[Rookie_OC_Lover]

Hi everybody.

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Short version of my question :

Is it possible for reaction 2 to yield well just like reaction 1 does ? (same conditions)
skip the rest of my question if you like.
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Background info :

today I noticed a real price difference between two products available at chemical-suppliers around here.
almost all chemicals in my country are bought from suppliers in INDIA or China.

first product is a plant growth hormone : IAA (that's Indole-3-Acetic-Acid)
the second one is another auxin : IPA (Indole-3-Propanoic-Acid)

a little search lead to a relatively easy synthesis for the first one, IAA (shown in picture as Reaction 1).
which based on my calculation is fair to be around 25$/5gr.

But the second one (which i couldn't find any synthesis method for) is around 90$/5gr.
that made me think of whether it's possible to use reaction 2 to prepare IPA or not ?
what is your opinion about reaction 2 ?
what do you think is the reason of price differences ?

TnX

[discodermolide]

I do not think the second reaction will work as described by you.
The first reaction probably proceeds via an alpha-lactone

which is then opened by the indole.

If the same mechanism applies to the second reaction you would need to have a beta-lactone

as a reaction intermediate.
As the ring strain is different in the two intermediates as is the point of attack by the nucleophile I don't think the process you propose would work and give the compound you propose.

[Rookie_OC_Lover]

I do not think the second reaction will work as described by you.
The first reaction probably proceeds via an alpha-lactone

which is then opened by the indole.

If the same mechanism applies to the second reaction you would need to have a beta-lactone

as a reaction intermediate.
As the ring strain is different in the two intermediates as is the point of attack by the nucleophile I don't think the process you propose would work and give the compound you propose.

Organic Synthesis Vol 5 says its done this way :

[discodermolide]

Yes that's OK for the first reaction, but not the second the one you proposed.

[Rookie_OC_Lover]

Yes that's OK for the first reaction, but not the second the one you proposed.

Why ?
what's the difference between Glycolic Acid and 3-Hydroxypropionic acid ?
just need some help to at least understand the reason, so that i consider it for similar situations.

[discodermolide]

In tried to explain in my first reply.

[Rookie_OC_Lover]

In tried to explain in my first reply.

why don't you answer clearly?

are you saying lactones are made only in the second reaction ?

TnX

[discodermolide]

There is no need to be rude.
I was clear enough. The first reaction goes via a alpha lactone.
I said the second reaction which is a proposal by you will not work the same way as the literature example. I suggested that if it did then it may well proceed via a beta-lactone, but would probably produce different products.

[camptzak]

Hello, please forgive my question as it seems that everyone else understands, and the literature shows that the reaction proceeds.

I do not understand how the glycolic acid forms a lactone in the presence of K⁺ OH^-
It seems that the base would form a carboxylate and nothing more.

Also, if the indole ring were to react with an alpha-lactone it seems to me that it would do so via nuceophilic addition to the carbonyl group, creating a ketone with an alkoxide tail.

I did make a drawing in which the carboxylic acid is created, but the only way I could make it work was with an Sn₂ reaction, which seemed strange looking.

I attached drawings to help with my description

[orgopete]

A couple of things, first, I'm not convinced this is an alpha lactone reaction, though I don't know the mechanism. I'm guessing a clue may be found in the second reaction. I'm guessing dehydration to the acrylate. This is an interesting question though.

Finally, I'm leary of the poster's prior question seemingly wondering about reagents to make amphetamines that won't be tracked by the authorities. I'd like to be convinced a serotonin analog is not being devised.

[Rookie_OC_Lover]

Finally, I'm leary of the poster's prior question seemingly wondering about reagents to make amphetamines that won't be tracked by the authorities. I'd like to be convinced a serotonin analog is not being devised.

I don't know how much do you know about the level of organic chemistry development here in my country , Iran.
Iran is a country rich in black-oil, and many other mines and natural sources; BUT not developed enough to take advantages of them.
Iran imports 90%+ of it's lab chemicals (even those used for school labs, universities, drug-making factories, .etc)
from other countries.
Price of pharmaceuticals are something between 2 to 3 fold compared to many other countries.
for someone like me, a simple chemical would cost around twice the price you pay for the same chemical.

So consider the reason I started this topic, and stop suspecting based on nothing.
would you tell me when I was going to make amphetamine ?
my last topic was closed because I mentioned Diethylamine.
in that topic my intention was any small secondary amines, not specifically Et2NH, and it was found to be used in illegal drugs synthesis and my topic got closed because of my inability to explain my reasons.

Ok, but now I'm explaining clearly.
I can assure you the only reason I want to do this procedure is to hopefully suggest a cheaper way to IPA synthesis.

any other questions about this, I'll answer.
thanks for understanding.

[orgopete]

@Rookie

If you know ochem, then you might know people do try to devise chemical syntheses that will not be tracked by the authorities. It was suggested you use LAH to reduce an acetamide to a dialkylamine, which if the acetic acid were phenylacetic acid, would give an amphetamine type of product. Look at your answer.

Why can't you use LAH etc.?

can't buy or order it.
don't wanna get into legality matters. as I'm not doing this as a organization .etc.

We don't know you. We don't your motivations. Concealing them doesn't help. If LAH isn't available in Iran, say so.

If your objective is to prepare indolepropionic acid, just tell us. This naturally leads to other reasonable questions, such as how has it been prepared. A factor in a high cost can be multiple, but lack of demand is often a contributing factor. I am not a process chemist, but I'm sure those with more knowledge could answer this more fully.

I have discovered from my experience the simple questions about preparing something from air, fire, and water are ultimately fundamental to costs. For example, m-nitroanisole is more expensive than p-nitro simply because little nitration occurs meta. I can think of many ways to prepare this product. What I don't know is how successful any one of them might be. However, just from the information provided, the suggested route probably would not be my first choice. None the less, none of my speculation should take away from the mechanistic question of how is indole acetic acid prepared.

[curiouscat]

I don't know how much do you know about the level of organic chemistry development here in my country , Iran.
Iran is a country rich in black-oil, and many other mines and natural sources; BUT not developed enough to take advantages of them.
Iran imports 90%+ of it's lab chemicals (even those used for school labs, universities, drug-making factories, .etc)
from other countries.

Is that a good reason to be rude to people trying to help you? For free too!

So consider the reason I started this topic, and stop suspecting based on nothing.
would you tell me when I was going to make amphetamine ?
my last topic was closed because I mentioned Diethylamine.

And I hope the mods close this one too. You are being rude, unhelpful and demanding.

[Rookie_OC_Lover]

please, I didn't want to be rude or seem rude.
sorry if my talking style or something else means rude.
I've learned English from movies & reading, all by myself.
sorry if anything was not clear enough, and if it was my fault.

by saying "legality matters" I did NOT mean DEA of America or other similar stuff.
Here, since all reagents are imported, Sanction becomes an important factor.
in fact it's possible to buy LAH in Iran, but only in 1 way :
  first you should be an approved pharmaceutical or industrial organization.
  you should fill forms to order it from mediators. (nothing can be done directly or online)
  worst part: you should wait at least around 3 weeks for them to do the importation part for you.
  much worse : if your ordered product is from countries that are sanctioning Iran, your chances drop
  to around absolute zero !

it seems you thought I'm worried about legality of my actions.
all one should be concerned about in Iran is the Import/Export stuff, which is hard as hell to pass.
and I'm not violating any country's rules. (as far as i know).


BTW, what happened to the flow ?

can anyone summary it up ?
1. is it a lactone intermediate forming reaction ?
2. if yes , this means chances of the second reaction working is nothing ?
3. is there other ways to syn it ?

thanks again.

[billnotgatez]

@Rookie_OC_Lover

As a MOD here I want to say we are VERY sensitive to providing cookbook drug discussion.
The CHEMISTs here (that are helping you) know this and try to help the MODs and ADMINs police people trying to violate our rules.
What you are doing is coming close to crossing the line between theoretical discussion and cookbook discussion.
We may lock this thread if we get too uncomfortable.
Please talk theoretically and generally about mechanisms and less about specific synthesis.
So as not to distract from the discussion -- please contact me directly using the messaging provided by this forum and I will help you understand the situation -- if you have any questions about what I am saying.

Another point -- underneath each persons name when they reply to you they have a title.
Mine is Global Moderator - yours is Regular Member - others are Chemist
Think about your response when when dealing with fellow members

Again contact me off thread if you have any questions

Regards
Bill