Carboxylic acids, conversion derivatives

Scheme 1.34. Formation of acyl-zirconocene derivatives by carbonylation and their conversion into aldehydes, carboxylic acids, and derivatives thereof.

Conversion of Aryl Substrates to Carboxylic Acids, Their Derivatives, Aldehydes, and Ketones 74... 

The conversion of thiol carboxylic acid 54 derived from the, vj -amide, sy -64 (Fig. (31)) to 8 was then investigated. Employing Poetsch and co-workere protocol [85] using DCC in the presence of p-TsOH in pyridine gave a moderate yield (57%) (Table 10, Entry 1). 

Conversions of Carboxylic Acids and Derivatives Esters to Acids 250, 395-397 ArC02R -+ ArC02H Amidines to Amides 242 ArN = CHNR2 —> ArNHCHO Acids to Amides 398-401 ArC02H ArCONH2... 

The decarboxylation of free carboxylic acids is often difficult except for some activated acids such as aryl carboxylic acid. Conversion of the free carboxylic acids into proper derivatives snch as acid anhydrides or esters makes the transition metal-catalysed decarboxylation reaction easy and these have also been applied to various coupling reactions. Water in a snpercritical stage (374°C, 22 MPa) was used for decarboxylation of free carboxylic acids using 10 wt% Pd on active carbon in a closed pot (Matsnbara et al., 2004) (Scheme 3.14). 

In addition to the information given in the general literature cited above, the oxidation of aldehydes has specifically been reviewed [19, 20]. The presentation here will begin with an overview of reagents that have been used for the conversion of aldehydes into carboxylic acids and derivatives thereof Subsequently, more specific oxidation reactions such as dismutations and oxidative rearrangements will be described. In the final part, oxidations of aldehyde derivatives such as acetals, oximes and hydrazones will be presented. 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Conversion of Acyl Chlorides to Other Carboxylic Acid Derivatives... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

There are ill-defined limits on EI/CI usage, based mostly on these issues of volatility and thermal stability. Sometimes these limits can be extended by preparation of a suitable chemical derivative. For example, polar carboxylic acids generally give either no or only a poor yield of molecular ions, but their conversion into methyl esters affords less polar, more volatile materials that can be examined easily by EL In the absence of an alternative method of ionization, EI/CI can still be used with clever manipulation of chemical derivatization techniques. 

The reaction of lithio derivatives with appropriate electrophiles has been utilized in the preparation of alkyl, aryl, acyl and carboxylic acid derivatives. Representative examples of these conversions are given in Scheme 79. Noteworthy is the two-step method of alkylation involving reaction with trialkylborane followed by treatment with iodine (78JOC4684). 

The six-position may be functionalized by electrophilic aromatic substitution. Either bromination (Br2/CH2Cl2/-5°) acetylation (acetyl chloride, aluminum chloride, nitrobenzene) " or chloromethylation (chloromethyl methyl ether, stannic chloride, -60°) " affords the 6,6 -disubstituted product. It should also be noted that treatment of the acetyl derivative with KOBr in THF affords the carboxylic acid in 84% yield. The brominated crown may then be metallated (n-BuLi) and treated with an electrophile to form a chain-extender. To this end, Cram has utilized both ethylene oxide " and dichlorodimethyl-silane in the conversion of bis-binaphthyl crowns into polymer-bound resolving agents. The acetylation/oxidation sequence is illustrated in Eq. (3.54). 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

For most cases, common fluoroacyl derivatives are sufficiently reactive and selective Thus conversion of perfluoroglutaric dichloride to a monomethyl ester by methanol proceeds smoothly under the appropriate reaction conditions [17] (equation 9) Perfluorosuccinic acid monoester fluoride, on the other hand, is prepared most conveniently from perfluorobutyrolacetone (equation 10) Owing to the strong acidity of a fluorinated carboxylic acids, Fischer esten-ficaiton with most aliphatic alcohols proceeds autocatalytically [79 20]... 

FIGURE 20.1 Structure, reactivity, and carbonyl-group stabilization in carboxylic acid derivatives. Acyl chlorides are the most reactive, amides the least reactive. Acyl chlorides have the least stabilized carbonyl group, amides the most. Conversion of one class of compounds to another is feasible only in the direction that leads to a more stabilized carbonyl group that is, from more reactive to less reactive. 

Non-oxidative conversion of a tetrahydro-)8-carboline into a 3,4-dihydro derivative has also been described. Dehydration of 1-hydroxymethyl-1,2,3,4-tetrahydro-j8-carboline (146) yielded 1-methyl-3,4-dihydro-j8-carboline (135). Harmaline and l-methyl-3,4-dihydro-j8-carboline-3-carboxylic acid were obtained in an analogous manner. ... 

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