Enhancer Decarboxylation

Enhanced decarboxylation in polar solvents may be due to stabilization of polar transition states and/or solvent coordination to the metal (20). Coordination of solvent or ligands may aid decarboxylation by weakening metal-oxygen bonding (10). It also reduces the electrophilicity of the metal, the consequences of which are considered later. 

The potential of the microwave-enhanced decarboxylation route in the radioactive waste area is immediately apparent - washing the tritium waste with a protic solvent leads to exchange of the labile tritium. The solvent can then be used with one of the carboxylic acids mentioned above and after the microwave-enhanced decarboxylation the waste is now in the form of a solid (greatly reduced volume) which may have some further use. 

Diethyl ether has been shown to enhance decarboxylation [32] as a secondary reaction after C—O bond cleavage when the ortho and para positions are blocked. Scheme 7 shows this effect for compound 17. Some esters with the ortho and para positions free to react but with bulky substiments at the meta position also undergo decarboxylation in ether, tetrahydrofuran, and dioxane [33,34],... 

Light enhances decarboxylation activity by proteinoids, with pyruvic acid, glucuronic, acid, glyoxalic acid, citric acid or indole-3-acetic acid as substrates 22,23). In a typical experiment, 20 mg of proteinoid is incubated with 20 pmoles of radioactive substrate for 2-3 days in 10 ml of buffer pH 4.5 (or 7.0) at 37 °C, under the irradiation of a tungsten filament bulb with a filter of 10 % CuS04 solution the COa evolved is trapped as sodium carbonate 22). 

A. Wood and H. G. Hardebeck, Light Enhanced Decarboxylations by Proteinoids, in Molecular Evolution (D. L. Rohlfing and A. I. Oparin, eds.). Plenum Press, New York... 

A combination of the enhanced decarboxylation and enhanced hydrolysis rates (see Sec. 9.6) has been utilized in an improved malonic ester synthesis as formulated in equation 15.14 [42]. 

The crown ether enhanced decarboxylation of potassium salts is used to synthetic advantage in the malonic ester sequence. After traditional alkylation of malonic ester. 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

Although Ce(IV) oxidation of carboxylic acids is slow and incomplete under similar reaction conditions , the rate is greatly enhanced on addition of perchloric acid. No kinetics were obtained but product analysis of the oxidations of -butyric, isobutyric, pivalic and acetic acids indicates an identical oxidative decarboxylation to take place. Photochemical decomposition of Ce(IV) carbo-xylates is highly efficient unity) and Cu(ll) diverts the course of reaction in the same way as in the thermal oxidation by Co(IIl). Direct spectroscopic evidence for the intermediate formation of alkyl radicals was obtained by Greatorex and Kemp ° who photoirradiated several Ce(IV) carboxylates in a degassed perchloric acid glass at 77 °K in the cavity of an electron spin resonance spectro-... 

With the extraction procedure we employed (22), ferulic acid was isolated as the most inhibitory component in wheat straw. There could also be other unknown compounds in the straw which would not be evident with this procedure. In addition, we ignored the possible influence of toxin-producing microorganisms. Microorganisms may have influenced the phytotoxicity exhibited by the aqueous wheat extract in Table IX. Although the present study was not concerned with the phytotoxic effects of microbially decomposed wheat straw, an influence of microbial activity on ferulic acid phytotoxicity was observed. From the results shown in Table XI, it appears that the presence of the prickly sida seed carpel enhanced the inhibitory effects of ferulic acid. In addition to ferulic acid in test solutions containing prickly sida seeds with carpels, a second compound, 4-hydroxy-3-methoxy styrene, was also found to be present. This compound is formed by the decarboxylation of ferulic acid and was produced by a bacterium present on the carpel of prickly sida seed. The decarboxylation of ferulic acid was detected in aqueous solutions of ferulic acid inoculated with the bacterium isolated from the carpels of prickly sida seed. No conversion occurred when the bacterium was not present. 

As previous examples have shown the development of microwave-enhanced labeling technology means more than accelerating reactions - it provides alternative opportunities. It follows therefore that some previously used methods now become much more attractive and this is the case for certain aromatic decarboxylations which can now be used for tritiations as well as in the treatment of tritiated waste. In previous studies [69] of the reaction the overriding feature was the harsh experimental conditions required. 

As can be expected, the high-temperature processing runs the risk of enhancing side and consecutive reactions. Decarboxylation of the main product was found and increases with temperature (see Fig. 7). This is illustrated at the example of the synthesis of 2,4,6-trihydroxy benzoic acid from phloroglucinol, as this molecule is even more sensitive to thermal destruction due to the enhanced electron richness of the aromatic core by presence of a third hydroxyl group (Hessel et al. 2007). 

One of the earliest reports on the use of dendrimers in catalysis is the unimolecu-lar decarboxylation of 6-nitro-benzisoxazole-3-carboxylate in the presence of a dendrimer comprising ether dendrons which are functionalized at their periphery with tetra-alkylammonium cations (e.g. 20, Scheme 21) [30]. In aqueous media, the quaternary ammonium groupings promote the reactivity of organic anions which presumably bind in high concentration to the polycationic periphery of the dendrimer. The latter species enhances the rate of the bimolecular hydrolysis of p-nitrophenyl diphenyl phosphate catalyzed by o-iodosobenzoate ion. 

The unusual rate enhancement of nucleophiles in micelles is a function of two interdependent effects, the enhanced nucleophilicity of the bound anion and the concentration of the reactants. In bimolecular reactions, it is not always easy to estimate the true reactivity of the bound anion separately. Unimolecular reactions would be better probes of the environmental effect on the anionic reactivity than bimolecular reactions, since one need not take the proximity term into account. The decarboxylation of carboxylic acids would meet this requirement, for it is unimolecular, almost free from acid and base catalysis, and the rate constants are extremely solvent dependent (Straub and Bender, 1972). 

Kemp et al., 1978). The rate is slowest in an aqueous solution and is enhanced in aprotic and/or dipolar solvents. The rate augmentation of 106—108 is attainable in dipolar aprotic solvents such as dimethyl sulfoxide and hexamethylphosphoramide (HMPA). Interestingly, the decarboxylation rate of 4-hydroxybenzisoxazole-3-carboxylate [53], a substance which contains its own protic environment, is very slow and hardly subject to a solvent effect (1.3 x 10-6 s-1 in water and 8.9 x 10-6 s-1 in dimethylformamide Kemp et al., 1975). The result is consistent with the fact that hydrogen-bonding with solvent molecules suppresses the decarboxylation. 

Esters are hydrolysed under basic conditions in the presence of quaternary ammonium salts [e.g. 1-7], Microwave activation of basic soliddiquid systems without an added solvent enhances the rate of saponification and the reaction is not affected by steric factors [3], Microwave irradiation has also been used in the hydrolysis and decarboxylation of malonic esters [8] and p-keto esters [9] (>90%). Lactones... 

From the practical viewpoint, enzyme-like synthetic catalysts, or syn-zymes, need not be specific for a given reactant structure. In nature enzymes distinguish among closely related molecules and transform only the substrate for which it is specific. Mixtures of molecules may not be involved in the industrial reaction to be catalyzed. Reaction specificity is, of course, a requirement. A synthetic hydrolase should not catalyze other reactions such as decarboxylation. Enzymes bring about rate enhancements of 10 -lO. A synzyme could be of great practical importance with far less efficiency than the natural enzyme if it is cheap and stable. In other words, a near miss in an attempt to mimic enzymes could be a fabulous success. 

The Klotz group has also found rate enhancements of decarboxylation reactions with PEI derivatives. Catalysis of decarboxylation of j -keto acids by small amines goes via a Schiff base intermediate. Mine s group has shown that unmodified PEI catalyzes dedeuteration effectively and that the reactions involve Schiff base intermediates 34, and references therein). Dodecyl-PEI containing free amino groups and quaternized nitrogens, dodecyl-PEI-Q-NHj, was found to be an effective catalyst for the decomposition of oxaloacetate (reaction 12) (92). At pH 4.5 the polymer is 10 times as effective as ethylamine. was found to be 3.5 x 10 " M at pH 4.5. 

C kinetic isotope effects (A ( C)/ ( C)) are more difficult to measure accurately. The values for a variety of metal ion-catalyzed decarboxylations of oxaloacetate (2.113) are similar (1.04-1.05). This suggests that the transition state for decarboxylation (a) involves a marked breakage of the C — C bond and (b) is similar for the various metal ions, even though enhancement rates vary widely. This apparent paradox is ascribed to an alteration of the distribution of oxaloacetate between the keto and enol forms. ... 

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