CN107573397B - A method of preparing betulic acid - Google Patents
A method of preparing betulic acid Download PDFInfo
- Publication number
- CN107573397B CN107573397B CN201710821556.0A CN201710821556A CN107573397B CN 107573397 B CN107573397 B CN 107573397B CN 201710821556 A CN201710821556 A CN 201710821556A CN 107573397 B CN107573397 B CN 107573397B
- Authority
- CN
- China
- Prior art keywords
- preparing
- betulic acid
- acid
- betulic
- weight ratio
- 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.)
- Active
Links
Abstract
The invention discloses a kind of methods for preparing betulic acid.Step of the invention is as follows: betulin is under conditions of imidazole type ionic liquid, through oxidant ClO2Oxidation, obtains betulonic acid, in tetrahydrofuran solvent, restores through sodium borohydride catalyzing, obtain betulic acid.Preparation method provided by the invention has the characteristics that raw material sources are abundant, cheap, reaction condition is mild, can be recycled, and is suitble to the industrialization production of betulic acid.
Description
Technical field
The invention belongs to organic chemical synthesis technical fields, are specifically related to a kind of method for preparing betulic acid.
Background technique
Betulic acid belongs to the pentacyclic triterpene of lupinane type, and structure is as shown below:
Betulic acid is primarily present in Japanese birch bark, but content therein is only 0.025%.Elephant skin are found in recent years
Pawpaw, Clausena dunniana leaf, the root bark of tree peony, the root bark of white mulberry, semen ziziphi spinosae, eucalyptus ball, fenugreek, chicken feet ginseng, common vineclethra, jujube, konjaku etc. are more
Also contain this ingredient in kind Chinese medicine, but content is very low.It is a kind of very valuable natural products, as a variety of diseases
Potential treatment reagent, there are multiple biological activities, such as antitumor, anti-malarial, anti HIV-1 virus, anti-inflammatory.With conventional medicament phase
Have many advantages, such as that anti-tumor activity is strong, small toxicity, strong inhibition capability than, betulic acid and betulic acid derivative, has good
Medicinal development prospect.
Currently, the preparation method of betulic acid has direct extraction method, chemical synthesis and microbe transformation method.Wherein directly
Extraction method, consumption of raw materials amount is big, at high cost, and obtained betulic acid impurity content is higher, is difficult to meet the market demand;Micro- life
Object conversion method, although microbe transformation method mild condition as described in publication number CN200810163820.7, highly-safe, to ring
Border is friendly, but its reaction time is long, and conversion ratio is low, is not suitable for industrialized production, needs to be further studied.And with white birch
Lipidol is that the semi-synthesis method of Material synthesis betulic acid mainly has following three kinds: 1. first to use Jnoes reagent (by chromium trioxide, sulphur
Acid and water are made into) betulin is oxidized to betulonic acid, it then again will with selective reduction agent (sodium borohydride/tetrahydrofuran)
Betulonic acid is reduced into betulic acid.The method yield is lower, and only 55%, and CrO3For heavy metal compound, toxicity is big, to ring
Serious pollution is caused in border, therefore the method is not suitable for industrialized production.2. betulin is aoxidized through Swern, white birch keto-aldehyde is obtained,
White birch keto-aldehyde obtains betulonic acid again through potassium permanganate oxidation, and yield is up to 70%.The reaction needs column to chromatograph, then again with selection
Property reducing agent reduction, and Swern oxidation reaction must carry out under anhydrous, cryogenic conditions, and Atom economy is poor, brings to operation tired
It is difficult.It can discharge while generating product with irritating dimethyl sulphide, environment is caused seriously to pollute.3.Barthel group
The method for directly preparing betulonic acid using 2- iodoxybenzoic acid (IBX)/HY system oxidation C-28 primary alconol, but yield has also been attempted
Only 5%, and IBX can just need to be such that reaction completes through high temperature and prolonged reaction in organic solvent, severe reaction conditions, the time
Long, yield is low, is not suitable for industrialized production.
In conclusion the preparation method of reported betulic acid is there are environmental pollution, toxicity is big, troublesome in poeration, yield
The problems such as low, is not suitable for industrialized production.A convenience, economic, practical chemical synthesis route are found to prepare white birch rouge
Acid is of great significance.
Ionic liquid (ionic liquids) refer to room temperature or close at room temperature present liquid, completely by yin-yang from
Liquid composed by son, also referred to as low temperature molten salt (fusing point general < 100 DEG C).Ionic liquid is melted as ionic compound
Point is lower, and the asymmetry for being primarily due to certain substituent groups in its structure prevents ion from being regularly piled into crystal.It one
As be made of organic cation and inorganic anion.Ionic liquid is based on its unique characteristic, the catalysis as many reactions
Agent, reaction medium.And the effect achieved, catalytic activity is improved, reaction selectivity is improved, simplifies the separation of product
Process may be implemented the green catalysis process that catalytic activity is high, stability is good, product can be easily separated, environmental-friendly, overcome tradition
Technique there are the problem of.Designability based on ionic liquid, can be according to specific catalystic converter system feature by ionic liquid
It is designed as acid or alkalinity, or the characteristics such as its solubility, fusing point, stability are adjusted.
ClO2Liquid is bronzing, solid be it is orange red, 11 DEG C of boiling point.Heat water then resolves into hypochlorous acid, chlorine, oxygen
Gas, light are also easily decomposed, and solution is relatively stable in dark cold place.It is heated and be illuminated by the light or meet organic matter etc. and can promote oxidation
Substance when, can promote decompose and easily set off an explosion.It is explosive if diluted with inert gases such as air, carbon dioxide, nitrogen
Then reduce.Belong to strong oxidizer, effective chlorine is 2.6 times of chlorine.Vigorous reaction can occur with many substances.But
[Emim]+In plasma liquid, the designability based on ionic liquid, by the selection to different anions, so that oxidant ClO2
Presence that can be stable, greatly reduces ClO2Risk, reduce ClO2Complicated reaction condition in organic solvent, makes
Obtain ClO2Chemical reaction can go on smoothly, significantly increase the safety of reaction.
Document and patent there is no to report ionic liquid catalyst synthesizing betulic acid at present.This patent is with imidazole type ion
Liquid is that solvent realizes that the selective oxidation of betulin generates betulonic acid, and betulonic acid is urged through sodium borohydride/tetrahydrofuran again
Change reduction and prepares betulic acid.The conclusion obtained according to pre-stage test, the reaction efficiency of imidazole type ionic liquid are significantly higher than other
Types of ion liquid, and after ionic liquid recycling five times, catalytic activity does not reduce, and the yield of betulic acid is 75%~87%.
The reaction dissolvent can make ClO2The catalysed oxidn played stably reduces reaction condition, and can be recycled, and drops significantly
The low pollution to environment, considerably reduces production cost, has very big Industry Development Prospect.It is the reaction below
React skeleton symbol:
Summary of the invention
Goal of the invention: aiming at the problems existing in the prior art, the present invention provides a kind of method for preparing betulic acid,
This method is easy to operate, can industrializing implementation, especially can solve low yield existing for background technique, reaction process it is not easy to control and
The problems such as severe reaction conditions.
Technical solution: the present invention provides a kind of methods for preparing betulic acid, comprising the following steps:
(1) betulin is added in a certain proportion of imidazole type ionic liquid;
(2) a certain amount of ClO is added in the solution of step (1)2, at a certain temperature, control speed of agitator, reaction one
The section time, then room temperature is evaporated under reduced pressure, and removes ClO2;
(3) it is extracted with solution of a certain amount of ethyl acetate to step (2), then concentration and recovery ethyl acetate is to thick
Paste, then with a certain amount of acetone recrystallization, filtering, obtain betulonic acid;
(4) betulonic acid obtained with a certain amount of tetrahydrofuran solvent dissolving step (3), adds a certain amount of boron hydrogen
Change sodium powder end, controls speed of agitator, react a period of time in ice-water bath;
(5) a certain amount of ammonium chloride is added, is filtered to remove the impurity such as the unreacted substrate of sodium borohydride and precipitation, then depressurize
Distillation, obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with a certain amount of methanol extremely to clarify, cooling, recrystallization,
Obtain betulic acid sterling.
In above-mentioned steps (1), imidazole type ionic liquid institute's cation is [Emim]+, contained anion is BF4 -、PF6 -、
AlCl4 -、NO2 -、ClO2 -、SbF6 -、(CF3SO2)3C-、CF3COO-One of.Ionic liquid and the weight ratio of betulin be (4~
8): 1, preferably 6:1.Ionic liquid is very few to be caused to react insufficient, and subsequent reactions quantity of solvent is excessively caused to increase, and production cost increases
Add.
In above-mentioned steps (2), ClO2Weight ratio with betulin is (0.1~0.6): 1, preferably 0.4:1.ClO2It crosses
At least oxidation reaction is insufficient, ClO2Excessive then side reaction increases, risk increases.
In above-mentioned steps (2), reaction temperature is -10~5 DEG C, preferably 0 DEG C.The excessively high then reaction of reaction temperature is acutely, no
Stablize.Speed of agitator is 90~200rpm, preferably 150rpm.Reaction time is 2~6h, preferably 4h.Mixing speed is excessively slow
Then the reaction time increases, and the too fast then byproduct of reaction of mixing speed increases.
In above-mentioned steps (3), the weight ratio of ethyl acetate and betulin is (4~12): 1, preferably 8:1.Extraction time
Number is 2~4 times, preferably 3 times.Ethyl acetate is very few, extraction times not enough then extract it is insufficient.
In above-mentioned steps (3), the weight ratio of acetone and betulin is (6~12): 1, preferably 9:1.Acetone lacks then excessively
It cleans insufficient, excessively then product yield is low.
In above-mentioned steps (4), the weight ratio of tetrahydrofuran solvent and betulonic acid is (3~10): 1, preferably 7:1.Four
Hydrogen THF solvent is excessively few then to be dissolved insufficient, and product yield is low.
In above-mentioned steps (4), the weight ratio of sodium borohydride powder and betulonic acid is (0.04~0.2): 1, preferably
0.12:1.The excessively few then reduction reaction of sodium borohydride powder is insufficient.
In above-mentioned steps (4), speed of agitator is 90~200rpm, preferably 150rpm.Reaction time is 1~5h, preferably
For 3h.The mixing speed excessively slow then reaction time increases, and the too fast then byproduct of reaction of mixing speed increases.
In above-mentioned steps (5), the weight ratio of ammonium chloride and betulonic acid is (0.4~2.0): 1, preferably 1.2:1.Chlorination
Ammonium then cleans insufficient less excessively.
In above-mentioned steps (6), the weight ratio of methanol and betulonic acid is (6~10): 1, preferably 8:1.Methanol lacks then excessively
Dissolve insufficient, product yield is low.
The utility model has the advantages that the raw materials used in the present invention betulin abundance, readily available, cheap, reaction is used molten
Agent imidazole type ion liquid is recyclable, environmentally protective, and reaction condition is mild, and the betulic acid yield which obtains is higher, fits
Close industrialized production.
Specific embodiment:
The present invention is described in further detail combined with specific embodiments below.
Embodiment 1:
(1) 160g betulin is added to 960g [Emim] BF4In ionic liquid;
(2) 64g ClO is added in the solution of step (1)2, under the conditions of 0 DEG C of temperature, control speed of agitator
150rpm reacts 4h, and then room temperature is evaporated under reduced pressure, and removes ClO2;
(3) use 1280g ethyl acetate to solution extraction 3 times of step (2), then concentration and recovery ethyl acetate to thick paste
Shape, then with 1440g acetone recrystallization, filtering, obtain 159g betulonic acid;
(4) betulonic acid obtained with 1113g tetrahydrofuran solvent dissolving step (3) adds 19.1g hydroboration sodium powder
End controls speed of agitator 150rpm, reacts 3h in ice-water bath;
(5) 191g ammonium chloride is added, is filtered to remove the impurity such as the unreacted substrate of sodium borohydride and precipitation, then depressurize steaming
It evaporates, obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with 1272g methanol extremely to clarify, cooling, recrystallization obtains
To 142.3g betulic acid sterling, betulic acid yield is 86.2%.
Embodiment 2:
(1) 160g betulin is added to 640g [Emim] BF4In ionic liquid;
(2) 16g ClO is added in the solution of step (1)2, under the conditions of -10 DEG C of temperature, control speed of agitator
90rpm reacts 2h, and then room temperature is evaporated under reduced pressure, and removes ClO2;
(3) use 640g ethyl acetate to solution extraction 2 times of step (2), then concentration and recovery ethyl acetate to paste,
Again with 960g acetone recrystallization, filtering, 152g betulonic acid is obtained;
(4) betulonic acid obtained with 456g tetrahydrofuran solvent dissolving step (3) adds 6.08g hydroboration sodium powder
End controls speed of agitator 90rpm, reacts 1h in ice-water bath;
(5) 60.8g ammonium chloride is added, is filtered to remove the impurity such as the unreacted substrate of sodium borohydride and precipitation, then depressurize steaming
It evaporates, obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with 912g methanol extremely to clarify, cooling, recrystallization obtains
125.3g betulic acid sterling, betulic acid yield are 75.9%.
Embodiment 3:
(1) 160g betulin is added to 1280g [Emim] PF6In ionic liquid;
(2) 96g ClO is added in the solution of step (1)2, under the conditions of 5 DEG C of temperature, control speed of agitator
200rpm reacts 6h, and then room temperature is evaporated under reduced pressure, and removes ClO2;
(3) use 1920g ethyl acetate to solution extraction 4 times of step (2), then concentration and recovery ethyl acetate to thick paste
Shape, then with 1920g acetone recrystallization, filtering, obtain 154.9g betulonic acid;
(4) betulonic acid obtained with 1549g tetrahydrofuran solvent dissolving step (3), adds 30.98g sodium borohydride
Powder controls speed of agitator 200rpm, reacts 5h in ice-water bath;
(5) 309.8g ammonium chloride is added, is filtered to remove the impurity such as the unreacted substrate of sodium borohydride and precipitation, then depressurize steaming
It evaporates, obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with 1549g methanol extremely to clarify, cooling, recrystallization obtains
To 128.3g betulic acid sterling, betulic acid yield is 77.7%.
Embodiment 4:
(1) 160g betulin is added to 1120g [Emim] PF6In ionic liquid;
(2) 80g ClO is added in the solution of step (1)2, under the conditions of 5 DEG C of temperature, control speed of agitator
170rpm reacts 5h, and then room temperature is evaporated under reduced pressure, and removes ClO2;
(3) use 1600g ethyl acetate to solution extraction 4 times of step (2), then concentration and recovery ethyl acetate to thick paste
Shape, then with 1600g acetone recrystallization, filtering, obtain 155g betulonic acid;
(4) betulonic acid obtained with 1240g tetrahydrofuran solvent dissolving step (3) adds 21.7g hydroboration sodium powder
End controls speed of agitator 170rpm, reacts 4h in ice-water bath;
(5) 217g ammonium chloride is added, is filtered to remove the impurity such as the unreacted substrate of sodium borohydride and precipitation, then depressurize steaming
It evaporates, obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with 1395g methanol extremely to clarify, cooling, recrystallization obtains
To 130.6g betulic acid sterling, betulic acid yield is 79.1%.
From the data of embodiment 1-3 can be seen that it is provided by the invention one kind with betulin in imidazole type ionic liquid
The method for catalyzing and synthesizing betulic acid, betulic acid yield is 75%~87%.This method reaction efficiency is high, whole operation technique
Securely and reliably, low in cost, environment-protecting and non-poisonous, therefore this method is easy to spread, has very strong practicability, puts suitable for production
Greatly.
It should be pointed out that the above specific embodiment is only illustrative of the invention and is not intended to limit the scope of the invention,
After having read the present invention, those skilled in the art fall within power appended by the application to the modification of various equivalent forms of the invention
Benefit requires limited range.
Claims (10)
1. a kind of method for preparing betulic acid, which comprises the following steps:
(1) betulin is added in a certain proportion of imidazole type ionic liquid;
(2) a certain amount of ClO2 is added in the solution of step (1), at a certain temperature, is stirred to react a period of time, room temperature subtracts
ClO2 is distilled off in pressure;
(3) it is extracted, concentration and recovery ethyl acetate to paste, is used with solution of a certain amount of ethyl acetate to step (2)
A certain amount of acetone recrystallization, filtering, obtain betulonic acid;
(4) betulonic acid obtained with a certain amount of tetrahydrofuran solvent dissolving step (3), is added a certain amount of hydroboration sodium powder
End is stirred to react a period of time in ice-water bath;
(5) a certain amount of ammonium chloride, filtering and impurity removing is added, vacuum distillation obtains betulic acid crude product;
(6) it dissolves by heating the betulic acid crude product that step (5) obtain with a certain amount of methanol extremely to clarify, cooling, recrystallization obtains
Betulic acid sterling.
2. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: imidazole type described in step (1)
Ionic liquid, cation be [Emim]+, anion BF4-, PF6-, AlCl4-, NO2-, ClO2-, SbF6-, (CF3SO2) 3C-,
One of CF3COO-;Ionic liquid and the weight ratio of betulin are (4~8): 1.
3. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: ClO2 described in step (2) with
The weight ratio of betulin is (0.1~0.6): 1.
4. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: certain temperature described in step (2)
Degree is -10~5 DEG C;The stirring, revolving speed are 90~200rpm;The reaction time is 2~6h.
5. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: acetic acid second described in step (3)
The weight ratio of ester and betulin is (4~12): 1;The weight ratio of the acetone and betulin is (6~12): 1.
6. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: it is extracted described in step (3), it is secondary
Number is 2~4 times.
7. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: tetrahydro furan described in step (4)
The weight ratio of solvent and betulonic acid of muttering is (3~10): 1;The weight ratio of the sodium borohydride powder and betulonic acid is (0.04
~0.2): 1.
8. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: stir, turn described in step (4)
Speed is 90~200rpm;The reaction time is 1~5h.
9. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: ammonium chloride described in step (5)
Weight ratio with betulonic acid is (0.4~2.0): 1.
10. a kind of method for preparing betulic acid according to claim 1, it is characterised in that: methanol described in step (6) with
The weight ratio of betulonic acid is (6~10): 1.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710821556.0A CN107573397B (en) | 2017-09-13 | 2017-09-13 | A method of preparing betulic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710821556.0A CN107573397B (en) | 2017-09-13 | 2017-09-13 | A method of preparing betulic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107573397A CN107573397A (en) | 2018-01-12 |
CN107573397B true CN107573397B (en) | 2019-07-30 |
Family
ID=61033291
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710821556.0A Active CN107573397B (en) | 2017-09-13 | 2017-09-13 | A method of preparing betulic acid |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107573397B (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2190622C1 (en) * | 2001-12-26 | 2002-10-10 | Рощин Виктор Иванович | Method of synthesis of betulinic acid |
RU2003119067A (en) * | 2003-06-24 | 2005-01-10 | Институт химии и химической технологии СО РАН (ИХХТ СО РАН) (RU) | METHOD FOR PRODUCING BETULIN ACID |
RU2269541C1 (en) * | 2004-12-21 | 2006-02-10 | Институт химии и химической технологии СО РАН (ИХХТ СО РАН) | Method for preparing betulinic acid |
CN101709322A (en) * | 2009-11-26 | 2010-05-19 | 浙江大学 | Method for synthesizing betulic acid by carrying out biocatalysis on betulin |
RU2458933C1 (en) * | 2011-05-10 | 2012-08-20 | Государственное образовательное учреждение высшего профессионального образования "Нижегородская государственная медицинская академия" Министерства здравоохранения и социального развития Российской Федерации (ГОУ ВПО НижГМА Минздравсоцразвития России) | Method for producing betulinic acid |
RU2463041C1 (en) * | 2011-05-10 | 2012-10-10 | Государственное образовательное учреждение высшего профессионального образования "Нижегородская государственная медицинская академия" Министерства здравоохранения и социального развития Российской Федерации (ГОУ ВПО НижГМА Минздравсоцразвития России) | Method of obtaining betulinic acid |
-
2017
- 2017-09-13 CN CN201710821556.0A patent/CN107573397B/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2190622C1 (en) * | 2001-12-26 | 2002-10-10 | Рощин Виктор Иванович | Method of synthesis of betulinic acid |
RU2003119067A (en) * | 2003-06-24 | 2005-01-10 | Институт химии и химической технологии СО РАН (ИХХТ СО РАН) (RU) | METHOD FOR PRODUCING BETULIN ACID |
RU2269541C1 (en) * | 2004-12-21 | 2006-02-10 | Институт химии и химической технологии СО РАН (ИХХТ СО РАН) | Method for preparing betulinic acid |
CN101709322A (en) * | 2009-11-26 | 2010-05-19 | 浙江大学 | Method for synthesizing betulic acid by carrying out biocatalysis on betulin |
RU2458933C1 (en) * | 2011-05-10 | 2012-08-20 | Государственное образовательное учреждение высшего профессионального образования "Нижегородская государственная медицинская академия" Министерства здравоохранения и социального развития Российской Федерации (ГОУ ВПО НижГМА Минздравсоцразвития России) | Method for producing betulinic acid |
RU2463041C1 (en) * | 2011-05-10 | 2012-10-10 | Государственное образовательное учреждение высшего профессионального образования "Нижегородская государственная медицинская академия" Министерства здравоохранения и социального развития Российской Федерации (ГОУ ВПО НижГМА Минздравсоцразвития России) | Method of obtaining betulinic acid |
Non-Patent Citations (1)
Title |
---|
《A Practical Synthesis of Betulonic Acid Using Selective Oxidation of Betulin on Aluminium Solid Support》;Nina Melnikova et al.;《Molecules》;20121009;第17卷(第10期);11849-11863 |
Also Published As
Publication number | Publication date |
---|---|
CN107573397A (en) | 2018-01-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2023116540A1 (en) | Pyridine pyrrole ruthenium complex, preparation method therefor and application thereof as catalyst for preparing hydrazine by electrocatalytic ammonia oxidation | |
CN108276409B (en) | Method for preparing medicine and medicine intermediate by continuous solid-liquid-gas three-phase reaction | |
CN102126960A (en) | High selectivity synthesis method of p-nitrobenzaldehyde | |
CN107573397B (en) | A method of preparing betulic acid | |
Sun et al. | Two-step continuous flow process of sodium tanshinone IIA sulfonate using a 3D circular cyclone-type microreactor | |
CN105669465A (en) | Preparing method of 1-cyclohexene ethylamine | |
CN102766061A (en) | Dehydroabietic acid base diarylamine compound, synthesis method and application thereof | |
CN107556197A (en) | A kind of preparation method of tri-iso-octylamine | |
CN107286218B (en) | A kind of preparation method of new oleanane-type triterpene saponin derivative | |
CN1312100C (en) | Method for synthesizing glyoxalic acid by oxidation of glyoxal with maleuric ozonide | |
CN102992989A (en) | Synthetic method of beta-menadione | |
CN102775290A (en) | Preparation method of 2-(chloromethyl)-5,6-dimethoxy-3-methyl-1,4-para benzoquinone | |
CN107935971A (en) | It is a kind of(S)The preparation method of 3 hydroxyl tetrahydrofurans | |
CN111454215B (en) | Process for synthesizing 2- (4, 6-dichloropyrimidine-5-yl) acetaldehyde by continuous flow ozone oxidation | |
CN108558758A (en) | A kind of synthetic method of 4- fluorine isoquinolin -5- amine | |
CN109776409B (en) | Method for synthesizing C-2-bit polyfluoro functional group substituted quinoline by using microchannel reaction device | |
CN111646911A (en) | Method for synthesizing o-aminoacetophenone | |
CN110655457A (en) | Novel method for preparing p-fluorobenzaldehyde by catalytic oxidation of hydrogen peroxide | |
CN115745938B (en) | Method for continuously preparing vitamin E acetate | |
CN106187703B (en) | A kind of preparation method of pyrogallic acid | |
CN110713442A (en) | Preparation method of o-nitrobenzaldehyde | |
CN106117129A (en) | A kind of preparation method of 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine. | |
CN102649054B (en) | Catalyst for preparation of oxalate through CO coupling | |
CN110105362B (en) | Safe and green folic acid synthesis method catalyzed by heteropoly acid | |
CN102649056B (en) | The catalyst of CO preparing oxalate coupling reaction |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |