CN106946858A - A kind of melamine class compound and preparation method thereof - Google Patents
A kind of melamine class compound and preparation method thereof Download PDFInfo
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- CN106946858A CN106946858A CN201710246403.8A CN201710246403A CN106946858A CN 106946858 A CN106946858 A CN 106946858A CN 201710246403 A CN201710246403 A CN 201710246403A CN 106946858 A CN106946858 A CN 106946858A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Abstract
The present invention relates to a kind of melamine class compound and preparation method thereof, chemical structural formula is：Wherein, substituent R1And R2For any one in the tert-butyl group, normal-butyl, cyclohexyl, phenyl or chloride, bromine, nitro.Substituting group position, number and conjugate position are not fixed.Synthetic method is that the Ugi occurred with quaternary phosphonium salt carboxylic acid compound and melamine, aryl ketones aldehyde compound and different nitrile compounds under the catalysis of the iron complex catalyst loaded of MCM 41 reacts, and the product of generation generates the important heterocyclic compounds such as the melamine of many heterocyclic substituteds in the presence of alkali through intramolecular wittig reaction cyclization.The invention provides the new synthetic method that a kind of step is few, yield is high to synthesize the melamine class compound of many heterocyclic substituteds of a class, again because there is melamine rings and benzazepine ring and multiple amido links simultaneously in product molecule structure, preferable potential source biomolecule activity is made it have.
Description
Technical field
The present invention relates to a kind of melamine class compound, and its synthetic method.
Background technology
In naturally occurring or artificial synthesized organic matter, the cyclic skeleton unit of many spline structures is widely present, especially
It is in some drug molecules or some natural products with special pharmacological activity, generally containing the Various Complex ring system such as heterocycle
Structure.Heterocyclic compound performer in the long process of human history very important role, as organic chemistry filed research most
For one of active direction, it plays huge effect in fields such as life science, material science, and correlative study achievement is continuous
Change mankind's daily life.Wherein triazine heterocyclic compounds have extremely important effect in dyestuff and pharmaceuticals industry,
The research of its synthetic method receives much concern.How to go efficient, quick, convenient to construct triazines Hete rocyclic derivatives, especially molecule
In also simultaneously containing the complexity heterocyclic compound such as other heterocycle such as azatropylidenes, be still the field more difficult task it
One.Based on this, invention introduces it is a kind of by the MCM-41 iron complex catalysts loaded by quaternary phosphonium salt carboxylic acids
Ugi reactions and the string of follow-up intramolecular wittig reaction that compound, melamine, aryl ketones aldehyde compound and isonitrile occur
Connection reaction prepares the melamine class Hete rocyclic derivatives of many heterocyclic substituteds.
The content of the invention
It is a primary object of the present invention to provide a kind of melamine class compound and its synthetic method.
Technical scheme is as follows：
A kind of melamine class compound, the compound chemical structure formula is：
Wherein, substituent R1And R2For in the substituted-phenyl such as the tert-butyl group, normal-butyl, cyclohexyl, phenyl or chloride, bromine, nitro
Any one.Substituting group position, number and conjugate position are not fixed.
The described method of synthesis, methods described includes following synthesis path：
It the described method comprises the following steps：
(1) under nitrogen protection, compound 1 is sequentially added into reactor, compound 2, compound 3, compound 4,
MeOH and EtOH mixed solvent, stirring makes after its dissolving, is stirred at room temperature, and adds catalyst, and react at this temperature
24h；
(2) solvent methanol and ethanol are removed under elevated pressure after reaction 24h, add meta-xylene, while adding bigeminy pyrrole
Pyridine, reaction temperature is increased to 50-80 DEG C, continues to react 6h；
(3) TLC is monitored, after completion of the reaction, removal of solvent under reduced pressure meta-xylene, and residue is through filtering, extraction and recrystallizes,
Target compound I is obtained, the synthesis of melamine class compound is completed.
Compound 1 in the step (1), compound 2, compound 3, the molar ratio of compound 4 is 2-5：0.1-2：
1-4：1-4.More preferably middle compound 1, compound 2, compound 3, the molar ratio of compound 4 is 3.3：1：3：
3.15。
The reaction temperature of the step (1) is preferably 25 DEG C；The reaction temperature of step (2) is preferably 75 DEG C.
Step (1) solvent is the mixed solvent of methanol and ethanol, and the volume ratio of methanol and ethanol is 2：1.
Catalyst described in the step (1) is MCM-41-2N-FeCl3, the catalyst is that MCM-41 loads bidentate nitrogen
Ferric trichloride composition catalyst, MCM-41-2N-FeCl3With the mass ratio 25 that feeds intake of compound 2：13.
Second bipyridine in the step (2) is as alkali, and its consumption is：Molar ratio with the 2 of compound is 1-5：
1.More preferably 2 molar ratio of second bipyridine and compound is 3.6：1.
The present invention has the beneficial effect that：
1st, a series of trimerizations are synthesized present invention firstly discloses the iron complex catalyst loaded with a kind of MCM-41
The synthetic route of cyanogen aminated compounds.This method yield is high, and accessory substance is few, there is higher use value.
2nd, the new melamine class compound of the present invention one class of synthesis prepare low cost there is provided one kind, it is simple to operate and
The high new synthetic method of reaction efficiency.
3rd, the present invention has synthesized a class melamine class compound, and such compound is being used as dyestuff and antibiotic and anti-
There are higher potentiality and wide research and application in terms of the important component of cancer drug.
Embodiment
The present invention is further illustrated with reference to embodiment, but the scope of protection of present invention is not limited to implement
The scope of example statement.
Instrument and reagent：
SHZ-E type circulating water types vavuum pump (the biochemical instrument plants of Shanghai Rong Ya)；DZE-6120 type vacuum drying chambers (Shanghai
Heng Tian scientific instrument manufacturing company)；WRS-1A numeral melting point instruments (Shanghai Suoguang Optoelectronic Technology Co., Ltd.)；EB2005A electronics
Balance；ZF-I type ultraviolet analysis instrument for three purposed；DE-102J heat collecting types constant-temperature heating magnetic stirring apparatus (Gongyi City's grey hair chemical apparatuses
Factory)；DFX-5L/30 cryogenic thermostats reactive bath technique (the river instrument plant of Wuxi City hundred)；(Linhai City is forever for 2YZ-4A type rotary vane types vacuum oil pump
Vast and boundless vacuum equipment factory).Phenylacetylene (AR), p-methyl benzenesulfonic acid (AR), tert-butyl lithium (AR), cyclopentanone (AR), cyclohexanone (AR), stone
Oily ether (60 DEG C -90 DEG C), tetrahydrofuran (AR), ethyl acetate (AR), toluene (AR), industrial nitrogen (AR).
Embodiment
The present invention is further illustrated with reference to embodiment, but the scope of protection of present invention is not limited to implement
The scope of example statement.
Instrument and reagent：
Fusing point is determined with X4 types melting point apparatus (production of the optical instrument factory of Beijing the 3rd), and thermometer is not calibrated；1H NMR and13C NMR Varian Mercury400 type 400MHz NMRs or the type 600MHz nuclear-magnetisms of Varian Mercury 600
The instrument that resonates is determined, deuterochloroform (CDCl3) or deuterated dimethyl sulfoxide (DMSO-d6) it is solvent, TMS is internal standard；MS is used
FinniganTrace mass spectrographs are determined；Elementary analysis is determined using Vario EL III elemental analysers；Agents useful for same is domestic
(or import) chemistry is pure or analyzes pure.Methylene chloride is dried.
Embodiment 1
One kind synthesis 2,2', 2 "-(1,3,5-triazine-2,4,6-triyl) tris (N- (tert-butyl) -4- (4-
chlorophenyl)-1-oxo-
2,3-dihydro-1H-benzo [c] azepine-3-carboxamide) method, including following experimental procedure：
Nitrogen protection under, sequentially added into reactor compound quaternary phosphonium salt carboxylic acid 1 (1.57g, 3.3mmol,
3.3eqv.), melamine 2 (0.13g, 1.0mmol, 1.0eqv.), parachloroacetophenone aldehyde 3a (0.56g, 3.0mmol,
3.0eqv.), tert-butyl isonitrile 4a (0.27g, 3.15mmol, 3.15eqv.), MeOH:EtOH=2:1 (10ml), stirring makes it
After dissolving, it is stirred at room temperature, adds MCM-41-2N-FeCl3(0.25g), and react 24h at this temperature, after reaction 24h
Pressurization is lower to remove solvent methanol and ethanol, adds meta-xylene (10ml), while addition second bipyridine (0.56g, 3.6mmol,
3.6eqv.), reaction temperature is increased to 75 DEG C, continues to react 6h, TLC is monitored, after completion of the reaction, diformazan between removal of solvent under reduced pressure
Benzene, residue is through filtering, extraction and recrystallizes, and has finally arrived target compound Ia with 56.03% yield.
Yield：56.03%
1HNMR(CDCl3,400MHz)δ(ppm)7.83-7.12(m,27H,Ar-H),6.53-5.18(m,6H,3CH,
3NH),1.42-1.21(m,27H,9CH3).
HRMS Calculatedfor[C66H60Cl3N9O6+H]+:1180.3810,Found:1180.3761.
Embodiment 2
One kind synthesis 2,2', 2 "-(1,3,5-triazine-2,4,6-triyl) tris (4- (4-bromophenyl)-N-
(tert-butyl)-1-oxo-
2,3-dihydro-1H-benzo [c] azepine-3-carboxamide) method, including following experimental procedure：
Nitrogen protection under, sequentially added into reactor compound quaternary phosphonium salt carboxylic acid 1 (1.57g, 3.3mmol,
3.3eqv.), melamine 2 (0.13g, 1.0mmol, 1.0eqv.), parabromoacetophenone aldehyde 3b (0.69g, 3.0mmol,
3.0eqv.), tert-butyl isonitrile 4a (0.27g, 3.15mmol, 3.15eqv.), MeOH:EtOH=2:1 (10ml), stirring makes it
After dissolving, it is stirred at room temperature, adds MCM-41-2N-FeCl3(0.25g), and react 24h at this temperature, after reaction 24h
Pressurization is lower to remove solvent methanol and ethanol, adds meta-xylene (10ml), while addition second bipyridine (0.56g, 3.6mmol,
3.6eqv.), reaction temperature is increased to 75 DEG C, continues to react 6h, TLC is monitored, after completion of the reaction, diformazan between removal of solvent under reduced pressure
Benzene, residue is through filtering, extraction and recrystallizes, and has finally arrived target compound Ib with 51.75% yield.
Yield：51.75%
1HNMR(CDCl3,400MHz)δ(ppm)7.81-7.11(m,27H,Ar-H),6.50-5.19(m,6H,3CH,
3NH),1.40-1.25(m,27H,9CH3).
HRMS Calculatedfor[C66H60Br3N9O6+H]+:1312.2295,Found:1312.2235.
Embodiment 3
One kind synthesis 2,2', 2 "-(1,3,5-triazine-2,4,6-triyl) tris (N-cyclohexyl-4- (4-
ethylphenyl)-1-oxo
- 2,3-dihydro-1H-benzo [c] azepine-3-carboxamide) method, including it is following experiment step
Suddenly：
Nitrogen protection under, sequentially added into reactor compound quaternary phosphonium salt carboxylic acid 1 (1.57g, 3.3mmol,
3.3eqv.), melamine 2 (0.13g, 1.0mmol, 1.0eqv.), p -ethylacetophenone aldehyde 3c (0.54g, 3.0mmol,
3.0eqv.), cyclohexyl isonitrile 4b (0.35g, 3.15mmol, 3.15eqv.), MeOH:EtOH=2:1 (10ml), stirring makes it
After dissolving, it is stirred at room temperature, adds MCM-41-2N-FeCl3(0.25g), and react 24h at this temperature, after reaction 24h
Pressurization is lower to remove solvent methanol and ethanol, adds meta-xylene (10ml), while addition second bipyridine (0.56g, 3.6mmol,
3.6eqv.), reaction temperature is increased to 75 DEG C, continues to react 6h, TLC is monitored, after completion of the reaction, diformazan between removal of solvent under reduced pressure
Benzene, residue is through filtering, extraction and recrystallizes, and has finally arrived target compound Ic with 42.57% yield.
Yield：42.57%
1H NMR(CDCl3,400MHz)δ(ppm)7.78-7.02(m,27H,Ar-H),6.43-5.14(m,6H,3CH,
3NH),3.49-0.81(m,48H,3CH,18CH2,3CH3).
HRMS Calculatedfor[C78H81N9O6+H]+:1240.6388,Found:1240.6303.
The melamine class compound of the present invention is in the important component as dyestuff and antibiotic and cancer therapy drug
Aspect has higher potentiality and wide research and application.The research of its novel synthesis is necessary and very urgent.This
Patent of invention provide it is a kind of prepare low cost, new synthetic method simple to operate and high reaction efficiency, and this method has yield
Height, accessory substance is few, there is higher use value.
Claims (9)
1. a kind of melamine class compound, it is characterised in that the chemical structural formula of the melamine class compound is：
Wherein, substituent R1And R2For appointing in the tert-butyl group, normal-butyl, cyclohexyl, phenyl or chloride, bromine, the substituted-phenyl of nitro
Meaning is a kind of, and substituting group position, number and conjugate position are not fixed.
2. synthesize the method for the melamine class compound described in claim 1, it is characterised in that methods described includes following close
Into path：
It the described method comprises the following steps：
(1) under nitrogen protection, sequentially add compound 1 into reactor, compound 2, compound 3, compound 4, MeOH with
EtOH mixed solvent, stirring makes after its dissolving, is stirred at room temperature, and adds catalyst, and react 24h at this temperature；
(2) solvent methanol and ethanol are removed under elevated pressure after reaction 24h, add meta-xylene, while adding second bipyridine, instead
Answer temperature to be increased to 50-80 DEG C, continue to react 6h；
(3) TLC is monitored, after completion of the reaction, removal of solvent under reduced pressure meta-xylene, and residue is through filtering, extraction and recrystallizes, and obtains
Target compound I, completes the synthesis of melamine class compound.
3. method according to claim 2, it is characterised in that：Compound 1, compound 2, compound in the step (1)
3, the molar ratio of compound 4 is 2-5：0.1-2：1-4：1-4.
4. method according to claim 2, it is characterised in that：Compound 1, compound 2, compound in the step (1)
3, the molar ratio of compound 4 is 3.3：1：3：3.15.
5. method according to claim 2, it is characterised in that：The reaction temperature of the step (1) is 25 DEG C；Step (2)
Reaction temperature be 75 DEG C.
6. method according to claim 2, it is characterised in that：Step (1) solvent is molten for the mixing of methanol and ethanol
Agent, and the volume ratio of methanol and ethanol is 2：1.
7. method according to claim 2, it is characterised in that：Catalyst described in the step (1) is MCM-41-
2N-FeCl3, the catalyst is that MCM-41 loads bidentate nitrogen ferric trichloride composition catalyst, MCM-41-2N-FeCl3With chemical combination
The mass ratio 25 that feeds intake of thing 2：13.
8. method according to claim 2, it is characterised in that：Second bipyridine in the step (2) is used as alkali, its consumption
For：Molar ratio with the 2 of compound is 1-5：1.
9. method according to claim 2, it is characterised in that：Second bipyridine in the step (2) is used as alkali, its consumption
For：Molar ratio with the 2 of compound is 3.6：1.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050004114A1 (en) * | 2003-04-30 | 2005-01-06 | Darren Whitehouse | Heterocycle substituted carboxylic acids |
| US20060122222A1 (en) * | 2004-11-18 | 2006-06-08 | The Institutes For Pharmaceutical Discovery, Llc | Heterocycle substituted carboxylic acids |
| PL216548B1 (en) * | 2008-05-08 | 2014-04-30 | Politechnika Łódzka | Method of obtaining triazine (isocyanuric) derivatives of nitric yperites |
| CN105294799A (en) * | 2015-10-15 | 2016-02-03 | 上海科技大学 | 3beta-hydroxyl-androstane-5-alkene-17-dipeptide compound and preparation and application thereof |
| CN105541823A (en) * | 2016-02-03 | 2016-05-04 | 三峡大学 | Oxazoline-ring-containing triazine compounds and preparation method thereof, and application of oxazoline-ring-containing triazine compounds in anticancer drugs |
-
2017
- 2017-04-15 CN CN201710246403.8A patent/CN106946858A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050004114A1 (en) * | 2003-04-30 | 2005-01-06 | Darren Whitehouse | Heterocycle substituted carboxylic acids |
| US20060122222A1 (en) * | 2004-11-18 | 2006-06-08 | The Institutes For Pharmaceutical Discovery, Llc | Heterocycle substituted carboxylic acids |
| PL216548B1 (en) * | 2008-05-08 | 2014-04-30 | Politechnika Łódzka | Method of obtaining triazine (isocyanuric) derivatives of nitric yperites |
| CN105294799A (en) * | 2015-10-15 | 2016-02-03 | 上海科技大学 | 3beta-hydroxyl-androstane-5-alkene-17-dipeptide compound and preparation and application thereof |
| CN105541823A (en) * | 2016-02-03 | 2016-05-04 | 三峡大学 | Oxazoline-ring-containing triazine compounds and preparation method thereof, and application of oxazoline-ring-containing triazine compounds in anticancer drugs |
Non-Patent Citations (3)
| Title |
|---|
| KHANFAR MOHAMMAD A ET AL: "Elaborate Ligand-Based Modeling Coupled with Multiple Linear Regression and k Nearest Neighbor QSAR Analyses Unveiled New Nanomolar mTOR Inhibitors", 《JOURNAL OF CHEMICAL INFORMATION AND MODELING》 * |
| LONG WANG ET AL: "Synthesis of 2,3-Dihydro‑1H‑2-benzazepin-1-ones and 3H‑2-Benzoxepin-1-ones by Isocyanide-Based Multicomponent Reaction/Wittig Sequence Starting from Phosphonium Salt Precursors", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| 段专: "Ugi反应合成新型多取代异喹啉酮类衍生物", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
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Application publication date: 20170714 |