CN108997227A - A method of synthesis 2,3- dihydroquinazoline -4 (1H) -one class compound - Google Patents
A method of synthesis 2,3- dihydroquinazoline -4 (1H) -one class compound Download PDFInfo
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- CN108997227A CN108997227A CN201810834858.6A CN201810834858A CN108997227A CN 108997227 A CN108997227 A CN 108997227A CN 201810834858 A CN201810834858 A CN 201810834858A CN 108997227 A CN108997227 A CN 108997227A
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- Prior art keywords
- dihydroquinazoline
- class compound
- synthesizing
- aldehyde
- substituted aniline
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- GTWJETSWSUWSEJ-UHFFFAOYSA-N C(c1ccccc1)Nc1ccccc1 Chemical compound C(c1ccccc1)Nc1ccccc1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
- 0 CC(*)NC1=CC=CC*1 Chemical compound CC(*)NC1=CC=CC*1 0.000 description 1
- OJGMBLNIHDZDGS-UHFFFAOYSA-N CCNc1ccccc1 Chemical compound CCNc1ccccc1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N CNc1ccccc1 Chemical compound CNc1ccccc1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of palladium chtalystsNSubstituted aniline ortho position c h bond mobilizing function is combined to 2,3- dihydroquinazoline -4 (1H) -one class compound method.With the simple convenient sources of structureNSubstituted aniline, amine, CO and aldehyde/ketone are starting material, make catalyst with palladium acetate, pass through palladium chtalystNThe multi-component reaction of substituted aniline ortho position c h bond mobilizing function directly synthesizes 2,3- dihydroquinazoline -4 (1H) -one, the new way that raw material is cheap and easy to get, step is brief, Atom economy is high, reaction condition is mild, environmental-friendly is opened up for the synthesis of such compound.
Description
Technical field
The invention belongs to the synthesis fields of nitrogen-containing heterocycle compound, and in particular to a kind of palladium chtalyst N- substituted aniline ortho position conjunction
At the method for 2,3- dihydroquinazoline -4 (1H) -one class compound.
Background technique
2,3- dihydroquinazoline -4 (1H) -one analog derivatives are widely present in natural products and drug molecule, because its
With good bioactivity and pharmacological activity, the close attention for the person that causes chemical research, the research of synthetic method is always
It is one of the hot spot of research.The synthetic method for such compound reported at present mainly have anthranilamide synthetic method,
Isatoic anhydride synthesis methods, ortho-nitrophenyl formamide synthetic method, o-amino benzoyl nitrile synthesis etc..Although obtained by various synthetic methods
Product yield is very high, but still there are a little shortcomings in various degree, such as: raw material mix complexity, higher cost, Atom economy
Difference, severe reaction conditions, catalyst preparation are complicated, reaction step is many and diverse, post-processing difficulty is big, pollute environment etc..Therefore, it is necessary to
The method of more economical, green synthesis 2,3- dihydroquinazoline -4 (1H) -one analog derivative is provided.
Summary of the invention
The object of the present invention is to provide a kind of more economical, simple, efficiently, green synthesis 2,3- dihydroquinazolines -4
The new method of (1H) -one class compound.
To achieve the above object, the technical solution adopted by the present invention is that one kind is with N- substituted aniline, primary amine, CO and aldehyde/ketone
For starting material, make catalyst with palladium acetate, the reaction of via palladium-catalyzed N- substituted aniline ortho position c h bond mobilizing functionization directly synthesizes
The method of 2,3- dihydroquinazoline -4 (1H) -one class compound.
Preferably, the N- substituted aniline is N- alkyl substituted benzene amine, the aryl-substituted amine of N-, aniline, band on phenyl ring
The N- substituted aniline of electron-withdrawing group or electron-donating group.
It is further preferred that the N- substituted aniline is Any one of.
Preferably, the primary amine is open chain Armeen, annular aliphatic primary amine or primary aromatic amine.
It is further preferred that the primary amine is Any one of.
Preferably, the aldehyde/ketone is open chain fatty aldehyde, ring-shaped fat aldehyde, aromatic aldehyde or aliphatic ketone.
It is further preferred that aldehyde/the ketone is Any one of.
Preferably, additive and oxidant are also added in synthesis process.
Preferably, the additive is any one or more of KI, AcOH or HCl.
Preferably, the oxidant is copper acetate or O2。
Preferably, the method for described synthesis 2,3- dihydroquinazoline -4 (1H) -one class compound, specific synthesis step is such as
Under: by N- substituted aniline 1.0mmol, palladium acetate 0.05mmol, copper acetate 2.0mmol, potassium iodide 0.2mmol, aldehyde/ketone
1.5mmol and acetonitrile 10mL are added sequentially in 50mL three-neck flask, and primary amine 3.0mmol and glacial acetic acid 5mL are mixed to join
In 25mL constant pressure funnel, constant pressure funnel is inserted into three-neck flask, and the neck among three-neck flask connects spherical condensation tube,
Another neck connects the tee tube full of CO gas；First with the air in CO gas displacement three-neck flask three times after, tee tube is inserted into
In three-neck flask and go deep into liquid level hereinafter, the CO bubble being passed through is made continuously to emerge, is passed through after condensed water and three-neck flask is put into 70
In DEG C oil bath, constant pressure funnel is opened, 8h is reacted under magnetic stirring, is then cooled to room temperature reaction solution, reaction solution adds
It is extracted 3 times after NaCl saturated solution with 10mL ethyl acetate, anhydrous Na2SO4Dry upper organic phase, filtering, after reduced pressure
Final product is obtained through column chromatography for separation.
The beneficial effect comprise that: the present invention with the N- substituted aniline of the simple convenient sources of structure, amine, CO and
Aldehyde/ketone is starting material, makees catalyst with palladium acetate, passes through the more of palladium chtalyst N- substituted aniline ortho position c h bond mobilizing function
Component reaction directly synthesizes 2,3- dihydroquinazoline -4 (1H) -one, is that open up a raw material cheap for the synthesis of such compound
It is easy to get, the new way that step is brief, Atom economy is high, reaction condition is mild, environmental-friendly.
Specific embodiment
Under 2,3- dihydroquinazoline -4 (1H) -one class compound synthesis route of the invention:
Using the reaction of methylphenylamine, aniline and benzaldehyde as template reaction, reaction condition is directed to embodiment 1-17 respectively
Different oxidant, additive, solvent, temperature and the combinations in reaction time has carried out 1- methyl -2,3- diphenyl -2,3- dihydro
The synthesis of quinazoline -4 (1H) -one (4be), the reaction result of different embodiments are as shown in table 1.
- 4 (1H) -one (4be) of 1- methyl -2,3- diphenyl -2,3- dihydroquinazoline is synthesized under the conditions of table 1. is variousa
aReaction condition: methylphenylamine (1.0mmol)；Aniline (3.0mmol)；Benzaldehyde (1.5mmol)；Pd(OAc)2
(5% mol)；Cu(OAc)2(2.0mmol)；KI(0.2mmol)；AcOH(5mL)；Solvent (10.0mL)；CO(1atm.)；70
℃；8 hoursbSeparation yieldcCO is bubbleddAniline is added dropwise after mixing with acetic acid, and CO is bubbledeCO:O2=5:1
Using different N- substituted aniline, aniline and benzaldehyde as substrate in embodiment 18-28, replace in palladium chtalyst N-
Under the conditions of the c h bond mobilizing function of aniline ortho position, a series of 2,3- dihydroquinazoline -4 (1H) -one class compounds have been synthesized, have been tied
Fruit is as shown in table 2.
Table 2.N- substituted aniline rangea
aReaction condition: N- substituted aniline (1.0mmol)；Aniline (3.0mmol)；Benzaldehyde (1.5mmol)；Pd(OAc)2
(5% mol)；Cu(OAc)2(2.0mmol)；KI(0.2mmol)；AcOH(5mL)；Acetonitrile (10.0mL)；Aniline is mixed with acetic acid
After be added dropwise, CO be bubbled；70℃；8 hoursbSeparation yield
Embodiment 29-47 passes through different aromatic primary amine and fat primary amine using methylphenylamine and benzaldehyde as substrate
Reaction has synthesized a series of 2,3- dihydroquinazoline -4 (1H) -one classes, and the results are shown in Table 3.
3 primary amine range of tablea
aReaction condition: methylphenylamine (1.0mmol)；Primary amine (3.0mmol)；Benzaldehyde (1.5mmol)；Pd(OAc)2
(5% mol)；Cu(OAc)2(2.0mmol)；KI(0.2mmol)；AcOH(5mL)；Acetonitrile (10.0mL)；Aniline is mixed with acetic acid
After be added dropwise, CO be bubbled；70℃；8 hoursbSeparation yield
Embodiment 48-67 is adjacent in palladium chtalyst methylphenylamine using methylphenylamine, aniline and various aldehyde/ketone as substrate
Under the conditions of position C-H key mobilizing function, a series of target products 2 have been synthesized, 3- dihydroquinazoline -4 (1H) -one class compound,
The results are shown in Table 4.
4. aldehyde of table/ketone rangea
aReaction condition: methylphenylamine (1.0mmol)；Primary amine (3.0mmol)；Aldehyde/ketone (1.5mmol)；Pd(OAc)2
(5% mol)；Cu(OAc)2(2.0mmol)；KI(0.2mmol)；AcOH(5mL)；Acetonitrile (10.0mL)；Aniline is mixed with acetic acid
After be added dropwise, CO be bubbled；70℃；8 hoursbSeparation yield.
Claims (10)
1. it is a kind of synthesize 2,3- dihydroquinazoline -4 (1H) -one class compound method, it is characterised in that: with N- substituted aniline,
Primary amine, CO and aldehyde/ketone are starting material, make catalyst with palladium acetate, directly synthesis 2,3- dihydroquinazoline -4 (1H) -one class
Close object.
2. synthesizing 2 according to claim 1, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
The N- substituted aniline is N- alkyl substituted benzene amine, the aryl-substituted amine of N-, aniline, band electron-withdrawing group or supplied for electronic on phenyl ring
The N- substituted aniline of base.
3. synthesizing 2 according to claim 2, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
The N- substituted aniline is In appoint
It is a kind of.
4. synthesizing 2 according to claim 1, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
The primary amine is open chain Armeen, annular aliphatic primary amine or primary aromatic amine.
5. synthesizing 2 according to claim 4, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
The primary amine is In appoint
It is a kind of.
6. synthesizing 2 according to claim 1, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
Aldehyde/the ketone is open chain fatty aldehyde, ring-shaped fat aldehyde, aromatic aldehyde or aliphatic ketone.
7. synthesizing 2 according to claim 6, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
Aldehyde/the ketone is Any one of.
8. synthesizing 2 according to claim 1, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
Additive and oxidant are also added in synthesis process.
9. synthesizing 2 according to claim 8, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
Additive is any one or more of KI, AcOH, HCl.
10. synthesizing 2 according to claim 8, the method for 3- dihydroquinazoline -4 (1H) -one class compound, it is characterised in that:
Oxidant is copper acetate or O2。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113045503A (en) * | 2020-07-31 | 2021-06-29 | 浙江警察学院 | Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of compound in synthesis of drug molecules |
-
2018
- 2018-07-26 CN CN201810834858.6A patent/CN108997227A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| EDGAR SAWATZKY ET AL.: "Experimental and theoretical investigations into the stability of cyclic aminals", 《BEILSTEIN J. ORG. CHEM.》 * |
| JIAN WU ET AL.: "Preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives in aqueous media with β-cyclodextrin-SO3H as a recyclable catalyst", 《GREEN CHEM.》 * |
| JIUXI CHEN ET AL.: "Eco-friendly synthesis of 2,3-dihydroquinazolin-4(1H)-ones in ionic liquids or ionic liquid–water without additional catalyst", 《GREEN CHEM.》 * |
| XIAOPENG ZHANG ET AL.: "Palladium-Catalyzed Ortho-Selective C-H Oxidative Carbonylation of N-Substituted Anilines with CO and Primary Amines for the Synthesis of o-Aminobenzamides", 《ORG. LETT.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113045503A (en) * | 2020-07-31 | 2021-06-29 | 浙江警察学院 | Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of compound in synthesis of drug molecules |
| CN113045503B (en) * | 2020-07-31 | 2022-11-04 | 浙江警察学院 | Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of compound in synthesis of drug molecules |
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Application publication date: 20181214 |