Carboxylic derivs., reactions acid hydrolysis

Carboxylic derivs., reaction, 230-244 acid hydrolysis, 240, base hydrolysis, 238 electronic effects in, 237 Grignard reagents, 238... 

Reaction of 2-aminoquinoline derivatives with BrCH2C0C02Et gave imidazoquinoline-2-carboxylate 473 which upon hydrolysis with sodium hydroxide gave the corresponding acid which had been tested against the passive cutaneous anaphylaxis (78GEP2802493, 78BEP858605) (Scheme 79). 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

Poly(methyl 3-(l-oxypyridinyl)siloxane) was synthesized and shown to have catalytic activity in transacylation reactions of carboxylic and phosphoric acid derivatives. 3-(Methyldichlorosilyl)pyridine (1) was made by metallation of 3-bromopyridine with n-BuLi followed by reaction with excess MeSiCl3. 1 was hydrolyzed in aqueous ammonia to give hydroxyl terminated poly(methyl 3-pyridinylsiloxane) (2) which was end-blocked to polymer 3 with (Me3Si)2NH and Me3SiCl. Polymer 3 was N-oxidized with m-ClC6H4C03H to give 4. Species 1-4 were characterized by IR and H NMR spectra. MS of 1 and thermal analysis (DSC and TGA) of 2-4 are discussed. 3-(Trimethylsilyl)-pyridine 1-oxide (6), l,3-dimethyl-l,3-bis-3-(l-oxypyridinyl) disiloxane (7) and 4 were effective catalysts for conversion of benzoyl chloride to benzoic anhydride in CH2Cl2/aqueous NaHCC>3 suspensions and for hydrolysis of diphenyl phosphorochloridate in aqueous NaHCC>3. The latter had a ti/2 of less than 10 min at 23°C. 

The final coupling reaction of l-cyclopropyl-6-fluoro-7-chloro-l,4-dihy-dro-4-oxo-l,8-naphthyridine-3-carboxylic acid (7a) and 4-( er -butoxycarbo-nylaminomethyl)pyrrolidin-3-one-0-methyloxime (15a) proceeds according to the methods described by Sanchez et al. [13], Domogala et al. [16], and Kimura et al. [17], followed by acid hydrolysis to afford gemifloxacin, 7 - (4 - (aminomethyl) - 3 - (methoxyimino)pyrrolidin -1 - yl) -1 - cyclopropyl - 6 -fluoro-4-oxo-l,4-dihydro[l,8]naphthyridine-3-carboxylic acid and other corresponding derivatives, according to Scheme 5. 

An enolate anion generated from a carboxylic acid derivative may be used in the same sorts of nucleophilic reactions that we have seen with aldehyde and ketone systems. It should be noted, however, that the base used to generate the enolate anion must be chosen carefully. If sodium hydroxide were used, then hydrolysis of the carboxylic derivative to the acid (see Section 7.9.2) would compete with enolate anion formation. However, the problem is avoided by using the same base, e.g. ethoxide, as is present in the ester... 

Procedures A and B illustrate the two current methods for preparation of N-9-phenylfluoren-9-yl derivatives of amino acids and amino acid esters. Free carboxylate (as in alanine in Step A) or free hydroxyl (e.g., serine7) functions can be blocked for the duration of the reaction as trimethylsilyl (TMS) esters or ethers, respectively, by treatment with chlorotrimethylsilane and triethylamine. The TMS group(s) are then removed by methanolysls from carboxylic acids (as in Step A) and mild acidic hydrolysis from hydroxyl groups, both being accomplished during product isolation. In addition to 2, the N-9-phenylfluoren-9-yl derivatives of serine,7 glutamic add y-methyl ester,8 and aspartic acid 3-methyl ester3 9 have been prepared in this manner. 

While this reaction is substantially exothermic (6), it provides an intriguing approach to the production of fuels from renewable resources, as the required acids (including acetic acid, butyric acid, and a variety of other simple aliphatic carboxylic acids) can be produced in abundant yields by the enzymatic fermentation of simple sugars which are, in turn, available from the microbiological hydrolysis of cellulosic biomass materials ( ] ) These considerations have led us to suggest the concept of a "tandem" photoelectrolysis system, in which a solar photoelectrolysis device for the production of fuels via the photo-Kolbe reaction might derive its acid-rich aqueous feedstock from a biomass conversion plant for the hydrolysis and fermentation of crop wastes or other cellulosic materials (4). 

Theoretical studies have been reported for the neutral29 and alkaline30,31 hydrolysis of formamide. A theoretical study of the acid hydrolysis of iV-formylaziridine concluded that both N- and O-protonated pathways compete.32 In an historical overview of tetrahedral intermediates in the reactions of carboxylic acid derivatives with nucleophiles, several citations of amide reactions are included.33... 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

The enzymatic role of the thieno[3,4-d]imidazole derivative biotin as the coenzyme for the transfer of carbon dioxide in carboxylation reactions is well established. Strong acidic hydrolysis of biocytin, a naturally occurring complex of biotin, yields biotin and L-lysine. 

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