Silver-catalyzed amidation of benzoylformic acids with tertiary amines via selective carbon-nitrogen bond cleavage

Article abstract of DOI:10.1039/c3ob40619a

A novel approach towards the synthesis of α-ketoamides using tertiary amines as nitrogen group sources via C-N bond cleavage has been developed. In the presence of Ag₂CO₃ and K₂S ₂O₈, α-keto acids reacted with tertiary amines to afford the corresponding α-ketoamides in good yields. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ob40619a

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Silver-catalyzed amidation of benzoylformic acids with
tertiary amines via selective carbon–nitrogen bond
cleavage†
Cite this: Org. Biomol. Chem., 2013, 11,
3649
Xiaobin Zhang,a Wenchao Yanga and Lei Wang*a,b
Received 28th March 2013,
Accepted 30th March 2013
A novel approach towards the synthesis of α-ketoamides using tertiary amines as nitrogen group sources
via C–N bond cleavage has been developed. In the presence of Ag2CO3 and K2S2O8, α-keto acids reacted
with tertiary amines to afford the corresponding α-ketoamides in good yields.
DOI: 10.1039/c3ob40619a
www.rsc.org/obc
α-Ketoamides are important intermediates in organic syn-
thesis that are widely found in natural products, biological
compounds and pharmaceuticals.1 Owing to their importance
and broad applications, a variety of synthetic methodologies
for their synthesis have been developed. Traditional synthetic
routes to α-ketoamides usually require multiple steps, harsh
reaction conditions, and toxic or expensive reagents.2 For
these reasons, considerable effort has been made on develop-
ing mild, efficient and environmentally friendly methods,
which are still highly desirable. Recently, transition-metal-
catalyzed and metal-free methodologies offer particularly
appealing approaches to α-ketoamides.3 In spite of the
environmentally benign character and the high efficiency of
these methods, the nitrogen group sources are only limited to
primary and secondary amines, which narrowed the substrate
scope of amines in the above processes. To our knowledge, the
synthesis of α-ketoamides using tertiary amines as nitrogen
group sources has not yet been reported.
The carbon–nitrogen bond (C–N) is difficult to cleave
because it is stronger than the C–H bond in tertiary amines,
and much work on α-H bond activation of tertiary amines has
been reported.4 Despite the big challenge in controlling C–H
bond activation for further C–N cleavage, great progress has
been made with transition-metal-catalyzed approaches
recently.5 For example, Zhang reported Pd-catalyzed allylic
alkylation of carbonyl compounds through C–N bond cleavage
of allylic amines.5a Takai reported Fe-catalyzed synthesis of
glycine derivatives via C–N bond cleavage using diazoacetate.5d
Scheme 1 The amidation of α-keto acids with tertiary amines.
Then, Huang and coworkers reported a Cu-catalyzed oxidative
amination of benzoxazoles using tertiary amines as nitrogen
group sources.5f As part of our ongoing efforts on the synthesis
of α-ketoamides,6 we herein firstly report the Ag-catalyzed ami-
dation reaction of α-keto acids with tertiary amines via C−N
bond cleavage, which illustrates an alternative route to α-keto-
amides (Scheme 1).
Results and discussion
Our initial investigation focused on the effect of transition-
metal catalysts on the model reaction of 2-oxo-2-phenylacetic
acid (1a) with Et3N (2a), and the results are summarized in
Table 1. Several Ag-, Cu- and Fe-salts were screened in the pres-
ence of K2S2O8 as an oxidant in CCl4, and the reactivity of Ag-
salts (Ag2CO3, Ag2O) is more than that of Cu-salts (CuBr2,
CuBr, Cu(OTf)2, Cu(OAc)2, CuI, Cu(acac)2), while Fe-salts
(FeCl3, Fe(acac)3, FeCl2) did not exhibit catalytic activity
(Table 1, entries 1–12).5d,f When 20 mol% of Cu(OTf)2 was
used, only 38% yield of 3a was obtained (Table 1, entry 5).
Among the tested transition-metal catalysts, Ag2CO3 showed
the highest catalytic reactivity and the desired product 3a was
isolated in 46% yield when the model reaction was performed
in CCl4 at 120 °C for 12 h (Table 1, entry 12). Among additional
oxidants, K2S2O8 was the best one in air. Other oxidants, such
as TBHP, (NH4)2S2O8, PhI(OAc)2 and BQ, were ineffective for
the generation of 3a (Table 1, entries 13–16). However, only 8%
yield of 3a was obtained when the model reaction was per-
formed under a nitrogen atmosphere (Table 1, entry 17). Next,
aDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000,
P. R. China. E-mail: leiwang@chnu.edu.cn; Fax: +86-561-309-0518;
Tel: +86-561-380-2069
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
†Electronic supplementary information (ESI) available: Detailed procedures,
analytical data, and 1H, 13C NMR and HRMS spectra of all intermediates and
products. See DOI: 10.1039/c3ob40619a
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Table 1 Optimization of the model reaction conditionsa
Table 2 Substrate scope of α-keto acidsa
Entry
Catal.
Solvent
Oxidant
Yieldb (%)
1
2
3
4
5
6
7
8
CuBr2
CuBr
CuI
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
CCl4
Dioxane
DMF
DMSO
CH3CN
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
(NH4)2S2O8
TBHP
26
23
25
Cu(OTf)2
Cu(OAc)2
Cu(OAc)2
Cu(acac)2
FeCl3
FeCl2
Fe(acac)3
Ag2O
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOAc
AgBF4
AgNO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
—
30
38c
27
24
Trace
Trace
Trace
38
46
Trace
35
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
PhI(OAc)2
BQ
19
18
Ag2CO3
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
8d
21
13
9
NR
NR
NR
NR
Trace
48
Toluene
CCl4–DMF (1 : 1, v/v)
CCl4–DMF (2 : 1, v/v)
CCl4–DMF (4 : 1, v/v)
CCl4–DMF (8 : 1, v/v)
CCl4–DMF (4 : 1, v/v)
CCl4–DMF (4 : 1, v/v)
50
54
a Reaction conditions: 1 (0.50 mmol), 2a (1.50 mmol), Ag2CO3
(0.10 mmol), K2S2O8 (1.0 mmol), CCl4–DMF (4 : 1, v/v, 3.0 mL), under
air, 120 °C, 12 h. b Isolated yield.
51
68e
NR
a Reaction conditions: 1a (0.50 mmol), 2a (1.50 mmol), catalyst
(10 mol%), oxidant (1.0 mmol), solvent (3.0 mL), under air, 120 °C,
12 h. b Isolated yields. c Cu(OTf)2 (20 mol%). d Under N2 atmosphere.
e Ag2CO3 (20 mol%).
acids and Et3N (2a). The results are summarized in Table 2.
The results indicated that 2-oxo-2-arylacetic acids with both
electron-rich and electron-deficient groups on the benzene
rings underwent the reaction smoothly with Et3N to generate
some other silver salts were examined. The use of AgOAc, the corresponding products in good yields. For example, 2-oxo-
AgBF4 and AgNO3 showed relatively lower efficiency, and 2-arylacetic acids with F, Cl, Br, Me, MeO, and tert-C4H9 at the
9–21% yields of 3a were obtained (Table 1, entries 18–20). The para-positions of benzene rings reacted with Et3N efficiently,
effect of solvent on the model reaction was also examined in and the corresponding products (3b–d, h–j) were isolated in
the presence of Ag2CO3 and K2S2O8, and the solvent plays an 56–77% yields. Meanwhile, 2-oxo-2-arylacetic acids, bearing a
important role in the reaction. When the model reaction was sterically hindered group, such as Cl or Br or Me at their
carried out in dioxane, DMF, DMSO, CH3CN and toluene, no ortho-/meta-positions, also underwent the reaction with Et3N
desired product 3a was detected by TLC (Table 1, entries smoothly, providing the corresponding products (3e, 3f, 3g
21–25). To our delight, when the model reaction was per- and 3k) in slightly lower yields (54–69%) compared with their
formed in a mixture of CCl4 and DMF (4 : 1, v/v), 3a was iso- corresponding para-substituted ones. However, a weak ortho-
lated in 54% yield (Table 1, entry 28). By changing the volume position effect was observed in the reaction (3f, 3g and 3l). In
ratios of CCl4 to DMF, the yields of 3a were not increased addition, 2-(naphthalen-1-yl)-2-oxoacetic acid and 2-(furan-
(Table 1, entries 26–29). The ground-breaking result came with 2-yl)-2-oxoacetic acid also underwent the reaction with Et3N to
the use of 20% Ag2CO3, affording the desired product 3a in generate 3l and 3m in 61% and 52% yields, respectively.
68% yield (Table 1, entry 30). It should be noted that no 3a
was observed when the model reaction was carried out in the surveyed under the present reaction conditions, as shown in
absence of Ag2CO3 (Table 1, entry 31).
Table 3. When (n-C3H7)3N and (n-C4H9)3N reacted with 2-oxo-
To expand the scope of amines, several tertiary amines were
With the optimized reaction conditions in hand, we next 2-phenylacetic acid (1a), the desired α-ketoamides 4a and 4b
investigated the scope of the reaction with a series of α-keto were obtained in 55% and 43% yields respectively (Table 3,
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Table 3 Substrate scope of tertiary aminesa
Entry
1
Tertiary amine
Product
4
Yieldb (%)
55
4a
2
4b
43
Scheme 2 The reactions of 1a with secondary amines.
3
4
5
4c
4d
4e
62
46
41
a Reaction conditions: 1a (0.50 mmol),
2 (1.50 mmol), Ag2CO3
(0.10 mmol), K2S2O8 (1.0 mmol), CCl4–DMF (4 : 1, v/v, 3.0 mL), under
air, 120 °C, 12 h. b Isolated yield.
Scheme 3 Possible reaction mechanism.
entries 1 and 2). It should be noted that the yield of α-keto-
amides was decreased along with the carbon chain increasing
of tertiary amines (3a vs. 4a vs. 4b). Furthermore, a selective
C–N bond cleavage of aliphatic tertiary amines, including
tetramethylethylenediamine (TMEDA) and 1-benzylpiperidine,
was observed in the reaction with 2-oxo-2-phenylacetic acid
under current reaction conditions, providing the sole product
4c and 4d in 62% and 46% yields respectively (Table 3, entries
3 and 4). It is important to note that the α-H of the tertiary
amine plays a key role in C–N cleavage under current condi-
tions.5f When N,N-diethylaniline as one of the substrates
reacted with 2-oxo-2-phenylacetic acid, the corresponding
product α-ketoamide 4e was isolated in 41% yield (Table 3,
entry 5), indicating that C–N bond cleavage took place at the
carbon containing α-H.
the oxygen atom in the aldehyde byproduct was possibly from
H2O in the system.9 The obtained B further undergoes reaction
with α-keto acid to afford the final product α-ketoamide and
regenerates Ag catalyst.10
Conclusion
In conclusion, we have demonstrated a novel protocol for the
direct synthesis of α-ketoamides through an Ag-catalyzed ami-
dation of benzoylformic acids with tertiary amines via selective
C–N bond cleavage. Compared with other reported α-keto-
amides preparation, the current approach shows that inacti-
vated tertiary amines can be used as available nitrogen group
sources, which make it more attractive for organic synthesis.
Further investigation on the reaction is ongoing in our
laboratory.
When the reactions of 1a with secondary amines, such as
morpholine, piperidine and dibenzylamine, were performed
under the present reaction conditions, only 18% yield, 12%
yield, and trace amounts of the corresponding products were
obtained. These results show the lower reactivity of secondary
amines in this reaction system (Scheme 2).
Experimental section
Although the exact mechanism of this reaction is not clear All H NMR and 13C NMR spectra were recorded on 400 MHz
till now, a possible amination pathway was proposed on the Bruker FT-NMR spectrometers (400 MHz or 100 MHz, respect-
basis of the above experimental results and the literature,5b,e,f,7 ively). All chemical shifts are given as δ values (ppm) with
as shown in Scheme 3. Firstly, iminium ion A is generated in reference to tetramethylsilane (TMS) as an internal standard.
this reaction system via one-electron oxidation of nitrogen, The peak patterns are indicated as follows: s, singlet; d,
deprotonation of C–H adjacent to a nitrogen atom, and further doublet; t, triplet; m, multiplet; q, quartet. The coupling con-
one-electron oxidation.8 Then hydrolysis of A leads to the key stants, J, are reported in Hertz (Hz). High resolution mass
intermediate B by elimination of aldehyde. The origination of spectroscopy data of the product were collected on a Waters
1
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Micromass GCT instrument. Products were purified by flash 130.95, 129.35, 42.16, 38.96, 14.15, 12.80. HRMS (ESI)
chromatography on 100–200 mesh silica gels, SiO2. α-Keto ([M] + H) Calcd for C12H15ClNO2: 240.0791, Found: 240.0788.
acids were prepared from the oxidation of corresponding aryl
methyl ketones with SeO2 and pyridine according to the
reported procedure (K. Wadhwa, C.-X. Yang, P. R. West,
K. C. Deming, S. R. Chemburkar and R. E. Reddy, Synth.
2-(4-Bromophenyl)-N,N-diethyl-2-oxoacetamide (3d): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 8.4 Hz, 2H),
7.66 (d, J = 8.4 Hz, 2H), 3.56 (q, J = 7.2 Hz, 2H), 3.24 (q, J =
Commun., 2008, 38, 4434). Unless otherwise noted, the
chemicals and solvents were purchased from commercial sup-
pliers either from Aldrich, USA or Shanghai Chemical
Company, China and were used without purification prior
to use.
7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H); 13
C
NMR (100 MHz, CDCl3): δ = 190.33, 166.17, 132.34, 132.10,
131.01, 130.00, 42.14, 38.94, 14.18, 12.82. HRMS (ESI)
([M] + H) Calcd for C12H15BrNO2: 284.0286, Found: 283.0283.
General procedure for the synthesis of α-ketoamides
A sealable reaction tube equipped with a magnetic stirrer bar
was charged with α-keto acid (0.50 mmol), tertiary amine
(1.50 mmol, 3.0 equiv.), Ag2CO3 (0.10 mmol, 20%), and K2S2O8
(1.0 mmol, 2 equiv.) in a mixture of CCl4–DMF (4 : 1, v/v,
3.0 mL). The reaction was carried out at 120 °C for 12 h. Then
the mixture was cooled and diluted with ethyl acetate. The
resulting solution was washed with brine (3 × 5.0 mL). The
organic phase was dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel (eluant: hexane–ethyl
acetate 5 : 1) to afford the corresponding product.
2-(3-Bromophenyl)-N,N-diethyl-2-oxoacetamide (3e): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1H), 7.84 (d, J =
7.6 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H),
3.55 (q, J = 7.2 Hz, 2H), 3.23 (q, J = 7.2 Hz, 2H), 1.28 (t, J =
7.2 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ = 189.89, 165.95, 137.34, 135.08, 132.24, 130.51,
128.29, 123.22, 42.18, 39.01, 14.15, 12.80. HRMS (ESI)
([M] + H) Calcd for C12H15BrNO2: 284.0286, Found: 283.0283.
N,N-Diethyl-2-oxo-2-phenylacetamide (3a): yellow oil.3a 1H
NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.2 Hz, 2H), 7.63 (t, J =
7.2 Hz, 1H), 7.50 (t, J = 8.0 Hz, 2H), 3.56 (q, J = 7.2 Hz, 2H),
3.24 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.15 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 191.55, 166.76,
134.55, 133.25, 129.59, 128.95, 42.12, 38.82, 14.07, 12.80.
2-(2-Chlorophenyl)-N,N-diethyl-2-oxoacetamide (3f): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 7.6 Hz, 1H),
7.51–7.48 (m, 1H), 7.44–7.38 (m, 2H), 3.52 (q, J = 7.2 Hz, 2H),
3.35 (q, J = 7.2 Hz, 2H), 1.28–1.23 (m, 6H); 13C NMR (100 MHz,
CDCl3): δ = 190.14, 166.49, 134.14, 133.82, 133.44, 132.32,
130.84, 127.18, 42.18, 39.09, 13.61, 11.89. HRMS (ESI) ([M] +
H) Calcd for C12H15ClNO2: 240.0791, Found: 240.0788.
N,N-Diethyl-2-(4-fluorophenyl)-2-oxoacetamide (3b): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.98–7.95 (m, 2H), 7.17 (t,
J = 8.4 Hz, 2H), 3.55 (q, J = 7.2 Hz, 2H), 3.24 (q, J = 7.2 Hz, 2H),
1.27 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ = 189.81, 166.56 (d, JCF = 256.0 Hz),
166.42, 132.40 (d, JCF = 9.6 Hz), 129.80 (d, JCF = 2.6 Hz), 116.25
(d, JCF = 22.1 Hz), 42.16, 38.92, 14.12, 12.79. HRMS (ESI)
([M] + H) Calcd for C12H15FNO2: 224.1087, Found: 240.1084.
2-(2,5-Dichlorophenyl)-N,N-diethyl-2-oxoacetamide (3g): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 2.0 Hz, 1H),
7.47–7.45 (m, 1H), 7.37 (d, J = 8.4 Hz, 1H), 3.52 (q, J = 7.2 Hz,
2H), 3.36 (q, J = 7.2 Hz, 2H), 1.28–1.23 (m, 6H); 13C NMR
(100 MHz, CDCl3): δ = 188.66, 165.79, 134.95, 133.89, 133.60,
131.89, 131.87, 131.80, 42.23, 39.26, 13.65, 11.85. HRMS (ESI)
([M] + H) Calcd for C12H12Cl2NO2: 274.0402, Found: 274.0405.
2-(4-Chlorophenyl)-N,N-diethyl-2-oxoacetamide (3c): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.4 Hz, 2H),
N,N-Diethyl-2-oxo-2-(p-tolyl)acetamide (3h): yellow oil.11 1H
7.47 (d, J = 8.4 Hz, 2H), 3.55 (q, J = 7.2 Hz, 2H), 3.23 (q, J = 7.2 NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8.0 Hz, 2H), 7.29 (d, J =
Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13C 8.0 Hz, 2H), 3.55 (q, J = 7.2 Hz, 2H), 3.23 (q, J = 7.2 Hz, 2H),
NMR (100 MHz, CDCl3): δ = 190.10, 166.24, 141.15, 131.69, 2.42 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H);
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13C NMR (100 MHz, CDCl3): δ = 191.33, 166.95, 145.74, 130.87, (t, J = 4.4 Hz, 1H), 3.54 (q, J = 7.2 Hz, 2H), 3.33 (q, J = 7.2 Hz,
129.71, 129.65, 42.08, 38.74, 21.83, 14.07, 12.80.
3H), 1.27 (t, J = 7.2 Hz, 3H), 1.20 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ = 183.62, 165.68, 140.60, 136.03, 135.84,
128.52, 42.38, 39.28, 14.25, 12.72.
N,N-Diethyl-2-(4-methoxyphenyl)-2-oxoacetamide (3i): yellow
oil.11 1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 8.8 Hz, 2H),
6.95 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 3.53 (q, J = 7.2 Hz, 2H),
3.22 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H), 1.13 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 190.34, 167.06,
164.70, 132.00, 126.34, 114.25, 55.58, 42.10, 38.70, 14.09,
12.81.
2-Oxo-2-phenyl-N,N-dipropylacetamide (4a): yellow oil.11 1H
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.6 Hz, 2H), 7.64 (t, J =
7.2 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 3.48 (t, J = 7.6 Hz, 2H), 3.14
(t, J = 7.6 Hz, 2H), 1.78–1.69 (m, 2H), 1.65–1.55 (m, 2H), 1.02
(t, J = 7.6 Hz, 3H), 0.80 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ = 191.52, 167.18, 134.46, 133.39, 129.63, 128.91,
49.32, 45.86, 21.81, 20.62, 11.40, 10.99.
2-(4-(tert-Butyl)phenyl)-N,N-diethyl-2-oxoacetamide
(3j):
yellow oil.12 1H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 8.4 Hz,
2H), 7.51 (d, J = 8.4 Hz, 2H), 3.56 (q, J = 7.2 Hz, 2H), 3.24 (q, J =
7.2 Hz, 2H), 1.34 (br, s, 9H), 1.28 (t, J = 7.2 Hz, 3H), 1.15 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 191.29, 166.98,
158.59, 130.75, 129.57, 125.94, 42.12, 38.75, 35.31, 30.98,
14.09, 12.80.
N,N-Dibutyl-2-oxo-2-phenylacetamide (4b): yellow oil.3e 1H
NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.2 Hz, 2H), 7.62 (t, J =
7.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 3.49 (t, J = 7.6 Hz, 2H), 3.14
(t, J = 7.6 Hz, 2H), 1.71–1.63 (m, 2H), 1.57–1.49 (m, 2H),
1.44–1.39 (m, 2H), 1.21–1.15 (m, 2H), 0.99 (t, J = 7.6 Hz, 3H),
0.81 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 191.56,
167.06, 134.44, 133.39, 129.56, 128.89, 47.41, 44.01, 30.61,
29.43, 20.22, 19.73, 13.80, 13.50.
N,N-Diethyl-2-oxo-2-(o-tolyl)acetamide (3k): yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 7.6 Hz, 1H), 7.46 (t, J =
7.2 Hz, 1H), 7.30 (t, J = 7.2 Hz, 2H), 3.54 (q, J = 7.2 Hz, 2H),
3.25 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H),
1.16 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 193.57,
167.43, 141.37, 133.48, 132.58, 132.53, 131.74, 126.08, 42.10,
38.74, 21.73, 13.88, 12.65. HRMS (ESI) ([M] + H) Calcd for
C13H18NO2: 220.1338, Found: 220.1335.
N,N-Dimethyl-2-oxo-2-phenylacetamide (4c): yellow oil.11 1H
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.6 Hz, 2H), 7.65 (t, J =
7.6 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 3.13 (s, 3H), 2.97 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 190.78, 167.04, 134.72, 133.06,
129.66, 129.01, 37.06, 34.01.
1-Phenyl-2-(piperidin-1-yl)ethane-1,2-dione
(4d):
yellow
N,N-Diethyl-2-(naphthalen-1-yl)-2-oxoacetamide (3l): yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 9.27 (d, J = 8.8 Hz, 1H),
8.10 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 7.2 Hz, 1H), 7.91 (d, J = 8.0
Hz, 1H), 7.72–7.68 (m, 1H), 7.61–7.52 (m, 2H), 3.60 (q, J = 7.2
Hz, 2H), 3.31 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.2 Hz, 3H), 1.18 (t,
J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 194.06, 167.27,
135.70, 134.23, 134.08, 131.03, 129.21, 128.71, 128.65, 126.91,
125.85, 124.51, 42.26, 38.86, 13.93, 12.76. HRMS (ESI) ([M] +
H) Calcd for C16H18NO2: 256.1338, Found: 240.1343.
oil.3e 1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 7.2 Hz, 2H),
7.65 (t, J = 7.6 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 3.72 (br s, 2H),
3.30 (t, J = 5.6 Hz, 2H), 1.71–1.70 (m, 4H), 1.56 (br s, 2H); 13C
NMR (100 MHz, CDCl3): δ = 191.94, 165.47, 134.67, 133.25,
129.59, 129.01, 47.06, 42.18, 26.20, 25.45, 24.38.
N-Ethyl-2-oxo-N,2-diphenylacetamide (4e): yellow oil.3d 1H
NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 7.2 Hz, 2H), 7.56 (t, J =
7.6 Hz, 1H), 7.43 (t, J = 8.0 Hz, 2H), 7.27–7.23 (m, 3H),
N,N-Diethyl-2-oxo-2-(thiophen-2-yl)acetamide (3m): yellow 7.14–7.12 (m, 2H), 3.98 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz,
oil.13 1H NMR (400 MHz, CDCl3): δ = 7.79–7.77 (m, 2H), 7.18 3H); 13C NMR (100 MHz, CDCl3): δ = 190.79, 166.59, 139.31,
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3654 | Org. Biomol. Chem., 2013, 11, 3649–3654
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