Synthesis and spectroscopic studies of 5-arylidene-3-substituted tetramic acids as possible substrates for catalytic asymmetric hydrogenation

Article abstract of DOI:10.1002/jhet.5570380527

A new series of 5-arylidene-3-substituted tetramic acids 6-19 have been synthesized by a condensation reaction of 3-butanoyl tetramic acid 3, 3-ethoxycarbonyl tetramic acid 4 and 3-acetyl tetramic acid 5 with a variety of substituted benzaldehydes. The st

Full text of DOI:10.1002/jhet.5570380527

Sep-Oct 2001
Synthesis and Spectroscopic Studies of
5-Arylidene-3-substituted Tetramic Acids as Possible
Substrates for Catalytic Asymmetric Hydrogenation
Giorgos Athanasellis, Efstathios Gavrielatos and Olga Igglessi-Markopoulou*
1203
Laboratory of Organic Chemistry, Department of Chemical Engineering, National Technical
University of Athens, Zografou Campus, 15773 Athens, Greece
Received March 2, 2001
A new series of 5-arylidene-3-substituted tetramic acids 6-19 have been synthesized by a condensation
reaction of 3-butanoyl tetramic acid 3, 3-ethoxycarbonyl tetramic acid 4 and 3-acetyl tetramic acid 5 with a
variety of substituted benzaldehydes. The structures of the isolated compounds 6-19 have been elucidated
1
13
using FT-IR, H and C-NMR spectroscopy, FAB-MS spectroscopy as well as elemental analyses.
J. Heterocyclic Chem., 38, 1203 (2001).
Derivatives of pyrrolidine-2,4-diones (Figure 1) are
During the last decade our research group has been
investigating the synthesis of heterocyclic compounds
bearing the β,β'-tricarbonyl moiety such as tetramic acids,
quinolin-2,4-diones and 1,8-napthyridin-2,4-diones. In the
course of these studies we have proposed a novel method
for the synthesis of 3-substituted tetramic acids [8]. This
method has been extended to the synthesis and structure
investigation of a large number of 3-substituted tetramic
acids [9-11]. In addition, we have examined the complexa-
tion of tetramic acids with transition metals [12,13]. Our
interest has been focused on 3-acyl and 3-alkoxycarbonyl-
5-arylidene tetramic acids (Figure 3).
naturally important substances which display diverse
structural and stereochemical features [1]. Tetramic
acids, pyrrolidine-2,4-diones, acylated at 3-position,
have been extensively studied because of their unique
structure and interesting biological and pharmacological
properties [1,2].
Figure 1. Pyrrolidine-2,4-dione ring.
Members of the 3-acyl tetramic acid group of compounds
are tenuazonic acid, tirandamycin, streptolydigin,
ikaguramycin and erythroskyrine [1], common derivatives
in a number of plants. These compounds exhibit a number
of biological properties from antiviral, antitumor, antibiotic
and antimicrobial to inhibition of DNA-directed RNA poly-
merase and terminal deoxynucleotidyl transferase [1]. As a
further example, 5-arylidene-3-phenyl tetramic acid
(Figure 2) has been designed as a novel glycine site
N-methyl-D-aspartate (NMDA) receptor antagonist in the
treatment of neurological diseases [3].
Figure 3. 3-Acyl- and 3-alkoxycarbonyl-5-arylidene tetramic acids.
These compounds contain important structural adjuncts
such as an enolic β,β'-tricarbonyl moiety, a lipophilic
substituent at position 3 and a hydrophobic group at the
5-position which allow them to exhibit versatile activity
(Figure 4). In addition, the β,β'-tricarbonyl moiety described
above provides them with sites available for complexation.
The antibiotic 'magnesidin' (Figure 4) isolated from
'Pseudomonas magnesiorubra' as a mixture of covalent
magnesium chelates of the 3-alkanoyl-5-ethylidene tetramic
acid derivatives is an example of such metal complexes
which exhibit a variety of biological properties [1,14-17].
Recently, 5-benzylidene-3-hexanoyl tetramic acid was
synthesized and used as the ligand for the complexation
with Mg (II), Zn (II) and Ba (II) chlorine salts [18].
Additionally, the double bonds between C-3 and C-4 as
well as C-5 and C-6 make these compounds very
promising substrates for catalytic asymmetric hydro-
genation. Stereospecific syntheses of 'statine' analogues
were reported via stereocontrolled reduction (C3-C4) of
tetramic acids [19].
Figure 2. 5-Arylidene-3-phenyl tetramic acid.
In recent years much attention has been given to the
synthesis of chiral tetramic acids using optically active
amino acid derived precursors. The applied methodologies
are modifications of the enantioselective Lacey-
Dieckmann cyclisation, requiring strong conditions
(sodium ethoxide in ethanol, reflux) [4-7].

1204
G. Athanasellis, E. Gavrielatos and O. Igglessi-Markopoulou
Vol. 38
Figure 4. 3-Acyl-5-arylidene tetramic acids (I), Magnesidine (II).
In this paper we wish to report a practical method for the
The synthesis of compounds 6-19 involved the conden-
sation of tetramic acids 3, 4 or 5 (1 equivalent) with
substituted-benzaldehydes (2 equivalent) in the presence
of a solution of 8% hydrochloric acid in ethanol. These
compounds were isolated in good yields and
recrystallised from hot ethanol. Previous strategies to
these compounds are less convenient and give lower
yields [20]. The Z configuration of the double bond was
assigned according to the literature based on a
synthesis of 5-arylidene-3-butanoyl-, 3-ethoxycarbonyl
and 3-acetyl tetramic acids 6-11, 12-18 and 19, respec-
tively (Figure 5). The structure of the newly prepared
1
13
compounds was supported by H and C-NMR, FT-IR
spectroscopy , and MS and HETCOR experiments.
1
comparison of the H NMR chemical shift data for the
vinyl proton signals at the region of 6.42-6.65 ppm with
those of similar tetramates [20] (see experimental,
compound 18).
Figure 5. Atom numbering for compounds 6-19.
Following the protocol previously developed in our
laboratory [8,9] we synthesized the required tetramic acids
3, 4 and 5 (Scheme 1).
The N-hydroxysuccinimide ester 1 was easily prepared
from the reaction of N-acetyl-glycine with N-hydroxy-
succinimide and N,N-dicyclohexylcarbodiimide in anhy-
drous tetrahydrofuran at 60 °C. The next step involved the
C-acylation of an active methylene compound 2 (2 equiva-
lents) in the presence of sodium hydride (2 equivalents)
with the N-hydroxysuccinimide ester 1 in anhydrous
tetrahydrofuran. The tetramic acids 3, 4 and 5 were the
products of this reaction after 2.5 hours of stirring at room
temperature.

Sep-Oct 2001
Synthesis and Spectroscopic Studies of 5-Arylidene-3-substituted
1205
1
The H-NMR spectra of 3-substituted tetramic acids 6,
12, 15, 16 and 17 show one set of signals for all protons in
hexadeuteriodimethylsulfoxide solution (polar solvent).
1
13
On the other hand, the H and C NMR spectra of
3-acetyl-5-benzylidene tetramic acid 19 show the
characteristic pair of signals, indicating that this compound
in deuteriochloroform solution exists to a great extent as
1
→
the 'external' tautomers a b. In addition, the H NMR
←
spectra of compounds 7-11, 13, 14 and 19 in deuterio-
chloroform solution, reveal the presence of two signals for
certain protons, showing that the dominant form should be
→
the a b tautomers.
←
The HETCOR experiment establishes the carbon and
proton connectivities for compounds 8, 10, 14, and 17. The
spectral assignments for compound 17 are representative
for the series of 3'substituted (meta) arylidene tetramic
acids. In particular, correlations were observed between
the carbons resonating at δ (ppm) 122.3 (C-f), 114.8 (C-c),
114.5 (C-b) and 134.9 (C-e) and protons resonating at δ
(ppm) 6.87 (1H, dd, H-f), 7.11 (1H, s, H-c), 7.18 (1H, d,
H-b) and 7.28 (1H, t, H-d), respectively.
3-Acyl tetramic acids can possibly exist in four
Another observation is that the carbon, which is attached
tautomeric forms a, b, c, d (Scheme 2) [21, 22]. In
to the OCH group, shows a chemical shift at lower field
3
→
deuteriochloroform solution, internal tautomers a b and
←
than that attached to the NO or Cl group. This observation
2
→
c
d are rapidly interconverted by intramolecular
←
is well explained through the electron donor character of
displacement of the enolic proton along with the hydrogen
bond, whereas the interconversion between external
the OCH group in contrast to the electron withdrawing
3
character of NO and Cl groups. This character also affects
2
→
tautomers ab cd is a comparatively slow process in the
the chemical shifts of the other carbons of the aromatic
ring through the resonance forms of this ring.
←
NMR time-scale; therefore the external tautomers give
separate NMR signals. The ratio between these two
tautomers has been sufficiently discussed and explained in
previous papers relating to tetramic acids [8-10,18].
The FT-IR spectra of the compounds 6-19 showed a
-1
moderate intensity absorption band at ca. 3200 cm attrib-
utable to the ν (NH). The carbonyl absorption bands were
Table 1
13
2
C NMR Spectra of Compounds 6-11 ( [H ]DMSO)
6
Compound
C-10 C-9
C-8
C-7
C-6
C-5
C-4
C-3
C-2
C-a
C-b
C-c
C-d
C-e
C-f OCH
3
6
7
8
9
10
11
13.5 18.6
13.5 18.5
13.5 18.3
13.5 18.6
13.5 18.5
13.5 18.4
35.9 181.3 104.2 134.9
36.0 181.1 106.6 132.9
36.1 181.3 109.1 132.0
35.9 181.2 105.0 134.1
36.0 181.2 106.1 132.9
36.0 181.0 108.3 131.9
190.7
192.5
192.2
190.6
190.8
191.0
101.2
99.9
102.0
101.5
101.8
101.6
171.5 140.6
170.0 141.0
171.0 137.6
171.3 135.6
171.0 133.8
171.5 159.7
123.8
128.8
114.6
130.5
131.4
132.2
146.3
145.7
125.4 55.3
-
-
130.2 122.5 148.4 135.3 124.0
128.9 128.1 135.6 130.6 128.4
129.9 122.3 134.6 114.6 114.8 55.2
-
-
Table 2
13
2
C NMR Spectra of Compounds 12-18 ( [H ]DMSO)
6
Compound
C-9 C-8
C-7
C-6
C-5
C-4
C-3
C-2
C-a
C-b
C-c
C-d
C-e
C-f
OCH
3
12
13
14
15
16
17
18
14.3 59.5 168.4 104.9 130.0 171.2
14.3 59.7 167.8 107.4 131.3 170.8
14.3 59.6 167.6 109.5 128.5 171.1
14.2 59.6 168.2 105.7 122.4 170.7
14.2 59.5 168.0 106.6 128.0 170.9
14.2 59.6 167.8 108.7 129.9 170.9
14.2 59.6 168.0 106.4 128.3 170.8
95.9
96.1
95 .7
96.2
96.0
96.0
96.1
162.9
163.1
163.5
162.9
163.0
163.2
163.1
134.5
132.6
137.0
133.2
133.8
159.7
132.9
130.5
128.9
114.5
123.9
131.5
131.5
140.8
133.0
126.1
135.5
130.5
122.3
130.2
-
-
55.3
-
-
55.2
-
124.1
128.4
114.5
130.2
128.9
114.8
133.3
132.0
134.9
135.6
135.8
130.9
121.1
130.7

1206
G. Athanasellis, E. Gavrielatos and O. Igglessi-Markopoulou
Vol. 38
5-Arylidene(4'-chloro)-3-butanoyl Tetramic Acid (7).
-1
-1
observed at 1720-1690 cm and 1650-1630 cm as
expected for the CO lactam and CO stretching of the
intramolecular hydrogen bonded carbonyl present in the
enol-form of β-keto esters. In addition, the carbonyl
absorptions of compounds 12-18 (ethoxycarbonyl
compounds) are in higher field (1725-1700 and 1660-1645
The compound was isolated as a light brown solid (0.40 g,
62%), mp 227-228 °C (from ethanol); ir (KBr): 3190-3210 (NH),
-1
1710 (C=O lactam), 1640 (C=O enol) and 1585 (C=C) cm ;
1
H-nmr (deuteriochloroform): δ 0.99-1.06 (two t, 3H, CH ),
3
1.70-1.82 (m, 2H, CH ), 2.93 (t, 2H, CH , J=7.2), 6.57/6.60
2
2
(two s, 1H, CH), 7.31-7.43 (m, 4H, phenyl protons) and 7.72/7.94
-1
cm respectively) than those of compounds 6-11
(butanoyl compounds). Finally, the strong band at
1600-1580 cm is assigned to the conjugated double bond
and the aromatic ring of these compounds.
The most important peaks in the FAB-Mass Spectra of
compounds 6, 7, 8, 10, 11 and 18, which have been
acquired, are listed at the experimental section.
In conclusion, we have synthesized 14 compounds
which have been extensively studied by means of H,
+
(two br s, 1H, NH); ms: m/z 292 [(M+H) , 20], 177 (8), 165 (23),
121 (28), 105 (40), 87 (11), 79 (43), 65 (64), 51 (86).
-1
Anal. Calcd. for C
H NO Cl: C, 61.75; H, 4.80; N, 4.80.
15 14 3
Found: C, 61.60; H, 4.70; N, 4.61.
5-Arylidene(4'-methoxy)-3-butanoyl Tetramic Acid (8).
The compound was isolated as an orange solid (0.35 g, 55%),
mp 176-177 °C (from ethanol); ir (KBr): 3190-3200 (NH), 1715,
-1
1
1690 (C=O lactam), 1640 (C=O enol) and 1580 (C=C) cm ;
1
13
H-nmr (deuteriochloroform): δ 0.99-1.06 (two t, 3H, CH ),
3
C-NMR, FT-IR and FAB-MS Spectroscopy. Their purity
1.70-1.82 (m, 2H, CH ), 2.94 (t, 2H, CH , J=8.1), 3.85 (d, 3H,
2
2
has also been checked through elemental analyses. These
compounds are very promising substrates for asymmetric
catalytic hydrogenation. Efforts towards this reaction are
under investigation and we believe that in the near future
we will have some positive results.
OCH , J=2.4), 6.61/6.63 (two s, 1H, CH), 6.93-7.04 (m, 2H,
3
H-d/H-e), 7.35-7.42 (m, 2H, H-b/H-c) and 7.77/8.19 (two br s,
+
1H, NH); ms: m/z 288 [(M+H) , 100], 177 (5), 165 (20), 121
(42), 105 (38), 79 (41), 63 (62), 51 (73).
Anal. Calcd. for C
H NO : C, 66.90; H, 5.92; N, 4.88.
16 17 4
Found: C, 67.17; H, 5.63; N, 4.62.
EXPERIMENTAL
5-Arylidene(3'-nitro)-3-butanoyl Tetramic Acid (9).
The compound was isolated as a brown solid (0.26 g, 39%), mp
205-206 °C (from ethanol); ir (KBr): 3190-3205 (NH), 1690 (C=O
Melting points were determined on a Gallenkamp MFB-595
melting point apparatus and are uncorrected. The FT-IR
spectra were recorded on a Nicolet Magna IR 560. The NMR
spectra were recorded on a Varian Gemini-2000 300 MHz
spectrometer; chemical shifts are quoted in ppm (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, br = broad);
J values are given in Hz. The Mass spectra were recorded on a
VG 7070E/DEC VAX 4000.60 instrument using Fast Atomic
Bombardment, University of Liverpool. Elemental analyses
were obtained on a Euro EA3000 Series Euro Vector CHNS
Elemental Analyser.
-1
1
lactam), 1630 (C=O enol) and 1585 (C=C) cm
; H-nmr
(deuteriochloroform): δ 0.99-1.06 (two t, 3H, CH ), 1.70-1.82
3
(m, 2H, CH ), 2.92 (t, 3H, CH , J=7.2), 6.63/6.65 (two s, 1H, CH),
2
2
7.62 (t, 1H, H-d, J=7.8), 7.74 (d, 1H, H-b, J=12.6), 8.18 (d, 1H,
H-f, J=6.1), 8.25 (s, 1H, H-c) and 8.35/8.62 (two br s, 1H, NH).
Anal. Calcd. for C
H N O : C, 59.60; H, 4.64; N, 9.27.
15 14 2 5
Found: C, 59.74; H, 4.53; N, 9.26.
5-Arylidene(3'-chloro)-3-butanoyl Tetramic Acid (10).
The compound was isolated as a brown solid (0.30 g, 47%) mp
181-182 °C (from ethanol); ir (KBr): 3195-3210 (NH), 1695
General Procedure for the Synthesis of Compounds 6-19.
-1
1
(C=O lactam), 1630 (C=O enol) and 1585 (C=C) cm ; H-nmr
(deuteriochloroform): δ 0.99-1.06 (two t, 3H, CH ), 1.70-1.82
The tetramic acid (0.0022 mole) was stirred in a solution of 8%
hydrochloric acid in ethanol, prepared from the addition of acetyl
chloride (4 mL) in anhydrous ethanol (30 mL) until it dissolved.
Afterwards, X-substituted benzaldehyde (0.0044 mole) was
added to the solution and the resulting solution was refluxed for
3 hours. Finally, it was left stirring overnight.
3
(m, 2H, CH ), 2.94 (t, 2H, CH , J=7.5), 6.54/6.58 (two s, 1H,
2
2
CH), 7.28-7.42 (m, 4H, phenyl protons) and 8.02/8.46 (two br s,
+
1H, NH); ms: m/z 292 [(M+H) , 34], 177 (8), 165 (25), 121 (34),
105 (43), 79 (46), 63 (70), 51 (84).
Anal. Calcd. for C
H NO : C, 61.75; H, 4.80; N, 4.80.
15 14 3
The precipitated solid was isolated by filtration, washed with
diethyl ether and dried under vacuo.
Found: C, 61.90; H, 4.80; N, 4.79.
5-Arylidene(3'-methoxy)-3-butanoyl Tetramic acid (11).
5-Arylidene(4'-nitro)-3-butanoyl Tetramic Acid (6).
The compound was isolated as a yellow solid (0.33 g, 52%),
mp 170-171 °C (from ethanol); ir (KBr): 3190-3200 (NH), 1690
The compound was isolated as a brown solid (0.28 g, 42%),
mp 258-260 °C (from ethanol); ir (KBr): 3180-3200 (NH), 1715,
-1
1
(C=O lactam), 1635 (C=O enol) and 1585 (C=C) cm ; H-nmr
-1
1695 (C=O lactam), 1640 (C=O enol) and 1585 (C=C) cm ;
(deuteriochloroform): δ 0.99-1.06 (two t, 3H, CH ), 1.70-1.82
3
1
H-nmr (dimethyl sulfoxide-d ): δ 0.92 (t, 3H, CH , J=7.2),
(m, 2H, CH ), 2.94 (t, 2H, CH , J=7.2), 3.83 (d, 3H, OCH ,
6
3
2
2
3
1.55-1.67 (m, 2H, CH ), 2.85 (t, 2H, CH , J=7.2), 6.47 (s, 1H,
J=2.1), 6.60/6.63 (two s, 1H, CH), 6.90 (d, 1H, H-f, J=8.1), 6.94
(s, 1H, H-c), 7.02 (d, 1H, H-b, J=7.8), 7.35 (t, 1H, H-d, J=8.1)
and 7.76/8.41 (two br s, 1H, NH); ms: m/z 288 [(M+H) , 100],
2
2
CH), 7.84 (d, 2H, H-b/H-c, J=8.7), 8.18 (d, 2H, H-d/H-e, J=8.7)
+
+
and 10.77 (br s, 1H, NH); ms: m/z 303 [(M + H) , 5], 165 (12),
121 (17), 105 (28), 89 (88), 77 (100), 63 (46), 51 (57).
177 (10), 165 (28), 121 (48), 105 (47), 79 (49), 63 (71), 51 (88).
Anal. Calcd. for C
H
N O : C, 59.60; H, 4.64; N, 9.27.
Anal. Calcd. for C H NO : C, 66.90; H, 5.92; N, 4.88.
15 14
2
5
16 17 4
Found: C, 60.0; H, 4.58; N, 9.25.
Found: C, 66.69; H, 5.74; N, 4.78.

Sep-Oct 2001
Synthesis and Spectroscopic Studies of 5-Arylidene-3-substituted
1207
5-Arylidene(4'-nitro)-3-ethoxycarbonyl Tetramic Acid (12).
Anal. Calcd. for C H NO : C, 62.28; H, 5.19; N, 4.84.
15 15 5
Found: C, 62.58; H, 5.03; N, 4.49.
The compound was isolated as a yellow solid (0.32 g, 48%) mp
280 °C (decomp.) (from ethanol); ir (KBr): 3185-3205 (NH),
5-Benzylidene-3-ethoxycarbonyl Tetramic Acid (18).
-1
1725 (C=O lactam), 1660 (C=O enol) and 1590 (C=C) cm ;
The compound was isolated as a pale yellow solid (0.14 g,
49%), mp 221-222 °C (from ethanol); ir (KBr): 3210 (NH), 1715
(C=O lactam), 1655 (C=O enol) and 1590 (C=C) cm ; H-nmr
(deuteriochloroform): δ 1.42 (t, 3H, CH , J=6.9), 4.44 (q, 4H,
1
H-nmr (dimethyl sulfoxide-d ): δ 1.25 (t, 3H, CH , J=6.9), 4.21
6
3
(q, 2H, CH , J=6.9), 6.53 (s, 1H, CH), 7.85 (d, 2H, H-b/H-c,
2
-1
1
J=8.7), 8.19 (d, 2H, H-d/H-e, J=8.7) and 10.14 (br s, 1H, NH).
3
Anal. Calcd. for C
H N O : C, 55.26; H, 3.95; N, 9.21.
14 12 2 6
CH , J=6.9), 6.64 (s, 1H, CH), 7.35-7.46 (m, 5H, phenyl protons)
2
Found: C, 55.11; H, 4.02; N, 9.29.
+
and 7.69 (br s, 1H, NH); ms: m/z 260 [(M+H) , 100], 214 (72),
5-Arylidene(4'-chloro)-3-ethoxycarbonyl Tetramic Acid (13).
205 (24), 165 (13), 118 (18), 79 (23), 63 (34), 51 (41).
Anal. Calcd. for C
Found: C, 65.16; H, 5.04; N, 5.43.
H NO : C, 64.86; H, 5.02; N, 5.41.
14 13 4
The compound was isolated as a yellow solid (0.36 g, 56%),
mp 253-255 °C (from ethanol); ir (KBr): 3185-3205 (NH), 1715
-1
1
(C=O lactam), 1650 (C=O enol) and 1590 (C=C) cm ; H-nmr
(deuteriochloroform): δ 1.43 (t, 3H, CH , J=7.2), 4.45 (q, 2H,
5-Benzylidene-3-acetyl Tetramic Acid (19).
3
The compound was isolated as a dark brown solid (0.32 g, 70%),
mp 218-219 °C (from ethanol); ir (KBr): 3190-3200 (NH), 1700
(C=O lactam), 1640 (C=O enol) and 1585 (C=C) cm ; H-nmr
CH , J=7.2), 6.58 (s, 1H, CH), 7.36-7.44 (m, 4H, phenyl protons)
2
and 7.52 (br s, 1H, NH).
-1
1
Anal. Calcd. for C
H NO Cl: C, 57.24; H, 4.09; N, 4.77.
14 12 4
(deuteriochloroform): 2.57 (s, 3H, COCH ), 6.65/6.68 (two s, 1H,
3
Found: C, 56.94; H, 4.06; N, 4.74.
CH), 7.33-7.49 (m, 5H, phenyl protons) and 8.26/8.62 (two br s,
13
5-Arylidene(4'-methoxy)-3-ethoxycarbonyl Tetramic Acid (14).
1H, NH); C-nmr (deuteriochloroform): 14.9/17.7 (C-8),
96.7/99.1 (C-3), 105.1/106.2 (C-5), 124.2/124.5/124.7/124.8/-
124.8/125.9/129.0/129.2 (C-a, C-b, C-c, C-d, C-e, C-f),
163.2/169.2 (C-2), 177.7/180.7 (C-7) and 180.1/187.5 (C-4).
The compound was isolated as a red solid (0.33 g, 48%), mp
214-216 °C (from ethanol); ir (KBr): 3190-3220 (NH), 1715
-1
1
(C=O lactam), 1650 (C=O enol) and 1585 (C=C) cm ; H-nmr
(deuteriochloroform): δ 1.42 (t, 3H, CH , J=6.9), 3.85 (s, 3H,
Anal. Calcd. for C
H NO : C, 68.12; H, 4.80; N, 6.11.
13 11 3
3
Found: C, 68.46; H, 4.84; N, 5.99.
OCH ), 4.44 (q, 2H, CH , J=6.9), 6.61/6.62 (two s, 1H, CH),
3
2
6.95-7.00 (m, 2H, H-d/H-e), 7.37-7.43 (m, 2H, H-b/H-e) and
7.56 (br s, 1H, NH).
Acknowledgements.
We thank the University of Liverpool, Chemistry Department,
for help with FAB Mass Spectrometry data collections. We also
thank the National Technical University of Athens for the
financial support (project 'Archimides').
Anal. Calcd. for C
H NO : C, 62.28; H, 5.19; N, 4.84.
15 15 5
Found: C, 62.51; H, 5.11; N, 4.71.
5-Arylidene(3'-nitro)-3-ethoxycarbonyl Tetramic acid (15).
The compound was isolated as a yellow solid (0.29 g, 43%),
mp 235-237 °C (from ethanol); ir (KBr): 3210 (NH), 1715 (C=O
REFERENCES AND NOTES
-1
1
lactam), 1660 (C=O enol) and 1600 (C=C) cm ; H-nmr
(dimethyl sulfoxide-d ): δ 1.23 (t, 3H, CH , J=7.2), 4.19 (q, 2H,
6
3
[1] B. Royles, Chem. Rev., 95, 1981 (1995).
[2] H. Henning and A. Gelbin, Ad. Heter. Chem., 57, 139 (1993).
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[4] L. A. Paquette, D. Macdonald, L. G. Anderson and J. Wright,
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CH , J=7.2), 6.51/6.58 (two s, 1H, CH), 7.63 (t, 1H, H-d, J=7.8),
2
7.99 (d, 1H, H-b, J=8.4), 8.10 (d, 1H, H-f, J=8.1), 8.33 (s, 1H,
H-c) and 10.10 (br s, 1H, NH).
Anal. Calcd. for C
H N O : C, 55.26; H, 3.95; N, 9.21.
14 12 2 6
Found: C, 54.96; H, 3.80; N, 9.00.
[5] R. C. Jones and M. Tankard, J. Chem. Soc. Perkin Trans 1,
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[8a] A. Detsi, J. Markopoulos and O. Igglessi-Markopoulou,
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Perkin Trans 1, 3543 (1997).
5-Arylidene(3'-chloro)-3-ethoxycarbonyl Tetramic Acid (16).
The compound was isolated as a yellow solid (0.27 g, 42%),
mp 208-209 °C (from ethanol); ir (KBr): 3210 (NH), 1715 (C=O
-1
1
lactam), 1650 (C=O enol) and 1610 (C=C) cm ; H-nmr
(dimethyl sulfoxide-d ): δ 1.23 (m, 3H, CH , J=7.5), 4.19 (q, 2H,
6
3
CH , J=7.5), 6.42 (s, 1H, CH), 7.32-7.67 (m, 4H, phenyl protons)
2
and 10.03 (br s, 1H, NH).
Anal. Calcd. for C
H NO Cl: C, 57.24; H, 4.09; N, 4.77.
14 12 4
Found: C, 57.01; H, 3.89; N, 4.69.
5-Arylidene(3'-methoxy)-3-ethoxycarbonyl Tetramic Acid (17).
The compound was isolated as an orange solid (0.21 g, 33%),
mp 186-187 °C (from ethanol); ir (KBr): 3215 (NH), 1700 (C=O
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[11] M. Petroliagi and O. Igglessi-Markopoulou, Tetrahedron
Asymmetry, 10, 1873 (1999).
-1
1
lactam), 1645 (C=O enol) and 1595 (C=C) cm
; H-nmr
(dimethyl sulfoxide-d ): δ 1.24 (t, 3H, CH , J=6.9), 3.79 (d, 3H,
6
3
OCH , J=2.3) 4.20 (q, 2H, CH , J=6.9), 6.44/6.45 (two s, 1H,
CH), 6.87 (dd, 1H, H-f, J=2.1, 7.5). 7.11 (s, 1H, H-c), 7.18 (d, 1H,
H-b, J=7.8), 7.28 (t, 1H, H-d, J=7.8) and 9.93 (br s, 1H, NH).
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3
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