Oxidative decarboxylation mechanism

These results are consistent with an oxidative decarboxylation mechanism for the formation of the vinyl group in (69a), and thus ketone or acrylic acid intermediates are eliminated. 

Synthetic phenol capacity in the United States was reported to be ca 1.6 x 10 t/yr in 1989 (206), almost completely based on the cumene process (see Cumene Phenol). Some synthetic phenol [108-95-2] is made from toluene by a process developed by The Dow Chemical Company (2,299—301). Toluene [108-88-3] is oxidized to benzoic acid in a conventional LPO process. Liquid-phase oxidative decarboxylation with a copper-containing catalyst gives phenol in high yield (2,299—304). The phenoHc hydroxyl group is located ortho to the position previously occupied by the carboxyl group of benzoic acid (2,299,301,305). This provides a means to produce meta-substituted phenols otherwise difficult to make (2,306). VPOs for the oxidative decarboxylation of benzoic acid have also been reported (2,307—309). Although the mechanism appears to be similar to the LPO scheme (309), the VPO reaction is reported not to work for toluic acids (310). 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

The first stage of the reaction is a special case of the oxidative decarboxylation of amino acids, for which two general mechanistic hypotheses are under discussion.This is followed by aromatiz-ation. A possible mechanism (241- 242- 243- 245) has been... 

TPP-dependent enzymes are involved in oxidative decarboxylation of a-keto acids, making them available for energy metabolism. Transketolase is involved in the formation of NADPH and pentose in the pentose phosphate pathway. This reaction is important for several other synthetic pathways. It is furthermore assumed that the above-mentioned enzymes are involved in the function of neurotransmitters and nerve conduction, though the exact mechanisms remain unclear. 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

Detailed product analyses indicate the major route of oxidation to be one of oxidative decarboxylation. The detailed mechanism is... 

For cinnamic acid at 9.6 °C, a = 0.107, b = 1.25 and k = 0.69 l.mole .sec E = 26.7 0.5 kcal.mole" and AS = 34.5 eu. Identification of products of oxidation of a number of acids indicates two concurrent mechanisms. Predominating is direct attack on the double bond to give, ultimately, cleavage products, e.g. benzaldehyde from cinnamic acid (some phenylacetaldehyde is also found, indicating oxidative decarboxylation to occur) and also acetophenone from 3-phenylcrotonic acid. 

A concerted mechanism is also possible for a-hydroxycarboxylic acids, and these compounds readily undergo oxidative decarboxylation to ketones.281... 

Where a metal has an established oxidation state two higher than the initial state, an oxidative addition (of R—C02 ) decarboxylation mechanism can be envisaged [Eq. (14)]. Decomposition of the oxidative addition... 

Ruthenium(in) catalyses the oxidative decarboxylation of n-butyric acid and isobutyric acid by ceric sulfate in aqueous acid. A mechanism for the Ru(III)-catalysed oxidation of o-hydroxybenzoic acid by an acidic solution of bromamine-B (PhS02-NNaBr, BAB) has been proposed based on a kinetic smdy. An ionic mechanism is suggested for the ruthenium(III) analogue of the Udenfriend-type system Ru(III)-EDTA-ascorbate-02, for the selective oxygen-atom transfer to saturated and unsaturated hydrocarbons. The kinetics of the oxidation of p-XC6H4CHPhOH(X =... 

The mechanism of metabolic degradation of indol-3-ylacetic acid (39) is a matter of debate. A possible route demonstrated in vitro includes oxidative decarboxylation to skatolyl hydroperoxide (40), catalyzed by horseradish peroxidase isoenzyme C (HRP-C), followed by rearrangement to 3-(hydroxymethyl)oxindole (41), as shown in equation 12 . 

MECHANISM FIGURE 16-11 Isocitrate dehydrogenase. In this reaction, the substrate, isocitrate, loses one carbon by oxidative decarboxylation. In step (T), isocitrate binds to the enzyme and is oxidized by hydride transfer to NAD+ or NADP+, depending on the isocitrate dehydrogenase isozyme. (See Fig. 14-12 for more information on hydride transfer reactions involving NAD+ and NADP+.) The resulting... 

One of the first persons to study the oxidation of organic compounds by animal tissues was T. Thunberg, who between 1911 and 1920 discovered about 40 organic compounds that could be oxidized by animal tissues. Salts of succinate, fumarate, malate, and citrate were oxidized the fastest. Well aware of Knoop s (3 oxidation theory, Thunberg proposed a cyclic mechanism for oxidation of acetate. Two molecules of this two-carbon compound were supposed to condense (with reduction) to succinate, which was then oxidized as in the citric acid cycle to oxaloacetate. The latter was decarboxylated to pyruvate, which was oxidatively decarboxylated to acetate to complete the cycle. One of the reactions essential for this cycle could not be verified experimentally. It is left to the reader to recognize which one. 

The reactions enclosed within the shaded box of Fig. 17-14 do not give the whole story about the coupling mechanism. A phospho group was transferred from ATP in step a and to complete the hydrolysis it must be removed in some future step. This is indicated in a general way in Fig. 17-14 by the reaction steps d, e, and/. Step/represents the action of specific phosphatases that remove phospho groups from the seven-carbon sedoheptulose bisphosphate and from fructose bisphosphate. In either case the resulting ketose monophosphate reacts with an aldose (via transketolase, step g) to regenerate ribulose 5-phosphate, the C02 acceptor. The overall reductive pentose phosphate cycle (Fig. 17-14B) is easy to understand as a reversal of the oxidative pentose phosphate pathway in which the oxidative decarboxylation system of Eq. 17-12 is... 

In contrast, the sex pheromone of the female housefly is (Z)-9-tricosene, a hydrocarbon apparently formed by an oxidative decarboxylative process from a precursor aldehyde by an enzyme that requires NAD-PH and 02 and is apparently a cytochrome P450.140 Oxidative deformylation by a cytochrome P450 converts aldehydes to alkenes, presumably via a peroxo intermediate.117 Formation of an alkene by decarboxylation has also been proposed,141 but a mechanism is not obvious. 

The persulfate ion S2OI-, with or without various transition metal ions, is a particularly effective oxidant, especially for the decarboxylation of carboxylic acids.535 In the presence of silver(I), persulfate oxidation to silver(II) readily occurs and for aliphatic carboxylic acids the decarboxylation mechanism given in Scheme 4 has been established. The aliphatic radicals produced may then disproportionate, abstract hydrogen or be further oxidized to an alcohol. In... 

One of the important mechanistic uses of isotopic substitution is that it can selectively affect different steps in a stepwise mechanism and so help resolve mechanisms and pathways. For example, in reactions where there is hydride transfer coupled to C—C bond formation, the measurement of both 13C/12C and D/H kinetic isotope effects can distinguish whether the steps are concerted or stepwise. Consider, for example, the oxidative decarboxylation of malate catalyzed by the malic enzyme, which could occur either via an intermediate mechanism (2.81) or in a concerted mechanism (2.82).59... 

Oxidation of oxalic acid with dimethyl-V,V-dichlorohydantoin and dichloroisocya-nuric acid is of first order with respect to the oxidant. The order with respect to the reductant is fractional. The reactions are catalysed by Mn(II). Suitable mechanisms are proposed.129 A mechanism involving synchronous oxidative decarboxylation has been suggested for the oxidation of a-amino acids with l,3-dichloro-5,5-dimethylhydantoin.130 Kinetic parameters have been determined and a mechanism has been proposed for the oxidation of thiadiazole and oxadiazole with trichloroiso-cyanuric acid.131 Oxidation of two phenoxazine dyes, Nile Blue and Meldola Blue, with acidic chlorite and hypochlorous acid is of first order with respect to each of the reductant and chlorite anion. The rate constants and activation parameters for the oxidation have been determined.132... 

Many desirable meat flavor volatiles are synthesized by heating water-soluble precursors such as amino acids and carbohydrates. These latter constituents interact to form intermediates which are converted to meat flavor compounds by oxidation, decarboxylation, condensation and cyclization. 0-, N-, and S-heterocyclics including furans, furanones, pyrazines, thiophenes, thiazoles, thiazolines and cyclic polysulfides contribute significantly to the overall desirable aroma impression of meat. The Maillard reaction, including formation of Strecker aldehydes, hydrogen sulfide and ammonia, is important in the mechanism of formation of these compounds. 

Although the mechanism of the transformation of single into double bonds has not been investigated in detail, a heteroatom attached to the single bond is necessary for an efficient introduction of the double bond. Trisubstituted pyrazo-lines 46 can be oxidized with (diacetoxyiodo)benzene 3 to the corresponding pyrazoles 47 in good yields [98]. Two double bonds can be introduced in easy accessible proline derivatives 48 [99] by an oxidative decarboxylation with [bis(trifluoroacetoxy)iodo]benzene 4 yielding tetrasubstituted pyrroles of type 49, Scheme 22 [100]. 

This mechanism is consistent with a number of observations. Kinetic studies on prolyl 4-hydroxylase [223] and thymine hydroxylase (EC 1.14.11.6) [224] suggest that cofactor binds first, followed by 02. The bound 02 appears to have superoxide character, as superoxide scavengers are competitive inhibitors of 02 consumption [225,226], It is also clear that the oxidative decarboxylation of the keto acid is a distinct phase of the mechanism from the alkane functionalization step, as these two phases can be uncoupled, particularly when poor substrate analogs are employed [227-229], Evidence for an Fe(IV) = 0 intermediate derives from studies with substrate analogs. Besides the hydroxylation of the 5-methyl group of thymine, thymine hydroxylase can also catalyze ally lie hydrox-ylations, epoxidation of olefins, oxidation of sulfides to sulfoxides, and N-de-... 

Recent model studies strongly support the proposed mechanism. The first crystal structures of Fe(II) complexed to benzoylformate show that an a-keto acid can coordinate to the iron as either a monodentate or didentate ligand [236]. Exposure of these [Fe(II)(L)(bf)]+ complexes (L = tmpa or 6-Me3-tmpa) to 02 results in the quantitative conversion of benzoylformate to benzoic acid and C02, modeling the oxidative decarboxylation reaction characteristic of this class of enzymes. As with the enzymes, the use of 1802 in the model studies results in the incorporation of the label into the benzoate product. For [Fe(6-Me3-tmpa)(bf)]+, the rate of the oxidative decarboxylation increases as the substituent of the benzoylformate becomes more electron-withdrawing, affording a Hammett p of +1.07. This suggests that the oxidative decarboxylation involves a nucleophilic attack, most plausibly by the iron-bound 02, on the keto carbon of benzoylformate to initiate decarboxylation as proposed in Figure 27. 

Answer Oxidative decarboxylation involving NADP+ or NAD+ as the electron acceptor the a-ketoglutarate dehydrogenase reaction is also an oxidative decarboxylation, but its mechanism is different and involves different cofactors TPP, lipoate, FAD, NAD+, and CoA-SH. 

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