Spectroscopic study of the conformation of 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides

Article abstract of DOI:10.1007/s007060070022

An NMR study of the equilibrium mixture of two conformers of 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides 3 allows to estimate their population ratio in solvents of increasing polarity. X-Ray analysis as well as IR spectroscopy confirmed that the con

Full text of DOI:10.1007/s007060070022

Monatshefte fuÈr Chemie 131, 1151±1160 (2000)
Spectroscopic Study of the Conformation
of 2-Anilino-2-ethoxy-3-oxothiobutyric
Acid Anilides
Barbara Zaleska1;Ã, Robert Socha1, Maria Ciechanowicz-Rutkowska2,
and Tulio Pilati3
1
Department of Organic Chemistry, Jagiellonian University, PL-30060 Cracow, Poland
2
Regional Laboratory of Physicochemical Analyses and Structural Research, PL-30060 Cracow,
Poland
Á
Centro del C.N.R. per lo Studio delle Relazioni tra Struttura e Reattivita Chimica, Dipartmento di
3
Á
Chimica, Fisica ed Elettrochimica, Universita di Milano, I-20133 Milano, Italy
Summary. An NMR study of the equilibrium mixture of two conformers of 2-anilino-2-ethoxy-3-
oxothiobutyric acid anilides 3 allows to estimate their population ratio in solvents of increasing
polarity. X-Ray analysis as well as IR spectroscopy con®rmed that the conformer present in the solid
state is stabilized by two hydrogen bonds. The structural basis of the second conformer observed in
solution is the 1,4-type SÁ Á ÁO interaction between the sulfur of the thioanilide moiety and the oxygen
Ê
of the ethoxy group with a distance of 2.878 A.
Keywords. 3-Oxothiobutyric acid; Conformational analysis.
Introduction
In continuation of the study on the synthesis and properties of Schiff bases
containing 1,3-heterodiene systems such as O=C±C=N± [1, 2] we have prepared the
hitherto unknown 2-anilino-3-oxothiobutyric acid anilides 2 (Scheme 1). It is known
that this 1,3-heterodiene system is prone to react with heterocumulenes yielding
®ve-membered heterocycles as a result of 1,3-dipolar cycloaddition [3±5]. This
particular reactivity results from the speci®c pseudo-gauche conformation of the
1,3-heterodiene system, in which unshared electrons of the azomethine nitrogen
play an important role.
In our present investigation attention was directed towards the addition reaction
of the azomethine C=N bond of compounds 2 with nucleophiles. Treatment of anils
2 with ethanol gave adducts 3 (Scheme 1). The reaction of the C=N bond with
nucleophiles is attributed to the enhanced electrophility of the azomethine carbon
atom of compounds 2.
The NMR spectra of the new compounds 3a±d displayed signi®cant differences
when compared with that of the known 2-anilino-2-ethoxy-3-oxobutyric acid anilide
Ã
Corresponding author

1152
B. Zaleska et al.
Scheme 1
4a [1]. For compounds 3a±d, unexpected signals were observed on the NMR
timescale, indicating that 3 exist in solution in an equilibrium mixture of two
stabilized conformers. To cast light on their spatial geometry, the solid-state
structure of 3d was established by X-ray single crystal analysis. Starting from the
geometry of this structure, a number of possible conformers was generated and
analysed.
Results and Discussion
X-Ray measurement
The molecular structure of compound 3d ((R)-con®guration) determined in a single
crystal X-ray analysis is shown in Fig. 1. The molecule has an asymmetric C(2)
atom, and since the compound crystallizes in the centrosymmetric space group
P21/n, both con®gurations (R) and (S) are present in the solid state (racemate).
In the crystal, the sulfur atom is located trans to the carbonyl oxygen atom O(1)
Ê
at a distance of 4.730(1) A. This conformation is stabilized by two intramolecular
Ê
hydrogen bonds: a strong one (2.960(1) A) between amine nitrogen N(2) and S
ꢀ
Ê
Ê
(N(2)-H(2) ˆ 0.87(2) A, H(2)Á Á ÁS ˆ 2.39(2) A, N(2)-H(2)Á Á ÁS ˆ 122(1) ) and a
Ê
weaker one (2.709(2) A) between amide nitrogen N(1) and O(2) (N(1)-H(1) ˆ
ꢀ
Ê
Ê
0.81 A, H(1)Á Á ÁO(2) ˆ 2.32 A, N(1)-H(1)Á Á ÁO(2) ˆ 110(1) ). The amide nitrogen is
also engaged in an intramolecular hydrogen bond with oxygen atom O1 of the
molecule related by symmetry x ‡ 1, y, z. The parameters of this bond are:
Ê
Ê
Ê
N(1)-H(1) ˆ 0.81 A, H(1)Á Á ÁO(1) ˆ 2.18 A, N(1)Á Á ÁO(1) ˆ 2.90 A, and N(1)-

Conformation of Oxothiobutyric Acid Anilides
1153
Fig. 1. Structure of 3d including the atom numbering scheme corresponding to that used in the
deposited tables (ORTEP-3 [15]); thermal vibration ellipsoids are scaled to enclose 40% probability;
H atoms are represented by circles of arbitrary size
H(1)Á Á ÁO(1) ˆ 148ꢀ. The ®ve-membered ring de®ned by S, C1, C2, N2, H2 is
Ê
planar, the average deviation of these atoms from the best-®t mean plane is 0.039 A.
The ring de®ned by C1, N1, H1, O2, C2 is distorted from planarity, the average
Ê
deviation being 0.206 A. It should also be noted that the thioamide group has (Z)
con®guration and is rather planar; the average deviation of the atoms S, C1, N1, H1,
Ê
and C7 from the best-®t mean plane amounting to 0.024 A. The angle between the
plane of the thioamide group and that of the hydrogen bond N2-H2Á Á ÁS is 4.28(2)ꢀ.
Calculations
It was postulated that the molecular structure of 3d found in the solid state (called
hereafter conformer A) corresponds to the structure of one of the conformers
existing in solution. To evaluate the structure of the other conformer, a number of
possible conformers was generated starting from the geometry of conformer A and
changing the torsional angle C3-C2-C1-S. The relative energy of these conformers,
their dipole moments, and the intramolecular distances SÁ Á ÁO(1) and SÁ Á ÁO(2) were
calculated with the MOPAC 6.00 program [6]; the results are shown in Table 1. For
the conformer in which the C=S group is eclipsed with the oxygen of the ethoxy
group (angle S-C1-C2-O: 10.2ꢀ), the intramolecular distance SÁ Á ÁO(2) is the
Ê
shortest and equal to 2.878 A, which is considerably less than sum of the van der
Ê
Waals radii (3.25 A).
This eclipsed conformation, called hereafter B, affords a nearly planar 4-
Ê
membered quasi-ring (S(1)-C(1)-C(2)-O(2)) with an SÁ Á ÁO(2) distance of 2.878 A.
This is characteristic for compounds with a close 1,4-contact [8±10]. As a result of
the 1,4-SÁ Á ÁO interaction, the geometry of the conformer B is stabilized by overlap
Ã
of the lone pair of oxygen O(2) with the antibonding orbital ꢀ of the C=S bond.
The structures of conformers A and B are compared in Fig. 2. The difference of the
relative energy of these conformers is considerable (Table 1) and can be attributed
to a different type of intramolecular interactions of the more stable conformer A in
the solid state and the higher in energy conformer B in solution which may be
stabilized by an SÁ Á ÁO interaction.

1154
B. Zaleska et al.
Fig. 2. Conformers of 3a±d present in solution
Table 1. Relative energy, dipole moments, selected torsion angles, and non-bonded distances
optimized for 11 conformers of 3d and the corresponding geometrical data
Relative energy
1
b
Ê
Ê
ꢁ/D
Torsion anglesa/o
SÁ Á ÁO(2) /A
SÁ Á ÁO(1)/A
kJ Á mol
ꢂ
ꢃ
ꢄ
0c
1.14c
1.07
2.04
3.74
4.82
5.12d
5.13
5.45
5.55
4.96
3.77
2.00
110.7c
150
170
160
130
100d
70
10.5c
26.46
45.5
135.7c
100.15
81.1
3.828c
3.459
3.249
3.023
2.929
2.878d
2.942
3.139
3.444
3.711
3.903
3.935
4.730c
4.764
4.719
4.495
4.051
3.698d
3.721
3.455
3.326
3.376
3.697
4.184
7.539
19.147
37.456
39.319
41.504d
44.145
44.706
41.449
29.465
19.573
4.709
76.35
107.93
136.8d
167.22
163.06
130.24
105.5
73.72
44.86
51.09
19.99
10.2d
41.38
70.85
100.35
130.22
161.62
169.22
40
10
20
50
80
a
b
ꢂ ˆ C(3)-C(2)-C(1)-S, ꢃ ˆ S-C(1)-C(2)-N(2), ꢄ ˆ S-C(1)-C(2)-O(2); sum of the van der Waals
c
d
Ê
radii ˆ 3.25 A [7]; conformer A (X-ray data); conformer B
NMR Measurements
1
All H NMR spectra (500 MHz) of compounds 3 (CDCl3) show the presence of
two conformers, called per analogy A and B, which differ in their chemical shifts
and intensities. Table 2 shows the chemical shifts for compound 3a and 4a
(Scheme 1).
1
Two conformations A and B which do not interconverted rapidly on the H
NMR time scale are accessible only for the thioamides 3. Large chemical shift
difference (Áꢀ ˆ 4 ppm) between conformers A and B for NH-Ph con®rms that the
sulfur atom in conformer B encounters a new steric situation. When the sulfur atom
was replaced by oxygen to yield compound 4a the individual conformers could not
be detected within the 1H NMR time scale. This suggests that the donor-aceptor 1,4-
interaction between sulfur and the oxygen atoms of the ethoxy group plays a crucial
role.

Conformation of Oxothiobutyric Acid Anilides
1155
1
Table 2. H NMR chemical shifts (ppm) for the two conformers A and B of compounds 3a and 4a
(CDCl3, 298 K, 500 MHz)
CH3CH2±O
CH3CH2±O
CH3±CO
NH±CS
NH±Ph
3a (A)
3a (B)
4a
1.33, t, 3H
1.24, t, 3H
1.29, t, 3H
3.44, 3.68, qq, 2H
3.47, 3.71, qq, 2H
3.44, 3.56, qq, 2H
2.24, s, 3H
2.15, s, 3H
2.23, s, 3H
10.45, s, 1H
10.77, s, 1H
8.73, s, 1H
6.21, s, 1H
2.17, s, 1H
5.88, s, 1H
Table 3. Relative population of the two conformers A and B in solvents of different polarity
(5:6 Â 10 2 mol Á dm 3, 298 K)
CDCl3
CD3COCD3
CD3OD
DMSO-d6
(" ˆ 4:8)
A/%
(" ˆ 20:7)
(" ˆ 33:6)
(" ˆ 47)
A/%
Ar
B/%
A/%
B/%
A/%
B/%
B/%
3a
3b
3c
3d
4a
C6H5
76
70
70
43
100
24
30
30
57
59
54
65
39
41
46
35
61
45
46
47
27
55
54
53
73
14
16
14
5
86
84
86
95
4-CH3-C6H4
4-CH3O-C6H4
4-Cl-C6H4
C6H5
100
100
100
In addition, the relative population of conformers A and B was determined by
measuring the intensities of their signals in solvents of different polarity (Table 3).
The more polar conformer B is strongly preferred in polar solvents such as
DMSO; the ratio of conformers A/B of 3d changes from 1:1 (CDCl3) to 1:20 (Table
3). Differences in the dipole moments (ꢁ ˆ 1:14 D for A and ꢁ ˆ 5:12 D for B) of
3d lead to differences in the solvatation energy of conformers. That is in agreement
1
with the interpretation of the H NMR spectra. On the other hand, the less polar
low-energy conformer A (Table 1) should be present in excess at low temperatures,
and the population of B should become higher at high temperature. This remarkable
fact was con®rmed by corresponding H NMR measurements for 3a. In fact, the
1
ratio changes from 3:1 in favour of A to 5:1 in favour of B over the temperature
range of 30 degrees.
The 13C NMR spectra also revealed that compounds 3 exist in solution in an
equilibrium of two conformers A and B. The 13C NMR chemical shifts (Table 4)
re¯ect the signi®cant change of electron density of the thiocarbonyl carbon atom
and the carbonyl carbon of the acetyl group. 13C NMR chemical shift differences
(Áꢀ ˆ 20 ppm) between conformers A and B observed for C1 suggest a strong
conformational preference for a possible 1,4-close contact OÁ Á ÁS [8] stabilizing the
structure of conformer B in the same way as the intramolecular interaction of
oxygen (C3) in the solid state.
IR Measurements
Infrared data for compounds 3 are given in Table 5. It can be seen that in the solid
1
state one characteristic frequency of the acetyl carbonyl absorption at 1734 cm is

1156
B. Zaleska et al.
Table 4. 13C NMR chemical shifts (ppm) for conformers A and B of compounds 3a±d and 4a
(5:6 Â 10 2 mol Á dm 3, CDCl3, 298 K, 125 MHz)
3a
A
3b
A
3c
A
3d
A
4a
B
B
B
B
C1
C2
C3
C4
C5
C6
182.9
95.1
194
161.4
95.1
201.6
31.5
58.4
18.4
181.9
95
161.5
95
181.9
95.1
193
161.5
95.1
201.7
31.5
58.4
18.4
183.2
95.3
194.3
23.5
59.7
15.2
161.2
95.2
201.5
31.4
58.4
18.4
165
92.16
201
42.17
193.6
23.6
59.5
15.3
201.7
31.5
58.4
18.4
23.5
59.6
15.2
23.6
59.5
15.3
59.16
15.23
Table 5. Infrared carbonyl absorption frequencies
1
1
Ar
ꢅ/cm
Ã
ꢅ/cm
solid state
(KBr)
CCl4
(3 Á 10 2 mol/dm3)
3a
3b
3c
3d
3e
C6H5
1734, 1722
1734, 1723
1733, 1720
1734, 1719
1734
1730
1734
1731
1735
1731
4-CH3-C6H4
4-CH3O-C6H4
4-Cl-C6H4
C6H5
present. This frequency can be assigned to conformer A, whose structure in the solid
state was determined by X-ray analysis. In CCl4, all spectra of 3 are characterized
by two carbonyl bands assigned to conformers A (higher frequency) and B. This is
also in good agreement with the NMR spectra.
Conclusions
Contrary to our earlier expectations, the structure with a 1,4-SÁ Á ÁO donor acceptor
interaction is not present in the solid state of compounds 3 [8] but only in solution.
As determined by X-ray analysis, the conformation of A is stabilized by two
intramolecular hydrogen bonds which successfully compete with the plausible
SÁ Á ÁO donor-acceptor interaction which is present in conformer B and has been
reported for similar compounds [7]. Moreover, this stereoelectronic situation
probably affects the intramolecular hydrogen bond of the C=O acetyl group. It
should also be stressed that in compound 4a, where the bulky sulfur atom is
replaced by an oxygen atom, the individual conformers are not detected. It is
pertinent to note that the presence of conformer B in solution is con®rmed by NMR

Conformation of Oxothiobutyric Acid Anilides
1157
and IR spectra as well as by calculations. Our current studies of heterocyclization
processes in which compounds 3 are involved seem to indicate that the intra-
molecular interactions observed in these compounds in¯uence the stereoselectivity
of the studied reactions to a high degree.
Experimental
Melting points were determined on an electrothermal IA9000 digital melting point apparatus and are
uncorrected. The IR spectra were obtained on a Bruker IFS 48 spectrometer at room temperature. 1H
and 13C spectra were recorded with a Bruker AMX 500 NMR spectrometer using TMS as internal
standard. Chemical shifts are reported in ppm down®eld from TMS. Semiempirical AM1 calculations
were performed using the MOPAC 6.00 program [6]. Conformers were generated by changing the
torsional angle ꢂ (C3-C2-C1-S) by 30ꢀ. The geometry of each conformer was optimized, and the
relative energies, dipole moments, and geometric parameters were computed.
General procedure for the preparation of 2a±d
To 25 cm3 of a tert-butanolic solution of the corresponding 3-oxothiobutyric acid anilide (1a±d,
25.9 mmol) and 2.6 g (25.9 mmol) freshly synthesized nitrosobenzene, 0.085 cm3 of a 33% aqueous
solution of NaOH was added with stirring. The mixture was stirred for 0.5 h at room temperature.
The precipitate was ®ltered and puri®ed by crystallization from tert-butanol.
3-Oxo-N-phenyl-2-phenylimino-thiobutyramide (2a; C16H14N2OS)
Yield: 65%; m.p.: 120ꢀC (orange needles); IR (KBr): ꢅ ˆ 3237 (NH amide), 1711 (C=O), 1632
(C=N), 1122 (C=S) cm 1; 1H NMR (CDCl3, ꢀ, 500 MHz): 2.15 (s, 3H, CH3CO), 7.01±7.99 (m, 10H,
CH aromat.), 10.77 (s, 1H, NH amide) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 31.46 (CH3CO), 120.5,
121.9, 126.7, 126.9, 129, 129.3, 137.7, 145.8 (C aromat), 161.4 (C=N), 182.9 (C=S), 201.6 (C=O)
ppm.
3-Oxo-N-(4-methylphenyl)-2-phenylimino-thiobutyramide (2b; C17H16N2OS)
Yield: 45%; m.p.: 110ꢀC (orange needles); IR (KBr): ꢅ ˆ 3235 (NH amide), 1709 (C=O), 1632
(C=N), 1120 (C=S) cm 1; 1H NMR (CDCl3, ꢀ, 500 MHz): 2.15 (s, 3H, CH3CO), 2.35 (s, 3H, CH3),
7.01±7.92 (m, 9H, CH aromat.) 10.67 (s, 1H, NH amide) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 21.1
(CH3), 31.5 (CH3CO), 120.6, 124.6, 126.8, 127.5, 129.3, 130.5, 139.1, 145.4 (C aromat.), 161.1
(C=N), 181.9 (C=S), 201.7 (C=O) ppm.
3-Oxo-N-(4-methoxyphenyl)-2-phenylimino-thiobutyramide (2c; C17H16N2O2S)
Yield: 50%; m.p.: 112ꢀC (orange needles); IR (KBr): ꢅ ˆ 3237 (NH amide), 1710 (C=O), 1630
(C=N), 1122 (C=S) cm 1; 1H NMR (CDCl3, ꢀ, 500 MHz); 2.15 (s, 3H, CH3CO), 3.82 (s, 3H, CH3O),
7.01±7.91 (m, 9H, CH aromat.), 10.65 (s, 1H, NH amide) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 31.4
(CH3CO), 55.5 (CH3O), 114.18, 120.49, 123.66, 124.58, 129.24, 130.87, 145.88, 158.4 (C aromat.),
161.5 (C=N), 181.9 (C=S), 201.7 (C=O) ppm.
3-Oxo-N-(4-chlorophenyl)-2-phenylimino-thiobutyramide (2d; C16H13N2OSCl)
Yield: 60%; m.p.: 122ꢀC (orange needles); IR (KBr): ꢅ ˆ 3230 (NH amide), 1710 (C=O), 1632
(C=N), 1123 (C=S) cm 1; 1H NMR (CDCl3, ꢀ, 500 MHz): 2.14 (s, 3H, CH3CO), 7.01±7.96 (m, 9H,

1158
B. Zaleska et al.
CH aromat.), 10.77 (s, 1H, NH amide) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 31.5 (CH3CO), 120.5,
123.1, 124.19, 126.87, 129.23, 129.33, 136.32, 145.67 (C aromat), 161.4 (C=N), 183.9 (C=S), 201.5
(C=O) ppm.
General procedure for the preparation of 3a±d
To 25 cm3 of an ethanolic solution of the corresponding 3-oxothiobutyric acid anilide (1a±d,
25.9 mmol) and 2.6 g (25.9 mmol) freshly synthesized nitrosobenzene, 0.085 cm3 of a 33% aqueous
solution of NaOH was added with stirring. The mixture was stirred for 0.5 h at room temperature.
The precipitate was ®ltered and puri®ed by crystallization from ethanol.
2-(Ethoxy-phenyl-amino)-3-oxo-N-phenyl-thiobutyramide (3a; C18H20O2N2S)
Yield: 75% m.p.: 95ꢀC (yellow needles); IR (KBr): ꢅ ˆ 3299 (NH amide), 3218 (NH amine), 1730
1
(C=O), 1120 (C=S) cm 1; conformer A: H NMR (CDCl3, ꢀ, 500 MHz): 1.33 (t, J ˆ 7:1 Hz, 3H,
CH3CH2), 2.24 (s, 1H, CH3CO), 3.44, 3.68 (qq, 2H, CH3CH2), 6.81±7.99 (m, 10H, CH aromat.),
10.45 (s, 1H, NH amide), 6.21 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 15.26
(CH3CH2), 23.5 (CH3CO), 59.6 (CH3CH2), 95.1 (C2), 115.34±145.77 (C aromat.), 182.9 (C=S),
1
194 (C=O) ppm; Conformer B: H NMR (CDCl3, ꢀ, 500 MHz): 1.24 (t, J ˆ 7:1 Hz, 3H, CH3CH2),
2.15 (s, 1H, CH3CO), 3.47, 3.71 (qq, 2H, CH3CH2), 6.81±7.99 (m, 10H, CH aromat.), 10.77
(s, 1H, NH amide), 2.17 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 18.4 (CH3CH2),
31.47 (CH3CO), 58.43 (CH3CH2), 95.1 (C2), 115.34±145.77 (C aromat.), 161.4 (C=S), 201.6
(C=O) ppm.
2-(Ethoxy-phenyl-amino)-3-oxo-N-(4-methylphenyl)-thiobutyramide (3b; C19H22O2N2S)
Yield: 45%; m.p.: 86ꢀC (yellow needles); IR (KBr): ꢅ ˆ 3318 (NH amide), 3230 (NH amine), 1734
1
(C=O), 1120 (C=S) cm 1; Conformer A: H NMR (CDCl3, ꢀ, 500 MHz): 1.31 (t, J ˆ 7:06, 3H,
CH3CH3), 2.24 (s, 1H, CH3CO), 2.35 (s, 3H, CH3), 3.44, 3.67 (qq, 2H, CH3CH2), 6.81±7.92 (m, 9H,
CH aromat), 10.35 (s, 1H, NH amide), 6.21 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz):
15.26 (CH3CH2), 21.1 (CH3), 23.59 (CH3CO), 59.51 (CH3CH2), 95 (C2), 115.4±145.2 (C aromat.),
1
181.9 (C=S), 193.65 (C=O) ppm; Conformer B: H NMR (CDCl3, ꢀ, 500 MHz): 1.24 (t, J ˆ 7:06,
3H, CH3CH2), 2.15 (s, 3H, CH3CO), 2.37 (s, 3H, CH3) 3.45, 3.72 (qq, 2H, CH3CH2), 6.81±7.92 (m,
9H, CH aromat.), 10.69 (s, 1H, NH amide), 2.51 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ,
125 MHz): 18.4 (CH3CH2), 21.1 (CH3), 31.5 (CH3CO), 58.44 (CH3CH2), 95 (C2), 115.4±145.2 (C
aromat.), 161.51 (C=S), 201.72 (C=O) ppm.
2-(Ethoxy-phenyl-amino)-3-oxo-N-(4-methoxyphenyl)-thiobutyramide (3c; C19H22O3N2S)
Yield: 50%; m.p.: 85ꢀC (yellow needles); IR (KBr): ꢅ ˆ 3314 (NH amide), 3230 (NH amine), 1731
1
(C=O), 1126 (C=S) cm 1; Conformer A: H NMR (CDCl3, ꢀ, 500 MHz): 1.31 (t, J ˆ 7:07 Hz, 3H,
CH3CH2), 2.24 (s, 3H, CH3CO), 3.81 (s, 3H, CH3O), 3.45, 3.67 (qq, 2H, CH3CH2), 6.81±7.91 (m,
9H, CH aromat.), 10.36 (s, 1H, NH amide), 6.21 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ,
125 MHz): 15.26 (CH3CH2), 23.59 (CH3CO), 55.49 (CH3O), 59.51 (CH3CH2). 95.1 (C2), 114.18±
158.42 (C aromat.) 181.89 (C=S), 193.56 (C=O) ppm; Conformer B: 1H NMR (CDCl3, ꢀ, 500 MHz):
1.24 (t, J ˆ 7:07 Hz, 3H, CH3CH2), 2.15 (s, 3H, CH3CO), 3.84 (s, 3H, CH3O), 3.47, 3.72 (qq, 2H,
CH3CH2), 6.81±7.91 (m, 9H, CH aromat), 10.69 (s, 1H, NH amide), 2.51 (s, 1H, NH amine) ppm;
13C NMR (CDCl3, ꢀ, 125 MHz): 18.4 (CH3CH2), 31.47 (CH3CO), 55.49 (CH3O), 58.44 (CH3CH2),
95.15 (C2), 114.18±158.42 (C aromat.), 161.5 (C=S), 201.71 (C=O) ppm.

Conformation of Oxothiobutyric Acid Anilides
1159
2-(Ethoxy-phenyl-amino)-3-oxo-N-(4-chlorophenyl)-thiobutyramide (3d; C18H19O2N2SCl)
Yield: 55%; m.p.: 99ꢀC (yellow needles); IR (KBr): ꢅ ˆ 3299 (NH amide), 3249 (NH amine), 1735
1
(C=O), 1120 (C=S) cm 1; Conformer A: H NMR (CDCl3, ꢀ, 500 MHz); 1.32 (t, J ˆ 7:05 Hz, 3H,
CH3CH2), 2.23 (s, 3H, CH3CO), 3.44, 3.69 (qq, 2H, CH3CH2), 6.81±796 (m, 9H, CH aromat.), 10.45
(s, 1H, NH amide), 6.14 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 15.25 (CH3CH2),
23.48 (CH3CO), 59.68 (CH3CH2), 95.3 (C2), 115.56±145.67 (C, aromat.), 183.21 (C=S), 194.36
(C=O) ppm; Conformer B: 1H NMR (CDCl3, ꢀ, 500 MHz): 1.24 (t, J ˆ 7:05 Hz, 3H, CH3CH2), 2.14
(s, 3H, CH3CO), 3.47, 3.71 (qq, 2H, CH3CH2) 6.81±7.96 (m, 9H, CH aromat.), 10.77 (s, 1H, NH
amide), 2.51 (s, 1H, NH amine) ppm; 13C NMR (CDCl3, ꢀ, 125 MHz): 18.4 (CH3CH2), 31.41
(CH3CO), 58.43 (CH3CH2), 95.2 (C2), 115.56±145.67 (C aromat.), 161.18 (C=S), 201.54 (C=O)
ppm.
X-Ray analysis
Crystal data: C18H19ClN2O2S, MW ˆ 362:86, monoclinic, P21/n, a ˆ 10:603(2), b ˆ 13:822(3), c ˆ
Ê 3
ꢀ
1
Ê
12:477(2) A, ꢂ ˆ 90:0, ꢃ ˆ 92:486(11), ꢄ ˆ 90:0 , V ˆ 1826:8(6) A , Z ˆ 4, D ˆ 1:319 Mg Á m
,
ꢆ(MoKꢂ) ˆ 0.71073 A, ꢁ ˆ 0:336 mm 1, F(000) ˆ 760, T ˆ 227 K.
Ê
Crystals of 3d suitable for X-ray analysis were grown from an ethanolic solution as gold yellow
rhombohedra. A crystal of dimensions of 0.50Â0.30Â0.28 mm was used for the X-ray measurements.
X-Ray intensities were collected at 227 K on a Siemens SMART CCD diffractometer equipped with a
nitrogen gas stream LT device (Bruker LT3) using graphite-monochromated MoKꢂ radiation.
Intensity measurements were carried out in the range 1:4 ꢁ ꢇ ꢁ 31:4ꢀ with the program SAINT [11]
giving 5528 symmetry-independent re¯ections used for structure solution and re®nement. They were
corrected for absorption effects using the program SADABS [12]. The structure was solved by direct
methods using the program SIR-92 [13] and re®ned against F2 by full-matrix least squares using
SHELXL-97 [14]. The H-atoms were initially introduced in calculated positions and then re®ned with
isotropic thermal parameters, whereas all non-hydrogen atoms were re®ned anisotropically. The
re®nement of 294 parameters by least-square method converged at R ˆ 0:0415 and wR ˆ 0:0846 for
2684 re¯ections with I > 2ꢈꢂI† and R ˆ 0:0920 and wR ˆ 0:0933 for all data. w ˆ ꢂꢈ2 Á ꢂFo2†‡
2
ꢂ0:0375p† † 1, where p ˆ ꢂFo2 ‡ 2FC2 †=3; extinction coef®cientˆ 0.0000 (4); max. and min. peak on
®nal difference Fourier map: 0.58 and 0.34 eA 3, respectively. Atomic coordinates, bond lengths,
Ê
bond angles, and thermal parameters have been deposited at the Cambridge Crystallographic Data
Center (CCDC No. 150154).
References
[1] Mirek J, Moskal J, Moskal A (1972) Rocz Chem Ann Soc Chim Polonorum 46: 2233
[2] Mirek J, Moskal J, Moskal A (1975) Rocz Chem Ann Soc Chim Polonorum 49: 517
[3] Moskal J (1984) Tetrahedron 21: 4447
[4] Moskal J, Moskal A (1979) Synthesis 10: 794
[5] Moskal J, Moskal A, Milart P (1982) Tetrahedron 35: 1787
[6] Dewar MJS (1985) J Am Chem Soc 107: 3902
[7] Distefano G, Dal Colle M, de Palo M, Jones D, Bombieri G, Del Pra A, Olivato PR, Mondino MG
(1996) J Chem Soc Perkin Trans 2, 1661
[8] Kucsman A, Kapovits I (1985) In: Csizmada JG, Mangini A, Bernardi F (eds) Organic Sulfur
Chemistry, Theoretical and Experimental Advances, p 191
[9] Szabo D, Kapovits J, Kucsman A (1990) Struct Chem 1: 305
[10] Szabo D, Kapovits J, Kucsman A (1991) Struct Chem 2: 529
[11] Siemens (1995) SAINT, Data Processing Software for the SMART System. Siemens Analytical
X-ray Instruments, Inc., Madison, Wisconsin, USA

1160
B. Zaleska et al.: Conformation of Oxothiobutyric Acid Anilides
[12] Sheldrick GM (1996) SADABS, Program for Empirical Absorption Correction of Area Detector
È
Data. University of Gottingen, Germany
[13] Altomare A, Cascarano G, Giacovazzo G, Guagliardi A, Burla MC, Polidori G, Camalli M
(1994) SIR-92. J Appl Cryst 27: 435
[14] Sheldrick GM (1997) SHELXL-97, Program for Re®nement of Crystal Structures. University of
È
Gottingen, Germany
[15] Farrugia LJ, ORTEP-3 for Windows, version 1.02 Beta. Univ of Glasgow, Scotland
Received May 29, 2000. Accepted (revised) July 14, 2000