CN106699576A - Method for synthesizing methoxyphenamine hydrochloride - Google Patents
Method for synthesizing methoxyphenamine hydrochloride Download PDFInfo
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- CN106699576A CN106699576A CN201611206130.6A CN201611206130A CN106699576A CN 106699576 A CN106699576 A CN 106699576A CN 201611206130 A CN201611206130 A CN 201611206130A CN 106699576 A CN106699576 A CN 106699576A
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- reaction
- methoxyphenamine
- schiff bases
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- alkali
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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
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
Abstract
The invention relates to the technical field of synthesis of medicinal raw materials and chemical intermediates, in particular to a method for synthesizing methoxyphenamine hydrochloride. The method comprises the following steps: adding o-methoxyl phenylacetone and a methylamine ethanol solution into a reaction kettle, performing a reaction to obtain Schiff base, and further adding a metal reducing agent into the Schiff base obtained through the reaction to reduce the Schiff base. The method for synthesizing the methoxyphenamine hydrochloride is low in cost, high in product content and easy to industrialize, and the mole yield is greater than 82%.
Description
Technical field
The present invention relates to the technical field that medical material and chemical intermediate synthesize, especially a kind of methoxyphenamine hydrochloride
Synthetic method.
Background technology
Methoxyphenamine hydrochloride, chemical name：2- methoxyl group-N, the hydrochloride of Ionamin is that beta-2 adrenoceptor swashs
Dynamic medicine, the effect of bronchial spasm is released with lax bronchial smooth muscle.Its antiasthmatic effect is better than ephedrine, central excitation and
Cardiovascular aspect is then weaker.At present, the synthetic method of methoxyphenamine hydrochloride is reacted using metal catalyzed hydrogenation mostly：
Zenichi H etc. report another synthetic method (Yakugaku Zasshi, 1957,77：256-8.), adjacent first
The methylamine methanol solution of phenyl acetone 3g and 20g 30%, 1.6g is obtained under the catalytic hydrogenation of Raney's nickel and platinous chloride
Product.
Chinese Patent Application No. is that 200910264415.9 patent application discloses a kind of synthesis of methoxyphenamine hydrochloride
Method, in the catalytic hydrogenation of o-methoxyphenyl acetone and methylamine alcohol solution, it is catalyst to use palladium carbon.
In above-mentioned use o-methoxyphenyl acetone and the method for methylamine methyl alcohol reaction, platinum oxide, platinous chloride, palladium carbon are used
Make catalyst, catalyst is expensive, production cost can be dramatically increased；And molar yield is not high.
The content of the invention
The technical problem to be solved in the present invention is：To overcome the deficiencies in the prior art, there is provided a kind of low cost, product
Product content is high, the synthetic method of the methoxyphenamine hydrochloride of easy industrialization, molar yield more than 82%.
The technical solution adopted for the present invention to solve the technical problems is：
Reaction formula is as follows：
The synthetic method of methoxyphenamine hydrochloride, enters during o-methoxyphenyl acetone and methylamine methanol solution are added into reactor
Row reaction, reaction obtains schiff bases；Adding metallic reducing agent in the schiff bases that reaction is obtained again carries out the reduction of schiff bases.
Specific synthesis step is as follows：
Step 1：Synthesis schiff bases：Carried out instead during o-methoxyphenyl acetone and methylamine methanol solution are added into reactor
Should, the reaction time is 15~18h, and reaction temperature is 20~35 DEG C, fully obtains schiff bases after reaction；
Step 2：Synthesis methoxyphenamine alkali：Metallic reducing agent is added in the schiff bases that step 1 reaction is obtained carries out Schiff
The reduction of alkali, the reaction time is 6~12h, and reaction temperature is -5~5 DEG C, fully obtains methoxyphenamine alkali after reaction；
Step 3：Synthetic hydrochloric acid methoxyphenamine：In the methoxyphenamine alkali that step 2 reaction is obtained, hydrochloric acid solution regulation is added
PH=1~2, the reaction time is 11~12h, and reaction temperature is -10~-5 DEG C, fully obtains methoxyphenamine hydrochloride after reaction.
The metallic reducing agent is in Lithium Aluminium Hydride, sodium cyanoborohydride, lithium borohydride or sodium triacetoxy borohydride
One kind.
The quality consumption of the metallic reducing agent is 0.18~0.2 times of o-methoxyphenyl acetone quality.
The beneficial effects of the invention are as follows：Using Lithium Aluminium Hydride, sodium cyanoborohydride, lithium borohydride or triacetoxy borohydride hydrogen
Change a kind of reduction for carrying out schiff bases in sodium, substantially reduce reaction cost, molar yield is more than 82%, is capable of achieving industrialization.
Specific embodiment
The present invention is further detailed explanation now.
Reaction formula is as follows：
Embodiment 1：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 15h, and reaction temperature is 28 DEG C, fully obtains schiff bases after reaction, adds 17g Lithium Aluminium Hydrides to enter in schiff bases
The reduction of row schiff bases, the reaction time is 7h, and reaction temperature is 2 DEG C, fully methoxyphenamine alkali is obtained after reaction, in methoxyphenamine
Hydrochloric acid solution regulation PH=2 is added in alkali, the reaction time is 12h, and reaction temperature is -6 DEG C, fully obtains 118.5g salt after reaction
Sour methoxyphenamine, molar yield is 90.2%.
Embodiment 2：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 16h, and reaction temperature is 25 DEG C, fully obtains schiff bases after reaction, and 18g cyano group hydroborations are added in schiff bases
Sodium carries out the reduction of schiff bases, and the reaction time is 6h, and reaction temperature is 3 DEG C, fully methoxyphenamine alkali is obtained after reaction, in methoxy
Hydrochloric acid solution regulation PH=1 is added in that bright alkali, the reaction time is 11h, and reaction temperature is -5 DEG C, is fully obtained after reaction
116.4g methoxyphenamine hydrochlorides, molar yield is 88.6%.
Embodiment 3：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 15h, and reaction temperature is 28 DEG C, fully obtains schiff bases after reaction, adds 17g lithium borohydrides to enter in schiff bases
The reduction of row schiff bases, the reaction time is 10h, and reaction temperature is 0 DEG C, fully obtains methoxyphenamine alkali after reaction, methoxy that
Hydrochloric acid solution regulation PH=2 is added in bright alkali, the reaction time is 12h, and reaction temperature is -8 DEG C, fully obtains 112.6g after reaction
Methoxyphenamine hydrochloride, molar yield is 85.7%.
Embodiment 4：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 17h, and reaction temperature is 20 DEG C, fully obtains schiff bases after reaction, and 19g triacetoxyl groups are added in schiff bases
Sodium borohydride carries out the reduction of schiff bases, and the reaction time is 9h, and reaction temperature is 1 DEG C, fully obtains methoxyphenamine alkali after reaction,
Hydrochloric acid solution regulation PH=1 is added in methoxyphenamine alkali, the reaction time is 11h, and reaction temperature is -7 DEG C, fully after reaction
To 111.5g methoxyphenamine hydrochlorides, molar yield is 84.9%.
Embodiment 5：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 16h, and reaction temperature is 30 DEG C, fully obtains schiff bases after reaction, adds 18g Lithium Aluminium Hydrides to enter in schiff bases
The reduction of row schiff bases, the reaction time is 8h, and reaction temperature is 0 DEG C, fully methoxyphenamine alkali is obtained after reaction, in methoxyphenamine
Hydrochloric acid solution regulation PH=2 is added in alkali, the reaction time is 12h, and reaction temperature is -8 DEG C, fully obtains 116.8g salt after reaction
Sour methoxyphenamine, molar yield is 88.9%.
Embodiment 6：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 17h, and reaction temperature is 27 DEG C, fully obtains schiff bases after reaction, and 19g cyano group hydroborations are added in schiff bases
Sodium carries out the reduction of schiff bases, and the reaction time is 7h, and reaction temperature is 1 DEG C, fully methoxyphenamine alkali is obtained after reaction, in methoxy
Hydrochloric acid solution regulation PH=1 is added in that bright alkali, the reaction time is 11h, and reaction temperature is -7 DEG C, is fully obtained after reaction
113.9g methoxyphenamine hydrochlorides, molar yield is 86.7%.
Embodiment 7：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 16h, and reaction temperature is 30 DEG C, fully obtains schiff bases after reaction, adds 18g lithium borohydrides to enter in schiff bases
The reduction of row schiff bases, the reaction time is 12h, and reaction temperature is -2 DEG C, fully obtains methoxyphenamine alkali after reaction, methoxy that
Hydrochloric acid solution regulation PH=2 is added in bright alkali, the reaction time is 12h, and reaction temperature is -10 DEG C, is fully obtained after reaction
109.7g methoxyphenamine hydrochlorides, molar yield is 83.5%.
Embodiment 8：Reacted during 100g o-methoxyphenyls acetone and 330g methylamine methanol solutions are added into reactor,
Reaction time is 18h, and reaction temperature is 24 DEG C, fully obtains schiff bases after reaction, and 20g triacetoxyl groups are added in schiff bases
Sodium borohydride carries out the reduction of schiff bases, and the reaction time is 11h, and reaction temperature is -1 DEG C, fully obtains methoxyphenamine after reaction
Alkali, adds hydrochloric acid solution regulation PH=1 in methoxyphenamine alkali, and the reaction time is 11h, and reaction temperature is -9 DEG C, fully reaction
After obtain 108.1g methoxyphenamine hydrochlorides, molar yield is 82.3%.
Molar yield in each embodiment, as shown in table 1：
With above-mentioned according to desirable embodiment of the invention as enlightenment, relevant staff completely can be without departing from this hair
In the range of bright technological thought, various changes and amendments are carried out.The technical scope of this invention is not limited to explanation
Content on book, it is necessary to its technical scope is determined according to right.
Claims (4)
1. the synthetic method of methoxyphenamine hydrochloride, it is characterized in that：O-methoxyphenyl acetone and methylamine methanol solution are added anti-
Answer and reacted in kettle, reaction obtains schiff bases；Adding metallic reducing agent in the schiff bases that reaction is obtained again carries out schiff bases
Reduction.
2. the synthetic method of methoxyphenamine hydrochloride as claimed in claim 1, it is characterized in that：Specific synthesis step is as follows：
Step 1：Synthesis schiff bases：Reacted during o-methoxyphenyl acetone and methylamine methanol solution are added into reactor, instead
It is 15~18h between seasonable, reaction temperature is 20~35 DEG C, fully obtains schiff bases after reaction；
Step 2：Synthesis methoxyphenamine alkali：Metallic reducing agent is added in the schiff bases that step 1 reaction is obtained carries out schiff bases
Reduction, the reaction time is 6~12h, and reaction temperature is -5~5 DEG C, fully obtains methoxyphenamine alkali after reaction；
Step 3：Synthetic hydrochloric acid methoxyphenamine：In the methoxyphenamine alkali that step 2 reaction is obtained, hydrochloric acid solution regulation PH=is added
1~2, the reaction time is 11~12h, and reaction temperature is -10~-5 DEG C, fully obtains methoxyphenamine hydrochloride after reaction.
3. the synthetic method of methoxyphenamine hydrochloride as claimed in claim 1, it is characterized in that：The metallic reducing agent is tetrahydrochysene aluminium
One kind in lithium, sodium cyanoborohydride, lithium borohydride or sodium triacetoxy borohydride.
4. the synthetic method of methoxyphenamine hydrochloride as claimed in claim 1, it is characterized in that：The quality consumption of the metallic reducing agent
It is 0.18~0.2 times of o-methoxyphenyl acetone quality.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113754549A (en) * | 2021-09-07 | 2021-12-07 | 青海制药厂有限公司 | Process for producing aralkylamine compounds and salts thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113754549A (en) * | 2021-09-07 | 2021-12-07 | 青海制药厂有限公司 | Process for producing aralkylamine compounds and salts thereof |
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