4-Dimethylamino-3-butyn-2-one

[20568-22-3]  · C6H9NO  · 4-Dimethylamino-3-butyn-2-one  · (MW 111.14)

(activates carboxylic acids)

Physical Data: bp 40 °C/10-4 mmHg.

Solubility: sol THF.

Preparative Methods: bromination of 4-(dimethylamino)but-3-en-2-one leads essentially in quantitative yield to the hydrobromide which is treated with Triethylamine. Further treatment with Potassium t-Butoxide leads to the title reagent.1,2

Purification: distillation at 40 °C/10-4 mmHg.

Handling, Storage, and Precautions: thermally unstable and is best stored at below -50 °C if kept for a prolonged period.

Introduction.

4-Dimethylamino-3-butyn-2-one is used to prepare activated enol esters,3 which are then reacted further. Aryl carboxylic acids, e.g. benzoic acid, undergo addition to 4-dimethylamino-3-butyn-2-one in THF at -60 °C in the presence of methanol, ethanol, 2-propanol, or t-butyl alcohol to give the enol ester (1) in high yield (eq 1).

No competing addition of alcohols is observed under these conditions. A diverse range of other carboxylic acids, including those incorporating phenolic, amino and thiol functions have been utilised in this reaction where only products of type (1) are seen.

Synthesis of Thiol and Selenol Esters.

Reaction of enol esters with Li, Na, and K salts of primary, secondary, and tertiary thiolates and enolates occurs at 0 °C to give the corresponding thiol and selenol esters (2) and (3), respectively, in good yields (eq 2).3

Synthesis of Carboxylic Acid Esters.

Alcohols react with (1) in the presence of protic or Lewis acids to give esters (eq 3);5 this esterification procedure has also been applied to the generation of large ring lactones (eq 4).4

Synthesis of Amide and Peptide Linkages.

Enol ester (1) reacts with amines to give amides (eq 5).6 4-Dimethylamino-3-butyn-2-one can also be used to achieve carboxyl activation of N-protected amino acids suitable for further coupling reactions with carboxyl-protected amino acids to give peptides.7,8 The amount of racemization observed in this process is low. Serine, tyrosine, 4-hydroxyproline, cysteine, and histidine can be linked to form a dipeptide without protection of the second functional group (OH, SH, NH).


1. Hafner, K.; Neuenschwander, M. AG(E) 1968, 7, 459.
2. Gais, H.; Hafner, K.; Neuenschwander, M. HCA 1969, 52, 2641.
3. Gais, H.; Lied T. AG(E) 1978, 17, 267.
4. Gais, H. TL 1984, 25, 273.
5. Niederhauser, A.; Frey, A; Neuenschwander, M. HCA 1973, 56, 944.
6. Neuenschwander, M.; Lienhard, U.; Fahrini, H.; Beat, H. HCA 1978, 61, 2428.
7. Neuenschwander, M.; Lienhard, U. HCA 1978, 61, 2437
8. Gais, H. AG(E) 1978, 17, 597.

Mark Prickett & Timothy Gallagher

University of Bristol, UK



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