Synthesis of imides and benzoylureas by direct oxidation of N-methylenes of amides and benzylureas

Article abstract of DOI:10.3184/174751912X13567968693695

Some amides and benzylureas can be oxidised to imides and benzoylureas, respectively, using silver(I) nitrate (20 mol %), copper(II) sulfate pentahydrate (20 mol %), ammonium persulfate (3.0 equiv.), and potassium fluoride (20 equiv.) in water at room temperature.

Full text of DOI:10.3184/174751912X13567968693695

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 77
FEBRUARY, 77–79
Synthesis of imides and benzoylureas by direct oxidation of
N-methylenes of amides and benzylureas
Wenhua Huang* and Mei-Li Xu
Department of Chemistry, Tianjin University, 92 Weijin Road, Tianjin 300072, P. R. China
Some amides and benzylureas can be oxidised to imides and benzoylureas, respectively, using silver(I) nitrate
(20 mol %), copper(II) sulfate pentahydrate (20 mol %), ammonium persulfate (3.0 equiv.), and potassium fluoride
(20 equiv.) in water at room temperature.
Keywords: amide, benzylurea, direct oxidation, imide, benzoylurea, persulfate, potassium fluoride, silver(I) ion, copper(II) ion
The synthesis of imides by direct oxidation of amides attracts
much attention in the context of mild reaction conditions com-
pared with the traditional methods of acylation of amides. A
number of oxidative systems have been developed, e.g. O2/N-
hydroxyphthalimide,1 ruthenium porphyrin/pyridine-N-oxide,2
chromium (VI)/periodic acid,3 Dess–Martin periodinane,4 and
Selectfluor/CuBr.5 However, these methods use either expen-
sive reagents, or organic solvents or both, so new and simple
methods are still needed. Here we report a mild method for
direction oxidation of amides to imides using persulfate as the
oxidative agent, with copper(II) and silver(I) catalysts, and
water as solvent in the presence of an excess of KF.
increased to 79%. Introducing a nitro group at the para-posi-
tion of the benzoyl moiety of 2a gave 3b in 59% yield and 2c
with a para-methoxy group gave 3c in 34% yield (Table 1,
entries 3 and 4), indicating a profound effect of substitution
on reaction efficiency. When we switched from benzoyl to
aliphatic acyl, we were pleased to find that amide 2d with an
acetyl group afforded 3d in the highest yield (83%) of these
substrates tested, and the other three amides 2e–g also smoothly
underwent oxidation to give 3e–g in 54–71% yields (Table 1,
entries 5–8). This oxidation method was also effective for
amide 2h with a pyrrolidine ring replacing the 4-methoxyben-
zylamine of 2a (Table 1, entry 9, 58% yield). Attempts to
oxidise amides with a substituent such as Cl, Me and H, in
place of the methoxy group of 2a were unsuccessful.
Our protocol is not limited to amides. 1-Benzylurea 2i can
also be oxidised to 1-benzoylurea 3i in 68% yield (Table 1,
entry 10). 1-(4-Methylbenzyl)urea 2j gave 3j in a moderate
yield whereas, 1-(4-methoxybenzyl)urea 2k gave 3k in a
low yield (Table 1, entries 11 and 12). Surprisingly, 1-(4-
methoxybenzyl)biuret 2l also worked well, generating the
desired 1-(4-methoxybenzoyl)biuret 3l in a good yield (Table 1,
entry 13, 79%). Although a number of methods have been
developed for the direction oxidation of amides to imides, the
direction oxidation of benzylurea to benzoylurea, to the best of
our knowledge, has not been reported.
Our previous work6 demonstrated that N-acyl amino acids
can be converted into imides by S2O82−/Ag+/Cu2+/water by
oxidative decarboxylation followed by hydrolysis and further
oxidation as shown at the top of Scheme 1. We speculated that
replacing the carboxyl group with hydrogen may also form
radical 4 through hydrogen abstraction by the sulfate anion
radical, which would give imide 3 by the same path as from
N-acyl amino acid, as shown at the bottom of Scheme 1.
When we first examined the oxidation of amide 2a under our
previous standard conditions (20 mol % AgNO3, 20 mol %
CuSO4⋅5H2O, 3.0 equiv. (NH4)2S2O8), we were delighted to
observe the formation of the desired imide 3a in 21% yield
(Table 1, entry 1). After numerous trials, we found that in the
presence of excess KF (20 equiv.), the yield of 3a dramatically
In summary, we have developed a new method to oxidise
amides and benzylureas to imides and benzoylureas respec-
tively. This represents the first example of direct oxidation of
O
COOH
O
O
+
2+
2-
Ag /Cu /S O
2
8
R1
N
R2
R1
N
R3
3
R2
Table 1 Synthesis of imides and benzoylureas by direct
oxidationa
water
R3
Pr evious work
1
Ag2+
Ag+
R2
2-
S2O8
+
-H
-CO
oxidation
2-
-
2
•
SO4 + SO4
R2
O
OH
R2
Entry
R1
R2
R3
2
3
Yield/% of 3
O
O
oxidation
hydrolysis
21b
79
R1
N
R1
N
R1
N
1
2
Ph
Ph
4-MeOC6H4
4-MeOC6H4
H
H
H
H
H
H
H
H
2a
2a
2b
2c
2d
2e
2f
2g
2h
2i
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
R3
R3
R3
3
4-O2NC6H4 4-MeOC6H4
4-MeOC6H4 4-MeOC6H4
59c
34
4
5
6
4
5
Me
MeOOCCH2 4-MeOC6H4
Bn 4-MeOC6H4
4-MeOC6H4
83
-
HSO4
6
71
oxidation
7
52
-
•
SO4
8
cyclohexyl 4-MeOC6H4
54c
58c
68
9
Ph
–(CH2)3–
Ph
4-MeC6H4
4-MeOC6H4
O
O
O
H
+
2+
2-
Ag /Cu /S O
10
11
12
13
H2N
H2N
H2N
H
H
H
H
2
8
2j
2k
2l
3j
3k
3l
48c
21
R1
N
R2
R1
N
R3
R2
water, KF
R3
H2NCONH 4-MeOC6H4
79
This work
2
3
a Reaction conditions: AgNO3 (20 mol %), CuSO4⋅5H2O (20 mol %),
(NH4)2S2O8 (3.0 equiv.), and KF (20 equiv.) in water (10 mL),
room temperature, 6 h except for those specified.
b In the absence of KF.
Scheme 1
c These reactions were run overnight.
* Correspondent. E-mail: huangwh@tju.edu.cn

78 JOURNAL OF CHEMICAL RESEARCH 2013
N-(4-Methoxybenzyl)-2-phenylacetamide (2f): A white solid, yield
43%, m.p. 142–144 °C (lit.13 142–144 °C). IR (KBr, νmax, cm−1): 1628
(C=O). 1H NMR (400 MHz, DMSO-d6) δ 3.48 (s 2H, CH2CO), 3.73
(s, 3H, OCH3), 4.21 (d, J = 5.6 Hz, 2H, NCH2), 6.87 (d, J = 8.4 Hz,
2H, ArH), 7.17 (d, J = 8.4 Hz, 2H, ArH), 7.21–7.31 (m, 5H, ArH),
8.50 (brs, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ 42.2, 42.9,
55.5, 114.1, 126.8, 128.7, 129.0, 129.5, 131.8, 136.9, 158.7, 170.5.
Crystallisation solvent: EtOAc: PE = 1: 5.
1-benzylurea to 1-benzoylurea. Our method features a cheap
and bench-stable oxidant, water as a solvent and mild reaction
conditions.
Experimental
Amide 2d7 and 1-benzylureas 2i–k8 were prepared according to the
literature procedure. Compound 2l was prepared from 1-nitrobiuret9
and benzylamines according to the reported procedure.10 1H and 13C
NMR spectra were recorded on a MercuPlus 400 NMR spectrometer.
IR spectra were recorded on a Thermo Nicolet Avatar 360 IR spec-
trometer. Electrospray ionisation mass spectra were obtained on an
LCQ Advantage MAX (Finnigan) instrument. All melting points were
measured on a melting apparatus with microscope and hot stage and
were uncorrected. Ammonium persulfate, CuSO4·5H2O, and AgNO3
were purchased from Jiangtian Chemical Reagent Company, China.
These chemicals were used directly as received. The deionised water
purchased from Water Centre of Nankai University, China, was
distilled before use. All reactions were necessarily carried out under
nitrogen. PE = petroleum ether (b.p. 60–90 °C).
N-(4-Methoxybenzyl)cyclohexanecarboxamide (2g): A white solid,
yield 17%, m.p. 119–121 °C (lit.14 118 °C). IR (KBr, νmax, cm−1): 1634
(C=O). 1H NMR (400 MHz, DMSO-d6) δ 1.13–1.27 (m, 3H,
cyclohexyl-H), 1.33–1.42 (m, 2H, cyclohexyl-H), 1.61–1.64 (m, 1H,
cyclohexyl-H), 1.70–1.73 (m, 4H, cyclohexyl-H), 2.12–2.19 (m, 1H,
CHC=O), 3.73 (s, 3H, OCH3), 4.19 (d, J = 6.0 Hz, 2H, NCH2), 6.87 (d,
J = 8.6 Hz, 2H, ArH), 7.15 (d, J = 8.6 Hz, 2H, ArH), 8.12 (t,
J = 5.6 Hz, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ 25.8, 26.0,
29.8, 41.7, 44.5, 55.5, 114.1, 128.7, 132.3, 158.6, 175.5. Eluent:
EtOAc: PE = 1: 3 (Rf = 0.29).
Phenyl(pyrrolidin-1-yl)methanone (2h): A colourless oil (mp: lit.15
1
46–47 °C), yield 20%. IR (KBr, νmax, cm−1): 1625 (C=O). H NMR
(400 MHz, CDCl3) δ 1.73–1.79 (m, 2H, pyrrole-CH2), 1.81–1.86 (m,
2H, pyrrole-CH2), 3.31 (t, J = 7.0 Hz, 2H, pyrrole-CH2), 3.54 (t,
J = 7.0 Hz, 2H, pyrrole-CH2), 7.28–7.30 (m, 3H, ArH), 7.40–7.44 (m,
2H, ArH). 13C NMR (100 MHz, CDCl3) δ 24.4, 26.3, 46.1, 49.5, 127.0,
128.1, 129.7, 137.2, 169.6. Eluent: EtOAc: PE = 1: 3 (Rf = 0.13).
Synthesis of amides 2a–c and 2e–h; general procedure
CH2Cl2 (100 mL) was added to a flask (250 mL) containing a carbox-
ylic acid (10 mmol) and HOBt (1.5 g, 11 mmol). After stirring at room
temperature for 15 min under nitrogen, the mixture was cooled to 0 °C
with ice-water bath and N,N′-dicyclohexylcarbodiimide (DCC) (2.3 g,
11 mmol) was added in portions. The reaction mixture was stirred for
15 min and then a solution of an amine (11 mmol) and triethylamine
(1.0 g, 10 mmol) in CH2Cl2 (5 mL) was added dropwise over about
5 min. The reaction mixture was allowed to stir at 0 °C for 30 min and
then at room temperature overnight. Then a solution of citric acid
(10%, w/w, 100 mL) was added to decompose unreacted DCC, and
the resulting mixture was stirred at room temperature for 1 h. The
white solids (1,3-dicyclohexylurea) were washed with CH2Cl2 (5 mL
× 2) after filtration. The combined filtrate was washed with citric acid
solution (10%, w/w, 100 mL × 2), saturated Na2CO3 (100 mL × 2), and
brine (50 mL), sequentially. The separated organic layer was dried
over anhydrous Na2SO4, evaporated under reduced pressure, and the
residue was purified by column chromatography (silica gel) or cryst-
allisation using solvent as specified to give amides 2a–c and 2e–h.
N-(4-Methoxybenzyl)benzamide (2a): A white solid, yield 75%,
m.p. 91–93 °C (lit.11 91–94 °C). IR (KBr, νmax, cm−1): 1634 (C=O). 1H
NMR (400 MHz, DMSO-d6) δ 3.73 (s, 3H, OCH3), 4.44 (d, J =
5.6 Hz, 2H, NCH2), 6.90 (d, J = 8.4 Hz, 2H, ArH), 7.28 (d, J =
8.4 Hz, 2H, ArH), 7.45–7.56 (m, 3H, ArH), 7.92 (d, J = 7.6 Hz, 2H,
ArH), 9.02 (t, J = 5.6 Hz, 1H, NH). 13C NMR (100 MHz, DMSO-d6)
δ 42.6, 55.5, 114.1, 127.7, 128.7, 129.1, 131.6, 132.1, 134.9, 158.7,
166.6. Crystallisation solvent: EtOAc: PE = 1: 5.
Oxidation of amides and benzylureas; general procedure
AgNO3 (13.6 mg, 0.08 mmol), CuSO4⋅5H2O (powder, 20.0 mg,
0.08 mmol), 1-benzylurea or amide (0.4 mmol), and (NH4)S2O8
(273.8 mg, 1.2 mmol) were added to a plastic tube (25 mL). Then a
solution of KF in water (0.8 M, 10 mL), which was degassed by purg-
ing with N2 before use, was added by syringe. After stirring at room
temperature for 6 h or overnight, the reaction mixture was treated with
EtOAc (10 mL), and was allowed to stir for 5 min. The organic layer
was separated, and the aqueous layer was extracted with EtOAc
(10 mL × 2). The combined extracts were dried over anhydrous
Na2SO4, evaporated, and separated by preparative TLC to give the
product 3a–k. For 2l, after reaction, the reaction mixture was directly
filtered, and the brown solids were washed with water (5 mL × 4)
and EtOAc (5 mL x 4), sequentially, and then dried under reduced
pressure to give the product 3l.
N-Benzoyl-4-methoxybenzamide (3a): A pale yellow solid, yield
79%, m.p. 103–105 °C (lit.16 109–110 °C). IR (KBr, νmax, cm−1): 1719
and 1665 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 3.85 (s, 3H,
OCH3), 7.06 (d, J = 8.8 Hz, 2H, ArH), 7.50–7.55 (m, 2H, ArH), 7.61–
7.66 (m, 1H, ArH), 7.90 (d, J = 7.2 Hz, 2H, ArH), 7.94 (d, J = 8.8 Hz,
2H, ArH), 11.18 (brs, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ
56.0, 114.1, 126.2, 128.8, 129.0, 131.4, 132.9, 134.6, 163.3, 167.2,
168.4. Eluent: EtOAc: PE = 1:2 (Rf = 0.22).
N-(4-Methoxybenzyl)-4-nitrobenzamide (2b): Yellow needles, yield
18%, m.p. 136–138 °C (lit.12 137–138.5 °C). IR (KBr, νmax, cm−1):
4-Methoxy-N-(4-nitrobenzoyl)benzamide (3b): A pale yellow solid,
yield 59%, m.p. 182–184 °C. IR (KBr, νmax, cm−1): 1709 and 1671
1
1641 (C=O). H NMR (400 MHz, DMSO-d6) δ 3.73 (s, 3H, OCH3),
1
(C=O). H NMR (400 MHz, acetone-d6) δ 3.92 (s, 3H, OCH3), 7.07
4.44 (d, J = 6.0 Hz, 2H, NCH2), 6.90 (d, J = 8.4 Hz, 2H, ArH),
7.27 (d, J = 8.4 Hz, 2H, ArH), 8.11 (d, J = 8.8 Hz, 2H, ArH), 8.32
(d, J = 8.8 Hz, 2H, ArH), 9.32 (t, J = 5.6 Hz, 1H, NH). 13C NMR
(100 MHz, DMSO-d6) δ 42.8, 55.5, 114.2, 124.0, 129.20, 129.21,
131.5, 140.5, 149.5, 158.8, 164.9. Crystallisation solvent: absolute
alcohol.
(d, J = 8.6 Hz, 2H, ArH), 8.03 (d, J = 8.6 Hz, 2H, ArH), 8.14 (d,
J = 8.8 Hz, 2H, ArH), 8.36 (d, J = 8.8 Hz, 2H, ArH), 10.52 (brs, 1H,
NH). 13C NMR (100 MHz, acetone-d6) δ 55.1, 113.8, 123.3, 125.5,
129.6, 130.8, 140.6, 149.9, 163.7, 165.8, 166.9. HRMS-ESI (posi-
tive): m/z [M+Na]+ calcd for C15H12N2NaO5+: 323.0638; found:
323.0634. Eluent: acetone: PE = 1:1 (Rf = 0.76).
4-Methoxyl-N-(4-methoxybenzoyl)benzamide (3c): A white solid,
yield 34%, m.p. 170–172 °C (known17 compound but no m.p. has
been reported). IR (KBr, νmax, cm−1): 1715 and 1670 (C=O). 1H NMR
(400 MHz, DMSO-d6) δ 3.85 (s, 6H, OCH3), 7.06 (d, J = 8.2 Hz, 4H,
ArH), 7.92 (d, J = 8.2 Hz, 4H, ArH), 11.00 (brs, 1H, NH). 13C NMR
(100 MHz, DMSO-d6) δ 56.0, 114.1, 126.5, 131.3, 163.2, 167.4.
Eluent: EtOAc: PE = 1:1 (Rf = 0.31).
N-Acetyl-4-methoxybenzamide (3d): A white solid, yield 83%, m.p.
116–118 °C (lit.18 119–119.5 °C). IR (KBr, νmax, cm−1): 1715 and 1676
(C=O). 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3H, C(O)CH3), 3.83
(s, 3H, OCH3), 7.03 (d, J = 8.8 Hz, 2H, ArH), 7.95 (d, J = 8.8 Hz,
2H, ArH), 10.87 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ 26.0,
55.9, 114.2, 125.6, 131.0, 163.3, 166.1, 172.8. Eluent: EtOAc: PE =
1:3 (Rf = 0.15).
Methyl 3-(4-methoxybenzamido)-3-oxopropanoate (3e): A pale
yellow solid, yield 71%, m.p. 153–154 °C (known19 compound but
no m.p. has been reported). IR (KBr, νmax, cm−1): 1740, 1701 and 1679
4-Methoxy-N-(4-methoxybenzyl)benzamide (2c): A white solid,
yield 77%, m.p. 132–134 °C (lit.12 127–129 °C). IR (KBr, νmax, cm−1):
1
1632 (C=O). H NMR (400 MHz, DMSO-d6) δ 3.73 (s, 3H, OCH3),
3.81 (s, 3H, OCH3), 4.42 (d, J = 5.2 Hz, 2H, NCH2), 6.89 (d, J =
8.2 Hz, 2H, ArH), 7.01 (d, J = 8.4 Hz, 2H, ArH), 7.26 (d, J = 8.2 Hz,
2H, ArH), 7.90 (d, J = 8.4 Hz, 2H, ArH), 8.85 (brs, 1H, NH). 13C NMR
(100 MHz, DMSO-d6) δ 42.5, 55.5, 55.8, 113.9, 114.1, 127.2, 129.0,
129.5, 132.4, 158.6, 162.0, 166.1. Crystallisation solvent: EtOAc: PE
= 1: 5.
Methyl 3-((4-methoxybenzyl)amino)-3-oxopropanoate (2e): A white
solid, yield 13%, m.p. 71–73 °C. IR (KBr, νmax, cm−1): 1746 (C=O),
1643 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 3.30 (s, 2H,
CH2CONH), 3.63 (s, 3H, COOCH3), 3.74 (s, 3H, ArOCH3), 4.22
(d, J = 5.6 Hz, 2H, NCH2), 6.89 (d, J = 8.6 Hz, 2H, ArH), 7.20 (d,
J = 8.6 Hz, 2H, ArH), 8.53 (brs, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ 42.2, 42.7, 52.3, 55.5, 114.2, 129.0, 131.4, 158.7, 165.5,
168.9. HRMS-ESI (negative): m/z [M+Na]+ calcd for C12H15NO4Na+:
260.0893; found: 260.0897. Eluent: EtOAc: PE = 1: 1 (Rf = 0.32).

JOURNAL OF CHEMICAL RESEARCH 2013 79
1
(C=O). H NMR (400 MHz, DMSO-d6) δ 3.65 (s, 3H, C(O)OCH3),
1H, NH). 13C NMR (100 MHz, DMSO-d6) δ 56.0, 114.2, 125.1, 130.7,
154.9, 163.3, 167.8. Eluent: CH2Cl2: MeOH = 12:1 (Rf = 0.59).
N-(Carbamoylcarbamoyl)-4-methoxybenzamide (3l): A brown solid,
yield 79%, m.p. 225–226 °C. IR (KBr, νmax, cm−1): 1752, 1719 and
3.82 (s, 2H, OOCCH2), 3.85 (s, 3H, ArOCH3), 7.05 (d, J = 9.0 Hz,
2H, ArH), 7.95 (d, J = 9.0 Hz, 2H, ArH), 11.20 (brs, 1H, NH). 13C
NMR (100 MHz, DMSO-d6) δ 45.2, 52.4, 56.0, 114.3, 129.0, 131.2,
163.6, 166.2, 168.1, 168.6. HRMS-ESI (negative): m/z [M+Na]+ calcd
for C12H13NO5Na+: 274.0686; found: 274.0689. Eluent: EtOAc: PE =
1:3 (Rf = 0.11).
1
1675 (C=O). H NMR (400 MHz, DMSO-d6) δ 3.85 (s, 3H, OCH3),
7.07 (d, J = 8.6 Hz, 2H, ArH), 7.44 (s, 2H, NH2), 7.99 (d, J = 8.6 Hz,
2H, ArH), 10.41 (s, 1H, NH), 11.19 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ 56.1, 114.4, 124.4, 131.0, 152.7, 153.6, 163.8, 167.8.
HRMS-ESI (negative): m/z [M-H]− calcd for C10H10N3O4−: 236.0677;
found: 236.0676. Eluent: CH2Cl2: MeOH = 10:1 (Rf = 0.56).
4-Methoxy-N-(2-phenylacetyl)benzamide (3f): A pale yellow solid,
yield 52%, m.p. 118–121 °C (lit.20 162–164 °C). IR (KBr, νmax, cm−1):
1710 and 1678 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 3.84 (s, 3H,
OCH3), 4.07 (s, 2H, CH2CO), 7.06 (d, J = 9.0 Hz, 2H, ArH), 7.24–7.34
(m, 5H, ArH), 7.96 (d, J = 9.0 Hz, 2H, ArH), 11.00 (brs, 1H, NH). 13
C
Financial support for W. H. from Tianjin University is grate-
fully acknowledged.
NMR (100 MHz, DMSO-d6) δ 43.9, 56.0, 114.2, 125.7, 127.0, 128.7,
130.1, 131.1, 135.5, 163.4, 166.1, 173.0. Eluent: EtOAc: PE = 1:2
(Rf = 0.46).
Received 22 September 2012; accepted 3 December 2012
Paper 1201529 doi: 10.3184/174751912X13567968693695
Published online: 13 February 2013
N-(Cyclohexanecarbonyl)-4-methoxybenzamide (3g): A white solid,
yield 54%, m.p. 124–126 °C. IR (KBr, νmax, cm−1): 1703 and 1674
(C=O). 1H NMR (400 MHz, DMSO-d6) δ 1.13–1.40 (m, 5H,
cyclohexyl-H), 1.62–1.87 (m, 5H, cyclohexyl-H), 2.85–2.93 (m, 1H,
cyclohexyl-H), 3.84 (s, 3H, OCH3), 7.03 (d, J = 8.8 Hz, 2H, ArH),
7.90 (d, J = 8.8 Hz, 2H, ArH), 10.64 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ 25.6, 25.9, 29.2, 44.6, 55.9, 114.1, 126.1, 131.0,
163.2, 166.0, 177.4. HRMS-ESI (negative): m/z [M-H]− calcd for
C15H18NO3−: 260.1292; found: 260.1299. Eluent: EtOAc: PE = 1:1 (Rf
= 0.60).
References
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F. Minisci, C. Punta, F. Recupero, F. Fontana and G.F. Pedulli, J. Org.
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R. Ito, N. Umezawa and T. Higuchi, J. Am. Chem. Soc., 2005, 127, 834.
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5992.
1-Benzoylpyrrolidin-2-one (3h): A white solid, yield 58%, m.p.
91–92 °C (lit.21 90–91 °C). IR (KBr, νmax, cm−1): 1744 and 1664 (C=O).
1H NMR (400 MHz, CDCl3) δ 2.09–2.17 (m, 2H, pyrrole-H), 2.59
(t, J = 8.0 Hz, 2H, pyrrole-CH2), 3.95 (t, J = 7.2 Hz, 2H, pyrrole-CH2),
7.28–7.40 (m, 2H, ArH), 7.49–7.54 (m, 1H, ArH), 7.59–7.63 (m, 2H,
ArH). 13C NMR (100 MHz, CDCl3) δ 17.6, 33.3, 46.5, 127.8, 128.9,
131.8, 134.4, 170.6, 174.5. Eluent: EtOAc: PE = 1:1 (Rf = 0.66).
N-Carbamoylbenzamide (3i): A white solid, yield 68%, m.p. 205–
208 °C (lit.22 208–210 °C). IR (KBr, νmax, cm−1): 1703 and 1660 (C=O).
1H NMR (400 MHz, DMSO-d6) δ 7.41 (brs, 1H, one proton of NH2),
7.48–7.53 (m, 2H, ArH), 7.59–7.64 (m, 1H, ArH), 7.95–7.98 (m, 2H,
5
6
7
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M.J. Plater, J.P. Sinclair, S. Aiken, T. Gelbrich and M.B. Hursthouse,
Tetrahedron, 2004, 60, 6385.
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16 T. Ogata and R. Goto, Nippon Kagaku Zasshi, 1963, 84, 849.
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ArH), 8.07 (brs, 1H, another proton of NH2), 10.54 (brs, 1H, NH). 13
C
NMR (100 MHz, DMSO-d6) δ 128.6, 128.9, 133.1, 133.2, 154.7,
168.6. Eluent: CH2Cl2: MeOH = 15:1 (Rf = 0.60).
N-Carbamoyl-4-methylbenzamide (3j): A white solid, yield 48%,
m.p. 223–225 °C (lit.23 224–225 °C). IR (KBr, νmax, cm−1): 1695 and
1674 (C=O). 1H NMR (400 MHz, DMSO-d6) δ 2.36 (s, 3H, CH3), 7.30
(d, J = 7.8 Hz, 2H, ArH), 7.38 (brs, 1H, one proton of NH2), 7.88 (d,
J = 7.8 Hz, 2H, ArH), 8.09 (brs, 1H, another proton of NH2), 10.46
(brs, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ 21.5, 128.6, 129.5,
130.3, 143.5, 154.8, 168.4. Eluent: CH2Cl2: MeOH = 15:1 (Rf = 0.61).
N-Carbamoyl-4-methoxybenzamide (3k): A white solid, yield 21%,
m.p. 214–216 °C (lit.24 215 °C). IR (KBr, νmax, cm−1): 1704 and 1665
(C=O). 1H NMR (400 MHz, DMSO-d6) δ 3.83 (s, 3H, OCH3), 7.03 (d,
J = 8.8 Hz, 2H, ArH), 7.35 (brs, 1H, one proton of NH2), 7.99 (d, J =
8.8 Hz, 2H, ArH), 8.11 (brs, 1H, another proton of NH2), 10.39 (brs,

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