Synthesis and single crystal X-ray structure of ethyl 2-(1,3-benzoxazol-2- yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate

Article abstract of DOI:10.1515/znb-2007-0513

Ethyl 5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate was prepared from the reaction of diethyl 2-(4-toluidinocarbothioyl)malonate with hydroxylamine. Its reaction with 2-chlorobenzoxazole gave the corresponding N-substituted isoxazolone. The str

Full text of DOI:10.1515/znb-2007-0513

Synthesis and Single Crystal X-Ray Structure of Ethyl 2-(1,3-Benzoxazol-
2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
a
b
b
c
´
Ali Souldozi , Jabbar Khalafy , Ahmad Poursattar Marjani , Katarzyna Slepokura ,
Tadeusz Lisc, and Ali Ramazania
a Department of Chemistry, the University of Zanjan, P O Box 45195-313, Zanjan, Iran
b Department of Chemistry, the University of Urmia, Urmia 57154, Urmia, Iran
c Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie St., 50-383 Wrocław, Poland
Reprint requests to Dr. A. Ramazani. Fax: +98 241 5283100. E-mail: aliramazani@yahoo.com
Z. Naturforsch. 2007, 62b, 705 – 710; received October 24, 2006
Ethyl 5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate was prepared from the reac-
tion of diethyl 2-(4-toluidinocarbothioyl)malonate with hydroxylamine. Its reaction with 2-
chlorobenzoxazole gave the corresponding N-substituted isoxazolone. The structure of the final prod-
1
uct 4 was confirmed by IR, H and 13C NMR spectroscopy and mass spectrometry, and by X-ray
single crystal structure determination.
Key words: Synthesis, Hydroxylamine, 2-Chlorobenzoxazole, N-Substituted Isoxazolone, X-Ray
Single Crystal Structure
Introduction
The reaction of isoxazol-5(2H)-ones, unsubstituted
at C-3, with base is well known [1 – 5] and the vari-
ous intermediates have been trapped to prepare a large
number of heterocyclic systems [6 – 9]. However, the
reaction of 3-substituted compounds with base is not
so well known.
The synthesis of isoxazol-5(2H)-one 1, bearing a
benzothiazole substituent at nitrogen has been reported
by Prager and co-workers [10] as shown is Scheme 1.
We have recently reported [11] the synthesis of
new N-substituted derivatives of 3-arylaminoisoxazol-
5(2H)-ones with benzoxazole and benzothiazole sub-
stituted at the nitrogen atom and their rearrangement
in the presence of triethylamine in ethanol under reflux
Scheme 1.
conditions to produce the corresponding indole
and imidazobenzothiazole derivatives, respectively
(Scheme 2), which are suitable synthetic intermediates
for a series of new heterocycles that could be expected
to have pharmaceutical applications [12, 13].
Scheme 2.
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706
A. Souldozi et al. · Ethyl 2-(1,3-Benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
Table 1. Crystal data and structure refinement details for 4.
Here we report a new and efficient synthe-
sis of ethyl 2-(1,3-benzoxazol-2-yl)-5-oxo-3-(4-toluid-
ino)-2,5-dihydro-4-isoxazolecarboxylate (4) and the
confirmation of its structure by single crystal X-ray
diffraction.
Crystal data
Empirical formula
C20H17N3O5
379.37
Formula weight [g mol−1
]
Crystal size [mm3]
0.45×0.25×0.23
colorless, needle
monoclinic, P21/n
8.907(2)
13.136(3)
15.780(3)
103.08(3)
1798.4(7)
4
Crystal color and form
Crystal system, space group
˚
a [A]
Results and Discussion
˚
b [A]
˚
The isoxazolone 3 was prepared from the reac-
tion of the corresponding thiocarbamate 2 with hy-
droxylamine by the general method of Worrall [14]
(Scheme 3).
c [A]
β [deg]
3
˚
V [A ]
Z
Dcalc [g cm−3
]
1.401
0.856
792
µ [mm−1
]
F(000) [e]
Data collection
Diffractometer
Data collection method
Monochromator
Radiation type
T [K]
Xcalibur PX
ω scans and φ scans
graphite
CuKα
120(2)
4.43 – 76.52
−5 ≤ h ≤ 11, −16 ≤ k ≤ 16,
−17 ≤ l ≤ 19
analytical
0.715/0.846
15656
Scheme 3.
The reaction of isoxazolone 3 with 2-chlorobenz-
oxazole under nitrogen atmosphere either in chloro-
form under reflux conditions, or upon heating without
solvent at 130 ◦C, afforded the corresponding N-benz-
oxazole derivative 4 in 42 and 40 % yield, respectively
(Scheme 4).
θ range [◦]
h, k, l range
Absorption correction
Tmin/Tmax
Measured reflections
Independent reflections
Observed refl. [I ≥ 2σ(I)]
Completeness to θ = 70.00◦
3541
3258
0.976
Refinement
Refinement on
F2
Data/restraints/parameters
R [Fo2 > 2σ(Fo2)]
R (all data)
3541/0/322
R1 = 0.0378, wR2 = 0.1062
R1 = 0.0400, wR2 = 0.1080
1.058
GooF = S
Weighting parameter a/b
0.0661/0.5987
0.27/−0.20
−3
˚
∆ρmax/∆ρmin [e A
]
ꢀ
R1 = ΣꢀFo| − |Fcꢀ/Σ|Fo|; wR2 = Σ[w(Fo −Fc2)2]/Σ[w(Fo2)2];
2
weighting scheme: w = 1/[σ2(Fo2)+(aP)2 +bP], where P = (Fo
2Fc2)/3.
+
2
a: in chloroform under reflux conditions;
b: heating neat at 130 ◦C under nitrogen atmosphere
Scheme 4.
atoms. The molecule consists of three planar moieties:
the ethyl 3-amino-5-oxo-2,5-dihydroisoxazole-4-carb-
oxylate unit (forming plane 1), the benzoxazol-2-yl
group (plane 2) and the p-toluidino moiety (plane 3).
All atoms of the benzoxazol and p-toluidino groups
The structure of compound 4 was confirmed by el-
1
emental analysis, IR, H and 13C NMR spectroscopy
and mass spectrometry, and by X-ray single crystal
structure determination.
˚
lie exactly in their planes (within 0.02 A). However,
atoms of the plane denoted as 1 slightly deviate from
˚
Description of the crystal structure of 4
the mean plane with atom O(3) deviating by 0.27 A and
˚
the remaining atoms being coplanar to within 0.16 A.
The crystal of 4 is built up from molecules, the struc-
ture of which is shown in Fig. 1. A summary of the
experimental details is given in Table 1.
Searching the Cambridge Structural Database [15]
revealed eleven hits for isoxazolones of related struc-
The dihedral angles between the planes of these three
moieties are 66.6(1)◦ (between planes 1 and 2) and
60.4(1)◦ (between planes 1 and 3).
Atoms N(3) and C(14) are both in plane with the
ture, i. e. substituted at the N atom and at both carbon isoxazolonyl ring (see torsion angle C(14)–N(3)–C(3)–
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A. Souldozi et al. · Ethyl 2-(1,3-Benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
707
˚
Table 2. Selected interatomic distances (A), valence angles
(deg) and torsion angles (deg) in 4.
O(1)–C(1)
O(1)–N(1)
O(3)–C(4)
O(4)–C(4)
O(5)–C(7)
O(5)–C(8)
N(1)–C(7)
N(1)–C(3)
1.413(2)
1.450(2)
1.221(2)
1.336(2)
1.360(2)
1.390(2)
1.401(2)
1.409(2)
N(2)–C(7)
N(2)–C(13)
N(3)–C(3)
N(3)–C(14)
C(1)–C(2)
C(2)–C(3)
C(2)–C(4)
1.283(2)
1.413(2)
1.328(2)
1.435(2)
1.430(2)
1.380(2)
1.454(2)
C(7)–N(1)–C(3) 119.93(10)
C(7)–N(1)–O(1) 107.12(9)
C(3)–N(1)–O(1) 106.48(9)
C(3)–N(3)–C(14) 126.15(11)
O(2)–C(1)–O(1) 117.56(12)
O(2)–C(1)–C(2) 135.14(13)
O(1)–C(1)–C(2) 107.27(11)
C(3)–C(2)–C(1) 108.58(11)
C(3)–C(2)–C(4) 123.43(11)
C(1)–C(2)–C(4) 127.98(11)
Fig. 1. Molecular structure of 4 in the crystal showing
the atom numbering scheme and the intramolecular N(3)–
H(3)···O(3) hydrogen bond forming an S(6) motif (dashed
line). Displacement ellipsoids are shown at the 50 % proba-
bility level.
C(1)–O(1)–N(1)–C(7)
129.8(1)
C(14)–N(3)–C(3)–C(2) −176.8(2)
C(7)–N(1)–C(3)–N(3)
59.6(2)
C(7)–N(1)–C(3)–C(2) −122.8(2)
C(2) in Table 2) because of the formal sp2 hybridiza-
tion of atom N(3). This results in a partial double bond
character of the N(3)–C(3) linkage, which is reflected
in the difference between its length and the length of
the N(3)–C(14) bond, which is typical for a C–N sin-
gle bond (see Table 2). Atom C(14) is only slightly
displaced from the isoxazolonyl ring plane; the dis-
C(5)–O(4)–C(4)–O(3)
C(5)–O(4)–C(4)–C(2)
C(3)–C(2)–C(4)–O(3)
−2.4(2)
175.0(1)
11.0(2)
C(1)–C(2)–C(4)–O(3) −170.4(2)
C(3)–C(2)–C(4)–O(4) −166.5(1)
C(4)–O(4)–C(5)–C(6)
174.1(2)
C(3)–N(1)–C(7)–O(5) −173.5(1)
O(1)–N(1)–C(7)–O(5)
C(3)–N(3)–C(14)–C(15)
65.2(2)
62.3(2)
˚
tance of C(14) from that plane is about 0.07 A. How-
ever, the p-tolyl substituent is twisted relative to the
isoxazolonyl ring by about 60◦, which is also reflected
by the C(3)–N(3)–C(14)–C(15) torsion angle value
of 62.3(2)◦. Such non-planar orientation of benzoxazyl
and p-toluidinyl groups in relation to an isoxazolonyl
ring prevents the steric hindrance between rather bulky
substituents at atoms N(1) and N(3).
The conformation of the molecule is stabilized by
the intramolecular N(3)–H(3)···O(3) hydrogen bond
forming the usual six-membered S(6) motif (see
Fig. 1). It is possible that this intramolecular inter-
action is of the resonance-assisted hydrogen bond
(RAHB) type, which often occurs when the hydrogen-
bond donor and acceptor are connected by a short chain
of conjugated single and double bonds [16] (compare
with the geometry of the fragment involved in the S(6)
ring motif H(3)–N(3)–C(3)–C(2)–C(4)–O(3); Tables 2
and 3).
Fig. 2. The centrosymmetric molecular dimer formed by
adjacent molecules joined by N(3)–H(3)···O(3)i hydrogen
bonds (dashed line) and C(5)–H(5A)···π[Cg(4)i] (dotted
line) to form R22 (4) rings in addition to intramolecular S(6)
motifs. Symmetry codes are given in Table 3.
The structure of the dimer is additionally stabilized
by C–H···π interactions, with atoms C(5) acting as
donors and the p-toluidinyl phenyl rings as acceptors
(Fig. 2 and Table 3).
The same amine hydrogen atoms, H(3), along with
the same donors, N(3), and carbonyl acceptors, O(3),
are additionally involved in N(3)–H(3)···O(3)i in-
termolecular contacts to form the centrosymmetric
Adjacent dimers are joined to each other by an ex-
molecular dimers shown in Fig. 2. This gives rise to tensive mode of interactions, i. e. by the hydrogen con-
a planar three-centre N–H···(O)2 system, with a sum tacts of the C–H···O, C–H···N and C–H···π types on
of angles at H(4) of 354(2)◦ and additional R22 (4) rings the one hand, and by the centrosymmetric C=O···C=O
formed by the two adjacent molecules (see Table 3). carbonyl interactions on the other. (For geometry
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708
A. Souldozi et al. · Ethyl 2-(1,3-Benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
˚
˚
˚
˚
Table 3. Geometry of proposed hy-
drogen bonds, C–H···O/N/π close
contacts and carbonyl interactions
D–H···A
D−H (A)
H···A (A) D···A (A) D−H···A (◦) Offset (A)
N(3)–H(3)···O(3)
0.92(2)
0.92(2)
1.03(2)
1.03(2)
1.00(2)
0.98(2)
0.94(3)
0.96(2)
0.98(2)
0.98(2)
1.01(2)
2.18(2)
2.23(2)
2.74(2)
2.77(2)
2.38(2)
2.65(2)
2.70(3)
2.58(2)
3.12(2)
3.27(2)
3.10(2)
3.15(3)
2.850(2)
2.952(2)
3.528(2)
3.763(2)
3.157(2)
3.324(2)
3.622(2)
3.372(2)
4.084(2)
4.138(2)
3.994(2)
3.845(2)
129(2)
134(2)
133(2)
164(2)
135(2)
127(2)
168(2)
140(2)
168(2)
150(2)
149(2)
127(2)
–
N(3)–H(3)···O(3)i
–
–
–
–
–
–
0.56
0.89
1.34
0.85
0.96
˚
C(6)–H(6A) ···O(1)ii
C(6)–H(6A) ···N(1)ii
C(11)–H(11) ···O(2)iii
C(15)–H(15) ···N(2)iv
C(20)–H(20C) ···O(2)iv
C(5)–H(5A) ···Cg(4)i
C(5)–H(5B) ···Cg(2)v
C(5)–H(5B) ···Cg(3)v
C(16)–H(16) ···Cg(1)iv
for 4 (A, deg).
i
Symmetry codes: −x, −y + 1, −z + 1;
ii
iii
−x + 1, −y + 1, −z + 1;
x − 1/2,
iv
−y + 1/2, z + 1/2;
−x + 1/2, y +
v
1/2, −z + 3/2;
x − 1/2, −y + 1/2,
vi
z − 1/2;
−x, −y + 1, −z + 2. Cg(1),
Cg(2), Cg(3) and Cg(4) are the centroids
of the isoxazyl, benzoxazyl O(5)–C(7)–
N(2)–C(13)–C(8) and C(8)–C(9)–C(10)–
C(11)–C(12)–C(13) rings, and toluidinyl
rings, respectively.
C(20)–H(20B) ···Cg(3)vi 1.00(3)
Carbonyl interactions (see text)
A1: C(1)=O(2) ···C(4)ii
A2: O2 ···C4ii=O3ii
A3: C4ii=O3ii···C1
A4: O3ii···C1=O2
107.12(9)◦
93.68(8)◦
55.34(7)◦
42.60(7)◦
B1: C1 ···O3ii
4.087(2) A
˚
˚
B2: O2 ···C4ii
2.991(2) A
T: C1=O2 ···C4ii=O3ii
140.6(1)◦
Fig. 4. Carbonyl interactions along with the accompanying
C–H···O/N contacts formed between two molecules of two
adjacent dimers. Symmetry codes are given in Table 3.
Fig. 3. The arrangement of the molecules within the lay-
ers parallel to the (101) plane. N(3)–H(3)···O(3), N(3)–
H(3)···O(3)i and C(11)–H(11)···O(2)iii contacts are shown
with dashed lines. Symmetry codes are given in Table 3.
served in the crystal of compound 4 gives rise to a
rather extensive three-dimensional network of hydro-
gen bonds and carbonyl interactions, which all stabi-
lize the crystal packing of 4.
and symmetry codes see Table 3.) Symmetry-related
dimers are linked by C(11)–H(11)···O(2)iii bonds to
form layers parallel to the (101) plane shown in Fig. 3.
These interact with each other by means of rather
weak C(15)–H(15)···N(2)iv, C(20)–H(20C)···O(2)iv
and C–H···π contacts, as well as carbonyl interactions
(Table 3).
Conclusions
In conclusion, we have developed a new and
efficient solvent-less method for preparing ethyl
2-(1,3-benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-di-
hydro-4-isoxazolecarboxylate (4). Other aspects of
this process are under investigation. The X-ray struc-
ture of 4 revealed a variety of intra- and intermolecular
interactions, from resonance-assisted N–H···O bonds
to N–H···O, C–H···O/N/π and carbonyl interactions.
The geometry of the carbonyl interactions, observed
between C(1)=O(2) and C(4)ii=O(3)ii groups, espe-
cially the characteristic A1, A2, A3 and A4 angles, re-
veal the so-called motif III of such interactions (by
Allen et al. [17]). The O(2) ···C(4)ii distance (B2 in
Experimental Section
General procedures
˚
Table 3) is rather short at 2.991(2) A even for this mo-
tif (see Fig. 4). It is probable that these interactions
may be accompanied by weak, bifurcated C–H···O/N
contacts formed by atom C(6) from one molecule and
O(1)ii, N(1)ii from the other (also shown in Fig. 4).
The combination of all these N–H···O, C–H···O,
Freshly distilled solvents were used throughout, and an-
hydrous solvents were dried according to Perrin and Ar-
marego [18]. Elemental analyses were performed using a
Heraeus CHN-O-Rapid analyzer. 1H (300 MHz) and 13C
C–H···N, C–H···π and C=O···C=O interactions ob- (75.5 MHz) NMR measurements were carried out on a
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A. Souldozi et al. · Ethyl 2-(1,3-Benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
709
Bruker 300 spectrometer in [D6]DMSO or CDCl3 with form (5 mL) for 24 h. The solvent was removed under re-
tetramethylsilane as internal standard. Infrared spectra were duced pressure to give a colorless oil. This residue was re-
recorded on a Thermonicolet (Nexus 670) FT-infrared spec- crystallized from ethanol to give 4 as white needles. Yield:
◦
trometer, using sodium chloride cells, measured as Nujol 61 mg (42 %); m. p. 129 – 131 C. – IR (KBr): ν = 3267,
mulls or films. Mass spectra were registered with an HP 5973 1790, 1667, 1630, 1561, 1514, 1491, 1450, 1356, 1294,
MSD instrument connected to an HP 6890 GC unit inter- 1234, 1201, 1030, 985, 931, 793, 763, 751 cm−1. – 1H NMR
faced by a Pentium PC. Relative abundances of fragments (CDCl3): δ = 1.45 (t, 3 H, 3J = 7.1 Hz, CH3 of Et), 2.12 (s,
are quoted in parentheses after the m/z values. Melting points 3H, CH3), 4.45 (q, 2 H, 3J = 7.1 Hz, CH2 of Et), 6.62 (d,
were determined on a Philip Harris C4954718 apparatus and 2 H, 3J = 7.9 Hz, arom.), 7.08 (d, 2 H, 3J = 8.3 Hz, arom.),
3
are uncorrected.
7.33 (t, 1 H, J = 7.7 Hz, arom.), 7.40 (t, 1 H, 3J = 8.2 Hz,
arom.), 7.53 (d, 1 H, 3J = 7.9 Hz, arom.), 9.90 (s, 1H, ex-
changed by D2O addition, NH). – 13C NMR (CDCl3): δ =
14.81, 21.11, 61.50, 78.91, 111.27, 121.08, 122.94, 125.74,
127.13, 130.29, 132.99, 137.44, 139.91, 150.15, 151.76,
164.01, 164.85, 165.38. – GC-MS: m/z (%) = 379 (7 %) M+,
335 (34) [M–CO2]+, 290 (23), 289 (100), 251 (11), 250 (46),
230 ( 57), 158 (60), 117 (55), 91 (100), 77 (44), 65 (50), 44
(9), 29 (66). – C20H17N3O5 (379.37): calcd. C 63.32, H 4.52,
N 11.08; found C 63.43, H 4.44, N 11.01.
(b) A mixture of 2-chlorobenzoxazole (58 mg, 0.38
mmol) and the corresponding isoxazolone (100 mg,
0.38 mmol) was heated neat to 130 ◦C in a sealed vial flushed
with nitrogen in an oven for 1 h. The mixture was left to cool
to r. t. and then extracted with dichloromethane. The solu-
tion was filtered and passed through a short plug of silica.
Removal of the solvent gave a pale-yellow oil, which was
crystallized from ethanol to give white needles. Yield: 59 mg
(40 %); m. p. 129 – 131 ◦C. Its spectral data agreed with those
given above.
Diethyl 2-(4-toluidinocarbothioyl)malonate (2)
This thioamide was prepared by a literature method [19]
as a pale-yellow solid. Yield: 90 %; m. p. 54 ◦C (lit. [16], 55 –
56 ◦C). – IR (KBr): ν = 3284, 1760, 1723, 1515, 1430, 1315,
1223, 1148, 1020, 831 cm−1. – 1H NMR (CDCl3): δ = 1.35
(t, 6 H, 3J = 7.15 Hz, 2 CH3 of 2 Et), 2.38 (s, 3H, CH3), 4.32
(q, 2 H, 3J = 7.15 Hz, CH2 of Et), 4.33 (q, 2 H, 3J = 7.15 Hz,
CH2 of Et), 5.11 (s, 1H, CH), 7.23 (d, 2 H, 3J = 8.3 Hz,
arom.), 7.66 (d, 2 H, 3J = 8.3 Hz, arom.), 10.77 (bs, 1H,
exchanged by D2O addition, NH). – 13C NMR (CDCl3): δ =
14.35, 21.57, 63.47, 67.62, 123.64, 129.86, 136.41, 137.43,
166.16, 187.68.
Ethyl 5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazole-
carboxylate (3)
To a 50 mL flask containing a solution of hydroxylamine
hydrochloride (4.71 g, 68 mmol) in water (20 mL), was
added slowly potassium bicarbonate (6.78 g, 68 mmol).
Ethanol (80 mL) was added and the resulting potassium
chloride precipitate was filtered off. Compound 2 (10.50 g,
34 mmol) was added to the filtrate and the mixture was re-
fluxed for 24 h. The reaction mixture was acidified with di-
lute hydrochloric acid and the white precipitate was collected
by vacuum filtration. The white solid was recrystallized
from ethanol to ◦give colorless crystals. ◦Yield: 7.85 g (85 %);
m. p. 164 – 166 C (lit. [20] 161 – 163 C). – IR (KBr): ν =
3409, 2976, 1708, 1619, 1572, 1515, 1249, 1204, 1072,
Preparation of single crystals of ethyl 2-(1,3-benzoxa-
zol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazole-
carboxylate (4)
Single crystals of 4 were prepared by using the branch
tube method with a mixture of n-hexane/1,4-dioxane (10 : 1)
kept at 45 ◦C for six weeks [21]. The colorless crystals were
filtered off, washed with a cold mixture of n-hexane/1,4-
dioxane (10 : 1 mL) and dried in vacuum over P4O10 (m. p.
130 ◦C).
1
787 cm−1. – H NMR (CDCl3 + [D6]DMSO): δ = 0.95 (t,
3 H, 3J = 7.0 Hz, CH3 of Et), 1.94 (s, 3H, CH3), 3.91 (q, 2 H,
Crystal structure determination of 4
3
3J = 7.0 Hz, CH2 of Et), 6.78 (d, 2 H, J = 9.2 Hz, arom.),
The crystallographic measurement was performed on a κ
geometry Xcalibur PX automated four-circle diffractometer
with graphite-monochromatized CuKα radiation. The crystal
data for the crystal were collected at 120(2) K using the Ox-
ford Cryosystems cooler. A summary of the conditions for
data collection and structure refinement parameters are given
in Table 1. The data were corrected for Lorentz and polar-
ization effects. Analytical absorption correction was applied.
Data collection, cell refinement, and data reduction and anal-
6.79 (bs, 1H, exchanged by D2O addition, NH), 6.80 (d, 2 H,
3J = 9.2 Hz, arom.), 8.85 (bs, 1 H, exchanged by D2O ad-
dition, NH). – 13C NMR (CDCl3 + [D6]DMSO): δ = 14.52,
20.85, 60.08, 74.69, 121.53, 130.13, 133.29, 135.64, 163.59,
165.51, 166.74.
Ethyl 2-(1,3-benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-
dihydro-4-isoxazolecarboxylate (4)
(a) Compound 3 (100 mg, 0.38 mmol) and 2-chloro- ysis were carried out with the Xcalibur PX software (Oxford
benzoxazole (58 mg, 0.38 mmol) were refluxed in chloro- Diffraction Poland): CrysAlis CCD and CrysAlis RED, re-
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710
A. Souldozi et al. · Ethyl 2-(1,3-Benzoxazol-2-yl)-5-oxo-3-(4-toluidino)-2,5-dihydro-4-isoxazolecarboxylate
spectively [22]. The structure was solved by Direct Meth- gram [25]. The extinction was also refined with the final ex-
ods using the SHELXS-97 program [23] and refined by a tinction coefficient of 0.0173(9).
full-matrix least-squares technique using SHELXL-97 [24]
CCDC 619511 contains the supplementary crystallo-
with anisotropic thermal parameters for non-H atoms. All graphic data for this paper. These data can be obtained free
H atoms were found in difference Fourier maps and were re- of charge from The Cambridge Crystallographic Data Centre
fined isotropically. All figures were made using the XP pro- via www.ccdc.cam.ac.uk/data request/cif.
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