Decarboxylation competing

Taken together, the various reactions and interconversions of these manganese porphyrin complexes have allowed the examination of each step in the activation of molecular oxygen by the mechanism suggested for P-450. Detailed mechanistic studies of the 0-0 bond cleavage event in 29 by kinetics, substituent effects, and product analysis showed that the reaction proceeds via heterolysis to produce 27 when acid is present, whereas homolysis is predominant in the absence of acid but in the presence of hydroxide ion (95). Under basic conditions, homo-lytic cleavage of the 0-0 bond of 29 forms Mn (=0)TMP (28) and an acyl-oxyl radical. Thus, when an alkyl peroxy acid is employed, decarboxylation competes with electron transfer, as shown in Scheme IX, to afford a mixture of 27 and 28. Yuan and Bruice have proposed a similar heterolysis mechanism based on the kinetic analysis for the reaction of mCPBA with catalytic amounts ofMn TPP(/(W). 

For the acetoxy radical, the for decarboxylation is about 6.5 kcal/mol and the rate is about 10 s at 60°C and 10 s at —80°C. Thus, only very rapid reactions can compete with decarboxylation. As would be expected because of the lower stability of aryl radicals, the rates of decarboxylation of aroyloxy radicals are slower. The rate for p-methoxybenzoyloxy radical has been determined to be 3 x 10 s near room temperature. Hydrogen donation by very reactive hydrogen-atom donors such as triethylsilane can compete with decarboxylation at moderate temperatures. 

Partenheimer showed (ref. 15) that when toluene was subjected to dioxygen in acetic acid no reaction occurred, even at 205 °C and 27 bar. He also showed that when a solution of cobalt(II) acetate in acetic acid at 113 °C was treated with dioxygen ca. 1 % of the cobalt was converted to the trivalent state. In the presence of a substituted toluene two reactions are possible formation of a benzyl radical via one-electron oxidation of the substrate or decarboxylation of the acetate ligand (Fig. 9). Unfortunately, at the temperatures required for a reasonable rate of ArCH3 oxidation (> 130 °C) competing decarboxylation predominates. As noted earlier, two methods have been devised to circumvent this undesirable... 

The next task was removal of the C3,C3 -esters. Although the palladium-catalyzed decarboxylation protocol performed well in previous systems, a competing C-H insertion reaction was discovered with the methylidene bridge needed for cercosporin (see below). Since reexamination of alternate decarboxylation methods [48] led to no success, a decarbonylation strategy was explored [49]. Formation of the requisite dialdehyde was best accomplished by overreduction using DIB AL and... 

The hydrolysis rate is measured manometrically by decarboxylating the L-tyrosine produced. The product P competes for the enzyme, thus inhibiting the hydrolysis reaction ... 

In the case of acyltellurides bearing sec- and tert-alkyl substituents, the decarboxylation of CO from the acyl radical competes with the imidoylation. Such a drawback is avoided by conducting the reaction under CO pressure (50 atm). 

Methyldopa (dopa = dihydroxy-phenylalanine), as an amino acid, is transported across the blood-brain barrier, decarboxylated in the brain to a-methyldopamine, and then hydroxylat-ed to a-methyl-NE The decarboxylation of methyldopa competes for a portion of the available enzymatic activity, so that the rate of conversion of L-dopa to NE (via dopamine) is decreased. The false transmitter a-methyl-NE can be stored however, unlike the endogenous mediator, it has a higher affinity for a2- than for ai-receptors and therefore produces effects similar to those of clonidine. The same events take place in peripheral adrenergic neurons. 

A minor route, which now accounts for 2% of phenol, takes advantage of the usual surplus of toluene from petroleum refining. Oxidation with a number of reagents gives benzoic acid. Further oxidation to p-hydroxybenzoic acid and decarboxylation yields phenol. Here phenol competes with benzene manufacture, also made from toluene when the surplus is large. The last 2% of phenol comes from distillation of petroleum and coal gasification. 

Imines from a-halo carbonyls treated with oxalyl chloride are reported to give a-halo isocyanates, which upon careful hydrolysis cyclize to l,3-oxazetidin-2-ones. However, it is difficult to tell how general such a procedure might be since decarboxylation could compete with cyclization (Scheme 69) (80S571). 

In individuals with PKU, a secondary, normally little-used pathway of phenylalanine metabolism comes into play. In this pathway phenylalanine undergoes transamination with pyruvate to yield phenylpyruvate (Fig. 18-25). Phenylalanine and phenylpyruvate accumulate in the blood and tissues and are excreted in the urine—hence the name phenylketonuria. Much of the phenylpyruvate, rather than being excreted as such, is either decarboxylated to phenylacetate or reduced to phenyllactate. Phenylacetate imparts a characteristic odor to the urine, which nurses have traditionally used to detect PKU in infants. The accumulation of phenylalanine or its metabolites in early life impairs normal development of the brain, causing severe mental retardation. This may be caused by excess phenylalanine competing with other amino acids for transport across the blood-brain barrier, resulting in a deficit of required metabolites. 

Both 2- and 3-alkoxybenzo[6 Jthiophenes may be obtained by alkylation of the appropriate hydroxy derivative, but there are competing side reactions (70AHC(11)177). 2-Methoxy-benzo[6 Jthiophene can be prepared by heating 2-bromobenzo[6 Jthiophene with sodium methoxide, and 3-methoxybenzo[7> Jthiophene is obtained by similar treatment of 3-bromobenzo[6 Jthiophene. Alkylation of 3-hydroxybenzo[6 Jthiophene-2-carboxylic ester is more efficient, giving the 3-alkoxy derivative in good yield, and this in turn can be hydrolyzed and decarboxylated in adequate yields (equation 81). 

There is some competing decarboxylation of the ethanoic acid, but the conversions in this kind of reaction are usually good. The key steps in the reaction probably are exchange of carboxylic acid groups on tetravalent lead, cleavage of the Pb-O bond to give the carboxylate radical, decarboxylation, oxidation... 

Kinetic evidence implicates a pre-association mechanism for catalysis that supports decarboxylation involving reversible formation of a complex of C02 and the carbanionic product.50 The catalyst is able to accelerate the reaction by competing for the carbanion. Such a situation would routinely be available in an enzyme active site.37 The complex cannot be observed spectroscopically because of its short lifetime and low concentration. However, catalysis after C C bond-breaking should alter the observed 12C/13C kinetic isotope effects (CKIE). 

The reactivity of enols was shown by Kresge61 to be very low with little carbanion character. Therefore, upon breaking the carbon-carbon bond in the decarboxylation of these acids, the adjacent leaving group possesses minimal carbanion character and will not be subject to significant carboxylation by carbon dioxide. Alternatively, if decarboxylation leads to the enolate, which has carbanion character, the internal return of C02 would become a competing factor. 

The resulting tetraethyl ester on hydrolysis and decarboxylation yields propane-1, 2,3-tricarboxylic acid.155 In this example the malonate anion is generated by using one molar proportion of sodium ethoxide this is Michael s original method. However, these conditions sometimes lead to competing side reactions and the formation of abnormal reaction products. Better yields of the required product are often obtained with small amounts of sodium ethoxide (the so-called catalytic method) or in the presence of a secondary amine (e.g. diethyl-amine, see below). 

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