[nguyenagain]

I am having a bit of trouble with a synthesis problem, I attached an image of the compound I am supposed to synthesize but here is a hyperlink. http://www.chemspider.com/Chemical-Structure.4646096.html?rid=f51e7401-1129-42f3-adde-9e9da96c62e8


I am starting from benzene:
I think my first step would be an FC Acylation to create a ketone with benzene and CH₂CH₃, so Propiophenone.
This would allow me to add the Cl in the meta position.
Then I think I need to remove the oxygen from the carbonyl.
Then I am kind of stuck...

I was thinking about reducing the ketone to an alcohol and then reducing that to an alkene but wouldn't the double bond form on the ring side of that carbon?
I am completely lost with how to add the aldehyde after that.

This is my first post, I am sorry if the formatting is atrocious!

[kriggy]

Propiophenone is not good starting material for your reaction. It allows you to add the chlorine into position you want but then you cant easily add the alhedyde functionality.
Also it is better to show us the scheme because Im am not 100% what is your proposed reaction scheme, Is it the one I drew?
Anyway, to add the aldehyde and double bond, I suggest you to look into Wittig or Wittig Horner reaction or into knovenagel reaction like http://www.orgsyn.org/Content/pdfs/procedures/CV4P0731.pdf but that would then require few more steps to get the aldehyde

[nguyenagain]

Yeah that's kind of what I was going for, what would for the opening step? I want to work through this if I can, but I'm not sure what to do if you can't go in that direction.

[nguyenagain]

Update:

This is what I decided on...
Benzene --ClCH₃/AlCl₃-->Toluene
Touluene --Etards Reaction--> Benzaldehyde
Benzaldehyde --Cl₂,FeCl₃--> Added Cl meta to the aldehyde group
Last Product --Wittig Reaction--> to add the Aldehyde on the end of the new C=C

I hope that all works, I think it does. If you see anything just yell at me!

Thanks for your help

[Babcock_Hall]

Can you show what kind of Wittig reagent you envision?

[nguyenagain]

This one, would that work?

[Babcock_Hall]

I defer to the judgment of the synthesis jocks here, but I would be concerned that such a reagent would react with itself.  Maybe the aldehyde could be protected in some way, or perhaps a different functional group could be used.

[Guitarmaniac86]

I defer to the judgment of the synthesis jocks here, but I would be concerned that such a reagent would react with itself.  Maybe the aldehyde could be protected in some way, or perhaps a different functional group could be used.

If you're refering to the phosphorus ylide, I agree with you that it will react with itself.

[kriggy]

What about using Wittig-Horner modification? Would it change the reactivity enough for it to not react with itself ? Also, one could have the aldehyde proceted in form of acetal and then deprotect after wittig
Also, some kind of allylic oxidation might be possible using reaction OP originaly suggested

[Guitarmaniac86]

What about using Wittig-Horner modification? Would it change the reactivity enough for it to not react with itself ? Also, one could have the aldehyde proceted in form of acetal and then deprotect after wittig
Also, some kind of allylic oxidation might be possible using reaction OP originaly suggested

I think the HWE will only change the configuration of the alkene product. Protecting the aldehyde as an acetal would work. I've done HWE with esters and they do not react with themselves so either acetal protection or an ester reduction with DIBAL would get the aldehyde.

[kriggy]

Well HWE is selective for E isomer in case of esters AFAIK. I think it could be same for compounds that can coordinate to lithium (acetal protected aldehyde) (it is not selective for compounds like Diethyl cyanomethylphosphonate is I learned the hard way :-D). Im not sure about selectivity of wittig reaction.

[sjb]

Other thoughts - aldol with acetaldehyde and m-chlorobenzaldehyde?

[rolnor]

I defer to the judgment of the synthesis jocks here, but I would be concerned that such a reagent would react with itself.  Maybe the aldehyde could be protected in some way, or perhaps a different functional group could be used.

If you're refering to the phosphorus ylide, I agree with you that it will react with itself.

I have seen this phosphonium reagent in the Aldrich catalogue and think the same, it will be polymere if base is added to form the ylide, I wonder what it is used for? As for aldolreaction with acetaldehyde and chlorobenzaldehyde it could be a mess, even if the acetaldehyde is subjected to LDA at low temperature, or? One could make a ylide with bromoacetaldehyde diethylacetal and triphenylphosphine perhaps, i think it should work? The last step would be hydrolysis of the acetal.

[NewmanProj]

Benzene => benzaldehyde => 3-chlorobenzaldehyde

Do Horner-Wittig using Ph3PCH2CO2Me on the 3-chlorobenzaledehyde. Prepare using PPh3 and methyl bromoacetate.

DIBAL-H reduction of methyl ester to aldehyde. Careful. 0.1 M, -78C, 1:1 toluene/hexanes, 1 eq DIBAL-H. Be certain to use a round bottom flask four times the volume of your reaction mixture for best cooling. Syringe pumps rock. Addition time no more than 30 min.

Use an internal thermometer. Work-up at -78C with anhydrous methanol, then Rochelle's solution.

Be happy