3-Dimethylaminoacrolein is an organic compound with the formula Me2NC(H)=CHCHO. It is a pale yellow, water-soluble liquid. A push-pull alkene, it has chemical similarities to malondialdehyde and dimethylformamide.
Pharmacology 3-Dimethylaminoacrolein is a stimulant in humans and animals. It reverses the hypnotic effect of morphine in mice.
Preparation The simplest notional synthesis of 3-dimethylaminoacrolein is a Reppe hydroamination:
However, propynal is too explosive to make this procedure viable.
Instead, 3-dimethylaminoacrolein typically arises from Vilsmeier formylation of a vinyl ether, which gives an enoliminium chloride. Weak bases then cleave the enoliminium cation and recover 3-dimethylaminoacrolein. (Strong bases decompose the product; see ).
For example, in the following reaction sequence, a mixture of phosgene and dimethylformamide forms the Vilsmeier reagent, which then attacks isobutyl vinyl ether. Quenching with dilute NaOH gives the 3-dimethylaminoacrolein:
Chemical properties 3-Dimethylaminoacrolein is weakly alkaline and forms a deep red complex with iron(III) chloride. It is much more stable than its notional parent, . As a tertiary amine, it cannot tautomerize to the corresponding imine without developing formal charges.
For organic synthesis, it resembles a vinylogous dimethylformamide, combining the unsaturated aldehyde and enamine functionalities. Applications generally fall into two categories: as a less toxic malondialdehyde substitute or as a (reversibly)-quenched enoliminium cation.
An excess of strong aqueous base hydrolyzes 3-dimethylaminoacrolein to malondial through an addition-elimination sequence. Malondial is relatively toxic, and 3-dimethylaminoacrolein is an appealing substitute in heterocycle syntheses. For example, it condenses with guanidine to form 2-aminopyrimidine:
A more elaborate reaction sequence converts 2-naphthylamine to 1-azaphenanthrene.
3-Dimethylaminoacrolein is not interchangeable with malondial, however, because the carbonyl equivalents are differentially activated. Vilsmeier conditions only cause a single addition to N-methylpyrrole:
Another similar electrophilic arene alkenylation occurs in fluvastatin synthesis.
3-dimethylaminoacrolein has been investigated for the industrial synthesis of 2-chloronicotinic acid (2-CNA):
The nitrogen heteroatom's electron-richness extends through the π system, so that the aldehyde is an unusually competent nucleophile. Sulfate diesters alkylate the compound at the aldehyde oxygen, giving an electrophilic cation susceptible to Knoevenagel- or aldol-like addition:
Reaction with an (non-quaternary) ammonium salt gives instead a hemiaminal cation, which can then dehydrate to a vinamidinium cation (discussed further in ).
In some reaction sequences, 3-dimethylaminoacrolein is not isolated, but rather the salt from Vilsmeier attack on the vinyl ether is used directly:
Vinamidinium salts Dimethylammonium salts (chloride, tetrafluoroborate, perchlorate) react with 3-dimethylaminoacrolein to give a vinamidinium cation:
The resulting salts also resemble malondial. Thus, they add to cyclopentadienide and α to lactones...
...and form a wide variety of heterocycles.
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