CN106565517B - A method of amide is prepared by arylmethane derivative and nitrile - Google Patents
A method of amide is prepared by arylmethane derivative and nitrile Download PDFInfo
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Abstract
The present invention provides a kind of methods being simple and efficient directly preparing amides compound by arylmethane derivative and nitrile.This method uses acetate dihydrate manganese as catalyst, and 2,3 dichloro, 5,6 dicyano Isosorbide-5-Nitrae benzoquinones (DDQ) is used as oxidant, have the characteristics that raw material is cheap and easy to get, nitrile source compared with extensively, reaction condition is mild, applicability is wide.The problems such as this method solve ammonium ceric nitrate (CAN) and fluorine reagent are more intractable, Atom economy is bad, nitrile source is relatively narrow used in the method for arylmethane and the direct synthesizing amide of nitrile compounds.
Description
【Technical field】
The present invention relates to organic synthesis fields, and in particular to a kind of side preparing amide by arylmethane derivative and nitrile
Method.
【Background technology】
Amides compound is important organic synthesis raw material and intermediate, has attracted very in industry and sphere of learning in recent years
The interest of more people.Peptide bond can be formed in the protein such as enzyme, and higher utility value is shown in terms of biology, pesticide, and
And also show good biological medicinal activity in field of medicaments.Amides compound not only there is excellent bioactivity also to have
Changeable chemical constitution is one of the hot spot of organic synthesis and pharmaceutical chemistry research, the spy about this kind of compound synthesis route
Rope also gos deep into constantly.
Carboxylic acid or acid chloride or anhydride compound are reacted with amine generates amides compound, is to apply wider synthesis side
Method.Also someone's aldehyde compound and azanol synthesize level-one amine.Metal cyanides is using cyanylation agent earlier.It is this
The shortcomings that method is：With toxic or hygroscopic catalyst, and costly metal trifluoroacetate methanesulfonates is also needed to, is not inconsistent combination
Work produces environmentally protective requirement.In recent years, more and more nitriles are utilized.2011, Kalkhambkar projects
Group, it was recently reported that using adamantane as substrate, nitrile compounds are nitrile source, mix catalyst, have synthesized required amides compound.
2013, Panduranga etc. was reported using ether compound as substrate, and cyanamide is nitrile source, you can obtains disubstituted urease
Product.
Report at present by there are five types of the methods of arylmethane and the direct synthesizing amide of nitrile compounds, but these method nitriles
Source is relatively narrow and nitrile is used as solvent, and more intractable using the oxidant being of little use, such as ammonium ceric nitrate (CAN) and fluorine reagent etc.
And Atom economy is bad, they are much higher for similar compound our productivity ratio.Therefore new mild condition, substrate are applicable in
Property is wide, and highly selective, the method for the synthesizing amide class compound of high atom economy is constantly subjected to the attention of people.【With reference to text
It offers：Kalkhambkar,R.G.,Waters,S.N.,Laali,K.K.,Tetrahedron Lett.,2011,52,867–871；
Panduranga,V.,Basavaprabhu,H.,Sureshbabu,V.V.,Tetrahedron Lett.,2013,54,975–
979.Sakaguchi,S.,Hirabayashi,T.,Ishii,Y.,Chem Comm.,2002,516；Nair,V.,Suja,
T.D.,Mohanan,K.,Tetrahedron Lett.,2005,46,3217；Michaudel,Q.,Thevenet,D.,
Baran,P.S.,J Am Chem Soc.,2012,134,2547.Liu,C.,Zhang,Q.,Li,H.,Guo,S.,Xiao,B.,
Deng,W.,Liu,L.,He,W.,Chem.-Eur.J.2016,22,1.】
For the deficiency of the above method, exploitation does not use reluctant oxidant, without using ligand strong acid, operation letter
Single, amides compound applied widely synthesis new way, has potential prospects for commercial application.
【Invention content】
It is a kind of under nitrogen atmosphere that the purpose of the present invention is exploitations, using Mn catalyst, with arylmethane derivative and nitrile
Class compound is raw material, the method for high conversion and high productivity synthesizing amide class compound.The purpose of the present invention is by such as
What lower technical solution was realized：
A kind of structural formula isAmides compound synthetic method, comprise the steps of：
Arylmethane derivative, nitrile compounds, Mn catalyst, oxidant, trifluoroacetic acid (TFA), solvent are placed in instead
It answers in container, mixes, be persistently to be stirred to react 8~16h, reaction terminates at 70~90 DEG C in reaction temperature under nitrogen atmosphere
Postcooling is added potassium carbonate to neutrality, is then extracted with organic solvent to room temperature, dry, and vacuum distillation concentration removes solvent, slightly
Product is through pillar layer separation to get amides compound.
In the structural formula I, R1It is aryl, fat-based, hydrogen；R2Be methyl, normal-butyl, isopropyl, tertiary butyl, cyclopropyl,
Vinyl, benzyl, phenyl.
In above-mentioned synthetic method, the Mn catalyst is to be selected from least one of manganese acetate and acetate dihydrate manganese.
In above-mentioned synthetic method, the nitrile compounds be acetonitrile, valeronitrile, isobutyronitrile, trimethylacetonitrile, cyclopropylniitrile,
At least one of acrylonitrile, benzonitrile, benzene acetonitrile.
In above-mentioned synthetic method, the oxidant is 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).
In above-mentioned synthetic method, the aromatic methane derivative be selected from diphenyl methane, ethylbenzene, isobutyl-benzene, indane,
Fluorenes, 1,2,3,4- naphthanes, 1- benzyl -4- chlorobenzenes, bis- (4- fluorophenyls) methane, 1- benzyl -4- fluorobenzene, 1- benzyl -4- methyl
Benzene, 1- benzyl -3- methylbenzenes, 1- benzyl -2- methylbenzenes.
In above-mentioned synthetic method, additive is trifluoroacetic acid (TFA) in the reaction process.
In above-mentioned synthetic method, solvent is selected from acetonitrile, 1,2- dichloroethanes (DCE) and toluene in the reaction process
At least one also functions as reaction reagent when acetonitrile solvent is.
In above-mentioned synthetic method, the Mn catalyst, DDQ oxidants, trifluoroacetic acid, nitrile compounds and arylmethane spread out
Molar ratio between biology is [0.1~0.3]：[1.0~3.0]：[15~25]：[15~50]：1, reaction temperature is 70~90
DEG C, the reaction time is 8~16h.
In above-mentioned synthetic method, the organic solvent in the extraction step is ethyl acetate, chloroform or dichloromethane.
According to experimental result, the present invention provides one kind directly preparing amides compound by arylmethane derivative and nitrile
The method being simple and efficient.This method uses acetate dihydrate manganese as catalyst, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ) be used as oxidant, have the characteristics that raw material is cheap and easy to get, nitrile source compared with extensively, reaction condition is mild, applicability is wide.This method
It is more difficult to solve ammonium ceric nitrate (CAN) and fluorine reagent used in the method for arylmethane and the direct synthesizing amide of nitrile compounds
Processing, the problems such as Atom economy is bad, nitrile source is relatively narrow.
【Brief Description Of Drawings】
Fig. 1 is the reaction equation that amides compound is prepared by aromatic methane.
【Specific implementation mode】
Synthetic method of the present invention is described further with reference to the synthesis example of the present invention, needs to illustrate
It is that embodiment does not constitute the limitation to the claimed scope of the invention.
As shown in Figure 1, the synthesis step of amides compound provided by the invention is：Arylmethane derivative, manganese are urged
Agent (molar ratio 10%~200% is based on aromatic methane), oxidant (molar ratio 100%~300% is based on aromatic methane), nitrile
Class compound (molar ratio 1500%~5000% is based on aromatic methane), trifluoroacetic acid and solvent are placed in reaction vessel, are mixed,
It is persistently to be stirred to react 8~16h at 70~90 DEG C, be cooled to room temperature after reaction in reaction temperature in nitrogen atmosphere,
Potassium carbonate is added to neutrality, is then extracted with organic solvent, dry, vacuum distillation concentration removes solvent, and crude product is through column chromatography
Separation is to get amides compound.
Synthesis example 1
The synthesis of N- benzhydryl acetamides
0.2mmol diphenyl methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL second are added in the reactor
Nitrile, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature, and carbon is added
Sour potassium is extracted to neutrality with ethyl acetate, dry, and vacuum distillation removes solvent, and crude product is produced through pillar layer separation up to target
Object, yield 90%.1H NMR(400MHz,CDCl3)：δ 7.34-7.26 (m, 6H), 7.24-7.21 (m, 4H), 6.24 (d, J=
8.0Hz, 1H), 6.09 (d, J=6.2Hz, 1H), 2.06 (s, 3H).
Synthesis example 2
The synthesis of N- (1- phenethyls) acetamide
Addition 0.2mmol ethylbenzene in the reactor, 0.04mmol acetate dihydrate manganese, 0.4mmol DDQ, 0.5mL acetonitriles,
0.15mL TFA, mixing, are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature, and potassium carbonate is added
It to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, and crude product is through pillar layer separation up to target product, production
Rate 59%.1H NMR(400MHz,CDCl3)：δ7.27-7.18(m,5H),5.83(s,1H),5.07–4.99(m,1H),1.89
(s, 3H), 1.40 (d, J=6.9Hz, 1H).
Synthesis example 3
The synthesis of N- (2- methyl-1s-phenyl propyl) acetamide
0.2mmol isobutyl-benzenes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL second are added in the reactor
Nitrile, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature, and carbon is added
Sour potassium is extracted to neutrality with ethyl acetate, dry, and vacuum distillation removes solvent, and crude product is produced through pillar layer separation up to target
Object, yield 20%.1H NMR(400MHz,CDCl3)：δ 7.25 (d, J=7.6Hz, 1H), 7.19-7.14 (m, 4H), 7.16 (d, J
=8.3Hz, 2H), 5.67 (d, J=7.4Hz, 1H), 4.69 (t, J=8.5Hz, 1H), 2.00-1.95 (m, 1H), 1.93 (s,
3H), 0.90 (d, J=6.7Hz, 3H), 0.76 (d, J=6.7Hz, 3H).
Synthesis example 4
The synthesis of N- (2,3- dihydro -1H- indenes -1- bases) acetamide
Addition 0.2mmol indanes in the reactor, 0.02mmol acetate dihydrate manganese, 0.24mmol DDQ, 0.15mL acetonitriles,
0.15mL TFA, 0.35mL DCE mixing, are heated to 70 DEG C, persistently stir 12h, stop reaction, be cooled to room temperature under a nitrogen,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 75%.1H NMR(400MHz,CDCl3)：δ7.18-7.08(m,4H),5.99(s,1H),5.35-5.28
(m,1H),2.89-2.83(m,2H),2.49-2.41(m,1H),1.89(s,3H),1.74-1.65(m,1H)。
Synthesis example 5
The synthesis of N- (1,2,3,4- naphthane -1- bases) acetamide
Addition 1,2,3,4- naphthanes of 0.2mmol in the reactor, 0.04mmol acetate dihydrate manganese, 0.4mmol DDQ,
0.5mL acetonitriles, 0.15mL TFA, mixing are heated to 60 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 57%.1H NMR(400MHz,CDCl3)：δ7.25-7.06(m,4H),5.92(s,1H),5.15-5.12
(m,1H),2.81-2.69(m,2H),2.02-1.99(m,1H),1.97(s,3H),1.84-1.77(m,3H)。
Synthesis example 6
The synthesis of N- (9H- fluorenes -9- bases) acetamide
Addition 0.2mmol fluorenes in the reactor, 0.04mmol acetate dihydrate manganese, 0.4mmol DDQ, 0.5mL acetonitriles,
0.15mL TFA, mixing, are heated to 120 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature, and carbonic acid is added
Potassium is extracted to neutrality with ethyl acetate, dry, and vacuum distillation removes solvent, crude product through pillar layer separation up to target product,
Yield 48%.1H NMR(400MHz,CDCl3)：δ 7.61 (d, J=7.5Hz, 2H), 7.49 (d, J=7.4Hz, 2H), 7.33 (t,
J=7.4Hz, 2H), 7.25-7.19 (m, 2H), 6.13 (d, J=8.9Hz, 1H), 5.79 (d, J=8.0Hz, 1H), 2.04 (s,
3H)。
Synthesis example 7
The synthesis of N- benzhydryl pentanamides
0.2mmol diphenyl methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL penta are added in the reactor
Nitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled to room under a nitrogen
Temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Obtain target product, yield 84%.1H NMR(400MHz,CDCl3)：δ 7.25-7.12 (m, 10H), 6.17 (d, J=8.0Hz,
1H), 6.08 (s, 1H), 2.17 (t, J=7.6Hz, 2H), 1.60-1.52 (m, 2H), 1.31-1.24 (m, 2H), 0.83 (t, J=
7.3Hz,3H)。
Synthesis example 8
The synthesis of N- benzhydryl -2- phenyl-acetamides
0.2mmol diphenyl methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL benzene are added in the reactor
Acetonitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled under a nitrogen
Room temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Up to target product, yield 70%.1H NMR(400MHz,CDCl3)：δ 7.37-7.27 (m, 9H), 7.24 (d, J=7.2Hz,
2H), 7.08 (d, J=7.2Hz, 4H), 6.23 (d, J=8.3Hz, 1H), 6.04 (s, 1H), 3.64 (s, 2H).
Synthesis example 9
The synthesis of N- benzhydryl benzamides
0.2mmol diphenyl methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL benzene are added in the reactor
Formonitrile HCN, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled under a nitrogen
Room temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Up to target product, yield 57%.1H NMR(400MHz,CDCl3)：δ 7.82 (d, J=7.6Hz, 2H), 7.51 (t, J=
7.3Hz, 1H), 7.43 (t, J=7.6Hz, 2H), 7.36-7.28 (m, 10H), 6.69 (s, 1H), 6.46 (d, J=7.8Hz,
1H)。
Synthesis example 10
The synthesis of N- benzhydryl isobutyramides
0.2mmol diphenyl methanes are added in the reactor, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL are different
Butyronitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled under a nitrogen
Room temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Up to target product, yield 75%.1H NMR(400MHz,CDCl3)：δ 7.33-7.27 (m, 5H), 7.22 (t, J=7.5Hz,
5H), 6.24 (d, J=7.9Hz, 1H), 6.09 (s, 1H), 2.46-2.39 (m, 1H), 1.19 (s, 3H), 1.17 (s, 3H).
Synthesis example 11
The synthesis of N- ((4- chlorphenyls) (phenyl) methyl) acetamide
Addition 0.2mmol 1- benzyl -4- chlorobenzenes in the reactor, 0.02mmol acetate dihydrate manganese, 0.24mmol DDQ,
0.15mL acetonitriles, 0.15mL TFA, 0.35mL DCE mixing, are heated to 70 DEG C, persistently stir 12h, stop reaction under a nitrogen,
It is cooled to room temperature, potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, and crude product is through column color
Spectrum detaches up to target product, yield 93%.1H NMR(400MHz,CDCl3)：δ7.32-7.26(m,5H),7.18-7.13(m,
4H), 6.25 (d, J=7.0Hz, 1H), 6.18 (d, J=7.8Hz, 1H), 2.05 (s, 3H).
Synthesis example 12
The synthesis of N- (bis- (4- fluorophenyls) methyl) acetamide
Bis- (4- fluorophenyls) methane of addition 0.2mmol, 0.04mmol acetate dihydrate manganese in the reactor, 0.4mmol DDQ,
0.15mL acetonitriles, 0.15mL TFA, 0.35mL DCE mixing, are heated to 90 DEG C, persistently stir 12h, stop reaction under a nitrogen,
It is cooled to room temperature, potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, and crude product is through column color
Spectrum detaches up to target product, yield 86%.1H NMR(400MHz,CDCl3)：δ 7.18-7.15 (m, 4H), 7.01 (t, J=
7.9Hz, 4H), 6.19 (d, J=7.7Hz, 1H), 6.06 (s, 1H), 2.05 (s, 3H).
Synthesis example 13
The synthesis of N- ((4- fluorophenyls) (phenyl) methyl) acetamide
Addition 0.2mmol 1- benzyl -4- fluorobenzene in the reactor, 0.04mmol acetate dihydrate manganese, 0.4mmol DDQ,
0.5mL acetonitriles, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 85%.1H NMR(400MHz,CDCl3)：δ7.33-7.26(m,3H),7.19-7.15(m,4H),6.99
(t, J=8.6Hz, 2H), 6.35 (d, J=7.1Hz, 1H), 6.19 (d, J=8.0Hz, 1H), 2.02 (s, 3H).
Synthesis example 14
The synthesis of N- hexichol pivaloyl amines
0.2mmol diphenyl-methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL front threes are added in the reactor
Base acetonitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h under a nitrogen, stops reaction, cooling
To room temperature, potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, and crude product is through column chromatography point
From up to target product, yield 51%.1H NMR(400MHz,CDCl3):δ=7.32-7.26 (m, 5H), 7.24-7.19 (m,
5H), 6.22 (d, J=7.4Hz, 1H), 6.16 (d, J=17.5Hz, 1H), 1.24 (s, 9H).
Synthesis example 15
The synthesis of bis- phenyl ring propyl formamides of N-
0.2mmol diphenyl-methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL rings third are added in the reactor
Nitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled to room under a nitrogen
Temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Obtain target product, yield 94%.1H NMR(400MHz,CDCl3):δ=7.37-7.33 (m, 4H), 7.29 (d, J=11.1Hz,
6H), 6.29 (d, J=7.9Hz, 1H), 6.22 (d, J=6.9Hz, 1H), 1.47-1.40 (m, 1H), 1.04-1.01 (m, 2H),
0.79–0.75(m,2H)。
Synthesis example 16
The synthesis of N- hexichol acrylamides
0.2mmol diphenyl-methanes, 0.04mmol acetate dihydrate manganese, 0.4mmolDDQ, 0.5mL propylene are added in the reactor
Nitrile, 0.15mL TFA, 0.35mL DCE mixing, is heated to 90 DEG C, persistently stirs 12h, stop reaction, be cooled to room under a nitrogen
Temperature is added potassium carbonate to neutrality, is extracted with ethyl acetate, and dry, vacuum distillation removes solvent, and crude product is through pillar layer separation
Obtain target product, yield 96%.1H NMR(400MHz,CDCl3):δ=7.28 (d, J=7.4Hz, 2H), 7.23-7.17 (m,
8H), 6.30-6.26 (m, 2H), 6.13-6.07 (m, 2H), 5.64 (d, J=10.2Hz, 1H).
Synthesis example 17
The synthesis of N- (1- phenylethyls) acrylamide
Addition 0.2mmol ethylbenzene, 0.04mmol acetate dihydrate manganese in the reactor, 0.4mmol DDQ, 0.5mL acrylonitrile,
0.15mL TFA, 0.35mL DCE mixing, are heated to 90 DEG C, persistently stir 12h, stop reaction, be cooled to room temperature under a nitrogen,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 43%.1H NMR(400MHz,CDCl3):δ=7.2-7.19 (m, 5H), 6.21 (d, J=16.9Hz, 1H),
6.03 (dd, J=16.9,10.3Hz, 1H), 5.90 (s, 1H), 5.57 (d, J=10.2Hz, 1H), 5.16-5.09 (m, 1H),
1.46 (d, J=6.9Hz, 3H).
Synthesis example 18
The synthesis of N- (phenyl (o-tolyl) methyl) acetamide
Addition 0.2mmol 1- benzyl -2- methylbenzenes, 0.04mmol acetate dihydrate manganese in the reactor, 0.4mmol DDQ,
0.5mL acetonitriles, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 81%.1H NMR(400MHz,CDCl3):δ=7.29 (t, J=7.2Hz, 2H), 7.24-7.13 (m, 6H),
7.10-7.08 (m, 1H), 6.39 (d, J=8.0Hz, 1H), 6.13 (s, 1H), 2.27 (s, 3H), 2.00 (s, 3H).
Synthesis example 19
The synthesis of N- (phenyl (tolyl) methyl) acetamide
Addition 0.2mmol 1- benzyl -3- methylbenzenes, 0.04mmol acetate dihydrate manganese in the reactor, 0.4mmol DDQ,
0.5mL acetonitriles, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 83%.1H NMR(400MHz,CDCl3):δ=7.40-7.27 (m, 6H), 7.15-7.06 (m, 3H), 6.27
(brs,2H),2.38(s,3H),2.10(s,3H)。
Synthesis example 20
The synthesis of N- (phenyl (p-methylphenyl) methyl) acetamide
Addition 0.2mmol 1- benzyl -4- methylbenzenes, 0.04mmol acetate dihydrate manganese in the reactor, 0.4mmol DDQ,
0.5mL acetonitriles, 0.15mL TFA, mixing are heated to 90 DEG C under a nitrogen, persistently stir 12h, stop reaction, are cooled to room temperature,
Potassium carbonate is added to neutrality, is extracted with ethyl acetate, dry, vacuum distillation removes solvent, crude product through pillar layer separation to obtain the final product
Target product, yield 88%.1H NMR(400MHz,CDCl3):δ=7.33-7.27 (m, 3H), 7.22 (d, J=7.1Hz, 2H),
7.12 (t, J=6.2 Hz, 4H), 6.20 (d, J=8.0 Hz, 1H), 6.12 (d, J=7.0 Hz, 1H), 2.32 (s, 3H),
2.04(s,3H)。
Claims (5)
1. a kind of method preparing amide by arylmethane derivative and nitrile, including following step：
By arylmethane derivative, nitrile compounds, manganese acetate or acetate dihydrate manganese, bis- chloro- 5,6- dicyanos -1,4- of 2,3-
Benzoquinones, trifluoroacetic acid, solvent are placed in reaction vessel, mixing, are to be held at 70~90 DEG C in reaction temperature under nitrogen atmosphere
It is continuous to be stirred to react 8~16h, it is cooled to room temperature after reaction, potassium carbonate is added to neutrality, is then extracted with organic solvent, does
Dry, vacuum distillation concentration removes solvent, and crude product, to get amides compound, has following structure formula through pillar layer separation：
In the structural formula I, R2It is methyl, normal-butyl, isopropyl, tertiary butyl, cyclopropyl, vinyl, benzyl, phenyl；Aryl first
Alkane derivatives are selected from diphenyl methane, ethylbenzene, isobutyl-benzene, indane, fluorenes, 1,2,3,4- naphthanes, 1- benzyl -4- chlorobenzenes, double
(4- fluorophenyls) methane, 1- benzyl -4- fluorobenzene, 1- benzyl -4- methoxybenzenes, 1- benzyl -4- ethylo benzenes, 1- benzyl -2- methyl
Benzene, 1- benzyl -3- methylbenzenes.
2. the method according to claim 1 for preparing amide by arylmethane derivative and nitrile, which is characterized in that described
Nitrile compounds are at least one in acetonitrile, valeronitrile, isobutyronitrile, trimethylacetonitrile, cyclopropylniitrile, acrylonitrile, benzonitrile, benzene acetonitrile
Kind.
3. the method according to claim 1 for preparing amide by arylmethane derivative and nitrile, which is characterized in that described anti-
Solvent is selected from least one of acetonitrile, 1,2- dichloroethanes and toluene during answering, and when acetonitrile solvent, also functions as anti-
Answer reagent.
4. the method according to claim 1 for preparing amide by arylmethane derivative and nitrile, which is characterized in that manganese acetate
Or acetate dihydrate manganese, bis- chloro- 5,6- dicyanos -1,4- benzoquinones of 2,3-, trifluoroacetic acid, nitrile compounds and arylmethane derive
Molar ratio between object is [0.1~0.3]：[1.0~3.0]：[15~25]：[15~50]：1, reaction temperature is 70~90 DEG C,
Reaction time is 8~16h.
5. the method according to claim 1 for preparing amide by arylmethane derivative and nitrile, which is characterized in that described to have
Solvent is ethyl acetate, chloroform or dichloromethane.
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