Sonochemical Preparation of Dipicolinamide Mn-complexes and Their Application as Catalysts Towards Sono-synthesis of Ketones

Article abstract of DOI:10.1002/jhet.3518

A series of non-heme Mn-complexes has been synthesized by the sonication of manganese (II)chloride and bis-amides (condensation products of 2-picolinic acid and o-phenylenediamines). The Mn-complexes effectively promote the oxidation of unactivated aliphatic and benzylic C─H and N-bearing heterocycles substrates with low catalyst loading using eco-friendly hydrogen peroxide in the presence of acetic acid as additive under ultrasonic irradiation. Chromatographic studies revealed that the corresponding ketones are the only detectable products. Noteworthy, the presence of electron donors in the catalyst structure significantly increased the reaction yields. The substantial lowering of the oxidation reaction yields by adding ionol (2,6-di-tert-butyl-4-methylphenol) as a free radical trap suggesting a free radical reaction pathway.

Full text of DOI:10.1002/jhet.3518

Month 2019
Sonochemical Preparation of Dipicolinamide Mn-complexes and Their
Application as Catalysts Towards Sono-synthesis of Ketones
Wael A. A. Arafaa,b
*
aDepartment of Chemistry, College of Science, Jouf University, P.O. Box 2014, Sakaka, Aljouf, Saudi Arabia
bDepartment of Chemistry, Faculty of Science, Fayoum University, P.O. Box 63514, Fayoum, Egypt
*E-mail: waarafa@ju.edu.sa; waa00@fayoum.edu.eg
Received October 20, 2018
DOI 10.1002/jhet.3518
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
A series of non-heme Mn-complexes has been synthesized by the sonication of manganese (II)chloride
and bis-amides (condensation products of 2-picolinic acid and o-phenylenediamines). The Mn-complexes ef-
fectively promote the oxidation of unactivated aliphatic and benzylic C─H and N-bearing heterocycles sub-
strates with low catalyst loading using eco-friendly hydrogen peroxide in the presence of acetic acid as
additive under ultrasonic irradiation. Chromatographic studies revealed that the corresponding ketones are
the only detectable products. Noteworthy, the presence of electron donors in the catalyst structure signifi-
cantly increased the reaction yields. The substantial lowering of the oxidation reaction yields by adding ionol
(2,6-di-tert-butyl-4-methylphenol) as a free radical trap suggesting a free radical reaction pathway.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
the oxidation of C─H bonds under lower catalyst
loadings and mild conditions [6]. In contrast, Mn-based
enzyme catalysts have not been studied extensively in the
case of biomimetic selective oxidation of C─H bonds.
Manganese catalysts have attracted much concern
because they have shown promising results in water
splitting by photosystem II and in the catalytic oxidation
of organic substrates [7]. Notably, Mn-complexes bearing
amido pyridine moiety demonstrated better selectivity
and reactivity than structurally related iron complexes,
thus represented an appealing construction for
overcoming the two main challenges that impede the
development of new catalysts, that is, controlling the
selectivity and creating adequately reactive metal
complexes [8]. Moreover, Sun et al. reported that
benzimidazole-based manganese complexes catalyze
aliphatic and benzylic C─H as well as tertiary C─H
oxidation selectivity [9]. Also, Nam et al. showed that
mononuclear Bn-TPEN-Mn (IV)-oxo complex displays
good reactivity in oxidation of C─H bonds of
ethylbenzenes [10]. But, in almost cases the reaction
accomplished with by-products, poor yields, and using
large amount of the catalyst. Herein, a series of ligands
containing tetradentate amido pyridine was synthesized
In perspective of the substantial scale production and
usage of different organic substances in the modern
world, effective catalytic approaches are required to
diminish the risks of these chemicals to humans and the
environment [1]. Oxidation of alkanes using synthetic
catalysts poses an immense challenge in the reaction
designs. Selective oxidation and functionalization of
C─H bonds have essential applications such as the
preparation of fine chemicals and commodities; therefore,
the continuous development of such appealing
methodologies has become a focal point for many
researches [2]. Functionalization of C─H bonds is
primarily performed by employing iron-containing
enzymes that use dioxygen as the terminal oxidant, such
as Rieske dioxygenase and methane monooxygenase [3].
Inspired by these biological iron-enzymes, diverse of
biomimetic iron-based complexes had been synthesized
and utilized to catalyze the oxidation of C─H bonds [4].
Comprehensive studies encompassing iron catalysts have
supplied the key for understanding the mechanisms about
the oxidation of unactivated C─H bonds [5]. These
studies indicated that the iron-based catalysts can mediate
© 2019 Wiley Periodicals, Inc.

W. A. A. Arafa
Vol 000
with the idea of studying their coordination with
manganese salt, as well as the performance of the
synthesized Mn-complexes in catalyzing the selective
oxidation of unactivated aliphatic and benzylic C─H
bonds under ultrasonic irradiation by using H2O2 as an
environmentally friendly green oxidant in the presence of
AcOH.
and an assorted scope of 1,2-phenylenediamines (1a–e)
reacted under microwave irradiation at 50°C for 5 min to
afford excellent yields of the required functionalized
diamides 2a–e (Scheme 1).
In continuation with our study aiming to utilize diamides
for developing libraries in a combinatorial manner [11],
herein, a straightforward method was suggested that can
readily get to assortment of oriented single-site Mn-
complexes under conventional and ultrasound irradiation
protocols (Scheme 1; Table 2). To test the feasibility of
our envisioned route, in a typical reaction, to a solution
of diamide 2c (0.25 mmol) in methanol, were added
sequentially MnCl2.4H2O (0.27 mmol) and NaOMe
(0.50 mmol) at room temperature. The reaction was
investigated under different conditions (Table 2, entries
RESULTS AND DISCUSSION
At the beginning, the present investigation started with
the optimization of the reaction using the commercially
available 2-picolinic acid and 1,2-phenylenediamine 1c in
the presence of triphenyl phosphite as model substrates
(Table 1). Initially, the bis-amide 2c was prepared by
condensation of 2-picolinic acid (2 equiv) and 1,2-
phenylenediamine 1c (1 equiv) in the presence of
triphenyl phosphite (2 equiv) as the coupling reagent
under pyridine reflux for 1 h follow our previously method
(Table 1, entry 1) [11]. In spite of the good result, different
other protocols for the aforementioned reaction are still
required aiming to achieve an optimum condition for this
transformation. To investigate the microwave irradiation
(140 W) impact on the coupling reaction, the reaction
mixture containing model substrates was irradiated at
different temperatures (Table 1, entries 3, 5) for several
time intervals (Table 1, entries 2–4). It was found that
reducing the microwave irradiation time from 10 to 5 min
remained evenly effective; while reducing it further for
2 min diminished the yield of 2c and a great amount of
starting material remained unreacted (Table 1, entry 2).
As well, lowering the temperature of the reaction did not
afford productive results (Table 1, entry 5). Consequently,
under the optimized reaction conditions, 2-picolinic acid
Scheme 1. Synthesis of diamide ligands (2a–e) and their corresponding
single-site Mn-complexes (3a–e). [Color figure can be viewed at
wileyonlinelibrary.com]
Table 1
Screening the reaction conditions for the synthesis of diamide 2c.
Entry
Method
Temperature (°C)
Time
Yield (%)
1
2
3
4
5
Conventional
MW
70
50
50
50
30
1 h
79
67
98
98
60
2 min
5 min
10 min
5 min
MW
MW
MW
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Dipicolinamide Mn-complexes
Table 2
Screening the reaction conditions for the synthesis of single-site Mn complex 3c.
Entry
Cat.
Method
Time (min)
Yield (%)
1
2
3
4
5
6
7
NaOMe
NaOMe
NaOMe
NaOMe
NaOH
TEA
Conventional
120
2
5
10
10
10
10
66
90
92
98
74
58
52
US
US
US
US
US
US
Pip.
1–7), and the best result was obtained under sonication at
room temperature using NaOMe (2 equiv) as a base to
grab the hydrogen of the amide groups (Table 2, entry 4).
Having achieved an effective protocol for the Mn-
complexes synthesis, we then shove off to evaluate the
generality and scope of the reaction by employing several
ranges of diamide ligands to acquire the corresponding
Mn-complexes (Scheme 1). It was noticed that the
electronic nature of diamides had a considerable impact
on the reaction effectiveness, for example, unsubstituted
diamide (2c) furnished the best reaction yields, that is, 3c
(98%). Likewise, excellent yields were obtained in case
of electron-withdrawing groups existing on the o-
phenylenediamine core; for example, trifluoromethyl
group afforded the product 3d in 90% yield.
Nevertheless, the presence of chloro atoms resulted in a
minor loss of reaction yield (82%). All the newly
synthesized derivatives were characterized by NMR
spectroscopy and high resolution mass spectrometry (see
Supporting Information).
Next, the efficiency of diamide complexes (C1–C5;
Scheme 2) was examined to selectively oxidize the C─H
bonds of diversity of unactivated benzylic and aliphatic
C─H bonds. Complex C1 was chosen for the initial test
in order to establish the optimal reaction conditions. The
manganese complex C1 (0.1 mol %) was tested as a
catalyst for the oxidation of ethylbenzene (0.4 mmol) in
acetonitrile (1 mL) at room temperature. Five equivalents
Scheme 2. Pictorial of the synthesized complexes C1–C5. [Color figure can be viewed at wileyonlinelibrary.com]
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W. A. A. Arafa
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of H2O2 (as the O-atom source) was added to the reaction
tube under nitrogen over a period of 10 min using a
syringe pump under sonication. The reaction provided
acetophenone in 80% yield by using 5.0 equiv of acetic
acid as an additive (Table 3, entry 1; the additive
supports the activation of hydrogen peroxide and thus
controls the catalytic performance). The supreme result
(97% yield of acetophenone, Table 3, entry 2) was
obtained when the amount of AcOH was increased to 10
equiv with respect to the substrate. Moreover, the molar
ratio of Mn-complex C1 was also examined and found
that the best outcome was obtained on using 0.1 mol %.
Therefore, the optimized conditions for the
aforementioned protocol comprise the ultrasonic
irradiation of ethylbenzene and C1 (0.1 mol %) for 5 min
at room temperature in acetonitrile that afforded excellent
yield (97% yield as estimated by GC–MS analysis, Fig.
S22) of the required product (Table 3, entry 3).
Moreover, it was also observed that side product such as
α-methyl benzyl alcohol was not detected on the basis of
GC–MS analysis, which might indicate the fast
conversion of this intermediate into the desired product
(5a). To demonstrate which species is the active oxidant,
the same reaction was conducted without C1 (Table 3,
entry 9). No oxidation product was detected, even after
conducting the reaction for prolonged time, indicating
that C1, undoubtedly, is the active oxidant in the
reaction. Also, increasing the amount of hydrogen
peroxide does not affect the reaction yields (Table 3,
entry 10). After the identification of the optimized
A
methodical screening of varied solvents was
accomplished in the same catalytic system (C1). Lower
reaction yield was observed with solvents such as EtOH,
DMF, and THF (Table 3, entries 5–7). No product was
observed when the reaction was proceeded under aqueous
condition (Table 3, entry 8). From the aforementioned
experiments (Table 3, entries 1–8), only acetonitrile can
make the present protocol occur efficiently (Table 3,
entry 3). Accordingly, the reaction was screened at
several operating time intervals, that is, 2, 5, and 10 min
(Table 3, entries 2–4), and it is found that the required
product (5a) was obtained in 92%, 97%, and 97% yields,
respectively. Also, other diverse oxidants, such as t-
BuOOH, m-CPBA, and AcOOH were tested in the
present protocol; only H2O2 as the oxidant led to a
comparable results. Moreover, on running the model
reaction under stirring condition (without ultrasonic
irradiation), the reaction yield was decreased significantly
(Table 3, entry 11).
conditions,
a series of benzylic derivatives (4a–i)
containing diverse substituents on the aromatic
counterpart were subjected to the oxidation reaction
catalyzed by
a variety of Mn-complexes C1–C5
(Table 4). Almost of the tested substrates afforded the
corresponding ketones in >95% yields (Table 4). Other
bulk benzylic compounds were also explored; the
oxidation reaction of diphenylmethane provided the
benzophenone (5h) in a 95% yield (Table 4, entry 8). An
enhanced yield was observed for the oxidation of 1,2-
diphenylethane (Table 4, entry 9) due to the existence of
two identical benzylic sites. Also, oxidation of the
benzylic sites in cycloalkanes having aromatic rings was
Table 3
Evaluation of reaction conditions for C-H oxidation.
Entry
C1 (mol%)
Solvent
H2O2 (equiv)
AcOH (equiv)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
DMF
THF
H2O
5
5
5
5
5
5
5
5
5
5
10
10
5
80
97
97
92
55
10
10
10
10
10
10
10
10
10
10
2
10
10
10
10
10
10
10
6
62
NRa
NRa
96
9
10
11
CH3CN
CH3CN
CH3CN
0.1
0.1
10
5
63b
aNR, no reaction.
bUnder stirring condition.
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Dipicolinamide Mn-complexes
Table 4
Oxidation of benzylic C─H bonds with different catalyst systemsa.
Yield (%)
Entry
Compound
R1
R2
C1
C2
C3b
C4
C5
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
5i
CH3
C2H5
(CH3)2CH
CH3
CH3
CH3
CH3
C6H5
C6H5-CH2
H
H
H
97
98
97
97
98
97
96
95
97
97
97
97
99
98
97
95
94
98
99
98
97
99
99
98
96
96
98
95
96
93
96
94
93
91
92
93
93
91
90
93
91
90
92
91
91
CH3
Cl
CN
CH3CO
H
H
aReaction conducted on a 0.4 mmol scale with Mn-complexes (0.1 mol %), H2O2 (5 equiv), AcOH (10 equiv).
bReactions conducted with 0.07 mol % of Mn-complexes.
achieved (Scheme 3). For example, oxidation of 2,3-
dihydro-1H-indene (4j) under optimized condition gave
2,3-dihydro-1H-inden-1-one (5j) in 96% yield. Moreover,
the oxidation of 1,2,3,4-tetrahydronaphthalene (4k) took
place at one of the benzylic sites with 51% yield of
ketone using 0.1 mol % of the catalysts. On the other
hand, increasing the catalyst load to 0.2 mol % afforded
the required product (5k) in 96% yield. Next, the scope
of the reaction for different complex substituents was also
investigated. The reaction worked well with catalysts C2
and C3 housing electron-donating methyl (Me) and
methoxy (MeO) groups on the o-phenylene counterpart,
respectively, and both of them showed higher activity
than other catalysts, C4 and C5. Nonetheless, the
trifluoromethyl (CF3) containing complex (C4) showed
higher activity than complex C5 containing chloro atoms.
The obtained results obviously indicated that the presence
of electron-donating substituents on the ligand part
diminished the oxidation potential of the Mn center;
consequently, the efficiency of catalyzing C─H oxidation
reaction increased with respect to parent complex C1.
The manganese complex C3 demonstrated a much higher
activity towards all the substrates used (Table 4), which
allowed the use of only 0.07 mol % of the catalyst to
fulfill excellent oxidation yields (up to 99%) within 10 min
(Table 4).
Of the five examined complexes, the two top
performer’s complexes (C2 and C3) were chosen for
comparative analysis in the oxidation of non-benzylic
C─H bonds (Table 5). Four substrates, (6a–d), were used
for the purpose of these experiments. Oxidation of
cyclohexane (Table 5, entry 1) under optimized
conditions using electron-rich catalysts C2 and C3 gave
cyclohexanone in 98% and 99% yield, respectively
(Table 5, entry 1). Also, the oxidation of cyclopentane
was tested by using both C2 and C3, which gave
cyclopentanone as the sole product in 96% and 99%
yield, respectively (Table 5, entry 2). On the other hand,
oxidation of tert-butylcyclohexane (Table 5, entry 3),
using complex C3, gave mixture of both 4-(tert-butyl)
cyclohexan-1-one and 3-(tert-butyl)cyclohexan-1-one in
28% and 66% yields, respectively (Table 5, entry 3). In
this reaction, the oxidation mainly took place at the C3
site, due to the less steric effect of the equatorial
substituent [9]. GC–MS analyses of the oxidation
reaction solution of the cycloalkanes (6a–d) by C2 and
Scheme 3. Oxidation of 4k,j using complexes C1–C5.
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Table 5
Oxidation of C─H bonds with different catalyst systemsa.
Yield (%)
Entry
Compound
n
R
C2
C3
1
2
3
7a
7b
7c
2
1
2
H
H
98
96
59
26
95
99
99
66
28
98
3-t-butyl
4-t-butyl
H
4
7d
4
aReaction conducted on a 0.4 mmol scale with Mn-complexes (0.1 mol %), H2O2 (5 equiv), and AcOH (10 equiv).
C3 disclosed the formation of the corresponding
cycloalkanones as the sole products, and there was no
any signals detected corresponding to the cycloalkanols
(Fig. S23). In comparison between the oxidation power
of both C2 and C3, oxidation of substrates (6a–d) with
the C3 complex resulted in higher yields of the ketones
(Table 5). Noteworthy, substrates that possess reactive
nitrogen centers, for example, 2- and 4-ethylpyridines
(8a,b, Scheme 4) are smoothly oxidized at the C─H
bonds center under both C2 and C3 reaction conditions
to afford the corresponding ketones (9a,b) as the sole
products in excellent yields (Scheme 4, GC–MS, Fig.
S24). The ability to oxidize this site (CH2) in the
presence of the basic nitrogen atoms can be explained on
the basis of the possibility of nitrogen atoms to be
protonated in acidic media. Consequently, upon addition
of AcOH to Mn-complexes (C2 and C3), the pyridyl
reactive Mn (III)-oxo complex (B) upon reaction with the
AcOH. Thus, the presence of AcOH would expedite the
heterolysis of the O─O bonds of the intermediate (B).
This suggestion is confirmed by the observation that
increasing the amount of AcOH added results in the
increase of the reaction yields. The oxygenation of C─H
bonds proceeds via hydrogen atom abstraction from the
CH2 group by the electrophilic Mn site, as a result, a
short-lived electron-deficient radical intermediate was
formed (C). Followed by this step, an oxygen was
rebound to form the corresponding alcohol, which in turn
underwent oxidation reaction to afford the ketone
(Scheme 5) [13]. In order to investigate the mechanism of
the oxidation reaction in the present study, 20 equiv of
ionol (as a free radical trap) was added to the reaction
mixture during the oxidation of cyclohexane using
complex C1. As a result, a significant lowering of the
reaction yield was detected. This denotes that the reaction
proceeds fundamentally by a free radical pathway.
Moreover, the UV/Vis spectroscopic measurements at
low temperature (ꢀ40°C) were also studied to observe
the proposed reactive intermediates, MnIII, MnV=O, and
MnIV-OH. As soon as 5 equiv of H2O2 were added to a
solution of C1 in the presence and in the absence of
ethylbenzene, UV/Vis spectra were recorded within 3 s
for 15 min. As shown in Figure S25, there is no change
observed in the spectral, suggesting that those reactive
nitrogen atoms (pKa
= 5.17) should be largely
protonated, thus mitigating the problems resulting from
their coordination with metal-center and enabling the
oxidation of the desired C─H bonds to occur efficiently.
A proposed mechanism “carboxylic acid-assisted” for
the oxidation of C─H bonds by Mn-complexes (C1–C5)
is described in Scheme 5. At the initial stage, the Mn (II)
complex is oxidized to the hydroperoxo-Mn (III) (A) on
treated with H2O2. Proof for the formation of comparable
intermediate has been previously reported [12]. The
hydroperoxo complex intermediate (A) converted into a
intermediates might be existing in
a
very low
concentration to be detected or not spectroscopically
observed.
Scheme 4. Oxidation of 8a,b using complexes C2 and C3.
EXPERIMENTAL
Commercially available chemicals were used without
further purification unless otherwise indicated. Solvents
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Dipicolinamide Mn-complexes
Scheme 5. Proposed consensus mechanism for the C─H oxidation with H2O2 in the presence of diamide manganese complexes. [Color figure can be
viewed at wileyonlinelibrary.com]
were dried according to published procedures. Column
chromatography was generally performed on silica gel
(200–300 mesh) and TLC inspections were on silica gel
GF254 plates. 1H, 19F, and 13C NMR spectra were
recorded at 400, 377, and 100 MHz, respectively. The
chemical shifts (δ) are reported in ppm and coupling
constants (J) in Hz. High resolution mass spectra
(HRMS) measurements were recorded on a Bruker
Daltonics microTOF spectrometer. GC–MS analyses
were performed on a Thermo Scientific™ TRACE™ 1310
GC and GC–MS with Rxi-624sil MS column (50 m).
Microwave irradiation was carried out using Biotage®
Initiator Classic (Biotage AB; Uppsala, Sweden) using
sealed vessels. Ultrasonication was performed in Clifton
Ultrasonic Bath (2× T2A, 300 W, DU-4) with an output
power of 250 W and a frequency of 25 kHz, made by
Nickel Electro Ltd., Weston-super-Mare, Somerset,
England.
of the solvent under reduced pleasure gave a brown solid
that was washed with H2O/MeOH (1:1, 3 × 5 mL) to
yield the crude product. The crude product was purified
by crystallization or flash chromatography.
Microwave irradiation method. 1,2-Phenylenediamines
(0.5 mmol, 69 mg of 1a, 61 mg of 1b, 54 mg of 1c,
88 mg of 1d, 87.5 mg of 1e) and triphenyl phosphite
(0.25 mL, 1 mmol) was added to a solution of 2-picolinic
acid (1 mmol, 123 mg) in pyridine (5 mL). The yellow
solution was irradiated under microwave for 5 min at
50°C. Evaporation of the solvent under reduced pleasure
gave a brown solid that was washed with H2O/MeOH
(1:1, 3 × 5 mL) to yield the crude product. The crude
product was purified by crystallization or flash
chromatography.
Synthesis of N,N0-(4-methoxy-1,2-phenylene)dipicolinamide
(2a). Using the general procedure, 170.5 mg of 2a were
obtained following silica gel flash chromatography
(Rf = 0.35 in DCM) as colorless crystals (98% yield). IR
(KBr, cmꢀ1): 3211 (NH), 1677 (C═O). 1H NMR
(400 MHz, CDCl3): δ = 10.36 (s, 1H, NH), 9.94 (s, 1H,
NH), 8.60 (d, J = 4.12 Hz, 1H, Ar─H), 8.49 (d, J = 4.12,
1H, Ar─H), 8.33–8.27 (m, 2H, Ar─H), 7.92–7.85 (m,
2H, Ar─H), 7.72 (d, J = 2.78 Hz, 1H, Ar─H), 7.58 (d,
J = 8.84 Hz, 1H, Ar─H), 7.49–7.40 (m, 2H, Ar─H),
General procedure for synthesis of diamide ligands 2a–e.
Conventional method [11].
1,2-Phenylenediamines
(0.5 mmol, 69 mg of 1a, 61 mg of 1b, 54 mg of 1c,
88 mg of 1d, 87.5 mg of 1e) and triphenyl phosphite
(0.25 mL, 1 mmol) was added to a stirred solution of 2-
picolinic acid (1 mmol, 123 mg) in pyridine (5 mL). The
yellow solution was heated at 70°C for 1 h. Evaporation
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6.82 (dd, J = 8.72, 2.78 Hz, 1H, Ar─H), 3.86 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3): δ = 163.4 (C═O), 162.8
(C═O), 158.4 (Ph-C4), 149.9 (Py-C2), 149.8 (Py-C20),
148.4 (Py-C6), 148.3 (Py-C60), 137.6 (Ph-C1), 132.7 (Py-
C4), 126.7 (Ph-C6), 126.6 (Py-C5), 126.5 (Py-C50),
122.7 (Py-C3), 122.6 (Py-C30), 121.9 (Ph-C2), 112.1 (Ph-
C3), 108.6 (Ph-C5), 55.8 (CH3); HRMS (ESI) Calcd for
C19H16N4O3 [M + Na]: 371.1115; found: 371.1119.
Anal. Calcd for C19H16N4O3: C, 65.51; H, 4.63; N,
16.08. Found: C, 65.59; H, 4.60; N, 16.11.
(dd, J = 7.62, 1.69 Hz, 1H, Ar─H), 7.57 (dd, J = 8.48,
1.85 Hz, 1H, Ar─H), 7.51 (ddd, J = 7.62, 4.73, 1.21 Hz,
1H, Ar─H), 7.48 (ddd, J = 7.62, 4.73, 1.21 Hz, 1H,
Ar─H); 13C NMR (100 MHz, CDCl3): δ = 163.3 (C═O),
163.1 (C═O), 149.3 (Ph-C1), 149.2 (Py-C2), 148.4 (Py-
C6), 148.3 (Py-C60), 137.9 (Py-C4), 137.7 (Py-C40),
133.7 (Ph-C6), 129.8 (Py-C5), 128.0 (d, JCF = 4.6 Hz,
Ph-C4), 127.0 (Py-C3), 126.9 (d, JCF = 6.1 Hz, Ph-C3),
124.4 (CF3), 123.2 (q, JCF = 3.4 Hz, Ph-C2), 122.1 (q,
JCF = 3.4 Hz, Ph-C5); 19F NMR (100 MHz, CDCl3);
Synthesis of N,N0-(4-methyl-1,2-phenylene)dipicolinamide
(2b). Using the general procedure, 162.5 mg of 2b were
δ
=
ꢀ62.27 (CF3); HRMS (ESI) Calcd for
C19H13F3N4O2 [M + Na]: 409.0883; found: 409.0877.
Anal. Calcd for C19H13F3N4O2: C, 59.07; H, 3.39; N,
14.50. Found: C, 59.12; H, 3.43; N, 14.57.
obtained by crystallization from methanol as colorless
crystals (98% yield). IR (KBr, cmꢀ1): 3218 (NH), 1684
1
Synthesis
of
N,N0-(4,5-dichloro-1,2-phenylene)
(C═O). H NMR (400 MHz, CDCl3): δ = 10.23 (s, 1H,
dipicolinamide (2e).
Using the general procedure,
NH), 10.13 (s, 1H, NH), 8.57–8.55 (m, 1H, Ar─H),
8.54–8.53 (m, 1H, Ar─H), 8.32–8.31 (m, 1H, Ar─H),
8.30–8.29 (m, 1H, Ar─H), 7.90–7.86 (m, 2H, Ar─H),
7.74 (d, J = 1.45 Hz, 1H, Ar─H), 7.69 (d, J = 8.15 Hz,
1H, Ar─H), 7.46–7.43 (m, 2H, Ar─H), 7.11 (dd,
J = 8.15, 1.45 Hz, 1H, Ar─H), 2.40 (s, 3H, CH3); 13C
NMR (100 MHz, CDCl3): δ = 163.1 (C═O), 162.9
(C═O), 149.9 (Py-C2), 148.3 (Ph-C1), 137.5 (Py-C6),
136.4 (Py-C4), 130.3 (Ph-C6), 127.4 (Ph-C4), 126.9 (Py-
C5), 126.5 (Py-C50), 125.0 (Py-C3), 124.8 (Py-C30),
122.7 (Ph-C2), 122.6 (Ph-C5), 112.7 (Ph-C3), 21.2 (CH3);
HRMS (ESI) Calcd for C19H16N4O2 [M + Na]: 355.1165;
found: 355.1179. Anal. Calcd for C19H16N4O2: C, 68.66;
H, 4.85; N, 16.86. Found: C, 68.58; H, 4.95; N, 16.79.
Synthesis of N,N0-(1,2-phenylene)dipicolinamide (2c)
187.2 mg of 2e were obtained by crystallization from
dioxane as colorless crystals (97% yield). IR (KBr,
1
cmꢀ1): 3205 (NH), 1686 (C═O). H NMR (400 MHz,
DMSO-d6): δ = 10.84 (s, 2H, NH), 8.66 (d, J = 3.54 Hz,
2H, Ar─H), 8.18 (d, J = 7.48 Hz, 2H, Ar─H), 8.13–8.05
(m, 4 H, Ar─H), 7.69 (t, J = 5.51 Hz, 2H, Ar─H); 13C
NMR (100 MHz, DMSO-d6): δ = 162.9 (C═O), 148.8
(Py-C2), 148.6 (Py-C6), 138.3 (Py-C4), 131.0 (Ph-C1),
127.4 (Py-C5), 127.2 (Ph-C2), 126.3 (Ph-C3), 122.6 (Py-
C3); HRMS (ESI) Calcd for C18H12Cl2N4O2 [M + Na]:
409.0230; found: 409.0220. Anal. Calcd for
C18H12Cl2N4O2: C, 55.83; H, 3.12; N, 14.47. Found: C,
55.89; H, 3.10; N, 14.43.
General procedure for synthesis of Mn-complexes 3a–e.
The corresponding ligands 2a-e (0.5 mmol, 174 mg of 2a,
166 mg of 2b, 159 mg of 2c, 183 mg of 2d, 193 mg of 2e)
were suspended in MeOH (20 mL), combined with
NaOMe (1 mmol, 0.054 g), and sonicated for 10 min.
MnCl2.4H2O (0.5 mmol, 0.989 g) was then added and
the solution was sonicated at room temperature for
another 10 min. The resulting solid was filtered off,
washed with H2O/MeOH (1:1, 3 × 5 mL), and then dried.
Complex 3a. Using the general procedure, 198.5 mg of
3a were obtained as brown crystals (99% yield). IR (KBr,
cmꢀ1): 3011, 2984, 2927, 1632, 1600, 1556, 1480, 1402,
1321, 1227, 1103, 944, 922, 762, 680, 672, 547. HRMS
(ESI) Calcd for C19H14MnN4O3 [M]+: 401.0441; found:
401.0448. Anal. Calcd for C19H18MnN4O5: C, 52.18; H,
4.15; Mn, 12.56; N, 12.81. Found: C, 52.24; H, 4.13;
Mn, 12.50; N, 12.77.
[14].
Using the general procedure, 156 mg of 2c was
obtained by crystallization from ethanol as colorless
crystals (98% yield). IR (KBr, cmꢀ1): 3281 (NH), 1672
1
(C═O). H NMR (400 MHz, DMSO-d6): δ = 10.28 (s,
2H, NH), 8.54 (dd, J = 0.86, 1.43 Hz, 1H, Ar─H), 8.53
(dd, J = 0.86, 1.43 Hz, 1H, Ar─H), 8.31 (s, 1H, Ar─H),
8.29 (s, 1H, Ar─H), 7.90–7.85 (m, 4H, Ar─H), 7.45–7.42
(m, 2H, Ar─H), 7.31–7.27 (m, 2H, Ar─H); 13C NMR
(100 MHz, DMSO-d6): δ = 163.0 (C═O), 149.8 (Ph-C1),
148.3 (Py-C2), 137.6 (Py-C6), 130.3 (Py-C4), 126.6 (Py-
C5), 126.3 (Ph-C2), 124.8 (Ph-C3), 122.7 (Py-C3);
HRMS (ESI) Calcd for C18H14N4O2 [M + Na]: 341.1009;
found: 341.1001. Anal. Calcd for C18H14N4O2: C, 67.92;
H, 4.43; N, 17.60. Found: C, 67.88; H, 4.37; N, 17.54.
Synthesis
of
N,N0-(4-(trifluoromethyl)-1,2-phenylene)
dipicolinamide (2d).
Using the general procedure,
191 mg of 2d were obtained following silica gel flash
chromatography (Rf = 0.4 in DCM) as colorless crystals
(99% yield). IR (KBr, cmꢀ1): 3264 (NH), 1680 (C═O).
1H NMR (400 MHz, CDCl3): δ = 10.44 (s, 1H, NH),
10.28 (s, 1H. NH), 8.57 (ddd, J = 4.73, 1.69, 0.85 Hz,
1H, Ar─H), 8.55 (ddd, J = 4.73, 1.69, 0.85 Hz, 1H,
Ar─H), 8.35–8.30 (m, 2H, Ar─H), 8.20–8.15 (m, 2H,
Ar─H), 7.95 (dd, J = 7.62, 1.69 Hz, 1H, Ar─H), 7.91
Complex 3b. Using the general procedure, 190.6 mg of
3b were obtained as brown crystals (99% yield). IR (KBr,
cmꢀ1): 3020, 2972, 2931, 1626, 1610, 1584, 1491, 1411,
1329, 1223, 1110, 941, 934, 771, 679, 662, 567. HRMS
(ESI) Calcd for C19H14MnN4O2 [M]+: 385.0492; found:
385.0473. Anal. Calcd for C19H18MnN4O4: C, 54.17; H,
4.31; Mn, 13.04; N, 13.30. Found: C, 54.22; H, 4.27;
Mn, 13.05; N, 13.25.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Dipicolinamide Mn-complexes
Complex 3c [15].
Using the general procedure,
catalytic activity was found to be highly reliant on the
substituents on the ligand framework and was displayed
to be improved by the presence of electron-donating
groups (which enhance the creation of high valent Mn
species, bringing about higher catalytic activity), whereas
the presence of electron withdrawing substituents brought
about diminished the activity (which reducing the
electronic density on the ligand frameworks, and hence,
decreasing their ability to oxidize the metal center and
diminishing the catalytic activity). A simple preparation
protocol, high oxidation products yields, high efficiency,
and short reaction times make this catalytic system
extremely valuable for the oxidation of C─H. Moreover,
the basics of catalyst design disclosed in the present work
constitute a unique platform for more development of
stereoselective C─H oxidation reactions
181.8 mg of 3c were obtained as brown crystals (98%
yield). IR (KBr, cmꢀ1): 3081, 2976, 2947, 1640, 1605,
1586, 1479, 1416, 1331, 1252, 1112, 972, 917, 769, 670,
675, 522. HRMS (ESI) Calcd for C18H12MnN4O2 [M]+:
371.0335; found: 371.0343. Anal. Calcd for
C18H16MnN4O4: C, 53.08; H, 3.96; Mn, 13.49; N, 13.76.
Found: C, 53.05; H, 4.04; Mn, 13.55; N, 13.70.
Complex 3d. Using the general procedure, 197.5 mg of
3d were obtained as yellow crystals (90% yield). IR (KBr,
cmꢀ1): 3016, 2990, 2976, 1647, 1621, 1562, 1463, 1422,
1357, 1238, 1108, 941, 911, 753, 664, 677, 538. HRMS
(ESI) Calcd. for C19H11F3MnN4O2 [M]+: 439.0209;
found: 439.0218. Anal. Calcd for C19H15F3MnN4O4: C,
48.02; H, 3.18; Mn, 11.56; N, 11.79. Found: C, 48.08; H,
3.12; Mn, 11.58; N, 11.82.
Complex 3e. Using the general procedure, 179.6 mg of
3e were obtained as yellow crystals (82% yield). IR (KBr,
cmꢀ1): 3031, 2981, 2966, 1648, 1663, 1589, 1490, 1452,
1327, 1258, 1142, 988, 926, 795, 633, 600, 554. HRMS
(ESI) Calcd for C18H10Cl2MnN4O2 [M]+: 438.9556;
found: 438.9567. Anal. Calcd for C18H14Cl2MnN4O4: C,
45.40; H, 2.96; Mn, 11.54; N, 11.77. Found: C, 45.49; H,
2.91; Mn, 11.50; N, 11.83.
CONFLICTS OF INTEREST
The author declares no conflicts of interest.
Acknowledgment. I am very thankful to the Department of
Organic Chemistry, Arrhenius Lab., Stockholm University for
providing laboratory facilities.
General procedure for the catalytic benzylic and aliphatic
C─H oxidation. In a typical reaction, a MeCN (1 mL)
solution of substrate (0.4 mmol), desired (4 × 10ꢀ4
mmol, 0.1% mol) of Mn (II) complexes and acetic acid
(4 mmol, 10 equiv) was mixed in a 10 mL flask under
nitrogen at room temperature. H2O2 (2 mmol in 0.5 mL
of MeCN, 5 equiv) was injected by a syringe pump over
10 min with stirring under sonication. The solution was
sonicated for another 5 min after the syringe-pump
addition was completed. The reaction was quenched with
saturated NaHCO3 aqueous solution, saturated Na2S2O3
aqueous solution, and extracted with ether, then
determined by GC and GC–MS analyses. All reactions
were run at least in duplicate, the reported yields being
the average of these reactions. The products were
identified by comparison of their GC retention times with
those of authentic compounds. Quantitative analyses were
made on the basis of comparisons of peak integration
between products and authentic samples.
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Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet