CN116041220A - Preparation method of aryl substituted amide compound - Google Patents

Preparation method of aryl substituted amide compound Download PDF

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CN116041220A
CN116041220A CN202211740238.9A CN202211740238A CN116041220A CN 116041220 A CN116041220 A CN 116041220A CN 202211740238 A CN202211740238 A CN 202211740238A CN 116041220 A CN116041220 A CN 116041220A
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aryl
substituted amide
amide compound
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CN116041220B (en
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张依凡
刘石惠
姜玉新
张兴贤
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Zhejiang University of Technology ZJUT
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    • 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
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • 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
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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Abstract

The invention discloses a preparation method of an aryl substituted amide compound, which comprises the following steps: mixing a benzyl compound, amines, a metal catalyst, a photocatalyst, an oxidant and an organic solvent to obtain a reaction system; under the condition of isolating oxygen, using visible light as driving force to irradiate the reaction system; after the reaction is finished, purifying to obtain the benzyl imine 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 medicines, pesticides, materials and the like.

Description

Preparation method of aryl substituted amide compound
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an aryl-substituted amide compound.
Background
Benzyl amine 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. The nitrogen-containing functional groups can be obtained by a wide range of synthetic methods. These reactions include coupling of amines and carboxylic acids (typically requiring the use of coupling reagents), nucleophilic acyl substitution, beckmann rearrangement, fabry-perot rearrangement, and the like. All of these methods involve the retrosynthetic cleavage of the N-carbon based bond or rearrangement of the substrate core structure, thereby limiting the synthetic pathways available for highly functionalized amines.
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. However, this strategy builds on aromatic C-N bonds, still lacking in terms of C (sp 3 ) Bonding with free amine groups. In addition, in the prior art scheme, most of methods for coupling the benzyl C-H bond and the amino group into a bond under the action of a metal catalyst need high temperature conditions and long reaction time, and are not mild and efficient. Thus, a green and efficient construction of C- (sp) with benzyl and simple amines was developed 3 ) The method of the-N bond is critical.
Disclosure of Invention
In view of the foregoing, it is desirable to provide a method for synthesizing aryl-substituted amides, which uses unmodified amines and benzyl compounds as starting materials, and uses visible light as driving force under the conditions of a metal catalyst, a ligand, a photocatalyst and an oxidant to prepare the aryl-substituted amides. 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 preparation method of an aryl substituted amide compound shown in a formula (III), which comprises the following steps:
Figure BDA0004033942740000011
mixing a compound shown in a formula (I), an amine compound shown in a formula (II), a metal catalyst, a photocatalyst, a ligand and an oxidant, adding the mixture into an organic solvent, and carrying out aftertreatment on the obtained reaction solution under a protective atmosphere (nitrogen in the embodiment of the invention) for 2-12 hours (preferably, blue light with a wavelength of 390-470nm and a wavelength of 20-35 ℃ for 12 hours) under visible light (360-830 nm) at 10-50 ℃ to obtain an aryl-substituted amide compound shown in the formula (III);
Figure BDA0004033942740000021
in the formula (I) and the formula (III), R 1 One selected from naphthyl and 2-chloro-5-bromophenyl, R 2 One selected from methyl, cyano and 4-ethoxyphenyl; or R is 1 And R is R 2 And C is connected between them to form { [ 7-acetyl-3, 3-dimethyl-5- (2-methylpropan-2-yl) -2, 3-dihydro-1H-indenyl ]]Methyl amino } methane; in general, the compound of formula (I) is selected from 1-ethylnaphthalene, 1-naphthylacetonitrile, 5-bromo-2-chloro-4' -ethoxydiphenylmethane, 1- [1, 1-dimethyl-6- (2-methylpropan-2-yl) -2, 3-dihydro-1H-inden-4-yl]One of the ethyl-1-ketone;
in the formula (II), R3 is selected from one of methoxycarbonyl, tert-butoxycarbonyl, 4-methylbenzenesulfonyl and benzyloxycarbonyl, and R4 is selected from one of hydrogen and methyl;
the ratio of the amounts of the compound shown in the formula (I), the amine compound shown in the formula (II), the metal catalyst, the photocatalyst, the ligand and the oxidant is 1:1.5:0.001 to 0.2:0.001 to 0.2: 0.001-0.2:1-5, preferably 1:1.5:0.05-0.1:0.02-0.05:0.05-0.1:2-4;
the metal catalyst is a copper catalyst and is selected from one of cuprous iodide, cuprous chloride, cupric chloride, cuprous bromide and cupric acetate (preferably cuprous iodide);
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 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile, 9-fluorenone, rose bengal, acid red, rhodamine, xanthone and 10-methyl-9-mesityl acridine perchlorate;
the ligand is selected from one of 1, 10-phenanthroline, 4, 7-dimethyl-1, 10-phenanthroline, 4,7' -dimethoxy-1, 10-phenanthroline, 4,7' -diphenyl-1, 10-phenanthroline, 4' -dimethyl bipyridine, 2' -di-tert-butyl-2, 2' -bipyridine and tetramethyl propylene diamine;
the oxidant is selected from one of ammonium sulfate, sodium persulfate, potassium persulfate, selectFluor reagent, N-fluoro-bis-benzenesulfonamide, [ bis (acetoxy) iodo ] benzene, [ bis (trifluoroacetoxy) iodo ] benzene, 2-iodoxybenzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide and tert-butyl hydroperoxide (SelectFluor reagent is preferred).
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, N-methylpyrrolidone and hexafluoroisopropanol (preferably acetonitrile).
The volume of the organic solvent is 0.01-0.1mL/mg based on the mass of the compound shown in the formula (I).
The post-treatment is as follows: extracting the reaction liquid with ethyl acetate, distilling an organic phase to remove a solvent, separating residues by column chromatography with 200-300 meshes of silica gel, eluting with a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1:1-1:50 as an eluent, collecting an eluent containing a target product, evaporating the eluent to remove the solvent, and drying to obtain the aryl substituted amide compound shown in the formula (III).
Specifically, the aryl substituted amide compound shown in the formula (III) and the corresponding compound shown in the formula (I) and amine compound shown in the formula (II) are prepared by the aryl substituted amide compound shown in the formula (III) as shown in the following table:
Figure BDA0004033942740000031
Figure BDA0004033942740000041
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 amine and benzyl compound as reaction substrates, directly obtains the aryl substituted amide compound by one-step reaction under the mild condition, has the advantages of wide cheap reaction substrates, 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.
Figure BDA0004033942740000042
The method can be used for structural modification of 5-bromo-2-chloro-4' -ethoxydiphenylmethane, the structure is an intermediate of the hypoglycemic drug dapagliflozin, and dapagliflozin is a sodium-glucose cotransporter 2 (SGLT-2) inhibitor and can be used for treating type 2 diabetes. Example 40
Figure BDA0004033942740000043
The method can be used for structural modification of the salix musk, amino is connected on the structure of the salix musk, and the methyl { [ 7-acetyl-3, 3-dimethyl-5- (2-methylpropan-2-yl) -2, 3-dihydro-1H-indenyl ] amino } methane synthesized by the method can be used as a fragrance-preserving and fixing agent to be applied to modern daily chemical products. Example 41
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.
(I)
The technical scheme of the invention is further described through specific examples.
Example 1
78.1mg of 1-ethylnaphthalene (0.5 mmol) and 56.3mg of methyl carbamate (0.75 mmol) were placed in 2.5mL of acetonitrile, then 4.8mg of copper iodide (0.025 mmol) as a metal catalyst, 5.2mg of ligand 2, 9-dimethyl-1, 10-phenanthroline (0.025 mmol), 10.3mg of photocatalyst 10-methyl-9-trimesoylacridine perchlorate (0.025 mol) and 354.3mg of oxidant SelectFluor reagent (1.0 mmol) were added, and the reaction apparatus was charged with inert gas (N) 2 ) Displacing air within the device;
taking visible light as driving force (12W, blue light), and reacting for 12h at 25 ℃; after the reaction is finished, extracting the obtained reaction solution with ethyl acetate, distilling to remove solvent, separating the residue by column chromatography with 200-300 mesh silica gel, eluting with a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1:10 as an eluent, evaporating the eluent to remove the solvent and drying to obtain the product { [1- (naphthalene-1-yl) ethyl]Methyl amino } methane ester 97.4mg was found to be 85% yield. 1 H NMR(400MHz,CDCl 3 )δ8.13(d,J＝6.7Hz,1H),7.87(d,J＝7.8Hz,1H),7.78(d,J＝7.8Hz,1H),7.60-7.37(m,4H),5.66(s,1H),5.03(s,1H),3.67(s,3H),1.66(d,J＝12.7Hz,3H)；HRMS(ESI)m/z:[M+H] + Calcd.for C 14 H 15 NO 2 229.1103,found 229.1103。
Example 2
This example uses the same implementation as example 1, except that: the photocatalyst used was [ Ir { dF (CF) 3 )ppy} 2 (dtbbpy)]PF 6 (2.8 mg,0.0025 mmol) to yield the product { [1- (naphthalen-1-yl) ethyl ]]Methyl amino } methane was 97.4mg in 85% yield.
Example 3
This example uses the same implementation as example 1, except that: the photocatalyst used was [ Ir (ppy) 2 (dtbbpy)]PF 6 (2.3 mg,0.0025 mmol) to yield the product { [1- (naphthalen-1-yl) ethyl ]]Methyl amino } methane was 75.6mg in 66% yield.
Example 4
This example uses the same implementation as example 1, except that: the photocatalyst used was Ir (ppy) 3 (1.6 mg,0.0025 mmol) product { [1- (naphthalen-1-yl) ethyl ]]Methyl amino } methane was 67.6mg in 59% yield.
Example 5
This example uses the same implementation as example 1, except that: the photocatalyst used was Ru (bpy) 3 Cl 2 ·6H 2 O (1.6 mg,0.0025 mmol), product { [1- (naphthalen-1-yl) ethyl]Methyl amino } methane was 67.6mg in 59% yield.
Example 6
This example uses the same implementation as example 1, except that: the photocatalyst used was 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (19.7 mg,0.025 mmol) as the photocatalyst, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane ester 85.9mg, 75% yield.
Example 7
This example uses the same implementation as example 1, except that: the photocatalyst used was xanthone (19.6 mg,0.1 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 91.6mg in 80% yield.
Example 8
This example uses the same implementation as example 1, except that: the photocatalyst used was acid red (16.2 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 83.6mg in 73% yield.
Example 9
This example uses the same implementation as example 1, except that: the amount of the photocatalyst used was 20.6mg,0.05mmol, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 74.5mg, yield 65%.
Example 10
This example uses the same implementation as example 1, except that: the amount of the photocatalyst used was 5.1mg,0.0125mmol, and the product was 56.1mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate in 49% yield.
Example 11
This example uses the same implementation as example 1, except that: the metal catalyst used was copper chloride (3.4 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 69.9mg in 61% yield.
Example 12
This example uses the same implementation as example 1, except that: the metal catalyst used was cuprous chloride (2.5 mg,0.025 mmol) and methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 68.7mg was 60% yield.
Example 13
This example uses the same implementation as example 1, except that: the metal catalyst used was copper acetate (5.0 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 90.1mg in 83% yield.
Example 14
This example uses the same implementation as example 1, except that: the metal catalyst used was nickel bromide (5.5 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 64.1mg in 56% yield.
Example 15
This example uses the same implementation as example 1, except that: the metal catalyst used was nickel tetra-acetylacetonate (6.4 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 40.1mg in 35% yield.
Example 16
This example uses the same implementation as example 1, except that: the metal catalyst used was nickel acetate tetrahydrate (6.2 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 19.5mg in 17% yield.
Example 17
This example uses the same implementation as example 1, except that: the metal catalyst used was cobalt chloride (3.2 mg,0.025 mmol), 38.9mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate, 34% yield, 23.8mg of by-product 1-acetylnaphthalene, 28% yield.
Example 18
This example uses the same implementation as example 1, except that: the amount of the metal catalyst used was 4.9mg,0.05mmol, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 61.9mg, yield 54%.
Example 19
This example uses the same implementation as example 1, except that: the ligand used was 1, 10-phenanthroline (4.5 mg,0.025 mmol) and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 72.2mg in 63% yield.
Example 20
This example uses the same implementation as example 1, except that: the ligand used was 4, 7-dimethyl-1, 10-phenanthroline (5.2 mg,0.025 mmol), and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane acid 63.0mg in 55% yield.
Example 21
This example uses the same implementation as example 1, except that: the ligand used was 4, 7-dimethoxy-1, 10-phenanthroline (6.0 mg,0.025 mmol), and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane acid 76.8mg, 67% yield.
Example 22
This example uses the same implementation as example 1, except that: the ligand used was 4, 7-diphenyl-1, 10-phenanthroline (8.3 mg,0.025 mmol), and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane acid 59.6mg in 52% yield.
Example 23
This example uses the same implementation as example 1, except that: the ligand used was 4,4 '-dimethyl-2, 2' -bipyridine (4.6 mg,0.025 mmol), methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 83.6mg in 73% yield.
Example 24
This example uses the same implementation as example 1, except that: the ligand used was 2,2' -bipyridine (3.9 mg,0.025 mmol), methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 22.9mg in 20% yield.
Example 25
This example uses the same implementation as example 1, except that: the ligand used was 4,4 '-di-tert-butyl-2, 2' -bipyridine (6.7 mg,0.025 mmol), methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane acid ester 37.8mg in 33% yield.
Example 26
This example uses the same implementation as example 1, except that: the ligand used was tetramethyl propylenediamine (3.3 mg,0.025 mmol), 30.0mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate was produced in 27% yield.
Example 27
This example uses the same implementation as example 1, except that: the oxidant employed was N-fluorobis-benzenesulfonamide (315.2 mg,1 mmol) and methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 75.6mg in 66% yield.
Example 28
This example uses the same implementation as example 1, except that: the amount of the oxidizing agent used was 708.6mg,2.0mmol, and 73.3mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate was produced in a yield of 64%.
Example 29
This example uses the same implementation as example 1, except that: the amount of the oxidizing agent used was 177.1mg,0.5mmol, and 53.8mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate was produced in a yield of 47%.
Example 30
This example uses the same implementation as example 1, except that: the solvent used was 2.5ml of methylene chloride, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 27.5mg was 24% yield.
Example 31
This example uses the same implementation as example 1, except that: the solvent used was 2.5ml of N, N-dimethylformamide, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate was 30.9mg in 27% yield.
Example 32
This example uses the same implementation as example 1, except that: the solvent used was 2.5ml of tetrahydrofuran, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 56.1mg was 49% yield.
Example 33
This example uses the same implementation as example 1, except that: the solvent used was 2.5ml of a mixture of dichloromethane and hexafluoroisopropanol in a volume ratio of 8:1, and the product was 19.5mg of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate in 17% yield.
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 methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 60.7mg was 53%.
Example 35
This example uses the same implementation as example 1, except that: the amount of solvent used was 5.0mL, and the yield was 62% of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 71.1 mg.
Example 36
This example uses the same implementation as example 1, except that: the reaction temperature used was 10deg.C, and the product methyl { [1- (naphthalen-1-yl) ethyl ] amino } methane 91.6mg was 80% yield.
Example 37
This example uses the same implementation as example 1, except that: the reaction temperature used was 35℃and the yield of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 97.4mg was 85%.
Example 38
This example uses the same implementation as example 1, except that: the reaction temperature used was 40℃and the yield of methyl { [1- (naphthalen-1-yl) ethyl ] amino } methanoate 71.1mg was 62%.
Example 39
This example uses the same implementation as example 1, except that: the benzyl compound used was 1-naphthalonitrile (83.6 mg,0.5 mmol). The product obtained was { [ cyano (naphthalen-1-yl) methyl]Methyl amino } methane ester 74.4mg was found to be 62% yield. 1 H NMR(400MHz,CDCl 3 )δ7.91(d,J＝6.8Hz,3H),7.85(d,J＝7.0Hz,1H),7.65–7.53(m,2H),7.50(t,J＝7.7Hz,1H),6.46(d,J＝7.8Hz,1H),5.34(s,1H),3.76(s,3H).HRMS(ESI)m/z:[M+H] + Calcd.for C 14 H 12 N 2 O 2 240.0899,found 240.0899。
Example 40
This example uses the same implementation as example 1, except that: the benzyl compound employed was 5-bromo-2-chloro-4' -ethoxydiphenylmethane (162.8 mg,0.5 mmol). The product obtained was { [ (5-bromo-2-chlorophenyl) (4-ethoxyphenyl) methyl]Methyl amino } methane 113.1mg was found to be 57% yield. 1 H NMR(400MHz,CDCl 3 )δ7.54(s,1H),7.34(d,J＝8.4Hz,1H),7.22(t,J＝11.8Hz,1H),7.07(d,J＝7.7Hz,2H),6.84(dd,J＝21.2,7.3Hz,2H),6.12(s,1H),5.31(s,1H),4.05–3.93(m,2H),3.68(s,3H),1.47–1.32(t,3H)；HRMS(ESI)m/z:[M+H] + Calcd.for C 17 H 17 BrClNO 3 397.0080,found 397.0080。
Example 41
This example uses the same implementation as example 1, except that: the benzyl compound employed is 1- [1, 1-dimethyl-6- (2-methylpropan-2-yl) -2, 3-dihydro-1H-inden-4-yl]Ethyl-1-one (122.2 mg,0.5 mmol). The product obtained was { [ 7-acetyl-3, 3-dimethyl-5- (2-methylpropan-2-yl) -2, 3-dihydro-1H-indenyl ]]Methyl amino } methane was 50.8mg in 32% yield. 1 H NMR(400MHz,CDCl 3 )δ7.61(s,1H),7.35(s,1H),5.42(t,1H),4.86(s,1H),3.67(s,3H),2.56(s,3H),2.05(d,J＝17.9Hz,2H),1.34(s,9H),1.26(s,6H)；HRMS(ESI)m/z:[M+H] + Calcd.For C 19 H 27 NO 3 317.1991,found 317.1991。
Example 42
This example uses the same implementation as example 1, except that: the amine compound used was benzyl carbamate (113.4 mg,0.75 mmol). The product obtained was { [1- (naphthalen-1-yl) ethyl ]]Benzyl amino } methanoate 111.4mg in 73% yield. 1 H NMR(400MHz,CDCl 3 )δ8.14(s,1H),7.87(d,J＝7.9Hz,1H),7.79(d,J＝7.9Hz,1H),7.63–7.38(m,5H),7.34(s,4H),5.69(s,1H),5.23–5.00(m,2H),1.63(d,J＝13.5Hz,3H)；HRMS(ESI)m/z:[M+H] + Calcd.For C 20 H 19 NO 2 305.1416,found 305.1416。
Example 43
This example uses the same implementation as example 1, except that: the amine compound used was tert-butyl carbamate (87.9 mg,0.75 mmol). The product obtained was { [1- (naphthalen-1-yl) ethyl ]]Amino } methanoic acid-2-methylpropan-2-yl ester 92.2mg, yield 68%. 1 H NMR(400MHz,CDCl 3 )δ8.12(s,1H),7.85(d,J＝7.1Hz,1H),7.76(d,J＝7.2Hz,1H),7.48(t,J＝19.5Hz,4H),5.60(s,1H),4.87(s,1H),1.60(s,3H),1.43(s,9H)；HRMS(ESI)m/z:[M+H] + Calcd.for C 17 H 21 NO 2 271.1572,found 271.1572。
Example 44
This example uses the same implementation as example 1, except that: the amine compound used was N-methyl-p-toluenesulfonamide (138.9 mg,0.75 mmol). The product obtained is 4, N-dimethyl-N- [1- (naphthalen-1-yl) ethyl]97.5mg of benzenesulfonamide gave a yield of 60%. 1 H NMR(400MHz,CDCl 3 )δ8.60(d,J＝8.5Hz,1H),7.92–7.73(m,4H),7.60(t,J＝7.5Hz,1H),7.52(t,J＝7.4Hz,1H),7.47–7.38(m,2H),7.38–7.22(m,2H),6.23–6.11(m,1H),2.44(s,3H),2.42(s,3H),1.49(t,J＝10.7Hz,3H)；HRMS(ESI)m/z:[M+H] + Calcd.For C 19 H 19 NO 2 S 325.1136,found 325.1136。
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 (10)

1. A method for preparing an aryl-substituted amide compound shown in a formula (III), which is characterized in that the method comprises the following steps: mixing a compound shown in a formula (I), an amine compound shown in a formula (II), a metal catalyst, a photocatalyst, a ligand and an oxidant, adding the mixture into an organic solvent, and carrying out visible light irradiation at a temperature of between 10 and 50 ℃ for 360 and 830nm for 2 to 12 hours under a protective atmosphere, wherein the obtained reaction solution is subjected to post-treatment to obtain an aryl substituted amide compound shown in a formula (III);
Figure FDA0004033942730000011
in the formula (I) and the formula (III), R 1 One selected from naphthyl and 2-chloro-5-bromophenyl, R 2 One selected from methyl, cyano and 4-ethoxyphenyl; or R is 1 And R is R 2 And C is connected between them to form { [ 7-acetyl-3, 3-dimethyl-5- (2-methylpropan-2-yl) -2, 3-dihydro-1H-indenyl ]]Methyl amino } methane;
in the formula (II) and the formula (III), R 3 One of methoxycarbonyl, t-butoxycarbonyl, 4-methylbenzenesulfonyl and benzyloxycarbonyl, and R4 is one of hydrogen and methyl;
the ratio of the amounts of the compound shown in the formula (I), the amine compound shown in the formula (II), the metal catalyst, the photocatalyst, the ligand and the oxidant is 1:1.5:0.001 to 0.2:0.001 to 0.2: 0.001-0.2:1-5;
the metal catalyst is a copper catalyst and is selected from one of cuprous iodide, cuprous chloride, cupric chloride, cuprous bromide and cupric acetate;
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 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile, 9-fluorenone, rose bengal, acid red, rhodamine, xanthone and 10-methyl-9-mesityl acridine perchlorate;
the ligand is selected from one of 1, 10-phenanthroline, 4, 7-dimethyl-1, 10-phenanthroline, 4,7' -dimethoxy-1, 10-phenanthroline, 4,7' -diphenyl-1, 10-phenanthroline, 4' -dimethyl bipyridine, 2' -di-tert-butyl-2, 2' -bipyridine and tetramethyl propylene diamine;
the oxidant is selected from one of ammonium sulfate, sodium persulfate, potassium persulfate, selectfluor reagent, N-fluoro-bis-benzene sulfonamide, [ bis (acetoxy) iodo ] benzene, [ bis (trifluoroacetoxy) iodo ] benzene, 2-iodoacyl benzoic acid, m-chloroperoxybenzoic acid, hydrogen peroxide and tert-butyl hydroperoxide.
2. The process for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein: the reaction is carried out for 12 hours under the conditions of blue light with the wavelength of 390-470nm and the temperature of 20-35 ℃.
3. The process for producing an aryl-substituted amide compound of the formula (III) according to claim 1, wherein the organic solvent is one or a mixture of two selected from acetonitrile, ethyl acetate, methylene chloride, tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 2-dichloroethane, N-methylpyrrolidone and hexafluoroisopropanol.
4. A process for the preparation of aryl substituted amides of formula (III) according to claim 3, characterized in that the organic solvent is selected from acetonitrile.
5. The process for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the volume of the organic solvent is 0.01 to 0.1mL/mg based on the mass of the compound represented by the formula (I).
6. The process for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the post-treatment is: extracting the reaction liquid with ethyl acetate, distilling an organic phase to remove a solvent, separating residues by column chromatography with 200-300 meshes of silica gel, eluting with a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1:1-50 as an eluent, collecting an eluent containing a target product, evaporating the eluent to remove the solvent, and drying to obtain the aryl substituted amide compound shown in the formula (III).
7. The method for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the amount ratio of the benzyl compound represented by the formula (I), the amine compound represented by the formula (II), the metal catalyst, the photocatalyst, the ligand and the oxidizing agent is 1:1.5:0.05 to 0.1:0.02 to 0.05:0.05 to 0.1:2 to 4.
8. The method for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the metal catalyst is cuprous iodide.
9. The method for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the oxidizing agent is a Selectfluor reagent.
10. The method for producing an aryl-substituted amide compound represented by the formula (III) according to claim 1, wherein the aryl-substituted amide compound represented by the formula (III) is one of the following formulas:
Figure FDA0004033942730000021
Figure FDA0004033942730000022
Figure FDA0004033942730000031
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Publication number Priority date Publication date Assignee Title
CN104003828A (en) * 2014-06-06 2014-08-27 天津师范大学 Preparation method of amine and aromaticnitrile coupling reaction catalyzed by copper complex under visible light

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Publication number Priority date Publication date Assignee Title
CN104003828A (en) * 2014-06-06 2014-08-27 天津师范大学 Preparation method of amine and aromaticnitrile coupling reaction catalyzed by copper complex under visible light

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LIU SHUAI等: ""Copper-catalyzed oxidative benzylic C(sp3)–H amination: direct synthesis of benzylic carbamates"", CHEM. COMMUN., vol. 56, pages 13013 - 13016 *
ZHANG YIFAN等: ""Photoredox/Copper Dual-Catalyzed Benzylic C-H Esterification via Radical-Polar Crossover"", ORG. LETT., vol. 24, pages 2679 - 2683 *
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