CN109206356A - Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method - Google Patents
Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method Download PDFInfo
- Publication number
- CN109206356A CN109206356A CN201811162576.2A CN201811162576A CN109206356A CN 109206356 A CN109206356 A CN 109206356A CN 201811162576 A CN201811162576 A CN 201811162576A CN 109206356 A CN109206356 A CN 109206356A
- Authority
- CN
- China
- Prior art keywords
- phenoxyphenyl
- oxygen
- balloon
- phthalimide
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses it is a kind of using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method.For this method using (E)-N- (4- Phenoxyphenyl) -1- phenyl azomethine as reaction raw materials through carbonylation, a step constructs N- (4- Phenoxyphenyl) phthalimide.The characteristics of this method has reaction condition mild, and operating procedure is succinct, good yields.
Description
Technical field
The present invention relates to the technical fields such as biology, medicine and life science, and in particular to arriving using imines is starting material
One step construct N-(4- Phenoxyphenyl) phthalimide method.
Background technique
The phthalimide derivatives that N- replaces are the important intermediates of synthetic fatty amine and a-amino acid, are closed
At classical way be phthalimide is reacted with potassium hydroxide generate sylvite, with dimethylformamide be react it is molten
Agent is acted on corresponding halides, but the reaction substrate applicability is limited, and reaction condition is extremely harsh.It faces
Such reaction limitation, the present invention construct N-(4- Phenoxyphenyl by one step of starting material of imines) phthalimide,
New synthesis path is provided for the synthesis of such compound.This method synthetic line is succinct, and reaction condition is mild, and yield is excellent
It is good, there is huge application value.
The N-(4- Phenoxyphenyl that the present invention synthesizes) phthalimide, structural formula is as follows:
Summary of the invention
It is that one step of starting material constructs N-(4- Phenoxyphenyl that the object of the present invention is to provide a kind of using imines) neighbour's benzene
The method of dicarboximide.
Specific steps are as follows:
(1) raw material is weighed according to following molar ratio, catalyst: oxidant: (E)-N-(4- Phenoxyphenyl) -1- phenyl first
Imines=0.05~0.5:1~4:1；
(2) by weighed (the E)-N-(4- Phenoxyphenyl of step (1)) -1- phenyl azomethine, catalyst and oxidant set
In reaction vessel, the water of solvent and an equivalent is added, the balloon filled with carbon monoxide and oxygen is put on, at 40~150 DEG C
Lower progress carbonylation 1~72 hour；
(3) product made from step (2) is isolated and purified using column chromatography, column chromatographic eluate is petroleum ether and acetic acid
The mixed solvent of ethyl ester, wherein the volume ratio of petroleum ether and ethyl acetate is 1~40:1, after isolating and purifying, obtains N- (4-
Phenoxyphenyl) phthalimide；
The catalyst is dichlorodiethyl nitrile palladium；
The oxidant is oxygen, 1,4-benzoquinone, manganese dioxide, silver carbonate, copper acetate, copper oxide or potassium peroxydisulfate；
The solvent is the mixed solvent of toluene and n,N-Dimethylformamide, wherein toluene and n,N-Dimethylformamide
Volume ratio be 1:0.01~100；
The volume ratio of carbon monoxide and oxygen is 1:0.1~10 in the balloon, and the pressure of balloon is 1~100 atmosphere
Pressure.
Compared with prior art, present invention has an advantage that
(1) CO gas is cheap and easy to get, and N-(4- Phenoxyphenyl is synthesized as carbonyl source using CO) phthalyl Asia
Amine increases the practicability of reaction.
(2) use imines for one step of starting material construct N-(4- Phenoxyphenyl) phthalimide synthesis hand
Section, experimental implementation is simple, and reaction condition is mild, good yields, improves the application value of reaction.
(3) proportion and reaction temperature of each substance of mixed solvent provided in the present invention, in the mixed solvent are for mesh
The preparation of mark product is played the role of critical.
Detailed description of the invention
Fig. 1 is the synthetic route chart of the method for the present invention.
Fig. 2 be embodiment 1 obtained in N-(4- Phenoxyphenyl) phthalimide nuclear magnetic resonance spectroscopy.
Fig. 3 be embodiment 1 obtained in N-(4- Phenoxyphenyl) phthalimide carbon-13 nmr spectra.
Specific embodiment
The invention is further described below by specific embodiment.
Embodiment 1
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 10:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, in 100 degrees Celsius
Lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, is removed balloon, is slowly put
Empty unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent, yield 60%.
The present embodiment structure of title compound is shown in Fig. 2 and Fig. 3.
Embodiment 2
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, be added toluene be used as solvent, addition 0.2 mM of water, then put on containing
The balloon of carbon monoxide and oxygen stirs 24 hours under 100 degrees Celsius as carbonyl source.TLC (thin-layered chromatography) tracking inspection
It surveys, does not detect target product.
Embodiment 3
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, n,N-Dimethylformamide is added as solvent, is added 0.2 mM of water,
Then the balloon for containing carbon monoxide and oxygen is put on as carbonyl source, is stirred 24 hours under 100 degrees Celsius.TLC (thin layer color
Spectrometry) tracing detection, do not detect target product.
Embodiment 4
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, be added acetonitrile be used as solvent, addition 0.2 mM of water, then put on containing
The balloon of carbon monoxide and oxygen stirs 24 hours under 100 degrees Celsius as carbonyl source.TLC (thin-layered chromatography) tracking inspection
It surveys, does not detect target product.
Embodiment 5
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, Isosorbide-5-Nitrae-dioxane is added as solvent, is added 0.2 mM of water, then
The balloon for containing carbon monoxide and oxygen is put on as carbonyl source, is stirred 24 hours under 100 degrees Celsius.TLC (thin-layer chromatography
Method) tracing detection, do not detect target product.
Embodiment 6
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, dimethyl sulfoxide is added as solvent, is added 0.2 mM of water, then covers
On contain carbon monoxide and oxygen balloon as carbonyl source, stirred 24 hours under 100 degrees Celsius.TLC (thin-layered chromatography)
Tracing detection does not detect target product.
Embodiment 7
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 5:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, in 100 degrees Celsius
Lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, is removed balloon, is slowly put
Empty unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent, yield are reduced to 20%.
Embodiment 8
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 1:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, in 100 degrees Celsius
Lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, is removed balloon, is slowly put
Empty unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent, yield only have 11%.
Embodiment 9
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 10:1, it is added 0.2 mM of water, the balloon for containing carbon monoxide and oxygen is then put on as carbonyl source, is stirred under room temperature
It mixes 24 hours.TLC (thin-layered chromatography) tracing detection, does not detect target product.
Embodiment 10
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 10:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, in 80 degrees Celsius
Lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, is removed balloon, is slowly put
Empty unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent, yield 31%.
Embodiment 11
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 10:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, in 90 degrees Celsius
Lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, is removed balloon, is slowly put
Empty unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent, yield 37%.
Embodiment 12
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, it is mixed solvent that toluene and n,N-Dimethylformamide, which is added, and volume ratio is
10:1 is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, under 110 degrees Celsius
Stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, removes balloon, is slowly vented
Unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then pass through column chromatographic isolation and purification,
Obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10:1 that column chromatographic eluate used, which is volume ratio,
Petroleum ether: ethyl acetate mixed solvent, yield 17%.
Embodiment 13
(E)-N-(4- Phenoxyphenyl is added in the test tube of 25mL) 0.2 mM of -1- phenyl azomethine, dichlorodiethyl
0.01 mM of nitrile palladium, 0.2 mM of copper oxide, toluene and n,N-Dimethylformamide is added as mixed solvent, volume ratio
For 10:1, it is added 0.2 mM of water, then puts on the balloon for containing carbon monoxide and oxygen as carbonyl source, it is Celsius in 120
Degree lower stirring 24 hours.Reaction solution is cooled to room temperature after reaction by TLC (thin-layered chromatography) detection, removes balloon, slowly
It is vented unreacted carbon monoxide and oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then it is pure by column chromatography for separation
Change, obtain target product N-(4- Phenoxyphenyl) phthalimide, it is 10 that column chromatographic eluate used, which is volume ratio:
1 petroleum ether: ethyl acetate mixed solvent obtains the N-(4- Phenoxyphenyl of trace) phthalimide.
Test result in above-described embodiment is shown in Tables 1 and 2.
Table 1
| Solvent (solvent) | Yield (%) |
| PhMe | 0 |
| DMF | 0 |
| CH3CN | 0 |
| dioxane | 0 |
| DMSO | 0 |
| PhMe/DMF(10:1) | 60 |
| PhMe/DMF(5:1) | 20 |
| PhMe/DMF(1:1) | 11 |
Table 2
Solvent of the invention and temperature parameter setting can be such that reaction yield significantly improves.At present about the conjunction of such compound
It uses single solvent as reaction dissolvent at majority, but when the present invention uses single solvent as reaction dissolvent, all detects not
To target product, when only using toluene and n,N-Dimethylformamide instead as mixed solvent, ability is reacted.And solvent
Proportion also have a significant impact to reaction yield, only solvent ratios be PhMe/DMF (10:1) when, the effect of reaction is only most
Alright；In addition to this, temperature parameter of the invention setting can also be such that reaction yield significantly improves.Most importantly the invention is based on
Imines is starting material, substantially increases reaction yield, for N-(4- Phenoxyphenyl) synthesis of phthalimide provides
New synthesis thinking.
Claims (1)
1. using imines it is that one step of starting material constructs N-(4- Phenoxyphenyl a kind of) method of phthalimide, it is special
Sign is specific steps are as follows:
(1) raw material is weighed according to following molar ratio, catalyst: oxidant: (E)-N-(4- Phenoxyphenyl) -1- phenyl azomethine
=0.05~0.5:1~4:1；
(2) by weighed (the E)-N-(4- Phenoxyphenyl of step (1)) -1- phenyl azomethine, catalyst and oxidant be placed in instead
Answer in container, be added solvent and an equivalent water, put on the balloon filled with carbon monoxide and oxygen, at 40~150 DEG C into
Row carbonylation 1~72 hour；
(3) product made from step (2) is isolated and purified using column chromatography, column chromatographic eluate is petroleum ether and ethyl acetate
Mixed solvent, wherein the volume ratio of petroleum ether and ethyl acetate be 1~40:1, after isolating and purifying, obtain N-(4- phenoxy group
Phenyl) phthalimide；
The catalyst is dichlorodiethyl nitrile palladium；
The oxidant is oxygen, 1,4-benzoquinone, manganese dioxide, silver carbonate, copper acetate, copper oxide or potassium peroxydisulfate；
The solvent is the mixed solvent of toluene and n,N-Dimethylformamide, wherein the body of toluene and n,N-Dimethylformamide
Product is than being 1:0.01~100；
The volume ratio of carbon monoxide and oxygen is 1:0.1~10 in the balloon, and the pressure of balloon is 1~100 atmospheric pressure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811162576.2A CN109206356A (en) | 2018-09-30 | 2018-09-30 | Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811162576.2A CN109206356A (en) | 2018-09-30 | 2018-09-30 | Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109206356A true CN109206356A (en) | 2019-01-15 |
Family
ID=64982644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811162576.2A Withdrawn CN109206356A (en) | 2018-09-30 | 2018-09-30 | Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109206356A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114437028B (en) * | 2022-03-27 | 2023-11-17 | 桂林理工大学 | Method for generating N-substituted phthalimide compound by nickel-catalyzed carbonylation reaction |
-
2018
- 2018-09-30 CN CN201811162576.2A patent/CN109206356A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114437028B (en) * | 2022-03-27 | 2023-11-17 | 桂林理工大学 | Method for generating N-substituted phthalimide compound by nickel-catalyzed carbonylation reaction |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109206356A (en) | Using imines be one step of starting material construct N-(4- Phenoxyphenyl) phthalimide method | |
| CN109020870A (en) | Using imines be one step of starting material construct N-(4- isopropyl phenyl) phthalimide method | |
| CN109206354A (en) | Using imines be one step of starting material construct N-(1- naphthalene) phthalimide method | |
| CN109293554A (en) | It is the method that one step of starting material constructs N- benzylphthalimide using imines | |
| CN109293560A (en) | Using imines be one step of starting material construct N-(4- chlorphenyl) phthalimide method | |
| CN109053545A (en) | Using imines be one step of starting material construct N-(4- bromophenyl) phthalimide new method | |
| CN109020869A (en) | Using imines be one step of starting material construct N-(4- tolyl) phthalimide method | |
| CN109180557A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- chlorine isoindoline -1,3- diketone using imines | |
| CN109232371A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- fluorine isoindoline -1,3- diketone using imines | |
| CN109232368A (en) | It is the method that one step of starting material constructs 2- cyclopenta -5- dimethylamino isoindoline -1,3- diketone using imines | |
| CN109232370A (en) | Using imines be one step of starting material construct N-(4- fluorophenyl) phthalimide method | |
| CN109232373A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- nitro isoindoline -1,3- diketone using imines | |
| CN109020866A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- methoxyl group isoindoline -1,3- diketone using imines | |
| CN109020868A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- dimethylamino isoindoline -1,3- diketone using imines | |
| CN109232372A (en) | It is the method that one step of starting material constructs 2- tert-butyl -4- methoxyl group isoindoline -1,3- diketone using imines | |
| CN109293555A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5,6- dichloro isoindoline -1,3- diketone using imines | |
| CN109293559A (en) | It is the method that one step of starting material constructs N- normal-butyl phthalimide using imines | |
| CN109081806A (en) | It is the method that one step of starting material constructs 2,5- di-t-butyl isoindoline -1,3- diketone using imines | |
| CN109232374A (en) | It is the method that one step of starting material constructs 2- tert-butyl -5- methylisoindoline -1,3- diketone using imines | |
| CN109206352A (en) | It is the method that one step of starting material constructs N- N-isopropyl phthalimide using imines | |
| CN109232367A (en) | The method of one step building drug molecule precursor 2- (2,2- diethoxy ethyl) isoindoline -1,3- diketone | |
| CN109096173A (en) | It is the method that one step of starting material constructs N- cyclohexyl phthalimide using imines | |
| CN109206355A (en) | It is the method that one step of starting material constructs N- isobutylphthalimide using imines | |
| CN109180558A (en) | It is the method that one step of starting material constructs N- cyclobutyl phthalimide using imines | |
| CN109020867A (en) | It is the method that one step of starting material constructs 2- tert-butyl -4,6- dimethyl isoindoline -1,3- diketone using imines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190115 |