CN108467382B - Preparation method of 4H-chromene derivative - Google Patents
Preparation method of 4H-chromene derivative Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 125000001819 4H-chromenyl group Chemical class O1C(=CCC2=CC=CC=C12)* 0.000 title claims abstract description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 16
- -1 p-methylene Chemical group 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 6
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 238000001308 synthesis method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 238000010898 silica gel chromatography Methods 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 150000000529 4H-chromenes Chemical class 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- WHQUHTXULUACFD-KRWDZBQOSA-N (3s)-4-[[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]methoxy-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1COP(O)(=O)C[C@@H](O)CC(O)=O WHQUHTXULUACFD-KRWDZBQOSA-N 0.000 description 1
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- 238000006960 Hosomi-Sakurai reaction Methods 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010027304 Menopausal symptoms Diseases 0.000 description 1
- 206010030247 Oestrogen deficiency Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- WEQHNIVLPMYPPS-WZNKSHDTSA-N deoxymiroestrol Natural products CC1(C)[C@H]2C[C@]3(O)CC(=O)[C@](O)([C@@H]2[C@H]3O)C4=COc5ccccc5[C@@H]14 WEQHNIVLPMYPPS-WZNKSHDTSA-N 0.000 description 1
- AZKZPXFWTQSDET-CAXYJRAJSA-N deoxymiroestrol Chemical compound C12=COC3=CC(O)=CC=C3[C@H]2C(C)(C)[C@H]2[C@@H]([C@H]3O)[C@H]1C(=O)C[C@@]3(O)C2 AZKZPXFWTQSDET-CAXYJRAJSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical class OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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Classifications
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- 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of a 4H-chromene derivative, belonging to the technical field of organic synthesis, wherein the method comprises the steps of adding substituted β -arylformyl thioamide, substituted p-methylene benzoquinone and triethylamine into a reactor, adding solvent ethanol, heating until the reaction is finished, and concentrating by a rotary evaporator to obtain a crude productThe product is separated by silica gel column chromatography to obtain pure product. The synthesis method of the 4H-chromene derivative provided by the invention has the characteristics of being scientific and reasonable, simple in synthesis route, simple in experimental operation, easy to purify the product and the like. The reaction equation is as follows:
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a 4H-chromene derivative.
Background
Among the various synthetic and naturally occurring heterocyclic structures, chromene building blocks are one of the most important heterocycles.
4H-chromene derivatives are widely present in various natural products and drugs, and have remarkable biological activity. Such as anti-tumor, antibacterial, anti-inflammatory, antirheumatic, etc. ((a) proc.natl.acad.sci.2000,97,7124.(b) curr.comput.aid.drug.des.2016, 12, 34.).
In addition, the 4H-chromene structure containing Geestrol and deoxymiroestrol are natural plant female hormones, and are widely used for improving female aging conditions, treating osteoporosis, relieving female estrogen deficiency, relieving climacteric symptoms and the like (Nature.1960,188, 774.).
In view of the wide application of the 4H-chromene derivative, the research on the synthetic method of the compound has important significance.
The conventional preparation method of the 4H-chromene derivative comprises the following steps:
1) the Sakae Uemura synthesis method utilizes ammonium tetrafluoroborate and noble metal ruthenium catalyst [ (η)5-C5Me5)RuCl(μ2-SMe)2Ru(η5-C5Me5)Cl]Under the combined action, the propiolic alcohol and the phenol derivative undergo a cycloaddition reaction to generate the 4H-chromene derivative.
2) Fujimoto-Sakurai synthesis: the multifunctional 4H-chromene compound is prepared by using salicylaldehyde and a cyanoacetate compound under the catalysis of ammonium acetate, the reaction temperature is strictly controlled at 5-10 ℃, and the 4H-chromene compound cannot be obtained if the temperature is slightly higher (15-25 ℃).
3) The Wanxingyong synthesis method uses the reaction of 2- (hydroxymethyl) phenol derivative and β -keto ester or β -diketone compound on FeCl3Synthesizing 4H-chromene compounds under the catalysis.
The preparation of 4H-derivatives in the laboratory using the above-described process has significant disadvantages: 1) expensive transition metal catalyst or Lewis acid is needed; 2) the preparation operation of the transition metal catalyst is complex;
3) the reaction temperature is critical.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a preparation method of a 4H-chromene derivative.
A method for preparing a 4H-chromene derivative, the 4H-chromene derivative having the structure of formula i:
wherein R is1The substituent group of the substituted phenyl is fluorine, methyl, methoxy, thiomethyl; r2The substituent group of the substituted phenyl is chlorine and methyl; r3Selected from tert-butyl; r4The method is characterized in that a substituted β -arylformyl thioamide and a substituted p-methylene benzoquinone compound with the molar ratio of 1:1.2 are added into a reactor, under the action of triethylamine, after the heating reaction in a solvent is finished, a rotary evaporator is concentrated to obtain a crude product, and the crude product is separated by silica gel column chromatography to obtain a product, wherein the chemical process is shown in a reaction formula II:
the molar ratio of the substituted β -arylformyl thioamide to the substituted p-methylene benzoquinone to the triethylamine is 1:1.2:0.5, the solvent is selected from ethanol, the reaction temperature is 70 ℃, and the reaction time is 10 hours.
The invention has the beneficial effects that: the synthesis method of the 4H-chromene derivative provided by the invention is scientific and reasonable, and the 4H-chromene derivative with various substituent groups can be synthesized; and has the characteristics of simple synthetic route, simple experimental operation, easy purification of products and the like.
Drawings
FIG. 1 is an NMR spectrum of Compound 3a prepared in example 1;
FIG. 2 is an NMR spectrum of compound 3f prepared in example 6;
FIG. 3 is an NMR spectrum of compound 3j prepared in example 10;
Detailed Description
The invention is described in further detail below with reference to the following figures and specific examples:
the test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
1) Preparation of 4H-chromene derivative 3a
Into a 25mL single-neck flask were added thioamide 1a (0.5mmol,127.7mg), p-methylenequinone 2a (0.6mmol,186.3mg), and NEt3(0.25mmol,25.3 mg). Ethanol (5mL) was added, and the mixture was stirred in an oil bath at 70 ℃ to react for 10 hours. After the reaction was completed, it was cooled to room temperature, the solvent was removed by a rotary evaporator, the residue was separated by column chromatography (200-mesh 300-mesh silica gel) (petroleum ether/ethyl acetate: 50/1), and the obtained solid 4H-chromene derivative 3a was rotary-evaporated in 85% yield.
Spectrogram analysis data 3a:
1H NMR(d-DMSO,500MHz)δ1.22(s,18H,CH3),4.95(s,1H,CH),6.57(s,2H,ArH),6.74(s,1H,-OH,missing after deuteriation),7.15(t,J＝7.7Hz,1H,ArH),7.17-7.22(m,3H,ArH),7.25-7.28(m,3H,ArH),7.34-7.37(m,2H,ArH),7.41-7.43(m,5H,ArH),12.73(s,1H,NH,missing after deuteriation).13C NMR(d-DMSO,125MHz)δ194.1,159.5,152.2,148.6,141.3,139.4,138.1,137.4,129.8,129.7,129.3,128.4,128.2,127.7,126.8,125.8,124.8,122.9,121.9,116.3,91.5,41.6,34.7,30.5.HRMS(ESI)m/z calcd forC36H38NO3 +[M+H]+532.2852,found,532.2851.
example 2
2a in example 1 is replaced by 2b, other conditions are the same as in example 1, and the experimental results are shown in Table 1.
Spectrogram analysis data 3b:
1H NMR(CDCl3,500MHz)δ1.30(s,18H,t-Bu),4.88(s,1H,CH),5.02(s,1H,OH),6.54(s,2H,ArH),7.01(d,J＝8.6Hz,1H,ArH),7.17-7.22(m,3H,ArH),7.25(s,1H,ArH),7.29-7.31(m,1H,ArH),7.35(t,J＝7.3Hz,2H,ArH),7.39-7.46(m,5H,ArH),13.20(s,1H,NH).13CNMR(CDCl3,125MHz)δ194.4,159.6,152.2,147.7,141.2,137.1,136.9,135.7,131.7,130.3,129.6,129.1,129.0,128.1,126.4,124.7,123.4,122.5,117.9,117.6,90.5,42.0,34.1,30.0.HRMS(ESI)m/z calcd for C36H36NO3BrNa+[M+Na]+632.1776,found,632.1774.
example 3
2a in example 1 was replaced by 2c, and the experimental results are shown in Table 1, except that the conditions were the same as in example 1.
Spectrogram analysis data 3c:
1H NMR(CDCl3,500MHz)δ1.29(s,18H,t-Bu),3.73(s,3H,-OCH3),4.87(s,1H,CH),4.99(s,1H,OH),6.58(s,2H,ArH),6.60-6.66(m,1H,ArH),6.69-6.77(m,1H,ArH),7.06(d,J＝8.9Hz,1H,ArH),7.15-7.23(m,3H,ArH),7.34(t,J＝7.2Hz,2H,ArH),7.37-7.44(m,3H,ArH),7.48(d,J＝7.8Hz,2H,ArH),13.27(s,1H,NH).13C NMR(CDCl3,125MHz)δ194.2,160.3,156.5,152.0,142.8,141.6,137.4,135.6,129.1,128.8,128.3,128.0,126.5,124.4,123.4,122.4,116.9,113.3,112.9,90.7,55.5,42.4,34.1,30.1.HRMS(ESI)m/z calcd forC37H39NO4Na+[M+Na]+584.2777,found,584.2776.
example 4
2a in example 1 is replaced by 2d, other conditions are the same as in example 1, and the experimental results are shown in Table 1.
Spectrogram analysis data 3d:
1H NMR(CDCl3,500MHz)δ1.29(s,18H,t-Bu),2.25(s,3H,-CH3),4.87(s,1H,CH),4.98(s,1H,OH),6.57(s,2H,ArH),6.92(s,1H,ArH),6.98(d,J＝8.5Hz,1H,ArH),7.02(d,J＝8.2Hz,1H,ArH),7.16-7.21(m,3H,ArH),7.34(t,J＝7.2Hz,2H,ArH),7.37-7.42(m,3H,ArH),7.48(d,J＝7.8Hz,2H,ArH),13.26(s,1H,NH).13C NMR(CDCl3,125MHz)δ194.3,160.2,152.0,146.7,141.6,137.7,137.4,135.5,134.7,129.2,129.1,128.8,128.0,128.0,127.0,126.5,124.4,123.4,122.4,115.8,91.2,42.1,34.1,30.1,20.8.HRMS(ESI)m/zcalcd for C37H39NO3Na+[M+Na]+568.2828,found,568.2825.
example 5
1a in example 1 is replaced by 1e, other conditions are the same as in example 1, and the experimental results are shown in Table 1.
Spectrogram analysis data 3e:
1H NMR(CDCl3,500MHz)δ1.30(s,18H,t-Bu),4.90(s,1H,CH),4.99(s,1H,-OH),6.60(s,2H,ArH),7.00-7.03(m,2H,ArH),7.07-7.15(m,3H,ArH),7.18-7.22(m,4H,ArH),7.40-7.44(m,2H,ArH),7.48-7.50(m,2H,ArH),13.25(s,1H,NH).13C NMR(CDCl3,125MHz)δ193.1,162.9(1JC-F＝248.3)160.1,152.1,148.5,137.7,137.4,137.2,135.7,129.1,128.6(3JC-F＝8.3Hz),128.5,127.4,127.2,125.1,124.6,123.3,122.5,116.1,114.9(2JC-F＝21.7Hz),90.7,42.0,34.1,30.1.HRMS(ESI)m/z calcd for C36H37NO3F+[M+H]+550.2757,found,550.2756.
example 6
1f is used instead of 1a in example 1, the conditions are the same as in example 1, and the experimental results are shown in Table 1.
1H NMR(CDCl3,500MHz)δ1.28(s,18H,t-Bu),2.39(s,3H,-CH3),4.96(s,1H,CH),4.99(s,1H,OH),6.59(s,2H,ArH),7.06-7.09(m,1H,ArH),7.11-7.16(m,6H,ArH),7.17-7.21(m,2H,ArH),7.38-7.41(m,2H,ArH),7.47-7.48(m,2H,ArH),13.25(s,1H,NH).13C NMR(CDCl3,125MHz)δ194.5,159.9,152.0,148.7,138.8,138.7,137.5,135.5,129.0,128.6,127.5,127.3,126.6,125.0,124.3,123.4,122.4,116.1,91.0,42.0,34.1,30.1,21.3.HRMS(ESI)m/z calcd for C37H39NO3Na+[M+Na]+568.2828,found,568.2830.
example 7
1a in example 1 was replaced by 1g, and the experimental results are shown in Table 1, except that the conditions were the same as in example 1.
3g of spectrogram analysis data:
1H NMR(CDCl3,500MHz)δ1.31(s,18H,t-Bu),3.87(s,3H,-OCH3),5.00(s,1H,CH),5.07(s,1H,OH),6.63(s,2H,ArH),6.90(d,J＝8.3Hz,2H,ArH),7.11-7.25(m,5H,ArH),7.28(d,J＝8.0Hz,2H,ArH),7.43(t,J＝7.6Hz,2H,ArH),7.50(d,J＝8.0Hz,2H,ArH),13.23(s,1H,NH).13C NMR(CDCl3,125MHz)δ193.8,160.2,159.9,152.0,148.9,137.5,137.4,135.5,134.1,129.0,128.9,128.5,127.5,127.3,125.0,124.2,123.4,122.3,116.1,113.3,91.0,55.2,42.0,34.1,30.1.HRMS(ESI)m/z calcd for C37H39NO4Na+[M+Na]+584.2777,found,584.2766.
example 8
1a in example 1 is replaced by 1h, other conditions are the same as example 1, and the experimental results are shown in Table 1.
Spectrogram analysis data 3h:
1H NMR(CDCl3,500MHz)δ1.29(s,18H,t-Bu),2.51(s,3H,-SCH3),4.97(s,1H,CH),4.98(s,1H,OH),6.59(s,2H,ArH),7.07-7.21(m,9H,ArH),7.41(t,J＝7.8Hz,2H,ArH),7.47(d,J＝7.9Hz,2H,ArH),13.24(s,1H,NH).13C NMR(CDCl3,125MHz)δ193.6,160.0,152.0,148.6,139.9,138.0,137.3,135.6,129.1,129.0,127.4,127.2,125.4,125.1,124.4,123.4,122.4,116.1,90.9,41.9,34.1,30.1,15.3.HRMS(ESI)m/z calcd for C37H40NO3S+[M+H]+578.2733,found,578.2729.
example 9
1a in example 1 is replaced by 1i, other conditions are the same as example 1, and the experimental results are shown in Table 1.
Spectrogram analysis data 3i:
1H NMR(CDCl3,500MHz)δ1.28(s,18H,t-Bu),4.94(s,1H,CH),4.98(s,1H,OH),6.55(s,2H,ArH),7.05-7.16(m,3H,ArH),7.17-7.24(m,3H,ArH),7.29-7.49(m,7H,ArH),13.27(s,1H,NH).13C NMR(CDCl3,125MHz)δ194.6,159.8,152.0,148.5,141.3,137.3,136.0,135.6,129.6,129.1,129.0,128.0,127.4,127.3,126.5,125.2,123.5,123.4,116.0,91.3,41.9,34.1,30.1.HRMS(ESI)m/z calcd for C36H37NO3Cl+[M+H]+566.2462,found,566.2465.
example 10
1j is used for replacing 1a in example 1, other conditions are the same as example 1, and the experimental results are shown in Table 1.
1H NMR(CDCl3,500MHz)δ1.28(s,18H,t-Bu),2.38(s,3H,-CH3),4.92(s,1H,CH),4.96(s,1H,OH),6.57(s,2H,ArH),7.05-7.14(m,3H,ArH),7.17-7.22(m,5H,ArH),7.33(t,J＝7.2Hz,2H,ArH),7.37(d,J＝7.9Hz,3H,ArH),13.23(s,1H,NH).13C NMR(CDCl3,125MHz)δ194.0,160.2,152.0,148.7,141.6,137.6,135.5,134.6,134.2,129.6,128.9,128.8,128.0,127.5,127.3,126.5,125.0,123.4,122.5,116.1,90.7,42.0,34.1,30.1,20.8.HRMS(ESI)m/z calcd for C37H39NO3Na+[M+Na]+568.2828,found,568.2832。
TABLE 1
Claims (2)
1. A method for preparing a 4H-chromene derivative, the 4H-chromene derivative having the structure of formula i:
wherein R is1The substituent group of the substituted phenyl is fluorine, methyl, methoxy, thiomethyl; r2The substituent group of the substituted phenyl is chlorine and methyl; r3Selected from tert-butyl; r4The preparation method is characterized in that a substituted β -arylformyl thioamide and a substituted p-methylene benzoquinone compound are heated in an ethanol solvent under the catalysis of triethylamine and at 70 ℃ to react, then a crude product is obtained by concentration through a rotary evaporator, and a column chromatography silica gel is used for separation to obtain the 4H-chromene derivative shown in the formula I, wherein the preparation method is represented by an equation shown in the formula II:
2. the process according to claim 1, wherein the molar ratio of the substituted β -arylformylthioamide to the substituted p-methylenequinone to the triethylamine as the catalyst is 1:1.2: 0.5.
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