Day 76 - Making Meth

Methamphetamine. If you've seen Breaking Bad, you'll know exactly what this is.

"Methamphetamine is a white crystalline drug that people take by snorting it, smoking it, or by injecting it with a needle. Some even take it orally, but all develop a strong desire to continue using it because the drug creates a false sense of happiness and well-being -- a rush (strong feeling) of confidence, hyper-activeness and energy. One also experiences decreased appetite. These drug effects generally last from six to eight hours, but can last up to twenty four hours. The first experience might involve some pleasure, but from the start, methamphetamine begins to destroy the user's life. It is one of the hardest drug addictions to break, and many die in its grip..."

So let's make it...

You'll notice that its structure is fairly simple. A benzene ring and four carbons with a single nitrogen atom somewhere in between. Let's break all this apart, shall we?

The first thing we can do is pull apart the benzene ring in the form of benzyl bromide, shown on the right. To make benzyl bromide, use the following reagents:

1. Toluene
2. Bromine (Br-Br)
3. Ether (solvent)
4. Energy (hv; to direct a free-radical halogenation reaction)

These three reagents will produce benzyl bromide, which you can easily turn into a grignard by adding "magnesium turnings" (essentially just magnesium metal) in an organic solvent like ether and heating it all up.

Now we have our grignard. In the next step, we can react it with acyl chloride shown below:



The next piece is methylamine, which you've heard lots about. This stuff costs $11,000 per gallon, so if you're on OSAP like me, you'll need a cheaper alternative. We can make methylamine with ammonia and a good receptive electrophile like methanol. Cheap. I've drawn out a mechanism:



Finally, methylamine adds to the compound we made just before. See below:

The end is near. You may see what we need to do now. We've pretty much assembled meth, except now all we have to do is remove the hydroxy "OH" group. Let's tosylate it. The goal is to convert oxygen into a leaving group. The nitrogen atom will then donate its lone pair to literally push off the oxygen once its ready:



I can almost taste it. The final product doesn't have a double bonded nitrogen. Actually, the final product had a hydrogen in place of the "OH" we just removed. So, the final step is to reduce this compound by throwing a hydride (H-) at it. We can do this by adding the weak reducing agent Sodium Cyanoborahydride. If we had used a stronger reducing agent like LAH, the hydride would simply act as a base and form an aza-enolate (which would also be conjugated with the benzene ring..) and everything would be messed up. Check out the mechanism below:

Ta-Da! Meth. 

Not so tough is it? On paper it's pretty straightforward, but actually making it in the lab is a real challenge.