CN101693649A - Process for preparing 1.3.5-trimethoxybenzene - Google Patents
Process for preparing 1.3.5-trimethoxybenzene Download PDFInfo
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- CN101693649A CN101693649A CN200910210382A CN200910210382A CN101693649A CN 101693649 A CN101693649 A CN 101693649A CN 200910210382 A CN200910210382 A CN 200910210382A CN 200910210382 A CN200910210382 A CN 200910210382A CN 101693649 A CN101693649 A CN 101693649A
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- 229940030010 trimethoxybenzene Drugs 0.000 title claims abstract description 36
- 238000004519 manufacturing process Methods 0.000 title abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 123
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 46
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 19
- 239000012043 crude product Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 7
- 238000006198 methoxylation reaction Methods 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 239000007806 chemical reaction intermediate Substances 0.000 claims abstract description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 24
- 229950001336 bromamide Drugs 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 17
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 15
- 229960004756 ethanol Drugs 0.000 claims description 13
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000011259 mixed solution Substances 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 238000011084 recovery Methods 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229940045803 cuprous chloride Drugs 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 3
- 239000002826 coolant Substances 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000009413 insulation Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 2
- 150000004820 halides Chemical class 0.000 abstract description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 1
- 239000007809 chemical reaction catalyst Substances 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 abstract 1
- 238000004064 recycling Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 2
- OWYLAEYXIQKAOL-UHFFFAOYSA-N 4-(1-pyrrolidinyl)-1-(2,4,6-trimethoxyphenyl)-1-butanone Chemical compound COC1=CC(OC)=CC(OC)=C1C(=O)CCCN1CCCC1 OWYLAEYXIQKAOL-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229960001415 buflomedil Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006298 dechlorination reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- CKAPSXZOOQJIBF-UHFFFAOYSA-N hexachlorobenzene Chemical compound ClC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl CKAPSXZOOQJIBF-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a process for preparing 1.3.5-trimethoxybenzene, which includes the following steps: A) preparing 2.4.6-tribromoaniline by employing the method of enabling aniline to react with hydrobromic acid and dripping bromine into a reaction intermediate; B) preparing 1.3.5-tribromobenzene by mixing and reacting absolute ethyl alcohol with the 2.4.6-tribromoaniline and sodium nitrite, then dripping the mixture of sulfuric acid and the absolute ethyl alcohol into a reaction vessel and separating and recycling ethanol; C) methoxylation by mixing and reacting methanol nano with the 1.3.5-tribromobenzene, then separating methanol from the mixture to obtain a crude product of the 1.3.5-trimethoxybenzene. By employing the 1.3.5-tribromobenzene as raw materials and adopting the methoxylation reaction, the process can synthesize the 1.3.5-trimethoxybenzene in a simple manner and high yield which can reach 92.4%. By adopting cuprous halide as a reaction catalyst and adopting the method without adding reaction solvent, the process improves product purity and yield and reduces production cost.
Description
Technical field
The present invention relates to a kind of preparation method of 1.3.5-trimethoxy-benzene.
Background technology
1.3.5-trimethoxy-benzene is a kind of white crystalline powder, water insoluble, being important organic synthesis intermediate, being mainly used in that medicine is made and the synthetic field of waiting of agricultural chemicals, is the important source material of synthesizing the expansion new drug buflomedil Bulllomedil of peripheral vessel obstacle.1.3.5-trimethoxy-benzene is developed by Bayer A.G at first.The Hu Yimin of organic chemistry institute of Anhui Normal University etc. are to being that raw material carries out etherificate, two step of dechlorination prepared in reaction 1.3.5-trimethoxy-benzene has been carried out research with the hexachlorobenzene, and yield is 67.5%.Yield is on the low side, is unfavorable for industrialized production.
Summary of the invention
The preparation method of a kind of 1.3.5-trimethoxy-benzene that the purpose of this invention is to provide a kind of environmental friendliness, do not have danger, production cost is low, yield is high.
For achieving the above object, the present invention is by the following technical solutions:
The preparation method of a kind of 1.3.5-trimethoxy-benzene of the present invention is characterized in that comprising the steps:
A) preparation 2.4.6-bromamide; Utilize the reaction of aniline and Hydrogen bromide, and the method for dropping bromine prepares the 2.4.6-bromamide in reaction intermediate;
B) preparation 1.3.5-tribromo-benzene; With dehydrated alcohol and above-mentioned 2.4.6-bromamide and Sodium Nitrite hybrid reaction, in reaction vessel, drip the mixture of sulfuric acid and dehydrated alcohol then, get the 1.3.5-tribromo-benzene;
C) methoxylation; Methyl alcohol is received and above-mentioned 1.3.5-tribromo-benzene hybrid reaction, isolated methyl alcohol wherein then, obtain crude product 1.3.5-trimethoxy-benzene.
In steps A) at first in reactor, add the water of quantitative aniline and 5-20 times of aniline quality, the Hydrogen bromide that with the purity of 1-10 times of aniline quality is 20-30% again is added dropwise in the still, steam heated method is elevated to 50-75 ℃ with the temperature in the reactor, and is incubated 1-4 hour; When soaking time arrives, adopt water coolant that the temperature in the reactor is reduced to 10-40 ℃, and drip the bromine that dilute with Hydrogen bromide, and the bromine quality of Cai Yonging is 5.2-5.3 a times of above-mentioned aniline quality here, the hydrobromic quality that is used to dilute bromine is 1-3 a times of bromine quality; After the dropping bromine finishes, again the temperature in the reactor is warmed up to 45-65 ℃, is incubated 1-3 hour, then cool to room temperature; Emit the material in the reactor, filter with the suction filtration jar, the Hydrogen bromide of isolating wherein recycles, and leftover materials obtain the 2.4.6-bromamide through washing, oven dry.
At step B) at first the quantitative first component dehydrated alcohol is added in the reactor, add above-mentioned 2.4.6-bromamide again, the 2.4.6-bromamide and the first component dehydrated alcohol mass ratio that add are 1: 3-5, open and stir, add the Sodium Nitrite of the 20-40% of 2.4.6-bromamide quality in the reactor again; Reactor temperature is elevated to 50-70 ℃, is incubated 1-3 hour; Get ethanol and vitriolic mixed solution then and drip in the reactor, the quality of the dehydrated alcohol and the vitriol oil is the 70-90% of 2.4.6-bromamide quality in the reactor in described ethanol and the vitriolic mixed solution; After above-mentioned ethanol and vitriolic mixed solution all are added dropwise to complete, temperature in the control reactor remains on 60-80 ℃, insulation backflow 3-10 hour, temperature in the reactor is dropped to room temperature, emit the material in the reactor, filter with the suction filtration jar, the ethanol of isolating wherein recycles, and leftover materials obtain the 1.3.5-tribromo-benzene through washing, oven dry.
At step C), earlier be the methanol solution received of the methyl alcohol of 27.5-31% with vacuum suction pressure kettle with purity, open and stir, add above-mentioned 1.3.5-tribromo-benzene again, the methanol solution quality that methyl alcohol is received is 8-10 a times of 1.3.5-tribromo-benzene quality, stir after 0.5-2 hour, the catalyzer that will be equivalent to 1.3.5-tribromo-benzene quality 1-5% is poured in the pressure kettle, continues behind the sealed pot cover to stir 0.5-2 hour; Then pressure kettle is heated, when pressure reaches 0.1-0.3Mpa in the pot, stop heating, when pressure reaches 0.4-0.6Mpa in the pot, pick up counting, adopt the method for heating or cooling to make the pressure in the pressure kettle remain on 0.4-0.9Mpa simultaneously, kept 5-10 hour; Cooling makes pot interior pressure drop to 0.05-0.1Mpa then, by self pressure in the pot feed liquid is pressed onto in the still kettle; Do not open stirring,, make the temperature temperature in the still kettle remain on 60-100 ℃, steam and the methyl alcohol that steams put into the Methanol Recovery bucket in 5-10 hour still kettle heating; Close methyl alcohol storage tank exhaust-valve then, still kettle is vacuumized, vacuum tightness is at-0.01--0.08Mpa, and temperature is controlled at 60-80 ℃, the about 1-4 of distillation time hour, the methyl alcohol that steams is put into the Methanol Recovery bucket; Emit the material in the still kettle, obtain crude product 1.3.5-trimethoxy-benzene.
At step C), obtain also will advancing centrifugal rectifying after the crude product 1.3.5-trimethoxy-benzene, its step is to add entry and hydrochloric acid in crude product 1.3.5-trimethoxy-benzene, temperature is controlled at 10-60 ℃ and soaks after 1-3 hour crawl and open stirring; Stir that to put into whizzer after 0.5-3 hour centrifugal, the crude product after centrifugal adds rectifying tower, rectifying finish finished product 1.3.5-trimethoxy-benzene.
Described catalyzer is one or more in cuprous chloride, cuprous bromide and the cuprous iodide.
This method is that raw material passes through easy, the synthetic 1.3.5-trimethoxy-benzene with high yield of methoxylation with the 1.3.5-tribromo-benzene, and yield reaches 92.4%.This method adopts cuprous halide as catalysts, adopts the method that does not add reaction solvent, has improved product purity and yield, has reduced production cost.
Embodiment
The preparation method of a kind of 1.3.5-trimethoxy-benzene of the present invention comprises following basic step: A) preparation 2.4.6-bromamide; Utilize the reaction of aniline and Hydrogen bromide, and the method for dropping bromine prepares the 2.4.6-bromamide in reaction intermediate; B) preparation 1.3.5-tribromo-benzene; With dehydrated alcohol and above-mentioned 2.4.6-bromamide and Sodium Nitrite hybrid reaction, in reaction vessel, drip the mixture of sulfuric acid and dehydrated alcohol then, Separation and Recovery ethanol obtains the 1.3.5-tribromo-benzene; C) methoxylation; Methyl alcohol is received and above-mentioned 1.3.5-tribromo-benzene hybrid reaction, isolated methyl alcohol wherein then, obtain crude product 1.3.5-trimethoxy-benzene.
Embodiment 1:
A) at first in reactor, add the water of quantitative aniline and 5-20 times of aniline quality, the Hydrogen bromide that with the purity of 1-10 times of aniline quality is 20-30% again is added dropwise in the still, steam heated method is elevated to 50-75 ℃ with the temperature in the reactor, and is incubated 1-4 hour; When soaking time arrives, adopt water coolant that the temperature in the reactor is reduced to 10-40 ℃, and drip the bromine that dilute with Hydrogen bromide, and the bromine quality of Cai Yonging is 5.2-5.3 a times of above-mentioned aniline quality here, the hydrobromic quality that is used to dilute bromine is 1-3 a times of bromine quality; After the dropping bromine finishes, again the temperature in the reactor is warmed up to 45-65 ℃, is incubated 1-3 hour, then cool to room temperature; Emit the material in the reactor, filter with the suction filtration jar, the Hydrogen bromide of isolating wherein recycles, and leftover materials are through washing 3-6 time, the impurity that flush away is wherein soluble in water, and each water consumption is 5-10 a times of quality of material during washing.To remain water-fast drying materials and obtain the 2.4.6-bromamide, bake out temperature is 100-120 ℃, and drying time is 5-10 hour, records moisture and can stop oven dry less than 0.1%.
B) at first the quantitative first component dehydrated alcohol is added in the reactor, add the 2.4.6-bromamide after the above-mentioned oven dry again, the 2.4.6-bromamide and the first component dehydrated alcohol mass ratio that add are 1: 3-5, open and stir, add the Sodium Nitrite of the 20-40% of 2.4.6-bromamide quality in the reactor again; Reactor temperature is elevated to 50-70 ℃, is incubated 1-3 hour; Get ethanol and vitriolic mixed solution then and drip in the reactor, the quality of the dehydrated alcohol and the vitriol oil is the 70-90% of 2.4.6-bromamide quality in the reactor in described ethanol and the vitriolic mixed solution; The vitriol oil is that concentration is the sulfuric acid more than 98%.After above-mentioned ethanol and vitriolic mixed solution all are added dropwise to complete, temperature in the control reactor remains on 60-80 ℃, insulation backflow 3-10 hour drops to room temperature with the temperature in the reactor, emits the material in the reactor, filter with the suction filtration jar, the ethanol of isolating wherein recycles, and leftover materials are through washing 5-6 time, the impurity that flush away is wherein soluble in water, during washing each water consumption be quality of material 5-10 doubly, water-fast drying materials can be obtained the 1.3.5-tribromo-benzene.
At step C), earlier be with purity the methanol solution received of the methyl alcohol of 27.5-31% with vacuum suction pressure kettle, open and stir.The methanol solution that described methyl alcohol is received is methyl alcohol to be received be dissolved in the liquid that obtains in the methyl alcohol.In the methanol solution that this methyl alcohol is received, add above-mentioned 1.3.5-tribromo-benzene, the quality of the methanol solution that methyl alcohol is received is 8-10 a times of 1.3.5-tribromo-benzene quality, stir after 0.5-2 hour, the cuprous chloride that will be equivalent to 1.3.5-tribromo-benzene quality 1-5% is poured in the pressure kettle, continues behind the sealed pot cover to stir 0.5-2 hour; To the pressure kettle heating, when pressure reaches 0.1-0.3Mpa in the pressure kettle, stop heating then, this moment, pot inner pressure can continue to rise owing to the generation thermopositive reaction in the pressure kettle.When pressure reaches 0.4-0.6Mpa in the pot, pick up counting, adopt the method for heating or cooling to make the pressure in the pressure kettle remain on 0.4-0.9Mpa simultaneously, kept 5-10 hour; Cooling makes pot interior pressure drop to 0.05-0.1Mpa then, by self pressure in the pot feed liquid is pressed onto in the still kettle; Do not open stirring,, make the temperature temperature in the still kettle remain on 60-100 ℃, steamed 5-10 hour, the methyl alcohol that steams is put into the Methanol Recovery bucket the still kettle heating; Close methyl alcohol storage tank exhaust-valve then, still kettle is vacuumized, vacuum tightness is at-0.01--0.08Mpa, and temperature is controlled at 60-80 ℃, the about 1-4 of distillation time hour, the methyl alcohol that steams is put into the Methanol Recovery bucket; Emit the material in the still kettle, obtain crude product 1.3.5-trimethoxy-benzene.
Embodiment 2:
With embodiment 1, after obtaining crude product 1.3.5-trimethoxy-benzene, also to advance centrifugal rectifying, its step is to add entry and hydrochloric acid in crude product 1.3.5-trimethoxy-benzene, the quality that adds entry is 3-5 a times of crude product 1.3.5-trimethoxy-benzene quality, the concentration of hydrochloric acid that adds be 28--35%, quality be crude product 1.3.5-trimethoxy-benzene quality 1-3 doubly, temperature is controlled at 10-60 ℃ and soaks after 1-3 hour crawl and open stirring; Stir that to put into whizzer after 0.5-3 hour centrifugal, the crude product after centrifugal adds rectifying tower and carries out rectification under vacuum, and vacuum degree control is at-0.09--0.1Mpa during rectifying, and the rectifying cut of collecting 253.5-255.5 ℃ gets finished product 1.3.5-trimethoxy-benzene.Rectifying gas-chromatography controlled contents, finished product content is greater than 99.5%.
Embodiment 3:
With embodiment 1, described catalyzer is one or more in cuprous chloride, cuprous bromide and the cuprous iodide.
Claims (6)
1. the preparation method of a 1.3.5-trimethoxy-benzene is characterized in that comprising the steps:
A) preparation 2.4.6-bromamide; Utilize the reaction of aniline and Hydrogen bromide, and the method for dropping bromine prepares the 2.4.6-bromamide in reaction intermediate;
B) preparation 1.3.5-tribromo-benzene; With dehydrated alcohol and above-mentioned 2.4.6-bromamide and Sodium Nitrite hybrid reaction, in reaction vessel, drip the mixture of sulfuric acid and dehydrated alcohol then, get the 1.3.5-tribromo-benzene;
C) methoxylation; Methyl alcohol is received and above-mentioned 1.3.5-tribromo-benzene hybrid reaction, isolated methyl alcohol wherein then, obtain crude product 1.3.5-trimethoxy-benzene.
2. the preparation method of a kind of 1.3.5-trimethoxy-benzene according to claim 1 is characterized in that:
In steps A) at first in reactor, add the water of quantitative aniline and 5-20 times of aniline quality, the Hydrogen bromide that with the purity of 1-10 times of aniline quality is 25-30% again is added dropwise in the still, steam heated method is elevated to 50-75 ℃ with the temperature in the reactor, and is incubated 1-4 hour; When soaking time arrives, adopt water coolant that the temperature in the reactor is reduced to 10-40 ℃, and drip the bromine that dilute with Hydrogen bromide, and the bromine quality of Cai Yonging is 5.2-5.3 a times of above-mentioned aniline quality here, the hydrobromic quality that is used to dilute bromine is 1-3 a times of bromine quality; After the dropping bromine finishes, again the temperature in the reactor is warmed up to 45-65 ℃, is incubated 1-3 hour, then cool to room temperature; Emit the material in the reactor, filter with the suction filtration jar, the Hydrogen bromide of isolating wherein recycles, and leftover materials obtain the 2.4.6-bromamide through washing, oven dry.
3. the preparation method of a kind of 1.3.5-trimethoxy-benzene according to claim 1 and 2 is characterized in that:
At step B) at first the quantitative first component dehydrated alcohol is added in the reactor, add above-mentioned 2.4.6-bromamide again, the 2.4.6-bromamide and the first component dehydrated alcohol mass ratio that add are 1: 3-5, open and stir, add the Sodium Nitrite of the 20-40% of 2.4.6-bromamide quality in the reactor again; Reactor temperature is elevated to 50-70 ℃, is incubated 1-3 hour; Get ethanol and vitriolic mixed solution then and drip in the reactor, the quality of the dehydrated alcohol and the vitriol oil is the 70-90% of 2.4.6-bromamide quality in the reactor in described ethanol and the vitriolic mixed solution; After above-mentioned ethanol and vitriolic mixed solution all are added dropwise to complete, temperature in the control reactor remains on 60-80 ℃, insulation backflow 3-10 hour, temperature in the reactor is dropped to room temperature, emit the material in the reactor, filter with the suction filtration jar, the ethanol of isolating wherein recycles, and leftover materials obtain the 1.3.5-tribromo-benzene through washing, oven dry.
4. the preparation method of a kind of 1.3.5-trimethoxy-benzene according to claim 1 and 2 is characterized in that:
At step C), earlier be the methanol solution received of the methyl alcohol of 27.5-31% with vacuum suction pressure kettle with purity, open and stir, add above-mentioned 1.3.5-tribromo-benzene again, the methanol solution quality that methyl alcohol is received is 8-10 a times of 1.3.5-tribromo-benzene quality, stir after 0.5-2 hour, the catalyzer that will be equivalent to 1.3.5-tribromo-benzene quality 1-5% is poured in the pressure kettle, continues behind the sealed pot cover to stir 0.5-2 hour; Then pressure kettle is heated, when pressure reaches 0.1-0.3Mpa in the pot, stop heating, when pressure reaches 0.4-0.6Mpa in the pot, pick up counting, adopt the method for heating or cooling to make the pressure in the pressure kettle remain on 0.4-0.9Mpa simultaneously, kept 5-10 hour; Cooling makes pot interior pressure drop to 0.05-0.1Mpa then, by self pressure in the pot feed liquid is pressed onto in the still kettle; Do not open stirring,, make the temperature temperature in the still kettle remain on 60-100 ℃, steam and the methyl alcohol that steams put into the Methanol Recovery bucket in 5-10 hour still kettle heating; Close methyl alcohol storage tank exhaust-valve then, still kettle is vacuumized, vacuum tightness is at-0.01--0.08Mpa, and temperature is controlled at 60-80 ℃, the about 1-4 of distillation time hour, the methyl alcohol that steams is put into the Methanol Recovery bucket; Emit the material in the still kettle, obtain crude product 1.3.5-trimethoxy-benzene.
5. the preparation method of a kind of 1.3.5-trimethoxy-benzene according to claim 1 and 2 is characterized in that:
At step C), obtain also will advancing centrifugal rectifying after the crude product 1.3.5-trimethoxy-benzene, its step is to add entry and hydrochloric acid in crude product 1.3.5-trimethoxy-benzene, temperature is controlled at 10-60 ℃ and soaks after 1-3 hour crawl and open stirring; Stir that to put into whizzer after 0.5-3 hour centrifugal, the crude product after centrifugal adds rectifying tower, rectifying finish finished product 1.3.5-trimethoxy-benzene.
6. the preparation method of a kind of 1.3.5-trimethoxy-benzene according to claim 4 is characterized in that: described catalyzer is one or more in cuprous chloride, cuprous bromide and the cuprous iodide.
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| CN109369350A (en) * | 2018-11-23 | 2019-02-22 | 深圳市第二人民医院 | The synthetic method of buflomedil hydrochloride intermediate 1,3,5-trimethoxybenzene |
| CN109487297A (en) * | 2018-11-12 | 2019-03-19 | 新乡市珺隆生物科技有限公司 | The electrochemical applications of trimethoxy-benzene synthesis |
| CN110195237A (en) * | 2019-06-28 | 2019-09-03 | 福建医科大学 | A method of using bromide as bromating agent, the electro-catalysis in water phase prepares more bromoaniline compounds |
| WO2022036636A1 (en) * | 2020-08-20 | 2022-02-24 | 江苏康龙医药有限公司 | Preparation method for 1,3,5-trimethoxybenzene |
| CN114634405A (en) * | 2022-03-15 | 2022-06-17 | 北京沃邦医药科技有限公司 | Purification method of trimethyl phloroglucinol |
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| CN1205158C (en) * | 2002-10-23 | 2005-06-08 | 浙江新和成股份有限公司 | Process for preparing phloroglucinol |
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| CN104447234A (en) * | 2014-12-08 | 2015-03-25 | 安徽万邦医药科技有限公司 | Preparation method of (3R,4R)-4-(3,4-dimethoxybenzyl)-3-(4-hydroxyl-3-methoxybenzyl)-dihydrofuran |
| CN109487297A (en) * | 2018-11-12 | 2019-03-19 | 新乡市珺隆生物科技有限公司 | The electrochemical applications of trimethoxy-benzene synthesis |
| CN109369350A (en) * | 2018-11-23 | 2019-02-22 | 深圳市第二人民医院 | The synthetic method of buflomedil hydrochloride intermediate 1,3,5-trimethoxybenzene |
| CN109369350B (en) * | 2018-11-23 | 2021-10-19 | 深圳市第二人民医院 | The synthetic method of buflomedil hydrochloride intermediate 1,3,5-trimethoxybenzene |
| CN110195237A (en) * | 2019-06-28 | 2019-09-03 | 福建医科大学 | A method of using bromide as bromating agent, the electro-catalysis in water phase prepares more bromoaniline compounds |
| WO2022036636A1 (en) * | 2020-08-20 | 2022-02-24 | 江苏康龙医药有限公司 | Preparation method for 1,3,5-trimethoxybenzene |
| CN114634405A (en) * | 2022-03-15 | 2022-06-17 | 北京沃邦医药科技有限公司 | Purification method of trimethyl phloroglucinol |
| CN114634405B (en) * | 2022-03-15 | 2022-09-13 | 北京沃邦医药科技有限公司 | Purification method of trimethyl phloroglucinol |
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