CN102816041A - Preparation method of diarylmethane derivatives - Google Patents
Preparation method of diarylmethane derivatives Download PDFInfo
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- CN102816041A CN102816041A CN2012102795752A CN201210279575A CN102816041A CN 102816041 A CN102816041 A CN 102816041A CN 2012102795752 A CN2012102795752 A CN 2012102795752A CN 201210279575 A CN201210279575 A CN 201210279575A CN 102816041 A CN102816041 A CN 102816041A
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- CBBKXGHQKKUQQJ-UHFFFAOYSA-N Bc1cc(C)ccc1 Chemical compound Bc1cc(C)ccc1 CBBKXGHQKKUQQJ-UHFFFAOYSA-N 0.000 description 1
- DMHZDOTYAVHSEH-UHFFFAOYSA-N Cc1ccc(CCl)cc1 Chemical compound Cc1ccc(CCl)cc1 DMHZDOTYAVHSEH-UHFFFAOYSA-N 0.000 description 1
- 0 Cc1ccc(Cc2cccc(*)c2)cc1 Chemical compound Cc1ccc(Cc2cccc(*)c2)cc1 0.000 description 1
- SFWBHKMWCCQRLN-UHFFFAOYSA-N Pc(cccc1-c2ccccc2)c1[N](C1P(Cl)Cl)(C=CN1c(c(-c1ccccc1)ccc1)c1-c1ccccc1)I Chemical compound Pc(cccc1-c2ccccc2)c1[N](C1P(Cl)Cl)(C=CN1c(c(-c1ccccc1)ccc1)c1-c1ccccc1)I SFWBHKMWCCQRLN-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a preparation method of diarylmethane derivatives. The preparation method is characterized in that a benzylchloride and an arylboronic acid or a potassium arylfluoborate undergo a coupling reaction in a pure water phase in the presence of an n-heterocyclic carbine-metal-imidazole complex as a catalyst to produce the diarylmethane derivative. The catalyst adopted by the preparation method can be massively synthesized easily only by a one-step reaction of a corresponding imidazole salt and is stable relatively to air and water vapor. Compared with other catalyst systems reported in literatures, the catalyst adopted by the preparation method has the advantages that raw materials are cheap and easily available; a reaction substrate has wide application; clean, nontoxic and easily available water as a solvent is used in a reaction; operation is easy; reaction equipment requirements are very low; large scale production requirements are satisfied; and industrial application prospects are good.
Description
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to a kind of preparation method of diarylmethanes verivate.
Background technology
The diarylmethanes verivate has good biology and pharmaceutical activity; And they still are the structural unit of important molecule in the pharmaceutical industry; The method of usually synthetic this compounds is the Friedel-Crafts alkylated reaction between aromatic compounds and the benzyl halohydrocarbon, in this type reaction, owing to using the above Lewis acid of equivalent and equivalent as catalyzer; Post-reaction treatment is not easy very much; And because the strong lewis acid catalyzer has stronger corrodibility, the height also suitable to the requirement of equipment is unfavorable for large-scale industrialization production.In the last few years; Transition metal-catalyzed Suzuki linked reaction has become the important method that forms C-C; This possibly give the credit to the organoboron reagent in the Suzuki linked reaction, than other metal reagent such as MAGNESIUM METAL 99 reagent, metallic tin reagent, metallic zinc reagent; Pure Silicon Metal reagent has hypotoxicity, high functional group compatibility and the higher stability to heat, air, steam etc.Yet the benzyl muriate is because strong C (sp
3The existence of)-Cl key is not widely used in transition metal-catalyzed Suzuki linked reaction.In the transition metal-catalyzed example of these successes, the catalytic effect that all must use highly active phosphine part just can obtain.Yet the phosphine part has easy oxidation by air, expensive, poisonous or the like shortcoming usually, also is unfavorable for large-scale industrial production.In the last few years, N-heterocyclic carbine and metal complex thereof because have higher thermostability than containing phosphine part and metal complex thereof, be difficult for oxidation by air, to insensitive or the like the advantage of steam, the application in synthetic has obtained paying close attention to widely.Yet; Though N-heterocyclic carbine-metal complex has these Inherent advantage; But their application in the halid Suzuki linked reaction of catalysis benzyl are still very limited; And in these known reported in literature, N-heterocyclic carbine-metal complex all is not easy synthetic or also need uses expensive starting raw material.Than organic solvent, water since have nontoxic, do not have volatility, cheap, advantage is easy to get or the like.Therefore if can development stability, N-heterocyclic carbine-metal complex of being easy to get, and be applied to the muriatic Suzuki linked reaction of catalysis aqueous phase benzyl, will have very important realistic meaning and prospects for commercial application.
Summary of the invention
The problem that the present invention will solve is to provide a kind of method: be simple and easy to N-heterocyclic carbine-palladium metal-imidazol complex be catalyzer; Realize the Suzuki linked reaction between benzyl halogenide and aryl boric acid or the aryl fluoride potassium borate, to reach the purpose that forms C-C.
A kind of preparation method of diarylmethanes verivate, said diarylmethanes derivant structure formula suc as formula
（Ⅰ）：
R wherein
1A substituting group or multi-substituent on the expression phenyl ring; And R
2A substituting group or multi-substituent on the expression phenyl ring, this method makes the benzyl halogenide shown in the formula II:
R wherein
1Definition is like I; X representes iodine, bromine or chlorine,
Under the 0-150 ℃ of temperature, in the presence of alkali, in the mixed solvent of water, THF, benzene, toluene, dioxane or organic solvent and water, under the catalysis of the N-heterocyclic carbine-metal shown in the formula III-imidazol complex:
R wherein
3Expression H, C
1-C
6Alkoxyl group or C
1-C
6Alkyl; R
4Expression H, C
1-C
6Alkoxyl group or C
1-C
6Alkyl; Z is I
-, Br
-, Cl
-, CH
3COO
-, CF
3COO
-Or CF
3SO
3 -R
5Expression C
1-C
6Alkyl or aryl or benzo aromatic ring; M representes iron, copper, silver, nickel, palladium, cobalt, rhodium or ruthenium,
Carry out linked reaction with aryl boric acid shown in the formula IV or aryl fluoride potassium borate,
R wherein
2Definition is like I; Y representes B (OH)
2Or BF
3K.
Preferably, R in the formula I
1Can be H, C
1-C
6Alkoxyl group, NO
2, CN, COR
6(R
6Be H, C
1-C
6Alkyl, aryl etc.), COO R
7(R
7Can be H or C
1-C
6Alkyl), C
1-C
6Alkyl, aryl or NR
8R
9(R
8, R
9Be H, C
1-C
6Alkyl, benzyl or aryl).X is a chlorine; R
1(substituting group is C also to represent aryl or substituted-phenyl
1-C
6Alkyl, C
1-C
6Alkoxyl group) or five to seven-membered ring heteroaryl such as pyridine ring, pyrrole ring, imidazole ring, furan nucleus, thiphene ring.
Formula IV R
2Represent the 2-on the aromatic nucleus, 3-, one of 4-position replaces, two replacement or multi-substituents.R
2Can be C
1-C
6Straight or branched alkyl or C
1-C
6Alkoxyl group.
In the reaction of the present invention, used N-heterocyclic carbine-metal-imidazol complex consumption is recommended as 0.001-10mol% (with respect to benzyl halogenide), and the mol ratio between employed benzyl halogenide and aryl boric acid or the aryl fluoride potassium borate is recommended as 1:1 to 1:5.
The temperature that reaction is carried out is recommended as 0-150 ℃, especially is recommended as 60-100 ℃, and the reaction times is recommended as 2-24 hour.
In the reaction of the present invention, employed alkali can be KHCO
3, K
2CO
3, Na
2CO
3, Cs
2CO
3, NaHCO
3, CH
3COOK, CH
3ONa, CsF, K
3PO
43H
2O, NaOH, KOH, KO
tBu or NaO
tBu.
In the reaction of the present invention, employed solvent can be the mixed solvent of water, THF, benzene, toluene, dioxane or organic solvent and water, further is recommended as water.
In the N-heterocyclic carbine-metal that relates among the present invention-imidazol complex: metal center M further is recommended as palladium.
Employed catalyzer is easy to preparation among the present invention, just can synthesize in a large number through single step reaction from corresponding imidazole salts, and this catalyzer is to air and steam quite stable.And, use this catalyzer, can be that substrate is realized the synthetic of diarylmethanes verivate with benzyl halogenide.Other system of reporting in this catalystsystem and the document is compared; Cost of material is cheap, be easy to get; And react and can use cleaning, water nontoxic, that be easy to get to be solvent, easy handling is very low to the requirement of conversion unit; Meet large-scale industrialization production demand, have favorable industrial application prospect.
Embodiment
To help to understand the present invention through following embodiment, but be not restricted to content of the present invention.
Embodiment 1
The reaction of benzyl chloride and phenylo boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), phenylo boric acid (121.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain ditan, yield 92%.
1H?NMR(500MHz,CDCl
3,TMS)δ3.97(s,2H),7.16-7.20(m,6H),7.24-7.27(m,4H).
13C?NMR(125MHz,CDCl
3)d41.9,126.0,128.4,128.9,141.1.
Embodiment 2
The reaction of benzyl chloride and 3-methylphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 3-methylphenylboronic acid (136.1mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-3-aminomethyl phenyl methane, yield 97%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.29(s,3H),3.93(s,2H),6.97-7.00(m,3H,Ar),7.14-7.18(m,4H,Ar),?7.26(t,J=7.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.4,41.9,125.96,125.98,126.8,128.3,128.4,128.9,129.7,138.0,141.0,141.2.
Embodiment 3
The reaction of benzyl chloride and 4-methoxyphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 4-methoxyphenylboronic acid (151.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-4-anisole methylmethane, yield 99%.
1H?NMR(500MHz,CDCl
3,TMS)δ3.76(s,3H),3.91(s,2H),6.82(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),7.16-7.28(m,5H).
13C?NMR(125MHz,CDCl
3)δ41.0,55.2,113.9,125.9,128.4,128.8,129.8,133.2,141.6,158.0.
Embodiment 4
The reaction of benzyl chloride and 4-methylphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 4-methylphenylboronic acid (136.1mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-4-aminomethyl phenyl methane, yield 94%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.30(s,3H),3.93(s,2H),7.11(d,J=8.5Hz,2H),7.08(d,J=8.5Hz,2H),7.16-7.19(m,3H,Ar),7.26(t,J=7.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.0,41.5,126.0,128.4,128.8,128.9,129.1,135.5,138.1,141.4.
Embodiment 5
The reaction of benzyl chloride and 3-fluorobenzoic boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 3-fluorobenzoic boric acid (139.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-3-fluorophenyl methane, yield 97%.
1H?NMR(500MHz,CDCl
3,TMS)δ3.94(s,2H),6.84-6.96(m,3H),7.15-7.31(m,6H,Ar).
13C?NMR(125MHz,CDCl
3)d41.6,112.9(d,J
C-F=20.9Hz),115.7(d,J
C-F=21.1Hz),124.5,126.3,128.6,128.9,129.8(d,J
C-F=8.3Hz),140.3,143.7(d,J
C-F=7.1Hz),163.0(d,J
C-F=244.0Hz).
Embodiment 6
The reaction of benzyl chloride and 4-fluorobenzoic boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 4-fluorobenzoic boric acid (139.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-4-fluorophenyl methane, yield 96%.
1H?NMR(500MHz,CDCl
3,TMS)δ3.93(s,2H),6.95(t,J=8.5Hz,2H),7.11-7.21(m,5H),7.28(t,J=7.5Hz,2H).
13CNMR(125MHz,CDCl
3)δ41.1,115.2(d,J
C-F=21.1Hz),126.2,128.5,128.8,130.3(d,J
C-F=7.8Hz),136.8(d,J
C-F=3.3Hz),140.9,161.4(d,J
C-F=242.4Hz).
Embodiment 7
The reaction of benzyl chloride and 1-naphthalene boronic acids
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 1-naphthalene boronic acids (171.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-1-naphthyl methane, yield 97%.
1H?NMR(500MHz,CDCl
3,TMS)δ4.43(s,2H),7.18-7.26(m,5H),7.39-7.45(m,3H),7.74-7.97(m,4H).
13CNMR(125MHz,CDCl
3)δ39.0,124.3,125.5,125.9,126.0,127.1,127.3,128.4,128.6,128.7,132.1,133.9,136.6,140.6.
Embodiment 8
The reaction of benzyl chloride and 2-furans boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), 2-furans boric acid (111.9mg, 1.0mmol), zero(ppm) water (2.0mL), benzyl chloride (86 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-2-furyl methane, yield 65%.
1H?NMR(500MHz,CDCl
3,TMS)δ3.97(s,2H),6.00(d,J=3.0Hz,1H),6.28(t,J=3.0Hz,1H),7.22(t,J=7.5Hz,3H),7.28-7.32(m,3H).
13C?NMR(125MHz,CDCl
3)δ34.5,106.2,110.2,126.5,128.5,128.7,138.1,141.5,154.6.
Embodiment 9
The reaction of 4-methyl benzyl chlorine and phenylo boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), phenylo boric acid (121.9mg, 1.0mmol), zero(ppm) water (2.0mL), 4-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-4-aminomethyl phenyl methane, yield 90%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.30(s,3H),3.93(s,2H),7.11(d,J=8.5Hz,2H),7.08(d,J=8.5Hz,2H),?7.16-7.19(m,3H,Ar),7.26(t,J=7.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.0,41.5,126.0,128.4,128.8,128.9,129.1,135.5,138.1,141.4.
Embodiment 10
The reaction of 2-methyl benzyl chlorine and phenylo boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), phenylo boric acid (121.9mg, 1.0mmol), zero(ppm) water (2.0mL), 2-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-2-tolyl methane, yield 90%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.23(s,3H),3.97(s,2H),7.08-7.18(m,7H),7.25(t,J=7.0Hz,2H).
13C?NMR(125MHz,CDCl
3)δ19.6,39.4,125.9,126.0,126.4,128.4,128.7,129.9,130.3,136.6,138.9,140.4.
Embodiment 11
The reaction of 3-methyl benzyl chlorine and phenylo boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), phenylo boric acid (121.9mg, 1.0mmol), zero(ppm) water (2.0mL), 3-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-3-tolyl methane, yield 97%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.29(s,3H),3.93(s,2H),6.97-7.00(m,3H,Ar),7.14-7.18(m,4H,Ar),7.26(t,J=7.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.4,41.9,125.96,125.98,126.8,128.3,128.4,128.9,129.7,138.0,141.0,141.2.
Embodiment 12
The reaction of 4-methyl benzyl chlorine and 3-methylphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 3-methylphenylboronic acid (135.9mg, 1.0mmol), zero(ppm) water (2.0mL), 4-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain 4-tolyl-3-tolyl methane, yield 90%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.29(s,3H),2.30(s,3H),6.96-6.99(m,3H),7.06(d,J=9.0Hz,2H),7.08(d,J=9.0Hz,2H),7.14-7.18(m,1H).
13C?NMR(125MHz,CDCl
3)δ21.0,21.4,41.4,125.9,126.7,128.3,128.8,129.1,129.6,135.4,137.9,138.2,141.3.
Embodiment 13
The reaction of 4-methyl benzyl chloride and 4-methylphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 4-methylphenylboronic acid (135.9mg, 1.0mmol), zero(ppm) water (2.0mL), 4-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain two (4-tolyl)-methane, yield 85%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.29(s,6H),3.89(s,2H),7.05(d,J=9.0Hz,4H),7.07(d,J=9.0Hz,4H).?
13C?NMR(125MHz,CDCl
3)δ21.0,41.1,128.7,129.1,135.4,138.3..
Embodiment 14
The reaction of 4-methyl benzyl chlorine and 4-tert.-butylbenzene boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), 4-tert.-butylbenzene boric acid (178.0mg, 1.0mmol), zero(ppm) water (2.0mL), 4-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain 4-tolyl-4-tert.-butylbenzene methylmethane, yield 93%.
1H?NMR(500MHz,CDCl
3,TMS)δ1.29(s,9H),2.30(s,3H),3.90(s,2H),7.08(s,4H),7.10(d,J=8.0Hz,2H),7.28(d,J=8.0Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.0,31.4,34.3,41.0,125.3,128.4,128.8,129.1,135.4,138.2,138.4,148.7.
Embodiment 15
The reaction of 4-fluorine benzyl chlorine and 4-methylphenylboronic acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the 4-methylphenylboronic acid (135.9mg, 1.0mmol), zero(ppm) water (2.0mL), 4-fluorine benzyl chlorine (90 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain 4-fluorophenyl-4-tolyl methane, yield 98%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.30(s,3H),3.88(s,2H),6.93(t,J=8.5Hz,2H),7.03(d,J=8.5Hz,2H),7.07-7.11(m,4H).
13C?NMR(125MHz,CDCl
3)δ20.9,40.6,115.1(d,J
C-F=21.1Hz),128.7,129.2,130.2(d,J
C-F=7.8Hz),135.7,137.0,137.9,161.4(d,J
C-F=242.4Hz).
Embodiment 16
The reaction of 4-fluorine benzyl chlorine and 4-tert.-butylbenzene boric acid
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), 4-tert.-butylbenzene boric acid (178.0mg, 1.0mmol), zero(ppm) water (2.0mL), 4-fluorine benzyl chlorine (90 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain 4-fluorophenyl-4-tert.-butylbenzene methylmethane, yield 99%.
1H?NMR(500MHz,CDCl
3,TMS)δ1.21(s,9H),3.82(s,2H),6.86(t,J=8.5Hz,2H),7.00(d,J=8.5Hz,2H),7.04(dd,J=5.5,9.0Hz,2H),7.21(d,J=9.0Hz,2H).
13C?NMR(125?MHz,CDCl
3)δ31.4,34.4,40.6,115.1(d,J
C-F=21.1Hz),125.4,128.4,130.3(d,J
C-F=7.9Hz),136.9,137.9,149.0,161.4(d,J
C-F=242.3Hz).
Embodiment 17
The reaction of 2-methyl benzyl chlorine and phenyl-fluoride potassium borate
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the phenyl-fluoride potassium borate (184.0mg, 1.0mmol), zero(ppm) water (2.0mL), 2-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-2-tolyl methane, yield 83%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.23(s,3H),3.97(s,2H),7.08-7.18(m,7H),7.25(t,J=7.0Hz,2H).
13CNMR(125MHz,CDCl
3)δ19.6,39.4,125.9,126.0,126.4,128.4,128.7,129.9,130.3,136.6,138.9,140.4.
Embodiment 18
The reaction of 3-methyl benzyl chlorine and phenyl-fluoride potassium borate
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the phenyl-fluoride potassium borate (184.0mg, 1.0mmol), zero(ppm) water (2.0mL), 3-methyl benzyl chlorine (100 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-3-tolyl methane, yield 98%.
1H?NMR(500MHz,CDCl
3,TMS)δ2.29(s,3H),3.93(s,2H),6.97-7.00(m,3H,Ar),7.14-7.18(m,4H,Ar),7.26(t,J=7.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ21.4,41.9,125.96,125.98,126.8,128.3,128.4,128.9,129.7,138.0,141.0,141.2.
Embodiment 19
The reaction of 4-tertiary butyl benzyl chlorine and phenyl-fluoride potassium borate
Under the nitrogen protection, in reaction tubes, add successively Pottasium Hydroxide (84.0mg, 1.5mmol), catalyzer (7.3mg, 1.5mol%), the phenyl-fluoride potassium borate (184.0mg, 1.0mmol), zero(ppm) water (2.0mL), 4-tertiary butyl benzyl chlorine (145 μ L, 0.75mmol).This reaction mixture was stirred 12 hours down at 60 ℃.Ethyl acetate extraction, dry back rapid column chromatography obtain phenyl-4-tert.-butylbenzene methylmethane, yield 90%.
1H?NMR(500MHz,CDCl
3,TMS)δ1.29(s,9H),3.94(s,2H),7.11(d,J=8.5Hz,2H),7.17-7.21(m,3H),7.26(d,J=7.0Hz,2H),7.30(d,J=8.5Hz,2H).
13C?NMR(125MHz,CDCl
3)δ31.4,34.3,41.4,125.3,126.0,128.4,128.5,129.0,138.1,141.3,148.8。
Claims (10)
1. the preparation method of a diarylmethanes verivate, said diarylmethanes derivant structure formula such as formula I:
R wherein
1A substituting group or multi-substituent on the expression phenyl ring; And R
2A substituting group or multi-substituent on the expression phenyl ring, this method makes the benzyl halogenide shown in the formula II:
R wherein
1Definition is like I; X representes iodine, bromine or chlorine,
Under the 0-150 ℃ of temperature, in the presence of alkali, in the mixed solvent of water, THF, benzene, toluene, dioxane or organic solvent and water, under the catalysis of the N-heterocyclic carbine-metal shown in the formula III-imidazol complex:
R wherein
3Expression H, C
1-C
6Alkoxyl group or C
1-C
6Alkyl; R
4Expression H, C
1-C
6Alkoxyl group or C
1-C
6Alkyl; Z is I
-, Br
-, Cl
-, CH
3COO
-, CF
3COO
-Or CF
3SO
3 -R
5Expression C
1-C
6Alkyl or aryl or benzo aromatic ring; M representes iron, copper, silver, nickel, palladium, cobalt, rhodium or ruthenium,
Carry out linked reaction with aryl boric acid shown in the formula IV or aryl fluoride potassium borate,
R wherein
2Definition is like I; Y representes B (OH)
2Or BF
3K.
(2) as claimed in claim 1, wherein a diaryl methane derivative thereof, wherein: R
1 represents H, C
1 -C
6 alkoxy, NO
2 , CN, Chuo, carboxy, C
1 -C
6 alkyl ketone, aryl ketone groups, C
1 -C
6 alkyl carboxyl, aryl carboxyl, amino, C
1 -C
6 alkylamino or arylamino.
3. the preparation method of a kind of diarylmethanes verivate according to claim 1 is characterized in that: R
1Expression aryl or heteroaryl.
4. the preparation method of a kind of diarylmethanes verivate according to claim 3 is characterized in that: R
1Expression phenyl, substituted-phenyl or five are to the seven-membered ring heteroaryl.
5. the preparation method of a kind of diarylmethanes verivate according to claim 4 is characterized in that: R
1Expression C
1-C
6Alkyl or C
1-C
6Alkoxy substituted phenyl.
6. the preparation method of a kind of diarylmethanes verivate according to claim 4 is characterized in that: R
1Expression pyridyl, pyrryl, imidazolyl, furyl or thienyl.
7. the preparation method of a kind of diarylmethanes verivate according to claim 1 is characterized in that: X is a chlorine in the benzyl halogenide shown in the formula II.
8. the preparation method of a kind of diarylmethanes verivate according to claim 1; It is characterized in that: the M in the N-heterocyclic carbine-metal shown in the formula III-imidazol complex representes palladium, and the consumption of N-heterocyclic carbine-metal-imidazol complex is the halid 0.001-10mol% of benzyl.
9. the preparation method of a kind of diarylmethanes verivate according to claim 1 is characterized in that: the mol ratio between aryl boric acid shown in benzyl halogenide shown in the formula II and the formula IV or the aryl fluoride potassium borate is that 1:1 is to 1:5.
10. the preparation method of a kind of diarylmethanes verivate according to claim 1 is characterized in that: described alkali is KHCO
3, K
2CO
3, Na
2CO
3, Cs
2CO
3, NaHCO
3, CH
3COOK, CH
3ONa, CsF, K
3PO
43H
2O, NaOH, KOH, KO
tBu or NaO
tBu.
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Cited By (4)
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| CN103130592A (en) * | 2013-01-25 | 2013-06-05 | 重庆大学 | Synthetic method for diaryl methane derivatives |
| CN103214341A (en) * | 2013-04-12 | 2013-07-24 | 重庆大学 | Method for synthesizing diarylmethane and triarylmethane in one step by using aromatic hydrocarbon and benzyl halid |
| CN104058909A (en) * | 2014-07-02 | 2014-09-24 | 魏建华 | Catalyzed synthesis method for drug intermediate diaryl-class compounds |
| CN110804021A (en) * | 2019-11-15 | 2020-02-18 | 温州大学 | Synthesis method of 2-aryl-4-aminoquinazoline |
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