Palladium-Catalyzed Regioselective Acylation of Diazines with Toluenes: A New Approach to the Synthesis of ortho-Diacylbenzenes

Article abstract of DOI:10.1002/ejoc.202000364

A highly efficient and practical procedure for chemo- and regioselective synthesis of ortho-diacylbenzenes through Pd-catalyzed oxidative C–H bond activation has been developed. Using this method, a variety of ortho-diacylbenzenes were prepared in moderate to good yields, by direct acylation of diazines with toluene derivatives as acylation source. Ortho-diacylbenzenes may be used as precursors in synthesis of pharmaceuticals and agrochemicals.

Full text of DOI:10.1002/ejoc.202000364

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C–H Functionalization
Palladium-Catalyzed Regioselective Acylation of Diazines
with Toluenes: A New Approach to the Synthesis of ortho-
Diacylbenzenes
Ebrahim Kianmehr,*[a] Behnoush Seifinoferest,[a] and Hadi Afaridoun[a]
Abstract: A highly efficient and practical procedure for chemo- were prepared in moderate to good yields, by direct acylation
and regioselective synthesis of ortho-diacylbenzenes through of diazines with toluene derivatives as acylation source. Ortho-
Pd-catalyzed oxidative C–H bond activation has been devel- diacylbenzenes may be used as precursors in synthesis of phar-
oped. Using this method, a variety of ortho-diacylbenzenes maceuticals and agrochemicals.
Introduction
Aryl ketones are crucial precursors for synthesis of many phar-
maceuticals and natural products.[1,2] For instance, benzophen-
one derivatives are proven to be of use in treating immune
deficiency disease.[3] Markably, ortho-diacylbenzenes are impor-
tant intermediates for the synthesis of biologically and pharma-
ceutically active compounds, such as phthalazines,[4] diox-
imes,[5] isoindoles,[6] isobenzofurans,[7] isoquinolines, anthra-
cene derivatives,[8] indanones and isoindolines[9] (Scheme 1).
Ortho-diacylbenzenes are also used as fluorescent reagents for
amino acids and peptide analysis.[10]
Furthermore, the ortho-diacylbenzene structural motif is
present at the core of pharmaceuticals e.g. morintrifolin A (A)
and morintrifolin B (B) (Scheme 2). It has been shown that this
class of compound exhibits a broad range of useful pharmaco-
logical effects, e.g. QR enzyme induction (cancer chemo-
prevention).[11]
Due to the need for efficient ways to synthesize more elabo-
rate structures possessing biological activity, the development
Scheme 1. ortho-Diacylbenzenes can be used as precursors for the synthesis
of various chemicals.
of novel and convenient methods for the preparation of ortho-
diacylbenzene derivatives is of considerable importance in or-
ganic chemistry and numerous synthetic methodologies for the
construction of this class of compound have been developed
over past decades. The Friedel Crafts reaction is the classic
method for the acylation reaction, but it suffers from harsh re-
action conditions, low regioselectivity, and limited functional
group tolerance. This method is more challenging for the syn-
thesis of ortho-diacylbenzenes since the acyl groups are deacti-
Scheme 2. Bioactive compounds with potential medical applications.
vating and meta-directing groups. Non-availability and han-
dling difficulty of the reagents are some of the other disadvan-
tages.
Oxidation of 1,3-diarylisobenzofurans to ortho-diacylbenz-
enes with lead tetra-acetate was reported by Newman in 1961
(Scheme 3, Equ. 1).[12] A Diels-Alder reaction between diacyleth-
ylene and butadiene was reported by Goldschmidt in 1961. The
reaction leads to the formation of 1,2-diacyl-4-cyclohexene
[a] Prof. E. Kianmehr, B. Seifinoferest, H. Afaridoun
School of Chemistry, College of Science, University of Tehran,
Tehran, Iran
E-mail: kianmehr@khayam.ut.ac.ir
https://schem.ut.ac.ir/en/~ekianmehr
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202000364.
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which can afford the desired ortho-diacylbenzene derivatives in
the presence of Pd/C (Scheme 3, Equ. 2).[13] Another classic
method for synthesizing ortho-diacylbenzenes is ozonolysis of
naphthalenes which was reported by Ito in 1984. The reaction
was conducted in various solvents and the best result was ob-
tained in chloroform/methanol (Scheme 3, Equ. 3).[14]
Scheme 4. Cross coupling reactions for synthesis of ortho-diacylbenzenes.
Scheme 3. Classic methods for the synthesis of ortho-diacylbenzenes.
For more efficient and greener methods to construct C–C
bonds, recent attention has been focused on direct C–H func-
tionalization.[15] This strategy is more appealing when it comes
to choosing two un-functionalized materials with two different
C–H bonds (CDC reactions) which makes synthetic routes
shorter, more efficient, easier and provides a straightforward
and economical approach for new C–C bond construction.[16]
Synthesis of ortho-diacylbenzenes from acylbenzenes via a tran-
sition metal-catalyzed C–H bond activation strategy is challeng-
ing because the acyl groups are considered to be weak direct-
ing groups.
A rhodium-catalyzed cross coupling reaction of aryl ketone
O-methyl oximes with aldehydes for direct acylation of sp2
C–H bonds was reported by Zhou in 2012 which can provide a
new route to ortho-diacylbenzenes after deprotection of the
oxime moiety (Scheme 4, Equ. 1).[17] A Pd(II)-catalyzed direct
C–H bond acylation of N-BoC–Hydrazones with aldehydes was
reported by Sharma in 2013 as a one-pot synthesis of 1,2-di-
acylbenzenes which removes the need for an additional depro-
tection step (Scheme 4, Equ. 2).[9a]
Scheme 5. Coupling reactions of aromatic ketazines.
toluenes as a low toxic, stable, and commercially available acyl-
ating agent.[21] This method provides a new approach to diacyl-
benzenes with high atom economy and without the need for
an extra step for removing the azine moiety (Scheme 6).
Recently, a few examples have been appeared in the litera-
ture for direct C–H bond functionalization starting with ket-
azines as the substrates. Namely, a Rhodium(III)-catalyzed cou-
pling of aromatic ketazines with 2-vinyloxirane via C–H activa-
tion was reported by Zhu in 2015 (Scheme 5, Equ. 1).[18] Also, a
Rhodium(III)-catalyzed directed ortho-C–H bond functionaliza-
tion of aromatic ketazines via C–S and C–C coupling was
reported by the same group in 2015 (Scheme 5, Equ. 2).[19]
Cui reported a regioselective method for ortho-C–H carbenoid
insertion to ketazines in 2017 (Scheme 5, Equ. 3).[20]
As part of our ongoing interest to explore C–C bond forma-
tions through CDC reactions, herein we report an efficient and
highly regioselective procedure for acylation of ketazines with
Scheme 6. Acylation of ketazines with toluenes.
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Results and Discussion
oxidants, including DTBP, H2O2, K2S2O8 and cumene peroxide.
The optimum amount of oxidant for the reaction was 4.0 equiv.
(Table1, entries 1, 13–15).
We also checked the reaction using acetophenone and tolu-
ene in the presence of a catalytic amount of hydrazinium
hydroxide to provide a transient directing group in situ but
unfortunately the desired product was not obtained.
With the optimized reaction conditions identified, a range of
acetophenone diazines were subjected to this protocol
(Table 2). Substituted substrates bearing both electron-donat-
ing and electron-withdrawing groups were all well tolerated
and gave the desired products (3a–3l) in moderate to good
yields. Electron-donating groups such as methyl and methoxy
groups on ketazine and toluene substrates were highly effective
in this method and gave the desired products in higher yields.
Substrates with electron-withdrawing groups such as halogens
performed the reaction smoothly to give the desired products
in lower yields although the reaction was not successful with
Our initial attempt toward this aim was started by an investiga-
tion of the reaction between (1E,2E)-1,2-bis[1-(p-tolyl)ethyl-
idene]hydrazine (1b) and toluene as the model reaction. To op-
timize the reaction parameters, the effects of different factors
e.g. catalysts, additives, solvents and temperature were exam-
ined (Table 1). The initial trial gave desired product 3b in 83 %
yield with 5 mol-% of PdCl2 as the catalyst (Table 1, entry 1).
An increase in catalyst loading to 10 mol-% did not improve
the reaction efficiency (Table 1, entry 2). Other catalysts such
as Pd(OAc)2, Pd2(dba)3 and PdCl2(COD), were employed, but
there was no increase in the yield. As shown in Table 1, the
use of some other copper and ruthenium catalysts provided
unsatisfying results (Table 1, entries 6–10).
Table 1. Optimization of the reaction conditions.
Table 2. Scope of direct acylation of diazines.
Entry
Catalyst [mol-%]
Oxidant
(equiv.)
Solvent
Temp
[°C].
Yield[a]
[%]
1
2
3
4
5
6
7
8
PdCl2 (5)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
CH3CN
DCE
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
120
100
80
83
74
40
37
PdCl2 (10)
Pd(OAc)2 (5)
Pd2(dba)3 (5)
PdCl2(COD) (5)
CuI (5)
CuCl (5)
NiBr2 (5)
Ni(OAc)2 (5)
[Ru(p-cymene)Cl2]2 (5) TBHP(4)
22
trace
trace
trace
trace
trace
0
0
trace
42
55
74
41
62
9
10
11
12
13
14
15
16
17
18
19
20
21
–
TBHP(4)
–
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
PdCl2 (5)
TBHP(1)
TBHP(2)
TBHP(3)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
TBHP(4)
PhCl
PhCl
PhCl
PhCl
46
trace
trace
60
[a] Reaction conditions: 1b (0.3 mmol), 2b (0.6 mmol), oxidant [equiv.], cata-
lyst [mol-%], solvent (1.0 mL) at given temperatures for 18 h.
Decreasing the temperature from 140 to 100 °C lowered the
reaction yield to 46 %, further decrease in temperature further
decreased the yield (Table 1, entries 1, 19–21). A variety of sol-
vents were also examined. As a result, chlorobenzene, which
gave the product in 83 % yield, was selected as the best solvent
among CH3CN, 1,2-dichloroethane (DCE), dimethyl sulfoxide
(DMSO) dimethylformamide (DMF), toluene and diglyme
(Table 1, entries 1, 16, 17).
Subsequent screening of a range of various oxidants re-
vealed that TBHP performed the best in comparison with other
[a] Reaction Conditions: Ketazine (0.3 mmol), Toluene (0.6 mmol), PdCl2 (5.0
mol-%), TBHP (1.2 mmol), PhCl (1.0 mL), 140 °C, 18 h.
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Scheme 7. A plausible mechanism.
the strong electron-withdrawing nitro group on either the ket- Conclusion
azine or the toluene substrate (3p). Ketazines derived from
We have explored an efficient method for the synthesis of
benzophenone derivatives, successfully reacted under the opti-
mal reaction conditions and gave the desired products in good
yields (3m–3o).
Unfortunately, 2-substituted acetophenone azines did not
lead to the corresponding products under the standard reac-
tion conditions (3q).
ortho-diacylbenzenes with toluenes as aroyl surrogates. The re-
action is applicable to numerous substrates with good toler-
ance of various functional groups, and it provides a new ap-
proach for ortho-acylation of aryl ketones. The reaction prod-
ucts are interesting compounds for research into pharmaceuti-
cals and agrochemicals.
On the basis of previous mechanistic reports[9a] a plausible
mechanism for the reaction is illustrated in Scheme 7. Initially,
a metalation reaction occurs preferentially at the C2-position of
the ketazine aryl ring which leads to the formation of palladacy-
cle B. Radical intermediate D is generated in-situ by hydrogen-
atom abstraction from toluene under the reaction conditions.
Next, coordination of palladium complex B with radical D fol-
lowed by addition of water or hydroxyl anion to imine bond
gives Pd(IV) intermediate E, which undergoes C–N bond discon-
nection and reductive elimination at Pd(IV) center to afford the
desired product 3 and hydrazone intermediate F. This interme-
diate is involved in a similar acylation cycle to produce the de-
sired product 3. To prove the radical mechanism, a control reac-
tion that involves the use of 2,6-di-tert-butyl-4-methylphenol
(BHT) as a radical scavenger was performed. When 1b was
treated in the presence of butylated hydroxytoluene
(2.0 equiv.), no desired product 3b was observed (Scheme 8).
Experimental Section
General
All commercially available chemicals and reagents were purchased
from Merck or Sigma or commercial distributors and were used
without further purification. Ketone azines were synthesized accord-
ing to the literature. Analytical thin layer chromatography (TLC) was
performed on precoated silica gel60 F254 plates. The products were
purified by preparative column chromatography on silica gel
(0.063–0.200 mm, Merck). 1H NMR (500 MHz) and 13C NMR
(125 MHz) spectra were recorded on an Inova Varian 500 Advanced
instrument in CDCl3 or [D6]DMSO. Electron ionization (EI) mass
spectra were obtained using an Agilent 5975C VL MSD (ion source:
EI+, 70 eV, 230 °C).
General Procedure for Synthesis of ortho-Diacylbenzene Deriv-
atives: A reaction vessel was charged with the diazine derivative
(0.3 mmol, 1.0 equiv.), the toluene derivative (0.6 mmol, 2.0 equiv.),
Palladium catalyst (0.015 mmol, 5 mol-%), TBHP (1.2 mmol, 4 equiv.),
and PhCl (1 mL) in air. The reaction vessel was then sealed. The
reaction mixture was allowed to stir at 140 °C for 18 h. Then, the
mixture was cooled to room temperature and diluted with ethyl
acetate. The organic phase was extracted with ethyl acetate and
washed with an aqueous solution of NaHCO3. The organic layer was
dried with anhydrous MgSO4, filtered and evaporated. The resulting
residue was purified by column chromatography using n-hexane/
ethyl acetate (5:1) as the mobile phase.
Scheme 8. Control experiment.
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Spectral Data
δ (ppm) 198.3, 196.0, 163.4, 143.6, 141.2, 134.4, 131.4, 130.6, 130.4,
130.3, 128.5, 114.3, 55.9, 27.7, 21.4. Ms (EI) m/z (relative intensity)
268 (M+, 14), 253 (100), 161 (14), 135 (42), 92 (10), 77 (14), 43 (9).
C17H16O3 (268.31): calcd. C 76.10, H 6.01; found C 76.28, H 6.03.
1-(2-Benzoylphenyl)ethan-1-one (3a):[22] Black oil; yield = 85 %,
114 mg. 1H NMR ([D]Chloroform, 500 MHz): δ (ppm) 7.89 (dd, J =
7.5, 1.5 Hz, 1H), 7.76–7.72 (m, 2H), 7.65–7.57 (m, 2H), 7.56–7.51 (m,
1H), 7.41 (td, J = 7.8, 1.6 Hz, 3H), 2.52 (s, 3H). 13C NMR ([D6]DMSO,
1-[2-(3-Chlorobenzoyl)-4-methylphenyl]ethan-1-one
(3h):
126 MHz): δ (ppm) 199.1, 197.3, 140.5, 137.2, 137.2, 133.4, 133.1, Brownish-red oil, Yield:78 %, 128 mg. 1H NMR ([D]Chloroform,
130.4, 130.3, 129.1, 129.0, 128.2, 27.8. Ms (EI) m/z (relative intensity) 500 MHz): δ (ppm) 7.82 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 1.8 Hz, 1H),
224 (M+, 8), 105 (66), 91 (16), 77 (83), 43 (100).
7.57 (dt, J = 7.6, 1.1 Hz, 1H), 7.46 (ddd, J = 8.1, 2.1, 1.1 Hz, 1H), 7.42–
7.36 (m, 1H), 7.32 (t, J = 7.9 Hz, 1H), 7.20–7.12 (m, 1H), 2.49 (s, 3H),
2.44 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ (ppm) 198.3, 196.1,
140.2, 139.3, 134.0, 133.0, 131.1, 131.0, 130.9, 130.1, 129.2, 128.5,
128.0, 127.7, 27.3, 21.4. Ms (EI) m/z (relative intensity) 274 (M + 2,
5), 272 (M+, 18), 259 (38), 257 (100), 161 (22), 43 (13). C16H13ClO2
(272.73): calcd. C 70.46, H 4.80; found C 70.63, H 4.83.
1-(2-Benzoyl-4-methylphenyl)ethan-1-one (3b): Brown oil;
1
yield = 83 %, 119 mg. H NMR ([D6]DMSO, 500 MHz): δ (ppm) 8.02
(d, J = 7.8 Hz, 1H), 7.58 (d, J = 7.6 Hz, 3H), 7.50 (d, J = 8.0 Hz, 1H),
7.48–7.43 (m, 2H), 7.20 (s, 1H), 2.48 (s, 3H), 2.41 (s, 3H). 13C NMR
([D6]DMSO, 126 MHz): δ (ppm) 198.3, 197.4, 143.9, 141.0, 137.3,
134.3, 133.3, 130.7, 130.6, 129.03, 129.00, 128.5, 27.5, 21.4. Ms (EI)
m/z (relative intensity) 238 (M+, 8), 223 (90), 105 (100), 77 (70), 43
(33). C16H14O2 (238.28): calcd. C 80.65, H 5.92; found C 80.92, H 5.89.
1-[4-Chloro-2-(4-methoxybenzoyl)phenyl]ethan-1-one
(3i):
Blood red oil, yield = 78 %, 135 mg. 1H NMR ([D]Chloroform,
500 MHz): δ (ppm) 7.82 (d, J = 8.3 Hz, 1H), 7.71 (d, J = 8.8 Hz, 2H),
7.53 (dd, J = 8.4, 2.1 Hz, 1H), 7.35 (d, J = 2.1 Hz, 1H), 6.91 (d, J =
9.0 Hz, 2H), 3.86 (s, 3H), 2.50 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz):
δ (ppm) 198.1, 194.2, 163.6, 142.8, 138.0, 135.6, 132.4, 131.6, 129.9,
129.7, 127.9, 114.4, 56.0, 27.9. Ms (EI) m/z (relative intensity) 290 (M
+ 2, 6), 288 (M+, 18), 273 (73), 167 (36), 135 (100), 77 (30), 43 (26).
1-[4-Methyl-2-(3-methylbenzoyl)phenyl]ethan-1-one (3c): Brown
oil; yield = 83 %, 126 mg. 1H NMR ([D6]DMSO, 500 MHz): δ (ppm)
8.01 (d, J = 8.1 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.44 (s, 1H), 7.41 (d,
J = 6.2 Hz, 1H), 7.37–7.31 (m, 2H), 7.19 (s, 1H), 2.48 (s, 3H), 2.41 (s,
3H), 2.32 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ (ppm) 198.3,
197.4, 143.8, 141.0, 138.4, 137.4, 134.4, 134.0, 130.7, 130.6, 129.2,
128.9, 128.5, 126.5, 27.6, 21.4, 21.3. Ms (EI) m/z (relative intensity)
252 (M+, 40), 237 (100), 209 (20), 161 (30), 119 (32), 91 (35), 84 (60),
66 (70). C17H16O2 (252.31): calcd. C 80.93, H 6.39; found C 80.68, H
6.42.
C16H13ClO3 (288.73): calcd. C 66.56, H 4.54; found C 66.40, H 4.51.
1-[4-Chloro-2-(3-methyoxybenzoyl)phenyl]ethan-1-one (3j):
1
Blood red oil, yield = 79 %, 137 mg. H NMR ([D6]DMSO, 500 MHz):
δ (ppm) 8.15 (d, J = 8.4 Hz, 1H), 7.79 (dd, J = 8.4, 2.2 Hz, 1H), 7.54
(d, J = 2.1 Hz, 1H), 7.42–7.33 (m, 1H), 7.26–7.17 (m, 2H), 7.06 (d, J =
7.7 Hz, 1H), 3.33 (s, 3H), 2.52 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz):
δ (ppm) 197.9, 195.3, 159.8, 142.5, 138.25, 138.19, 135.5, 132.5,
130.3, 130.2, 128.0, 122.1, 119.5, 113.3, 55.7, 27.7. Ms (EI) m/z (rela-
tive intensity) 290 (M + 2, 21), 288 (M+, 73), 273 (100), 181 (53), 183
(16), 135 (86), 107 (53), 92 (45), 77 (66), 43 (60). C16H13ClO3 (288.73):
calcd. C 66.56, H 4.54; found C 66.75, H 4.58.
1-[4-Methyl-2-(4-methylbezoyl)phenyl]ethan-1-one (3d): Red-
dish brown oil, yield = 81 %, 123 mg. 1H NMR ([D]Chloroform,
500 MHz): δ (ppm) 7.78 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.3 Hz, 2H),
7.35 (dd, J = 8.2, 1.7 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 7.17 (s, 1H),
2.47 (s, 3H), 2.43 (s, 3H), 2.38 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz):
δ (ppm) 198.3, 196.9, 143.7, 141.1, 134.9, 134.4, 130.6, 130.5, 130.1,
129.5, 129.2, 128.5, 27.6, 21.6, 21.4. Ms (EI) m/z (relative intensity)
252 (M+, 11), 237 (83), 119 (100), 91 (88), 43 (33). C17H16O2 (252.31): 1-(2-Benzoyl-4-chlorophenyl)ethan-1-one (3k):[9a] Red oil, yield =
calcd. C 80.93, H 6.39; found C 80.70, H 6.38.
63 %, 98 mg. 1H NMR ([D6]DMSO, 500 MHz): δ (ppm) 8.14 (d, J =
8.4 Hz, 1H), 7.76 (dd, J = 8.4, 2.1 Hz, 1H), 7.63–7.57 (m, 3H), 7.52 (d,
J = 2.0 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 2.50 (s, 3H). 13C NMR
([D6]DMSO, 126 MHz): δ (ppm) 198.0, 195.6, 142.6, 138.3, 136.8,
135.4, 133.6, 132.5, 130.1, 129.13, 129.09, 128.0, 27.6. Ms (EI) m/z
(relative intensity) 260 (M + 2, 9), 258 (M+, 21), 243 (28), 153 (34),
105 (100), 77 (73), 43 (35).
1-[2-(4-Isopropylbenzoyl)-4-methylphenyl]ethan-1-one
(3e):
Reddish brown oil, Yield = 83 %, 140 mg. 1H NMR ([D6]DMSO,
500 MHz): δ (ppm) 7.80 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.3 Hz, 2H),
7.37 (dd, J = 7.9, 1.9 Hz, 1H), 7.27 (d, J = 8.7 Hz, 2H), 7.18 (d, J =
1.7 Hz, 1H), 2.95 (p, J = 6.9 Hz, 1H), 2.50 (s, 3H), 2.44 (s, 3H), 1.27 (s,
3H), 1.25 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ (ppm) 198.3,
196.9, 154.2, 143.7, 141.2, 135.2, 134.3, 130.7, 130.4, 129.9, 129.4, 1-[2-(4-Bromobenzoyl)-4-chlorophenyl]ethan-1-one (3l): Dark
128.5, 127.0, 126.9, 33.9, 27.6, 24.0, 23.9, 21.4. Ms (EI) m/z (relative red oil, yield = 60 %, 121 mg. 1H NMR ([D6]DMSO, 500 MHz): δ
intensity) 280 (M+, 6), 265 (53), 223 (50), 161 (51), 147 (56), 118 (41),
103 (62), 91 (80), 77 (67), 43 (100). C19H20O2 (280.36): calcd. C 81.40,
H 7.19; found C 81.48, H 7.17.
(ppm) 8.16 (d, J = 8.4 Hz, 1H), 7.79 (dd, J = 8.4, 2.2 Hz, 1H), 7.68 (d,
J = 8.6 Hz, 2H), 7.57 (d, J = 2.1 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 2.52
(s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ (ppm) 198.9, 193.8, 134.6,
132.3, 131.7, 131.0, 130.3, 127.9, 125.9, 125.2, 123.5, 111.1, 27.6. Ms
(EI) m/z (relative intensity) 340 (M + 4, 23), 338 (M + 2, 84), 336 (M+,
68), 325 (23), 323 (61), 321(53), 292 (15), 229 (42), 212 (38), 194 (69),
176 (46), 167 (100), 112 (11), 105 (34), 75 (65), 50 (36), 43 (39).
C15H10BrClO2 (337.60): calcd. C 53.37, H 2.99; found C 53.51, H 2.96.
1-[2-(1-Naphtoyl)-4-methylphenyl]ethan-1-one (3f): Dark red oil,
1
yield = 72 %, 124 mg. H NMR ([D]Chloroform, 500 MHz): δ (ppm)
9.04 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.2 Hz,
1H), 7.73 (d, J = 7.9 Hz, 1H), 7.69 (ddd, J = 8.5, 6.8, 1.3 Hz, 1H), 7.61–
7.54 (m, 1H), 7.42–7.36 (m, 2H), 7.35–7.28 (m, 2H), 2.45 (s, 3H), 2.42
(s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ (ppm) 199.2, 199.0, 146.0,
1,2-Phenylenebis(phenylmethanone) (3m):[22] Brown oil, yield =
143.4, 142.1, 135.1, 134.9, 133.9, 133.4, 131.0, 130.6, 130.5, 129.6, 74 %, 127 mg. 1H NMR ([D]Chloroform, 500 MHz): δ (ppm) 7.73–
128.7, 128.3, 126.9, 126.7, 124.8, 27.7, 21.4. Ms (EI) m/z (relative in- 7.69 (m, 4H), 7.64–7.59 (m, 4H), 7.54–7.49 (m, 1H), 7.40–7.34 (m, 4H),
tensity) 288 (M+, 73), 273 (100), 245 (46), 127 (82), 43 (37). C20H16O2 7.26 (s, 1H). 13C NMR ([D]Chloroform, 126 MHz): δ (ppm) 196.6,
(288.34): calcd. C 83.31, H 5.59; found C 83.49, H 5.63.
140.0, 137.2, 133.0, 130.4, 129.8, 129.7, 128.4. Ms (EI) m/z (relative
intensity) 286 (M+, 60), 209 (100), 152 (75), 105 (75), 77 (100), 51
(56).
1-[2-(4-Methoxybenzoyl)-4-methylphenyl]ethan-1-one
(3g):
Blood red oil, yield = 80 %, 129 mg. 1H NMR ([D]Chloroform,
500 MHz): δ (ppm) 7.77 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.9 Hz, 2H),
7.33 (dd, J = 8.1, 2.0 Hz, 1H), 7.14 (s, 1H), 6.87 (d, J = 8.9 Hz, 2H),
3.81 (s, 3H), 2.46 (s, 3H), 2.41 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz):
(2-Benzoylphenyl)(m-tolyl)methanone (3n): Dull red oil, yield =
88 %, 159 mg. 1H NMR ([D6]DMSO, 500 MHz): δ (ppm) 7.75–7.66 (m,
4H), 7.64–7.57 (m, 3H), 7.49–7.43 (m, 4H), 7.38 (d, J = 7.5 Hz, 1H),
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7.35–7.29 (m, 1H), 2.26 (s, 3H). 13C NMR ([D6]DMSO, 126 MHz): δ
(ppm) 196.4, 196.3, 139.9, 139.7, 138.4, 137.1, 137.0, 134.3, 133.7,
131.3, 131.1, 130.2, 130.0, 129.93, 129.92, 129.0, 128.9, 127.2, 21.2.
Ms (EI) m/z (relative intensity) 300 (M+, 96), 285 (7), 223 (92), 209
(100), 165 (38), 152 (53), 119 (76), 105 (69), 91 (69), 77 (76), 65 (26),
51 (23), 43 (7). C12H16O2 (300.35): calcd. C 83.98, H 5.37, found C
83.71, H 5.40.
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Acknowledgments
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We gratefully acknowledge the financial support from the Re-
search Council of the University of Tehran. We thank Dr Karol
Gajewski, Natural Resources Canada, for helpful comments on
this work.
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Keywords: Cross-coupling reactions · C–H activation ·
Acylation · Palladium · ortho-Diacylbenzenes
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Received: March 18, 2020
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C–H Functionalization
E. Kianmehr,* B. Seifinoferest,
H. Afaridoun ........................................ 1–7
Palladium-Catalyzed Regioselective
Acylation of Diazines with Toluenes:
A New Approach to the Synthesis of
ortho-Diacylbenzenes
A practical, versatile, and efficient with toluene has been developed
method for the palladium catalyzed which provides a new approach for
regioselective acylation of ketazines ortho-acylation of aryl ketones.
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