[SinkingTako]

So problem of the week has been dead for quite a while, and Borek is not very not keen on having something new. So let's start a organic synthesis revival!

Each week someone will post a molecule (I can do this for the first few weeks), and anyone can propose a total synthesis. The feasible submission with the least number of steps wins!

The Rules:

• Unless otherwise stated, the starting material(s) should be something relatively affordable and easily accessible in labs. To check, look up the price of the molecule on the Sigma Aldrich website. Something like
  http://www.sigmaaldrich.com/catalog/product/aldrich/586366?lang=en&region=SG
  is not allowed.
• "Feasibility" is defined as reactions that are known to have a moderate yield, and can take place without difficulty. Reactions that may occur by chance during a reaction, but is not part of the main reaction, are not allowed. (the definition of this is also so iffy)
• All intermediate compounds, reactants and conditions should be stated clearly, either written or typed.
• That's all for now, rule suggestions welcome!

The First Problem
Let's start with something really really easy:

Using benzene as the starting material, propose a synthesis of aspirin.

To start the ball rolling, see below for my proposal. I have done it in 6 steps. How many steps will you take?

[OrgXemProf]

Kolbe-Schmitt carboxylation of phenol via base-promoted reaction of phenol with CO₂ works very nicely at 125 degrees C and 100 atm. pressure. Do these conditions qualify as "feasible" and "take place without difficulty" when performed in a student laboratory in the absence of an autoclave?

"Efficient regioselective carboxylation of phenol to salicylic acid with supercritical CO₂ in the presence of aluminium bromide" has been reported (Iijima, T.; Yamaguchi, T. J. Mol. Catalysis A: Chemical, 2008, 295, 52-56). But the use of supercritical CO₂ once again requires an autoclave.

[curiouscat]

Kolbe-Schmitt carboxylation of phenol via base-promoted reaction of phenol with CO₂ works very nicely at 125 degrees C and 100 atm. pressure. Do these conditions qualify as "feasible" and "take place without difficulty" when performed in a student laboratory in the absence of an autoclave?

Can you do a 100 atm reaction at all without an autoclave?

[SinkingTako]

Kolbe-Schmitt carboxylation of phenol via base-promoted reaction of phenol with CO₂ works very nicely at 125 degrees C and 100 atm. pressure. Do these conditions qualify as "feasible" and "take place without difficulty" when performed in a student laboratory in the absence of an autoclave?

Okay then shall we change the rules to "something that can only be done in a student lab"?

Actually for feasibility I'm thinking more towards the lines of anything that can be done in a synthesis lab (not a student lab), where there's more equipment. So reactions that may require high temperature and pressure are acceptable unless it really require some special piece of equipment that only exist one copy in the world or something. And non-feasible stuff are also like making buckyballs through flash vacuum pyrolysis (something like http://www.synarchive.com/syn/100) where the yield is like 0.1%.

Back to the initial problem I've actually come up with something that only require 3 steps, but meanwhile we shall wait for the rest to come up with more interesting stuff

[nirhananya]

Well, there are shorter routes for the synthesis of phenol, but they involove organometallic catalysis and not classic "old" reactions.
For example, you can borylate the benzene by Hartwig-Miyaura reaction and then make hydrolysis with hydrogen peroxide and water to get the phenol.

[kriggy]

Wow dude, I realy like this (we can take turns in who propose the next exercise)
anyway my attempt

btw I realy like that fulerene syntesis, that last step.. :-D

[SinkingTako]

Wow dude, I realy like this (we can take turns in who propose the next exercise)
anyway my attempt

Wow glad you like this:) Let's make it such that the winner propose a new compound to synthesize every week!

Oh one thing: wouldn't the conditions for haloform destroy the ester? Or what base will you use such that the ester won't be destroyed? So probably need another step to reinstall the ester right?

Yay:D

[Dan]

I was trying to think of a non-classical approach to mix things up a bit. Here's a route using Pd catalysis.

This may of course not qualify on the grounds that only half of the aromatic carbon in the final product is derived from benzene (the other half comes from styrene).

References:

For styrene coupling: Shi Chem. Commun., 2012, 48, 7028-7030 Link
For hydroxylation: Yu J. Am. Chem. Soc., 2009, 131, 14654–14655 Link

[Shadow]

Wow dude, I realy like this (we can take turns in who propose the next exercise)
anyway my attempt

Wow glad you like this:) Let's make it such that the winner propose a new compound to synthesize every week!

Oh one thing: wouldn't the conditions for haloform destroy the ester? Or what base will you use such that the ester won't be destroyed? So probably need another step to reinstall the ester right?

Yay:D

Keep it up Ms. +1

[Altered State]

I was trying to think of a non-classical approach to mix things up a bit. Here's a route using Pd catalysis.

This may of course not qualify on the grounds that only half of the aromatic carbon in the final product is derived from benzene (the other half comes from styrene).

References:

For styrene coupling: Shi Chem. Commun., 2012, 48, 7028-7030 Link
For hydroxylation: Yu J. Am. Chem. Soc., 2009, 131, 14654–14655 Link

Love it.

Now I can't think of a way of performing this synthesis in less than 4 steps.
One step should be to form the acetyl group.
So to use less than 4 steps, you need a rxn that allows you to transform benzene directly into phenol or benzoic acid in one step. I know plenty of them to do it in two steps, but no less



BTW, Keep this up!

Wow dude, I realy like this (we can take turns in who propose the next exercise)
anyway my attempt

Won't haloform aqueous basic conditions remove the acetyl group?



I love LSD synthesis, got Woodward's on the wall of my room

[kriggy]

Hm yeah there is a possibility that haloform would hydrolyze the ester (I didnt think of that when I posted it). Im thinking maybe it could be possible to use hypobromite and other base than NaOH? But it seems like a wish :-D

[Dan]

you need a rxn that allows you to transform benzene directly into phenol or benzoic acid in one step. I know plenty of them to do it in two steps, but no less

There are methods to make benzoic acid from benzene in one step - transition metal catalysis with CO or CO₂, but I couldn't find an example with a commercially available catalyst/ligand.

[Shadow]

Just don't put vitamin B12 as the next challenge .

[kriggy]

Just don't put vitamin B12 as the next challenge .

Well that would be something.. :-D

Ok well since not much happened here since last week, I take the liberty of giving another POTW, this one is more difficult (much more?):


Enjoy

[SinkingTako]

yes! thanks kriggy! okay we can make it such that new problem is posted every Saturday then?