CN108467382A - A kind of preparation method of 4H- chromene derivatives - Google Patents
A kind of preparation method of 4H- chromene derivatives Download PDFInfo
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- CN108467382A CN108467382A CN201810271393.8A CN201810271393A CN108467382A CN 108467382 A CN108467382 A CN 108467382A CN 201810271393 A CN201810271393 A CN 201810271393A CN 108467382 A CN108467382 A CN 108467382A
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- JCIDEANDDNSHQC-UHFFFAOYSA-N 4H-chromene Chemical class C1=CC=C2CC=COC2=C1 JCIDEANDDNSHQC-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 150000003556 thioamides Chemical class 0.000 claims abstract description 6
- 238000006467 substitution reaction Methods 0.000 claims abstract description 4
- 239000012043 crude product Substances 0.000 claims abstract 2
- -1 substituted-phenyl Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 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
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- OSBSXTGABLIDRX-UHFFFAOYSA-N 5-methylidenecyclohexa-1,3-diene Chemical compound C=C1CC=CC=C1 OSBSXTGABLIDRX-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 125000005909 ethyl alcohol group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- VTWDKFNVVLAELH-UHFFFAOYSA-N 2-methylcyclohexa-2,5-diene-1,4-dione Chemical compound CC1=CC(=O)C=CC1=O VTWDKFNVVLAELH-UHFFFAOYSA-N 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 abstract description 6
- UAJJKCMRKMOVEC-UHFFFAOYSA-N 5-methylidenecyclohex-2-ene-1,4-dione Chemical class C=C1CC(=O)C=CC1=O UAJJKCMRKMOVEC-UHFFFAOYSA-N 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 238000010898 silica gel chromatography Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 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
- 230000000694 effects Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 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
- YUOVZJMEWHMILQ-UHFFFAOYSA-N CC(C)(C)C(C(C(C(C)(C)C)=C1)=O)=CC1=Cc1ccccc1O Chemical compound CC(C)(C)C(C(C(C(C)(C)C)=C1)=O)=CC1=Cc1ccccc1O YUOVZJMEWHMILQ-UHFFFAOYSA-N 0.000 description 1
- 0 CCCCC(C)c1cc(C2C(C(*)=O)=C(Nc(cc3)ccc3Cl)Oc3ccccc23)cc(C(C)(C)C)c1O Chemical compound CCCCC(C)c1cc(C2C(C(*)=O)=C(Nc(cc3)ccc3Cl)Oc3ccccc23)cc(C(C)(C)C)c1O 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- MQCJOSPOECUGQA-UHFFFAOYSA-N O=C(CC(Nc(cc1)ccc1Cl)=S)c1ccccc1 Chemical compound O=C(CC(Nc(cc1)ccc1Cl)=S)c1ccccc1 MQCJOSPOECUGQA-UHFFFAOYSA-N 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 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
- 230000007812 deficiency Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- CKEZIBBDMDFHQQ-ILKNQKGPSA-N miroestrol Natural products CC1(C)[C@H]2C[C@]3(O)CC(=O)[C@H]([C@@H]2[C@H]3O)C4=COc5ccccc5[C@@H]14 CKEZIBBDMDFHQQ-ILKNQKGPSA-N 0.000 description 1
- RJKLDOLOCIQYFS-PRTISISMSA-N miroestrol Chemical compound C12=COC3=CC(O)=CC=C3[C@H]2C(C)(C)[C@@H]2[C@@H]([C@H]3O)[C@@]1(O)C(=O)C[C@]3(O)C2 RJKLDOLOCIQYFS-PRTISISMSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 150000002989 phenols Chemical class 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
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a kind of preparation methods for the 4H chromene derivatives for belonging to technical field of organic synthesis.The method is：Into reactor, substituted beta sweet-smelling formacyl thioamides is added, substitution is added etoh solvent, is heated to after completion of the reaction, Rotary Evaporators are concentrated to give crude product, with the isolated sterling of silica gel column chromatography to methylene benzoquinones and triethylamine.The features such as synthetic method of 4H chromene derivatives provided by the invention is scientific and reasonable, and synthetic route is simple, and experimental implementation is simple, and product is easy to purifying.Its reaction equation is as follows：
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation method of 4H- chromene derivatives.
Background technology
In various synthesis and naturally occurring heterocycle structure, chromene structural unit is one of most important heterocycle.
4H- chromene derivatives are widely present in various natural products and drug, have significant bioactivity.Such as it is anti-
Tumour, antibacterial anti-inflammatory, antirheumatic isoreactivity etc..((a)Proc.Natl.Acad.Sci.2000,97,7124.(b)
Curr.Comput.Aided.Drug.Des.2016,12,34.)。
In addition, the micro- female alcohol of miroestrol and deoxidation containing 4H- chromene structures is natural plants female hormone, it is widely used in and changes
Kind female aging situation treats osteoporosis and alleviates the missing of female estrogen, alleviates menopause symptom etc.
(Nature.1960,188,774.)。
Have been widely used in view of 4H- chromene derivatives tool, the synthetic method for studying such compound has important meaning
Justice.
The traditional preparation method of 4H- chromene derivatives has：
1) Sakae Uemura synthetic methods：Utilize ammonium tetrafluoroborate and noble ruthenium catalyst [(η5-C5Me5)RuCl(μ2-
SMe)2Ru(η5-C5Me5) Cl] make under collective effect propilolic alcohol and phenol derivatives that cycloaddition reaction occur to generate 4H- chromene classes
Derivative.
2) Fujimoto-Sakurai synthetic methods：Using salicylide and cyanoacetate compound under ammonium acetate catalysis
Multiple functionalized 4H- chromene compounds are prepared, reaction temperature requires to be strict controlled in 5-10 DEG C, the little higher (15- of temperature
25 DEG C) then it is unable to get 4H- chromene compounds.
3) the brave synthetic methods of Wang Zhi：It is reacted using 2- (methylol) phenol analog derivatives and 'beta '-ketoester or beta-diketone compounds
In FeCl34H- chromene compounds are synthesized under catalytic action.
It prepares 4H- derivatives in the lab using the above method, has the shortcomings that apparent：1) it need to select expensive
Transition-metal catalyst uses lewis acid；2) transition-metal catalyst preparation manipulation is complicated；
3) reaction temperature requires harsh.
Invention content
In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides a kind of preparation methods of 4H- chromene derivatives.
A kind of preparation method of 4H- chromene derivatives, the 4H- chromene derivatives have structure shown in formula I：
Wherein, R1Selected from phenyl, substituted-phenyl, the substituent group of substituted-phenyl is fluorine, methyl, methoxyl group, sulfidomethyl；R2
Selected from phenyl, substituted-phenyl, the substituent group of substituted-phenyl is chlorine, methyl；R3Selected from tertiary butyl；R4Selected from hydrogen, bromine, methyl, first
Oxygroup；It is characterized in that, into reactor, it is 1 that molar ratio, which is added,:1.2 substituted beta-sweet-smelling formacyl thioamides and substitution pair
Methylene-benzene naphtoquinone compounds heat after completion of the reaction, Rotary Evaporators are concentrated to give thick production under triethylamine effect in solvent
Object, with the isolated product of silica gel column chromatography, chemical process is shown in reaction equation II：
The substituted beta-sweet-smelling formacyl thioamides, substitution are 1 to the molar ratio of methylene benzoquinones and triethylamine:
1.2:0.5.The solvent is selected from ethyl alcohol, and reaction temperature is 70 DEG C, reaction time 10h.
Beneficial effects of the present invention are：The synthetic method of 4H- chromene derivatives provided by the invention is scientific and reasonable, Ke Yihe
At the 4H- chromene derivatives for obtaining that there are a variety of substituent groups；But also it is simple with synthetic route, experimental implementation is simple, product
The features such as being easy to purifying.
Description of the drawings
Fig. 1 is the NMR spectra of compound 3a prepared by embodiment 1；
Fig. 2 is the NMR spectra of compound 3f prepared by embodiment 6；
Fig. 3 is the NMR spectra of compound 3j prepared by embodiment 10；
Specific implementation mode
The present invention is described in more detail with specific embodiment below in conjunction with the accompanying drawings：
Test method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as
Without specified otherwise, commercially obtain.
Embodiment 1
1) preparation of 4H- chromene derivatives 3a
Thioamides 1a (0.5mmol, 127.7mg) is added into 25mL single-necked flasks, to methylene benzoquinones 2a
(0.6mmol, 186.3mg) and NEt3(0.25mmol,25.3mg).Ethyl alcohol (5mL) is added, is stirred in 70 DEG C of oil bath, instead
It answers 10 hours.After completion of the reaction, it is cooled to room temperature, removes solvent with Rotary Evaporators, residue is through column chromatography for separation (200-
300 mesh silica gel) (petrol ether/ethyl acetate=50/1), the solid 4H- chromene derivative 3a rotated, yield 85%.
Spectrum elucidation 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 for
C36H38NO3 +[M+H]+532.2852,found,532.2851.
Embodiment 2
The 2a in example 1 is replaced with 2b, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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)13C
NMR(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.
Embodiment 3
The 2a in example 1 is replaced with 2c, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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 for
C37H39NO4Na+[M+Na]+584.2777,found,584.2776.
Embodiment 4
The 2a in example 1 is replaced with 2d, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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/z
calcd for C37H39NO3Na+[M+Na]+568.2828,found,568.2825.
Embodiment 5
The 1a in example 1 is replaced with 1e, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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)δ
193.1,162.9(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.
Embodiment 6
The 1a in example 1 is replaced with 1f, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3f:
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.
Embodiment 7
The 1a in example 1 is replaced with 1g, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3g:
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.
Embodiment 8
The 1a in example 1 is replaced with 1h, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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.
Embodiment 9
The 1a in example 1 is replaced with 1i, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation 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.
Embodiment 10
The 1a in example 1 is replaced with 1j, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3j:
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)δ
194.0,160.2,152.0,148.7,141.6,137.6,135.5,134.6,134.2,129.6,128.9,128.8,
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 (3)
1. a kind of preparation method of 4H- chromene derivatives, the 4H- chromene derivatives have structure shown in formula I：
Wherein, R1Selected from phenyl, substituted-phenyl, the substituent group of substituted-phenyl is fluorine, methyl, methoxyl group, sulfidomethyl；R2It is selected from
The substituent group of phenyl, substituted-phenyl, substituted-phenyl is chlorine, methyl；R3Selected from tertiary butyl；R4Selected from hydrogen, bromine, methyl, methoxy
Base；It is characterized in that, into reactor, substituted beta-sweet-smelling formacyl thioamides is added and replaces to methylene-benzene naphtoquinone compounds,
Under the action of catalyst, it is heated in solvent after completion of the reaction, Rotary Evaporators are concentrated to give crude product, are detached with column chromatography silica gel
Obtain 4H- chromene derivatives shown in formula I；The preparation method is indicated with following equation：
2. preparation method according to claim 1, it is characterised in that：Substituted beta-sweet-smelling formacyl thioamides, substitution are to Asia
Methylbenzoquinone, catalyst of triethylamine molar ratio be 1:1.2:0.5.
3. preparation method described in accordance with the claim 1, it is characterised in that：Solvent is ethyl alcohol, and reaction temperature is 70 DEG C, when reaction
Between be 10h.
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| CONG DUAN等: "Organocatalytic cascade 1,6-conjugate addition/annulation/tautomerization of functionalized para-quinone methides: Access to chiral 2-amino-4-aryl-4H-chromenes", 《CHINESE CHEMICAL LETTERS》 * |
| LILI ZHANG等: "Asymmetric synthesis of chromene skeletons via organocatalytic domino reactions of in situ generated ortho-quinone methide with malononitrile and b-functionalized ketone", 《RSC ADV.》 * |
| 崔涛: "基于硫代酰胺和对亚甲基苯醌合成4H-色烯衍生物的反应研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
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| CN114149311B (en) * | 2021-12-08 | 2023-11-03 | 上海应用技术大学 | Method for preparing 4-hydroxybenzophenone compound by taking p-methylene quinone as substrate |
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