Copper-Catalyzed Oxidative Synthesis of α-Ketoamides from Aryl Methyl Ketones and N -Bromobutanimide Using N, N -Dimethylformamide as Dimethylamine Source

Article abstract of DOI:10.1055/s-0039-1691568

A novel and practical Cu(OAc) ₂ -catalyzed oxidative synthesis of α-ketoamides from aryl methyl ketones and N -bromobutanimide (NBS) using N, N -dimethylformamide (DMF) as dimethylamine (HNMe ₂) source and solvent has been developed under mild conditions. DMF was used as a HNMe ₂ source and can be easily converted into HNMe ₂ by acid hydrolysis. The mechanistic studies indicate that Cu(OAc) ₂ plays a dual role in providing both catalyst and oxidant.

Full text of DOI:10.1055/s-0039-1691568

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2020, 31, A–E
letter
A
en
Y. Wei et al.
Letter
Synlett
Copper-Catalyzed Oxidative Synthesis of -Ketoamides from Aryl
Methyl Ketones and N-Bromobutanimide Using N,N-Dimethylfor-
mamide as Dimethylamine Source
Ying Wei*
0
0
0
0-0
0
0
1-7
8
0
4-2
7
1
9
One-pot cascade
R2
N
Yongxia Yan
Xiaoyan Li
O
O
O
Cu(OAc)2
R2
R2
H2O
+
+
Ar
R1
N
R2
NBS, 80 °C
Ar
O
Center for Molecular Systems and Organic Devices (CMSOD),
Key Laboratory for Organic Electronics and Information Displays
(KLOEID) & Institute of Advanced Materials (IAM), Jiangsu National
Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing
University of Posts & Telecommunications, Nanjing 210023,
P. R. of China
12 examples
31–90% yield
N,N-dimethylformamide as dimethylamine source
iamywei@njupt.edu.cn
Received: 27.11.2019
Accepted after revision: 02.01.2020
Published online: 24.01.2020
Cu(I)/oxygen combination. Therefore, in this work, we fo-
cused on developing a new oxidative reagent and masked
amine sources reagent combination for the synthesis of -
ketoamides.
DOI: 10.1055/s-0039-1691568; Art ID: st-2019-l0637-l
Abstract A novel and practical Cu(OAc)2-catalyzed oxidative synthesis
of -ketoamides from aryl methyl ketones and N-bromobutanimide
(NBS) using N,N-dimethylformamide (DMF) as dimethylamine (HNMe2)
source and solvent has been developed under mild conditions. DMF was
used as a HNMe2 source and can be easily converted into HNMe2 by acid
hydrolysis. The mechanistic studies indicate that Cu(OAc)2 plays a dual
role in providing both catalyst and oxidant.
O
CF3
H
N
O
N
O
MeO
Cl
O
Cl
Key words dimethylamine, -ketoamides, N-bromobutanimide, aryl
methyl ketones, N,N-dimethylformamide
Cytokine inhibitor
O
Oxerin receptor agonist
O
O
H
N
F
HN
O
HN
R
O
The -ketoamides is a key structural unit in a number of
biologically active natural compounds, drugs and drug can-
didates such as oxerin receptor agonist, cytokine inhibitor,
RARagonist, eurystatin A and B, and poststatin (Figure 1).1–5
Because of their importance, the synthesis of -ketoamides
have attracted significant attention in recent years. So far, a
wide variety of synthetic methodologies for constructing -
ketoamides have been developed towards achieving high ef-
ficiency and novelty.6 Several oxidative amidation methods
have been described for the preparation of -ketoamides.
The common routes involve Cu-catalyzed oxidative amida-
tion of aryl acetaldehydes,7 aryl methyl ketones,8–11 or 1-
arylethanols,12 Cu-catalyzed oxidative amidation–diketon-
ization of terminal alkynes,13–15 the halogen-catalyzed oxi-
dative amidation of aryl methyl ketones,16,17 alkynes,18 or
terminal alkenes,19 the TBAI-catalyzed decarbonylative
amidation of aryl methyl ketones20 or ethyl arenes,21 and
the benzoic acid assisted iodine-catalyzed decarbonylative
oxidative amidation of aryl methyl ketones.22 Among them,
aryl methyl ketones as starting materials are widely used in
the synthesis of -ketoamides. However, the most com-
monly used oxidants in these reactions are TBHP or
NH
O
CO2H
NH
O
Eurystatin A: R = Me
Eurystatin B: R = Et
RARγagonist
O
O
O
H
H
N
N
H2N
N
H
N
OH
H
O
O
O
Poststatin
Pos = (S)-3-amino-2-oxopentanoic acid
Figure 1 Biologically active molecules
N-Dimethylformamide (DMF) has been widely used as a
multifunctional reagent in organic synthesis. For example,
DMF can participate in many reactions as a dehydrating
agent, as a catalyst, as a reducing agent, or even as a source
for various units (O, –CO, –NMe2, –CONMe2, –Me, –CHO,
etc.).23 Inspired by these aspects, we became interested in
the possibility of preparing -ketoamides using DMF as di-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Wei et al.
Letter
Synlett
alkylamine source. For example, recently, Li and co-workers
have developed a copper-catalyzed oxidative C–H amina-
tion of benzoxazoles using DMF as a dimethylamine
source.24 Yang et al. reported a zinc-catalyzed reductive am-
ination of carbonyl compounds with DMF as HNMe2
source.25 Herein, in this context, we show a concise and ef-
ficient synthetic approach for preparing -ketoamides
through a Cu-catalyzed oxidative reaction of aryl methyl
ketones and NBS using DMF as dialkylamine source and as a
solvent. This protocol provides not only a new strategy to
construct -ketoamides but also extends the application
range of DMF as dialkylamine source. The mechanistic
studies indicate that the copper catalyst plays a dual role in
providing both catalyst and oxidant.
The reaction of acetophenone (1a) with NBS was chosen
as a model reaction for optimization of the reaction condi-
tions (Table 1). First, several Cu catalysts were investigated
by using DMF as the dimethylamine source and solvent at
80 °C (Table 1, entries 1–5). The reaction with Cu(OAc)2 as
the catalyst in DMF gave N,N-dimethyl-2-oxo-2-phenylac-
etamide (2a) in 84% yield. CuBr2 exhibited the same reactiv-
ity. When Cu(OTf)2 was selected as the catalyst, the yields
decreased. Besides Cu(II) catalysts, both Cu(I) catalysts like
CuBr and CuI proved to be suitable, giving 2a in moderate
yields. No reaction occurred in DMF at 80 °C, by the utiliza-
tion of FeSO4, and AgOTf as the catalyst (Table 1, entries 6
and 7). However, when the reaction temperature was low-
ered to 60 °C, only 52% of 2a was observed (Table 1, entry
8). Additionally, the yield decreased significantly to 43%,
when the quantity of the catalyst was reduced to 20 mol%
(Table 1, entry 9). When toluene was selected as the sol-
vent, the yields decreased (Table 1, entry 10).
tion occurred with piperidine-1-carbaldehyde or morpho-
line-4-carbaldehyde as the amine source and solvent. In ad-
dition, we use N,N-diphenylformamide as an aromatic
amine source. As a result, the target product 2p was not ob-
Table 1 Optimization of the Reaction Conditionsa
O
O
cat.
N
NBS
+
Ph
Ph
DMF, temp
O
1a
2a
Entry
Catalyst (equiv)
Temp (°C)
Yield of 2a (%)b
1
2
Cu(OAc)2 (1.2)
CuBr2 (1.2)
80
80
80
80
80
80
80
60
80
80
84
81
47
78
80
0
3
Cu(OTf)2 (1.2)
CuBr (1.2)
4
5
CuI (1.2)
6
AgOTf (1.2)
FeSO4 (1.2)
7
0
8
Cu(OAc)2 (1.2)
Cu(OAc)2 (0.2)
Cu(OAc)2 (1.2)
52
43
40c
9
10
a Reaction conditions: 1a (1.0 mmol), NBS (1.2 mmol), with catalyst (1.2
equiv) in DMF (2 mL).
b Isolated yield.
c DMF (5 mmol) in toluene (2 mL).
Table 2 Substrate Scope of Aryl Methyl Ketonesa
With the optimal conditions established above (Table 1,
entry 1), the scope of the ketones was investigated (Table 2).
Catalyzed by Cu(OAc)2, aryl methyl ketones containing both
electron-donating and electron-withdrawing groups could
react with piperidine smoothly, giving the desired products
2a–h in moderate yields (76–90%, Table 2, entries 1–8). It is
noteworthy that an electron-donating substituent on the
benzene ring proceeded more efficiently than an electron-
withdrawing substituent on the benzene ring. In addition,
the naphthyl-substituted ketone also provided the target
product 2i in 81% yield (Table 2, entry 9). Encouraged by the
results obtained with aryl methyl ketones, we turned our
attention to the heteroaryl methyl ketones. The heterocy-
cles, including furan 1j and thiophene 1k, were converted
into the corresponding products 2j and 2k in 76% and 72%
yields, respectively (Table 2, entries 10 and 11). Neverthe-
less, when 2-acetyl pyridine was used as substrates, none of
the desired products was detected.
O
O
Cu(OAc)2
N
NBS
+
Ar
Ar
DMF, 80 °C
O
1
2
Entry
1
Ar
2
Yield (%)b
1
2
1a
Ph
2a
2b
2c
2d
2e
2f
84
87
90
86
81
80
79
76
81
76
72
1b
1c
1d
1e
1f
4-MeOC6H4
3
4-MeC6H4
2-MeC6H4
4-BrC6H4
4-ClC6H4
4-O2NC6H4
3-O2NC6H4
2-naphthyl
2-thienyl
2-furyl
4
5
6
7
1g
1h
1i
2g
2h
2i
8
9
10
11
1j
2j
Then, we examined the efficacy of another amine
source (Table 3). As a result, N,N-diethylformamide (DEF) is
also efficient in the explored reactions, giving the corre-
sponding products 2m in 31% yield. Nevertheless, no reac-
1k
2k
a Reaction conditions: 1 (1.0 mmol), NBS (1.2 mmol), Cu(OAc)2 (1.2 mmol)
in DMF (2 mL) at 80 °C.
b Isolated yield.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

C
Y. Wei et al.
Letter
Synlett
served. Interestingly, N,N-dimethylacetamide (DMA) was
used instead of DMF under otherwise the same conditions,
and product 2a was also produced in 78% yield.
O
Cu(OAc)2 (1.2 mmol)
DMF (2 mL), 80 °C
O
N
(1)
Ph
Br
Ph
O
2a (90%)
4, 1 mmol
Table 3 Substrate Scope of Amidesa
O
NBS
O
C
O
R
N
O
Cu(OAc)2 (1.2 mmol)
O
N
Cu(OAc)2
(2)
R
NBS
+
Ph
R
N
R
+
Ph
R
Ph
DMF (2 mL), 80 °C
N2
Ph
O
80 °C
O
2a (84%)
1a, 1 mmol
1.2 mmol
1a
3
2
O
Entry
1
3
2
Yield (%)b
31
Cu(OAc)2 (1.2 mmol)
DMF (2 mL), 80 °C
O
Ph
N
(3)
Ph
NBS
+
O
O
O
N
N
N
H
N
N
N
1a, 1 mmol
1.2 mmol
2a (0%)
Ph
O
Scheme 1 Control experiments
2m
3a
O
O
O
O
H
yl ketone II is formed via nucleophilic substitution of I by
the dimethylamine. Finally, -aminomethyl ketone II could
be oxidized to iminium III by Cu(OAc)2.26,27 Followed by the
nucleophilic substitution attack of III by H2O leads to the
formation of intermediate IV, which is further oxidized to
afford the desired -ketoamides 2.
2
0
Ph
O
2n
3b
O
O
O
O
H
3
4
5
0
Ph
O
O
O
O
3c
2o
DMF
Ph
N
Cu(OAc)2
Ph
0c
H
N
Ph
Ph
HCOOH
H2O
Ph
3d
2p
O
O
NBS
O
HN
O
Cu(OAc)2
Br
N
R1
R1
N
R1
O
R1
Cu(OAc)2
N
III
I
II
1
Ph
N
78
H2O
N
3e
2a
a Reaction conditions: 1a (1.0 mmol), NBS (1.2 mmol), Cu(OAc)2 (1.2
mmol) in 3 (2 mL) at 80 °C.
O
O
Cu(OAc)2
N
R1
R1
b Isolated yield.
c N,N-Diphenylformamide (5 mmol) in toluene (2mL).
OH
IV
O
2
Scheme 2 Proposed mechanism
To gain insight into the mechanism, several control ex-
periments were performed (Scheme 1). The reaction of -
bromoacetophenone (4) and Cu(OAc)2 was conducted in
DMF at 80 °C and gave product 2a in 90% yield (Scheme 1,
eq. 1). The results indicate that the -bromoacetophenone
might be involved in the mechanism. To explore the origin
of the two oxygen atoms of the -ketoamide, the reaction
under N2 protection gave 2a in 84% yield (Scheme 1, eq. 2),
while the reaction performed in anhydrous DMF (Scheme 1,
eq. 3), no 2a could be observed. Thus, the results indicate
that water is crucial for the reaction to proceed.
In conclusion, we have successfully developed a novel
and atom-efficient copper-catalyzed one-pot oxidative syn-
thesis of -ketoamides by the reaction of aryl methyl ke-
tones and NBS using N,N-dimethylformamide as dimethyl-
amine, in which Cu(OAc)2 plays a dual role in providing
both catalyst and oxidant.28 The mechanistic studies indi-
cate that H2O plays an important role in the reaction. The
reaction features mild conditions, a broad substrate scope,
and atom efficiency.
On the basis of all the results described above, a possible
mechanism for the formation of -ketoamides is shown in
Scheme 2. First, in the presence of Cu(OAc)2, aryl methyl ke-
tones 1 and NBS react to form -bromoketone I. At the
same time, catalyzed by Cu(OAc)2, DMF is hydrolyzed to
give dimethylamine and formic acid.25 Then, -aminometh-
Funding Information
The project was supported by the National Natural Science Founda-
tion of China (Grant No. 21602111), the Synergetic Innovation Centre
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

D
Y. Wei et al.
Letter
Synlett
for Organic Electronics and Information Displays, and the Jiangsu Na-
(28) General Procedure for the Preparation of -Ketoamides 2 –
Synthesis of Compound 2a
tional Synergetic Innovation Center for Advanced Materials (SICAM).
N
ati
o
NnaltucSireaFlnouc
e
n
dCahtiofi
n
a
(2
1
6
0
2
1
1
1)J
i
a
n
gsu
N
ati
o
n
a
lS
y
n
ergeticI
n
n
o
v
ati
o
n
C
e
nterfor
A
d
v
a
n
c
e
d
M
ateri
a
l
s
()
To a solution of acetophenone (0.12 mL, 1.0 mmol) and
Cu(OAc)2 (218 mg, 1.2 mmol) in DMF (2 mL). NBS (213 mg, 1.2
mmol) was then added to the flask in succession. The reaction
mixture was stirred at 80 °C for 12 h. After the starting material
1a was consumed as indicated by TLC, the reaction mixture was
poured into water and then extracted with CH2Cl2 (3 × 10 mL).
The combined organic phase was washed with water (3 × 10
mL), dried over anhydrous MgSO4, filtered, and concentrated
under reduced pressure. The crude product was purified by
flash chromatography (silica gel, petroleum ether/ethyl acetate
= 2:1) to give 2a (148 mg, 84%) as a white solid.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691568.
S
u
p
p
orti
n
gInformati
o
n
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u
p
p
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gInformati
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n
References and Notes
(1) Knust, H.; Nettekoven, M.; Pinard, E.; Roche, O.; Rogers-Evans,
M. WO 2009016087, 2009.
(2) Crowley, C. A.; Delaet, N. G. J.; Ernst, J.; Grove, C. G.; Hepburn, B.;
King, B.; Larson, C. J.; Miller, S.; Pryor, K.; Shuster, L. J. WO
2007146712, 2007.
(3) Álvarez, S.; Álvarez, R.; Khanwalkar, H.; Germain, P.; Lemaire,
G.; Rodríguez-Barrios, F.; Gronemeyer, H.; de Lera, A. R. Bioorg.
Med. Chem. 2009, 17, 4345.
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Chaturvedi, P. R.; Courtney, L. F.; Decker, C. J.; Dinehart, K.;
Gates, C. A.; Harbeson, S. L. Antimicrob. Agents Chemother. 2006,
50, 899.
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Blackman, M.; Chen, K. X.; Hendrata, S.; Huang, Y.; Huelgas, R.
M.; Nair, L. ACS Med. Chem. Lett. 2010, 1, 64.
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50, 11088.
(8) Duab, F. T.; Ji, J. X. Chem. Sci. 2012, 3, 460.
(9) Zhang, J.; Wei, Y.; Lin, S.; Liang, F.; Liu, P. Org. Biomol. Chem.
2012, 10, 9237.
N,N-Dimethyl-2-oxo-2-phenylacetamide (2a)
Yellow solid-liquid mixtures (148 mg, 84%). 1H NMR (500 MHz,
CDCl3):  = 2.96 (s, 3 H), 3.12 (s, 3 H), 7.50–7.53 (t, J = 7.5 Hz, 2
H), 7.63–7.66 (t, J = 7.5 Hz, 1 H), 7.94–7.95 (t, J = 7.5 Hz, 2 H). 13
C
NMR (125 MHz, CDCl3):  = 33.9, 37.0, 128.9, 129.6, 132.9,
134.7, 166.9, 191.7. MS: m/z calcd: 177.0; found: 178.1 [M + 1]+.
Anal. Calcd for C10H11NO2: C, 67.78; H, 6.26; N, 7.90. Found: C,
67.69; H, 6.27; N, 7.89.
2-(4-Methoxyphenyl)-N,N-dimethyl-2-oxoacetamide (2b)
Colourless oil (180 mg, 87%). 1H NMR (500 MHz, CDCl3):  = 2.95
(s, 3 H), 3.11 (s, 3 H), 3.89 (s, 3 H), 6.96–6.98 (m, 2 H), 7.90–7.92
(m, 2H). 13C NMR (125 MHz, CDCl3):  = 33.8, 37.0, 55.5, 114.2,
126.0, 132.0, 164.7, 167.2, 190.4. MS: m/z calcd: 207.0; found:
208.1 [M + 1]+. Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32; N,
6.76. Found: C, 63.88; H, 6.33; N, 6.77.
N,N-Dimethyl-2-oxo-2-(p-tolyl)acetamide (2c)
Colourless oil (171 mg, 90%). 1H NMR (500 MHz, CDCl3):  = 2.43
(s, 3 H), 2.95 (s, 3 H), 3.11 (s, 3 H), 7.30–7.31 (d, J = 8.0 Hz, 2 H),
7.83–7.84 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3):  =
21.8, 33.8, 37.0, 129.6, 129.7, 130.5, 145.9, 167.1, 191.5. MS: m/z
calcd: 191.0; found: 192.4 [M + 1]+. Anal. Calcd for C11H13NO2: C,
69.09; H, 6.85; N, 7.32. Found: C, 69.00; H, 6.84; N, 7.31.
N,N-Dimethyl-2-oxo-2-(o-tolyl)acetamide (2d)
(10) Zhou, M.; Song, Q. Synthesis 2014, 46, 1853.
(11) Sharma, R. K.; Sharma, S.; Gaba, G.; Dutta, S. J. Mater. Sci. 2016,
51, 2121.
(12) Sharma, N.; Kotha, S. S.; Lahiri, N.; Sekar, G. Synthesis 2015, 47,
726.
(13) Zhang, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28.
(14) Kumar, M.; Devari, S.; Kumar, A.; Sultan, S.; Ahmed, Q. N.; Rizvi,
M.; Shah, B. A. Asian J. Org. Chem. 2015, 4, 438.
(15) Sagadevan, A.; Ragupathi, A.; Lin, C. C.; Hwu, J. R.; Hwang, K. C.
Green Chem. 2015, 17, 1113.
Solid-liquid mixtures (164 mg, 86%). 1H NMR (500 MHz, CDCl3):
 = 2.65 (s, 3 H), 2.96 (s, 3 H), 3.09 (s, 3 H), 7.25–7.31 (m, 2 H),
7.43–7.46 (t, J = 7.5 Hz, 1 H), 7.66–7.68 (d, J = 7.5 Hz, 1 H). 13C
NMR (125 MHz, CDCl3):  = 21.7, 33.9, 36.9, 126.1, 132.5, 132.6,
133.6, 141.4, 167.7, 193.6. MS: m/z calcd 191.0; found: 192.5 [M
+ 1]+. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32.
Found: C, 69.20; H, 6.86; N, 7.31.
2-(4-Bromophenyl)-N,N-dimethyl-2-oxoacetamide (2e)
Solid-liquid mixtures (206 mg, 81%). 1H NMR (500 MHz, CDCl3):
 = 2.96 (s, 3 H), 3.12 (s, 3 H), 7.65–7.66 (d, J = 8.0 Hz, 2 H), 7.81–
7.82 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3):  = 34.0,
37.0, 131.0, 131.9, 132.3, 132.6, 166.3, 190.5. MS: m/z calcd:
254.9; found: 256.7 [M + 1]+. Anal. Calcd for C10H10BrNO2: C,
46.90; H, 3.94; N, 5.47. Found: C, 47.00; H, 3.93; N, 5.48.
2-(4-Chlorophenyl)-N,N-dimethyl-2-oxoacetamide (2f)
Solid-liquid mixtures (168 mg, 80%). 1H NMR (500 MHz, CDCl3):
 = 2.97 (s, 3 H), 3.12 (s, 3 H), 7.48–7.50 (d, J = 8.5 Hz, 2 H), 7.89–
7.90 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3):  = 34.0,
37.0, 129.3, 130.9, 132.5, 141.2, 166.4, 190.2. MS: m/z calcd:
211.0; found: 212.3 [M + 1]+. Anal. Calcd for C10H10ClNO2: C,
56.75; H, 4.76; N, 6.62. Found: C, 56.82; H, 4.75; N, 6.61.
N,N-Dimethyl-2-(4-nitrophenyl)-2-oxoacetamide (2g)
Light yellow solid-liquid mixtures (175 mg, 79%). 1H NMR (500
MHz, CDCl3):  = 3.01 (s, 3 H), 3.15 (s, 3 H), 8.14–8.16 (m, 2 H),
8.34–8.36 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3):  =
34.2, 37.0, 124.0, 130.7, 137.4, 151.0, 165.5, 189.2. MS: m/z
calcd: 222.0; found: 223.4 [M + 1]+. Anal. Calcd for C10H10N2O4:
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J. Org. Chem. 2012, 77, 7157.
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Ahmed, Q. N.; Vishwakarma, R. A. Org. Lett. 2014, 16, 1152.
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Y. Wei et al.
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Synlett
C, 54.05; H, 4.54; N, 12.61. Found: C, 54.15; H, 4.55; N, 12.62.
N,N-Dimethyl-2-(3-nitrophenyl)-2-oxoacetamide (2h)
Light yellow solid-liquid mixtures (168 mg, 76%). 1H NMR (500
MHz, CDCl3):  = 3.03 (s, 3 H), 3.17 (s, 3 H), 7.73–7.76 (t, J = 7.5
Hz, 1 H), 8.30–8.32 (d, J = 7.5 Hz, 1 H), 8.49–8.50 (d, J = 8.0 Hz, 1
H), 8.78 (m, 1 H). 13C NMR (125 MHz, CDCl3):  = 34.3, 37.0,
124.4, 128.6, 130.2, 134.4, 135.1, 148.4, 165.3, 188.6. MS: m/z
calcd: 222.0; found: 223.2 [M + 1]+. Anal. Calcd for C10H10N2O4:
C, 54.05; H, 4.54; N, 12.61. Found: C, 53.93; H, 4.53; N, 12.62.
N,N-Dimethyl-2-(naphthalen-1-yl)-2-oxoacetamide (2i)
Solid-liquid mixtures (183 mg, 81%). 1H NMR (500 MHz, CDCl3):
 = 3.00 (s, 3 H), 3.18 (s, 3 H), 7.56–7.59 (m, 1 H), 7.63–7.66 (m,
1 H), 7.88–7.90 (d, J = 8.5 Hz, 1 H), 7.93–7.98 (m, 2 H), 8.02–8.04
(m, 1 H), 8.43 (s, 1 H). 13C NMR (125 MHz, CDCl3):  = 34.0, 37.1,
123.5, 127.0, 127.8, 129.0, 129.3, 129.8, 130.3, 132.3, 132.9,
136.2, 167.1, 191.8. MS: m/z calcd: 227.0; found: 228.3 [M + 1]+.
Anal. Calcd for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C,
73.89; H, 5.78; N, 6.15.
3.04 (s, 3 H), 3.10 (s, 3 H), 7.18–7.19 (t, J = 4.5 Hz, 1 H), 7.79–
7.82 (m, 2 H). 13C NMR (125 MHz, CDCl3):  = 34.3, 37.2, 128.5,
136.1, 136.4, 140.2, 165.7, 183.4. MS: m/z calcd: 183.0; found:
184.5 [M + 1]+. Anal. Calcd for C8H9NO2S: C, 52.44; H, 4.95; N,
7.64. Found: C, 52.33; H, 4.94; N, 7.65.
2-(Furan-2-yl)-N,N-dimethyl-2-oxoacetamide (2k)
Light yellow oil (120 mg, 72%). 1H NMR (500 MHz, CDCl3):  =
3.04 (s, 3 H), 3.09 (s, 3 H), 6.61 (s, 1 H), 7.38 (s, 1 H), 7.72 (s, 1 H).
13C NMR (125 MHz, CDCl3):  = 34.5, 37.2, 112.8, 122.4, 148.7,
150.1, 165.3, 178.4. MS: m/z calcd: 167.0; found: 168.2 [M + 1]+.
Anal. Calcd for C8H9NO3: C, 57.48; H, 5.43; N, 8.38. Found: C,
57.59; H, 5.42; N, 8.37.
N,N-Diethyl-2-oxo-2-phenylacetamide (2m)
Yellow solid-liquid mixtures (63 mg, 31%). 1H NMR (500 MHz,
CDCl3):  = 1.14–1.17 (m, 3 H), 1.28–1.30 (m, 3 H), 3.22–3.26 (m,
2 H), 3.54–3.59 (m, 2 H),7.49–7.52 (m, 2 H), 7.62–7.65 (m, 1 H),
7.93–7.95 (m, 2 H). 13C NMR (125 MHz, CDCl3):  = 12.8, 14.0,
38.7, 42.0, 128.9, 129.5, 133.1, 134.5, 166.6, 191.5. MS: m/z
calcd: 205.1; found: 206.4 [M + 1]+. Anal. Calcd for C12H15NO2: C,
70.22; H, 7.37; N, 6.82. Found: C, 70.31; H, 7.36; N, 6.83.
N,N-Dimethyl-2-oxo-2-(thiophen-2-yl)acetamide (2j)
Light yellow oil (139 mg, 76%). 1H NMR (500 MHz, CDCl3):  =
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E