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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: OrganicSyn1.0 on May 15, 2013, 11:42:59 AM

Title: Is this synthesis pathway viable???
Post by: OrganicSyn1.0 on May 15, 2013, 11:42:59 AM: Here is the link to the synthesis:

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Foi39.tinypic.com%2F6zbwhf.jpg&hash=ccbf94bdd16ad6abc9b23cff5a86dbdf5965a906)

Would these synthetic steps work to affect each corresponding transformations??? The Ketones are just a derivative of wanting to protect other reactive benzylic carbons to enhance regioselectivity of the free-radical chlorination via N-chlorosuccinimide. I personally think this synthesis would work. However it's possible I overlooked something.
PS Could the fused cyclopentane ring have to much angle strain?

Thanks! Looking forward to hearing your thoughts!

Mod edit: img tags added. Please use put the URI of the image in img tags rather than linking to an external website - e.g. [img]http://site.com/image.jpg[/img]. Dan
Title: Re: Is this synthesis pathway viable???
Post by: orgopete on May 15, 2013, 11:36:31 PM: Can you succeed in doing a Friedel-Crafts alkylation on a benzene ring with four carbonyl groups?

If the dione is written in the conjugated enol form, will it react with NBS or NCS?
Title: Re: Is this synthesis pathway viable???
Post by: kriggy on May 16, 2013, 03:06:52 AM: Im curious.. any reason why you are doing the methylation and then halogenation? Isnt better just use benzyl chloride and do it in one step insted of 3?
Title: Re: Is this synthesis pathway viable???
Post by: OrganicSyn1.0 on May 16, 2013, 01:05:40 PM: Orgopete: Good point! I overlooked the enolate reacting with NCS...And the nucleophilicity of the arene would be severely decreased by the poly keto substituents. Good call.

Kriggy: Great idea! That would be much more efficient to use benzyl chloride. That would also eliminate the need of protecting the other benzyl carbons with the harsh chromium oxidizing agent, making the synthesis greener. That would lower the steps to about three total (chlorination via SOCl2, intramolecular Friedel-Crafts alkylation, and friedel crafts w/ benzyl chloride)

Great Ideas Guys! Thanks for the insight! Quick question though.....is the intramolecular friedel-crafts viable??? or would it be unfavorable from a angle strain point of view?
Title: Re: Is this synthesis pathway viable???
Post by: opsomath on May 16, 2013, 03:20:18 PM: I am not sure I believe in your Friedel-Crafts alkylation with a primary chloride. If anything, you should make the acyl chloride and do it as an acylation one step at at time, doing Wolff-Kishner in between to avoid the deactivating effect of the ketone ALTHOUGH I vaguely recall seeing a successful double intramolecular FC acylation one time; it seems that the intramolecular reaction is favorable enough to overcome the deactivating effect of the ketone on the ring.
Title: Re: Is this synthesis pathway viable???
Post by: orgopete on May 16, 2013, 04:36:24 PM: Quote from: opsomath on May 16, 2013, 03:20:18 PM
I am not sure I believe in your Friedel-Crafts alkylation with a primary chloride. If anything, you should make the acyl chloride and do it as an acylation one step at at time, doing Wolff-Kishner in between to avoid the deactivating effect of the ketone ALTHOUGH I vaguely recall seeing a successful double intramolecular FC acylation one time; it seems that the intramolecular reaction is favorable enough to overcome the deactivating effect of the ketone on the ring.

I agree. I'm pretty sure succinic acid works(?), but if I wanted to do a reaction, I'd look it up.
Title: Re: Is this synthesis pathway viable???
Post by: OrganicSyn1.0 on May 16, 2013, 05:01:28 PM: Alright this seems to be a more efficient greener synthesis:

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Foi42.tinypic.com%2F2rqehlg.jpg&hash=94f569d6fa49261874aefcca81c654d29165f9e4)

I believe this would resolve any questionable steps, limiting side reactions. Correct me if I am wrong.