Choosing an appropriate base for deprotonation

[Mayhem]

Homework Statement

Can acetate deprotonate ketone alpha carbons?

Relevant Equations

pK = -log(K)

Normally you would deprotonate a ketone alpha carbon with a strong base like KOH or LDA, but in compounds where ester functional groups are also present, this would cause annoying side reactions.

Since the pKb of acetate (around 9.25) isn't much lower than the pKa of an alpha carbon (let's say it's 15) the equilibrium would be heavily shifted towards the protonated form of the ketone. However, this doesn't mean that none of the deprotonated form would be formed, just that it is much less than if we used a stronger base.

I'm asking because I am working on a reaction mechanism (homework problem) that works out if I deprotonate a ketone using acetate, but I'm just curious if this is plausible at all.

 

[epenguin]

I'm surely not the best expert here on this area but firstly I wondered where you got the idea that the pK of acetic acid is close to that of a ketone - they are about 15 units apart! Then I realized you were comparing a pKa of one thing with a pKb of the other. Compare either pKa s with pK a s or pKb s with pKb s.

Maybe your problem was with beta diketones which are much more acid than ketones but still a difference of about 6 pH units.

Then what does 'deprotonate with acetate' mean? Acetate is what you have when you have deprotonated acetic acid by adding base to it. So really all it means here is an alkaline solution, maybe only a weakly alkaline (pH > 7, OK at a pinch, 6).

You would have to spell out what the reactions desired are and your thoughts about the side reactions for anyone to help you here I'd think.

 

[Mayhem]

I'm surely not the best expert here on this area but firstly I wondered where you got the idea that the pK of acetic acid is close to that of a ketone - they are about 15 units apart! Then I realized you were comparing a pKa of one thing with a pKb of the other. Compare either pKa s with pK a s or pKb s with pKb s.

Maybe your problem was with beta diketones which are much more acid than ketones but still a difference of about 6 pH units.

Then what does 'deprotonate with acetate' mean? Acetate is what you have when you have deprotonated acetic acid by adding base to it. So really all it means here is an alkaline solution, maybe only a weakly alkaline (pH > 7, OK at a pinch, 6).

You would have to spell out what the reactions desired are and your thoughts about the side reactions for anyone to help you here I'd think.

Unless my math is wrong, you can express the pK of any acid-base reaction (or at least one in an acid-base inert solvent) as pK = pKa + pKb ... no?

 

[epenguin]

Unless my math is wrong, you can express the pK of any acid-base reaction (or at least one in an acid-base inert solvent) as pK = pKa + pKb ... no?

Maybe you mean
pKa + pKb = pKw = 14 .
?

 

[mjc123]

Or pK = pKa(HA) + pKb(B^-) - pKw = pKa(HA) - pKa(HB)

 

[Mayhem]

Or pK = pKa(HA) + pKb(B^-) - pKw = pKa(HA) - pKa(HB)

Is that a minus?

 

[Borek]

My bet is OP means something like

K_a=\frac{[H^+][A^-]}{[HA]}

K_b=\frac{[HB^+]}{[H^+][ B]}

and

K=\frac{[HB^+][A^-]}{[HA][ B]}=K_a\times K_b

(hence the "in an acid-base inert solvent" statement)

 

[Mayhem]

My bet is OP means something like

K_a=\frac{[H^+][A^-]}{[HA]}

K_b=\frac{[HB^+]}{[H^+][ B]}

and

K=\frac{[HB^+][A^-]}{[HA][ B]}=K_a\times K_b

(hence the "in an acid-base inert solvent" statement)

Yes. And then taking the logarithm of the bottom equations yields pK = pKa + pKb.

 

[mjc123]

Yes, but that's not what Kb usually means. Conventionally it refers to aqueous solution;
Kb = [BH⁺][OH^-]/[B ]
and that's what will generally be meant by Kb values you find in the literature.
Plus, it's important to specify if Ka and Kb refer to different things, not just the conjugate acid/base of each other.

 

[Mayhem]

Yes, but that's not what Kb usually means. Conventionally it refers to aqueous solution;
Kb = [BH⁺][OH^-]/[B ]
and that's what will generally be meant by Kb values you find in the literature.
Plus, it's important to specify if Ka and Kb refer to different things, not just the conjugate acid/base of each other.

True. I suppose this is a trash way to model it then.

 

[chemisttree]

You want a non-nucleophilic base. Good search term. I’d use NaH in an aprotic solvent.

 

[Mayhem]

You want a non-nucleophilic base. Good search term. I’d use NaH in an aprotic solvent.

Good point. What makes NaH non-nucleophilic? I understand that the reaction $\mathrm{Na^+ + H^- + H^+ \rightarrow Na^+ + H_2}$ is very favorable, but you won't get any side reactions?

 

[chemisttree]

Hydride is a poor nucleophile. Why? The generally recognized answer is that hydride is very “soft” ( very large ionic radius) and is highly polarizable... both of which contribute to it not being a good nucleophile.

I think you should be more careful with your language. Nobody can answer the question, “... you won’t get any side reactions?,” without knowing the nature of the other parts of the ketone you are given.
It’s a gotcha question and I won’t answer it. You asked about ketones with esters present and I gave you a reasonable answer given those two, but without seeing the molecule you are working with, nobody can say much more than that.

Review the acetoacetate and Malonic ester synthesis for some background.

And to clean up a bit of the discussion...
It’s enough to discuss the acidity of alpha hydrogens using pKa only. No need to complicate anything with pKb! The pKa of acetic acid is nominally 4.75. Therefore, acetate can deprotonate compounds more acidic than that and perhaps have an effect on compounds that have acidic hydrogens within a pKa unit of that. Alpha hydrogens on ketones have pKa of around 19-20, so acetate will have essentially no effect on them. That’s the end of that discussion... period.

 

[epenguin]

And to clean up a bit of the discussion...
It’s enough to discuss the acidity of alpha hydrogens using pKa only. No need to complicate anything with pKb!

Would you concord with what for me is by now just memory - that the main place you ever meet pKb 's is textbooks? I don't remember working biochemists or their primary literature ever talking other than in terms of pKa's which as you say is all you need.

 

[chemisttree]

I never use it but sometimes a professor will throw it into a problem just to make it spicy.