a Reaction
conditions: Arylhydrazine hydrochloride (1.0 mmol), Catalyst (2 mol
%), base (2 equiv.), co-catalyst (5 mol%), solvent (10 mL), 4 bar
CO/O2 with ratio (3:1), byield
determined by GC-MS.
Initially, phenylhydrazine hydrochloride 1a with 4 bar
CO/O2 with the ratio (3:1) was examined in 1,4 dioxane
at 100 °C for 12 h in the presence of 5 mol% Pd/C and
K2CO3 as a base, the targeted yield of
benzophenone was obtained below 5%. Surprisingly, when CuBr was used as
a co-catalyst, the yield of benzophenone was increased to 25% (Table 1,
entry 2). Subsequently, we evaluate the various copper co-catalyst,
among them CuI was the best and afforded a 56% yield of 2aalong with 12% of iodobenzene byproduct (Table 1, entry 3). Henceforth,
CuI co-catalyst was used as a cocatalyst for further study of symmetric
biaryl ketone synthesis. Notably, we found that the co-catalyst with
molecular oxygen as an oxidant is important for this transformation.
Next, we screened the various Palladium sources, and the homogeneous
PdCl2(PPh3)2 catalyst
was found to be effective compared to the other catalysts (Table 1,
entry 9). Then we studied the effects of solvents involves of 1,4
dioxane, THF, DMSO, acetonitrile, and toluene, among these solvents’
acetonitrile is the more effective solvent and provides a good yield of2a, and byproduct 3a was suppressed in this solvent
(Table 2, entry 17). The impact of the base was then investigated using
a variety of organic and inorganic bases, including
Na2CO3,
K2CO3,
Cs2CO3, Et3N, and DBU.
Among these, Na2CO3 is the most
effective for driving the C-N bond cleavage process. According to the
time and temperature study, a reaction time of 12 hours and a
temperature of 100 °C are necessary to achieve the highest yield of
desired products (Table 1, entries 20-23).
With the optimal reaction
conditions in hand (Table 1, entry 17), We began to explore the
substrate scope of various substituted aryl hydrazine hydrochlorides. As
concisely in Table 2, Gratifyingly, a series of aryl hydrazines
hydrochlorides successfully underwent denitrogenative self-carbonylation
reaction to synthesize symmetrical biaryl ketones.
Table 2. Carbonylative homo-coupling reactions of aryl
hydrazinesa