MAKING EPHEDRINE BY SIMPLEST METHORD
20GM OF N-methyl-d,L-alanine
50GM OF benzaldehyde
ADD IT IN A ROUND BOTTOM FLASK PUT IT IN A OIL BATH AT 150-160 DEGREE C.
(NOTE: PUT THE FLASK IN OIL AT ABOUT 60 DEG. ) AND GRADUALLY INCREASE THE TEMPERATURE ABOUT IN THE TIME PERIOUD OF 30-40 MIN AND MAINTAIN IT WITHIN +- 10 DEG.
CO2 WILL FIZZLE OUT FOR SOME TIME AMD AFTER IT STOPS TAKE IT OUT OF OIL AND THEN COOL THE MIXTURE
AND MIX THROUGHLY WITH ABOUT 250ML OF TOULINE (AS PURE AS YOU CAN GET) SOMETIMES THE MIXTURE DOSENT COMPLETLY MIX WITH THE TOULINE SO THE LEFTOVER UNMIXED MIXTURE IS REMOVED.
SO NOW YOU HAVE GOT A MIXTURE OF EPHIDERINE AND PSEUDOEPHIDERINE.
EXTRACTION OF EPHIDERINE AND PSEUDOEPHIDERINE
- THE MIXTURE STILL CONTAIN UNUSED BENZALDEHYDE AND TOULENE TO REMOVE TOULENE ADD EQUAL AMOUNT OF 10% HCL COMMOUNLY FOUND IN HARPIC NOW TOULENE CAN BE DISTILLED AT 111 DEG. USING A EXTENSVE DISTILATION APPRATUS
- NOW YOU HAVETHE SOLUTION CONTANING HCL MIXTURE SO NOW TO CONCENTRATE THE MIXTURE BOIL IT UNTIL IT IS REDUCED TO 70-75ML (I WOULD SUGGEST THAT YOU SHOULD BE AWARE OF THE FUMES OTHERWISE YOUR LUNGS WILL BURN)
- ALLOW IT YO COOL THEN ALL ACTIVATING CHARCOAL (JUST A LITTLE BIT) AND STIR FOR A WILE THEN FILTER OUT THE SOLUTION NOW THE MIXTURE WILL HAVE CLEAR YOLLOWISH OR BROWNISH.
(USE NITRILE GLOVES IN THIS PROCESS)
- SO THE SOLUTION WAS AN ACIDIC ONE NOW WE HAVE TO NUTRILISE THE MIXTURE.
- NOW TAKE SOME SODIUM HYDROXIDE PALLETS AND ADD SLOWLY TO WATER UNTIL THE SOL BECOMES HIGHLY BASIC (TO CHECK USE PH PAPER) ADD IT TO THE SOLUTION.
- EXTRACT THE BASIC SOLUTION FOR ABOUT FEW TIMES THE SOULTION
- NEXT STEP IS TO ADD THE HCL (GAS) TO THE MIXTURE TO GIVE THE CRYSTALS OF EPHIDERINE AND PSEUDOEPHEDERINE
YIELDS
d.l-pseudoephedrine = 8gmd,l-ephiderine =4gm
RECOVERING EPHIDERINE
THE RECOVERY OF EPHIDERINE FROM WATE SOLUTION IS BIT DIFICULT .
SO WE HAVE TO ADD DILUTE ACID SOLUTION TO THE EPHIDERINE AND BOIL IT DOWN ONCE IT IS CONCENTRATED, THEN IT IS MADE BASIC USING SODIUM HYDROXIDE.
BY DOING SO THE GOOD RECOVERY OF EPHEDINE IS POSSIBLE.
(NOTE:- BY ADDING TOO MUCH WATER IN THE SOLUTION THE EXTRATION OF EPHEDRINE IS MADE MORE HARDER AND NEAR TO IMPOSSIBLE.)
PROBLEMS:- THIS THE EASIEST METHORD COMPARED TO OTHER METHORDS LIKE THE FERMENTATION OF BENZELDEHYDE TO i-PAC THEN REDUCTION TO l-EPHEDRINE.
1) BUT THIS PROCIDUE MAKES THE TAR (TERRIBLE GUNK AND HARD TO REMOVE )
2) REDUCED YIELD OF PRODUCT
THE STARTING MATERIAL N-methly alanine IS NOT AVIABLE IN MOST OF THE CHEMICAL FACTORIES OR NOT AT A RESONABLE PRICE TO CONTINUE TO REACTION.
NOW LET US SEE THE SOLUTIONS OF THE PROBLEMS:-
THE TAR PRODUCED CAN BE ELIMINATED BY USING THE DMSO (DIMETHYL SULFOXIDE) AS A SOLVENT INTHE SOLUTION.DMSO ALLOWED THE THEMPURATURE TO BE LOWERED TO 120-130 DEG C. (NOW THE QUESTION IS HOW TO GET YOUR HANDS ON DMSO :- THE SIMPLE ANSWERS IS TO GO TO A VET SHOP AS DMSO IS USED AS A PAIN KILLER FOR ANIMALS MOSTLY HORSES AND COWS JUST BUY THEM AND YOU HAVE IT JUST AVOID CREAMS AND STICKS ONLY PURE LIQUID DMSO SOLVENT)
BY USING DMSO YOU GET A HIGH YIELDS OF METHYLCNEDIOXY DERIVATIVE OF EPHEDRINE AND PSEUDOEPHEDRINE
[IF WE USE PIPERONAL IN THE REACTION INSTEAD OF BENZALDEHYDE (IF YOU WISH TO ABUSE IT LEADS TO MAKING OF MDMA. YOU CAN REACT PIPERONAL WITH N-methylalanine, THEN REDUCE THE PRODUCT SUBSTITUTED EPHEDRINE WITH LITHIUM {GET IT FROM A OLD/NEW RECHARGABLE TORCH CELL OR AN OLD BATTERY} IN ANHYDROUS AMMONIA BE SURE IT IS ANHYDROUS AMMONIA BECAUSE LITHIUM IS EXTREMLY REACTIVE WITH WATER YOU CAN ALSO USE THE REDUCTION METHODS BY HI BECAUSE IT MAKING CLEAVES ETHERS ON A BENZENE RING)]
NOW AS WE KNOW N-methylalanine IS HARD TO FIND AND EXPENSIVE(NORMAL CHEMICAL SHOPS OR OTHER SOURCES MOSTLY GIVE 1,2-diphenylethanolamine. N,N-dimethylalanine BUT IT WILL NOT GIVE ANY REACTION)
NOW WE WILL DO WHAT IS CHEMIST DOES MAKE YOUR OWN
SO THIS SYNTHESIS WAS PUBLISHED IN 2007 IN VOLUME 48, OF TETRAHEDRON LETTERS. IN THEORY IT IS A HIGH YIELDING PROCESS AND IN PRACTICAL 80-90% YIELD IS GIVEN.
(IN THIS REACTION WE WILL USE FORMALDEHYDE AND ZINC POWDER FINE ONE TO DO THE METHYLATION IN WATER SOLVENT CONTAINING PARTLY NEUTRALIZED PHOSPHORIC ACID.)
- FORMALDEHYDE IS VERY CHEAP AND WIDLY ACCESIBLE AND OTHER CHEMICALS CAN BE PURCHASED FROM A MEDIUM SIZED CHEMICAL SHOP OR JUST ORDER ONLINE
MAKING N-methylalanine USING ZINC AND FORMALDEHYDE
- DO IT IN VERY SMALL PORTIONS BECAUSE ZINC IS QUITE HEAVY AND MAGNETIC STRRER CAN’T TAKE THAT LOAD SO I WILL TAKE THE PORTIONS OF 10GM
- TAKE A CONTAINER AND ADD 200 ML OF WATER AND ADD 16 ML OF PHOSPHORIC ACID (GET YOUR HANDS ON IT BY A NOWMAL CHEMICAL SHOP OR JUST A DAIRY CHEMICAL SHOP)
- ADD 9.5GM OF NaOH TO MAKE A MONOBASIC SODIUM PHOSPHATE
stir constantly and make a average buffer solution by adding 40gm of trisodium phosphate (TSP) to 200ml of water and add 30ml HCL
- NOW ADD 10GM OF ALANINE DISSOLVE IT THE TEMPERATURE OF THE SOLUTION WILL BE ABOUT 30-35 C DUE TO THE NEUTRALIZATION OF PHOSPHORIC ACID BY NaOH
- ADD 10ML OF 37% FORMALDEHYDE, THEN ADD 15GM OF ZINC POWDER AND STIR IT FOR 40-50 MIN (IF YOU WONDER THAT WHY WE GIVE IT SO LONG TIME, YOU SHOULD KNOW THAT FORMALDEHYDE IS VERY TOXIC AND UNTIL YOU HAVE MASTERED BASIC OF CHEMISTRY IN CLASS 11 YOU SHOULD USE LESS FORMALDEHYDE AND GIVE MORE TIME TO REACT)
- IF YOU HEAR A CONSTANT FIZZING SOUND IT IS ZINC POWDER REACTING AND RELEASING H2 GAS AND ZINC COLOUR CHANGES FROM GREY TO BLUE THIS IS ZINC PHOSPHATE.
- LET THE ZINC SETTLE AND FILTER OUT ALMOST CLEAR WATER WHITE LIQUID I WOULD RECOMEND USING LABORATORY GRADE FILTER PAPER OR A DOUBBLE FILTER PAPER. (NOW ADD SOME ABOUT 50ML OF WATER TO THE SETTLED ZINCMIX IT AND RE FILTER IT)
- ADD BICARB POWDER UNTIL THE PH ID DECREASED TO ABOUT 7 BE SURE TO USE A GOOD QUALITY LITMUS PAPER. I WOULD SAY TO ADD PH 7 BUFFER TO SOL OR JUST USE TAP WATER.
- NOW PH IS ADJUSTED TO THE PH OF 7 AND LET THE WATER CLEAR SOLUTION TO THE FRIDGE 12-15 HOURS SOMETIMES MORE THAN THAT. WHEN THE CRYSTAL MASS STOPS GROWING FILTER IT OFF (I WOULD SUGGEST USING VACCUM FILTER YOU CAN PURCHAS ONE FROM AMAZON FOR ABOUT 7500 RUPEES) OR YOU CAN SIMPLY USE GRAVITAIONAL FILTERATION JUST HANG THE CRYSTALS FOR 24-30 HOURS BUT RINSE IT OFF WITH ALCOHOL TO PREVENT TO BE A FOOD OF BACTERIA BUT USE LESS THEN 60 ML OF ALCOHOL.
NOW IF YOU KNOW THAT THERE IS STILL N-methylalanine IN THE SOLUTION SO WE WILL NOW DO RECRYSTALISTAION. BOIL THE SOLUTION UNTIL IT IS REDUCED TO ABOUT 50% ( NOTE:- IN PREVIOUS STEPS I TOLD YOU TO USE LESS FORMALDEHYDE BECAUSE IN THIS STEP YOU WILL GET SOME SMALL AMOUNT OF FORMALDEHYDE IN FORM OF STREAM AND IT CAN EVEN GET INTO YOUR CRYSTALS AND MAKE IT TOXIC) THEN THE REDUCED YELLOWISH LIQUID IS RINSED WITH THE PREVIOUSLY USED ALCOHOL IN THE FIRST CRYSTALIZATION, NOW PUT THE LIQ IN THE FRIDGE FOR 3-4 HOURS AND I WOULD SUGGEST TO ADD A SEED CRYSTAL OF N- methylalanine FROM PREVIOUS CRYSTALIZATION TO MAKE IT FASTER THE AGAIN PUT THE SOLUTION IN THE FRIDGE AND LET THE CRYSTALS GROW FILTER THE NIDDLE LIKE CRYSTALS BY PREVIOUSLY TOLD METHORD.
- THE TOTAL YIELD OF N- methylalanine WAS ABOUT 10GM.
REACTION OF N- methylalanine WITH Benzaldehyde TO GIVE EPHEDRINE
(IN PRESENCE OF DMSO SOLVENT)
- THE HIGH YIELDING AND LESS PROBLEMATIC PROCESS IS TO:-
- REACT 1 MOLE OF BENZALDEHYDE WITH 2 MOLE OF N- methylalanine WITH DMSO SOLVENT.
- WE REACT 30ML OF BENZALDEHYDE AND 60GM OF N-methylalanine (IN PREVIOUS STEPS WE MAKE 10 GM OF N-methylalanine, WE KNOW THIS SYNTHESIS TAKES A LOT OF TIME SO YOU SHOULD MAKE 6 BATCHES SIMULTANIOUSLY TO SAVE TIME).
- THIS REACTION WILL GIVE YOU A PRETTY GOOD YIELD OF 27.5-30GM OF A MIXTURE OF EPHIDERINE AND PSEUDOEPHEDRINE (POINT TO BE NOTED THAT THESE BOTH ARE ISOMERS AND WORKS IN VERY SIMILAR WAYS ITS JUST EPHEDRINE IS MORE POTENT THAN PSEUDOEPHEDRINE, IF YOU WANT PURE EPHIDERINE I HAVE ANOTHER METHORD FOR LARGE SCALE PRODUCTION BUT FOR THAT YOU SHOULD HAVE A FINE KNOWLEDGE ABOUT BREWING WINE OR WISKY. AND A SURPLUS OF MONEY AND TIME AS UNTIL YOU HAVE MASTERED IT YOU WILL MAKE A MESS EVERY TIME.)
YIELDS:- 27GM OF EPHEDRINE AND PSEUDOEPHEDRINE HYDROCHLORIDE MIXTURE
- NOW PUT THE 250ML OF DMSO IN A ROUND BOTTOM FLASK WITH A CONDENSER ON (REFLUX CONDENSER). ADD A MAGNETIC STIR BAR AND 60GM OF N-methylalanine
- TAKE 30ML OF BENZALDEHYDE AND POUR 10ML OF IT IN DMSO FLASK (POURING IT IN SMALL AMOUNT AT A TIME MAKES THE REACTION MORE EASIER TO PROCEED)
- HEAT THE MIXTURE TO ABOUT ~ 100-110 DEG. C (OR SIMPLY RAISE THE TEMPURATE TILL IT STARTS TO BUBBLE AS FIZZING OF PEPSI) AFTER FIZZING STARTS LOWER THE TEMPERATURE AND LET IT FIZZLE FOR ~ 1 HOUR 30 MIN.
- NEW ADD ANOTHER 10 ML OF 30 ML BENZALDEHYDE AGAIN LET IT FIZZLE OUT FOR AN HOUR AND THIRTY MINUTES. AFTER THAT ADD AGAIN LAST 10 ML OF 30 ML OF BENZALDEHYDE AFTER THAT LET IT FIZZLE FOR QUITE SOME TIME (THE TEMPERATURE IN THIS STEP SHULD BE THE LOWEST SETTING ON YOUR HEAT PLATE) THEN RAISE THE TEMPERATURE SLOWLY TILL IT REACHES ~110-120 DEG. C
(POINT: THE TEMPERATURE SHOULD NOT CROSS 130 DEG. C)
FROM THIS STEP WE WILL WORK IN MY WAY
- GO TO YOUR NEAREST GENERAL STORE AND PURCHASE WHITE VINEGAR, USE THE SYNTHETIC AND DISTILLED ONE {DO NOT USE APPLE CYDER OR RICE VINEGAR}
- (WE USE VINEGAR BECAUSE OF IT SPROPERTIES TO BREAK THE DIMER CHAIN) FOR ABOVE USED PORTIONS WE WILL REQUIRE ABOUT 600ML OF VINEGAR. ADD IT AND THEN ADD ~ 80 ML OF TOULENE IN IT (TOULENE IS REQUIRED TO STOP FORMING NASTY BI-PRODUCTS)
- AFTER ADDING THEM YOU WILL SEE A LAYER OF TOULENE ABOVE DMSO AND MIXTURE. NOW HEAT THE MIXTURE (DO REFLUX BOILING) FOR 4-6 HOURS (IT IS LONG BECAUSE WE WANT TI BREAK THE DIMERS) [REMEMBER THE BOILING TEMPERATURE SHOULD TO RAISED SLOWLY IN A RANGE OF 3-5 HOURS].
- NOW LET THE MIXTURE COOL. BY DOING SO YOU HAVE SUCCESSFULLY BROKEN UP HE DIMERS AND THIS WILL INCREASE THE YIELD. NOW ADD ~ 40-45ML OF HCL (37% HYDROCHLORIC ACID) COMMONLY SOLD IN CHEMICAL SHOPS AS MUTARIC ACID [BY DOING SO YOU ENSURE THAT EPHEDRINE REMAINS AWAY FROM TOULENE LAYER]
- IN THIS STEP PUT THE MIXTURE INTO THE SEP FUNNEL (SEPERATION FUNNEL) AND SHAKE IT. NOW WAIT TILL IT AGAIN SEPERATES IN FORM OF LAYERS (THE TOP LAYER WILL BE TOULENE CONTAINING ALL THE UNREACTED BENZALEDHYDE AND OTHER BI-PRODUCTS) --------- (THE OTHER LAYER WHICH HAS ALL THE PRODUCT WE NEED DISSOLVED IN WATER)
- GET ALL THE WATER AND DMSO AND PRODUCT LAYER AND MAKE IT BASIC USING SODIUM HYDROXIDE UNTIL THE PH LEVEL CROSSES 13 (ADD EXTREMLY SMALL AMOUNT OF NaOH AT A TIME)
- TO GET ALL THE PRODUCTS FROM THE SOLUTION USE ~100 ML OF TOULENE EXTRACT AGAIN AND ADD 50ML OF TOULENE.
- NOW WASH THE MIXTURE WITH WATER AS TOULENE IS INSOLUBLE AND DMSO IS SOLUBLE (BY DOING SO YOU WILL REMOVE DMSO FROM THE MIXTURE).
LET THE WATER DRIP FROM SEP. THEN TRANSFER THE TOULENE MIXTURE TO A DRY BEAKER AND PASS DRY HCL GAS IN THE SOLUTION.
BY DOING SO YOU WILL GET ABOUT 30 GM OF PURE PSEUDOEPHEDRINE AND EPHEDERINE MIXTURE.
