By which of the following can ortho-chloromethylbenzene be prepared? a) Reduction of phenol then halogenation of the product. b) Halogenation of toluene. c) Reduction of phenol then alkylation of the product. Or d) Alkylation of toluene.
Let’s work out the structure of ortho-chloromethylbenzene so that we know where we’re going. The easiest thing to start with is the benzene ring. The ortho- in ortho-chloromethylbenzene means that the chloro group and the methyl group are separated by adjacent carbons. That methyl group can go anywhere on the benzene ring. And these are the positions ortho to the methyl group. It doesn’t matter which one of these the chlorine occupies because, by symmetry, they are equivalent. I’m placing it on the right hand ortho position, giving us the structure of ortho-chloromethylbenzene.
Now, we can start analysing the synthetic routes to see which one would result in our desired product. Option a) is reduction of phenol and then halogenation of the product. Let’s start off with the reduction of phenol. This is the structure of phenol. In organic chemistry, the term reduction means either the addition of hydrogen or the removal of oxygen. The addition of hydrogen to phenol to produce cyclohexanol would remove the aromatic ring that we’re looking for in our product. Therefore, this is moving in the wrong direction. Let’s have a look at the removal of oxygen instead.
Phenol can be heated with zinc to remove the oxygen in the hydroxyl group, producing benzene and zinc oxide as a byproduct. This method seems to be getting us some other way towards ortho-chloromethylbenzene. So let’s have a look at the halogenation of benzene. Since it’s a chloro group, an ortho-chloromethylbenzene, we’re going to want to perform a chlorination. This is done by treatment of benzene with chlorine gas, iron, and UV light. This cocktail generates the catalyst iron(III) chloride necessary to trigger the chlorination. This yields us the product chlorobenzene. So the reduction of phenol followed by halogenation of the product benzene does not produce ortho-chloromethylbenzene. This is therefore not the correct answer.
In order to produce ortho-chloromethylbenzene, we would’ve needed some kind of methylation step. This wasn’t mentioned. Therefore, we can move on to the next option. The halogenation of toluene begins with toluene, otherwise known as methylbenzene. Again, since we aim to produce a chloro group, we will need to do a chlorination, using chlorine gas, iron, and UV light. A methyl group on a benzene ring directs incoming electrophiles to the ortho and para positions. That’s these positions here. So the products of chlorination of toluene is a mixture of ortho- and para-chloromethylbenzene. While this synthesis does produce para-chloromethylbenzene, it does produce ortho-chloromethylbenzene, which is the desired product. This is therefore a correct answer. However, I am going to continue through options c) and d) to see how they come out.
We’ve already discussed the reduction of phenol by zinc to form benzene. So we can jump ahead to look at the alkylation of benzene. As it turns out, it is very difficult to directly alkylate benzene. The common workaround is to perform a halogenation, for instance, a chlorination, and then a Friedel-Crafts alkylation, replacing the halogen with an alkyl group, in this case a methyl group. However, methyl benzene or any alkylated benzene is not the same as ortho- chloromethylbenzene. Therefore, reduction of phenol and then alkylation of the product is not a viable synthesis for ortho-chloromethylbenzene.
Now we’ve eliminated option c), we can move on to option d). The direct alkylation of toluene suffers from the same problems as the direct alkylation of benzene. There simply aren’t reagents that will do this economically. However, if we were to find a workaround that would alkylate toluene, we wouldn’t produce the chloro group necessary for ortho-chloromethylbenzene. Therefore, the alkylation of toluene is not a viable synthesis of ortho-chloromethylbenzene.
Of the four options given, the only viable synthesis for ortho-chloromethylbenzene is the halogenation of toluene.