Sciencemadness Discussion Board

successfull synthesis of 3-hexyl-5-(indol-3-yl)imidazolidin-2,4-dion

karlos³ - 10-1-2011 at 04:09

I have synthesised this compound, and i wanted to describe how it was done.

3g l-Tryptophan (0,0146mol) and 4g (0,0493mol) potassiumcyanate in water were stirred for a half hour standing in an oil bath to ensure the temperature does not fall under 80°C. After this time, the reaction was quenched with 10ml 6M hydrochloric acid and cooled.
The hydantoic acid precipitated and was filtered, washed with water and refluxed 2 hours in 50ml EtOH and 100ml 3M HCl. The formerly clear solution turned dark blue, probably because some indigolike compound that formed but that is just speculation.
The intermediate precipitated and was collected via filtration. After rekristallisation in boiling iPrOh twice the yield was 1,8g.
But it had more of this Intermediate lying around, so i continued using 2,4g (0,01mol) of it in dimethylsulfoxid, 2g 1-bromhexan(0,012mol) and added 5,5g potassiumcarbonate (0,04mol). This mixture was stirred over night and a bit longer, ca. twelve hours, and then quenched with water to precipitate the final product. this was filtered and recrystallised a few times with iPrOH. It yielded 1,29g of an light grey powder which can be turned into a preferred salt.
My references are:
Exploration of the Pharmacophore of 3-Alkyl-5-Arylimidazolidinediones as New
CB1 Cannabinoid Receptor Ligands and Potential Antagonists: Synthesis,
Lipophilicity, Affinity, and Molecular Modeling
and
Comparative HPLC enantioseparation of new chiral
hydantoin derivatives on three different polysaccharide type
chiral stationary phases
which were both published in 2002

Nicodem - 10-1-2011 at 10:56

And what are the analyses you performed?
Please provide references or DOI instead of useless titles for those two papers.

turd - 10-1-2011 at 11:10

That's interesting, but could you also please provide trivial names or pictures for the IUPAC challenged idiots like me?
Are you sure it is an indol-3-yl which is attached to the imidazole and not a (indol-3-yl-methyl) or something? I.e. aren't you missing a -CH2- group from tryptophan?

Thanks.

PS: People please, "X-ray structure" is bullshit. Do not use this abomination of a word. :(

[Edited on 10-1-2011 by turd]

Nicodem - 10-1-2011 at 11:22

The product name should be 5-((1H-indol-3-yl)methyl)-3-hexylimidazolidine-2,4-dione (3-hexyl-5-(indol-3-ylmethyl)hydantoin), as he alkylates the hydantoin derived from tryptophan which is 5-((1H-indol-3-yl)methyl)imidazolidine-2,4-dione (5-(indol-3-ylmethyl)hydantoin).

The corresponding SMILES are:
O=C1C(NC(=O)N1CCCCCC)Cc3cnc2ccccc23
O=C3NC(=O)C(Cc1cnc2ccccc12)N3
Quote: Originally posted by karlos³  
It yielded 1,29g of an light grey powder which can be turned into a preferred salt.

This is confusing. Are you saying you can make, for example, a sodium salt of the product and isolate it? Why? The pKa2 of hydantoins is from 9 to 10, so what rationale would it be of making it a salt if this would be unstable to CO2 or hydrolysis.

[Edited on 10/1/2011 by Nicodem]

karlos³ - 10-1-2011 at 11:40

Thank you for replying!
i have only because of lack of the proper equipment tested the melting point, which was between 130-140°C, depending on the sample that i used, and tested the solubility of the compound, as it is rather difficult to identify a compound without a liquid chromatography tube in your living room.
Which references else should i post? This two papers are the only ones i used, as i dont know what else you could mean, I will give direct links i hope thats what you meant.
http://www.farm.ucl.ac.be/Full-texts-FARM/Ooms-2002-1.pdf
this paper is uncorrect in the molecule drawings as the indolring is of course not 2-substituted. There is also a one-page document as a correction for this existing.
www.farm.ucl.ac.be/Full-texts-FARM/Kartozia-2002-1.pdf
This is the another document. The molecule drawings of the indole based compounds is also wrong in this document.

Hmm i dont think it has a trivial name yet, but i have a molecule drawing, the problem is that i have to convert it into some format that is windows suitable, because i am using an unix system. i will add this in a few minutes.
So, i have attached it, this is correct, as tryptophan and also the title compound of course are 3-substituted not 2-.

[Edited on 10-1-2011 by karlos³]

Attachment: hydantoin.svg (10kB)
This file has been downloaded 837 times

turd - 10-1-2011 at 11:43

Quote: Originally posted by karlos³  
Hmm i dont think it has a trivial name yet, but i have a molecule drawing, the problem is that i have to convert it into some format that is windows suitable, because i am using an unix system. i will add this in a few minutes.

No worries... I was just confused about the missing -CH2- group. The original paper seems to be quite confused on the matter too. :o

karlos³ - 10-1-2011 at 12:07

hehe yes, seemed like someone in the second one just draw the molecules with the errors they made in the first document :D. So i will also add the correction they have made, just to have it the way it should be. Didn´t found it online where it is accessible for everyone so it is attached below.
Oh i forgot to say, a fearless and/or stupid person known to me had made a bioassay using 50mg and stated that it have to be this substance, but i dont see this as a serious analysis, but think it could be useful to know.

Attachment: Exploration_of_the_Pharmacophore_of_3-Alkyl-5-arylimidazolidinediones.pdf (12kB)
This file has been downloaded 460 times

[Edited on 10-1-2011 by karlos³]

Nicodem - 10-1-2011 at 13:13

Quote: Originally posted by karlos³  
Thank you for replying!
i have only because of lack of the proper equipment tested the melting point, which was between 130-140°C, depending on the sample that i used, and tested the solubility of the compound, as it is rather difficult to identify a compound without a liquid chromatography tube in your living room.

The melting point is well enough for products of syntheses which were followed from published experimental (often it is enough also for products made by new methods). But it is proper to always present some evidence of identity and purity after stating the mass and yield of the reaction product or else the value for mass and yield has no meaning. If you follow a literature procedure by the letter then you can almost safely assume your product is what is supposed to be, if at least chemically and physically behaves as it should. But since you did not provide the reference we could not know how reliable the synthetic method used is. An experimental without analyses is futile. If no analyses were done (due to lack of equipment, or due to laziness, etc.) one needs to state this so that others can realize the identity and purity are only speculative.
Quote:
Which references else should i post? This two papers are the only ones i used, as i dont know what else you could mean, I will give direct links i hope thats what you meant.

I can't believe I'm actually explaining this, but providing a reference means giving at least the minimum needed for easily locating the article either from the publisher or library. In your case the minimum reference would be:

J. Pharm. Biomed. Anal. 27 (2002) 457–465.
J. Med. Chem., 45 (2002) 1748-1756.

Or by using DOI it would be:

DOI:10.1016/S0731-7085(01)00649-5
DOI:10.1021/jm010896y

Both citation systems have their ups and downs. Literature citing is more human and library friendly, but requires more clicking to find the article. DOI is less human friendly, it requires internet access, but is only a copy-paste away from locating the article.

karlos³ - 11-1-2011 at 01:05

Sorry I have tried to make my references userfriendly as possible so a quick google search will give the correct papers as first hit. In future, i will keep it in the suggested formate.
Nicodem, the use in turning it into an salt is obvioisly to make it water soluble, this is for medical purposes, and i didnt done it.

[Edited on 11-1-2011 by karlos³]