CN104829583A - A preparing method of tetrahydro benzopyran derivatives - Google Patents
A preparing method of tetrahydro benzopyran derivatives Download PDFInfo
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- CN104829583A CN104829583A CN201510132441.1A CN201510132441A CN104829583A CN 104829583 A CN104829583 A CN 104829583A CN 201510132441 A CN201510132441 A CN 201510132441A CN 104829583 A CN104829583 A CN 104829583A
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- 238000000034 method Methods 0.000 title abstract description 9
- CUEVICGNKLQJPW-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-chromene Chemical class C1=CCC2CCCOC2=C1 CUEVICGNKLQJPW-UHFFFAOYSA-N 0.000 title abstract 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 39
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 17
- 150000003934 aromatic aldehydes Chemical class 0.000 claims abstract description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 4
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 31
- 241001136616 Methone Species 0.000 claims description 24
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 claims description 10
- 239000001116 FEMA 4028 Substances 0.000 claims description 10
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 10
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 10
- 229960004853 betadex Drugs 0.000 claims description 10
- -1 phenyl aldehyde Chemical class 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- ZXJUGAOBVOUBLB-UHFFFAOYSA-N 5,6,7,8-tetrahydro-4h-chromene Chemical compound C1C=COC2=C1CCCC2 ZXJUGAOBVOUBLB-UHFFFAOYSA-N 0.000 claims description 7
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 6
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 claims description 6
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 claims description 5
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 claims description 5
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 claims description 5
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 5
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 claims description 5
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 claims description 5
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims description 5
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims description 5
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 5
- 239000002994 raw material Substances 0.000 abstract description 17
- 238000001953 recrystallisation Methods 0.000 abstract description 14
- 238000004440 column chromatography Methods 0.000 abstract 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 230000003292 diminished effect Effects 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000001291 vacuum drying Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- UQQROBHFUDBOOK-UHFFFAOYSA-N 2-bromo-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC(Br)=C(C=O)C=C1OC UQQROBHFUDBOOK-UHFFFAOYSA-N 0.000 description 1
- MLIREBYILWEBDM-UHFFFAOYSA-M 2-cyanoacetate Chemical compound [O-]C(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-M 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical class C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 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
- C07D311/74—Benzo[b]pyrans, hydrogenated in the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
A preparing method of tetrahydro benzopyran derivatives is disclosed. The method adopts cyclodextrin as a catalyst, adopts aromatic aldehyde, dimedone and malononitrile as raw materials and adopts water, ethanol or methanol as a solvent. A reaction is performed at 15-30 DEG C, and the tetrahydro benzopyran derivatives can be prepared by recrystallization or column chromatography separation after the reaction is finished. The method is mild in reaction conditions, short in process steps, simple and convenient in operation, low in cost and high in yield, and has a good industrial application prospect.
Description
Technical field
The present invention relates to a kind of preparation method of tetrahydro benzo pyrans, specifically 2-Amino 3 cyano-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysene-4
hthe preparation method of-chromene series derivatives compound, belongs to organic synthesis field.
Background technology
It is active that chromene (or tetrahydro benzo pyrans) compounds has physiological and pharmacological widely, as antitumor (Tumor Biol., 2014,35,5845-5855; Bioorg. Med. Chem. Lett., 2012,4458-4461.), anti-oxidant (Med. Chem. Res., 2014,23,4907-4914.), antibacterial (Med. Chem. Res., 2014,23,3569-3584.; Med. Chem. Res., 2014,23,2955-2963.) and antimicrobial (Med. Chem. Res., 2013,22,3831-3842.) etc.
At present, the method for synthesizing benzopyrans compounds has many reports.As the addition under the catalysis of Potassium monofluoride or proline(Pro) of aromatic aldehyde and cyan-acetic ester is first obtained 2-cyano group-3-aryl-acrylic acid esters by (CN 102424675 B) such as Han Guangfan, obtained 2-amino-5-oxo-4-aryl-5,6 is reacted again with hydroresorcinol, 7,8-tetrahydrochysene-4
h-chromene-3-acid ethyl ester derivatives, last and propane dinitrile in a solvent catalysis obtains 2-Amino 3 cyano-5-oxo-5,6,7,8-tetrahydrochysene-4
h-1-benzopyran derivatives.History reaches and waits clearly (organic chemistry, 2002,22,1053-1056.) to be reacted in DMF by salicylic aldehyde, cyanoacetate and catalyzer Potassium monofluoride/aluminum oxide and prepare 4
h-benzopyrans compounds.Luo etc. (Chem. Commun., 2009,2878-2880.) have prepared a kind of novel ionic liquid PEG
1000-DAIL with aromatic aldehyde, methone and propane dinitrile for raw material is at toluene and PEG
1000in the mixed solvent of-DAIL, heating prepares 1-benzopyran derivatives.Although above method has respective advantage, but still there is obvious shortcoming, as long in reaction scheme, substrate not easily obtain, use noxious solvent and temperature of reaction more high.
Summary of the invention
The technical problem to be solved in the present invention is: provide a kind of reaction conditions gentleness, operational path is short, easy and simple to handle, cost is low and the method preparing tetrahydro benzo pyran derivative compound that yield is high, in the presence of a catalyst, aromatic aldehyde, methone and propane dinitrile are placed in solvent react, 2-Amino 3 cyano-4-aryl-7 is obtained by separation and purification after having reacted, 7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysene-4
h-chromene series derivates.
Described catalyzer is alpha-cylodextrin, beta-cyclodextrin or γ-cyclodextrin, and the mol ratio of aromatic aldehyde and catalyzer is 1:0.01 ~ 0.1.
Described aromatic aldehyde is phenyl aldehyde, p-tolyl aldehyde, 4-chloro-benzaldehyde, p-Fluorobenzenecarboxaldehyde, 3,4-dichlorobenzaldehyde, 3-hydroxy benzaldehyde, 3-pyridylaldehyde, 2 furan carboxyaldehyde, Ortho Nitro Benzaldehyde, m-nitrobenzaldehyde, paranitrobenzaldehyde, 3,4-dimethoxy benzaldehyde, 2-bromo-4,5-dimethoxy phenyl aldehyde, terephthalaldehyde or m-terephthal aldehyde.
Described solvent is the one in methyl alcohol, second alcohol and water, and temperature of reaction is 15 ~ 30 DEG C.
The mol ratio of described methone and propane dinitrile is 1:1.
Described when aromatic aldehyde be phenyl aldehyde, p-tolyl aldehyde, 4-chloro-benzaldehyde, p-Fluorobenzenecarboxaldehyde, 3,4-dichlorobenzaldehyde, 3-hydroxy benzaldehyde, 3-pyridylaldehyde, 2 furan carboxyaldehyde, Ortho Nitro Benzaldehyde, m-nitrobenzaldehyde, paranitrobenzaldehyde, 3,4-dimethoxy benzaldehyde or 2-bromo-4, during 5-dimethoxy benzaldehyde, the mol ratio of aromatic aldehyde and methone is 1:1 ~ 1:1.2; When aromatic aldehyde be terephthalaldehyde or m-terephthal aldehyde time, the mol ratio of aromatic aldehyde and methone is 1:2 ~ 1:2.4.
Described aromatic aldehyde and 2-Amino 3 cyano-4-aryl-7,7-dimethyl-5-oxo-5,6,7, the 8-tetrahydrochysene-4 prepared
h-chromene series compound corresponds to: (1) phenyl aldehyde, 2-Amino 3 cyano-4-phenyl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysene-4
h-chromene; (2) p-tolyl aldehyde, 2-Amino 3 cyano-4-(4-aminomethyl phenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (3) 4-chloro-benzaldehyde, 2-Amino 3 cyano-4-(4-chloro-phenyl-)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (4) p-Fluorobenzenecarboxaldehyde, 2-Amino 3 cyano-4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (5) 3,4-dichlorobenzaldehydes, 2-Amino 3 cyano-4-(3,4-dichlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (6) 3-hydroxy benzaldehyde, 2-Amino 3 cyano-4-(3-hydroxy phenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (7) 3-pyridylaldehyde, 2-Amino 3 cyano-4-(3-pyridyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (8) 2 furan carboxyaldehyde, 2-Amino 3 cyano-4-(2-furyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (9) Ortho Nitro Benzaldehyde, 2-Amino 3 cyano-4-(2-nitrophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (10) m-nitrobenzaldehyde, 2-Amino 3 cyano-4-(3-nitrophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (11) paranitrobenzaldehyde, 2-Amino 3 cyano-4-(4-nitrophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (12) Veratraldehyde, 2-Amino 3 cyano-4-(3,4-Dimethoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (13) 2-bromo-4,5-dimethoxy phenyl aldehyde, 2-Amino 3 cyano-4-(2-bromo-4,5-dimethoxy phenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrochysenes-4
h-chromene; (14) terephthalaldehyde, Isosorbide-5-Nitrae-two (2-Amino 3 cyano-5,6,7,8-tetrahydrochysene-5-oxo-7,7 ,-dimethyl-4-(4H-benzo [b] pyrans-4-base) benzene; (15) m-terephthal aldehyde, 1,3-bis-(2-Amino 3 cyano-5,6,7,8-tetrahydrochysene-5-oxo-7,7-dimethyl-4-(4H-benzo [b] pyrans-4-base) benzene.
Described separation and purification means are silica gel column chromatography (eluent is petrol ether/ethyl acetate mixed solvent) or ethanol (mass percent concentration 95%) recrystallization.
The inventive method reaction conditions is gentle, operational path is short, easy and simple to handle, cost is low, and yield can reach 80 ~ 95%.
Embodiment
Below with reference to embodiment, the invention will be further described.Embodiments of the invention are only for illustration of technical scheme of the present invention, and non-limiting the present invention.
Embodiment 1
Take phenyl aldehyde 106 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 25 DEG C, react about 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, purification by silica gel column chromatography, petrol ether/ethyl acetate system wash-out (sherwood oil: the volume ratio of ethyl acetate is 10:1), evaporated under reduced pressure obtains product 2-Amino 3 cyano-4-phenyl-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 280 mg, yield 95%,
Product structure characterizes:
Fusing point: 230-235 DEG C; IR (KBr) cm
-1: 3403 (NH
2), 2962 (C-H), 2216 (CN), 1677 (C=O), 1664 (C=C), 1593 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.27 (t, J=7.3 Hz, 2H, ArH), 7.20-7.12 (m, 3H, ArH), 6.98 (s, 2H, NH
2), 4.15 (s, 1H), 2.51 (s, 2H, H-8), 2.25 (d, J=16.1 Hz, 1H, H-6), 2.10 (d, J=16.1 Hz, 1H, H-6 '), 1.02 (s, 3H), 0.94 (s, 3H); HRMS (ESI) m/z:calcd for C
18h
18n
2naO
2[M+Na
+]: 317.1266, found [M+Na
+]: 317.1259.
Embodiment 2
Take p-tolyl aldehyde 120 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL ethanol, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 11.3 mg(0.01 mmol) stir at 25 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(4-aminomethyl phenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 290 mg, yield 94%,
Product structure characterizes:
Fusing point: 235 DEG C; IR (KBr) cm
-1: 3383 (NH
2), 2968 (C-H), 2190 (CN), 1690 (C=O), 1645 (C=C), 1606 (C=C);
1h NMR (500 MHz, DMSO-d6): δ 7.07 (d, 2H, ArH), 7.01-7.00 (d, 2H, ArH), 6.94 (s, 2H, NH
2), 4.11 (s, 1H), 2.53 (d, 1H, H-8), 2.48 (d, 1H, H-8 '), 2.24-2.21 (d, 1H, H-6), 2.23 (s, 3H, CH
3), 2.09 (d, 1H, H-6 '), 1.01 (s, 3H), 0.93 (s, 3H); HRMS (ESI) m/z calcd for C
19h
20n
2naO
2[M+Na]
+: 331.1422, found [M+Na
+]: 331.1423.
Embodiment 3
Take 4-chloro-benzaldehyde 140 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL ethanol, be uniformly mixed, add propane dinitrile 79.2 mg(1.2 mmol more wherein successively), methone 168 mg(1.2 mmol), alpha-cylodextrin 48.7 mg(0.05 mmol) stir at 15 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(4-chloro-phenyl-)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 294 mg, yield 90%,
Product structure characterizes:
Fusing point: 225 DEG C; IR (KBr) cm
-1: 3448 (NH
2), 3040 (C-H), 2242 (CN), 1600 (C=O), 1593 (C=C), 1487 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.34 (d, J=8.4 Hz, 2H, ArH), 7.16 (d, J=8.4 Hz, 2H, ArH), 7.04 (s, 2H, NH
2), 4.17 (s, 1H), 2.48 (s, 2H, H-8), 2.25 (d, J=16.1 Hz, 1H, H-6), 2.10 (d, J=16.1 Hz, 1H, H-6 '), 1.01 (s, 3H), 0.93 (s, 3H); HRMS (ESI) m/z:calcd for C
18h
18clN
2o
2[M+H]
+: 329.1057, found [M+H
+]: 329.1050.
Embodiment 4
Take p-Fluorobenzenecarboxaldehyde 124 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 113.5 mg(0.1 mmol) stir at 25 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(4-fluorophenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 289 mg, yield 93%,
Product structure characterizes:
Fusing point: 196 DEG C; IR(KBr) cm
-1: 3448 (NH
2), 3046 (C-H), 2242 (CN), 1606 (C=O), 1580 (C=C), 1522 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.19 (d, J=8.4 Hz, 2H, ArH), 7.07 (d, J=8.4 Hz, 2H, ArH), 7.04 (s, 2H, NH2), 4.19 (s, 1H), 2.48 (s, 2H, H-8), 2.24 (d, J=16.1 Hz, 1H, H-6), 2.10 (d, J=16.1 Hz, 1H, H-6 '), 1.01 (s, 3H), 0.93 (s, 3H); HRMS (ESI) m/z calcd for C
18h
17fN
2naO
2[M+Na]
+: 335.1172, found [M+Na]
+: 335.2535.
Embodiment 5
Take 3, 4-dichlorobenzaldehyde 174 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 30 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(3, 4-dichlorophenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 336 mg, yield 92%,
Product structure characterizes:
Fusing point: 225-230 DEG C; IR (KBr) cm
-1: 3409 (NH
2), 2955 (C-H), 2203 (CN), 1677 (C=O), 1613 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.56 (d, 1H, ArH), 7.37 (d, 1H, ArH), 7.14 (d, 1H, ArH), 7.12 (s, 2H, NH
2), 4.23 (s, 1H), 2.48 (dd, 2H, H-8), 2.24-2.21 (d, 1H, H-6), 2.12-2.09 (d, 1H, H-6 '), 1.01 (s, 3H), 0.94 (s, 3H); HRMS (ESI) m/z calcd for C
18h
17cl
2n
2o
2[M+H]
+: 363.0667, found [M+H]
+: 363.0642.
Embodiment 6
Take 3-hydroxy benzaldehyde 122 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 66.0 mg(1.0 mmol more wherein successively), methone 140.0 mg(1.0 mmol), γ-cyclodextrin 77.8 mg(0.06 mmol) stir at 25 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(3-hydroxy phenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 287 mg, yield 93%,
Product structure characterizes:
Fusing point: 295-300 DEG C; IR (KBr) cm
-1: 3461 (OH), 3318,3208 (NH
2), 2203 (CN), 1684 (C=O), 1645 (C=C), 1600 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 9.32 (s, 1H, OH), 7.06 (t, 1H, ArH), 6.96 (s, 2H, NH
2), 6.56 (m, 3H, ArH), 4.04 (s, 1H), 2.54 (d, 1H, H-8), 2.46 (d, 1H, H-8 '), 2.25 (d, 1H, H-6), 2.10 (d, 1H, H-6 '), 1.02 (s, 3H), 0.95 (s, 3H); HRMS (ESI) m/z:calcd for C
18h
18n
2naO
3[M+Na]
+: 333.1215, found [M+Na]
+: 333.1191.
Embodiment 7
Take 3-pyridylaldehyde 107 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL methyl alcohol, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), alpha-cylodextrin 77.8 mg(0.08 mmol) stir at 20 DEG C, react 5 hours, TLC detects without raw material, separate out a large amount of yellow solid in reaction solution, filtration under diminished pressure obtains pale yellow powder shape solid, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtain product (
15) 269 mg, yield 91%;
Product structure characterizes:
Fusing point 255-256 DEG C; IR (KBr) cm
-13325 (NH
2), 2949 (C-H), 2196 (CN), 1690 (C=O), 1671 (C=C), 1600 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 8.39 (dd, 2H, ArH), 7.53-7.51 (m, 1H, ArH), 7.32-7.30 (dd, 1H, ArH), 7.10 (s, 2H, NH
2), 4.23 (s, 1H), 2.51 (s, 2H, H-8), 2.25 (d, J=16.1 Hz, 1H, H-6), 2.12 (d, J=16.1 Hz, 1H, H-6 '), 1.02 (s, 3H), 0.93 (s, 3H); HRMS (ESI) m/z:calcd for C
17h
18n
3o
2[M+H]
+: 296.1399, found [M+H]
+: 296.7947.
Embodiment 8
Take 2 furan carboxyaldehyde 96 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 25 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(2-furyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 258 mg, yield 91%,
Product structure characterizes:
Fusing point: 225-226 DEG C; IR (KBr) cm
-1: 3403 (NH
2), 2955 (C-H), 2196 (CN), 1690 (C=O), 1677 (C=C), 1613 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.46 (s, 1H, furan-H), 7.06 (s, 2H, NH
2), 6.31 (dd, 1H, furan-H), 6.04 (d, 1H, furan-H), 4.31 (s, 1H), 2.53 (d, 1H, H-8), 2.44 (d, 1H, H-8 '), 2.28 (d, 1H, H-6), 2.17 (d, 1H, H-6 '), 1.02 (s, 3H), 0.97 (s, 3H); HRMS (ESI) m/z:calcd for C
16h
16n
2naO
3[M+Na]
+: 307.1059, found [M+Na]
+: 307.1037.
Embodiment 9
Take 2-nitrobenzaldehyde 151 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 79.2 mg(1.2 mmol more wherein successively), methone 168 mg(1.2 mmol), γ-cyclodextrin 13.0 mg(0.01 mmol) stir at 18 DEG C, react 5 hours, TLC detects without raw material, a large amount of yellow solid is separated out in reaction solution, filtration under diminished pressure obtains pale yellow powder shape solid, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(2-nitrophenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 245 mg, yield 86%,
Product structure characterizes:
Fusing point: 232-234 DEG C; IR (KBr) cm
-1: 3481 (NH
2), 2955 (C-H), 2203 (CN), 1697 (C=O), 1677 (C=C), 1606 (C=C), 1541 (NO
2);
1h NMR (400 MHz, DMSO-d
6): δ 7.81 (d, J=8.1 Hz, 1H), 7.66 (t, J=7.3 Hz, 1H), 7.42 (t, J=7.7 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.17 (s, 2H), 4.93 (s, 1H), 2.50 (s, 2H), 2.20 (d, J=16.1 Hz, 1H), 2.01 (d, J=16.1 Hz, 1H), 1.01 (s, 3H), 0.88 (s, 3H); HRMS (ESI) m/z:calcd for C
18h
17n
3naO
4[M+Na]
+: 362.1117, found [M+Na]
+: 362.1101.
Embodiment 10
Take 3-nitrobenzaldehyde 151 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 25 DEG C, react 5 hours, TLC detects without raw material, a large amount of yellow solid is separated out in reaction solution, filtration under diminished pressure obtains pale yellow powder shape solid, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(3-nitrophenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 308 mg, yield 91%,
Product structure characterizes:
Fusing point: 206-208 DEG C; IR (KBr) cm
-1: 3440 (NH
2), 2968 (C-H), 2190 (CN), 1690 (C=O), 1613 (C=C), 1528 (NO
2);
1h NMR (500 MHz, DMSO-d
6): δ 8.10-8.04 (m, 2H, ArH), 7.48-7.68 (m, 2H, ArH), 6.04 (brs, 2H, NH
2), 4.53 (s, 1H), 2.48 (d, 2H, H-8), 2.29 (d, J=16.1 Hz, 1H, H-6), 2.17 (d, J=16.1 Hz, 1H, H-6 '), 1.11 (s, 3H), 1.03 (s, 3H); HRMS (ESI) m/z:calcd for C
18h
17n
3naO
4[M+Na]
+: 362.1117, found [M+Na]
+: 362.1111.
Embodiment 11
Take 4-nitrobenzaldehyde 151 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL ethanol, be uniformly mixed, add propane dinitrile 69.3 mg(1.05 mmol more wherein successively), methone 147 mg(1.05 mmol), alpha-cylodextrin 48.7 mg(0.05 mmol) stir at 30 DEG C, react 5 hours, TLC detects without raw material, a large amount of yellow solid is separated out in reaction solution, filtration under diminished pressure obtains pale yellow powder shape solid, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(4-nitrophenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 272 mg, yield 80%,
Product structure characterizes:
Fusing point: 150-153 DEG C; IR (KBr) cm
-1: 3409 (NH
2), 2962 (C-H), 2196 (CN), 1697 (C=O), 1671 (C=C), 1600 (C=C), 1522 (NO
2);
1h NMR (400 MHz, DMSO-d
6): δ 8.17 (d, J=8.1 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H), 7.17 (s, 2H), 4.36 (s, 1H), 2.50 (s, 2H), 2.26 (d, J=15.7 Hz, 1H), 2.11 (d, J=15.7 Hz, 1H), 1.04 (s, 3H), 0.96 (s, 3H); HRMS (ESI) m/z calcd for C
18h
18n
3o
4[M+H]
+: 340.1297, found [M+H]
+: 340.1272.
Embodiment 12
Take 3, 4-dimethoxy benzaldehyde 166 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 69.3mg(1.05 mmol wherein successively again), methone 147 mg(1.05 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 25 DEG C, react about 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(3, 4-Dimethoxyphenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 318 mg, yield 90%,
Product structure characterizes:
Fusing point: 206-208 DEG C; IR (KBr) cm
-1: 3409 (NH
2), 2962 (C-H), 2203 (CN), 1697 (C=O), 1658 (C=C), 1606 (C=C);
1h NMR (400 MHz, DMSO-d
6): δ 6.96 (s, 2H), 6.87 – 6.85 (d, 1H, J=8.4 Hz), 6.69 – 6.68 (d, J=2.0 Hz, 1H), 6.66 – 6.64 (dd, J=2.0,8.0 Hz, 1H), 4.12 (s, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 2.52-2.49 (m, 2H), 2.28-2.08 (m, 2H), 1.03 (s, 3H), 0.97 (s, 3H); HRMS (ESI) m/z:calcd for C
20h
22n
2naO
4[M+Na]
+: 377.1477, found [M+Na]
+: 377.1472.
Embodiment 13
Take 2-bromo-4, 5-dimethoxy benzaldehyde 243 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL ethanol, be uniformly mixed, add propane dinitrile 72.6 mg(1.1 mmol more wherein successively), methone 154 mg(1.1 mmol), γ-cyclodextrin 259.4 mg(0.2 mmol) stir under 20 ° of C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, ethanol (95%, mass percent concentration) recrystallization, vacuum-drying obtains product 2-Amino 3 cyano-4-(2-bromo-4, 5-Dimethoxyphenyl)-7, 7-dimethyl-5-oxo-5, 6, 7, 8-tetrahydrochysene-4
h-chromene 401 mg, yield 93%,
Product structure characterizes:
Fusing point: 186 DEG C; IR (KBr) cm
-1: 3487 (NH
2), 2968 (C-H), 2190 (CN), 1671 (C=O), 1638 (C=C), 1593 (C=C); 1H NMR (500 MHz, DMSO-d
6): δ 6.98 (s, 1H, ArH), 6.65 (s, 1H, ArH), 4.77 (s, 1H), 4.66 (brs, 2H, NH
2), 3.84 (s, 3H), 3.82 (s, 3H), 2.52-2.39 (dd, 2H, H-8), 2.29 (d, J=16.1 Hz, 1H, H-6), 2.17 (d, J=16.1 Hz, 1H, H-6 '), 1.12 (s, 3H), 1.09 (s, 3H); HRMS (ESI) m/z:calcd for C
20h
21brN
2naO
4[M+Na]
+: 455.0582, found [M+Na]
+: 455.0577.
Embodiment 14
Take terephthalaldehyde 134 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL methyl alcohol, be uniformly mixed, add propane dinitrile 158.4 mg(2.4 mmol more wherein successively), methone 336 mg(2.4 mmol), γ-cyclodextrin 51.9 mg(0.04 mmol) stir under 25 ° of C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, purification by silica gel column chromatography, petrol ether/ethyl acetate system wash-out (sherwood oil: the volume ratio of ethyl acetate is 20:1), evaporated under reduced pressure obtains product 1, 4-bis-(2-Amino 3 cyano-5, 6, 7, 8-tetrahydrochysene-5-oxo-7, 7,-dimethyl-4-(4H-benzo [b] pyrans-4-base) benzene 480 mg, yield 94%,
Product structure characterizes:
Fusing point: 300-310 DEG C; IR (KBr) cm
-13435 (NH
2), 2942 (C-H), 2235 (CN), 1606 (C=O), 1590 (C=C), 1496 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.04 (s, 4H, ArH), 6.97 (s, 4H, 2 × NH
2), 4.14 (s, 2H), 2.56 (d, 2H, H-8), 2.47 (d, 2H, H-8 '), 2.25 (d, 2H, H-6), 2.18 (d, 2H, H-6 '), 1.03 (s, 6H), 0.98 (s, 6H); HRMS (ESI) m/z:calcd for C
30h
30n
4o
4[M+Na]
+: 533.2165, found [M+Na]
+: 533.7909.
Embodiment 15
Take m-terephthal aldehyde 134 mg(1.0 mmol) in single neck bottle of 25 mL, add 5 mL water, be uniformly mixed, add propane dinitrile 138.6 mg(2.10 mmol more wherein successively), methone 294 mg(2.10 mmol), beta-cyclodextrin 22.7 mg(0.02 mmol) stir at 30 DEG C, react 5 hours, TLC detects without raw material, a large amount of white solid is separated out in reaction solution, filtration under diminished pressure obtains white powdery solids, purification by silica gel column chromatography, petrol ether/ethyl acetate system wash-out (sherwood oil: the volume ratio of ethyl acetate is Re:20:1), evaporated under reduced pressure obtains product 1, 3-bis-(2-Amino 3 cyano-5, 6, 7, 8-tetrahydrochysene-5-oxo-7, 7-dimethyl-4-(4H-benzo [b] pyrans-4-base) benzene 423 mg, yield 83%,
Product structure characterizes:
Fusing point: 300 DEG C (decomposition); IR (KBr) cm
-1: 3455 (NH
2), 2942 (C-H), 2248 (CN), 1613 (C=O), 1574 (C=C), 1483 (C=C);
1h NMR (500 MHz, DMSO-d
6): δ 7.02-6.92 (m, 4H, ArH), 6.79 (brs, 4H, 2 × NH
2), 4.11 (s, 2H), 2.61 (d, 2H, H-8), 2.47 (d, 2H, H-8 '), 2.15 (d, 2H, H-6), 2.02 (d, 2H, H-6 '), 1.03 (s, 6H), 0.95 (s, 6H); HRMS (ESI) m/z:calcd for C
30h
30n
4o
4[M+Na]
+: 533.2165, found [M+Na]
+: 533.7487.
Claims (6)
1. a preparation method for tetrahydro benzo pyran derivate, is characterized in that: in the presence of a catalyst, aromatic aldehyde, methone and propane dinitrile is placed in solvent and reacts, 2-Amino 3 cyano-4-aryl-7,7-dimethyl-5-oxo-5,6 is obtained by separation and purification after having reacted, 7,8-tetrahydrochysene-4
h-chromene series derivates.
2. the preparation method of tetrahydro benzo pyran derivate according to claim 1, is characterized in that: described catalyzer is alpha-cylodextrin, beta-cyclodextrin or γ-cyclodextrin, and the mol ratio of aromatic aldehyde and catalyzer is 1:0.01 ~ 0.1.
3. the preparation method of tetrahydro benzo pyran derivate according to claim 1 and 2, it is characterized in that: described aromatic aldehyde is phenyl aldehyde, p-tolyl aldehyde, 4-chloro-benzaldehyde, p-Fluorobenzenecarboxaldehyde, 3,4-dichlorobenzaldehyde, 3-hydroxy benzaldehyde, 3-pyridylaldehyde, 2 furan carboxyaldehyde, Ortho Nitro Benzaldehyde, m-nitrobenzaldehyde, paranitrobenzaldehyde, 3, one in 4-dimethoxy benzaldehyde, 2-bromo-4,5-dimethoxy phenyl aldehyde, terephthalaldehyde, m-terephthal aldehyde.
4. the preparation method of tetrahydro benzo pyran derivate according to claim 3, is characterized in that: described solvent is in methyl alcohol, ethanol or water, and temperature of reaction is 15 ~ 30 DEG C.
5. the preparation method of tetrahydro benzo pyran derivate according to claim 4, is characterized in that: when aromatic aldehyde be terephthalaldehyde or m-terephthal aldehyde time, the mol ratio of aromatic aldehyde and methone is 1:2 ~ 1:2.4; The mol ratio of remaining aromatic aldehyde and methone is 1:1 ~ 1:1.2.
6. the preparation method of tetrahydro benzo pyran derivate according to claim 5, is characterized in that: the mol ratio of methone and propane dinitrile is 1:1.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109136935A (en) * | 2018-10-25 | 2019-01-04 | 西南石油大学 | A kind of purposes of pyran derivate and preparation method thereof |
| CN110105317A (en) * | 2019-06-06 | 2019-08-09 | 四川大学 | A kind of synthetic method of 2- amino -4H- pyrans and its derivative |
| CN110252400A (en) * | 2019-06-21 | 2019-09-20 | 华侨大学 | A kind of preparation method of walnut shell graft beta-cyclodextrin type catalyst and 2- Amino 3 cyano -4H- pyran derivate |
-
2015
- 2015-03-25 CN CN201510132441.1A patent/CN104829583A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| ISMAIL ABULKALAM AZATH ET AL.: "One-Pot Multicomponent Solvent-Free Synthesis of 2-Amino-4Hbenzo[b]pyrans Catalyzed by Per-6-amino-β-cyclodextrin", 《ACS SUSTAINABLE CHEMISTRY & ENGINEERING》 * |
| SIDDHARTH R KAMAT ET AL.: "β -CYCLODEXTRIN – GLYCERIN AS A VERSATILE GREEN SYSTEM FOR SYNTHESIS OF 2-AMINO-TETRAHYDRO-4H-CHROMENES", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES》 * |
| 张伟: "金鸡纳碱衍生的催化剂及环糊精催化的三组分反应", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109136935A (en) * | 2018-10-25 | 2019-01-04 | 西南石油大学 | A kind of purposes of pyran derivate and preparation method thereof |
| CN109136935B (en) * | 2018-10-25 | 2021-03-23 | 西南石油大学 | Application and preparation method of pyran derivative |
| CN110105317A (en) * | 2019-06-06 | 2019-08-09 | 四川大学 | A kind of synthetic method of 2- amino -4H- pyrans and its derivative |
| CN110105317B (en) * | 2019-06-06 | 2021-03-16 | 四川大学 | Synthesis method of 2-amino-4H-pyran and derivatives thereof |
| CN110252400A (en) * | 2019-06-21 | 2019-09-20 | 华侨大学 | A kind of preparation method of walnut shell graft beta-cyclodextrin type catalyst and 2- Amino 3 cyano -4H- pyran derivate |
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