Formation of Carboxylic Acid Derivatives

Hexane, CeH,4, an alkane, burns cleanly in air to give CO2 and H2O ((op). 1-Hexene, CsHu, an alkene, burns with a flame that contains soot midille). Burning o-xylene, an aromatic hydrocarbon, produces large amounts of soot bottom). 

The acyl halides are much more reactive than their parent acids. Consequently, they are often used in reactions to introduce an acyl group into another molecule. 

When an organic acid is heated with an alcohol, an equilibrium is established with the resulting ester and water. The reaction is catalyzed by traces of strong inorganic acids, such as a few drops of concentrated H2SO4. 

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Matsumura and Bousch (1966) isolated carboxy lest erase (s) enzymes from the soil fungus Trichoderma viride und a bacterium Pseudomonas sp., obtained from Ohio soil samples, that were capable of degrading malathion. Compounds identified included diethyl maleate, desmethyl malathion, carboxylesterase products, other hydrolysis products, and unidentified metabolites. The authors found that these microbial populations did not have the capability to oxidize malathion due to the absence of malaoxon. However, the major degradative pathway appeared to be desmethylation and the formation of carboxylic acid derivatives. 

The insertion of carbon monoxide into azolylpalladium complexes proceeds readily and in most cases leads to the formation of carboxylic acid derivatives or ketones. In a modified version of the carbonylation 3-bromothiophene was reacted with carbon monoxide in the presence of sodium formate. This reagents converts the intermediate acylpalladium formate complex, through the release of carbon dioxide into the acylpalladium hydride (c.f 7.47.), which in turn releases thiophene carboxaldehyde as the sole product (6.62.),92 If sodium formate was replaced... 

Tris- and tetrakis(imidazol-l-yl)silanes are effective dehydrating reagents for the formation of carboxylic acid derivatives via 1-acylimidazole intermediates <2005CL734>. 

Formation of Carboxylic Acid Derivatives 28-7 Hydrolysis of Esters... 

Side reactions such as double-bond migration and others are observed, similar to hydroformylation. Mechanistically, hydrocarboxylation is related to hydroformylation up until the metal acyl formation stage13. The presence of an acidic compound shifts the reaction towards formation of carboxylic acid derivatives and suppresses reductive elimination which forms aldehydes. The mechanism of the final steps is unclear13. 

Oxidation-Reduction Reactions 24-6 Formation of Carboxylic Acid Derivatives... 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

The kinetics of deuterium isotope exchange between diphenyl phosphine and t-butylthiol have been studied by H n.m.r. spectroscopy.274 A negative temperature coefficient was observed for the reaction of a perf1uoroalky1 phosphite with a fluorinated aldehyde.275 The kinetics for the reaction of alcohols with phosphoryl trichloride bore strong similarities to those of carboxylic acid derivatives.276 An interesting report desribed the solvolysis of ary 1 hydroxymethyl-phosphonates. It was shown that a phosphoryl group does not prevent carbocation formation on an immediately adjacent carbon atom.277... 

Formally related reactions are observed when anthracene [210] or arylole-fines [211-213] are reduced in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the yield of acylated products largely depends on the counterion of the reduced hydrocarbon species. It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the carboxylic acid by ion-pair formation. In contrast to alkylation, acylation is assumed to prefer an Sn2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species. The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [211-213]. 

Favorskii rearrangement org chem A reaction In which a-halogenated ketones undergo rearrangement in the presence of bases, with loss of the halogen and formation of carboxylic acids or their derivatives with the same number of carbon atoms. fa vor-ske, re-3 ran -m3nt)... 

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

Transacylation is the transfer of the acyl group from one G group to another, resulting in the formation of various acid derivatives. Figure 16-1 summarizes the transacylation reactions. Notice that the more reactive derivatives are convertible to the less reactive ones. Because acetic anhydride reacts less violently, it is used instead of the more reactive acetyl chloride to make derivatives of acetic acid. In aqueous acid, the four kinds of carboxylic acid derivatives in the figure are hydrolyzed to RCOOH in base, to RCOO". 

Ultraviolet irradiation of CCXLV, which is obtained by the condensation of diphenylketene and diphenyldiazomethane, in hydroxylic solvents, effects its cleavage into the starting materials in the presence of carboxylic acids or alcohols, photoaddition takes place with the formation of benzilic acid derivatives.167 On the other hand, irradiation of CCXLV in benzene containing acetic acid and/or methanol produces CCXLVI and CCXLVII, respectively. Irradiation in the presence of diphenylmethane under nitrogen atmosphere yields phenylacetic acid. 

Table 3.41. Formation of aldehydes and ketones by cleavage of carboxylic acid derivatives, alkenes, diols, and ethers.

Many of these reactions an1 reversible, but equilibrium will prefer the more stable products. In other words, since a strong base makes a poor leaving group, the equilibrium will favor the formation of the compound whose leaving group is a stronger base. This explains the order of reactivity of carboxylic acid derivatives. 

Enolates prepared by deprotonation of carboxylic acid derivatives can also undergo elimination to yield ketenes. This is rarely seen with amides, but esters, thiolesters, imides, or N-acylsulfonamides can readily decompose to ketenes if left to warm to room temperature (Scheme 5.58). At -78 °C, however, even aryl esters can be converted into enolates stoichiometrically without ketene formation [462, 463],... 

The reactivity of carboxylic acid derivatives that react with nucleophiles according to the mechanism in Figure 6.4 cannot he measured via the rate of formation of the substitution product. Instead, the decrease in the concentration of the starting material serves as a measure of the reactivity. 

NH3 or RNH2 or R2NH Amide formation from carboxylic acid derivatives (mild) or from carboxylic acids (A technical synthesis of nylon-6,6) transamidation [capro-lactame —> nylon-6 (perlon)] Peptide synthesis (Section 6.4.3)... 

The reverse reaction, i.e., the addition of water to the heterocumulene B with formation of carbonic acid derivatives A, is also known. With very few exceptions this reaction occurs spontaneously with catalysis by an acid or base. The hydration of a heterocumulene is a special example of an entire class of heterocumulene reactions, namely the addition of heteroatom nucleophiles H-Het3 (you have already come across such a reaction briefly in Section 6.1.1 in the context of the DCC activation of carboxylic acids). Occasionally, this addition... 

In all of these reactions, a nucleophile adds to a positively polarized carbonyl carbon to form a tetrahedral intermediate. There are three possible fates for the tetrahedral intermediate (1) The intermediate can be protonated, as occurs in Grignard reactions, reductions, and cyanohydrin formation. (2) The intermediate can lose water (or OH), as happens in imine and enamine formation. (3) The intermediate can lose a leaving group, as occurs in most reactions of carboxylic acid derivatives. 

Formation of Carboxylic Acids and Carboxylic Acid Derivatives 2.1.2.3.1. Aliphatic Compounds... 

At oxidation level 3, acid chlorides occupy a key position, since they may serve as a nearly universal substrate for an isohypsic transformation into any kind of carboxylic acid derivative. Acid halides are electrophiles that are synthetically equivalent to acyl cations (RCO ). In this capacity they are used for the synthesis of such important compounds as esters, amides (and hence, nitriles), thioesters, etc. (see Scheme 2.57), and for the formation of C-C bonds in the Friedel-Crafts reaction (see above). Acid chlorides may readily lose HCl upon treatment with triethylamine. This isohypsic conversion leads to ketenes, important reagents widely employed in [2 + 2] cycloadditions, as we will see later. 

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