3-Dimethylaminoacrolein
Chemical compound
From Wikipedia, the free encyclopedia
3-Dimethylaminoacrolein is an organic compound with the formula Me2NC(H)=CHCHO. It is a pale yellow water-soluble liquid. The compound has a number of useful and unusual properties. When used on mice given morphine, it can reverse the hypnotic effect of the drug, while the compound has a more stimulating effect on human subjects.[3]
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| Names | |
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| Preferred IUPAC name
(2E)-3-(Dimethylamino)prop-2-enal | |
| Other names
3-Dimethylaminopropenal | |
| Identifiers | |
3D model (JSmol) |
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| ChemSpider | |
| ECHA InfoCard | 100.011.962 |
| EC Number |
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PubChem CID |
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| UNII | |
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| Properties | |
| C5H9NO | |
| Molar mass | 99.133 g·molâ1 |
| Appearance | Clear, faintly yellow[1] to dark brown liquid[2] |
| Density | 0.99 g·cmâ3 at 25°C[1] |
| Boiling point | *91 °C at 0.1 kPa[1] |
| Soluble[3] | |
| Solubility in methanol,[4] 1,2-dichloroethane[5] | Soluble |
| Hazards | |
| GHS labelling: | |
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| Danger | |
| H314 | |
| P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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It is a stable chemical, unlike the parent compound 3-aminoacrolein,[6] and can be used as a comparably nontoxic precursor to malondialdehyde.[7] The compound can be thought of as vinylogous dimethylformamide (DMF) and combines the functionalities of an unsaturated aldehyde and an enamine. Therefore, 3-dimethylaminoacrolein and its vinamidines derivates[8] can be used as molecular building blocks for the formation of nitrogen-containing heterocycles, such as pyridines, pyrimidines, pyrroles or pyrazoles.[9]
Preparation
3-Dimethylaminoacrolein is obtained by the addition of dimethylamine to the triple bond of propynal (propiolic aldehyde) via a Reppe vinylation.[3]
Propynal is an inappropriate starting material for industrial synthesis, because of its high explosion risk.[10] Vinyl ethers, such as ethyl vinyl ether, are more suited.[11] They react with phosgene and dimethylformamide (which forms in-situ the Vilsmeier reagent) in 68% yield to 3-ethoxypropenylidene dimethylammonium chloride. In the weakly alkaline medium, 3-dimethylaminoacrolein is formed, cleaving dimethylamine to form propanedial upon exposure to strong bases (such as sodium hydroxide).
In an alternative route, isobutyl vinyl ether reacts with the Vilsmeier reagent. The reaction can be implemented in a continuous process.[4] That process gives 3-dimethylaminoacrolein in dilute sodium hydroxide solution, with 86% yield.[12]
Instead of phosgene, the Vilsmeier reagent can also be prepared via phosphoryl trichloride or oxalyl chloride.
Use
Reactions with 3-dimethylaminoacrolein
3-Dimethylaminoacrolein can be used to introduce unsaturated and reactive C3 groups into CH-acidic and nucleophilic compounds.
The activated aldehyde group of 3-dimethylaminoacrolein reacts quantitatively with dialkyl sulfates such as dimethyl sulfate. The products are reactive but unstable[13] and decompose at 110 °C. The products can be easily transformed with nucleophiles into the corresponding vinylogous amide acetals or amidines.[14]
The stable 3-dimethylaminoacrolein dimethyl acetal is obtained by reaction with sodium methoxide in 62% yield. 3-Dimethylaminoacrolein can be reacted with CH-acidic compounds to form 1,3-butadiene derivatives or with cyclopentadiene to an aminofulvene.
With guanidine, 3-dimethylaminoacrolein forms 2-aminopyrimidine.[4]
The amidine formed with 2-naphthylamine and the dimethyl sulfate adduct can be cyclized with sodium methoxide to give 1-azaphenanthrene.[15]
![Synthese von Benzo[f]chinolin mit 3-Dimethylaminoacrolein](#/media/File:Synthese_von_1-Azaphenanthren.svg)
N-methylpyrrole forms the 3-(2-N-methylpyrrole)propenal with 3-dimethylaminoacrolein and POCl3 in 49% yield.[16]
The preparation of an intermediate for the cholesterol lowering drug fluvastatin via the reaction of a fluoroaryl-substituted N-isopropylindole with 3-dimethylaminoacrolein and POCl3 proceeds similarly.[17][18]
Occasionally, the salt from the reaction of the Vilsmeier reagent and the vinyl ether is directly used for synthesis, such as for pyrazoles.[19]
When hydrazine hydrate is used, a pyrazole parent body is formed.
Reactions to vinamidinium salts
The reaction of 3-dimethylaminoacrolein with dimethylammonium tetrafluoroborate produces the vinamidinium salt 3-dimethylaminoacrolein dimethyliminium tetrafluoroborate, which crystallizes better as the perchlorate salt. The salt reacts also with cyclopentadiene in the presence of sodium amide in liquid ammonia to give the aminofulvene derivative.[20]
The same salt (1,1,5,5-tetramethyl-1,5-diazapentadienium chloride) is also formed by the reaction of 3-dimethylaminoacrolein with dimethylamine hydrochloride.[21] The two-step reaction of dimethylamine and 70% perchloric acid with 3-dimethylaminoacrolein forms the same salt (referred to as 1,3-bis(dimethylamino)trimethinium perchlorate).[22]
Lactones (e.g. γ-butyrolactone) or cyclic ketones (such as cyclopentanone) form with the vinylamidinium salt of 3-dimethylaminoacrolein and dimethylamine hydrochloride the corresponding dienaminones in 91% and 88% yield.[23]
The vinamidinium salt 1,1,5,5-tetramethyl-1,5-diazapentadienium chloride reacts with heterocycles bearing CH-acidic groups to form the corresponding dienamines which can be cyclized with bases to form fused heteroaromatics, such as carbazoles, benzofurans or benzothiophenes.[8]
N-alkylpyrroles are obtained in good yield (86%) in the reaction of the vinamidinium salt with glycine esters,[24] substituted thiophenes (up to 87%) in the reaction with mercaptoacetic acid esters.[25]
The use of 3-dimethylaminoacrolein for the synthesis of 2-chloronicotinic acid (2-CNA) is of industrial interest as an important starting material for agrochemicals and pharmaceuticals. For this purpose, 3-dimethylaminoacrolein is reacted with ethyl cyanoacetate[26] to 2-chloronicotinic acid ester or with cyanoacetic acid n-butyl ester to 2-chloronicotinic-n-butyl ester[27] in a Knoevenagel reaction.
The resulting esters of 2-chloropyridine carboxylic acid can be hydrolyzed smoothly to 2-chloronicotinic acid.
Other reactions
It is weakly alkaline and turns deep red when reacted with iron(III) chloride.