Synthesis and spectroscopic properties of a series of novel 2-aryl-3-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones

Abstract

A series of thirteen novel 2-aryl-3-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thiosalicylic acid. The spectroscopic and physical properties are reported and discussed.1 H-19 F and 13 C-19 F couplings were observed in the NMR spectra of fluorinated compounds. Through-space interactions were observed in the 1 H and 13 C NMR spectra of the ortho-nitro compound. Trends were observed in the IR and UV absorptions of the ortho/meta/para-nitro series.

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

“…The condensation of 1 equivalent thiosalicylic acid 5 with 1 equivalent imines 2a-h and 2j-m was performed in the same manner as previously reported, [14][15][16][20][21][22][23] using T3P as a promoter and pyridine as a base in 2-methyltetrahydrofuran at RT (Scheme 1). The reaction is operationally simple and does not require dry solvents.…”

“…Yields of recrystallized compounds 1b-m were modest, ranging from 17% to 43% and averaging 31% (Table 1) but are similar to those observed in the 2-aryl-3-phenyl series (12%-43%, average 29%). [16] The one example of an N-aryl compound prepared by Kitsiou et al was done using 1.2 equivalents thiosalicylic acid, and the product was not recrystallized. [24] The lowest yield was of compound 1j, which gave a good yield of product from chromatography, but whose recrystallization proved difficult, and ultimately a poor recovery was realized.…”

“…A series of novel 3-aryl-2-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones has been synthesized in modest yields from N-aryl-C-phenyl imines using the T3P/pyridine method. [14][15][16][20][21][22][23] The para-nitro compound 1a did not form, presumably because the imine nitrogen was not nucleophilic enough. Combined with our prior results using C-aryl-N-phenyl imines, [16] it has been demonstrated that a wide range of 2,3-diaryl-2,3-dihydro-4H-1,3-benzothiazin-4-ones can be readily accessed by this chemistry.…”

“…[18] T3P has several advantages over other amide-forming reagents, including that the byproducts are water soluble and easily removed, the reagent is safe, and in combination with pyridine epimerization at the carbon alpha to the carboxylic acid is minimized. [19] We have demonstrated that 1i and other Naryl-2,3-dihydro-4H-1,3-benzothiazin-4-ones can be successfully prepared using T3P and pyridine at room temperature (RT), [14][15][16][20][21][22][23] including the preparation of a series of 2-aryl-3-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones, where substituents were varied on the aryl ring which is attached to the 2-position of the heterocycle. [16] Kitsiou et al [24] and Unsworth et al [25] have reported similar chemistry for the reaction of imines with thiosalicylic acid (T3P, DIPEA, 90 C), but only one example had an N-aryl group, and the yield was notably lower than the N-alkyl examples (53%, compared with 99% for a similar N-alkyl), which again shows the difficulty of N-aryls.…”

“…[19] We have demonstrated that 1i and other Naryl-2,3-dihydro-4H-1,3-benzothiazin-4-ones can be successfully prepared using T3P and pyridine at room temperature (RT), [14][15][16][20][21][22][23] including the preparation of a series of 2-aryl-3-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones, where substituents were varied on the aryl ring which is attached to the 2-position of the heterocycle. [16] Kitsiou et al [24] and Unsworth et al [25] have reported similar chemistry for the reaction of imines with thiosalicylic acid (T3P, DIPEA, 90 C), but only one example had an N-aryl group, and the yield was notably lower than the N-alkyl examples (53%, compared with 99% for a similar N-alkyl), which again shows the difficulty of N-aryls. [24] Herein, we report the further exploration of the scope of this reaction by preparing a series of 3-aryl-2-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones in which various substituents are on the aryl ring which is attached to the 3-position (the nitrogen) of the heterocycle.…”