CN109438288A - A kind of N- nitrone substituted aroma amide derivatives and preparation method thereof - Google Patents
A kind of N- nitrone substituted aroma amide derivatives and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Abstract
The present invention relates to a kind of N- nitrone substituted aroma amide derivatives and preparation method thereof.The structural formula of the N- nitrone substituted aroma amide derivatives is shown in formula I.The N- nitrone substituted aroma amide derivatives, adjacent position has tert-butylnitrone group and amide group on phenyl ring, it is a kind of widely used organic synthesis intermediate, there is important application value in medicine production and organic synthesis field, it is usually used in producing vitamin, hormone, it can also be used to preparation sterilization and anti-malarial class drug；Tert-butylnitrone group has the function of capturing free radical simultaneously, the compound can be used for preparing reduction and prevent the drug of damage caused by free radical in biosystem, such as have the drug of anti-platelet aggregation, anti-oxidant, free radical resisting, reducing blood lipid pharmacological effect.
Description
Technical field
The invention belongs to aromatic amides derivative fields, and in particular to a kind of N- nitrone substituted aroma amide derivatives and its
Preparation method.
Background technique
Amide derivatives are a kind of important organic synthesis intermediates, in natural products synthesis, chemical industry, medicine and other fields
In have important application value, extensive concern of the synthetic method by related fields researcher, exploitation green, efficiently,
The synthetic method of economic amide derivatives is of great significance.
In the prior art, it is known that aromatic amides analog derivative has sterilization or antimalarial active.As publication No. is
The Chinese patent application of CN106699732A discloses a kind of pyrazole amide analog derivative and its application as fungicide.It announces
Number a kind of acetamides are disclosed for the Chinese patent application of CN106905247A, had to wild, drug resistance plasmodium
There is inhibiting effect, wherein the acetamides have the structure as shown in formula IV:
Wherein, R1For group shown in A in formula or B, R2Linear or branched alkyl group for the C1-C4 replaced by phenyl, C4-C10
Naphthenic base, heterocycle or aromatic ring yl, or replace C4-C10 naphthenic base, heterocycle or aromatic ring yl.Shown in above formula IV
Compound has certain antimalarial agent activity.
Existing aromatic amides analog derivative, the Nature comparison of active group is single, limits it and closes in natural products
At, the application effect of chemical industry, medicine and other fields.
Summary of the invention
The purpose of the present invention is to provide a kind of N- nitrone substituted aroma amide derivatives, to solve existing aromatic amides class
The limited problem of the active group single property of derivative, application field.
Second object of the present invention is to provide the preparation method of above-mentioned N- nitrone substituted aroma amide derivatives, with solution
Certainly existing preparation method reaction efficiency is low, and condition is harsh, the small problem of the substrate scope of application.
To achieve the above object, the technical solution of N- nitrone substituted aroma amide derivatives of the invention is:
A kind of N- nitrone substituted aroma amide derivatives, structural formula are shown in formula I:
In Formulas I, R1~R4Independent is hydrogen, halogen, alkyl, substituted alkyl, phenyl, substituted phenyl or alcoxyl
Base；R5For phenyl, substituted phenyl, alkyl or benzyl.
N- nitrone substituted aroma amide derivatives provided by the invention, adjacent position has tert-butylnitrone group on phenyl ring
And amide group, it is a kind of widely used organic synthesis intermediate, has in medicine production and organic synthesis field important
Application value is usually used in producing vitamin, hormone, it can also be used to preparation sterilization and anti-malarial class drug；Tert-butylnitrone simultaneously
Group has the function of that capture free radical, the compound can be used for preparing in reduction and prevention biosystem caused by free radical
Damage drug, such as with anti-platelet aggregation, anti-oxidant, free radical resisting, reducing blood lipid pharmacological effect drug.
Occur from improving product yield and reducing side reaction in order to industrialized production aspect, it is preferred that Formulas I
In, R1~R4Independent is hydrogen, halogen, C1-C4 alkyl, trifluoromethyl, phenyl or C1-C4 alkoxy, R5For phenyl, take
The phenyl in generation, alkyl or benzyl.Further to obtain the product that reaction yield is high, is convenient for industrialized production, further preferably
, R5When for substituted phenyl, R5Substituent group on middle phenyl ring is C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, second
Acyl group or nitro.
The technical solution of the preparation method of N- nitrone substituted aroma amide derivatives of the invention is:
A kind of preparation method of N- nitrone substituted aroma amide derivatives, comprising the following steps: by fragrance shown in Formula II
1,4,2 shown in nitrone, formula III, it is anti-that-dioxazole -5- ketone derivatives carry out amination after mixing with catalyst, additive, solvent
It should be to get；
In Formula II, R1~R4Independent is hydrogen, halogen, alkyl, substituted alkyl, phenyl, substituted phenyl or alcoxyl
Base；In formula III, R5For phenyl, substituted phenyl, alkyl or benzyl.
The preparation method of N- nitrone substituted aroma amide derivatives provided by the invention is by fragrant nitrone, Isosorbide-5-Nitrae 2 ,-two
Oxazole -5- ketone derivatives carry out aminating reaction after mixing with catalyst, additive, solvent, realize the fragrance of N- nitrone substitution
The synthesis of amide derivatives；The preparation method can be carried out in air and under room temperature, and reaction condition is mild, easily controllable；Institute
It is easy to get with raw material, wide application range of substrates；Addition oxidant, acid or alkali are not had in reaction process, reaction specificity is strong, shorter
Available higher selectivity and yield in time, and post-process easy, environmentally protective, suitable large-scale industrial production.
In above-mentioned preparation method, if the dosage for the raw material that above-mentioned aminating reaction can be promoted to occur all be it is feasible, in order to
Improve reaction yield and raw material availability, it is preferred that Isosorbide-5-Nitrae shown in fragrance nitrone shown in Formula II and formula III, 2 ,-dioxazole-
The molar ratio of 5- ketone derivatives is 1:(1~2).
In above-mentioned preparation method, as long as above-mentioned aminating reaction can be promoted to occur and not will lead to the temperature of raw material and product denaturation
Degree condition is all feasible；In order to energy saving and facilitate control, production efficiency is improved, it is preferred that the temperature of the aminating reaction
Degree is room temperature, and the reaction time is 0.5~2 hour.
For the generation for preferably promoting aminating reaction, aminating reaction efficiency is improved, it is preferred that the catalyst is dichloro
(pentamethylcyclopentadiene base) closes iridium (III), palladium acetate, dichloro (pentamethylcyclopentadiene base) conjunction rhodium (III) or the bis- (first of dichloro
Base isopropyl phenyl) ruthenium (II).Comprehensively consider from reaction yield and utmostly in terms of the dosage of reduction catalyst, it is further excellent
Choosing, the molar ratio of fragrance nitrone shown in the catalyst and Formula II is (0.01~0.04): 1.
For the generation for preferably reducing side reaction, the reaction selectivity for generating target product is improved, it is preferred that the addition
Agent is sodium carbonate, pivalic acid, potassium persulfate, double trifluoromethanesulfonimide silver salt, silver hexafluoroantimonate or silver tetrafluoroborate.From
It improves reaction selectivity and comprehensively considers in terms of utmostly reducing the dosage of additive, it is further preferred that the additive
Molar ratio with fragrance nitrone shown in Formula II is (0.04~0.16): 1.
Specific embodiment
The reaction equation that the present invention prepares N- nitrone substituted aroma amide derivatives is as follows:
Wherein, R1~R4Independent is hydrogen, halogen, alkyl, substituted alkyl, phenyl (Ph), the phenyl or alkane replaced
Oxygroup；R5For phenyl (Ph), the phenyl replaced, alkyl or benzyl.1,4,2 shown in formula III,-dioxazole -5- ketone derivatives can
It is synthesized with reference to the prior art (J.Am.Chem.Soc.2015,137,4534.) method recorded.Specific synthetic method summary
It is as follows: by 5mmol corresponding oxime acid dissolution in 50mL methylene chloride, 1,1 '-N,N'-carbonyldiimidazole of 5mmol to be then added, stirs at room temperature
Mix reaction 30 minutes.30mL 1N HCl solution is added into reaction system after reaction；It is extracted with dichloromethane later；It closes
And organic phase and dry with anhydrous sodium sulfate；Accordingly 1,4,2 can be obtained by being removed under reduced pressure after solvent directly, and-dioxazole -5- ketone is derivative
Object.
From reactable and reaction yield aspect is improved, works as R1~R4When being hydrogen, R5For phenyl, substituted phenyl,
Alkyl or benzyl；Work as R1~R4Any of be halogen, methyl (Me), trifluoromethyl, phenyl (Ph) or methoxyl group, remaining is hydrogen
When, R5For phenyl, substituted phenyl, alkyl or benzyl.
When preparing above-mentioned N- nitrone substituted aroma amide derivatives, to improve reaction yield, fragrance nitre shown in Formula II
1,4,2 shown in ketone and formula III, the dosage of-dioxazole -5- ketone derivatives is 1,4,2 shown in chemical equivalent or formula III-two
Oxazole -5- ketone derivatives are excessive.
In above-mentioned preparation method, as long as Isosorbide-5-Nitrae shown in fragrance nitrone shown in energy dissolution type II and formula III, 2 ,-two are disliked
Azoles -5- ketone derivatives, and the organic solvent not reacted with raw material and product is all feasible；Preferably, the solvent is
Methanol, 1,2- dichloroethanes, toluene, methylene chloride, N,N-dimethylformamide, tetrahydrofuran, acetonitrile, in 1,4- dioxane
Any one or combinations thereof.The dosage of solvent meets sufficiently dissolution raw material；Preferably, the dosage of the solvent are as follows: every
Fragrance nitrone shown in mole Formula II is corresponding to use 2~10L solvent.
In order to further increase the purity of product, in above-mentioned preparation method, after the aminating reaction, also to reaction solution
It is successively filtered, is concentrated, column chromatographic purifying is to get N- nitrone substituted aroma amide derivatives.The filtering is using diatom
Soil is filtered.Filler used in column chromatographic purifying is 200-300 mesh column chromatography silica gel, and eluant, eluent is petroleum ether: acetic acid
Ethyl ester=(1~2): 1 (v/v).
Embodiments of the present invention are described further combined with specific embodiments below.
The embodiment 1 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
Benzamide, structural formula is as shown in Formulas I -1:
The embodiment 2 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- methyl benzamide, structural formula is as shown in Formulas I -2:
The embodiment 3 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- methoxy benzamide, structural formula is as shown in Formulas I -3:
The embodiment 4 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- fluorobenzamide, structural formula is as shown in Formulas I -4:
The embodiment 5 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- chlorobenzamide, structural formula is as shown in Formulas I -5:
The embodiment 6 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- brombenzamide, structural formula is as shown in Formulas I -6:
The embodiment 7 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- trifluoromethyl benzamide, structural formula is as shown in Formulas I -7:
The embodiment 8 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
4- nitrobenzene sulfonamide, structural formula is as shown in Formulas I -8:
The embodiment 9 of N- nitrone substituted aroma amide derivatives of the invention, for N- [2- (N- tert-butylnitrone) phenyl]-
3- methyl benzamide, structural formula is as shown in Formulas I -9:
The embodiment 10 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- first
Base phenyl]-benzamide, structural formula is as shown in Formulas I -10:
The embodiment 11 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- first
Phenyl]-benzamide, structural formula is as shown in Formulas I -11:
The embodiment 12 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- fluorine
Phenyl]-benzamide, structural formula is as shown in Formulas I -12:
The embodiment 13 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- chlorine
Phenyl]-benzamide, structural formula is as shown in Formulas I -13:
The embodiment 14 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- benzene
Base phenyl]-benzamide, structural formula is as shown in Formulas I -14:
The embodiment 15 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -5- three
Trifluoromethylphenyl]-benzamide, structural formula is as shown in Formulas I -15:
The embodiment 16 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -3- first
Base phenyl]-benzamide, structural formula is as shown in Formulas I -16:
The embodiment 17 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone) -4- first
Base phenyl]-benzamide, structural formula is as shown in Formulas I -17:
The embodiment 18 of N- nitrone substituted aroma amide derivatives of the invention is N- [2- (N- tert-butylnitrone)-benzene
Base]-adamantane formamide, structural formula is as shown in Formulas I -18:
The preparation method embodiment 1 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -1
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- phenyl-
1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double fluoroforms
Alkane sulfimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, under room temperature
Reaction 30 minutes, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains 47mg target product, and yield is
80%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3): δ 11.33 (br, 1H), 8.15 (d, J=
8.2Hz,1H),8.12-8.10(m,2H),7.85(s,1H),7.51-7.43(m,4H),7.14-7.10(m,1H),1.58(s,
9H)；13C NMR(100MHz,CDCl3):δ165.30,138.32,134.75,131.55,130.99,130.85,128.35,
127.69,125.14,123.94,122.17,70.92,28.28。
The preparation method embodiment 2 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -2
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- first
Base phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol,
Double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloroethane solvent, room
It being reacted 30 minutes under the conditions of temperature, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 47mg target product,
Yield is 80%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.21(br,1H),8.15(d,J
=8.0Hz, 1H), 8.01 (d, J=8.2Hz, 1H), 7.86 (s, 1H), 7.52-7.48 (m, 1H), 7.26-7.23 (m, 2H),
7.17-7.13(m,1H),2.41(s,3H),1.61(s,9H)；13C NMR(100MHz,CDCl3):δ165.29,141.88,
138.50,134.45,131.95,131.03,130.69,129.03,127.75,125.28,123.83,122.06,70.89,
28.35,21.48。
The preparation method embodiment 3 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -3
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- first
Phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 30 minutes under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains
42mg target product, yield 70%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.18(br,
1H), 8.12 (d, J=8.6Hz, 1H), 8.09 (d, J=8.8Hz, 2H), 7.86 (s, 1H), 7.24 (td, J1=7.3Hz, J2=
1.0Hz, 1H), 7.16-7.12 (m, 1H), 6.95 (d, J=8.8Hz, 2H), 3.86 (s, 3H), 1.61 (s, 9H)；13C NMR
(100MHz,CDCl3):δ164.91,162.29,138.54,134.61,131.03,130.74,129.61,127.13,
125.23,123.77,122.01,113.54,70.88,55.39,28.33。
The preparation method embodiment 4 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -4
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- fluorine
Phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double
Trifluoromethanesulfonimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature
Under the conditions of react 30 minutes, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 60mg target product, receives
Rate is 96%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.38(br,1H),8.16-8.12
(m,3H),7.87(s,1H),7.53-7.49(m,1H),7.25(dd,J1=7.8Hz, J2=1.4Hz, 1H), 7.18-7.11 (m,
3H),1.60(s,9H)；13C NMR(100MHz,CDCl3): δ 164.90 (d, J=250.1Hz), 164.20,138.31,
134.67,131.16,130.86,130.14,130.05,125.12,124.01,122.03 115.31 (d, J=21.7Hz),
70.97,28.30。
The preparation method embodiment 5 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -5
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- chlorine
Phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double
Trifluoromethanesulfonimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature
Under the conditions of react 30 minutes, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 62.4mg target product,
Yield is 95%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.45(br,1H),8.13(d,J
=8.2Hz, 1H), 8.01 (dd, J1=6.8Hz, J2=1.9Hz, 2H), 7.86 (s, 1H), 7.87 (d, J=8.6Hz, 2H),
7.54-7.49(m,1H),7.45-7.42(m,2H),7.25(dd,J1=7.8Hz, J2=1.4Hz, 1H), 7.19-7.15 (m,
1H),1.60(s,9H)；13C NMR(100MHz,CDCl3):δ164.19,138.19,137.78,134.72,133.20,
131.20,130.90,129.19,128.59,125.10,124.11,122.02,71.00,28.31。
The preparation method embodiment 6 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -6
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- bromine
Phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double
Trifluoromethanesulfonimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature
Under the conditions of react 30 minutes, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 67.3mg target product,
Yield is 90%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.46(br,1H),8.14(d,J
=8.2Hz, 1H), 8.01 (d, J=8.6Hz, 2H), 7.86 (s, 1H), 7.59 (d, J=8.6Hz, 2H), 7.53-7.49 (m,
1H),7.24(dd,J1=7.9Hz, J2=1.4Hz, 1H), 7.18-7.14 (m, 1H), 1.60 (s, 9H)；13C NMR(100MHz,
CDCl3):δ164.26,138.20,134.68,133.68,131.57,131.20,130.90,129.39,126.34,
125.08,124.09,122.01,71.01,28.32。
The preparation method embodiment 7 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -7
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- tri-
Trifluoromethylphenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 30 minutes under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains
53.8mg target product, yield 74%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.65
(br, 1H), 8.23 (d, J=8.2Hz, 2H), 8.17 (d, J=8.3Hz, 1H), 7.88 (s, 1H), 7.72 (d, J=8.2Hz,
2H), 7.56-7.52 (m, 1H), 7.27 (d, J=1.1Hz, 1H), 7.22-7.18 (m, 1H), 1.62 (s, 9H)；13C NMR
(100MHz,CDCl3): δ 163.89,138.07,134.71,133.11 (q, J=32.5Hz), 131.31,130.97,
128.16,125.35 (q, J=3.6Hz), 125.07,124.29,123.86 (q, J=271.0Hz), 122.03,71.08,
28.32。
The preparation method embodiment 8 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -8
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (4- nitre
Base phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol,
Double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloroethane solvent, room
It being reacted 30 minutes under the conditions of temperature, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 52mg target product,
Yield is 76%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.87(br,1H),8.33-8.28
(m, 4H), 8.17 (d, J=8.3Hz, 1H), 7.90 (s, 1H), 7.57-7.53 (m, 1H), 7.29 (dd, J1=7.8Hz, J2=
1.2Hz,1H),7.23-7.19(m,1H),1.63(s,9H)；13C NMR(100MHz,CDCl3):δ163.04,149.64,
140.47,137.89,134.88,131.42,131.14,128.86,124.90,124.48,123.53,121.99,71.17,
28.32。
The preparation method embodiment 9 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitrone shown in Formulas I -9
The preparation of substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- (3- first
Base phenyl) -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol,
Double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloroethane solvent, room
It being reacted 30 minutes under the conditions of temperature, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 36mg target product,
Yield is 58%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.25(br,1H),8.17(d,J
=8.3Hz, 1H), 7.92 (d, J=11.1Hz, 2H), 7.86 (s, 1H), 7.52-7.48 (m, 1H), 7.36-7.30 (m, 2H),
7.23 (d, J=7.2Hz, 1H), 7.15 (t, J=7.7Hz, 1H), 2.42 (s, 3H), 1.61 (s, 9H)；13C NMR
(100MHz,CDCl3):δ165.45,138.42,138.05,134.72,134.40,132.26,131.03,128.32,
128.22,125.22,124.80,123.88,122.10,70.90,28.35,21.40。
The preparation method embodiment 10 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -10
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- aminomethyl phenyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains
53.7mg target product, yield 87%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.45
(br, 1H), 8.12 (t, J=7.6Hz, 2H), 7.99 (s, 1H), 7.81 (s, 1H), 7.51-7.43 (m, 3H), 7.13 (d, J=
8.0Hz,1H),7.13(dd,J1=8.0Hz, J2=0.8Hz, 1H), 2.42 (s, 3H), 1.60 (s, 9H)；13C NMR
(100MHz,CDCl3):δ165.27,141.83,138.25,134.81,131.51,131.45,130.68,128.31,
127.73,125.62,125.09,119.41,70.64,28.32,21.67。
The preparation method embodiment 11 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -11
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- methoxyphenyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains 54mg
Target product, yield 83%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.84(br,1H),
8.14 (t, J=7.7Hz, 2H), 7.85 (d, J=2.5Hz, 1H), 7.76 (s, 1H), 7.51-7.46 (m, 3H), 7.13 (d, J=
8.7Hz,1H),7.13(dd,J1=8.7Hz, J2=2.6Hz, 1H), 3.88 (s, 3H), 1.60 (s, 9H)；13C NMR
(100MHz,CDCl3):δ165.51,162.16,140.27,134.84,134.48,132.21,131.53,128.33,
127.78,114.44,111.93,108.59,70.33,55.56,28.32。
The preparation method embodiment 12 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -12
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- fluorophenyl) nitrone 0.2mmol,
Phenyl -1,4,2 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double
Trifluoromethanesulfonimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature
Under the conditions of react 1 hour, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 31mg target product, yield
It is 49%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.58(br,1H),8.12-8.10(m,
2H),8.02(dd,J1=11.2Hz, J2=2.6Hz, 1H), 7.82 (s, 1H), 7.53-7.51 (m, 1H), 7.49-7.45 (m,
2H),7.20(dd,J1=8.7Hz, J2=6.1Hz, 1H), 6.90-6.85 (m, 1H), 1.62 (s, 9H)；13C NMR(100MHz,
CDCl3): δ 165.48,164.42 (d, J=249.3Hz), 140.53 (d, J=11.8Hz), 134.44,133.88,132.47
(d, J=10.1Hz), 131.76,128.41,127.74,118.0 (d, J=3.0Hz), 111.84 (d, J=43.8Hz),
111.60 (d, J=40.8Hz), 70.98,28.30.
The preparation method embodiment 13 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -13
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- chlorphenyl) nitrone 0.2mmol,
Phenyl -1,4,2 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double
Trifluoromethanesulfonimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature
Under the conditions of react 1 hour, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 44.2mg target product, receives
Rate is 67%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3): δ 11.42 (br, 1H), 8.26 (d, J=
1.9Hz, 1H), 8.09 (dt, J=7.8Hz, 2H), 7.82 (s, 1H), 7.53-7.50 (m, 1H), 7.48-7.45 (m, 2H),
7.15-7.11(m,2H),1.61(s,9H)；13C NMR(100MHz,CDCl3):δ165.36,139.42,137.3,134.36,
133.75,131.79,131.70,128.42,127.71,124.96,124.19,120.40,71.2,28.30。
The preparation method embodiment 14 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -14
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- phenyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains 59mg
Target product, yield 80%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ10.60(br,1H),
9.11 (d, J=1.5Hz, 1H), 8.02 (d, J=7.1Hz, 1H), 7.69 (d, J=7.4Hz, 1H), 7.55-7.49 (m, 4H),
7.47-7.43 (m, 2H), 7.36 (t, J=7.1Hz, 1H), 1.25 (s, 9H)；13C NMR(100MHz,CDCl3):δ165.47,
144.24,140.18,139.82,135.43,132.14,131.66,128.78,128.53,127.88,127.44,127.36,
121.43,119.70,118.87,77.21,58.80,25.16。
The preparation method embodiment 15 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -15
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(4- trifluoromethyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains 65mg
Target product, yield 89%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.22(br,1H),
8.53 (s, 1H), 8.08 (td, J=7.1Hz, 1.5Hz, 2H), 7.91 (s, 1H), 7.55-7.51 (m, 1H), 7.49-7.45 (m,
2H),7.39-7.33(m,2H),1.63(s,9H)；13C NMR(100MHz,CDCl3):δ165.41,138.83,134.19,
(133.38,132.66 q, J=32.7Hz), 131.9,131.25,128.47,127.66,124.97,123.71 (q, J=
271.2Hz), 122.08 (q, J=3.9Hz), 120.29 (q, J=3.6Hz), 71.71,28.29.
The preparation method embodiment 16 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -16
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(2- aminomethyl phenyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains
51.2mg target product, yield 83%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ10.91
(br, 1H), 8.09 (td, J=7.7Hz, 1.5Hz, 2H), 7.90 (s, 1H), 7.50-7.39 (m, 4H), 7.01 (d, J=
7.5Hz,1H),2.32(s,3H)1.58(s,9H)；13C NMR(100MHz,CDCl3):δ165.36,138.59,137.96,
134.63,133.30,131.50,130.81,128.32,127.69,126.23,123.30,121.43,71.12,28.40,
20.25。
The preparation method embodiment 17 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -17
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-(3- aminomethyl phenyl) nitrone
Phenyl -1,4,2 0.2mmol, 3-,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III)
0.004mmol, double trifluoromethanesulfonimide silver salt 0.016mmol are added in Shrek pipe, are dissolved in 1.0mL 1,2- dichloro
Ethane solvent reacts 1 hour under room temperature, reaction solution is filtered through diatomite, and filtrate concentration, column chromatographic purifying obtains 28mg
Target product, yield 34%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3):δ11.23(br,1H),
8.10 (td, J=7.6Hz, 1.4Hz, 2H), 8.02 (d, J=8.4Hz, 1H), 7.83 (s, 1H), 7.50-7.43 (m, 3H),
7.32(dd,J1=8.4Hz, J2=1.4Hz, 1H), 7.04 (d, J=0.6Hz, 1H), 2.31 (s, 3H) 1.59 (s, 9H)；13C
NMR(100MHz,CDCl3):δ165.20,135.84,134.79,134.50,133.60,131.97,131.42,130.81,
128.31,127.67,125.17,122.05,70.81,28.31,20.69。
The preparation method embodiment 18 of N- nitrone substituted aroma amide derivatives of the invention, to N- nitre shown in Formulas I -18
The preparation of ketone substituted aroma amide derivatives is illustrated, specifically: by N- tert-butyl-α-phenyinitrone 0.2mmol, 3- Buddha's warrior attendant
Alkyl -1,4,2,-dioxazole -5- ketone 0.22mmol, dichloro (pentamethylcyclopentadiene base) close iridium (III) 0.004mmol, double three
Fluoromethane sulfimide silver salt 0.016mmol is added in Shrek pipe, is dissolved in 1.0mL 1,2- dichloroethane solvent, room temperature item
It is reacted 1 hour under part, reaction solution is filtered through diatomite, filtrate concentration, column chromatographic purifying obtains 63mg target product, and yield is
88%.The nuclear-magnetism of the compound is characterized as below:1H NMR(400MHz,CDCl3): δ 10.36 (br, 1H), 7.98 (d, J=
8.3Hz,1H),7.79(s,1H),7.44-7.40(m,1H),7.17(dd,J1=7.8Hz, J2=1.2Hz, 1H), 7.11-7.07
(m, 1H), 2.05 (d, J=8.7Hz, 3H), 1.98 (d, J=2.7Hz, 6H), 1.74 (s, 3H), 1.65 (s, 9H)；13C NMR
(100MHz,CDCl3):δ177.17,138.35,134.00,130.70,130.59,125.34,123.49,121.86,
70.82,41.67,39.16,36.64,28.53,28.28。
In the other embodiments of N- nitrone substituted aroma amide derivatives of the invention, in formula III compound represented,
R5It can choose as methyl, ethyl, benzyl or acetylphenyl, then corresponding N- nitre is obtained by the preparation method of embodiment 1
Ketone substituted aroma amide derivatives.Palladium acetate, dichloro (pentamethylcyclopentadiene base) can be used to close rhodium (III) or dichloro for catalyst
Bis- (isopropyl methyl phenyl) rutheniums (II) are closed iridium (III) to the dichloro (pentamethylcyclopentadiene base) in above embodiments and are carried out etc.
Amount replacement；Sodium carbonate, pivalic acid, potassium persulfate, silver hexafluoroantimonate or silver tetrafluoroborate may be selected in additive implements to above
Double trifluoromethanesulfonimide silver salt in example carry out equivalent replacement；1,4 shown in fragrance nitrone shown in Formula II and formula III,
2, the molar ratio of-dioxazole -5- ketone derivatives, the relative amounts of catalyst, additive can be according to reaction temperature, yield
Situations such as be adaptively adjusted, in the preferred scope that limits of the present invention, can get the higher corresponding product of yield.
Above implementations show the implementation situation that solvent is 1,2- dichloroethanes, other solvents such as methanol, toluene, dichloros
Methane, n,N-Dimethylformamide, tetrahydrofuran, acetonitrile, Isosorbide-5-Nitrae-dioxane etc. can meet corresponding requirements, solvent it is specific
Dosage can be adaptively adjusted according to actual conditions such as dissolution of raw material dispersion, reaction yields, general every mole of Formula II institute
The fragrant nitrone shown is corresponding can to meet reaction requirement using 2~10L solvent.
N- nitrone substituted aroma amide derivatives prepared by the present invention, adjacent position has tert-butylnitrone base on phenyl ring
Group and amide group, according to the existing research of aromatic amides group (reference can be made to publication No. is the Chinese patent of CN108368030A
Apply for disclosure), which has important application value in terms of preparation sterilization and anti-malarial class drug；In addition,
According to the existing research of tert-butylnitrone group (reference can be made to publication No. be US20180117115A1 U.S. Patent application, announce
Number for CN1394200A the prior arts disclosure such as Chinese patent application), the compound can be used for preparing reduction and
Prevent the drug of damage caused by free radical in biosystem, such as there is anti-platelet aggregation, anti-oxidant, free radical resisting, drop
The drug of the pharmacological effects such as blood lipid.
Claims (10)
1. a kind of N- nitrone substituted aroma amide derivatives, which is characterized in that its structural formula is shown in formula I:
In Formulas I, R1~R4Independent is hydrogen, halogen, alkyl, substituted alkyl, phenyl, substituted phenyl or alkoxy；R5
For phenyl, substituted phenyl, alkyl or benzyl.
2. N- nitrone substituted aroma amide derivatives as described in claim 1, which is characterized in that in Formulas I, R1~R4Respectively solely
Vertical is hydrogen, halogen, C1-C4 alkyl, trifluoromethyl, phenyl or C1-C4 alkoxy, R5For phenyl, substituted phenyl, alkyl or
Benzyl.
3. N- nitrone substituted aroma amide derivatives as claimed in claim 2, which is characterized in that R5When for substituted phenyl, R5
Substituent group on middle phenyl ring is C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, acetyl group or nitro.
4. a kind of preparation method of N- nitrone substituted aroma amide derivatives, which comprises the following steps: by Formula II institute
1,4,2 shown in the fragrant nitrone that shows, formula III,-dioxazole -5- ketone derivatives mix laggard with catalyst, additive, solvent
Row aminating reaction to get；
In Formula II, R1~R4Independent is hydrogen, halogen, alkyl, substituted alkyl, phenyl, substituted phenyl or alkoxy；
In formula III, R5For phenyl, substituted phenyl, alkyl or benzyl.
5. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 4, which is characterized in that shown in Formula II
Fragrant nitrone and formula III shown in 1,4,2, the molar ratios of-dioxazole -5- ketone derivatives is 1:(1~2).
6. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 4, which is characterized in that the amination
The temperature of reaction is room temperature, and the reaction time is 0.5~2 hour.
7. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 4, which is characterized in that the catalysis
Agent be dichloro (pentamethylcyclopentadiene base) close iridium (III), palladium acetate, dichloro (pentamethylcyclopentadiene base) close rhodium (III) or
Bis- (isopropyl methyl phenyl) rutheniums (II) of dichloro.
8. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 7, which is characterized in that the catalysis
The molar ratio of fragrance nitrone shown in agent and Formula II is (0.01~0.04): 1.
9. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 4, which is characterized in that the addition
Agent is sodium carbonate, pivalic acid, potassium persulfate, double trifluoromethanesulfonimide silver salt, silver hexafluoroantimonate or silver tetrafluoroborate.
10. the preparation method of N- nitrone substituted aroma amide derivatives as claimed in claim 9, which is characterized in that described to add
The molar ratio for adding fragrance nitrone shown in agent and Formula II is (0.04~0.16): 1.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281432A (en) * | 1997-10-17 | 2001-01-24 | 桑道药品有限公司 | Alpha-aryl-N-alkylnitrones and pharmaceutical compositions containing same |
| CN1334800A (en) * | 1998-12-02 | 2002-02-06 | 仙陶尔药品公司 | 3,4,5-trisubstd. aryl nitrone compounds and pharmaceutical compositions contg. same |
| CN101434564A (en) * | 2007-11-15 | 2009-05-20 | 罗门哈斯公司 | Preparation method of nitrone |
| CN101851176A (en) * | 2010-06-07 | 2010-10-06 | 苏州欣诺科生物科技有限公司 | Novel nitrone ligand, organic metal iridium catalyst and preparation method and application thereof |
| CN104661641A (en) * | 2011-11-30 | 2015-05-27 | 陶氏环球技术有限公司 | Nitrone compounds and their use in personal care |
| CN104910051A (en) * | 2015-04-23 | 2015-09-16 | 郑州大学 | Nitrone-substituted sulfonylarylamine derivative and preparation method thereof |
| CN108640869A (en) * | 2018-05-29 | 2018-10-12 | 四川大学 | Transition metal-catalyzed C-H couplings efficiently prepare mebenil aryl-heterocyclic analog derivative |
-
2018
- 2018-10-22 CN CN201811230212.3A patent/CN109438288B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281432A (en) * | 1997-10-17 | 2001-01-24 | 桑道药品有限公司 | Alpha-aryl-N-alkylnitrones and pharmaceutical compositions containing same |
| CN1334800A (en) * | 1998-12-02 | 2002-02-06 | 仙陶尔药品公司 | 3,4,5-trisubstd. aryl nitrone compounds and pharmaceutical compositions contg. same |
| CN101434564A (en) * | 2007-11-15 | 2009-05-20 | 罗门哈斯公司 | Preparation method of nitrone |
| CN101851176A (en) * | 2010-06-07 | 2010-10-06 | 苏州欣诺科生物科技有限公司 | Novel nitrone ligand, organic metal iridium catalyst and preparation method and application thereof |
| CN104661641A (en) * | 2011-11-30 | 2015-05-27 | 陶氏环球技术有限公司 | Nitrone compounds and their use in personal care |
| CN104910051A (en) * | 2015-04-23 | 2015-09-16 | 郑州大学 | Nitrone-substituted sulfonylarylamine derivative and preparation method thereof |
| CN108640869A (en) * | 2018-05-29 | 2018-10-12 | 四川大学 | Transition metal-catalyzed C-H couplings efficiently prepare mebenil aryl-heterocyclic analog derivative |
Non-Patent Citations (6)
| Title |
|---|
| ANIKET MISHRA等: "Ir(III)/MPAA-Catalyzed Mild and Selective C −H Amidation of N‑ Sulfonyl Ketimines: Access To Benzosultam-Fused Quinazolines Quinazolinones", 《J.ORG.CHEM.》 * |
| HONG DENG等: "RhIII-Catalyzed site-selective amidation with nitrone as a traceless directing group: an approach to functionalized arylaldehydes", 《CHEM. COMMUN.》 * |
| WENGE ZHANG等: "Ir( III )-Catalyzed site-selective amidation of azoxybenzenes and late-stage transformation", 《ORG .CHEM .FRONT》 * |
| YEONGYU HWANG等: "Mechanism-Driven Approach To Develop a Mild and Versatile C-H Amidation through IrIII Catalysis", 《CHEM.EUR.J.》 * |
| YOONSU PARK等: "Study of Sustainability and Scalability in the Cp *Rh(III)-Catalzed Direct C−H Amidation with 1,4,2-Dioxazol-5-ones", 《ORG. PROCESS RES. DEV.》 * |
| 无: "无", 《STN REG》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113149858A (en) * | 2021-01-22 | 2021-07-23 | 南开大学 | Synthesis method of intermolecular N-N bonding and compound correspondingly synthesized |
| CN113149858B (en) * | 2021-01-22 | 2023-01-17 | 南开大学 | Synthesis method of intermolecular N-N bonding and compound correspondingly synthesized |
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