Efficient synthesis of new 4-arylideneimidazolin-5-ones related to the GFP chromophore by 2+3 cyclocondensation of arylideneimines with imidate ylides

Article abstract of DOI:10.1055/s-0029-1218796

A 2+3 condensation of a wide assortment of Schiff bases, prepared from aromatic aldehydes and primary amines, with methyl (1-ethoxyethylideneamino) acetate allows convenient access to an extensive family of substituted 4-arylideneimidazolin-5-one analogues of the green fluorescent protein (GFP) chromophore. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218796

2424
PAPER
Efficient Synthesis of New 4-Arylideneimidazolin-5-ones Related to the GFP
Chromophore by 2+3 Cyclocondensation of Arylideneimines with Imidate
Ylides
Synthesis of
N
ew 4
n
-Arylidenei
t
midazo
h
lin-5-ones ony Baldridge, Janusz Kowalik,* Laren M. Tolbert
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA
Fax +1(404)8947452; E-mail: janusz.kowalik@chemistry.gatech.edu
Received 22 December 2009; revised 31 March 2010
purposes. In this paper we expand upon that synthesis to
provide a general approach to arbitrarily substituted
arylideneimidazolin-5-ones.
Abstract: A 2+3 condensation of a wide assortment of Schiff bases,
prepared from aromatic aldehydes and primary amines, with methyl
2-(1-ethoxyethylideneamino)acetate allows convenient access to an
extensive family of substituted 4-arylideneimidazolin-5-one ana-
logues of the green fluorescent protein (GFP) chromophore.
H
N
N
CO2Me
Key words: 4-arylideneimidazolin-5-one, azomethine ylide, Schiff
bases, heterocycle, 2+3 cycloaddition
N
H
1,2 H+ shift
N
CO2Me
R
O
N
R
The chromophore of the green fluorescent protein (GFP)
has gained significant attention in the literature due to its
unusual photophysical and photochemical properties.1
Denaturation of the protein b-barrel leads to a loss in
emission quantum yield, and numerous studies have
sought to regain that brightness by incorporation into
rings2,3 or restriction in hydrophobic capsules.4 In order to
study the mechanisms by which these phenomena arise,
convenient access to a wide spectrum of substituted
arylideneimidazolinones is required. Thus, we sought a
high-yielding, functional group-tolerant methodology
adaptable to a combinatorial approach.
The Plöchl–Erlenmeyer synthesis,5 which is an old classic
in organic chemistry, provides access to arylidene-
imidazolinones6 and continues to dominate the synthesis
of GFP chromophores as well as supplement7 more recent
methods. This two-step methodology requires initial prep-
aration of an arylideneoxazolone followed by reaction
with amines to yield respective imidazolinones.8 Alterna-
tive methods include the de novo formation of the imida-
zolinone ring9 or interconversions of imidazolinones.10 A
recent excellent review of the former approach has
appeared.11
Scheme 1 Mode of [2+3] cycloaddition via ylide mechanism
R2
CHO
R2-NH2
N
N
(A)
(B)
(C)
R1
R1
stirring, r.t., 12 h
1
Cl
NH2
H
O
K2CO3
Cl
NH3
+
Et2O, H2O
mix
OEt CO2Me
MeO
O
2
O
neat or in EtOH
stirring
R2
N
R1
1
2
+
N
Scheme 2 The synthesis of 4-arylideneimidazolin-5-ones by [2+3]
cycloaddition
The synthesis begins with iminoesters of a-aminoacid es-
ters, which owe their synthetic versatility to easy equili-
bration (self-enolization) to a bipolar nitrogen ylide via a
facile 1,2-prototropic shift (Scheme 1).The resulting sta-
bilized imine ylide is an adaptable enophile in a [2+3] cy-
cloaddition that can lead to an assortment of heterocycles,
including arylideneimidazolinones.15 The required imi-
noglycine methyl ester is readily produced from the reac-
tion of ethyl acetimidate hydrochloride with glycine
methyl ester hydrochloride (Scheme 2, B). The requisite
Schiff base, acting as a dipolarophile, is conveniently syn-
thesized in high yields by a condensation of aromatic al-
dehydes and primary amines (Scheme 2, A). In the
resulting 4-arylideneimidazolin-5-one, the Schiff base
provides the aromatic substituent as well as the amide ni-
trogen of the imidazolinone with its substituent, while the
second reagent, (1-ethoxyethylideneamino) acetate,
which is common for all reactions, contributes all other
Despite this progress, the need for reliable, quick and con-
venient access to a variety of substituted imidazolinones
with varying substitution patterns remains, since such
chromophores are of increasing interest in other disci-
plines,12 including biosciences and medicine.13 Such syn-
thetic methods must provide efficiency, directness and a
diversity of functional groups. We have found that the
methodology proposed by Bazureau et al.,9c which is a
very clever adaptation of earlier chemistry developed by
Grigg et al.14 and other authors, is most adaptable for our
SYNTHESIS 2010, No. 14, pp 2424–2436
x
x.
x
x
.
2
0
1
0
Advanced online publication: 20.05.2010
DOI: 10.1055/s-0029-1218796; Art ID: M06809SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2425
atoms in the imidazolinone ring (Scheme 2). Since both cess amine were removed in vacuo. All Schiff base reac-
aromatic aldehydes and aliphatic amines are commercial- tions gave at, or near, quantitative yields16 (Scheme 2, A).
ly available, the synthetic method provides convenient ac-
Synthesis of the imidate was carried out according to the
cess to extensive structural variety using an assortment of
literature.17 The cycloaddition itself was carried out by
amines and aldehydes, all of which are readily tolerated.
mixing the corresponding Schiff base (1 equiv) with the
Syntheses of the various Schiff bases were carried out ac- imidate (1.1 equiv). In cases where the Schiff base con-
cording to the literature by combining the given aromatic tained acidic groups, a spontaneous reaction took place
aldehyde (1 mmol) with the corresponding amine (1.1 with the generation of considerable amounts of heat. The
mmol). In cases where either the aldehyde or the amine exothermic nature of this reaction was not as sizable when
was solid, ethanol (~3 mL) was used to solubilize the re- acidic groups were absent. For better heat control, mini-
agents. The reaction was allowed to stir under ambient mal amounts of ethanol were used as solvent. Magnetic
conditions for 12 hours. In cases where a precipitate was stirring overnight under ambient conditions generally re-
noted, the product was isolated by filtration and washed sulted in precipitation of a pure reaction product. In cases
with cold ethanol (~2 mL) to afford pure product. When where no solid was obtained, the reaction product was iso-
both reagents were initially liquids, the solvents and ex- lated and purified by column chromatography.
Table 1 Synthesized Compounds Grouped by General Substitution Patterns Discussed in this Papera
O
R2
N
R1
N
R1
R2
Yield
(%)b
R1
R2
Yield
(%)b
R1
R2
Yield
(%)b
1a
1b
1c
1d
1e
1f
4-Me
Me
n-Pr
n-Pr
Me
Me
n-Pr
Me
Me
Me
Me
Me
Me
Me
Me
Me
i-Pr
n-Pr
81c
84c
63d
55c
66c
70d
99c
75c
72c
80c
96c
54c
65c
96c
49c
62c
72c
85c
64c
7b
4-N(Me)2
4-N(Me)2
n-Pr
i-Pr
48d
46d
95c
90c
69c
70c
55c
45c
71c
42c
67c
60d
60c
49c
59c
72d
57d
60d
60d
13g
13h
14a
14b
14c
14d
14e
15a
16a
17a
18a
19a
19b
20a
21a
22a
22b
23a
24a
3-Me
Me
70c
72c
69c
50c
44c
46c
94c
64c
74c
75c
30e
76c
43d
46c
64c
79c
96c
71c
70
4-Me
7c
3-Me
n-Pr
4-Et
8a
1-naphthyl Me
1-naphthyl Et
2-naphthyl Me
4-OH
4-OH
4-OH
4-OH
4-OH
4-OBz
4-OH
2-quinoline
4-OH
4-CF3
4-CF3
Me
4-Et
8b
n-Pr
4-t-Bu
4-i-Pr
8c
n-Pentyl
n-Bu
9a
2,4-Me
2,5-Me
2,6-Me
3-indole
2-tetralin
2-F
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
n-Pr
Et
2a
2b
3a
3b
3c
3d
4a
5a
6a
6b
6c
6d
7a
4-NO2
3-NO2
2,3-OMe
2,4,5-OMe
2,5-OMe
3-OMe
4-CO2H
4-CN
9b
C16H33
Me
9c
10a
11a
12a
12b
12c
13a
13b
13c
13d
13e
13f
C3H6CO2H
Me
CH2(CF2)6CF3
Me
3-F
4-F
n-Pr
2-Me
2-Et
3,5-t-Bu, 4-OH Me
4-N(Et)2
4-N(Et)2
4-N(Et)2
H
Me
2-Me
2-Me
2-Et
3-OH
3-OH
4-Cl
4-OH
Me
C16H33
2-OH, 4-N(Et)2 Me
4-N(Me)2 Me
Et
Me
2-Et
n-Pr
C2NHC(O)-Xf
a Full characterization of each compound can be found in Table 2.
b Yields indicate pure product following washing/purification.
c Precipitation with overnight stirring.
d Precipitation at 0 °C.
e Column chromatography, silica gel (hexane–EtOAc, 1:1).
f X = cholesterol (as substituent).
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2426
A. Baldridge et al.
PAPER
The yields were good to very good, which made the pro- outcomes and yields are noted in Table 1, and analytical
cess amenable to a combinatorial approach. The reaction data are collected in Table 2.
Table 2 Characterization of 4-Arylideneimidazolin-5-ones
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
1a18
2.35 (s, 3 H), 2.37 (s,
3 H), 3.16 (s, 3 H), 7.08 26.81, 127.77,
15.87, 21.89,
214.1 (45),
55.6 (100)
141–
143
Me
(s, 1 H), 7.21 (d, JHH
8.2 Hz, 2 H), 8.01 (d,
JHH = 7.7 Hz, 2 H)
=
129.73, 131.68,
132.38, 138.40,
140.89, 162.17,
171.00
1b
0.95 (t, JHH = 7.2 Hz,
11.15, 15.71,
242.1 (100), Calcd
109–
3 H), 1.65 (sext, JHH
7.7 Hz, 2 H), 2.37 (s,
3 H), 3.55 (t, JHH = 7.0
Hz, 2 H), 7.07 (s, 1 H),
7.21 (d, JHH = 7.8 Hz,
=
21.61, 22.57,
225.1 (24),
185.1 (24),
159.1 (21),
130.1 (20),
84.1 (34),
55.0 (17)
(1b·1/4H2O): C, 110
73.59; H, 7.61;
N, 11.44.
Found: C,
73.26; H, 7.58;
N, 11.52
42.09, 122.15,
127.31, 129.44,
131.45, 132.04,
137.86, 140.52,
2 H), 8.01 (d, JHH = 8.4 161.90, 170.76
Hz, 2 H)
1c
0.93 (t, JHH = 7.1 Hz,
3 H), 1.22 (t, JHH = 7.1
Hz, 3 H), 1.64 (sext,
11.11, 15.23,
15.65, 22.51,
28.84, 42.03,
256.1 (100),
239.2 (15),
185.2 (23),
130.1 (12),
83.9 (27),
54.6 (12)
Oil
JHH = 7.1 Hz, 2 H), 2.36 127.28, 128.19,
(s, 3 H), 2.65 (q, JHH
=
131.61, 132.08,
137.84, 146.75,
7.7 Hz, 2 H), 3.54 (t,
JHH = 7.1 Hz, 2 H), 7.07 161.90, 170.71
(s, 1 H), 7.22 (d, JHH
=
8.2 Hz, 2 H), 8.03 (d,
JHH = 8.2 Hz, 2 H)
1d
1.24 (t, JHH = 7.6 Hz,
3 H), 2.37 (s, 3 H), 2.67 26.52, 28.89,
(q, JHH = 7.8 Hz, 3 H),
3.18 (s, 3 H), 7.10 (s,
15.27, 15.62,
228.1 (100),
213.1 (21),
199.1 (14),
58.0 (95),
56.0 (97)
85–
86
Me
127.51, 128.24,
131.60, 132.14,
1 H), 7.25 (d, JHH = 9.0 137.95, 146.84,
Hz, 2 H), 8.04 (d, JHH
=
161.88, 170.56
7.5 Hz, 2 H)
1e
1f
1.32 (s, 9 H), 2.36 (s,
3 H), 3.16 (s, 3 H), 7.10 31.05, 34.86,
15.62, 26.52,
256.0 (82),
241.0 (100),
55.5 (95)
141–
142
Me
(s, 1 H), 7.43 (d, JHH
=
122.13, 125.66,
127.36, 131.35,
131.84, 138.12,
153.53, 161.90
8.2 Hz, 2 H), 8.04 (d,
JHH = 8.8 Hz, 2 H)
0.95 (t, JHH = 7.7 Hz,
3 H), 1.24 (d, JHH = 6.6 22.51, 23.62,
Hz, 6 H), 1.65 (sext, 34.07, 42.03,
JHH = 7.2 Hz, 2 H), 2.37 126.75, 127.27,
(s, 3 H), 2.92 (sept, JHH = 131.76, 132.08,
11.11, 15.64,
270.2 (100),
255.1 (82),
185.1 (32),
144.1 (21),
84.1 (49),
55.0 (23)
73–
74
7.2 Hz, 1 H), 3.55 (t,
JHH = 7.7 Hz, 2 H), 7.08 161.88, 170.71
(s, 1 H), 7.27 (d, JHH
137.89, 151.26,
=
8.3 Hz, 2 H), 8.04 (d,
JHH = 8.8 Hz, 2 H)
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2427
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
2a
2.41 (s, 3 H), 3.20 (s,
3 H), 7.04 (s, 3 H), 8.19– 123.52, 123.94,
8.29 (m, 4 H)
16.08, 26.95,
245.1 (100), Calcd: C, 58.77; 173–
Me
Me
215.2 (75),
199.2 (14),
55.1 (97)
H, 4.52; N,
174
132.69, 140.63,
141.61, 147.91,
165.65, 170.55
17.13. Found:
C, 58.39; H,
4.47; N, 16.74
O2N
2b
3a
3b
2.37 (s, 3 H), 3.19 (s,
3 H), 7.49 (s, 2 H), 7.66 120.85, 124.61,
(t, JHH = 7.7 Hz, 1 H),
7.99 (d, JHH = 8.2 Hz,
1 H), 8.46 (d, JHH = 7.7 133.62, 141.25,
15.74, 26.65,
245.0 (28),
215.0 (21),
199.0 (24),
119.0 (85),
91.9 (78),
55.5 (100)
171–
172
128.74, 129.68,
132.89, 133.62,
NO2
Hz, 1 H)
141.75, 165.21,
169.86
2.37 (s, 3 H), 3.18 (s,
3 H), 3.87 (s, 3 H), 3.88 56.05, 62.03,
(s, 3 H), 6.94 (dd, JHH 114.32, 121.62,
7.8, 1.8 Hz, 1 H), 7.12 (t, 124.41, 124.46,
JHH = 8.1 Hz, 1 H), 7.57 139.43, 145.50,
15.96, 26.84,
260.1 (30),
229.1 (95),
55.6 (100)
Calcd
144–
Me
(3a·1/8H2O): C, 145
64.05; H, 7.23;
N, 10.67.
=
OMe
Found: C,
63.95; H, 6.20;
N, 10.54
OMe
(s, 1 H), 8.31 (dd, JHH
8.1, 1.3 Hz, 1 H)
=
149.77, 152.83,
162.80, 170.90
2.34 (s, 3 H), 3.17 (s,
3 H), 3.87 (s, 3 H), 3.92 55.89, 56.22,
(s, 3 H), 3.93 (s, 3 H),
6.46 (s, 1 H), 7.62 (s,
1 H), 8.54 (s, 1 H)
15.71, 26.52,
290.1 (94),
259.1 (87),
181.1 (20),
154.1 (32),
137.1 (28),
56.0 (100)
178–
179
MeO
Me
56.38, 95.90,
114.70, 115.20,
121.39, 136.07,
143.15, 152.26,
155.33, 160.15,
170.67
MeO
OMe
3c
2.35 (s, 3 H), 3.17 (s,
3 H), 3.82 (s, 3 H), 3.83 55.71, 56.12,
15.70, 26.53,
260.1 (100),
229.1 (99),
188.1 (49),
160.1 (47),
137.0 (31),
55.1 (95)
142–
143
MeO
Me
(s, 3 H), 6.80 (d, JHH
=
111.74, 116.90,
117.83, 121.12,
OMe
8.8 Hz, 1 H), 6.90 (dd,
JHH = 9.3, 3.4 Hz, 2 H), 123.65, 138.30,
7.62 (s, 1 H), 8.41 (d,
JHH = 2.7 Hz, 1 H)
153.80, 161.90,
170.64
3d
4a
2.36 (s, 3 H), 3.16 (s,
15.99, 26.84,
230.1 (40),
149.0 (12),
68.8 (27),
55.6 (100)
139–
140
Me
3 H), 3.84 (s, 3 H), 6.92 55.51, 116.63,
(dd, JHH = 8.2, 1.2 Hz, 116.78, 125.17,
1 H), 7.06 (s, 1 H), 7.31 127.41, 129.82,
(t, JHH = 7.8 Hz, 1 H),
7.63 (d, JHH = 7.5 Hz,
1 H), 7.80 (s, 1 H)
OMe
135.63, 139.11,
159.85, 162.86,
170.96
In DMSO-d6: 2.36 (s,
3 H), 3.10 (s, 3 H), 6.95 15.32, 26.20,
In DMSO-d6:
244.1 (16),
111.8 (17),
55.1 (100)
Calcd
274
Me
(4a·4H2O): C, (dec)
49.84; H, 5.46;
N, 8.94. Found:
C, 50.05; H,
(s, 1 H), 7.88 (d, JHH
=
122.90, 124.71,
129.07, 130.91,
134.03, 138.60,
164.22, 169.83
HO2C
8.2 Hz, 2 H), 8.10 (d,
JHH = 8.2 Hz, 2 H)
5.06; N, 8.77
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2428
A. Baldridge et al.
PAPER
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
5a
2.39 (s, 3 H), 3.18 (s,
3 H), 6.99 (s, 1 H), 7.65 112.47, 118.70,
(d, JHH = 9.0 Hz, 1 H),
8.19 (d, JHH = 8.1 Hz,
1 H)
15.76, 26.65,
225.1 (22),
58.0 (100),
56.0 (41)
Calcd
209–
Me
(5a·1/8H2O): C, 210
68.64; H, 4.98;
N, 18.47.
Found: C,
68.66; H, 4.87;
N, 18.44
123.88, 132.11,
132.14, 138.44,
140.94, 164.88,
170.29
NC
6a
6b
1.17 (t, JHH = 7.2 Hz,
6 H), 2.33 (s, 3 H), 3.15 26.47, 44.45,
(s, 3 H), 3.39 (q, JHH
7.2 Hz, 4 H), 6.64 (d,
JHH = 8.7 Hz, 2 H), 7.05 134.39, 149.09,
(s, 1 H), 8.01 (d, JHH
9.0 Hz, 2 H)
12.55, 15.52,
271.2 (87),
256.1 (100), H, 7.80; N,
227.1 (29),
143.1 (18),
56.0 (79)
Calcd: C, 70.82; 146–
Me
147
=
111.16, 121.36,
128.89, 134.21,
15.49. Found:
C, 70.57; H,
7.80; N, 15.42
N
=
158.48, 170.65
1.17 (t, JHH = 7.1 Hz,
6 H), 1.45 (d, JHH = 7.1 20.61, 44.42,
Hz, 3 H), 2.38 (s, 3 H),
3.39 (q, JHH = 7.1 Hz,
12.55, 16.96,
299.2 (88),
284.2 (100),
242.1 (11),
187.1 (12),
172.1 (11),
143.1 (18)
124–
125
44.92, 111.16,
121.51, 122.13,
128.28, 134.27,
149.00, 158.54,
N
4 H), 4.26 (sept, JHH
=
7.1 Hz, 1 H), 6.65 (d,
JHH = 8.8 Hz, 2 H), 6.99 170.74
(s, 1 H), 8.00 (d, JHH
=
8.8 Hz, 2 H)
6c
0.94 (t, JHH = 7.1 Hz,
3 H), 1.18 (t, JHH = 7.1
Hz, 6 H), 1.64 (sext,
JHH = 7.7 Hz, 2 H), 2.35 111.16, 121.52,
(s, 3 H), 3.40 (q, JHH
6.6 Hz, 4 H), 3.55 (t,
JHH = 7.7 Hz, 2 H), 6.65 158.50, 170.67
(d, JHH = 9.3 Hz, 2 H),
11.17, 12.55,
15.59, 22.61,
41.97, 44.43,
299.1 (72),
284.0 (100),
162.1 (32),
143.0 (12),
83.9 (12),
68.7 (15),
54.5 (27)
76–
77
N
=
128.73, 134.17,
134.35, 149.06,
7.04 (s, 1 H), 8.01 (d,
JHH = 8.8 Hz, 2 H)
6d
1.19 (t, JHH = 7.1 Hz,
6 H), 2.33 (s, 3 H), 3.20 26.61, 44.52,
(s, 3 H), 3.38 (q, JHH
6.6 Hz, 4 H), 6.16 (s,
1 H), 6.22 (dd, JHH = 8.8, 127.56, 131.35,
2.7 Hz, 1 H), 7.12 (s, 138.57, 152.89,
12.70, 14.85,
287.2 (100),
272.1 (83),
232.1 (72),
217.0 (32),
56.1 (73)
203–
204
Me
=
99.15, 104.50,
109.34, 122.13,
N
1 H), 7.11 (d, JHH = 8.8 160.82, 167.72
Hz, 1 H)
7a
2.35 (s, 3 H), 3.04 (s,
6 H), 3.17 (s, 3 H), 6.69 55.78, 61.77,
(d, JHH = 9.3 Hz, 2 H),
7.08 (s, 1 H), 8.04 (d,
JHH = 9.0 Hz, 2 H)
15.70, 26.58,
243.1 (94),
159.1 (10),
134.1 (11),
56.0 (100)
Calcd
199–
Me
(7a·1/8H2O): C, 200
68.48; H, 7.07;
N, 17.11.
Found: C,
68.51; H, 7.01;
N, 17.05
114.06, 121.36,
124.15, 124.20,
139.17, 145.24,
149.51, 152.57,
162.54, 170.53
N
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2429
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
7b
0.95 (t, JHH = 7.2 Hz,
11.20, 15.65,
22.64, 40.01,
42.03, 111.69,
271.2 (100),
254.2 (13),
229.1 (15),
159.1 (35),
143.1 (15),
134.1 (13),
84.1 (38)
117–
118
3 H), 1.65 (sext, JHH
=
7.7 Hz, 2 H), 2.36 (s,
3 H), 3.04 (s, 6 H), 3.55 122.16, 122.24,
(t, JHH = 7.5 Hz, 2 H),
6.70 (d, JHH = 8.7 Hz,
2 H), 7.06 (s, 1 H), 8.05 170.71
N
128.62, 134.04,
151.38, 159.01,
(d, JHH = 9.3 Hz, 2 H)
7c
8a
1.45 (d, JHH = 7.1 Hz,
6 H), 2.39 (s, 3 H), 3.03 40.03, 45.01,
(s, 6 H), 4.26 (sept, JHH = 110.95, 111.71,
7.1 Hz, 1 H), 6.69 (dd,
JHH = 6.6, 2.2 Hz, 2 H), 133.98, 151.35,
17.02, 20.64,
271.0 (100),
229.0 (14),
159.1 (36),
143.0 (11),
134.1 (12),
83.9 (17)
oil
N
122.33, 128.22,
7.01 (s, 1 H), 8.03 (d,
JHH = 8.8 Hz, 2 H)
159.07, 170.80
2.40 (s, 3 H), 3.23 (s,
3 H), 7.47–7.62 (m, 3 H), 122.89, 123.15,
7.83–7.90 (m, 2 H), 7.98 125.69, 125.88,
15.65, 26.56,
250.1 (93),
167.1 (21),
139.1 (11),
56.0 (100)
Calcd
186–
Me
(8a·1/4H2O): C, 187
75.43; H, 5.73;
N, 10.99.
(s, 1 H), 8.31 (d, JHH
=
126.83, 128.80,
129.90, 130.55,
131.19, 132.40,
133.54, 139.38,
163.22, 170.48
8.4 Hz, 1 H), 8.79 (d,
JHH = 7.2 Hz, 1 H)
Found: C,
75.20; H, 5.61;
N, 10.93
8b
1.27 (t, JHH = 7.1 Hz,
3 H), 2.40 (s, 3 H), 3.68 35.36, 122.74,
(q, JHH = 7.1 Hz, 2 H),
7.48–7.62 (m, 3 H),
7.84–7.91 (m, 2 H), 7.97 128.82, 129.96,
(s, 1 H), 8.31 (d, JHH
8.2 Hz, 1 H), 8.80 (d,
JHH = 8.2 Hz, 1 H)
14.62, 15.64,
264.1 (100),
235.1 (15),
166.1 (39),
141.1 (20),
139.1 (25),
70.1 (81),
101–
102
123.18, 125.69,
125.88, 126.81,
=
130.52, 131.16,
132.43, 133.56,
139.41, 163.01,
170.33
51.0 (16)
8c
2.40 (s, 3 H), 3.19 (s,
3 H), 7.45–7.54 (m, 2 H), 126.32, 127.37,
7.84–7.91 (m, 3 H), 8.42 127.65, 128.10,
15.71, 26.59,
250.1 (82),
141.1 (10),
56.0 (100)
192–
193
Me
(s, 1 H), 8.43 (d, JHH
7.7 Hz, 1 H)
=
128.30, 128.88,
131.92, 133.12,
133.21, 133.89,
138.82, 162.48,
170.71
9a
2.36 (s, 3 H), 2.37 (s,
3 H), 2.43 (s,3 H), 3.18 21.12, 26.55,
(s, 3 H), 7.07 (s, 2 H),
7.36 (s, 1 H), 8.40 (s,
1 H)
15.65, 19.62,
228.1 (91),
213.1 (36),
156.1 (68),
145.1 (67),
129.1 (14),
115.0 (19),
56.0 (100)
Calcd: C, 73.66; 120–
Me
H, 7.06; N,
121
122.15, 124.68,
130.28, 130.94,
132.21, 132.33,
135.65, 136.38,
138.36, 170.96
12.27. Found:
C, 73.59; H,
7.03; N, 12.31
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2430
A. Baldridge et al.
PAPER
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
9b
2.32 (s, 3 H), 2.36 (s,
3 H), 2.45 (s,3 H), 3.18 21.47, 26.55,
(s, 3 H), 7.02 (s, 1 H),
7.08 (d, JHH = 8.2 Hz,
1 H), 7.37 (s, 1 H), 8.53 131.96, 137.93,
(d, JHH = 7.7 Hz, 1 H)
15.64, 19.97,
228.1 (60),
213.1 (11),
156.1 (34),
145.1 (28),
56.0 (100)
137–
138
Me
Me
Me
124.52, 127.19,
129.83, 131.20,
139.33, 140.41,
162.50, 170.73
9c
2.26 (s, 6 H), 2.30 (s,
3 H), 3.18 (s, 3 H), 7.05 26.55, 127.60,
(d, JHH = 7.7 Hz, 2 H),
7.13 (t, JHH = 8.2 Hz,
1 H), 7.32 (s, 1 H)
15.61, 20.88,
228.0 (98),
213.0 (48),
156.0 (92),
145.1 (85),
128.0 (36),
115.0 (34),
55.5 (100)
70–
71
128.19, 128.42,
132.54, 136.72,
140.49, 162.63,
169.50
10a
In DMSO-d6: 2.34 (s,
In DMSO-d6:
239.0 (88),
155.0 (12),
130.0 (10),
55.5 (100)
Calcd (10a·
144–
3 H), 3.10 (s, 3 H), 7.09– 15.23, 26.12,
7.21 (m, 2 H), 7.30 (s, 111.01, 112.07,
1 H), 7.47 (dd, JHH = 7.1, 119.38, 120.64,
1.1 Hz, 1 H), 8.20 (d, 122.43, 126.61,
JHH = 7.1 Hz, 1 H), 8.39 132.65, 133.89,
1/4MeOH): C, 145
69.22; H, 5.70;
N, 16.99.
H
N
Found: C,
69.17; H, 5.35;
N, 17.17
(s, 1 H), 11.93 (s, 1 H)
136.28, 159.28,
169.10
11a
1.28 (s, 6 H), 1.30 (s,
6 H), 1.68 (s, 4 H), 2.36 31.56, 31.76,
15.68, 26.53,
310.1 (77),
295.1 (100), 1/4EtOH): C,
Calcd (11a·
173–
174
Me
(s, 3 H), 3.17 (s, 3 H),
7.09 (s, 1 H), 7.35 (d,
JHH = 8.2 Hz, 1 H), 7.91 128.00, 128.92,
(d, JHH = 1.7 Hz, 1 H), 131.04, 131.43,
8.03 (dd, JHH = 8.2, 1.7 137.96, 147.60,
34.46, 34.83,
34.89, 127.04,
253.0 (21),
55.6 (78)
76.48; H, 8.60;
N, 8.70. Found:
C, 76.80; H,
8.54; N, 9.03
Hz, 1 H)
161.58, 170.80
12a
2.37 (s, 3 H), 3.18 (s,
3 H), 7.04 (s, 1 H), 7.08 115.82 (JCF = 21.8 199.1 (45),
15.65, 26.56,
218.1 (92),
Calcd: C, 66.05; 168–
F
Me
H, 5.08; N,
169
(AA¢ of a AA¢BB¢X spin Hz), 122.16,
134.0 (12),
107.0 (16),
12.84. Found:
C, 65.83; H,
4.98; N, 12.78
system, 2 H), 8.12 (BB¢ 125.85, 130.44,
of a AA¢BB¢X spin sys- 134.13 (JCF = 8.0 56.0 (100)
tem, 2 H)
Hz), 138.24,
162.64, 163.57
(JCF = 252.4 Hz),
170.59
12b
2.37 (d, JHH = 0.6 Hz,
15.67, 26.58,
218.1 (64),
150–
151
Me
3 H), 3.17 (s, 3 H), 7.02 116.75 (JCF = 22.0 56.1 (100)
(s, 1 H), 7.00–7.10 (m, Hz), 118.25 (JCF
1 H), 7.30–7.4 (m, 1 H), 22.0 Hz), 125.45,
=
F
7.70–7.75 (m, 1 H),
8.00–8.08 (m, 1 H)
127.97, 130.01
(JCF = 7.7 Hz),
136.20, 139.51,
162.69 (JCF
=
245.5 Hz), 163.4,
170.50
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2431
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
12c
2.35 (s, 3 H), 3.16 (s,
3 H), 7.03 (s, 1 H), 7.08 115.79 (JCF = 21.8 148.8 (10),
15.01, 26.53,
218.0 (93),
151–
152
Me
(AA¢ of a AA¢BB¢X spin Hz), 125.81,
system, 2 H), 8.12 (BB¢ 130.43, 134.10
of a AA¢BB¢X spin sys- (JCF = 9.2 Hz),
58.0 (17),
56.1 (100)
F
tem, 2 H)
162.64, 163.54
(JCF = 252.4 Hz),
170.56
13a
13b
2.37 (s, 3 H), 2.48 (s,
3 H), 3.19 (s, 2 H), 7.18– 26.59, 124.4,
7.21 (m, 1 H), 7.22–7.29 126.32, 129.96,
(m, 2 H), 7.39 (s, 1 H),
8.59 (dd, JHH = 6.1, 2.8 132.59, 138.65,
15.70, 20.09,
214.1 (83),
199.1 (19),
142.0 (31),
131.1 (44),
115.0 (17),
56.0 (100)
Calcd (13a·
1/2H2O): C,
69.94; H, 6.77;
N, 12.55.
Found: C,
70.98; H, 6.41;
N, 12.68
109–
110
Me
130.40, 131.95,
Hz, 1 H)
139.29, 162.75,
170.70
1.23 (m, 6 H), 2.38 (s,
3 H), 2.83 (q, JHH = 7.1 16.02, 26.61,
Hz, 2 H), 3.66 (q, JHH 35.30, 124.00,
7.1 Hz, 2 H), 7.19–7.22 126.22, 128.85,
(m, 1 H), 7.22–7.31 (m, 130.05, 132.16,
2 H), 7.40 (s, 1 H), 8.51– 138.72, 145.41,
14.60, 15.61,
228.1 (84),
213.1 (53),
199.2 (23),
156.1 (37),
145.2 (42),
128.1 (21),
115.0 (20),
55.6 (100)
90–
91
Me
=
8.60 (m, 1 H)
162.41, 170.45
13c
0.97 (t, JHH = 7.1 Hz,
3 H), 1.23 (t, JHH = 7.7
Hz, 3 H), 1.67 (sext,
11.11, 15.65,
19.97, 22.49,
42.05, 124.06,
242.1 (100),
199.2 (28),
142.1 (25),
131.1 (34),
115.0 (24),
103.0 (19),
83.9 (78)
64–
65
JHH = 7.1 Hz, 2 H), 2.38 126.20, 129.82,
(s, 3 H), 2.84 (q, JHH
=
130.29, 131.83,
132.52, 138.46,
7.7 Hz, 2 H), 3.57 (t,
JHH = 7.1 Hz, 2 H), 7.15– 139.17, 162.72,
7.21 (m, 1 H), 7.22–7.30 170.65
(m, 2 H), 7.41 (s, 1 H),
8.57–8.63 (m, 1 H)
13d
13e
1.26 (t, JHH = 7.1 Hz,
3 H), 2.39 (s, 3 H), 2.48 20.07, 35.35,
(s, 3 H), 3.67 (q, JHH 124.20, 126.31,
7.1 Hz, 2 H), 7.17–7.23 129.91, 130.38,
(m, 1 H), 7.23–7.31 (m, 130.61, 131.92,
2 H), 7.38 (s, 1 H), 8.57– 132.62, 139.27,
14,65, 15.65,
228.0 (98),
199.0 (31),
142.0 (37),
131.0 (51),
115.0 (29),
102.9 (24),
69.7 (100)
128–
129
=
8.62 (m, 1 H)
162.52, 170.48
1.15–1.34 (m, 6 H), 2.38 14.60, 16.61,
242.1 (100),
227.1 (29),
213.0 (31),
155.9 (23),
144.9 (27),
70.0 (67)
73–
74
(s, 3 H), 2.83 (q, JHH
7.1 Hz, 2 H), 3.66 (q,
=
16.06, 26.61,
35.30, 124.00,
JHH = 7.1 Hz, 2 H), 7.16– 126.22, 128.85,
7.32 (m, 3 H), 7.40 (s, 130.05, 131.72,
1 H), 8.53–8.63 (m, 1 H) 132.16, 138.73,
145.41, 162.41,
170.45
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2432
A. Baldridge et al.
PAPER
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
13f
0.97 (t, JHH = 7.7 Hz,
3 H), 1.23 (t, JHH = 7.7
Hz, 3 H), 1.67 (sext,
11.17, 15.71,
16.05, 22.54,
26.59, 42.11,
256.0 (100),
241.0 (35),
213.0 (27),
156.0 (29),
145.1 (31),
83.9 (68),
74–
75
JHH = 7.7 Hz, 2 H), 2.38 123.97, 126.20,
(s, 3 H), 2.84 (q, JHH
=
128.83, 130.03,
131.73, 132.16,
7.7 Hz, 2 H), 3.57 (t,
JHH = 7.1 Hz, 2 H), 7.19– 138.65, 145.41,
7.25 (m, 1 H), 7.25–7.32 162.66, 170.71
(m, 2 H), 7.41 (s, 1 H),
57.6 (30)
8.55–8.62 (m, 1 H)
13g
13h
2.38 (s, 3 H), 2.39 (s,
3 H), 3.18 (s, 3 H), 7.08 26.58, 127.65,
15.67, 21.40,
214.1 (100),
199.1 (21),
130.1 (13),
115.1 (22),
103.0 (20),
77.1 (21),
148–
149
Me
(s, 1 H), 7.18 (d, JHH
=
128.57, 129.33,
131.00, 132.60,
7.7 Hz, 1 H), 7.30 (t,
JHH = 7.7 Hz, 1 H), 7.93 134.03, 138.27,
(d, JHH = 9.4 Hz, 2 H)
138.47, 162.38,
170.74
56.0 (97)
In DMSO-d6: 0.85 (t,
JHH = 7.7 Hz, 3 H), 1.56 10.96, 15.35,
(sext, JHH = 7.1 Hz, 2 H), 20.93, 21.81,
In DMSO-d6:
242.1 (100),
225.0 (53),
158.9 (47),
143.9 (40),
130.9 (52),
83.9 (63),
121–
122
2.32 (s, 3 H), 2.37 (s,
3 H), 3.52 (t, JHH = 7.2
Hz, 2 H), 6.91 (s, 1 H),
7.22 (d, JHH = 7.2 Hz,
1 H), 7.33 (t, JHH = 7.2
Hz, 1 H), 7.98 (s, 1 H),
8.04 (d, JHH = 7.7 Hz,
1 H)
41.36, 124.82,
128.34, 128.48,
129.03, 130.62,
132.24, 133.92,
137.64, 163.92,
169.88
55.1 (19)
14a19
In DMSO-d6: 2.31 (s,
3 H), 3.07 (s, 3 H), 6.82 15.20, 26.12,
(d, JHH = 8.8 Hz, 2 H),
6.88 (s, 1 H), 8.07 (d,
In DMSO-d6:
216.1 (48),
82.5 (14),
68.4 (16),
55.2 (100)
137–
138
Me
115.67, 125.29,
125.41, 134.03,
HO
JHH = 8.8 Hz, 2 H), 10.11 136.20, 159.50,
(s, 1 H)
162.20, 169.75
14b
0.94 (t, JHH = 7.8 Hz,
11.18, 15.42,
22.58, 42.26,
116.10, 126.07,
128.85, 134.33,
135.59, 158.95,
161.24, 170.85
242.1 (100), Calcd (14b·
139–
140
3 H), 1.65 (sext, JHH
7.1 Hz, 2 H), 2.36 (s,
3 H), 3.56 (t, JHH = 7.2
=
225.1 (24),
185.1 (24),
159.1 (21),
130.1 (20),
84.1 (34),
55.0 (17)
1/4H2O): C,
68.21; H, 6.64;
N, 11.36.
Found: C,
68.28; H, 6.55;
N, 11.36
HO
Hz, 2 H), 6.82 (d, JHH
8.1 Hz, 2 H), 7.09 (s,
1 H), 7.94 (d, JHH = 9.0
Hz, 2 H)
=
14c
0.88 (t, JHH = 7.0 Hz,
13.88, 15.47,
272.1 (100),
255.1 (81),
216.1 (31),
161.0 (32),
146.1 (23),
132.0 (25),
71.1 (26),
98–
99
3 H), 1.25–1.40 (m, 4 H), 22.26, 28.82,
1.60 (pent, JHH = 7.3 Hz, 29.01, 40.70,
2 H), 2.36 (s, 3 H), 3.58 116.06, 126.13,
(t, JHH = 7.0 Hz, 2 H),
6.83 (d, JHH = 8.7 Hz,
HO
128.59, 134.30,
135.75, 158.92,
2 H), 7.08 (s, 1 H), 7.94 161.19, 170.78
(d, JHH = 8.7 Hz, 2 H)
55.0 (37)
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2433
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
14d
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
0.94 (t, JHH = 7.2 Hz,
3 H), 1.36 (sext, JHH
7.7 Hz, 2 H), 1.60 (pen- 40.51, 116.08,
tet, JHH = 7.7 Hz, 2 H),
2.38 (s, 3 H), 3.60 (t,
JHH = 7.2 Hz, 2 H), 6.82 158.89, 161.28,
13.65, 15.41,
19.97, 31.36,
258.1 (100),
241.1 (88),
216.1 (58),
161.1 (58),
133.1 (40),
57.1 (62)
141–
142
=
HO
126.11, 128.82,
134.32, 135.62,
(d, JHH = 8.7 Hz, 2 H),
7.09 (s, 1 H), 7.95 (d,
JHH = 8.7 Hz, 2 H)
170.82
14e
0.88 (t, JHH = 6.7 Hz,
3 H), 1.18–1.37 (m, 26
H), 1.60 (t, JHH = 7.0 Hz, 26.78, 29.21,
2 H), 2.38 (s, 3 H), 3.59 29.34, 29.47,
14.12, 15.47,
22.67, 26.78,
426.2 (100),
409.2 (14),
216.1 (12),
56.2 (11)
109–
111
15
HO
(t, JHH = 7.6 Hz, 2 H),
6.85 (d, JHH = 8.5 Hz,
29.54, 29.60,
29.63, 29.66,
2 H), 7.07 (s, 1 H), 8.02 31.90, 40.76,
(d, JHH = 8.8 Hz, 2 H)
116.10, 126.14,
128.62, 134.32,
135.75, 158.95,
161.17, 170.77
15a
2.35 (s, 3 H), 3.17 (s,
15.64, 26.56,
306.1 (84),
215.1 (58),
91.0 (100),
65.0 (17),
56.0 (87)
Calcd (15a·
1/2H2O): C,
72.09; H, 5.72;
N, 8.75. Found:
C, 72.37; H,
6.07; N, 8.88
180–
181
Me
3 H), 5.11 (s, 2 H), 7.00 69.98, 115.13,
(d, JHH = 8.7 Hz, 2 H), 122.18, 127.30,
7.29–7.49 (m, 5 H), 8.10 127.45, 128.09,
O
(d, JHH = 9.0 Hz, 2 H)
128.62, 134.00,
136.43, 136.95,
160.35, 161.28,
170.73
16a
In DMSO-d6: 1.67 (pen- In DMSO-d6:
288.2 (10),
274.1 (100), 1/2H2O): C,
Calcd (16a·
237
(dec)
CO2H
tet, JHH = 7.6 Hz, 2 H),
1.91 (t, JHH = 7.0 Hz,
15.19, 25.75,
34.24, 116.25,
146.1 (18),
132.1 (15),
114.1 (23),
86.1 (65),
55.1 (25)
60.81; H, 5.44;
N, 9.46. Found:
C, 60.58; H,
HO
2 H), 2.34 (s, 3 H), 3.53 123.81, 126.02,
(t, JHH = 7.6 Hz, 2 H),
6.77 (d, JHH = 8.5 Hz,
134.12, 135.18,
161.10, 162.01,
4.99; N, 9.96
2 H), 6.83 (s, 1 H), 8.01 169.77, 175.99
(d, JHH = 8.8 Hz, 2 H)
17a
2.40 (s, 3 H), 3.18 (s,
3 H), 7.42 (s, 1 H), 7.54 123.95, 127.15,
(td, JHH = 8.2, 1.1 Hz, 127.40, 127.51,
1 H), 7.70 (td, JHH = 8.2, 129.64, 129.76,
1.1 Hz, 1 H), 7.79 (d, 135.96, 141.79,
JHH = 8.2 Hz, 1 H), 8.10 154.03, 164.79,
15.82, 26.61,
251.1 (52),
223.1 (12),
168.1 (12),
140.1 (10),
56.0 (100)
Calcd (18a·
1/8H2O): C,
71.06; H, 5.26;
N, 16.57.
Found: C,
71.13; H, 5.15;
N, 16.59
169–
170
Me
N
(d, JHH = 8.8 Hz, 1 H),
8.17 (d, JHH = 8.8 Hz,
1 H), 8.85 (d, JHH = 8.8
Hz, 1 H)
170.50
18a
In acetone-d6: 2.46 (d,
JHF = 0.6 Hz, 3 H), 4.59
(tt, JHF = 16.5 Hz, 2 H),
6.93 (AA¢ part of AA¢BB¢
spin system, 2 H), 7.02
(s, 1 H), 8.18 (BB¢ part of
AA¢BB¢ spin system,
2 H), 9.06 (br s, 1 H)
584.1 (98),
565.1 (18),
424.0 (100), 48.77; N, 4.79.
132.1 (9),
69.0 (12)
Calcd: C, 39.06; 207–
H, 1.90; F, 209
CF2
6
CF3
HO
Found: C,
39.01; H, 1.84;
F, 49.07; N,
4.77
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2434
A. Baldridge et al.
PAPER
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
19a
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
2.39 (s, 3 H), 3.19 (s,
3 H), 7.07 (s, 1 H), 7.64 124.79, 125.36
(d, JHH = 8.2 Hz, 2 H),
8.21 (d, JHH = 8.2 Hz,
2 H)
15.74, 26.63,
268.1 (79),
249.1 (10),
55.2 (100)
Calcd (19a·
1/4H2O): C,
152–
153
Me
(JCF = 4.4 Hz),
125.47 (JCF = 4.4
Hz), 131.98,
57.25; H, 4.25;
N, 10.27; F,
20.89. Found:
C, 57.55; H,
4.07; N, 10.48;
F, 20.93
F3C
137.42, 140.30,
144.50, 164.16,
170.46
19b
0.96 (t, JHH = 7.3 Hz,
11.16, 15.80,
22.55, 42.24,
124.57, 125.36
(JCF = 3.3 Hz),
125.46 (JCF = 3.3 54.2 (18)
Hz), 130.71,
296.1 (100),
279.1 (14),
185.0 (42),
198.1 (15),
76–
77
3 H), 1.66 (sext, JHH
=
7.3 Hz, 2 H), 2.40 (s,
3 H), 3.60 (t, JHH = 7.3
Hz, 2 H), 7.05 (s, 1 H),
7.64 (d, JHH = 7.9 Hz,
F3C
2 H), 8.22 (d, JHH = 8.2 131.95, 137.49,
Hz, 2 H)
140.24, 164.22,
170.53
20a
1.47 (s, 18 H), 2.35 (s,
3 H), 3.18 (s, 3 H), 5.59 30.16, 34.34,
15.77, 26.55,
Calcd: C, 73.14; 163–
t-Bu
Me
H, 8.59; N,
164
(s, 2 H), 7.08 (s, 1 H),
8.06 (s, 2 H)
125.91, 129.00,
130.07, 136.19,
156.21, 160.38,
170.88
8.53. Found: C,
73.07; H, 8.60;
N, 8.50
HO
t-Bu
21a9a
2.36 (s, 3 H), 3.16 (s,
3 H), 7.09 (s, 1 H), 7.31– 127.24, 128.63,
7.44 (m, 3 H), 8.11 (dd, 130.00, 132.05,
15.67, 26.56,
200.0 (100),
116.0 (14),
101.9 (12),
88.9 (18),
55.6 (97)
107–
108
Me
Me
JHH = 8.2, 2.2 Hz, 2 H)
134.10, 138.66,
162.57, 170.68
22a20
In DMSO-d6: 2.33 (s,
In DMSO-d6:
216.1 (45),
55.6 (100)
188–
189
3 H), 3.07 (s, 3 H), 6.79 16.07, 26.93,
(dd, JHH = 7.8, 2.0 Hz, 118.08, 118.59,
1 H), 6.84 (s, 1 H), 7.21 124.02, 125.63,
(t, JHH = 7.6 Hz, 1 H),
7.50 (d, JHH = 7.8 Hz,
130.20, 135.84,
139.47, 158.04,
OH
1 H), 7.72 (s, 1 H), 9.58 164.97, 170.56
(s, 1 H)
22b
0.87 (t, JHH = 7.0 Hz,
3 H), 1.19–1.39 (m,
26 H), 1.60 (t, JHH = 7.0 29.19, 29.34,
Hz, 2 H), 2.34 (s, 3 H),
14.10, 15.55,
22.66, 26.76,
426.1 (100),
411.1 (17),
216.1 (21),
203.1 (19),
56.2 (14)
83–
84
15
29.45, 29.53,
29.58, 29.63,
OH
3.57 (t, JHH = 7.6 Hz,
2 H), 6.86 (dd, JHH = 8.2, 29.66, 31.90,
2.1 Hz, 1 H), 7.09 (s,
1 H), 7.24 (t, JHH = 7.9
Hz, 1 H), 7.44 (d, JHH
7.6 Hz, 1 H), 7.78 (s,
1 H)
40.74, 117.82,
124.49, 127.77,
129.86, 135.10,
138.08, 156.38,
163.19, 170.47
=
23a18
2.36 (s, 3 H), 3.16 (s,
3 H), 7.01 (s, 1 H), 7.36 125.53, 128.86,
15.64, 26.55,
234.1 (72),
55.2 (100)
154–
155
Me
(d, JHH = 8.5 Hz, 2 H),
8.05 (d, JHH = 8.8 Hz,
2 H)
132.58, 133.16,
135.88, 138.91,
162.97, 170.46
Cl
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

PAPER
Synthesis of New 4-Arylideneimidazolin-5-ones
2435
Table 2 Characterization of 4-Arylideneimidazolin-5-ones (continued)
O
R2
R1
N
N
Comp R1
24a
R2
1H NMR (ppm)a,b
13C NMR (ppm)a MS [M]+ (%) Anal.c
Mp
(°C)
In 1,1,2,2-tetrachloro-
ethane-d2 at 80 °C: 0.73 chloroethane-d2 at 386.2 (100), H, 9.04; N,
In 1,1,2,2-tetra-
657.5 (3),
Calcd: C, 74.85; 230–
231
(s, 3 H), 0.92 (d, JHH
6.6 Hz, 6 H), 0.97 (d,
JHH = 6.3 Hz, 3 H), 1.04 19.12, 20.97,
=
80 °C: 11.73,
15.27, 18.68,
368.2 (81),
353.2 (33),
301.2 (33),
289.1 (91),
275.3 (45),
271.1 (62),
255.2 (24),
213.3 (28),
161.2 (34),
145.1 (39),
133.1 (30),
119.0 (27),
106.9 (42),
94.8 (41),
6.39. Found: C,
74.48; H, 9.30;
N, 6.06
HO
(s, 3 H), 1.29–1.05 (m,
10 H), 1,70–1.29 (m,
13 H), 2.10–1.79 (m,
6 H), 2.40–2.25 (m, 3 H), 31.76, 31.82,
2.41 (s, 3 H), 3.43 (q, 35.53, 36.15,
JHH = 6 Hz, 2 H), 3.76 (t, 36.44, 36.89,
JHH = 6 Hz, 2 H), 4.50 38.33, 39.42,
(sept, JHH = 4.8 Hz), 4.95 39.72, 39.97,
(t, JHH = 5.7 Hz, 1 H),
5.38 (d, JHH = 4.5 Hz,
1 H), 6.92 (d, JHH = 8.7 56.60, 74.03,
Hz, 2 H), 7.06 (s, 1 H),
8.09 (d, JHH = 8.7 Hz,
2 H)
22.39, 22.57,
23.77, 24.12,
27.76, 27.99,
H
O
H
H
H
H
H
40.37, 42.25,
50.08, 56.25,
O
N
H
74.86, 115.79,
122.35, 127.02,
127.44, 134.31,
136.47, 139.70,
156.04, 157.76,
160.70, 170.83.
80.6 (43)
a Unless otherwise noted, NMR spectra were recorded in CDCl3.
b In cases where 1H NMR spectra were not of the first order, the H–H and H–F coupling constants were not optimized but were assigned by
visual inspection.
c Compounds are grouped by general phenyl substitution for elemental analysis, which was performed for one compound in each block.
Synthesis of Imidate 2 (Scheme 2, B)17b
K2CO3 (50 mmol) and methyl glycinate hydrochloride (50 mmol)
In summary, the synthetic preparation presented here en-
ables convenient access to a variety of arylideneimida-
were suspended in Et2O (125 mL), followed by addition of H2O (20
zolinones through a 1,3-dipolar, [2+3] cycloaddition of an
mL) then addition of ethyl acetimidate hydrochloride (50 mmol).
imide ylide with aromatic Schiff bases. The reaction pro-
The mixture was shaken for 6 min then the ether was decanted off.
duces the required products in good to excellent yields
An additional portion of Et2O (75 mL) was added, the mixture was
(30–99%) with minimal purification required. New appli-
cations and studies of these arylideneimidazolinones are
currently underway.
shaken for 6 min then the Et2O was decanted off. The combined or-
ganic portions were dried over anhydrous MgSO4 and the solvent
was removed in vacuo to afford the pure imidate (4.30 g, 54%) as
confirmed by NMR analysis.
Melting points were measured on an Electrothermal melting point
apparatus and are uncorrected. H NMR spectra were determined
General Procedure (Scheme 2, C)
1
The required aromatic Schiff base 1 (1 mmol) was combined with
the imidate 2 (1.1 mmol) in absolute EtOH (~1 mL) and the reaction
was allowed to stir in a capped vial overnight under ambient condi-
tions. In cases where the Schiff base was solid, additional EtOH was
used to solubilize the reactants. In some cases, as indicated in
Table 1, the precipitated product was filtered and washed sequen-
tially with Et2O (~2 mL) and EtOH (~1 mL) to yield the pure prod-
uct. In cases where precipitation did not occur at r.t., the reaction
mixture was held at 0 °C for 1–4 d to allow precipitation to occur.
Following this, the product was filtered and washed sequentially
with cold Et2O (~2 mL) and cold EtOH (~1 mL). If precipitation did
not occur by either method, flash column chromatography on silica
gel was performed.
with Varian Mercury Vx 300 spectrometer operating at 300 MHz
(1H) and at 75 MHz (13C), in appropriate solvents, as indicated in
Table 2. Chemical shifts were referenced to TMS. Low-resolution
MS spectra (EI, 70 eV) were measured on a Micromass AutoSpec
spectrometer. Elemental analyses were performed by the Atlantic
Microlab, Inc., Norcross, Georgia (USA). TLC was carried out on
Analtech Uniplate Silica Gel GF plates. Column chromatography
was performed using Sorbent Technologies 40–63 mm standard
grade silica gel. The organic solvents and the reagents used in this
study were used as received from commercial sources (Acros Organics,
Fisher Scientific, Aldrich). The (3S,8S,9S,10R,13R,17R)-10,13-dimeth-
yl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-
tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-aminoeth-
yl)carbamate, an amine employed in entry 24a, was prepared ac-
cording to the reported procedure.21
Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York

2436
A. Baldridge et al.
PAPER
571. (e) Niwa, H.; Inouye, S.; Hirano, T.; Matsuno, T.;
Kojima, S.; Kubota, M.; Ohashi, M.; Tsui, F. I. Proc. Natl.
Acad. Sci. U.S.A. 1996, 93, 13617. (f) Oumouch, S.;
Bourotte, M.; Schmitt, M.; Bourguignon, J.-J. Synthesis
2005, 25.
Acknowledgment
We thank the National Science Foundation (CHE-0809179) for
support. A.B. acknowledges the Center for Organic Photonics and
Electronics (COPE) at Georgia Tech for a research fellowship.
(10) (a) Bhattacharjya, G.; Agasti, S. S.; Ramanathan, G.
ARKIVOC 2006, (x), 152. (b) Yampolsky, I. V.; Kislukhin,
A. A.; Armatov, T. T.; Shcherbo, D.; Potapov, V. K.;
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(11) Ivashkin, P. E.; Yampolsky, I. V.; Lukyanov, K. A. Russ. J.
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Synthesis 2010, No. 14, 2424–2436 © Thieme Stuttgart · New York