Sciencemadness Discussion Board

DIPEA from alanine?

McLovin382 - 7-3-2009 at 02:36

I'm contemplating the N-dialkylation of alanine using IpOH in acidic conditions, followed by thermal decarboxylation and basification of the N,N-diisopropylalanine to yield diisopropylethylamine.

It looks good to me, anyone else see a reason this wouldn't work?

Nicodem - 7-3-2009 at 06:09

What is IpOH? And what kind of thermal decarboxylation is supposed to work on such a substrate?

PS: When opening threads without a single reference and with vague content please do so in the Beginnings section where I'm moving this anyway.

McLovin382 - 7-3-2009 at 06:52

Isopropanol...and okay.

Anyways why wouldn't a standard amino acid decarboxylation work on N,N-diisopropylalanine? It's just essentially refluxing in a high boiling point nonpolar suspension until CO2 is evolved.

[Edited on 7-3-2009 by McLovin382]

Nicodem - 7-3-2009 at 07:32

Please provide a reference for N-alkylation of aminoacids with isopropanol under acidic conditions.
Provide also a reference for the decarboxylation of N,N-dialkyl-alpha-aminoacids.

McLovin382 - 7-3-2009 at 19:37

Alright, well I found some references for the alkylation of amino acids and for their decarboxylation, however neither are speaking directly about alanine and are mostly talking about more substituted amino acids - which I do understand that the decarboxylation of simpler amino acids is tougher to pull off than it is with more complex ones.

http://www.erowid.org/archive/rhodium/chemistry/trp.decarbox... This paper refers to the decarboxylation of alpha-amino acids with heat and a ketone catalyst suspended in a nonpolar high-boiling point solvent (such as diphenylmethane, but surely others can be used). Also, there is the thread here http://www.sciencemadness.org/talk/viewthread.php?tid=11631 which talks about the decarboxylation of an alpha-halopropionic acid (made from alanine) and subsequent nitrosation to yield nitroethane. Thus it appears to me that similar alpha-carboxylic-acid bearing groups can be decarboxylated with not too much trouble.

I wasn't able to find too much info on the N-alkylation of amino acids - only (and unfortunately) just a vague talk from Shulgin about the 'discrete' methylation of tryptophan to yield methyltryptophan, dimethyltryptophan and the trimethyl version (http://www.cognitiveliberty.org/shulgin/adsarchive/dmt.htm). I've read once that trimethyl-compounds can be converted to their dimethyl counterparts by strongly heating them but I have yet to find any proof on that word.

Anyways from what I understand, an amino acid such as alanine can definitely be N-alkylated with an alkyl halide or alkyl sulfate (in this case isopropyl bromide/iodide) but that this will also alkylate the carboxylic acid group, forming an ester. If this is a problem for the subsequent decarboxylation then either the acid group would have to be protected somehow from alkylation, or it would have to be converted first back into an acid then decarboxylated.

Wish I was able to find more reputable references for this, sowwy. And also my bad about being so vague last night...it was like 2 in the morning when I posted my question and I was already half asleep :p

Nicodem - 8-3-2009 at 23:58

In that trp.decarbox.enone.html page I could not find a single example of a N,N-dialkyl-alpha-aminoacid being decarboxylated. Can you please point out what example are you talking about? The SciMad thread you pointed at was pure speculation that beta-nitrocarboxylic acids decarboxylate on heating, which is however erroneous (only alpha-nitrocarboxylic acids do due to obvious reasons).
Your link that is supposed to be about N-alkylation of aminoacids, does not contain anything really related to the topic.
I suggest you to start using libraries with all their literature search possibilities they offer. The more you will use internet to search for scientific information, the more ignorant you will became. Additionally, you might want to read organic chemistry books to understand the basics (it is obvious you are unfamiliar with reaction mechanisms, etc. - knowledge without which one can not understand anything about what is going on during a reaction and thus can not plan any synthesis either).

Globey - 9-3-2009 at 05:38

McLovin,

I'm guessing the bulkier the amino substituent, the more sensitive that moiety to heat (like if you are planning on boiling this with a high bp ketone). There are better ways of achieving this result, but then again, you have to work with what you have. If you need to go this route, some sort of bacterial or yeast final step might be a possible route? Best luck! =)

Nicodem - 10-3-2009 at 03:29

A quick SciFinder search gives no examples of N-disopropylations of alpha-amino acids. Of course, N-diisopropylation of primary amines with isopropyl halides or sulfonates is not feasible since the reaction stops at the mono-isopropyl derivative, but I would have expected at least some reference for diisopropylation using reductive alkylation with acetone (of which several examples are known for primary amines, after all even diisopropylethylamine is made from ethylamine this way). Yet I could only find examples of N-monoisopropylation of aminoacids with acetone (using NaBH3CN, NaBH(OAc)3, NaBH4 or hydrogenation).
Similarly, I could not find any useful examples of decarboxylations of N,N-dialkyl-alpha-amino acids, except for a couple of examples of radical decarboxylations applying multistep routes with AIBN, pyrithione, etc.

McLovin382, I guess you are not asking because you would actually need diisopropylethylamine? This reagent is relatively cheap and available at any chemical supplier, and besides there are much easier ways to prepare it (there is a thread about its preparations). Yet, you might want to know that in most cases you can just use K2CO3 or any other non-nucleophilic weak base instead.

Ebao-lu - 10-3-2009 at 08:11

What is the supposed mechanism for cyclohexenone catalysed decarboxylation? I wonder.. (just to resuscitate the topic)
ps: Nicodem, i'd like to say few words about literature. For amateur chemists it is practically not possible to make a good literature review, because most of the information is not avaliable in the internet.
You have written
Quote:
I suggest you to start using libraries with all their literature search possibilities they offer. The more you will use internet to search for scientific information, the more ignorant you will became.

See, internet is the only place for amateur chemists to find information, most of us here are not having access to libraries, and to online journals. Thats why, you'd better consider all the ideas as _proposals_. When a chemist does not understand the mechanisms and theory, or does not want to understand - that is realy annoying, and a person should learn it. But if it is a question of literature reviews, you should understand that amateurs do not have means to make a good review. Because looking through online patents would also not give an appropriate scientific review. Such journals like tatrahedron/JACS are not avalible online. I understand your irritation, but take it easy, Nicodem;)

Nicodem - 10-3-2009 at 08:52

Quote:
Originally posted by Ebao-lu
What is the supposed mechanism for cyclohexenone catalysed decarboxylation? I wonder.. (just to resuscitate the topic)

The cyclohexenone (or other ketones, though less efficiently) catalyse the decarboxylation by forming the imine/enamine with the alpha-amino acid, thus stabilizing the carboanionic intermediate at the alpha position so that the decarboxylation can proceed (through the same mechanism as malonic acid, nitroacetic acid, beta-keto acids, and similar do). That is why it can not work on N.N-dialkyl-alpha-amino acids.
Quote:
ps: Nicodem, i'd like to say few words about literature. For amateur chemists it is practically not possible to make a good literature review, because most of the information is not avaliable in the internet.

I don't know exactly what you are talking about. As an employee in a lab I have more or less the same access to the scientific literature like any other civilian. For example, from my PC at work I can not access to Tetrahedron, but I can access to it at the library. The only difference between me and an average amateur is in that coincidently the library is physically very near so I don't have to drive there with a car. On the other hand, I do have access to ACS journals from my PC, but I can't use Beilstein on my computer - again I have to go to the library. I do have access to SciFinder from my PC at work, which I guess most amateurs don't (except those that are students living in campuses). But then again many amateurs can use SciFinder at their nearest scientific libraries (which I admit is troublesome since they are mostly located only in cities or near universities). In short, the difference is not in access but in accessibility. I might have the literature relatively more accessible when compared to an average person, but have more or less exactly the same access as you do.

Ebao-lu - 10-3-2009 at 10:54

Ok fine. But are you confident that usual civilian are allowed to enter scientific libraries (since the access there is usually for students and PHD's)? Otherwise, i'm not sure that enough chemical info can be found in usual folks libraries, if they do not belong to chemical institutions.
If searching online among limited number of sources, what's the use of that(except self-education)? There are many patent journals avaliable online, but that can only help if one's question or a proposal is somehow related to patents. And if not, that does not mean anything! Better not to search at all, then to have such kind of search results. That was my IMHO only.
As for Di-isopropylation with isopropanol in acidic conditions, i dont mean it is a good idea of an amateur - it seems unbelievably and unworthy of any literature search (untill McLovin382 provides any related example).



[Edited on 10-3-2009 by Ebao-lu]

Nicodem - 12-3-2009 at 04:00

Quote:
Originally posted by Ebao-lu
Ok fine. But are you confident that usual civilian are allowed to enter scientific libraries (since the access there is usually for students and PHD's)?

My god! If you really live in a country where it is not allowed to use scientific libraries unless you have some kind of a special status, then I suggest you to either became a revolutionary or migrate to some other country. Do such countries even exist? Where I live, there is absolutely no difference in literature access regardless if you are a student or not, the registration fee is minimal (if at all) and they gladly give you access to everything they have, electronic sources included (except for some rare literature that you can not take home, but can use or photocopy there). Even libraries in the research or academic institutions allow you to use what they have if you just ask them (and they do not even ask you to register). The right of the citizen to have access to scientific literature is something that can not be discussed, it is a basic right!

Honestly, I think you are confusing the laziness with accessibility. There is an ever larger proportion of youth that will rather remain ignorant than ever enter any scientific library or academic institution. If something can not be found on the internet, for them it is like nonexistent. You can see more and more of this even on this forum which is supposed to be for amateur chemistry, yet the new (and I suppose younger) members will simply refuse to read any (paper) book about chemistry, but cite a lot of useless claims found on internet. It is like self reproduction of crap - if you cite crap, your citation will be even more of a crap.
This is why I often remind new members to actually take a scientific books in their hands, or even search in the primary literature, and read about the things that they are interested in.

Ebao-lu - 12-3-2009 at 05:04

Quote:
You can see more and more of this even on this forum which is supposed to be for amateur chemistry, yet the new (and I suppose younger) members will simply refuse to read any (paper) book about chemistry, but cite a lot of useless claims found on internet. It is like self reproduction of crap - if you cite crap, your citation will be even more of a crap.
This is why I often remind new members to actually take a scientific books in their hands, or even search in the primary literature, and read about the things that they are interested in.

Thanks for this notice. It realy does make sence.

And the most i loved this phrase
Quote:
It is like self reproduction of crap - if you cite crap, your citation will be even more of a crap..

+100%
Ok, i understood your point and next time will try to find good literature rather then crap(except it is a proposal unworthy of a new thread)

[Edited on 12-3-2009 by Ebao-lu]