Formation of imines from primary amines and ketones
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.
Notes: Acid is commonly used to catalyze the reaction. Examples of acids that can be used for this purpose are TsOH and H2SO4
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.