Synthesis of 6-substituted 2-phenacylpyridines from 2-(phenylethynyl)pyridine via isoxazolo[2,3-a]pyridinium salt

Article abstract of DOI:10.1039/c6ob01942k

When 2-(phenylethynyl)pyridine was oxidized, the formed N-oxide immediately cyclized at the ethynyl group to form isoxazolo[2,3-a]pyridinium salt. This salt underwent Reissert-Henze-type reactions with alcohol in the presence of a base to afford 6-substituted 2-phenacylpyridines, which are not easily synthesized through alternative procedures. When acetonitrile was used as a solvent, an amide functional group was introduced into the phenacylpyridine framework. Moreover, a hetero-atom at the 6-position facilitated the oxidation of the phenacyl group to afford α-diketones upon simple exposure of the reaction mixture to air.

Full text of DOI:10.1039/c6ob01942k

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Synthesis of 6-substituted 2-phenacylpyridines from 2-
(phenylethynyl)pyridine via isoxazolo[2,3-a]pyridinium salt
Song T. Le,a,b Toshiki Fujimoto,b Haruyasu Asahara*b,c and Nagatoshi Nishiwaki*b,c
Received 00th January 20xx,
Accepted 00th January 20xx
Abstract. When 2-(phenylethynyl)pyridine was oxidized, the formed N-oxide immediately cyclized at the ethynyl group to
form isoxazolo[2,3-a]pyridinium salt. This salt underwent Reissert-Henze-type reactions with alcohol in the presence of a
base to afford 6-substituted 2-phenacylpyridines, which are not easily synthesized through alternative procedures. When
acetonitrile was used as a solvent, an amide functional group was introduced into the phenacylpyridine framework.
Moreover, hetero-atom at the 6-position facilitated the oxidation of the phenacyl group to afford α-diketone upon simple
DOI: 10.1039/x0xx00000x
www.rsc.org/
exposure
of
the
reaction
mixture
to
air.
Introduction
Reissert-Henze reactions using N-acyloxypyridinium halides
1
various bicyclic pyrido compounds has also been reported.3
Ethynylpyridine N-oxides can serve as key precursors for the
construction of a larger compound library using Reissert-
Henze reactions if they become easily available. While 4-
ethynylpyridine N-oxides are readily obtained by the
(Reissert-Henze salts) are known as one of the most useful
methods for the functionalization of pyridine rings, leading to
2-functionalized pyridines via nucleophilic addition and,
rearomatization with the concomitant elimination of
carboxylic acid (Scheme 1).1 Ethynylpyridines
a
2
have been
oxidation of 4-ethynylpyridine,4 2-ethynylpyridine N-oxides
are hitherto unknown. This fact prompted us to study the
oxidation of 2-ethynylpyridine
3
widely used as synthetic intermediates for DNA-cleaving
antitumor agents,2 lobelane. Their transformation into
2.
Electronic Supplementary Information (ESI) available: 1H and 13C NMR spectral data of
compounds 7, 9, 11 and 14. X-ray crystallographic data of 9a. CCDC 1502083. For ESI
and crystallographic data in CIF or other electronic format. See
DOI: 10.1039/x0xx00000x
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Scheme 1 Reiisert-Henze reaction and similar type reaction using isoxazolopyridinium salt 4A
It was found that the initially formed N-oxide
3
Henze salt
1. These structural features are considered to
spontaneously converted to an isoxazolopyridinium salt 4A
by the intramolecular attack of the N-oxide onto an ethynyl
group. This salt has both an electron-deficient pyridinium ring
and a good enolate ion leaving group, similar to Reissert-
facilitate the synthesis of versatile 6-substituted 2-
phenacylpyridines
nucleophile.
3 upon treatment of salt 2a with a
2-Phenacylpyridine derivatives
5
are widely used as
the most suitable for this reaction (entries 1–4). The reaction
proceeded to completion within 1 h (entry 5). Although NEt3
could also be used as a base, the efficiency in this case was
lower than that observed when using t-BuOK. Consequently,
the reaction conditions corresponding to entry 5 were
determined to be the optimal conditions.
antibacterial agents,5 11βHSD inhibitors,6 and ligands.7 In
addition, 2-phenacylpyridines are important synthetic
intermediates for the construction of the 4H-quinolizin-4-one
scaffold, which has potential applications in the treatment of
Alzheimer’s disease,8 Type 2 diabetes9 and HIV,10 and serves
as precursors for some interesting alkaloids such as
hydrangea,11 lamellarins,12 and sedamine.13 Furthermore, 2-
phenacylpyridine derivatives serve as precursors to indolizine
derivatives for CRTH2 receptors,14 bicyclic pyridines,3 and
bioactive natural products.13
Table 1. Optimization of reaction conditions
i-PrOH 6a
Pri
Base
N
Pri
X
O
N
O
N
O
Solvent
rt
2-Phenacylpyridine derivatives
hydration of the corresponding 2-(phenylethylnyl)pyridines
) or by condensation of 2-picolyllithium with methyl
5 are generally synthesized by
Ph
HO
Ph
O
Ph
X = OAc 4A
BF4 4B
7a
HBF4
CHCl3
quant.
(
2
benzoate.15 However, these methods suffer from poor
availability of the starting materials, require strong acidic
conditions, and involve the use of toxic mercury salt as the
catalysts. Transition-metal catalyzed carbonylative coupling
reactions have recently been identified as possible routes to
functionalized phenacylpyridines;16 however, a purification
step to avoid contamination of the products by metal species
entry
Solv.
DMSO
THF
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
Time/h
Base
Yield/%
0
1
2
3
4
5
6
3
3
3
3
1
20
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
NEt3
0
60
81
79
45
is necessary, which increases the cost of preparation of 5.
Other synthetic methods using a strong base such as BuLi,
LDA, PhLi, or NaNH2 sometimes suffer from low yields of the
products and poor functional group tolerance.17 Therefore,
the development of efficient inexpensive, facile, and
Table 2. Synthesis of 6-alkoxylated phenacylpyridines
7
environmentally benign
methods
for synthesizing
t-BuOK
(1.2 equiv.)
functionalized phenacylpyridines is highly desired. From this
viewpoint, the development of a new synthetic method for 6-
N
+
ROH
RO
N
CH2Cl2
rt, 1 h
O
BF4
Ph
(5.0 equiv.)
substituted 2-phenacylpyridines
5 was considered in this
O
Ph
work. The obtained compounds were found to undergo
oxidation, affording the corresponding α-diketones without
any further treatment.
4B
6
7
entry
R
Me
Et
Yield/%
98
87
1
2
3
4
5
6
7
8
b
c
d
e
f
g
h
i
t-Bu
PhCH2
PhCh2CH2
HOCH2CH2
ClCH2CH2CH2
CH2=CHCH2
HC≡CCH2
H
42
25
37
58
56
41
14
48
Results and Discussion
Initially, oxidation of ethynylpyridine
2 with H2O2-AcOH was
carried out at 80 °C for 4 h. NMR examination of the reaction
mixture indicated that isoxazolo[2,3-a]pyridinium acetate
4A18 was formed as an oily liquid, which was difficult to
handle because of its instability and high viscosity. Thus,
anion exchange was performed by the addition of HBF4 to the
reaction mixture affording salt 4B as a yellow solid in
quantitative yield; this salt was more stable and easily
treatable than salt 4A. The reaction of salt 4B with i-PrOH 6a
in the presence of t-BuOK yielded alkoxylated
phenacylpyridine 7a and a mixture of keto-enol tautomers in
3:2 ratio. Optimization of the reaction conditions was
performed using this reaction as the model reaction (Table 1).
Among the several solvents tested, CH2Cl2 was found to be
9
j
k
10a
a K2CO3 was used as a base.
With the optimized conditions in hand, we studied the
substtrate scope of this method by conducting the reaction of
salt 4B with alcohols 6b–k in the presence of t-BuOK (Table 2).
In the reaction with MeOH 6b, 6-methoxy-2-phenacylpyridine
7b was obtained in excellent yield (entry 1). A bulky alkoxy
2 | J. Name., 2012, 00, 1-3
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group could be introduced into the 6-position of the 2-
phenacylpyridine framework, although the yields were
reduced because of the competitive reaction of 4B with
water in the solvent (entries 2–5). This method was also
applicable to alcohols 6g–j having a functional group such as
OH, Cl, CH=CH2, and C≡CH and a series of 6-functionalized 2-
phenacylpyridines 7g–j were obtained (entries 6–9). Water
reacted in a similar fashion, furnishing 6-hydroxy derivative
3k. However, a complex mixture was obtained because 3k is
somewhat reactive, which results in further transformation to
afford unidentified products (entry 10). It was also confirmed
that alkyl substituted isoxazolopyridinium salt 4C also
underwent the reaction similarly to afford 2,6-disubstituted
pyridine 7l although the reaction conditions should be
optimized (Scheme 2).
attack of intermediate 10 generated by the addition of
hydroxide ion to nitrile (Scheme 3).
Table 3. Synthesis of 6-acylaminated 2-phenacylpyridines 9
O
Base
RCN
+
N
R
N
N
rt, time
H
BF4
Ph
O
O
Ph
4B
9
entry
1a
R
Time/h
3
Base (equiv.)
t-BuOK (5)
Na2CO3 (1)
K2CO3 (1.2)
K2CO3 (1.2)
K2CO3 (1.2)
K2CO3 (1.2)
K2CO3 (1.2)
K2CO3 (1.2)
Yield/%
24
Me
Me
Me
Et
a
a
a
b
c
2a
20
47
3a
20
91
4a
20
98
5b
i-Pr
20
64
6b
CH2=CH
PhCH2
d
e
f
20
43
7b
20
38
K2CO3
8b
p-ClC6H4
20
52
(1.2 equiv.)
N
+
MeOH
a
b
Nitrile was used as the solvent. 5 equivalents of nitrile were added to a
MeO
N
CH2Cl2
rt, 2 d
O
OAc
Bu
(1.2 equiv.)
solution of 4B in CH2Cl2.
O
Bu
4C
7l
Scheme 2. Ring opening reaction of alkyl substituted isoxazolopyridinium salt
4C
Base
H
OH
OH
N
R
N
R
N
O
BF4
Ph
8
10
4B
O
R
N
N
R
N
N
O
H
H
O
H
O
Ph
Base
Ph
9
Scheme 3. A plausible mechanism for forming 9
Figure 1. An ORTEP drawing of 9a
Unexpectedly, the obtained 6-alkoxy-2-phenacylpyridines 7a
and 7b underwent oxidation to yield the corresponding α-
diketones 11a and 11b when allowed to stand at room
temperature in air or oxygen atmosphere under light (Table 4,
entries 1–3).19 Unsubstituted phenacylpyridine 12 showed no
change under the same conditions (entry 4). When oxidation
of 7b was performed using oxidants such as mCPBA, diketone
11b was efficiently obtained (entry 5). Although 6-methoxy-2-
phenacylpyridine 7b was readily oxidized, it could be stored
without any problem under nitrogen atmosphere under dark
When the reaction of isoxazolopyridinium salt 4B with i-PrOH
6a was conducted in MeCN 8a, a different reactivity was
observed. Namely, an acetylamino group was introduced to
the 6-position of 2-phenacylpyridine, affording 9a without
any detectable amount of alkoxylated 2-phenacylpyridine 7a
.
The product 9a also exists as a mixture of keto-enol
tautomers in 6:1 ratio. The structure of 9a was confirmed by
both X-ray crystallography and spectral data (Figure 1). In this
case, K2CO3 is the best choice, as it affords the highest yield
of product 9a (Table 3, entries 1–3). Furthermore,
propanoylamino, isopropanoylamino, acryloylamino and
phenylacetyl groups could be introduced to afford products
(entry 6). Similar oxidations were also observed for 7a and 9a
yielding the corresponding α-diketones 11a and 14
,
,
respectively, although the yield was lower (entries 7–10). On
the other hand, no conversion of 7b was observed upon
treatment with TEMPO resulting in the quantitative recovery
of 7b (entry 11). These results indicate that a hetero-atom at
9b–e in good yields (entries 4–7).Furthermore, this reaction
was applicable to aromatic nitrile leading to aroylamino
pyridine 9f. This reaction is considered to proceed by the N-
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the 6-position is crucial for oxidation of the phenacyl group,
and this oxidation proceeds via the radical mechanism, as
illustrated in Scheme 4. The hetero-atom is considered to
serve as a single electron donor to form diradical 15, which
traps molecular oxygen to give hydroperoxide 16. The
subsequent dehydration furnishes α-diketones 11 and 14. A
detailed study of the reaction mechanism is now in progress,
and the results will be reported in due course.
Conclusions
In summary, we present a facile and efficient synthetic route
to 6-functionalized 2-phenacylpyridines starting from the
cheap and readily available 2-(phenylethynyl)pyridine. The
oxidation of these products was also investigated, which
furnished the corresponding α-diketones in good yields
without any further treatment. This method requires only
simple manipulations under mild conditions, and is transition-
metal free. Thus, this method would be advantageous for the
Table 4. Oxidation of the phenacyl group leading to α-diketone
construction of
phenacylpyridines.
a
vast library of functionalized
neat
rt
O
R
N
R
N
Experimental Section
HO
Ph
O
Ph
General information
entry
Substrate
R
Time/d Atmosphere Product Yield/%
All the reagents and solvents were commercially available
and used as received. The 1H NMR spectra were measured on
a Bruker Ascend-400 at 400 MHz with TMS as an internal
standard. The 13C NMR spectra were measured on a Bruker
Ascend-400 at 100 MHz, and assignments were performed by
DEPT experiments. The IR spectra were recorded on a JASCO
FT/IR-4200 spectrometer. The melting points were
determined on a Yanaco micro-melting-points apparatus, and
were uncorrected. The high resolution mass spectra were
measured on a AB SCIEX Triple TOF 4600. X-ray diffraction
was made on a Rigaku AFC7R diffractometer with graphite
1
2
MeO
7b
7b
7b
12
7b
7b
7a
7a
9a
9a
7b
3
12
5
air
air
O2
O2
Ar
N2
air
Ar
air
Ar
air
11b
11b
11b
13
17
52
36
0
MeO
MeO
H
3
4 a
5b
6
5
MeO
MeO
i-PrO
i-PrO
AcNH
AcNH
MeO
1
11b
11b
11a
11a
14
86
0
5
7
8b
5
27
40
trace
49
0
1
9
3
10b
11c
4
14
12
11b
monochromatized Mo-Kα radiation.
a Heated at 60 °C. b mCPBA (2equiv.) was added. c TEMPO (5 equiv.) was added.
General procedure for the formation of salt 4
To a solution of 2-(phenylethynyl)pyridine
1 (360 mg, 2
mmol), were added H2O2 (412 µl, 4 mmol) and AcOH (1.8 ml,
4 mmol), and the resultant mixture was heated at 80 °C for 4
h. The reaction mixture was then concentrated in vacuo to
afford salt 4A as oily liquid. Then, a solution of HBF4 (134 µl, 4
mmol) in CH2Cl2 (100 µl) was added to salt 4A; and the
mixture was washed with ethyl acetate (1 × 10 mL). After
removal of solvent, the yellow solid 4B was obtained (549.0
mg, 1.94 mmol, 97%).
O2
O
O
MeO
N
H
MeO
N
H
MeO
N
H
O
Ph
O
Ph
O
Ph
7b
15
H
O
OH
O
MeO
N
MeO
N
2-Phenylisoxazolo[2,3-a]pyridinium tetrafluoroborate (4B)
Yellow solid; mp = 162–163 °C
O
Ph
O
Ph
1H NMR (DMSO-d6, 400 MHz): 9.86 (d, J = 7.1 Hz, 1H), 8.44
(dd, J = 8.4, 8.4 Hz, 1H), 8.41 (dd, J = 8.4, 1.6 Hz, 1H), 8.16 (s,
1H), 8.11–8.08 (m, 2H), 7.94 (ddd, J = 8.4, 7.1, 1.6 Hz, 1H),
7.76–7.70 (m, 3H); 13C NMR (DMSO-d6, 100 MHz): 194.0 (C),
145.4 (C), 139.7 (CH), 133.2 (CH), 131.1 (CH), 129.8 (CH),
126.8 (CH), 123.4 (C), 121.6 (CH), 121.1 (C), 98.9 (CH); 11B
NMR (DMSO-d6, 128 MHz): –1.29; 19F NMR (DMSO-d6, 376
16
11
Scheme 4. A plausible mechanism for the oxidation of phenacylpyridine 7b
Recently, hetaryl α-diketones have attracted much attention
because of their interesting physiological and biological
activities.20 These compounds are useful synthetic
intermediates
for
pharmaceuticals
exhibiting
-
antiinflammatory,21 antinociceptive,21a antipyretic21a and
antirheumatiod activities.22 However, the synthetic methods
for α-diketones suffer from several disadvantages.23
Fortunately, our synthetic method proceeds under mild
conditions, gives good product yields, and has operational
simplicity. Thus, we believe that this new approach will find
broad utility in the design and synthesis of aforementioned α-
diketones.
MHz): –148.4;HRMS Calcd for (M–BF4 ) C13H9NO: 196.0749,
found: 196.0757.
General experimental procedure for the formation of 2-
benzoylmethyl-6-(2-propoxy)pyridine (7a)
To a solution of salt 4B (57 mg, 0.2 mmol) in CHCl3 (5 mL), i-
PrOH (6a, 0.8 ml, 1 mmol) and t-BuOK (27 mg, 0.24 mmol)
were added, and the resultant mixture was stirred at room
temperature for 1 h. The insoluble materials were removed
by filtration and the filtrate was concentrated. Extraction of
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the residue with acetonitrile (1 × 10 mL) afforded almost pure
Hz, 1H), 4.41 (q, J = 7.2 Hz, 2H), 4.36 (s, 2H), 1.47 (t, J = 7.2 Hz,
3H); enol form: 14.10 (s, 1H), 7.82 (dd, J = 6.8, 2.4 Hz, 2H),
7.55–7.36 (m, 4H), 6.67 (d, J = 7.6 Hz, 1H), 6.55 (d, J = 8.0 Hz,
1H), 6.05 (s, 1H), 4.27 (q, J = 6.8 Hz, 2H), 1.31 (t, J = 6.8 Hz,
3H); 13C NMR (CDCl3, 100 MHz): keto form: 197.1 (C), 163.5
(C), 152.8 (C), 139.0 (CH), 138.7 (C), 133.0 (CH), 129.0 (CH),
128.5 (CH), 116.4 (CH), 108.7 (CH), 62.2 (CH2), 62.6 (CH2), 29.1
(CH3); enol form: 161.5 (C), 160.5 (C), 156.0 (C), 139.6 (CH),
136.8 (C), 129.2 (CH), 128.3 (CH), 125.2 (CH), 113.9 (CH),
106.7 (CH), 95.8 (CH), 48.2 (CH2), 14.6 (CH3); IR (neat): 1684,
1265 cm-1; HRMS Calcd for (M+H) C15H16NO2: 242.1176,
found: 242.1177.
phenacylpyridine 7a as yellow oil (31 mg, 0.12 mmol, 60%).
The reactions of the salt 4B with other alcohols
6 were
performed in a similar manner.
O
N
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 3 : 2)
1H NMR (CDCl3, 400 MHz): keto form: 8.08 (dd, J = 7.2, 2.0 Hz,
2H), 7.53–7.38 (m, 4H), 6.81 (d, J = 7.2 Hz, 1H), 6.51 (d, J = 7.6
Hz, 1H), 5.19 (sep, J = 6.0 Hz, 1H), 4.33 (s, 2H), 1.24 (d, J = 6.0
Hz, 6H); enol form: 14.03 (s, 1H), 7.80 (dd, J = 8.0, 2.0 Hz, 2H),
7.53–7.38 (m, 4H), 6.65 (d, J = 7.6 Hz, 1H), 6.46 (dd, J = 8.4,
0.8 Hz, 1H), 6.05 (s, 1H), 5.19 (sep, J = 6.4 Hz, 1H), 1.38 (d, J =
6.4 Hz, 6H); 13C NMR (CDCl3, 100 MHz): keto form: 197.2 (C),
163.1 (C), 152.8 (C), 139.0 (CH), 136.8 (C), 133.0 (CH), 129.0
(CH), 128.4 (CH), 116.0 (CH), 109.3 (CH), 67.9 (CH), 48.2 (CH2),
21.9 (CH3); enol form: 161.0 (C), 160.4 (C), 155.9 (C), 139.7
(CH), 136.0 (C), 129.1 (CH), 128.3 (CH), 125.3 (CH), 113.8 (CH),
107.4 (CH), 95.8 (CH), 69.0 (CH), 22.9 (CH3); IR (neat): 1683,
1275 cm-1; HRMS Calcd for (M+H) C16H18NO2: 256.1332,
found: 256.1337.
2-Benzoylmethyl-(6-tert-butoxy)pyridine (7d)
O
N
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 7 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.08 (dd, J = 8.8, 1.2 Hz,
2H), 7.54–7.37 (m, 4H), 6.80 (d, J = 7.2 Hz, 1H), 6.48 (d, J = 8.0
Hz, 1H), 4.32 (s, 2H), 1.46 (s, 9H); enol form: 14.02 (s, 1H),
7.82 (dd, J = 8.4, 2.0 Hz, 2H), 7.54–7.37 (m, 4H), 6.79 (d, J =
7.6 Hz, 1H), 6.49 (d, J = 8.0 Hz, 1H), 6.03 (s, 1H), 1.60 (s, 9H);
13C NMR (CDCl3, 100 MHz): keto form: 197.3 (C), 163.5 (C),
152.6 (C), 138.7 (CH), 136.8 (C), 132.9 (CH), 129.0 (CH), 128.7
(CH), 115.8 (CH), 111.2 (CH), 79.5 (C), 48.1 (CH2), 28.6 (CH3);
enol form: 161.3 (C), 155.9 (C), 139.4 (CH), 135.9 (C), 129.1
(CH), 128.9 (C), 128.5 (CH), 125.3 (CH), 114.8 (CH), 110.5 (CH),
95.9 (CH), 79.5 (C), 29.1 (CH3); IR (neat): 1643, 1262 cm-1;
HRMS Calcd for (M+H) C17H20NO2: 270.1488, found:
270.1478.
2- Benzoylmethyl-6-methoxypyridine (7b)
O
N
O
N
HO
Ph
O
Ph
2-Benzoylmethyl-6-benzyloxypyridine (7e)
Yellow oil (keto form : enol form = 2 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.08 (dd, J = 8.0, 1.2 Hz,
2H), 7.55–7.35 (m, 4H), 6.84 (d, J = 7.2 Hz, 1H), 6.57 (d, J = 8.4
Hz, 1H), 4.35 (s, 2H), 3.83 (s, 3H); enol form: 14.05 (s, 1H),
7.80 (dd, J = 8.4, 2.0 Hz, 2H), 7.55–7.35 (m, 4H), 6.66 (dd, J =
7.2, 0.4 Hz, 1H), 6.50 (dd, J = 8.0, 0.4 Hz, 1H), 6.05 (s, 1H),
3.99 (s, 3H); 13C NMR (CDCl3, 100 MHz): keto form: 197.1 (C),
163.8 (C), 152.8 (C), 139.0 (CH), 136.8 (C), 132.9 (CH), 128.9
(CH), 128.5 (CH), 116.6 (CH), 108.7 (CH), 53.3 (CH3), 48.2
(CH2); enol form: 161.9 (C), 160.5 (C), 156.0 (C), 139.7 (CH),
135.9 (C), 129.2 (CH), 128.4 (CH), 125.3 (CH), 114.1 (CH),
106.5 (CH), 95.8 (CH), 53.4 (CH3); IR (neat): 1685, 1268 cm-1;
HRMS Calcd for (M+H) C14H14NO2: 228.1019, found:
228.1016.
O
N
O
N
Ph
HO
Ph
Ph
O
Ph
Yellow oil (keto form : enol form = 3 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.07 (dd, J = 8.0, 0.8 Hz,
2H), 7.58–7.28 (m, 9H), 6.87 (d, J = 7.2 Hz, 1H), 6.64 (d, J = 8.0
Hz, 1H), 5.29 (s, 2H), 4.36 (s, 2H); enol form: 13.90 (s, 1H),
7.82 (dd, J = 8.0, 0.8 Hz, 2H), 7.58–7.28 (m, 9H), 6.71 (d, J =
7.6 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 6.09 (s, 1H), 5.39 (s, 2H);
13C NMR (CDCl3, 100 MHz): keto form: 197.0 (C), 163.2 (C),
152.8 (C), 139.2 (CH), 137.5 (C), 136.8 (C), 133.1 (CH), 129.0
(CH), 128.5 (CH), 128.4 (CH), 128.1 (CH), 127.1 (CH), 116.8
(CH), 109.2 (CH), 67.5 (CH2), 48.2 (CH2); enol form: 161.4 (C),
160.5 (C), 156.0 (C), 139.8 (CH), 136.3 (C), 135.9 (C), 129.2
(CH), 128.6 (CH), 128.4 (CH), 128.2 (CH), 128.0 (CH), 125.3
(CH), 114.4 (CH), 106.9 (CH), 95.8 (CH), 68.3 (CH2); IR (neat):
1684, 1305 cm-1; HRMS Calcd for (M+H) C20H18NO2: 304.1132,
found: 304.1135.
2- Benzoylmethyl-6-ethoxypyridine (7c)
O
N
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 1 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.09 (dd, J = 7.6, 0.8 Hz,
2H), 7.55–7.36 (m, 4H), 6.84 (d, J = 7.2 Hz, 1H), 6.49 (d, J = 8.4
2-Benzoylmethyl-6-(2-phenylethoxy)pyridine (7f)
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1H), 6.50 (d, J = 8.0 Hz, 1H), 6.06 (s, 1H), 4.48 (t, J = 6.4 Hz,
2H), 3.76 (t, J = 6.4 Hz, 2H), 2.29 (tt, J = 6.4, 6.4 Hz, 2H); 13C
NMR (CDCl3, 100 MHz): keto form: 197.0 (C), 163.2 (C), 152.9
(C), 139.2 (CH), 136.8 (C), 133.1 (CH), 128.9 (CH), 128.5 (CH),
116.7 (CH), 108.8 (CH), 62.4 (CH2),48.1 (CH2), 41.7 (CH2), 32.1
(CH2); enol form: 161.3 (C), 160.6 (C), 156.1 (C), 139.8 (CH),
135.8 (C), 129.2 (CH), 128.3 (CH), 125.2 (CH), 114.3 (CH),
106.5 (CH), 95.7 (CH), 62.8 (CH2), 41.3 (CH2), 31.9 (CH2); IR
(neat): 1681, 1154 cm-1; HRMS Calcd for (M+H) C16H17ClNO2:
290.0942, found: 290.0949.
O
N
O
N
Ph
Ph
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 3 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.06 (dd, J = 8.4, 0.8 Hz,
2H), 7.53–7.28 (m, 9H), 6.84 (d, J = 7.2 Hz, 1H), 6.55 (d, J = 8.4
Hz, 1H), 4.43 (t, J = 7.2 Hz, 2H), 4.33 (s, 2H), 2.99 (t, J = 7.2 Hz,
2H); enol form: 13.99 (s, 1H), 7.80 (dd, J = 8.0, 0.8 Hz, 2H),
7.53 –7.28 (m, 9H), 6.67 (d, J = 7.6 Hz, 1H), 6.49 (d, J = 8.4 Hz,
1H), 6.04 (s, 1H), 4.55 (t, J = 6.8 Hz, 2H), 3.15 (t, J = 6.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz): keto form: 197.1 (C), 163.3
(C), 152.8 (C), 139.1 (CH), 138.6 (C), 136.8 (C), 133.1 (CH),
129.0 (three CH signals overlapped), 128.4 (CH), 126.3 (CH),
116.5 (CH), 108.9 (CH), 66.4 (CH2), 48.1 (CH2), 35.4 (CH2); enol
form: 161.4 (C), 160.5 (C), 156.0 (C), 139.7 (CH), 138.1 (C),
135.9 (C), 129.2 (CH), 129.1 (CH), 128.3 (two CH signals
overlapped), 126.5 (CH), 125.3 (CH), 114.1 (CH), 106.8 (CH),
95.8 (CH), 66.9 (CH2), 35.5 (CH2); IR (neat): 1695, 1266 cm-1;
HRMS Calcd for (M+H) C21H20NO2: 318.1488, found:
318.1473.
2-Benzoylmethyl-6-(2-propen-1-oxy)pyridine (7i)
O
N
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 3 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.06 (dd, J = 8.0, 1.2 Hz,
2H), 7.57–7.38 (m, 4H), 6.85 (d, J = 7.2 Hz, 1H), 6.60 (d, J = 8.0
Hz, 1H), 6.02 - 5.98 (m, 1H), 5.35 (dd, J = 17.2, 1.6 Hz, 1H),
5.18 (dd, J = 11.2, 1.2 Hz, 1H), 4.75 (dd, J = 6.4, 1.2 Hz, 2H),
4.34 (s, 2H); enol form: 13.85 (s, 1H), 7.80 (dd, J = 8.0, 1.6 Hz,
2H), 7.57 –7.38 (m, 4H), 6.69 (d, J = 7.6 Hz, 1H), 6.56 (d, J =
8.4 Hz, 1H), 6.17 - 6.06 (m, 1H), 6.05 (s, 1H), 5.48 (dd, J =
17.2, 1.6 Hz, 1H), 5.34 (dd, J = 10.4, 1.6 Hz, 1H), 4.87 (dd, J =
5.2, 1.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz): keto form: 197.0
(C), 163.0 (C), 152.8 (C), 139.1 (CH), 136.8 (C), 133.1 (CH),
132.6 (CH), 129.0 (CH), 128.5 (CH), 117.4 (CH2), 116.7 (CH),
108.9 (CH), 66.5(CH2), 48.2 (CH2); enol form: 161.6 (C), 160.4
(C), 155.9 (C), 139.8 (CH), 135.9 (C), 133.7 (CH), 129.2 (CH),
128.4 (CH), 125.3 (CH), 118.2 (CH2), 114.3 (CH), 106.8 (CH),
95.8 (CH), 67.1 (CH2); IR (neat): 1682, 1263 cm-1; HRMS Calcd
for (M+H) C16H16NO2: 254.1176, found: 254.1165.
2-Benzoylmethyl-6-(2-hydroxyethoxy)pyridine (7g)
O
N
O
N
HO
HO
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 6 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.07–8.03 (m, 2H), 7.58
–7.38 (m, 4H), 6.90 (d, J = 7.2 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H),
4.40 (t, J = 6.4 Hz, 2H), 4.36 (s, 2H), 3.88 (t, J = 6.4 Hz, 2H),
1.58 (br s, 1H); enol form: 13.90 (s, 1H), 7.80 (dd, J = 8.0, 1.6
Hz, 2H), 7.58–7.38 (m, 4H), 6.72 (dd, J = 7.6, 0.8 Hz, 1H), 6.55
(dd, J = 8.4, 0.8 Hz, 1H), 6.10 (s, 1H), 4.01 (t, J = 9.2 Hz, 2H),
3.95 (t, J = 9.2 Hz, 2H), 2.17 (s, 1H); 13C NMR (CDCl3, 100
MHz): keto form: 196.6 (C), 163.5 (C), 152.5 (C), 139.6 (CH),
136.6 (C), 133.2 (CH), 128.6 (CH), 128.4 (CH), 117.2 (CH),
109.3 (CH), 68.4 (CH2), 62.6 (CH2), 47.7 (CH2); enol form:
160.1 (C), 156.5 (C), 139.9 (CH), 135.9 (C), 133.1(C), 129.7
(CH), 128.4 (CH), 125.3 (CH), 114.5 (CH), 106.6 (CH), 95.7
(CH), 67.7 (CH2), 61.2 (CH2); IR (neat): 1682, 1265, 1207 cm-1;
HRMS Calcd for (M+H) C15H16NO3: 258.1125, found:
258.1123.
2-Benzoylmethyl-6-(2-propynyloxy)pyridine (7j)
O
N
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 5 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.08 (dd, J = 7.2, 1.2 Hz,
2H), 7.58–7.37 (m, 4H), 6.91 (d, J = 7.6 Hz, 1H), 6.66 (d, J = 8.4
Hz, 1H), 4.88 (d, J = 2.4 Hz, 2H), 4.37 (s, 2H), 2.40 (t, J = 2.4 Hz,
1H); enol form: 13.35 (s, 1H), 7.81 (dd, J = 8.4, 2.0 Hz, 2H),
7.58 –7.37 (m, 4H), 6.75 (d, J = 7.6 Hz, 1H), 6.58 (d, J = 8.0 Hz,
1H), 6.06 (s, 1H), 4.98 (d, J = 2.4 Hz, 2H), 2.55 (t, J = 2.4 Hz,
1H); 13C NMR (CDCl3, 100 MHz): keto form: 196.9 (C), 161.9
(C), 152.7 (C), 139.4 (CH), 136.8 (C), 133.1 (CH), 129.0 (CH),
128.5 (CH), 117.4 (CH), 109.1 (CH), 79.3 (C), 74.0 (CH), 53.3
(CH2), 48.0 (CH2); enol form: 161.5 (C),160.4 (C), 155.9 (C),
139.9 (CH), 135.8 (C), 129.3 (CH), 128.3 (CH), 125.3 (CH),
115.1 (CH), 106.8 (CH), 95.8 (CH), 77.2 (C), 75.4 (CH), 53.9
(CH2); IR (neat): 1685, 1173 cm-1; HRMS Calcd for (M+H)
C16H14NO2: 252.1019, found: 252.1011.
2-Benzoylmethyl-6-(3-chloro-1-propoxy)pyridine (7h)
Cl
O
N
Cl
O
N
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 3 : 2)
1H NMR (CDCl3, 400 MHz): keto form: 8.07 (dd, J = 7.2, 1.2 Hz,
2H), 7.57–7.37 (m, 4H), 6.87 (d, J = 7.2 Hz, 1H), 6.58 (d, J = 8.4
Hz, 1H), 4.36 (t, J = 6.4 Hz, 2H), 4.34 (s, 2H), 3.65 (t, J = 6.4 Hz,
2H), 2.13 (tt, J = 6.4, 6.4 Hz, 2H); enol form: 13.90 (s, 1H), 7.81
(dd, J = 8.4, 1.6 Hz, 2H), 7.57–7.37 (m, 4H), 6.69 (d, J = 7.6 Hz,
2-Benzoylmethyl-6-hydroxypyridine (7k)
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Mp = 155–156 °C; H NMR (CDCl3, 400 MHz): keto form: 8.06
(d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.84 (br s, 1H), 7.66
(dd, J = 8.0, 7.6 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.45 (dd, J =
8.0, 7.6 Hz, 2H), 7.02 (d, J = 7.6 Hz, 1H), 4.36 (s, 2H), 2.17 (s,
3H); enol form: 13.79 (s, 1H), 7.85 (br s, 1H), 7.82 (d, J = 8.0
Hz, 2H), 7.66 (t, J = 8.0 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.40
(dd, J = 8.0, 7.6 Hz, 1H), 7.39 (dd, J = 8.0, 8.0 Hz, 2H), 6.86 (d, J
= 8.0 Hz, 1H), 6.05 (s, 1H), 2.24 (s, 3H); 13C NMR (CDCl3, 100
MHz): keto form: 196.6 (C), (one signal for quaternary carbon
lacked ), 153.6 (C), 151.0 (C), 139.0 (CH), 136.6 (C), 133.3
(CH), 128.7 (two CH groups overlapped), 119.9 (CH), 111.8
(CH), 47.8 (CH2), 24.7 (CH3); enol form: 168.5 (C), 161.1 (C),
156.9 (C), (two signals for quaternary carbon lacked), 139.4
(CH), 128.6 (CH), 128.4 (CH), 125.3 (CH), 117.7 (CH), 109.5
(CH), 95.4 (CH), 24.8 (CH3); IR (neat): 3430, 1642, 1455 cm-1;
HRMS Calcd for (M+H) C15H15N2O2: 255.1128, found:
255.1132.
HO
N
HO
N
HO
Ph
O
Ph
Yellow solid (keto form : enol form = 1 : 1); mp = 168–169 °C
1H NMR (CDCl3, 400 MHz): keto form: 12.29–12.20 (br, 1H),
8.03 (d, J = 7.6 Hz, 2H), 7.61 (t, J = 9.2 Hz, 1H), 7.50 (dd, J =
9.2, 7.6 Hz, 2H), 7.37 (dd, J = 9.2, 6.8 Hz, 1H), 6.42 (d, J = 9.2
Hz, 1H), 6.13 (d, J = 6.8 Hz, 1H), 4.25 (s, 2H); enol form: 14.40
(s, 1H), 7.72 (d, J = 7.2 Hz, 2H), 7.29–7.21 (m, 3H), 7.02 (dd, J
= 8.4, 8.4 Hz, 1H), 5.75 (s, 1H), 5.42 (d, J = 8.4 Hz, 2H), 5.40 (s,
1H); 13C NMR (CDCl3, 100 MHz): keto form: 194.6 (C), 165.1
(C), 149.9 (C), 141.4 (CH), 136.0 (C), 133.9 (CH), 128.9 (CH),
128.6 (CH), 118.5 (CH), 107.1 (CH), 41.9 (CH2); enol form:
174.1 (C), 161.9 (C), 153.9 (C), 143.4 (C), 140.0 (CH), 127.4
(CH), 125.6 (CH), 104.2 (CH), 96.2 (CH), 83.5 (CH), 79.1 (CH);
IR (neat): 1680 cm-1; HRMS Calcd for (M+H) C13H12NO2:
214.0863, found: 214.0855.
2-Benzoylmethyl-6-propanolaminopyridine (9b)
O
O
2-Methoxy-6-(2-oxo-1-hexyl)pyridine (7l)
N
N
N
N
H
H
MeO
N
MeO
N
HO
Ph
O
Ph
O
Bu
HO
Bu
Yellow oil (keto form : enol form = 6 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.09 (d, J = 8.0 Hz, 1H),
8.01 (d, J = 7.6 Hz, 2H), 7.89 (br s, 1H), 7.66 (dd, J = 8.0, 7.6
Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.46 (dd, J = 7.6, 7.6 Hz, 2H),
6.99 (d, J = 7.6 Hz, 1H), 4.35 (s, 2H), 2.39 (q, J = 7.6 Hz, 2H),
1.23 (t, J = 7.6 Hz, 3H); enol form: 13.04 (s, 1H), 7.92 (d, J =
8.0 Hz, 2H), 7.80 (br s, 1H), 7.78 (dd, J = 8.0, 6.8 Hz, 1H), 7.66
(t, J = 8.0 Hz, 1H), 7.40–7.37 (m, 3H), 6.84 (d, J = 8.0 Hz, 1H),
Yellow oil (keto form : enol form = 8 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 7.50 (dd, J = 8.3, 7.2 Hz,
1H), 6.76 (d, J = 7.2 Hz, 1H), 6.61 (d, J = 8.3 Hz, 1H), 3.90 (s,
3H), 3.76 (s, 2H), 2.53 (t, J = 7.4 Hz, 2H), 1.60–1.53 (m, 2H),
1.34–1.24 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H); enol form: 13.54 (s,
1H), 7.47 (dd, J = 8.2, 7.5 Hz, 1H), 6.49 (d, J = 7.5 Hz, 1H), 6.44
(d, J = 8.3 Hz, 1H), 5.29 (s, 1H), 3.94 (s, 3H), 2.25 (t, J = 7.6 Hz,
2H), 1.76–1.68 (m, 2H), 1.46–1.36 (m, 2H), 0.94 (t, J = 7.3 Hz,
3H); 13C NMR (CDCl3, 100 MHz): keto form: 208.0 (C), 163.8
(C), 152.6 (C), 139.0 (CH), 116.5 (CH), 108.2 (CH), 53.3 (CH3),
52.1 (CH2), 42.3 (CH2), 25.8 (CH2), 22.3 (CH2), 13.8 (CH3); enol
form: signals of enol form were too small to be assigned; IR
(ATR): 1712, 1265 cm-1; HMRS Calcd for (M+H) C12H17NO2:
208.1332, found: 208.1325.
6.04 (s, 1H), 2.45 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H); 13
C
NMR (CDCl3, 100 MHz): keto form: 196.6 (C), 172.3 (C), 153.5
(C), 151.1 (C), 138.9 (CH), 136.6 (C), 133.3 (CH), 128.9 (CH),
128.7 (CH), 119.8 (CH), 111.9 (CH), 47.8 (CH2), 30.8 (CH2), 9.3
(CH3); enol form: 172.2 (C), 161.1 (C), 156.8 (C), 148.1 (C),
139.3 (CH), 135.7 (C), 129.4 (CH), 128.4 (CH), 125.3 (CH),
117.6 (CH), 109.5 (CH), 95.4 (CH), 30.9 (CH2), 9.3 (CH3); IR
(neat): 3433, 1677, 1630 cm-1; HRMS Calcd for (M+H)
C16H17N2O2: 269.1286, found: 269.1289.
General method for amidation of 4B
To a solution of salt 4B (85 mg, 0.3 mmol) in acetonitrile (5
mL), potassium carbonate (50 mg, 0.36 mmol) was added,
and the resultant mixture was stirred at room temperature
for 20 h. The insoluble materials were removed by filtration
and the filtrate was concentrated to afford amidated
phenacylpyridine 9a as yellow oil (70 mg, 0.273 mmol, 91%).
In the case of 9b, propionitrile was used as a solvent instead
of acetonitrile. In the case of 9c, 5 equivalents of acrylonitrile
2-Benzoylmethyl-6-(2-methylpropanoyl)aminopyridine (9c)
O
O
N
N
N
N
H
H
O
Ph
HO
Ph
Yellow oil (keto form : enol form = 3 : 2)
1H NMR (CDCl3, 400 MHz): keto form: 8.10 (d, J = 8.3 Hz, 1H),
8.03–8.01 (m, 2H), 7.85 (br, 1H), 7.64 (t, J = 7.9 Hz, 1H), 7.55
(tt, J = 7.4, 1.3 Hz, 1H), 7.48–7.36 (m, 2H), 7.00 (d, J = 7.1 Hz,
1H), 4.36 (s, 2H), 2.55–2.46 (m, 1H) 1.23 (d, J = 6.9 Hz, 6H);
enol form: 13.83 (s, 1H), 7.93 (dd, J = 8.3, 0.7 Hz, 1H), 7.85
(br, 1H), 7.80–7.78 (m, 2H), 7.64 (t, J = 7.9 Hz, 1H), 7.48–7.36
(m, 3H), 6.84 (dd, J = 7.7, 0.7 Hz, 1H), 6.04 (s, 1H), 2.62–2.53
(m, 1H), 1.25 (d, J = 6.9 Hz, 6H); 13C NMR (CDCl3, 100 MHz):
keto form: 196.6 (C), 175.5 (C), 153.5 (C), 151.2 (C), 138.9
were added in dichloromethane solution of 4B
.
6-Benzoylmethyl-2-ethanoylaminopyridine (9a)
O
O
N
N
N
N
H
H
HO
Ph
O
Ph
Yellow plates (keto form : enol form = 6 : 1)
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(CH), 136.6 (C), 133.3 (CH), 128.7 (CH), 128.6 (CH), 119.9 (CH),
111.9 (CH), 47.9 (CH2), 36.8 (CH), 19.4 (CH3); enol form: 161.0
(C), 156.8 (C), 148.3 (C), 139.3 (CH), 135.7 (C), 129.4 (CH),
128.4 (CH), 125.3 (CH), 117.6 (CH), 109.6 (CH), 95.4 (CH), 36.8
(CH), 19.4 (CH3); IR (ATR): 1693, 1681 cm-1; HMRS Calcd for
(M+H) C17H18N2O2: 283.1441, found: 283.1443.
1H NMR (CDCl3, 400 MHz): keto form: 8.42 (br, 1H), 8.21 (d, J
= 8.2 Hz, 1H), 8.05–8.01 (m, 3H), 7.87–7.82 (m, 2H), 7.70 (t, J
= 7.9 Hz, 1H), 7.56 (tt, J = 7.4, 1.3 Hz, 1H), 7.48–7.38 (m, 2H),
7.06 (d, J = 7.4 Hz, 1H), 4.38 (s, 2H); enol form: 13.73 (s, 1H),
8.36 (br, 1H), 7.87–7.82 (m, 2H), 7.80–7.78 (m, 2H), 7.48–7.38
(m, 7H), 6.90 (d, J = 7.7 Hz, 1H), 6.07 (s, 1H); 13C NMR (CDCl3,
100 MHz): keto form: 196.6 (C), 164.5 (C), 153.8 (C), 151.0
(C), 139.1 (CH), 138.6 (C), 136.6 (C), 133.4 (CH), 132.6 (C),
129.1 (CH), 128.7 (CH), 128.7 (CH), 128.6 (CH), 120.5 (CH),
112.2 (CH), 47.8 (CH2); enol form: 164.6 (C), 161.2 (C), 157.1
(C), 148.1 (C), 139.4 (CH), 138.8 (C), 138.6 (C), 135.6 (C), 132.5
(C), 129.5 (CH), 129.2 (CH), 129.1 (CH), 128.7 (CH), 128.4 (CH),
118.2 (CH), 109.9 (CH), 95.4 (CH); IR (ATR): 1687, 1680 cm-1;
HMRS Calcd for (M+H) C20H15ClN2O2: 351.0895, found:
351.0911.
2-Benzoylmethyl-6-propenoylaminopyridine (9d)
O
O
N
N
N
N
H
H
HO
Ph
O
Ph
Yellow oil (keto form : enol form = 6 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.21 (br s, 1H), 8.20 (d,
J = 8.4 Hz, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.69 (t, J = 8.0 Hz, 1H),
7.59 (dd, J = 8.4, 7.6 Hz, 1H), 7.48 (dd, J = 8.4, 8.0 Hz, 2H),
7.04 (d, J = 7.6 Hz, 1H), 6.46 (dd, J = 16.8, 0.8 Hz, 1H), 6.28
(dd, J = 16.8, 6.4 Hz, 1H), 5.80 (dd, J = 6.4, 0.8 Hz, 1H), 4.38 (s,
2H); enol form: 9.93 (s, 1H), 7.96–7.92 (m, 6H), 7.80 (dd, J =
8.0, 2.0 Hz, 2H), 7.70 (t, J = 8.0 Hz, 1H), 6.48 (dd, J = 17.6, 0.8
Hz, 1H), 6.34 (dd, J = 7.6, 0.8 Hz, 1H), 6.06 (s, 1H), 5.87 (dd, J
= 17.6, 7.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz): keto form:
196.5 (C), 163.6 (C), 153.6 (C), 151.1 (C), 132.9 (CH), 136.5 (C),
133.4 (CH), 128.7 (two CH groups overlapped), 128.5 (CH2),
125.3 (CH), 120.3 (CH), 112.4 (CH), 27.6 (CH2); enol form:
signals of enol form were too small to be assigned; IR (neat):
3418, 1676, 1634 cm-1; HRMS Calcd for (M+H) C16H15N2O2:
267.1128, found: 267.1138.
6-Isopropoxy-2-(1,2-dioxo-2-phenylethyl)pyridine (11a)
Yellow oil
1H NMR (CDCl3, 400 MHz): 7.90 (dd, J = 8.4, 1.2 Hz, 2H), 7.78 -
7.74 (m, 2H), 7.62 (t, J = 7.6 Hz, 1H), 7.51–7.47 (m, 2H), 6.89
(dd, J = 7.6, 2.8 Hz, 1H), 4.84 (sep, J = 6.4 Hz, 1H), 1.05 (d, J =
6.4 Hz, 6H); 13C NMR (CDCl3, 100 MHz): 197.2 (C), 195.4 (C),
162.9 (C), 148.8 (C), 139.3 (CH), 134.2 (CH), 133.7 (C), 129.1
(CH), 128.8 (CH), 117.5 (CH), 115.8 (CH), 62.9 (CH), 21.4 (CH3);
IR (neat): 1680, 1673, 1274 cm-1; HRMS Calcd for (M+H)
C16H16NO3: 270.1125, found: 270.1123.
6-Methoxy-2-(1,2-dioxo-2-phenylethyl)pyridine (11b)
Yellow oil
1H NMR (CDCl3, 400 MHz): 7.91 (dd, J = 6.8, 6.8 Hz, 2H), 7.79
(d, J = 6.8 Hz, 2H), 7.63 (dd, J = 6.8, 2.0 Hz, 1H), 7.50 (dd, J =
6.8, 6.8 Hz, 1H), 7.49 (t, J = 6.8 Hz, 1H), 6.98 (dd, J = 6.8, 2.0
Hz, 1H), 3.64 (s, 3H); 13C NMR (CDCl3, 100 MHz): 196.7 (C),
195.1 (C), 163.6 (C), 148.8 (C), 139.3 (CH), 134.3 (CH), 133.6
(C), 129.2 (CH), 128.8 (CH), 116.9 (CH), 116.5 (CH), 53.5 (CH3);
IR (neat): 1791, 1680, 1275 cm-1; HRMS Calcd for (M+H)
C14H12NO3: 242.0812, found: 242.0813.
2-Benzoylmethyl-6-phenylethanoylaminopyridine (9e)
O
O
N
N
N
N
H
H
Ph
Ph
O
Ph
O
Ph
Dark brown oil (keto form : enol form = 2 : 1)
1H NMR (CDCl3, 400 MHz): keto form: 8.08 (d, J = 8.2 Hz, 1H),
8.00–7.98 (m, 2H), 7.75 (br, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.55
(tt, J = 7.4, 1.2 Hz, 1H), 7.46–7.31 (m, 7H), 6.99 (d, J = 7.4 Hz,
1H), 4.31 (s, 2H), 3.72 (s, 2H); enol form: 13.16 (s, 1H), 7.89
(d, J = 8.2 Hz, 1H), 7.80–7.76 (m, 2H), 7.69 (s, 1H), 7.46–7.31
(m, 8H), 6.83 (d, J = 7.7 Hz, 1H), 6.01 (s, 1H), 3.77 (s, 2H); 13C
NMR (CDCl3, 100 MHz): keto form: 196.6 (C), 169.3 (C), 153.5
(C), 150.8 (C), 138.9 (CH), 136.5 (C), 134.0 (C), 133.3 (CH)
129.4 (CH), 129.1 (CH), 128.7 (CH), 128.6 (CH), 127.6 (CH),
120.2 (CH), 111.9 (CH), 47.8 (CH2), 45.0 (CH2); enol form:
signals of enol form were too small to be assigned; IR (ATR):
1693, 1687 cm-1; HMRS Calcd for (M+H) C21H18N2O2:
331.1441, found: 331.1449.
6-Ethanoylamino-2-(1,2-dioxo-2-phenylethyl)pyridine (14)
Yellow oil
1H NMR (CDCl3, 400 MHz): 8.47 (br s, 1H), 8.09–7.91 (m, 5H),
7.68 (t, J = 6.0 Hz, 1H), 7.50 (dd, J = 8.0, 8.0 Hz, 2H), 2.16 (s,
3H); 13C NMR (CDCl3, 100 MHz): 195.6 (C), 194.2 (C), 152.2
(C), 149.4 (C), 139.6 (CH), 134.7 (CH), 133.6 (C), 133.2 (C),
129.6 (CH), 128.9 (CH), 119.2 (CH), 118.8 (CH), 24.6 (CH3);
HRMS Calcd for (M+H) C15H13N2O2: 269.0921, found:
269.0920.
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8 | J. Name., 2012, 00, 1-3
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