CN102898385A - Synthesis of 4(3H)-quinazolone through catalysis of recyclable copper oxide - Google Patents
Synthesis of 4(3H)-quinazolone through catalysis of recyclable copper oxide Download PDFInfo
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- CN102898385A CN102898385A CN2012103661717A CN201210366171A CN102898385A CN 102898385 A CN102898385 A CN 102898385A CN 2012103661717 A CN2012103661717 A CN 2012103661717A CN 201210366171 A CN201210366171 A CN 201210366171A CN 102898385 A CN102898385 A CN 102898385A
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- copper oxide
- quinazolone
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Abstract
The invention provides a process for synthesizing 4(3H)-quinazolone through the catalysis of recyclable copper oxide. In the process, copper oxide is used as a catalyst, air is used as an oxidizer, and o-aminoaryl amide and aldehydes are subjected to one-pot reaction to obtain 4(3H)-quinazolone compounds. The method is low in toxicity and cost; the recyclable copper oxide is used as the catalyst, and the consumption of the catalyst is low; and the raw materials are accessible and stable, the cost is low, the process is environment-friendly, and the requirements for atom economy are met. Thus, the invention is suitable for industrial big production.
Description
Technical field
This patent relates to organic synthesis, organic chemical industry, the synthetic research field of medicine, concretely, is exactly the synthetic of 2-arylquinazolinethione.
Background technology
2-aryl-quinazoline ketone compound has the good biological activity, shows preferably pharmacologically active at aspects such as antitumor, hypertension, anti-inflammatory, pain relieving, sterilizations.
2-arylquinazolinethione with multiple important use has multiple synthetic method.
Croce etc. obtain 2 one phenyl substituted quinazolinones in reflux in toluene with l one aryl one 4 one dimethylin, one 2 one phenyl one 1,3 one phenodiazines, one 1,3 one divinyl and phenylisocyanate under nitrogen protection; productive rate 70%-88%(Heterocycles; 1997,45,1309).One of method raw material of Croce needs multistep synthetic.
The logical HCl gas in the methanol solution of aromatic nitriles such as Connolly reacts, and obtains the imines methyl ester hydrochloride, and the latter obtains the 2-arylquinazolinethione with the o-amino benzoyl acid-respons again, yield 42%-70%(Synlett, 2001, (11), 1707).
Couture and co-worker thereof are at the proton of highly basic LDA on-30 ℃ of amino that seize the anthranoyl diethylamide, then obtain 2-arylquinazolinethione, productive rate 15%～75%(Synthesis, 1991 with fragrant nitrile or fatty nitrile reaction, (11), 1609).
Human Ga (OTf) 3 catalysis isatoic anhydrides, ammonium acetate or amine and aldehyde three components synthesizing dihydro quinazolinones in ethanol such as Su, then obtain 2-arylquinazolinethione (Tetrahedron Letters with DMSO oxidation dihydroquinazoline ketone, 2008,49,3814).
More relevant with this patent is one piece of paper of Tetrahedron Letters in 2004, the method in two steps of this piece the thesis is synthesized, the first step anthranilamide and phenyl aldehyde reaction generate imine intermediate, and second step need to use the CuCl of 3 times of molar weights of imine intermediate
2Come the oxidation imine intermediate to obtain target product 2-arylalkyl quinazolinone (Tetrahedron Letters 2004,45,3475).
These methods of front all need to synthesize 2-arylalkyl quinazolinone through polystep reaction.Following document just can be finished synthetic 2-arylalkyl quinazolinone reaction in one pot.
2010, Wang etc. used catalysis of iodine anthranilamide and phenyl aldehyde at ionic liquid [bmim
+] [BF4
-] the synthetic 2-arylalkyl quinazolinone (Synthetic Communications, 2010,40,2633) of middle one pot reaction.But, the consumption that this paper is not mentioned iodine from start to finish specifically what.With reference to the bibliographical information of some other catalysis of iodine organic reaction, general 10 (mol) % of iodine consumption or more than.In addition, although ionic liquid can be by reclaiming, removal process is cumbersome, and the ionic liquid cost is high, expensive.
2011, Fu and co-worker thereof be the synthetic 2-arylalkyl quinazolinone of one pot reaction under air, in dimethylsulfoxide solvent with the adjacent iodine aryl carboxamides of 10% cupric bromide catalysis and benzylamine.The iodo reagent of adjacent iodine virtue methane amide that the method is used and so on, expensive, in addition, generate hydrogen iodide in the reaction process, also need to add acid binding agent salt of wormwood.
A few days ago, we find that 1 (mol) % vanadic salts can catalyze and synthesize 2-aryl-quinazoline ketone compounds (number of patent application 201110365727.6) effectively in air.In view of the toxicity of vanadic salts, we do further research and find, cupric oxide heterogeneous, that can be recycled also can be used for the synthetic of 2-aryl-quinazoline ketone compounds.
Summary of the invention
The new synthetic method that the purpose of this invention is to provide a kind of 2-aryl-quinazoline ketone compounds.
The present invention is take air as oxygenant, take the cupric oxide of capable of circulation, 3 (mol) % as catalyzer, finishes the synthetic of 2-aryl-quinazoline ketone compounds for one pot.
The experimental implementation step of this synthetic method: 1mmol anthranilamide, 1mmol aromatic aldehyde, 0.03 mmol cupric oxide, a certain amount of solvent add in the test tube successively, heated and stirred reaction certain hour.After the cooling, add certain water gaging, with a certain amount of ethyl acetate extraction 3 times, organic phase washes twice with water, then take the mixed solvent of sherwood oil and ethyl acetate as eluent, uses silica gel column chromatography separating purification, perhaps by recrystallization in ethanol, obtain product 2-aryl-quinazoline ketone compounds.
Table 1 is to investigate various reaction conditionss to the impact of this reaction.
Table 2 is that synthetic various 2-replace and 2,3-disubstituted quinazoline ketone compounds under optimal conditions.
Table 3 investigation catalyst oxidation copper recycles the impact on this reaction.
Embodiment
Further set forth the present invention below by embodiment, therefore do not limit the present invention among the described scope of embodiments.Majority provides (number of patent application 201110365727.6) in the patent that is characterized in our front of compound, no longer repeats at this.
Embodiment 1
The cupric oxide of the phenyl aldehyde of the anthranilamide of 1 mmole, 1 mmole, 0.03 mmole, 3 milliliters of N, N-diethyl acetamide solvent added in the test tube successively, 120 ℃ of stirring reactions 24 hours.After the cooling, add 10 ml waters, with 10 milliliters of ethyl acetate extractions 3 times, organic phase washes twice with water, then take the mixed solvent of sherwood oil and ethyl acetate as eluent, with silica gel column chromatography separating purification obtain 2-phenylquinazoline ketone (
3a), productive rate 96.66%.
Embodiment 2
With the phenyl aldehyde in the n-hexyl aldehyde alternative embodiment 1 of 1 mmole, other condition is identical, obtain productive rate 58.52% 2-n-pentyl quinazolinone (
3l).Mp.?152-154?
oC.?
1 H?NMR?(300?MHz,?DMSO-
d 6 )?,?δ(ppm):?12.15?(s?,?1H?)?,?8.07?(d?,
?J=7.89Hz?,?1H?)?,?7.72-7.78?(m?,?1H?)?,?7.58?(d?,?
J=8.10Hz?,?1H?)?,?7.41-7.46?(m?,?1H?)?,?2.49-2.60?(m?,?2H.)?,?1.67-1.72?(m?,?2H)?,?1.29?(d?,
?J=7.14Hz?,?4H)?,?0.85?(d?,?
J=6.66Hz?,?3H)?.?
13C?NMR?(75?MHz,?DMSO-
d 6 )?δ?(ppm):?162.0?,?157.7?,?149.0?,?134.4?,?126.8?,?126.0?,?125.8?,?120.8?.?IR(KBr)?,?ν?(cm
-1)：3846,?3696,?3121,?2925,?1845,?1675,?1614,?1564,?1470,?1380,?1324,?1254,?1027,?976,?737,?647.
Embodiment 3
The cupric oxide of the phenyl aldehyde of the anthranilamide of 1 mmole, 1 mmole, 0.05 mmole, 3 milliliters of N, the N-diethyl acetamide added in the test tube successively, 120 ℃ of stirring reactions 24 hours.After the cooling, add 10 milliliters of ethyl acetate, the static cupric oxide that allows is deposited to the bottom, gently with glue head dropper sucking-off supernatant layer to remaining a little contain lower floor's solution of cupric oxide, add again 10 milliliters of ethyl acetate, use again gently sucking-off supernatant liquor of glue head dropper, totally three times so repeatedly.Upper solution is carried out normal aftertreatment by embodiment 1, obtain behind the column chromatography separating purification 2-phenylquinazoline ketone (
3a), productive rate 97.53%.Lower floor contains a little solution decompression of cupric oxide and removes ethyl acetate solvent, adds reaction raw materials again, that is, the phenyl aldehyde of the anthranilamide of 1 mmole, 1 mmole, 3 milliliters of N, the N-diethyl acetamide was 120 ℃ of stirring reactions 24 hours.According to a conventional method aftertreatment and separation and purification, cupric oxide recycle 1 time, and the productive rate of reaction is 95.22%.Recycle copper oxide catalyst by similar approach, for the second time, for the third time, the 4th time reaction yield is respectively: 95.06%, 92.92%, 90.78%.
Claims (1)
1. the copper oxide catalyzation that can be recycled synthesizes 4 (3H)-quinazolinones, it is characterized in that under air, in the presence of 1 ~ 10% powdery copper oxide catalyst, replace adjacent amino fragrant acid amides and fragrance or alkanoic and generated 4 (3H)-quianzolinones in 20 ~ 30 hours 80 ~ 150 degrees centigrade of lower heated and stirred reactions.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103613550A (en) * | 2013-11-29 | 2014-03-05 | 成都理工大学 | Environment-friendly synthesis method for 4(3H)-quinazolinone |
| CN103864702A (en) * | 2014-02-27 | 2014-06-18 | 福建医科大学 | Method for preparing quinazolinone in water phase through microwave catalysis |
| CN105272926A (en) * | 2014-07-24 | 2016-01-27 | 中国科学院大连化学物理研究所 | Method for preparing quinazoline derivatives from synthesis of alcohol and 2-aminobenzylamine |
| 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 |
| CN115028588A (en) * | 2022-06-24 | 2022-09-09 | 徐州医科大学 | Green synthesis method of heterocyclic compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432551A (en) * | 2011-11-18 | 2012-05-02 | 成都理工大学 | Method for synthesizing 2-arylquinazolinethione |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432551A (en) * | 2011-11-18 | 2012-05-02 | 成都理工大学 | Method for synthesizing 2-arylquinazolinethione |
Non-Patent Citations (3)
| Title |
|---|
| JINTANG ZHANG等: "A novel and efficient methodology for construction of quinazolines based on supported copper oxide nanoparticles", 《CHEMICAL COMMUNICATIONS》, vol. 46, no. 29, 24 June 2010 (2010-06-24), pages 5245 * |
| TAO LIU等: "Copper-Catalyzed Synthesis of N-Heterocyclic Compounds", 《SYNTHESIS》, vol. 44, no. 18, 13 August 2012 (2012-08-13) * |
| XIAOWEI LIU等: "A Simple and Efficient Approach to Quinazolinones under Mild Copper-Catalyzed Conditions", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION》, vol. 48, no. 2, 3 December 2008 (2008-12-03) * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103613550A (en) * | 2013-11-29 | 2014-03-05 | 成都理工大学 | Environment-friendly synthesis method for 4(3H)-quinazolinone |
| CN103864702A (en) * | 2014-02-27 | 2014-06-18 | 福建医科大学 | Method for preparing quinazolinone in water phase through microwave catalysis |
| CN103864702B (en) * | 2014-02-27 | 2016-05-11 | 福建医科大学 | A kind of in water microwave catalysis prepare the method for Quinazolinone compounds |
| CN105272926A (en) * | 2014-07-24 | 2016-01-27 | 中国科学院大连化学物理研究所 | Method for preparing quinazoline derivatives from synthesis of alcohol and 2-aminobenzylamine |
| 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 |
| 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 |
| CN115028588A (en) * | 2022-06-24 | 2022-09-09 | 徐州医科大学 | Green synthesis method of heterocyclic compound |
| CN115028588B (en) * | 2022-06-24 | 2023-08-11 | 徐州医科大学 | Green synthesis method of heterocyclic compound |
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