[Nomeru]

Hello. I'm nearly finished with a year in organic chem. I'm looking for a little guidance on a synthesis problem I've got.

I can start with benzene, any alkyl halide or alcohol (but not both on one), use KCN and H2O as carbon sources, and use any reagents I've learned. (I cant exactly list what I've learned, but you get the idea hopefully).

What I must create:

So to start, I know I must have 2 benzenes. I must also have a ketone, which I can get from an alcohol. Isopropanol + H2CrO4 ----> CH3C=OCH3 (acetone). I'm not really sure what direction I should go from here though. I know I can add a halogen to either side of my ketone easily enough. CH3C=OCH3 + Cl2 in H3O ---> ClCH2C=OCH2Cl (1,3-dichloroacetone).

The problem I run into with this is I can think of no way to add it to add benzene to this. Would Friedal-Crafts alkylation work? So Benzene + my chloroacetone + AlCl3? The carbonyl is in the wrong place to be acylation, and alkylation often has rearrangement, though I do not believe this can rearrange, unless perhaps to create an alcohol.
Another thing I've considered is using a gilman. 2((C6H5)2)CuLi + chloroacetone in THF ----> product? I recall Gilmans not working well when oxygen's involved. Specifically, I recall issues with alcohols and ethers, but do not know about carbonyls. Much less sure about this option.
I also considered starting by making C6H5MgBr to react with an alkyl halide, but this seems worse. I would have to make an alkenyl dihalide, add both grignards, add an alcohol to the right carbon which would not be favored, and oxidize.

I've been searching through my book and my notes, and I feel like I've missed some things but I'm not sure what else could be done at the moment. I'm leaning towards friedal-crafts right now, but I do not know if that would work. Is there a better option that I've missed? Thanks.

[Guitarmaniac86]

I have a very long synthesis but I wont give you all the answers.

1) Put a cyanide group on the benzene ring. How would you go about this?
2) This can be turned into a carboxylic acid. How?
3) If you react product in 2) with a cyanide ion, what do you get?
4) Can you reduce the product in 3) to leave the cyano group? If so how (hint: 2 methods I know of to do this, one beginning with a W)
5) Hydrolyse the cyano group and convert to an aldehyde.

6) To the other benzene ring, can you add a two carbon group via Friedel Crafts acylation, that, when reacted with sodium ethoxide, will form an enol that can react with the product in 5).
7) If this is the case, how can you then end up with the product you need?

[Nomeru]

I have a very long synthesis but I wont give you all the answers.

1) Put a cyanide group on the benzene ring. How would you go about this?
2) This can be turned into a carboxylic acid. How?
3) If you react product in 2) with a cyanide ion, what do you get?
4) Can you reduce the product in 3) to leave the cyano group? If so how (hint: 2 methods I know of to do this, one beginning with a W)
5) Hydrolyse the cyano group and convert to an aldehyde.

6) To the other benzene ring, can you add a two carbon group via Friedel Crafts acylation, that, when reacted with sodium ethoxide, will form an enol that can react with the product in 5).
7) If this is the case, how can you then end up with the product you need?

Thanks for the reply, lets see.

1) Benzene + HNO3 in H2SO4 to get Nitrobenzene. Reduce with H2/pd to Aniline. Aniline+NaNO2, HCl, 0C -->diazonium group + KCN = C6H5-CN.
2) From here, react with H2O, HCl + Heat --> benzoic acid.
3) I am not aware of a way to react a carboxylic acid with a cyanide ion. I know aldehydes and ketones + Cyanide will form a cyanohydrin.
Perhaps react with SOCl2+Heat to form an acyl chloride, H2/Pd ->benzaldehyde. Benzaldehyde + Cyanide ion ---> C6H5-CH(OH)CN
4) Cannot find a way to do this.
5) Assuming there is a way and C6H5-CH2-CN is formed, 1. SOCl2+Heat -> C6H5-CH2COOH 2. H2/Pd -> C6H5-CH2-CHO

For the last two steps, Yes and no. Adding Cl-C=OCH3 .. this would be able to form an enolate, but then there are 1 too many carbons.

[Guitarmaniac86]

I analysed this problem by retrosynthesis.

3) You can reduce a carboxylic acid to an aldehyde, which then allows nucleophilic attack of a cyanide ion.

4) To get rid of the carbonyl after the cyano group has been added, you can do a wolf kishner reduction.

At point 5) in my haste to solve it, I made a mistake, and a silly one at that. What you want to do at step 5) is hydrolyse the cyanide group to a carboxylic acid, then convert it to an ester with ethanol.

React this with a grignard of bromomethylbenzene.

Sorry about the mistake, I accidently counted 4 carbons not 3.

[orgopete]

I would target making benzyl bromide as a useful intermediate. I think you can use it for both sides of the ketone.

[Nomeru]

Alright, looks like I got it.

Thanks for the input.