Copper catalyzed oxidative ortho-C-H benzoxylation of 2-phenylpyridines with benzyl alcohols and benzyl amines as benzoxylation sources

Article abstract of DOI:10.1039/c4ob01912a

A simple and efficient protocol for the oxidative ortho benzoxylation of 2-phenylpyridines with benzyl alcohols and benzyl amines via C-H bond activation has been developed. The present protocol uses benzyl alcohol and benzyl amine as inexpensive and easi

Full text of DOI:10.1039/c4ob01912a

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Copper catalyzed oxidative ortho-C–H
benzoxylation of 2-phenylpyridines with benzyl
alcohols and benzyl amines as benzoxylation
sources†
Cite this: DOI: 10.1039/c4ob01912a
Ashok B. Khemnar and Bhalchandra M. Bhanage*
Received 9th September 2014,
Accepted 1st October 2014
A simple and efficient protocol for the oxidative ortho benzoxylation of 2-phenylpyridines with benzyl
alcohols and benzyl amines via C–H bond activation has been developed. The present protocol uses
benzyl alcohol and benzyl amine as inexpensive and easily available starting materials to afford benzoxyla-
tion products in moderate to good yields in the presence of the Cu/TBHP catalytic system.
DOI: 10.1039/c4ob01912a
www.rsc.org/obc
The transition metal catalyzed C–H bond functionalization has However, longer reaction time and the use of unstable carb-
become a highly efficient and atom-economical protocol in the oxylic salts as well as acyl chlorides were undesirable. Very
organic synthesis.1 The transformation of the unreactive ortho recently, Rout et al., developed the o-benzoxylation of 2-phenyl-
C–H bond of aromatic compounds to C–C, C–N, C–O and C–X pyridine using terminal aryl alkenes and alkynes as aryl-
bonds is a useful methodology for building complex mole- carboxy surrogates.13 Hence, the domino reactions using an
cules.2 The C–O bond formation via C–H bond activation is inexpensive copper catalyst with less reaction time can reduce
one of the most attractive processes. Consequently, various the environmental impacts as well as productive costs.
groups have reported the acetoxylation of an sp2 C–H bond of
In continuation of our ongoing research on the develop-
different aromatic substrates using various oxidizing reagents.3 ment of facile and efficient protocols,14 herein, we have develo-
Furthermore, Yu, Corey and Sanford have also demonstrated ped a simple, convenient and cost effective methodology for
the palladium catalyzed sp3 C–H bond acetoxylation reac- the o-benzoxylation of 2-phenylpyridines with benzyl alcohols
tions.4 However, these protocols were limited to acetoxylation and benzyl amines using an inexpensive and easily available
and hydroxylation reactions.
copper catalyst (Scheme 1).
The benzoxylation via transition-metal catalyzed C–H bond
The reaction of 2-phenylpyridine (1a) with benzyl alcohol
activation is also reported by some research groups. In this (2a) as an arylcarboxy source was chosen as a model system for
context, Sanford and co-workers reported the o-benzoxylation the oxidative benzoxylation reaction. A series of experiments
of 2-phenylpyridine with benzoate iodonium salts using a pal-
ladium catalyst.5 Subsequently, some groups have developed
palladium,6 rhodium7 and ruthenium8 catalyzed o-benzoxyla-
tion protocols using carboxylic acids and aryl acylperoxides as
benzoxylation sources. However, despite their potential utility,
the above reported methods suffer from one or more draw-
backs such as the use of air/moisture sensitive phosphine
ligands/additives and employing expensive palladium, rhodium
and ruthenium catalysts.
To overcome these drawbacks, some groups reported the
o-benzoxylation of 2-phenylpyridine using copper precursors
with different benzoxylation sources such as carboxylic salts,9
anhydrides,10 acid chlorides,11 aldehydes and alkylbenzene.12
Department of Chemistry, Institute of Chemical Technology, Mumbai, Maharashtra,
India. E-mail: bm.bhanage@gmail.com
†Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ob01912a
Scheme 1 Copper catalyzed benzoxylation of 2-phenylpyridine.
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Table 1 Optimization of the reaction conditionsa
did not proceed when m-CPBA and H2O2 were used as oxidants
(Table 1, entries 15 and 16). Furthermore, we have investigated
the effect of various solvents on the reaction outcome and it
was found that chlorobenzene is superior to other solvents
(Table 1, entries 7 and 17–19). Further investigations revealed
that the mole ratio of 1a : 2a played an important role to
increase the reaction yield. As the mole ratio of 1a : 2a was
changed from 1 : 2 to 1 : 1.5 and 1 : 2.5, the yield of 3a obtained
was 70%, 56% and 71%, respectively (Table 1, entries 7, 20 and
21). Therefore, the 1 : 2 mole ratio of 1a : 2a is the best choice.
The effect of variation in the reaction temperature was also
studied for the effective progress of benzoxylation reaction and
120 °C was found to be the optimum temperature (Table 1,
entry 7). With the increase or decrease in the reaction tempera-
ture, the yield of 3a was found to decrease (Table 1, entries 22
and 23). Furthermore, an increase in the reaction time does
not affect the reaction yield (Table 1, entry 24), whereas a
decrease in the reaction time from 11 h to 8 h resulted in low
yield of 3a (Table 1, entry 25). It shows that 11 h was an
optimum reaction time to afford the high yield of 3a (Table 1,
entry 7). The lower loading of CuI or TBHP led to decrease in
the reaction yield. Hence, the optimized reaction parameters
were: 2-phenylpyridine (0.5 mmol), benzyl alcohol (1 mmol),
CuI (0.1 mmol), TBHP (2 mmol) in 2 mL chlorobenzene at
120 °C for 11 h.
With these optimized reaction conditions in hand, we have
investigated the scope of the developed protocol for the syn-
thesis of diverse ortho benzoxylated products from various
ortho, meta and para-substituted benzyl alcohols with 2-phenyl-
pyridine (Table 2). The reaction of 1a with 2a under the
optimized reaction conditions provided 63% yield of the
desired product 3a (Table 2, entry 1). The p-Me, o-Me and
m-Me benzyl alcohols smoothly react with 1a and furnished
benzoxylated products 3b–3d with 75%, 69% and 73% yields,
respectively (Table 2, entries 2–4). It shows that the position of
the methyl substituent on the phenyl ring of benzyl alcohol
marginally affects the reaction yield. Next, p-tert-butyl benzyl
alcohol (2e) efficiently undergoes oxidative benzoxylation reac-
tion with 1a to deliver 3e in 78% yield (Table 2, entry 5). The
oxidative benzoxylation reaction of p-methoxy benzyl alcohol
(2f) with 1a also provided the desired product 3f in good yield
(Table 2, entry 6). Notably, 1-naphthalenemethanol also served
as a surrogate of the benzoxy group providing the naphthyl-
carboxylation product 3g in good yield (Table 2, entry 7). Further-
more, the halogen substituents like –Cl, –Br on the phenyl ring
of benzyl alcohols were compatible under the present reaction
conditions and deliver the corresponding benzoxylation pro-
ducts 3h and 3i in good yields (Table 2, entries 8 and 9). On
the other hand, the highly electron-deficient p-nitro benzyl
alcohol and aliphatic alcohols such as 1-ethanol as well as
2-phenyl-1-ethanol failed to provide the corresponding products.
Moreover, the benzoxylation of 2-(p-tolyl) pyridine (1b) was
also explored with a variety of benzyl alcohols under the opti-
mized reaction conditions and the obtained results are sum-
marised in Table 2. It was observed that 1b shows the same
pattern of reactivity as observed for 1a (Table 2, entries 10–15).
Catalyst
(mmol)
Oxidant
(mmol)
Solvent
(mL)
Yieldb
(%)
Entry
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2·H2O
CuO
CuBr2
CuCO3·Cu(OH)2
Cu2O
CuI
CuBr
CuCl
—
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
—
TBHP (aq.)
TBPB
TBP
m-CPBA
H2O2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCN
DCE
DCB
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
20
26
08
35
54
62
70 (20)c
38
27
00
00
34
30
10
00
00
20
07
31
56
71
59
23
70
58
9
10
11
12
13
14
15
16
17
18
19
20d
21e
22f
23g
24h
25i
CuI
CuI
CuI
a Reaction conditions: 1a (0.5 mmol), 2a (1 mmol), catalyst (0.1 mmol),
oxidant (2 mmol), solvent (2 mL), 120 °C, 11 h, open to air. b GC yield.
c Reaction was carried out in a closed vessel. d 2a (0.75 mmol). e 2a
(1.25 mmol). f 130 °C. g 110 °C. h 15 h. i 8 h.
were carried out to optimize reaction parameters such as cata-
lyst, oxidant, solvent, temperature and time on the model reac-
tion and the obtained results are summarized in Table 1.
Initially, our study focused on the screening of different
copper precursors such as Cu(OAc)2, Cu(OAc)2·H2O, CuBr2,
CuO, CuCO3·Cu(OH)2, Cu2O, CuI, CuBr and CuCl for the oxi-
dative benzoxylation reaction using tert-butyl hydroperoxide
(5.0–6.0 M in decane) (TBHP) as an oxidant at 120 °C (Table 1,
entries 1–9). The CuCO3·Cu(OH)2, Cu2O and CuI provided the
desired product 3a in 54%, 62% and 70% yield, respectively
(Table 1, entries 5–7). However, the other copper precursors
provided the benzoxylation product 3a in moderate to poor
yield. Next, when the reaction was carried out in the closed
reaction vessel, the yield of 3a decreases (Table 1, entry 7). The
desired product 3a was not observed either in the absence of
a catalyst or an oxidant, indicating that both the catalyst as
well as the oxidant are required for the progress of reaction
(Table 1, entries 10 and 11).
Next, we have tested various oxidants to enhance the yield
of 3a and it was observed that other organic peroxides such as
TBHP (aq.), tert-butyl perbenzoate (TBPB) and di-tertiary butyl
peroxide (TBP) have lower reactivities than TBHP (5.0–6.0 M in
decane) (Table 1, entries 7 and 12–14). However, the reaction
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Table 2 Substrate scope for oxidative benzoxylation of 2-arylpyridine
with benzyl alcoholsa
Table 2 (Contd.)
Benzyl
Entry 2-Arylpyridines alcohols
Yieldb
(%)
Yieldb
(%)
Product
Benzyl
Entry 2-Arylpyridines alcohols
Product
14
1b
62c
1
63
75
69
73
78
2
3
4
5
1a
1a
1a
1a
15
1b
61c
a Reaction conditions: 2-phenylpyridine (0.5 mmol), benzyl alcohols
(1 mmol), CuI (0.1 mmol), TBHP (2 mmol), PhCl (2 mL), 120 °C, 11 h,
open to air. b Isolated yield. c 16 h.
Proceeding further toward the substrate exploration of this
protocol, a broad range of readily available benzyl amines were
also screened for the oxidative benzoxylation of 2-phenyl-
pyridine, as summarized in Table 3. The optimized reaction
parameters using benzyl amine as the arylcarboxy surrogate
were: 2-phenylpyridine (0.5 mmol), benzyl amine (1 mmol),
Cu(OAc)2 (0.1 mmol), and TBHP (2.5 mmol) at 120 °C for 17 h
(see ESI† for the optimization table and the plausible reaction
mechanism of 1a with 2j). The reaction of 2-phenylpyridine
with ortho, meta and para substituents like –Me, –t-Bu, –OMe
and –Cl on the phenyl ring of benzyl amines delivered the
corresponding benzoxylation products in moderate yields
(Table 3, entries 1–7). Furthermore, N-methyl benzylamine (2q)
also served as a surrogate of the benzoxy group to provide the
product 3a′ in moderate yield (Table 3, entry 8). However, N,N-
dimethyl benzylamine failed to provide the desired product 3a′
under the optimized reaction conditions.
To probe the reaction mechanism of this transformation, a
series of experiments were performed (Scheme 2). When the
reaction mixture of 1a with 2a was examined using GC–MS
analysis, it shows the presence of benzaldehyde, benzoic acid
and benzyl benzoate in the reaction medium. To ascertain the
reaction pathway the reaction of 1a with benzaldehyde,
benzoic acid and benzyl benzoate was performed separately
and the benzoxylation product 3a was obtained in 72%, 60%
and 0% yields, respectively (Scheme 2). Furthermore, the reac-
tion of 1a with 2a in the presence of the radical scavenger
TEMPO provided very low yield of 3a (<5%) (Scheme 2). This
result indicates that the benzoxylation reaction may proceed
through a radical pathway.
6
7
1a
1a
63
57
8
1a
1a
60c
60c
71
9
10
11
1b
77
12
13
1b
1b
74
80
On the basis of the above mechanistic investigation and
previous reports,13,15 a tentative mechanism for the copper-
catalyzed ortho-C–H benzoxylation of 1a is depicted in
Scheme 3. The oxidative benzoxylation of 2-phenylpyridine
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Table 3 Substrate scope for oxidative benzoxylation of 2-arylpyridine
with benzyl aminesa
Yieldb
(%)
Entry 2-Phenylpyridine Benzyl amines Product
1
41
2
3
4
5
1a
1a
1a
1a
49
46
47
51
Scheme 2 Control experiments.
6
7
1a
1a
36
36
8
1a
41
Scheme 3 Plausible reaction mechanism of 1a with 2a.
a Reaction conditions: 1a (0.5 mmol), benzyl amines (1 mmol),
Cu(OAc)2 (0.1 mmol), TBHP (2 mmol), PhCl (2 mL), 120 °C, 17 h, open
to air. b Isolated yield.
In summary, a simple and efficient protocol has been deve-
loped for the benzoxylation of 2-phenylpyridine via C–H bond
activation using a commercially available copper catalyst and
TBHP as an oxidant. The present catalytic system uses inexpen-
sive, facile and readily available benzyl alcohols and benzyl
amines as benzoxylation sources. The developed protocol gives
benzoxylation products of 2-phenylpyridine in moderate to
good yields under the present reaction conditions.
(1a) is probably initiated by oxidation of Cu(I) to active Cu(II)
species. Then, the active Cu(II) species forms a chelation with
the 2-phenylpyridine via C–H bond activation to give the inter-
mediate A. Meanwhile, benzyl alcohol gets converted to benz-
aldehyde B via C–H bond activation in the presence of the Cu/
TBHP catalytic system. Next, benzaldehyde reacts with the tert-
butylperoxy radical generated from TBHP which gives tert-butyl
perester C.13 Homolytic cleavage of tert-butyl perester C
provides the benzoxy radical D along with the tert-butoxyl
radical.13 Then, the benzoxy radical D reacts with an inter-
mediate A to provide the Cu(III) intermediate E, which under-
goes reductive elimination to give the desired product 3a and
regenerate the Cu(I) catalyst for the next catalytic cycle.
Experimental section
General
All the chemicals were purchased from Sigma Aldrich, S.D.
Fine Chemical and Commercial Suppliers and were used
without further purification. The progress of the reaction was
monitored by gas chromatography Perkin Elmer Clarus 400
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GC equipped with a flame ionization detector (FID) with a acetate (3 × 5 mL). Consequently, the ethyl acetate layer was
capillary column (30 m × 0.25 mm × 0.25 μm) and thin layer washed with 5% solution of sodium bicarbonate solution (2 ×
chromatography using Merck silica gel 60 F254 plates. The 5 mL) followed by water (2 × 5 mL). The ethyl acetate extracts
products were visualized with a 254 nm UV lamp. GC-MS-QP were dried over Na2SO4 and the solvent was evaporated by
2010 instrument (Rtx-17, 30 m × 25 mm ID, film thickness (df) rotary evaporation to obtain the crude product which was then
= 0.25 µm) (column flow 2 mL min−1, 80 °C to 240 °C at 10 °C purified by column chromatography (silica gel, 100–200 mesh
min−1 rise) was used for the mass analysis of the products. size), with petroleum ether–ethyl acetate as the eluent to afford
1
Products were purified by column chromatography on a pure product. All compounds were confirmed by GC–MS, H
100–200 mesh silica gel. The 1H NMR spectra were recorded NMR and 13C NMR spectroscopic analysis.
on 300 MHz and 400 MHz spectrometers in CDCl3 using tetra-
methylsilane (TMS) as an internal standard. The 13C NMR
spectra were recorded on 75 MHz and 100 MHz spectrometers
Characterisation data of products
in CDCl3. Chemical shifts were reported in parts per million
2-(Pyridin-2-yl)phenyl benzoate (3a). Yellow oil; 86 mg
(δ) relative to tetramethylsilane as an internal standard. (63%); 1H NMR (500 MHz, CDCl3) δ 8.62–8.60 (m, 1H),
J (coupling constant) values were reported in hertz. Splitting 8.10–8.07 (m, 2H), 7.79–7.77 (m, 1H), 7.64–7.56 (m, 3H),
patterns of proton are described as s (singlet), d (doublet), dd 7.50–7.39 (m, 4H), 7.32–7.29 (m, 1H), 7.18–7.16 (m, 1H);
(doublet of doublets), t (triplet) and m (multiplet). The pro- 13C NMR (100 MHz, CDCl3) δ 165.16, 155.54, 149.58, 148.30,
ducts were confirmed by GC–MS, 1H and 13C NMR spectro- 136.19, 133.45, 133.30, 130.93, 130.17, 129.74, 129.48, 128.59,
scopic analysis.
126.41, 123.74, 123.32, 122.16; GCMS (EI, 70 eV): m/z (%): 275
(14, M+), 105 (100), 77 (33).
2-(Pyridin-2-yl)phenyl 4-methylbenzoate (3b). Yellow oil;
108 mg (75%); 1H NMR (400 MHz, CDCl3) δ 8.61–8.60 (m, 1H),
General experimental procedure for oxidative benzoxylation of
2-phenylpyridine with benzyl alcohol
2-Phenylpyridine (1a, 0.5 mmol), benzyl alcohol (2a, 1 mmol) 7.97 (d, J = 8.0 Hz, 2H), 7.78 (dd, J = 7.6, 1.8 Hz, 1H), 7.63–7.54
and CuI (0.1 mmol) in 2 mL chlorobenzene were charged in an (m, 2H), 7.49–7.45 (m, 1H), 7.41–7.37 (m, 1H), 7.30 (dd, J = 8.0,
oven dried 10 mL two-necked round bottom flask. At room 1.2 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.16–7.13 (m, 1H), 2.42 (s,
temperature TBHP (5–6 M in decane, 2 mmol) was added drop- 3H); 13C NMR (100 MHz, CDCl3) δ 165.20, 155.57, 149.62,
wise to the reaction flask with stirring. The flask was then 148.35, 144.29, 136.12, 133.35, 130.91, 130.24, 129.69, 129.22,
equipped with a condenser and the reaction mixture was 126.71, 126.32, 123.76, 123.37, 122.10, 21.73; GCMS (EI, 70
stirred at 120 °C for 11 h in open air and the progress of reac- eV): m/z (%): 289 (9, M+), 119 (100), 91 (29), 40 (13).
tion was monitored by TLC and GC. After completion, the reac-
2-(Pyridin-2-yl)phenyl 2-methylbenzoate (3c). Yellow oil;
1
tion mixture was allowed to cool to room temperature, diluted 99 mg (69%); H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 5.0 Hz,
with ethyl acetate (10 mL) and filtered through a celite bed. 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.66–7.63
The celite bed was washed with ethyl acetate (3 × 5 mL). Conse- (m, 1H), 7.56–7.54 (m, 1H), 7.50–7.47 (m, 1H), 7.43–7.38 (m,
quently, the ethyl acetate layer was washed with 5% aqueous 2H), 7.30–7.24 (m, 4H), 2.53 (s, 3H); 13C NMR (100 MHz,
solution of sodium bicarbonate (2 × 5 mL) followed by water CDCl3) δ 165.71, 155.83, 149.54, 148.33, 141.21, 136.22, 133.51,
(2 × 5 mL). The combined ethyl acetate extracts were dried over 132.49, 131.76, 131.07, 130.88, 129.73, 128.56, 126.33, 125.77,
Na2SO4 and the solvent was evaporated by rotary evaporation 123.73, 123.42, 122.15, 21.60; GCMS (EI, 70 eV): m/z (%): 289
to obtain the crude product which was then purified by (3, M+), 119 (100), 91 (36), 40 (5).
column chromatography (silica gel, 100–200 mesh size), with
2-(Pyridin-2-yl)phenyl 3-methylbenzoate (3d). Yellow oil;
petroleum ether–ethyl acetate as the eluent to afford a pure 105 mg (73%); 1H NMR (300 MHz, CDCl3) δ 8.64–8.62 (m, 1H),
1
product. The products were confirmed by GC-MS, H and 13C 7.90–7.86 (m, 2H), 7.77 (d, J = 8.0 Hz, 1H), 7.61–7.53 (m, 2H),
NMR spectroscopic analysis.
7.45 (d, J = 8.0 Hz, 1H), 7.40–7.30 (m, 4H), 7.17–7.12 (m, 1H),
2.37 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 165.27, 155.42,
149.42, 148.31, 138.30, 136.36, 134.27, 133.14, 130.93, 130.69,
129.78, 129.28, 128.37, 127.29, 126.36, 123.86, 123.27, 122.23;
General experimental procedure for oxidative benzoxylation of
2-phenylpyridine with benzyl amine
A mixture of 2-phenylpyridine (1a, 0.5 mmol), benzyl amine GCMS (EI, 70 eV): m/z (%): 289 (13.6, M+), 119 (100), 91 (37.4),
(2j, 1 mmol) and Cu(OAc)2 (0.1 mmol) in 2 mL chlorobenzene 65 (10.5).
was placed in an oven dried 10 mL two-necked round bottom
2-(Pyridin-2-yl)phenyl 4-(tert-butyl)benzoate (3e). Yellow oil;
flask. At room temperature TBHP (5–6 M in decane, 2.5 mmol) 129 mg (78%); 1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 4.9 Hz,
was added dropwise to the reaction flask with stirring. The 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 7.6 Hz, 1H), 7.65–7.61
flask was then equipped with a condenser and the reaction (m, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.49–7.45 (m, 3H), 7.39 (t, J =
mixture was stirred at 120 °C for 17 h in open air. The progress 7.6 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 7.18–7.15 (m, 1H), 1.34 (s,
of the reaction was monitored by TLC and GC. After com- 9H); 13C NMR (100 MHz, CDCl3) δ 165.15, 157.26, 155.56,
pletion, the reaction mixture was allowed to cool to room 149.65, 148.33, 136.15, 133.36, 130.96, 130.08, 129.69, 126.64,
temperature, diluted with ethyl acetate (10 mL) and filtered 126.31, 125.51, 123.81, 123.34, 122.12, 35.18, 31.10; GCMS (EI,
through a celite bed. The celite bed was washed with ethyl 70 eV): m/z (%): 331 (7, M+), 162 (12), 161 (100).
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2-(Pyridin-2-yl)phenyl 4-methoxybenzoate6c (3f). Yellow oil;
5-Methyl-2-(pyridin-2-yl)phenyl 2-methylbenzoate (3l).
96 mg (63%); H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 4.8 Hz, Yellow oil; 112 mg (74%); 1H NMR (300 MHz, CDCl3)
1H), 8.04 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 7.6, 1.7 Hz, 1H), δ 8.59–8.57 (m, 1H), 8.02–7.99 (m, 1H), 7.70–7.39 (m, 4H),
7.62–7.59 (m, 1H), 7.56–7.54 (m, 1H), 7.48–7.45 (m, 1H), 7.26–7.10 (m, 5H), 2.53 (s, 3H), 2.43 (s, 3H); 13C NMR (75 MHz,
7.40–7.36 (m, 1H), 7.30–7.28 (m, 1H), 7.17–7.14 (m, 1H), 6.92 CDCl3) δ 165.80, 155.78, 149.41, 148.08, 141.12, 140.18, 136.18,
(d, J = 8.8 Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) 132.42, 131.72, 131.03, 130.57, 130.48, 128.60, 127.18, 125.73,
δ 164.86, 163.82, 155.58, 149.58, 148.38, 136.14, 133.34, 132.31, 123.82, 123.57, 121.90, 21.59, 21.17; GCMS (EI, 70 eV): m/z (%):
130.90, 129.69, 126.25, 123.80, 123.40, 122.11, 121.74, 113.78, 303 (2.5, M+), 119 (100), 91 (37.2), 65 (10.4).
1
55.48; GCMS (EI, 70 eV): m/z (%): 305 (5, M+), 135 (100),
77 (12), 40 (6).
5-Methyl-2-(pyridin-2-yl)phenyl 4-(tert-butyl)benzoate (3m).
Yellow oil; 138 mg (80%); 1H NMR (300 MHz, CDCl3)
2-(Pyridin-2-yl)phenyl 1-naphthoate (3g). Yellow oil; 92 mg δ 8.62–8.59 (m, 1H), 8.06–7.98 (m, 1H), 7.87–7.84 (m, 1H), 7.69
(57%); 1H NMR (500 MHz, CDCl3) δ 8.86 (d, J = 8.8 Hz, 1H), (d, J = 8.0 Hz, 1H), 7.62–7.54 (m, 2H), 7.48–7.38 (m, 3H),
8.59 (d, J = 5.0 Hz, 1H), 8.31 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 7.8 7.26–7.23 (m, 1H), 7.11–7.06 (m, 1H), 2.43 (s, 3H), 1.35 (s, 9H);
Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 13C NMR (75 MHz, CDCl3) δ 165.28, 157.23, 155.53, 149.51,
7.62–7.49 (m, 6H), 7.45–7.42 (m, 1H), 7.37 (d, J = 8.0 Hz, 1H), 148.17, 140.19, 136.23, 130.72, 130.10, 130.00, 127.23, 126.72,
7.17–7.13 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 165.70, 125.52, 125.41, 123.80, 121.96, 35.18, 31.12, 21.23; GCMS (EI,
155.84, 149.54, 148.38, 136.31, 134.01, 133.80, 133.59, 131.58, 70 eV): m/z (%): 345 (8.6, M+), 162 (12.2), 161 (100), 118 (9.4).
131.03, 130.91, 129.81, 128.53, 128.01, 126.45, 126.33, 125.96,
125.81, 124.46, 123.65, 123.50, 122.18; GCMS (EI, 70 eV): m/z Yellow oil; 100 mg (62%); 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
(%): 325 (5, M+), 155 (100), 127 (48).
J = 4.8 Hz, 1H), 8.00 (d, J = 8.8 Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H),
5-Methyl-2-(pyridin-2-yl)phenyl 4-chlorobenzoate (3n).
2-(Pyridin-2-yl)phenyl 4-chlorobenzoate (3h). Yellow oil; 7.63–7.58 (m, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.6 Hz,
1
92 mg (60%); H NMR (500 MHz, CDCl3) δ 8.57–8.56 (m, 1H), 2H), 7.21 (d, J = 8.6 Hz, 1H), 7.14–7.10 (m, 2H), 2.43 (s, 3H);
8.01 (d, J = 8.8 Hz, 2H), 7.76 (dd, J = 8.0, 1.6 Hz, 1H), 7.66–7.62 13C NMR (100 MHz, CDCl3) δ 164.48, 155.60, 149.49, 147.94,
(m, 1H), 7.55–7.45 (m, 2H), 7.44–7.40 (m, 3H), 7.30 (d, J = 8.0 140.29, 139.91, 136.21, 131.53, 130.61, 130.25, 128.85, 128.04,
Hz, 1H), 7.18–7.15 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 127.42, 123.71, 123.45, 121.96, 21.20; GCMS (EI, 70 eV): m/z
164.35, 155.55, 149.53, 148.12, 139.98, 136.29, 133.19, 131.54, (%): 323 (16, M+), 141 (34), 140 (8), 139 (100), 111 (24).
131.08, 130.90, 129.80, 128.85, 126.55, 123.63, 123.26, 122.23;
GCMS (EI, 70 eV): m/z (%): 309 (10.2, M+), 141 (33.8), 139 (100), Yellow oil; 112 mg (61%); 1H NMR (300 MHz, CDCl3)
111 (26.9), 75 (9.4), 44 (9.7). δ 8.51–8.50 (m, 1H), 7.94–7.90 (m, 2H), 7.61–7.55 (m, 3H), 7.49
5-Methyl-2-(pyridin-2-yl)phenyl 4-bromobenzoate (3o).
2-(Pyridin-2-yl)phenyl 4-bromobenzoate (3i). Yellow oil; (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.17–7.09 (m, 3H),
105 mg (60%); 1H NMR (300 MHz, CDCl3) δ 8.55 (d, J = 8.0 Hz, 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.60, 155.50,
1H), 7.92 (d, J = 8.5 Hz, 2H), 7.73 (dd, J = 7.6, 1.6 Hz, 1H), 149.37, 147.90, 140.35, 136.36, 131.86, 131.63, 131.41, 130.61,
7.60–7.38 (m, 6H), 7.29 (d, J = 7.9 Hz, 1H), 7.18–7.13 (m, 1H); 128.47, 128.42, 127.43, 123.68, 123.54, 122.05, 21.20; GCMS
13C NMR (75 MHz, CDCl3) δ 164.49, 155.46, 149.46, 148.08, (EI, 70 eV): m/z (%): 369 (20.1, (M + 2)+), 367 (20.4, M+), 185
136.41, 133.08, 131.87, 131.53, 130.90, 129.84, 128.71, 128.49, (96.9), 184 (12.1), 183 (100), 157 (21.5), 155 (23.4), 76 (14.2),
126.57, 123.69, 123.24, 122.29; GCMS (EI, 70 eV): m/z (%): 355 75 (9.8).
(18.7, (M + 2)+), 353 (18.9, M+), 185 (95), 183 (100), 157 (22.5),
155 (24.2), 76 (16.6), 75 (12.3).
5-Methyl-2-(pyridin-2-yl)phenyl benzoate (3j). Yellow oil;
Acknowledgements
102 mg (71%); 1H NMR (300 MHz, CDCl3) δ 8.57–8.54
(m, 1H), 8.10–8.06 (m, 2H), 7.68 (d, J = 8.0 Hz, 1H), 7.60–7.50 A. B. Khemnar is greatly thankful to the Council of Scientific
(m, 3H), 7.46–7.38 (m, 2H), 7.21–7.17 (m, 1H), 7.12–7.02 and Industrial Research (CSIR), New Delhi, India for providing
(m, 2H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 165.32, senior research fellowship (SRF).
155.54, 149.52, 148.15, 140.24, 136.22, 133.48, 130.70,
130.36, 130.17, 129.55, 128.52, 127.33, 123.81, 123.62, 121.98,
21.22; GCMS (EI, 70 eV): m/z (%): 289 (11.3, M+), 105 (100),
77 (34.4).
Notes and references
5-Methyl-2-(pyridin-2-yl)phenyl 4-methylbenzoate (3k).
Yellow oil; 116 mg (77%); 1H NMR (400 MHz, CDCl3)
δ 8.58–8.57 (m, 1H), 7.97 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 7.8 Hz,
1H), 7.60–7.52 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.6
Hz, 1H), 7.13–7.09 (m, 2H), 2.42 (s, 3H), 2.41 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 165.32, 155.58, 149.54, 148.16, 144.23,
140.13, 136.06, 130.64, 130.41, 130.22, 129.21, 127.20, 126.79,
123.80, 123.59, 121.86, 21.72, 21.19; GCMS (EI, 70 eV): m/z (%):
303 (11, M+), 120 (9), 119 (100), 91 (28).
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