A novel and efficient reaction of imidazolidin-2-one and N-acylbenzotriazoles: A facile synthesis of 1-acylimidazolidin-2-one

Article abstract of DOI:10.1080/00397910903531615

Acylation of imidazolidin-2-one with readily available N- acylbenzotriazoles, in the presence of K₂CO₃, produced 1-acylimidazolidin-2-ones and N,N'-diacyl-imidazolidin-2-one in moderate to good yields. The utilization of N-acylbenzotriazoles which make the reaction simple and mild, may be especially advantageous when the corresponding acid chlorides are not stable or not easily prepared. It's also an example of the reaction of N-acylbenzotriazoles and amide. Copyright

Full text of DOI:10.1080/00397910903531615

Synthetic Communications1, 40: 3669–3677, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531615
A NOVEL AND EFFICIENT REACTION OF
IMIDAZOLIDIN-2-ONE AND N-ACYLBENZOTRIAZOLES:
A FACILE SYNTHESIS OF 1-ACYLIMIDAZOLIDIN-2-ONE
Jianjun Li, Yan Sun, Zhiwei Chen, and Weike Su
Key Laboratory of Pharmaceutical Engineering of Ministry of Education,
College of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou, P.R. China
Acylation of imidazolidin-2-one with readily available N-acylbenzotriazoles, in the presence
of K2CO3, produced 1-acylimidazolidin-2-ones and N,N0-diacyl-imidazolidin-2-one in mod-
erate to good yields. The utilization of N-acylbenzotriazoles which make the reaction simple
and mild, may be especially advantageous when the corresponding acid chlorides are not
stable or not easily prepared. It’s also an example of the reaction of N-acylbenzotriazoles
and amide.
Keywords: Acylation; N-acylbenzotriazoles; 1-acylimidazolidin-2-one; amides
INTRODUCTION
1-Acylimidazolidin-2-ones are important derivates of imidazolidin-2-one and
have received considerable attention due to their diverse activities as chemotherapeutic
agent for biological process.[1] Moreover, they are also important class of intermedi-
ates in the field of drugs and pharmaceuticals.[1c–e] Most derivatives occur widely in
the synthesis of biologically active compounds such as penicillin, insecticide and other
pesticide.[2]
General procedures of the synthesis of 1-acylimidazolidin-2-one were the inter-
action of imidazolidin-2-one with the activated derivatives of acids, acyl chloride
or acetic anhydride[3] in the presence of base.[4] The use of acyl chloride and acetic
anhydride makes the conditions rather acidic. Strong base, such as NaH is needed
in some procedure to promote the reaction, which makes the conditions harsh.
Direct acylation of imidazolidin-2-one with acid chlorides without base has also been
used by our group[5] to form 1-acyl-imidazolidin-2-one. The above methods offer
many useful synthetic procedures. However, these methods have certain limitations
more or less such as: lower yield, instability, harsh reaction conditions and environ-
ment unfriendly.
Received May 16, 2008.
Address correspondence to Weike Su, Key Laboratory of Pharmaceutical Engineering of Ministry
of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014,
P.R. China. E-mail: suweike@zjut.edu.cn
3669

3670
J. LI ET AL.
N-acylbenzotriazoles are efficient neutral acylation agents[6] and can be easily
prepared from carboxylic acids in one pot.[7] Recently, Katritzky has disclosed
efficient acylations using N-acylbenzotriazoles, which are used widely in organic
synthesis, such as O-acylation of aldehydes,[8] alcohols,[9] and steroids,[10]
C-acylation,[11] N-acylation of amines[7a] and sulfamide,[12] and syntheses of some
biologically active synthetic compounds.[13] More recently, N-aroylation of substi-
tuted indoles with N-aroylbenzotriazoles under base conditions has been reported.[14]
However, few methods have been reported for the acylation of imides from N-
acylbenzotriazoles to our best knowledge.
Recently much attention has been paid to green chemistry. The sustainable
environment needs clean procedures which can avoid using toxic organic reagents.
In continuation with our previous study and the acylation of amide with
N-acylbenzotriazoles, we now present a new method using N-acylbenzotriazoles
as N-acylation agents to prepare 1-acyl-imidazolidin-2-ones. The use of crystalline
N-acylbenzotriazoles can avoid strong acid and base conditions. This method is
especially useful when the corresponding acyl chloride is unstable or unavailable.
And the procedures are mild and environment friendly in good yields.
The starting N-acylbenzotriazoles (1) were prepared according to the literature
procedure[7] in good yields. R1 can be alkyl, aryl and heterocyclic groups, including
the case where the corresponding acyl halide is not stable, for instance furyl halide.
Our first attempt was carried out by using 4-methoxybenzoylbenzotriazoles as
model substrates. A series of bases were investigated to promote this reaction
(Scheme 1) and the results are listed in Table 1. In the study, we undertook the reac-
tion in the presence of base (1 equiv) at room temperature (Table 1, entries 1–5) or at
80 ꢀC (Table 1, entry 1, entries 6–10) for 2 hours. It was found that NaOH, CH3ONa
could not promote the reaction efficiently (Table 1, entries 1–2). In the presence of
triethylamine, we obtained low yield of 3a (Table 1, entry 3). When NaH was used
as base, the yield was increased to 83%, but the conditions were harsh. While K2CO3
was used, the reaction proceeded smoothly in 82% at the same conditions (Table 1,
entry 7). Furthermore, we found that the amount of base could also affect the
yield of the product. When the mole ratio of imidazolidin-2-one and K2CO3 were
1:0.5, 1:0.75, 1:1, 1:2, the yield were 51%, 76%, 82%, and 78%, respectively
(Table 1, entries 7–10).
We also examined some other solvents using K2CO3 as base. The results were
showed in Table 2. From Table 2 we found that the reaction is affected by solvents.
No product appeared when stirred at room temperature for 3 h. Increasing the tem-
perature to 80 ꢀC, trace of 3a was detected in THF=H2O, CHCl3 and EtOH (Table 2,
Scheme 1. The N-acylation of 1a and imidazolidin-2-one.

SYNTHESIS OF 1-ACYLIMIDAZOLIDIN-2-ONE
3671
Table 1. Base effect on the reaction of 4-methoxy-benzoylbenzotriazoles and imidazolidin-2-onea
Entry
Base
Mole ratiob
Solvent
Time (h)
Yield (%)c
1
2
NaOH
CH3ONa
(C2H5)3N
NaH
1:1
1:1
H2O
2
2
2
2
2
2
2
5
2
2
trace
trace
24
CH3OH
THF
THF
3
1:1
1:1
4
83
79
5
NaH
1:1
1:1
Toluene
THF
6
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
47
82
7
1:1
Toluene
Toluene
Toluene
Toluene
8
1:0.5
1:0.75
1:2
51
76
9
10
78
aThe reactions were all carried out at 80 ꢀC, except that entries 2, 3, 4, and 6 were at reflux temperature.
bThe mole ratio was 2: Base.
cIsolated yield.
entries 1–3). However, increasing the reaction temperature made the yield improved
obviously in other solvents selected (Table 2, entries 4–9). Toluene was found to
give maximum yield followed by dioxane.
In light of this, subsequent studies were carried out under the optimized
conditions: in toluene at 80 ꢀC in the presence of K2CO3 as the base.
On the basis of the above results, this process was then extended to other
substituted N-acylbenzotriazoles to investigate the scope and generality (Scheme 2).
The results are summarized in Table 3. Both short chains and long chains alkyl,
substitutive aryl containing electron-donating as well as electron-withdrawing
groups N-acylbenzotriazoles (including the case where the corresponding acyl halide
is not stable, for instance furan-2-carbonyl chloride) were applicable to this reaction.
The acylation of imidazolidin-2-one using N-acylbenzotriazoles as the agents
gave the acylation products smoothly in moderate to good yields. Compared with
longer train alkyl N-acylbenzotriazoles, we obtained better results when the
trains is shorter. (Table 3, entries 11–13). This maybe owe to spacial steric effect.
Table 2. Solvent effect on the reaction of 4-methoxy-benzoylbenzotriazoles and imidazolidin-2-one
catalyzed by K2CO3
Entry
Solvent
Time (h)
Temp (ꢀC)
Yield (%)a
1
2
3
4
5
6
7
8
9
THF:H2O ¼ 6:1
CHCl3
EtOH
2
2
2
2
2
2
2
2
2
80
reflux
reflux
reflux
reflux
reflux
80
trace
trace
trace
68
Acetone
THF
CH3CN
47
75
CH2ClCH2Cl
Toluene
Dioxane
73
82
80
80
78
aIsolated yield.

3672
J. LI ET AL.
Scheme 2. Reactions for synthesizing 1-acyl-imidazolidin-2-ones.
Furthermore, as showned in Table 3, using aromatic N-acylbenzotriazoles as the
starting materials, the substituted groups on the aromatic ring have evident influence
on the reaction. The aromatic ring bearing electron-donating groups required short
time with high yield (Table 3).
Moreover, the reaction of imidazolidin-2-one with 2 equal N-acylbenzotria-
zoles to provide the N,N0-diacylimidazolidin-2-one was studied (Scheme 3). Under
the same conditions, we got low yields of 4 in the presence of K2CO3. However,
when NaH was used as the base, the yield increased to 48%, and 52%, respectively
(Table 3, entries 16, 17).
In summery, an efficient and environment friendly method has been found to
prepare 1-acylimidazolidin-2-ones using N-acylbenzotriazoles as the useful neutral
acylation agents. Compared to previous reported methodologies, the procedure
offers some advantages including environment friendly procedure, mild and neutral
conditions, and simple work up procedure. The method could be advantageous
especially when the corresponding acyl chlorides are not stable or not easily pre-
pared. Hence, it is a useful addition to the existing methods.
a
Table 3. The N-acylation of imidazolidin-2-ones with N-acylbenzotriazoles in the presence of K2CO3
Entry
R
Time (h)
Temp (ꢀC)
Product
Yield (%)c
1
2
p-CH3O-C6H4
C6H5
1
4
80
80
3a
3b
3c
3d
3e
3f
82
73
3
p-NO2-C6H4
m-NO2-C6H4
o-CH3O-C6H4
o-Cl-C6H4
2-Cl-4-NO2-C6H3
2-F-6-Cl-C6H3
3,4-CH3O-C6H3
1-cinnamoyl
CH3
8
80
80
65
70
4
2
5
2
80
80
81
76
6
2
7
10
2
80
80
3g
3h
3i
63
78
8
9
2
80
80
86
69
10
11
12
13
14
15
16
17
2
3j
2
80
80
3k
3l
87
71
C2H5
n-C11H23
2
6
80
80
3m
3n
3o
4a
4b
46
83
2-furyl
2-thienyl
2
2
80
80c, 25d
80c, 25d
91
8c, 48d
10c, 52d
o-Cl-C6H4
p-CH3O-C6H4
12
12
aThe reactions were all carried out at 80 ꢀC in toluene except entries 16 and 17.
bIsolated yield.
cThe reactions were carried out at 80 ꢀC in toluene using K2CO3 as base.
dThe reactions were carried out at room temperature in THF using NaH as base.

SYNTHESIS OF 1-ACYLIMIDAZOLIDIN-2-ONE
3673
Scheme 3. The diacylation of imidazolidin-2-one in the presence of NaH.
EXPERIMENTAL
Melting points were obtained with a capillary melting point apparatus
and uncorrected. Infrared spectra were recorded on a Thermo Nicolet Avatar 370
1
spectrophotometer. H NMR spectra were performed on a Varian Mercur plus-400
spectrometer (400 MHz) in DMSO using TMS as internal standard. 13C NMR spec-
tra were measured in DMSO and recorded on Varian Mercur plus-100 spectrometer
(100 MHz) with TMS as internal standard. Chemical shifts (d) are expressed in ppm
and coupling constants J are given in Hz. Mass spectra were obtained on a Trace
DSQ mass spectrometer. Elemental analysis was performed on a VarioEL-3 instru-
ment. The starting materials N-acylbenzotriazoles 2 were prepared according to
the literature.[7] Organic solvents and imidazolidin-2-one were obtained from
commercial sources.
General Procedure for the N-Acylimidazolidin-2-ones
A mixture of imidazolidin-2-one (0.086g, 1 mmol), K2CO3 (0.138g, 1 mmol) and
toluene (2 mL) was stirred at room temperature for 0.5 h. Then N-acylbenzotriazole
was added to the solution. The resulting mixture was heated to 80ꢀC for indicated
time until the disappearance of N-acylbenzotriazole (monitored by TLC). The solution
was concentrated under reduced pressure. Then the residue was purified by flash chro-
matography (silica gel: hexane=CH2Cl2=EtOAc, 1:1:1) to afford the pure products.
General Procedure for the N,N’-Diacylimidazolidin-2-ones
A mixture of imidazolidin-2-one (0.086 g, 1 mmol), NaH (0.080 g, 60%,
2 mmol) and THF (2 mL) was stirred at room temperature for 0.5 h. Then
N-acylbenzotriazole was added to the solution. The resulting mixture was stirred
at r.t. for indicated time until the disappearance of N-acylbenzotriazole (monitored
by TLC). The solution was concentrated under reduced pressure. Then the residue
was purified by flash chromatography (silica gel: hexane=CH2Cl2=EtOAc, 1:1:1) to
afford the pure products.
Data
1-(4-Methoxybenzoyl)imidazolidin-2-one 3a. White crystal; mp: 167.5–
1
169.7 ꢀC (lit.[15] 167–168 ꢀC); MS (EI): m=z (%) 220 (49), 135 (100), 77 (15); H
NMR (DMSO-d6, 400 MHz): dH 3.38 (t, J ¼ 7.2 Hz, 2H, CH2), 3.81 (s, 3H, CH3),
3.88 (t, J ¼ 7.2 Hz, 2H, CH2), 6.92 (d, J ¼ 8.8 Hz, 2H, PhH), 7.52 (d, J ¼ 7.6 Hz,

3674
J. LI ET AL.
2H, PhH), 7.63 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): 36.1, 43.4, 55.3,
112.6, 127.0, 131.0, 155.5, 161.5; IR (KBr) nmax: 3225, 1741, 1655 cmꢁ1
.
1-Benzoylimidazolidin-2-one 3b. White crystal; mp: 167.3–169.1 ꢀC (lit.[15]
1
169–171 ꢀC); MS (EI): m=z (%) 190 (52), 105 (100), 77 (29); H NMR (DMSO-d6,
400 MHz): dH 3.39 (t, J ¼ 7.6 Hz, 2H, CH2), 3.91 (t, J ¼ 7.6 Hz, 2H, CH2), 7.37
(t, J ¼ 7.2 Hz, 2H, PhH), 7.45–7.52 (m, 3H, PhH), 7.64 (s, 1H, NH); 13C NMR
(DMSO-d6, 100 MHz): 36.1, 43.0, 127.3, 128.4, 130.6, 135.3, 155.2, 169.4; IR
(KBr) nmax: 3425, 1727, 1665 cmꢁ1
.
1-(4-Nitrobenzoyl)imidazolidin-2-one 3c. Yellow crystal; mp: 227.3–
1
229.4 ꢀC; MS (EI): m=z (%) 235 (51), 207 (34), 150 (100); H NMR (DMSO-d6,
400 MHz): dH 3.42 (t, J ¼ 8.0 Hz, 2H, CH2), 3.95 (t, J ¼ 8.0 Hz, 2H, CH2), 7.72
(d, J ¼ 8.8 Hz, 2H, PhH), 7.80 (s, 1H, NH), 8.22 (d, J ¼ 8.8 Hz, 2H, PhH);
13C NMR (DMSO-d6, 100 MHz): 36.2, 42.5, 93.9, 122.6, 129.2, 141.8, 154.9,
167.4; IR (KBr) nmax: 3425, 1754, 1660 cmꢁ1
.
1-(3-Nitrobenzoyl)imidazolidin-2-one 3d. Yellow crystal; mp: 196.2–
197.6 ꢀC; MS (EI): m=z (%) 235 (21), 218 (34), 150 (100), 104 (22); 1H NMR
(DMSO-d6, 400 MHz): dH 3.43 (t, J ¼ 7.6 Hz, 2H, CH2), 3.95 (t, J ¼ 7.6 Hz, 2H,
CH2), 7.69 (t, J ¼ 8.0 Hz, 1H, PhH), 7.79 (s, 1H, NH), 7.93 (d, J ¼ 8.8 Hz, 1H,
PhH), 8.31 (s, 1H, PhH), 8.33 (d, J ¼ 8.0 Hz, 1H, PhH); 13C NMR (DMSO-d6,
100 MHz): 36.1, 42.7, 123.1, 125.0, 129.1, 134.6, 136.9, 146.7, 155.1, 166.9; Anal.
Calcd. for C10H9N3O4: C, 51.06; H, 3.83; N, 17.87. Found: C, 51.16; H, 3.85; N,
17.92; IR (KBr) nmax: 3425, 1754, 1674 cmꢁ1
.
1-(2-Methoxybenzoyl)imidazolidin-2-one 3e. White crystal; mp: 126–
128 ꢀC; MS (EI): m=z (%) 220 (21), 189 (40), 135 (100); 1H NMR (DMSO-d6,
400 MHz): dH 3.36 (t, J ¼ 8.0 Hz, 2H, CH2), 3.71 (s, 3H, CH3), 3.89 (t, J ¼ 8.0 Hz,
2H, CH2), 6.90–6.94 (m, 1H, PhH), 6.97–6.99 (m, 1H, PhH), 7.13–7.15 (m, 1H,
PhH), 7.32–7.37 (m, 1H, PhH), 7.51 (s, 1H, NH); 13C NMR (DMSO-d6,
100 MHz): 34.9, 42.1, 58.5, 111.0, 119.8, 126.4, 127.6, 130.4, 133.1, 154.6, 166.8;
Anal. Calcd. for C11H12N2O3: C, 60.00; H, 5.45; N, 12.72. Found: C, 59.75; H,
5.46; N, 12.51; IR (KBr) nmax: 3333, 1757, 1670 cmꢁ1
.
1-(2-Chlorobenzoyl)imidazolidin-2-one 3f. Yellow crystal; mp: 116.2–
118.9 ꢀC; MS (EI): m=z (%) 225 (7), 189 (100), 139 (34), 111 (21); 1H NMR
(DMSO-d6, 400 MHz): dH 3.41 (t, J ¼ 8.0 Hz, 2H, CH2), 3.94 (t, J ¼ 8.0 Hz, 2H,
CH2), 7.33–7.42 (m, 4H, PhH), 7.70 (s, 1H, NH); 13C NMR (DMSO-d6,
100 MHz): 35.9, 41.7, 126.7, 128.0, 128.6, 129.3, 130.2, 136.4, 154.3, 165.8; IR
(KBr) nmax: 3299, 1759, 1638 cmꢁ1
.
1-(2-Chloro-4-nitrobenzoyl)imidazolidin-2-one 3g. Yellow crystal; mp: 221–
223.2 ꢀC; MS (EI): m=z (%) 225 (7), 189 (100), 139 (34), 111 (21); 1H NMR (DMSO-
d6, 400 MHz): dH 3.45 (t, J ¼ 8.0 Hz, 2H, CH2), 3.98 (t, J ¼ 8.0 Hz, 2H, CH2), 7.68 (d,
J ¼ 8.4 Hz, 1H), 7.88 (s, 1H, NH), 8.20–8.23 (m, 1H, PhH), 8.31 (d, J ¼ 2.4 Hz, 1H,
PhH); 13C NMR (DMSO-d6, 100 MHz): 36.2, 41.5, 122.1, 123.7, 129.0, 130.3, 142.6,
147.9, 154.2, 164.1; IR (KBr) nmax: 3424, 1746, 1677 cmꢁ1
.

SYNTHESIS OF 1-ACYLIMIDAZOLIDIN-2-ONE
3675
1-(2-Chloro-6-fluorobenzoyl)imidazolidin-2-one 3h. White crystal; mp:
162.4–164.0 ꢀC; MS (EI): m=z (%) 207 (100), 157 (47), 129 (12); 1H NMR
(DMSO-d6, 400 MHz): dH 3.43 (t, J ¼ 7.6 Hz, 2H, CH2), 3.98 (t, J ¼ 7.6 Hz, 2H,
CH2), 7.25 (t, J ¼ 8.8 Hz, 1H, PhH), 7.33 (d, J ¼ 8.0 Hz, 1H, PhH), 7.42–7.48 (m,
1H, PhH), 7.87 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): 35.8, 41.5, 114.2,
125.0, 130.1, 131.3, 154.0, 156.9, 159,3, 160.9; Anal. Calcd. for C10H8N2O2Cl: C,
49.48; H, 3.30; N, 11.55. Found: C, 49.45; H, 3.30; N, 11.56; IR (KBr) nmax: 3287,
1749, 1636 cmꢁ1
.
1-(3,4-Dimethoxybenzoyl)imidazolidin-2-one 3i. White crystal; mp:
180.1–182.9 ꢀC (lit.[15] 182–184 ꢀC); MS (EI): m=z (%) 250 (30), 210 (14), 182 (18),
1
165 (100); H NMR (DMSO-d6, 400 MHz): dH 3.38 (t, J ¼ 7.6 Hz, 2H, CH2), 3.75
(s, 3H, CH3), 3.80 (s, 3H, CH3), 3.88 (t, J ¼ 7.6 Hz, 2H, CH2), 6.95 (d, J ¼ 8.4 Hz,
1H, PhH), 7.13–7.17 (m, 2H, PhH), 7.59 (s, 1H, NH); 13C NMR (DMSO-d6,
100 MHz): 36.1, 43.4, 55.5, 110.1, 112.6, 122.8, 127.0, 147.4, 151.3, 155.5, 169.0;
IR (KBr) nmax: 3405, 1737, 1660 cmꢁ1
.
1-Cinnamoylimidazolidin-2-one 3j. Yellow crystal; mp: 203.8–205.6 ꢀC
1
(lit.[15] 203–205 ꢀC); MS (EI): m=z (%) 216 (53), 131 (100), 103 (59), 85 (26); H
NMR (DMSO-d6, 400 MHz): dH 3.36 (t, J ¼ 7.2 Hz, 2H, CH2), 3.87 (t, J ¼ 7.2 Hz,
2H, CH2), 7.42–7.46 (m, 3H, PhH, CH), 7.61–7.67 (m, 3H, PhH), 7.79 (s, 1H,
NH), 8.02 (d, J ¼ 8.0 Hz, 1H, PhH); 13C NMR (DMSO-d6, 100 MHz): 35.8, 42.1,
119.1, 127.9, 128.9, 130.0, 134.8, 141.9, 156.0, 164.6; IR (KBr) nmax: 3425, 1737,
1658 cmꢁ1
.
1-Acetylimidazolidin-2-one 3k. White crystal; mp: 185.9–187.9 ꢀC (lit.[15]
1
186–187 ꢀC); MS (EI): m=z (%) 128 (83), 85 (100), 59 (13); H NMR (DMSO-d6,
400 MHz): dH 2.32 (s, 3H, CH3), 3.29 (t, J ¼ 8.0 Hz, 2H, CH2), 3.73 (t, J ¼ 8.0 Hz,
2H, CH2), 7.59 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): 22.9, 35.6, 41.7,
156.1, 169.6; IR (KBr) nmax: 3258, 1754, 1652 cmꢁ1
.
1-Propionylimidazolidin-2-one 3l. White crystal; mp: 147.5–149.2 ꢀC (lit.[15]
1
148–149 ꢀC); MS (EI): m=z (%) 142 (100), 85 (94), 57 (47); H NMR (DMSO-d6,
400 MHz): dH 1.01 (t, J ¼ 7.2 Hz, 3H, CH3), 2.76–2.81 (q, J ¼ 7.2 Hz, 2H, CH2),
3.30 (t, J ¼ 8.0 Hz, 2H, CH2), 3.74 (t, J ¼ 8.0 Hz, 2H, CH2), 7.55 (s, 1H, NH); 13C
NMR (DMSO-d6, 100 MHz): 8.9, 27.9, 35.8, 41.9, 156.1, 173.3; IR (KBr) nmax
:
3252, 1683, 1623 cmꢁ1
.
1-Dodecanoylimidazolidin-2-one 3m. White crystal; mp: 98.4–99.1 ꢀC; MS
(EI): m=z (%) 269 (21), 183 (63), 155 (100); 1H NMR (DMSO-d6, 400 MHz): dH 0.85
(t, J ¼ 6.4 Hz, 3H, CH3), 1.20–1.30 (m, 16H, CH2), 1.51 (t, J ¼ 6.4 Hz, 2H, CH2),
2.77–2.80 (m, 2H, CH2), 3.32 (t, J ¼ 8.0 Hz, 2H, CH2), 3.73 (t, J ¼ 8.0 Hz, 2H,
CH2), 7.53 (s, 1H, NH); 13C NMR (DMSO-d6, 100 MHz): 13.9, 22.1, 24.3, 28.7,
28.8, 28.9, 29.0, 31.3, 34.3, 35.7, 41.8, 156.0, 172.5; IR (KBr) nmax: 3249, 1738,
1677 cmꢁ1
.
1-(Furan-5-carbonyl) imidazolidin-2-one 3n. White crystal; mp: 150.5–
1
152.1 ꢀC; MS (EI): m=z (%) 180 (100), 152 (49), 95 (98); H NMR (DMSO-d6,
400 MHz): dH 3.38 (t, J ¼ 7.6 Hz, 2H, CH2), 3.88 (t, J ¼ 7.6 Hz, 2H, CH2),
6.63–6.64 (m, 1H, CH), 7.27–7.28 (m, 1H, CH), 7.71 (s, 1H, NH), 7.88 (s, 1H,

3676
J. LI ET AL.
CH); 13C NMR (DMSO-d6, 100 MHz): 36.3, 43.3, 111.5, 118.7, 146.0, 146.1, 155.0,
158.1; IR (KBr) nmax: 3425, 1755, 1626 cmꢁ1
.
1-(Thiophene-5-carbonyl)imidazolidin-2-one 3o. Yellow crystal; mp: 243.5–
1
246.8 ꢀC; MS (EI): m=z (%) 196 (36), 168 (34), 111 (100); H NMR (DMSO-d6,
400 MHz): dH 3.39 (t, J ¼ 7.6 Hz, 2H, CH2), 3.92 (t, J ¼ 7.6 Hz, 2H, CH2),
7.12–7.14 (m, 1H, CH), 7.73 (s, 1H, NH), 7.84–7.85 (m, 2H, CH); 13C NMR
(DMSO-d6, 100 MHz): 36.2, 43.9, 127.1, 132.4, 134.1, 136.6, 155.3, 162.1; IR
(KBr) nmax: 3223, 1748, 1630 cmꢁ1
.
(2-Oxoimidazolidine-1,3-diyl)bis((2-chlorophenyl)methanone) 4a. Yellow
1
crystal; mp: 174.4–175.8 ꢀC; MS (EI): m=z (%) 327 (55), 139 (100), 111 (30); H
NMR (CDCl3, 400 MHz): dH 4.02 (s, 4H, CH2), 7.31–7.55 (m, 8H, PhH); 13C
NMR (CDCl3, 100 MHz): 36.3, 127.4, 128.7, 129.5, 131.1, 133.0, 135.5, 166.6, 167.2.
(2-Oxoimidazolidine-1,3-diyl)bis((4-methoxyphenylmethanone) 4b. White
1
crystal; mp: 94.1–94.9 ꢀC; MS (EI): m=z (%) 354 (4), 152 (18), 135 (100); H NMR
(CDCl3, 500 MHz): dH 3.86 (m, 4H, CH2), 3.88 (s, 6H, CH3), 6.95 (d, J ¼ 8.0 Hz,
4H, PhH), 8.07 (d, J ¼ 8.0 Hz, 4H, PhH);. 13C NMR (CDCl3, 125 MHz): 29.7,
55.5, 113.8, 121.6, 131.8, 132.4, 164.0, 171.0.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(No. 20676123) and National Key Technology R&D Program (No. 2007 BAI34B06)
for financial support.
REFERENCES
1. (a) Kohn, H. Model Studies on the Mechanism of Biotin Dependent Carboxylations. J.
Am. Chem. Soc. 1976, 98, 3690–3694; (b) Pratt, R. F.; Bruice, T. C. Reactions of
S-acylisothioureas.II. Effects of structure and stereochemistry on the rates of hydrolysis,
thiol elimination, and S to N acyl migration in acylic systems. J. Am. Chem. Soc. 1972, 94,
2823–2837; (c) Kohn, H.; Kohn, B. A.; Steenberg, M. L.; Buckley, J. P. Syntheses and
pharmacological activity of substituted imidazolidinethiones and thioimidazolines. J.
Med. Chem. 1977, 20, 158–160; (d) Marx, J. L. Cancer immunotherapy: Focus on the drug
levamisole. Science 1976, 191, 57.
2. (a) Euis, C. J. Mezlocillin and azlocillin: An evaluation of two new b-lactam antibiotics.
Antimicrob Chemother. 1979, 5, 517–525; (b) Baker, M. J. Infection 1979, 7, 67.
3. Gudzenko, V. I.; Salov, B. V. Method for preparing 1-acetyl-2-imidazolidone. Patent, Ru
2237662, 2004.
4. Kohn, H.; Cravey, M. J. Syntheses and spectral properties of substituted imidazolidones
and imidazolines. J. Org. Chem. 1977, 42, 941–948.
5. Su, W. K.; Yin, X. J.; Lu, Y. J. Synthesis of N-Actyl-Imidazolidone-2. J. Zhejiang Univ of
Technol (China) 1995, 23, 136–140.
6. Katritzky, A. R.; Suzuki, K.; Wang, Z. Acylbenzotriazoles as advantageous N-, C-, S-,
and O-acylation agents. Synlett 2005, 1656–1665.
7. (a) Katritzky, A. R.; He, H. Y.; Suzuki, K. N-Acylbenzotriazoles: Neutral acylating
reagents for the preparation of primary, secondary, and tertiary amides. J. Org. Chem.

SYNTHESIS OF 1-ACYLIMIDAZOLIDIN-2-ONE
3677
2000, 65, 8210–8213; (b) Katritzky, A. R.; Zhang, Y.; Singh, S. K. Efficient conversion of
carboxylic acids into N-acylbenzotriazoles. Synthesis 2003, 2795–2798.
8. Katritzky, A. R.; Pastor, A.; Voronkov, M. V. An efficient general synthesis of
1-(benzotriazol-1-yl)alkyl esters. J. Heterocycl. Chem. 1999, 36, 777–782.
9. Zou, X.; Wang, X.; Cheng, C.; Kong, L.; Mao, H. Highly regioselective Friedel–Crafts
alkylation of indoles with a,b-unsaturated N-acylbenzotriazoles. Tetrahedron Lett. 2006,
47, 3767–3771.
10. Katritzky, A. R.; Suzuki, K.; Singh, S. K.; He, H.-Y. Regiospecific C-acylation of pyrroles
and indoles using N-acylbenzotriazoles. J. Org. Chem. 2003, 68, 5720–5723.
11. (a) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. Expedient acylations of primary
and secondary alkyl cyanides to a-substituted b-ketonitriles. J. Org. Chem. 2003, 68,
4932–4934; (b) Katritzky, A. R.; Pastor, A. Synthesis of b-dicarbonyl compounds using
1-acylbenzotriazoles as regioselective C-acylating reagents. J. Org. Chem. 2000, 65,
3679–3682; (c) Katritzky, A. R.; Meher, N. K.; Singh, S. K. c,d-Unsaturated b-diketones
by acylation of ketones. J. Org. Chem. 2005, 70, 7792–7794; (d) Katritzky, A. R.;
Abdel-Fattah, A. A. A.; Gromova, A. V.; Witek, R.; Steel, P. J. a-Nitro ketone synthesis
using N-acylbenzotriazoles. J. Org. Chem. 2005, 70, 9211–9214; (e) Katritzky, A. R.;
Jiang, R.; Suzuki, K. N-Tfa- and N-Fmoc-(a-aminoacyl)benzotriazoles as chiral C-
acylating reagents under Friedel-Crafts reaction conditions. J. Org. Chem. 2005, 70,
4993–5000; (f) Katritzky, A. R.; Angrish, P.; Hur, D.; Suzuki, K. N-(Cbz- and fmoc-a-
¨
aminoacyl)benzotriazoles: Stable derivatives enabling peptide coupling of Tyr, Trp,
Cys, Met, and Gln with free amino acids in aqueous media with complete retention of
chirality. Synthesis 2005, 397–402.
12. Katritzky, A. R.; Hoffmann, S.; Suzuki, K. N-Acylation of sulfonamides using
N-acylbenzotriazoles. ARKIVOC 2004, xii, 14–22.
13. (a) Katritzky, A. R.; Angrish, P.; Suzuki, K. The efficient preparation of Di- and Tripep-
tides by coupling N-(Cbz- or Fmoc-a -aminoacyl)benzotriazoles with unprotected amino
acids. Synthesis 2006, 411–424; (b) Katritzky, A. R.; Tao, H.; Jiang, R.; Suzuki, K.;
Kirichenko, K. Novel Syntheses of chiral b- and c-amino acid derivatives utilizing
N-protected(aminoacyl)benzotriazoles from aspartic and glutamic acids. J. Org. Chem.
2007, 72, 407–414; (c) Katritzky, A. R.; Singh, S. K.; Akhmedova, R.; Cai, C.; Bobrov,
S. Efficient synthesis of 1,3-benzodixin-4-one and benzoxazine-2,4-diones. ARKIVOC
2007, vi, 6–13; (d) Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. A new convenient
preparation of thiol esters utilizing N-acylbenzotriazoles. Synthesis 2004, 1806–1813; (e)
Singh, K. N.; Kaur, A. Facile and chemoselective reduction of carboxylic acids into
alcohols via sodium borohydride reduction of N-Acylbenzotriazoles. Synth. Commun.
2005, 35, 2935–2937; (f) Katritzky, A. R.; Angrish, P. Convenient and efficient prep-
aration of N-Protected(a-Aminoacyl)oxy-substituted terpenes and alkanes. Synthesis
2006, 4135–4142; (g) Wang, X.; Zou, X.; Li, J.; Hu, Q. Efficient syntheses of b-amino-
N-acylbenzotriazoles and cinnamides through regioselective 1,4- or 1,2-addition of amines
to N-cinnamoylbenzotriazoles. Synlett 2005, 3042–3046.
14. Katritzky, A. R.; Khelashvili, L.; Mohapatra, P. P.; Steel, P. J. Efficient N-Aroylation of
substituted indoles with N-Aroylbenzotriazoles. Synthesis 2007, 3673–3677.
15. May, Hans-Joachim; Konig, Horst. Neue 1-acyl-2-imidazoline und Verfahren zu ihrer
Herstellung. Patent, Ger Offen DE 2652004 A1, 1978.

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