CN102675202A - Preparation method of amino-substituted 2(1H)-quinolinone compounds - Google Patents
Preparation method of amino-substituted 2(1H)-quinolinone compounds Download PDFInfo
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- CN102675202A CN102675202A CN201210112540XA CN201210112540A CN102675202A CN 102675202 A CN102675202 A CN 102675202A CN 201210112540X A CN201210112540X A CN 201210112540XA CN 201210112540 A CN201210112540 A CN 201210112540A CN 102675202 A CN102675202 A CN 102675202A
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Abstract
The invention discloses a preparation method of amino-substituted 2(1H)-quinolinone compounds, which mainly comprises the steps of: reacting phenylenediamine, ionic liquid, a solid base catalyst and ethoxy acryloyl chloride under stirring at the temperature of 10-120 DEG C for 1-8h according to a certain mass ratio, then adding a solid acid catalyst, heating to 100-150 DEG C, continuing reaction under stirring for 1-12h cooling, extracting with dichloromethane or toluene, concentrating extract, and recrystallizing remnant with methanol to obtain a white solid product. The synthesis method is simple and convenient, inexpensive and easily available in raw materials, good in yield and low in cost, and is suitable for industrialized operation.
Description
Technical field
The present invention relates in a kind of ion liquid medium, under solid alkali and solid acid catalyst effect, employing cascade reaction technology synthesizing amino replacement 2 (
1HThe method of)-quinolinone compounds.
Background technology
Amino replacement 2 (
1H)-quinolinone is important medicine intermediate and industrial chemicals; Have antibiotic and positive inotropic action; Can be used for synthetic cardiotonic drug, cardiovascular agent, thrombocyte stopper and thrombocyte cAMP (cyclic monophosphate) specific phosphodiesterase enzyme (PDE-III or IV hypotype) suppressor factor, be widely used in the treatment of cardiovascular disorder; The feelings agent and the regulator that can also be used for synthetic androgen and progestin.
Ionic liquid is as emerging Green Chemistry solvent; Nonflammable explosive, stable to water and air, stability and security are preferably arranged in industrial production; Reaction can be carried out in homogeneous catalysis system; Be convenient to operation and processing, be prone to reclaim, be expected to solve the pollution problem that occurs in the chemical reaction process.
Solid acid-base is as a kind of novel heterogeneous catalyst in the industrial production; Have not etching apparatus, pollution is little, high temperature resistant, aftertreatment is simple, advantage such as easily separated, reusable; Obtained widespread use at catalytic field; Be expected to solve the pollution problem that occurs in the chemical reaction process, obtained widespread use at catalytic field.
Therefore, in order to reach environmental friendliness and to be easy to industrialized production purpose, utilize ionic liquid as reaction medium and solid acid-base as catalyzer, adopt the cascade reaction technology, but the amino replacement 2 of exploitation suitability for industrialized production (
1HThe operational path of)-quinolinones compound pharmaceutical intermediate is very important.
Summary of the invention
It is a kind of in the ionic liquid reaction medium that the object of the invention is to provide, under the solid acid alkali catalytic, with cascade reaction technology synthesizing amino replace 2 (
1HThe method of)-quinolinones compound, this method helps large-scale industrial production.
Amino replacement 2 of the present invention (
1HThe structure of)-quinolinones compound is shown in formula I:
（Ⅰ）
The amino replacement 2 of preparation of the present invention (
1H)-quinolinone compounds, be by adjacent,, Ursol D is as reaction raw materials, obtain with the chloride compounds reaction.Reaction formula is as follows:
Described solid acid catalyst expression formula is one of following: SO
4 2-/ SnO
2-Fe
2O
3Or S
2O
8 2-/ SnO
2-Fe
2O
3Or SO
4 2-/ SnO
2-ZnO or S
2O
8 2-/ SnO
2-ZnO or SO
4 2-/ SnO
2-Al
2O
3Or S
2O
8 2-/ SnO
2-Al
2O
3The preparation method specifically can be with reference to chemistry world the 48th volume the 1st phase (2007) " solid super-strong acid SO
4 2-/ SnO
2-Al
2O
3Preparation and structural characterization ".
Described solid base catalyst is the magnetic solid base that magnetic mg_al hydrotalcite makes.The preparation method specifically can be with reference to the 29th volume the 3rd phase (2002) " preparation of magnetic mg_al hydrotalcite solid alkali and sign " of applicating technology.
Described ionic liquid is 1-alkyl-3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-Methylimidazole hexafluorophosphate, and wherein alkyl is the alkyl of carbon atom quantity n=0～18." ionic liquid---from the fundamental research to the industrial application " Science Press (2006) that the preparation method specifically can write with reference to Zhang Suojiang etc.
Amino replacement 2 (
1HThe preparation method of)-quinolinones compound is characterized in that may further comprise the steps:
In there-necked flask, add phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides successively, the mass ratio of phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides is 1:1～10:1～10:1～10; Stirring reaction is 1～8 hour under 10～120 ℃ of temperature, and reaction finishes, directly the solid acid catalyst of quality such as adding and solid base catalyst; Be heated to 100～150 ℃ and continued stirring reaction 1～12 hour; Reaction finishes postcooling, the extraction liquid extraction, and extraction liquid concentrates; Resistates is used recrystallizing methanol, gets white solid product.
Described amino replacement 2 (
1HThe preparation method of)-quinolinones compound is characterized in that: described temperature of reaction after adding solid alkali is preferably 70～100 ℃; Reaction times is preferably 3～5 hours.
Described amino replacement 2 (
1HThe preparation method of)-quinolinones compound is characterized in that: described temperature of reaction after adding solid acid catalyst is preferably 110～130 ℃; Reaction times is preferably 8～10 hours.
Described amino replacement 2 (
1HThe preparation method of)-quinolinones compound; It is characterized in that: described ionic liquid is selected from alkyl imidazole Tetrafluoroboric acid salt ion or alkyl-imidazole hexafluorophosphate ion; When ionic liquid is the alkyl imidazole tetrafluoroborate ion liquid, extract with the extracted in toluene reaction system; When with the alkyl-imidazole hexafluorophosphate ionic liquid, extract with the dichloromethane extraction reaction system.
Described amino replacement 2 (
1HThe preparation method of)-quinolinones compound is characterized in that: the preferred 1:3～5:3 of mass ratio～5:3～5 of described phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides.
Beneficial effect of the present invention:
Simple synthetic method of the present invention, raw material cheaply is easy to get, and yield is good, and cost is low, is suitable for carrying out the industriallization operation.
Embodiment
Below in conjunction with embodiment and Comparative Examples the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1: 8-amino-2 (
1HSynthesizing of)-quinolinone
In the 150mL there-necked flask, add O-Phenylene Diamine (10.8g, 0.1 mol); Ethoxy propylene acyl chlorides (14.8g, 0.11 mol), solid base catalyst 12g; 1-octyl group-3-methyl imidazolium tetrafluoroborate 15g after 3 hours, adds solid acid catalyst SO in reaction under 100 ℃ of stirrings
4 2-/ SnO
2-Al
2O
318g slowly is warmed up to 120 ℃ then, continues stirring reaction 8 hours, and with toluene 30 mL extraction three times, the combining methylbenzene layer concentrates, and enriched material is used recrystallizing methanol, gets light yellow solid 1.45g, yield 91%, m.p.250-250 ℃; IR (KBr): 3469,3030,, 1682,1648,1629,1459,1338cm
-1.
1H NMR (DMSO-d
6) δ: 5.48 (s, 1H), 6.43 (d, 1H), 6.61-7.25 (m, 3H), 7.46 (1H), 10.64 (1H); MS (m/z): 160 (M
+).
Embodiment 2: 7-amino-2 (
1HSynthesizing of)-quinolinone
In the 150mL there-necked flask, add mphenylenediamine (10.8g, 0.1 mol); Ethoxy propylene acyl chlorides (14.8g, 0.11 mol), solid base catalyst 20g; 1-octyl group-3-methyl imidazolium tetrafluoroborate 50g after 5 hours, adds solid acid catalyst SO in reaction under 110 ℃ of stirrings
4 2-/ SnO
2-Fe
2O
325g slowly is warmed up to 120 ℃ then, continues stirring reaction 5 hours, and with toluene 30 mL extraction three times, the combining methylbenzene layer concentrates, and enriched material is used recrystallizing methanol, gets light yellow solid 1.15g, yield 72%; IR (KBr): 3409,3010,1662,1648,1625,1450,1318cm
-1.
1H NMR (DMSO-d
6) δ: 4.68 (s, 1H), 6.25 (d, 1H), 6.56-7.37 (m, 4H), 10.56 (1H); MS (m/z): 160 (M
+).
Embodiment 3: 6-amino-2 (
1HSynthesizing of)-quinolinone
In the 150mL there-necked flask, add Ursol D (10.8g, 0.1 mol); Ethoxy propylene acyl chlorides (14.8g, 0.11 mol), solid base catalyst 12g; 1-octyl group-3-methyl imidazolium tetrafluoroborate 15g after 3 hours, adds solid acid catalyst SO in reaction under 100 ℃ of stirrings
4 2-/ SnO
2-Al
2O
318g slowly is warmed up to 120 ℃ then, continues stirring reaction 8 hours, and with toluene 30 mL extraction three times, the combining methylbenzene layer concentrates, and enriched material is used recrystallizing methanol, gets light yellow solid 1.45g, yield 91%, m.p.250-250 ℃; IR (KBr): 3469,3040,1664,1638,1620,1450,1330cm
-1.
1H NMR (DMSO-d
6) δ: 5.48 (s, 1H), 6.40 (d, 1H), 6.66-7.45 (m, 4H), 10.04 (1H); MS (m/z): 160 (M
+).
Embodiment 4: 8-amino-2 (
1HSynthesizing of)-quinolinone
In the 150mL there-necked flask, add O-Phenylene Diamine (10.8g, 0.1 mol); Ethoxy propylene acyl chlorides (14.8g, 0.11 mol), solid base catalyst 50g; 1-octyl group-3-Methylimidazole hexafluorophosphate 15g after 1 hour, adds solid acid catalyst S in reaction under 130 ℃ of stirrings
2O
8 2-/ SnO
2-Fe
2O
318g slowly is warmed up to 120 ℃ then, continues stirring reaction 10 hours, with methylene dichloride 30 mL extraction three times, merges organic layer, concentrates, and enriched material is used recrystallizing methanol, gets light yellow solid 1.45g, yield 91%.
Embodiment 5: 8-amino-2 (
1HSynthesizing of)-quinolinone
In the 150mL there-necked flask, add O-Phenylene Diamine (10.8g, 0.1 mol); Ethoxy propylene acyl chlorides (14.8g, 0.11 mol), solid base catalyst 11g; 1-hexyl-3-Methylimidazole hexafluorophosphate 15g after 10 hours, adds solid acid catalyst S in reaction under 100 ℃ of stirrings
2O
8 2-/ SnO
2-ZnO 18g slowly is warmed up to 130 ℃ then, continues stirring reaction 6 hours, with methylene dichloride 30 mL extraction three times, merges organic layer, concentrates, and enriched material is used recrystallizing methanol, gets light yellow solid 1.45g, yield 91%.
Claims (5)
- One kind amino replace 2 ( 1HThe preparation method of)-quinolinones compound is characterized in that may further comprise the steps:In there-necked flask, add phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides successively, the mass ratio of phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides is 1:1～10:1～10:1～10; Stirring reaction is 1～8 hour under 10～120 ℃ of temperature, and reaction finishes, directly the solid acid catalyst of quality such as adding and solid base catalyst; Be heated to 100～150 ℃ and continued stirring reaction 1～12 hour; Reaction finishes postcooling, the extraction liquid extraction, and extraction liquid concentrates; Resistates is used recrystallizing methanol, gets white solid product.
- Amino replacement 2 2. according to claim 1 ( 1HThe preparation method of)-quinolinones compound is characterized in that: described temperature of reaction after adding solid alkali is preferably 70～100 ℃; Reaction times is preferably 3～5 hours.
- Amino replacement 2 3. according to claim 1 ( 1HThe preparation method of)-quinolinones compound is characterized in that: described temperature of reaction after adding solid acid catalyst is preferably 110～130 ℃; Reaction times is preferably 8～10 hours.
- Amino replacement 2 4. according to claim 1 ( 1HThe preparation method of)-quinolinones compound; It is characterized in that: described ionic liquid is selected from alkyl imidazole Tetrafluoroboric acid salt ion or alkyl-imidazole hexafluorophosphate ion; When ionic liquid was the alkyl imidazole tetrafluoroborate ion liquid, extraction liquid was selected toluene for use; When with the alkyl-imidazole hexafluorophosphate ionic liquid, extraction liquid is selected methylene dichloride for use.
- Amino replacement 2 5. according to claim 1 ( 1HThe preparation method of)-quinolinones compound is characterized in that: the preferred 1:3～5:3 of mass ratio～5:3～5 of described phenylenediamine, ionic liquid, solid base catalyst and ethoxy propylene acyl chlorides.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911084A (en) * | 2012-09-25 | 2013-02-06 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102030706A (en) * | 2010-12-22 | 2011-04-27 | 江苏食品职业技术学院 | Method for preparing 6-hydroxy-2(1H)-quinolone in ionic liquid by using one-pot method |
-
2012
- 2012-04-17 CN CN201210112540XA patent/CN102675202A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102030706A (en) * | 2010-12-22 | 2011-04-27 | 江苏食品职业技术学院 | Method for preparing 6-hydroxy-2(1H)-quinolone in ionic liquid by using one-pot method |
Non-Patent Citations (8)
| Title |
|---|
| MICHIAKI TOMINAGA,ET AL.: "Studies on positive inotropic agents.I. Synthesis of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone and related compounds", 《CHEMICAL & PHARMACEUTICAL BULLETIN》 * |
| 孙莉,等.: "在离子液体中6-羟基-2(1H)喹啉酮的合成及反应性研究", 《有机化学》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911084A (en) * | 2012-09-25 | 2013-02-06 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
| CN102911084B (en) * | 2012-09-25 | 2014-03-26 | 浙江工业大学 | Preparation method of tert-butyl carbazate |
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Application publication date: 20120919 |