Retrosynthesis

[FrankenNeko]

How would I perform a retrosynthesis on this molecule? The starting material should be commercially available. Any idea on how many steps it would take?

[mississippichem]

Have you made any attempts at getting a good retro-synthesis? Show us some of your attempted work and I'm sure we can help out.

 

It's a policy thing. We don't give answers but we can guide you to the answer. That's more intellectually rewarding for you anyway.

[Horza2002]

As Mississippichem said, we wont give you the anwser, but we can help you get there. The idea of retro-synthesis is to look at a compound and see what bonds are easy to make and then work backwards. In your compound there, there is at least one very obvious bond that is easy to form...so I suggest you start with that one.

[FrankenNeko]

I have to go to work right now but will get right back at this when I get home. I know there is the ester bond smack dab in the middle. I will work form there! Unless I'm wrong.... Is there a more obvious starting point?

As Mississippichem said, we wont give you the anwser, but we can help you get there. The idea of retro-synthesis is to look at a compound and see what bonds are easy to make and then work backwards. In your compound there, there is at least one very obvious bond that is easy to form...so I suggest you start with that one.

[Horza2002]

That is where I would start yes, work backwards to see which alcohol and which carboxylic acid you need. You'll discover one of them in commerically avaliable, so thats sorted. Then you will need to break down the other half of the ester to see how you would go about making that.

 

With a little bit more thought, breaking the ester is not actually as useful as I first thought. With that said, it does not mean that you can't do it that way...

 

The thing with these retrosynthetic problems is if you ask 5 different chemists, they'll give you 5 different routes, with each one based on what that particular individual has mroe experience with. If you star with that ester breakage seeing as thats the one you first noticed, then have a go at breaking down the required compound.

[FrankenNeko]

So far I have H2C=C=O + benzyl alcohol -----> benzyl acetate which is the left hand side of the molecule. Is this correct? The next part is the part that is confusing me most. I'm not sure how to put those two benzene rings together in that way.

[Horza2002]

If you break an ester down, then you will get an alcohol and a carboxylic acid. You have rightly got benzyl alcohol...however your other is not correct.

 

Firstly, H2C=C=O is not a carbxoylic acid its a ketene. A secondly the carboxylic acid fragment should contain the two benzene rings. As you knew to break the ester bond, I have shown you the first step of the retrosynthesis in the attached file...you now need to do the same thing with the carboxylic acid section.

 

In order to do this next section, think about how you make alkyl bonds to benzene rings, or maybe some chemistry of a carbonyl type compound, maybe some substitution chemistry. You may need to do several steps in order to get commerically avalaible starting materials

Edited November 30, 2011 by Horza2002

[FrankenNeko]

That attached thumbnail is extremely helpful. I was going about it all the wrong way. As for making alkyl bonds to benzene rings, i believe i will have to do a synthesis of nitrobenzene and aniline in order to get the F attached to the benzene. And you use an electrophilic substitution reaction between benzene and bromine.

 

My thoughts are the next disconnect is at the carboxylic acid RCOOH

 

Or what do you think about doing a functional group interconversion to give the ester form of the carboxylic acid?

[Horza2002]

While it is very good your thinking of a way to make the C-F bond, a lot of halogenated aryl rings are commecially avaliable. So you might want to have a look what ones are avlaiable so you roughly know what you need to do.

 

Ok, so if you disconnect at the carboxylic acid, what are the two starting materials your going to need? Also remember, that you dont always need to break a bond, you can also use a functional group interconverstion step (i.e. like you said, make a different ester).

 

When I do these things myself, I would now be making a list of all the ways I know how to make a carboxylic acid; what ways do you know of too make a carboyxlic acid? Then once I have all the methods, I would draw out the structures of the starting materials needed for each of those steps. Once I have all the starting materials, I would then see how to synthesis them...and then basically repeat this process until you get to commercially avaliable material.

Edited November 30, 2011 by Horza2002

[FrankenNeko]

I know carboxyl have a carbonyl group and a hyroxyl group....

I am thinking I need to do an FGI and from there I can break up the molecule into two.

4-Fluorophenethyl alcohol is commercially available 4-Bromobenzaldehyde is also commercially available, but i'm still unsure how to put those two together...

[hypervalent_iodine]

YOu won't be able to combine those two together in a useful fashion for your end-product. Break this down some more. Instead of looking up commercially available material, try thinking about what kind of reactions make carbon-carbon bonds - Horza suggested you think about what kind of reactions you know of that make carbon-carbon bonds onto phenyl rings, and this is a very apt hint. Try writing reactions you know down and have a look at how you can apply them to your substrate.

[Horza2002]

Ok I will now give you some hints to one possible route, but I'm not going to give you an anwser.

 

What do you get if you treat a carbonyl compound with a strong base (such as LDA (lithium diisopropyl amide))? Is the resulting intermediate a nucelophile/electrophile and what sort of reactions can it do? Will it do conjugate additions, eliminations, substitutions, rearrangements?

 

Also, what type of carbonyl compound should you use here? Is treating a carboxylic acid with LDA going to be a give you what I've implied above?

[FrankenNeko]

Going on one hour of sleep is really starting to affect me...

 

 

[Horza2002]

How are you going FrankenNeko?