CN109734691A - 4- (3, 5-di-tert-butyl-4-hydroxyphenyl) substituted dihydrocoumarin derivative and preparation method thereof - Google Patents
4- (3, 5-di-tert-butyl-4-hydroxyphenyl) substituted dihydrocoumarin derivative and preparation method thereof Download PDFInfo
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- -1 3, 5-di-tert-butyl-4-hydroxyphenyl Chemical group 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- VMUXSMXIQBNMGZ-UHFFFAOYSA-N 3,4-dihydrocoumarin Chemical class C1=CC=C2OC(=O)CCC2=C1 VMUXSMXIQBNMGZ-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000012544 monitoring process Methods 0.000 claims abstract description 3
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000000463 material Substances 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 238000004587 chromatography analysis Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 239000012954 diazonium Substances 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000003756 stirring Methods 0.000 abstract description 3
- 238000004809 thin layer chromatography Methods 0.000 abstract description 3
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 abstract 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 abstract 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 64
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 150000002148 esters Chemical class 0.000 description 14
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 14
- 150000004702 methyl esters Chemical class 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- DMSHWWDRAYHEBS-UHFFFAOYSA-N dihydrocoumarin Natural products C1CC(=O)OC2=C1C=C(OC)C(OC)=C2 DMSHWWDRAYHEBS-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- OXGMMZMMYUEHRV-UHFFFAOYSA-N 9-[4-[(2-fluorophenyl)methoxy]-3-methoxyphenyl]-3,3,6,6-tetramethyl-4,5,7,9-tetrahydro-2h-xanthene-1,8-dione Chemical compound COC1=CC(C2C3=C(CC(C)(C)CC3=O)OC3=C2C(CC(C)(C)C3)=O)=CC=C1OCC1=CC=CC=C1F OXGMMZMMYUEHRV-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- GOKQOZYJEDDDOC-UHFFFAOYSA-N C(=O)OC.C1=CC=CC=C1 Chemical compound C(=O)OC.C1=CC=CC=C1 GOKQOZYJEDDDOC-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940095102 methyl benzoate Drugs 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a 4- (3, 5-di-tert-butyl-4-hydroxyphenyl) substituted dihydrocoumarin derivative and a preparation method thereof, wherein the dihydrocoumarin derivative has a structure shown in a formula 3, and the preparation process comprises the following steps: in an organic solvent system, taking o-hydroxyphenyl-substituted p-methylenebenzoquinone and high phthalic anhydride as reaction raw materials, stirring and reacting for 16-96 h at 30 ℃, monitoring the reaction through thin-layer chromatography, adding trimethylsilyldiazomethane and methanol, stirring for 0.5h, and separating and purifying through thin-layer chromatography after the reaction is finished to obtain the compound shown in the formula 3. The preparation method provided by the invention does not need any catalyst, has the advantages of easily available raw materials, simple and safe operation, mild reaction conditions and high product yield, enriches the variety of the dihydrocoumarin derivatives, and has great implementation value and potential social and economic benefits.
Description
Technical field
The present invention relates to technical field of organic synthesis, are related to a kind of preparation of dihydrocoumarin derivative, and in particular to one
The dihydrocoumarin derivative and preparation method thereof that kind 4- (3,5- di-t-butyl -4- hydroxyphenyl) replaces.
Background technique
Dihydrocoumarin derivative is a kind of highly important Oxygenic heterocyclic compounds, is widely present in natural products and medicine
In object molecule.Research shows that the compound of the skeleton containing dihydrocoumarin have it is antitumor, remove free radical, it is antiviral, prevent from coagulating
The important biomolecules such as blood activity, therefore the synthesis of such compound is constantly subjected to chemistry and the extensive concern of drug research worker.
But the dihydrocoumarin analog derivative that 4- (3,5- di-t-butyl -4- hydroxyphenyl) replaces is as a kind of new chemical combination
Object, its synthesis are but rarely reported, and the synthesis of most of dihydrocoumarin analog derivative be required to selection strong acid, highly basic or
Therefore noble metal develops one kind and does not need using any catalyst, is simple and efficient as catalyst, separating-purifying complex steps
Such multifarious compound of method composite structure have important practical significance and wide application prospect.
Summary of the invention
The dihydrocoumarin replaced the object of the present invention is to provide a kind of 4- (3,5- di-t-butyl -4- hydroxyphenyl) is derivative
Object has widened the range of structures of dihydrocoumarin derivative.
The dihydrocoumarin replaced it is a further object of the present invention to provide above-mentioned 4- (3,5- di-t-butyl -4- hydroxyphenyl) spreads out
The preparation method of biology does not use catalyst, is simple and efficient.
To achieve the above object, the dihydrocoumarin that a kind of 4- of the invention (3,5- di-t-butyl -4- hydroxyphenyl) replaces
Derivative has structural formula shown in formula 3:
In formula, R1Selected from hydrogen or methoxyl group, R2Selected from one of hydrogen, methoxyl group, bromine, R3Selected from hydrogen, methoxyl group, methyl,
One of tert-butyl, chlorine, fluorine, bromine, R4Selected from hydrogen or fluorine, R5Selected from one of hydrogen, methyl, fluorine.
The present invention also provides the preparations for the dihydrocoumarin derivative that above-mentioned 4- (3,5- di-t-butyl -4- hydroxyphenyl) replaces
Method comprises the concrete steps that: in organic solvent system, using 1 compound of formula, 2 compound of formula as reaction raw materials, stirring at 30 DEG C
16~96h is reacted, after monitoring fully reacting by thin-layered chromatography, trimethyl silicane diazomethane and methanol is added, is stirred for
0.5h, to by thin-layered chromatography separating-purifying, obtain 3 compound of formula after reaction；
The structural formula of 1 compound of formula isIn formula, R1Selected from hydrogen or methoxyl group, R2It is selected from
One of hydrogen, methoxyl group, bromine, R3Selected from one of hydrogen, methoxyl group, methyl, tert-butyl, chlorine, fluorine, bromine；
The structural formula of 2 compound of formula isIn formula, R4Selected from hydrogen or fluorine, R5Selected from hydrogen, first
One of base, fluorine.
Its reaction route is as follows:
Preferably, 1 compound of formula, 2 compound of formula molar ratio be 1:3.
Preferably, the molal volume ratio of 1 compound of formula and the trimethyl silicane diazomethane is 1mmol:2mL, institute
The molal volume ratio for stating 1 compound of formula and the methanol is 1mmol:0.4mL.
Preferably, the organic solvent is meta-xylene.
Preferably, the solvent that the thin-layered chromatography uses is petrol ether/ethyl acetate=4/1, V/V.
Compared with prior art, the present invention can realize the diversity and complexity of product molecule not only with a step, obtain high
Cis-selectivity, enrich the type of dihydrocoumarin class compound, and do not need easy using any catalyst, raw material
It obtains, safety easy to operate, reaction condition is mild, the reaction time is short, separating-purifying step is simple, Atom economy is high, environment is friendly
It is good, applied widely, thus there are biggish implementary value and potential economic results in society.
Specific embodiment
Invention is further described in detail combined with specific embodiments below.
Embodiment 1
It is that reaction is former with formula 1a compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, is stirred to react 16h at 30 DEG C, monitors fully reacting by thin-layered chromatography (petrol ether/ethyl acetate=4/1, V/V)
Later, 200 μ L trimethyl silicane diazomethanes and 40 μ L methanol are added, 0.5h are stirred for, to pass through thin-layer chromatography after reaction
Method (petrol ether/ethyl acetate=4/1, V/V) separating-purifying, obtains formula 3aa compound；
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) methyl benzoate
(3aa): yield: 86%；91:9dr；Yellow solid；m.p.55-58℃；1H NMR(400MHz,CDCl3)δ (ppm):8.01–
7.93 (m, 1H), 7.44-7.27 (m, 2H), 7.25-7.12 (m, 2H), 7.09-7.01 (m, 1H), 6.96 (d, J=7.4Hz,
1H), 6.87-6.77 (m, 1H), 6.71 (s, 2H), 5.06 (s, 1H), 4.95-4.72 (m, 1H), 4.63 (d, J=11.0Hz,
1H),3.85(s,3H),1.29(s,18H)；13C NMR(100 MHz,CDCl3)δ(ppm):168.9,167.5,152.7,
151.5,138.5,135.8,132.0,131.5,131.3, 129.9,128.9,128.7,128.5,127.3,126.2,
125.6,124.3,116.9,52.5,52.2,48.4,34.2, 30.2；IR(KBr):2922,2851,1763,1713,1487,
1269,1164,758,707cm-1；ESI FTMS: (C31H34O5+H)+m/z 487.2484,found m/z 487.2479.
Embodiment 2
It is that reaction is former with formula 1b compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ba with embodiment 1.
2- (4- (3,5- di-t-butyl -4- hydroxy phenyl) -8- methoxyl group -2- oxo chroman -3- base) methyl benzoate
(3ba): yield: 66%；85:15dr；Yellow solid；m.p.72-75℃；1H NMR(400MHz, CDCl3)δ(ppm):7.99–
7.88 (m, 1H), 7.34-7.17 (m, 2H), 6.99 (d, J=8.0Hz, 1H), 6.90 (d, J=8.1Hz, 1H), 6.84 (d, J
=7.2Hz, 1H), 6.71 (s, 2H), 6.52 (d, J=7.7Hz, 1H), 5.05 (s, 1H), 4.93-4.83 (m, 1H), 4.63
(d, J=11.3Hz, 1H), 3.95 (s, 3H), 3.84 (s, 3H), 1.28 (s, 18H)；13C NMR(100MHz,CDCl3)δ
(ppm):168.2,167.5,152.7,147.6, 140.9,138.5,135.8,131.9,131.5,131.2,129.9,
128.9,127.4,127.2,125.6,123.9, 120.4,111.1,56.2,52.2,51.9,48.6,34.2,30.2；IR
(KBr):3631,2917,1767,1482, 1282,1134,1080,948,770cm-1；ESI FTMS:(C32H36O6+H)+m/z
517.2590,found m/z 517.2592.
Embodiment 3
It is that reaction is former with formula 1c compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ca with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -7- methoxyl group -2- oxo benzodihydropyran -3- base) benzene first
Sour methyl esters (3ca): yield: 98%；80:20dr；Yellow solid；m.p.76-79℃；1H NMR(400 MHz,CDCl3)δ
(ppm): 8.01-7.92 (m, 1H), 7.32-7.24 (m, 2H), 6.85 (d, J=8.5Hz, 1H), 6.82-6.78 (m, 1H),
6.76–6.73(m,1H),6.69(s,2H),6.64–6.60(m,1H),5.06 (s,1H),4.79–4.69(m,1H),4.53
(d, J=11.0Hz, 1H), 3.85 (s, 3H), 3.83 (s, 3H), 1.28 (s, 18H)；13C NMR(100MHz,CDCl3)δ
(ppm):168.9,167.5,159.7,152.7,152.2, 138.7,135.8,132.0,131.3,130.4,129.6,
128.7,127.3,125.5,118.0,110.5,102.1, 55.5,52.2,48.0,34.2,30.2；IR(KBr):3482,
3130,2956,1765,1713,1625,1400, 1121,748,707cm-1；ESI FTMS:(C32H36O6+H)+m/z
517.2590,found m/z 517.2573.
Embodiment 4
It is that reaction is former with formula 1d compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ca with embodiment 1.
2- (the bromo- 4- of 7- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) benzoic acid first
Ester (3da): yield: 99%；91:9dr；Yellow solid；m.p.85-87℃；1H NMR(400MHz, CDCl3)δ(ppm):
8.01-7.98 (m, 1H), 7.37-7.34 (m, 1H), 7.30-7.26 (m, 2H), 7.19-7.16 (m, 1H), 6.85 (d, J=
8.3Hz, 1H), 6.74 (s, 1H), 6.65 (s, 2H), 5.09 (s, 1H), 4.79-4.60 (m, 1H), 4.56 (d, J=11.3Hz,
1H),3.86(s,3H),1.28(s,18H)；13C NMR(100 MHz,CDCl3)δ(ppm):168.0,167.5,152.9,
152.0,138.3,136.0,132.1,131.5,130.3, 129.6,128.4,127.5,127.3,125.5,125.3,
121.2,120.1,52.3,48.2,34.2,34.1,30.2；IR (KBr):3619,3131,2962,1773,1710,1483,
1401,1264,1089,952,802,707cm-1； ESI FTMS:(C31H33BrO5+H)+m/z 565.1589,found m/z
565.1568.
Embodiment 5
In meta-xylene system, with formula 1e compound (0.1mmol), formula 2a compound (0.3mmol) for reaction raw materials,
Preparation process obtains product 3ea with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -6- methyl -2- oxo benzodihydropyran -3- base) benzoic acid
Methyl esters (3ea): yield: 79% (39.7mg)；91:9dr；Yellow solid；m.p.95-97℃；1H NMR (400MHz,CDCl3)δ
(ppm):7.98–7.93(m,1H),7.29–7.23(m,2H),7.09(s,2H), 6.86–6.80(m,1H),6.78(s,1H),
6.73 (s, 2H), 5.07 (s, 1H), 4.89-4.73 (m, 1H), 4.57 (d, J=10.5Hz, 1H), 3.85 (s, 3H), 2.23
(s,3H),1.30(s,18H)；13C NMR(100MHz, CDCl3)δ(ppm):169.1,167.5,152.7,149.5,138.6,
135.8,133.9,132.0,131.3,130.2, 129.2,129.0,128.8,127.3,125.5,125.4,116.6,
52.2,48.6,40.7,34.2,30.2,20.8；IR (KBr):3629,3127,2956,1765,1712,1435,1400,
1267,1254,1134,975,816,718 cm-1；ESI FTMS:(C32H36O5+H)+m/z 501.2641,found m/z
501.2665.
Embodiment 6
It is that reaction is former with formula 1f compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3fa with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -6- methoxyl group -2- oxo benzodihydropyran -3- base) benzene first
Sour methyl esters (3fa): yield: 77% (39.7mg)；91:9dr；Yellow solid；m.p.85-87℃；1H NMR (400MHz,
CDCl3) δ (ppm): 7.97-7.94 (m, 1H), 7.31-7.21 (m, 2H), 7.13 (d, J=8.8 Hz, 1H), 6.86-6.81
(m, 2H), 6.73 (s, 2H), 6.49-6.45 (m, 1H), 5.07 (s, 1H), 4.92-4.77 (m, 1H), 4.59 (d, J=
10.8Hz,1H),3.86(s,3H),3.67(s,3H),1.29(s,18H)；13C NMR(100MHz,CDCl3)δ(ppm):
169.1,167.5,156.1,152.8,145.6,138.6,135.8, 132.0,131.3,129.8,128.8,127.3,
127.1,125.5,117.6,113.9,113.8,55.7,52.2,48.6, 48.3,34.2,30.2；IR(KBr):3629,
3125,2954,1769,1707,1491,1435,1400,1259, 1126,1042,818,772cm-1；ESI FTMS:
(C32H36O6+H)+m/z 517.2590,found m/z 517.2596.
Embodiment 7
It is that reaction is former with formula 1g compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ga with embodiment 1.
2- (6- (tert-butyl) -4- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) benzene
Methyl formate (3ga): yield: 82%；91:9dr；Yellow solid；m.p.85-87℃；1H NMR(400 MHz,CDCl3)δ
(ppm): 8.01-7.92 (m, 1H), 7.33-7.26 (m, 3H), 7.12 (d, J=8.5Hz, 1H), 6.96 (s, 1H), 6.87-
6.77 (m, 1H), 6.66 (s, 2H), 5.06 (s, 1H), 4.90-4.68 (m, 1H), 4.63 (d, J=11.4Hz, 1H), 3.84
(s,3H),1.28(s,18H),1.21(s,9H)；13C NMR(100 MHz,CDCl3)δ(ppm):169.2,167.5,152.6,
149.5,146.9,138.7,135.6,132.0,131.9, 131.3,129.9,128.8,127.2,126.1,125.7,
125.3,125.1,116.3,52.2,48.6,34.5,34.2, 31.4,30.2,30.1；IR(KBr):3631,3126,2962,
1771,1710,1493,1437,1400,1256, 1114,823,754cm-1；ESI FTMS:(C35H42O5+H)+m/z
543.3110,found m/z 543.3108.
Embodiment 8
It is that reaction is former with formula 1h compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ha with embodiment 1.
2- (the fluoro- 2- oxo benzodihydropyran -3- base of 4- (3,5- di-tert-butyl-hydroxy phenyl) -6-) benzoic acid first
Ester (3ha): yield: 90%；91:9dr；Yellow solid；m.p.85-88℃；1H NMR(400MHz, CDCl3)δ(ppm):
8.01–7.96(m,1H),7.30–7.26(m,2H),7.18–7.13(m,1H),7.02 –6.97(m,1H),6.82–6.75(m,
1H), 6.72-6.65 (m, 3H), 5.10 (s, 1H), 4.84-4.71 (m, 1H), 4.63 (d, J=11.3Hz, 1H), 3.86 (s,
3H),1.29(s,18H)；13C NMR(100MHz, CDCl3) δ (ppm): 168.5,167.5,159.0 (J=241.4Hz),
(152.9,147.5 J=2.4Hz), 138.3,136.1,132.1,131.4,129.3,128.6,128.2 (J=7.6Hz),
127.5,125.5,118.2 (J=8.4Hz), 115.4 (J=14.3Hz), 115.2 (J=13.3Hz), 52.3,48.4,
34.2,30.2；IR(KBr):3602,3128, 1765,1715,1401,1270,981,818,712cm-1；ESI FTMS:
(C31H33FO5+H)+m/z 505.2390,found m/z 505.2370.
Embodiment 9
It is that reaction is former with formula 1i compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ia with embodiment 1, reaction time 96h.
2- (the chloro- 4- of 6- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) benzoic acid first
Ester (3ia): yield: 46%；>95:5dr；Yellow solid；m.p.85-87℃；1H NMR(400MHz, CDCl3)δ(ppm):
8.03-7.95 (m, 1H), 7.31-7.26 (m, 3H), 7.14 (d, J=8.6Hz, 1H), 6.98-6.95 (m, 1H), 6.79-
6.72 (m, 1H), 6.69 (s, 2H), 5.10 (s, 1H), 4.83-4.66 (m, 1H), 4.61 (d, J=11.1Hz, 1H), 3.86
(s,3H),1.30(s,18H)；13C NMR(100MHz, CDCl3)δ(ppm):168.1,167.5,152.9,150.1,138.2,
136.1,132.1,131.6,131.4,129.4, 129.3,128.7,128.6,128.5,127.9,127.5,125.5,
118.3,52.4,52.3,48.4,34.3,30.2；IR (KBr):3609,3131,2961,1770,1712,1401,1264,
1084,972,817,712cm-1；ESI FTMS:(C31H33ClO5+Na)+m/z 543.1915,found m/z 543.1935.
Embodiment 10
It is that reaction is former with formula 1j compound (0.1mmol), formula 2a compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ja with embodiment 1, reaction time 48h.
2- (the bromo- 4- of 6- (3,5- di-t-butyl -4- hydroxy phenyl) -2- oxo chroman -3- base) methyl benzoate (3ja):
Yield: 44%；91:9dr；Yellow solid；m.p.80-82℃；1H NMR(400MHz,CDCl3)δ(ppm): 8.04–7.93(m,
1H),7.44–7.37(m,1H),7.29–7.27(m,2H),7.17–7.04(m,2H), 6.79–6.72(m,1H),6.68(s,
2H), 5.11 (s, 1H), 4.77-4.67 (m, 1H), 4.61 (d, J=10.9 Hz, 1H), 3.86 (s, 3H), 1.29 (s, 18H)；13C NMR(100MHz,CDCl3)δ(ppm):168.1, 167.5,153.0,150.7,138.2,136.1,132.1,131.7,
131.5,131.4,129.3,128.5,128.3, 127.5,125.5,118.7,117.0,52.3,48.4,34.3,30.2；IR
(KBr):3608,3132,2960,1771, 1712,1479,1340,1265,1162,1084,971,817,712cm-1；ESI
FTMS: (C31H33BrO5+H)+m/z 565.1589,found m/z 565.1575.
Embodiment 11
It is that reaction is former with formula 1a compound (0.1mmol), formula 2b compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ab with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) -4- fluobenzoic acid first
Ester (3ab): yield: 88% (44.2mg)；88:12dr；Yellow solid；m.p.92-95℃；1H NMR (400MHz,CDCl3)δ
(ppm):8.03–7.96(m,1H),7.34–7.28(m,1H),7.22–7.18(m, 1H),7.10–7.03(m,1H),6.99–
6.92(m,2H),6.72(s,2H),6.58–6.49(m,1H),5.10 (s,1H),4.97–4.79(m,1H),4.74–4.52
(m,1H),3.84(s,3H),1.30(s,18H)；13C NMR(100MHz,CDCl3)δ(ppm):168.3,166.5,164.4(J
=252.6Hz), 152.9,151.4,142.0 (J=8.5Hz), 136.1,133.9,133.8,129.4,128.8,128.6,
(126.1,125.5,124.4,118.8 J=22.4Hz), 116.9,114.3 (J=21Hz), 52.3,48.2,48.1,34.3,
30.2；IR(KBr): 3593,3130,2967,1765,1713,1589,1435,1400,1260,1123,774,758cm-1；
ESI FTMS:(C31H33FO5+H)+m/z 505.2390,found m/z 505.2373.
Embodiment 12
It is that reaction is former with formula 1a compound (0.1mmol), formula 2c compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ac with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) -5- methyl benzoic acid
Methyl esters (3ac): yield: 56%；91:9dr；Yellow solid；m.p.95-97℃；1H NMR(400MHz, CDCl3)δ(ppm):
7.82-7.72 (m, 1H), 7.35-7.27 (m, 1H), 7.22-7.14 (m, 1H), 7.12-7.01 (m, 2H), 6.96 (d, J=
7.6Hz, 1H), 6.88-6.77 (m, 1H), 6.72 (s, 2H), 5.06 (s, 1H), 4.87-4.76 (m, 1H), 4.60 (d, J=
10.9Hz,1H),3.84(s,3H),2.29(s,3H),1.29(s, 18H)；13C NMR(100MHz,CDCl3)δ(ppm):
169.1,167.6,152.7,151.6,137.1,135.8, 135.5,132.8,131.8,131.3,130.1,128.9,
128.5,128.4,126.2,125.6,124.2,116.9, 52.1,48.4,34.2,30.2,30.0,20.8；IR(KBr):
3645,3126,2962,1756,1713,1435, 1400,1148,948,772cm-1；ESI FTMS:(C32H36O5+H)+m/z
501.2641,found m/z 501.2625.
Embodiment 13
It is that reaction is former with formula 1a compound (0.1mmol), formula 2d compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3ad with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -2- oxo benzodihydropyran -3- base) -5- fluobenzoic acid first
Ester (3ad): yield: 78%；85:15dr；Yellow solid；m.p.85-87℃；1H NMR(400MHz, CDCl3)δ(ppm):
7.72–7.60(m,1H),7.34–7.28(m,1H),7.22–7.17(m,1H),7.09 –7.04(m,1H),7.03–6.97(m,
1H), 6.94 (d, J=7.7Hz, 1H), 6.86-6.80 (m, 1H), 6.71 (s, 2H), 5.09 (s, 1H), 4.94-4.81 (m,
1H), 4.60 (d, J=11.6Hz, 1H), 3.86 (s, 3H), 1.30 (s, 18H)；13C NMR(100MHz,CDCl3)δ(ppm):
168.8,166.4,166.3,161.3 (J=246.2Hz), 152.8,151.4,136.0,134.5,134.4,130.5 (J=
7.3Hz), 129.6,128.8,128.6,126.2,125.6,124.3,119.0 (J=21.2Hz), 118.1 (J=
23.3Hz),117.0,52.5,51.6,48.4, 34.2,30.2；IR(KBr):3607,3126,2960,1760,1718,
1455,1400,1270,1191,758, 727cm-1；ESI FTMS:(C31H33FO5+Na)+m/z 527.2210,found m/z
527.2230.
Embodiment 14
It is that reaction is former with formula 1f compound (0.1mmol), formula 2b compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3fb with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -6- methoxyl group -2- oxo benzodihydropyran -3- base) -4-
Fluorophenyl carbamate (3fb): yield: 63%；83:17dr；Yellow solid；m.p.84-86℃；1H NMR(400 MHz,CDCl3)
δ (ppm): 8.05-7.92 (m, 1H), 7.13 (d, J=8.8Hz, 1H), 6.99-6.89 (m, 1H), 6.87-6.80 (m, 1H),
6.74(s,2H),6.59–6.53(m,1H),6.48–6.43(m,1H),5.09 (s,1H),4.91–4.81(m,1H),4.58
(d, J=11.4Hz, 1H), 3.85 (s, 3H), 3.67 (s, 3H), 1.30 (s, 18H)；13C NMR(100MHz,CDCl3)δ
(ppm): 168.5,166.5,164.4 (J=252.4Hz), 156.2,152.9,145.4,142. (J=8.7Hz), 136.1,
133.8 (J=9.2Hz), 129.3,127.1,125.5,117.7,114.2 (J=21.1Hz), 113.9,113.8,56.1,
55.7,52.3,48.4,34.3,30.2；IR(KBr): 3603,3130,2964,1767,1715,1400,1261,1122,
802,724,612cm-1；ESI FTMS: (C32H35FO6+Na)+m/z 557.2316,found m/z 557.2339.
Embodiment 15
It is that reaction is former with formula 1f compound (0.1mmol), formula 2c compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3fc with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -6- methoxyl group -2- oxo benzodihydropyran -3- base) -5-
Methyl toluate (3fc): yield: 95%；87:13dr；Yellow solid；m.p.95-98℃；1H NMR (400MHz,
CDCl3)δ(ppm):7.81–7.71(m,1H),7.14–7.06(m,2H),6.86–6.79(m, 1H),6.78–6.69(m,
3H), 6.51-6.43 (m, 1H), 5.06 (s, 1H), 4.92-4.73 (m, 1H), 4.56 (d, J=10.5Hz, 1H), 3.85 (s,
3H),3.67(s,3H),2.29(s,3H),1.30(s,18H)；13C NMR (100MHz,CDCl3)δ(ppm):169.3,
167.6,156.1,152.7,145.6,137.1,135.8,135.5, 132.8,131.8,131.1,129.9,128.6,
127.1,125.5,117.6,113.9,113.8,55.7,52.1,48.6, 34.2,30.2,30.0,20.8；IR(KBr):
3566,3127,2953,1757,1705,1489,1400,1259, 1207,1142,950,809cm-1；ESI FTMS:
(C33H38O6+Na)+requires m/z 553.2566,found m/z 553.2589.
Embodiment 16
It is that reaction is former with formula 1f compound (0.1mmol), formula 2d compound (0.3mmol) in meta-xylene system
Material, preparation process obtain product 3fd with embodiment 1.
2- (4- (3,5- di-tert-butyl-hydroxy phenyl) -6- methoxyl group -2- oxo benzodihydropyran -3- base) -5-
Fluorophenyl carbamate (3fd): yield: 71%；77:23dr；Yellow solid；m.p.97-99℃；1H NMR(400 MHz,CDCl3)
δ (ppm): 7.67-7.63 (m, 1H), 7.12 (d, J=8.9Hz, 1H), 7.04-6.96 (m, 1H), 6.87-6.80 (m, 2H),
6.73 (s, 2H), 6.48-6.42 (m, 1H), 5.09 (s, 1H), 4.86 (d, J=10.8 Hz, 1H), 4.56 (d, J=11.2
Hz,1H),3.86(s,3H),3.67(s,3H),1.31(s,18H)；13C NMR(100 MHz,CDCl3)δ(ppm):168.9,
(166.4,166.3,161.2 J=246.0 Hz), 156.1,152.9,145.5,136.0,134.5 (J=3.6 Hz),
130.6 (J=7.1 Hz), 129.4,128.0 (J=17.9 Hz), 127.2,125.5,119.0 (J=21.0 Hz), 118.0
(J=23.3 Hz), 117.7,117.6,113.9,113.8,55.7,52.5,48.6,47.7,34.3,30.2；IR(KBr):
3362,2975,2900,1653,1401,1088, 1049,881,669 cm-1；ESI FTMS:(C32H35FO6+Na)+m/z
557.2316,found m/z 557.2333。
Claims (6)
1. the dihydrocoumarin derivative that a kind of 4- (3,5- di-t-butyl -4- hydroxyphenyl) replaces, which is characterized in that have formula 3
Shown in structural formula:
In formula, R1Selected from hydrogen or methoxyl group, R2Selected from one of hydrogen, methoxyl group, bromine, R3Selected from hydrogen, methoxyl group, methyl, tertiary fourth
One of base, chlorine, fluorine, bromine, R4Selected from hydrogen or fluorine, R5Selected from one of hydrogen, methyl, fluorine.
2. a kind of system for the dihydrocoumarin derivative that 4- described in claim 1 (3,5- di-t-butyl -4- hydroxyphenyl) replaces
Preparation Method, which is characterized in that comprise the concrete steps that: being that reaction is former with 1 compound of formula, 2 compound of formula in organic solvent system
Material, is stirred to react 16~96h at 30 DEG C, after monitoring fully reacting by thin-layered chromatography, adds trimethyl silicane diazonium first
Alkane and methanol, are stirred for 0.5h, to by thin-layered chromatography separating-purifying, obtain 3 compound of formula after reaction；
The structural formula of 1 compound of formula isIn formula, R1Selected from hydrogen or methoxyl group, R2Selected from hydrogen, first
One of oxygroup, bromine, R3Selected from one of hydrogen, methoxyl group, methyl, tert-butyl, chlorine, fluorine, bromine；
The structural formula of 2 compound of formula isIn formula, R4Selected from hydrogen or fluorine, R5Selected from hydrogen, methyl, fluorine
One of.
3. the system for the dihydrocoumarin derivative that 4- (3,5- di-t-butyl -4- hydroxyphenyl) according to claim 2 replaces
Preparation Method, which is characterized in that 1 compound of formula, 2 compound of formula molar ratio be 1:3.
4. the dihydrocoumarin derivative that 4- (3,5- di-t-butyl -4- hydroxyphenyl) according to claim 2 or 3 replaces
Preparation method, which is characterized in that the molal volume ratio of 1 compound of formula and the trimethyl silicane diazomethane is 1mmol:
The molal volume ratio of 2mL, 1 compound of formula and the methanol is 1mmol:0.4mL.
5. the dihydrocoumarin derivative that 4- (3,5- di-t-butyl -4- hydroxyphenyl) according to claim 2 or 3 replaces
Preparation method, which is characterized in that the organic solvent is meta-xylene.
6. the dihydrocoumarin derivative that 4- (3,5- di-t-butyl -4- hydroxyphenyl) according to claim 2 or 3 replaces
Preparation method, which is characterized in that the solvent that the thin-layered chromatography uses is petrol ether/ethyl acetate=4/1, V/V.
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