Safe and Practical Large-Scale Synthesis of 2-Aminoquinoline-6-Carboxylic Acid Benzyl Ester

Abstract

An efficient three-step sequence has been developed for the synthesis of 2-aminoquinoline-6-carboxylic acid benzyl ester starting from commercially available 6-quinolinecarboxylic acid. The process features a novel and exceptionally mild conversion of a quinoline N-oxide to a 2-aminoquinoline using a triethylamine/ammonium chloride buffered system. The development of this procedure is especially important since gaseous ammonia, ammonium hydroxide, and solutions of ammonia in alcohols all failed to deliver a safe and reliable process.

Aza-boron-diquinomethene complexes bearing N-aryl chromophores: synthesis, crystal structures, tunable photophysics, the protonation effect and their application as pH sensors

“…All the products are airstable and soluble in CH 2 Cl 2 , ethylacetate (EA), tetrahydrofuran (THF), dimethylformamide (DMF) and dimethyl sulphoxide (DMSO) in varying degrees. 1 H NMR, 13 C NMR, 19 F NMR and elemental analyses confirmed the proposed structures for all complexes except for 1a. 13 C NMR data for 1a were not obtained due to their poor solubility, although different solvents were attempted.…”

“…Chemical shifts were referred to the internal standard tetramethylsilane (TMS). 19 F NMR spectra were recorded at room temperature with CFCl 3 as the internal standard at 376 MHz. Melting points (m.p.)…”

“…1 H NMR (400 MHz, CDCl 3 ) d 8.48 (d, J = 9.6 Hz, 4H), 7.93 (d, J = 9.2 Hz, 4H), 7.84 (d, J = 2 Hz, 4H), 7.80 (d, J = 2.4 Hz, 2H), 7.78 (d, J = 2.4 Hz, 2H), 7.21 (d, J = 8.8Hz, 4H). 19 F NMR (376 MHz, CDCl 3 ) d À126.25 (q, J B,F = 78.0 Hz).…”

N-p-Toluenesulfinylimidazole: A New in situ Reagent for the Mild and Efficient Synthesis of p-Toluenesulfinate Alkyl Esters and Aryl Esters

“…The use of CDI in the formation of esters from carboxylic acids has been well documented in the chemical literature. [12][13][14][15][16][17] It is proposed that CDI might serve as an activating agent that would act on sulfinic acids 18 to create reactive sulfinylimidazoles 19 in the same fashion as CDI reacts with carboxylic acids to create acyl imidazoles 16. This pathway would be attractive in terms of the ease of formation of the sulfinylimidazole and would then presumably react to displace the labile imidazole group.…”

“…When the p-toluenesulfinic acid and CDI were combined, the reactions were noticed to undergo bubbling, presumably representing the loss of carbon dioxide via a mechanistic pathway similar to that described in the case of the reaction between carboxylic acids and CDI. [12][13][14][15][16][17] It was determined that the longer induction time was deleterious to the overall success of the reaction. When the induction time was 90 minutes (Table 1, entry 1), the ratio of product to starting material was 86:14 as determined by analysis of the 1 H NMR spectrum of the crude reaction mixture.…”