[a]Reaction conditions: Arylhydrazine hydrochloride (1.0 mmol), PdCl2(PPh3)2 (2 mol %), Na2CO3 (2 equiv.), CuI (5.0 mol %), Acetonitrile (10 mL), 4 bar CO/O2 with ratio (3:1),[b] isolated yield.
Simple phenylhydrazine hydrochloride subjected to the oxidative carbonylation reaction affords a 75% yield of the benzophenone compound. A wide range of functional groups on phenyl hydrazine, such as electron-donating and electron-withdrawing groups are compatible. Generally, phenyl hydrazine with methyl substituents at o -,m -, and p -position to the phenyl ring underwent smooth carbonylation to form corresponding symmetric biaryl ketone product 2b,2c,2d in moderate to good yield.
The phenyl rings bearing with di and tri substituted methyl groups could also work well to produce the corresponding desired products 2e and 2f . Moreover, the electron-rich arylhydrazine containing m -OMe, and p -OMe are effectively worked, and the targeted biaryl ketone in yields of 61%, and 60% (2g-2h ). The naphthalene-2-ylhydrazine hydrochloride, a poly aromatic could undergo carbonylative self-coupling to form symmetric polyaromatic ketone (2i ) in 55% yield. Further, phenylhydrazine hydrochloride with electron-withdrawing substituents such as ortho, meta, and para (F, Cl, Br) could be afforded to corresponding biaryl ketones are 2j, 2k, 2l, 2m, 2n, and 2owith a yield of d 64%, 67%, 61%, 63%, 65%, 60%, respectively. Notable, the carbonyl group-containing arylhydrazine moiety is also compatible with this optimal reaction condition to give 2p in 52%, this methodology demonstrating that phenylhydrazine steric hindrance has little effect on the efficacy of the reaction. However, biologically active thiophen-3-ylhydrazine (2q ) also performed well in the standard reaction condition, unfortunately, heteroaryl hydrazine are not worked well under the optimized condition. After evaluating the substrate scope for aryl hydrazine hydrochloride, we conduct a series of control experiments to acquire some insight into the reaction process. First, we accomplish the reaction in the absence of oxygen giving only 5% iodobenzene instated of homo-coupled biaryl ketone, and without CuI, no carbonylative homo-coupled product was noted. Furthermore, the reaction was performed in the absence of CO, we obtained selectively 92% yield of symmetric azobenzene. Notably, no biaryl ketone product was observed when the reaction was performed in the absence of base and Pd-catalyst. These results are shows that PdCl2(PPh3)2, base, and CuI in the presence of molecular oxygen are essential for the reaction, as the lack of either fails to produce a homo-coupling biaryl ketone product.
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Scheme 3. Control Experiments
A plausible reaction mechanism for denitrogenative self-carbonylation of aryl hydrazine hydrochloride is proposed according to the previous related literature work and the above experiments (Scheme 5).[20] Initially, arylhydrazine hydrochloride1 is converted into the simple arylhydrazine by sodium carbonate, and aryl palladium complex A is formed in situ through oxidative C-N bond activation of arylhydrazine with Pd(II) catalyst using Cu/O2.[21] Next, the insertion of CO to species A to form acylpalladim complexB . Subsequently, acyl palladium complex B reacts again with arylhydrazine 1 via C-N bond activation to generate complexC . Finally, reductive elimination of complex C to form symmetric coupling biaryl ketone 2a , and regenerated Pd(0) species reoxidize to Pd(II) for the next cycle.[21a]
Scheme 4. Plausible Reaction Mechanism
Conclusions
In summary, we have developed the first Palladium-catalyzed denitrogenative self-carbonylation of arylhydrazine hydrochloride with Cu/O2 to afford symmetric biaryl ketones via C-N bond activation. The reaction performed well with PdCl2(PPh3)2as a catalyst with CO/O2 and Na2CO3 as a base under mild reaction conditions. In this protocol the arylhydrazines are employed as a green arylating agent that released N2 and H2O as a byproduct. Additionally, this protocol provides a series of symmetric carbonylative ketones with a wide variety of functional group tolerance under CO/O2 pressure.
Experimental
Materials and Methods:
All chemicals were procured from commercial providers and used without any purification technique. The reaction was studied by thin-layer chromatography (TLC) and GC-MS. The products were purified by column chromatography using a PET ether/EtOAc system. The 1H and 13C NMR spectroscopic data of purified products were recorded on Agilent- 400 MHz (at 400, and 101 MHz respectively) spectrometer, The residual solvent signals such as (CHCl3) and (CDCl3) for1H and 13C NMR spectra. Coupling constant (J) values were expressed in Hz.