CN103880675A - Improved catalyzed synthesis method for 1,4-dicarbonyl compound - Google Patents
Improved catalyzed synthesis method for 1,4-dicarbonyl compound Download PDFInfo
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- CN103880675A CN103880675A CN201410143047.3A CN201410143047A CN103880675A CN 103880675 A CN103880675 A CN 103880675A CN 201410143047 A CN201410143047 A CN 201410143047A CN 103880675 A CN103880675 A CN 103880675A
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- dipyridyl
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- 238000001308 synthesis method Methods 0.000 title abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 72
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 45
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- 239000003054 catalyst Substances 0.000 claims abstract description 27
- 239000002131 composite material Substances 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 17
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims abstract description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000001704 evaporation Methods 0.000 claims abstract description 10
- 239000012074 organic phase Substances 0.000 claims abstract description 10
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 238000007036 catalytic synthesis reaction Methods 0.000 claims abstract description 6
- 238000010189 synthetic method Methods 0.000 claims description 24
- 238000000746 purification Methods 0.000 claims description 16
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims description 13
- 150000003222 pyridines Chemical class 0.000 claims description 10
- 230000008020 evaporation Effects 0.000 claims description 9
- 239000000284 extract Substances 0.000 claims description 9
- 238000000605 extraction Methods 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 9
- NBPGPQJFYXNFKN-UHFFFAOYSA-N 4-methyl-2-(4-methylpyridin-2-yl)pyridine Chemical group CC1=CC=NC(C=2N=CC=C(C)C=2)=C1 NBPGPQJFYXNFKN-UHFFFAOYSA-N 0.000 claims description 8
- 238000009413 insulation Methods 0.000 claims description 8
- 238000007789 sealing Methods 0.000 claims description 8
- 230000006872 improvement Effects 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical group [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- MWVTWFVJZLCBMC-UHFFFAOYSA-N 4,4'-bipyridine Chemical group C1=NC=CC(C=2C=CN=CC=2)=C1 MWVTWFVJZLCBMC-UHFFFAOYSA-N 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 238000010791 quenching Methods 0.000 abstract 1
- 230000000171 quenching effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- JBAKCAZIROEXGK-LNKPDPKZSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O JBAKCAZIROEXGK-LNKPDPKZSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 3
- -1 Zinc Halides Chemical class 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000004032 porphyrins Chemical group 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005837 enolization reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Catalysts (AREA)
Abstract
The invention relates to an improved catalyzed synthesis method for a 1,4-dicarbonyl compound. The method comprises the following steps: adding a compound as shown in a formula I and a compound as shown in a formula II into a reactor; adding triethylamine, a composite catalyst and TBHP (Tert-Butyl Hydroperoxide) in sequence; performing sealed thermal reaction; after reacting, adding a saturated sodium thiosulfate aqueous solution for performing a quenching reaction; extracting the obtained mixture by using ethyl acetate; drying an organic phase by using anhydrous magnesium sulfate; evaporating to remove an extracting solvent; purifying residues by use of a column to obtain the 1,4-dicarbonyl compound as shown in a formula (III). The method is mild in reaction conditions and high in product yield and purity, so that an efficient composite catalytic synthesis method is provided for the preparation of the type of compound, the requirement of preparation of intermediates for use in the fields of organics, chemical industry, medicine and the like is met, and the method has wide industrial application prospect and high market value.
Description
Technical field
The present invention relates to a kind of synthetic method of carbonyl compound, relate to especially a kind of improvement process for catalytic synthesis of Isosorbide-5-Nitrae-dicarbonyl compound, belong to the synthetic field of chemical intermediate.
Background technology
Isosorbide-5-Nitrae-dicarbonyl compound is the multi-functional structure slice unit for the synthesis of carbocyclic ring and heterogeneous ring compound, for example, can be used for building derivative fragments such as cyclopentenone, furans, thiophene, pyridazine and pyrroles.As can be seen here, the method that Isosorbide-5-Nitrae-dicarbonyl compound synthesis unit is prepared in development directly, efficiently will be extremely important for the progress of organic, chemical industry, medicine and other fields.
At present, in prior art, there is the synthetic method of multiple Isosorbide-5-Nitrae-dicarbonyl compound or similar compound, for example:
Makoto Yasuda etc. (" Cross-Coupling Reaction of α – Chloroketones and Organotin Enollates Catalyzed by Zinc Halides for Synthesis of γ-Diketones ", J.Am.Chem.Soc., 2002,124,7440-7447) report a kind of 1, the preparation method of 4-dicarbonyl compound, it is experienced by alpha-chloro ketone and the enolate of tin, and aldol-type reacts, rearrangement reaction prepares.Reaction formula is as follows:
Michael C.Myers etc. (" Catalytic Conjugate Addition of Carbonyl Anions under Neutral Aqueous Conditions ", J.Am.Chem.Soc., 2005,127,14675-14680) report a kind of reaction of catalysis of carbonyl negatively charged ion, it is applicable to wide in range pH scope, under neutrallty condition, alpha-keto carboxylic acid salt and thiazole salt generate corresponding active carbonyl group nucleophile, when conjugation receptor have can enolization proton time can react generation Isosorbide-5-Nitrae-dicarbonyl compound.Its reaction formula is as follows:
Shen Zhi-Liang etc. (" Synthesis of Water-Tolerant Indium Homoenolate in Aqueous Media and Its Application in the Synthesis of1; 4-Dicarbonyl Compounds via Palladium-Catalyzed Coupling with Acid Chloride ", J.Am.Chem.Soc., 2010,132,15852-15855) reported first a kind of ketone type indium enolate, this compound can prepare Isosorbide-5-Nitrae-dicarbonyl compound with acyl chlorides under palladium catalyst effect.Its reaction formula is as follows:
Michael Rossle etc. (" Formation of1; 4-Diketone by Aerobic Oxidative C-C Coupling of Styrene with1; 3-Dicarbonyl Compounds ", Angew.Chem.Int.Ed., 2004,43,6547-6549) one is disclosed by vinylbenzene and 1,3-dicarbonyl compound is prepared the method for Isosorbide-5-Nitrae-dicarbonyl compound in the coupling of atmospheric oxidation C-C key.Its reaction formula is as follows:
Many drawbacks such as mentioned above, although there is the preparation method of multiple Isosorbide-5-Nitrae-dicarbonyl compound in prior art, these methods still exist certain defect, and the such as substrate scope of application is little, reaction yield is not high, aftertreatment is loaded down with trivial details.
For the foregoing reasons, the assembly type that the inventor is intended to by exploring existing composite catalyst starts a kind of 1, the improvement process for catalytic synthesis of 4-dicarbonyl compound, significantly improve product yield thereby realize, with the demand that meets organic, chemical industry of present stage, medicine and other fields research and development and produce, and continue to explore and improve existing synthetic method.
Summary of the invention
In order to overcome above-mentioned pointed many defects, the inventor conducts in-depth research and explores, and is paying after enough creative works, thereby is completing the present invention.
Particularly, technical scheme of the present invention and content relate to a kind of 1, the improvement process for catalytic synthesis of 4-dicarbonyl compound, described method comprises: in reactor, add following formula (I) compound and following formula (II) compound, then add successively triethylamine, composite catalyst, TBHP (tertbutyl peroxide), sealing thermal insulation reaction, add after completion of the reaction saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained shown in formula (III) 1, 4-dicarbonyl compound:
Wherein:
R
1be selected from H, halogen, C
1-C
6alkyl or C
1-C
6alkoxyl group;
R
2be selected from H, C
1-C
6alkyl, C
1-C
6alkoxyl group;
R
3be selected from C
1-C
6alkyl, C
1-C
6alkoxyl group or C
1-C
6alkylamino, phenyl amino.
In described synthetic method of the present invention, R
1can be positioned at ortho position, a position or the contraposition of vinyl.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6the implication of alkyl refers to the straight or branched alkyl with 1-6 carbon atom, and it has comprised C
1alkyl, C
2alkyl, C
3alkyl, C
4alkyl, C
5alkyl or C
6alkyl, for example can be to indefiniteness methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl or n-hexyl etc.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6alkoxyl group refers to " C defined above
1-C
6alkyl " group after being connected with O atom.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, C
1-C
6alkylamino refers to " C defined above
1-C
6alkyl " replacement-NH
2on the group that forms of H atom.
In described synthetic method of the present invention, unless otherwise prescribed, from start to finish, the implication of halogen refers to haloid element, non-exclusively for example can be F, Cl, Br or I.
In described synthetic method of the present invention, described composite catalyst is Cu (acac)
2, phthalocyanine and pyridine compounds mixture, wherein Cu (acac)
2, phthalocyanine and pyridine compounds mol ratio be 1:0.1-0.3:0.5-0.8, be preferably 1:0.2:0.6.
In described synthetic method of the present invention, described pyridine compounds is 2,2 '-dipyridyl, 3,3 '-dimethyl-2,2 '-dipyridyl, 4,4'-Bipyridine, 4,4 '-dimethyl-2, any one in 2 '-dipyridyl, be preferably 4,4 '-dimethyl-2,2 '-dipyridyl.
In described synthetic method of the present invention, formula (I) is 1:1-3 with the mol ratio of formula (II) compound, for example can be to indefiniteness 1:1,1:1.5,1:2,1:2.5 or 1:3.
In described synthetic method of the present invention, the mol ratio of formula (I) compound and composite catalyst is 1:0.01-0.05, for example can be to indefiniteness 1:0.01,1:0.02,1:0.03,1:0.04 or 1:0.05.The mole number of the composite catalyst wherein contrasting is Cu (acac)
2, phthalocyanine and pyridine compounds three mole number sum.
In described synthetic method of the present invention, formula (I) compound is 1:4-5mol/L with the molecular volume ratio of triethylamine, be that every 1mol formula (I) compound uses 4-5L triethylamine, the molecular volume ratio of these both materials is as can be 1:4mol/L, 1:4.1mol/L, 1:4.2mol/L, 1:4.3mol/L, 1:4.4mol/L, 1:4.5mol/L, 1:4.6mol/L, 1:4.7mol/L, 1:4.8mol/L, 1:4.9mol/L or 1:5mol/L.
In described synthetic method of the present invention, TBHP is with the molecular volume of triethylamine than being 1:1mol/L, and every 1mol TBHP uses 1L triethylamine.
In described synthetic method of the present invention, temperature of reaction is 40-120 ℃, for example can be to indefiniteness 40 ℃, 50 ℃, 55 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃, 110 ℃ or 120 ℃, is preferably 50-60 ℃.
In described synthetic method of the present invention, reaction times can be determined by the residual quantity of liquid chromatography or TLC detection raw material, for example can be 10-15 hour, is indefiniteness for example 10 hours, 11 hours, 12 hours, 13 hours, 14 hours or 15 hours.
In described synthetic method of the present invention, aftertreatment after reaction finishes can be: after completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the described column purification process of crossing can be used TLC tracing and monitoring and determine suitable wash-out terminal, the mixture that the elutriant using is petrol ether/ethyl acetate, wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.
As mentioned above, the inventor filters out suitable component by a large amount of scientific experiments and prepares novel complex catalyst system, effectively improve 1, the reaction yield of 4-dicarbonyl compound, have that reaction conditions gentleness, reaction times are short, the plurality of advantages such as product yield and purity height, there is industrial applications prospect widely, met the common requirements of organic, chemical industry, medicine and other fields.
Embodiment
Below by specific embodiment, the present invention is described in detail; but the purposes of these exemplary embodiments and object are only used for exemplifying the present invention; not real protection scope of the present invention is formed to any type of any restriction, more non-protection scope of the present invention is confined to this.
Embodiment 1
Take Cu (acac) according to mol ratio 1:0.2:0.6
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 30mmol formula (II) compound, then add successively 50ml triethylamine, 0.4mmol composite catalyst, 50mmol TBHP, 55 ℃ of reactions of sealing thermal insulation 12 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.The productive rate of formula (III) compound is 96.7%, purity 98.6% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,400MHz):δ7.84(d,J=10.0Hz,2H),7.56(d,J=10.0Hz,2H),4.13(q,J=8.0Hz,2H),3.42(dd,J=19.0,8.0Hz,1H),3.12-3.01(m,1H),2.94(dd,J=19.0,6.0Hz,1H),1.31-1.22(m,6H)。
Embodiment 2
Take Cu (acac) according to mol ratio 1:0.1:0.8
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 20mmol formula (II) compound, then add successively 40ml triethylamine, 0.3mmol composite catalyst, 40mmol TBHP, 60 ℃ of reactions of sealing thermal insulation 10 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.Productive rate is 96.4%, purity 98.7% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,400MHz):δ7.91(d,J=8.0Hz,2H),6.94(d,J=8.0Hz,2H),4.16(q,J=8.0Hz,2H),3.84(s,3H),3.41(dd,J=17.0,8.0Hz,1H),3.15-3.05(m,1H),2.96(dd,J=17.0,6.0Hz,1H),1.31-1.23(m,6H)。
Embodiment 3
Take Cu (acac) according to mol ratio 1:0.3:0.5
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 10mmol formula (II) compound, then add successively 45ml triethylamine, 0.1mmol composite catalyst, 45mmol TBHP, 50 ℃ of reactions of sealing thermal insulation 15 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.Productive rate is 96.1%, purity 98.3% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,400MHz):δ7.93(d,J=8.0Hz,2H),7.48(d,J=8.0Hz,2H),3.71(s,3H),3.45(dd,J=18.0,10.0Hz,1H),3.09-3.02(m,2H),1.77-1.55(m,2H),1.40-1.31(m,13H),0.92(t,J=8.0Hz,3H)。
Embodiment 4
Take Cu (acac) according to mol ratio 1:0.1:0.7
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 30mmol formula (II) compound, then add successively 46ml triethylamine, 0.5mmol composite catalyst, 46mmolTBHP, 55 ℃ of reactions of sealing thermal insulation 13 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.Productive rate is 96.2%, purity 98.5% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,400MHz):δ7.95(d,J=10.0Hz,2H),7.49(d,J=10.0Hz,2H),3.25(t,J=6.0Hz,2H),2.69(t,J=6.0Hz,2H),1.46(s,9H),1.36(s,9H)。
Embodiment 5
Take Cu (acac) according to mol ratio 1:0.2:0.8
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 20mmol formula (II) compound, then add successively 42ml triethylamine, 0.2mmol composite catalyst, 42mmolTBHP, 50 ℃ of reactions of sealing thermal insulation 11 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.Productive rate is 95.9%, purity 98.8% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,500MHz):δ7.92(d,J=8.0Hz,2H),7.45(d,J=8.0Hz,2H),3.57(dd,J=17.0,8.0Hz,1H),3.45-3.18(m,4H),2.91(dd,J=17.0,6.0Hz,1H),1.81-1.69(m,1H),1.67-1.55(m,1H),1.51-1.41(m,2H),1.40-1.33(m,2H),1.31(s,9H),1.26-1.22(m,3H),1.20(d,J=8.0Hz,3H),0.95(t,J=8.0Hz,3H),0.87(t,J=8.0Hz,3H)。
Embodiment 6
Take Cu (acac) according to mol ratio 1:0.2:0.5
2, phthalocyanine and 4,4 '-dimethyl-2,2 '-dipyridyl, by its ground and mixed evenly after, obtain the composite catalyst for the present embodiment.
In reactor, add 10mmol formula (I) compound and 30mmol formula (II) compound, then add successively 46ml triethylamine, 0.5mmol composite catalyst, 46mmol TBHP, 55 ℃ of reactions of sealing thermal insulation 13 hours.After completion of the reaction, add saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained formula (III) compound, the mixture that the described excessively elutriant that column purification uses is petrol ether/ethyl acetate, and wherein the volume ratio of sherwood oil and ethyl acetate is 2:1.Productive rate is 96.2%, purity 98.5% (HPLC).Product formula (III) compound nuclear magnetic resonance data as follows:
1H?NMR(CDCl
3,500MHz):δ7.93(d,J=10.0Hz,2H),7.48(d,J=10.0Hz,2H),7.43-7.16(m,10H),3.34(t,J=7.0Hz,2H),2.65(t,J=7.0Hz,2H),1.34(s,9H)。
Embodiment 7-12
Remove the corresponding Cu (acac) in the catalyzer in preparation example 1
2replace with outside following component, implemented respectively embodiment 7-12 in the mode identical with embodiment 1-6, the corresponding relation of component and experimental result is as shown in table 1 below.
Table 1
As seen from the above table, the inventor has carried out great many of experiments screening to the kind of metal-salt, wherein, in the time using other metal-salt, finds all can not obtain with Cu (acac)
2identical high reaction yield.
Embodiment 13-18
Remove corresponding 4 in the catalyzer in preparation example 1,4 '-dimethyl-2,2 '-dipyridyl replaces with outside following pyridine compounds component, has implemented respectively embodiment 13-18 in the mode identical with embodiment 1-6, and the corresponding relation of component and experimental result is as shown in table 2 below.
Table 2
As seen from the above table, the kind of pyridine compounds has critical impact to the overall performance of composite catalyst, wherein 4,4 '-dimethyl-2, the function that 2 '-dipyridyl is risen in catalyzer will obviously be better than other pyridine compounds, comprises and its structure very similar 3,3 '-dimethyl-2,2 '-dipyridyl, have significantly synergy, and this synergy only just can be put up the best performance under the collocation of suitable ingredients between each component of visible composite catalyst.
Embodiment 19-24
Except the corresponding phthalocyanine component in the catalyzer in preparation example 1 is replaced with porphyrin, implement respectively embodiment 19-24 in the mode identical with embodiment 1-6, the corresponding relation of component and experimental result is as shown in table 3 below.
Table 3
As seen from the above table, phthalocyanine component in composite catalyst can play obvious transfer transport, metal complex and catalysis induction performance, itself and other two component close association and effectively strengthen catalytic performance, can not reach corresponding yield with the porphyrin of its structural similitude, produce unforeseeable technique effect.
In sum, the inventor has developed a kind of novel, efficient 1 in a creative way, the preparation technology of 4-dicarbonyl compound, in the time adopting NEW TYPE OF COMPOSITE catalyst system of the present invention, can show the technique effect of significant high yield, and the change of catalyst component or replacement all can not reach identical product yield, this is creative place of the present invention just.
The purposes that should be appreciated that these embodiment only limits the scope of the invention for the present invention being described but not being intended to.In addition; also should understand; after having read technology contents of the present invention, those skilled in the art can make various changes, modification and/or modification to the present invention, within these all equivalent form of values fall within the protection domain that the application's appended claims limits equally.
Claims (9)
1. one kind 1, the improvement process for catalytic synthesis of 4-dicarbonyl compound, described method comprises: in reactor, add following formula (I) compound and following formula (II) compound, then add successively triethylamine, composite catalyst, TBHP (tertbutyl peroxide), sealing thermal insulation reaction, add after completion of the reaction saturated aqueous sodium thiosulfate cancellation reaction, gained mixture extracts through ethyl acetate, organic phase anhydrous magnesium sulfate drying, then extraction solvent is removed in evaporation, residue is crossed column purification and is obtained Isosorbide-5-Nitrae-dicarbonyl compound shown in formula (III):
Wherein:
R
1be selected from H, halogen, C
1-C
6alkyl or C
1-C
6alkoxyl group;
R
2be selected from H, C
1-C
6alkyl, C
1-C
6alkoxyl group;
R
3be selected from C
1-C
6alkyl, C
1-C
6alkoxyl group or C
1-C
6alkylamino, phenyl amino.
2. synthetic method as claimed in claim 1, is characterized in that: described composite catalyst is Cu (acac)
2, phthalocyanine and pyridine compounds mixture.
3. method as claimed in claim 2, is characterized in that: Cu in described catalyzer (acac)
2, phthalocyanine and pyridine compounds mol ratio be 1:0.1-0.3:0.5-0.8, be preferably 1:0.2:0.6.
4. the synthetic method as described in claim 1-3 any one, it is characterized in that: described pyridine compounds is 2,2 '-dipyridyl, 3,3 '-dimethyl-2,2 '-dipyridyl, 4,4 '-dipyridyl, 4,4 '-dimethyl-2, any one in 2 '-dipyridyl, is preferably 4,4 '-dimethyl-2,2 '-dipyridyl.
5. the synthetic method as described in claim 1-4 any one, is characterized in that: described formula (I) is 1:1-3 with the mol ratio of formula (II) compound.
6. the synthetic method as described in claim 1-5 any one, is characterized in that: the mol ratio of described formula (I) compound and catalyzer is 1:0.01-0.05.
7. the synthetic method as described in claim 1-6 any one, is characterized in that: described formula (I) compound is 1:4-5mol/L with the molecular volume ratio of triethylamine.
8. the synthetic method as described in claim 1-7 any one, is characterized in that: the molecular volume of described TBHP and triethylamine is 1:1mol/L.
9. the synthetic method as described in claim 1-8 any one, is characterized in that: temperature of reaction is 40-120 ℃; Reaction times is 10-15 hour.
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| CN108912001A (en) * | 2018-06-01 | 2018-11-30 | 华侨大学 | A kind of process for catalytic synthesis of 1,3- dicarbapentaborane class compound |
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| MICHAEL ROSSLE ET AL: "Formation of 1,4-Diketones by Aerobic Oxidative C-C Coupling of Styrene with 1,3-Dicarbonyl Compounds", 《ANGEW. CHEM. INT. ED.》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966877A (en) * | 2017-04-27 | 2017-07-21 | 郑州大学 | A kind of 1,4 dicarbonyl compounds and preparation method thereof |
| CN106966877B (en) * | 2017-04-27 | 2020-02-07 | 郑州大学 | 1, 4-dicarbonyl compound and preparation method thereof |
| CN108912001A (en) * | 2018-06-01 | 2018-11-30 | 华侨大学 | A kind of process for catalytic synthesis of 1,3- dicarbapentaborane class compound |
| CN108912001B (en) * | 2018-06-01 | 2021-03-23 | 华侨大学 | Catalytic synthesis method of 1, 3-dicarbonyl compound |
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