2,2-Dimethyl-1,3-dioxane-4,6-dione

Description

In 1908, A. N. Meldrum condensed malonic acid with acetone to produce a compound he misidentified as a carboxylic acid—hence the name “Meldrum’s acid”. Not until 1948 did D. Davidson and S. A. Bernhard show that the compound has the dioxane-dione structure shown here. Its acidity derives from the lability of the hydrogen atoms between the carbonyl groups. The same authors noted that Meldrum’s acid is a ketene precursor. Recently B. Moon and C. J. Hawker?used this property to create polymers with reactive ketene substituents.

Description

Meldrum's acid, also known as 2,2-dimethyl-1,3-dioxane-4,6-dione, is an organic compound with the formula C6H8O4. The compound was first made in 1908 by Andrew Norman Meldrum by a condensation reaction of malonic acid with acetone in acetic anhydride and sulfuric acid. Meldrum misidentified the structure as a β-lactone of β-hydroxyisopropylmalonic acid. Yet Meldrum's acid has a high acidity with a pKa of 4.97, because like ascorbic acid, deprotonation at the methylene next to the carbonyls produces a stable enolate. Because of this property Meldrum's acid like malonic acid is a reactant in Knoevenagel condensations.

Chemical properties

The compound appears as white to beige crystals. It has a melting point of 94-95℃ (decomposition), is insoluble in water, and is soluble in ethanol and acetone.

The Uses of 2,2-Dimethyl-1,3-dioxane-4,6-dione

2,2-Dimethyl-1,3-dioxane-4,6-dione was used in the synthesis of:

• macrocyclic β-keto lactone
• 4-pyridyl-substituted heterocycles
• 2-substituted indoles
• isofraxidin.

The Uses of 2,2-Dimethyl-1,3-dioxane-4,6-dione

Meldrum's acid serves as an intermediate in a variety of organic synthesis reactions. It is commonly used as an alternative to acyclic malonic esters and generally acts as a C3O2 synthon in organic synthesis.

The Uses of 2,2-Dimethyl-1,3-dioxane-4,6-dione

An antimicrobial agent

Preparation

2,2-Dimethyl-1,3-dioxane-4,6-dione is usually prepared by condensation of malonic acid with acetone in acetic anhydride in the presence of sulfuric acid. Excellent yield of the product was achieved when acetic anhydride was added in a slow, controlled manner to a mixture of acetone, malonic acid and an acid catalyst.

Synthesis Reference(s)

Journal of the American Chemical Society, 70, p. 3426, 1948 DOI: 10.1021/ja01190a060

General Description

2,2-Dimethyl-1,3-dioxane-4,6-dione (Meldrum′s acid) is widely used in organic synthesis, especially for multiple C-C bond formations due to its adequate acidity (pK_a 4.83) and steric rigidity. Knoevenagel condensation reaction between aldehydes and Meldrum′s acid are accelerated in ionic liquids.

Flammability and Explosibility

Non flammable

Purification Methods

Crystallise the dione from Me2CO/H2O. It is a synthon for the C3 malonic acid moiety. [Arnette et al. J Am Chem Soc 106 6759 1984, Bihlmayer et al. Monatsh Chem 98 564 1967, Review: McNab Chem Soc, Rev 7 345 1978, Chan & Huang Synthesis 452 1982, Beilstein 19/5 V 8.]