I am studying Syntex's naproxene syntheses and I came across a couple of electrophilic substitutions whose mechanism I can't understand.
The first one is a Friedel-Crafts acylation: the products are the ones indicated in the picture and they are separated before proceeding. No other byproducts are shown.
Why did the acetyl go in pos. 6? As far as I know, When an electrophilic substitution is made on an activated substituted naphthalene, the electrophile will go in the substituted ring, in the pos. 1 (kinetic control) or in pos. 2 (thermodynamic control), which is in ortho or para to the activating substituent. So I would expect these products, in theory:
I assume the contributing structures that represent the electron-donating effect are the following:
Therefore, although I would expect a 6-acetyl derivative as a byproduct (at least in theory, since (4) might allow it), I don't understand why it is the main product. No clues at all about the 5-acetyl byproduct, since the 5-acetyl intermediate is not stabilized by the electron-donating effect: could it possibly be an error?
The second reaction is a bromination on 2-naphthol:
Likewise, I can think that bromine would first go in pos. 1, and then, since it is only slightly deactivating, another bromine can be added. But again, why in pos. 6? Why not in pos. 3, in ortho to the activating substituent?
And in the end, are these reactions done under kinetic or thermodynamic control?