuteromethoxy) -2- (4-methoxyphenyl) acetonitrile in 82% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )δ7.41(d,J＝8.7Hz,2H),6.94(d,J＝8.7Hz,2H),5.14(s,1H),3.83(s,3H). 13 C NMR(100MHz,CDCl 3 )δ160.8,128.9,125.4,117.2,114.4,71.8,55.4.HRMS(ESI)Calcd.for C 10 H 9 D 3 NO 2 [(M+H) + ]181.1056,found 181.1063。
example 43
This example uses the same implementation as example 1, except that: the benzyl substrate used was diphenylmethane. The product obtained was ((deuterated methoxy) methylene) diphenyl in 84% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )δ7.25(q,J＝7.7Hz,8H),7.16(t,J＝6.7Hz,2H),5.16(s,1H). 13 C NMR(150MHz,CDCl 3 )δ142.1,128.4,127.5,126.9,85.4,56.2(quin,J＝21.3Hz).HRMS(ESI)Calcd.for C 14 H 12 D 3 O[(M+H) + ]202.1311,found 202.1317。
example 44
This example uses the same implementation as example 1, except that: the benzyl substrate used was 2-hexylthiophene. The product obtained was 2- (1- (deuterated methoxy) hexyl) thiophene in 71% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 11 H 16 D 3 OS[(M+H) + ]202.1345,found 202.1348。
example 45
This example uses the same implementation as example 1, except that: the benzyl substrate used was ibuprofen methyl ester. The product obtained was methyl 2- (4- (1- (deuterated methoxy) -2-methylpropyl) phenyl) propionate in a yield of 70%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 15 H 20 D 3 O 3 [(M+H) + ]254.1835,found 254.1837。
example 46
This example uses the same implementation as example 1, except that: the benzyl substrate employed 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 were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(150MHz,CDCl 3 )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 C 19 H 14 D 3 BrFOS[(M+H) + ]394.0356,found 394.0359。
example 47
This example uses the same implementation 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 were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 14 H 17 O[(M+H) + ]201.1279,found 201.1283。
example 48
This example uses the same implementation as example 1, except that: the alcohol substrate used is t-butanol. The product obtained was 1- (1- (tert-butyl) ethyl) naphthalene in a yield of 68%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 16 H 21 O[(M+H) + ]229.1592,found 229.1601。
example 49
This example uses the same implementation as example 1, except that: the alcohol substrate used is cyclohexanol. The product obtained was 1- (1- (cyclohexyloxyethyl) naphthalene in 60% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 18 H 23 O[(M+H) + ]255.1749,found 255.1753。
example 50
This example uses the same implementation as example 1, except that: the alcohol substrate used is 2, 2-trifluoroethan-1-ol. The product obtained was 1- (1- (2, 2-trifluoroethoxy) ethyl) naphthalene in a yield of 65%.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 14 H 14 F 3 O[(M+H) + ]255.0997,found 255.1003。
example 51
This example uses the same implementation as example 1, except that: the alcohol substrate used is 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 were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 19 H 26 NO 3 [(M+H) + ]316.1913,found 316.1917。
example 52
This example uses the same implementation as example 1, except that: the alcohol substrate used is ethylene glycol. The product obtained was 2- (1- (naphthalen-1-yl) ethoxy) ethan-1-ol in 88% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 14 H 17 O 2 [(M+H) + ]217.1229,found 217.1240。
example 53
This example uses the same implementation 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 were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 17 H 21 O 2 [(M+H) + ]257.1542,found 257.1549。
example 54
This example uses the same implementation as example 1, except that: the alcohol substrate used 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 were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 17 H 21 O 2 [(M+H) + ]257.1542,found 257.1544。
example 55
This example uses the same implementation as example 1, except that: the alcohol substrate used was ((3 aR,5R,5aS,8 bR) -2, 7-tetramethyltetrahydro-5H-bis ([ 1,3] dioxin) [4,5-b:4',5' -d ] pyran-5-yl) methanol. The product obtained was (3 aR,5R,5aS,8 bR) -2, 7-tetramethyl-5- ((1- (naphthalen-1-yl) ethoxy) methyl) tetrahydro-5H-bis ([ 1,3] dioxan) [4,5-b:4',5' -d ] pyran in 82% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 24 H 31 O 6 [(M+H) + ]415.2121,found 415.2125。
example 56
This example uses the same implementation as example 1, except that: the alcohol substrate employed was 1- ((3 ar,4r,6 ar) -6- (hydroxymethyl) -2, 2-dimethyltetrahydrofuran [3,4-d ] [1,3] dioxan-4-yl) pyrimidine-2, 4 (1 h,3 h) -dione. The product obtained was 1- ((3 ar,4r,6 ar) -2, 2-dimethyl-6- ((1- (naphthalen-1-yl) ethoxy) methyl) tetrahydrofuran [3,4-d ] [1,3] dioxo-4-yl) pyrimidine-2, 4 (1 h,3 h) -dione in 73% yield.
The nuclear magnetic resonance results were: 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(100MHz,CDCl 3 )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 C 24 H 27 N 2 O 6 [(M+H) + ]439.1869,found 439.1877。
the technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (5)

1. The synthesis method of the benzyl ether compound is characterized by comprising the following steps:
mixing benzyl compound, alcohols, metal catalyst, photocatalyst, oxidant and organic solvent to obtain a reaction system;
under the condition of isolating oxygen, using visible light as driving force to irradiate the reaction system, wherein the reaction temperature is-20-80 ℃; after the reaction is finished, purifying to obtain benzyl ether compounds;
the benzyl compound is an organic compound which is not modified and has the following structural general formula:
，
wherein Ar is selected from the group consisting of-Ph, 4-MeO-Ph, 3-MeO-Ph, 2-MeO-Ph, 4-Br-Ph, 4-Cl-Ph, 4-Ac-Ph, 4-CN-Ph, 4-COOCH 3 -Ph、4-CH 2 CH 2 COOCH 3 -any one of Ph, 4-PhO-Ph, 4-BzO-Ph, 4-Ph, 1-naphthyl, 2-thienyl, 2-furyl, 2-pyridyl, 2-pyrimidinyl; r is R 2 Selected from-H, -CH 3 、-nBu、-iPr、-Ph、-4-MeO-Ph、-4-Cl-Ph、-CN、-COOMe、-CH 2 CH 2 Br、-CH 2 CH 2 Cl、-CH 2 CH 2 OBz、-CH 2 CH 2 Any one of OAc;
the structural general formula of the alcohol is as follows:
，
wherein R is 1 Selected from-CH 3 、-Et、-CD 3 、-nPr、-iPr、-nBu、-tBu、-Cy、-CH 2 Ph、-CH 2 CF 3 、-CH 2 COOMe、-CH 2 CH 2 OCH 3 、-CH 2 CH 2 OPh、-CH 2 CH 2 OH、-CH 2 CH 2 NHBoc、-2-
Any one of methylene tetrahydrofuranyl, -3-tetrahydrofuranyl, -2-methylene tetrahydro-2H-pyranyl, -4-tetrahydro-2H-pyranyl, -glucose, -mannose, -ribose, -deoxyribose, -rhamnosyl;
the metal catalyst is a nickel catalyst;
the photocatalyst is selected from Ru (bpy) 3 Cl 2 ·6H 2 O、Ir(ppy) 3 、[Ir{dF(CF 3 )ppy} 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 One of 4CzIPN, benzaldehyde, benzophenone, 9-fluorenone, rose bengal, acid red, rhodamine and riboflavin; the dosage of the photocatalyst is 0.1-20 mol percent;
the oxidant is selected from one of ammonium persulfate, sodium persulfate, potassium persulfate, selected fluorine, N-fluoro-bis-benzene sulfonamide, [ bis (acetoxy) iodine ] benzene, [ bis (trifluoroacetoxy) iodine ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide and tert-butyl hydroperoxide; the dosage of the oxidant is 100-500 mol percent;
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;
the structural general formula of the benzyl ether compound is shown as the following formula:
。
2. the synthesis method according to claim 1, wherein the nickel-based catalyst is one selected from the group consisting of nickel acetylacetonate, nickel chloride, nickel bromide and nickel acetate.
3. The method of synthesis according to claim 1, wherein the metal catalyst is used in an amount of 0.1 to 20 mol%.
4. The method according to claim 1, wherein the light irradiation time of the reaction system is 2 to 48 hours.
5. The synthetic method of claim 1 wherein the purification is performed by column chromatography.
CN202111040688.2A 2021-09-07 2021-09-07 Benzyl ether compound and synthesis method thereof Active CN113717033B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111040688.2A CN113717033B (en) 2021-09-07 2021-09-07 Benzyl ether compound and synthesis method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111040688.2A CN113717033B (en) 2021-09-07 2021-09-07 Benzyl ether compound and synthesis method thereof

Publications (2)

Publication Number Publication Date
CN113717033A CN113717033A (en) 2021-11-30
CN113717033B true CN113717033B (en) 2024-03-15

Family

ID=78682242

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111040688.2A Active CN113717033B (en) 2021-09-07 2021-09-07 Benzyl ether compound and synthesis method thereof

Country Status (1)

Country Link
CN (1) CN113717033B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104844427A (en) * 2015-04-14 2015-08-19 哈尔滨工业大学 Synthetic method of benzyl ether compound
CN112645821A (en) * 2021-01-22 2021-04-13 苏州大学 Method for synthesizing aryl benzyl ether compound

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104844427A (en) * 2015-04-14 2015-08-19 哈尔滨工业大学 Synthetic method of benzyl ether compound
CN112645821A (en) * 2021-01-22 2021-04-13 苏州大学 Method for synthesizing aryl benzyl ether compound

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Balfe Michael Philip et al.Alkyl-Oxygen Fission in Carboxylic Esters Part III.Journal of the Chemical Society.1946,第797-803页. *
Byung Joo Lee et al.Site-Selective Alkoxylation of Benzylic C–H Bonds via Photoredox Catalysis.Angewandte Chemie.2019,第132卷(第1期),第1-7页. *
Min Dong et al.A photoredox/nickel dual-catalytic strategy for benzylic C–H alkoxylation.Organic Chemistry Frontiers.2021,第8卷(第24期),第6881-6887页. *
Wolfram Sander et al.Hydrogen bonding switches the spin state of diphenylcarbene from triplet to singlet.Angew Chem Int Ed Engl.2014,第53卷(第20期),第5122-5125页，支持信息第1-28页. *

Also Published As

Publication number Publication date
CN113717033A (en) 2021-11-30

Similar Documents

Publication Publication Date Title
CN101274915B (en) Method for synthesizing isoxazole
CN104910104B (en) A kind of method of utilization copper catalysis synthesizing dihydro furan derivatives
CN113717033B (en) Benzyl ether compound and synthesis method thereof
US20140200355A1 (en) Method for Preparing Optically Pure (-)-Clausenamide Compound
CN101402582A (en) Synthesis of alpha-hydroxyl-beta-aminophenol with optical activity
Rychnovsky et al. 1-methylcyclopropyl (MCP) ethers as protecting groups
WO2015067110A1 (en) Ticagrelor intermediate preparation method
CN102344431B (en) Method for preparing nebivolol hydrochloride
CN111116530A (en) Method for synthesizing beraprost
CN114907197B (en) Preparation method of biaziridine-based photocrosslinking probe intermediate and derivative
CN114105869B (en) Preparation method of 2-propyl-4-cyanopyridine
CN115340481A (en) Method for industrially producing deuterated medical intermediate by adopting immobilized nickel catalysis
CN114716361B (en) Method for synthesizing chiral spiro indenone-pyrrole compound
CN109438402B (en) Benzofuranone derivatives and synthesis method thereof
CN101875658B (en) Preparation method of 3-carbonyl-2,8-diazepine helix[4.5]decane-8-carboxylic acid tert-butyl ester
JP3999028B2 (en) Process for producing optically active 2-acylated 1,2-diol compound derivative
RU2282633C9 (en) Method for preparing 1,11-dialkyl-3,5-dihydrofuro-[2',3':3,4]-cyclohepta[c]isochromens
Chen et al. Total synthesis of γ-trifluoromethylated analogs of goniothalamin and their derivatives
JP2001139508A (en) Optically active fluorine-containing binaphthol derivative
CN104857989B (en) A kind of biguanide base aluminium gold metal catalyst and its preparation method and application
CN105272957B (en) A kind of green synthesis method of neutral ion liquid catalyst glycerine converting carbonic ester
CN115124472B (en) Indolizole compound and photoinduced synthesis method thereof
WO2024040754A1 (en) Method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane
CN110407677B (en) Preparation method and application of diphenylethanedione compound
CN108912077B (en) Preparation method of chiral phthalide derivative

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant