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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: cheimist on August 01, 2008, 08:38:54 PM

Title: Need help with a synthesis
Post by: cheimist on August 01, 2008, 08:38:54 PM

I have been trying to convert an aldehyde to an alkyne for months.  I've been using dimethyl-2-oxopropyl phosphonate, p-toluene-sulfonyl-azide, K2CO3, and my aldehyde in MeCN.  I added the aldehyde after ~2 hours of letting the other stuff react.  I mocked the synthesis proposed by Roth et. al. (Synthesis, 2004, 59-62), with the only variation being my aldehyde... I have an aldehyde attached to a 1,2,3-triazole, which is attached to a sugar. 

At first I thought the potassium carbonate was cleaving Acetal protecting groups i have on my sugar, but NMR showed acetal signals.  Mass spec gave me a mass of 44 m/z higher than what my compound should be.  NMR showed the addition of 3 signals and loss of my aldehyde signal, so something is happening at the carbonyl carbon, but it is not making an alkyne. 

I am looking for suggestions as to maybe what is going on here, and any alternative routes one would suggest.

Thanks

Title: Re: Need help with a synthesis
Post by: Mitch on August 02, 2008, 04:00:34 AM

Try doing a Wittig on the aldehyde and then brominating with Br2 and then follow that with a double elimination to get the alkyne.

Title: Re: Need help with a synthesis
Post by: Transmutation on August 04, 2008, 01:39:34 PM

http://en.wikipedia.org/wiki/Corey-Fuchs_reaction

 ;D

Title: Re: Need help with a synthesis
Post by: Mitch on August 04, 2008, 03:00:55 PM

The Corey-Fuchs reaction is basically what I suggested to do. ;)

Title: Re: Need help with a synthesis
Post by: kiwi on August 05, 2008, 07:05:04 AM

Sounds to me like your issue is the in-situ preparation of your homologation reagent. If the azo formation fails then you are left with an electron-deficient phosphonate, which will react in a normal Horner-Wadsworth-Emmons reaction with your aldehyde, giving instead of the alkyne an alpha,beta-unsaturated methyl ketone. Which incidently, by my back of napkin sketch here, is 44 mass units heavier than the expected alkyne.
In short - preform your homologation reagent. I'm without literature access right now, but I am 99% sure both the Seyferth-Gilbert and Bestmann reagents were originally used with the azo portion preformed.

Title: Re: Need help with a synthesis
Post by: cheimist on August 21, 2008, 12:30:09 PM

kiwi, you are definately correct... NMR agrees.  I am now trying this reaction on something that it worked on in literature.  I isolated, and got a crystal structure of, p-toluene-sulfonyl-amine, which tells me that the diazo reaction occurs, but something must happen leading to the loss of N2 before the alkyne reaction occurs. 

I will try isolating the diazo first.  Does anyone have access to P. Callant et al., "An Efficient Preparation and the Intramolecular Cyclopropanation of Alpha-Diazo-Beta-Ketophosphonates and Alpha-Diazophosphonoacetates", Synthetic Communications, vol. 14, No. 2, pp. 155-161 (1984) no month. (7 pages).   This paper has the diazo synthesis I am looking for, but I do not have access to it.

I will also try the other methods stated in this thread.  Thanks for your *delete me*