CN106008434B - A kind of synthetic method of 3- benzoyls coumarin kind compound - Google Patents
A kind of synthetic method of 3- benzoyls coumarin kind compound Download PDFInfo
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- CN106008434B CN106008434B CN201610428012.3A CN201610428012A CN106008434B CN 106008434 B CN106008434 B CN 106008434B CN 201610428012 A CN201610428012 A CN 201610428012A CN 106008434 B CN106008434 B CN 106008434B
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- coumarin
- benzoyl
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- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960000956 coumarin Drugs 0.000 title claims abstract description 23
- 235000001671 coumarin Nutrition 0.000 title claims abstract description 23
- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 title abstract description 12
- -1 aldehyde compound Chemical class 0.000 claims abstract description 66
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000012074 organic phase Substances 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 238000013375 chromatographic separation Methods 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 7
- 238000001308 synthesis method Methods 0.000 claims description 6
- 150000004775 coumarins Chemical class 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 3
- LPBMPRKJYKSRLL-UHFFFAOYSA-N 3-benzoylchromen-2-one Chemical compound C=1C2=CC=CC=C2OC(=O)C=1C(=O)C1=CC=CC=C1 LPBMPRKJYKSRLL-UHFFFAOYSA-N 0.000 abstract description 9
- 229910052751 metal Inorganic materials 0.000 abstract description 6
- 239000002184 metal Substances 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 2
- 238000007445 Chromatographic isolation Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 239000012071 phase Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 230000002194 synthesizing effect Effects 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 230000003595 spectral effect Effects 0.000 description 8
- 238000010183 spectrum analysis Methods 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 5
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 4
- HURNEONJBQTXHV-UHFFFAOYSA-N 3-(2-chlorobenzoyl)chromen-2-one Chemical compound ClC1=C(C(=O)C=2C(OC3=CC=CC=C3C=2)=O)C=CC=C1 HURNEONJBQTXHV-UHFFFAOYSA-N 0.000 description 4
- FCTQJVZKUQOJIW-UHFFFAOYSA-N 3-(4-methoxybenzoyl)-6-methylchromen-2-one Chemical compound COC1=CC=C(C(=O)C=2C(OC3=CC=C(C=C3C=2)C)=O)C=C1 FCTQJVZKUQOJIW-UHFFFAOYSA-N 0.000 description 4
- NLUSZZRJUQXTCN-UHFFFAOYSA-N 3-(4-methoxybenzoyl)-6-nitrochromen-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC2=CC([N+]([O-])=O)=CC=C2OC1=O NLUSZZRJUQXTCN-UHFFFAOYSA-N 0.000 description 4
- AZESABVBPAGIPJ-UHFFFAOYSA-N 3-(4-methoxybenzoyl)chromen-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC2=CC=CC=C2OC1=O AZESABVBPAGIPJ-UHFFFAOYSA-N 0.000 description 4
- GWPYXJVTFVEDSI-UHFFFAOYSA-N 3-benzoyl-7-hydroxy-4-methylchromen-2-one Chemical compound O=C1OC=2C=C(O)C=CC=2C(C)=C1C(=O)C1=CC=CC=C1 GWPYXJVTFVEDSI-UHFFFAOYSA-N 0.000 description 4
- PVAUILUXKAAGKT-UHFFFAOYSA-N 7-hydroxy-3-(4-methoxybenzoyl)chromen-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC2=CC=C(O)C=C2OC1=O PVAUILUXKAAGKT-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
- FXFYOPQLGGEACP-UHFFFAOYSA-N 6-methylcoumarin Chemical compound O1C(=O)C=CC2=CC(C)=CC=C21 FXFYOPQLGGEACP-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- AWDSCPCHQFTJQT-UHFFFAOYSA-N 3-oxo-2-phenylprop-2-enoic acid Chemical compound OC(=O)C(=C=O)C1=CC=CC=C1 AWDSCPCHQFTJQT-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- VKVCJIMMVPXDQD-UHFFFAOYSA-N 6-methoxycoumarin Chemical compound O1C(=O)C=CC2=CC(OC)=CC=C21 VKVCJIMMVPXDQD-UHFFFAOYSA-N 0.000 description 1
- XYFXTIBDEAZMAH-UHFFFAOYSA-N 6-methoxycoumarin Natural products O1C(=O)C=CC2=C1C=CC=C2OC XYFXTIBDEAZMAH-UHFFFAOYSA-N 0.000 description 1
- RMERXEXZXIVNBF-UHFFFAOYSA-N 6-nitrochromen-2-one Chemical compound O1C(=O)C=CC2=CC([N+](=O)[O-])=CC=C21 RMERXEXZXIVNBF-UHFFFAOYSA-N 0.000 description 1
- CFNMUZCFSDMZPQ-GHXNOFRVSA-N 7-[(z)-3-methyl-4-(4-methyl-5-oxo-2h-furan-2-yl)but-2-enoxy]chromen-2-one Chemical compound C=1C=C2C=CC(=O)OC2=CC=1OC/C=C(/C)CC1OC(=O)C(C)=C1 CFNMUZCFSDMZPQ-GHXNOFRVSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 229960002089 ferrous chloride Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000006897 homolysis reaction Methods 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- FWYIBGHGBOVPNL-UHFFFAOYSA-N scopoletin Natural products COC=1C=C2C=CC(OC2=C(C1)O)=O FWYIBGHGBOVPNL-UHFFFAOYSA-N 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/12—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 3 and unsubstituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/14—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 6 and unsubstituted in position 7
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention provides a kind of synthetic methods of 3 benzoyl coumarin kind compound; belong to organic synthesis field; can be 3 benzoyl coumarin kind compound of Material synthesis directly using coumarin kind compound and aldehyde compound; this method is simple; synthetic product yield is high; and participated in without metal, it is environmental-friendly.The synthetic method includes the following steps：Coumarin kind compound, aldehyde compound and di-tert-butyl peroxide are separately added into reaction bulb, and is reacted 10 24 hours at a temperature of 100 200 DEG C；It treats after reaction, to be extracted using organic solvent, merges organic phase；After being dried to the organic phase, chromatographic isolation is carried out, obtains 3 benzoyl coumarin kind compounds.The present invention can be used in being synthetically prepared of 3 benzoyl coumarin kind compounds.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a synthetic method of a 3-benzoyl coumarin compound.
Background
At present, most of the existing methods for synthesizing coumarin compounds need the participation of metal catalysts and organic solvents, such as: in 2015, it was reported that coumarin and 2-carbonyl-2-phenylacetic acid can synthesize coumarin compounds under the action of silver nitrate with a yield of 24% (see Tetrahedron, volume 71 in 2015, 4 th, page 630 in 636). In addition, it was proposed to synthesize coumarin compounds in 2015 using 3-benzyl in the presence of ferrous chloride as catalyst and chlorobenzene as solvent, with a yield of 54% (see RSC Adv (royal chemical society of uk), vol 5, 107, 88258, 88265, 2015).
However, when the coumarin compound is synthesized by the method, the used reaction systems are complex, the reaction time is long, the yield is low, and meanwhile, the environment is not friendly because metal is needed to participate in the reaction systems.
Disclosure of Invention
The invention aims to provide a method for synthesizing a 3-benzoyl coumarin compound, which can be used for synthesizing the 3-benzoyl coumarin compound by directly using the coumarin compound and an aldehyde compound as raw materials.
One aspect of the invention provides a synthetic method of a 3-benzoyl coumarin compound, which comprises the following steps:
adding coumarin compounds, aldehyde compounds and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at the temperature of 100-200 ℃ for 10-24 hours;
after the reaction is finished, extracting by using an organic solvent, and combining organic phases;
and after the organic phase is dried, carrying out chromatographic separation to obtain the 3-benzoyl coumarin compound.
The millimole ratio of the coumarin compound to the aldehyde compound to the di-tert-butyl peroxide is 1:1-2: 1-3.
The millimole ratio of the coumarin compound to the aldehyde compound to the di-tert-butyl peroxide is 1:2: 2.
The coumarin compound has a structure shown as a formula (A):wherein,
R1is selected from-H, -CH3、-NO2、-CH3Any one of O and-OH;
R2is selected from-H or-CH3。
The aldehyde compound has a structure shown as a formula (B):wherein,
R3is selected from-CH3Any one of O, -H, -Br and-Cl.
The chromatographic column used in the chromatographic separation is a silica gel column, and the used eluent is a mixed solvent of ethyl acetate and petroleum ether, wherein the volume ratio of the mixed solvent to the ethyl acetate to the petroleum ether is 1:3-2: 1.
The organic phase was dried over anhydrous sodium sulfate.
The organic solvent is selected from dichloromethane or ethyl acetate.
Another aspect of the present invention provides a 3-benzoyl coumarin compound synthesized by the method for synthesizing a 3-benzoyl coumarin compound according to any one of the above technical solutions, which has a structure represented by formula (C):
wherein R is1Is selected from-CH3、-NO2、-CH3Any one of O and-OH; r2Is selected from-H or-CH3；R3Is selected from-CH3Any one of O, -H, -Br and-Cl.
The structure of formula (C) specifically includes the following compounds:
compared with the prior art, the synthesis method provided by the invention can be used for synthesizing the 3-benzoyl coumarin compound by directly using the coumarin compound and the aldehyde compound as raw materials. The method is simple, mild in condition, high in yield of the synthesized product, and capable of reaching more than 80%, does not need metal participation in the method, is environment-friendly, and can provide a novel method for synthesizing the 3-benzoyl coumarin compound for technicians in the field.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of one aspect of the invention provides a synthetic method of a 3-benzoyl coumarin compound, which comprises the following steps:
s1: adding coumarin compound, aldehyde compound and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at 100-200 ℃ for 10-24 hours.
In the step, the 3-benzoyl coumarin compound is synthesized by using the coumarin compound, the aldehyde compound and the di-tert-butyl peroxide, in the step, the di-tert-butyl peroxide is subjected to homolysis under heating condition to generate tert-butoxy free radicals to initiate reaction, and in the step, metal is not required to participate. It is understood that the temperature and the reaction time set in the step can be selected by those skilled in the art according to actual reaction conditions, as long as sufficient and thorough reaction of the reaction raw materials is ensured.
S2: after the reaction is finished, extracting by using an organic solvent, and combining organic phases.
In this step, the reactant obtained in S1 is extracted with an organic solvent, and may be extracted several times to extract the obtained coumarin compound more completely.
S3: and after the organic phase is dried, carrying out chromatographic separation to obtain the 3-benzoyl coumarin compound.
In this step, the organic phase is dried to remove the water content and then chromatographed, eluting through a gradient to obtain the 3-benzoyl coumarin compound.
Compared with the prior art, the synthesis method provided by the invention can be used for synthesizing the 3-benzoyl coumarin compound by directly using the coumarin compound and the aldehyde compound as raw materials. The method is simple, mild in condition and high in yield of the synthesized product, does not need metal participation, is environment-friendly, and can provide a novel method for synthesizing the 3-benzoyl coumarin compound for technicians in the field.
In an embodiment of the invention, the millimole ratio of the coumarin compound, the aldehyde compound and the di-tert-butyl peroxide is 1:1-2: 1-3. In this embodiment, the amount of the three raw materials is set to 1:1-2:1-3, i.e. the millimolar ratio, wherein the di-tert-butyl peroxide can be added in excess relative to the other two raw materials, so as to ensure the completion of the reaction between the coumarin compound and the aldehyde compound; in a preferred embodiment, the millimole ratio of the coumarin compound, the aldehyde compound and the di-tert-butyl peroxide is 1:2:2, and under the proportion, the sufficient reaction of each reaction raw material can be ensured, and the addition amount of each raw material can be effectively controlled, so that the reaction cost can be reduced.
In one embodiment of the present invention, the coumarin compound has the structure of formula (a):wherein R is1Is selected from-H, -CH3、-NO2、-CH3Any one of O and-OH; r2Is selected from-H or-CH3. In this example, the coumarin-based compound used is specifically definedStructural formula, it is understood that the coumarin compound defined in this embodiment is a compound derived from coumarin, and the structure is relatively simple, but this embodiment does not exclude that the coumarin derivative with a relatively complex structure is used to prepare the 3-benzoyl coumarin compound finally obtained in this application.
In one embodiment of the present invention, the aldehyde compound has the structure of formula (B):wherein R is3Is selected from-CH3Any one of O, -H, -Br and-Cl. In this embodiment, specific structural formulas of the aldehyde compounds used are specifically defined, and it is understood that the aldehyde compounds defined in this embodiment are compounds derived from benzaldehyde, and the structures are relatively simple, but this embodiment does not exclude the preparation of the 3-benzoyl coumarin compounds finally obtained in this application from benzaldehyde derivatives having relatively complex structures.
In an embodiment of the present invention, the chromatographic column used in the chromatographic separation is a silica gel column, and the eluent used is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:3-2: 1. In this example, the fractions subsequently extracted from the organic phase were subjected to gradient elution using a silica gel column to isolate the desired synthetic product. In this embodiment, gradient elution is performed by using a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1:3 to 2:1, according to the principle of similar phase solubility and considering the polarity of the synthesized product, and within this range, the skilled person can adjust the gradient elution according to the actual situation.
In one embodiment of the invention, the organic phase is dried with anhydrous sodium sulfate. In this example, the water in the organic phase was removed using anhydrous sodium sulfate, and it is understood that other materials or methods familiar to those skilled in the art may be used to dry the organic phase.
In one embodiment of the present invention, the organic solvent is selected from dichloromethane or ethyl acetate. In this example, the organic solvent is limited to dichloromethane or ethyl acetate in consideration of the polarity of the desired synthesis product, and both are preferable as the organic solvent in this example from the viewpoint of extraction efficiency and cost, but it is to be understood that the alternative range of the organic solvent is not limited to the above-listed solvents, and other solvents having similar polarity may be suitably used for extraction of the desired synthesis product.
Another embodiment of the present invention provides a 3-benzoyl coumarin compound synthesized by the method for synthesizing a 3-benzoyl coumarin compound according to any one of the above embodiments, which has a structure represented by formula (C):
wherein R is1Is selected from-CH3、-NO2、-CH3Any one of O and-OH; r2Is selected from-H or-CH3；R3Is selected from-CH3Any one of O, -H, -Br and-Cl.
In one embodiment of the present invention, the structure of formula (C) specifically includes the following compounds:
in order to more clearly and specifically describe the synthesis method of the 3-benzoyl coumarin compound provided in the embodiments of the present invention, the following description will be made with reference to specific embodiments.
Example 1
Adding coumarin, benzaldehyde and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at 100 ℃ for 10 hours; after the reaction is finished, extracting by using ethyl acetate, and combining ethyl acetate phases; and after the ethyl acetate phase is dried, carrying out chromatographic separation to obtain a colorless crystal, namely 3-benzoyl-2H-chromen-2-one (1):
the above colorless crystal powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,CDCl3)δ:8.08(s,1H),7.90(d,7.4Hz,2H),7.85(td,J＝8.7Hz,J＝1.5Hz,1H),7.64(dd,J＝7.9Hz,J＝1.5Hz,1H),7.49(d,J＝7.9Hz,2H),7.38(t,J＝8.3Hz,1H),7.39(td,J＝7.9Hz,J＝0.7Hz,1H)；
13C NMR(100MHz,CDCl3)d:191.7,158.4,154.7,145.4,136.2,133.8,133.7,129.6,129.2,128.6,125.0,118.2,116.9；
after identification, the spectral data correspond to the structural formula, and the synthesized 3-benzoyl-2H-chromen-2-one is proved to have the yield of 85 percent.
Example 2
Adding coumarin, 4-hydroxybenzaldehyde and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at the temperature of 120 ℃ for 12 hours; after the reaction is finished, extracting by using ethyl acetate, and combining ethyl acetate phases; and (3) after the ethyl acetate phase is dried, carrying out chromatographic separation to obtain a white solid, namely 3- (4-methoxybenzoyl) -2H-chromen-2-one (2):
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,CDCl3)δ:8.02(s,1H),7.89(d,J＝8.7Hz,2H),7.68(td,J＝8.7Hz,J＝1.4Hz,1H),7.63(dd,J＝7.7Hz,J＝1.1Hz,1H),7.42(d,J＝8.1Hz,1H),7.35(t,J＝7.3Hz,1H),6.96(d,J＝8.9Hz,1H),3.89(s,3H)；
13C NMR(100MHz,CDCl3)d:190.5,164.6,158.9,154.6,144.8,133.1,132.2,129.2,129.0,127.6,124.8,118.2,116.9,113.9,55.9；
after identification, the spectral data correspond to the structural formula, and the synthesized 3- (4-methoxybenzoyl) -2H-chromen-2-one is proved to be 81 percent.
Example 3
Respectively adding 6-methylcoumarin, 4-methoxybenzaldehyde and di-tert-butyl peroxide into a reaction bottle, and reacting at 140 ℃ for 14 hours; after the reaction is finished, extracting by using dichloromethane, and combining dichloromethane phases; after drying the dichloromethane phase, chromatography gave a white solid, i.e. 3- (4-methoxybenzoyl) -6-methyl-2H-chromen-2-one (3):
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1HNMR(400MHz,CDCl3):δ：7.98(s,1H),7.88(d,J＝8.4Hz,2H),7.46–7.42(m,1H),7.38(s,1H),7.32(d,J＝8.4Hz,1H),6.98(d,J＝8.0Hz,2H),3.90(s,3H),2.45(s,3H)；
13C NMR(100MHz,CDCl3):δ＝190.3,164.4,158.9,152.8,144.8,134.5,134.3,132.2,129.2,128.5,127.3,118.2,116.8,113.7,55.8,20.9；
after identification, the spectral data correspond to the structural formula, and the synthesized 3- (4-methoxybenzoyl) -6-methyl-2H-chromen-2-one is proved to have the yield of 93%.
Example 4
Respectively adding 6-nitrocoumarin, 4-methoxybenzaldehyde and di-tert-butyl peroxide into a reaction bottle, and reacting at 160 ℃ for 16 hours; after the reaction is finished, extracting by using dichloromethane, and combining dichloromethane phases; after drying the dichloromethane phase, chromatography gave a pale yellow solid, i.e. 3- (4-methoxybenzoyl) -6-nitro-2H-chromen-2-one (4):
the light yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,DMSO)δ:8.84(d,J＝2.6Hz,1H),8.53(dd,J＝9.1Hz,J＝2.8Hz,1H),8.47(s,1H),7.99(dd,J＝7.1Hz,J＝2.2Hz,2H),7.75(d,J＝9.1Hz,1H),7.06(dd,J＝7.2Hz,J＝2.1Hz,2H),3.86(s,3H)；
13C NMR(100MHz,DMSO)d:189.9,164.7,158.1,157.9,144.1,143.7,132.5,129.0,128.5,128.0,125.6,119.2,118.1,114.7,56.1；
after identification, the spectral data correspond to the structural formula, and the synthesized 3- (4-methoxybenzoyl) -6-nitro-2H-chromen-2-one is proved to have the yield of 95%.
Example 5
Respectively adding 7-hydroxycoumarin, 4-methoxybenzaldehyde and di-tert-butyl peroxide into a reaction bottle, and reacting at the temperature of 180 ℃ for 18 hours; after the reaction is finished, extracting by using dichloromethane, and combining dichloromethane phases; after drying the dichloromethane phase, chromatography gave a pale yellow solid, i.e. 7-hydroxy-3- (4-methoxybenzoyl) -2H-chromen-2-one (5):
the light yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,DMSO)δ:10.96(s,1H),8.24(s,1H),7.86(dd,J＝6.8Hz,J＝2.0Hz,2H),7.69(d,J＝8.5Hz,1H),7.06(dd,J＝6.8Hz,J＝2.0Hz,2H),6.89(dd,J＝8.5Hz,J＝2.2Hz,1H),6.82(d,J＝2.2Hz,1H),3.83(s,3H)；
13C NMR(100MHz,DMSO)d:190.8,164.2,163.4,158.7,156.8,146.4,132.2,131.6,129.6,122.1,114.1,114.0,111.1,102.6,56.1；
after identification, the spectral data correspond to the structural formula, and the synthesized 7-hydroxy-3- (4-methoxybenzoyl) -2H-chromen-2-one is proved to have the yield of 80%.
Example 6
Respectively adding 6-methoxycoumarin, 4-bromobenzaldehyde and di-tert-butyl peroxide into a reaction bottle, and reacting for 20 hours at the temperature of 200 ℃; after the reaction is finished, extracting by using ethyl acetate, and combining ethyl acetate phases; after the ethyl acetate phase was dried, chromatography gave a pale yellow solid, i.e., 3- (4-bromobenzoyl) -6-methoxy-2H-chromen-2-one (6):
the light yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,CDCl3):δ：8.11(s,1H),7.78(d,J＝8.6Hz,2H),7.66(d,J＝8.3Hz,2H),7.36(d,J＝9.2Hz,1H),7.24(dd,J＝9.2,2.8Hz,1H),7.04(d,J＝2.8Hz,1H),3.89(s,1H)；
13C NMR(100MHz,CDCl3):δ：190.8,158.4,156.2,149.6,145.8,135.2,131.9,131.2,129.0,126.8,122.2,118.4,118.1,110.6,55.7；
after identification, the spectral data correspond to the structural formula, and the synthesized 3- (4-bromobenzoyl) -6-methoxy-2H-chromen-2-one is proved to have the yield of 89%.
Example 7
Respectively adding 7-hydroxy-4-methylcoumarin, benzaldehyde and di-tert-butyl peroxide into a reaction bottle, and reacting at 130 ℃ for 22 hours; after the reaction is finished, extracting by using ethyl acetate, and combining ethyl acetate phases; after the ethyl acetate phase was dried, chromatographic separation was carried out to obtain a white solid, i.e. 3-benzoyl-7-hydroxy-4-methyl-chromen-2-one (7):
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1HNMR (400MHz, acetone-d 6): delta: 8.00-7.98(m,2H),7.78-7.76(dd, J ═ 8.8,1.2Hz,1H),7.72-7.66(td, J ═ 8.0,1.2Hz,1H),7.57-7.52(t, J ═ 7.6Hz,2H),6.96-6.93(dd, J ═ 8.8,2.4Hz,1H),6.84-6.82(d, J ═ 2.4Hz,1H),3.00(s,1H),2.33(s, 3H);
13c NMR (100MHz, acetone-d 6): delta: 194.2,162.4,159.3,156.0,151.4,137.9,134.7,130.1,129.8,128.4,123.3,114.2,113.1,103.1, 15.8;
after identification, the spectral data correspond to the structural formula, which proves that the synthesized 3-benzoyl-7-hydroxy-4-methyl-chromen-2-one has the yield of 85 percent.
Example 8
Adding coumarin, 2-chlorobenzaldehyde and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at the temperature of 150 ℃ for 24 hours; after the reaction is finished, extracting by using dichloromethane, and combining dichloromethane phases; after drying the dichloromethane phase, chromatography gave a pale yellow solid, i.e. 3- (2-chlorobenzoyl) -2H-chromen-2-one (8):
the light yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(400MHz,CDCl3)δ：8.39(s,1H),7.68–7.64(m,2H),7.57(d,J＝7.5Hz,1H),7.45(d,J＝6.2Hz,1H),7.47–7.32(m,4H)；
13C NMR(100MHz,CDCl3)δ：191.4,158.2,155.3,147.2,138.2,134.5,132.1,131.6,129.7,129.6,127.3,126.2,124.9,118.5,116.9；
after identification, the spectral data correspond to the structural formula, and the synthesized 3- (2-chlorobenzoyl) -2H-chromen-2-one is proved to be 95 percent.
Claims (6)
1. A synthetic method of a 3-benzoyl coumarin compound is characterized by comprising the following steps:
adding coumarin compounds, aldehyde compounds and di-tert-butyl peroxide into a reaction bottle respectively, and reacting at the temperature of 100-200 ℃ for 10-24 hours;
after the reaction is finished, extracting by using an organic solvent, and combining organic phases;
after the organic phase is dried, carrying out chromatographic separation to obtain a 3-benzoyl coumarin compound;
the coumarin compound has a structure shown as a formula (A):wherein,
R1is selected from-H, -CH3、-NO2、-CH3Any one of O and-OH; r2Is selected from-H or-CH3；
The aldehyde compound has a structure shown as a formula (B):wherein,
R3is selected from-CH3Any one of O, -H, -Br and-Cl;
the obtained 3-benzoyl coumarin compound has a structure shown in a formula (C):
wherein R is1Is selected from-CH3、-NO2、-CH3Any one of O and-OH; r2Is selected from-H or-CH3；R3Is selected from-CH3Any one of O, -H, -Br and-Cl.
2. The synthesis method according to claim 1, wherein the millimole ratio of the coumarin compound, the aldehyde compound and the di-tert-butyl peroxide is 1:1-2: 1-3.
3. The synthesis method according to claim 2, wherein the millimole ratio of the coumarin compound, the aldehyde compound and the di-tert-butyl peroxide is 1:2: 2.
4. The synthesis method according to claim 1, wherein the chromatographic column used in the chromatographic separation is a silica gel column, and the eluent used is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:3-2: 1.
5. The synthesis process according to claim 1, characterized in that the organic phase is dried with anhydrous sodium sulfate.
6. The method of claim 1, wherein the organic solvent is selected from dichloromethane or ethyl acetate.
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