CN103588714A - Potassium hydroxide promoted 2-aryl quinazolone quinazolinone synthesis method - Google Patents
Potassium hydroxide promoted 2-aryl quinazolone quinazolinone synthesis method Download PDFInfo
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- CN103588714A CN103588714A CN201310618968.6A CN201310618968A CN103588714A CN 103588714 A CN103588714 A CN 103588714A CN 201310618968 A CN201310618968 A CN 201310618968A CN 103588714 A CN103588714 A CN 103588714A
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- aryl
- quinazolinone
- potassium hydroxide
- quinazolone
- phenylcarbinol
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
Abstract
The present invention provides a method for synthesizing 2-aryl quinazolone quinazolinone and derivatives thereof in a green and economical manner, wherein anthranilamide and aryl methanol are subjected to a one-pot reaction under air in the presence of potassium hydroxide to obtain the 2-aryl quinazolone quinazolinone compound. The method has characteristics of convenience, high yield, environmental protection, easily available raw materials and low cost, and is suitable for industrial production.
Description
Technical field
Relating to organic synthesis and medicine synthetic, is specifically the synthetic of 2-arylquinazolinethione and derivative thereof.
Background technology
Quinazolinones has good biological activity.2-arylquinazolinethione shows good pharmacologically active at aspects such as antitumor, hypertension, anti-inflammatory, pain relieving, sterilizations.
The synthetic method that has at present multiple 2-arylquinazolinethione.With regard to its raw material classification, mainly contain anthranilamide and phenyl aldehyde, anthranilamide and Benzoyl chloride, adjacent halobenzene formic acid and benzenyl amidine, anthranilamide and phenylcarbinol.
For example, 2010, Wang etc. used catalysis of iodine anthranilamide and phenyl aldehyde at ionic liquid [bmim
+] [BF
4 -] the synthetic 2-arylalkyl quinazolinone (Synthetic Communications, 2010,40,2633) of middle one pot reaction.Although this reaction solvent can reclaim, building-up process is complicated, and production cost is high, only as research, is not suitable for industrial production at present.And this reaction is used has stronger volatility and corrosive elemental iodine.
2005, Potewar etc. used anthranilamide and Benzoyl chloride at ionic liquid [bmim
+] [BF
4 -] the synthetic 2-phenylquinazoline ketone (Synthetic Communications, 2005,35,231) of middle one kettle way.120 ℃ of temperature, 3.5 hours reaction times.This reaction times is shorter, but substrate narrow range, and with complicated ionic liquid [bmim
+] [BF
4 -] as solvent, make the method be difficult to industrialization.
2009 Nian， Liu research groups have reported that microwave-assisted, cesium carbonate make the adjacent halobenzene formic acid of alkali, iron catalysis and the synthetic 2-arylquinazolinethione of NSC 2020.The adjacent halobenzene formic acid of raw material and NSC 2020 are difficult for preparation, expensive, and cesium carbonate is more expensive, so the method operates more complicated, deficiency in economic performance.
2011, the use iridium chloride catalysis anthranilamides such as Zhou and phenylcarbinol refluxed and obtain 2-(mixing) arylalkyl quinazolinone (Journal of Organic Chemistry, 2011,76,7730) in dimethylbenzene.The people such as Watson in 2012 found to take the hydrogen transference synthetic method that crotononitrile is hydrogen acceptor, ruthenium catalysis (
org. Biomol. Chem. 2012,
10, 240).Then, or Hikawa group in 2012 reported the 2-arylquinazolinethione of palladium catalysis synthetic method (
j. Org. Chem. 2012,
77, 7046).These synthetic methods all need the precious metals such as iridium, palladium, ruthenium to make catalyzer, and raw materials cost is high, so the method does not have economic benefit, is not suitable for suitability for industrialized production.
Summary of the invention
The synthetic method that the object of this invention is to provide a kind of 2-aryl-quinazoline ketone compounds.
The present invention be take air as oxygenant, adds the potassium hydroxide of 1.5 equivalents, and one pot completes the synthetic of 2-aryl-quinazoline ketone compounds.
The experimental implementation step of this synthetic method: 1 mmol anthranilamide, 1 mmol aryl methyl alcohol, 1.5 mmol potassium hydroxide, 4 mL toluene add in test tube successively, at 90 ℃, heated and stirred reaction is 20 hours.After cooling, concentrating under reduced pressure, the mixed solvent of sherwood oil and ethyl acetate (4:1) of then take is eluent, with silica gel column chromatography separating purification, or after diluted acid washing, direct filtration is dried and is obtained product 2-arylquinazolinethione.
Embodiment
Below by embodiment, further set forth the present invention, therefore do not limit the present invention among described scope of embodiments.
embodiment 1
1mmol anthranilamide, 1 mmol phenylcarbinol, 1.5 mmol potassium hydroxide, 4 milliliters of toluene solvants added in test tube successively, 90 ℃ of stirring reactions 20 hours.After cooling, be spin-dried for, the mixed solvent of sherwood oil and ethyl acetate of then take is eluent, with silica gel column chromatography separating purification, obtains 2-phenylquinazoline ketone, 97% productive rate.2-phenylquinazoline ketone:
1 h NMR (300 MHz, DMSO-d
6), δ (ppm): 11.12 (s, 1H), 8.33 (d,
j=7.52 Hz, 1H), 8.20-8.22 (m, 2H) 7.78-7.85 (m, 2H), 7.59 (t,
j=2.78 Hz, 3H), 7.51 (t,
j=3.19 Hz, 1H). IR (KBr), ν (cm
-1): 2924,1730,1664,1601,1451,1375,1212,1045,942,752,694.
embodiment 2
Examination on experimental operation is with embodiment 1.Reaction times shortens to 17 hours in 20 hours in embodiment 1, obtains 2-phenylquinazoline ketone, productive rate 94%.
embodiment 3
Examination on experimental operation is with embodiment 1.So that methylbenzyl alcohol is replaced to the phenylcarbinol in embodiment 1, obtain 2-(4-aminomethyl phenyl) quinazolinone, productive rate 97%.
1 H?NMR?(300?MHz,?DMSO-
d 6 ),?δ?(ppm):?12.46?(s,?1H),?8.14?(d,?
J?=?7.95Hz,?1H),?8.09?(d,?
J?=?8.21Hz,?2H),?7.83?(t,?
J?=?6.87Hz,?1H),?7.72?(d,?
J?=?7.68Hz,?1H),?7.51?(t,?
J?=?7.02Hz,?1H),?7.35?(d,?
J?=?8.07Hz,?2H),?2.50?(d,?
J?=?1.65Hz,?3H).
embodiment 4
Examination on experimental operation is with embodiment 1.With isopropylbenzyl alcohol, replace the phenylcarbinol in embodiment 1, obtain 2-(4-isopropyl phenyl) quinazolinone, productive rate 89.
embodiment 5
Examination on experimental operation is with embodiment 1.With p-methoxybenzyl alcohol, replace the phenylcarbinol in embodiment 1, obtain 2-(4-p-methoxy-phenyl) quinazolinone, productive rate 48%.
embodiment 6
Examination on experimental operation is with embodiment 1.So that methylthio phenyl methyl alcohol is replaced to the phenylcarbinol in embodiment 1, obtain 2-(4-methylthio group phenyl) quinazolinone, productive rate 91%.
embodiment 7
Examination on experimental operation is with embodiment 1.With p-nitrophenyl methyl alcohol, replace the phenylcarbinol in embodiment 1, obtain 2-(4-nitrophenyl) quinazolinone, productive rate 75%.
embodiment 8
Examination on experimental operation is with embodiment 1.With m-phenoxy phenylcarbinol, replace the phenylcarbinol in embodiment 1, obtain 2-(3-Phenoxyphenyl) quinazolinone, productive rate 82%.
embodiment 9
Examination on experimental operation is with embodiment 1.With a methylbenzyl alcohol, replace the phenylcarbinol in embodiment 1, obtain 2-(3-aminomethyl phenyl) quinazolinone, productive rate 98%.
embodiment 10
Examination on experimental operation is with embodiment 1.With a fluorophenyl methanol, replace the phenylcarbinol in embodiment 1, obtain 2-(3-fluorophenyl) quinazolinone, productive rate 95%.
embodiment 11
Examination on experimental operation is with embodiment 1.With m-trifluoromethyl phenylcarbinol, replace the phenylcarbinol in embodiment 1, obtain 2-(3-trifluoromethyl) quinazolinone, productive rate 91%.
embodiment 12
Examination on experimental operation is with embodiment 1.With o-methyl-benzene methyl alcohol, replace the phenylcarbinol in embodiment 1, obtain 2-(2-aminomethyl phenyl) quinazolinone, productive rate 84%.
embodiment 13
Examination on experimental operation is with embodiment 1.With adjacent fluorophenyl methanol, replace the phenylcarbinol in embodiment 1, obtain 2-(2-fluorophenyl) quinazolinone, productive rate 86%.
embodiment 14
Examination on experimental operation is with embodiment 1.So that chlorobenzene methanol is replaced to the phenylcarbinol in embodiment 1, obtain 2-(4-chloro-phenyl-) quinazolinone, productive rate 78%.
1 H?NMR?(300?MHz,?DMSO-
d 6 ),?δ?(ppm):?12.61?(s,?1H),?8.20?(d,?
J?=?8.55Hz,?2H),?8.15?(d,?
J?=?7.92Hz,?1H),?7.85?(t,?
J?=?7.10Hz,?1H),?7.74?(d,?
J?=?8.16Hz,?1H),?7.63?(d,?
J?=?8.55Hz,?2H),?7.53?(t,?
J?=?7.37Hz,?1H).
Claims (2)
1. a synthetic method for 2-aryl-quinazoline ketone compounds, under its feature is that potassium hydroxide exists, adjacent amino fragrant methane amide and aryl methyl alcohol reacts generation 2-aryl-quinazoline ketone compounds under air.
2. the synthetic method of a kind of 2-aryl-quinazoline ketone compounds claimed in claim 1, adjacent amino fragrant methane amide: aryl methyl alcohol: the mol ratio of potassium hydroxide is 1 ﹕ 1:1 ~ 2, and toluene is solvent, reacts under air, 90 ℃ of temperature, 10 ~ 20 hours reaction times.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104356076A (en) * | 2014-10-12 | 2015-02-18 | 渤海大学 | Synthesis method for substituted 2, 3-dihydro-4(1H)-quinazolinone compound |
| CN107043326A (en) * | 2016-02-05 | 2017-08-15 | 超微体生医科技股份有限公司 | Method for preparing anticarcinogenic component artemisin C in propolis and anticarcinogenic component artemisin C |
Citations (3)
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|---|---|---|---|---|
| KR20010098092A (en) * | 2000-04-28 | 2001-11-08 | 박노중 | A new method for the synthesis of 2-(fluoromethyl)-3-aryl-4(3h)-quinazolinone derivatives |
| CN102432551A (en) * | 2011-11-18 | 2012-05-02 | 成都理工大学 | Method for synthesizing 2-arylquinazolinethione |
| CN103570632A (en) * | 2013-07-22 | 2014-02-12 | 成都理工大学 | Synthesis method of catalyst-free 4(3H)-quinazolinone |
-
2013
- 2013-11-29 CN CN201310618968.6A patent/CN103588714A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010098092A (en) * | 2000-04-28 | 2001-11-08 | 박노중 | A new method for the synthesis of 2-(fluoromethyl)-3-aryl-4(3h)-quinazolinone derivatives |
| CN102432551A (en) * | 2011-11-18 | 2012-05-02 | 成都理工大学 | Method for synthesizing 2-arylquinazolinethione |
| CN103570632A (en) * | 2013-07-22 | 2014-02-12 | 成都理工大学 | Synthesis method of catalyst-free 4(3H)-quinazolinone |
Non-Patent Citations (3)
| Title |
|---|
| KOUROSH MOTEVALLI等: "One-pot tandem approach for the synthesis of quinazolinones from ortho-aminobenzamides, benzyl halides and benzyl alcohols", 《JOURNAL OF CHEMICAL RESEARCH》, vol. 36, no. 12, 5 December 2012 (2012-12-05) * |
| RAID J. ABDEL-JALIL等: "A novel method for the synthesis of 4(3H)-quinazolinones", 《TETRAHEDRON LETTERS》, vol. 45, no. 17, 31 December 2004 (2004-12-31), pages 3475 - 3476, XP004500102, DOI: 10.1016/j.tetlet.2004.03.003 * |
| 张陈，等: "2-取代-4(3H)-喹唑啉酮类化合物合成研究进展", 《精细化工中间体》, vol. 36, no. 5, 30 October 2006 (2006-10-30), pages 12 - 15 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104356076A (en) * | 2014-10-12 | 2015-02-18 | 渤海大学 | Synthesis method for substituted 2, 3-dihydro-4(1H)-quinazolinone compound |
| CN107043326A (en) * | 2016-02-05 | 2017-08-15 | 超微体生医科技股份有限公司 | Method for preparing anticarcinogenic component artemisin C in propolis and anticarcinogenic component artemisin C |
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Application publication date: 20140219 |