Formation of imines from primary amines and ketones

by James

Description: Reaction of a primary amine with an aldehyde or ketone results in an imine. The reaction results in the formation of one equivalent of water.
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Notes: Acid is commonly used to catalyze the reaction. Examples of acids that can be used for this purpose are TsOH and H2SO4

Examples:

Notes: Imines made from aldehydes are called “aldimines” (e.g. example 1) while imines made from ketones are sometimes called “ketimines” (e.g. example 2). Example 3 shows an intramolecular reaction.

Mechanism: Under conditions where acid is present, the mechanism begins with protonation of the oxygen of the carbonyl (Step 1, arrows A and B) which makes the carbonyl carbon a better electrophile. Next, the amine attacks the carbonyl carbon in a 1,2-addition (step 2, arrows C and D) and then a proton is transferred to the oxygen (Step 3, arrows E and F). The nitrogen lone pair then forms a π bond with the carbon, expelling water in a 1,2-elimination (Step 4, arrows G and H) leaving a positively charged nitrogen, which is then deprotonated by a base (Step 5, arrows I and J).

Notes: Acid assists the reaction in two ways. First, it makes the carbonyl more reactive for step 2, and it also allows for formation of water (H2O) which is a better leaving group than HO(–)

Note that it is reasonable to use many other types of acids (e.g. H+, TsOH, etc.) for the first step. There are other reasonable mechanisms for showing transfer of a proton other than that shown in step 3. It’s also OK to use water instead of OSO3H as the base in Step 5.

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{ 9 comments… read them below or add one }

sreekanth

why primary amines under diazonium reaction

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james

If you use secondary amines you can’t form the triple bond.

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Seah

For the first step, why does e proton source attack the carbonyl oxygen instead of the more basic amine in the reaction mixture? Is it because of resonance in e protonated carbonyl?

Do we add e acid and e amine at the same time?

Can the acid be a weak acid as strong acidic conditions may protonate e amine and render it non nucleophilic?

Thanks :)

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Rich Aversa

I was wondering this as well.

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James

The amine is more basic, this is true! Acid can attack the amine, but it doesn’t go anywhere (the amine and protonated amine are in equilibrium). It’s a dead end, in other words.

You just need a little bit of protonated carbonyl to get the reaction going.

It’s important that the solution not be too acidic, since if all the amine is protonated (irreversibly) then there is no nucleophile that would be able to attack the carbonyl.

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eabee

My textbook shows this reaction in water. Without acid, is the carbinolamine a stable form?

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James

Imine formation IN water – or is it imine hydrolysis?

Imine formation in water is not going to be successful unless you are forming a particularly stable imine (such as a cyclic 5 or 6 membered imine) and even then you’ll probably get a lot of the carbinolamine.

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Kim Estoque

Is this the same mechanism for the 2,4-dinitrophenylhydrazine (2,4-DNP) and ketones?

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James

Yes it is!!

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