CN103951637A - Method for synthesizing 6-(2-(3,3-dimethyl oxirane-2-yl) ethyl) naphthalene-1,4-diketone - Google Patents
Method for synthesizing 6-(2-(3,3-dimethyl oxirane-2-yl) ethyl) naphthalene-1,4-diketone Download PDFInfo
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- CN103951637A CN103951637A CN201410149529.XA CN201410149529A CN103951637A CN 103951637 A CN103951637 A CN 103951637A CN 201410149529 A CN201410149529 A CN 201410149529A CN 103951637 A CN103951637 A CN 103951637A
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- naphthalene
- nitrae
- isosorbide
- ethyl
- diketone
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 title abstract 3
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims abstract description 84
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000002904 solvent Substances 0.000 claims abstract description 24
- 238000005406 washing Methods 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims description 33
- 239000002253 acid Substances 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 2
- 239000012265 solid product Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract 2
- 230000001590 oxidative effect Effects 0.000 abstract 2
- 229960001701 chloroform Drugs 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 12
- 238000006735 epoxidation reaction Methods 0.000 description 11
- 230000035484 reaction time Effects 0.000 description 11
- 230000009466 transformation Effects 0.000 description 11
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- 239000004593 Epoxy Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000001569 carbon dioxide Substances 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 150000001335 aliphatic alkanes Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 208000012839 conversion disease Diseases 0.000 description 3
- 150000002500 ions Chemical group 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 238000005698 Diels-Alder reaction Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- -1 hydrogen oxanthranol diacetate esters Chemical class 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 150000004053 quinones Chemical class 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 101100400999 Caenorhabditis elegans mel-28 gene Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical group O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- HZVGIXIRNANSHU-UHFFFAOYSA-N naphthalene-1,2,3,4-tetrone Chemical compound C1=CC=C2C(=O)C(=O)C(=O)C(=O)C2=C1 HZVGIXIRNANSHU-UHFFFAOYSA-N 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000000192 social effect Effects 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
- C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
- C07D301/14—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a method for synthesizing 6-(2-(3,3-dimethyl oxirane-2-yl) ethyl) naphthalene-1,4-diketone. The method comprises the following steps: on the basis of using 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone as a raw material, peroxyacetic acid as an oxidant and chloroform as a solvent, performing reaction at 30 DEG C, and washing and purifying a product after completing the reaction. Compared with the prior art, the method for synthesizing 6-(2-(3,3-dimethyl oxirane-2-yl) ethyl) naphthalene-1,4-diketone, disclosed by the invention, has the outstanding advantages as follows: peroxyacetic acid with cheap price and low concentration is adopted as the oxidant; the method is high in reaction yield, strong in selectivity, simple in operation, low in preparation cost and good in practicability, and can be used for generating good economic and social benefits.
Description
Technical field
The invention belongs to organic compound synthesis technical field, be specifically related to a kind of method of synthetic 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone.
Background technology
Quinones is that a class is extensively present in natural natural organic-compound, and except can be used for dyestuffs industries, its biological activity all has a wide range of applications in pharmacy and medical field.In the molecule of quinones, having undersaturated cyclohexanedione structure, have the redox characteristic of easy generation, is the important connector that in bio-metabolic process, electronics transmits, and this makes it have multiple biological activity, has pharmacological action widely.At present, by the synthetic hydroquinone derivative of Diels-Alder method, the clones such as P-388 muroid leukemia, A-549 Human Lung Cancer, HT-29 and H-460 human colon carcinoma, MEL-28 malignant melanoma, mammary cancer MCF-7 mammary cancer are all had to higher inhibition activity with para benzoquinone or 1,4-naphthoquinone so that bay is rare.
6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone, deep yellow oily liquid, molecular formula C16H15O2, molecular weight 240.12, density (20 DEG C) 3.078g/cm3,184.71 DEG C of fusing points, 483.69 DEG C of boiling points, be insoluble in water, be soluble in methylene dichloride, ethyl acetate, chloroform etc., mainly taking the rare and para benzoquinone of bay as raw material, after Diels-Alder reaction, prepare through aromatization again.6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone structural modification is mainly comprised: aromizing, epoxidation reaction, cracking, oxidation or reduction etc.
In the research of the synthetic naphthaquinone derivatives of the people such as Aurora Molinari, select metachloroperbenzoic acid to make oxygenant, select methylene dichloride as solvent, be 76% through the synthetic epoxy efficiency of pcr product of epoxidation reaction, this reaction oxygenant metachloroperbenzoic acid price is high, and efficiency of pcr product is lower.
Summary of the invention
Goal of the invention: for the deficiencies in the prior art, the object of the present invention is to provide a kind of method of synthetic 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, make its preparation method simple, finished product yield is high.
Technical scheme: in order to realize foregoing invention object, the technical solution used in the present invention is:
A kind of method of synthetic 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone: add 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone and solvent in reaction vessel, stir, drip Peracetic Acid; 10～50 DEG C of temperature controls, reaction 4～8h, successively with hypo solution, saturated nacl aqueous solution washing, removes Peracetic Acid after finishing, and separatory, gets organic phase, and with anhydrous sodium sulfate drying, product rotation is steamed except desolventizing; With column chromatography purification, sherwood oil-acetone is eluent, and the target components obtaining, through vacuum-drying, obtains deep yellow solid product; Wherein, 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:1～5 with the mol ratio of Peracetic Acid; Solvent is toluene, methylene dichloride, ethyl acetate or chloroform;
Described reaction is 6h.
Described 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:4 with the mol of Peracetic Acid ratio.
Described solvent is chloroform.
Described temperature control is 30 DEG C.
In dripping Peracetic Acid, add acid acceptor, described acid acceptor is selected from Na
2cO
3, NaHCO
3, K
2cO
3, KHCO
3; 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:1.0～1.6 with the mol ratio of acid acceptor.
Described acid acceptor is NaHCO
3, 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone and NaHCO
3mol than for 1:1.2～1.3.
Beneficial effect: compared with prior art, synthetic 6-(2-(3 of the present invention, 3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-1, the method of 4-diketone, adopt cheap, the Peracetic Acid of lower concentration is oxygenant, selectivity is strong, simple to operate, preparation cost is low, when oxygenant is Peracetic Acid (18%-20%), n(6-(4-methyl-3-pentenyl) naphthalene-1, 4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL chloroform, 30 DEG C of temperature of reaction, n(6-(4-methyl-3-pentenyl) naphthalene-1, 4-diquinone): n(sodium bicarbonate) when=1:1.2-1:1.3 (mol/mol), 6-(2-(3, 3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-1, 4-diketone yield is 94.3%.There is good practicality, can produce good economic benefit and social effect.
Brief description of the drawings
Fig. 1 is the infrared spectrum of 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone;
Fig. 2 is the mass spectrum of 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone;
Fig. 3 is 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone leading ion fragment and fragmentation figure;
Fig. 4 is the 1H NMR figure of 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone.
Embodiment
Below in conjunction with specific embodiment, the present invention is further illustrated.
Instrument and reagent that following examples are used are as follows:
Peracetic Acid (commercially available 18%-20%), anhydrous sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus, toluene, methylene dichloride, ethyl acetate, chloroform, sherwood oil, acetone, Sulfothiorine, sodium-chlor, chromatographic silica gel (38 μ m-63 μ m), silica-gel plate (GF-254) etc.The U.S. 7890A of Agilent company gas chromatograph; Agilent 5975C mass spectrograph; Nicolet380FT-IR infrared spectrometer; Avance AV-500 nuclear magnetic resonance spectrometer.
Embodiment 1
6-(4-methyl-3-pentenyl) naphthalene-1, the preparation of 4-diquinone, with reference to Chinese patent ZL201110219585.2 or document 1(Luo Jin high mountain, soar and fly, sea dimension .5,5-dimethyl-5,6,7,8,9, the study on the synthesis [J] of 10-six hydrogen oxanthranol diacetate esters. Nanjing Normal University's journal (natural science edition), 2012,35 (2): 61-65) or document 2(soar and fly, Luo Jin high mountain .6-(4-methyl-3-pentenyl)-5,8-dihydro-1, the study on the synthesis [J] of 4-naphthalenediol. chemistry of forest product and industry, 2012,32(4): 102-106) carry out.
In the 250mL there-necked flask that magnetic agitation is housed, add 2.40g(10mmol) 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone and 50mL solvent, stir, and drip Peracetic Acid with constant pressure funnel, add acid acceptor simultaneously.After reaction finishes, successively with hypo solution, saturated nacl aqueous solution washing, remove Peracetic Acid, separatory, gets organic phase, and with anhydrous sodium sulfate drying, product rotation is steamed except desolventizing.With column chromatography purification, sherwood oil-acetone (3:1, v/v) is eluent, and the target components obtaining, through vacuum-drying, obtains deep yellow solid.Between 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone and solvent with magnitude relation can be for often adding naphthalene diquinone 2.4g(10mmol), solvent load is 50mL.
The Analysis and Identification of product: infrared spectra adopts liquid-film method.Adopt gas chromatograph, mass spectrograph coupling to analyze product, analysis condition is: (m), 80 DEG C of initial temperature, retain 2min to 30m × 0.25mm × 0.25 μ to HP-5 capillary column, and 10 DEG C/min is warming up to 260 DEG C, retains 10min.Carrier gas is helium, flow velocity 1mL/min, and injector temperature is 280 DEG C, and ion source temperature is 230 DEG C, and level Four bar temperature is 150 DEG C, and transmission line temperature is 250 DEG C, sample size 0.4 μ L, area normalization standard measure.1H NMR analysis condition is: tetramethylsilane (TMS) is interior mark, deuterated trichloromethane (CDCl
3) be solvent, proton resonance frequency 500MHz.
Use Nicolet380FT-IR infrared spectrometer to carry out infrared analysis qualification to experimental product, analytical results as shown in Figure 1, as shown in Figure 1,2959.07cm
-1, 2919.10cm
-1for the C-H stretching vibration of saturated alkane group; 1671.53cm
-1for carbonylic stretching vibration; 1598.49cm
-1for the skeletal vibration of aromatic ring; 1381.41cm
-1for the C-H out-of-plane deformation vibration of methyl; 1300.00cm
-1for C-O-C symmetrical stretching vibration; 820.60cm
-1for C-O-C asymmetrical stretching vibration; 1041.21cm
-1, 1141.71cm
-1for C-H in-plane bending vibration.
Product is carried out to GC-MS analysis, and as shown in Figure 2, wherein molecular ion peak is m/z=256 to result, and base peak is m/z=198.Main fragment ion and fragmentation are as shown in Figure 3.
For the structure of further confirmatory test product, adopt nuclear magnetic resonance spectroscopy means, obtain the 1H-NMR spectrogram of experimental product, as shown in Figure 4,
1the data of H NMR are as follows: δ 6.99 (1H, 1, No. 2 upper naphthoquinones ring hydrogen); δ 7.96(s, 1H, No. 3 benzene ring hydrogens); δ 8.0(d, 1H, No. 4 benzene ring hydrogens); δ 7.63(d, 1H, No. 5 benzene ring hydrogens); δ 2.92,3.0(t, 2H, the hydrogen on No. 6 alkane); δ 1.94(m, 2H, the hydrogen on No. 7 alkane); δ 2.78(t, 1H, the hydrogen on No. 8 alkane); δ 1.30(s, 3H, No. 9-CH
3the hydrogen connecting); δ 1.23(s, 3H, the hydrogen that No. 10-CH3 connects); Water peak in δ 1.61(solvent DMSO).
Final definite, the structural formula of product is as follows:
Embodiment 26-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone is synthetic
The reaction of preparation 6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone is the epoxidation reaction under Peracetic Acid (commercially available 18%-20%).Due in reaction process, 6-(the 2-(3 generating, 3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-1,, can there is acid ring-opening reaction in 4-diketone, therefore in reaction, need to add acid acceptor under different condition, neutralizing acid, and add acid acceptor dripping in Peracetic Acid, can prevent from dripping like this time, because [H+] is local too high, and ring-opening reaction occurs.The present invention analyzes factors such as time, Peracetic Acid consumption, type of solvent, temperature, acid acceptor kind and consumptions respectively, and reaction process is as follows:
(1) impact of reaction times on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, oxygenant consumption is n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:3(mol/mol), 50mL methylene dichloride, temperature of reaction≤10 DEG C, Carbon Dioxide 1.39g (13mmol).The differential responses time is as shown in table 1 on efficiency of pcr product and reaction preference impact.
The impact of table 1 reaction times on epoxidation reaction
| Reaction times/h | Reaction conversion ratio/% | Reaction preference/% | Yield/% |
| 4.0 | 72.0 | 71.2 | 51.3 |
| 5.0 | 73.5 | 78.9 | 58.0 |
| 6.0 | 75.1 | 87.4 | 65.6 |
| 7.0 | 81.1 | 72.0 | 58.4 |
| 8.0 | 89.8 | 65.1 | 58.5 |
From table 1, at a certain temperature, along with the continuous prolongation in reaction times, the transformation efficiency of 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone increases gradually.But when reaction proceeded to after 6 hours, along with the prolongation in reaction times, the selectivity of epoxy product starts continuous reduction, this is because the ring-opening reaction of epoxy product is accelerated along with the prolongation of time.Therefore, the reaction times is that 6h is comparatively suitable.
(2) impact of Peracetic Acid consumption on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, 50mL methylene dichloride, reaction times 6h, temperature of reaction≤10 DEG C, Carbon Dioxide 1.39g (13mmol).Peracetic Acid consumption is as shown in table 2 on efficiency of pcr product and reaction preference impact.
The impact of table 2 Peracetic Acid consumption on epoxidation reaction
Result shows, when Peracetic Acid consumption reaches 1:4 (mol/mol) when above, 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone could almost transform completely, is far longer than its theoretical value.From table 2, along with the continuous increase of Peracetic Acid consumption, 6-(4-methyl-3-pentenyl) naphthalene-1, the transformation efficiency of 4-diquinone also improves gradually, but in the time that Peracetic Acid consumption reaches 1:4 (mol/mol), continuing increases Peracetic Acid consumption, and the selectivity of epoxy product starts sharply to reduce.Therefore, n(6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol) is more suitable.
(3) impact of type of solvent on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL solvent, reaction times 6h, temperature of reaction≤10 DEG C, Carbon Dioxide 1.39g (13mmol).Different solvents is as shown in table 3 on efficiency of pcr product and reaction preference impact.
The impact of table 3 different solvents on epoxidation reaction
| Solvent | Reaction conversion ratio/% | Reaction preference/% | Yield/% |
| Toluene | 54.4 | 60.9 | 33.1 |
| Methylene dichloride | 96.6 | 81.7 | 78.8 |
| Ethyl acetate | 44.8 | 77.3 | 34.6 |
| Chloroform | 95.3 | 87.3 | 83.2 |
From table 3, different solvents is larger on epoxidation reaction impact.While making solvent with toluene and ethyl acetate, the transformation efficiency of 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is not ideal; During with methylene dichloride and chloroform give solvent, both transformation efficiencys are all similar, but when chloroform give solvent, the transformation efficiency of reaction is slightly high, and the boiling point of chloroform is higher than methylene dichloride, not volatile.Therefore, select chloroform give solvent comparatively suitable.
(4) impact of temperature of reaction on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL chloroform, reaction times 6h, temperature of reaction≤10 DEG C, Carbon Dioxide 1.39g (13mmol).Differential responses temperature is as shown in table 4 on efficiency of pcr product and reaction preference impact.
The impact of table 4 temperature of reaction on epoxidation reaction
From table 4, in certain temperature range, along with the raising of temperature, 6-(4-methyl-3-pentenyl) naphthalene-1, the selectivity of the transformation efficiency of 4-diquinone and epoxy product also improves constantly, but in the time that temperature is raised to 40 DEG C, transformation efficiency and selectivity all start to decline.Therefore selected 30 DEG C of optimal temperatures as epoxidation reaction.
(5) impact of acid acceptor type on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL chloroform, reaction times 6h, 30 DEG C of temperature of reaction, Carbon Dioxide 1.39g (13mmol).Different acid acceptor kinds are as shown in table 5 on efficiency of pcr product and reaction preference impact.
The impact of table 5 acid acceptor kind on epoxidation reaction
From table 5, the transformation efficiency of 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone does not change substantially, but does not add acid acceptor in reaction system, and the selectivity of epoxy product is lower, and after adding acid acceptor, selectivity all obviously promotes.Add NaHCO
3and KHCO
3the selectivity of rear epoxy product is the highest, and both effects differ and are not very large, consider NaHCO
3more cheap, so select NaHCO
3as acid acceptor.
(6) impact of acid acceptor consumption on efficiency of pcr product
Add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone 2.40g (10mmol), oxygenant is Peracetic Acid, n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL chloroform, reaction times 6h, 30 DEG C of temperature of reaction, acid acceptor is sodium bicarbonate.Acid acceptor consumption is as shown in table 6 on efficiency of pcr product and reaction preference impact.
The impact of table 6 acid acceptor consumption on epoxidation reaction
From table 6, along with the increase (within the scope of 1:1.0-1.1:1.3) of sodium bicarbonate consumption, the transformation efficiency of epoxy product improves constantly, but while continuing to increase the consumption of sodium bicarbonate, transformation efficiency and selectivity all obviously reduce.Therefore, the Optimum of sodium bicarbonate is n(6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone): n(sodium bicarbonate)=1:1.2-1:1.3 (mol/mol).
Embodiment 3
According to the result of embodiment 2,6-(2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-1, the suitable preparation process condition of building-up reactions of 4-diketone is: oxygenant is Peracetic Acid (18%-20%), n(6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone): the agent of n(Peracetic Acid)=1:4 (mol/mol), 50mL chloroform, 30 DEG C of temperature of reaction, n(6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone): n(sodium bicarbonate)=1:1.2-1.3 (mol/mol).With reference to the method for embodiment 2, stability experiment with this understanding, its result is as shown in table 7.With this understanding, the transformation efficiency of 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is greater than 99%, and reaction selection rate is also more than 94%, and four times experimental result is all more stable.
The impact of table 7 test number (TN) on experiment stability
| Test number (TN) | Reaction conversion ratio/% | Reaction preference/% | Yield/% |
| 1 | 99.4 | 94.1 | 93.5 |
| 2 | 99.9 | 94.7 | 94.6 |
| 3 | 99.1 | 95.2 | 94.3 |
| 4 | 99.8 | 94.8 | 94.6 |
Claims (7)
1. the method for a synthetic 6-(2-(3,3-, bis-first base Evil the third encircle-2-yls) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, it is characterized in that: in reaction vessel, add 6-(4-methyl-3-pentenyl) naphthalene-1,4-diquinone and solvent, stir, and drips Peracetic Acid; 10 ~ 50 DEG C of temperature controls, reaction 4 ~ 8h, successively with hypo solution, saturated nacl aqueous solution washing, removes Peracetic Acid after finishing, and separatory, gets organic phase, and with anhydrous sodium sulfate drying, product rotation is steamed except desolventizing; With column chromatography purification, sherwood oil-acetone is eluent, and the target components obtaining, through vacuum-drying, obtains deep yellow solid product; Wherein, 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:1 ~ 5 with the mol ratio of Peracetic Acid; Solvent is toluene, methylene dichloride, ethyl acetate or chloroform.
2. the method for synthetic 6-according to claim 1 (2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, is characterized in that, described reaction is 6h.
3. synthetic 6-(2-(3 according to claim 1,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) method of naphthalene-Isosorbide-5-Nitrae-diketone, it is characterized in that, described 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:4 with the mol of Peracetic Acid ratio.
4. the method for synthetic 6-according to claim 1 (2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, is characterized in that, described solvent is chloroform.
5. the method for synthetic 6-according to claim 1 (2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, is characterized in that, described temperature control is 30 DEG C.
6. the method for synthetic 6-according to claim 1 (2-(3,3-, bis-first base Evil the third encircle-2-yls) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, is characterized in that, in dripping Peracetic Acid, adds acid acceptor, and described acid acceptor is selected from Na
2cO
3, NaHCO
3, K
2cO
3, KHCO
3; 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone is 1:1.0 ~ 1.6 with the mol ratio of acid acceptor.
7. the method for synthetic 6-according to claim 6 (2-(3,3-bis-Jia Ji Evil the third encircle-2-yl) ethyl) naphthalene-Isosorbide-5-Nitrae-diketone, is characterized in that, described acid acceptor is NaHCO
3, 6-(4-methyl-3-pentenyl) naphthalene-Isosorbide-5-Nitrae-diquinone and NaHCO
3mol than for 1:1.2 ~ 1.3.
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| CN101362739A (en) * | 2008-09-18 | 2009-02-11 | 华东师范大学 | Method for preparing olefin epoxide |
| CN102320935A (en) * | 2011-08-02 | 2012-01-18 | 南京林业大学 | Method for synthesizing 6-(4-methyl-3-pentenyl)-5,8-dihydro-1,4-naphthalenediol |
| CN102511478A (en) * | 2011-11-01 | 2012-06-27 | 苏州晶瑞化学有限公司 | Stable peroxyacetic acid solution |
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| CN101362739A (en) * | 2008-09-18 | 2009-02-11 | 华东师范大学 | Method for preparing olefin epoxide |
| CN102320935A (en) * | 2011-08-02 | 2012-01-18 | 南京林业大学 | Method for synthesizing 6-(4-methyl-3-pentenyl)-5,8-dihydro-1,4-naphthalenediol |
| CN102511478A (en) * | 2011-11-01 | 2012-06-27 | 苏州晶瑞化学有限公司 | Stable peroxyacetic acid solution |
Non-Patent Citations (2)
| Title |
|---|
| JOSE MA MIGUEL DE1 CORRALA ET AL: "Further antineoplastic terpenylquinones and terpenylhydroquinones", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| 章亚东 等: "烯烃液相环氧化反应研究进展", 《化工进展》 * |
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