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Meldrum's acid or 2,2-dimethyl-1,3-dioxane-4,6-dione is an
The acid dissociation constant, ionization constant p''K''a is 4.97; which makes it behave as a Acid, monobasic acid even though it contains no carboxylic acid groups. In this and other properties, the compound resembles dimedone and barbituric acid. However, while dimedone exists in solution predominantly as the mono-enol tautomer, Meldrum's acid is almost entirely as the ketone, diketone form.
The unusually high acidity of this compound was long considered anomalous—it is 8 orders of magnitude more acidic than the closely related compound dimethyl malonate. In 2004, Ohwada and coworkers determined that the energy-minimizing conformation structure of the compound places the alpha proton's σCH orbital in the proper geometry to align with the π*CO, so that the ground state poses unusually strong destabilization of the C-H bond.
The analogous reaction with an acyl chloride () attaches the acyl () instead:
These two reactions allow Meldrum's acid to serve as a starting scaffold for the synthesis of many different structures with various functional groups. The alkylated products can be further manipulated to produce various amide and ester compounds. Heating the acyl product in the presence of an alcohol leads to ester exchange and decarboxylation in a process similar to the malonic ester synthesis. The reactive nature of the cyclic-diester allows good reactivity even for alcohols as hindered as tert-butanol, ''t''-butanol, and this reactivity of Meldrum's acid and it's derivatives has been used to develop a range of reactions. Ketoesters formed from the reaction of alcohols with Meldrum's acid derivatives are useful in the Knorr pyrrole synthesis.
These ketenes can be isolated using flash vacuum pyrolysis (FVP). Ketenes are highly electrophilic and can undergo addition reaction with a range of other chemicals, particularly ketene cycloadditions, or dimerisation to diketene. With this approach it is possible to form new C–C bonds, rings, amides, esters, and acids:
Alternately, the pyrolysis can be performed in solution, to obtain the same results without isolating the ketene, in a one-pot reaction. The ability to form such diverse products makes Meldrum's acid a very useful reagent for synthetic chemists.
The compound is named after Andrew Norman Meldrum who reported its synthesis in 1908. He misidentified its structure as a β-lactone of β-hydroxyisopropylmalonic acid; the correct structure, the bislactone of 1,3-dioxane was reported in 1948.
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
with formula . Its molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
has a heterocyclic
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
core with four carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
and two oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
atoms; the formula can also be written as .
It is a crystalline colorless solid, sparingly soluble in water. It decomposes on heating with release of carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
and acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
.
Properties
Acidity
The compound can easily lose a hydrogen ion from the methylene element in the ring (carbon 5); which creates a double bond between it and one of the adjacent carbons (number 4 or 6), and a negative charge in the corresponding oxygen. The resultinganion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
is stabilized by resonance (chemistry), resonance between the two alternatives, so that the double bond is delocalized bond, delocalized and each oxygen in the carbonyl group, carbonyls has a formal charge of −1/2.
The acid dissociation constant, ionization constant p''K''a is 4.97; which makes it behave as a Acid, monobasic acid even though it contains no carboxylic acid groups. In this and other properties, the compound resembles dimedone and barbituric acid. However, while dimedone exists in solution predominantly as the mono-enol tautomer, Meldrum's acid is almost entirely as the ketone, diketone form.
The unusually high acidity of this compound was long considered anomalous—it is 8 orders of magnitude more acidic than the closely related compound dimethyl malonate. In 2004, Ohwada and coworkers determined that the energy-minimizing conformation structure of the compound places the alpha proton's σCH orbital in the proper geometry to align with the π*CO, so that the ground state poses unusually strong destabilization of the C-H bond.
Preparation
Original synthesis
The compound was first made by Meldrum by a condensation reaction of acetone with malonic acid in acetic anhydride and sulfuric acid.
Alternative syntheses
As an alternative to its original preparation, Meldrum's acid can be synthesized from malonic acid, isopropenyl acetate (an enol derivative of acetone), and catalytic sulfuric acid. A third route is the reaction of carbon suboxide with acetone in the presence of oxalic acid.Uses
Like malonic acid and its ester derivatives, and other 1,3-dicarbonyl compounds, Meldrum's acid can and serve as a reactant for a variety of nucleophilic reactions.Alkylation and acylation
The acidity of carbon 5 (between the two carbonyl groups) allows simple derivatization of Meldrum's acid at this position, through reactions such as alkylation and acylation. For example, deprotonation and reaction with a simple alkyl halide () attaches the alkyl group () at that position:
The analogous reaction with an acyl chloride () attaches the acyl () instead:
These two reactions allow Meldrum's acid to serve as a starting scaffold for the synthesis of many different structures with various functional groups. The alkylated products can be further manipulated to produce various amide and ester compounds. Heating the acyl product in the presence of an alcohol leads to ester exchange and decarboxylation in a process similar to the malonic ester synthesis. The reactive nature of the cyclic-diester allows good reactivity even for alcohols as hindered as tert-butanol, ''t''-butanol, and this reactivity of Meldrum's acid and it's derivatives has been used to develop a range of reactions. Ketoesters formed from the reaction of alcohols with Meldrum's acid derivatives are useful in the Knorr pyrrole synthesis.
Synthesis of ketenes
At temperatures greater than 200 °C Meldrum's acid undergoes a pericyclic reaction that releasesacetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
and carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
and produces a highly reactive ketene compound:
These ketenes can be isolated using flash vacuum pyrolysis (FVP). Ketenes are highly electrophilic and can undergo addition reaction with a range of other chemicals, particularly ketene cycloadditions, or dimerisation to diketene. With this approach it is possible to form new C–C bonds, rings, amides, esters, and acids:
Alternately, the pyrolysis can be performed in solution, to obtain the same results without isolating the ketene, in a one-pot reaction. The ability to form such diverse products makes Meldrum's acid a very useful reagent for synthetic chemists.
History
The compound is named after Andrew Norman Meldrum who reported its synthesis in 1908. He misidentified its structure as a β-lactone of β-hydroxyisopropylmalonic acid; the correct structure, the bislactone of 1,3-dioxane was reported in 1948.
References
Further reading
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