(+)-pseudoephedrine transforms the method for (-)-ephedrine
The present invention relates to the method that a kind of (+)-pseudoephedrine transforms (-)-ephedrine.Be to belong to natural ephedrine technology of preparing transition.
The herbal medicine Chinese ephedra has good pharmaceutical use, has the advantage that drug safety is reliable, tolerance is strong, side effect is little.Its main effective constituent is (-)-ephedrine and (+)-pseudoephedrine, and the drug effect of wherein (-)-ephedrine is higher than (+)-pseudoephedrine far away, and the content of (+)-pseudoephedrine accounts for 1/3rd of total ephedrine.Therefore (+)-pseudoephedrine being changed into (-)-ephedrine is very significant work.To this; people have done a large amount of work; wherein main method for transformation is: (+)-pseudoephedrine carries out acetylize earlier and gets the N-acetyl compound; certain hour then refluxes in Glacial acetic acid; use the alkaline solution hydrolysis after reclaiming Glacial acetic acid; use extracted with diethyl ether again, extraction liquid feeds hydrogen chloride gas, can obtain (-)-ephedrine sulfate.This method is a two step method, and yield is lower, only is 50～60%.
Purpose of the present invention is to provide a kind of (+)-pseudoephedrine to transform the method for (-)-ephedrine.This method steps is simple, the transformation efficiency height, and production cost is low.
For achieving the above object, the present invention is realized by following technical proposals.Urge at acetic anhydride under the effect of into agent, (+)-pseudoephedrine is dissolved in the Glacial acetic acid, conversion was finished in reaction in 1.5～4 hours under 110～120 ℃, reclaim Glacial acetic acid, added the NaOH aqueous hydrolysis then 2～5 hours, and extracted with ether or benzene again, extraction liquid drying, feeding hydrogen chloride gas, obtain containing the mixture of (-)-ephedrine sulfate of 84～90%, it is characterized in that:
A. moles such as the acetic anhydride that is added and (+)-pseudoephedrine;
Mass/volume (grams per milliliter) percentage concentration of the amount of b. (+)-pseudoephedrine in Glacial acetic acid is 4～5%;
C.NaOH aqueous solution mass/volume (grams per milliliter) percentage concentration is 20%;
D. the siccative of extraction liquid is an anhydrous sodium carbonate.
Below the present invention is elaborated.
The present invention adopts single stage method to finish reaction, in the reaction with acetic anhydride for urging into agent, the add-on of acetic anhydride is one of important factor of decision yield, adds and the equimolar acetic anhydride of ephedrine in reaction, fully guarantee the consumption of acetic anhydride, helped improving conversion rate and transformation efficiency.On the other hand, the consumption of grasping Glacial acetic acid also is one of gordian technique, and consumption is too much, can increase the recovery operation amount of Glacial acetic acid; Consumption is very few, can reduce transformation efficiency again.The present invention is that mass/volume (grams per milliliter) percentage concentration of definite (+)-pseudoephedrine in Glacial acetic acid is 4～5%, and this had both guaranteed high transformation efficiency, had guaranteed that again the recovery operation of Glacial acetic acid has been reduced to minimum workload.In addition, adopt excessive alkali during hydrolysis, fully keep the thoroughness of hydrolysis, help to improve the yield and the purity of product.
With embodiment the present invention is further specified again below.
Embodiment one:
After 1.0 gram (+)-pseudoephedrines and 1.0 milliliters of acetic anhydrides, 20 milliliters of Glacial acetic acid short mix, reflux stirred 2 hours, change water distilling apparatus immediately into and reclaim Glacial acetic acid, add 10 milliliters of mass/volume (grams per milliliter) percentage concentration and be 20% sodium hydroxide hydrolysis after 3 hours, with extracted with diethyl ether and dry extraction liquid, the dry HCl gas of feeding capacity in the extraction liquid, with solid filtering, the drying of separating out, weigh 0.92 the gram, productive rate 76%, specific rotatory power is-12.8 °.The content of (-)-ephedrine sulfate is 78%.
Embodiment two:
After 1.0 gram (+)-pseudoephedrines and 0.574 milliliters, 20 milliliters of Glacial acetic acid short mix of acetic anhydride, reflux stirred 2 hours, change water distilling apparatus immediately into and reclaim Glacial acetic acid, add 20 milliliters of mass/volume (grams per milliliter) percentage concentration and be 20% sodium hydroxide hydrolysis after 3 hours, with extracted with diethyl ether and dry extraction liquid, the dry HCl gas of feeding capacity in the extraction liquid, with solid filtering, the drying of separating out, weigh 1.1 the gram, productive rate 90%, specific rotatory power is-11.3 °.The content of (-)-ephedrine sulfate is 77%.
Embodiment three:
After 1.0 gram (+)-pseudoephedrines and 0.50 milliliter of acetic anhydride, 20 milliliters of Glacial acetic acid short mix, reflux stirred 2 hours, change water distilling apparatus immediately into and reclaim Glacial acetic acid, add 20 milliliters of mass/volume (grams per milliliter) percentage concentration and be 20% sodium hydroxide hydrolysis after 3 hours, with extracted with diethyl ether and dry extraction liquid, feed the dry HCl gas of capacity in the extraction liquid, with solid filtering, the drying separated out, weighing 1.1 restrains, productive rate 90%, specific rotatory power are-11.3 °.The content of (-)-ephedrine sulfate is 77%.
Embodiment four:
After 1.0 gram (+)-pseudoephedrines and 0.574 milliliter of acetic anhydride, 25 milliliters of Glacial acetic acid short mix, reflux stirred 2 hours, change water distilling apparatus immediately into and reclaim Glacial acetic acid, add 20 milliliters of mass/volume (grams per milliliter) percentage concentration and be 20% sodium hydroxide hydrolysis after 3 hours, with extracted with diethyl ether and dry extraction liquid, feed the dry HCl gas of capacity in the extraction liquid, with solid filtering, the drying separated out, weighing 1.1 restrains, productive rate 90%, specific rotatory power are-21.3 °.The content of (-)-ephedrine sulfate is 87%.
Embodiment five:
1.0 gram (+)-pseudoephedrines and 0.574 milliliter of acetic anhydride were reacted 10 minutes down at 70 ℃, room temperature was placed 30 minutes, add 25 milliliters of Glacial acetic acid, reflux stirred 2 hours, change water distilling apparatus immediately into and reclaim Glacial acetic acid, add 20 milliliters of mass/volume (grams per milliliter) percentage concentration and be 20% sodium hydroxide hydrolysis after 3 hours, with extracted with diethyl ether and dry extraction liquid, feed the dry HCl gas of capacity in the extraction liquid, with solid filtering, the drying of separating out, weigh 1.2 the gram, productive rate 95%, specific rotatory power is-23.9 °.The content of (-)-ephedrine sulfate is 90%.
It is simple that the present invention has technical process, the characteristics that the conversion rate is high, and its receipts rate can reach 80～85%.