CN108516940A - A kind of synthetic method of 2- aminobenzophenones class compound - Google Patents
A kind of synthetic method of 2- aminobenzophenones class compound Download PDFInfo
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Abstract
The present invention provides a kind of synthetic methods of 2 aminobenzophenone class compound, belong to technical field of organic synthesis.Technical scheme of the present invention main points are：A kind of synthetic method of 2 aminobenzophenone class compound, building-up process the specific steps are：Connection ketene compounds, primary amine compound and ketene compounds are dissolved in solvent, the obtained 2 aminobenzophenone class compounds of heat temperature raising reaction under oxidant effect.The present invention has many advantages, such as easy to operate, mild condition, wide application range of substrates, is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of synthesis side of 2- aminobenzophenones class compound
Method.
Background technology
2- aminobenzophenone class compounds are a kind of important organic synthesis intermediates, be now widely used for drug,
In the synthesis of functional material and household chemicals.In addition, many compounds containing 2- aminobenzophenone structural units also have
There are the significant pharmaceutical activity such as antiviral, anticancer and anti-inflammatory, sterilization, is the important sources of new drug discovery.Currently, 2- aminodiphenyls
First ketone compounds are mainly synthesized by the F-K reaction of anil.This method although relatively reliable,
But there are still clearly disadvantageous places, such as：(1) lewis acid catalyst and acylting agent are not only expensive used in
And it is easy to happen moisture absorption hydrolysis；(2) severe reaction conditions；(3) regioselectivity reacted is low；(4) Atom economy is poor.Cause
This, studies and develops from cheap and easy to get with the raw material of performance stabilization, under conditions of without using catalyst via simplicity
Operating procedure synthesizes the new method of 2- aminobenzophenone class compounds, has important practical value.
Invention content
The technical problem to be solved by the present invention is to provide a kind of synthetic method of 2- aminobenzophenones class compound, the conjunctions
Synthesis 2- is reacted with the multicomponent tandem between primary amine compound, ketene compounds by joining ketene compounds at method
Aminobenzophenone class compound, has many advantages, such as easy to operate, mild condition, wide application range of substrates, is suitable for industrializing
Production.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of 2- aminobenzophenones class compound
Synthetic method, it is characterised in that building-up process the specific steps are：It will connection ketene compounds 1, primary amine compound 2 and ketenes
Class compound 3 is dissolved in solvent, the obtained 2- aminobenzophenone classes compound 4 of heat temperature raising reaction under oxidant effect, should
Reaction equation in synthetic method is：
Wherein R1For phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring is fluorine, chlorine, bromine, methyl or methoxy,
R2For C1-4Linear or branched alkyl group, phenyl replace C1-4Alkyl, phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring are
Fluorine, chlorine, bromine, methyl or methoxy, R3For phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring is fluorine, chlorine, bromine, first
Base or methoxyl group, oxidant are oxygen, tert-butyl hydroperoxide, di-tert-butyl peroxide or 2,2,6,6- tetramethyl piperidine oxygen
Compound.
Further preferably, the solvent is 1,2- dichloroethanes, toluene, chlorobenzene or Isosorbide-5-Nitrae-dioxane.
Further preferably, heat temperature raising reaction temperature is 80-140 DEG C.
Further preferably, the substance that feeds intake of the ketene compounds 1, primary amine compound 2 and ketene compounds 3
The ratio between amount be 1:1-1.5:1-1.5.
Further preferably, the oxidant is tert-butyl hydroperoxide, di-tert-butyl peroxide or 2,2,6,6- tetramethyls
When phenylpiperidines oxide, join the substance that feeds intake of ketene compounds 1, primary amine compound 2, ketene compounds 3 and oxidant
The ratio between amount be 1:1-1.5:1-1.5:0.5-1.5.
Further preferably, 2- aminobenzophenone classes are made in heat temperature raising reaction in nitrogen atmosphere under oxidant effect
Compound 4.
Compared with the prior art, the present invention has the following advantages：(1) present invention is by joining ketene compounds, primary amine class
The multicomponent tandem reaction between object and ketene compounds is closed, 2- aminobenzophenone class chemical combination is directly synthesized in one pot
Object, operating process are simple, efficient；(2) synthetic reaction can be smoothed out without using alkali or metallic catalyst, have it is economical,
Green, environmentally friendly feature；(3) Atom economy reacted is high, meets the requirement of Green Chemistry；(4) substrate is applicable
Range is wide.Therefore, the present invention provides a kind of economical and practical and environmentally protective for the synthesis of 2- aminobenzophenone class compounds
New method.
Specific implementation mode
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on the above of the present invention belong to this hair
Bright range.
Embodiment 1
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.5mmol, 78mg) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (81mg, 45%).
The characterize data of the compound is as follows：1H NMR(600MHz,CDCl3)δ:4.57 (d, J=4.8Hz, 2H), 6.78 (d, J=
7.8Hz, 1H), 6.94 (s, 1H), 7.28 (t, J=7.2Hz, 1H), 7.36 (t, J=7.2Hz, 3H), 7.40-7.44 (m, 4H),
7.47 (t, J=7.2Hz, 2H), 7.52 (d, J=7.2Hz, 3H), 7.58 (d, J=8.4Hz, 1H), 7.65 (d, J=7.2Hz,
2H),9.14(br s,1H).13C NMR(100MHz,CDCl3)δ:47.1,110.4,113.5,116.5,127.28,127.31,
127.34,128.1,128.2,128.8,129.1,130.8,136.1,138.5,140.6,140.7,147.6,151.9,
199.1.HRMS calcd for C26H21NNaO:386.1515[M+Na]+,found:386.1504。
Embodiment 2
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
Tert-butyl hydroperoxide (0.5mmol, 64 μ L) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C.Then it is spin-dried for molten
Agent crosses silica gel post separation (petrol ether/ethyl acetate=100/1) and obtains orange oil product 4a (27mg, 15%).
Embodiment 3
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
Di-tert-butyl peroxide (0.5mmol, 92 μ L) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C.Then it is spin-dried for
Solvent crosses silica gel post separation (petrol ether/ethyl acetate=100/1) and obtains orange oil product 4a (40mg, 22%).
Embodiment 4
1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg) are sequentially added in reaction tube
With Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C under oxygen (1atm) atmosphere.Then it is spin-dried for solvent, crosses silica gel
Post separation (petrol ether/ethyl acetate=100/1) obtains orange oil product 4a (45mg, 25%).
Embodiment 5
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.25mmol, 39mg) and Isosorbide-5-Nitrae-dioxane (3mL), are stirred to react in 120 DEG C
12h.Then be spin-dried for solvent, cross silica gel post separation (petrol ether/ethyl acetate=100/1) orange oil product 4a (60mg,
33%).
Embodiment 6
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (89mg, 49%).
Embodiment 7
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.75mmol, 117mg) and Isosorbide-5-Nitrae-dioxane (3mL), are stirred to react in 120 DEG C
12h.Then be spin-dried for solvent, cross silica gel post separation (petrol ether/ethyl acetate=100/1) orange oil product 4a (90mg,
50%).
Embodiment 8
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.5mmol, 55 μ L), 3a (0.5mmol, 66mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 120 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (76mg, 42%).
Embodiment 9
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.75mmol, 82 μ L), 3a (0.75mmol,
99mg), 2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL) are anti-in 120 DEG C of stirrings
Answer 12h.Then be spin-dried for solvent, cross silica gel post separation (petrol ether/ethyl acetate=100/1) orange oil product 4a (93mg,
51%).
Embodiment 10
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and 1,2- dichloroethanes (3mL) are stirred to react 12h in 120 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (64mg, 35%).
Embodiment 11
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and chlorobenzene (3mL), 12h is stirred to react in 120 DEG C.Then it is spin-dried for
Solvent crosses silica gel post separation (petrol ether/ethyl acetate=100/1) and obtains orange oil product 4a (47mg, 26%).
Embodiment 12
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and toluene (3mL), 12h is stirred to react in 120 DEG C.Then it is spin-dried for
Solvent crosses silica gel post separation (petrol ether/ethyl acetate=100/1) and obtains orange oil product 4a (40mg, 22%).
Embodiment 13
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 80 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (25mg, 14%).
Embodiment 14
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), 12h is stirred to react in 140 DEG C.
Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil product 4a (85mg, 47%).
Embodiment 15
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil
Shape product 4a (133mg, 73%).
Embodiment 16
Sequentially added in reaction tube 1b (0.5mmol, 111mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol,
79mg), 2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), at nitrogen (1atm)
Under atmosphere 12h is stirred to react in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains
Yellow oil product 4b (93mg, 42%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:4.56(d,
J=5.2Hz, 2H), 6.66 (dd, J1=8.0Hz, J2=1.2Hz, 1H), 6.85 (d, J=1.2Hz, 1H), 7.20-7.35 (m,
10H), 7.37-7.43 (m, 4H), 7.58 (d, J=8.0Hz, 1H), 9.40 (t, J=5.2Hz, 1H)13C NMR(100MHz,
CDCl3)δ:47.0,110.5,114.0,115.8,119.4,127.16,127.23,127.3,127.4,128.4,128.5,
128.78,128.81,130.3,133.0,136.1,138.3,140.5,142.1,148.4,152.2,197.6.HRMS
calcd forC26H20BrNNaO:464.0620[M+Na]+,found:464.0624。
Embodiment 17
Sequentially added in reaction tube 1c (0.5mmol, 87mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains orange oil
Shape product 4c (140mg, 71%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:3.85(s,3H),
4.57 (d, J=5.2Hz, 2H), 6.78 (d, J=8.0Hz, 1H), 6.94 (s, 1H), 7.06 (dd, J1=8.0Hz, J2=
2.0Hz, 1H), 7.18-7.22 (m, 2H), 7.26-7.30 (m, 1H), 7.35-7.44 (m, 8H), 7.52 (d, J=7.2Hz,
2H), 7.60 (d, J=8.4Hz, 1H), 9.12 (t, J=4.8Hz, 1H)13C NMR(150MHz,CDCl3)δ:47.1,55.5,
110.4,113.5,113.7,116.5,117.0,121.6,127.28,127.32,127.4,128.3,128.8,129.1,
136.1,138.5,140.7,141.9,147.6,151.9,159.4,198.8.HRMS calcd for C27H23NNaO2:
416.1621[M+Na]+,found:416.1616。
Embodiment 18
Sequentially added in reaction tube 1d (0.5mmol, 81mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, it is solid to obtain yellow for silica gel post separation (petrol ether/ethyl acetate=100/1) excessively
Body product 4d (110mg, 58%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:4.57 (d, J=
5.6Hz, 2H), 6.80 (d, J=8.4Hz, 1H), 6.94 (s, 1H), 7.15 (t, J=8.8Hz, 2H), 7.29 (d, J=7.6Hz,
1H),7.35-7.39(m,3H),7.40-7.44(m,4H),7.51-7.56(m,3H),7.67-7.70(m,2H),9.01(br
s,1H).13C NMR(150MHz,CDCl3)δ:47.1,110.5,113.6,115.2(d,2JC-F=20.9Hz), 116.4,
127.2,127.3,127.4,128.3,128.8,131.5(d,3JC-F=8.9Hz), 135.7,136.7 (d,4JC-F=3.3Hz),
138.4,140.6,147.7,151.8,164.4(d,1JC-F=249.5Hz), 197.6.HRMS calcd for C26H21FNO:
382.1602[M+H]+,found:382.1602。
Embodiment 19
Sequentially added in reaction tube 1e (0.5mmol, 89mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, it is solid to obtain yellow for silica gel post separation (petrol ether/ethyl acetate=100/1) excessively
Body product 4e (109mg, 55%).The characterize data of the compound is as follows：1H NMR(600MHz,CDCl3)δ:4.50 (d, J=
5.4Hz,2H),6.72(dd,J1=8.4Hz, J2=1.2Hz, 1H), 6.87 (d, J=1.2Hz, 1H), 7.22 (t, J=7.2Hz,
1H), 7.28-7.31 (m, 3H), 7.34-7.39 (m, 6H), 7.45 (t, J=7.8Hz, 3H), 7.53 (d, J=8.4Hz, 2H),
9.01 (t, J=4.8Hz, 1H)13C NMR(150MHz,CDCl3)δ:47.1,110.5,113.6,116.2,127.2,127.3,
127.4,128.3,128.4,128.8,130.5,135.7,137.1,138.4,138.9,140.5,147.8,151.9,
197.6.HRMScalcd for C26H20ClNNaO:420.1126[M+Na]+,found:420.1110。
Embodiment 20
Sequentially added in reaction tube 1f (0.5mmol, 87mg), 2a (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, it is solid to obtain yellow for silica gel post separation (petrol ether/ethyl acetate=100/1) excessively
Body product 4f (156mg, 79%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:3.88(s,3H),
4.55 (d, J=5.2Hz, 2H), 6.80 (d, J=8.4Hz, 1H), 6.93 (s, 1H), 6.97 (d, J=8.4Hz, 2H), 7.28
(d, J=7.2Hz, 1H), 7.35 (t, J=7.6Hz, 3H), 7.40-7.43 (m, 4H), 7.52 (d, J=7.2Hz, 2H), 7.61
(d, J=8.0Hz, 1H) 7.69 (d, J=8.8Hz, 2H), 8.83 (t, J=4.8Hz, 1H)13C NMR(150MHz,CDCl3)δ:
47.2,55.5,110.4,113.40,113.44,117.1,127.28,127.30,127.34,128.1,128.8,131.6,
132.9,135.6,138.6,140.8,147.1,151.5,162.1,197.9.HRMS calcd for C27H23NNaO2:
416.1621[M+Na]+,found:416.1619。
Embodiment 21
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, it is solid to obtain yellow for silica gel post separation (petrol ether/ethyl acetate=100/1) excessively
Body product 4g (98mg, 62%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:0.97 (t, J=
7.6Hz, 3H), 1.62-1.71 (m, 2H), 3.18 (q, J=6.4Hz, 2H), 6.62 (d, J=8.0Hz, 1H), 6.83 (s, 1H),
7.24-7.39 (m, 6H), 7.43 (d, J=8.4Hz, 1H), 7.50-7.52 (m, 4H), 8.68 (br s, 1H)13C NMR
(100MHz,CDCl3)δ:11.9,22.5,44.7,110.0,113.0,116.0,127.4,128.1,128.3,128.9,
129.0,130.7,136.2,140.8,140.9,147.7,152.4,199.0.HRMS calcd for C22H21NNaO:
338.1515[M+Na]+,found:338.1510。
Embodiment 22
Sequentially added in reaction tube 1b (0.5mmol, 111mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol,
79mg), 2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), at nitrogen (1atm)
Under atmosphere 12h is stirred to react in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains
Yellow oil product 4h (84mg, 43%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:1.01(t,
J=7.2Hz, 3H), 1.69-1.78 (m, 2H), 3.25 (q, J=6.8Hz, 2H), 6.60 (d, J=7.6Hz, 1H), 6.85 (s,
1H), 7.14 (d, J=8.4Hz, 1H), 7.19-7.23 (m, 2H), 7.28-7.37 (m, 4H), 7.51-7.55 (m, 3H), 9.00
(brs,1H).13C NMR(100MHz,CDCl3)δ:11.9,22.4,44.7,110.0,113.5,115.4,119.5,127.2,
127.4,128.4,128.6,128.9,130.3,133.0,136.2,140.8,142.2,148.5,152.6,197.4.HRMS
calcd for C22H21BrNO:394.0801[M+H]+,found:394.0794。
Embodiment 23
Sequentially added in reaction tube 1c (0.5mmol, 87mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4i (116mg, 67%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:1.09 (t, J=
7.2Hz, 3H), 1.75-1.84 (m, 2H), 3.31 (q, J=6.8Hz, 2H), 3.85 (s, 3H), 6.74 (d, J=8.4Hz, 1H),
6.94(s,1H),7.05(dd,J1=8.4Hz, J2=2.0Hz, 1H), 7.17-7.20 (m, 2H), 7.34-7.41 (m, 2H),
7.44-7.47 (m, 2H), 7.57 (d, J=8.4Hz, 1H), 7.63 (d, J=7.6Hz, 2H), 8.76 (br s, 1H)13C NMR
(150MHz,CDCl3)δ:11.8,22.4,44.7,55.4,109.9,112.9,113.6,115.9,116.9,121.5,
127.3,128.2,128.8,129.1,136.2,140.9,142.1,147.7,152.3,159.4,198.7.HRMS calcd
for C23H23NNaO2:368.1621[M+Na]+,found:368.1620。
Embodiment 24
Sequentially added in reaction tube 1g (0.5mmol, 111mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol,
79mg), 2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), at nitrogen (1atm)
Under atmosphere 12h is stirred to react in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains
Yellow solid product 4j (104mg, 53%).The characterize data of the compound is as follows：1H NMR(600MHz,CDCl3)δ:1.01
(t, J=7.8Hz, 3H), 1.69-1.75 (m, 2H), 3.23 (q, J=7.2Hz, 2H), 6.67 (d, J=8.4Hz, 1H), 6.87
(s,1H),7.32-7.34(m,1H),7.38-7.44(m,5H),7.52-7.56(m,4H),8.66(br s,1H).13C NMR
(150MHz,CDCl3)δ:11.8,22.4,44.7,110.1,113.0,115.6,125.3,127.3,128.3,128.8,
130.6,131.4,135.8,139.5,140.8,148.0,152.4,197.6.HRMS calcd for C22H20BrNNaO:
416.0620[M+Na]+,found:416.0603。
Embodiment 25
Sequentially added in reaction tube 1h (0.5mmol, 79mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4k (102mg, 62%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:1.08 (t, J=
7.6Hz, 3H), 1.74-1.83 (m, 2H), 2.43 (s, 3H), 3.29 (q, J=6.4Hz, 2H), 6.74 (d, J=8.4Hz, 1H),
6.94 (s, 1H), 7.26 (d, J=6.8Hz, 2H), 7.39 (t, J=7.2Hz, 1H), 7.46 (t, J=7.2Hz, 2H), 7.54-
7.58 (m, 3H), 7.62 (d, J=7.6Hz, 2H), 8.66 (br s, 1H)13C NMR(150MHz,CDCl3)δ:11.8,21.5,
22.4,44.7,109.9,112.8,116.3,127.3,128.2,128.7,128.8,129.3,136.0,137.9,141.0,
141.2,147.4,152.2,198.8.HRMS calcd for C23H24NO:330.1852[M+H]+,found:330.1850。
Embodiment 26
Sequentially added in reaction tube 1f (0.5mmol, 87mg), 2b (0.6mmol, 49 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4l (126mg, 73%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:1.00 (t, J=
7.2Hz, 3H), 1.66-1.75 (m, 2H), 3.21 (q, J=6.8Hz, 2H), 3.81 (s, 3H), 6.69 (dd, J1=8.0Hz, J2
=1.2Hz, 1H), 6.86-6.90 (m, 3H), 7.30-7.34 (m, 1H), 7.37-7.41 (m, 2H), 7.51 (d, J=8.0Hz,
1H),7.56-7.61(m,4H),8.42(br s,1H).13C NMR(150MHz,CDCl3)δ:11.8,22.4,44.7,55.5,
109.9,112.8,113.4,116.6,127.3,128.1,128.8,131.5,133.1,135.7,141.0,147.2,
152.0,162.0,197.9.HRMS calcd for C23H24NO2:346.1802[M+H]+,found:346.1799。
Embodiment 27
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2c (0.6mmol, 76 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4m (111mg, 59%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.99 (t, J=
7.6Hz, 2H), 3.52 (t, J=7.2Hz, 2H), 6.68 (dd, J1=8.4Hz, J2=1.6Hz, 1H), 6.88 (d, J=1.2Hz,
1H),7.15-7.17(m,1H),7.23-7.26(m,4H),7.31-7.33(m,1H),7.35-7.40(m,4H),7.42-7.48
(m,2H),7.52-7.55(m,4H),8.74(br s,1H).13C NMR(150MHz,CDCl3)δ:34.7,43.7,108.9,
112.2,115.2,125.5,126.3,127.1,127.2,127.6,127.8,127.9,129.6,135.1,138.1,
139.6,139.7,146.6,150.9,197.9.HRMS calcd for C27H23NNaO:400.1672[M+Na]+,found:
400.1669。
Embodiment 28
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2d (0.6mmol, 77 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4n (109mg, 58%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:1.57 (d, J=
6.8Hz,3H),4.61-4.68(m,1H),6.63(dd,J1=8.0Hz, J2=1.6,1H), 6.69 (d, J=1.6Hz, 1H),
7.14-7.18(m,1H),7.23-7.28(m,7H),7.33-7.40(m,4H),7.42-7.48(m,2H),7.57-7.59(m,
2H), 9.10 (d, J=5.6Hz, 1H)13C NMR(150MHz,CDCl3)δ:25.0,53.0,111.6,113.3,116.4,
126.0,127.1,127.2,128.1,128.8,128.9,129.1,130.9,136.0,140.6,140.7,144.8,
147.2,151.1,199.2.HRMS calcd for C27H23NNaO:400.1672[M+Na]+,found:400.1667。
Embodiment 29
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2e (0.6mmol, 54 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4o (98mg, 56%).The characterize data of the compound is as follows：1H NMR(600MHz,CDCl3)δ:6.93(dd,J1=
7.8Hz,J2=1.8Hz, 1H), 7.11 (t, J=7.2Hz, 1H), 7.35-7.39 (m, 5H), 7.40-7.43 (m, 2H), 7.48-
7.51(m,2H),7.54-7.57(m,3H),7.60-7.62(m,2H),7.72-7.74(m,2H),10.28(br s,1H).13C
NMR(100MHz,CDCl3)δ:112.9,115.7,118.5,122.3,123.7,127.3,128.2,128.3,128.8,
129.4,129.5,131.3,135.7,140.0,140.3,140.6,147.0,148.5,198.9.HRMS calcd
forC25H19NNaO:372.1359[M+Na]+,found:372.1360。
Embodiment 30
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2f (0.6mmol, 66 μ L), 3a (0.6mmol, 79mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains yellow oil
Shape product 4p (91mg, 50%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.29(s,3H),
6.82(dd,J1=8.4Hz, J2=1.6Hz, 1H), 7.11-7.13 (m, 2H), 7.17-7.19 (m, 2H), 7.27-7.36 (m,
3H), 7.41-7.49 (m, 6H), 7.54 (d, J=8.4Hz, 1H), 7.64-7.66 (m, 2H), 10.20 (br s, 1H)13C NMR
(150MHz,CDCl3)δ:20.9,112.5,115.2,117.9,123.0,127.3,128.2,128.3,128.8,129.3,
130.1,131.2,133.7,135.7,137.7,140.2,140.4,147.0,149.3,198.9.HRMS calcd for
C26H21NNaO:386.1515[M+Na]+,found:386.1513。
Embodiment 31
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3b (0.6mmol, 90mg),
2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), under nitrogen (1atm) atmosphere
It is stirred to react 12h in 120 DEG C.Then it is spin-dried for solvent, it is solid to obtain yellow for silica gel post separation (petrol ether/ethyl acetate=100/1) excessively
Body product 4q (86mg, 45%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:4.50(s,2H),
6.66(dd,J1=8.0Hz, J2=1.6Hz, 1H), 6.81 (d, J=1.2Hz, 1H), 7.01-7.05 (m, 2H), 7.20-7.23
(m,1H),7.28-7.31(m,2H),7.35-7.42(m,6H),7.44-7.51(m,2H),7.56-7.58(m,2H),9.09
(br s,1H).13C NMR(150MHz,CDCl3)δ:47.1,110.3,113.3,115.7(d,2JC-F=21.9Hz), 116.5,
127.3,127.4,128.1,128.8,128.9(d,3JC-F=8.7Hz), 129.1,130.9,136.2,136.7 (d,4JC-F=
3.3Hz),138.5,140.5,146.5,151.9,163.0(d,1JC-F=247.2Hz), 199.1.HRMS calcd for
C26H20FNNaO:404.1421[M+Na]+,found:404.1419。
Embodiment 32
Sequentially added in reaction tube 1a (0.5mmol, 72mg), 2a (0.6mmol, 66 μ L), 3c (0.6mmol,
126mg), 2,2,6,6- tetramethyl piperidine oxides (0.6mmol, 94mg) and Isosorbide-5-Nitrae-dioxane (3mL), at nitrogen (1atm)
Under atmosphere 12h is stirred to react in 120 DEG C.Then it is spin-dried for solvent, silica gel post separation (petrol ether/ethyl acetate=100/1) is crossed and obtains
Yellow oil product 4r (73mg, 33%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:4.50(d,
J=5.6Hz, 2H), 6.66 (dd, J1=8.4Hz, J2=1.6Hz, 1H), 6.80 (d, J=1.6Hz, 1H), 7.20-7.24 (m,
1H), 7.28-7.32 (m, 4H), 7.35-7.42 (m, 4H), 7.45-7.48 (m, 3H), 7.51 (d, J=8.4Hz, 1H), 7.57-
7.59 (m, 2H), 9.07 (t, J=4.8Hz, 1H)13C NMR(100MHz,CDCl3)δ:47.1,110.2,113.1,116.8,
122.6,127.3,127.4,128.1,128.8,129.1,130.9,131.9,136.2,138.4,139.6,140.4,
146.2,151.9,199.1.HRMS calcd for C26H20BrNNaO:464.0620[M+Na]+,found:464.0655。
Embodiment above describes the basic principles and main features and advantage of the present invention.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe the originals of the present invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (6)
1. a kind of synthetic method of 2- aminobenzophenones class compound, it is characterised in that building-up process the specific steps are：It will
Connection ketene compounds 1, primary amine compound 2 and ketene compounds 3 are dissolved in solvent, the heat temperature raising under oxidant effect
2- aminobenzophenone classes compound 4 is made in reaction, and the reaction equation in the synthetic method is：
Wherein R1For phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring is fluorine, chlorine, bromine, methyl or methoxy, R2For
C1-4Linear or branched alkyl group, phenyl replace C1-4Alkyl, phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring be fluorine,
Chlorine, bromine, methyl or methoxy, R3For phenyl or substituted-phenyl, the substituent group on substituted-phenyl phenyl ring be fluorine, chlorine, bromine, methyl or
Methoxyl group, oxidant are oxygen, tert-butyl hydroperoxide, di-tert-butyl peroxide or 2, the oxidation of 2,6,6- tetramethyl piperidines
Object.
2. the synthetic method of 2- aminobenzophenones class compound according to claim 1, it is characterised in that：The solvent
For 1,2- dichloroethanes, toluene, chlorobenzene or 1,4- dioxane.
3. the synthetic method of 2- aminobenzophenones class compound according to claim 1, it is characterised in that：Heat temperature raising
Reaction temperature is 80-140 DEG C.
4. the synthetic method of 2- aminobenzophenones class compound according to claim 1, it is characterised in that：The alkene
The ratio between amount for the substance that feeds intake of ketone compounds 1, primary amine compound 2 and ketene compounds 3 is 1:1-1.5:1-1.5.
5. the synthetic method of 2- aminobenzophenones class compound according to claim 1, it is characterised in that：The oxidation
Agent is tert-butyl hydroperoxide, di-tert-butyl peroxide or 2, when 2,6,6- tetramethyl piperidine oxides, joins ketene chemical combination
The ratio between amount for the substance that feeds intake of object 1, primary amine compound 2, ketene compounds 3 and oxidant is 1:1-1.5:1-1.5:0.5-
1.5。
6. the synthetic method of 2- aminobenzophenones class compound according to claim 1, it is characterised in that：In oxidant
2- aminobenzophenone classes compound 4 is made in heat temperature raising reaction in nitrogen atmosphere under effect.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109438245A (en) * | 2018-12-17 | 2019-03-08 | 河南师范大学 | A kind of nitro replaces the synthetic method of cyclobutane and naphthalenedione class compound |
| CN113143897A (en) * | 2021-04-20 | 2021-07-23 | 中国科学院武汉病毒研究所 | Application of 4-aminobenzophenone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107141207A (en) * | 2017-06-22 | 2017-09-08 | 河南师范大学 | A kind of synthetic method of the double hydroxy benzophenone ketone compounds of 3 ' acyl group 2,4 ' |
| CN107188792A (en) * | 2017-06-22 | 2017-09-22 | 河南师范大学 | A kind of synthetic method of 2,4 ' double hydroxy benzophenone ketone compounds |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107141207A (en) * | 2017-06-22 | 2017-09-08 | 河南师范大学 | A kind of synthetic method of the double hydroxy benzophenone ketone compounds of 3 ' acyl group 2,4 ' |
| CN107188792A (en) * | 2017-06-22 | 2017-09-22 | 河南师范大学 | A kind of synthetic method of 2,4 ' double hydroxy benzophenone ketone compounds |
Non-Patent Citations (3)
| Title |
|---|
| ASHISH KAPUR ET AL.: "Thermal reactions involving 1-azadienes and allenic esters-(II):1a reactions of 3-(N-aryliminomethyl)chromones with allenic esters-tandem reorganization of [2+2] cycloadducts to novel compounds", 《TETRAHEDRON LETTERS》 * |
| SHIBO XU ET AL.: "Isocyanide-Based Multicomponent Reactions: Rapid Synthesis of a 5,5-Fused Bicyclic Skeleton from α,β-Unsaturated Ketones and Allenoates", 《SYNTHESIS》 * |
| TIAN FENG ET AL.: "Tunable Synthesis of Functionalized Cyclohexa-1,3-dienes and 2‑Aminobenzophenones/Benzoate from the Cascade Reactions of Allenic Ketones/Allenoate with Amines and Enones", 《J. ORG. CHEM.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109438245A (en) * | 2018-12-17 | 2019-03-08 | 河南师范大学 | A kind of nitro replaces the synthetic method of cyclobutane and naphthalenedione class compound |
| CN109438245B (en) * | 2018-12-17 | 2021-07-20 | 河南师范大学 | Synthetic method of nitro-substituted cyclobutane-naphthaline diketone compound |
| CN113143897A (en) * | 2021-04-20 | 2021-07-23 | 中国科学院武汉病毒研究所 | Application of 4-aminobenzophenone |
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