Interesting Carboxylic Acids

Sometimes the OH absorption of a carboxylic acid is very broad, so that it is almost buried in the baseline of the NMR spectrum, making it difficult to see. 

NMR spectrum There are three signals due to three different kinds of carbon atoms. 

Several simple carboxylic acids have characteristic odors and flavors. 

Pure acetic acid is often called glacial acetic acid, because it freezes just below room temperature (mp = 17 °C), forming white crystals reminiscent of the ice in a glacier. 

Formic acid, a carboxylic acid with an acrid odor and a biting taste, is responsible for the sting of some types of ants The name is derived from the Latin word formica, meaning ant.  

Acetic acid is the sour-tasting component of vinegar. The name comes from the Latin acetum, meaning vinegar. The air oxidation of ethanol to acetic acid is the process that makes bad wine taste sour. Acetic acid is an industrial starting material for polymers used in paints and adhesives. 

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Oxidation of trialkyl borates and of trialkoxyboroxines. Trialkyl borates, B(0R)3, prepared by reaction of primary and secondary alcohols with borane-dimethyl sulfide, are oxidized by PCC to aldehydes and ketones in good yield. This indirect oxidation of alcohols does not involve formation of water, which could be detrimental in some cases. Of even greater interest, carboxylic acids can be converted into aldehydes by reaction with borane-dimethyl sulfide to form a tri-alkoxyboroxine followed by oxidation with PCC (equation I). 

Interestingly, carboxylic acids can be converted into the corresponding methylthiomethyi derivatives (169) in high yield by the addition of a solution of DMSO and r-butyl bromide to a suspension of the carboxylic acid in DMSO containing a weak base (Scheme 42). This transformation is believed to involve activation of the sulfoxide through formation of (168), followed by displacement of the f-butoxide anion by the carboxylic acid and a normal Pummerer reaction. 

More interestingly, carboxylic acids can be employed in the acylation of aromatic compounds. The acylation of toluene and anisole with C2-C42 aliphatic carboxylic acids can be carried out with CsPW, affording the corresponding products in 41%-71% yield. These solid acids are superior in activity to the conventional acid catalysts such as sulfuric acid and zeolites, and can be reused after a simple workup, albeit with reduced activity. 

Electron tunnelling tlirough monolayers of long-chain carboxylic acids is one aspect of interest since it was assumed tliat such films could be used as gate electrodes in field-effect transistors or even in devices depending on electron tunnelling [24, 26, 35, 36, 37 and 38]- It was found, however, tliat tlie whole subject depends critically on... 

Heating Kemp s acid with appropriate aromatic diamines yields bis-imides with two convergently oriented carboxylic acid groups on the edges of a hydrophobic pocket. Dozens of interesting molecular complexes have been obtained from such compounds and can be traced in the Journal of the American Chemical Society under the authorship of J. Rebek, Jr., (1985 and later e.g. T. Tjivikua, 1990 B). 

Although these humble origins make interesting historical notes m most cases the large scale preparation of carboxylic acids relies on chemical synthesis Virtually none of the 3 X 10 lb of acetic acid produced m the United States each year is obtained from vinegar Instead most industrial acetic acid comes from the reaction of methanol with carbon monoxide... 

Interest in synthetic naphthenic acid has grown as the supply of natural product has fluctuated. Oxidation of naphthene-based hydrocarbons has been studied extensively (35—37), but no commercially viable processes are known. Extensive purification schemes must be employed to maximize naphthene content in the feedstock and remove hydroxy acids and nonacidic by-products from the oxidation product. Free-radical addition of carboxylic acids to olefins (38,39) and addition of unsaturated fatty acids to cycloparaffins (40) have also been studied but have not been commercialized. 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

Finally, a new class of antispermatogenic agents containing the same fundamental structure cited above has been described (76JMC778). 1-Halobenzyl-l J/-indazole-3-carboxylic acids are potentially useful for birth control, and because they act after a single administration they are of interest for the physiological study of the male reproductive system. 

The discussion of acylation reactions in this chapter is focused on fluonnated carboxylic acid derivatives and their use to build up new fluorine-containing molecules of a general preparative interest Fifteen years ago, fluonnated carboxylic acids and their derivatives were used mainly for technical applications [/] Since then, an ever growing interest for selectively fluonnated molecules for biological applications [2, 3, 4, 5] has challenged many chemists to use bulk chemicals such as tnfluoroacetic acid and chlorodifluoroacetic acid as starting materials for the solution of the inherent synthetic problems [d, 7,, 9]... 

An interesting class ot covalent Inflates are vin l and ar>/ or heteroaryl Inflates Vinyl inflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyridine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Reactant and product structures. Because the transition state stmcture is normally different from but intermediate to those of the initial and final states, it is evident that the stmctures of the reactants and products should be known. One should, however, be aware of a possible source of misinterpretation. Suppose the products generated in the reaction of kinetic interest undergo conversion, on a time scale fast relative to the experimental manipulations, to thermodynamically more stable substances then the observed products will not be the actual products of the reaction. In this case the products are said to be under thermodynamic control rather than kinetic control. A possible example has been given in the earlier description of the reaction of hydroxide ion with ester, when it seems likely that the products are the carboxylic acid and the alkoxide ion, which, however, are transformed in accordance with the relative acidities of carboxylic acids and alcohols into the isolated products of carboxylate salt and alcohol. 

A very interesting steric effect is shown by the data in Table 7-12 on the rate of acid-catalyzed esterification of aliphatic carboxylic acids. The dissociation constants of these acids are all of the order 1(T, the small variations presumably being caused by minor differences in polar effects. The variations in esterification rates for these acids are quite large, however, so that polar effects are not responsible. Steric effects are, therefore, implicated indeed, this argument and these data were used to obtain the Es steric constants. Newman has drawn attention to the conformational role of the acyl group in limiting access to the carboxyl carbon. He represents maximum steric hindrance to attack as arising from a coiled conformation, shown for M-butyric acid in 5. 

A -Methylation of the NH of heterocycles using 1 is also known as exemplified by the methylation of indole/ The interesting mechanism is delineated below. O-methylation of weak acids such as phenols, carboxylic acids and oximes as well as 5-methylation such as A -phenylisorhodanine, certain thioketones, and dithiocarboxylic acids have also been reported." ... 

A formal Pictet-Spengler condensation to give 2,3-dihydro-lH-2-benzazepine-3-carboxylic acid 36 was achieved in quantitative yield via a sigmatropic rearrangement of ci5-2,3-methanophenylalanine 35 in the presence of paraformaldehyde and hydrochloric acid at room temperature. It is interesting to note that homophenylalanine 38 did not cyclize to give 37, even under vigorous reaction conditions. 

The methylation of 2-phenyl-/9-quinindene-9-carboxylic acid (42) takes an interesting course (see reaction scheme 42 46), In addition... 

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