trans-4-(Dimethylamino)-3-buten-2-one
[CAS# 2802-08-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Ketones
• Name: trans-4-(Dimethylamino)-3-buten-2-one
• Synonyms: (E)-4-(dimethylamino)but-3-en-2-one
• Molecular Formula: C₆H₁₁NO
• Molecular Weight: 113.16
• CAS Registry Number: 2802-08-6
• EC Number: 627-627-8
• SMILES: CC(=O)/C=C/N(C)C

Properties

• Density: 0.9±0.1 g/cm³ Calc.^*
• Boiling point: 169.2±23.0 °C 760 mmHg (Calc.)^*, 276.5 - 277.9 °C (Expl.)
• Flash point: 54.3±12.0 °C (Calc.)^*
• Index of refraction: 1.449 (Calc.)^*, 1.557 (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

trans-4-(Dimethylamino)-3-buten-2-one is an organic compound known for its use as a reactive intermediate in organic synthesis, particularly in the development of heterocyclic compounds and pharmaceuticals. It belongs to the class of enaminones, which are characterized by having both an enamine and a ketone functional group within the same molecule. This dual functionality makes such compounds valuable synthetic building blocks due to their versatile reactivity under mild conditions.

The compound features a conjugated system comprising a double bond between the C-3 and C-4 positions and a carbonyl group at the C-2 position. The presence of a dimethylamino group at C-4 contributes to the electron-donating characteristics of the molecule, enhancing its nucleophilicity and stability under various reaction conditions. The trans geometry of the C=C double bond gives this compound a well-defined stereochemistry, which is important in reactions where stereoselectivity affects the outcome.

The synthesis of trans-4-(dimethylamino)-3-buten-2-one typically involves the condensation of dimethylamine with methyl vinyl ketone or related substrates under controlled conditions. This reaction is usually carried out in a polar solvent under acidic or neutral conditions to favor formation of the enaminone product over potential polymerization or side reactions. The product is a yellowish liquid at room temperature and is moderately soluble in polar organic solvents such as ethanol, acetone, or methanol.

Applications of trans-4-(dimethylamino)-3-buten-2-one center on its role as a precursor in the formation of heterocyclic ring systems. Its reactivity toward nucleophiles and electrophiles makes it particularly valuable in the synthesis of pyrroles, pyrazoles, and other nitrogen-containing heterocycles. The compound undergoes Michael addition and nucleophilic substitution reactions readily, and its enamine moiety can participate in cyclization reactions that are fundamental to medicinal chemistry research.

One notable use of trans-4-(dimethylamino)-3-buten-2-one is in the synthesis of biologically active molecules, including potential drug candidates and intermediates for agrochemicals. Its role as a Michael acceptor is key to its utility, allowing it to form carbon-carbon or carbon-heteroatom bonds with a wide range of nucleophilic species. Furthermore, the conjugated system within the molecule facilitates electrophilic substitution reactions, allowing for the selective modification of the molecule's structure for further chemical elaboration.

Another significant application is in dye and pigment chemistry, where related enaminones are used to create conjugated systems that absorb light in the visible spectrum. While trans-4-(dimethylamino)-3-buten-2-one itself is not widely commercialized in dye manufacture, its structural features make it a useful template or model compound for the design of chromophores and fluorophores.

In terms of safety and handling, trans-4-(dimethylamino)-3-buten-2-one is generally handled as a laboratory chemical. It may pose risks associated with skin or eye contact due to its reactivity and potential for forming irritating intermediates. It should be stored under dry, cool conditions, away from strong oxidizing agents or acids. Due to its potential for nucleophilic substitution and addition reactions, care must be taken to avoid unintended polymerization or degradation, especially under light or heat exposure.

Overall, trans-4-(dimethylamino)-3-buten-2-one represents a class of highly functionalized organic molecules with broad utility in synthetic chemistry. Its ease of preparation and predictable reactivity profile make it a staple reagent in the development of diverse molecular architectures. Its contributions to organic synthesis, particularly in medicinal and heterocyclic chemistry, underscore its importance in chemical research and development.

References

1953. 2-Aminovinyl ketones. Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science, 2(6).
DOI: 10.1007/bf01167531

2006. A One-Pot Method for the Synthesis of Naphthyridines via Modified Friedländer Reaction. Synlett, 2006(3).
DOI: 10.1055/s-2006-926229

2019. Synthesis of β-azolyl- and β-azolylcarbonylenamines and their reactions with aromatic azides. Chemistry of Heterocyclic Compounds, 55(8).
DOI: 10.1007/s10593-019-02525-2