Labelled carboxylic acids

It has been shown by employing the radioactive tracer method with C-labeled carboxylic acids [79] and with rotating disc electrode experiments [80] that carbo-xylates are adsorbed at the anode surface. 

With 6-alkenoic acids the intermediate radical partially cyclizes to a cyclopentyl-methyl radical in a 5-exo-trig cycHzation [139] (Eq. 6) [138 a, 140] (see also chap. 6). To prevent double bond migration with enoic acids the electrolyte has to be hindered to become alkaline by using a mercury cathode. Z-4-Enoic acids partially isomerize to -configurated products. Results from methyl and deuterium labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropyl-carbinyl radicals. The double bonds of Z-N-enoic acids with N > 5 fully retain their configuration [140]. 

Non-Kolbe electrolysis of carboxylic acids in acetonitrile/water leads to acetamides as main products [294] (Table 10). The mechanism has been investigated by using " C-labeled carboxylic acids. The results are rationalized by assuming a reaction layer rich of carboxylate resulting in the formation of a diacylamide that is hydrolyzed... 

He then reacted these derivatives with water to make labelled carboxylic acids. However, he added insufficient water for complete consumption of the starting material. At the end of the reaction, he found that the proportion of labelled molecules in the remaining starting material had decreased significantly in other words, it was no longer completely labelled with lsO some contained normal 160. 

The tetrahedral intermediate T can eliminate any one of the three -OH groups to reform either the original carboxylic acid or labeled caiboxylic acid. Further reaction of water with mono-labeled carboxylic acid leads to the doubly labeled product. 

Hydrolysis with 0H2 gives 0-labelled carboxylic acid, but no 0-labelled alcohol... 

What products are formed when the m-phenyl-labeled carboxylic acid 14-phenyltetradecanoic acid is degraded by (3-oxidation ... 

In similar fashion to the decarboxylative sulfonylation described above, the trapping of the intermediate alkyl radical by an electron-withdrawing isocyanide is a kinetically favorable process, and hydrolysis of the resultant adduct can then lead to the structure of the original carboxylic acid, thereby providing a method for the preparation of labeled carboxylic acids as indicated [25]. A disadvantage of this... 

Z-4-Enoic acids partially isomerize to -configured products. Results from methyl- and deuterium- labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropylcarbinyl radicals. The double bonds of Z-n-enoic acids with n > 5 fully retain their configuration [48]. 

We don t expect you to be satisfied with the bland statement that tetrahedral intermediates are formed in these reactions of course, you wonder how we know that this is true. The first evidence for tetrahedral intermediates in the substitution reactions of carboxylic acid derivatives was provided by Bender in 1951. He made carboxylic acid derivatives RCOX that had been labelled with an isotope of oxygen, 0. This is a non-radioactive isotope that is detected by mass spectrometry. He then reacted these derivatives with water to make labelled carboxylic acids. By any reasonable mechanism, the products would have one i 0 atom from the labelled starting material. Because the proton on a carboxylic acid migrates rapidly from one oxygen to another, both oxygens are labelled equally. 

This result cannot be explained by direct substitution of X by H2O, but is consistent with the existence of an intermediate in which the unlabelled and labelled i 0 can change places. This intermediate is the tetrahedral intermediate for this reaction. Either isomer can lose X and in each case labelled carboxylic acid is formed. 

The oxidation of primary alkyl aryl sulfones by O2 in THF resulted in formation of the corresponding carboxylic acids in fair to excellent yield in the presence of a base used for double deprotonation of the sulfones. The method was used for the convenient synthesis of C-labelled carboxylic acids. ... 

Labeled benzene ring from 1,5-dlbromldes and labeled carboxylic acid esters via cyclohexanols and cyclohexenes... 

Cyanide salts are available with either inorganic or organic cations, and a cyanide group can be conveniently prepared with radioactive " C-labeled atoms. The cyanohydrin reaction serves for the preparation of more complex " C-labeled carboxylic acids and their derivatives intended for pharmacological studies. 

Kabalka, G. W., Delgado, M. C., Sastry, U., Sastry, K. A. R. 1982. Synthesis of carbon-13 labeled carboxylic acids via organoborane reactions. J. Chem. Soc. Chem. Commun. 21 1273-1274. 

The incorporation of isotopic labels via organoboron chemistry has been the subject of previous communications from Kabalka and co-workers, and two further examples have been reported this year. For example, the preparation of primary alkylamines by the reaction of organoboranes with NH4OH, described in 1981, has now been used to give N-labelled primary amines, and C-labelled carboxylic acids are readily prepared from the reaction of organoboranes with C-enriched carbon monoxide. ... 

Related free-radical alkylation reactions include the trapping of isocyanides and the decarboxylative cyanation reaction. Both methods allow entry to the preparation of labeled carboxylic acids. 

---