CN102775290A - Preparation method of 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone - Google Patents
Preparation method of 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone Download PDFInfo
- Publication number
- CN102775290A CN102775290A CN201210253858XA CN201210253858A CN102775290A CN 102775290 A CN102775290 A CN 102775290A CN 201210253858X A CN201210253858X A CN 201210253858XA CN 201210253858 A CN201210253858 A CN 201210253858A CN 102775290 A CN102775290 A CN 102775290A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- chloromethyl
- dimethoxy
- para benzoquinone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 53
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000010464 Blanc reaction Methods 0.000 claims abstract description 5
- 238000007027 Dakin phenol oxidation reaction Methods 0.000 claims abstract description 4
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- 238000000605 extraction Methods 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 229940126214 compound 3 Drugs 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- 229940125782 compound 2 Drugs 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 150000002978 peroxides Chemical class 0.000 claims description 18
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000001035 drying Methods 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 11
- 229920002866 paraformaldehyde Polymers 0.000 claims description 11
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 claims description 10
- 239000007810 chemical reaction solvent Substances 0.000 claims description 10
- 238000010792 warming Methods 0.000 claims description 10
- 229910019213 POCl3 Inorganic materials 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 7
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical group Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 7
- -1 2,3,4-trimethoxy-6-tolyl Chemical group 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- KBRXQGLNRLPLSY-UHFFFAOYSA-N CC1(C=C(C(=C(C1CCl)C(=O)O)OC)OC)C(=O)O Chemical compound CC1(C=C(C(=C(C1CCl)C(=O)O)OC)OC)C(=O)O KBRXQGLNRLPLSY-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000010813 municipal solid waste Substances 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 235000010265 sodium sulphite Nutrition 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- UGNJWQMNCJYWHG-UHFFFAOYSA-N 2,3,4-trimethoxy-6-methylphenol Chemical compound COC1=CC(C)=C(O)C(OC)=C1OC UGNJWQMNCJYWHG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007524 organic acids Chemical group 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- YXGSRLNKDJGJLH-UHFFFAOYSA-N CC1(CC=C(C(C1)(C(=O)O)OC)OC)C(=O)O Chemical compound CC1(CC=C(C(C1)(C(=O)O)OC)OC)C(=O)O YXGSRLNKDJGJLH-UHFFFAOYSA-N 0.000 claims 4
- SENQMZMEMJVCBE-UHFFFAOYSA-N COC1=CC(CC(C(=O)O)=C1OC)(C(=O)O)C Chemical compound COC1=CC(CC(C(=O)O)=C1OC)(C(=O)O)C SENQMZMEMJVCBE-UHFFFAOYSA-N 0.000 claims 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 2
- 229940125904 compound 1 Drugs 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical class COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 14
- KCIZTNZGSBSSRM-UHFFFAOYSA-N 3,4,5-Trimethoxytoluene Chemical compound COC1=CC(C)=CC(OC)=C1OC KCIZTNZGSBSSRM-UHFFFAOYSA-N 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 239000007788 liquid Substances 0.000 description 16
- 238000005303 weighing Methods 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 235000017471 coenzyme Q10 Nutrition 0.000 description 7
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 5
- 229940035936 ubiquinone Drugs 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 2
- 229960004135 idebenone Drugs 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000004203 pancreatic function Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone, wherein the 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone is the key intermediate for preparation of coenzyme Q compounds. The preparation method comprises the steps of using 3,4,5-trimethoxytoluene as raw material, and carrying out four steps of Vilsmeier-Haack reaction, Blanc chloromethylation reaction, Dakin reaction and oxidation reaction to obtain 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone with high purity. The overall yield is up to more than 50%. The method provided by the invention has the advantages of rich source of raw material, high yield, good quality and purity of the product, simple process, low cost and wide application prospect.
Description
Technical field
The present invention relates to a kind of key intermediate 2-chloromethyl-5 for preparing coenzyme Q compounds, 6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone belongs to the organic synthesis field.
Background technology
Ubiquinone is one type of natural lipid-soluble substance that is present on all eukaryotic cell membranes; On the cell mitochondrial respiratory chain, participate in the conversion process of energy of relevant bio-oxidation as the electron transit mediator of key; Have simultaneously biomacromolecule in plastosome and the cell such as protein; Enzyme, membrane phospholipid, the anti-oxidation protection effect of DNA/RNA etc.Further relevant research in recent years shows again; Coenzyme Q compounds also has the growth of regulation and control biological cell, metabolism, differentiation; Energy distribution and adjusting immunity of organism; Improve effect (Turunen M, Olsson J, the Dallner G. Metabolism and function of coenzyme Q. of aspects such as blood vessel endothelium system function
Biochimica et Biophysica Acta, 2004,1660:171-199; Watts GF, Playford DA, Craft KD, et al.
Diabetologia, 2002,45:420-426; Linnane AW, Eastwood H. Cellular redox poise modulation; The over arching role of coenzyme Q
10, gene and metabolic regulation. Mitochondron, 2004, XX:1-11).The some of them coenzyme Q compounds is (like ubiquinone
10, plug Qu Site, idebenone) developed the medicine that becomes the clinical treatment relative disease (woods Guoqiang, You Qidong. chiral drug research with use. Beijing. the .615 of Chemical Industry Press; Shinkawa N, Ichino T, Tsuruki T, et al.
JP: 05148183,1993-06-15.).Ubiquinone
10Cardiovascular disorder there is therapeutic action well as congested mental energy weakness, stenocardia, irregular pulse, hypertension, aplastic anemia etc.; And can improve liver pancreatic functions obstacle, tumour and AIDS there are certain assisting therapy effect.In addition, ubiquinone
10, idebenone also begun to be used to the health care and makeup in.
In view of the broad prospect of application of coenzyme Q compounds, company all begins to adopt in succession chemical semi-synthesis method to carry out the mass production of coenzyme Q compounds both at home and abroad.Bruce H. Lipshutz etc. has reported 2-chloromethyl-5,6-dimethoxy-3-methyl-1, and the 4-para benzoquinone is as compound method (the Bruce H. Lipshutz etc. of the key intermediate of the homologue of synthesizing coenzyme Q and verivate thereof
Organic Letters., 2005,7,19,4095-4097).This method is with ubiquinone
0Be starting raw material, through lithium aluminium hydride reduction, methyl-sulfate methylates, the Blanc chloromethylation, and four-step reactions such as ceric ammonium nitrate oxidation make 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the method for 4-para benzoquinone.This synthetic route severe reaction conditions, the agents useful for same lithium aluminum hydride is inflammable and explosive, costs an arm and a leg be difficult for to obtain or be difficult for preparation, and the agents useful for same methyl-sulfate is highly toxic product, total yield of products only 34%, industrial application value is limited.Therefore, research and develop one easy, safe, prepare 2-chloromethyl-5 in a large number efficiently, 6-dimethoxy-3-methyl-1, the novel method of 4-para benzoquinone is significant for the homologue and the verivate product thereof of synthetic exploitation ubiquinone.
Summary of the invention
The objective of the invention is to overcome the defective of prior art, a kind of key intermediate 2-chloromethyl-5 of easy preparation ubiquinone is provided, 6-dimethoxy-3-methyl isophthalic acid; The preparation method of 4-para benzoquinone; The raw materials used source of this law is abundant, and price is low, and it is simple that each goes on foot operation; Yield is higher, and the four-step reaction total recovery can reach more than 50%.
In order to achieve the above object, the present invention prepares coenzyme Q compounds key intermediate 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, and the preparation method of 4-para benzoquinone may further comprise the steps:
A, 3,4,5-trimethoxytoluene make compound 2 through Vilsmeier – Haack reaction under the effect of Vilsmeier reagent, and promptly 2,3,4-trimethoxy-6-tolyl aldehyde;
B, compound 2 make compound 3 through the Blanc chloromethylation at Paraformaldehyde 96 under the effect of concentrated hydrochloric acid, and promptly 2,3,4-trimethoxy-5-chloromethyl-6-tolyl aldehyde;
C, compound 3 are under the effect of catalyzer and H
2O
2Make compound 4 through Dakin reaction, promptly 2,3,4-trimethoxy-6-methylphenol;
D, compound 4 make compound 5 through oxidizing reaction under the effect of oxygenant, i.e. 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, 4-para benzoquinone.
The method of the invention technical process is as follows:
Wherein a) step concrete steps and processing condition are: with 3,4, the N that the 5-trimethoxytoluene is dissolved in is in the dinethylformamide; Under the nitrogen protection, slowly drip POCl3 down, dripped off in 1~2 hour, be warming up to 60~100 ℃ of reaction 6~10h then at 0~5 ℃; Stopped reaction is poured reaction solution in the 150-300g trash ice into and to be stirred, and is neutralized to neutrality with sodium hydroxide solution; Separate out solid, promptly get compound 2 after the filtration, wherein 3; 4,5-trimethoxytoluene: N, dinethylformamide: the mol ratio of POCl3 is 1:1.2~2:1.2~2.
B wherein) concrete steps and the processing condition of step are: after compound 2 and Paraformaldehyde 96 are mixed, be 37% commercially available concentrated hydrochloric acid to wherein adding mass percent concentration, at 0~60 ℃ of following stirring reaction 2~6h; Stopped reaction is used petroleum ether extraction, and sherwood oil is washed to neutrality mutually; Dry; Filter, revolve steaming except that desolvating and obtain compound 3, wherein compound 2: Paraformaldehyde 96: the mol ratio of hydrochloric acid is 1:1~5:5~20.
C wherein) concrete steps and the processing condition of step are: compound 3 is dissolved in the reaction solvent of 3~10 times of compound 3 weight; Adding the catalyzer stirring and dissolving, is 30~50% ydrogen peroxide 50 to wherein dripping mass percent concentration slowly down at-10 ℃~30 ℃ then, at room temperature reacts then to add after 3~5 hours in the sodium sulfite solution and excessive ydrogen peroxide 50; Use dichloromethane extraction; Washing is to neutral, and drying is filtered; Revolve to steam except that desolvating and obtain compound 4, wherein catalyzer: compound 3: the mol ratio of ydrogen peroxide 50 is 1:1~3:2~6.
Among the present invention from the reaction solvent of compound 3 preparation feedback things 4 be carbonatoms be not more than 6 lower alcohols solvent or can and the organic solvent that dissolves each other of water, catalyzer is organic acid or mineral acid.
Reaction solvent from said compound 3 preparation feedback things 4 among the present invention is a kind of methyl alcohol, ethanol, the THF.
Catalysts from said compound 3 preparation feedback things 4 among the present invention is a kind of tosic acid, sodium pyrosulfate, SODIUM PHOSPHATE, MONOBASIC, glacial acetic acid, the phosphoric acid.
Wherein the concrete steps of d step and processing condition are: compound 4 is dissolved in 5~10 times of reaction solvents of compound 4 weight, then under-10 ℃~30 ℃ to the aqueous solution that wherein slowly drips the oxygenant of suitable volume, at room temperature react after dripping after 1~3 hour and use dichloromethane extraction; Washing is to neutral, and drying is filtered; Revolve to steam and obtain 2-chloromethyl-5 except that desolvating; 6-dimethoxy-3-methyl isophthalic acid, the 4-para benzoquinone, wherein the mol ratio of oxygenant and compound 4 is 2~5:1.
Reaction solvent in the d step of the present invention is a kind of in alcohols, acetonitrile, acetone, the THF, and oxygenant is a tri-chlorination
Iron or ceric ammonium nitrate.
With respect to existing technology, the advantage and the technique effect of the inventive method are following:
1, the present invention is raw materials used and reagent is cheap and easy to get, and is safe in utilization;
2, it is simple respectively to go on foot operation in the inventive method, and method is simple and practical, and cost is low;
3, yield is high, and overall yield of reaction can reach more than 50%, and the product purity quality is good;
4, environmental friendliness does not produce the technology three wastes, is with a wide range of applications, and is suitable for industrial applications.
Embodiment
Through embodiment the inventive method is done further explain below, but protection domain of the present invention is not limited to said content.
Embodiment 1:2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone, concrete operations are following:
(1) take by weighing 3,4,5-trimethoxytoluene 9.1g (0.05mol) is dissolved in 6.5mlN, in the dinethylformamide (0.09mol); Under the nitrogen protection, control reaction temperature slowly drips POCl3 9.2g (0.06mol) then at 0 ℃, drips off after 1 hour; Be warming up to 60 ℃ of reactions 10 hours then, stopped reaction is with stirring reaction in the trash ice of reaction solution impouring 200g; It is that 30% sodium hydroxide solution is neutralized to neutrality that last solution uses mass percent concentration, separates out a large amount of solids, filters and promptly gets compound 2; Be faint yellow solid, fusing point: 59~60 ℃, yield: 97%.
1HNMR(500MHz,?CDCl
3):10.28(s,?1H,?-CHO),3.86-3.73(t,?9H,?-OCH
3),?2.44(s,3H,?-CH
3);
(2) take by weighing after 3.2g (0.015mol) compound 2 mixes with Paraformaldehyde 96 0.9g (0.03mol), adding mass percent concentration is 37% concentrated hydrochloric acid 7.5ml (containing the about 0.075mol of HCl), is warming up to 35 ℃ of stirring reactions after 4 hours; Stopped reaction; Use the 60ml petroleum ether extraction, the washing of sherwood oil phase extraction liquid is to neutrality, drying; Filter, revolve steam remove desolvate compound 3
,Be the off-white color solid.Fusing point: 68~69 ℃, yield: 98%.
1HNMR(500MHz,?CDCl
3):10.43(s,?1H,?-CHO),4.78(s,2H)3.87-4.06(t,?9H,?-OCH
3),?2.59(s,3H,?-CH
3);
(3) taking by weighing 3.8g (0.015mol) compound 3 and tosic acid 0.85g (0.005mol), use the 38g dissolve with methanol, is 30% ydrogen peroxide 50 3.4ml (containing the about 0.03mol of ydrogen peroxide 50) at 0 ℃ of slow down dropping mass percent concentration; Be warming up to room temperature reaction then and add in the semi-saturation sodium sulfite solution after 3 hours and excessive ydrogen peroxide 50, use the 60ml dichloromethane extraction, the extraction liquid washing is to neutral; Drying is filtered, revolve steam remove desolvate compound 4; Be yellow liquid, yield: 77%.
1HNMR(500MHz,?CDCl
3):5.75(s,?1H,?-OH),4.45(s,2H),3.81-3.97(t,?9H,?-OCH
3),?2.22(s,3H,?-CH
3);
(4) take by weighing 2.8g (0.011mol) compound 4 and use the 20g dissolve with ethanol, at 0 ℃ of aqueous solution 20ml (wherein iron trichloride 0.022mol) that slowly drips iron trichloride down, 1.0h drips; Rose to normal-temperature reaction then 2 hours, with 60ml dichloromethane extraction product, the extraction liquid washing is to neutral; Anhydrous magnesium sulfate drying filters, revolve steam remove desolvate compound 5; Be red liquid, yield: 76%.
1HNMR?(500MHz,?CDCl3):?4.42?(s,?2H,?ArCH2Cl-),?4.01?(s,?3H,?-OCH3),?3.99?(s,?3H,?OCH3),?2.16?(s,?3H,?-CH3)。
Embodiment 2:2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone, concrete operations are following:
(1) take by weighing 3,4,5-trimethoxy-benzene 9.1g (0.05mol) is dissolved in 4.5mlN, in the dinethylformamide (0.06mol); Under the nitrogen protection, control reaction temperature slowly drips POCl3 9.20g (0.06mol) at 5 ℃, drips off in about 1.5 hours, is warming up to 80 ℃ of reactions 7 hours then; Stopped reaction, with stirring reaction in the trash ice of reaction solution impouring 150g, last solution is neutralized to neutrality with 30% sodium hydroxide solution; Separate out a large amount of solids, filter and promptly get compound 2, be faint yellow solid; Fusing point: 59~60 ℃, yield: 98%.
1HNMR(500MHz,?CDCl
3):10.28(s,?1H,?-CHO),3.86-3.73(t,?9H,?-OCH
3),?2.44(s,3H,?-CH
3);
(2) take by weighing after 3.2g (0.015mol) compound 2 mixes with Paraformaldehyde 96 1.2g (0.04mol), adding mass percent concentration is 37% hydrochloric acid 10ml (containing the about 0.10mol of HCl), is warming up to 60 ℃ and reacts 2 hours; Stopped reaction; Use the 60ml petroleum ether extraction, washing is to neutrality, anhydrous magnesium sulfate drying; Filter, revolve steam remove desolvate compound 3
,Be the off-white color solid; Fusing point: 68~69 ℃, yield: 99%.
1HNMR(500MHz,?CDCl
3):10.43(s,?1H,?-CHO),4.78(s,2H)3.87-4.06(t,?9H,?-OCH
3),?2.59(s,3H,?-CH
3);
(3) taking by weighing 3.8g (0.015mol) compound 3 and sodium pyrosulfate 0.60g (0.005mol), use the 30g dissolve with ethanol, is 50% ydrogen peroxide 50 2ml (containing the about 0.03mol of ydrogen peroxide 50) at-10 ℃ of slow down dropping mass percent concentrations; Being warming up to room temperature reaction then adds in the semi-saturation sodium sulfite solution and excessive ydrogen peroxide 50 after 5 hours; Use the 60ml dichloromethane extraction, the extraction liquid washing is to neutrality, anhydrous magnesium sulfate drying; Filter; Revolve steam to remove desolvate compound 4, be yellow liquid, yield: 87%.
1HNMR(500MHz,?CDCl
3):5.75(s,?1H,?-OH),4.45(s,2H),3.81-3.97(t,?9H,?-OCH
3),?2.22(s,3H,?-CH
3);
(4) take by weighing the dissolving of 2.8g (0.011mol) compound 4 usefulness 15g acetonitriles,, rise to normal-temperature reaction after 3 hours at-10 ℃ of aqueous solution 20ml (wherein contain ceric ammonium nitrate 0.025mol and be roughly equal to 13.7g) that slowly drip ceric ammonium nitrate down; Use the 60ml dichloromethane extraction; The extraction liquid washing is to neutral, and drying is filtered; Revolve steam to remove desolvate compound 5, be red liquid; Yield: 85%.
1HNMR?(500MHz,?CDCl3):?4.42?(s,?2H,?ArCH2Cl-),?4.01?(s,?3H,?-OCH3),?3.99?(s,?3H,?OCH3),?2.16?(s,?3H,?-CH3)。
Embodiment 3:2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone, concrete operations are following:
(1) take by weighing 3,4,5-trimethoxy-benzene 9.1g (0.05mol) is dissolved in 7.5ml N, in the dinethylformamide (0.1mol); Under the nitrogen protection, control reaction temperature slowly drips POCl3 15.2g (0.10mol) then at 3 ℃, drips off after 2 hours; Be warming up to 100 ℃ of reactions 4 hours then, stopped reaction is with stirring reaction in the trash ice of reaction solution impouring 300g; Last solution is neutralized to neutrality with 30% sodium hydroxide solution, separates out a large amount of solids, filters and promptly gets compound 2; Be faint yellow solid, fusing point: 59~60 ℃, yield: 95%.
1HNMR(500MHz,?CDCl
3):10.28(s,?1H,?-CHO),3.86-3.73(t,?9H,?-OCH
3),?2.44(s,3H,?-CH
3);
(2) take by weighing after 3.2g (0.015mol) compound 2 mixes with Paraformaldehyde 96 2.25g (0.075mol), dripping mass percent concentration under the vigorous stirring is 37% hydrochloric acid 27.0ml (containing the about 0.30mol of HCl), 0 ℃ react 6 hours after; Stopped reaction; Use the 60ml petroleum ether extraction, washing is to neutrality, anhydrous magnesium sulfate drying; Filter, revolve steam remove desolvate compound 3
,Be the off-white color solid; Fusing point: 68~69 ℃, yield: 93%.
1HNMR(500MHz,?CDCl
3):10.43(s,?1H,?-CHO),4.78(s,2H)3.87-4.06(t,?9H,?-OCH
3),?2.59(s,3H,?-CH
3);
(3) take by weighing 7.2g (0.028mol) compound 3 and SODIUM PHOSPHATE, MONOBASIC 1.70g (0.014mol), with the dissolving of 25g THF, slow dropping mass percent concentrations are 40% ydrogen peroxide 50 2.55ml (containing the about 0.03mmol of ydrogen peroxide 50) under 30 ℃; Add in the semi-saturation sodium sulfite solution after 3 hours and excessive ydrogen peroxide 50 at room temperature reaction then; Use the 60ml dichloromethane extraction, the extraction liquid washing is to neutrality, anhydrous magnesium sulfate drying; Filter; Revolve steam to remove desolvate compound 4, be yellow liquid, yield: 91%.
1HNMR(500MHz,?CDCl
3):5.75(s,?1H,?-OH),4.45(s,2H),3.81-3.97(t,?9H,?-OCH
3),?2.22(s,3H,?-CH
3);
(4) take by weighing 2.8g (0.011mol) compound 4 and use the 20g acetone solution, at 30 ℃ of aqueous solution 20ml (wherein containing iron trichloride 0.055mol) that drip down slowly iron trichlorides, then normal-temperature reaction 1 hour; Use the 60ml dichloromethane extraction, the extraction liquid washing is to neutrality, anhydrous magnesium sulfate drying; Filter; Revolve steam to remove desolvate compound 5, be red liquid.Yield: 75%.
1HNMR?(500MHz,?CDCl3):?4.42?(s,?2H,?ArCH2Cl-),?4.01?(s,?3H,?-OCH3),?3.99?(s,?3H,?OCH3),?2.16?(s,?3H,?-CH3)。
Embodiment 4:2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone, concrete operations are following:
(1) take by weighing 3,4,5-trimethoxy-benzene 9.1g (0.05mol) is dissolved in 7ml N, in the dinethylformamide (0.09mol); Under the nitrogen protection, control reaction temperature slowly drips POCl3 11.4g (0.075mol) then at about 2 ℃, drips off after 1 hour; Be warming up to 70 ℃ of reactions 5 hours then, stopped reaction is with vigorous stirring in the trash ice of reaction solution impouring 250g; Last solution is neutralized to neutrality with 30% sodium hydroxide solution, separates out a large amount of solids, filters and promptly gets compound 2; Be faint yellow solid, fusing point: 59~60 ℃, yield: 92%.
1HNMR(500MHz,?CDCl
3):10.28(s,?1H,?-CHO),3.86-3.73(t,?9H,?-OCH
3),?2.44(s,3H,?-CH
3);
(2) take by weighing after 3.2g (0.015mol) compound 2 mixes with Paraformaldehyde 96 0.45g (0.015mol), dripping mass percent concentration under the vigorous stirring is 37% hydrochloric acid 13.5ml (0.15mol), 20 ℃ of reactions after 6 hours; Stopped reaction; Use the 60ml petroleum ether extraction, washing is to neutrality, anhydrous magnesium sulfate drying; Filter, revolve steam remove desolvate compound 3
,Be the off-white color solid; Fusing point: 68~69 ℃, yield: 93%.
1HNMR(500MHz,?CDCl
3):10.43(s,?1H,?-CHO),4.78(s,2H)3.87-4.06(t,?9H,?-OCH
3),?2.59(s,3H,?-CH
3);
(3) taking by weighing 4.8g (0.019mol) compound 3 and SODIUM PHOSPHATE, MONOBASIC 2.25g (0.019mol), add 15g methyl alcohol stirring and dissolving, is 30% ydrogen peroxide 50 6.8ml (containing ydrogen peroxide 50 0.06mol) then at 10 ℃ of slow down dropping mass percent concentrations; Add in the semi-saturation sodium sulfite solution after 5 hours and excessive ydrogen peroxide 50 at room temperature reaction then; Use the 60ml dichloromethane extraction, the extraction liquid washing is to neutrality, anhydrous magnesium sulfate drying; Filter; Revolve steam to remove desolvate compound 4, be yellow liquid, yield: 89%.
1HNMR(500MHz,?CDCl
3):5.75(s,?1H,?-OH),4.45(s,2H),3.81-3.97(t,?9H,?-OCH
3),?2.22(s,3H,?-CH
3);
(4) take by weighing 2.8g (0.011mol) compound 4 usefulness 28g THFs dissolvings, at 10 ℃ of aqueous solution 20ml (wherein iron trichloride 0.044mol) that slowly drip iron trichlorides down, then normal-temperature reaction 1.5 hours; Use the 60ml dichloromethane extraction, the cuiquye washing is to neutrality, anhydrous magnesium sulfate drying; Filter; Revolve steam to remove desolvate compound 5, be red liquid.Yield: 78%.
1HNMR?(500MHz,?CDCl3):?4.42?(s,?2H,?ArCH2Cl-),?4.01?(s,?3H,?-OCH3),?3.99?(s,?3H,?OCH3),?2.16?(s,?3H,?-CH3)。
Claims (9)
1. 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone is characterized in that may further comprise the steps:
A, with compound 1, promptly 3,4, the 5-trimethoxytoluene is that raw material makes compound 2 through Vilsmeier – Haack reaction under the effect of Vilsmeier reagent, promptly 2,3,4-trimethoxy-6-tolyl aldehyde;
B, compound 2 make compound 3 through the Blanc chloromethylation under the effect of Paraformaldehyde 96, concentrated hydrochloric acid, and promptly 2,3,4-trimethoxy-5-chloromethyl-6-tolyl aldehyde;
Compound 3 is under the effect of catalyzer and H
2O
2Make compound 4 through Dakin reaction, promptly 2,3,4-trimethoxy-6-methylphenol;
Compound 4 makes 2-chloromethyl-5 through oxidizing reaction under the effect of oxygenant, 6-dimethoxy-3-methyl isophthalic acid, 4-para benzoquinone;
2. according to the said 2-chloromethyl-5 of claim 1,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone is characterized in that 3; 4, the 5-trimethoxytoluene through concrete steps and the processing condition that the Vilsmeier-Haack reaction makes compound 2 is: with 3,4, the 5-trimethoxytoluene is dissolved in N; In the dinethylformamide, under the nitrogen protection, slowly drip POCl3 down, dripped off in 1~2 hour at 0~5 ℃; Be warming up to 60~100 ℃ of reaction 4~10h then, stopped reaction is poured reaction solution in the trash ice into and to be stirred, and is neutralized to neutrality with sodium hydroxide solution; Separate out solid, filter and promptly to get compound 2, wherein 3; 4,5-trimethoxytoluene: N, dinethylformamide: the mol ratio of POCl3 is 1:1.2~2:1.2~2.
3. according to the said 2-chloromethyl-5 of claim 1,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone; It is characterized in that compound 2 under the effect of Paraformaldehyde 96 and concentrated hydrochloric acid through concrete steps and processing condition that the Blanc chloromethylation makes compound 3 is being: after compound 2 and Paraformaldehyde 96 are mixed, be 37% concentrated hydrochloric acid to wherein adding mass percent concentration, at 0~60 ℃ of following stirring reaction 2~6h; Stopped reaction is used petroleum ether extraction, and sherwood oil phase water is washed till neutrality; Dry; Filter, revolve steaming except that desolvating and obtain compound 3, wherein compound 2: Paraformaldehyde 96: the mol ratio of hydrochloric acid is 1:1~5:5~20.
4. according to the said 2-chloromethyl-5 of claim 1,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone is characterized in that compound 3 is under the effect of catalyzer and H
2O
2The concrete steps and the processing condition that make compound 4 through the Dakin reaction are: compound 3 is dissolved in the reaction solvent; Adding catalyzer, is 30~50% ydrogen peroxide 50 to wherein dripping mass percent concentration slowly down at-10~30 ℃ then, continues at room temperature to react to add after 3~5 hours in the semi-saturation sodium sulfite solution and excessive ydrogen peroxide 50; Use dichloromethane extraction; Washing is to neutral, and drying is filtered; Revolve to steam except that desolvating and obtain compound 4, wherein catalyzer: compound 3: the mol ratio of ydrogen peroxide 50 is 1:1~3:2~6.
5. according to the said 2-chloromethyl-5 of claim 4; 6-dimethoxy-3-methyl isophthalic acid; The preparation method of 4-para benzoquinone is characterized in that: reaction solvent be carbonatoms be not more than 6 lower alcohols solvent or can and the organic solvent that dissolves each other of water, catalyzer is organic acid or mineral acid.
6. according to the said 2-chloromethyl-5 of claim 5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone is characterized in that: reaction solvent is a kind of in methyl alcohol, ethanol, the THF.
7. according to the said 2-chloromethyl-5 of claim 5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone is characterized in that: catalyzer is a kind of in tosic acid, sodium pyrosulfate, SODIUM PHOSPHATE, MONOBASIC, glacial acetic acid, the phosphoric acid.
8. according to the said 2-chloromethyl-5 of claim 1,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone; It is characterized in that compound 4 makes 2-chloromethyl-5 through oxidizing reaction under the oxygenant effect, 6-dimethoxy-3-methyl isophthalic acid, the concrete steps of 4-para benzoquinone and processing condition are: compound 4 is dissolved in reaction solvent; Then under-10~30 ℃ to the slow aqueous solution of dropping oxidizing agent wherein, at room temperature continue reaction after dripping and use dichloromethane extraction after 1~3 hour, washing is to neutrality; Dry; Filter, revolve steaming except that desolvating and obtain 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid; The 4-para benzoquinone, wherein the mol ratio of oxygenant and compound 4 is 2~5:1.
9. according to the said 2-chloromethyl-5 of claim 7; 6-dimethoxy-3-methyl isophthalic acid; The preparation method of 4-para benzoquinone is characterized in that: reaction solvent is a kind of in methyl alcohol, ethanol, propyl alcohol, acetonitrile, acetone, the THF, and oxygenant is iron trichloride or ceric ammonium nitrate.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210253858.XA CN102775290B (en) | 2012-07-23 | 2012-07-23 | 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210253858.XA CN102775290B (en) | 2012-07-23 | 2012-07-23 | 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102775290A true CN102775290A (en) | 2012-11-14 |
CN102775290B CN102775290B (en) | 2015-08-26 |
Family
ID=47120426
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210253858.XA Expired - Fee Related CN102775290B (en) | 2012-07-23 | 2012-07-23 | 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102775290B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107032974A (en) * | 2017-06-14 | 2017-08-11 | 西北大学 | The preparation method of the geranyl p-benzoquinone derivative of 2 methoxyl group 5 and Scabellone A |
CN108299170A (en) * | 2017-12-26 | 2018-07-20 | 河北大学 | A kind of preparation method of 2,4,6- trimethylbenzaldehydes |
CN110935475A (en) * | 2019-12-04 | 2020-03-31 | 滁州学院 | Preparation of recyclable supported catalyst and application method thereof in carbonyl oxidation reaction |
CN111807945A (en) * | 2020-07-10 | 2020-10-23 | 盐城师范学院 | Method for synthesizing coenzyme Q compounds |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7528271B2 (en) * | 2007-05-16 | 2009-05-05 | Bergen Teknologioverforing As | Intermediates, process for their preparation and synthesis of 1,4-benzoquiones |
-
2012
- 2012-07-23 CN CN201210253858.XA patent/CN102775290B/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7528271B2 (en) * | 2007-05-16 | 2009-05-05 | Bergen Teknologioverforing As | Intermediates, process for their preparation and synthesis of 1,4-benzoquiones |
Non-Patent Citations (1)
Title |
---|
JIN WANG ET AL.: "Alternative synthesis of 5-chloromethyl-2,3-dimethoxy-6-methyl-1,4-benzoquinone: a key intermediate for preparing coenzyme Q analogues", 《JOURNAL OF CHEMICAL RESEARCH》, vol. 34, no. 12, 23 December 2010 (2010-12-23), pages 724 - 725 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107032974A (en) * | 2017-06-14 | 2017-08-11 | 西北大学 | The preparation method of the geranyl p-benzoquinone derivative of 2 methoxyl group 5 and Scabellone A |
CN107032974B (en) * | 2017-06-14 | 2020-10-09 | 西北大学 | Preparation method of 2-methoxy-6-geranyl p-benzoquinone derivative and Scabellone A |
CN108299170A (en) * | 2017-12-26 | 2018-07-20 | 河北大学 | A kind of preparation method of 2,4,6- trimethylbenzaldehydes |
CN110935475A (en) * | 2019-12-04 | 2020-03-31 | 滁州学院 | Preparation of recyclable supported catalyst and application method thereof in carbonyl oxidation reaction |
CN110935475B (en) * | 2019-12-04 | 2022-08-02 | 滁州学院 | Preparation of recyclable supported catalyst and application method thereof in carbonyl oxidation reaction |
CN111807945A (en) * | 2020-07-10 | 2020-10-23 | 盐城师范学院 | Method for synthesizing coenzyme Q compounds |
Also Published As
Publication number | Publication date |
---|---|
CN102775290B (en) | 2015-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102775290B (en) | 2-chloromethyl-5,6-dimethoxy-3-methyl isophthalic acid, the preparation method of 4-para benzoquinone | |
CN103265426A (en) | Environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction | |
CN104892614B (en) | A kind of synthetic method of 6H iso-indoles simultaneously ketone derivatives of [2,1 α] indoles 6 | |
CN103113308A (en) | Method for preparing dihydropyrimidinone derivative | |
CN107188834B (en) | The preparation method of 2- aryl-ethylene base sulfonyl fluoride compound | |
CN102992989A (en) | Synthesis method of beta-menadione | |
CN113181850A (en) | Microchannel preparation method of indole compound | |
CN106187855B (en) | A method of 2- (hetero) aryl indole class compound is prepared using deep eutectic solvent | |
CN102391175B (en) | The green synthesis method of 2,2 '-dipyridyl-4,4 '-dicarbaldehyde | |
CN103880852A (en) | Continuous production process of tetraaryl porphin | |
CN102627626B (en) | Preparation method of 2, 3-thiophenedicarboxaldehyde | |
CN109608423A (en) | Using α-phenoxy group ketone as the method for Material synthesis benzofuran derivatives | |
CN101333161B (en) | Method for preparing alpha-chloro-fatty acid | |
Tang et al. | Silver (i)-catalyzed addition of pyridine-N-oxides to alkynes: a practical approach for N-alkenoxypyridinium salts | |
CN103183599A (en) | Method for preparing 2-valproic acid | |
CN113121318A (en) | Biheteroaromatic hydrocarbon compound and preparation method thereof | |
CN108383754B (en) | Preparation method and application of aryl oxime ester compound | |
CN102010345A (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
CN105749967A (en) | Method for preparing tributyl citrate in presence of bamboo-charcoal-based solid sulfonic acid catalyst | |
CN105601517A (en) | Synthetic method of methyl 3,3,3-trifluoropropionate | |
ES2875151T3 (en) | Procedures for the preparation of unsaturated malonates | |
CN105859620B (en) | A kind of 6- trichloromethyls phenanthridines class compound and its preparation method and application | |
CN104945234B (en) | The preparation method of the methoxy benzophenone of 2,2 ' dihydroxy 4 | |
CN103288628A (en) | Method for preparing 1,3-acetone dicarboxylic acid diester and intermediate thereof by oxidizing citric acid and hydrogen peroxide | |
CN103435450B (en) | A kind of synthetic method of the TMHQ of environmental protection |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150826 Termination date: 20210723 |