CN108358913A - A kind of green synthesis process of rotundine sulfate - Google Patents
A kind of green synthesis process of rotundine sulfate Download PDFInfo
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- CN108358913A CN108358913A CN201810169960.9A CN201810169960A CN108358913A CN 108358913 A CN108358913 A CN 108358913A CN 201810169960 A CN201810169960 A CN 201810169960A CN 108358913 A CN108358913 A CN 108358913A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
Abstract
The present invention provides a kind of green synthesis process of rotundine sulfate, elder generation is using catechol as initial reactant, and through esterification, acylation, nitration, deoxidation and reduction obtains 3,4 dimethoxy-phenylethylamines again；Again with 3,4 dimethoxy-phenylethylamine of gained and 2,3 dimethoxy benzaldehydes are condensed and restore (3,4 dimethoxy) phenethyl (2,3 dimethoxy) benzyl amine；Finished product sulfuric acid rotundin is finally obtained through cyclization, reduction and sulphation with gained (3,4 dimethoxy) phenethyl (2,3 dimethoxy) benzyl amine.The present invention develops the fully synthetic technique using catechol as raw material, and a kind of green synthesis process environmental-friendly, at low cost, yield is high is provided for rotundine sulfate synthesis.
Description
Technical field
The present invention relates to pharmaceutical synthesis fields, and in particular to a kind of green synthesis process of rotundine sulfate.
Background technology
Rotundin Rotundine, also known as rotundine, rotundin L-
Tetrahydropalmatine, 2,3,9,10- tetramethoxy -5,8 of chemical name, 13,13a- tetrahydrochysene -6H- dibenzo [a, g]
Quinolizine, chemical formula C21H25N04, it is the chemicals of a kind of white or yellowish crystallization.It medically has analgesia, calm, hypnosis
And stable effect, it is clinical in after the pain for the treatment of gastric ulcer and duodenal ulcer, cramp, childbirth uterine contraction pain, tonicity
The upper important role such as insomnia, spasmodic cough.Natural, rotundin can be from pappy shell corydalis tuber, the raw purple silkworm of volt
It detaches and is prepared in stem tuber, small chrysanthemum cocoon, Huang Quangen and menispermaceous plants stephania sinica root, greenyellow stephania root root tuber.But by
In be easy to extract, sell, profit it is high, in addition market demand steps up, natural plant resource containing rotundin is located always
In random mining, this also causes resource seriously to be destroyed and deficient.Therefore, a kind of next sieve that manually prepares of chemical synthesis process is found to lead to
Surely it is necessary.
Currently, purification, crystal controlling and the medicinal application of rotundin are focused primarily upon about the report of rotundin, it is complete to close
At the rare report of method.Known complete synthesizing process method mainly also rests on the laboratory research stage.Although its rotundin synthesized
Product has the characteristics that purity is high, but because of factors such as manufacturing cost height, synthesis condition harshnesses, it is extensive to be not suitable for industrialization
Production.
Currently, generally there are two types of paths for the fully synthetic technique of rotundin of industrialization large-scale application.Wherein, with using more wound
The wooden phenol is for starting material：Guaiacol is after Hypermethylation, chloromethylation, cyaniding, condensation hydrogenation, cyclization and reduction reaction
It is made, processing step is more, and the production cycle is long, and yield is low, of high cost；In the synthesis process, the severe toxicity such as cyanide or environment are harmful
The participation of substance greatly reduces the environmental-friendly degree of synthesis technology itself, and subsequent pollution processing also further increases production
Cost.In another synthesis path, although not using cyanide, the extremely heavy huge sum of money of this kind of environmental pollution of zinc amalgam can be also used
Belong to reducing agent, the problem that similar technique step is more, yield is low in addition still remains.
Invention content
The present invention provides a kind of green synthesis process of rotundine sulfate, with solve above-mentioned synthesis technology environment it is unfriendly,
The problem of production cost height, low yield.
Synthetic schemes provided by the invention is as follows：
A kind of green synthesis process of rotundine sulfate, steps are as follows：
(1) catechol is esterified to obtain o-dimethoxybenzene；
(2) o-dimethoxybenzene formylated obtains Veratraldehyde；
(3) Veratraldehyde nitration obtains 3,4- Dimethoxyphenyls-β-nitroethylene；
(4) 3,4- Dimethoxyphenyl-β-nitroethylene deoxidation and reduction obtain 3,4- dimethoxy-phenylethylamines；
(5) 3,4- dimethoxy-phenylethylamine and 2,3- dimethoxy benzaldehydes are condensed and restore (3,4- dimethoxy) benzene
Ethyl (2,3- dimethoxy) benzyl amine；
(6) (3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine cyclization obtains palmatin hydrochloride；
(7) palmatin hydrochloride restores to obtain rotundin；
(8) rotundin sulphation obtains rotundine sulfate.
Brief synthetic route chart of the present invention is as shown in Fig. 1, and principle is：The green of rotundine sulfate is fully synthetic
Reaction is using catechol as initial reactant, and through esterification, acylation, nitration, deoxidation and reduction obtains 3,4- dimethoxy-phenylethylamines again；
Intermediate production is changed by new reaction mechanism instead of substitution reaction in the prior art with addition condensation reaction during this
Object avoids the use of hypertoxic cyanide, also do not use mercurous reducing agent, while to obtain 3 from basic reaction object,
The comprehensive yield of 4- Dimethoxyphenyls-β-nitroethylene is up to 89%, better than 3,4- dimethoxybenzeneacetonitriles in the prior art
40% yield.Again with gained 3,4- dimethoxy-phenylethylamines and 2,3- dimethoxy benzaldehydes are condensed and restore (3,4- bis-
Methoxyl group) phenethyl (2,3- dimethoxy) benzyl amine；Finally with gained (3,4- dimethoxy) phenethyl (2,3- dimethoxies
Base) benzyl amine obtains finished product sulfuric acid rotundin through cyclization, reduction and sulphation.
Further, the specific method of step (1) is：O-phenol is in dimethyl suflfate, sodium hydroxide, 30 DEG C of heat preservation strips
Esterification is carried out under part obtains o-dimethoxybenzene.Compared with prior art, based on new start material, exploitation is provided
The possibility in new and green fully synthetic path.
Further, the reactant ratio of step (1) is：O-phenol: dimethyl suflfate: water=0.9~1.1: 0.5
~0.6: 2.4~2.9.
Preferably, the reactant ratio of step (1) is：O-phenol: dimethyl suflfate: water=1: 0.55: 2.64.
Further, the specific method of step (2)：O-dimethoxybenzene in n,N-Dimethylformamide with phosphorus trichloride
Through Wei Er David Smails reaction Vilsmeier Reaction it is acylated Veratraldehyde.
Further, the reactant ratio of step (2) is：1,2-dimethoxy benzene: phosphorus oxychloride: DMF=0.9~1.1:
3.7~4.6: 2.5~3.
Preferably, the reactant ratio of step (2) is：1,2-dimethoxy benzene: phosphorus oxychloride: DMF=1: 4.14: 2.76.
Further, the specific method of step (3)：Veratraldehyde is in nitromethane, methanol, water, hydrogen-oxygen
Under the conditions of change sodium 3,4- Dimethoxyphenyls-β-nitroethylene is obtained through back flow reaction nitration.
Further, the reactant ratio of step (3) is：Veratraldehyde: nitromethane: methanol: hydrogen
Sodium oxide molybdena: water=0.9~1.1: 1~1.2: 6.4~7.8: 2.7~3.3: 2.3~2.9.
Preferably, the reactant ratio of step (3) is：Veratraldehyde: nitromethane: methanol: hydroxide
Sodium：Water=1: 1.1: 7.15: 3.01: 2.6.
Further, the specific method of step (4)：3,4- Dimethoxyphenyl-β-nitroethylene is in potassium borohydride, trifluoro
Deoxidation and reduction obtains 3,4- dimethoxy-phenylethylamines under the conditions of changing borate ether, tetrahydrofuran.
Further, the reactant ratio of step (4) is：4- Dimethoxyphenyls-β-nitroethylene: potassium borohydride:
Boron trifluoride ether: tetrahydrofuran: water: hydrochloric acid=0.9~1.1: 1.2~1.5: 3.8~4.6: 30~37: 56~69: 22.8
~28.
Preferably, the reactant ratio of step (4) is：4- Dimethoxyphenyls-β-nitroethylene: potassium borohydride: trifluoro
Change borate ether: tetrahydrofuran: water: hydrochloric acid=1: 1.33: 4.22: 33.38: 62.5: 25.38.
Further, the specific method of step (5)：3,4- dimethoxy-phenylethylamines under the conditions of 110 DEG C with 2,3- diformazans
After oxygroup benzaldehyde, 3,4- diformazans are restored to obtain under Raney's nickel, 60~65 DEG C, the pure hydrogen environmental condition of 20~30atm
Oxygroup) phenethyl (2,3- dimethoxy) benzyl amine.
Further, the reactant ratio of step (5) is：3,4- dimethoxy-phenylethylamines: 2,3- dimethoxy benzene first
Aldehyde: absolute ethyl alcohol: Raney's nickel=0.9~1.1: 0.9~1.1: 7.8~9.6: 0.15~0.19.
Preferably, the reactant ratio of step (5) is：3,4- dimethoxy-phenylethylamines: 2,3- dimethoxy benzaldehydes: nothing
Water-ethanol: Raney's nickel=1: 0.99: 8.72: 0.17.
Further, the specific method of step (6)：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine
Cyclization obtains palmatin hydrochloride under the conditions of glyoxal, organic acid, copper sulphate, sodium chloride.
Further, the reactant ratio of step (6) is：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzene
Methyl amine sulfate: 50% glyoxal: organic acid: copper sulphate: sodium chloride=0.9~1.1: 0.37~0.45: 5.7~9.1:
0.74~0.9: 0.53~0.65.
Preferably, the reactant ratio of step (6) is：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl
Amine sulfate: 50% glyoxal: acetic acid: copper sulphate: sodium chloride=1: 0.41: 8.24: 0.82: 0.59.
Preferably, the reactant ratio of step (6) is：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl
Amine sulfate: 50% glyoxal: formic acid: copper sulphate: sodium chloride=1: 0.41: 6.32: 0.82: 0.59.
Further, the specific method of step (7)：Palmatin hydrochloride is in Raney's nickel, absolute ethyl alcohol, sodium acetate, 80~90
DEG C, restore to obtain rotundin under the pure hydrogen environmental condition of 20atm.
Further, the reactant ratio of step (7) is：Palmatin hydrochloride: Raney's nickel: sodium acetate: absolute ethyl alcohol=
0.9~1.1: 0.2~0.25: 0.29~0.35: 19.4~23.7.
Preferably, the reactant ratio of step (7) is：Palmatin hydrochloride: Raney's nickel: sodium acetate: absolute ethyl alcohol=1:
0.23∶0.32∶21.52。
Further, the specific method of step (8)：Palmatin hydrochloride obtains under conditions of distilled water, sulfuric acid after sulphation
Rotundine sulfate.
Further, the reactant ratio of step (8) is：Rotundin: anhydrous slufuric acid: water=0.9~1.1: 3.6~
4.4: 0.36~0.44
Preferably, the reactant ratio of step (8) is：Rotundin: anhydrous slufuric acid: water=1: 4: 0.4.
Further, the rotundine sulfate is through decolourizing, recrystallizing and obtaining rotundine sulfate.
Compared to the prior art, the beneficial effects of the invention are as follows：
(1) the fully synthetic technique using catechol as starting material is developed, is the commercial scale chemical combination of rotundine sulfate
At providing a kind of efficient synthesis environmental-friendly, at low cost, yield is high；
(2) intermediate product is changed by new reaction mechanism, that is, avoids the use of hypertoxic cyanide, also do not used mercurous
Reducing agent reduces technique behaviour's risk, improves the environment friendly of technique, more conducively industrial scale operation and popularization；
(3) by the change of synthetic route and perfect, invention significantly improves the yields of rotundine sulfate commercial synthesis.
Similarly, yield significantly improves, and production cost also obtained apparent reduction；
(4) preparation process of 3,4- dimethoxy-phenylethylamines is optimized, compared to the prior art, without the anti-of high temperature and pressure
Condition is answered, operation difficulty and equipment requirement in building-up process, the mesh for having reached simplified technique, having reduced cost are significantly reduced
's；
(5) cyanide, zinc amalgam etc. are thoroughly avoided from the root cause from reaction mechanism and response path in this technique
The participation of hypertoxic adverse reaction object, the comprehensive receipts for the synthesis technology that thoroughly taken on a new look simultaneously also by the yield for improving intermediate steps
Rate, this is in the fully synthetic field of rotundine sulfate, and especially its fully synthetic field of green still belongs to the first, therefore has important research
With application value and high economic value, suitable for being widely applied in the art.
Description of the drawings
Fig. 1 is that the present invention relates to a kind of brief synthetic route charts of the green synthesis process of rotundine sulfate.
Specific implementation mode
In order to make those skilled in the art more fully understand technical scheme of the present invention, with reference to specific embodiment pair
The present invention is described in further detail.
Embodiment 1
Step 1：The synthesis of o-dimethoxybenzene
Proportioning：O-phenol: dimethyl suflfate: water=1: 0.55: 2.64
In the 1000ml four-hole bottles equipped with blender, reflux condensing tube, dropping funel and thermometer, 550g neighbour two is added
1450g dimethyl suflfates are added dropwise at 30 DEG C, while sodium hydroxide solution is added dropwise for phenol and 300ml water under stirring, make reaction solution
PH value is kept within 8~11.Dimethyl suflfate reacts 1 hour after being added dropwise to complete, by reaction solution liquid separation, organic phase, washing, drying
100-105 DEG C/18mmHg fractions are collected in vacuum distillation, as adjacent dimethyl benzene.
Step 2：The synthesis of Veratraldehyde
Proportioning：1,2-dimethoxy benzene: phosphorus oxychloride: DMF=1: 4.14: 2.76
13.7g 1,2-dimethoxy benzenes and 60ml DMF are sufficiently mixed stirring, 23ml phosphorus oxychloride is added dropwise under ice bath, is dripped
Finish, be heated to 40 DEG C, react 3 hours, then be warming up to 85 DEG C, react 1 hour, is poured into ice water after cooling.Gained mixed solution
PH value to more than 7 is adjusted, is flowed back 4 hours, crystallisation by cooling, ethanol/water recrystallizes to obtain 15.8g white crystals, as 3,4- diformazans
Oxygroup benzaldehyde, yield 95.2%.
The infrared signature peak value of Veratraldehyde：
IR(KBr V/cm-1)：1726.89(-CHO)；2985.32、1074.18(-OCH3)；3035.85(C6H4-)
Step 3：The synthesis of 3,4- Dimethoxyphenyl-β-nitroethylene
Proportioning：Veratraldehyde: nitromethane: methanol: sodium hydroxide: water=1: 1.1: 7.15: 3.01:
2.6
75ml methanol, 25ml water and 15ml sodium hydroxide solutions are added in round-bottomed flask, stirs evenly, adds 8.3g3,
4- dimethoxy benzaldehydes and 8ml nitromethanes, back flow reaction 4 hours, crystallisation by cooling obtain crude product, then molten with ethanol/water mixing
Agent recrystallizes to obtain yellow crystals 9.8g, as 3,4- Dimethoxyphenyls-β-nitroethylene, yield 93.6%.
The infrared signature peak value of 3,4- Dimethoxyphenyl-β-nitroethylene：
IR(KBr V/cm-1)：1385.23(-NO2)；1625.14 (- CH=CH-), 2978.56 (- OCH3)；
Step 4：The synthesis of 3,4- dimethoxy-phenylethylamines
Proportioning：4- Dimethoxyphenyls-β-nitroethylene: potassium borohydride: boron trifluoride ether: tetrahydrofuran: water: hydrochloric acid
=1: 1.33: 4.22: 33.38: 62.5: 25.38
5.3g potassium borohydrides and 15ml boron trifluoride ether are dissolved in 150ml tetrahydrofurans under ice bath, are added with stirring
4g4- Dimethoxyphenyls-β-nitroethylene, back flow reaction 3 hours, is cooled to room temperature, add 250ml water and
100ml1mol/L hydrochloric acid, back flow reaction 3 hours adjust the pH value to more than 7 of mixed solution after cooling, dichloromethane extraction is anti-
Solution is answered, colorless oil 3.2g, as 3,4- dimethoxy-phenylethylamines, yield are obtained after the drying of gained water phase anhydrous sodium sulfate
87.5%.
The infrared signature peak value of 3,4- dimethoxy-phenylethylamines：
IR(KBr V/cm-1)：2856.16、2934.5(-CH-CH-)；3436.59(-NH2)
Step 5：The synthesis of (3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine
Proportioning：3,4- dimethoxy-phenylethylamines: 2,3- dimethoxy benzaldehydes: absolute ethyl alcohol: Raney's nickel=1: 0.99:
8.72∶0.17
181g 3,4- dimethoxy-phenylethylamines and 180g 2,3- bis- are added in the 500ml Claisen flasks equipped with thermometer
Methoxybenzaldehyde is down to room temperature and obtains transparent oil after being reacted 1 hour at 110 DEG C and depressurizing and steam the moisture content of generation.With
Grease is transferred in autoclave by 2000ml absolute ethyl alcohols, and 30g Raney's nickels, nitrogen displacement is added, and hydrogen displacement is filled with hydrogen
Gas is heated to 60-65 DEG C and reacts 2 hours, be cooled to room temperature, filter to 20-30atm, adjusts reaction liquid pH value to 2~3 analysis
Go out crystallization, ethyl alcohol washs to obtain white crystals, and mother liquor concentrations must be crystallized and be washed again, merge to obtain 232-240g crystals, as (3,4-
Dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine, yield 80%.
Step 6：The synthesis of palmatin hydrochloride
Proportioning：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine sulfate: 50% glyoxal: acetic acid
: copper sulphate: sodium chloride=1: 0.41: 8.24: 0.82: 0.59
The addition 280g acetic acid in the 500ml three-necked flasks equipped with blender, condenser pipe and thermometer, 28g copper sulphate,
20g sodium chloride, 50% glyoxals of 14g, heating water bath is to 80 DEG C and is stirred to react 30 minutes, and then (3,4- diformazans are added in 34g
Oxygroup) phenethyl (2,3- dimethoxy) benzyl amine sulfate, it is heated to 85 DEG C and is stirred to react 6 hours, water pump decompression is steamed
Recovery of acetic acid is evaporated, residue is added 200ml water and is heated to 90 DEG C, and cooled and filtered is washed.Filter cake adds water and is heated to 90
DEG C, pH=8~9 are adjusted with sodium carbonate liquor, are filtered while hot.Filtrate presses 1：1 hydrochloric acid is acidified, crystallisation by cooling, is filtered, dry, is obtained
25g products, as palmatin hydrochloride, yield 71.4%.
Step 7：The synthesis of rotundin
Proportioning：Palmatin hydrochloride: Raney's nickel: sodium acetate: absolute ethyl alcohol=1: 0.23: 0.32: 21.52
88g palmatin hydrochlorides, 20g Raney's nickels, 2400ml absolute ethyl alcohols and 28g sodium acetates, gas are added in autoclave
Body is replaced, and hydrogen is pressurized to 20atm, after 3 hours are stirred to react at 85-90 DEG C, is cooled to room temperature, and is filtered, is added water 210ml simultaneously
It is alkalized with weak aqua ammonia, filtering washing, ethanol/water recrystallizes to obtain product.
Step 8：The synthesis of rotundine sulfate
Proportioning：Rotundin: anhydrous slufuric acid: water=1: 4: 0.4
By step 7 gained rotundin, 4 times of distilled water and equiv. sulfuric acid (press 1g distilled water：Anhydrous slufuric acid 0.1g) it is added instead
It answers in bottle, heating water bath to complete molten, activated carbon decolorizing, filtering, hot water washing.Filtrate stands overnight at 5 DEG C, filters to obtain knot
It is brilliant；Filtrate concentrates, cooling, then water crystallization；Two steps synthesis there are 60-64g products, as rotundine sulfate, yield 75-80%.
Embodiment 2
As embodiment, in the synthesis technology, step (6) can also be：
Step 6：The synthesis of palmatin hydrochloride
Proportioning：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine sulfate: 50% glyoxal: formic acid
: copper sulphate: sodium chloride=1: 0.41: 6.32: 0.82: 0.59
The addition 215g formic acid in the 500ml three-necked flasks equipped with blender, condenser pipe and thermometer, 28g copper sulphate,
20g sodium chloride, 50% glyoxals of 14g, heating water bath is to 80 DEG C and is stirred to react 30 minutes, and then (3,4- diformazans are added in 34g
Oxygroup) phenethyl (2,3- dimethoxy) benzyl amine sulfate, it is heated to 85 DEG C and is stirred to react 6 hours, water pump decompression is steamed
Recovery of acetic acid is evaporated, residue is added 200ml water and is heated to 90 DEG C, and cooled and filtered is washed.Filter cake adds water and is heated to 90
DEG C, pH=8~9 are adjusted with sodium carbonate liquor, are filtered while hot.Filtrate is acidified by 1: 1 hydrochloric acid, crystallisation by cooling, is filtered, dry, is obtained
25g products, as palmatin hydrochloride, yield 71%.
The specific implementation mode of the application above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
Cannot the limitation to the application protection domain therefore be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, under the premise of not departing from technical scheme design, various modifications and improvements can be made, these belong to this
The protection domain of application.
Claims (10)
1. a kind of green synthesis process of rotundine sulfate, which is characterized in that steps are as follows：
(1) catechol is esterified to obtain o-dimethoxybenzene；
(2) o-dimethoxybenzene formylated obtains Veratraldehyde；
(3) Veratraldehyde nitration obtains 3,4- Dimethoxyphenyls-β-nitroethylene；
(4) 3,4- Dimethoxyphenyl-β-nitroethylene deoxidation and reduction obtain 3,4- dimethoxy-phenylethylamines；
(5) 3,4- dimethoxy-phenylethylamine and 2,3- dimethoxy benzaldehydes are condensed and restore (3,4- dimethoxy) phenethyl
(2,3- dimethoxy) benzyl amine；
(6) (3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl amine cyclization obtains palmatin hydrochloride；
(7) palmatin hydrochloride restores to obtain rotundin；
(8) rotundine sulfate is obtained after rotundin sulphation.
2. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (1) is specific
For：O-phenol ester under dimethyl suflfate, sodium hydroxide, 30 DEG C of heat-retaining conditions carries out esterification and obtains adjacent dimethoxy
Benzene.
3. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (2) is specific
For：The o-dimethoxybenzene reacts acylated 3,4- bis- with phosphorus trichloride in n,N-Dimethylformamide through Wei Er David Smails
Methoxybenzaldehyde.
4. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (3) is specific
For：The Veratraldehyde obtains under the conditions of nitromethane, methanol, water, sodium hydroxide through back flow reaction nitration
3,4- Dimethoxyphenyl-β-nitroethylene.
5. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (4) is specific
For：3,4- Dimethoxyphenyls-β-nitroethylene deoxidation under the conditions of potassium borohydride, boron trifluoride ether, tetrahydrofuran
Restore to obtain 3,4- dimethoxy-phenylethylamines.
6. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (5) is specific
For：After 3,4- dimethoxy-phenylethylamines are condensed under the conditions of 110 DEG C with 2,3- dimethoxy benzaldehydes, in Raney's nickel, 60~65
DEG C, restore (3,4- dimethoxy) phenethyl (2,3- dimethoxy) benzyl under the pure hydrogen environmental condition of 20~30atm
Amine.
7. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (6) is specific
For：(3,4- dimethoxy) phenethyl (2,3- dimethoxy) the benzyl amine is in glyoxal, organic acid, copper sulphate, chlorination
Cyclization obtains palmatin hydrochloride under the conditions of sodium.
8. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (7) is specific
For：Palmatin hydrochloride restores under Raney's nickel, absolute ethyl alcohol, sodium acetate, 80~90 DEG C, the pure hydrogen environmental condition of 20atm
Rotundin.
9. a kind of green synthesis process of rotundine sulfate according to claim 1, which is characterized in that step (8) is specific
For：The palmatin hydrochloride obtains rotundine sulfate under conditions of sulfuric acid, distilled water after sulphation.
10. a kind of green synthesis process of rotundine sulfate according to claim 9, it is further characterized in that：The sulfuric acid
Rotundin is through decolourizing, recrystallizing and obtaining finished product sulfuric acid rotundin.
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| CN109575011A (en) * | 2019-01-09 | 2019-04-05 | 沈阳化工大学 | A kind of method of fully synthetic jamaicin |
| CN111100122A (en) * | 2018-10-26 | 2020-05-05 | 刘力 | Novel levo-tetrahydropalmatine compound |
| CN111925293A (en) * | 2020-08-24 | 2020-11-13 | 山东达冠医药科技有限公司 | Preparation method of dopamine hydrochloride |
| CN117551094A (en) * | 2024-01-12 | 2024-02-13 | 云南省药物研究所 | Preparation method of high-optical-purity rotundine |
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| CN111100122A (en) * | 2018-10-26 | 2020-05-05 | 刘力 | Novel levo-tetrahydropalmatine compound |
| CN109575011A (en) * | 2019-01-09 | 2019-04-05 | 沈阳化工大学 | A kind of method of fully synthetic jamaicin |
| CN111925293A (en) * | 2020-08-24 | 2020-11-13 | 山东达冠医药科技有限公司 | Preparation method of dopamine hydrochloride |
| CN111925293B (en) * | 2020-08-24 | 2022-06-14 | 山东达冠医药科技有限公司 | Preparation method of dopamine hydrochloride |
| CN117551094A (en) * | 2024-01-12 | 2024-02-13 | 云南省药物研究所 | Preparation method of high-optical-purity rotundine |
| CN117551094B (en) * | 2024-01-12 | 2024-04-05 | 云南省药物研究所 | Preparation method of high-optical-purity rotundine |
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