Synthesis (1) – “What’s Different?”

by James

Every synthesis problem is different, but there are still some common problem solving techniques you can use to solve each synthesis problem in turn.

One thing you *don’t* want to do is try to look at a problem and see if you “just get it”. That strategy has a pretty low success rate. You have to have a method. 

Solving a synthesis problem is like eating a really big steak. If you tried to eat it whole, you’d probably choke. What you want to do is to cut it into tiny little pieces. Then it’s manageable.

My advice is to break it down into 3 questions. I’ll go through them in 3 separate posts.

Today’s question to ask is, “what’s different?“.

And by different, I mean – you guessed it – what bonds have formed, and what have broken. If you can’t answer that, you want to be as *specific* as possible about what has changed in the molecule. What new atoms are there? What atoms have disappeared? Every tiny little piece of information helps in solving the puzzle.

Let’s look at this example.

  • Here, it should be easy to spot the fact that we’ve lost an ester. Specifically, we’re missing OMe and C=O. One carbonyl is left behind.
  • Also, we’ve added some carbons. There are a methyl group and an ethyl group that weren’t there before. That means we’ve formed C-C bonds.
  • Here’s the most subtle tip. If you’re really good, you’ll be able to spot the loss of C-H bonds. Note how each of the carbons on the starting material are either C=O, CH2, or CH3, but our product has a tertiary carbon (C-H). It’s a good guess that our starting material lost a C-H somewhere.

Making a list of bonds that form and break focuses our attention. Think of it like a “to do” list.

The next step will be to make a candidate list of reactions that will accomplish these “tasks” on our to-do list.  More on that tomorrow.

Try applying this to the next synthesis problem you see and tell me how you do.

Thanks for reading! James

 

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