CN106967138A - Diosmin production method based on dimethyl sulfoxide system - Google Patents
Diosmin production method based on dimethyl sulfoxide system Download PDFInfo
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- CN106967138A CN106967138A CN201710255134.1A CN201710255134A CN106967138A CN 106967138 A CN106967138 A CN 106967138A CN 201710255134 A CN201710255134 A CN 201710255134A CN 106967138 A CN106967138 A CN 106967138A
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- diosmin
- dimethyl sulfoxide
- aurantiamarin
- dmso
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- Engineering & Computer Science (AREA)
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Abstract
The invention discloses the diosmin production method based on dimethyl sulfoxide system, comprise the following steps：In being fitted into after aurantiamarin and KI dmso solution in the first container；Dimethyl sulfoxide (DMSO) and the concentrated sulfuric acid are added in second container；Solution inside first container is fed into reactor with the solution inside second container and mixes progress reaction response reaction solution is collected in cooling afterwards completely；The reaction solution of collection is transferred in reactor, diosmin wet product is obtained；80 DEG C of forced air drying 12h of diosmin wet product obtain diosmin.Microreactor is combined and develops new diosmin production technology by the present invention with new dehydrogenation systems (KI/sulfuric acid/dimethyl sulfoxide (DMSO)), and security does not pollute the environment well, and the diosmin purity produced is high, yield is high.
Description
Technical field
The present invention relates to a kind of diosmin production method, and in particular to the diosmin production based on dimethyl sulfoxide system
Method.
Background technology
Diosmin (Diosmin), also known as diosmin, molecular formula C28H32O15, CAS：520-27-4.It is used to control
Treat acute and chronic hemorrhoid breaking-out, it can also be used to chronic venous insufficiency, such as varication, edema of lower extremity, chronic ulcer of leg
Deng.Diosmin content in plant is less, it is difficult to meet the great demand in market.Therefore the production of diosmin is mainly logical
The method for crossing synthesis is obtained.Hesperidine content in the dried immature fruit of citron orange is very big, according to the place of production with pick that season is different, the content of hesperidine
Between 15-40%, and hesperidine and diosmin structure are much like, and diosmin can be obtained by the dehydrogenation reaction of hesperidine：
It is to use sodium hydroxide/KI/iodine, acetic anhydride/pyridine/selenium oxide, diformazan earliest in existing production technology
Sulfoxide/pyridine/iodine, dimethyl sulfoxide/tetra- polyvinyl resin/iodine, methanol/sodium acetate/iodine and acetic anhydride/pyridine/bromine etc. take off
Hydrogen reagent produces diosmin, recently using relatively advanced, pyridine/iodine is used during the production technology of main flow for dehydrating agent, so
And the technique have the shortcomings that it is as follows：1) 1 ton of diosmin is produced not consider to reclaim, it is necessary to consume 0.3 ton of iodine, atom economy
Property is excessively poor；2) iodine and pyridine all have volatility and corrosivity, and pyridine also has strong foul smell and toxicity, it is easy to make
Into the body loss and environmental pollution of workman, 3) price of iodine and pyridine is very big with turn of the market, and the price of current iodine is 230,000
Per ton, the price of pyridine is per ton 50,000, makes pyridine and iodine be the diosmin production technology cost of dehydrating agent increasingly without technology
Advantage.
The content of the invention
The technical problems to be solved by the invention are that traditionally the environmental pollution of Ao Siming production methods is big, it is therefore intended that provided
Diosmin production method based on dimethyl sulfoxide system, solves the problem of traditionally environmental pollution of Ao Siming production methods is big.
The present invention is achieved through the following technical solutions：
Diosmin production method based on dimethyl sulfoxide system, comprises the following steps：
S1：In being fitted into after aurantiamarin and KI dmso solution in the first container, the KI and orange
The ratio between amount of material of skin glycosides is：0.05-0.1:1.0, the aurantiamarin and with the mass ratio of dimethyl sulfoxide (DMSO) be：1.0-
2.0:1.0；
S2：Dimethyl sulfoxide (DMSO) and the concentrated sulfuric acid, the mass ratio of the dimethyl sulfoxide (DMSO) and aurantiamarin are added in second container
For：0.5：1.0, the ratio between amount of material of the concentrated sulfuric acid and aurantiamarin is 0.1:1.0；
S3：By the solution in the solution in step S1 inside the first container and step S2 inside second container according to charge ratio
For 2:1 volume ratio feeds to mix into reactor is reacted, and reaction temperature is 90-98 DEG C, cools after reaction completely and collects
Reaction solution；
S4：The reaction solution collected in step S3 is transferred in reactor, under agitation 0-10 DEG C of temperature control, first is then added dropwise
Alcohol separates out solid, and solid carries out suction filtration after separating out, is washed with deionized, drains and obtain diosmin wet product；
S5：80 DEG C of forced air drying 12h of diosmin wet product in step S4 are obtained into diosmin.
Double bond and benzene that two hydrogen atoms that hesperidine and diosmin are only differed on a double bond, aurantiamarin are obtained after eliminating
Ring and carbonyl conjugation, ultimately form the lower diosmin of energy barrier, in the prior art, occur in that dense with catalytic amount iodine/catalytic amount
The hydrogen atom that sulfuric acid/dimethyl sulfoxide (DMSO) (DMSO) system is sloughed on flavanone obtains flavones, such as：
Therefore, by repeatedly the research present invention should by catalytic amount KI/catalytic amount concentrated sulfuric acid/dimethyl sulfoxide (DMSO) (DMSO) system
Diosmin is synthesized for aurantiamarin dehydrogenation, Ao Siming can be successfully synthesized and solve conventional method environmental pollution asking greatly
Topic.
Reactor in the step S3 is that the response location that charging mixing is reacted in microreactor, reactor is micro-
The first container in the reaction channel of reactor, step S1 is that the second container in the A pumps of microreactor, step S2 is micro- reaction
The B pumps of device.For aurantiamarin, the glycosyl containing polyhydroxy on its 7 uses the KI/concentrated sulfuric acid/diformazan of the present invention
Base sulfoxide (DMSO) system can occur hydroxyl and be oxidized at normal reaction conditions, the side reaction that glycosyl is sloughed, so that ground
Ao Siming purity is low, low yield；Therefore, the present invention is solved by using microreactor as the reaction vessel for preparing diosmin
Diosmin purity is low, low yield the problem of, microreactor have it is seasonable between it is short, without enlarge-effect, solvent load be small, yield
High, easy to operate the advantages of.
When charging mixing is reacted in reactor in step S3, the reaction channel of microreactor is heated to 90- in advance
98 DEG C of reaction temperature, reaction channel end is cooled to 0-10 DEG C of collection reaction solution.The present invention is with prior art in reaction temperature
Upper and no significant difference.
The ratio between amount of material of KI and aurantiamarin is in step S1：0.05:1.0, aurantiamarin and and dimethyl sulfoxide (DMSO)
Mass ratio be：1.0:1.0.The amount that the present invention passes through the preferred each material for participating in preparing of many experiments.
The ratio between amount of material of KI and aurantiamarin is in step S1：0.1:1.0, aurantiamarin and with dimethyl sulfoxide (DMSO)
Mass ratio is：2.0:1.0.The amount that the present invention passes through the preferred each material for participating in preparing of many experiments.
The present invention compared with prior art, has the following advantages and advantages：
1st, the diosmin production method of the invention based on dimethyl sulfoxide system need not use the high toxicities such as iodine and pyridine
Reagent, workman produce when operation be very easy to, no potential safety hazard；
2nd, the diosmin production method agents useful for same (KI and sulfuric acid) of the invention based on dimethyl sulfoxide system is normal
General reagent is advised, reagent price is small with market fluctuation；
3rd, the diosmin production method based on dimethyl sulfoxide system is with short production cycle greatly shortens (microreactor by the present invention
Reaction time only 6-10 seconds), production auxiliary facility is few, and scale of investment is substantially reduced, production cost is low.
Embodiment
For the object, technical solutions and advantages of the present invention are more clearly understood, with reference to embodiment, to present invention work
Further to describe in detail, exemplary embodiment and its explanation of the invention is only used for explaining the present invention, is not intended as to this
The restriction of invention.
Embodiment 1
Diosmin production method of the invention based on dimethyl sulfoxide system, comprises the following steps：
S1：In being fitted into after aurantiamarin and KI dmso solution in the first container, the KI and orange
The ratio between amount of material of skin glycosides is：0.05-0.1:1.0, the aurantiamarin and with the mass ratio of dimethyl sulfoxide (DMSO) be：1.0-
2.0:1.0；
S2：Dimethyl sulfoxide (DMSO) and the concentrated sulfuric acid, the mass ratio of the dimethyl sulfoxide (DMSO) and aurantiamarin are added in second container
For：0.5：1.0, the ratio between amount of material of the concentrated sulfuric acid and aurantiamarin is 0.1:1.0；
S3：By the solution in the solution in step S1 inside the first container and step S2 inside second container according to charge ratio
For 2:1 volume ratio feeds to mix into reactor is reacted, and reaction temperature is 90-98 DEG C, cools after reaction completely and collects
Reaction solution；
S4：The reaction solution collected in step S3 is transferred in reactor, under agitation 0-10 DEG C of temperature control, first is then added dropwise
Alcohol separates out solid, and solid carries out suction filtration after separating out, is washed with deionized, drains and obtain diosmin wet product；
S5：80 DEG C of forced air drying 12h of diosmin wet product in step S4 are obtained into diosmin.In the step S3
Reactor is the reaction channel that the response location that charging mixing is reacted in microreactor, reactor is microreactor, step
The first container in S1 is the B pumps that second container in the A pumps of microreactor, step S2 is microreactor.Reacted in step S3
When charging mixing is reacted in device, the reaction channel of microreactor is heated to 90-98 DEG C of reaction temperature in advance, reaction is logical
Road end is cooled to 0-10 DEG C of collection reaction solution.
The present invention develops microreactor and new dehydrogenation systems (KI/sulfuric acid/dimethyl sulfoxide (DMSO)) combination new
Diosmin production technology, security does not pollute the environment well, and the diosmin purity produced is high, yield is high.
Embodiment 2
Based on embodiment 1, the ratio between amount of material of KI and aurantiamarin is in step S1：0.05:1.0, aurantiamarin and
Mass ratio with dimethyl sulfoxide (DMSO) is：1.0:1.0.Specifically include following production stage：
(1) the loading microreactor after 12.5kg dmso solutions by 12.5kg aurantiamarins and 0.17kg KIs
In A pumps；(2) 6.25kg dimethyl sulfoxide (DMSO)s and the 0.2kg concentrated sulfuric acids are added in the B pumps of microreactor；(3) by the anti-of microreactor
Channel temperature is answered to be heated to 90-98 DEG C；(4) charge ratio (volume of regulation A pumps and B pumps：V/V it is) 2：1, while opening A pumps and B
Pump charging mixing is reacted, while controlling reaction time to be 6-10 seconds, 0-10 DEG C of reaction channel end temperature control collects anti-
Answer liquid；(5) after having reacted, reaction solution is transferred in reactor, lower 0-10 DEG C of the temperature control of stirring is added dropwise methanol and separates out solid, takes out
Filter, is washed with 12.5kg deionized waters, drains to obtain diosmin wet product；(6) 80 DEG C of forced air drying 12h obtain diosmin
9.88kg, yield 95%, purity 96%
Embodiment 3
Based on embodiment 1, the ratio between amount of material of KI and aurantiamarin is in step S1：0.1:1.0, aurantiamarin and with
The mass ratio of dimethyl sulfoxide (DMSO) is：2.0:1.0.Comprise the following steps that：(1) 12.5kg aurantiamarins and 0.34kg KIs are used
It is fitted into after 6.25kg dmso solutions in the A pumps of microreactor；(2) 6.25kg diformazans are added in the B pumps of microreactor
Base sulfoxide and the 0.2kg concentrated sulfuric acids；(3) the reaction channel temperature of microreactor is heated to 90-98 DEG C；(4) regulation A pumps and B pumps
Charge ratio (volume：V/V it is) 1/1, while unlatching A pumps and the charging mixing of B pumps are reacted, while controlling reaction time
For 6-10 seconds, 0-10 DEG C of collection reaction solution of reaction channel end temperature control；(5) after having reacted, reaction solution is transferred in reactor,
Lower 0-10 DEG C of the temperature control of stirring, is added dropwise methanol and separates out solid, suction filtration is washed with 12.5kg deionized waters, drain diosmin is wet
Product；(6) 80 DEG C of forced air drying 12h obtain diosmin 9.35kg, yield 89.9%, purity 95%
Above-described embodiment, has been carried out further to the purpose of the present invention, technical scheme and beneficial effect
Describe in detail, should be understood that the embodiment that the foregoing is only the present invention, be not intended to limit the present invention
Protection domain, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc. all should be included
Within protection scope of the present invention.
Claims (5)
1. the diosmin production method based on dimethyl sulfoxide system, it is characterised in that comprise the following steps：
S1：In being fitted into after aurantiamarin and KI dmso solution in the first container, the KI and aurantiamarin
The ratio between the amount of material be：0.05-0.1:1.0, the aurantiamarin and with the mass ratio of dimethyl sulfoxide (DMSO) be：1.0-2.0:
1.0；
S2：Dimethyl sulfoxide (DMSO) and the concentrated sulfuric acid are added in second container, the mass ratio of the dimethyl sulfoxide (DMSO) and aurantiamarin is：
0.5：1.0, the ratio between amount of material of the concentrated sulfuric acid and aurantiamarin is 0.1:1.0；
S3：According to charge ratio it is 2 by the solution inside second container in the solution in step S1 inside the first container and step S2:
1 volume ratio feeds to mix into reactor is reacted, and reaction temperature is 90-98 DEG C, cools after reaction completely and collects reaction
Liquid；
S4：The reaction solution collected in step S3 is transferred in reactor, under agitation 0-10 DEG C of temperature control, methanol analysis is then added dropwise
Go out solid, solid carries out suction filtration after separating out, is washed with deionized, drains and obtain diosmin wet product；
S5：80 DEG C of forced air drying 12h of diosmin wet product in step S4 are obtained into diosmin.
2. the diosmin production method according to claim 1 based on dimethyl sulfoxide system, it is characterised in that the step
Reactor in rapid S3 is that the response location that charging mixing is reacted in microreactor, reactor leads to for the reaction of microreactor
The first container in road, step S1 is the B pumps that second container in the A pumps of microreactor, step S2 is microreactor.
3. the diosmin production method according to claim 2 based on dimethyl sulfoxide system, it is characterised in that step S3
When charging mixing is reacted in middle reactor, the reaction channel of microreactor is heated to 90-98 DEG C of reaction temperature in advance,
Reaction channel end is cooled to 0-10 DEG C of collection reaction solution.
4. the diosmin production method according to claim 3 based on dimethyl sulfoxide system, it is characterised in that step S1
The ratio between amount of material of middle KI and aurantiamarin is：0.05:1.0, aurantiamarin and with the mass ratio of dimethyl sulfoxide (DMSO) be：
1.0:1.0。
5. the diosmin production method according to claim 3 based on dimethyl sulfoxide system, it is characterised in that step S1
The ratio between amount of material of middle KI and aurantiamarin is：0.1:1.0, aurantiamarin and with the mass ratio of dimethyl sulfoxide (DMSO) be：
2.0:1.0。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111004199A (en) * | 2019-12-26 | 2020-04-14 | 陕西嘉禾药业有限公司 | Preparation method of apigenin |
| CN111018819A (en) * | 2019-12-26 | 2020-04-17 | 陕西嘉禾药业有限公司 | Preparation method of luteolin |
| CN111100104A (en) * | 2019-12-26 | 2020-05-05 | 陕西嘉禾药业有限公司 | Preparation method of diosmetin |
| CN112979603A (en) * | 2021-03-08 | 2021-06-18 | 宜宾西华大学研究院 | Continuous flow micro-channel synthesis process of flavonoid compound |
| CN113698440A (en) * | 2020-05-21 | 2021-11-26 | 西华大学 | Method for preparing diosmin by adopting continuous-flow microreactor |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111004199A (en) * | 2019-12-26 | 2020-04-14 | 陕西嘉禾药业有限公司 | Preparation method of apigenin |
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| CN113698440A (en) * | 2020-05-21 | 2021-11-26 | 西华大学 | Method for preparing diosmin by adopting continuous-flow microreactor |
| CN112979603A (en) * | 2021-03-08 | 2021-06-18 | 宜宾西华大学研究院 | Continuous flow micro-channel synthesis process of flavonoid compound |
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