Carboxylic acids from formate isomerization

Such an easy isomerization of acetylenylbenzoic acid amides implies the formation of a five-membered nonaromatic ring condensed with the pyrazole ring. However, the pyrazole analog of o-iodobenzamide (amide of 4-iodo-l-methylpyrazole-3-carboxylic acid) formed under heating with CuC=CPh in pyridine for 9 h only the disubstituted acetylene in 71 % yield is identical in all respects to the compound obtained from the corresponding acid by successive action of SOCI2 and NH3 (90IZV2089) (Scheme 126). 

Apart from the isomeric relation between 7 and 1, the appearence of the ternary associate now showing coordinatoclathrate properties gives a reasonable motive for putting up these compounds for discussion here. The dimer formation of carboxylic acids known from the related inclusions of 1 and 26 does not occur here. Instead, one observes a well-balanced system of H-bonds between groups of different acid/base properties. It is left to future studies to find other acid/base combinations which give a comparable situation. Actually, such H-bonded systems remind one of the multiple non-bonded interactions at the active centers of enzymes. 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

Hydroperoxide formation is characteristic of alkenes possessing tertiary allylic hydrogen. Allylic rearrangement resulting in the formation of isomeric products is common. Secondary products (alcohols, carbonyl compounds, carboxylic acids) may arise from the decomposition of alkenyl hydroperoxide at higher temperature. 

In ergosterol biosynthesis, side chain alkylation of lanosterol normally takes place to build 24-methylenedihydrolanosterol, which itself is then the substrate for demethylation reactions at and C. The C -demethylation has been studied in detail. It is an oxidative demethylation catalyzed by a cytochrome P -system. The first step involved in this reaction is the hydroxylation of the Cj -methy1-group to form the C -hydroxymethyl derivative. A second hydroxylation and loss of water lead to the C -formyl intermediate, which is hydroxylized a third time to form the corresponding carboxylic acid. Decarboxylation does not directly take place, but proceeds instead by abstraction of a proton from C, followed by elimination and formation of a A 4-double bond. The NADPH-dependent reduction of the A14 -double bond finishes the demethylation reaction. Subsequently, demethylation at has to take place twice, followed by a dehydrogenation reaction in A" -position and isomerization from A8 to A7 and A24(28) to A22. respectively. 

Formation of 1,1,4-trimethylcycloheptane from car-3-ene depends on two properties of palladium, the strong tendency of palladium to promote isomerization and to hydrogenolyze vinylcyclopropane systems. In the bicyclic unsaturated acid, IV, prior isomerization is not necessary to move the double bond into conjugation, yet here, too, platinum and palladium give quite different results. The saturated bicyclic acid is formed over platinum, whereas over palladium a mixture of cyclohexane-carboxylic acid and benzoic acid results through hydrogenolysis and disproportionation (20). 

Mechanistic studies of the pyrolysis of disodium peifluoropentanedioate and derivatives have shown that the acid fluorides are formed during the reaction. The formation of dienes from the salts of halogcnalcd carboxylic acids with a terminal C = C bond is also possible. The thermal decomposition of sodium (Z)-6//-perfluoro 6-chlorohex-5-cnoate) gives (Z)-l//-perfluoro(l-chloropenta-l,4-diene) (7) in 75% yield.The decarboxylation of potassium 5H-pcrfluoropcnt-4-enoate, however, gives 1//-perfluorobut-2-yne (8) via the isomerization of the intermediate butadiene by potassium fluoride. ... 

Treatment of dehydrooxoheteratisine (CD) with potassium tert-butoxide in feri-butanol leads to the y-lactone carboxylic acid, characterized as its methyl ester (CDXIV) [1787 cm i, (y-lactone), 1748 cm (cyclopentanone), 1728 cm i (C02Me, 1648 cm i (S-lactam)]. Its formation by cleavage of the initial retroaldol product (CDXII) to a S-lactone carboxylic acid (CDXIII) and subsequent isomerization to the y-lactone provides decisive proof for location of the tertiary hydroxyl at a position j8 to both the cyclopentanone and S-lactone carbonyls and four carbons removed from the S-lactone ether oxygen. 

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