CN106243011A - The preparation method of indole 3 methanol - Google Patents
The preparation method of indole 3 methanol Download PDFInfo
- Publication number
- CN106243011A CN106243011A CN201610629664.3A CN201610629664A CN106243011A CN 106243011 A CN106243011 A CN 106243011A CN 201610629664 A CN201610629664 A CN 201610629664A CN 106243011 A CN106243011 A CN 106243011A
- Authority
- CN
- China
- Prior art keywords
- indole
- hours
- montmorillonite
- stirring
- carbinol
- 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.)
- Withdrawn
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
- B01J2531/48—Zirconium
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
- Cosmetics (AREA)
Abstract
The present invention provides the preparation method of indole 3 methanol, comprises the steps: that zirconium chloride, cyclopentadiene are carried out reaction by Diethylamine method in mixed solvent and prepared bis cyclopentadienyl zirconium dichloride by (1)；(2) just montmorillonite is modified process by cystine and obtains modified montmorillonoid；(3) modified montmorillonoid is combined with bis cyclopentadienyl zirconium dichloride, obtains montmorillonite load bis cyclopentadienyl zirconium dichloride；(4) modified montmorillonoid is combined with potassium borohydride, obtains montmorillonite load potassium borohydride；(5) indole, toluidines are occurred under montmorillonite load bis cyclopentadienyl zirconium dichloride effect the acylation reaction on third place, obtains indole 3 formaldehyde；(6) indole 3 formaldehyde is prepared indole 3 methanol by montmorillonite load potassium borohydride reduction.The productivity of the present invention is higher, and preparation cost is relatively low.
Description
Technical field
The present invention relates to medicine intermediate field, particularly relate to the preparation method of Indole-3-carbinol.
Background technology
Indole-3-carbinol is the natural composition of food of cross section vegetable, has the tumor of body many organs and presses down
Make use, cancer is had the most again certain elemental abundances, and multi-drug resistance of the tumor can be made to reverse, therefore indole-3-
Methanol is a kind of important medicine intermediate.At present, the preparation method of Indole-3-carbinol mostly with indole-3-formaldehyde as raw material,
In different reaction systems, obtain Indole-3-carbinol with different reducing agent reduction indole-3-formaldehydes, there is problems of
The separating difficulty of reducing agent is relatively big, adds preparation cost；The preparation method of indole-3-formaldehyde is mostly with indole, N, N-diformazan
Base Methanamide is that raw material reacts under phosphorous oxychloride effect and makes, and productivity is general.
Publication No. CN102766082A, publication date are 2012.11.07, apply for that the gloomy biotechnology of artificial Xi'an alliance is limited
The Chinese patent application of company discloses " new method of a kind of synthesis of indole-3-methanol ", comprises the steps: 1) accurately weigh
Indole 3 formaldehyde 0.2mol, concentration is the ethanol 200 milliliters of 99%, potassium borohydride 0.2mol, room temperature reaction 3 hours；2) decompression
To-0.8mpa, concentrate；3) add water 500 milliliters, separate out solid, be indole 3 methanol crude product.This invention employing medical alcohol is
Solvent, solves benzene residual excessive problem, and reduces cost.But, this synthetic method productivity is general, and solvent is medical
The difficulty that ethanol is separated from product is relatively big, and preparation cost is higher.
Summary of the invention
The technical problem to be solved in the present invention is to provide the preparation method of Indole-3-carbinol, and the productivity of this preparation method is relatively
Height, and preparation cost is relatively low.
For solving above-mentioned technical problem, the technical scheme is that
The preparation method of Indole-3-carbinol, comprises the steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, continue 2 hours post-heating of stirring extremely
45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, filter cake sucking filtration again after formic acid cyclic washing,
The filter cake chloroform obtained is recrystallized to give bis cyclopentadienyl zirconium dichloride；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains montmorillonite solution in 10 minutes, by double mercaptos third
Propylhomoserin adds in distilled water, and after being heated to 70 DEG C, stirring obtains cystine solution in 10 minutes, is added by cystine solution
Entering in montmorillonite solution, stir 2 hours at 70 DEG C, filtered by the product obtained after being cooled to room temperature, filter cake deionized water is anti-
After backwashing is washed, and is vacuum dried 20 hours, obtains modified montmorillonoid after grinding at 70 DEG C；
(3) step (2) gained modified montmorillonoid, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added in maceration tank, after being heated to 70 DEG C
Stir 7 hours, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite load dichloro two cyclopentadienyl
Zirconium；
(4) step (2) gained modified montmorillonoid, potassium borohydride, ethanol are added in maceration tank, stir after being heated to 70 DEG C
7 hours, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor by indole, continues stirring 1 hour, then by hydrogen-oxygen after being added dropwise to complete
Change sodium solution and add reactor, continue to stir 1 hour, the product centrifugal filtration that will obtain after standing 2 hours, with distilled water repeatedly
Washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water after being cooled to 16 DEG C, and the product centrifugal filtration that will obtain, with steaming
Distilled water cyclic washing post-drying, obtains Indole-3-carbinol.
Preferably, in step of the present invention (1), dichloromethane, zirconium chloride, oxolane, diethylamine, cyclopentadiene
Mass ratio is 2.47:1.45:3.87:1:1.02.
Preferably, in step of the present invention (1), the time for adding of oxolane is 30 minutes.
Preferably, in step of the present invention (2), the concentration of montmorillonite solution is 1.25g/mL, cystine solution
Concentration be 1.6g/mL.
Preferably, in step of the present invention (2), montmorillonite, the mass ratio of cystine are 5:2.
Preferably, in step of the present invention (3), modified montmorillonoid, bis cyclopentadienyl zirconium dichloride, the mass ratio of dimethylbenzene are 1:
47:(14-15)。
Preferably, in step of the present invention (3), modified montmorillonoid, potassium borohydride, the mass ratio of ethanol are 1:26:(8-
9)。
Preferably, in step of the present invention (5), the mass concentration of sodium hydroxide solution is 16%, toluidines, montmorillonite
Load bis cyclopentadienyl zirconium dichloride, indole, the mass ratio of sodium hydroxide solution are 20:5:6:60.
Preferably, in step of the present invention (5), the time for adding of indole is 1 hour.
Preferably, in step of the present invention (6), indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron hydrogen
Change potassium, the mass ratio of distilled water is 1:18:1:5.
Compared with prior art, the method have the advantages that
The syntheti c route of the present invention is that indole, toluidines occur under catalyst action the acylation on third place anti-
Should, obtain indole-3-formaldehyde, then pass through reducing agent reduction prepare Indole-3-carbinol, the present invention use catalyst with
Reducing agent is all different from existing method, and zirconium chloride, cyclopentadiene were passed through Diethylamine method in mixed solvent by the present invention before this
Carry out reaction and prepared bis cyclopentadienyl zirconium dichloride, then by montmorillonite by cystine be modified process obtain modified cover de-
Soil, cystine is effectively increased the absorbability of montmorillonite, then by modified montmorillonoid respectively with bis cyclopentadienyl zirconium dichloride and boron hydrogen
Change potassium to be combined, obtain catalyst montmorillonite load bis cyclopentadienyl zirconium dichloride and reducing agent montmorillonite load hydroboration
Potassium, the former catalysis activity is better than existing catalyst, substantially increases productivity, and be easily separated regeneration, the most repeatable
Using, therefore can effectively reduce preparation cost, the latter and solvent methanol can be effectively improved the extent of reaction, improve product further
Amount, and be easy to separate from product, preparation cost can be reduced further.
Detailed description of the invention
The present invention is described in detail, in illustrative examples and the explanation of this present invention below in conjunction with specific embodiment
It is used for explaining the present invention, but not as a limitation of the invention.
Embodiment 1
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:14, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added dipping
In groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, covered
De-soil load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:8, potassium borohydride, ethanol are added in maceration tank,
Stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite and bear
Carry potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Embodiment 2
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:14.2, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added leaching
In stain groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain
Montmorillonite load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:8.2, potassium borohydride, ethanol are added maceration tank
In, stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite
Load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Embodiment 3
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:14.4, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added leaching
In stain groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain
Montmorillonite load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:8.4, potassium borohydride, ethanol are added maceration tank
In, stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite
Load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Embodiment 4
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:14.6, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added leaching
In stain groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain
Montmorillonite load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:8.6, potassium borohydride, ethanol are added maceration tank
In, stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite
Load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Embodiment 5
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:14.8, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added leaching
In stain groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain
Montmorillonite load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:8.8, potassium borohydride, ethanol are added maceration tank
In, stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite
Load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Embodiment 6
Synthesis of indole-3-methanol in accordance with the following steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, after opening stirring, adds zirconium chloride,
Then it is added dropwise to oxolane in 30 minutes, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, dichloromethane, chlorination
Zirconium, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02, add after continuing stirring 2 hours
Heat, to 45 DEG C of back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, is taken out after filter cake formic acid cyclic washing again
Filter, is recrystallized to give bis cyclopentadienyl zirconium dichloride by the filter cake chloroform obtained；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains the illiteracy that concentration is 1.25g/mL for 10 minutes
De-soil solution, adds cystine in distilled water, and after being heated to 70 DEG C, stirring obtains concentration for 10 minutes is the double of 1.6g/mL
Mercapto alanine solution, montmorillonite, the mass ratio of cystine are 5:2, are added by cystine solution in montmorillonite solution,
Stir 2 hours at 70 DEG C, after being cooled to room temperature, the product obtained is filtered, filter cake deionized water cyclic washing, true at 70 DEG C
Empty dry 20 hours, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid that mass ratio is 1:47:15, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added dipping
In groove, stir 7 hours after being heated to 70 DEG C, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, covered
De-soil load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid that mass ratio is 1:26:9, potassium borohydride, ethanol are added in maceration tank,
Stir 7 hours after being heated to 70 DEG C, after taking-up, use ethanol cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite and bear
Carry potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load dichloro two cyclopentadienyl
Zirconium, is maintained at 25 DEG C in reactor, be added dropwise in reactor in 1 hour by indole, continues stirring 1 hour, so after being added dropwise to complete
After sodium hydroxide solution that mass concentration is 16% added reactor, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole,
The mass ratio of sodium hydroxide solution is 20:5:6:60, continues stirring 1 hour, was centrifuged by the product obtained after standing 2 hours
Filter, by distilled water cyclic washing post-drying, obtains indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load boron are added in a kettle.
Hydrofining, reacts 6 hours after being heated to 55 DEG C, adds distilled water, indole-3-formaldehyde, methanol, step (4) after being cooled to 16 DEG C
Gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5, and distilled water is used in the product centrifugal filtration that will obtain
Cyclic washing post-drying, obtains Indole-3-carbinol.
Through test, the productivity of embodiment 1-6 and comparative example is as shown in the table, and comparative example is Publication No.
The Chinese patent of CN102766082A:
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Comparative example | |
| Productivity/% | 77.5 | 77.6 | 78.4 | 78.5 | 77.2 | 77.8 | 62.3 |
As seen from the above table, the productivity of embodiment of the present invention 1-6 is above comparative example.
The principle of above-described embodiment only illustrative present invention and effect thereof, not for limiting the present invention.Any ripe
Above-described embodiment all can be modified under the spirit and the scope of the present invention or change by the personage knowing this technology.Cause
This, have usually intellectual such as complete with institute under technological thought without departing from disclosed spirit in art
All equivalences become are modified or change, and must be contained by the claim of the present invention.
Claims (10)
1. the preparation method of Indole-3-carbinol, it is characterised in that comprise the steps:
(1) under logical nitrogen protection, dichloromethane is added in the reaction bulb in ice-water bath, add zirconium chloride after opening stirring, then
It is added dropwise to oxolane, after continuing stirring 1 hour, adds diethylamine and cyclopentadiene, continue 2 hours post-heating of stirring to 45 DEG C
Back flow reaction 7 hours, the product sucking filtration that will obtain after being cooled to room temperature, filter cake sucking filtration again after formic acid cyclic washing, will
To filter cake chloroform be recrystallized to give bis cyclopentadienyl zirconium dichloride；
(2) adding in distilled water by montmorillonite, after being heated to 70 DEG C, stirring obtains montmorillonite solution, by cystine in 10 minutes
Adding in distilled water, after being heated to 70 DEG C, stirring obtains cystine solution in 10 minutes, is added by cystine solution and covers
In de-soil solution, stirring 2 hours at 70 DEG C, filtered by the product obtained after being cooled to room temperature, filter cake deionized water is washed repeatedly
Wash, be vacuum dried 20 hours at 70 DEG C, after grinding, obtain modified montmorillonoid；
(3) step (2) gained modified montmorillonoid, bis cyclopentadienyl zirconium dichloride, dimethylbenzene are added in maceration tank, stir after being heated to 70 DEG C
7 hours, after taking-up, use dimethylbenzene cyclic washing, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite load bis cyclopentadienyl zirconium dichloride；
(4) step (2) gained modified montmorillonoid, potassium borohydride, ethanol are added in maceration tank, stir 7 after being heated to 70 DEG C little
Time, use ethanol cyclic washing after taking-up, be vacuum dried 10 hours at 70 DEG C, obtain montmorillonite load potassium borohydride；
(5) add toluidines in a kettle., after stirring 10 minutes, add step (3) gained montmorillonite load bis cyclopentadienyl zirconium dichloride,
It is maintained at 25 DEG C in reactor, indole is added dropwise in reactor, continue stirring 1 hour after being added dropwise to complete, then by hydroxide
Sodium solution adds reactor, continues stirring 1 hour, the product centrifugal filtration that will obtain after standing 2 hours, repeatedly washes with distilled water
Wash post-drying, obtain indole-3-formaldehyde；
(6) step (5) gained indole-3-formaldehyde, methanol, step (4) gained montmorillonite load hydroboration are added in a kettle.
Potassium, reacts 6 hours after being heated to 55 DEG C, adds distilled water, the product centrifugal filtration that will obtain, use distilled water after being cooled to 16 DEG C
Cyclic washing post-drying, obtains Indole-3-carbinol.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (1), dichloro
Methane, zirconium chloride, oxolane, diethylamine, the mass ratio of cyclopentadiene are 2.47:1.45:3.87:1:1.02.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (1), tetrahydrochysene
The time for adding of furan is 30 minutes.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (2), cover de-
The concentration of soil solution is 1.25g/mL, and the concentration of cystine solution is 1.6g/mL.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (2), cover de-
Soil, the mass ratio of cystine are 5:2.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (3), modified
Montmorillonite, bis cyclopentadienyl zirconium dichloride, the mass ratio of dimethylbenzene are 1:47:(14-15).
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (3), modified
Montmorillonite, potassium borohydride, the mass ratio of ethanol are 1:26:(8-9).
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (5), hydrogen-oxygen
The mass concentration changing sodium solution is 16%, toluidines, montmorillonite load bis cyclopentadienyl zirconium dichloride, indole, the quality of sodium hydroxide solution
Ratio is 20:5:6:60.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (5), indole
Time for adding be 1 hour.
The preparation method of Indole-3-carbinol the most according to claim 1, it is characterised in that: in described step (6), Yin
Diindyl-3-formaldehyde, methanol, step (4) gained montmorillonite load potassium borohydride, the mass ratio of distilled water are 1:18:1:5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610629664.3A CN106243011A (en) | 2016-08-02 | 2016-08-02 | The preparation method of indole 3 methanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610629664.3A CN106243011A (en) | 2016-08-02 | 2016-08-02 | The preparation method of indole 3 methanol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106243011A true CN106243011A (en) | 2016-12-21 |
Family
ID=57606415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610629664.3A Withdrawn CN106243011A (en) | 2016-08-02 | 2016-08-02 | The preparation method of indole 3 methanol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106243011A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997101A (en) * | 2018-06-15 | 2018-12-14 | 苏州科技大学 | Response type luminous agent 9,10- diphenylanthrancene derivative and preparation method thereof and converting system on efficient dim light prepared therefrom |
| CN113845463A (en) * | 2021-11-15 | 2021-12-28 | 西安久中生物科技有限公司 | Environment-friendly preparation process of indole-3-methanol |
-
2016
- 2016-08-02 CN CN201610629664.3A patent/CN106243011A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997101A (en) * | 2018-06-15 | 2018-12-14 | 苏州科技大学 | Response type luminous agent 9,10- diphenylanthrancene derivative and preparation method thereof and converting system on efficient dim light prepared therefrom |
| CN108997101B (en) * | 2018-06-15 | 2021-10-08 | 苏州科技大学 | Reaction type luminescent agent 9, 10-diphenyl anthracene derivative, preparation method thereof and high-efficiency weak light up-conversion system prepared from same |
| CN113845463A (en) * | 2021-11-15 | 2021-12-28 | 西安久中生物科技有限公司 | Environment-friendly preparation process of indole-3-methanol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101735340B (en) | Method for preparing heparin sodium by combining enzymolysis and salt decomposition | |
| CN106391001A (en) | Active carbon loaded ruthenium-platinum bimetallic composite catalyst, and preparation method and applications thereof | |
| CN107937024B (en) | Method for producing high-quality light white oil from base oil | |
| CN106243011A (en) | The preparation method of indole 3 methanol | |
| CN105170143B (en) | A kind of preparation method and applications of ruthenium Pd/carbon catalyst | |
| CN110394158A (en) | A kind of application of titanium-based metal organic backbone adsorbent material and preparation method thereof and separate palladium | |
| JP2017520616A (en) | Extraction method of chlorogenic acid from Tochu leaves | |
| CN104258900B (en) | A kind of method of preparation and use of coking benzene hydrogenation desulfurization catalyst | |
| CN101940951B (en) | Load-type chiral catalyst and application thereof in catalysis preparation of Fluoxetine intermediate | |
| CN109232200B (en) | Preparation method of isoeugenol | |
| CN106397210A (en) | Preparation method of 2-chloracetylamino-5-nitro benzophenone | |
| CN101209415B (en) | Catalyst for preparing linalyl acetate by hydrogenation of dehydrogenated linalyl acetate | |
| CN107999073B (en) | Preparation method of formaldehyde ethynylation reaction catalyst | |
| CN105198734B (en) | Method of preparing gallic acid | |
| CN103102386A (en) | Preparation method of Tigogenin | |
| CN111482178A (en) | Supported nano nickel-based catalyst and preparation method and application thereof | |
| CN109876806A (en) | A kind of catalyst for hydrogenation and preparation method thereof and purposes | |
| CN104689824A (en) | Preparation method of Fe/Mo-Al2O3 catalyst and method of synthesizing leaf alcohol by virtue of piperylene | |
| CN105152938B (en) | A kind of technique efficiently synthesizing secondary carbon primary amine N1923 | |
| CN102961637A (en) | Method for extracting and purifying general flavones in corn stigma | |
| US2237980A (en) | Manufacture of optically active menthones and menthols | |
| CN109772331B (en) | CoFe catalyst for preparing allyl alcohol by glycerol hydrogenation, and preparation method and application thereof | |
| CN110437284B (en) | 5', 8-di (dimethyldiguanidino) luteolin-chromium (III) complex | |
| CN114570376B (en) | Catalyst for synthesizing menthone and method for synthesizing menthone | |
| CN107999036A (en) | The high pressure resistant affinity chromatography medium of chromatographic column |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20161221 |