[Dynamo22]

Have to do this reaction without any other possible isomers being produced throughout the reaction. I was trying to add CH3 first, then throwing on SO3 (para) to the CH3, adding Cl, removing the SO3, adding H2CrO4 to make the carboxylic acid out of the CH3, then acylating with ketone. But, wouldn't the Cl direct the ketone o/p to itself? I am having a hard time trying to determine what order or combination of directing effects to use to complete this reaction without producing any other isomers. Any hints/help would be much apprecaited, thanks!

[discodermolide]

How would you have put 1) the methyl group on, without forming isomers 2) how would you have put the SO₃ group on and then removed it?

[Dynamo22]

I think he assumes the CH3 would add to one spot only in the reaction unless you try putting it on twice. Remove the SO3 with hot dilute H2SO4.

[discodermolide]

Do you not think that alkyl groups are activating? Therefore you will get positional isomers formed.
How does one remove the sulphonate with H₂SO₄?

[Dynamo22]

I apologize for the SO3, its actually SO3H, my mistake. Not sure if that changes anything. But, my professor wrote the book for our course and shows in a Friedel-Crafts Alkylation only one CH3 adding. Reagents would be CH3Cl/AlCl3

[discodermolide]

As far as I am aware upon adding one alkyl group you make the ring more active towards the addition of more alkyl groups.
To try and avoid the formation of positional isomers would it not be better to start by adding a deactivator?

[Dynamo22]

Agreed, when adding a deactivator you can push that Cl to the meta position. But how do you add either the carboxylic acid or ketone para to the deactivating group with Cl pushing any group ortho/para to it?

[discodermolide]

What would happen if you chlorinated first and then alkylated?

[Dynamo22]

I think you would get a mixture of o/p alkylated products.

[orgopete]

In the original scheme, Friedel-Crafts acylation reactions are sensitive to electron withdrawing groups. I suggest you begin with an acylation, then you can direct the additions from there. Hint, a cyanide can also be converted to a carboxylic acid.

[Dynamo22]

Seems reasonable, how do you not disturb the ketone when converting the cyanide group to a carboxylic acid?

[orgopete]

It will be okay in aqueous acid.