Activated carboxylic acids for

V, /VCarbonyl di i m ida/.o e (CDI) 15 is another reagent to activate carboxylic acids for nucleophilic substitution at the carbonyl group.9... 

A new reagent for activating carboxylic acids for amide formation is the phosphonate (396). The azomethine imine (397), obtained from diphenyl-keten and diethyl azodicarboxylate, forms the 1,3-cyclo-adduct (398) with... 

Reactions of Isoxazoles. The chloroisoxazolium salt (483) activates carboxylic acids for condensation with alcohols and amines.The Lewis-acid-catalysed addition of ammonia to the unsaturated acid (484) yields ( )-homoibotenic acid... 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

Chirazymes. These are commercially available enzymes e.g. lipases, esterases, that can be used for the preparation of a variety of optically active carboxylic acids, alcohols and amines. They can cause regio and stereospecific hydrolysis and do not require cofactors. Some can be used also for esterification or transesterification in neat organic solvents. The proteases, amidases and oxidases are obtained from bacteria or fungi, whereas esterases are from pig liver and thermophilic bacteria. For preparative work the enzymes are covalently bound to a carrier and do not therefore contaminate the reaction products. Chirazymes are available form Roche Molecular Biochemicals and are used without further purification. 

In 2000, an efficient three-step procedure for the synthesis of 5-substituted 3-isoxazolols (without formation of undesired 5-isoxazolone byproduct) was published. The method uses an activated carboxylic acid derivative to acylate Meldrum s acid, which is treated with A,0-bis(ten-butoxycarbonyl)hydroxylamine to provide the N,0-di-Boc-protected P-keto hydroxamic acids 14. Cyclization to the corresponding 5-substituted 3-isoxazolols 15 occurs upon treatment with hydrochloric acid in 76-99% yield. 

Compound A, C/H, was found to be optically active. On catalytic reductior over a palladium catalyst, 2 equivalents of hydrogen were absorbed, yielding compound B, CyH. On ozonolysis of A, two fragments were obtained. One fragment was identified as acetic acid. The other fragment, compound C, wa an optically active carboxylic acid, C5Hl002- Write the reactions, and drav structures for A. B and C. 

Compounds 137 and 138 are thus synthons for carboxylic acids this is another indirect method for the a alkylation of a carboxylic acid, representing an alternative to the malonic ester synthesis (10-104) and to 10-106 and 10-109. The method can be adapted to the preparation of optically active carboxylic acids by the use of a chiral reagent. Note that, unlike 132, 137 can be alkylated even if R is alkyl. However, the C=N bond of 137 and 138 cannot be effectively reduced, so that aldehyde synthesis is not feasible here. ... 

The phosphinic isocyanates (116) and isothiocyanates (117) react with oxygen, nitrogen, and phosphorus nucleophiles by attack at carbon rather than phosphorus. Phenyl phosphonodichloridate has been recommended as a useful reagent for the activation (presumably by mixed anhydride formation) of carboxylic acids for conversion to amides and hydrazides. ... 

Although there were some trials to prepare optically active carboxylic acids via asymmetric decarboxylation, the optical yields of the products were not high enough for practical use. Thus, it is strongly desirable to find an enzyme which catalyzes asymmetric decarboxylation of arylmethylmalonates to give optically pure arylpropionates. 

The dinuclear iridium(l) diphosphine complexes 42 can also activate carboxylic acids easily. For example, the reaction of [IrCl(binap)]2 (42b) with an excess of acetic acid or benzoic acid in toluene at room temperature gave the corresponding (hydri-... 

The combination of carboxyl activation by DCCI and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols. The reaction proceeds at room temperature.119... 

The best yields are obtained when the ketene has an electronegative substituent, such as halogen. Simple ketenes are not very stable and must usually be generated in situ. The most common method for generating ketenes for synthesis is by dehydrohalo-genation of acyl chlorides. This is usually done with an amine such as triethylamine.167 Other activated carboxylic acid derivatives, such as acyloxypyridinium ions, have also been used as ketene precursors.168 Ketene itself and certain alkyl derivatives can be generated by pyrolysis of carboxylic anhydrides.169... 

The imidazolide group at the amino end of an amino acid is as reactive toward nucleophiles as the imidazolide group at the carboxylic end of an amino acid. If an N-protected amino acid is selected as nucleophile, this method can also be used for peptide synthesis. The amino-activated amino acids, for example N-( 1 -imidazolylcarbonyl)-amino acid esters, are prepared from a-isocyanatocarboxylic acids and imidazole. 

Owing to steric hindrance, the acylation reaction must be carried out using a large excess (4-10 Eq.) of the activated acid and for an extended period. In some cases, repeat acylation is recommended. Acylation has also been successfully carried out using Fmoc-amino acid fluorides (e.g., Fmoc-Phe-F4, 4Eq. in the presence of DIEA, 1.1 Eq. 18h >98% acylation efficiency). While acylation with unhindered activated carboxylic acids are achieved in >98%, acylation with hindered carboxylic acids generally resulted in ca. 80% efficiencies. 

For insufficiently understood reasons, there exist relatively few reports on the use of phenols and hydroxylamines as pro-moieties of active carboxylic acids. Medicinal chemists perhaps perceive these pro-moieties as potential sources of toxicity problems (see below). Furthermore, an aryl pro-moiety may unfavorably influence on solubility. 

Amino-terminated organosilanes were used to immobilize rifamycin B via its active carboxylic acid functionality leading to the formation of stable amide bonds between antibiotics and modified silica [7]. The organosilanes used were (3-aminopropyl)triethoxysilane or (3-aminopropyl)dimethylethoxysilane, and the procedure for preparation was as described in Section 2.2.1.1. Surface coverage data were not provided by the authors [7],... 

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