[spankytank]

Hi!
I have a couple of questions regarding the synthesis of an intermediate (4) to Practolol.
I've attached a picture of the reaction-scheme. (If not, it can be seen here,   https://imgur.com/ZT4TWdo  )

1) In step 1, when the alkoxide (1 equivalent of NaOH used to generate alkoxide) reacts with epichlorohydrin (2), the formation of 3a is greater than 3b when we add more equivalents of epichlorohydrin (2). I ran the reaction with 2 equivalents of 2 and another one with 10 equivalents of 2, and the reaction with 10 equivalents of 2 gave more 3a. Why is this? What kind of stabilizing effects can explain this?

2) In step 2 the epoxide ring-opening with the use of acetyl chloride + water (which forms acetic acid and hydrochloric acid) reacts better than if I just add pure hydrochloric acid. Again, why is this? Some sort of stabilizing effects from water?

[wildfyr]

for 2) What do you mean add pure HCl? The gas? or 12 M solution, which is still about 65% water.

[spankytank]

Oh yeah, my bad. Meant to say stabilizing effect from the acetic acid.

[pgk]

1). This is a question of chemical kinetics. Both reactions occur simultaneously but by adding more equivalents of epichlorhydrine, you favor the formation of 3a, because:
u = k[alkoxide]10[epichlorhydrine] > k[alkoxide]2[epichlorhydrine] > k[alkoxide][epichlorhydrine]
Note that 3a and 3b have different rate constants of formation.
2). HCl is a gas and thus, it will quickly evaporate before opening the oxirane ring. Contrary controlled hydrolysis of acetyl chloride will slowly release HCl in situ, during the progress of the reaction that gives the necessary time to react.

[spankytank]

2) When using purely HCl I'm adding it in excess, so that can't be the (only) reason.

[pgk]

“ …’acetyl chloride + water’ reacts better than hydrochloric acid” does not obligatory mean that (concentrated?) hydrochloric acid does not work at all.