T3P‐promoted synthesis of a series of novel 3‐aryl‐2‐phenyl‐2,3‐dihydro‐4H‐1,3‐benzothiazin‐4‐ones

Abstract

A series of 11 novel 3‐aryl‐2‐phenyl‐2,3‐dihydro‐4H‐1,3‐benzothiazin‐4‐ones was prepared at room temperature by T3P‐mediated cyclization of N‐aryl‐C‐phenyl imines with thiosalicylic acid. This provides simple and ready access to N‐aryl compounds in this family, which have been generally difficult to prepare.

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

“…Typical conditions for 1 H acquisition were 2 s relaxation delay, acquisition time of 4.089 s, spectral width of 8 kHz, 16 scans. Spectra were zero-filled to 128k points, and multiplied by exponential multiplication (EM with LB = 0.3 Hz) prior to FT. For 13 C experiments, data were acquired with power-gated 1 H decoupling using a 2 s relaxation delay, with acquisition time of 1.1 s, spectral width of 29.8 kHz, and 256 scans. Spectra were zero-filled once, and multiplied by EM with LB = 2 Hz prior to FT. 19 F NMR data were acquired with acquisition time of 0.58 s, spectral width of 240 ppm, 32 scans, and relaxation delay of 2 s. Exact mass of synthesized compounds was determined LC- (10 4 ) are represented by 0, and are not shown on the graph.…”

“…Infrared spectra of 1a, 1b, 1c, 1d, 1i, 1k, and 1m were run on another Thermo-Fisher NICOLET iS50 FT-IR using a diamond-ATR attachment for direct powder analysis (Penn State Schuylkill). 1 H, 13 C NMR, and 19 F NMR experiments (Penn State's shared NMR facility, University Park) were carried out on a Bruker Avance-III-HD 500.20-MHz ( 1 H frequency) instrument using a 5 mm Prodigy (liquid nitrogen cooled) BBO BB-1H/19F/D Z-GRD cryoprobe. Samples were dissolved in CDCl 3 and analyzed at RT.…”

“…A common method used for preparation of a variety of 2,3-dihydro-4H-1,3-thiazin-4-ones is the cyclization of an imine with a 3-thiocarboxylic acid [11]. However, it is known that N-aryl imines are less reactive in the preparation of similar 2,3-dihydro-4H-1,3-thiazin-4-ones than N-alkyl imines [12][13][14]. Furthermore, Dandia et al reported in 2004 that reaction of N-aryl imines with thionicotinic acid (2-mercaptopyridine-3-carboxylic acid) 3 by thermal methods with various catalysts and solvents failed, which they attributed to the "low reactivity" of 3 [9].…”

“…Where both of these methods involved specialized equipment (microwave oven, ultrasonic processor) and high temperature, we have previously reported simple, room temperature synthesis of various 2,3-diaryl-2,3-dihydro-4H-1,3-thiazin-4-ones [5,[12][13][14], including a few 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones [4,5,15], using amide coupling agent 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (T3P). T3P has several advantages over other amide-forming reagents, including that the reagent is safe, the by-products are water soluble and easily removed, and in combination with pyridine epimerization at the carbon alpha to the carboxylic acid is minimized [16].…”

“…mp: 142.6-143.5 • C. 1 H NMR (CDCl 3 ): δ(ppm): δ 8.53 (dd, 3 J HH 4.8, 4 J HH 1.9 Hz, 1H, para to pyridine N), 8.48 (dd, 3 J HH 7.9, 4 J HH 1.9 Hz, 1H, ortho to pyridine N), 7.63 (s, 1H, Ar), 7.47-7.37 (m, 4H, Ar), 7.34 (d, 3 J HH 9.0 Hz, 3H, Ar), 7.24 (dd, 3 J HH 7.9, 4.8 Hz, 1H, meta to pyridine N), 7.18 (t, 3 J HH 7.9 Hz, 1H, Ar), 6.12 (s, 1H, C2-H). 13…”