Communication
radical pathway. When N-(naphthalen-1-yl)benzamide 4 or with other known methods, the acetone by-product generated
quinolin-8-yl benzoate 6 was treated under standard condi- from DTBP can be easily removed since it is a low boiling com-
tions, no desired product was obtained, suggesting that 8- pound. Therefore, it has no negative effect on the separation
aminoquinoline played a key role in the C–H activation of the desired products. Further investigations on the reaction
(Scheme 4, Eq. 2 and Eq. 3). Moreover, we also carried out an mechanism as well as synthetic application of this method are
intermolecular competition reaction to investigate the elec- currently underway, and the results will be reported in due
tronic effect of the benzamide. When the reaction was explored course.
using a mixture of equal moles of 1g and 1h under the stan-
dard conditions (Scheme 4, Eq. 4), 1H NMR analysis of the prod-
uct mixture (2g and 2h) demonstrated that the ratio of 2g: 2h
was 7.5: 1, which indicates that an electron-withdrawing group
is favored for the reaction.
Experimental Section
General Procedure for Introduction of Methyl Group: Benzamide
1 (0.15 mmol), Ni(OAc)2·4H2O (8 mg, 0.03 mmol), DTBP(88 mg,
On the basis of the above investigations and previous re- 0.60 mmol), and anhydrous CH3CN (1 mL) were added to a 25-mL
ports,[14,15,17c,17d]
a plausible mechanism is proposed in
Schlenk flask equipped with a high-vacuum PTFE valve-to-glass
seal. Then the flask was sealed under N2 and stirred at 140 °C for
12–19 h. After the completion of the reaction, It was then cooled
to room temperature. The solvent was evaporated under reduced
pressure, and the product was isolated by silica gel column purifica-
tion with petroleum ether/ethyl acetate eluent to give the desired
products product 2.
Scheme 5. Initially, the amide-coordinated Ni(II) intermediate I
is generated by the reaction of amide 1a with Ni(OAc)2·4H2O.
Subsequently the intermediate I undergoes cleavage of the or-
tho C–H bonds and forms the intermediate II. Next the II under-
goes a single electron transfer (SET) with DTBP, which gives the
Ni(III) species III and tert-butoxyl radical, The tert-butoxyl radical
undergoes C–C bond scission to give a molecule of acetone
and a methyl radical, which immediately adds to the Ni(III) spe-
cies III to give the Ni(IV) intermediate IV. After reductive elimi-
nation and protonation, the product 2a and Ni(II) are released,
thus completing the catalytic cycle.
Keywords: Ni-catalysis · Di-tert-butyl peroxide ·
Methylation · Base-free conditions · Ligand-free conditions
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In summary, we have developed a novel and efficient process
for the ortho-methylation of benzamides with DTBP via Ni(II)-
catalyzed C–H activation assisted by 8-aminoquinoline. Our
method features simple reaction conditions, broad substrate
scope, and use of cheap and commercially available reagents.
Another notable feature is that the reaction is performed under
base-free, and ligand-free conditions. In addition, compared
Eur. J. Org. Chem. 0000, 0–0
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