CN116789626A - Preparation method of aromatic chroman-4-one compound containing amide group - Google Patents
Preparation method of aromatic chroman-4-one compound containing amide group Download PDFInfo
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- 125000003368 amide group Chemical group 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- -1 aromatic chroman-4-one compound Chemical class 0.000 title description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 69
- 125000003118 aryl group Chemical group 0.000 claims abstract description 31
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 24
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000012298 atmosphere Substances 0.000 claims abstract description 22
- 125000005336 allyloxy group Chemical group 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- 235000006408 oxalic acid Nutrition 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 123
- 239000012043 crude product Substances 0.000 claims description 36
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 239000007858 starting material Substances 0.000 claims description 23
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 239000003208 petroleum Substances 0.000 claims description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 19
- 239000012046 mixed solvent Substances 0.000 claims description 19
- 239000012074 organic phase Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical group C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 125000002723 alicyclic group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical group C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Chemical group C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 230000002209 hydrophobic effect Effects 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000003003 spiro group Chemical group 0.000 claims description 2
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical class NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000007306 functionalization reaction Methods 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 description 34
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical class C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 21
- 239000007810 chemical reaction solvent Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- 239000012265 solid product Substances 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 15
- PQJZHMCWDKOPQG-UHFFFAOYSA-N 2-anilino-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1=CC=CC=C1 PQJZHMCWDKOPQG-UHFFFAOYSA-N 0.000 description 11
- BXCJDECTRRMSCV-UHFFFAOYSA-N 2-prop-2-enoxybenzaldehyde Chemical compound C=CCOC1=CC=CC=C1C=O BXCJDECTRRMSCV-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 150000001555 benzenes Chemical group 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- COJGVNSLWDCUHP-UHFFFAOYSA-N 2-(4-methylanilino)-2-oxoacetic acid Chemical compound CC1=CC=C(NC(=O)C(O)=O)C=C1 COJGVNSLWDCUHP-UHFFFAOYSA-N 0.000 description 1
- XYYFQOQNHIZVBG-UHFFFAOYSA-N 2-(cyclopentylamino)-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1CCCC1 XYYFQOQNHIZVBG-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- LWQBRUUHCKGAEN-UHFFFAOYSA-N 2-prop-2-enoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(OCC=C)=CC=C21 LWQBRUUHCKGAEN-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical group NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- OKKOLCSGONNEPL-UHFFFAOYSA-N 4-methoxy-2-prop-2-enoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OCC=C)=C1 OKKOLCSGONNEPL-UHFFFAOYSA-N 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000002192 fatty aldehydes Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000005499 phosphonyl group Chemical group 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Pyrane Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of an amido-containing aromatic ring-dihydropyran-4-ketone compound, which comprises the step of reacting a raw material solution containing 2- (allyloxy) -aromatic aldehyde derivative shown in a formula 1, N-substituted oxalic acid shown in a formula 2, ammonium persulfate and DMSO in an oxygen-free atmosphere at a temperature of 40-100 ℃ to prepare an amido-containing aromatic ring-dihydropyran-4-ketone product shown in a formula 3. The invention adopts a metal-free catalytic means to act the raw material of the 2- (allyloxy) -aromatic aldehyde derivative with N-substituted oxalic acid, and can obtain a target product by simply adding ammonium persulfate, thereby solving the problems of complicated synthesis steps, poor substrate applicability, poor yield, unfriendly method and the like in the prior synthesis technology, and providing a novel method for functionalization of the aromatic ring-combined dihydropyran-4-ketone compound.
Description
Technical field:
the invention relates to the field of organic synthesis, in particular to an aromatic ring dihydro pyran-4-ketone compound containing amide groups and a preparation method thereof.
The background technology is as follows:
aromatic chromans such as the common chroman-4-ones are an important class of oxygen-containing heterocyclic compounds, are basic building blocks for many drugs and natural products, and have biological activities such as anti-cancer, anti-inflammatory, anti-platelet aggregation, anti-HIV, and the like. In recent years, the literature reports that the synthesis of chroman-4-ones mainly comprises the following preparation methods: (1) Condensation reaction of o-hydroxyacetophenone and fatty aldehyde, which needs to be carried out at high temperature and has a plurality of byproducts; (2) Allyl salicylaldehyde is used as a raw material, and is prepared through intramolecular cyclization reaction under the catalysis of N-heterocyclic carbene, and the reaction requires expensive carbene catalyst, so that the reaction temperature is high; (3) The chromone compound and various nucleophilic reagents are prepared through Michael addition reaction, and the reaction has the defects that the chromone compound needs to be prepared through multi-step reaction, and the step economy is poor; (4) The allylsalicylaldehyde and the free radical are subjected to serial cyclization to synthesize the corresponding 3-substituted chroman-4-ketone compound.
Among them, the cascade cyclization reaction of allyl aromatic aldehyde and free radical has made great progress in recent years, various free radicals including alkyl, trifluoromethyl, sulfonyl, acyl, difluoro aryl, phosphonyl etc. initiated cascade cyclization reaction of allyl salicylaldehyde has all been reported in the relevant literature, and a novel method is provided for functionalization of chroman-4-one compounds. However, no report has been made on the synthesis of chroman-4-ones containing amide groups, and by introducing amide groups into chroman-4-ones, improvement and enhancement of the biological activity of such compounds are expected, providing an important compound source and screening platform for drug molecular screening.
Disclosure of Invention
Aiming at the problem of the lack of synthesis technology of an aromatic ring dihydro-pyran-4-one product containing an amide group, the invention aims to provide a preparation method of the aromatic ring dihydro-pyran-4-one compound containing the amide group, which aims to successfully prepare the aromatic ring dihydro-pyran-4-one compound containing the amide group and obtain a considerable yield.
The preparation method of the amido-containing aromatic ring dihydropyran-4-ketone compound comprises the steps of reacting a raw material solution containing 2- (allyloxy) -aromatic aldehyde derivative shown in a formula 1, N-substituted oxalic acid shown in a formula 2, ammonium persulfate and DMSO in an oxygen-free atmosphere at a temperature of 40-100 ℃ to prepare an amido-containing aromatic ring dihydropyran-4-ketone product shown in a formula 3;
ar is an aromatic ring or a substituted aromatic ring with a substituent;
said R is 1 Is hydrogen, C1-C6 alkyl, trifluoromethyl, aromatic ring, substituted aromatic ring or alicyclic ring with substituent;
the aromatic ring is five-membered aromatic heterocycle, six-membered aromatic heterocycle, and condensed ring formed by combining two or more aromatic rings in five-membered aromatic heterocycle, six-membered aromatic heterocycle;
the substituent of the substituted aromatic ring being C 1 ～C 6 Alkyl, C of (2) 1 ～C 6 At least one of an alkoxy group, a trifluoromethyl group, an ester group, and a halogen.
The industry has not synthesized amide-containing aromatic chroman-4-ones. To fill this gap, the present inventors tried to conduct the reaction using the starting materials of formula 1 and formula 2, however, the earlier invention was developed, and the reaction progress of formula 1 and formula 2 was greatly affected due to the interference of the ortho-amide group of formula 2, resulting in difficulty in the reaction. Aiming at the problem that the compounds in the formula 1 and the formula 2 are difficult to react, the invention innovatively discovers that the reactions in the formula 1 and the formula 2 can be unexpectedly and successfully realized under the cooperative control of the DMSO and the ammonium persulfate, thereby being beneficial to the synthesis of the aromatic ring chroman-4-ketone compounds for the first time in the industry and being capable of effectively improving the reaction efficiency and the effect.
In the present invention, ar is a ring having aromatic character, which is known in the industry. For example, ar is a benzene ring or a substituted benzene ring. The substituent of the substituted benzene ring is C 1 ～C 6 At least one of an alkyl group, an alkoxy group, a trifluoromethyl group, an ester group, and a halogen.
In the invention, R is 1 Is benzene ring, substituted benzene ring, cyclopentane, cyclohexane, spiro ring or bridged ring. The alicyclic may be, for example, adamantyl. The substituent of the substituted benzene ringIs C 1 ～C 6 At least one of an alkyl group, an alkoxy group, a trifluoromethyl group, an ester group, and a halogen.
Preferably, the molar ratio of the 2- (allyloxy) -aromatic aldehyde raw material and the N-substituted oxalic acid in the formula 1 is 1:1 to 10; further preferably 1:1.5 to 4; more preferably 1:2 to 4.
In the invention, the dosage of ammonium persulfate can be adjusted according to the need, for example, the mol ratio of the raw material of the 2- (allyloxy) -aromatic aldehyde derivative of the formula 1 to the ammonium persulfate is 1:1-10; further preferably 1:1.5 to 4; more preferably 1:2 to 4.
In the present invention, the concentration of the 2- (allyloxy) -aromatic aldehyde starting material of formula 1 in the starting material solution is not particularly limited, and may be, for example, 0.1 to 0.5moL/L.
In the invention, the anaerobic atmosphere is at least one of nitrogen and inert gas.
In the present invention, the reaction temperature is 50 to 100℃and preferably 60 to 70 ℃.
In the present invention, the reaction time can be confirmed by the existing central control means, for example, the reaction time is 5 to 24 hours.
In the invention, after reaction, water and an organic solvent are added for extraction, anhydrous sodium sulfate is added into an organic phase for drying, filtration and concentration are carried out to obtain a crude product, and a target product is obtained through column chromatography separation;
wherein the organic solvent is a hydrophobic solvent, preferably ethyl acetate or dichloromethane;
preferably, the purifying solvent in the column chromatography stage is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio is 1-10:1.
The invention relates to a preparation method of a chroman-4-ketone compound containing amide preferably, which comprises the steps of adding a raw material solution containing a raw material of 2- (allyloxy) -benzaldehyde derivative of a formula 1-A, N-substituted oxalic acid of the formula 2-A, ammonium persulfate and DMSO in N 2 Protecting, and reacting under the heating condition of 60-70 ℃ to obtain the chroman-4-one product containing amide group in the formula 3-A;
said R is a H, C of a shape of H, C 1 ～C 6 Alkyl, alkoxy, trifluoromethyl, ester, halogen, etc. Said R is b Phenyl substituted by at least one substituent selected from phenyl, cycloalkyl, C1-C5 alkyl, C1-C5 alkoxy, halogen atom, trifluoromethyl and ester group. The molar ratio of the 2- (allyloxy) -aromatic aldehyde raw material and the N-substituted oxalic acid in the formula 1 is 1:1.5-4. The molar ratio of the 2- (allyloxy) -aromatic aldehyde raw material of the formula 1 to the oxidant is 1:1.5-4. In the reaction starting solution, the molar volume ratio of the 2- (allyloxy) -aromatic aldehyde raw material of the formula 1 to DMSO is 0.1-0.5 moL/L.
Advantageous effects
In order to fill the blank of preparing the aromatic ring-containing dihydropyran-4-ketone compound and solve the problem of difficult preparation in the preparation process of the aromatic ring-containing dihydropyran-4-ketone compound, the invention innovatively adopts the formula 1 and the formula 2 as substrates and combines the combined control of DMSO and ammonium persulfate, so that the synergy can be realized, the problem of difficult reaction of the formula 1 and the formula 2 is solved, the successful preparation of the aromatic ring-containing dihydropyran-4-ketone compound without noble metal catalysis in industry is facilitated, and the improvement of the reaction conversion rate and the reaction efficiency is facilitated.
Detailed Description
Example 1
To a round bottom flask was successively added a 2- (allyloxy) -benzaldehyde starting material (1 a:0.3 mmol), N-substituted oxalic acid (2 a:0.9 mmol), an oxidant (peroxosulfate or selective oxidant, 4 equiv.) and a reaction solvent (2.0 mL; see Table 1), and the reaction mixture was reacted in N 2 The reaction was monitored by thin layer chromatography under atmosphere protection, stirring for 12h at a temperature range of 50-80℃as shown in Table 1.
After the completion of the reaction, water (10 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (10 ml×3), and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product;
the crude product is separated and purified by silica gel column chromatography by using a mixed solvent (the volume ratio of the ethyl acetate to the petroleum ether is 1:3) composed of the ethyl acetate and the petroleum ether, and is filtered and dried to obtain the chroman-4-one solid product 3aa containing amido. The yields of the products are shown in Table 1.
Note that: in Table 1, a is the isolation yield (isolated yields);
the reference number 16b is a number which is different from the reference number 13 only in that the amount of ammonium persulfate is 3 equiv;
17c is different from 13 in that the amount of 2a is 0.6mmol and 2equiv;
the reference number 18d is a number which differs from the reference number 13 only in that it is carried out under an open air atmosphere.
Example 2
The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; separating the crude product with mixed solvent of ethyl acetate and petroleum ether by silica gel column chromatography to obtain chroman-4-ketone containing amidoSolid product, yellow solid; 60.8mg (isolated yield 81%); 1 H NMR(400MHz,Chloroform-d)δ8.13(s,1H),7.89(d,J＝7.8Hz,1H),7.60-7.44(m,3H),7.31(t,J＝7.5Hz,2H),7.10(t,J＝7.3Hz,1H),7.06-6.93(m,2H),4.68(dd,J＝11.2,5.3Hz,1H),4.31(t,J＝11.9Hz,1H),3.46-3.37(m,1H),2.92(dd,J＝15.0,5.9Hz,1H),2.49(dd,J＝15.0,5.9Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ194.3,168.6,161.9,137.7,136.4,129.0,127.3,124.3,121.5,120.3,119.8,117.9,70.5,42.9,33.7.
example 3
To a round bottom flask was added in sequence 2- (allyloxy) -3-methylbenzaldehyde starting material (0.05284 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Stirring at 60deg.C for 12 hr under atmosphere protection, adding water (10 mL) to the reaction mixture, extracting with ethyl acetate (10 mL×3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain crude product; performing silica gel column chromatography on the crude product by using a mixed solvent consisting of ethyl acetate and petroleum ether to obtain a chroman-4-one solid product containing amido, and obtaining an off-white solid; 73.54mg (isolated yield 83%). 1 H NMR(400MHz,Chloroform-d)δ8.22(s,1H),7.74(d,J＝7.8Hz,1H),7.52(d,J＝7.9Hz,2H),7.38-7.27(m,3H),7.09(t,J＝7.3Hz,1H),6.92(t,J＝7.6Hz,1H),4.71(dd,J＝11.2,5.3Hz,1H),4.28(t,J＝11.9Hz,1H),3.42-3.35(m,1H),2.91(dd,J＝15.0,6.0Hz,1H),2.48(dd,J＝15.0,5.9Hz,1H),2.23(s,3H)； 13 C NMR(100MHz,Chloroform-d)δ194.7,168.7,160.2,137.8,137.2,128.9,127.3,124.9,124.3,120.9,119.9,119.8,70.3,42.8,33.8,15.5.
Example 4
To a round bottom flask was added in sequence 2- (allyloxy) -5-methylbenzaldehyde starting material (0.0528 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and (3) separating the crude product by silica gel column chromatography by using a mixed solvent consisting of ethyl acetate and petroleum ether to obtain a chroman-4-one solid product containing amido. An off-white solid; 67.33mg (isolated yield 76%); 1 H NMR(400MHz,Chloroform-d)δ8.13(s,1H),7.68(s,1H),7.52(d,J＝7.9Hz,2H),7.31(t,J＝7.1Hz,3H),7.10(t,J＝7.3Hz,1H),6.88(d,J＝8.4Hz,1H),4.65(dd,J＝11.2,5.3Hz,1H),4.27(t,J＝11.8Hz,1H),3.43–3.34(m,1H),2.90(dd,J＝15.0,6.0Hz,1H),2.49(dd,J＝15.0,5.9Hz,1H),2.30(s,3H)； 13 C NMR(101MHz,Chloroform-d)δ194.6,168.6,160.0,137.8,137.5,131.0,129.0,126.9,124.3,119.8,119.9,117.7,70.5,43.0,33.9,20.4.
example 5
To a round bottom flask was added in sequence 2- (allyloxy) -4-methoxybenzaldehyde starting material (0.0577 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and (3) performing silica gel column chromatography separation on the crude product by using a mixed solvent lotion consisting of ethyl acetate and petroleum ether to obtain a chroman-4-one solid product containing amido. Yellow solid; 67.20mg (isolated collection)Rate 72%); 1 H NMR(400MHz,Chloroform-d)δ8.36(s,1H),7.82(d,J＝8.8Hz,1H),7.53(d,J＝7.9Hz,2H),7.30(t,J＝7.7Hz,2H),7.09(t,J＝7.3Hz,1H),6.59(d,J＝8.8Hz,1H),6.41(s,1H),4.65(dd,J＝11.1,5.3Hz,1H),4.28(t,J＝11.8Hz,1H),3.83(s,3H),3.38–3.29(m,1H),2.91(dd,J＝15.0,6.1Hz,1H),2.46(dd,J＝15.0,5.8Hz,1H)； 13 CNMR(100MHz,Chloroform-d)δ192.9,168.8,166.4,164.0,137.8,129.1,128.9,124.2,119.8,114.1,110.4,100.6,70.8,55.7,42.5,34.0.
example 6
To a round bottom flask was added in sequence 2- (allyloxy) -3-tert-butylbenzaldehyde starting material (0.0655 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and (3) performing column chromatography separation on the crude product by using a mixed solvent lotion (the volume ratio of ethyl acetate to petroleum ether is 3:1) composed of ethyl acetate and petroleum ether to obtain a chroman-4-one solid product containing amido. An off-white solid; 70.8mg (isolation yield 70%); 1 H NMR(400MHz,Chloroform-d)δ8.25(s,1H),7.81(d,J＝7.8Hz,1H),7.51(dd,J＝13.8,7.8Hz,3H),7.31(t,J＝7.6Hz,2H),7.09(t,J＝7.3Hz,1H),6.96(t,J＝7.7Hz,1H),4.74(dd,J＝11.1,5.3Hz,1H),4.28(t,J＝11.9Hz,1H),3.45–3.36(m,1H),2.93(dd,J＝15.0,5.9Hz,1H),2.50(dd,J＝15.0,5.9Hz,1H),1.38(s,9H)； 13 C NMR(100MHz,Chloroform-d)δ195.1,168.8,161.1,139.1,137.8,133.4,128.9,125.4,124.3,121.1,121.0,119.8,70.0,42.8,34.9,33.9,29.5.
example 7
To a round bottom flask was added in sequence 2- (allyloxy) -4-fluorobenzaldehyde starting material (0.0541 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and (3) performing column chromatography separation on the crude product by using a mixed solvent lotion (the volume ratio of ethyl acetate to petroleum ether is 3:1) composed of ethyl acetate and petroleum ether to obtain a chroman-4-one solid product containing amido. An off-white solid; 68.20mg (isolated yield 76%); 1 H NMR(400MHz,Chloroform-d)δ8.03(s,1H),7.96–7.84(m,1H),7.51(d,J＝7.9Hz,2H),7.31(t,J＝7.7Hz,2H),7.10(t,J＝7.3Hz,1H),6.75(t,J＝8.3Hz,1H),6.67(d,J＝9.7Hz,1H),4.70(dd,J＝11.2,5.4Hz,1H),4.33(t,J＝11.9Hz,1H),3.47–3.35(m,1H),2.91(dd,J＝15.1,5.8Hz,1H),2.49(dd,J＝15.1,6.1Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ192.7,168.4,167.6(d,J C-F ＝256.0Hz),163.6(d,J C-F ＝14.0Hz),137.7,130.0(d,J C-F ＝12.0Hz),129.0,124.4,119.8,117.3(d,J C-F ＝23.0Hz),110.1(d,J C-F ＝23.0Hz),104.7(d,J C-F ＝24.0Hz),70.9,42.6,33.5； 19 F NMR(376MHz,Chloroform-d)δ-99.6.
example 8
To a round bottom flask was added in sequence 2- (allyloxy) -3-chlorobenzaldehyde starting material (0.0541 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring at 60 ℃ for 1After completion of the reaction for 2 hours, water (10 mL) was added to the reaction mixture, and extraction was performed with ethyl acetate (10 ml×3), and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product; and separating the crude product by using a mixed solvent of ethyl acetate and petroleum ether through silica gel column chromatography to obtain a chroman-4-one solid product containing amido. Yellow solid; 72.0mg (isolation yield 78%); melting point 274-275 ℃. 1 H NMR(400MHz,Chloroform-d)δ7.97(s,1H),7.80(d,J＝7.8Hz,1H),7.57(d,J＝7.7Hz,1H),7.50(d,J＝7.8Hz,2H),7.30(t,J＝7.6Hz,2H),7.10(t,J＝7.3Hz,1H),6.97(t,J＝7.8Hz,1H),4.80(dd,J＝11.2,5.3Hz,1H),4.40(t,J＝11.9Hz,1H),3.49–3.38(m,1H),2.89(dd,J＝15.2,5.6Hz,1H),2.52(dd,J＝15.3,6.2Hz,1H)； 13 C NMR(101MHz,Chloroform-d)δ193.2,168.2,157.3,137.6,136.3,129.0,125.9,124.4,122.7,121.6,121.6,119.9,70.9,42.6,33.4.
Example 9
To a round bottom flask was added in sequence 2- (allyloxy) -6-chlorobenzaldehyde starting material (0.0541 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.205 g,0.9 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. Pale yellow solid; 72.78mg (isolation yield 77%). 1 H NMR(400MHz,Chloroform-d)δ8.06(s,1H),7.51(d,J＝8.0Hz,2H),7.36–7.27(m,3H),7.09(t,J＝7.3Hz,1H),7.03(d,J＝7.8Hz,1H),6.90(d,J＝8.4Hz,1H),4.67(dd,J＝11.2,5.4Hz,1H),4.30(t,J＝12.0Hz,1H),3.49–3.40(m,1H),2.91(dd,J＝15.1,5.9Hz,1H),2.48(dd,J＝15.1,6.1Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ192.2,168.5,163.2,137.7,135.0,134.4,128.9,124.7,124.4,119.9,117.7,117.0,70.0,43.5,33.4.
Example 10
To a round bottom flask was added in sequence 2- (allyloxy) -4-bromobenzaldehyde starting material (0.0723 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. A pale white solid; 88.61mg (isolated yield 82%). 1 H NMR(400MHz,Chloroform-d)δ7.98(s,1H),7.73(d,J＝8.4Hz,1H),7.50(d,J＝7.8Hz,2H),7.31(t,J＝7.6Hz,2H),7.22–7.06(m,3H),4.68(dd,J＝11.1,5.4Hz,1H),4.31(t,J＝11.9Hz,1H),3.44–3.36(m,1H),2.90(dd,J＝15.2,5.6Hz,1H),2.48(dd,J＝15.2,6.1Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ193.2,168.3,162.0,137.6,130.8,129.0,128.5,125.2,124.5,121.1,119.8,119.3,70.7,42.7,33.4.
Example 11
To a round bottom flask was added successively methyl 2- (allyloxy) -5-formate benzaldehyde starting material (0.0661 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring at 60 ℃ for 12h, and after the reaction is completed, turning toWater (10 mL) was added to the reaction mixture, extraction was performed with ethyl acetate (10 mL. Times.3), and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to give a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. White solid; 82.46mg (isolated yield 81%). 1 H NMR(400MHz,Chloroform-d)δ8.57(s,1H),8.14(d,J＝8.7Hz,1H),8.05(s,1H),7.51(d,J＝7.9Hz,2H),7.30(t,J＝7.7Hz,2H),7.10(t,J＝7.4Hz,1H),7.02(d,J＝8.7Hz,1H),4.76(dd,J＝11.3,5.5Hz,1H),4.36(t,J＝12.0Hz,1H),3.90(s,3H),3.49–3.40(m,1H),2.95(dd,J＝15.3,5.5Hz,1H),2.51(dd,J＝15.3,6.4Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ193.1,168.3,165.9,164.9,137.6,136.9,129.8,129.0,124.4,123.7,119.8,118.3,70.6,52.2,42.7,33.3.
Example 12
To a round bottom flask was added in sequence 2- (allyloxy) -1-naphthaldehyde starting material (0.0637 g,0.3 mmol), 2-oxo-2-anilino acetic acid (0.1485 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. Pale yellow solid; 50.70mg (isolated yield 51%). 1 H NMR(400MHz,Chloroform-d)δ9.42(d,J＝8.7Hz,1H),8.21(s,1H),7.94(d,J＝9.0Hz,1H),7.76(d,J＝8.0Hz,1H),7.64(t,J＝7.7Hz,1H),7.55(d,J＝7.9Hz,2H),7.44(t,J＝7.5Hz,1H),7.32(t,J＝7.5Hz,2H),7.10(d,J＝8.8Hz,2H),4.76(dd,J＝11.1,5.4Hz,1H),4.43(t,J＝11.8Hz,1H),3.54–3.45(m,1H),2.95(dd,J＝14.9,6.2Hz,1H),2.55(dd,J＝14.8,5.6Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ195.1,168.9,164.1,138.0,137.8,131.5,129.8,129.2,129.0,128.5,125.6,125.0,124.3,119.8,118.6,111.9,70.4,43.4,34.2.
Example 13
To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 2-oxo-2- (p-toluidino) acetic acid (0.1613 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. An off-white solid; 69.11mg (isolated yield 78%). 1 H NMR(400MHz,DMSO-d 6 )δ12.00(s,1H),7.27(dd,J＝10.8,2.4Hz,1H),7.20-7.10(m,1H),7.02(td,J＝8.6,2.5Hz,1H),3.48(s,3H)； 13 C NMR(100MHz,DMSO-d 6 )δ158.6(d,J C-F ＝238.4Hz),155.7,153.5,128.9(d,J C-F ＝11.1Hz),122.7,116.9(d,J C-F ＝10.1Hz),110.5(d,J C-F ＝24.2Hz),103.0(d,J C-F ＝28.3Hz),30.4； 19 F NMR(376MHz,DMSO-d 6 )δ-118.6.
Example 14
To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 2-oxo-2- [ (4 fluorophenyl) amine group]Acetic acid (0.1648 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL)) The reaction mixture is reacted in N 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent of ethyl acetate and petroleum ether through silica gel column chromatography to obtain a chroman-4-ketone solid product containing amido. Yellow solid; 70.04mg (isolated yield 78%). 1 H NMR(400MHz,Chloroform-d)δ8.14(s,1H),7.89(d,J＝7.8Hz,1H),7.61-7.38(m,3H),7.14-6.89(m,4H),4.67(dd,J＝11.2,5.4Hz,1H),4.31(t,J＝11.9Hz,1H),3.46–3.35(m,1H),2.89(dd,J＝15.0,6.2Hz,1H),2.49(dd,J＝15.0,5.6Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ194.4,168.6,161.9,159.3(d,J C-F ＝243.0Hz),136.5,133.7(d,J C-F ＝3.0Hz),127.4,121.7,121.6,120.3,118.0,115.6(d,J C-F ＝22.0Hz),70.5,43.0,33.7； 19 F NMR(376MHz,Chloroform-d)δ-117.9.
Example 15
To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 2-oxo-2- [ (4-trifluoromethylphenyl) amine group]Acetic acid (0.2098 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent of ethyl acetate and petroleum ether through silica gel column chromatography to obtain a chroman-4-one solid product containing amido. Yellow solid; 86.98mg (isolated yield 83%). 1 H NMR(400MHz,Chloroform-d)δ8.50(s,1H),7.90(d,J＝7.9Hz,1H),7.65(d,J＝8.3Hz,2H),7.53-7.45(m,3H),7.09-6.95(m,2H),4.67(dd,J＝11.2,5.5Hz,1H),4.32(t,J＝12.0Hz,1H),3.49-3.37(m,1H),2.91(dd,J＝15.0,6.5Hz,1H),2.52(dd,J＝15.0,5.2Hz,1H)； 13 C NMR(100MHz,Chloroform-d)δ194.6,168.9,161.9,140.8,136.7,127.4,126.2(q,J C-F ＝4.0Hz),125.8,124.0(q,J C-F ＝270.0Hz),121.7,120.2,119.3,118.0,70.4,42.9,34.0； 19 F NMR(376MHz,Chloroform-d)δ-62.1.
Example 16
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To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 5-cyclopentylamino-2-oxoacetic acid (0.1415 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent of ethyl acetate and petroleum ether through silica gel column chromatography to obtain a chroman-4-one solid product containing amido. Yellow solid; 67.24mg (isolated yield 82%). 1 H NMR(400MHz,Chloroform-d)δ7.87(d,J＝7.8Hz,1H),7.48(t,J＝7.8Hz,1H),7.11-6.87(m,2H),5.93(s,1H),4.64(dd,J＝11.3,5.3Hz,1H),4.26(t,J＝11.7Hz,1H),4.18(q,J＝6.9Hz,1H),3.36-3.26(m,1H),2.70(dd,J＝15.0,5.5Hz,1H),2.28(dd,J＝15.0,6.8Hz,1H),1.97(dd,J＝11.3,4.5Hz,2H),1.84-1.61(m,4H),1.45-1.31(m,2H)； 13 C NMR(100MHz,Chloroform-d)δ193.9,169.7,161.8,136.1,127.3,121.4,120.4,117.9,70.5,51.3,43.0,33.1,33.0,32.6,23.7.
Example 17
To a round bottom flask was added in sequence 2- (allyloxy) -benzaldehyde starting material (0.0486 g,0.3 mmol), 2-oxo-2-adamantanamino acetic acid (0.2010 g,0.9 mmol), (NH) 4 ) 2 S 2 O 8 (0.274 g,1.2 mmol) and reaction solvent DMSO (2.0 mL) were added to the reaction mixture 2 Atmosphere protection, stirring for 12h at 60 ℃, adding water (10 mL) into the reaction mixture after the reaction is completed, extracting with ethyl acetate (10 mL multiplied by 3), drying the organic phase with anhydrous sodium sulfate, filtering, and concentrating to obtain a crude product; and separating the crude product by using a mixed solvent comprising ethyl acetate and petroleum ether through silica gel column chromatography to obtain the chroman-4-one solid product containing amido. Yellow solid; 73.32mg (isolated yield 72%). 1 H NMR(400MHz,Chloroform-d)δ7.87(d,J＝7.9Hz,1H),7.47(t,J＝7.7Hz,1H),7.08-6.81(m,2H),5.57(s,1H),4.63(dd,J＝11.2,5.2Hz,1H),4.27(t,J＝11.6Hz,1H),3.34-3.22(m,1H),2.65(dd,J＝15.0,5.1Hz,1H),2.23(dd,J＝14.9,7.1Hz,1H),2.14-1.93(m,9H),1.82-1.51(m,6H)； 13 C NMR(100MHz,Chloroform-d)δ193.9,169.2,161.8,136.0,127.3,121.4,120.5,117.8,70.5,52.1,43.1,41.5,36.3,33.5,29.4.
Claims (10)
1. A preparation method of an amido-containing aromatic ring dihydropyran-4-ketone compound is characterized in that a raw material solution containing 2- (allyloxy) -aromatic aldehyde derivatives of a formula 1, N-substituted oxalic acid of a formula 2, ammonium persulfate and DMSO is reacted in an oxygen-free atmosphere at a temperature of 40-100 ℃ to prepare an amido-containing aromatic ring dihydropyran-4-ketone product of a formula 3;
ar is an aromatic ring or a substituted aromatic ring with a substituent;
said R is 1 Is hydrogen, C1-C6 alkyl, trifluoromethyl, aromatic ring, substituted aromatic ring or alicyclic ring with substituent;
the aromatic ring is five-membered aromatic heterocycle, six-membered aromatic heterocycle, and condensed ring formed by combining two or more aromatic rings in five-membered aromatic heterocycle, six-membered aromatic heterocycle;
the substituent of the substituted aromatic ring being C 1 ～C 6 Alkyl, C of (2) 1 ～C 6 At least one of an alkoxy group, a trifluoromethyl group, an ester group, and a halogen.
2. The method of claim 1, wherein Ar is a benzene ring or a substituted benzene ring;
the substituent of the substituted benzene ring is C 1 ～C 6 At least one of an alkyl group, an alkoxy group, a trifluoromethyl group, an ester group, and a halogen.
3. The process of claim 1, wherein R is 1 Is benzene ring, substituted benzene ring, cyclopentane, cyclohexane, spiro ring or bridged ring;
the substituent of the substituted benzene ring is C 1 ～C 6 Alkyl, alkoxy, trifluoromethyl, ester or halogen.
4. The method according to claim 1, wherein the molar ratio of the 2- (allyloxy) -araldehyde starting material of formula 1 to the N-substituted oxamic acid is 1:1 to 10; further preferably 1:1.5 to 4.
5. The process according to claim 1, wherein the molar ratio of the starting 2- (allyloxy) -araldehyde derivative of formula 1 to ammonium persulfate is 1:1-10; further preferably 1:1.5 to 4.
6. The process according to claim 1, wherein the molar volume ratio of the 2- (allyloxy) -araldehyde starting material of formula 1 in the starting material solution is 0.1 to 0.5moL/L.
7. The method according to claim 1, wherein the oxygen-free atmosphere is at least one of nitrogen and inert gas.
8. The process according to claim 1, wherein the reaction temperature is 50 to 100 ℃, preferably 60 to 70 ℃.
9. The process of claim 1, wherein the reaction time is from 5 to 24 hours.
10. The preparation method according to any one of claims 1 to 9, wherein after the reaction, water and an organic solvent are added for extraction, anhydrous sodium sulfate is added into an organic phase for drying, filtration and concentration are carried out to obtain a crude product, and a target product is obtained by column chromatography separation;
wherein the organic solvent is a hydrophobic solvent, preferably ethyl acetate or dichloromethane;
preferably, the purifying solvent in the column chromatography stage is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio is 1-10:1.
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