Decarboxylation of malonic acid

Transition state in thermal decarboxylation of malonic acid... 

The thermal decarboxylation of malonic acid derivatives is the last step m a multistep synthesis of carboxylic acids known as the malonic ester synthesis This synthetic method will be described m Section 21 7... 

Notice that the caiboxyl group that stays behind during the decarboxylation of malonic acid has a hydroxyl function that is not directly involved in the process. Compounds that have substituents other than hydroxyl groups at this position undergo an analogous decarboxylation. 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Problem 16.18 (a) Suggest a mechanism for a ready decarboxylation of malonic acid, HOOCCH,COOH, that proceeds through an activated, intramolecular H-bonded, intermediate complex, (b) Give the decarboxylation products of (i) oxalic acid. HOOC—COOH, and (ii) pyruvic acid, CHjCOCOOH. 

A typical chemical system is the oxidative decarboxylation of malonic acid catalyzed by cerium ions and bromine, the so-called Zhabotinsky reaction this reaction in a given domain leads to the evolution of sustained oscillations and chemical waves. Furthermore, these states have been observed in a number of enzyme systems. The simplest case is the reaction catalyzed by the enzyme peroxidase. The reaction kinetics display either steady states, bistability, or oscillations. A more complex system is the ubiquitous process of glycolysis catalyzed by a sequence of coordinated enzyme reactions. In a given domain the process readily exhibits continuous oscillations of chemical concentrations and fluxes, which can be recorded by spectroscopic and electrometric techniques. The source of the periodicity is the enzyme phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate by ATP, resulting in the formation of fructose-1,6 biphosphate and ADP. The overall activity of the octameric enzyme is described by an allosteric model with fructose-6-phosphate, ATP, and AMP as controlling ligands. 

SAMPLE SOLUTION (a) Thermal decarboxylation of malonic acid derivatives leads to the replacement of one of the carboxyl groups by a hydrogen. 

SAMPLE SOLUTION (a) By analogy to the thermal decarboxylation of malonic acid, we represent the corresponding reaction of benzoylacetic acid as... 

Previous work on this reaction has included the use of triethanolamine as catalyst, as well as triethylamine as catalyst and solvent. [21-24] The use of elevated temperatures (>75°C) can lead to uncontrolled decarboxylation of malonic acid before condensation, giving acetic acid, which is then too weak a carbon acid to condense. This difficulty means that often up to 3 equivalents of the malonic acid need to be used to achieve good conversion. Our aim in this work was therefore to find a catalyst which would cause the condensation to occur efficiently, but at low enough temperatures to avoid decomposition of the malonic acid. Using THF as solvent and a 1 1 ratio of malonic acid to aldehyde, with 15g of catalyst per mole of reagent, we obtained high levels of conversion of aldehyde in a reasonable time (Table 3). 

A greater contrast is provided by the first-order rate of decarboxylation of malonic acid. In Table XV.4 are gathered some data from a compilation of Clark (Zoc. dt) on the effect of different solvents. The data in H2O of Hall (Zoc. cit.) are included for comparison purposes. Here, over a range... 

It was shown that an enol intermediate was initially formed in the decarboxylation of l -ketoacids and presumably in the decarboxylation of malonic acids. It was found that the rate of decarboxylation of a,a-dimethylacetoacetic acid equalled the rate of disappearance of added bromine or iodine. Yet the reaction was zero order in the halogen . Qualitative rate studies in bicyclic systems support the need for orbital overlap in the transition state between the developing p-orbital on the carbon atom bearing the carboxyl group and the p-orbital on the i -carbonyl carbon atom . It was also demonstrated that the keto, not the enol form, of p ketoacids is responsible for decarboxylation of the free acids from the observa-tion that the rate of decarboxylation of a,a-dimethylacetoacetic acid k cid = 12.1 xlO sec ) is greater than that of acetoacetic acid (fcacw = 2.68x10 sec ) in water at 18 °C. Enolization is not possible for the former acid, but is permissible for the latter. Presumably this conclusion can be extended to malonic acids. 

In octanoic acid solvent, alkyl substitution of malonic acids causes a small decrease in AG and thus an increase in rate as seen from Table 47. This is in contrast to the alkyl substituent effect in water (Table 46). The enthalpy of activation is clearly more favorable for decarboxylation of alkyl malonic acids than malonic acid in octanoic acid. Both Ai/ and AG are less favorable for decarboxylation of malonic acid in octanoic acid compared to water. This is expected on the basis of either the concerted (2) or the zwitterion mechanism (3) and (4). Association of the carboxyl groups of malonic acid with the octanoic acid solvent would thwart the attainment of the concerted transition state. Also generation of the zwitterion would be suppressed in octanoic acid. It is clear that additional work is required... 

The data for this solvent were not used to calculate the parameters in Table 54. Similarly the data for decarboxylation of oxanilic acid in anisole were not used for the AH -AS correlation. With the reported AH value of 32.6 kcal.mole , the entropy of activation is calculated to be 3.59 0.03 eu compared to the reported value of 11.1 eu. In the decarboxylation of malonic acid, the data obtained with pyridine and ) -mercaptopropionic acid solvents deviated considerably from the plots and were not included in the correlation. The data for malonic acid decarboxylation appeared to be best correlated by two lines. One line was described by the following solvents acids, phenols, nitro-aromatics, benzaldehyde, and the melt the other line involved amines, alcohols, dimethylsulfoxide and triethyl phosphate. The latter line was not as well defined as the former. However, it was our intention to correlate as many solvents as possible with a minimum number of lines. The data for decarboxylation of malonic acid in water and in benzyl alcohol fell between these two lines and were not included in either correlation. The data for decarboxylation of benzylmalonic acid also appeared to be best correlated with two lines. One line was defined by the cresols, acids and the melt, while the other line was defined by the amines. Decarboxylation of cinnamalmalonic acid was correlated by two lines as indicated in Table 54. Similarly j8-resorcylic acid was correlated by two lines. The separation of data into parallel lines is presumably due to multiple solvation mechanisms . In support of this interpretation it is seen that when two lines are observed, acids fall into one line and amines into the other. It is not unexpected that the solvation mechanisms for these two classes of solvents would differ. It is interesting to note that all of the nitrogen containing acids are correlated reasonably well with one line for both basic and acidic solvents. Also the AHq values fall in a rather narrow range for all of the acids. From the values of p in Table 54, there appears to be little correlation between this parameter and the melting point of the acids, contrary to prior reports " ... 

INTERMOLECULAR ISOTOPE EFFECTS IN THE DECARBOXYLATION OF MALONIC ACID... 

Problem 26.11 Decarboxylation of malonic acid involves both the free acid and the monoanion, but not the doubly-charged anion, (a) Account for the ease of decarboxylation of the monoanion. Which end loses carbon dioxide (b) How do you account for the lack of reactivity of the doubly-charged anion Hint Sec Sec. 18.20.)... 

Lynn Zara, C., Jin, T., Giguere, R. J. Microwave heating in organic synthesis decarboxylation of malonic acid derivatives in water. Synth. Commun. 2000, 30, 2099-2104. 

Bronsted LFERs also apply to reactions of metal ions (Lewis acids). Dissociation rates of Ni(II) complexes are correlated with corresponding dissociation equilibrium constants. This suggests that the reactions occur by dissociative interchange, in which breakage of the Ni(II)-ligand bond predominates over formation of the Ni(II)-water bond in the rate-determining step (Hoffmann, 1981). In addition, rates of metal-catalyzed decarboxylation of malonic acid are correlated with the stability constants for the metal-malonate complexes (Prue, 1952). 

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