阅读说明：本技术 一种色原酮衍生物的合成方法 (Synthesis method of chromone derivative ) 是由 郑子圣 许智 王雷 汤海波 于 2020-06-30 设计创作，主要内容包括：本发明公开了一种色原酮衍生物的合成方法,包括如下步骤：将化合物RXXR溶于溶剂中,加入简写为PIFA的[双(三氟乙酰氧基)碘]苯,反应8-15min,加入2-甲氧基苯基炔酮衍生物(II),进行反应,得到色原酮衍生物(I)；<Image he="196" wi="700" file="DDA0002561869220000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明具有操作简单,原料价廉易得,无金属参与,底物适应性广,反应条件温和,反应时间短,收率理想等优点。(The invention discloses a synthetic method of a chromone derivative, which comprises the following steps: dissolving compound RXR in solvent, adding [ bis (trifluoroacetoxy) iodine abbreviated as PIFA]Benzene is reacted for 8-15min, and 2-methoxy phenyl alkynone derivative (II) is added for reaction to obtain chromone derivative (I); the method has the advantages of simple operation, cheap and easily obtained raw materials, no metal participation, wide substrate adaptability, mild reaction conditions, short reaction time, ideal yield and the like.)

1. A synthetic method of a chromone derivative is characterized by comprising the following steps:

dissolving a compound RXR in a solvent, adding [ bis (trifluoroacetoxy) iodine ] benzene abbreviated as PIFA, reacting for 8-15min, adding a 2-methoxyphenyl alkynone derivative (II), and reacting to obtain a chromone derivative (I);

wherein:

x is a selenium atom or a sulfur atom;

r is methyl, phenyl, 4-methylphenyl or 4-chlorophenyl;

R¹is cyclopropyl, 3-thienyl, phenyl, 2-methylphenyl, 3-methylphenyl, 2-fluorophenyl, 3-bromophenyl, 4-chlorophenyl or 4-methoxyphenyl;

R²is a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom or a bromine atom.

2. The method according to claim 1, wherein the solvent is acetonitrile, dichloromethane or dichloroethane.

3. The method as set forth in claim 2, wherein the solvent is acetonitrile.

Technical Field

The invention relates to a synthetic method of a chromone derivative.

Background

Chromone derivatives are heterocyclic compounds with important value and are widely distributed in various natural products^[1-10]Has various pharmacological activities including antioxidant, antifungal, antiinflammatory, HIV resisting, antitumor, etc. For example, flavoxate (iii) is a chromone derivative useful as an anticholinergic with antimuscarinic action; apigenin (IV) is useful as an antiviral agent for the treatment of HIV, cancer and other viral infections.

The report of the preparation of 3-selenochronone derivatives using 2-methoxyarylalkynone as substrate is as follows: 2011, Zeni et al^[11]The 3-selenochronone derivative is obtained by taking 2-methoxyaryl alkynone and diselenide compounds as raw materials, ferric trichloride as an additive and dichloromethane as a solvent under the condition of room temperature, but the method has long reaction time and uses excessive (1.5 equivalent) ferric trichloride as a metal additive. 2016, Zhang^[12]Similar work is published, 2-methoxy aryl alkynone and benzamide aryl sulfide are used as raw materials, ferric trichloride is used as an additive, and dichloromethane is used as a solvent, so that the 3-thiochromanone derivative is successfully obtained. However, this process has a long reaction time, a low yield and uses an excess (2.0 equivalents) of ferric trichloride as a metal additive. See in particular the following references:

1.Mears,J.A.Journal of Natural Products 1980,43,708-716.

2.Meragelman,T.L.；Tucker,K.D.；McCloud,T.G.；Cardellina,J.H.；Shoemaker,R.H.Journal of Natural Products 2005,68,1790-1792.

3.Zhou,K.；Zhao,F.；Liu,Z.；Zhuang,Y.；Chen,L.；Qiu,F.Journal of NaturalProducts 2009,72,1563-1567.

4.Ribeiro,A.；Piló-Veloso,D.；Romanha,A.J.；Zani,C.L.Journal of NaturalProducts 1997,60,836-838.

5.

M.J.C.；Pouliquem,Y.B.M.；Lima,M.A.S.；Gramosa,N.V.；Costa-Lotufo,L.V.；G.C.G.；Pessoa,C.；Odorico de Moraes,M.；Silveira,E.R.Journalof Natural Products 2005,68,423-426.

6.Bhaskar Reddy,M.V.；Kishore,P.H.；Rao,C.V.；Gunasekar,D.；Caux,C.；Bodo,B.Journal of Natural Products 2003,66,295-297.

7.Wu,M.-C.；Peng,C.-F.；Chen,I.-S.；Tsai,I.-L.Journal of NaturalProducts 2011,74,976-982.8.Duong,T.-H.；Beniddir,M.A.；Nguyen,V.-K.；Aree,T.；Gallard,J.-F.；Mac,D.-H.；Nguyen,H.-H.；Bui,X.-H.；Boustie,J.；Nguyen,K.-P.-P.；Chavasiri,W.；Le Pogam,P.Journal of Natural Products 2018,81,2026-2031.

9.Meesakul,P.；Richardson,C.；Pyne,S.G.；Laphookhieo,S.Journal ofNatural Products 2019,82,741-747.

10.Jaidee,W.；Andersen,R.J.；Chavez,M.A.G.；Wang,Y.A.；Patrick,B.O.；Pyne,S.G.；Muanprasat,C.；Borwornpinyo,S.；Laphookhieo,S.Journal of Natural Products2019,82,283-292.

11Godoi,B.；A.；Bruning,C.A.；Back,D.F.；Menezes,P.H.；Nogueira,C.W.；Zeni,G.AdvancedSynthesis&Catalysis 2011,353,2042-2050.

12.Shi,L.-F.；Zhang,X.-G.；Zhang,X.-H.Tetrahedron 2016,72,8617-8622.

disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a simple, green and rapid synthetic method of a chromone derivative for realizing intramolecular cyclization and sulfide tandem cyclization.

The technical scheme of the invention is summarized as follows:

a method for synthesizing chromone derivatives comprises the following steps:

dissolving a compound RXR in a solvent, adding [ bis (trifluoroacetoxy) iodine ] benzene abbreviated as PIFA, reacting for 8-15min, adding a 2-methoxyphenyl alkynone derivative (II), and reacting to obtain a chromone derivative (I);

wherein:

x is a selenium atom or a sulfur atom;

r is methyl, phenyl, 4-methylphenyl or 4-chlorophenyl;

R¹is cyclopropyl, 3-thienyl, phenyl, 2-methylphenyl, 3-methylphenyl, 2-fluorophenyl, 3-bromophenyl, 4-chlorophenyl

Or 4-methoxyphenyl;

R²is a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom or a bromine atom.

The solvent is preferably acetonitrile, dichloromethane or dichloroethane, but other solvents having properties similar to those described above may also be used.

Acetonitrile is preferred.

The method has the advantages of simple operation, cheap and easily obtained raw materials, no metal participation, wide substrate adaptability, mild reaction conditions, short reaction time, ideal yield and the like.

Detailed Description

Acetonitrile (CH)₃CN) was a commercially purchased analytical grade.

[ bis (trifluoroacetoxy) iodine ] benzene (PIFA) was prepared according to literature methods (Nathaniel, W.A.; W, D.H.; Colin, H.J.chem.Soc.Dalton trans.1984,1709-1716.)

2-methoxy aryl alkynone derivatives (II) were prepared for reference. (Russell, J.C.; Dougal, J.R.; Thomas, A.D.; John, B.Jonathan, P.H.C.; Anob K.chem.Commun.2005,1037-1039.)

The present invention will be further illustrated by the following specific examples.