IIB.3. Present Work
III. Ceric Ammonium Nitrate (CAN) Promoted Pd(II)- Catalyzed Substrate Directed o-Benzoxylation
III.4. Experimental Section
situ generated benzoxy radical that is obtained by the action of CAN with benzoic acid.
The proximity of the two Pd-centers might facilitate a cooperative redox chemistry, in which both metals participate synergistically to lower the barrier of the redox transformation. The oxidative addition product is a dimeric Pd(III) intermediate7 II as was detected by mass spectral analysis of the reaction mixture. Furthermore, the detection of a monomeric Pd(IV) species8 in the reaction aliquot9 may be the result of a PdPd cleavage in dimeric Pd(III) intermediate II to give monomeric Pd(IV) and Pd(II) species.8d A reductive elimination leads to the o-benzoxylated product and forms the active dimeric species III. Intermediate III further releases another o-benzoxylated product by CO bond formation and regenerates dinuclear Pd(II) active species II for the next catalytic cycle (Scheme III.3.4).
In conclusion, a simple and efficient protocol has been developed for the ortho- benzoxylation of directing arenes using Pd(II)-catalyst and inexpensive terminal oxidant CAN. The terminal oxidant CAN as an efficient substitute for a set of expensive oxidants/additives in the Pd-catalyzed substrate directed o-benzoxylation that proceeds through a CDC reaction. Mechanistic investigations reveal the radical pathway for this strategy.
Crystallographic Description of 1a: Crystal dimension (mm): 0.44 x 0.34 x 0.32.
C20H13NO2S, Mr = 331.07. monoclinic, space group p 21/n; a = 8.9143 (3) Å, b = 16.4329 (5) Å, c = 11.7355 (4) Å; = 90o, = 111.800 (2) o, = 90o, V = 1596.17 (9)Å3 ; Z = 4;
ρcal= 1.379 g/cm3; (mm-1) = 0.214; F (000) = 688.0; Reflection collected / unique = 2802 / 2164; Refinement method = Full-matrix least-squares on F2; Final R indices [I>2σl ] R1
= 0.0444, wR2 = 0.1173, R indices (all data) R1 = 0.0553, wR2 = 0.1232; goodness of fit
= 1.057.
III.4.3. Synthesis of 2-(Benzo[d]thiazol-2-yl)phenyl benzoate (1a) and 2- (Benzo[d]thiazol-2-yl)-3-benzoylphenyl benzoate (1aa′)
III.4.3.1. General Procedure for the Synthesis of 2-(Benzo[d]thiazol-2-yl)phenyl benzoate (1a) from 2-Phenylbenzothiazole (1) and Benzoic acid (a): To an oven-dried round bottom flask (25 mL) 2-phenylbenzothiazole (1) (0.105g, 0.5 mmol), benzoic acid (0.073g, 0.6 mmol), Pd(OAc)2 (0.006g, 0.025 mmol), ceric ammonium nitrate (0.411g, 0.75 mmol), 1,2-dichloroethane (2.5 mL) and acetonitrile (0.5 mL) were added. The reaction mixture was heated at reflux in an oil bath that was preheated to 110 oC. Upon completion of the reaction (12 h), the excess solvent was removed under reduced pressure and the reaction mixture was combined with ethyl acetate (30 mL). The ethyl acetate layer was carefully washed with saturated sodium bicarbonate solution (2 x 5 mL), dried with anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure. The crude product was purified over a silica gel column (hexane / ethyl acetate, 9.8:0.2) to give pure 2-(benzo[d]thiazol-2-yl)phenyl benzoate (1a) (0.117g, yield 71%). The identity and purity of the product was confirmed by spectroscopic analysis.
III.4.3.2. General Procedure for the Synthesis of 2-(Benzo[d]thiazol-2-yl)-3- benzoylphenyl benzoate (1aa′) from 2-Phenylbenzothiazole (1), Benzoic acid (a) and Phenylglyoxalic acid (a´): To an oven-dried round bottom flask (25 mL) 2- phenylbenzothiazole (1) (0.105g, 0.5 mmol), benzoic acid (0.073g, 0.6 mmol), Pd(OAc)2
(0.006g, 0.025 mmol), ceric ammonium nitrate (0.411g, 0.75 mmol), 1,2-dichloroethane (2.5 mL) and acetonitrile (0.5 mL) were added. The reaction mixture was heated at reflux in an oil bath that was preheated to 110 oC. Upon completion of the reaction (12 h), phenylglyoxalic acid (a´) (0.090g, 0.6 mmol), Pd(OAc)2 (0.011g, 0.05 mmol), ceric ammonium nitrate (0.411g, 0.75 mmol) and DMF (1.5 mL) were added to the same round bottom flask and heated at 110 oC. After 8 h the reaction mixture was combined with ethyl
acetate (30 mL). The ethyl acetate layer was carefully washed with saturated sodium bicarbonate solution (2 x 5 mL), dried with anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure. The crude product was purified over a silica gel column (hexane / ethyl acetate, 9.5:0.5) to give pure 2-(benzo[d]thiazol-2-yl)-3- benzoylphenyl benzoate (1aa′) (0.065g, yield 30%). The identity and purity of the product was confirmed by spectroscopic analysis.
III.4.4. Mechanistic Investigations
III.4.4.1. o-Benzoxylation of 2-Phenylbenzothiazole (1) in the Presence of Radical Scavenger TEMPO: In an oven-dried 25 mL round bottom flask 2-phenylbenzothiazole (1) (0.105g, 0.5 mmol), benzoic acid (0.073g, 0.6 mmol), Pd(OAc)2 (0.006g, 0.025 mmol), ceric ammonium nitrate (0.329g, 0.6 mmol), TEMPO (0.078g, 0.5 mmol), 1,2- dichloroethane (2.5 mL) and acetonitrile (0.5 mL) were added. The flask was fitted to a condenser and the reaction mixture was stirred in a preheated oil bath at 110 oC for 12 h.
After 12 h only trace amount (<10%) of the desired product (1a) was observed. This experiment supports the formation of benzoxy radical in the medium from benzoic acid induced by Pd/CAN and also the radical nature of the mechanism.
III.4.4.2. ESI-MS Study for the Detection of Reaction Intermediates During o- Benzoxylation: In order to detect the intermediate species in the reaction mixture an electrospray mass spectrometry was performed. In this study, an oven-dried flask was charged with 2-phenylbenzothiazole (1) (0.105g, 0.5 mmol), benzoic acid (0.073g, 0.6 mmol), Pd(OAc)2 (0.006g, 0.025 mmol), ceric ammonium nitrate (0.411g, 0.75 mmol), 1,2- dichloroethane (2.5 mL) and acetonitrile (0.5 mL). Then the reaction mixture was stirred in an oil bath at 110 oC. After 1.5 h of reaction, aliquot (100 L) was withdrawn and diluted with acetonitrile (1 mL). A 20 μL of the diluted solution was injected to run ESI-MS analysis. Various cationic and neutral Pd species were detected in the ESI-MS analysis as shown below in Figure III.4.4.1. The cationic and neutral Pd-species observed in the spectrum are as follows: peaks at m/z 315.9412 corresponding to [(C13H8NS)Pd(II)]+ (A) (Fig. III.4.4.1), at m/z 356.9694 corresponding to [(C13H8NS)Pd(II)(NCCH3)]+ (B) (Fig.
III.4.4.1), at m/z 437.9790 corresponding to [(C13H8NS)Pd(II)(OCOPh)] (C) (Fig. III.4.4.1), at m/z 526.9886 corresponding to [(C13H8NS)Pd(II)(C13H8NS)] (D) (Fig. III.4.4.1), at m/z 647.0109 corresponding to [(C13H8NS)Pd(IV)(C13H8NS)(OCOPh)]+ (E) (Fig. III.4.4.1), at
m/z 870.9362 corresponding to [(C13H8NS)Pd(III) (C13H8NS)(OAc)2(OCOPh)]+ (F) (Fig.
III.4.4.1).
Fig. III.4.4.1. ESI-MS spectrum of the reaction mixture A
B
C
D
E
F
A = B =