Alcoholysis of 4-chloroquinolines to 4(1H)-quinolones

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

“…The transformation of quinoline 9 to quinolone 10 was very simple to execute experimentally. The 4-quinolone ethyl ester 10 precipitated in 90% yield after exposing 9 to refluxing ethanol for 24 h. When working on this transformation, we managed to isolate trace quantities of the 4-ethoxy-quinoline derivate (not shown) of 9 , hereby supporting the two-step process proposed by Heindel and Fine [33]. The N -ethyl group was introduced with Et-I under weakly basic conditions in 85% yield [36].…”

“…After exposing 4 to refluxing ethanol, the desired ethyl 4-quinolone-3-carboxylate ( 6 ) precipitated in 65% yield. The quinoline 4 to quinolone 6 transformation is a two-step process [33]. The 4-chloro substituent is displaced by ethanol giving ethyl 4-ethoxy-quinoline-3-carboxylate ( 5 , not isolated).…”

“…Heindel and Fine reported back in 1970 that 4-(1 H )-quinolones can be synthesized in a straightforward fashion by simply heating 4-chloroquinolines in ethanol [33]. This transformation is particularly well suited for 4-chloroquinolines with electron withdrawing substituents (ester and nitro) in the 3-position.…”

Synthetic Routes to Three Novel Scaffolds for Potential Glycosidase Inhibitors

“…A mechanistic rationale of this reaction consists of a nucleophilic aromatic substitution of chloride by methoxide and a subsequent S N 2 attack of chloride to yield the hydroxypyridine and methyl chloride which is converted into dimethyl ether. [31] An X-ray crystal structure analysis confirmed the constitution of 56. The following debenzylation suffered from the low solubility of 56 in most common solvents.…”

“…106°C; [α] D 21 = -20.8 (c = 2.40, in CHCl 3 ). 1 H NMR (300 MHz, CDCl 3 ): δ = 1.28 (s, 3 H, C q CH 3 ), 1.46 (s, 3 H, C q CH 3 ), 1.96 (d, J = 14.0 Hz, 1 H, 5-H a ), 2.44 (dt, J = 14.0, 7.3 Hz, 1 H, 5-H b ), 3.02 (dt, J = 8.1, 1.8 Hz, 1 H, 1-H), 3.71 (s, 3 H, OCH 3 ), 4.17 (t, J = 6.4 Hz, 1 H, 4-H), 4.52 (d, J = 5.4 Hz, 1 H, 2/3-H), 4.83 (d, J = 5.6 Hz, 1 H, 2/3-H), 5.06 (d, J = 12.5 Hz, 1 H, PhCH 2 ), 5.12 (d, J = 12.5 Hz, 1 H, PhCH 2 ), 5.73 (d, J = 6.6 Hz, 1 H, NH), 7.28-7.42 (m, 5 H, CH ar ) ppm.13 C NMR (75 MHz, CDCl 3 ): δ = 24.4,26.8 (C q CH 3 ),31.9 (C-5), 50.8 (C-1), 52.6 (OCH3 ), 57.5 (C-4), 66.8 (PhCH 2 ), 83.3, 86.4 (C-2, C-3), 111.4 [C q (CH 3 ) 2 ], 128.2 (2 C), 128.3, 128.6 (2 C, CH ar ), 136.7 (C q,ar ), 155.8 (OCONH), 176.0 (CO 2 Me) ppm. IR (KBr): ν = 3353 (s), 2988 (m), 1730 (br.…”