CN109180436A - A kind of synthetic method of phloroglucin - Google Patents
A kind of synthetic method of phloroglucin Download PDFInfo
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- CN109180436A CN109180436A CN201811076169.XA CN201811076169A CN109180436A CN 109180436 A CN109180436 A CN 109180436A CN 201811076169 A CN201811076169 A CN 201811076169A CN 109180436 A CN109180436 A CN 109180436A
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- phloroglucin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/685—Processes comprising at least two steps in series
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/84—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by crystallisation
Abstract
The present invention relates to pharmaceutical chemistry technical fields, specifically disclose a kind of synthetic method of phloroglucin.1,3,5- trimethoxy-benzene and the concentrated sulfuric acid are carried out mixing treatment by the synthetic method, are warming up to 60-65 DEG C, insulation reaction 1-2 hours, are cooled to 10 DEG C hereinafter, being slowly added to sodium bicarbonate or sodium carbonate under stirring, adjusting pH to 2~3, filtering obtains filtrate;With n-butyl acetate extraction 3 times, combining extraction liquid is concentrated into the 15%-20% of original volume, obtains concentrate filtrate, is cooled to 10 DEG C hereinafter, crystallization, filtering, obtain phloroglucin crude product;The phloroglucin crude product is added in the mixed liquor of purified water and alcohols solvent and is dissolved by heating, keep the temperature and be added activated carbon adsorption impurity, filtered, filtrate is cooled to 10 DEG C hereinafter, crystallization, is filtered, and washing is dried in vacuo.Bright synthetic method provided by the invention, raw material is easy to get, reaction condition is mild, the reaction time is short, high income, and product purity is high, and simple process, easy to operate, pollution are less, are conducive to industrialized production.
Description
Technical field
The present invention relates to pharmaceutical chemistry technical field more particularly to a kind of synthetic methods of phloroglucin.
Background technique
Phloroglucin (Phloroglucinol) is phloroglucinol dihydrate, is clinically used for smooth muscle spasmolysis
Medicine.To acute painful muscle spasms caused by digestive system and biliary tract function of patients obstacle;Acute spastic urethra, bladder, renal colic;Woman
Section's spasmic pain has relaxation effect;In addition uterotonic adjuvant treatment during can also be used to be pregnant.Phloroglucin conduct
Injection sterile powder and oral disintegrating tablet can be made when drug, also, avoid it is general with morphine and its derivative species medicine because this
Class medicine, which has, causes convulsion effect.
A variety of synthetic methods of phloroglucin have been disclosed in the prior art, with trinitrotoluene (TNT) for raw material, by it
Decarbonylation base after oxidation, then obtained phloroglucin is restored and is hydrolyzed, yield 50%, the method advantage is that raw material is cheap, produces work
The problem of skill is mature, the disadvantage is that seriously polluted, is unfavorable for environmental protection, and raw material is explosive, dangerous etc.;It is original with aniline
Phloroglucin is made after 1,3,5- trimethoxy-benzene through 2,4,6- tribromanilines in material.The route disadvantage is that reaction step is long, excellent
Point is that raw material is easy to get, and pollution is few, yield 55% or so;Taking trimethoxy-benzene is starting material, and nitration mixture, acid and complexing agent is added
Or acid and catalyst hydrolyze, and obtain phloroglucin, operation is complicated, and the reaction time is long, and is also easy to produce by-product.Therefore, it grinds
Sending out the reaction time a kind of, short, easy to operate and high income phloroglucin synthetic method has great importance.
Summary of the invention
Complicated for the technical operation of existing method for synthesizing phloroglucinol, the reaction time is long, is also easy to produce by-product and yield is lower
The problems such as, the present invention provides a kind of synthetic method of phloroglucin.
To achieve the above object of the invention, the embodiment of the present invention uses the following technical solution:
A kind of synthetic method of phloroglucin, concrete technology route are as follows:
Include the following steps:
(1) 1,3,5- trimethoxy-benzene and the concentrated sulfuric acid are subjected to mixing treatment, are warming up to 60~65 DEG C, insulation reaction 1-2
Hour, 10 DEG C are cooled to hereinafter, sodium bicarbonate or sodium carbonate is added, and adjusting pH to 2~3, filtering obtains filtrate;
(2) filtrate is concentrated into the 15%-20% of original volume, is obtained concentrate with n-butyl acetate extraction 3 times, combining extraction liquid,
10 DEG C are cooled to hereinafter, crystallization, filtering, obtain phloroglucin crude product;
(3) the phloroglucin crude product is added in the mixed liquor of purified water and alcohols solvent and is dissolved by heating, kept the temperature and added
Enter activated carbon adsorption impurity, filter, filtrate is cooled to 10 DEG C hereinafter, crystallization, is filtered, and washing is dried in vacuo.
Wherein, phloroglucin crude product appropriate purifying water washing, centrifugal drying, sampling, according to phloroglucin crude product quality
Standard and the detection of checked operation regulation carry out fusing point (200 DEG C of fusing point >) and thin layer identifies, if not entering purification work in 48 hours
Sequence then needs under the conditions of -0.05~-0.08Mpa, to be dried under reduced pressure 4~5h at 45 ± 5 DEG C, obtains white to pale yellow crystals or powder
The phloroglucin crude product at end, is fitted into specialized package, spare.
Further, described 1, H in 3,5- trimethoxy-benzenes and the concentrated sulfuric acid2SO4Molar ratio be 1:5-7, guarantee trimethoxy
Base benzene can be fully hydrolyzed, and obtain target product.
Further, the mass fraction of the concentrated sulfuric acid is 70%-85%, improves hydrolysis efficiency.
Further, in extraction process, the mass ratio of the volume of each butyl acetate and 1,3,5- trimethoxy-benzenes is
Target product phloroglucin is sufficiently extracted into from water phase organic phase, improves yield by 2.5-4:1.
Further, the thickening temperature is 40-45 DEG C.
Further, 6-8 times that water consumption is phloroglucin crude product weight is purified during the heating for dissolving, alcohols is molten
The volume of agent is 1-2 times of phloroglucin crude product weight, and alcohols solvent is methanol, ethyl alcohol or isopropanol, heating temperature 64-82
DEG C, convenient for removal impurity, improve purity.
Further, the activated carbon dosage is the 2%-8% of phloroglucin crude product weight, abundant adsorbing contaminant.
Further, in step (2), the crystallization time is in 18-24h and/or step (3), and the crystallization time is
18-24h guarantees that crystallization is abundant.
Further, the extract liquor is dry with anhydrous sodium sulfate.
Further, in step (3), the vacuum drying temperature be 45-55 DEG C, relative degree of vacuum be -0.086~-
0.096MPa, time 10-12h.
Compared with the existing technology, the synthetic method of phloroglucin provided by the invention, with 1,3,5- trimethoxy-benzene with it is dense
Sulfuric acid is primary raw material, and raw material is easy to get, reaction condition is mild, the reaction time is short, no coupling product, and yield is passed through up to 75% or more
Cross organic solvent low temperature crystallization, active carbon decoloring and purified water and alcohols solvent mixed liquor low temperature crystallization, the isophthalic three made
Phenol very high purity, impurity is few, and product purity meets the requirement of pharmaceutical field, and simple process, operation side up to 99.8% or more
Just, pollution is few, is conducive to industrialized production.
Detailed description of the invention
It to describe the technical solutions in the embodiments of the present invention more clearly, below will be to needed in the embodiment
Attached drawing is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for ability
For the those of ordinary skill of domain, without creative efforts, it can also be obtained according to these attached drawings other attached
Figure.
Fig. 1 is the liquid phase spectrogram of phloroglucin provided in an embodiment of the present invention.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Embodiment provides in order to better illustrate the present invention, is illustrated below by embodiment is further.
Embodiment 1
The synthesis of phloroglucin, includes the following steps:
(1) 80% concentrated sulfuric acid of the 1 of 15kg, 3,5- trimethoxy-benzene and 65kg are put into reaction kettle, are warming up to 65 DEG C,
Insulation reaction 2 hours, 10 DEG C are cooled to hereinafter, being slowly added to 90kg sodium bicarbonate under stirring, adjusting pH=2.5, filtering must filter
Liquid;
(2) n-butyl acetate extraction 3 times with 3 × 60L of the filtrate, combining extraction liquid are dry with the anhydrous sodium sulfate of 10kg
After dry 24 hours, the butyl acetate of 150L is removed in 45 DEG C of vacuum distillations, concentrate is obtained, is cooled to 5 DEG C hereinafter, being slowly stirred
Crystallization for 24 hours, filtering, drains, obtains phloroglucin crude product 10.2kg, purity 95.5%, yield 90.7%;
(3) the phloroglucin crude product is added in the mixed liquor of the purified water of 61.2kg and the ethyl alcohol of 10L and is heated to 78
DEG C dissolution, keeps the temperature and is added the 767 type injection-use activated carbons of 205g, keeps the temperature 60min, adsorbing contaminant, filtering, and filtrate is cooled to 10
DEG C hereinafter, be slowly stirred crystallization for 24 hours, it is centrifuged, purify water washing 1 time with 10 DEG C of 20L below, drying, in 45 DEG C ,-
It is dried in vacuo 10h under the conditions of 0.095MPa, crosses 32 meshes, after being cooled to room temperature, obtain phloroglucin (containing two crystallizations water)
12.6kg, purity 99.8% (HPLC method), yield 87%.
Embodiment 2
The synthesis of phloroglucin, includes the following steps:
(1) 75% concentrated sulfuric acid of the 1 of 15kg, 3,5- trimethoxy-benzene and 58.3kg are put into reaction kettle, is warming up to 60
DEG C, insulation reaction 1.2 hours, it is slowly added to 45.4kg sodium carbonate under being cooled to 10 DEG C hereinafter, stirring, adjusts pH=2.6, mistake
Filter, obtains filtrate;
(2) n-butyl acetate extraction 3 times with 3 × 37.5L of the filtrate, combining extraction liquid, with the anhydrous sodium sulfate of 10kg
After drying, the butyl acetate of 96L is removed in 40 DEG C of vacuum distillations, obtains concentrate, is cooled to 10 DEG C hereinafter, being slowly stirred 18h analysis
Crystalline substance, filtering, obtains phloroglucin crude product 9.1kg, purity 97.6%, yield 81.3%;
(3) the phloroglucin crude product is added in the purified water of 73kg and the mixed liquor of 18.2L methanol and is heated to 65 DEG C
Dissolution keeps the temperature and is added the 767 type injection-use activated carbons of 728g, keeps the temperature 50min, and adsorbing contaminant filters, and filtrate is cooled to 10 DEG C
Hereinafter, being slowly stirred crystallization for 24 hours, filters, purified water washing 1 time with 10 DEG C of 20L below, in 55 DEG C, under the conditions of -0.086MPa
It is dried in vacuo 12h, after being cooled to room temperature, obtains phloroglucin (containing the crystallization water) 10.9kg, purity 100% (HPLC method, such as Fig. 1
It is shown), yield 75.6%.
Embodiment 3
The synthesis of phloroglucin, includes the following steps:
(1) 78% concentrated sulfuric acid of the 1 of 15kg, 3,5- trimethoxy-benzene and 78kg are put into reaction kettle, are warming up to 62 DEG C,
Insulation reaction 1 hour, 10 DEG C are cooled to hereinafter, being slowly added to 64.3kg sodium carbonate under stirring, adjusting pH=2.8, filtering must filter
Liquid;
(2) n-butyl acetate extraction 3 times with 3 × 52L of the filtrate, combining extraction liquid are dry with the anhydrous sodium sulfate of 10kg
After dry, the butyl acetate of 126L is removed in 43 DEG C of vacuum distillations, obtains concentrate, is cooled to 10 DEG C hereinafter, being slowly stirred 20h analysis
Crystalline substance, filtering, obtains phloroglucin crude product 9.5kg, purity 96.5%, yield 84.3%;
(3) the phloroglucin crude product is added in the purified water and 10L isopropanol mixed liquor of 66.5kg and is heated to 80 DEG C
Dissolution keeps the temperature and is added the 767 type injection-use activated carbons of 475g, keeps the temperature 60min, and adsorbing contaminant filters, and filtrate is cooled to 10 DEG C
Hereinafter, being slowly stirred 20h crystallization, filters, purified water washing 1 time with 10 DEG C of 20L below, in 50 DEG C, under the conditions of -0.092MPa
It is dried in vacuo 12h, after being cooled to room temperature, obtains phloroglucin (containing the crystallization water) 11.1kg, purity 99.9% (HPLC method), yield
76.5%.
By the temperature and reaction time, pH value, Solvent quantity and extraction times of regulation reaction in hydrolyzing process, improve
Yield;Regulate and control the dosage and solution temperature of purified water, the dosage of active carbon and bleaching temperature and time in refining step, when crystallization
Between, improve purity and yield.
Technical solution in order to better illustrate the present invention is done by comparative example and the embodiment of the present invention into one further below
The comparison of step.
Comparative example 1
Reaction temperature in 1 step of embodiment (1) is changed to room temperature, the reaction time is changed to 8 hours, acetic acid fourth in step (2)
Ester is directly evaporated under reduced pressure removing.
(1) 80% concentrated sulfuric acid of the 1 of 15kg, 3,5- trimethoxy-benzene and 65kg are put into reaction kettle, room temperature reaction 8 is small
When, 10 DEG C are cooled to hereinafter, being slowly added to 90kg sodium bicarbonate under stirring, and adjusting pH=2.5, filtering obtains filtrate;
(2) n-butyl acetate extraction 3 times with 3 × 60L of the filtrate, combining extraction liquid are dry with the anhydrous sodium sulfate of 10kg
After dry, butyl acetate is removed in 45 DEG C of vacuum distillations, obtains phloroglucin crude product 7.9kg, purity 95.4%, yield is
70.1%;
(3) the phloroglucin crude product is added in the purified water of 61.2kg and the mixed liquor of 10L ethyl alcohol and is heated to 73 DEG C
Dissolution keeps the temperature and is added the 767 type injection-use activated carbons of 205g, keeps the temperature 60min, and adsorbing contaminant filters, and filtrate is cooled to 10 DEG C
Hereinafter, be slowly stirred crystallization for 24 hours, it is centrifuged, purify water washing 1 time with 10 DEG C of 20L below, drying, in 45 DEG C, -0.095MPa
Under the conditions of be dried in vacuo 10h, cross 32 meshes, after being cooled to room temperature, obtain phloroglucin (containing the crystallization water) 9.3kg, purity
99.8% (HPLC method), yield 64%.
By the way that the synthetic method of phloroglucin provided in an embodiment of the present invention can be obtained, 60~65 compared with comparative example 1
Under DEG C reaction condition, the reaction time is shorter, and yield is higher, and through butylperacetate low temperature crystallization, active carbon decoloring and purified water
With alcohols solvent mixed liquor low temperature crystallization collective effect, the phloroglucin very high purity made, impurity is few, and product purity reaches
99.8% or more.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modification, equivalent replacement or improvement etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (10)
1. a kind of synthetic method of phloroglucin, characterized by the following steps:
(1) 1,3,5- trimethoxy-benzene and the concentrated sulfuric acid are subjected to mixing treatment, are warming up to 60~65 DEG C, insulation reaction 1-2 hours,
10 DEG C are cooled to hereinafter, sodium bicarbonate or sodium carbonate is added, adjusting pH to 2~3, filtering obtains filtrate;
(2) filtrate is concentrated into the 15%-20% of original volume with n-butyl acetate extraction 3 times, combining extraction liquid, obtains concentrate, cooling
To 10 DEG C hereinafter, crystallization, filtering, obtain phloroglucin crude product;
(3) the phloroglucin crude product is added in the mixed liquor of purified water and alcohols solvent and is dissolved by heating, kept the temperature and work is added
Property charcoal adsorbing contaminant, filtering, filtrate is cooled to 10 DEG C hereinafter, crystallization, filters, wash, vacuum drying.
2. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: described 1,3,5- trimethoxy-benzenes with it is dense
H in sulfuric acid2SO4Molar ratio be 1:5-7.
3. the synthetic method of phloroglucin as claimed in claim 2, it is characterised in that: the mass fraction of the concentrated sulfuric acid is
70%-85%.
4. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: in extraction process, each butyl acetate
Volume and 1,3,5- trimethoxy-benzene mass ratio be 2.5-4:1.
5. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: the thickening temperature is 40-45 DEG C.
6. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: purified water during the heating for dissolving
Dosage is 6-8 times of phloroglucin crude product weight, and the volume of alcohols solvent is 1-2 times of phloroglucin crude product weight, and alcohols is molten
Agent is methanol, ethyl alcohol or isopropanol, and heating temperature is 64-82 DEG C.
7. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: the activated carbon dosage is phloroglucin
The 2%-8% of crude product weight.
8. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: in step (2), the crystallization time is
In 18-24h and/or step (3), the crystallization time is 18-24h.
9. the synthetic method of phloroglucin as described in claim 1, it is characterised in that: the extract liquor is dry with anhydrous sodium sulfate
It is dry.
10. such as the synthetic method of the described in any item phloroglucins of claim 1-9, it is characterised in that: described in step (3)
Vacuum drying temperature is 45-55 DEG C, and relative degree of vacuum is -0.086~-0.096MPa, time 10-12h.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111004173A (en) * | 2019-12-31 | 2020-04-14 | 北京康蒂尼药业有限公司 | Preparation method of hydroxyl-niatone |
CN113480413A (en) * | 2021-07-05 | 2021-10-08 | 四川海梦智森生物制药有限公司 | Preparation method of phloroglucinol |
CN114890871A (en) * | 2021-07-06 | 2022-08-12 | 海口天行健药物研究有限公司 | Preparation method of trimethyl phloroglucinol crude product and preparation method of trimethyl phloroglucinol |
CN115490573A (en) * | 2022-09-27 | 2022-12-20 | 康普药业股份有限公司 | Novel phloroglucinol synthesis process |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1491927A (en) * | 2002-10-23 | 2004-04-28 | 浙江新和成股份有限公司 | Process for preparing phloroglucinol |
CN1513821A (en) * | 2003-05-19 | 2004-07-21 | 浙江大学 | Preparation method of resorcinol |
CN102452902A (en) * | 2010-10-29 | 2012-05-16 | 天津三农金科技有限公司 | Preparation method for phloroglucinol |
CN103755529A (en) * | 2013-08-20 | 2014-04-30 | 寿光富康制药有限公司 | Method for preparing pyrogallol and phloroglucinol |
-
2018
- 2018-09-14 CN CN201811076169.XA patent/CN109180436A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1491927A (en) * | 2002-10-23 | 2004-04-28 | 浙江新和成股份有限公司 | Process for preparing phloroglucinol |
CN1513821A (en) * | 2003-05-19 | 2004-07-21 | 浙江大学 | Preparation method of resorcinol |
CN102452902A (en) * | 2010-10-29 | 2012-05-16 | 天津三农金科技有限公司 | Preparation method for phloroglucinol |
CN103755529A (en) * | 2013-08-20 | 2014-04-30 | 寿光富康制药有限公司 | Method for preparing pyrogallol and phloroglucinol |
Non-Patent Citations (3)
Title |
---|
《化工百科全书》编辑委员会编: "《化工百科全书 第3卷 刀具材料-发电 dao-fa》", 31 March 1993 * |
诸爱士等: "新法合成间苯三酚", 《化学反应工程与工艺》 * |
赵克健主编: "《现代药学名词手册》", 31 October 2004 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111004173A (en) * | 2019-12-31 | 2020-04-14 | 北京康蒂尼药业有限公司 | Preparation method of hydroxyl-niatone |
CN113480413A (en) * | 2021-07-05 | 2021-10-08 | 四川海梦智森生物制药有限公司 | Preparation method of phloroglucinol |
CN114890871A (en) * | 2021-07-06 | 2022-08-12 | 海口天行健药物研究有限公司 | Preparation method of trimethyl phloroglucinol crude product and preparation method of trimethyl phloroglucinol |
CN115490573A (en) * | 2022-09-27 | 2022-12-20 | 康普药业股份有限公司 | Novel phloroglucinol synthesis process |
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