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I have found it to be rather strange that neutral amines, such as triethylamine or DIPEA, find applications in organic chemistry in deprotonating alcohols or even α-carbonyl compounds. Amines are basic but they aren't really that basic, compared to negatively-charged hydroxides or alkoxides. According to Wikipedia, the $\mathrm{p}K_\mathrm{a}$ (in water) of the conjugate acid of triethylamine is $10.75.$ The same values for alcohols are in the range of $16 - 18.$ For water, it is $14.$ Thus, hydroxides and alkoxides are superior alternatives to these amines.

My motivation for asking about this is that I recently encountered a question in my school chemistry course on why the protection of alcohols with $\ce{MOMCl}$ uses large bulky amines to deprotonate the alcohols, rather than using hydroxides. The answer given was that hydroxides would not be able to deprotonate the alcohols to a significant extent as alcohols are not acidic enough. I find this answer very strange and inconsistent with what I know since as shown by the data above, amines are less basic than alkoxides and hydroxides.

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  • $\begingroup$ After reacting with lithium, e. g. LDA? images.app.goo.gl/Rx379FHyus1i5kMc9 $\endgroup$
    – Karsten ♦
    Jun 14, 2019 at 2:38
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    $\begingroup$ @KarstenTheis No. I specifically refer to neutral amines, such as the two I have written above. $\endgroup$
    – Tan Yong Boon
    Jun 14, 2019 at 2:39
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    $\begingroup$ Alkoxides and hydroxide are too nucleophilic. The textbook explanation does not make sense. $\endgroup$
    – Karsten ♦
    Jun 14, 2019 at 2:50
  • $\begingroup$ In spite of the downvote on my answer to your concern about the reaction of MOMCl with alcohols, in my experience it is an SN1 process. The hindered base's role is to scavenge HCl. MOMCl is unstable in water. $\endgroup$
    – user55119
    Jun 15, 2019 at 2:30
  • $\begingroup$ @user55119 I see... It is unstable in water. I suppose there is neighbouring group participation in the reaction of the chloride with water, hastening the reaction. Thank you for your insight. $\endgroup$
    – Tan Yong Boon
    Jun 15, 2019 at 2:43

2 Answers 2

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There are several interesting aspects to your question.

How are neutral amines effective bases in organic chemistry?

First of all, recall the definition of a base. Anything which accepts a proton (or donates a pair of electrons) is a base. Organic bases are very strong and corrosive! These bases should not be undermined, even though they may sound weak (and their stench is worse than inorganic bases). Your lye-free oven cleaner has an organic base, an neutral organic amine such as ethanolamine, which dissolves dirty grease stuck in the oven. This molecule has no charge yet it is a strong base, acting just like sodium hydroxide based oven cleaner in terms of performance.

Thus, hydroxides and alkoxides are superior alternatives to these amines.

The second reason to avoid hydroxides and alkoxides is their solubility in organic solvents. Neutal organic amines easily dissolve in toluene and a variety of organic solvents. NaOH or NaH remain as a suspension.

MOMCl uses large bulky amines to deprotonate the alcohols, rather than using hydroxides

Again you have to think about the reaction solvent. Is an inorganic hydroxide soluble in your solvent? Then comes an important point. Why use bulky amines? Their sole purpose is to act as a proton sponge in the reaction mixture and prevent the formation of free acid. Bulky amines are preferred so that they don't react easily with the alkyl chlorides or acyl chlorides, thus prevent the formation of their own undesired side products.

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MOMCl reacts via an SN1 reaction and alcohol is the nucleophile, not an alkoxide. The amine serves to scavenge HCl.

ADDENDUM: Typically, a generic alcohol in an inert solvent is treated with MOMCl 1 in the presence of a hindered tertiary amine such as Hunig's base 2. MOMCl, which is prone to ionization by virtue of the participation of the oxygen atom, forms intermediate 3. This species reacts with the substrate alcohol to form the mixed acetal 4 and the amine hydrochloride 5. MOMCl is a very reactive "alkyl" chloride. It reacts with water to form hemiacetal 6 and, in the presence of liberated HCl, forms formaldehyde and methanol. Under these conditions the formaldehyde will be present as its hydrate 7.

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  • $\begingroup$ Oh I see what you ate trying to say finally! Can you also include your comment on MOMCl being unstable in water for a complete answer? $\endgroup$
    – Tan Yong Boon
    Jun 15, 2019 at 4:35
  • $\begingroup$ Did you mean what I said and you were trying to understand? ;) I expanded the answer per your request. $\endgroup$
    – user55119
    Jun 15, 2019 at 14:53
  • $\begingroup$ Although your answer doesn''t directly answer my question, I think it tackles the root cause of my confusion. $\endgroup$
    – Tan Yong Boon
    Jun 15, 2019 at 15:09
  • $\begingroup$ To my mind you had two questions, one in each paragraph. I was addressing your specific question about MOMCl. $\endgroup$
    – user55119
    Jun 15, 2019 at 19:35

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