CN109516945A - A kind of preparation method of 5- methoxy-Indole - Google Patents
A kind of preparation method of 5- methoxy-Indole Download PDFInfo
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- CN109516945A CN109516945A CN201811381171.8A CN201811381171A CN109516945A CN 109516945 A CN109516945 A CN 109516945A CN 201811381171 A CN201811381171 A CN 201811381171A CN 109516945 A CN109516945 A CN 109516945A
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- methoxy
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- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000000843 powder Substances 0.000 claims abstract description 66
- 239000003054 catalyst Substances 0.000 claims abstract description 29
- 150000002475 indoles Chemical class 0.000 claims abstract description 19
- 239000005995 Aluminium silicate Substances 0.000 claims abstract description 18
- 235000012211 aluminium silicate Nutrition 0.000 claims abstract description 18
- 239000002131 composite material Substances 0.000 claims abstract description 18
- 239000010881 fly ash Substances 0.000 claims abstract description 18
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000010445 mica Substances 0.000 claims abstract description 18
- 229910052618 mica group Inorganic materials 0.000 claims abstract description 18
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims abstract description 17
- 239000001119 stannous chloride Substances 0.000 claims abstract description 17
- 235000011150 stannous chloride Nutrition 0.000 claims abstract description 17
- 239000010902 straw Substances 0.000 claims abstract description 17
- 239000004926 polymethyl methacrylate Substances 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 239000013067 intermediate product Substances 0.000 claims description 63
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 48
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 32
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 30
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 25
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 239000012429 reaction media Substances 0.000 claims description 24
- 239000011812 mixed powder Substances 0.000 claims description 17
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 16
- 238000000498 ball milling Methods 0.000 claims description 16
- 235000009518 sodium iodide Nutrition 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 13
- 238000000227 grinding Methods 0.000 claims description 9
- 239000012298 atmosphere Substances 0.000 claims description 8
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 229960004756 ethanol Drugs 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 8
- 239000005457 ice water Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000005245 sintering Methods 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- -1 sawdust Substances 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- HWBFKIWJBCELRA-UHFFFAOYSA-N 1-phenylethyl nitrate Chemical compound [O-][N+](=O)OC(C)C1=CC=CC=C1 HWBFKIWJBCELRA-UHFFFAOYSA-N 0.000 description 1
- NQAHQFLGDQZLPL-UHFFFAOYSA-N 2-(5-amino-2-methoxyphenyl)ethanol Chemical compound COC1=CC=C(N)C=C1CCO NQAHQFLGDQZLPL-UHFFFAOYSA-N 0.000 description 1
- 229940097276 5-methoxytryptamine Drugs 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/122—Halides of copper
-
- 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
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/60—Catalysts, in general, characterised by their form or physical properties characterised by their surface properties or porosity
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a kind of preparation methods of 5- methoxy-Indole, specifically includes the following steps: voluminous powder is made using mica powder, kaolin, flyash, plant straw powder, sawdust, polymethyl methacrylate as raw material first, then by itself and the compound obtained composite catalyst of stannous chloride；Then using indoles as raw material, by series reaction, target product is made under the catalysis of above-mentioned catalyst.This method is easy to operate, and product separation is simple, high income.
Description
Technical field:
The present invention relates to medicine intermediate preparation fields, are specifically related to a kind of preparation method of 5- methoxy-Indole.
Background technique:
5- methoxy-Indole is important medicine intermediate, is production prevention and cure of cardiovascular disease, neurological disease, tumour and increasing
The important source material of strong immunity drug.Its important use first is that secondary colour aminated compounds, wherein epiphysin and its derivative
Circadian rhythm and sleep are being adjusted, it is antitumor etc. largely effective.5- methoxyl group -2- benzyl tryptamines has antitumaous effect.
Serotonine, cardiovascular disease and mental disease prevention and treatment and it is anti-in terms of have an obvious effect, it is also controllable to inhale
Cigarette is excessive.5- methoxytryptamine hydrochlorides are tranquillizer and anti-ray agent.5- methoxy-Indole still manufactures fragrance and amino acid
Raw material.
Chinese patent (200610016357.4) discloses a kind of synthetic method of 5- methoxy-Indole, detailed process are as follows:
It is anti-with paraformaldehyde or gaseous formaldehyde, formalin under the action of basic catalyst first using ortho-methylnitrobenzene as raw material
O-nitrophenylethanol should be made；Then it is reacted and 2- (beta-hydroxy ethyl)-phenyl is made under the action of zinc powder with ammonium chloride
Then azanol reacts it under the action of the concentrated sulfuric acid, 2- (beta-hydroxy ethyl) -4- aminoanisole is made；Finally will
It is reacted under the action of three the machine phosphine ruthenic chlorides is made 5- methoxy-Indole.This method mild condition.But reaction process compared with
Complexity, route are long.
Summary of the invention:
In view of the deficiencies of the prior art, it is an object of the present invention to provide a kind of preparation method of 5- methoxy-Indole, the party
Method is easy to operate, and route is short, and mild condition is easily controllable, and product purity is high, is easily isolated, high income.
To achieve the above object, the invention adopts the following technical scheme:
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 500-800 DEG C and is burnt under the conditions of air atmosphere
Knot processing 3-5h, after treatment cool to room temperature with the furnace, grind, and voluminous powder is made；The voluminous powder, stannous chloride are mixed
Grinding is closed, composite catalyst is made；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 0.5-1.5h under the conditions of ice-water bath with sodium iodide, then
Continue to be stirred to react 0.5h at room temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 8-15h, is made intermediate
Product 3；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
2-4h is reacted under the action of conjunction catalyst, just benzene is extracted as extractant after reaction, collects organic phase, takes out extraction
Target product is made in agent, vacuum distillation.
As a preferred embodiment of the above technical solution, in step (1), the amount ratio of each component is respectively as follows: mica in parts by weight
3-9 parts of powder, 2-4 parts of kaolin, 10-20 parts of flyash, 5-11 parts of plant straw powder, 1-5 parts of sawdust, poly-methyl methacrylate
1.5-3.5 parts of ester.
As a preferred embodiment of the above technical solution, in step (2), voluminous powder, stannous chloride mass ratio be 1:(1.25-
1.55)。
As a preferred embodiment of the above technical solution, in step (3), the mass concentration of solution of sodium bisulfite is 15-25%.
As a preferred embodiment of the above technical solution, in step (3), indoles, solution of sodium bisulfite amount ratio be (1-4.5)
G:(4-8) mL.
As a preferred embodiment of the above technical solution, in step (4), the amount ratio of intermediate product 1 and acetic anhydride is 1g:(50-
60)mL。
As a preferred embodiment of the above technical solution, in step (4), the time of the reaction is 0.1-0.5h, the reaction
Temperature is 80-90 DEG C.
As a preferred embodiment of the above technical solution, in step (5), intermediate product 2, sodium iodide mass ratio be (2.35-
3.5): 1.
As a preferred embodiment of the above technical solution, in step (6), the temperature of the reaction is 60-100 DEG C, and the reaction time is
1-4h。
As a preferred embodiment of the above technical solution, in step (6), intermediate product 3, sodium methoxide, composite catalyst mass ratio
For 5:(1-2): (0.45-0.76).
The invention has the following advantages:
Target product 5- methoxy-Indole, the reaction process is made using indoles as raw material, by series reaction in the present invention
Simply, easily operated, it may be implemented to industrialize, and product separation is simpler, without the methods of pillar layer separation, operation
Simply.
The present invention is carried out during preparing 5- methoxy-Indole by 5- halogeno indole using homemade composite catalyst
Catalysis, the catalyst are that raw material auxiliary adds polymethyl methacrylate, and and chlorination with mica powder, kaolin, flyash etc.
Cuprous progress is compound, and porosity is high, can be come into full contact with reaction substrate, and catalytic activity is high, can be effectively improved the yield of product,
And cost is relatively low for the catalyst preparation.The yield of present invention sintetics in terms of indoles is 89.5% or more.
Specific embodiment:
In order to better understand the present invention, below by embodiment, the present invention is further described, and embodiment is served only for solving
The present invention is released, any restriction will not be constituted to the present invention.
Embodiment 1
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than being respectively as follows: 3 parts of mica powder in parts by weight, 2 parts of kaolin, 10 parts of flyash, 5 parts of plant straw powder, 1 part of sawdust, gathering
1.5 parts of methyl methacrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 500 DEG C under the conditions of air atmosphere at sintering
3h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.25；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 1g:4mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 0.5h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 8h, intermediate product 3 is made；Its
In, intermediate product 2, sodium iodide mass ratio be 2.35:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
2h is reacted under the action of conjunction catalyst, target product is made；Wherein；Intermediate product 3, sodium methoxide, composite catalyst mass ratio
For 5:1:0.45.
Embodiment 2
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than being respectively as follows: 9 parts of mica powder in parts by weight, 4 parts of kaolin, 20 parts of flyash, 11 parts of plant straw powder, 5 parts of sawdust, gathering
3.5 parts of methyl methacrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 800 DEG C under the conditions of air atmosphere at sintering
5h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.55；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 4.5g:
8mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 1.5h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 15h, intermediate product 3 is made；
Wherein, intermediate product 2, sodium iodide mass ratio be 3.5:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
4h is reacted under the action of conjunction catalyst, target product is made；Wherein；Intermediate product 3, sodium methoxide, composite catalyst mass ratio
For 5:2:0.76.
Embodiment 3
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than be respectively as follows: in parts by weight 4 parts of mica powder, 2.5 parts of kaolin, 12 parts of flyash, 6 parts of plant straw powder, 2 parts of sawdust,
2 parts of polymethyl methacrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 600 DEG C under the conditions of air atmosphere at sintering
3.5h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.35；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 1.5g:
5mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 0.7h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 9h, intermediate product 3 is made；Its
In, intermediate product 2, sodium iodide mass ratio be (2.55:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
2h is reacted under the action of conjunction catalyst, target product is made；Wherein；Intermediate product 3, sodium methoxide, composite catalyst mass ratio
For 5:1.4:0.5.
Embodiment 4
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than being respectively as follows: 5 parts of mica powder, 3 parts of kaolin, 4 parts of flyash, 7 parts of plant straw powder, 3 parts of sawdust, poly- first in parts by weight
2 parts of base methyl acrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 700 DEG C under the conditions of air atmosphere at sintering
4h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.45；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 2g:6mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 0.9h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 11h, intermediate product 3 is made；
Wherein, intermediate product 2, sodium iodide mass ratio be 2.85:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
2.5h is reacted under the action of conjunction catalyst, target product is made；Wherein；The quality of intermediate product 3, sodium methoxide, composite catalyst
Than for 5:1.4:0.65.
Embodiment 5
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than being respectively as follows: 6 parts of mica powder in parts by weight, 3 parts of kaolin, 16 parts of flyash, 8 parts of plant straw powder, 3 parts of sawdust, gathering
2 parts of methyl methacrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 700 DEG C under the conditions of air atmosphere at sintering
4.5h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.45；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 3g:6mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 1.1h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 12h, intermediate product 3 is made；
Wherein, intermediate product 2, sodium iodide mass ratio be 3.0:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
3.5h is reacted under the action of conjunction catalyst, target product is made；Wherein；The quality of intermediate product 3, sodium methoxide, composite catalyst
Than for 5:1.6:0.65.
Embodiment 6
A kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, it is mixed that refinement is made
Close powder；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid is then added,
It stirs while adding, then cools to room temperature, continue milled processed, pretreatment mixed-powder is made；Wherein, the dosage of each component
Than being respectively as follows: 8 parts of mica powder, 3.5 parts of kaolin, 18 parts of flyash, 10 parts of plant straw powder, sawdust 4.5 in parts by weight
Part, 3.2 parts of polymethyl methacrylate；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 700 DEG C under the conditions of air atmosphere at sintering
4.5h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；Wherein, voluminous powder, stannous chloride mass ratio be 1:1.45；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reacts
After filter, solid is dry, intermediate product 1 is made；Wherein, indoles, solution of sodium bisulfite amount ratio be 4.3g:
7mL；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product is made
2；
(5) using water as reaction medium, intermediate product 2 is reacted into 1.3h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 13h, intermediate product 3 is made；
Wherein, intermediate product 2, sodium iodide mass ratio be 3.2:1；
(6) using n,N-Dimethylformamide as reaction medium, intermediate product 3 and sodium methoxide is multiple made from step (2)
3.5h is reacted under the action of conjunction catalyst, target product is made；Wherein；The quality of intermediate product 3, sodium methoxide, composite catalyst
Than for 5:1.8:0.65.
Claims (10)
1. a kind of preparation method of 5- methoxy-Indole, which comprises the following steps:
(1) ball-milling treatment after mixing mica powder, kaolin and dehydrated alcohol, it is dry after ball milling, refinement mixed powder is made
End；By itself and flyash, plant straw powder, sawdust mixed grinding, the polymethyl methacrylate of liquid, Bian Jia is then added
Enter side stirring, then cool to room temperature, continue milled processed, pretreatment mixed-powder is made；
(2) pretreatment mixed-powder obtained above is placed in Muffle furnace at 500-800 DEG C under the conditions of air atmosphere at sintering
3-5h is managed, after treatment cools to room temperature with the furnace, grinds, and voluminous powder is made；The voluminous powder, stannous chloride are mixed and ground
Composite catalyst is made in mill；
(3) first using indoles as raw material, using ethyl alcohol as solvent, solution of sodium bisulfite is added and is stirred to react, reaction terminates
After filter, solid is dry, intermediate product 1 is made；
(4) it by intermediate product 1 and acetic anhydride in reactor, using dimethylbenzene as reaction medium, reacts and intermediate product 2 is made；
(5) using water as reaction medium, intermediate product 2 is reacted into 0.5-1.5h under the conditions of ice-water bath with sodium iodide, then in room
Continue to be stirred to react 0.5h under temperature, solution of sodium bisulfite and sodium hydroxide is added, is stirred to react 8-15h, intermediate product is made
3；
(6) it using n,N-Dimethylformamide as reaction medium, urges intermediate product 3 and sodium methoxide are compound made from step (2)
2-4h is reacted under the action of agent, and target product is made.
2. a kind of preparation method of 5- methoxy-Indole as described in claim 1, which is characterized in that in step (1), each component
Amount ratio be respectively as follows: 3-9 parts of mica powder, 2-4 parts of kaolin, 10-20 parts of flyash, plant straw powder 5- in parts by weight
11 parts, 1-5 parts of sawdust, 1.5-3.5 parts of polymethyl methacrylate.
3. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: in step (2), periporate
Last, stannous chloride mass ratio is 1:(1.25-1.55).
4. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: in step (3), sulfurous acid
The mass concentration of hydrogen sodium solution is 15-25%.
5. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: in step (3), indoles,
The amount ratio of solution of sodium bisulfite is (1-4.5) g:(4-8) mL.
6. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: in step (4), is produced from centre
The amount ratio of object 1 and acetic anhydride is 1g:(50-60) mL.
7. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: described anti-in step (4)
The time answered is 0.1-0.5h, and the temperature of the reaction is 80-90 DEG C.
8. a kind of preparation method of 5- methoxy-Indole as described in claim 1, which is characterized in that in step (5), is produced from centre
Object 2, sodium iodide mass ratio be (2.35-3.5): 1.
9. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: described anti-in step (6)
The temperature answered is 60-100 DEG C, reaction time 1-4h.
10. a kind of preparation method of 5- methoxy-Indole as described in claim 1, it is characterised in that: intermediate in step (6)
Product 3, sodium methoxide, composite catalyst mass ratio be 5:(1-2): (0.45-0.76).
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