With Activated Carboxylic Acids

The next step is an unusual approach to making an ester via an Sn2 reaction. We usually make esters by the reaction of alcohols with activated carboxylic acid derivatives like acyl chlorides, or anhydrides as we have just seen. We do not particularly want to have to convert the carboxylic acid (X) into a more reactive... 

Dihydrotetrazines (340), which can easily be oxidized to 1,2,4,5-tetrazines, can be formed by dimerization of thiohydrazides (337) or amidrazones (338). The ring closure of hydrazidines (339) in a [5 + 1] fashion proceeds well with activated carboxylic acid derivatives such as imidates (341), orthocarboxylates (342) or dithiocarboxylates (343). The [4 + 2] procedure is found in the transformation of 1,3,4-oxadiazoles (346) or 1,4-dichloroazines (345) with hydrazine. Finally diazoalkanes (344) can be dimerized in a [3 - - 3] manner under the influence of a base the dimerization of diazoacetic ester is an early example, leading to 3,6-tetrazinedicarboxylate (48), which is frequently used in (4 -I- 2) cycloaddition reactions with inverse electron demand. Nitrile imines, reactive intermediates which are formed from many precursors, can dimerize in a [3 -I- 3] fashion to form 1,3,4,6-tetrasubstituted 1,4-dihydrotetrazines. These reactions are summarized in Scheme 57. 

Keto esters and amides are versatile intermediates in organic synthesis and often are prepared from acyl Meldrum s acid adducts. This method involves formation of acyl Meldrum s adducts by reaction of Meldrum s acid with activated carboxylic acids followed by decarboxylation in the presence of nucleophiles such as alcohols or amines (Scheme 21.2). The ability of readily available acyl Meldrum s acids to react with various nucleophiles allows quick access to a variety of functionalized compounds. Apphcation of this methodology in synthetic chemistry has been widely exploited. For example, acyl Meldrum s adducts can react with imines to prepare pyridinones or... 

Reactions with active carboxylic acid esters prepared from carbonic acid esters s. 18 434 serine peptides cf. H. Voss, Z. Naturf. 20b, 122 (1965)... 

Reactions with active carboxylic acid esters prepared... 

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... 

The cinnamyl ester can be prepared from an activated carboxylic acid derivative and cinnamyl alcohol or by transesterification with cinnamyl alcohol in the presence of the H-Beta Zeolite (toluene, reflux, 8 h, 59-96% yield). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°, 2-A h KSCN, H2O, 23°, 12-16 h, 90% yield]or by treatment with Sulfated-Sn02, toluene, anisole, reflux. The latter conditions also cleave crotyl and prenyl esters. 

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. 

Some hydroxamic acids of the isoxazole series also display a marked antituberculosis activity. The penicillin derivatives, acylated with isoxazole carboxylic acids possess an antibacterial activity similar to that of penicillin, against resistant species.Among other isoxazole derivatives possessing activity one should especially mention the sulfonamides of this series, and 4-hydroxyiminoisoxazol-5-... 

Changing the functionality on the alicyclic ring from an amine to a carboxylic acid leads to a compound that shows antiallergic activity, acting possibly by means of inhibition of the release of allergic mediators. Thus, condensation of acylated indole with cyclohexanone carboxylic acid affords directly oxarbazole (29). ... 

Within the wide range of phosphorus compounds described as activating agents for polyesterification reactions,2,310 triphenylphosphine dichloride and diphenylchlorophosphate (DPCP) were found to be the most effective and convenient ones. In pyridine solution, DPCP forms a A-phosphonium salt which reacts with the carboxylic acid giving the activated acyloxy A -phosphonium salt. A favorable effect of LiBr on reaction rate and molar masses has been reported and assumed to originate from the formation of a complex with the A-phosphonium salt. This decreases the electron density of the phosphorus atom... 

It is proposed that the boric acid reacts with the carboxylic acid to form a mixed anhydride as the actual acylating agent.913 Upon reaction with an amine, this intermediate forms the desired carboxamide and regenerates the catalytically active boric acid. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

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-... 

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