/sci/ - Science & Math

[Anonymous No.6112065]

Is anyone able to name the steps in this reaction. It's for a project i'm doing in uni. Deadline is tonight FUCK.

[Anonymous No.6112068]

I will be following Shulgin's method from TiKHAL #45. Many thanks if somebody responds.. This is for my research proposal.

[Anonymous No.6112080]

>>6112065
>name the steps in this reaction.
The first is just conversion of an acid into an acid chloride, not sure if that really has a special name.
The second (reaction of the acid chloride with an amine) is an "amidation" reaction. You could call the two step process an amidation; you can call any process which turns an acid into an amide an amidation.

[Anonymous No.6112082]

>>6112080
Thank you very much. I really should know this but my brain just wont work right now.

[Anonymous No.6112084]

>>6112065

How do you propose to get just that acid chloride rather than the glyoxyl chloride? Why on earth do you think you can react aqueous dimethylamine with an acid chloride and get away with it? Why doesn't your first step in the second picture make any sense?

This is a research proposal, you seriously think your university is just going to let you make some illegal psychedelic drugs? I guess you're proposing to make the methylated analoge so you can cook some of the real stuff "on the side".

Nobody in their right mind would accept this research proposal.

[Anonymous No.6112089]

>>6112080
re: the first step "formation of the (/an) acyl chloride" would be another way to describe it

regarding this pic (>>6112068): are you really going to treat that acid chloride with strong aqueous base? You'll hydrolyze it back to the acid. I think you meant to put the dimethylamide in that pic.
This presents another problem, if you have two amides, how are you going to get selective basic hydrolysis of one of them? Sure they aren't the same, and the p-chlorobenzoyl amide with the indole N-atom might be easier to cleave but you better have some good literature precedent for that selective hydrolysis. Does the Shulgin prep show this is possible in good yield/selectivity?

[Anonymous No.6112093]

>>6112084
>This is a research proposal, you seriously think your university is just going to let you make some illegal psychedelic drugs?
Dave Nichols group did it all the time, with approval. Who knows where OP goes to school or what group he'd be working with.

>How do you propose to get just that acid chloride rather than the glyoxyl chloride?
He should be using SOCl2, right?
Really he should be using some peptide coulping agent (there are dozens, BOP, EDCI, HATU, etc), the amine (or amine hydrochloride) and the free acid, provided it's not on a huge scale.

[Anonymous No.6112339]

>>6112084
The reaction scheme was shown to me by my supervisor based on shulgins work and I redrew it on chemdraw software. My uni has a home office lisence to do this work. I was allocated the project and have to justify the need for it with a lit. review.
>>6112093
Can you explain your reasoning for your last point? Everything in this reaction scheme is from shulgins work. Basically I am doing this work to validate whether shulgins synthesis actually does work.

Thanks for all your help guys.

[Anonymous No.6112348]

>>6112089
The shulgin prep does not show yields/selectivity. I guess that's the exciting part of this research I get to figure all that out :)

I've done 24 of labs so far. Today I thought I had the 3rd intermediate but it had a peak at 246 after a GC run instead of 300 and something. Will hopefully find out what's went wrong next week.

[Anonymous No.6112471]

>>6112339
>Basically I am doing this work to validate whether shulgins synthesis actually does work.
Then you want to use exactly the reagents and conditions that he used. Much of his work is decades old - which doesn't mean there's anything wrong with it. However in the last 25 years lots of reagents have been developed for the purpose of high yielding amide formation from the free acids - this was driven by the need for efficient, selective formation of polypeptides (especially with a desire for retention of configuration at the alpha carbon of the amino acids).
These reagents work great, and they also work for simple amides like the one you're trying to make. If you used a reagent like the ones I mentioned above, you probably wouldn't even have to protect the indole N-H, so that would shorten the synthesis.

>>6112348
GC/MSD, can be useful but sometimes unexpected fragmentation gives you something other than the parent ion. If these are known compounds, just get a proton NMR spectrum and compare to the literature values.
>inb4 Shugin didn't characterize by NMR

[Anonymous No.6112510]

>>6112471
More, b/c I'm bored and procrastinating, and also not sure exactly what you wanted clarified.
Here's a pic about that acid chloride formation, I meant to suggest SO2Cl2 not SOCl2.
One of the curvy arrows is really small, sorry about that.

[I am derp, sorry OP No.6112608]

>>6112510
Goodness, there are at least two mistakes in the pic:
a) There's clearly one curved arrow missing (breaking of the carbonyl double bond during formation of the tetrahedral intermediate) in the mechanism part.
b) I should have stuck with SOCl2 in the bottom half, that's how you'd get loss of SO2 in the formation of the acid chloride.
http://en.wikipedia.org/wiki/Thionyl_chloride#Organic_chemistry

[Anonymous No.6112840]

>>6112608
Thank you very much for all your help. Submitted my work before I saw your replies. Left my work far too late, have to get my fucking act together. You helped me get some of that shit round my head though mate. Heavy weekend and my brain just wont function.
Wish I could get into chemistry. I'm a third year pharmaceutical chemistry student but have always struggled with the subject. This research project literally is what I have wanted to do for so many years though, so grateful.