Synthesizing THC

THC is the chemical component of marijuana that gives it its unique effect on the body. Below is my proposed synthesis for this molecule. As you look through the synthesis, keep the whole molecular structure, shown above, in mind. You'll get a better understanding of where I'm going with each step. Feel free to click the image below to enlarge it.

Line 1: Start with Benzene. Nitrosylate it twice using H2SO4 and HNO3. Then, perform a friedel crafts acylation. Then, remove the carbonyl group using hydrazine and base to produce product A. 

Line 2: Product A is hydrogenated, converting both NO2 groups to NH2. One group is converted into an N2+ ion using NaNO2 and HCl. The ion is displaced using a lithium enolate -- which would attack from the oxygen, according to the "hard-hard" argument, producing product B.

Line 3: The remaining NH2 group is converted to an N2+ ion using NaNO2 and HCl. The ion is displaced with a hydroxy group from potassium hydroxide. Next, the double bond in the molecule is iodine-ized using hydrogen iodide. Another substituent is added to the least substituted ortho position, between the two oxy-substituents on the ring. See the column on the far right, which shows how to produce the reactant we're going to use. The benzene ring will attack the carbon adjacent to the double bond in our reactant, because conjugation will make SN2 attack at that position easier.

Line 4: The remaining bromine group on the new substituent is treated with magnesium, forming a grignard reagent. The possibility of a 6-membered ring is possible now.

Mechanism: The SP3 carbon bonded with oxygen and iodine is in equilibrium (or at least I would believe so) with the SP2 form, which is produced when oxygen donates its lone pair to carbon, kicking off I- in the process. The reason I say it's in equilibrium is because I- can just attack the electrophilic carbonyl again, taking us back to square one. Let's say I- has been kicked off, and the carbon is SP2 hybridized, and the oxygen has a positive charge. In this state, its really electrophilic. The intramolecular grignard will see this an instantly join the party - forming a favourable 6-membered heterocyclic ring.

And there you have it, that's the synthesis for THC. 

If you look at original molecular structure, you'll notice the stereochemistry of the two hydrogen atoms on the ring. One is up, one is down. I took this account when creating the proper reagent on the far right column. Using Br2 on an alkene produces trans bromines, and if we use one of the two enantiomers, we'll get the right product. Remember, SN2 attack inverts stereochemistry of the carbon it attacks.. you've got to be careful when choosing the enantiomer.