Tandem reactions of 2-methylimidazoline and 1,2-dimethylimidazoline with various benzoyl chlorides

Article abstract of DOI:10.1055/s-0029-1217048

The reactions of 2-methylimidazoline with excess benzoyl chlorides under mild conditions generated N,N′-diacyl - keto cyclic ketene-N,N′- acetals. Conversely, the corresponding reactions of 1,2-dimethylimidazoline under the same conditions stereoselective

Full text of DOI:10.1055/s-0029-1217048

PAPER
141
Tandem Reactions of 2-Methylimidazoline and 1,2-Dimethylimidazoline with
Various Benzoyl Chlorides
Tandem
Reaction
u
of Imidazolin
o
es
w
ithBenzoyl Chlorid
h
es ong Ye,*a Chunlong Chen,b Sabornie Chatterjee,a Willard E. Collier,a Aihua Zhou,c Yingquan Song,a
Debbie J. Beard,a Charles U. Pittman Jr. *a
a
Department of Chemistry, Mississippi State University, Starkville, MS 39762, USA
Fax +1(662)3257611; E-mail: cpittman@chemistry.msstate.edu; E-mail: gye001@gmail.com
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Pharmacy School, University of Wisconsin-Madison, Madison, WI 53706, USA
b
c
Received 19 July 2009; revised 29 August 2009
two nitrogens were benzoylated; no C–C bond was
Abstract: The reactions of 2-methylimidazoline with excess ben-
zoyl chlorides under mild conditions generated N,N¢-diacyl-b-keto
cyclic ketene-N,N¢-acetals. Conversely, the corresponding reactions
of 1,2-dimethylimidazoline under the same conditions stereoselec-
formed. An extremely strong electrophile, trifluoroacetic
anhydride, was reported to react with 2-methylimidazo-
line, forming ring-retained triacylated products
tively formed the ring-opened (Z)-vinyl benzoates. The latter reac- (Scheme 2).23b This was the first and, so far, the only ex-
tions feature the formation of carbon–carbon bonds, carbon–
nitrogen bonds, and carbon–oxygen bonds in one sequential cas-
cade.
ample that showed the nucleophilicity of a diacyl cyclic
ketene-N,N¢-acetal. Recently, 2-methylthiazolines 7,
which are analogues of 4, were reported to react with acid
chlorides in triethylamine/acetonitrile to give ring-
retained product 8 in good yields;24–26 in this case, one C–
C bond formed at the b-carbon (Scheme 3). The N-acyl
cyclic ketene-N,S-acetal intermediates 7¢ acted as carbon
nucleophiles, reacting with more acid chloride in these re-
actions.
Key words: acyl ketene-N,N¢-acetal, carbon–carbon bond forma-
tion, 2-methylimidazoline, 1,2-dimethylimidazoline
Carbon–carbon bond construction is fundamental to or-
ganic synthesis. Enamines are important substrates for C–
C bond forming reactions based on their b-carbon nucleo-
philicities. Ketene-N,N¢-acetals, also known as 1,1-enedi-
amines (Figure 1), with two electron-donating nitrogens
connected to one end of a double bond, are of particular
interest due to their enhanced nucleophilicities. The acy-
clic ketene-N,N¢-acetals 1, where both R1 and R2 are alkyl
groups, were first synthesized by McElvain and Tate in
the 1940s.1 Later, substantial research efforts were ex-
pended to develop preparative methods for the ketene-
N,N¢-acetals2–6 and to explore their reactions with various
electrophiles,7–13 dienes14–18 and dipolar reagents.19–22
Compared to the dialkyl ketene-N,N¢-acetals 1, much less
attention has been paid to the acyl ketene-N,N¢-acetals 2
and 3, where one or both alkyl groups are replaced by an
acyl group.
We speculated that 2-methylimidazoline 4 may also react
with various acid chlorides to generate acyl cyclic ketene
acetal intermediates that could then further react, forming
ring-retained products under appropriate conditions. In-
Ph
O
O
PhCOCl
N
N
NH
N
Ph
Na2CO3, H2O
H
O
4
5
Scheme 1 Reaction of 2-methylimidazoline with benzoyl chloride
in aqueous carbonate
O
CF3
O
O
(CF3CO)2O
1, R1, R2 = alkyl
β
N
NH
N
N
α
F3C
CF3
R1
R2
2, R1, R2 = acyl
N
N
6
4
3, R1, R2 = acyl, alkyl
Scheme 2 Reaction of 2-methylimidazoline with trifluoroacetic an-
hydride
Figure 1 Structure of ketene-N,N¢-acetals
O
2-Methylimidazoline 4, which is a precursor of cyclic
ketene-N,N¢-acetals,2 was reported to react with two
equivalents of benzoyl chloride in aqueous carbonate to
give ring-opened product 5 (Scheme 1).23a In this reaction,
β
O
R4
β
O
R4COCl
N
S
R4
N
S
N
S
Et3N, MeCN
R4
R1
R1
R3
R3
R2
R2
R1
R3
R2
R1, R2, R3 = Me, H
R4 = aryl, alkyl
SYNTHESIS 2010, No. 1, pp 0141–0152
x
x
.
x
x
.2
0
0
9
8
7
7'
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217048; Art ID: M04409SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 3 Reaction of 2-methylthiazolines with acid chlorides

142
G. Ye et al.
PAPER
deed, tricyclic 1,8-naphthyridinetetraones were conve- produced. At this point, the b-carbons in 9a–c were deac-
niently synthesized recently in our lab via tandem tivated enough to prevent further reaction with benzoyl
reactions of 4 with diacid chlorides.27 Herein, we report chloride (Scheme 5).
the reactions of 4 with various substituted benzoyl chlo-
Table 1 Reactions of 2-Methylimidazoline 4 with Various Benzoyl
rides in refluxing triethylamine in either tetrahydrofuran
or acetonitrile. Ring-retained triacylated products 9 were
obtained in moderate to good yields. Two C–N bonds and
one C–C bond were formed in each reaction (Table 1).
Acetonitrile appeared to be a superior solvent to tetrahy-
drofuran due to its larger polarity and higher boiling point
(bp: 82 °C vs. 69 °C). Better yields were obtained for 9a
and 9c in acetonitrile than in tetrahydrofuran after reflux-
ing for three hours (entries 1, 2, 4 and 6). Prolonged re-
fluxing (16 h) in tetrahydrofuran enhanced the yield of 9c
(entries 4 and 5) but this was still lower than using aceto-
nitrile for only three hours (entries 5 and 6).
Chloridesa
R
O
O
O
O
THF or MeCN
Et3N
R
Cl
R
N
N
R
N
NH
+
reflux
4
9
Entry
1
R
H
H
Solvent
THF
Time (h) Product Yield (%)b
3
3
9a
9a
9b
9c
9c
9c
9d
9e
9f
71
80
65
58
67
78
73
75
76
72
75
76
78
69
68
70
2
MeCN
THF
The electronic nature of the R group has no apparent im-
pact on the product yield under these conditions (Table 1,
entries 6–16). When the R group increases the electrophi-
licity of a benzoyl chloride, it simultaneously decreases
the nucleophilicity of the diacyl ketene-N,N¢-acetal inter-
mediate, and vice versa. Thus, the substituent effect was
largely cancelled out because the same substituent ap-
pears in both nucleophile (diacyl ketene-N,N¢-acetal) and
electrophile (benzoyl chloride). These tandem reactions
clearly demonstrate the pronounced nucleophilicity of the
diacyl ketene-N,N¢-acetal 2. These results are of special
interest because 2-alkyl imidazoline derivatives constitute
an important class of biologically active compounds.28
3
4-Cl
3
4
4-Me
4-Me
4-Me
4-MeO
4-F
THF
3
5
THF
16
3
6
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
7
6
8
6
9
3-Cl
6
10
11
12
13
14
15
16
3-Me
3-MeO
3-F
6
9g
9h
9i
6
The mechanism shown in Scheme 4 accounts for the for-
mation of 9a. The first acylation takes place on the sp2 ni-
trogen to generate zwitterion intermediate 4a, followed by
loss of HCl to give Et3NH+ Cl– and mono-acylated product
4c. The second N-acylation occurs on the second nitrogen
followed by proton removal from the b-carbon to give the
N,N¢-diacyl ketene acetal 4f. Both nitrogens in 4f activate
the double bond to initiate nucleophilic attack by the b-
carbon on a third equivalent of acid chloride, despite the
fact that both nitrogens are benzoylated. After chloride
loss and proton abstraction from 4h, tribenzoylated 9a is
6
3-Br
2-Cl
6
9j
6
9k
9l
2-F
6
2-Br
6
9m
a The ratio of 4/acid chloride/Et3N = 1:3.5:4.
b Isolated yield after column chromatography.
O
O
O
Cl
N
Cl
Cl
Et3N
Ph
H
H
N
N
N
N
NH
Ph
Ph
– Et3N⋅HCl
4
4a
4b
H
O
CH2
O
O
O
O
O
Cl
N
Cl
Et3N
Cl
N
N
Ph
N
N
N
N
Ph
Ph
Ph
Ph
Ph
– Et3N⋅HCl
4c
4d
4e
Ph
Cl
N
Ph
O
Cl
H
Ph
O
O
Cl
H
O
Et3N
O
O
O
O
O
9a
– Et3N⋅HCl
N
N
N
N
Ph
Ph
Ph
Ph
Ph
Ph
4f
4g
4h
Scheme 4 Proposed mechanism for the formation of 9a
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

PAPER
Tandem Reaction of Imidazolines with Benzoyl Chlorides
143
O
O
O
O
R
R
R
Cl
O
O
O
O
R
N
N
N
N
Et3N, THF or MeCN
reflux, 3 h
9
R
R
R
R
R = H, Me, Cl
Scheme 5 Unsuccessful tetrabenzoylation
O
PhCOCl
(1 equiv)
O
N
N
Ph
O
p-Tolyl
O
Et3N, MeCN
r.t.
O
Cl
4c
4f
N
N
Ph
N
NH
Ph
reflux
H2O
O
O
9n
PhCOCl
(2 equiv)
4
N
N
Ph
Ph
Et3N, MeCN
r.t.
Ph
O
O
N
N
Ph
silica gel
H
O
5
Scheme 6 Experimental support for the proposed mechanism
The proposed mechanism (Scheme 4) was supported by group on the b-carbon in ketene acetals 12a–c blocked the
the following experiments: 2-methylimidazoline reacted b-carbon’s further reaction with benzoyl chlorides.
with one equivalent of benzoyl chloride (Scheme 6) af- Ketene acetals 12a–c were not stable to silica-gel column
fording mono-N-benzoylated product 4c; two equivalents chromatography; in every case, these acetals ring-opened
of benzoyl chloride gave dibenzoyl ketene acetal 4f. The to give products 13a–c.
latter was moisture-sensitive and hydrolyzed to ring-
opened product 5 during silica-gel column chromatogra-
phy. Moreover, ketene acetal 4f generated in-situ, without
isolation, could further react with a different acid chloride
Surprisingly, the replacement of the amine hydrogen in 4
with a methyl group dramatically altered the reaction out-
come. Thus, 1,2-dimethylimidazoline (11) produced the
ring-opened vinyl benzoates 14a–k, where formation of
generating product 9n.
carbon–carbon bonds, carbon–nitrogen bonds, and car-
2-Ethylimidazoline 10 was also studied as a substrate to bon–oxygen bonds occurred in a one-pot procedure
generate nucleophilic N,N¢-diacyl ketene acetals (Table 3). A Z-double bond was stereoselectively formed
(Table 2). However, the steric hindrance from the methyl between the methyl carbon at C-2 and benzoyl chloride’s
Table 2 Reactions of 2-Ethylimidazoline 10 with Various Benzoyl Chloridesa
O
Ar
O
O
O
N
N
Ar
Ar
Ar
Ar
excess
11a–c
ArCOCl
N
NH
Ar
O
β
Et3N, MeCN
reflux
O
O
H2O
N
10
N
N
silica gel
N
Ar
H
O
12a–c
13a–c
Entry
Ar
Ph
Product
13a
Yield (%)b
1
2
3
82
87
83
4-MeC6H4
4-ClC6H4
13b
13c
a The ratio of 10/acid chloride/Et3N = 1:3.5:4.
b Isolated yield after column chromatography.
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

144
G. Ye et al.
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Table 3 Reactions of 1,2-Dimethylimidazoline 11 with Various Benzoyl Chloridesa
O
R
R
O
O
O
H
N
R
THF, Et3N
reflux
Me
Cl
N
N
N
+
Me
O
14
R
11
Entry
R
Time (h)
Product
14a
14b
14c
Yield (%)b
1
2
H
3
3
3
3
6
3
6
6
6
6
3
74
63
65
70
56
60
36
52
60
55
43
p-MeO
p-Me
p-Cl
3
4
14d
14e
5
p-F
6
o-Me
o-F
14f
7
14g
14h
14i
8
m-Cl
m-Me
m-MeO
m-F
9
10
11
14j
14k
a The ratio of 11/acid chloride/Et3N = 1:3.5:4.
b Isolated yield after column chromatography.
carbonyl carbon in all examples (14a–k); no E-isomer deprotonation of 11e, gives diacylated products 11f–i with
was ever observed in the NMR spectra of ring-opened both E- and Z-geometries about the C=C double bond, and
products 14a–k. The X-ray crystal structure of 14a was s-cis/s-trans conformations about the a,b-unsaturated car-
obtained and is shown in Figure 2.29–31
bonyl group. Steric hindrance between the phenyl group
and the N-substituents of the imidazoline ring strongly fa-
vors s-cis conformers 11g and 11i over s-trans conformers
11f and 11h (by 9.06 and 6.50 kcal/mol, respectively, by
Gaussian 03/DFT/B3LYP/6-31g computations). These
predominant s-cis conformations of 11g or 11i determine
the formation of the Z-double bond geometry in the final
product 14a.
The b-keto oxygen in 11g and/or 11i serves as the nucleo-
phile, reacting with a third benzoyl chloride instead of nu-
cleophilic attack by the b-carbon. Steric hindrance exerted
by the vicinal substituents and the substantial 1,4-dipolar
nature of both 11g/11i, favor nucleophilic attack by oxy-
gen versus the b-carbon. The s-cis conformers 11g and 11i
must allow substantial conjugation from nitrogen to the
carbonyl oxygen although the minimum energy confor-
mations are not completely planar due to steric factors.
Chloride loss from the intermediate 11j gives amidinium
salt 11k. Unlike intermediate 4e (Scheme 3), which loses
a proton to form ring-retained product, amidinium salt
11k contains no proton that can be removed by triethyl-
amine, so it undergoes ring-opening hydrolysis32 during
work-up, forming benzoate 14a. The net result of this re-
action is the formation of one C=C bond, one C–N bond,
one C–O bond, one C=O bond and the cleavage of one
C=N bond.
Figure 2 X-ray crystal structure of compound 14a (gray: C; red: O;
blue: N)
The mechanism shown in Scheme 7 accounts for the reac-
tion cascade and the Z-stereoselectivity observed during
the formation of 14a. The N-acylation of 11 and deproto-
nation of 11b generates N-benzoyl-N¢-methyl ketene-
N,N¢-acetal (11c). The b-carbon in 11c, which is activated
by two nitrogens, attacks a second benzoyl chloride, giv-
ing the zwitterion 11d. Loss of chloride, followed by
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

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Tandem Reaction of Imidazolines with Benzoyl Chlorides
145
Cl
Cl
O
Ph
Ph
Cl
O
O
Me
Me
O
Me
H
N
H
Ph
H2C
Ph
N
O
N
Cl
N
H
Et3N
Et3N
Ph
Me
Cl
Me
Me
O
N
O
N
O
N
N
N
N
N
N
– Et3N⋅HCl
– Et3N⋅HCl
Ph
O
Cl
Ph
Ph
Ph
11b
11
11a
11c
11d
11e
Ph
O
Ph
H
O
O
Ph
Cl
Me
Me
H
N
N
Ph
O
Cl
Ph
N
Ph
O
O
N
O
N
O
Ph
O
Ph
O
Ph
H
Ph
O
Ph
O
O
Ph
Ph
Me
Cl
11g: E/s-cis
Me
11f: E/s-trans
Me
Et3N
Cl
O
N
Me
N
N
14a
H
H2O
work-up
– Et3N⋅HCl
Ph
N
O
N
O
O
N
Ph
O
O
O
N
Ph
O
Cl
O
11j
11k
11l
Ph
Ph
Ph
Ph
O
H
11m
Ph
H
N
N
Ph
N
N
Me
Me
11h: Z/s-trans
11i: Z/s-cis
Scheme 7 Proposed mechanism for the formation of 14a
vent was removed by rotary evaporation. CH2Cl2 (15 mL) was
added to the residue to give a brown solution, which was washed
with sat. aq NaHCO3 (3 × 15 mL), dried over MgSO4, and concen-
trated. The residue was purified by flash column chromatography
(silica gel; hexane–EtOAc, 3:1→2:1) to give 9a.
In conclusion, two tandem reactions of either 2-methyl-
imidazoline or 1,2-dimethylimidazoline with various ben-
zoyl chlorides were demonstrated. These reactions
generate highly functionalized compounds and many of
these reactions proceed readily under mild conditions,
providing moderate to good isolated yields. The reactions
of 2-methylimidazolines as multidentate nucleophiles will
be further explored.
Yield: 282 mg (71%); yellow solid; mp 188–190 °C; Rf = 0.42 (hex-
ane–EtOAc, 1:1).
IR (KBr): 1705, 1668, 1645, 1577, 1555 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.76–7.29 (m, 16 H, ArH and
C=CH), 3.92 (m, 4 H, CH2CH2).
Melting points were recorded with a Mel-Temp apparatus and are
uncorrected. The FT-IR spectra were recorded on a Thermo Nicolet
spectrometer as films on KBr plates. The 1H and 13C NMR spectra
were recorded using a Bruker model AMX-300 spectrometer oper-
ating at 300 MHz for proton and 75 MHz for carbon. Chemical
shifts (d) are reported in ppm units downfield from TMS, which was
used as the internal standard for all NMR spectra. Splitting patterns
are designed: s, d, t, q and m; these symbols indicate: singlet, dou-
blet, triplet, quartet and multiplet, respectively. All reactions were
carried out under nitrogen. Tetrahydrofuran (THF) was distilled
from Na metal/benzophenone under nitrogen. MeCN and Et3N were
distilled from CaH2 under nitrogen. CH2Cl2 was pre-dried with
CaCl2 and then distilled from CaH2 under nitrogen. The starting
substrates, 2-methylimidazoline (4) and 1,2-dimethylimidazoline
(11), were prepared according to literature procedures.1,33 All other
commercially obtained reagents were used as received. The silica
gel used for the column chromatography was purchased from Ald-
rich (70–230 mesh, 60 Å).
13C NMR (75 MHz, CDCl3): d = 187.6 (=CHCOPh), 169.6 (NCO-
Ph), 169.5 (NCOPh), 145.9 (C=CH), 139.3 (ArC), 135.6 (ArC),
134.2 (ArC), 131.9 (ArC), 131.6 (ArC), 131.2 (ArC), 128.8 (ArC),
128.2 (ArC), 127.9 (ArC), 127.0 (ArC), 95.5 (C=CH), 47.6 (NCH2),
47.2 (NCH2).
HRMS: m/z [M]+ calcd for C25H20N2O3: 396.1474; found:
396.1462.
{2-[2-(4-Chlorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(4-chlorophenyl)methanone] (9b)
The title compound 9b was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 4-chlorobenzoyl chloride (0.613 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 3:1→2:1).
Yield: 325 mg (65%); yellow solid; mp 195–197 °C; Rf = 0.26 (hex-
ane–EtOAc, 2:1).
IR (KBr): 1695, 1665, 1634, 1588, 1571 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.68–7.28 (m, 13 H, ArH and
C=CH), 3.90 (m, 4 H, CH2CH2).
13C NMR (75 MHz, CDCl3): d = 186.2 (=CHCOPh), 168.6 (NCO-
Ph), 168.4 (NCOPh), 146.2 (C=CH), 138.4 (ArC), 138.2 (ArC),
137.8 (ArC), 137.4 (ArC), 133.7 (ArC), 132.4 (ArC), 130.2 (ArC),
129.2 (ArC), 129.0 (ArC), 128.6 (ArC), 128.4 (ArC), 95.0 (C=CH),
47.5 (NCH2), 47.4 (NCH2).
[2-(2-Oxo-2-phenylethylidene)imidazolidine-1,3-diyl]bis(phe-
nylmethanone) (9a)
To a stirred solution of benzoyl chloride (0.492 g, 3.5 mmol) in THF
(10 mL), Et3N (0.405 g, 4 mmol) was added at r.t. under nitrogen.
2-Methylimidazoline (4; 0.084 g, 1 mmol) was dissolved in THF (2
mL) and then added dropwise at r.t. into the above solution. The re-
action system was then refluxed for 3 h. After cooling to r.t., the sol-
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

146
G. Ye et al.
PAPER
2
HRMS: m/z [M]+ calcd for C25H17Cl3N2O3: 498.0305; found:
2JCF = 22.1 Hz, ArC), 115.12 (d, JCF = 21.8 Hz, ArC), 95.11
498.0318.
(C=CH), 47.7 (NCH2), 47.6 (NCH2).
[2-(2-Oxo-2-p-tolylethylidene)imidazolidine-1,3-diyl]bis(p-tol-
ylmethanone) (9c)
The title compound 9c was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 4-methylbenzoyl chloride (0.541 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 3:1→2:1).
{2-[2-(3-Chlorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(3-chlorophenyl)methanone] (9f)
The title compound 9f was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 3-chlorobenzoyl chloride (0.613 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 2:1).
Yield: 255 mg (58%); yellow solid; mp 168–170 °C; Rf = 0.50 (hex-
Yield: 380 mg (76%); yellow solid; mp 83–85 °C; Rf = 0.29 (hex-
ane–EtOAc, 1:1).
ane–EtOAc, 2:1).
IR (KBr): 1705, 1664, 1606 cm–1.
IR (KBr): 1703, 1673, 1651, 1567, 1557 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.62 (d, J = 7.9 Hz, 2 H, ArH),
7.56 (d, J = 7.9 Hz, 2 H, ArH), 7.48 (d, J = 7.9 Hz, 2 H, ArH), 7.25
(d, J = 7.9 Hz, 2 H, ArH), 7.19 (s, 1 H, C=CH), 7.14 (d, J = 7.9 Hz,
2 H, ArH), 7.07 (d, J = 7.9 Hz, 2 H, ArH), 3.87 (m, 4 H, CH2CH2),
2.39 (s, 3 H, ArCH3), 2.31 (s, 3 H, ArCH3), 2.30 (s, 3 H, ArCH3).
13C NMR (75 MHz, CDCl3): d = 187.2 (=CHCOPh), 169.7 (NCO-
Ph), 169.5 (NCOPh), 145.9 (C=CH), 142.3 (ArC), 141.9 (ArC),
141.6 (ArC), 136.8 (ArC), 132.8 (ArC), 131.4 (ArC), 129.2 (ArC),
128.9 (ArC), 128.7 (ArC), 128.5 (ArC), 127.7 (ArC), 127.1 (ArC),
95.3 (C=CH), 47.6 (NCH2), 47.2 (NCH2), 21.3 (ArCH3).
1H NMR (300 MHz, CDCl3): d = 7.68–7.22 (m, 13 H, ArH and
C=CH), 3.89 (m, 4 H, CH2CH2).
13C NMR (75 MHz, CDCl3): d = 186.22 (=CHCOPh), 167.98
(NCOPh), 167.79 (NCOPh), 145.98 (C=CH), 140.46 (ArC), 136.80
(ArC), 135.44 (ArC), 134.81 (ArC), 134.16 (ArC), 134.12 (ArC),
131.92 (ArC), 131.67 (ArC), 131.37 (ArC), 130.18 (ArC), 129.54
(ArC), 129.36 (ArC) 128.60 (ArC), 127.52 (ArC), 126.94 (ArC),
126.69 (ArC), 125.57 (ArC), 124.82 (ArC), 94.97 (C=CH), 47.40
(NCH2), 47.22 (NCH2).
HRMS: m/z [M]+ calcd for C25H17Cl3N2O3: 498.0305; found:
498.0301.
HRMS: m/z [M]+ calcd for C28H26N2O3: 438.1943; found:
438.1930.
[2-(2-Oxo-2-m-tolylethylidene)imidazolidine-1,3-diyl]bis(m-
tolylmethanone) (9g)
The title compound 9g was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 3-methylbenzoyl chloride (0.541 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 2:1).
{2-[2-(4-Methoxyphenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(4-methoxyphenyl)methanone] (9d)
The title compound 9d was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 4-methoxylbenzoyl chloride (0.597 g, 3.5
mmol) by the general procedure, and purified by flash column chro-
matography (silica gel; hexane–EtOAc, 1:1→1:2).
Yield: 316 mg (72%); yellow solid; mp 81–83 °C; Rf = 0.27 (hex-
Yield: 355 mg (73%); yellow solid; mp 93–95 °C; Rf = 0.18 (hex-
ane–EtOAc, 2:1).
ane–EtOAc, 1:1).
IR (KBr): 1693, 1660, 1651, 1598, 1573 cm–1.
IR (KBr): 1699, 1669, 1603, 1584, 1558 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.53–7.11 (m, 13 H, ArH and
C=CH), 3.86 (m, 4 H, CH2CH2), 2.34 (s, 3 H, CH3), 2.28 (s, 3 H,
CH3), 2.25 (s, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 187.47 (=CHCOPh), 169.45
(NCOPh), 169.21 (NCOPh), 145.53 (C=CH), 138.96 (ArC), 138.26
(ArC), 137.54 (ArC), 137.11 (ArC), 135.28 (ArC), 133.78 (ArC),
132.22 (ArC), 131.94 (ArC), 131.45 (ArC), 128.95 (ArC), 128.21
(ArC), 127.77 (ArC), 127.62 (ArC), 127.42 (ArC), 127.07 (ArC),
125.49 (ArC), 124.39 (ArC), 123.53 (ArC), 94.99 (C=CH), 47.31
(NCH2), 46.89 (NCH2), 20.85 (CH3), 20.78 (CH3), 20.75 (CH3).
1H NMR (300 MHz, CDCl3): d = 7.74–7.57 (m, 6 H, ArH), 7.16 (s,
1 H, C=CH), 6.96–6.76 (m, 6 H, ArH), 3.90 (m, 4 H, CH2CH2),
3.83 (s, 3 H, OCH3), 3.78 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3).
13C NMR (75 MHz, CDCl3): d = 186.3 (=CHCOPh), 169.4 (NCO-
Ph), 169.3 (NCOPh), 162.4 (ArC), 162.2 (ArC), 161.9 (ArC), 146.1
(C=CH), 132.3 (ArC), 131.0 (ArC), 129.7 (ArC), 129.4 (ArC),
127.5 (ArC), 126.3 (ArC), 113.8 (ArC), 113.4 (ArC), 113.0 (ArC),
94.8 (C=CH), 55.3 (OCH3), 55.24 (OCH3), 55.16 (OCH3), 47.96
(NCH2), 47.58 (NCH2).
{2-[2-(4-Fluorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(4-fluorophenyl)methanone] (9e)
The title compound 9e was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 4-fluorobenzoyl chloride (0.555 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 2:1).
{2-[2-(3-Methoxyphenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(3-methoxyphenyl)methanone] (9h)
The title compound 9h was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 3-methoxylbenzoyl chloride (0.597 g, 3.5
mmol) by the general procedure, and purified by flash column chro-
matography (silica gel; hexane–EtOAc, 2:1→1:1).
Yield: 338 mg (75%); yellow solid; mp 143–145 °C; Rf = 0.26 (hex-
Yield: 365 mg (75%); yellow solid; mp 140–142 °C; Rf = 0.43 (hex-
ane–EtOAc, 2:1).
ane–EtOAc, 1:1).
IR (KBr): 1690, 1682, 1660, 1640, 1594 cm–1.
IR (KBr): 1707, 1670, 1653, 1560 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.79–7.60 (m, 6 H, ArH), 7.26 (s,
1 H, C=CH), 7.21–6.98 (m, 6 H, ArH), 3.92 (m, 4 H, CH2CH2).
1H NMR (300 MHz, CDCl3): d = 7.36–6.93 (m, 13 H, ArH and
C=CH), 3.84 (m, 4 H, CH2CH2), 3.77 (s, 3 H, OCH3), 3.74 (s, 3 H,
OCH3), 3.72 (s, 3 H, OCH3).
13C NMR (75 MHz, CDCl3): d = 187.14 (=CHCOPh), 169.16
(NCOPh), 168.92 (NCOPh), 159.39 (ArC), 159.10 (ArC), 159.05
(ArC), 145.42 (C=CH), 140.51 (ArC), 136.57 (ArC), 135.15 (ArC),
129.68 (ArC), 129.02 (ArC), 128.69 (ArC), 120.68 (ArC), 119.93
(ArC), 118.53 (ArC), 118.12 (ArC), 117.74 (ArC), 116.68 (ArC),
113.62 (ArC), 111.91 (ArC), 111.52 (ArC), 95.30 (C=CH), 55.07
13C NMR (75 MHz, CDCl3): d = 186.39 (=CHCOPh), 168.76
1
(NCOPh), 168.53 (NCOPh), 164.98 (d, JCF = 252.8 Hz, ArC),
164.86 (d, 1JCF = 253.7 Hz, ArC), 164.28 (d, 1JCF = 253.4 Hz, ArC),
4
146.16 (C=CH), 135.41 (d, JCF = 2.9 Hz, ArC), 131.50 (d,
3
4JCF = 3.5 Hz, ArC), 131.34 (d, JCF = 9.1 Hz, ArC), 129.6 (d,
3
3JCF = 8.8 Hz, ArC), 130.09 (d, JCF = 9.0 Hz, ArC), 130.13 (d,
2
4JCF = 3.3 Hz, ArC), 116.06 (d, JCF = 22.1 Hz, ArC), 115.49 (d,
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

PAPER
Tandem Reaction of Imidazolines with Benzoyl Chlorides
147
(OCH3), 55.01 (OCH3), 54.90 (OCH3), 47.59 (NCH2), 47.20
(NCH2).
130.89 (ArC), 130.74 (ArC), 130.26 (ArC), 130.05 (ArC), 129.57
(ArC), 129.03 (ArC), 127.67 (ArC), 127.20 (ArC), 126.88 (ArC),
126.35 (ArC), 99.01 (C=CH), 45.77 (NCH2), 45.25 (NCH2).
{2-[2-(3-Fluorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(3-fluorophenyl)methanone] (9i)
The title compound 9i was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 3-fluorobenzoyl chloride (0.555 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 2:1).
{2-[2-(2-Fluorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(2-fluorophenyl)methanone] (9l)
The title compound 9l was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 2-fluorobenzoyl chloride (0.613 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 3:1→5:3).
Yield: 342 mg (76%); yellow solid; mp 88–90 °C; Rf = 0.29 (hex-
ane–EtOAc, 2:1).
Yield: 306 mg (68%); yellow liquid; Rf = 0.40 (hexane–EtOAc,
1:1).
IR (KBr): 1703, 1672, 1611, 1586, 1556 cm–1.
IR (KBr): 1672, 1611, 1581, 1556 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.52–7.08 (m, 13 H, ArH and
C=CH), 3.89 (m, 4 H, CH2CH2).
13C NMR (75 MHz, CDCl3): d = 186.3 (=CHCOPh), 168.17 (d,
4JCF = 2.5 Hz, NCOPh), 167.98 (d, 4JCF = 2.6 Hz, NCOPh), 162.45
(d, 1JCF = 246.9 Hz, ArC), 162.36 (d, 1JCF = 249.5 Hz, ArC), 162.08
(d, 1JCF = 247.9 Hz, ArC), 145.96 (C=CH), 141.22 (d, 3JCF = 6.2 Hz,
1H NMR (300 MHz, CDCl3): d = 7.69–7.00 (m, 13 H, ArH and
C=CH), 4.08 (t, J = 7.0 Hz, 4 H, CH2), 3.83 (t, J = 7.0 Hz, 4 H,
CH2).
13C NMR (75 MHz, CDCl3): d = 185.72 (d, JCF = 2.2 Hz,
3
=CHCOPh), 165.67 (NCOPh), 165.12 (NCOPh), 160.25 (d,
3
3
ArC), 137.21 (d, JCF = 6.9 Hz, ArC), 135.91 (d, JCF = 7.0 Hz,
1JCF = 253.8 Hz, ArC), 158.63 (d, 1JCF = 250.7 Hz, ArC), 157.71 (d,
3
3
3
ArC), 130.73 (d, JCF = 8.0 Hz, ArC), 129.98 (d, JCF = 7.8 Hz,
1JCF = 249.3 Hz, ArC), 146.00 (C=CH), 132.77 (d, JCF = 8.8 Hz,
3
4
3
3
ArC), 129.67 (d, JCF = 7.6 Hz, ArC), 124.31 (d, JCF = 3.0 Hz,
ArC), 132.73 (d, JCF = 8.5 Hz, ArC), 132.62 (d, JCF = 7.9 Hz,
4
4
4
4
ArC), 123.21 (d, JCF = 2.8 Hz, ArC), 122.45 (d, JCF = 3.2 Hz,
ArC), 131.77 (d, JCF = 1.8 Hz, ArC), 130.02 (d, JCF = 2.4 Hz,
2
2
4
2
ArC), 119.05 (d, JCF = 21.2 Hz, ArC), 118.71 (d, JCF = 21.5 Hz,
ArC), 118.37 (d, JCF = 21.1 Hz, ArC), 115.72 (d, JCF = 23.0 Hz,
ArC), 114.28 (d, JCF = 22.3 Hz, ArC), 114.15 (d, JCF = 23.3 Hz,
ArC), 95.16 (C=CH), 47.60 (NCH2), 47.42 (NCH2).
ArC), 128.53 (d, JCF = 2.9 Hz, ArC), 128.17 (d, JCF = 12.3 Hz,
2
2
3
3
ArC), 124.91 (d, JCF = 3.4 Hz, ArC), 124.08 (d, JCF = 3.7 Hz,
2
2
2
3
ArC), 124.00 (d, JCF = 16.5 Hz, ArC), 123.68 (d, JCF = 3.5 Hz,
ArC), 122.50 (d, 2JCF = 12.6 Hz, ArC), 116.119 (d, 2JCF = 20.9 Hz,
2
2
ArC), 115.98 (d, JCF = 23.2 Hz, ArC), 115.28 (d, JCF = 22.2 Hz,
ArC), 98.29 (C=CH), 46.06 (NCH2), 45.67 (NCH2).
{2-[2-(3-Bromophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(3-bromophenyl)methanone] (9j)
The title compound 9j was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 3-bromobenzoyl chloride (0.768 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; hexane–EtOAc, 2:1).
{2-[2-(2-Bromophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(2-bromophenyl)methanone] (9m)
The title compound 9m was prepared using 2-methylimidazoline
(4; 0.084 g, 1 mmol) and 2-bromobenzoyl chloride (0.768 g, 3.5
mmol) by the general procedure, and purified by flash column chro-
matography (silica gel; toluene–EtOAc, 6:1).
Yield: 494 mg (78%); yellow solid; mp 152–154 °C; Rf = 0.30 (hex-
ane–EtOAc, 2:1).
Yield: 443 mg (70%); yellow solid; mp 86–87 °C; Rf = 0.56 (tolu-
ene–EtOAc, 3:1).
IR (KBr): 1682, 1651, 1588, 1567 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.64–7.02 (m, 13 H, ArH and
C=CH), 4.01 (br, 2 H, CH2), 3.69 (br, 2 H, CH2).
13C NMR (75 MHz, CDCl3): d = 189.93 (=CHCOPh), 167.43
(NCOPh), 166.85 (NCOPh), 145.07 (C=CH), 141.97 (ArC), 137.41
(ArC), 136.13 (ArC), 133.11 (ArC), 132.96 (ArC), 132.14 (ArC),
131.43 (ArC), 131.30 (ArC), 130.87 (ArC), 129.01 (ArC), 128.81
(ArC), 128.08 (ArC), 127.30 (ArC), 127.08 (ArC), 126.80 (ArC),
118.86 (ArC), 118.79 (ArC), 117.90 (ArC), 98.82 (C=CH), 45.81
(NCH2), 45.37 (NCH2).
IR (KBr): 1690, 1646, 1587, 1551 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.83–7.17 (m, 13 H, ArH and
C=CH), 3.90 (m, 4 H, CH2CH2).
13C NMR (75 MHz, CDCl3): d = 186.12 (=CHCOPh), 167.82
(NCOPh), 167.65 (NCOPh), 145.97 (C=CH), 140.64 (ArC), 136.98
(ArC), 135.63 (ArC), 134.86 (ArC), 134.62 (ArC), 134.35 (ArC),
131.49 (ArC), 130.47 (ArC), 130.42 (ArC), 129.83 (ArC), 129.81
(ArC), 129.66 (ArC), 127.17 (ArC), 126.06 (ArC), 125.30 (ArC),
122.82 (ArC), 122.33 (ArC), 122.14 (ArC), 94.96 (C=CH), 47.39
(NCH2), 47.19 (NCH2).
HRMS: m/z [M]+ calcd for C25H17Br3N2O3: 629.8789; found:
629.8774.
[2-(2-Oxo-2-p-tolylethylidene)imidazolidine-1,3-diyl]bis(phe-
nylmethanone) (9n)
Yellow solid; mp 195–196 °C.
IR (KBr): 1677, 1657, 1638, 1604, 1537 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.77–7.09 (m, 15 H, ArH and
C=CH), 3.99–3.55 (m, 4 H, CH2CH2), 2.33 (s, 3 H, PhCH3).
{2-[2-(2-Chlorophenyl)-2-oxoethylidene]imidazolidine-1,3-
diyl}bis[(2-chlorophenyl)methanone] (9k)
The title compound 9k was prepared using 2-methylimidazoline (4;
0.084 g, 1 mmol) and 2-chlorobenzoyl chloride (0.613 g, 3.5 mmol)
by the general procedure, and purified by flash column chromatog-
raphy (silica gel; toluene–EtOAc, 10:1→6:1).
Yield: 345 mg (69%); yellow solid; mp 77–79 °C; Rf = 0.36 (tolu-
ene–EtOAc, 6:1).
IR (KBr): 1667, 1651, 1589, 1567 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.69–7.02 (m, 13 H, ArH and
C=CH), 4.10 (br, 2 H, CH2), 3.73 (br, 2 H, CH2).
13C NMR (75 MHz, CDCl3): d = 187.2 (=CHCOAr), 169.6 (NCO-
Ph), 169.5 (NCOPh), 145.5 (C=CH), 142.2 (ArC), 136.3 (ArC),
135.6 (ArC), 134.1 (ArC), 131.9 (ArC), 131.2 (ArC), 128.8 (ArC),
128.7 (ArC), 128.2 (ArC), 127.8 (ArC), 127.0 (ArC), 95.8 (C=CH),
47.6 (NCH2), 47.2 (NCH2), 21.4 (ArCH3).
13C NMR (75 MHz, CDCl3): d = 189.31 (=CHCOPh), 167.39
(NCOPh), 166.45 (NCOPh), 145.71 (C=CH), 140.31 (ArC), 135.54
(ArC), 134.09 (ArC), 132.18 (ArC), 131.48 (ArC), 131.35 (ArC),
(2-Methyl-4,5-dihydro-1H-imidazol-1-yl)(phenyl)methanone
(4c)
White solid; mp 155–157 °C.
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

148
G. Ye et al.
PAPER
IR (KBr): 1665, 1632, 1557 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.54–7.38 (m, 5 H, ArH), 3.87–
3.72 (m, 4 H, CH2CH2), 2.18 (s, 3 H, CCH3).
13C NMR (75 MHz, CDCl3): d = 167.8 (NCOPh), 157.8 (NCN),
135.5 (ArC), 130.2 (ArC), 127.7 (ArC), 126.4 (ArC), 52.0 (NCH2),
48.2 (NCH2), 17.9 (CCH3).
by the general procedure, and purified by flash column chromatog-
1
raphy (silica gel; hexane–acetone, 3:1→2:1). Both the H and 13C
NMR spectra of 14a confirmed the presence of two rotational con-
formations, which interconvert slowly on the NMR time scale, due
to restricted rotation about an amide carbonyl carbon to nitrogen
bond. These conformations were present in a 2.87:1 ratio based on
the relative integral areas of the 3.21 and 2.87 ppm resonances of the
N-CH3 group in the 1H NMR spectrum.
N-Acetyl-N-(2-benzamidoethyl)benzamide (5)
Yield: 318 mg (74%); white solid; mp 157–159 °C; Rf = 0.39 (hex-
ane–acetone, 1:1).
IR (KBr): 3329, 1728, 1650, 1613 cm–1.
White solid; mp 115–116 °C (Lit.23a 115 °C).
IR (KBr): 3316, 1694, 1686, 1636, 1527 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78–7.42 (m, 10 H, ArH), 7.11
(br, 1 H, NH), 4.12 (t, J = 5.2 Hz, 2 H, CH2CH2), 3.66 (q, J = 5.2
Hz, 2 H, CH2CH2), 2.10 (s, 3 H, CCH3).
13C NMR (75 MHz, CDCl3): d = 174.7 (CH3CO), 174.1 (PhCON),
167.4 (PhCONH), 134.9 (ArC), 133.8 (ArC), 132.8 (ArC), 131.3
(ArC), 128.8 (ArC), 128.5 (ArC), 128.4 (ArC), 126.8 (ArC), 45.3
(NCH2), 39.9 (NHCH2), 26.2 (CH3CO).
1H NMR (300 MHz, CDCl3): d = 8.14 and 8.09 (2 × d, J = 7.7 Hz
and J = 7.6 Hz, 2 H, NH and ArH), 7.75–7.24 (m, 14 H, ArH), 6.63
and 6.55 (s, 1 H, COCH=C), 3.70 and 3.61 (m, 4 H, CH2CH2), 3.21
and 2.87 (2 × s, 3 H, NCH3).
13C NMR (75 MHz, CDCl3): d = 168.10 (HNCOPh), 167.24
(HNCOPh), 166.77 (COCH=C), 164.90 (COCH=C), 164.24
[CH=C(Ph)O], 163.95 [CH=C(Ph)O], 153.54 (PhCOO), 152.98
(PhCOO), 133.80 (ArC), 133.74 (ArC), 133.67 (ArC), 133.65
(ArC), 133.57 (ArC), 131.35 (ArC), 131.10 (ArC), 130.30 (ArC),
130.25 (ArC), 130.10 (ArC), 130.06 (ArC), 129.07 (ArC), 128.76
(ArC), 128.69 (ArC), 128.64 (ArC), 128.58 (ArC), 128.29 (ArC),
128.21 (ArC), 127.18 (ArC), 126.88 (ArC), 125.53 (ArC), 125.45
(ArC), 108.33 (COCH=C), 107.07 (COCH=C), 49.52
[CON(CH3)CH2], 47.26 [CON(CH3)CH2], 39.25 (CH2NHCOPh),
N-(2-Benzamidoethyl)-N-propionylbenzamide (13a)
Colorless liquid.
IR (KBr): 3345, 1683, 1660, 1601, 1537 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.79–7.64 (m, 11 H, ArH and
NH), 4.08 (t, J = 5.5 Hz, 2 H, CH2CH2), 3.63 (q, J = 5.5 Hz, 2 H,
CH2CH2), 2.36 (q, J = 7.3 Hz, 2 H, CH2CH3), 1.02 (t, J = 7.3 Hz,
3 H, CH2CH3).
13C NMR (75 MHz, CDCl3): d = 178.0 (CH2CO), 174.4 (PhCON),
167.3 (PhCONH), 135.0 (ArC), 133.7 (ArC), 132.4 (ArC), 131.1
(ArC), 128.6 (ArC), 128.2 (ArC), 128.1 (ArC), 126.7 (ArC), 45.2
(NCH2), 39.7 (NHCH2), 31.4 (CH2CO), 9.4 (CH3CH2).
38.46
(CH2NHCOPh),
37.09
[CON(CH3)CH2],
33.77
[CON(CH3)CH2].
HRMS: m/z [M]+ calcd for C26H24N2O4: 428.1736; found:
428.1743.
(Z)-3-{[2-(4-Methoxybenzamido)ethyl](methyl)amino}-1-(4-
methoxyphenyl)-1-(4-methoxyphenylcarbonyloxy)-3-oxoprop-
1-ene (14b)
4-Methyl-N-[2-(4-methylbenzamido)ethyl]-N-propionylbenz-
amide (13b)
The title compound 14b was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 4-methoxybenzoyl chloride (0.597
g, 3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–EtOAc, 3:1→1:1). The ratio of
the two rotational conformations was 2.84:1 based on the relative
integrals of the 3.19 and 2.87 ppm resonances of the 1H NMR spec-
trum.
White solid; mp 70–72 °C.
1H NMR (300 MHz, CDCl3): d = 7.70–7.20 (m, 9 H, ArH and NH),
4.09 (t, J = 5.3 Hz, 2 H, CH2CH2), 3.63 (q, J = 5.3 Hz, 2 H,
CH2CH2), 2.39 (s, 6 H, ArCH3), 2.33 (q, J = 7.3 Hz, CH2CH3, 2 H),
1.04 (t, J = 7.3 Hz, 3 H, CH2CH3).
13C NMR (75 MHz, CDCl3): d = 178.2 (CH2CO), 174.7 (PhCON),
167.3 (PhCONH), 143.7 (ArC), 141.6 (ArC), 132.2 (ArC), 131.0
(ArC), 129.5 (ArC), 129.0 (ArC), 128.7 (ArC), 126.8 (ArC), 45.4
(NCH2), 39.9 (NHCH2), 31.6 (CH2CO), 21.5 (ArCH3), 21.3
(ArCH3), 9.6 (CH3CH2).
Yield: 326 mg (63%); white solid; mp 151–153 °C; Rf = 0.21 (hex-
ane–actone, 1:1).
IR (KBr): 3275, 1721, 1650, 1602 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.10 and 8.01 (2 × d, J = 8.5 Hz
and J = 8.5 Hz, 2 H, NH and ArH), 7.70 (m, 3 H, ArH), 7.53 and
7.41 (2 × d, J = 8.6 Hz and J = 8.5 Hz, 2 H, ArH), 6.94–6.70 (m,
6 H, ArH), 6.52 and 6.42 (s, 1 H, COCH=C), 3.84, 3.82, 3.81, 3.78
and 3.76 (5 × s, 9 H, CH3OC), 3.59 (m, 4 H, CH2CH2), 3.19 and
2.87 (2 × s, 3 H, NCH3).
IR (KBr): 3301, 1688, 1636, 1609, 1537 cm–1.
4-Chloro-N-[2-(4-chlorobenzamido)ethyl]-N-propionylbenz-
amide (13c)
White solid; mp 97–99 °C.
IR (KBr): 3346, 1660, 1595, 1537 cm–1.
13C NMR (75 MHz, CDCl3): d = 167.51 (HNCOAr), 167.25
(HNCOAr), 166.69 (COCH=C), 165.14 (COCH=C), 163.95
(CH3OC), 163.89 [CH=C(Ar)O], 163.86 [CH=C(Ar)O], 163.54
(CH3OC), 161.86 (CH3OC), 161.64 (CH3OC), 161.10 (CH3OC),
160.90 (CH3OC), 153.49 (ArCOO), 152.90 (ArCOO), 132.41
(ArC), 132.20 (ArC), 129.02 (ArC), 128.63 (ArC), 127.06 (ArC),
126.95 (ArC), 126.23 (ArC), 126.20 (ArC), 126.13 (ArC), 126.06
(ArC), 121.49 (ArC), 120.97 (ArC), 114.05 (ArC), 113.86 (ArC),
113.79 (ArC), 113.30 (ArC), 113.23 (ArC), 106.37 (COCH=C),
104.91 (COCH=C), 55.44 (CH3OC), 55.31 (CH3OC), 55.23
1H NMR (300 MHz, CDCl3): d = 7.72–7.34 (m, 9 H, ArH and NH),
4.08 (t, J = 5.5 Hz, 2 H, CH2CH2), 3.62 (q, J = 5.5 Hz, 2 H,
CH2CH2), 2.39 (q, J = 7.3 Hz, 2 H, CH2CH3), 1.05 (t, J = 7.3 Hz,
3 H, CH2CH3).
13C NMR (75 MHz, CDCl3): d = 177.8 (CH2CO), 173.5 (PhCON),
166.4 (PhCONH), 138.9 (ArC), 137.5 (ArC), 133.3 (ArC), 132.0
(ArC), 129.6 (ArC), 129.0 (ArC), 128.5 (ArC), 128.2 (ArC), 45.2
(NCH2), 39.7 (NHCH2), 31.3 (CH2CO), 9.4 (CH3CH2).
(Z)-3-[(2-Benzamidoethyl)(methyl)amino]-3-oxo-1-phenyl-
prop-1-enyl Benzoate (14a)
The title compound 14a was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and benzoyl chloride (0.492 g, 3.5 mmol)
(CH3OC),
[CON(CH3)CH2], 47.32 [CON(CH3)CH2], 39.39 (CH2NHCOAr),
38.51 (CH2NHCOAr), 37.03 [CON(CH3)CH2], 33.83
[CON(CH3)CH2].
55.16
(CH3OC),
55.11
(CH3OC),
49.70
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

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Tandem Reaction of Imidazolines with Benzoyl Chlorides
149
(Z)-3-{[2-(4-Methylbenzamido)ethyl](methyl)amino}-1-(4-
methylphenyl)-1-(4-methylphenylcarbonyloxy)-3-oxoprop-1-
ene (14c)
The title compound 14c was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 4-methylbenzoyl chloride (0.541 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→3:1). The ratio of
the two rotational conformations was 2.92:1 based on the relative
integrals of the 3.19 and 2.87 ppm resonances of the 1H NMR spec-
trum.
(Z)-3-{[2-(4-Fluorobenzamido)ethyl](methyl)amino}-1-(4-fluo-
rophenyl)-1-(4-fluorophenylcarbonyloxy)-3-oxoprop-1-ene
(14e)
The title compound 14e was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 4-fluorobenzoyl chloride (0.555 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→2:1). The ratio of
the two rotational conformations was 2.06:1 based on the relative
integrals of the 3.16 and 2.78 ppm resonances of the 1H NMR spec-
trum.
Yield: 306 mg (65%); white solid; mp 158–160 °C; Rf = 0.46 (hex-
Yield: 269 mg (56%); white solid; mp 143–144 °C; Rf = 0.45 (hex-
ane–acetone, 1:1).
ane–acetone, 1:1).
IR (KBr): 3360, 1735, 1640, 1607 cm–1.
IR (KBr): 3327, 1749, 1645, 1602 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.03 and 7.97 (2 × d, J = 7.8 Hz
and J = 8.0 Hz, 2 H, NH and ArH), 7.63–7.02 (m, 11 H , ArH), 6.57
and 6.48 (2 × s, 1 H, COCH=C), 3.69–3.56 (m, 4 H, CH2CH2), 3.19
and 2.87 (2 × s, 3 H, NCH3), 2.41, 2.40, 2.38, 2.36 and 2.33 (5 × s,
9 H, CH3Ar).
13C NMR (75 MHz, CDCl3): d = 167.94 (HNCOPh), 167.16
(HNCOPh), 166.91 (COCH=C), 165.07 (COCH=C), 164.27
[CH=C(Ar)O], 163.96 [CH=C(Ar)O], 153.58 (ArCOO), 153.10
(ArCOO), 144.49 (ArC), 141.53 (ArC), 141.16 (ArC), 140.44
(ArC), 140.16 (ArC), 130.98 (ArC), 130.95 (ArC), 130.33 (ArC),
130.16 (ArC), 129.39 (ArC), 129.28 (ArC), 129.21 (ArC), 128.87
(ArC), 128.79 (ArC), 127.18 (ArC), 126.88 (ArC), 126.46 (ArC),
126.09 (ArC), 125.44 (ArC), 125.37 (ArC), 107.48 (COCH=C),
1H NMR (300 MHz, CDCl3): d = 8.10–8.62 (m, 13 H, NH and
ArH), 6.57 and 6.47 (2 × s, 1 H, COCH=C), 3.65–3.51 (m, 4 H,
CH2CH2), 3.16 and 2.78 (2 × s, 3 H, NCH3).
13C NMR (75 MHz, CDCl3): d = 166.85 (HNCOPh), 166.45
(HNCOPh), 165.98 (d, 1JCF = 253.8 Hz, ArC), 165.97 (COCH=C),
1
164.73 (d, JCF = 252.3 Hz, ArC), 164.45 (COCH=C), 164.40 (d,
1JCF = 251.8 Hz, ArC), 164.25 (d, 1JCF = 253.1 Hz, ArC), 163.67 (d,
1
1JCF = 251.3 Hz, ArC), 163.58 (d, JCF = 252.1 Hz, ArC), 163.06
[CH=C(Ar)O], 162.58 [CH=C(Ar)O], 152.97 (ArCOO), 152.16
3
3
(ArCOO), 132.67 (d, JCF = 10.6 Hz, ArC), 132.53 (d, JCF = 9.8
Hz, ArC), 129.67 (d, 4JCF = 3.0 Hz, ArC), 129.57 (d, 4JCF = 3.2 Hz,
ArC), 129.47 (d, JCF = 3.0 Hz, ArC), 129.33 (d, JCF = 2.7 Hz,
ArC), 129.07 (d, JCF = 8.9 Hz, ArC), 129.07 (d, JCF = 8.9 Hz,
ArC), 127.44 (d, JCF = 8.6 Hz, ArC), 127.30 (d, JCF = 8.9 Hz,
ArC), 125.03 (d, JCF = 3.0 Hz, ArC), 124.57 (d, JCF = 2.9 Hz,
ArC), 115.78 (d, JCF = 22.1 Hz, ArC), 115.70 (d, JCF = 22.2 Hz,
ArC), 115.63 (d, JCF = 22.3 Hz, ArC), 115.56 (d, JCF = 21.5 Hz,
ArC), 114.98 (d, JCF = 22.8 Hz, ArC), 114.91 (d, JCF = 21.6 Hz,
ArC), 107.88 (COCH=C), 106.20 (COCH=C), 49.17
[CON(CH3)CH2], 47.01 [CON(CH3)CH2], 39.14 (CH2NHCOPh),
4
4
3
3
3
3
106.25
(COCH=C),
49.55
[CON(CH3)CH2],
47.27
4
4
[CON(CH3)CH2], 39.18 (CH2NHCOPh), 38.46 (CH2NHCOPh),
37.02 [CON(CH3)CH2], 33.80 [CON(CH3)CH2], 21.65 (CH3Ar),
21.31 (CH3Ar), 21.26 (CH3Ar).
HRMS (ESI): m/z [M + Na]+ calcd for C29H30N2NaO4: 493.2103;
2
2
2
2
2
2
found: 493.2067.
38.17
[CON(CH3)CH2].
HRMS: m/z [M]+ calcd for C26H21F3N2O4: 482.1453; found:
(CH2NHCOPh),
36.67
[CON(CH3)CH2],
33.27
(Z)-3-{[2-(4-Chlorobenzamido)ethyl](methyl)amino}-1-(4-chlo-
rophenyl)-1-(4-chlorophenylcarbonyloxy)-3-oxoprop-1-ene
(14d)
The title compound 14d was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 4-chlorobenzoyl chloride (0.613 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→3:1). The ratio of
the two rotational conformations was 3.35:1 based on the relative
integrals of the 3.22 and 2.92 ppm resonances of the 1H NMR spec-
trum.
482.1445.
(Z)-3-{[2-(2-Methylbenzamido)ethyl](methyl)amino}-1-(2-
methylphenyl)-1-(2-methylphenylcarbonyloxy)-3-oxoprop-1-
ene (14f)
The title compound 14f was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 2-methylbenzoyl chloride (0.541 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→3:1). The ratio of
the two rotational conformations was 2.37:1 based on the relative
integrals of the 3.21 and 2.97 ppm resonances of the 1H NMR spec-
trum.
Yield: 373 mg (70%); white solid; mp 184–185 °C; Rf = 0.65 (hex-
ane–acetone, 1:1).
IR (KBr): 3297, 1750, 1661, 1608 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.07–7.17 (m, 13 H, NH and
ArH), 6.60 and 6.53 (2 × s, 1 H, COCH=C), 3.70–3.60 (m, 4 H,
CH2CH2), 3.22 and 2.92 (2 × s, 3 H, NCH3).
Yield: 283 mg (60%); white solid; mp 117–119 °C; Rf = 0.53 (hex-
ane–acetone, 1:1).
13C NMR (75 MHz, CDCl3): d = 167.01 (HNCOPh), 166.78
(HNCOPh), 165.96 (COCH=C), 164.46 (COCH=C), 163.46
[CH=C(Ar)O], 162.85 [CH=C(Ar)O], 152.62 (ArCOO), 152.21
(ArCOO), 140.64 (ArC), 140.50 (ArC), 137.67 (ArC), 137.35
(ArC), 136.49 (ArC), 136.28 (ArC), 131.93 (ArC), 131.85 (ArC),
131.71 (ArC), 131.61 (ArC), 131.35 (ArC), 129.09 (ArC), 129.01
(ArC), 128.84 (ArC), 128.59 (ArC), 128.42 (ArC), 128.29 (ArC),
128.23 (ArC), 127.29 (ArC), 126.81 (ArC), 126.72 (ArC), 126.49
(ArC), 108.60 (COCH=C), 106.64 (COCH=C), 49.60
[CON(CH3)CH2], 47.25 [CON(CH3)CH2], 39.70 (CH2NHCOPh),
IR (KBr): 3300, 1739, 1650, 1611 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.00 and 7.98 (2 × d, J = 8.2 Hz
and J = 8.2 Hz, 1 H, ArH), 7.46–7.04 (m, 11 H, ArH), 6.94 and 6.72
(2 × s, 1 H, NH), 6.18 and 6.09 (2 × s, 1 H, COCH=C), 3.71–3.58
(m, 4 H, CH2CH2), 3.21 and 2.97 (2 × s, 3 H, NCH3), 2.48, 2.46,
2.45, 2.41 and 2.33 (5 × s, 9 H, CH3Ar).
13C NMR (75 MHz, CDCl3): d = 170.44 (HNCOPh), 170.19
(HNCOPh), 166.03 (COCH=C), 164.91 (COCH=C), 164.24
[CH=C(Ar)O], 163.94 [CH=C(Ar)O], 154.33 (ArCOO), 154.17
(ArCOO), 141.09 (ArC), 136.35 (ArC), 136.24 (ArC), 136.16
(ArC), 136.08 (ArC), 135.68 (ArC), 135.64 (ArC), 134.76 (ArC),
134.53 (ArC), 132.60 (ArC), 132.56 (ArC), 131.71 (ArC), 131.59
(ArC), 131.24 (ArC), 131.04 (ArC), 130.89 (ArC), 130.83 (ArC),
130.76 (ArC), 130.72 (ArC), 129.79 (ArC), 129.66 (ArC), 129.52
38.61
(CH2NHCOPh),
36.88
[CON(CH3)CH2],
33.75
[CON(CH3)CH2].
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

150
G. Ye et al.
PAPER
(ArC), 129.48 (ArC), 129.16 (ArC), 129.07 (ArC), 128.11 (ArC),
127.92 (ArC), 126.94 (ArC), 126.77 (ArC), 125.85 (ArC), 125.81
(ArC), 125.59 (ArC), 125.45 (ArC), 112.12 (COCH=C), 111.45
(COCH=C), 49.47 [CON(CH3)CH2], 46.84 [CON(CH3)CH2],
13C NMR (75 MHz, CDCl3): d = 166.56 (HNCOPh), 166.19
(HNCOPh), 165.84 (COCH=C), 164.36 (COCH=C), 162.97
[CH=C(Ar)O], 162.43 (CH=C(Ar)O], 152.59 (ArCOO), 151.71
(ArCOO), 135.25 (ArC), 135.15 (ArC), 134.98 (ArC), 134.92
(ArC), 134.82 (ArC), 134.70 (ArC), 134.64 (ArC), 134.37 (ArC),
134.17 (ArC), 133.84 (ArC), 133.75 (ArC), 131.41 (ArC), 131.12
(ArC), 130.41 (ArC), 130.33 (ArC), 130.23 (ArC), 130.10 (ArC),
130.05 (ArC), 129.99 (ArC), 129.90 (ArC), 129.87 (ArC), 129.46
(ArC), 129.41 (ArC), 128.29 (ArC), 128.08 (ArC), 127.44 (ArC),
125.52 (ArC), 125.40 (ArC), 125.27 (ArC), 124.56 (ArC), 123.63
(ArC), 123.38 (ArC), 109.17 (COCH=C), 107.38 (COCH=C),
49.35 [CON(CH3)CH2], 47.07 [CON(CH3)CH2], 39.11
(CH2NHCOPh), 38.27 (CH2NHCOPh), 36.78 [CON(CH3)CH2],
33.53 [CON(CH3)CH2].
38.29
(CH2NHCOPh),
37.99
(CH2NHCOPh),
36.67
[CON(CH3)CH2], 33.52 [CON(CH3)CH2], 21.56 (CH3Ar), 21.50
(CH3Ar), 20.43 (CH3Ar), 20.32 (CH3Ar), 19.89 (CH3Ar), 19.72
(CH3Ar).
(Z)-3-{[2-(2-Fluorobenzamido)ethyl](methyl)amino}-1-(2-fluo-
rophenyl)-1-(2-fluorophenylcarbonyloxy)-3-oxoprop-1-ene
(14g)
The title compound 14g was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 2-fluorobenzoyl chloride (0.555 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→2:1). The ratio of
the two rotational conformations was 2.68:1 based on the relative
integrals of the 3.23 and 3.01 ppm resonance of the 1H NMR spec-
trum.
(Z)-3-{[2-(3-Methylbenzamido)ethyl](methyl)amino}-1-(3-
methylphenyl)-1-(3-methylphenylcarbonyloxy)-3-oxoprop-1-
ene (14i)
The title compound 14i was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 3-methylbenzoyl chloride (0.541 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→2:1). The ratio of
the two rotational conformations was 2.35:1 based on the relative
integrals of the 3.21 and 2.89 ppm resonances of the 1H NMR spec-
trum.
Yield: 173 mg (36%); white solid; mp 91–93 °C; Rf = 0.44 (hex-
ane–acetone, 1:1).
IR (KBr): 3259, 1738, 1651, 1613 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.09–6.97 (m, 13 H, NH and
ArH), 6.73 and 6.68 (s, 1 H, COCH=C), 3.75–3.66 (m, 4 H,
CH2CH2), 3.23 and 3.01 (s, 3 H, NCH3).
Yield: 282 mg (65%); white solid; mp 118–120 °C; Rf = 0.56 (hex-
ane–acetone, 1:1).
IR (KBr): 3319, 1729, 1650, 1615 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.97–7.10 (m, 13 H, NH and
ArH), 6.60 and 6.51 (2 × s, 1 H, COCH=C), 3.72–3.58 (m, 4 H,
CH2CH2), 3.21 and 2.89 (2 × s, 3 H, NCH3), 2.39, 2.35, 2.32, 2.29
and 2.26 (5 × s, 9 H, CH3Ar).
13C NMR (75 MHz, CDCl3): d = 168.16 (HNCOPh), 167.48
(HNCOPh), 166.75 (COCH=C), 164.98 (COCH=C), 164.42
[CH=C(Ar)O], 164.13 [CH=C(Ar)O], 153.71 (ArCOO), 153.01
(ArCOO), 138.46 (ArC), 138.40 (ArC), 138.23 (ArC), 138.01
(ArC), 137.91 (ArC), 134.54 (ArC), 134.49 (ArC), 133.68 (ArC),
133.66 (ArC), 133.55 (ArC), 132.05 (ArC), 131.83 (ArC), 131.01
(ArC), 130.87 (ArC), 130.77 (ArC), 130.60 (ArC), 129.06 (ArC),
128.67 (ArC), 128.63 (ArC), 128.50 (ArC), 128.46 (ArC), 128.16
(ArC), 128.04 (ArC), 127.88 (ArC), 127.79 (ArC), 127.48 (ArC),
127.23 (ArC), 126.09 (ArC), 126.00 (ArC), 124.20 (ArC), 123.69
(ArC), 122.74 (ArC), 122.67 (ArC), 108.27 (COCH=C), 106.75
(COCH=C), 49.61 [CON(CH3)CH2], 47.21 [CON(CH3)CH2],
13C NMR (75 MHz, CDCl3): d = 166.89 (d, 3JCF = 3.2 Hz, HNCO-
Ph), 166.68 (d, 3JCF = 3.1 Hz, HNCOPh), 163.97 [d, 3JCF = 2.0 Hz,
3
CH=C(Ar)O], 163.75 [d, JCF = 2.0 Hz, CH=C(Ar)O], 160.48 (d,
1JCF = 249.1 Hz, ArC), 160.02 (d, 1JCF = 252.8 Hz, ArC), 159.49 (d,
1JCF = 251.6 Hz, ArC), 159.35 (d, 1JCF = 252.7 Hz, ArC), 159.30 (d,
1JCF = 252.3 Hz, ArC), 158.85 (d, 1JCF = 250.8 Hz, ArC), 147.43 (d,
3JCF = 3.7 Hz, ArCOO), 146.54 (d, 3JCF = 4.3 Hz, ArCOO), 135.29
(d, 3JCF = 9.1 Hz, ArC), 135.18 (d, 3JCF = 7.4 Hz, ArC), 133.25 (d,
3JCF = 9.2 Hz, ArC), 132.99 (d, 3JCF = 9.1 Hz, ArC), 132.69 (ArC),
132.50 (ArC), 131.61 (d, 4JCF = 1.1 Hz, ArC), 131.51 (d, 4JCF = 2.1
Hz, ArC), 131.31 (d, 3JCF = 8.9 Hz, ArC), 131.25 (d, 3JCF = 9.1 Hz,
4
3
ArC), 128.56 (d, JCF = 1.6 Hz, ArC), 124.56 (d, JCF = 3.3 Hz,
4
3
ArC), 124.42 (d, JCF = 2.5 Hz, ArC), 124.38 (d, JCF = 3.5 Hz,
3
3
ArC), 124.33 (d, JCF = 3.9 Hz, ArC), 124.15 (d, JCF = 3.9 Hz,
2
2
ArC), 121.73 (d, JCF = 10.4 Hz, ArC), 120.71 (d, JCF = 11.8 Hz,
2
2
ArC), 117.53 (d, JCF = 9.0 Hz, ArC), 117.28 (d, JCF = 9.0 Hz,
2
2
ArC), 117.01 (d, JCF = 22.0 Hz, ArC), 116.97 (d, JCF = 22.0 Hz,
ArC), 116.42 (d, JCF = 22.8 Hz, ArC), 116.39 (d, JCF = 22.6 Hz,
ArC), 115.98 (d, JCF = 24.3 Hz, ArC), 115.92 (d, JCF = 24.3 Hz,
ArC), 113.98 (d, 4JCF = 11.2 Hz, COCH=C), 113.12 (d, 4JCF = 11.2
Hz, COCH=C), 49.41 [CON(CH3)CH2], 46.90 [CON(CH3)CH2],
2
2
2
2
39.11
(CH2NHCOPh),
38.49
(CH2NHCOPh),
37.11
[CON(CH3)CH2], 33.92 [CON(CH3)CH2], 21.41 (CH3Ar), 21.35
38.57
(CH2NHCOPh),
38.52
(CH2NHCOPh),
37.00
(CH3Ar), 21.28 (CH3Ar), 21.21 (CH3Ar), 21.19 (CH3Ar).
[CON(CH3)CH2], 33.93 [CON(CH3)CH2].
HRMS: m/z [M]+ calcd for C29H30N2O4: 470.2206; found:
470.2201.
(Z)-3-{[2-(3-Chlorobenzamido)ethyl](methyl)amino}-1-(3-chlo-
rophenyl)-1-(3-chlorophenylcarbonyloxy)-3-oxoprop-1-ene
(14h)
The title compound 14h was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 3-chlorobenzoyl chloride (0.613 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–EtOAc, 1:2→EtOAc). The ra-
tio of the two rotational conformations was 2.16:1 based on the rel-
ative integrals of the 3.23 and 2.93 ppm resonances of the 1H NMR
spectrum.
(Z)-3-{[2-(3-Methoxybenzamido)ethyl](methyl)amino}-1-(3-
methoxyphenyl)-1-(3-methoxyphenylcarbonyloxy)-3-oxoprop-
1-ene (14j)
The title compound 14j was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 3-methoxybenzoyl chloride (0.597
g, 3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 3:1→1:1). The ratio of
the two rotational conformations was 2.91:1 based on the relative
integrals of the 3.21 and 2.91 ppm resonances of the 1H NMR spec-
trum.
Yield: 276 mg (52%); white solid; mp 94–96 °C; Rf = 0.43
(EtOAc).
Yield: 284 mg (63%); white solid; mp 100–102 °C; Rf = 0.31 (hex-
ane–actone, 1:1).
IR (KBr): 3317, 1738, 1651, 1602 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.11–7.14 (m, 13 H, NH and
ArH), 6.63 and 6.55 (2 × s, 1 H, COCH=C), 3.74–3.59 (m, 4 H,
CH2CH2), 3.23 and 2.93 (2 × s, 3 H, NCH3).
IR (KBr): 3320, 1731, 1643, 1619 cm–1.
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

PAPER
Tandem Reaction of Imidazolines with Benzoyl Chlorides
151
1H NMR (300 MHz, CDCl3): d = 7.76–6.86 (m, 13 H, NH and
ArH), 6.64 and 6.52 (2 × s, 1 H, COCH=C), 3.83, 3.79, 3.77, 3.75
and 3.72 (5 × s, 9 H, CH3OC), 3.62 (m, 4 H, CH2CH2), 3.21 and
2.91 (2 × s, 3 H, NCH3).
39.22
(CH2NHCOPh),
38.26
(CH2NHCOPh),
36.79
[CON(CH3)CH2], 33.41 [CON(CH3)CH2].
HRMS: m/z [M]+ calcd for C26H21F3N2O4: 482.1453; found:
482.1459.
13C NMR (75 MHz, CDCl3): d = 167.96 (HNCOAr), 167.04
(HNCOAr), 166.84 (COCH=C), 164.85 (COCH=C), 164.09
[CH=C(Ar)O], 163.79 [CH=C(Ar)O], 161.05 (CH3OC), 159.74
(CH3OC), 159.61 (CH3OC), 159.54 (CH3OC), 159.47 (CH3OC),
159.40 (CH3OC), 153.30 (ArCOO), 152.48 (ArCOO), 135.20
(ArC), 135.06 (ArC), 130.27 (ArC), 129.85 (ArC), 129.78 (ArC),
129.63 (ArC), 129.28 (ArC), 129.16 (ArC), 128.97 (ArC), 122.76
(ArC), 122.43 (ArC), 120.56 (ArC), 120.37 (ArC), 119.09 (ArC),
118.73 (ArC), 117.98 (ArC), 117.93 (ArC), 117.86 (ArC), 115.58
(ArC), 115.37 (ArC), 115.36 (ArC), 114.56 (ArC), 114.14 (ArC),
112.08 (ArC), 111.87 (ArC), 111.57 (ArC), 111.48 (ArC), 108.89
(COCH=C), 107.18 (COCH=C), 55.41 (CH3OC), 55.31 (CH3OC),
55.28 (CH3OC), 55.23 (CH3OC), 55.15 (CH3OC), 49.63
[CON(CH3)CH2], 47.24 [CON(CH3)CH2], 39.31 (CH2NHCOAr),
Acknowledgment
The authors acknowledge the educational and general funds of Mis-
sissippi State University for partial financial support of this work.
References
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38.59
(CH2NHCOAr),
37.09
[CON(CH3)CH2],
33.87
[CON(CH3)CH2].
HRMS: m/z [M]+ calcd for C29H30N2O7: 518.2053; found:
518.2067.
(Z)-3-{[2-(3-Fluorobenzamido)ethyl](methyl)amino}-1-(3-fluo-
rophenyl)-1-(3-fluorophenylcarbonyloxy)-3-oxoprop-1-ene
(14k)
The title compound 14k was prepared using 1,2-dimethylimidazo-
line (11; 0.098 g, 1 mmol) and 3-fluorobenzoyl chloride (0.555 g,
3.5 mmol) by the general procedure, and purified by flash column
chromatography (silica gel; hexane–acetone, 4:1→2:1). The ratio of
the two rotational conformations was 2.36:1 based on the relative
integrals of the 3.23 and 2.89 ppm resonances of the 1H NMR spec-
trum.
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45, 2693.
Yield: 207 mg (43%); white solid; mp 154–156 °C; Rf = 0.44 (hex-
ane–acetone, 1:1).
IR (KBr): 3325, 1747, 1656, 1614 cm–1.
1H NMR (300 MHz, CDCl3): d= 7.94–7.06 (m, 13 H, NH and ArH),
6.64 and 6.57 (2 × s, 1 H, COCH=C), 3.73–3.57 (m, 4 H, CH2CH2),
3.23 and 2.89 (2 × s, 3 H, NCH3).
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Heterocycles 1987, 25, 433.
13C NMR (75 MHz, CDCl3): d = 166.66 (d, 4JCF = 2.5 Hz, HNCO-
4
(20) Rajagopalan, P.; Talaty, C. N. Tetrahedron Lett. 1966, 38,
4537.
Ph), 166.25 (COCH=C), 165.85 (d, JCF = 2.5 Hz, HNCOPh),
164.28 (COCH=C), 163.04 (d, 4JCF = 3.1 Hz, COCH=C), 162.74 (d,
1JCF = 247.0 Hz, ArC), 162.65 (d, 1JCF = 245.5 Hz, ArC), 162.53 (d,
4JCF = 3.1 Hz, COCH=C), 162.45 (d, 1JCF = 246.9 Hz, ArC), 162.39
(d, 1JCF = 247.7 Hz, ArC), 162.33 (d, 1JCF = 248.2 Hz, ArC), 162.30
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D. J.; French, N.; Handley, S.; Hudson, A.; Husband, S.;
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1
4
(d, JCF = 246.9 Hz, ArC), 152.55 (d, JCF = 2.8 Hz, ArCOO),
151.75 (d, 4JCF = 2.9 Hz, ArCOO), 135.89 (d, 3JCF = 6.8 Hz, ArC),
135.68 (d, JCF = 6.4 Hz, ArC), 135.59 (d, JCF = 7.7 Hz, ArC),
135.48 (d, JCF = 8.1 Hz, ArC), 130.83 (d, JCF = 7.6 Hz, ArC),
130.45 (d, JCF = 8.5 Hz, ArC), 130.42 (d, JCF = 7.8 Hz, ArC),
130.32 (d, JCF = 8.1 Hz, ArC), 130.27 (d, JCF = 7.7 Hz, ArC),
130.25 (d, JCF = 8.2 Hz, ArC), 129.80 (d, JCF = 7.8 Hz, ArC),
129.73 (d, JCF = 7.7 Hz, ArC), 125.92 (d, JCF = 3.1 Hz, ArC),
125.75 (d, JCF = 3.0 Hz, ArC), 122.86 (d, JCF = 2.9 Hz, ArC),
122.19 (d, JCF = 2.9 Hz, ArC), 121.15 (d, JCF = 3.1 Hz, ArC),
120.98 (d, JCF = 22.6 Hz, ArC), 120.95 (d, JCF = 2.9 Hz, ArC),
120.86 (d, JCF = 21.1 Hz, ArC), 118.34 (d, JCF = 22.2 Hz, ArC),
118.06 (d, JCF = 21.5 Hz, ArC), 117.27 (d, JCF = 21.1 Hz, ArC),
117.10 (d, JCF = 22.5 Hz, ArC), 116.99 (d, JCF = 22.0 Hz, ArC),
116.80 (d, JCF = 23.4 Hz, ArC), 114.37 (d, JCF = 23.0 Hz, ArC),
114.19 (d, JCF = 22.9 Hz, ArC), 112.50 (d, JCF = 23.6 Hz, ArC),
112.31 (d, JCF = 23.6 Hz, ArC), 109.08 (COCH=C), 107.62
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
2
4
2
2
2
2
2
2
2
2
2
2
2
(COCH=C), 49.26 [CON(CH3)CH2], 47.08 [CON(CH3)CH2],
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York

152
G. Ye et al.
PAPER
D.; Willatts, S. M.; Grounds, R. M. Anaesthesia 1999, 54,
1136. (e) Buerkle, H.; Yaksh, T. Br. J. Anaesth. 1998, 81,
208. (f) Lemke, K. A. Can. Vet. J. 2004, 45, 475.
method: full-matrix least-squares on F2; final R indices [I >
2σ (I)]. R1 = 0.0468, wR2 = 0.1099, R indices (all data)
R1 = 0.1093, wR2 = 0.1370; goodness of fit on F2 = 1.000.
Crystals were grown by slow evaporization of pentane into a
CHCl3–EtOAc solution of 12a. CCDC number for
compound 12a is CCDC 683239. This data can be obtained
free of charge from the Cambridge Crystallographic Data
Centre via ww.ccdc.cam.ac.uk/datarequest/cif.
(g) Emanuel, B.; Kompatscher, P.; Meyer, V. E. Plast.
Reconstr. Surg. 2001, 108, 637. (h) Pigini, M.; Bousquet,
P.; Brasili, L.; Carrieri, A.; Cavagna, R.; Dontenwill, M.;
Gentili, F.; Giannella, M.; Leonetti, F.; Piergentili, A.;
Quaglia, W.; Carotti, A. Bioorg. Med. Chem. 1998, 6, 2245.
(i) Van Zwieten, P. A. J. Hypertens. 1997, 15, 117.
(j) LeBrigand, L.; Virsolvy, A.; Peyrollier, K.; Manechez,
D.; Godfroid, J. J.; Guardiola Lemaitre, B.; Bataille, D. Br.
J. Pharmacol. 1997, 122, 786. (k) Molderings, G. J.;
Donecker, K.; Burian, M.; Simon, W. A.; Schroeder, D. W.;
Göthert, M. J. Pharmacol. Exp. Ther. 1998, 285, 170.
(30) SMART Version 5.625, SAINT+Version 6.22, 2001. Bruker
Analytical X-ray Systems, Inc., Madison, Wisconsin, USA.
(31) G. M. Sheldrick; SHELXTL Version 6.1, 2000; Bruker
Analytical X-ray Systems, Inc., Madison, Wisconsin, USA.
(32) Cyclic amidinium salts readily undergo ring-opening
hydrolysis in the presence of water, see: (a) DeWolfe, R.
H.; Cheng, M. W. L. J. Org. Chem. 1969, 34, 2595.
(b) DeWolfe, R. H. J. Am. Chem. Soc. 1960, 82, 1585.
(c) Perrin, C. L.; Thoburn, J. D. J. Am. Chem. Soc. 1993, 115,
3140.
(29) X-ray crystallographic description of 12a: Crystal
dimensions (mm): 0.38 × 0.35 × 0.22. C26H25.5N2O4.25
;
Mr = 433.98. Triclinic; space group P1; a = 8.571(2) Å,
b = 10.140(2) Å, c = 14.383(3) Å; a = 103.687(3)°, b =
106.909(3)°, g = 96.759(4)°; V = 1138.5(4) Å3; Z = 2;
D(calcd) = 1.266 g/cm3; m (mm–1) = 0.086; F(000) = 459;
Reflections collected/unique = 8421/4000; refinement
(33) Forsberg, J. H.; Spaziano, V. T.; Balasubramanian, T. M.;
Liu, G. K.; Kinsley, S. A.; Duckworth, C. A.; Poteruca, J. J.;
Brown, P. S.; Miller, J. L. J. Org. Chem. 1987, 52, 1017.
Synthesis 2010, No. 1, 141–152 © Thieme Stuttgart · New York