IIIB.3. Present Work
III.4. Experimental Section
III.4.1. General information.
All the reagents were commercial grade and purified according to the established procedures. Organic extracts were dried over anhydrous sodium sulphate. Solvents were removed in a rotary evaporator under reduced pressure. Silica gel (60-120 mesh size) was used for the column chromatography. Reactions were monitored by TLC on silica gel 60 F254 (0.25mm).NMR spectra were recorded in CDCl3 with tetramethylsilane as the internal standard for 1H NMR (400 MHz) CDCl3 solvent as the internal standard for 13C NMR (100 MHz). MS spectra were recorded using ESI mode. IR spectra were recorded in KBr or neat. The 2-arylbenzothiazoles were prepared from corresponding N- phenylbenzothioamides using hypervalent iodine mediated oxidative cyclization following the reported procedure.26a The 2-arylbenoxazoles were prepared from corresponding ortho-halobenzanilides via ligand-accelerated copper-catalyzed cyclizations.26b3,5-Diarylisoxazoles were prepared by the method of click chemistry using phenyl acetylene derivatives with substituted aldoximes.26c
III.4.2. Crystallographic description
IIIA.4.2:
CCDC number for compounds 1a and 8a: CCDC 889591 and 889592. This data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif.
Crystallographic description of 1a: Crystal dimension (mm): 0.32 x 0.28 x 0.26.
C20H13NOS, Mr = 315.38. Triclinic, space group P-1; a = 7.300(2) Å, b = 10.932(3) Å, c = 11.142(2) Å; α = 118.643(14)o, β = 96.025(17) o, γ = 94.158(18)o, V =
collected / unique = 3894 / 2438; Refinement method = Full-matrix least-squares on F2; Final R indices [I>2σl ] R1 = 0.1103, wR2 = 0.2606, R indices (all data) R1 = 0.1315, wR2 = 0.2739; goodness of fit = 1.477.
Crystallographic description of 8a: Crystal dimension (mm): 0.30 x 0.26 x 0.24.
C20H12FNOS, Mr = 333.38. Triclinic, space group P-1; a = 7.5170(7) Å, b = 8.8619(8) Å, c = 12.8151(11) Å; α = 86.442(7)o, β = 74.225(7)o, γ = 81.160(7)o, V
= 811.58(13) Å3; Z = 2; ρcal = 1.364 g/cm3; µ (mm-1) = 0.215; F (000) = 344.0;
Reflection collected / unique = 3952 / 2849; Refinement method = Full-matrix least- squares on F2; Final R indices [I>2σl ] R1 = 0.0441, wR2 = 0.1070, R indices (all data) R1 = 0.0609, wR2 = 0.1181; goodness of fit = 1.024.
IIIB.4.2
CCDC number for compounds 1''b and 1''j: CCDC 945395 and 945394. This data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif.
Crystallographic description of 1''b: Crystal dimension (mm): 0.38 x 0.28 x 0.24.
C23H17NO3, Mr = 355.38 Triclinic, space group P -1; a = 8.8993 (11) Å, b = 10.4759 (13) Å, c = 11.0032 (14) Å; α = 70.634 (7)o, β = 72.001 (5) o, γ = 73.148 (7)o, V = 900.14 (19) Å3; Z = 2; ρcal = 1.311 mg/m3; µ (mm-1) = 0.087; F (000) = 372.0;
Reflection collected / unique = 2964 / 2188; Refinement method = Full-matrix least- squares on F2; Final R indices [I>2σl ] R1 = 0.1770, wR2 = 0.4251, R indices (all data) R1 = 0.1980, wR2 = 0.4315; goodness of fit = 1.131.
Crystallographic description of 1''j: Crystal dimension (mm): 0.54 x 0.42 x 0.30.
C24H17NO4, Mr = 241.31. triclinic, space group P -1; a = 6.2208 (3) Å, b = 12.7931 (5) Å, c = 13.3551 (5) Å; α = 113.491 (2)o, β = 91.551 (2) o, γ = 97.433 (2)o, V = 962.95 (7) Å3; Z = 2; ρcal = 1.322 mg/m3; µ (mm-1) = 0.091; F (000) = 400.0;
Reflection collected / unique = 1645 / 1333; Refinement method = Full-matrix least- squares on F2; Final R indices [I>2σl ] R1 = 0.0338, wR2 = 0.0825, R indices (all data) R1 = 0.0441, wR2 = 0.0893; goodness of fit = 1.070.
III.4.3. Synthesis of o-aroylated 2-arylbenzothiazole and 3,5- diarylisoxazole
IIIA.4.3. General procedure for the synthesis of (2-(benzo[d]thiazol-2- yl)phenyl)(phenyl)methanone (1a) from 2-phenylbenzothiazole (1): An oven- dried flask was charged with Pd(OAc)2 (0.011 g, 0.05 mmol), benzaldehyde (0.127 g, 1.2 mmol), 2-phenylbenzo[d]thiazole (1) (0.211 g, 1.0 mmol), and toluene (2 mL).
TBHP (1.5 mmol) was added in 5 lots over a period of 5 hrs. Then the reaction vessel was kept in an oil bath preheated to 110 oC and allowed to stir for the stipulated period of time. The progress of the reaction was monitored by TLC. The reaction mixture was then cooled and admixed with water (5 mL). The product was extracted with ethyl acetate (3 x 10 mL) and the combined organic layer was washed with saturated sodium bicarbonate (NaHCO3) solution. Organic layer was dried over anhydrous sodium sulphate (Na2SO4), and evaporated under reduced pressure. The crude product so obtained was further purified through silica gel column chromatography (hexane / ethyl acetate, 10:0.7) to yield the pure (2-(benzo[d]thiazol- 2-yl)phenyl)(phenyl)methanone (1a) (0.236 g, yield 75%). The identity and purity of the product was confirmed by spectroscopic analysis. The same procedure was also followed for o-aroylation of other substituted benzothiazole (2-9) benzoxazole (1'- 10') derrivatives with various aldehydes (a-s).
IIIB.4.3. General procedure for the synthesis of phenyl(2-(5-phenylisoxazol- 3-yl)phenyl)methanone (1''a) from 3,5-diphenylisoxazole (1''): An oven-dried flask was charged with Pd(OAc)2 (0.022 g, 0.10 mmol), benzaldehyde (0.127 g, 1.2 mmol), 3,5-diphenylisoxazole (1'') (0.221 g, 1.0 mmol) and 1,2-dichloroethane DCE (2 mL). The reaction vessel was then subjected to reflux in an oil bath preheated to 110 oC and stirring was maintained for the stipulated period of time. TBHP (1.2 mmol) was then added in 4 equal portions over a period of 12 h. The progress of the reaction was monitored by TLC. The reaction mixture was then cooled and admixed with water (5 mL). The product was extracted with ethyl acetate (3 x 10 mL) and the combined organic layer was washed with saturated sodium bicarbonate (NaHCO3) solution. Organic layer was dried over anhydrous sodium sulphate (Na2SO4), and evaporated under reduced pressure. Further purification of crude product was done
phenyl(2-(5-phenylisoxazol-3-yl)phenyl)methanone (1''a) (0.208 g, yield 64%). The identity and purity of the product was confirmed by spectroscopic analysis. The same procedure was also followed for o-aroylation of other isoxazole (2''-3'') derrivatives with various aldehydes (a-t).
III.4.4. Mechanistic investigations
IIIA.4.4. o-Aroylation of 2-arylbenzothiazole in the presence of radical scavenger TEMPO: An oven-dried reaction vessel was charged with 2- phenylbenzo[d]thiazole (1) (0.211 g, 1.0 mmol), Pd(OAc)2 (0.011 g, 0.05 mmol), benzaldehyde (0.127 g, 1.2 mmol), TBHP in decane (5-6 M) (300 µL, 1.5 mmol) and TEMPO (0.187 g, 1.2 mmol) in toluene (2 mL). The flask was fitted to a condenser and the resultant reaction mixture was stirred in a preheated oil bath at 120 oC for 5 h. The reaction after 5 h afforded the benzoyl-TEMPO adduct 2,2,6,6- tetramethylpiperidin-1-yl benzoate (A) in 41% yield along with paltry yield (15%) of the desired product (1a). This experiment supports the formation of benzoyl radical in the medium from benzaldehyde (1) induced radically by Pd(OAc)2/TBHP and also the radical nature of the mechanism.
IIIB.4.4. o-Aroylation of 3,5-diarylisoxazole in the presence of radical scavenger TEMPO: An oven-dried reaction vessel was charged with 3,5- diphenylisoxazole (1'') (0.221 g, 1.0 mmol), benzaldehyde (0.127 g, 1.2 mmol), Pd(OAc)2 (0.022 g, 0.10 mmol), TBHP in decane (5-6 M) (240 µL, 1.2 mmol) and TEMPO (0.187 g, 1.2 mmol) in DCE (2 mL). The flask was fitted to a condenser and the resultant reaction mixture was stirred in a preheated oil bath at 120 oC for 12 h. The reaction after 12 h afforded the benzoyl-TEMPO adduct 2,2,6,6- tetramethylpiperidin-1-yl benzoate (A) in 66% yield along with traces (<8%) of the desired product (1''a). This experiment supports the formation of benzoyl radical in the medium from benzaldehyde (a) induced radically by Pd/TBHP and also the radical nature of the mechanism.