Substituted carboxylic

They are easily accessible, and all possible substituted carboxylic acids are known. 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Figure 7 Free energy changes of halo-substituted carboxyl acid in aqueous solution upon deproto-nation referred to acetic acid.

The reactivity of mercury salts is a fimction of both the solvent and the counterion in the mercury salt. Mercuric chloride, for example, is unreactive, and mercuric acetate is usually used. When higher reactivity is required, salts of electronegatively substituted carboxylic acids such as mercuric trifiuoroacetate can be used. Mercuric nitrate and mercuric perchlorate are also highly reactive. Soft anions reduce the reactivity of the Hg " son by coordination, which reduces the electrophilicity of the cation. The harder oxygen anions leave the mercuric ion in a more reactive state. Organomercury compounds have a number of valuable synthetic applications, and these will be discussed in Chapter 8 of Part B. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Electrochemical fluorination of a-cyclohexenyl-substituted carboxylic (acetic, propanoic, butanoic, and pentanoic) acid esters (methyl, ethyl, and propyl) results in a series of both perfluoro-9-alkyl-7-oxabicyclo[4 3 OJnonanes and per-fluoro-8-alkoxy-9-alkyl-7-oxabicyclo[4.3.0]nonanes [<8S] (equation 19)... 

Electrochemical fluonnation ot N,N dialkylammo-substituted carboxylic acids as their methyl esters produces the analogous perfluonnated tertiary amine carboxylic acid derivatives in 18-30% yields as well as cyclic amine ethers [JOO]... 

Rearrangement of oximes to give TV-substituted carboxylic amides... 

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

The cationic species 4 thus formed reacts with water to give the iminol 5, which tautomerizes to a more stable amide tautomer, the N-substituted carboxylic amide 2. Those steps correspond to the formation of amides by the Schmidt reaction. A side reaction can give rise to the formation of nitriles. 

AryIsulfanyl)phenyl-Substituted Carboxylic Acids (Fragment C — C — Arene — S — Arene)... 

In aqueous solution especially, the current yield is distinctly lower furthermore, solubility problems can occur when the salt-deficit method is used. In aqueous solution, a-amino- or a-phenyl substituted carboxylates lead mainly to decomposition products, whilst in dry methanol or methanol-pyridine, coupling products were obtained with a-phenyl- and a-acetylaminocarboxylates [49]. 

Dimethylformamide is also a suitable solvent [50], it has, however, the disadvantage of being oxidized at fairly low potentials to A-acyloxy-iV-methyl formamide [51]. The influence of the composition of the ternary system water/methanol/dimethyl-formamide on the material and current yield has been systematically studied in the electrolysis of co-acetoxy or -acetamido substituted carboxylates [32]. Acetonitrile can also be used, when some water is.added [52]. The influence of various solvents on the ratio of Kolbe to non-Kolbe products is shown in Table 1 [53]. 

Table 6. Cross-coupling by Kolbe electrolysis of unsubstituted (A) with substituted carboxylic acids (B)...

Data for twenty-three sets of substituted carboxylic acid equilibria and six sets of rate data are available in the literature. It will be useful to consider separately the equilibrium and rate data. 

Acylamino)-substituted carboxylate esters and amides can be alkylated with good anti-2,4 stereoselectivity using two equivalents of a strong base. The stereoselectivity is independent of the steric bulk of the remainder of the carboxylate structure. Propose a TS that is consistent with these observations. 

Figure 13.10.2 The structure of a beta hydroxy acid, a substituted carboxylic acid in which the hydroxyl substituent is attached to the beta position, i.e., at a carbon atom two positions away from the carboxylic acid functionality.

F.O. Giilagar, A. Buchs, A. Susini, Capillary gas chromatography mass spectrometry and identification of substituted carboxylic acids in lipids extracted from a 4000 year old Nubian burial, Journal of Chromatography, 479, 61 72 (1989). 

As a suitable model reaction, the coupling of various substituted carboxylic acids to polymer resins has been investigated by Stadler and Kappe (Scheme 7.8) [28]. The resulting polymer-bound esters served as useful building blocks in a variety of further solid-phase transformations. In a preliminary experiment, benzoic acid was attached to Merrifield resin under microwave conditions within 5 min (Scheme 7.8 a). This functionalization was additionally used to determine the effect of micro-wave irradiation on the cleavage of substrates from polymer supports (see Section 7.1.10). The benzoic acid was quantitatively coupled within 5 min via its cesium salt utilizing standard glassware under atmospheric reflux conditions at 200 °C. 

In a more extensive study, 33 substituted carboxylic acids were coupled to chlorinated Wang resin employing an identical reaction protocol (Scheme 7.8b). In the majority of cases, the microwave-mediated conversion reached at least 85% after 3-15 min at 200 °C. These microwave conditions represented a significant rate enhancement with respect to the conventional protocol, which required 24-48 h. The microwave protocol has additional benefits in comparison to the conventional method, as the amounts of acid and base equivalents can be reduced and potassium iodide is no longer needed as an additive [28]. While no attempt was made to opti-... 

In recent years, the use of a-substituted phosphoryl compounds has mushroomed as they have become recognized as useful analogues of a-substituted carboxyl compounds (including the a-amino acids), as well as materials with their own applications. We will begin here by reviewing the well-established approaches toward such materials, specifically the Abramov and Pudovik reactions, including the associated conjugate addition reactions, and then consider the newer approaches toward such compounds. 

The previous section discussed chelation enforced intra-annular chirality transfer in the asymmetric synthesis of substituted carbonyl compounds. These compounds can be used as building blocks in the asymmetric synthesis of important chiral ligands or biologically active natural compounds. Asymmetric synthesis of chiral quaternary carbon centers has been of significant interest because several types of natural products with bioactivity possess a quaternary stereocenter, so the synthesis of such compounds raises the challenge of enantiomer construction. This applies especially to the asymmetric synthesis of amino group-substituted carboxylic acids with quaternary chiral centers. 

Oxidative Decarboxylation of a-heteroatom-substituted Carboxylic Acids... 

The syn-configuration of the resulting aldols 4i and 42 can be deduced from the coupling constants in the H-NMR spectra (4.5 Hz), and the absolute stereochemical assignments were made by degradative removal of the hydroxyl group and correlation of the resulting a-substituted carboxylic acids. 

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