Studies on the preparation of 4-ethoxyalkyliden and 4-aminoalkyliden-5(4H)-oxazolones

Article abstract of DOI:10.1081/SCC-120018688

Optimized conditions for the preparation of 4-ethoxyalkyliden5(4H)-oxazolones were developed. A considerable steric hindrance was observed on the nucleophilic substitution of the ethoxy group by amines.

Full text of DOI:10.1081/SCC-120018688

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Studies on the Preparation of 4-Ethoxyalkyliden
and 4-Aminoalkyliden-5(4H)-oxazolones
Marta R. P. Norton Matos , Pedro M. P. Gois , Maria L. E. N. Mata , Eurico J.
Cabrita & Carlos A. M. Afonso
To cite this article: Marta R. P. Norton Matos , Pedro M. P. Gois , Maria L. E. N. Mata , Eurico J.
Cabrita & Carlos A. M. Afonso (2003) Studies on the Preparation of 4-Ethoxyalkyliden and 4-
Aminoalkyliden-5(4H)-oxazolones, Synthetic Communications, 33:8, 1285-1299, DOI: 10.1081/
SCC-120018688
To link to this article: http://dx.doi.org/10.1081/SCC-120018688
Published online: 15 Aug 2006.
Submit your article to this journal
Article views: 57
View related articles
Citing articles: 7 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [University of Nebraska, Lincoln]
Date: 01 November 2015, At: 06:52

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 8, pp. 1285–1299, 2003
Studies on the Preparation of 4-Ethoxyalkyliden
and 4-Aminoalkyliden-5(4H)-oxazolones
Marta R. P. Norton Matos, Pedro M. P. Gois,
Maria L. E. N. Mata, Eurico J. Cabrita,
*
and Carlos A. M. Afonso
REQUIMTE/CQFB, Departamento de Quımica,
Faculdade de Ciencias e Tecnologia, Universidade Nova
de Lisboa, Caparica, Portugal
ABSTRACT
Optimized conditions for the preparation of 4-ethoxyalkyliden-
5(4H )-oxazolones were developed. A considerable steric hindrance
was observed on the nucleophilic substitution of the ethoxy group by
amines.
Key Words: Oxazolones; Nucleophilic substitution; 4-aminoalkyli-
den-5(4H)-oxazolones; E/Z-configuration; Heterocycles.
*Correspondence: Carlos A. M. Afonso, REQUIMTE/CQFB, Departamento de
Quımica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa,
2829-516 Caparica, Portugal; Fax: þ351-21-2948550; E-mail: cma@dq.fct.unl.pt.
1285
DOI: 10.1081/SCC-120018688
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1286
Norton Matos et al.
5(4H)-Oxazolones 1 and 2 are versatile substrates in organic
synthesis.[1] Some recent applications of this type of compounds include
the synthesis of heterocycles,[2] a-aminoacids,[3] peptides,[4] a,b-dehydro-
a-aminoacids,[5] and other units.[6] Among them, 4-ethoxymethylene-2-
phenyl-5(4H)-oxazolone 3a has found wide use as a synthon for different
heterocycles due to the ease of substitution of the ethoxy group by
halogen,[7] nitrogen,[1c,2a,2b,4a,8] sulphur,[3d,9] and carbon[10] nucleophiles.
4-Alkyl-5(4H)-oxazolones 1 and the unsaturated 5(4H)-oxazolones 2
have been prepared, respectively, by dehydration of the N-acylated
aminoacids[3c,4c] and by the Erlenmeyer method. This last method, works
as a one-pot synthesis by heating the aldehyde, acylglycine, acetic
[12]
anhydride with the additives sodium acetate,[1,11] Pb(OAc)4
or zinc
chloride.[13] The ethoxymethylene-2-phenyl-5(4H)-oxazolone 3a has
been formerly prepared in 34% yield by the Erlenmeyer method using
hippuric acid, ethyl orthoformate and acetic anhydride.[14] In spite of
this fact, our attempts to prepare the analogues 3b–3d under the same
conditions[14] were unsuccessful. However, the use of 4-(dimethylamino)-
pyridine (DMAP) and the control of the reaction time and temperature
allowed us to obtain the 5(4H)-oxazolones 3a–3d in moderate to high
yields (Table 1).
The observed effect of DMAP on the formation of 5(4H)-oxazolones
3a–3d can be easily explained by an activation of the acetic anhydride,
which promotes the formation of the intermediate 2-phenyl-5(4H)-
oxazolone enol form, which then reacts with the activated ortho ester.
We have also noticed that the preparation of 3b and 3c required lower
reaction temperature for better conversions (Entries 2 and 3).
The reactivity of the 5(4H)-oxazolones 3a–3d towards nucleophilic
substitution was further explored using representative amines (Table 2).
The substitution with benzylamine occurred readily at 0ꢀC for the
5(4H)-oxazolones 3a–3c, but for 3d (R¼Ph), only moderate conversion

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1287
Table 1. Optimized conditions for the preparation of the 5(4H)-oxazolones
3a–3d from hippuric acid.
Entry
Temperature (ꢀC)
Time
Product
Yielda (%)
1
2
3
4
140
90
30 min
1 h
1 h
3a R ¼ H
3b R ¼ Me
3c R ¼ Et
3d R ¼ Ph
88b
39b
48b
30c
90
140
4 h
aIsolated yield after purification by flash chomatography and crystallization.
bIsolated only one isomer.
cIsolated as a 4.9:1.0 mixture of isomers.
was obtained at room temperature (Entry 11). For the more hindered
dibenzylamine, the required reaction temperature increased with the bulki-
ness of the substituent R of the 5(4H)-oxazolones (R¼H at 0ꢀC; R¼Me
at 40ꢀC, R ¼ Et at 80ꢀC and R¼Ph at 110ꢀC). In the case of the preparation
of 3d we have also isolated the ring opened compound 9, formed by a
competitive attack of the dibenzylamine on the carbonyl group.
The lower reactivity observed for 3b and 3c, when compared with 3a,
should be due to the steric hindrance on the attack of the amino group
on the C10 carbon. For 3d (R¼Ph) the observed lowest reactivity, is
consistent both with the steric hindrance and the predicted less electro-
fillic character of the C10 carbon due to extended conjugation with the
phenyl group.
When concerning the stability of the 5(4H)-oxazolones, in general, the
more stable isomer corresponds to the case were the bulkier group is cis
relative to the nitrogen atom of the 5(4H)-oxazolone.[1d] Reported exam-
ples of general structure 10 (R2 ¼ H) with the Z-configuration includes
for R1 ¼ Aryl,[1d,11,7a,15] Alkyl,[1d,16] OH,[7b] OEt,[14] OAc,[7b] OPiv,[7b]
SPh,[3d,7a] and NMe[2].[17] On the other hand, in case of monoalkylated
amino groups, the more stable isomer corresponds to the E-configuration,
due to the formation of intramolecular hydrogen bond with the carbonyl

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1288
Norton Matos et al.
Table 2. Substitution of 5(4H)-oxazolones 3a-3d with amines.
Entry Substrate
Amine
Solvent Temp.
Time
Product Yielda (%)
1
2
3a R ¼ H Benzylamine
3a R ¼ H (R)-(þ)-1-
CH2Cl2 0ꢀC
CH2Cl2 r.t.
5 h
24 h
4a
5a
69b
55b
Phenylethylamine
3
4
5
6
7
3a R ¼ H Diethylamine
3a R ¼ H Morpholine
3a R ¼ H DiBenzylamine
3b R ¼ Me Benzylamine
3b R ¼ Me (R)-(þ)-1-
CH2Cl2 Reflux
CH2Cl2 Reflux
CH2Cl2 0ꢀC
CH2Cl2 0ꢀC
CH2Cl2 r.t.
2.5 h
3.7 h
20 h
7 h
6a
7a
8a
4b
5b
93b
76b
69b
86c
d
24 h
51
Phenylethylamine
8
9
3b R ¼ Me DiBenzylamine
3c R ¼ Et Benzylamine
3c R ¼ Et DiBenzylamine
3d R ¼ Ph Benzylamine
3d R ¼ Ph DiBenzylamine
CH2Cl2 Reflux
CH2Cl2 0ꢀC
12 days
6 h
8b
4c
8c
4d
8d
9b,e
62f
57g
34h
13i
10
11
12
Benzene Reflux
CH2Cl2 r.t.
Toluene Reflux
12 days
4 days
6 days
aIsolated yield obtained after purification by flash chomatography and crystal-
lization; bIsolated only one isomer; cIsolated as a 2.0:1.0 mixture of isomers;
dIsolated as a 1.7:1.0 mixture of isomers; eRecovered starting substrate 3b in 36%;
fIsolated as a 1.3:1.0 mixture of isomers; g Recovered starting substrate 3c in 19%;
hIsolated as a 5.7:1.0 mixture of isomers; iIsolated the ring opened product 9 in 35%.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1289
3
Table 3. JC-5,H-1 and E/Z configurations determined from 13C NMR.
0
3
0
ꢀ C5
(ppm)
JC-5,H-1
(Hz)
E/Z
configuration
Entry
Compound
1
2
3
4
3a
4a
5a
12
168.3
168.2
167.7
167.5
2.2
9.4
2.2
5.5
Z
E
Z
Z
oxygen as has been illustrated for 10 (R ¼ Ph, R1 ¼ H, R2 ¼ NHBzl,
NHAlk).[17]
The assignment of the E,Z-configuration of 5(4H)-oxazolones of the
general structure 10 where R1 or R2 ¼ H is possible by means of
3
13C NMR by measuring the JC-5,H-1 vicinal coupling constant between
0
the carbonyl carbon and the olefinic b proton. For the 3a related
compounds with an aryl substituent instead of the ethoxy group, as for
example in the case of the isomers 11 and 12 it has been shown that there
0
3
is a significant difference between the JC-5,H-1 coupling of trans- and
cis-isomers of 12.5 Hz and 5.5 Hz respectively.[15] Compound 12 was
3
0
therefore prepared and its JC-5,H-1 coupling constant measured in the
proton coupled 13C NMR spectra, obtained through the inverse gated
decoupling technique. A value of 5.5 Hz was measured which when
compared with the previous reported values indicates that the Z isomer
was obtained (Table 3, Entry 4).[15] This methodology was then further
employed to determine the configuration of compounds 3a, 4a, and 5a.
The values of the coupling constants obtained are reported in Table 3.
The value of the coupling constant measured for 3a (3JC-5,H-1 ¼ 2.2 Hz,
0
Entry 1) indicates that the Z isomer was obtained, being this assignment
also in agreement with the previous reported spectral and physical data.[14]
In case of the 4-aminomethylen-5(4H)-oxazolone 4a the higher value of the
measured coupling constant (3JC-5,H-1 ¼ 9.4 Hz, Entry 2) indicates that the
0
isomer with the E configuration was obtained. As was mentioned pre-
viously, the possibility of formation of an intramolecular hydrogen bond
between the amine proton and the carbonyl oxygen should account for the
higher stability of this isomer. Unexpected was however the result obtained
for 5a, which corresponds to the isomer Z according to the NMR data
(3JC-5,H-1 ¼ 2.2 Hz, Entry 3), but where the same stabilization effect of
0
an intramolecular hydrogen bond leading to formation of the E isomer
was expected. The 4-aminomethylen-5(4H)-oxazolones 6a–8a should
correspond to the E-isomers on basis of the expected more stable isomer.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1290
Norton Matos et al.
The compound 3b correspond to the E-isomer by comparison with
reported physical data. The new compound 3c should correspond to the
E-isomer by comparison of the 13C NMR with the 3b and the expected
effect of the ethyl group. For the other derivatives 4b, 5b, 8b, 4c, and 8c,
we have isolated a mixture of isomers which is rationalized on the basis of
competitive steric effect of the methyl and ethyl groups.
In summary, the conditions presented here allowed the preparation
of 5(4H)-oxazolones 3b–3d in moderate yields and an improved yield for
the preparation of the 5(4H)-oxazolones 3a. The study presented on the
nucleophilic substitution of the ethoxy group by amines, also showed that
the nucleophilic substitution on the C10 carbon by simple amines is
strongly dependent of the steric hindrance on the reactive center. These
results suggest that a careful choice of the reaction conditions is essential
for the preparation 4-aminoalkyliden-5(4H)-oxazolones.
EXPERIMENTAL
All glassware was oven dried and cooled in a desiccator (P2O5 desic-
cant) prior to use. Dichloromethane was distilled from P2O5 powder
under a nitrogen atmosphere. Triethylamine was distilled from NaOH
powder under a nitrogen atmosphere. Commercially supplied reagents
were used as supplied. Anhydrous toluene, benzene and tetrahydrofuran
were prepared by distillation from sodium/benzophenone ketyl under
argon. Flash column chromatography was carried out using Merck 60
silica gel (70–240 mm). Thin layer chromatography was carried out using
Merck Kieselgel 60 F254 precoated, glass backed plates. The plates were
visualized using ultraviolet light (254 nm), KMnO4 solution, ninhydrin or
iodine as appropriate.
1H NMR spectra were recorded on Bruker ARX 400 spectrometer.
Chemical shifts are reported downfield in parts per million (ppm) from
a tetramethyl silane reference. 13C NMR spectra were recorded on

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1291
Bruker ARX 400 spectrometer at 100 MHz. 13C NMR spectra for the
3
determination of the JC-5,H-1 coupling constants were recorded on a
0
Bruker DRX 399 spectrometer. The inverse gated decoupling technique
was employed. Infrared (IR) spectra were recorded on a Buck Scientific
M-500 spectrometer as thinly dispersed films (from CH2Cl2) between
sodium chloride plates unless otherwise stated. Low resolution (EI/FAB)
mass spectra were recorded using a Fisons Autospec or Kratos mass
spectrometer. Optical rotations were carried out using a Optical Activity
Mod. AA-1000 digital polarimeter with a cell path length of 5 cm. Melting
points were carried out on a Gallenkamp melting point apparatus and are
uncorrected.
Preparation of 4Z-(ethoxymethylen)-2-phenyl-5(4H)-oxazolone 3a: To
a stirred mixture of hippuric acid (2.47 g, 13.8 mmol), ethyl orthoformate
(2.3 mL, 13.8 mmol),4-(dimethylamino)pyridine (catalytic amount aprox.
3 mg) at room temperature and under an argon atmosphere was added
acetic anhydride (2.6 mL, 27.6 mmol) and then refluxed for 30 min. The
reaction mixture was concentrated under vacuo and the obtained brown
oil was purified by column chromatography (SiO2, ethyl acetate/n-hexane
2:8) and crystallized from n-hexane to give 3a (2.65 g, 88%), orange
needles, m.p. 94–96ꢀC; Lit.[14] m.p. 94–95ꢀC; Rf ¼ 0.36 (ethyl acetate/
1
n-hexane 2:8); IR and H NMR similar to those reported.[14] 13C NMR
100 MHz (CDCl3): ꢀ 168.3 (>C¼O), 159.2 (-N¼C-), 152.5 (¼CH-), 132.2
(¼CH-, Ar), 128.6 (¼CH-, Ar), 127.5 (¼CH-, Ar), 125.7 (-C-, Ar), 117.6
(-HC¼C<), 72.7 (-OCH2-), 15.1 (-CH3). Compound 3a was slowly dis-
solved (2 days) in iso-propanol, left at room temperature for 24 days and
then new crystals of 4-(iso-propoxymethylen)-2-phenyl-5(4H)-oxazolone
were obtained as yellow plates, m.p. 122–124ꢀC; IR (film): 3065, 3025,
2985, 2930, 1790 (C¼O), 1620 (C¼N), 1280, 1225, 1150, 980, 940, 830,
1
770, 715 cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 8.07 (1H, d, J ¼ 7.6, Ar),
7.54 (1H, dd, J ¼ 7.2, 7.0, Ar), 7.60–7.40 (3H, m, Ar), 7.40 (1H, s, vinyl
H), 5.13 (0.5H, heptet, J ¼ 6.2, CHMe2), 4.62 (0.5H, heptet, J ¼ 6.2,
CHMe2), 1.48 (3H, d, J ¼ 6.2, CH(CH3)2), 1.31 (3H, d, J ¼ 6.2,
CH(CH3)2); 13C NMR 100 MHz (CDCl3): ꢀ 168.6, 159.2, 151.7, 132.3,
128.7, 127.7, 125.9, 117.5, 81.0, 22.4; Anal. calcd. for C13H13NO3: C,
67.5; H, 5.7; N, 6.1. Found: C, 67.7; H, 5.7; N, 5.9.
Preparation of 4-(10-ethoxyethylen)-2-phenyl-5(4H)-oxazolone 3b: To
a stirred mixture of hippuric acid (2.00 g, 11.2 mmol), triethyl orthoace-
tate (2.1 mL, 11.2 mmol), 4-(dimethylamino)pyridine (catalytic amount
aprox. 3 mg) at room temperature and under an argon atmosphere was
added acetic anhydride (2.1 mL, 21.1 mmol) and heated to 90ꢀC (oil bath
temperature) for 1 h. The reaction mixture was concentrated under vacuo
and the obtained brown oil was purified by column chromatography

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1292
Norton Matos et al.
(SiO2, ethyl acetate/n-hexane 1:9) and crystallized from ethyl acetate to
give 3b (1.01 g, 39%), yellow needles, m.p. 112–114ꢀC; Lit.[1d] m.p. 112–
113ꢀC for E isomer and 136–138ꢀC for Z isomer; Rf ¼ 0.97 (ethyl acetate/
n-hexane 2:8); IR (film): 3050, 2990, 2920, 1745 (C¼O), 1620 (C¼N),
1
1574, 1540, 1440, 1380, 1280, 1150, 1053, 973, 890, 790 cmꢁ1; H NMR
400 MHz (CDCl3): ꢀ 8.00 (2H, d, J ¼ 7.1, Ar), 7.49–7.43 (3H, m, Ar), 4.74
(2H, q, J ¼ 7.0, CH2O), 2.53 (3H, s, C¼CCH3), 1.47 (3H, t, J ¼ 7.0,
CH3CH2O); 13C NMR 100 MHz (CDCl3): ꢀ 168.2, 166.6, 154.9,
131.2, 128.3, 126.7, 126.2, 114.6, 68.69, 17.1, 15.01; Anal. calcd. for
C13H13NO3: C, 67.5; H, 5.7; N, 6.1. Found: C, 67.4; H, 5.7; N, 6.1.
Preparation of 4-(10-ethoxypropylen)-2-phenyl-5(4H)-oxazolone 3c: To
a stirred mixture of hippuric acid (1.62 g, 8.94 mmol), triethyl orthopro-
pionate (1.8 mL, 8.9 mmol), 4-(dimethylamino)pyridine (catalytic amount
aprox. 3 mg) at room temperature and under an argon atmosphere was
added acetic anhydride (1.7 mL, 17.4 mmol) and heated to 90ꢀC (oil bath
temperature) for 1 h. The reaction mixture was concentrated under vacuo
and the obtained brown oil was purified by column chromatography
(SiO2, ethyl acetate/n-hexane 0.5:9.5) and the product crystallized from
ethyl acetate to give 3c (0.55 g, 48%), plates, m.p. 58–59ꢀC; Rf ¼ 0.54
(ethyl acetate/n-hexane 1:9); IR (film): 3050, 2990, 2967, 2922, 2866,
1778 (C¼O), 1642 (C¼N), 1585, 1563, 1450, 1393, 1308, 1250, 1150,
1
1211, 1075, 970, 883, 770, 700 cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 7.97
(2H, d, J ¼ 7.1, Ar), 7.49–7.42 (3H, m, Ar), 4.87 (2H, q, J ¼ 7.0, CH2O),
2.90 (2H, q, J ¼ 7.4, CH2C¼C), 1.44 (3H, t, J ¼ 7.0, CH3CH2O), 1.20 (2H,
t, J ¼ 7.5, CH3CH2C¼C); 13C NMR (100 MHz, CDCl3) ꢀ 171.9, 168.3,
154.9, 131.4, 128.6, 126.9, 126.6, 113.8, 70.0, 25.0, 15.3, 11.6; Anal. calcd.
for C14H15NO3: C, 68.6; H, 6.2; N, 5.7. Found: C, 68.5; H, 6.2; N, 5.5.
Preparation of 4-(10-ethoxy-10-phenylmethylen)-2-phenyl-5(4H)-
oxazolone 3d: To a stirred mixture of hippuric acid (1.49 g, 8.32 mmol),
triethyl orthobenzoate (1.9 mL, 8.32 mmol), 4-(dimethylamino)pyridine
(catalytic amount aprox. 3 mg) at room temperature and under an argon
atmosphere was added acetic anhydride (1.5 mL, 16.2 mmol) and then was
refluxed for 4 h. The reaction mixture was concentrated under vacuo and
the obtained brown oil was purified by column chromatography (SiO2,
ethyl acetate/n-hexane 1:9) to give 3d (735 mg, 30%) as viscous yellow oil;
mixture of isomers in the ratio of 4.9:1.0 determined by 1H NMR;
Rf ¼ 0.64 (ethyl acetate/n-hexane 1:9); IR (film): 3058, 2980, 2900, 2930,
2840, 1790 (C¼O), 1630 (C¼N), 1597 (C¼C), 1495, 1450, 1300, 1290,
1
1195, 1098, 996, 883, 849, 770 cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 8.06
(0.34H, d, J ¼ 7.1, Ar), 8.01 (1.66H, d, J ¼ 7.1, Ar), 7.91–7.89 (2H, m, Ar),
7.58–7.42 (6H, m, Ar), 4.69 (0.34H, q, J ¼ 7.0, MeCH2O), 4.29 (1.66H, q,
J ¼ 7.0, MeCH2O), 1.46 (3H, t, J ¼ 7.0, CH3CH2O); 13C NMR 100 MHz

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1293
(CDCl3): ꢀ 165.1, 164.9, 158.1, 131.9, 131.4, 130.5, 129.5, 128.6, 128.3,
127.3, 126.2, 121.8, 70.5, 70.1, 15.5; Acc Mass (FAB): C18H16NO3
(MHþ); calcd. 294.1130 found 294.1110.
Preparation of (E)-4-(N-benzylaminomethylen)-2-phenyl-5(4H)-
oxazolone 4a: To a stirred solution of 3a (501 mg, 2.31 mmol) in anhydrous
dichloromethane (10 mL) at 0ꢀC and under an argon atmosphere was
added dropwise benzylamine (277 mL, 2.54 mmol). After 5 h the
solvent was removed under vacuo and the crude product crystallized
from ethyl acetate to give 4a (440 mg, 69%), plates, m.p. 141–143ꢀC;
Lit.[17] m.p. 136–138ꢀC (ethanol); Rf ¼ 0.34 (ethyl acetate/n-hexane 3:7);
IR and 1H NMR similar to those reported;17 13C NMR 100 MHz (CDCl3):
ꢀ 168.2 (>C¼O), 155.3, 147.2 (¼CH-), 135.9, 130.5, 129.1, 128.6, 128.4,
127.6, 127.0, 126.1, 110.4 (-HC¼C<), 52.9 (-CH2Ph); Anal. calcd. for
C17H14N2O2: C, 73.4; H, 5.1; N, 10.1. Found: C, 73.3; H, 5.1; N, 9.7.
Preparation of (10R)-(Z )-4-[N-(10-phenylethylamino)-methylen]-2-
phenyl-5(4H)-oxazolone 5a: To a stirred solution of 3a (481.4 mg,
2.2 mmol) in anhydrous dichloromethane (5 mL) at room temperature
and under an argon atmosphere was added dropwise (R)-(þ)-1-phenyl-
ethylamine (314 mL, 2.4 mmol). After 24 h the solvent was evaporated
under vacuo. The crude product was purified by column chromatography
(SiO2, diethyl ether/n-hexane 3:7) and crystallized from ethyl acetate/
n-hexane to give 5a (355 mg, 55%), yellow plates, m.p. 114–118ꢀC;
Rf ¼ 0.40 (diethyl ether/n-hexane 3:7); [a]2D0 ¼ ꢁ174.0 (c 1.0, CHCl3); IR
(KBr): 3262 (NH), 3062, 2976, 1742 (C¼O), 1644 (C¼N), 1492, 1449,
1323, 1291, 1199, 1110, 984, 894, 845, 754, 697 cmꢁ1; 1H NMR 400 MHz
(CDCl3): ꢀ 7.94 (2H, d, J ¼ 7.5, Ar), 7.47–7.26 (8H, m, vinyl H and Ar), 6.5
(1H, d, J ¼ 9.0, N–H), 4.65 (1H, m, MeCHNH), 1.68 (3H, d, J ¼ 6.8,
CH3HC); 13C NMR 100 MHz (CDCl3): ꢀ 167.8 (>C¼O), 155.3 (-C-, Ar),
141.5 (¼CH-), 140.9, 131.0, 129.2, 128.7, 128.4, 126.9 (-C-, Ar), 126.6,
126.3, 110.0 (-HC¼C<), 57.1 (-CH-), 22.7 (-CH3); Anal. calcd. for
C18H16N2O2: C, 74.0; H, 5.5; N, 9.6. Found: C, 74.0; H, 5.4; N, 9.6.
Preparation of 4-(N,N-diethylaminomethylen)-2-phenyl-5(4H)-oxazo-
lone 6a: To a stirred solution of 3a (100 mg, 0.46 mmol) in anhydrous
dichloromethane (1 mL) at reflux and under an argon atmosphere was
added dropwise diethylamine (52 mL, 0.51 mmol). After 2.5 h the solvent
was evaporated under vacuo and the crude product was purified by
column chromatography (SiO2, ethyl acetate/n-hexane 2:8) to give 6a
(105 mg, 93%), yellow viscous liquid at room temperature, solid in the
fridge, m.p. 45–50ꢀC; Lit.[7b] oil, Rf ¼ 0.83 (ethyl acetate/n-hexane 2:8);
1
Spectral data (IR, H and 13C NMR) identical to those reported[7b]; MS
(FAB) m/z 245 (MHþ), 244, 229, 128, 111; Acc Mass (FAB): C14H17N2O2
(MHþ); calcd. 245.12900. Found: 245.12905.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1294
Norton Matos et al.
Preparation of 4-(N-morpholinomethylen)-2-phenyl-5(4H)-oxazolone
7a: To a stirred solution of 3a (200 mg, 0.92 mmol) in anhydrous dichloro-
methane (4 mL) at reflux and under an argon atmosphere was added
dropwise morpholine (88 mL, 0.10 mmol). After 3.7 h the solvent was
evaporated under vacuo and crystallized from ethyl acetate/n-hexane
to give 7a (180 mg, 76%), prisms, m.p. 157–158ꢀC; Rf ¼ 0.84 (ethyl
acetate/n-hexane 4:6); IR (film): 3014, 2971, 2910, 1750 (C¼O),
1
1643 (C¼N), 1266, 740 cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 7.93–7.89
(2H, m, Ar), 7.44–7.38 (4H, m, Ar), 7.07 (1H, s, vinyl H), 4.42 (2H,
dd, J ¼ 4.8, 4.4, CH2N), 3.81 (4H, dd, J ¼ 4.4, 9.6, CH2O), 3.50
(2H, dd, J ¼ 4.8, 4.4, CH2N); 13C NMR 100 MHz (CDCl3): ꢀ 170.2,
153.6, 140.7, 130.8, 128.6, 127.1, 126.5, 107.9, 66.9, 66.3, 54.3,
47.6; Acc Mass (EI): C14H14N2O3 (Mþ); calcd. 259.1083. Found:
259.1069.
Preparation
of
4-(N,N-dibenzylaminomethylen)-2-phenyl-5(4H)-
oxazolone 8a: To a stirred solution of 3a (101.6 mg, 0.47 mmol) in anhy-
drous dichloromethane (3.5 mL) at 0ꢀC and under an argon atmosphere
was added dropwise dibenzylamine (99 mL, 0.52 mmol). After 20 h the
solvent was removed under vacuo and the crude product was crystallized
from ethyl acetate to give 8a (118.4 mg, 69%), plates, m.p. 164–165ꢀC;
Rf ¼ 0.65 (ethyl acetate/n-hexane 3:7); IR (film): 3024, 2990, 2910,
2840, 1733 (C¼O), 1640 (N¼C), 1585, 1574, 1450, 1390, 1325, 1235,
1210, 1130, 1064, 974, 860, 758, cmꢁ1 1H NMR 400 MHz (CDCl3):
;
ꢀ 7.93 (2H, d, J ¼ 6.5, Ar), 7.41–7.34 (12H, m, Ar and vinyl H), 7.22
(2H, d, J ¼ 7.6, Ar), 5.28 (2H, s, CH2NR2), 4.40 (2H, s, CH2NR2);
13C NMR 100 MHz (CDCl3): ꢀ 170.3, 153.7, 142.2, 135.8, 134.6,
130.7, 129.1, 128.9, 128.6, 128.5, 128.1, 127.0, 127.1, 126.5, 108.2, 59.2,
51.5; Anal. calcd. for C24H20N2O2: C, 78.2; H, 5.5; N, 7.6. Found: C, 78.0;
H, 5.3; N, 7.4.
Preparation of 4-[10-(N-benzylamino)-ethylen]-2-phenyl-5(4H)-
oxazolone 4b: To a stirred solution of 3b (370 mg, 1.6 mmol) in anhydrous
dichloromethane (10 mL) at 0ꢀC and under an argon atmosphere was
added dropwise benzylamine (192 mL, 1.8 mmol). After 7 h the solvent
was evaporated under vacuo and the crude product was crystallized
from ethyl acetate to give 4b (400.7 mg, 86%), yellow needles, m.p.
143–145ꢀC; mixture of isomers in the ratio of 2.0:1.0 determined by
1H NMR; Lit.[1d,18] Z-isomer m.p. 127–129ꢀC; Rf ¼ 0.40 (ethyl acetate/
n-hexane 3:7); IR (film): 3270 (NH), 3047, 3024, 2920, 1720 (C¼O),
1630 (N¼C), 1574, 1550, 1450, 1430, 1360, 1325, 1087, 1053, 985, 940,
1
860, 735, 700 cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 8.83 (1H, s, NHR2),
7.93 (2H, dd, J ¼ 4.7 and 3.5, Ar) 7.40–7.26 (8H, m, Ar), 4.6 and 4.55
(2H, d, J ¼ 5.6, CH2NH), 2.52 and 2.45 (3H, s, H3CC¼C); 13C NMR

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1295
100 MHz (CDCl3): ꢀ 166.6, 157.0, 153.0, 136.4, 130.4, 130.0, 129.0, 128.5,
128.0, 127.1, 127.0, 126.8, 126.3, 125.9; 108.2, 47.3, 46.8, 14.2, 12.4;
Anal. calcd. for C18H16N2O2: C, 74.0; H, 5.5; N, 9.6. Found: C, 74.0;
H, 5.6; N, 9.6.
Preparation of (100R)-4-[10-[N-(100-phenylethylamino)-]-methylen]-
2-phenyl-5(4H )-oxazolone 5b: To a stirred solution of 3b (183.9 mg,
0.80 mmol) in anhydrous dichloromethane (4 mL) at room temperature
and under an argon atmosphere was added dropwise (R)-(þ)-1-phenyl-
ethylamine (113 mL, 0.88 mmol). After 24 h the solvent was evaporated
under vacuo and the crude product was purified by column chromato-
graphy (SiO2, ethyl acetate/n-hexane 3:7) to give 5b (123 mg, 51%),
as a yellow viscous liquid, mixture of isomers in the ratio of 1.7:1.0
determined by 1H NMR; Rf ¼ 0.40 (diethyl ether/n-hexane 3:7);
[a]2D0 ¼ ꢁ495.6 (c 1.5, CHCl3); IR (film): 3365 (NH), 3062, 2979, 2929,
1728 (C¼O), 1626 (C¼N), 1494, 1418, 1325, 1232, 1123, 1087, 969, 880,
768, 694 cmꢁ1; 1H NMR 400 MHz (CDCl3): ꢀ 8.80 (2H, d, J ¼ 7.4, N–H),
7.99–7.91 (2H, m, Ar), 7.41–7.11 (8H, m, Ar), 4.79 (1H, m, PhCHMe),
2.36 and 2.29 (3H, s, CH3C¼C), 1.60 (3H, d, J ¼ 6.8, PhCHCH3);
13C NMR 100 MHz (CDCl3): ꢀ 167.8, 166.4, 159.3, 156.5, 152.5, 151.2,
142.7, 142.6, 130.3, 129.8, 128.9, 128.4, 127.6, 127.4, 127.1, 126.2, 126.0,
125.8, 125.3, 109.4, 108.0, 53.5, 52.8, 24.1, 23.8, 14.4, 14.0; MS (FAB) m/z
307 (MHþ), 306, 203, 202, 105; Acc Mass (EI ): C19H18N2O2 (Mþ);
calcd. 306.13683. Found: 306.13835.
Preparation of 4-[10-(N,N-dibenzylamino)-ethylen]-2-phenyl-5(4H)-
oxazolone 8b: To a stirred solution of 3b (446 mg, 1.9 mmol) in anhydrous
dichloromethane (10 mL) at 0ꢀC and under an argon atmosphere was
added dropwise dibenzylamine (408 mL, 2.1 mmol). After 3 h at 0ꢀC and
18 h at room temperature (no reaction by TLC) the reaction mixture was
refluxed. After 12 days, the solvent was evaporated under vacuo and the
crude product was purified by column chromatography (SiO2, ethyl
acetate/n-hexane 2:8) and crystallized from ethyl acetate/n-hexane to
give recovered 3b (162.6 mg, 36%) and 8b (63.5 mg, 9%), as white
plates, m.p. 188–190ꢀC; Rf ¼ 0.8 (ethyl acetate/n-hexane 3:7); IR (film):
3100, 3090, 3060, 3035, 3015, 2990, 1700 (C¼O), 1640 (N¼C), 1619,
1560, 1545, 1505, 1450, 1430, 1390, 1257, 962, 690 cmꢁ1 1H NMR
;
400 MHz (CDCl3): ꢀ 7.79 (2H, d, J ¼ 6.7, Ar), 7.40–7.25 (13H, m, Ar),
4.5–5.5 (4H, br, PhCH2N), 2.74 (3H, s, CH3C¼C); 13C NMR 100 MHz
(CDCl3): 169.2, 156.5, 150.5, 130.1, 128.9, 128.5, 127.7, 127.4, 126.9,
126.2, 108.3, 54.7, 16.2; Anal. calcd. for C25H22N2O2: C, 78.5; H, 5.8;
N, 7.3. Found: C, 78.5; H, 5.6; N, 7.2.
Preparation of 4-[10-(N-benzylamino)-propylen]-2-phenyl-5(4H)-
oxazolone 4c: To a stirred solution of 3c (73 mg, 0.30 mmol) in anhydrous

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1296
Norton Matos et al.
dichloromethane (3 mL) at 0ꢀC and under an argon atmosphere was
added dropwise benzylamine (36 mL, 0.33 mmol). After 6 h the solvent
was evaporated under vacuo and the crude product was crystallized
from ethyl acetate to give 4c (55.2 mg, 62%), yellow needles, m.p.
105–108ꢀC; Rf ¼ 0.60 (ethyl acetate/n-hexane 3:7); mixture of isomers in
1
the ratio of 1.3:1.0 determined by H NMR; IR (film): 3260 (NH), 3035,
3024, 2970, 2920, 2870, 1710 (C¼O), 1642 (N¼C), 1600, 1585, 1563,
1540, 1506, 1460, 1390, 1340, 1235, 1166, 1087, 1030, 883, 725 cmꢁ1
;
1H NMR 400 MHz (CDCl3): ꢀ 8.76 and 7.05 (1H, s, NH), 7.93 (2H, d,
J ¼ 7.6, Ar), 7.40–7.25 (8H, m, Ar), 4.61 (1.12H, d, J ¼ 6.6, PhCH2NH),
4.59 (0.88H, d, J ¼ 8.3, PhCH2NH), 3.00 (1.12H, q, J ¼ 7.4, CH3CH2),
2.88 (0.88H, q, J ¼ 7.4, CH3CH2), 1.28 (1.68H, t, J ¼ 7.4, CH3CH2), 1.27
(1.32H, t, J ¼ 7.4, CH3CH2); 13C NMR 100 MHz (CDCl3): ꢀ 167.0, 164.8,
162.1, 136.8, 130.4, 129.9, 129.1, 129.0, 128.5, 128.2, 128.0, 127.7, 127.1,
126.8, 126.3, 126.0, 118.0, 109.0, 107.0, 47.0, 46.6, 21.1, 19.3, 12.4, 12.3;
Anal. calcd. for C19H18N2O2: C, 74.5; H, 5.9; N, 9.1; Found: C, 74.5;
H, 5.8; N, 9.1.
Preparation of 4-(N,N-dibenzylaminopropylen)-2-phenyl-5(4H)-
oxazolone 8c: To a stirred solution of 3c (339 mg, 1.4 mmol) in anhydrous
benzene (3 mL) at room temperature and under an argon atmosphere was
added dropwise dibenzylamine (291 mL, 1.5 mmol) and refluxed for
12 days. The solvent was evaporated under vacuo and the crude product
was purified by column chromatography (SiO2, ethyl acetate/n-hexane
3:7) and crystallized from ethyl acetate/n-hexane to give recovered 3c
(65.6 mg, 19%) and 8c (314.5 mg, 57%), plates, m.p. 140–142ꢀC;
Rf ¼ 0.50 (ethyl acetate/n-hexane 3:7); IR (film): 3070, 3050, 3020, 1700
(C¼O), 1670 (N¼C), 1565, 1560, 1460, 1420, 1240, 1120, 1100, 1008, 940,
1
cmꢁ1; H NMR 400 MHz (CDCl3): ꢀ 7.79 (2H, d, J ¼ 5.6, Ar), 7.38–7.25
(13H, m, Ar), 4.6–5.5 (4H, br, PhCH2N), 3.19 (2H, q, J ¼ 6.5, CH2CH3),
1.29 (3H, t, J ¼ 6.5, CH2CH3); 13C NMR 100 MHz (CDCl3): ꢀ 168.4,
162.1, 150.8, 136.7, 130.1, 129.0, 128.5, 127.8, 127.5, 126.9, 126.2, 107.5,
54.1, 22.5, 13.3; Anal. calcd. for C26H24N2O2: C, 78.7; H, 6.1; N, 7.1.
Found: C, 79.4; H, 6.2; N, 7.1.
Preparation of 4-[10-(N-benzylamino)-10-phenylmethylen]-2-phenyl-
5(4H)-oxazolone 4d: To a stirred solution of 3d (513 mg, 1.8 mmol)
in anhydrous dichloromethane (3 mL) at 0ꢀC and under an argon
atmosphere was added dropwise benzylamine (210 mL, 1.9 mmol). After
6 h at 0ꢀC and 4 days at room temperature the solvent was evaporated
under vacuo purified by column chromatography (SiO2, dichloro-
methane/n-hexane 7:3) and the crude product was crystallized from
ethyl acetate/n-hexane to give 4d (217 mg, 34%), as yellow plates,
m.p. 144–146ꢀC; Rf ¼ 0.45 (dichloromethane/n-hexane 7:3); mixture of

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1297
1
isomers in the ratio of 5.7:1.0 determined by H NMR; IR (film): 3260
(N–H), 3110, 3090, 3045, 3024, 1710 (C¼O), 1642 (N¼C), 1620, 1563,
1540, 1495, 1450, 1430, 1390, 1221, 1098, 1007, 962, 883, 769 cmꢁ1
;
1H NMR 400 MHz 8.89 (1H, s, NH), 7.88 (0.3H, m, Ar), 7.87
(1.7H, m, Ar), 7.51–7.18 (13H, m, Ar), 4.47 (1.7H, q, J ¼ 6.4, CH2N),
4.33 (0.3 H, q, J ¼ 6.4, CH2N); 13C NMR 100 MHz (CDCl3): ꢀ 169.0,
160.0, 137.3, 130.7, 130.5, 130.2, 129.4, 128.9, 128.8, 128.6, 128.5,
128.4, 127.8, 127.3, 127.2, 126.9, 126.6, 126.3, 110.3, 48.8, 48.1; Anal.
calcd. for C23H18N2O2: C, 78.0; H, 5.2; N, 7.9. Found: C, 77.9;
H, 5.1; N, 7.9.
Preparation of 4-[10-(N-dibenzylamino)-10-phenylmethylen]-2-phenyl-
5(4H)-oxazolone 8d: To a stirred solution of 3d (422 mg, 1.4 mmol) in
anhydrous toluene (6 mL) at room temperature and under an argon
atmosphere was added dropwise dibenzylamine (304 mL, 1.6 mmol) and
was refluxed for 6 days. The solvent was evaporated under vacuo and the
crude product was purified by column chromatography (SiO2, ethyl
acetate/n-hexane 3:7) to give 8d (80 mg, 13%) as viscous yellow oil,
Rf ¼ 0.80 (ethyl acetate/n-hexane 3:7) and the opened product 9 (246 mg,
35%), as plates, m.p. 145–150ꢀC; Rf ¼ 0.25 (ethyl acetate/n-hexane 3:7);
8d: IR (film): 3060, 3027, 2925, 2858, 1747 (C¼O), 1616 (N¼C), 1536,
1
1448, 1328, 1294, 1193, 1106, 1072, 1008, 933 cmꢁ1; H NMR 400 MHz
(CDCl3): 7.95 (2H, d, J ¼ 6.9, Ar), 7.94 (2H, d, J ¼ 7.7, Ar), 7.54–7.22
(16H, m, Ar), 5.6 and 4.2 (4H, s, PhCH2N); 13C NMR 100 MHz (CDCl3):
ꢀ 167.4, 156.8, 152.8, 133.6, 130.4, 129.8, 128.9, 128.7, 128.6, 128.4, 127.7,
126.3, 109.1, 53.9; MS (EI) m/z 444 (Mþ), 353, 335, 105, 91, 77; Acc Mass
(EI): C30H24N2O2 (Mþ); calcd. 444.18378, found 444.18466; 9: IR
(KBr): 3239 (N–H), 3060, 3027, 2975, 1660 (C¼O), 1610 (C¼O), 1515,
1
1481, 1444, 1305, 1108, 1076, 1027 cmꢁ1; H NMR 400 MHz (CDCl3):
ꢀ 8.22 (1H, s, NH), 7.85 (2H, d, J ¼ 7.4, Ar), 7.54–6.82 (18H, m, Ar),
4.45 (2H, s, PhCH2N), 4.27 (2H, s, PhCH2N), 3.74 (2H, q, J ¼ 6.7,
CH2CH3), 1.29 (3H, t, J ¼ 6.7, CH2CH3); 13C NMR 100 MHz (CDCl3):
ꢀ 165.8, 163.7, 142.6, 136.1, 135.7, 134.0, 131.8, 131.6, 129.2, 129.0,
128.6, 128.4, 128.3, 128.0, 127.2, 126.9, 117.5, 65.7, 52.0, 46.7, 15.6;
Anal. calcd. for C32H26N2O3: C, 79.0; H, 5.4; N, 5.8. Found: C, 78.2;
H, 6.0; N, 5.7.
Preparation of 4Z-(phenyl-methylen)-2-phenyl-5(4H)-oxazolone 12:
This compound was prepared from hippuric acid following reported
procedure,[13] m.p. 163–164ꢀC; Lit.[15] m.p. 165–166ꢀC, Lit.[13] m.p. 170ꢀC,
IR and 1H NMR similar to those reported[13] 13C NMR 100 MHz
;
0
(CDCl3): ꢀ 167.6 (>C¼O) (C5, JC5,H1 ¼ 5.4 Hz), 163.5, 134.1, 133.5,
133.2, 132.5, 131.9, 131.7 (-HC¼C<), 130.9, 130.4, 129.7, 129.2, 128.1,
127.5, 125.6 (¼CH-).

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1298
Norton Matos et al.
ACKNOWLEDGMENTS
This work was supported by the Fundacao para a Ciencia e
Tecnologia (FCT, project PRAXIS XXI PCEX/C/QUI/53/96).
REFERENCES
1. Reviews: (a) Hartner,
F.W., Jr. Comprehensive Heterocyclic
Chemistry II: Oxazoles; Katritzky, A.R., Rees, C.W., Scriven,
E.F.C., Eds.; Pergamon: Oxford, 1996; Vol. 3, 261–318; (b)
Schmidt, U.; Lieberknecht, A.; Wild, J. Synthesis 1988, 159–172;
(c) Mukerjee, A.K. Heterocycles 1987, 26, 1077–1097; (d) Rao,
Y.S.; Filler, R. Synthesis 1975, 749–764; For natural compounds
containing the unit 2 see: (e) Bergman, J.; Roue, N. Tetrahedron
1999, 55, 14729–14738 and references cited therein.
2. (a) Kepe, V.; Kozjan, V.; Polanc, S.; Kocevar, M. Heterocycles 1999,
50, 315–322; (b) Kepe, V.; Pozgan, F.; Golobic, A.; Polanc, S.;
Kocevar, M. J. Chem. Soc. Perkin 1 1998, 2813–2816; (c) Adachi,
M.; Sasatani, T.; Chomei, N.; Takada, S. Tetrahedron Lett. 1996, 37,
8871–8874; (d) Cannella, R.; Clerici, F.; Gelmi, M.L.; Penso, M.;
Pocar, D. J. Org. Chem. 1996, 61, 1854–1856.
3. (a) Brown, S.A.; Parker, M.-C.; Turner, N. J. Tetrahedron: Asymm.
2000, 11, 1687–1690; (b) Trost, B.M.; Ariza, X. J. Am. Chem. Soc.
1999, 121, 10727–10737; (c) Gottwald, K.; Seebach, D. Tetrahedron
1999, 55, 723–738; Clerici, F.; Gelmi, M.L.; Pocar, D. J. Org. Chem.
1999, 64, 726–730; (d) Liang, J.; Ruble, J.C.; Fu, G.C. J. Org. Chem.
1998, 63, 3154–3155; (e) Avenoza, A.; Busto, J.H.; Peregrina, J.M.;
Cataviela, C. Synthesis 1998, 1335–1338; (f ) Avenoza, A.; Busto,
J.H.; Parıs, M.; Peregrina, J.M.; Cataviela, C. J. Heterocyclic
Chem. 1997, 34, 1099–1110; (g) Schmidt,U.; Kumpf, S.; Neumann,
K. J. Chem. Soc., Chem. Commun. 1994, 1915–1916.
4. (a) Beholz, L.G.; Benovsky, P.; Ward, D.L.; Barta, N.S.; Stille, J.R.
J. Org. Chem. 1997, 62, 1033–1042; (b) Stock, H.T.; Turner, N.J.
Tetrahedron Lett. 1996, 37, 6575–6578; (c) Obrecht, D.; Altorfer, M.;
Lehmann, C.; Schonholzer, P.; Muller, K. J. Org. Chem. 1996,
61, 4080–4086; (d) Ojima, I.; Kojure, T.; Yoda, N.; Suzuki, T.;
Yatabe, M.; Tanaka, T. J. Org. Chem. 1982, 47, 1329–1334.
5. (a) Kralj, L.; Hvala, A.; Svete, J.; Golic, L.; Stanovnik, B.
J. Hetereocyclic Chem. 1997, 34, 247–255; (b) Palacios, F.; Legido, M.;
Heredia, I.P.; Rubiales, G. Heterocycles 2000, 52, 1057–1064.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
4-Ethoxyalkyliden and 4-Aminoalkyliden-5(4H )-oxazolones
1299
6. (a) Park, B.S.; Oh, C.M.; Chun, K.H.; Lee, J.O. Tetrahedron Lett.
1998, 39, 9711–9714; (b) Bratusek, U.; Hvala, A.; Stanovnik, B.
J. Hetereocyclic Chem. 1998, 35, 1281–1284.
7. (a) Beccalli, E.M.; Clerici, F.; Gelmi, M.L. Tetrahedron 1999, 55,
781–786; (b) Wick, L.; Tamm, C.; Neuburger, M.; Zehnder, M.
Tetrahedron 1995, 51, 10219–10230.
8. (a) Kepe, V.; Kocevar, M.; Polanc, S. Heterocycles 1993, 35,
955–963; (b) Tikdari, A.M.; Tripathy, P.K.; Mukerjee, A.K.
J. Chem. Soc. Perkin Trans I 1988, 1659–1662.
9. Mukerjee, A.K.; Rao, L.; Homani, S.S.; Joseph, K. Can. J. Chem.
1994, 72, 1383–1387.
10. Gelmi, M.L.; Pocar, D. Synthesis 1992, 453–455.
11. (a) Alkaabi, S.S.; Shawali, A. Can. J. Chem. 1992, 70, 2515–2519;
(b) Cataviela, C.; Villegas, M.D.D.; Mayoral, J.A. Synthesis 1983,
899–902.
12. (a) Gelmi, M.L.; Clerici, F.; Melis, A. Tetrahedron 1997, 53,
1843–1854; (b) Cativiela, C.; Melendez, E. Synthesis 1978, 832–834.
13. Rao, P.S.; Venkataratnam, R.V. Indian J. Chem. 1994, 33B,
984–985.
14. Bland, J.M.; Stammer, C.H. J. Org. Chem. 1984, 49, 1634–1636.
15. Prokof’ev, E.P.; Karpeiskaya, E.I. Tetrahedron Lett. 1979, 737–740.
16. (a) Jung, B.; Kim, H.; Park, B.S. Tetrahedron Lett. 1996, 37,
4019–4022; (b) Cativiela, C.; Dıaz-de-Villegas, M.D.; Jimenez, A.I.;
Lahoz, F. Tetrahedron Lett. 1994, 35, 617–620; (c) Combs, A.P.;
Armstrong, R.W. Tetrahedron Lett. 1992, 33, 6419–6422.
17. Singh, M.K.; Singh, K.K.; Singh, R.S.; Singh, R.M. Indian. J.
Chem. 1997, 36B, 137–141.
18. Cook, D.C.; Lawson, A. J. Chem. Soc. Perkin 1 1973, 465–468.
Received in the USA April 1, 2002

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.