Symmetrical carboxylic acid

Acyl chlorides are converted in good yield into symmetrical carboxylic acid anhydrides upon treatment with dilute aqueous sodium hydroxide at -I0°C in the presence of a tetra- -butylammonium salt [76, 77]. Yields are considerably lower when Aliquat is used. In a similar manner, chloroformates and ethyl oxalyl chloride are converted into carbonic hemi-ester anhydrides. 

Table 6 Symmetrical Carboxylic Acid Anhydrides from Carboxylic Acids and Reagents (3) and (4)...

A facile one-pot procedure for the s)mthesis of symmetric carboxylic acid anhydrides utilizes tosyl chloride (0.5-0.6 equiv) in K2CO3 media under solvent-free conditions. The desired anhydrides are formed by grinding the reaction mixture for 15 5 min in a mortar. The products were isolated by stirring the reaction mixture with CH2CI2 or CHCI3 followed by filtration and concentration. ... 

Unhindered thiolesters give excellent yields of symmetrical carboxylic acid anhydrides when oxidized with ozone. However, with hindered thiolesters, mixed carboxylic acid-sulphonic acid anhydrides are obtained in good yield. Steroidal alcohols may be converted into the corresponding fluorides, albeit in variable yields, with Et2NSF3. ... 

Generally, phenyl iV-phenylphosphoramidochloridate and other very similar related organophosphorus reagents e.g. phosphorus oxychloride, phenyl dichlorophosphate, diphenylchlorophos-phate and iV,W -bis(2-oxo-3-oxazolinyl)phosphorodiamidic chloride have been utilised in recent years not only to form symmetrical carboxylic acid anhydrides but also in esterification and thiol esterification reactions although phenyl N-phenylphosphoramidochloridate is not so efficient for the latter two reactions compared to its analogs but is probably the best choice for forming the anhydride. ... 

Infrared IR spectroscopy is quite useful in identifying carboxylic acid derivatives The, carbonyl stretching vibration is very strong and its position is sensitive to the nature of IKT the carbonyl group In general electron donation from the substituent decreases the double bond character of the bond between carbon and oxygen and decreases the stretch mg frequency Two distinct absorptions are observed for the symmetric and antisym metric stretching vibrations of the anhydride function... 

The reaction is not suitable for hindered carboxylic acids, since considerable symmetrical anhydride formation (52% with pivalic acid) results. Symmetrical anhydride formation can sometimes be suppressed by the use of stoichiometric quantities of DMAP. 

Aliphatic carboxylic acids react with sulfur tetrafluonde to give, in addition to 1,1,1-trifluoromethylalkanes, considerable amounts of symmetrical bis(l,l-di-fluoroalkyl)ethers. Yields of the ethers are related to the nature of the acids and to the reaction conditions. The optimum conditions for the formation of the ethers depend on their stability in highly acidic reaction medium and on the reactivity of the acids toward sulfur tetrafluonde Simple unsubstituted acids form the ethers only at low temperatures, whereas longer chain and cycloaliphatic acids give the corresponding ethers at somewhat higher temperatures Halosubstituted acids form the ethers at the relatively high reaction temperatures necessary for these reactions to proceed [203, 204, 205] (equation 101). 

Ketones are inert to most oxidizing agents but undergo a slow cleavage reaction when treated with hot alkaline KMnO The C-C bond next to the carbonyl group is broken, and carboxylic acids are produced. The reaction is useful primarily for symmetrical ketones such as cyclohexanone because product mixtures are formed from unsymmetrical ketones. 

Kolbe electrolysis is a powerful method of generating radicals for synthetic applications. These radicals can combine to symmetrical dimers (chap 4), to unsymmetrical coupling products (chap 5), or can be added to double bonds (chap 6) (Eq. 1, path a). The reaction is performed in the laboratory and in the technical scale. Depending on the reaction conditions (electrode material, pH of the electrolyte, current density, additives) and structural parameters of the carboxylates, the intermediate radical can be further oxidized to a carbocation (Eq. 1, path b). The cation can rearrange, undergo fragmentation and subsequently solvolyse or eliminate to products. This path is frequently called non-Kolbe electrolysis. In this way radical and carbenium-ion derived products can be obtained from a wide variety of carboxylic acids. 

Table 2. Symmetrical coupling of selected carboxylic acids...

Despite of the disadvantage, that at least one symmetrical dimer is formed as a major side product, mixed Kolbe electrolysis has turned out to be a powerful synthetic method. It enables the efficient synthesis of rare fatty acids, pheromones, chiral building blocks or non proteinogenic amino acids. The starting compounds are either accessible from the large pool of fatty acids or can be easily prepared via the potent methodologies for the construction of carboxylic acids. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Carboxylic acids can be converted to symmetrical ketones by pyrolysis in the presence of thorium oxide. In a mixed reaction, formic acid and another acid heated... 

Although decarboxylation reaction seems to be a simple one-carbon removing reaction, it is demonstrated that this reaction is a unique and useful reaction in the preparation of optically active carboxylic acids. If the starting material is a racemic carboxylic acid, the optically active compound can be obtained via symmetrization by chemical carboxylation followed by asymmetrization via enzymatic reaction. Accordingly, the whole process can be said as chemicoenzymatic deracemization (Fig. 24). 

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

By use of TV-(trifluoroacetyl)- or TV-(trichloroacetyl)-imidazoleare obtained symmetric aliphatic and aromatic anhydrides even from carboxylic acids that do not form insoluble salts in benzene, ether, or THF (Table 13—1). In this case the acid is treated with the imidazolide in a 2 1 molar ratio, and an insoluble imidazolium trifluoro- or tri-chloroacetate is formed. 

In view of this finding, it was proposed (135-138) (Scheme 22) that in the case of cocaine (98) the ornithine (201) is incorporated through free putrescine (202), which is a symmetrical intermediate and therefore would afford the pyrrolinium salt 206 equally labeled at C-2 and C-5. As above, condensation of the (V-methyl-A1 -pyrrolinium salt (206) with acetyl coenzyme A leads to the coenzyme A ester of hygrine-1 -carboxylic acid (207), which by transester-... 

We reported the first synthesis of a symmetrical, four-directional, saturated hydrocarbon dendrimer containing 36 carboxylic acid moieties equidistant... 

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