CN103570632B - The synthetic method of 4 (3H)-quinazolinones of catalyst-free - Google Patents
The synthetic method of 4 (3H)-quinazolinones of catalyst-free Download PDFInfo
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- CN103570632B CN103570632B CN201310306663.1A CN201310306663A CN103570632B CN 103570632 B CN103570632 B CN 103570632B CN 201310306663 A CN201310306663 A CN 201310306663A CN 103570632 B CN103570632 B CN 103570632B
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- quinazolinone
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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
Abstract
The invention provides a kind of catalyst-free, the method for synthesis 2-aryl-4 (3H)-quinazolinone that caustic alkali promotes.Do promotor with caustic alkali, air oxidant, adjacent amino aryl methane amide and alkyl methyl alcohol one pot reaction obtain 2-and replace 4 (3H)-quianzolinones.The method raw material is easy to get, with low cost, technique is green, simple to operate, be applicable to suitability for industrialized production.
Description
Technical field
This patent includes the research field of chemical machine, organic chemical industry, pharmaceutical synthesis, concretely, is exactly the synthesis of 2-aryl 4 (3H)-quinazolinone.
Background technology
2-aryl-4 (3H)-quinazolinones has pharmacological action widely, in antitumor, hypertension, anti-inflammatory, pain relieving, sterilization etc., show good pharmacologically active.
2-aryl-4 (the 3H)-quinazolinone of medicine importance has many synthetic methods.
Such as; l mono-aryl 1 dimethylin 1 phenyl 1 such as Croce; 3 one phenodiazines 1; 3 one divinyl and phenylisocyanate obtain 2 one phenyl-4 (3H)-quinazolinones in reflux in toluene under nitrogen protection; productive rate 70%-88%(Heterocycles; 1997,45,1309).One of method raw material of Croce needs to synthesize through multistep.
The logical HCl gas in the methanol solution of aromatic nitriles such as Connolly reacts, and obtain imines methyl ester hydrochloride, the latter is obtained by reacting 2-aryl-4 (3H)-quinazolinone again with anthranilic acid, yield 42%-70%(Synlett, 2001, (11), 1707).
Couture and co-worker thereof seize the proton on the amino of anthranoyl diethylamide at highly basic LDA at-30 DEG C, then 2-aryl-4 (3H)-quinazolinone is obtained by reacting with fragrant nitrile or fatty nitrile, productive rate 15% ~ 75%(Synthesis, 1991, (11), 1609).
The people such as Su are with Ga (OTf)
3catalysis isatoic anhydride, ammonium acetate or amine and aldehyde three components synthesizing dihydro quinazolinone in ethanol, is then oxidized dihydroquinazoline ketone with DMSO and obtains 2-aryl-4 (3H)-quinazolinone (Tetrahedron Lett., 2008,49,3814).
2010, Wang etc. used catalysis of iodine anthranilamide and phenyl aldehyde at ionic liquid [bmim
+] [BF
4 -] middle one pot reaction synthesis 2-aryl-4 (3H)-quinazolinone (Synth. Commun., 2010,40,2633).But the consumption that this paper does not mention iodine is from start to finish specifically how many.With reference to the bibliographical information of the similar organic reaction of some other catalysis of iodine, iodine consumption general 10 (mol) % or more.In addition, although ionic liquid can by reclaiming, removal process is cumbersome, and ionic liquid cost is high, expensive.
2011, one pot reaction synthesized 2-aryl-4 (3H)-quinazolinone under air, in dimethylsulfoxide solvent with the adjacent iodine aryl carboxamides of 10% cupric bromide catalysis and benzylamine for Fu and co-worker thereof.The iodo reagent of the adjacent iodine virtue methane amide that the method uses and so on, expensive, generate hydrogen iodide in reaction in addition, also need to add acid binding agent salt of wormwood.
Within 2004, Abdel-Jalil reports the method for two steps to synthesize 2-aryl-4 (3H)-quinazolinone, and the first step anthranilamide and phenyl aldehyde react and generate imine intermediate, and second step needs the CuCl using imine intermediate 3 times of molar weights
2carry out iminoxy intermediate and obtain target product (Tetrahedron Lett. 2004,45,3475).
Catalyzer made by vanadic salts and the cupric oxide such as 2011-2013, Zeng Qingle, and air makees oxygenant, by anthranilamide and phenyl aldehyde one pot process 2-aryl-4 (3H)-quinazolinone (RSC Adv. 2013,3,9325; Synth. Commun. 2013,43,2493).Metal catalyst is used in this reaction, and phenyl aldehyde is industrially usual is obtained by benzyl alcohol oxidation, compares expensive.
With document relatively relevant be herein three sections with the document of aryl methyl alcohol for Material synthesis 4 (3H)-quinazolinone.It is hydrogen acceptor that Zhou in 2011 reports with vinylbenzene, iridium catalytic hydrogen transfer synthesis 4 (3H)-quinazolinones (J. Org. Chem. 2011,76,7730).Within 2012, Watson study group reports using the crotononitrile of 2.5 equivalents as hydrogen acceptor, the Ru (PPh of 5 mol%
3)
3(CO) (H)
2with the Xantphos of 5 mol% as catalyst system, from benzylalcohol and anthranilamide synthesis 4 (3H)-quinazolinones (Org. Biomol. Chem., 2012,10,240).Within 2012, Hikawa reports 5 mol % Pd (OAc)
2with realize in 10 mol% diphenylphosphine-3-benzene sulfonic acid sodium salts under air water benzylalcohol and anthranilamide synthesis 4 (3H)-quinazolinones, he thinks that water plays keying action (J. Org. Chem. 2012,77,7046).
In deeply studying 4 (3H)-quinazolinones, we find without the need to transition-metal catalyst, and highly basic potassium hydroxide can promote benzylalcohol and anthranilamide synthesis 4 (3H)-quinazolinones.
Summary of the invention
The object of this invention is to provide a kind of new synthetic method of 2-aryl-4 (3H)-quianzolinones.
The present invention is oxygenant with air, adds appropriate masses alkali as promotor, and one pot from the synthesis completing 2-aryl-4 (3H)-quianzolinones.
The experimental implementation general step of this synthetic method: the adjacent amino aryl methane amide of 1 mmol, 1 mmol alkyl methyl alcohol, appropriate masses alkali, q. s. toluene solvent add in test tube successively, and heated and stirred is reacted to the scheduled time at 90 DEG C.After cooling, reaction mixture add water cancellation reaction, be extracted with ethyl acetate, be spin-dried for, then with the mixed solvent of sherwood oil and ethyl acetate for eluent, with silica gel column chromatography separating purification, or after diluted acid washing, direct filtration obtains product 2-alkyl-4 (3H)-quianzolinones after drying washing.
Embodiment
Set forth the present invention further below by embodiment, therefore do not limit the present invention among described scope of embodiments.
Embodiment 1
1 mmol anthranilamide, 1 mmol phenylcarbinol, 1.5 mmol potassium hydroxide, 4 mL toluene solvants added in test tube successively, 90 DEG C of stirring reactions 20 hours.After cooling, be spin-dried for, then with the mixed solvent of sherwood oil and ethyl acetate for eluent, obtain 2-phenyl-4 (3H)-quinazolinone with silica gel column chromatography separating purification, productive rate 97%.2-phenyl-4 (3H)-quinazolinone:
1h NMR (300 MHz, CDCl
3), 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 (neat), 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 by 20 in embodiment 1 hour, obtains 2-phenyl-4 (3H)-quinazolinone, productive rate 94%.
Embodiment 3
Examination on experimental operation is with embodiment 1.To replace the phenylcarbinol in embodiment 1 to methylbenzyl alcohol, obtain 2-(4-aminomethyl phenyl)-4 (3H)-quinazolinone, productive rate 97%.
1H NMR (300 MHz, DMSO-d6), 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.Replace the phenylcarbinol in embodiment 1 with isopropylbenzyl alcohol, obtain 2-(4-isopropyl phenyl)-4 (3H)-quinazolinone, productive rate 89.
Embodiment 5
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with p-methoxybenzyl alcohol, obtain 2-(4-p-methoxy-phenyl)-4 (3H)-quinazolinone, productive rate 48%.
Embodiment 6
Examination on experimental operation is with embodiment 1.To replace the phenylcarbinol in embodiment 1 to methylthio phenyl methyl alcohol, obtain 2-(4-methylthio group phenyl)-4 (3H)-quinazolinones, productive rate 91%.
Embodiment 7
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with p nitrobenzyl alcohol, obtain 2-(4-nitrophenyl)-4 (3H)-quinazolinone, productive rate 75%.
Embodiment 8
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with m-phenoxy phenylcarbinol, obtain 2-(3-Phenoxyphenyl)-4 (3H)-quinazolinone, productive rate 82%.
Embodiment 9
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with a methylbenzyl alcohol, obtain 2-(3-aminomethyl phenyl)-4 (3H)-quinazolinone, productive rate 98%.
Embodiment 10
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with a fluorophenyl methanol, obtain 2-(3-fluorophenyl)-4 (3H)-quinazolinone, productive rate 95%.
Embodiment 11
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with m-trifluoromethyl phenylcarbinol, obtain 2-(3-trifluoromethyl)-4 (3H)-quinazolinone, productive rate 91%.
Embodiment 12
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with o-methyl-benzene methyl alcohol, obtain 2-(2-aminomethyl phenyl)-4 (3H)-quinazolinone, productive rate 84%.
Embodiment 13
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with adjacent fluorophenyl methanol, obtain 2-(2-fluorophenyl)-4 (3H)-quinazolinone, productive rate 86%.
Embodiment 14
Examination on experimental operation is with embodiment 1.To replace the phenylcarbinol in embodiment 1 to chlorobenzene methanol, obtain 2-(4-chloro-phenyl-)-4 (3H)-quinazolinone, productive rate 78%.1H NMR (300 MHz, DMSO-d6), 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).
Embodiment 15
Examination on experimental operation is with embodiment 1.Replace the phenylcarbinol in embodiment 1 with 3-trifluoromethyl benzyl alcohol, obtain 2-(3-trifluoromethyl compares)-4 (the 3H)-quinazolinone of 91% productive rate.
Embodiment 16
Examination on experimental operation is with embodiment 1.0.2 mmol cesium hydroxide replaces 2 mmol potassium hydroxide of embodiment 1, obtains 85% productive rate.
Embodiment 17
Examination on experimental operation is with embodiment 1.Replace 2 mmol potassium hydroxide in embodiment 1 with 2 mmol sodium hydroxide, obtain 2-phenyl-4 (the 3H)-quinazolinone of 72% productive rate.
Embodiment 18
Examination on experimental operation is with embodiment 1.Replace toluene to make solvent with dimethylbenzene, obtain 2-phenyl-4 (the 3H)-quinazolinone of 96% productive rate.
Embodiment 19
Examination on experimental operation is with embodiment 1.Replace toluene to make solvent with dioxane, obtain 2-phenyl-4 (the 3H)-quinazolinone of 89% productive rate.
Embodiment 20
Examination on experimental operation is with embodiment 1.Replace toluene to make solvent with glycol dimethyl ether, obtain 2-phenyl-4 (the 3H)-quinazolinone of 91% productive rate.
Embodiment 21
Examination on experimental operation is with embodiment 1.At 70 DEG C, reaction is reacted at replacing 90 DEG C in embodiment 1, obtains 2-phenyl-4 (the 3H)-quinazolinone of 70% productive rate.
Embodiment 22
Examination on experimental operation is with embodiment 1.2.0 mmol potassium hydroxide replace 1.5 mmol potassium hydroxide in embodiment 1, obtain 2-phenyl-4 (the 3H)-quinazolinone of 99% productive rate.
Embodiment 23
Examination on experimental operation is with embodiment 1.0.8 mmol potassium hydroxide replaces 1.5 mmol potassium hydroxide in embodiment 1, obtains 2-phenyl-4 (the 3H)-quinazolinone of 76% productive rate.
Claims (2)
1. the synthetic method of (3H)-quianzolinones, it is characterized in that caustic alkali promotes that anthranilamide and the reaction of aryl methyl alcohol generate 2-aryl-4 (3H)-quianzolinones under air, the consumption of caustic alkali is 0.8 ~ 2 times of the molar weight of anthranilamide.
2. the synthetic method of a kind of 4 (3H)-quianzolinones according to claim 1, it is characterized in that said caustic alkali refers to potassium hydroxide, cesium hydroxide and sodium hydroxide, aryl comprises naphthyl and the phenyl with the alkyl of any one or two, fluorine, chlorine, bromine, nitro, carbalkoxy,-oxyl, sulfenyl, trifluoromethyl, aryl methyl alcohol is identical with the mole dosage of anthranilamide, solvent is toluene, dimethylbenzene, dioxane, glycol dimethyl ether, temperature is 70 ~ 90 DEG C, and the reaction times is 17 ~ 20 hours.
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| CN103588714A (en) * | 2013-11-29 | 2014-02-19 | 成都理工大学 | Potassium hydroxide promoted 2-aryl quinazolone quinazolinone synthesis method |
| CN105272926B (en) * | 2014-07-24 | 2018-09-25 | 中国科学院大连化学物理研究所 | A kind of method that alcohol and 2- amino-benzylamines are synthetically prepared quinazoline derivant |
| CN105327703B (en) * | 2014-08-08 | 2017-11-24 | 中国科学技术大学 | The preparation method of gold nano catalyst and the catalyst prod obtained and application |
| CN104356076A (en) * | 2014-10-12 | 2015-02-18 | 渤海大学 | Synthesis method for substituted 2, 3-dihydro-4(1H)-quinazolinone compound |
| CN105732520A (en) * | 2014-12-11 | 2016-07-06 | 中国科学院大连化学物理研究所 | Method of synthesizing quinazolinone-structured compound |
| CN104744379B (en) * | 2015-03-13 | 2017-10-27 | 三峡大学 | A kind of quianzolinones and its synthetic method |
| CN104725326B (en) * | 2015-04-15 | 2016-12-14 | 王文明 | A kind of synthetic method of quianzolinones |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (4)
| Title |
|---|
| 4(3H)和4(1H)-喹唑啉酮衍生物的合成研究;张婷婷;《渤海大学硕士学位论文》;20121030;49-59 * |
| H Amidation with Benzyl Alcohols in Water:A Strategy To Construct Quinazolinones.《J. Org. Chem.》.2012,第77卷7046-7051. * |
| Hidemasa Hikawa等.Pd-Catalyzed Benzylic C− * |
| 聂兴桥,董定龙.苯.《石油化工危险品安全手册》.黑龙江科学技术出版社,1997,414. * |
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