CN108440264A - A kind of synthetic method of isoliquiritigenin - Google Patents
A kind of synthetic method of isoliquiritigenin Download PDFInfo
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- CN108440264A CN108440264A CN201810373979.5A CN201810373979A CN108440264A CN 108440264 A CN108440264 A CN 108440264A CN 201810373979 A CN201810373979 A CN 201810373979A CN 108440264 A CN108440264 A CN 108440264A
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- Prior art keywords
- isoliquiritigenin
- synthetic method
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- hydroxy
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- JBQATDIMBVLPRB-UHFFFAOYSA-N isoliquiritigenin Natural products OC1=CC(O)=CC=C1C1OC2=CC(O)=CC=C2C(=O)C1 JBQATDIMBVLPRB-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 235000008718 isoliquiritigenin Nutrition 0.000 title claims abstract description 46
- DXDRHHKMWQZJHT-FPYGCLRLSA-N isoliquiritigenin Chemical compound C1=CC(O)=CC=C1\C=C\C(=O)C1=CC=C(O)C=C1O DXDRHHKMWQZJHT-FPYGCLRLSA-N 0.000 title claims abstract description 46
- 238000010189 synthetic method Methods 0.000 title claims abstract description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 43
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- 239000000047 product Substances 0.000 claims abstract description 18
- 238000005882 aldol condensation reaction Methods 0.000 claims abstract description 17
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 claims description 34
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical class OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 20
- 239000007859 condensation product Substances 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000003960 organic solvent Substances 0.000 claims description 16
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003223 protective agent Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000012545 processing Methods 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000002879 Lewis base Substances 0.000 claims description 7
- 150000007527 lewis bases Chemical class 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- ZVVSSOQAYNYNPP-UHFFFAOYSA-N olaflur Chemical compound F.F.CCCCCCCCCCCCCCCCCCN(CCO)CCCN(CCO)CCO ZVVSSOQAYNYNPP-UHFFFAOYSA-N 0.000 claims description 6
- 229960001245 olaflur Drugs 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 150000002460 imidazoles Chemical group 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 239000005457 ice water Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012312 sodium hydride Substances 0.000 claims description 3
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 3
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 claims 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 2
- 239000005046 Chlorosilane Substances 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 claims 1
- 235000009508 confectionery Nutrition 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 150000003462 sulfoxides Chemical class 0.000 claims 1
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000006227 byproduct Substances 0.000 abstract description 3
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 abstract 2
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical class OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 abstract 1
- 239000012074 organic phase Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000005292 vacuum distillation Methods 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- -1 liquorice flavonoids compound Chemical class 0.000 description 3
- LMXSKKDUYFXOEX-UHFFFAOYSA-N 2-chloropropane silane Chemical compound [SiH4].C(C)(C)Cl LMXSKKDUYFXOEX-UHFFFAOYSA-N 0.000 description 2
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 244000303040 Glycyrrhiza glabra Species 0.000 description 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- CRIVIYPBVUGWSC-UHFFFAOYSA-N chloro(propan-2-yl)silane Chemical class CC(C)[SiH2]Cl CRIVIYPBVUGWSC-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- MLNKXLRYCLKJSS-RMKNXTFCSA-N (2e)-2-hydroxyimino-1-phenylethanone Chemical compound O\N=C\C(=O)C1=CC=CC=C1 MLNKXLRYCLKJSS-RMKNXTFCSA-N 0.000 description 1
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 235000011477 liquorice Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- UILPJVPSNHJFIK-UHFFFAOYSA-N p-methoxy-o-hydroxyacetophenone Natural products COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 229920006395 saturated elastomer Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to technical field of organic synthesis, specifically disclose a kind of synthetic method of isoliquiritigenin.The synthetic method of the isoliquiritigenin, with 2,4 hydroxy acetophenones and 4 hydroxy benzaldehydes for raw material, by hydroxyl protection, aldol condensation, hydroxyl deprotection reaction, you can obtain product isoliquiritigenin.The synthetic method of isoliquiritigenin provided by the invention; method is simple and practicable, and reaction condition is mild, securely and reliably; raw material is easy to get; it is cheap, it is at low cost, using at least one of dimethyl tertiary butyl chlorosilane, tri isopropyl chlorosilane to 4 hydroxy benzaldehydes and 2; 4 hydroxyls of 4 resacetophenones carry out hydroxyl protection; the risk that by-product generates is reduced, the yield of isoliquiritigenin is improved, is suitble to industrialized production.
Description
Technical field
The present invention relates to technical field of organic synthesis more particularly to a kind of synthetic methods of isoliquiritigenin.
Background technology
Radix Glycyrrhizae is herbaceos perennial, and the root and rhizome of Radix Glycyrrhizae has tonifying middle-Jiao and Qi, expelling phlegm and arresting coughing, relieving spasm to stop pain, solution
The effect of poison and coordinating the drug actions of a prescription.The active constituent of Radix Glycyrrhizae includes mainly three note saponin(es and a variety of flavones.And isoliquiritigenin is exactly it
In the compound of a kind of chalcone separated from the hydrolysate of licorice.
Isoliquiritigenin is important one of medicinal active ingredient in liquorice flavonoids compound, in multiple pharmacological effect
In show stronger bioactivity, it is such as antitumor, it is antiviral, the effects that Green Tea Extract, anti-arrhythmia.It is wherein antitumor
Activity is the hot spot of Recent study, and research finds that isoliquiritigenin has prevention and inhibits tumour growth, protects liver and kidney, confrontation
Toxic effect caused by chemotherapy.It can inhibit lung cancer, prostate cancer, liver cancer, colon cancer, gastric cancer, the kinds of tumors such as cervical carcinoma are thin
The proliferation of born of the same parents, and be in concentration and time dependence, there can be the suppression of bigger to cancer cell by the isoliquiritigenin of high concentration for a long time
Effect processed.In addition isoliquiritigenin also has the function of potential anti-inflammatory, this will have exploitation novel anti-inflammatory drug important
Meaning.In addition it can also effectively inhibit and kill AIDS virus, enhance human immunity；Inhibit ulcer, the work(such as delaying human body caducity
Energy.It is now widely used for medicine and food service industry, as drug, cosmetics, food additives etc..
So far, report that the document of related isoliquiritigenin synthesis is not very much, the production of synthesizing isoliquiritigenin both at home and abroad
Rate is relatively low, and cost is higher, and reaction condition is more demanding, is not suitable for industrialized production.
Invention content
Relatively low for the yield of existing isoliquiritigenin, the problems such as cost is higher, and reaction condition is more demanding, the present invention provides
A kind of synthetic method of isoliquiritigenin.
To achieve the above object of the invention, the embodiment of the present invention uses the following technical solution：
A kind of synthetic method of isoliquiritigenin, with 2,4-hydroxyacetophenone and 4- hydroxy benzaldehydes are raw material, reactional equation
Formula is as follows：
Wherein, BASE is one kind in imidazoles, diisopropylethylamine；TBAF is tetrabutyl amine fluoride；Hydroxy protecting agent
For at least one of dimethyl tertiary butyl chlorosilane, tri isopropyl chlorosilane；Lewis base be sodium hydroxide, potassium hydroxide,
It is a kind of in sodium hydride, sodium methoxide or sodium ethoxide.
Specific synthesis step is as follows：
(1) 2,4-dihydroxyacetophenone is provided, the 2,4-dihydroxyacetophenone is mixed with alkaline reagent, organic solvent
Afterwards, hydroxy protecting agent is added, is stirred to react under the conditions of 0-100 DEG C, to 4 hydroxyls of the 2,4-dihydroxyacetophenone into
Row hydroxyl protection；
(2) 4- hydroxy benzaldehydes are provided, after the 4- hydroxy benzaldehydes are mixed with alkaline reagent, organic solvent, are added
Hydroxy protecting agent is stirred to react under the conditions of 0-100 DEG C, and hydroxyl protection is carried out to the 4- hydroxy benzaldehydes；
It (3) will be through the 2,4- resacetophenones after step (1) hydroxyl protection, the 4- hydroxyls after step (2) hydroxyl protection
Benzaldehyde mixes in organic solvent, and lewis base is added, is stirred to react under the conditions of 25~100 DEG C, obtains aldol condensation
Product；
(4) Aldol Condensation Products described in step (3) are added in organic solvent, the tetrahydrochysene of tetrabutyl amine fluoride is added
Tetrahydrofuran solution, is stirred to react under the conditions of 10~100 DEG C, carries out deprotection processing to the Aldol Condensation Products, is prepared
Isoliquiritigenin；
Wherein, step (1), the hydroxy protecting agent described in step (2) are independently chosen from dimethyl tertiary butyl chlorosilane, three
At least one of isopropyl chloride silane.
Compared with the existing technology, the synthetic method of isoliquiritigenin provided by the invention, method is simple and practicable, reaction condition temperature
With securely and reliably, raw material is easy to get, cheap, at low cost, using in dimethyl tertiary butyl chlorosilane, tri isopropyl chlorosilane
At least one 4- hydroxyls to 4- hydroxy benzaldehydes and 2,4-dihydroxyacetophenone carry out hydroxyl protection, reduce by-product and generate
Risk, improve the yield of isoliquiritigenin, be suitble to industrialized production.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
The embodiment of the present invention provides a kind of synthetic method of isoliquiritigenin.The synthetic method of the isoliquiritigenin, with 2,4- hydroxyls
Benzoylformaldoxime and 4- hydroxy benzaldehydes are raw material, by hydroxyl protection, aldol condensation, hydroxyl deprotection reaction, you can produced
Object isoliquiritigenin, specific synthesis step are as follows：
(1) 2,4-dihydroxyacetophenone is provided, the 2,4-dihydroxyacetophenone is mixed with alkaline reagent, organic solvent
Afterwards, hydroxy protecting agent is added, is stirred to react under the conditions of 0-100 DEG C, to 4 hydroxyls of the 2,4-dihydroxyacetophenone into
Row hydroxyl protection；
(2) 4- hydroxy benzaldehydes are provided, after the 4- hydroxy benzaldehydes are mixed with alkaline reagent, organic solvent, are added
Hydroxy protecting agent is stirred to react under the conditions of 0-100 DEG C, and hydroxyl protection is carried out to the 4- hydroxy benzaldehydes；
It (3) will be through the 2,4- resacetophenones after step (1) hydroxyl protection, the 4- hydroxyls after step (2) hydroxyl protection
Benzaldehyde mixes in organic solvent, and lewis base is added, is stirred to react under the conditions of 25~100 DEG C, obtains aldol condensation
Product；
(4) Aldol Condensation Products described in step (3) are added in organic solvent, the tetrahydrochysene of tetrabutyl amine fluoride is added
Tetrahydrofuran solution, is stirred to react under the conditions of 10~100 DEG C, carries out deprotection processing to the Aldol Condensation Products, is prepared
Isoliquiritigenin；
Wherein, step (1), the hydroxy protecting agent described in step (2) are independently chosen from dimethyl tertiary butyl chlorosilane, three
At least one of isopropyl chloride silane.
Specifically, in step (1), (2), the alkaline reagent provides alkaline environment, for 4- hydroxy benzaldehydes and 2,4-
The 4- hydroxyls of resacetophenone carry out hydroxyl protection and provide suitable chemical environment, meanwhile, the alkaline reagent is used as and urges
Agent promotes the progress of hydroxyl protection reaction.Preferably, the alkaline reagent in imidazoles, diisopropylethylamine at least
It is a kind of.
Preferably, the lewis base in sodium hydroxide, potassium hydroxide, sodium hydride, sodium methoxide, sodium ethoxide at least
One kind, catalyst of the lewis base as aldol condensation promote the progress of reaction.
In the embodiment of the present invention, the organic solvent provides environment for dissolving reactant, for reaction.Preferably, described
Organic solvent is in methanol, ethyl alcohol, N,N-dimethylformamide, tetrahydrofuran, dichloromethane, isopropyl ether, dimethyl sulfoxide (DMSO)
At least one.
Preferably, in step (1), the molar ratio of the 2,4-dihydroxyacetophenone and hydroxy protecting agent is 1:1.2-1:
1.8, ensure the thorough progress of hydroxyl protection reaction, the 4- hydroxyls of 2,4-dihydroxyacetophenone is made to be fully protected.
Preferably, in step (1), the reaction temperature being stirred to react is 0~50 DEG C, and the reaction time is 4~6h, into one
Preferably, in step (1), the reaction temperature being stirred to react is 25-30 DEG C to step, and reaction temperature is milder, securely and reliably,
And ensure the abundant progress of reaction.
Preferably, in step (2), the molar ratio of the 4- hydroxy benzaldehydes and hydroxy protecting agent is 1:1.2-1:1.8
The thorough progress for ensureing hydroxyl protection reaction, makes the 4- hydroxyls of 4- hydroxy benzaldehydes be fully protected.
Preferably, in step (2), the reaction temperature being stirred to react is 0~50 DEG C, and the reaction time is 3~5h, into one
Preferably, in step (2), the reaction temperature being stirred to react is 25-30 DEG C to step, and reaction temperature is milder, securely and reliably,
And ensure the abundant progress of reaction.
Preferably, further include being carried out to obtained product after being stirred to react under the conditions of 0-100 DEG C in step (1), (2)
The method of purification processes, the purification processes is：Water quenching is added to go out reaction, organic phase is after acid, saturated common salt water washing, progress
Dry, vacuum distillation processing, obtains product.
Preferably, in step (3), 2,4-dihydroxyacetophenone after step (1) hydroxyl protection and through step (2) hydroxyl
The mole dosage ratio of 4- hydroxy benzaldehydes after protection is 1:1~1:2, ensure the complete progress of aldol reaction, obtains hydroxyl
Aldehyde condensation products.
Preferably, further include to obtaining after the step of being stirred to react under the conditions of 25~100 DEG C in step (3)
Product carries out purification processes, and the method for the purification processes is：After removing the solvent in product, acid solution is added dropwise to mixture pH=
6-7 extracts obtained mixture using dichloromethane, is concentrated to give Aldol Condensation Products, under slightly acidic condition, makes production
Object is easier to detach with water-solubility impurity and be extracted to organic phase, ensures the yield and purity of Aldol Condensation Products, is follow-up
Deprotection reaction is prepared.
Preferably, the acid solution is selected from least one of hydrochloric acid, phosphoric acid, sulfuric acid, for the post-processing of reaction, neutralizes body
Alkali in system is convenient for the extraction and separation of product.
Preferably, in step (3), the reaction temperature being stirred to react be 25~50 DEG C, the reaction time be 10~for 24 hours,
It is further preferred that in step (3), the reaction temperature being stirred to react is 25-30 DEG C, and reaction temperature is milder, safety
Reliably, and ensure the abundant progress reacted.
Preferably, in step (4), the reaction temperature being stirred to react is 25~40 DEG C, and the reaction time is 3~6h, instead
It answers temperature milder, securely and reliably, and ensures the abundant progress of reaction.
Preferably, in step (4), a concentration of 1mol/L of tetrahydrofuran solution of the tetrabutyl amine fluoride, as going to protect
Reagent is protected, the removing of hydroxyl protection base is completed, obtains isoliquiritigenin.
Preferably, in step (4), the molar ratio of the Aldol Condensation Products and tetrabutyl amine fluoride is 1:2-2.5 ensures
Blocking group completely removes.
Preferably, further include that will obtain after carrying out the step of deprotection is handled to the Aldol Condensation Products in step (4)
The product arrived is mixed with ice water, after removing solvent, is extracted using dichloromethane, by extract liquor successively through hydrochloric acid, saturated salt solution
After washing, dichloromethane is removed, isoliquiritigenin is obtained.
The synthetic method of isoliquiritigenin provided in an embodiment of the present invention, method is simple and practicable, and reaction condition is mild, safely may be used
It leans on, raw material is easy to get, cheap, at low cost, using at least one of dimethyl tertiary butyl chlorosilane, tri isopropyl chlorosilane
Hydroxyl protection is carried out to the 4- hydroxyls of 4- hydroxy benzaldehydes and 2,4-dihydroxyacetophenone, the risk that by-product generates is reduced, carries
The yield of high isoliquiritigenin is suitble to industrialized production.
In order to better illustrate the synthetic method of isoliquiritigenin provided in an embodiment of the present invention, below by embodiment do into
The illustration of one step.
Embodiment 1
A kind of synthetic method of isoliquiritigenin, specific synthesis step are as follows：
(1) the 4- hydroxy benzaldehydes of 12.2g and 14.3g imidazoles are added in round-bottomed flask, dichloromethane stirring is added
Uniformly, system is down to 0-5 DEG C, is slowly dropped into 21.12g dimethyl tertiary butyl chlorosilanes, is then stirred at 25-30 DEG C, TLC
It detects, reacts and finish after 6h, water, organic phase 1N salt acid elutions are added into system, then with after saturated common salt water washing, carry out
Dry, vacuum distillation processing, obtains oil product 21.08g, yield 89%.
(2) 2,4-dihydroxyacetophenone of 13.71g and 17.02g imidazoles are added in round-bottomed flask, dichloromethane is added
Alkane stirs evenly, and system is down to 0-5 DEG C, is slowly dropped into 22.60g dimethyl tertiary butyl chlorosilanes, is then stirred at 25-30 DEG C
It mixes, water is added into system after stirring 5h in TLC detections, organic phase 1N salt acid elutions, then with after saturated common salt water washing, into
Row drying, vacuum distillation processing, obtain solid product 22.64g, yield 85%；
(3) step (1) product 9.46g and step (2) product 10.66g are dissolved in 300mL ethyl alcohol, sodium hydroxide is added
16.01g stirs 18h in 25-30 DEG C, after reaction, dilute hydrochloric acid is added dropwise to subacidity, revolving removes solvent, uses dichloromethane
Extraction, after organic phase drying, evaporated under reduced pressure obtains condensation product 15.9g, yield 82%；
(4) the product 9.70g of step (3) is added in 160mL tetrahydrofurans, the 1mol/L tetrabutyl fluorine of 40mL is added
Change amine-THF solution, 30 DEG C of stirrings, TLC is detected, poured into reaction solution in ice water after 4h, and revolving removes organic solvent, dichloro
Methane extract, organic phase 1N salt acid elutions, then with after saturated common salt water washing, be dried, vacuum distillation processing, obtain different
Glycyrrhizin 4.77g, yield 93%.
Embodiment 2
A kind of synthetic method of isoliquiritigenin, specific synthesis step are as follows：
(1) the 4- hydroxy benzaldehydes of 4.88g are added in round-bottomed flask, after addition dichloromethane stirring and dissolving is complete,
10.84g diisopropylethylamine is added, system is cooled to 0-5 DEG C, is slowly dropped into 10.75g tri isopropyl chlorosilanes, then
It is stirred at 25-30 DEG C, TLC detections reacts after 5h and finished, and are added water into system, organic phase 1N salt acid elutions, then with satisfying
After brine It, organic phase drying, vacuum distillation removes solvent and obtains oil product 9.68g, yield 87%；
(2) 2,4-dihydroxyacetophenone of 4.56g is added in round-bottomed flask, it is complete that dichloromethane stirring and dissolving is added
Afterwards, 9.68g diisopropylethylamine is added, system is cooled to 0-5 DEG C, is slowly dropped into 8.64g tri isopropyl chlorosilanes, then
It is stirred at 25-30 DEG C, TLC detections, after stirring 4h, water, organic phase 1N salt acid elutions is added into system, then eaten with saturation
After salt water washing, organic phase drying, vacuum distillation removes solvent and obtains solid product 7.58g, yield 82%；
(3) step (1) product 5.56g and step (2) product 6.16g are dissolved in 150mL ethyl alcohol, potassium hydroxide is added
11.20g stirs 12h in 25-30 DEG C and is after reaction spin-dried for solvent, dilute sulfuric acid is added dropwise to subacidity, is extracted with dichloromethane
It takes, after organic phase drying, vacuum distillation removes solvent and obtains condensation product 9.08g, yield 80%；
(4) the product 5.68g of step (3) is added in 100mL tetrahydrofurans, the 1mol/L tetrabutyl fluorine of 20mL is added
Change amine-THF solution, 30 DEG C of stirrings, TLC is detected, poured into reaction solution in ice water after 3h, and revolving removes solvent, dichloromethane
Extraction, organic phase 1N salt acid elutions, then with after saturated common salt water washing, organic phase drying, vacuum distillation removes solvent, washes
It washs, isoliquiritigenin 2.28g, yield 89% is obtained after dry.
The synthetic method of the isoliquiritigenin provided in the embodiment of the present invention, method is simple and practicable, and reaction condition is mild, safety
Reliably, raw material is easy to get, of low cost, and the yield of isoliquiritigenin is higher, is suitble to industrialized production.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Any modification, equivalent replacement or improvement etc., should all be included in the protection scope of the present invention made by within refreshing and principle.
Claims (10)
1. a kind of synthetic method of isoliquiritigenin, it is characterised in that：Include the following steps：
(1) 2,4-dihydroxyacetophenone is provided, after the 2,4-dihydroxyacetophenone is mixed with alkaline reagent, organic solvent,
Hydroxy protecting agent is added, is stirred to react under the conditions of 0-100 DEG C, 4 hydroxyls of the 2,4-dihydroxyacetophenone are carried out
Hydroxyl protection；
(2) 4- hydroxy benzaldehydes are provided, after the 4- hydroxy benzaldehydes are mixed with alkaline reagent, organic solvent, hydroxyl is added
Reagent is protected, is stirred to react under the conditions of 0-100 DEG C, hydroxyl protection is carried out to the 4- hydroxy benzaldehydes；
It (3) will be through the 2,4- resacetophenones after step (1) hydroxyl protection, the 4- hydroxy benzenes after step (2) hydroxyl protection
Formaldehyde mixes in organic solvent, and lewis base is added, is stirred to react under the conditions of 25~100 DEG C, obtains Aldol Condensation Products；
(4) Aldol Condensation Products described in step (3) are added in organic solvent, the tetrahydrofuran of tetrabutyl amine fluoride is added
Solution, is stirred to react under the conditions of 10~100 DEG C, and deprotection processing is carried out to the Aldol Condensation Products, is prepared different sweet
Careless element；
Wherein, step (1), the hydroxy protecting agent described in step (2) are independently chosen from dimethyl tertiary butyl chlorosilane, three isopropyls
At least one of base chlorosilane.
2. the synthetic method of isoliquiritigenin as described in claim 1, it is characterised in that：The alkaline reagent is selected from imidazoles, two
At least one of wopropyl ethyl amine；And/or
The lewis base is selected from least one of sodium hydroxide, potassium hydroxide, sodium hydride, sodium methoxide, sodium ethoxide；And/or
The organic solvent is selected from methanol, ethyl alcohol, N,N-dimethylformamide, tetrahydrofuran, dichloromethane, isopropyl ether, diformazan
At least one of base sulfoxide.
3. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (1), the stirring is anti-
The reaction temperature answered is 0~50 DEG C, and the reaction time is 4~6h.
4. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (2), the stirring is anti-
The reaction temperature answered is 0~50 DEG C, and the reaction time is 3~5h.
5. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (3), through step (1) hydroxyl
The mole dosage ratio of 2,4- resacetophenones after base protection and the 4- hydroxy benzaldehydes after step (2) hydroxyl protection is 1:
1~1:2.
6. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (3), at 25~100 DEG C
Under the conditions of after the step of being stirred to react, further include that purification processes, the method for the purification processes are carried out to obtained product
For：After removing the solvent in product, acid solution is added dropwise to mixture pH=6-7, obtained mixture is carried out using dichloromethane
Extraction, is concentrated to give Aldol Condensation Products.
7. the synthetic method of isoliquiritigenin as claimed in claim 6, it is characterised in that：The acid solution is selected from hydrochloric acid, phosphoric acid, sulphur
At least one of acid.
8. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (3), the stirring is anti-
The reaction temperature answered be 25~50 DEG C, the reaction time be 10~for 24 hours.
9. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (4), the stirring is anti-
The reaction temperature answered is 25~40 DEG C, and the reaction time is 3~6h.
10. the synthetic method of isoliquiritigenin as claimed in claim 1 or 2, it is characterised in that：In step (4), to the aldol
Further include that the product that will be obtained is mixed with ice water after condensation product carries out the step of deprotection processing, after removing solvent, using two
Chloromethanes extracts, and by extract liquor successively after hydrochloric acid, saturated common salt water washing, removes dichloromethane, obtains isoliquiritigenin.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109400567A (en) * | 2018-12-05 | 2019-03-01 | 华中药业股份有限公司 | A method of synthesis glycyrrhizin |
| CN109705238A (en) * | 2018-12-19 | 2019-05-03 | 江苏乘鹰新材料股份有限公司 | A kind of low acetone release Low mobility photoinitiator and its preparation method and application |
| CN110559958A (en) * | 2019-09-12 | 2019-12-13 | 凯莱英医药化学（阜新）技术有限公司 | device for continuously preparing 2, 6-dihydroxy benzaldehyde and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353299A (en) * | 2008-09-11 | 2009-01-28 | 武汉大学 | Method for synthesizing isoliquirtigenin |
| CN101648856A (en) * | 2009-09-08 | 2010-02-17 | 东北林业大学 | Method for synthesizing isoliquiritigenin |
-
2018
- 2018-04-24 CN CN201810373979.5A patent/CN108440264A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353299A (en) * | 2008-09-11 | 2009-01-28 | 武汉大学 | Method for synthesizing isoliquirtigenin |
| CN101648856A (en) * | 2009-09-08 | 2010-02-17 | 东北林业大学 | Method for synthesizing isoliquiritigenin |
Non-Patent Citations (1)
| Title |
|---|
| 赵玉芬等: "《元素有机化学》", 31 December 1998, 清华大学出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109400567A (en) * | 2018-12-05 | 2019-03-01 | 华中药业股份有限公司 | A method of synthesis glycyrrhizin |
| CN109705238A (en) * | 2018-12-19 | 2019-05-03 | 江苏乘鹰新材料股份有限公司 | A kind of low acetone release Low mobility photoinitiator and its preparation method and application |
| CN110559958A (en) * | 2019-09-12 | 2019-12-13 | 凯莱英医药化学（阜新）技术有限公司 | device for continuously preparing 2, 6-dihydroxy benzaldehyde and application thereof |
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