Ethylphenidate racemic (l-isomer) to d-Ethylphenidate (d-isomer)

[Sunbane]

Not sure if i am posting in the right place but i looked around and thought to start here.

Can the racemic form of Ethylphenidate which i think is the l-isomer to converted into the d-isomer?

Searched and found one old topic with no answers. Thanks if anyone can answer.

EDit:
Should have been in original post. What i am doing and why i am asking question.

I have some Ethylphenidate powder and have been running basic experiments. Experiments like determining its melting point, vaporization point, and solubility (can it be dissolved and max capacity mg/ml) in water and other solvents. I tried one experiment that i did not get my intended results. I wanted to recrystallize the powder which i though should be fun and work. So i supersaturated the regent in a solution using heat (hot plate) so that the solvent would hold more in solution than it did at room temp. I I I also added a crystal seed (small crystal from Crystal EPH) to get crystals forming on the seed as i cooled the solution. What i got was the ethylphenidate formed big clumps of the powder on the seed but no crystallization.

I then began to looking to why.

I came across some sources but not sure if they are correct. They said racemic form will not crystallize it is always a powder the d-isomer is the form that can crystallize and be recrystallized from ground up crystals. This doesn't make sense to me as the information why was over my head but i will go back and try to understand it, obviously the isomers have differences so just not sure what difference causes one to be powder of crystalline.

So that is why i was hoping to synthesize the d-isomer from the l-isomer. It should be interesting and help me understand the differences and relationship that make one crystallize.

I am learning so please be patient if my jargon is wrong or im missing the big picture.

 

[sekio]

They said racemic form will not crystallize it is always a powder the d-isomer is the form that can crystallize and be recrystallized from ground up crystals.

this is wrong. you very likely just need to find the right crystallization conditions (slow cooling)

So that is why i was hoping to synthesize the d-isomer from the l-isomer.

"racemic" ethylphenidate is not the L-isomer. "racemic" ethylphenidate is definitionally a mixture of both D and L isomers. it is possible to seperate the two by crystallization of e.g. optically active tartrates (see also how amphetamine is resolved) but the maximum yield is going to be 50% in any case

and no there is no easy way to turn D into L isomers. besides you can easily tell what isomer you have by measuring specific rotation of a solution with a polarized yellow sodium lamp. (e.g. build a polarimeter... )

 

[Sunbane]

Thanks for helping understand.

this is wrong. you very likely just need to find the right crystallization conditions (slow cooling)

Just to clarify:
So the racemic, L and D can all be crystallized just need to be done right.

i thought was slow cooling i just let it sit in room temp in my basement for a few hours overnight. For reference it was about 120F when i supersaturated it and then my basement ambient temp was 65F. I will have to see if i use a water bath to cool it since water will be even slower i think since the water will hold and release the 120F heat more slowly and the the cooling container inside it will cool more slowly...

"racemic" ethylphenidate is not the L-isomer. "racemic" ethylphenidate is definitionally a mixture of both D and L isomers.

Ok that might have been something i misinterpreted when reading and digesting the info i found or it was just wrong.

So for clarification some quick questions:

Fact: racemic means it is a mixture contain both L-isomer and D-isomer
Q1.) So is Ethlyphenidate racemic when its produce meaning it contains both isomers in some ratio? or is its isomer make up dependent on differing paths of synthesis in turn creating D-isomer, L-isomer, or combination (the racemic)?

it is possible to seperate the two by crystallization of e.g. optically active tartrates (see also how amphetamine is resolved) but the maximum yield is going to be 50% in any case

So if i have racemic then i can separate by crystallization. I know a little about this as there are many methods to crystallization simplest was the one i used but i saw others that while more complicated could separate chemicals by filtering out things as they crystallize at different points at least from what i understood. I will look into this and your referenced topic.

Q2: How do i tell if i have a racemic form? Should i build the polarimeter and see if the result indicate one of the isomers and if not then assume racemic? Do i just try a crystallization on it using the more involved method and see? Either? or any simpler way?

there is no easy way to turn D into L isomers

Q3:Guessing than the reverse L to D is same, complicated?

Thanks again i really appreciate the help in understanding don't worry if you cant answer my questions you have helped enough. Going to get reading.

 

[SKL]

Succinctly put,

the isomer fairy isn't going to wave her magic wand

 

[Sunbane]

i don't even believe in the isomer fairy but id like her wand right now

 

[aced126]

You could turn the isomers into each other possibly...

Here are the isomers.
R,R

R,S

S,S

S,R

So if you have say mixture of the S,R isomer (L-ethylphenidate), you could add a strong base which deprotonates the central/beta carbon. The deprotonated structure is resonance stabilised because of the carbonyl. When reprotonated, the hydrogen can add on to both sides of the plane, thus giving you a mixture of S,R and R,R (d-eph, the most centrally acting I'm guessing).

 

[Sunbane]

edit wrong paste:

well lost my post oh well going to be will write post again tomarrow

 

[sekio]

I think the commercial "racemic" ethylphenidate is a mixture of the D and L-threo forms. (e.g., the S,R and R,S isomers). Only the D-threo form is active as a stimulant in man, I thought. (the L- form is rapidly destroyed by liver)

There exist chiral-specific synthesis of D-threo-methylphenidate but they are more complicated than making the racemic mixture.

Conversion of D- to L- isomer is effectively impossible, so is converting L- to D- isomer.

You cannot seperate D- and L-methylphenidate by "simple" crystallization, you must likely form a freebase and then convert it to an optically active tartaric acid salt with (+) or (-) tartaric acid.

The easiest way to tell if you have racemic or opticalyl active ethylphenidate is build a polarimeter. Otherwise there is no trivial way to tell D- from DL. Do not be decieved into thinking crystal shape/consistency is going to be a reliable variable.

 

[clubcard]

Both threo forms are active, but like speed, 1 isomer is much stronger than the other. AFAIK all 4 isomers were in the mix, they didn't even bother to make it into the threo forms which is achieved by reflux with a catalyst. THAT is how lazy RC chemists are. For the sake of having a safer, stronger product, they forgo US 7164025 or one of the many, earlier versions that use the difference in the solubility of the threo/ethreo thus crashing one out. A reflux will break down unwanted isomer and convert to the threo precursor.... so your product is twice as strong and can be sold for twice as much... THATS HOW LAZY THEY ARE!

 

[Nagelfar]

You could turn the isomers into each other possibly...

Here are the isomers.
R,R

R,S

S,S

S,R

So if you have say mixture of the S,R isomer (L-ethylphenidate), you could add a strong base which deprotonates the central/beta carbon. The deprotonated structure is resonance stabilised because of the carbonyl. When reprotonated, the hydrogen can add on to both sides of the plane, thus giving you a mixture of S,R and R,R (d-eph, the most centrally acting I'm guessing).

So I see the names are as thus: (S,R)-(+)-ethyl 2-phenyl-2-(2-piperidyl)acetate, if they were "(S,R)-(-)-ethyl…" would it be possible, would that be active? I notice that WP has the "dextro-rotatory" as having the wedge on the beginning of the carbmethoxy and that hidden jutting out hydrogen on the solid wedge bond; in MPH, or two stars/asterisks on the EPH I presume denoting the same (enantiopure D-?), to distinguish it, as per:

threo or erythro is just a classification of a set of these, am I right?, but which and how many isomers are *possible* absolutely altogether?

 

[Wowbagger]

there are two chiral centers on the molecule(*), making 4 possible diastereomers. (shown correctly above)

i'm pretty sure the RC eph that has been available was produced using a synthesis that was selective for the threo isomers. so in that case, we're down to 2 isomers that would be found in what we're calling the racemic mixture. is that lazy?, dunno sounds reasonable to me.

 

[dopamimetic]

While it is commonly said that only one of the isomers is actually active, there's something weird about that. D-MPH (Focalin) has a higher NE: DA ratio than racemic MPH, something I thought to feel after taking the very first Focalin capsule (I didn't like it, more jittery/speedy and less effective than rac-MPH for me and some others) and it's been confirmed now in a recent paper. So the l-MPH must have some effect.

Also afaik with ethanol co-ingestion, only l-EPH gets formed ... which should be inactive then (but apparently isn't)...?

 

[Nagelfar]

there are two chiral centers on the molecule(*), making 4 possible diastereomers. (shown correctly above)

Hey, could someone draw the asterisk type 2D of cocaine marking it's chiral centers like the ethylphenidate above and like morphine given here:

That would be a great boon to my WP pet project page. (or my WPPPP ;-p )

 

[white55]

A well known and quality vendor had a test batch of pure d-eph once. It was better, but not at that price premium.

 

[dopamimetic]

A well known and quality vendor had a test batch of pure d-eph once. It was better, but not at that price premium.

Could you explain the differences felt between racemic and d-eph? Just more potent, or different?

 

[white55]

Could you explain the differences felt between racemic and d-eph? Just more potent, or different?

Didn't get to try it myself, but from the descriptions it was slightly stronger and with less peripheral side effects. It also cost almost twice as much so only that test batch was made.

 

[dopamimetic]

This makes me really curious about the effects of d-/l-IPPD. Even the racemic IPPD has an unique quality of pure dopaminergic 'stimulation' that is so smooth that it isn't really stimulating at low doses. Despite that, and the relative lack of comedown (when combined with emoxypine, there is next to none) it hits almost instantly when insufflated. I've read previously that some prefer it over coke, and I have to agree. The best part is the lack of negatives - that removes much of the addictiveness for me personally.

So what could d-threo-IPPD be like...!? If there is a chance for it to have even fewer side effects (cold hands and feet, nausea, accelerated bowel movements mainly, in higher dosages some say it's dehydrating) then it will be well worth the price.

 

[clubcard]

The synthetic route used ends up with 80% trans isomer - so only 40% of it is active. I KNOW it's as simple as add catalyst, reflux to make the whole thing trans but guess what? NOPE - under GC/MS & NMR, 2 compounds are shown, the 20% totally inactive and SO simple to make 50% of the mix active. EP was totally bilked out of being a MUCH better compound as the cis isomers add body-load.

PS Nokia - I replied.

FREEDOM OF SPEECH

 

[white55]

So what could d-threo-IPPD be like...!? If there is a chance for it to have even fewer side effects (cold hands and feet, nausea, accelerated bowel movements mainly, in higher dosages some say it's dehydrating) then it will be well worth the price.

Probably. But ippd is already so light on the side effects that I wonder if it is worth it. I'd rather have mxe isomers separated (supposedly this actually is available). Also heard a vendor saying they were considering separating the isomers of their fluoroamphs.

 

[clubcard]

How can you compare the body load? How many people have tried the (R,R) isomer to compare with the mixture of 4 isomers?