Mononuclear heterocyclic rearrangement of 5-arylisoxazole-3-hydroxamic acids into 3,4-substituted 1,2,5-oxadiazoles

Article abstract of DOI:10.1055/s-0032-1317947

By a series of successive transformations, 5-arylisoxazole-3-carboxylic acids (aryl=phenyl, p-tolyl, 2,5-dimethylphenyl) have been converted into 5-arylisoxazole-3-hydroxamic acids, which undergo rearrangement by the action of aqueous KOH to form 3,4-substituted 1,2,5-oxadiazoles. The structure of one of them, 1-(2,5-dimethylphenyl)-2-(4-hydroxy-1,2,5-oxadiazol-3-yl)ethanone, has been confirmed by single crystal X-ray analysis. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1317947

260▌
PAPER
paper
Mononuclear Heterocyclic Rearrangement of 5-Arylisoxazole-3-hydroxamic
Acids into 3,4-Substituted 1,2,5-Oxadiazoles
Rearrangement of 5-Arylisoxazole-3-hydroxamic Acids
Vladimir I. Potkin,*a Sergey K. Petkevich,a Alexander S. Lyakhov,b Ludmila S. Ivashkevichb
a
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Surganova Str., 13, Minsk 220072, Belarus
Fax +375(17)2841679; E-mail: potkin@ifoch.bas-net.by
b
Research Institute for Physical Chemical Problems of Belarusian State University, Leningradskaya Str., 14, Minsk 220030, Belarus
Received: 15.10.2012; Accepted after revision: 05.12.2012
Two approaches were tested for the synthesis of arylisox-
Abstract: By a series of successive transformations, 5-arylisoxa-
azole-3-hydroxamic acids 1–3. One of them included the
zole-3-carboxylic acids (aryl = phenyl, p-tolyl, 2,5-dimethylphe-
amidation of methyl 5-arylisoxazole-3-carboxylates 10–
nyl) have been converted into 5-arylisoxazole-3-hydroxamic acids,
12 by reaction with hydroxylamine. Another path consist-
which undergo rearrangement by the action of aqueous KOH to
form 3,4-substituted 1,2,5-oxadiazoles. The structure of one of ed in acylation of hydroxylamine by the action of 5-aryl-
them,
1-(2,5-dimethylphenyl)-2-(4-hydroxy-1,2,5-oxadiazol-3-
isoxazole-3-carbonyl chlorides 13–15, easily obtained by
the reaction of acids 7–9 with thionyl chloride. The former
approach was found to be more preferable, as it allows to
obtain the target hydroxamic acids 1–3 in higher yields
(75–88% instead of 51–60% in the latter approach) and
with higher purity. Thus, the first approach was used in
yl)ethanone, has been confirmed by single crystal X-ray analysis.
Key words: isoxazoles, 1,2,5-oxadiazoles, furazans, rearrange-
ment, crystal structure, hydroxamic acids
The chemistry of 1,2,5-oxadiazole (trivial name furazan) practice. Acetylation of hydroxamic acids proceeded se-
is of great interest, because a large number of compounds lectively on the hydroxy group and led to the correspond-
incorporating furazan cycle possess a wide spectrum of ing acetyl derivatives 4–6 in 83–96% yields (Scheme 2).
biological activity.1 Moreover, they attract great attention
At first it was planned to convert the O-acetylhydroxamic
acids 4–6 into 3-amino-5-arylisoxazoles by heating with
aqueous alkali. The conversion of O-acylhydroxamic
as energetic materials,2 dyes, and precursors for organic
synthesis of useful products.3 There are different methods
available for the synthesis of furazans. One of them is
acids to isocyanates and further to amines or ureas is well
based on the mononuclear heterocyclic rearrangement of
known as Lossen rearrangement.7 However, the process
the isoxazoles bearing an oxime group in the 3 position of
proceeded quite differently and led to 1-aryl-2-(4-hy-
droxy-1,2,5-oxadiazol-3-yl)ethanones 16–18, that is, sub-
stituted furazans (Scheme 2).
the heterocycle.4 Hydroxamic acids can be considered as
synthetic equivalents of oximes as they can exist in two
tautomeric forms, keto or enol (Scheme 1).5 The latter is
The hydrolysis of acylated fragment was supposed to be
produced in low percentage, is less stable, and contains
the first step of the process and further mononuclear rear-
the oxime moiety.
rangement of the enol form of hydroxamic acids into the
furazan systems occurred. To test this hypothesis, aryl-
O
OH
isoxazole-3-hydroxamic acids 1–3 were subjected to heat-
ing in aqueous alkali (KOH) and the reaction resulted in
the formation of the corresponding substituted furazans
16–18. Yields of the furazans obtained from the hy-
droxamic acids 1–3 (70–76%, method A), were slightly
higher than those of the products obtained from the acety-
lated derivatives 4–6 (54–62%, method B). Given the
findings, a sequence of the arylisoxazole-3-hydroxamic
acid molecules transformations in mononuclear heterocy-
clic rearrangement is suggested, which is presented in
Scheme 3.
R
R
HN OH
keto form
N
OH
enol form
Scheme 1 Tautomeric forms of hydoxamic acids
The transformation of isoxazolylhydroxamic acids and
their derivatives into furazans is not described up till now.
We intended to synthesize the 5-arylisoxazole-3-hy-
droxamic acids (aryl = Ph, 3-MeC6H4, 2,5-Me2C6H3) 1–3
and their O-acetyl derivatives 4–6, and to study the possi-
bility of their use in obtaining substituted 1,2,5-oxadia-
zoles via mononuclear heterocyclic rearrangement. The 5-
arylisoxazole-3-carboxylic acids 7–9 were taken as start-
ing compounds. Recently, we have reported their synthe-
sis from the corresponding available 5-arylisoxazole-3-
carbaldehyde oximes.6
The structure of furazan derivatives 16–18 was confirmed
by IR, 1H, and 13C NMR spectra as well as by single crys-
tal X-ray analysis at 296 K for compound 18. Single crys-
tals of 18 suitable for X-ray analysis were obtained by
slow evaporation of a dichloromethane–hexane (2:1) so-
lution of the compound.
Compound 18 was found to crystallize in the monoclinic
space group P21/c (Z = 4). The asymmetric unit comprises
one molecule of 1-(2,5-dimethylphenyl)-2-(4-hydroxy-
SYNTHESIS 2013, 45, 0260–0264
Advanced online publication: 18.12.2012
DOI: 10.1055/s-0032-1317947; Art ID: SS-2012-Z0796-OP
© Georg Thieme Verlag Stuttgart · New York
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0
3
9
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7
8
8
1
1
4
3
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Rearrangement of 5-Arylisoxazole-3-hydroxamic Acids
261
O
OH
N
O
R
7-9
MeOH
[H+]
SOCl2
DMFA
O
O
OMe
Cl
N
N
R
R
O
O
10–12
13–15
NH2OH
NH2OH
Me
O
O
O
N
O
NH-OH
AcCl
NH
N
R
R
O
O
1–3
KOH
KOH
H2O
4–6
KOH
H2O
Δ
H2O
Δ
Δ
NH2
N
O
OH
R
R
N
N
O
O
16–18
R = H (1,4,7,10,13,16), 4-Me (2,5,8,11,14,17), 2,5-Me2 (3,6,9,12,15,18)
Scheme 2 Preparation of 3,4-substituted 1,2,5-oxadiazoles
O
HO
HO
NH-OH
H2O
N–OH
OH
N-OH
N
N
O
N
O
O
R
R
OH–
R
– OH–
OH
H2O
C
R
OH
N-OH
OH
N
O
N
N
R
O
O
R = H, 4-Me, 2,5-Me2
Scheme 3 A probable route of mononuclear rearrangement of 5-ar-
ylisoxazole-3-hydroxamic acids
1,2,5-oxadiazol-3-yl)ethanone (Figure 1). The furazan
and benzene rings are planar within 0.0035(10) and
0.0059(12) Å, respectively. In the molecule, the dihedral
angle between the least squares planes of the rings is of
64.08(6)°. Bond lengths and valence angles (Table 1) lie
in the expected ranges.8
Figure 1 The molecular structure of 18, showing the atom-number-
ing scheme and displacement ellipsoids drawn at the 50% probability
level
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262
V. I. Potkin et al.
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All reagents were of analytical grade and used as purchased without
further purification. Melting points were determined on Boetius
heating table. The IR spectra were recorded on a Nicolet Protégé
spectrometer, using KBr discs. The NMR spectra were recorded on
a Bruker Avance-500 spectrometer. GC-MS analysis was carried
out on Hewlett Packard 5890/5972 spectrometer.
Table 1 Selected Bond Lengths and Angles for Furazan 18
Bond lengths (Å)
Angles (°)
O(1)–N(1)
O(1)–N(2)
C(10)–N(2)
C(9)–C(10)
C(9)–N(1)
C(10)–O(10)
C(8)–C(9)
C(7)–C(8)
C(7)–O(7)
1.3880(19) N(1)–C(9)–C(10)
108.36(14)
110.74(12)
105.97(14)
104.31(13)
110.61(15)
121.39(15)
1.391(2)
1.296(2)
1.423(2)
1.293(2)
1.331(2)
1.487(2)
1.521(2)
N(1)–O(1)–N(2)
C(9)–N(1)–O(1)
C(10)–N(2)–O(1)
N(2)–C(10)–C(9)
N(1)–C(9)–C(8)
Methyl 5-Arylisoxazole-3-carboxylates 10–12; General Proce-
dure
To a solution of the corresponding 5-arylisoxazol-3-carboxylic acid
7–9 (10 mmol) in anhyd MeOH (50 mL) was added concd H2SO4
(2 drops) and the mixture was refluxed for 4 h. The solution was al-
lowed to cool to r.t., then H2O (200 mL) was added, the product ex-
tracted with CH2Cl2 (50 mL), and the extract was dried (CaCl2).
After removal of the solvent by rotary evaporation, the residue was
recrystallized from hexane.
N(2)–C(10)–O(10) 124.86(15)
Methyl 5-Phenylisoxazole-3-carboxylate (10)
Yield: 1.75 g (86%); white solid; mp 80–82 °C.
O(7)–C(7)–C(1)
122.50(13)
119.20(13)
1.2178(17) O(7)–C(7)–C(8)
IR (KBr): 3148, 3131, 3059, 2952, 2922, 1728, 1613, 1592, 1572,
1477, 1447, 1426, 1296, 1252 1143, 1005, 948, 936, 809, 782, 767,
685, 675 cm–1.
1H NMR (500 MHz, CDCl3): δ = 3.92 (s, 3 H, OCH3), 6.85 (s, 1
Hisoxazole), 7.39 (m, 3 Harom), 7.71 (m, 2 Harom).
13C NMR (125 MHz, CDCl3): δ = 52.89 (OCH3), 99.99 (CHisoxazole),
125.95 (2 CHarom), 129.20 (2 CHarom), 130.88 (1 CHarom), 126.60,
156.74, 160.45 (3 Cq), 171.79 (C=O).
The carbonyl and hydroxy groups of neighboring mole-
cules are involved in intermolecular hydrogen bonds
O10–H10···O7a (symmetry code as in Figure 2) responsi-
ble for the formation of centrosymmetric dimers, with
only van der Waals interactions between them.
GC-MS (EI, 70 eV): m/z = 203 [M+].
Anal. Calcd for C11H9NO3: C, 65.02; H, 4.46; N, 6.89. Found: C,
65.16; H, 4.75; N, 6.95.
Methyl 5-(p-Tolyl)isoxazole-3-carboxylate (11)
Yield: 1.93 g (89%); white solid; mp 116–117 °C.
IR (KBr): 3139, 3030, 2954, 2926, 1727, 1616, 1595, 1522, 1474,
1447, 1425, 1412, 1248, 1143, 1005, 947, 938, 809, 782, 676, 502
cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3 H, CH3), 3.98 (s, 3 H,
OCH3), 6.85 (s, 1 Hisoxazole), 7.26 (d, J = 8.0 Hz, 2 Harom), 7.66 (d,
J = 8.0 Hz, 2 Harom).
13C NMR (125 MHz, CDCl3): δ = 21.59 (CH3), 52.94 (OCH3),
99.39 (CHisoxazole), 125.94 (2 CHarom), 129.90 (2 CHarom), 123.94,
141.36, 156.69, 160.61 (4 Cq), 172.07 (C=O).
GC-MS (EI, 70 eV): m/z = 217 [M+].
Anal. Calcd for C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found: C,
66.54; H, 5.29; N, 6.57.
Methyl 5-(2,5-Dimethylphenyl)isoxazole-3-carboxylate (12)
Yield: 2.17 g (94%); white solid; mp 53–54 °C.
IR (KBr): 3171, 3008, 2957, 2925, 1735, 1726, 1575, 1505, 1471,
1451, 1424, 1384, 1295, 1248 1189, 1180, 1154, 1116, 1002, 936,
820, 806, 775 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3), 2.45 (s, 3 H,
CH3), 4.00 (s, 3 H, OCH3), 6.81 (s, 1 Hisoxazole), 7.17 (m, 2 Harom),
7.54 (m, 1 Harom).
13C NMR (125 MHz, CDCl3): δ = 20.92 (CH3), 21.02 (CH3), 52.97
(OCH3), 102.93 (CHisoxazole), 128.97 (CHarom), 131.51 (2 CHarom),
125.89, 133.30, 136.09, 156.39, 160.70 (5 Cq), 172.03 (C=O).
Figure 2 A hydrogen-bonded dimer in the crystal structure of 18;
symmetry code (a): 1–x, 1–y, 1–z
In conclusion, we have successfully developed an effi-
cient synthetic approach for the preparation of 3,4-substi-
tuted 1,2,5-oxadiazoles (furazans) based on mononuclear
heterocyclic rearrangement of accessible 5-arylisoxazole-
3-hydroxamic acids. The furazans formed contain reac-
tive exocyclic hydroxy and keto groups and can be used in
further target transformations.
GC-MS (EI, 70 eV): m/z = 231 [M+].
Anal. Calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C,
67.69; H, 5.78; N, 6.12.
5-Arylisoxazole-3-hydroxamic Acids 1–3; General Procedure
A solution of hydroxylamine hydrochloride (1.39 g, 20 mmol) and
Et3N (20.02 g, 20 mmol) in MeOH (40 mL) was stirred at r.t. for 30
min. The corresponding ester 10–12 (10 mmol) was then added and
Synthesis 2013, 45, 260–264
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Rearrangement of 5-Arylisoxazole-3-hydroxamic Acids
263
the mixture was refluxed for 8 h. After cooling to r.t., the reaction
mixture was diluted with H2O (250 mL), the precipitate was filtered,
washed with H2O (3 × 25 mL), dried in vacuo, and recrystallized
from CHCl3.
Anal. Calcd for C12H10N2O4: C, 58.54; H, 4.09; N, 11.38. Found: C,
58.77; H, 4.26; N, 11.40.
N-Acetoxy-5-(p-tolyl)isoxazole-3-carboxamide (5)
Yield: 2.50 g (96%); white solid; mp 152–154 °C.
5-Phenylisoxazole-3-hydroxamic Acid (1)
Yield: 1.59 g (78%); white solid; mp 167–169 °C.
IR (KBr): 3216, 3132, 2924, 1797, 1705, 1613, 1593, 1567, 1508,
1447, 1367, 1253, 1182, 1045, 1000, 947, 879, 815, 807, 763 cm–1.
IR (KBr): 3327, 3160, 3068, 1664, 1608, 1570, 1538, 1449, 1261,
1167, 1050, 1003, 948, 868, 769, 694 cm–1.
1H NMR (500 MHz, acetone-d6): δ = 7.15 (s, 1 Hisoxazole), 7.52 (m, 3
1H NMR (500 MHz, CDCl3): δ = 2.31 (s, 3 H, CH3), 2.41 (s, 3 H,
CH3), 6.95 (s, 1 Hisoxazole), 7.28 (d, J = 8.0 Hz, 2 Harom), 7.67 (d,
J = 8.0 Hz, 2 Harom), 10.23 (s, 1 H, NH).
H
arom), 7.90 (m, 2 Harom), 8.69 (s, 1 H, OH), 10.86 (s, 1 H, NH).
13C NMR (125 MHz, CDCl3): δ = 18.27 (CH3), 21.60 (CH3), 98.82
(CHisoxazole), 126.02 (2 CHarom), 129.94 (2 CHarom), 123.69, 141.60,
156.57, 156.67 (4 Cq), 168.27 (C=O), 172.18 (C=O).
13C NMR (125 MHz, acetone-d6): δ = 99.36 (CHisoxazole), 125.94 (2
CHarom), 129.53 (2 CHarom), 130.86 (CHarom), 126.90, 156.64,
158.28 (3 Cq), 170.97 (C=O).
Anal. Calcd for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C,
60.11; H, 4.95; N, 10.68.
Anal. Calcd for C10H8N2O3: C, 58.82; H, 3.95; N, 13.72. Found: C,
59.03; H, 4.35; N, 13.91.
N-Acetoxy-5-(2,5-dimethylphenyl)isoxazole-3-carboxamide (6)
Yield: 2.28 g (83%); white solid; mp 115–117 °C.
5-(p-Tolyl)isoxazole-3-hydroxamic Acid (2)
Yield: 1.92 g (88%); white solid; mp 168–170 °C.
IR (KBr): 3223, 3162, 2924, 2867, 1801, 1709, 1673, 1573, 1506,
1452, 1434, 1370, 1248, 1174, 1039, 1003, 962, 944, 881, 848, 813
cm–1.
IR (KBr): 3286, 3164, 3033, 2923, 1650, 1614, 1594, 1542, 1509,
1450, 1388, 1263, 1159, 1046, 1034, 947, 869, 807 cm–1.
1H NMR (500 MHz, acetone-d6): δ = 2.36 (s, 3 H, CH3), 7.07 (s, 1
Hisoxazole), 7.33 (d, J = 8.0 Hz, 2 Harom), 7.77 (d, J = 8.0 Hz, 2 Harom),
8.76 (s, 1 H, OH), 10.81 (s, 1 H, NH).
1H NMR (500 MHz, CDCl3): δ = 2.32 (s, 3 H, CH3), 2.37 (s, 3 H,
CH3), 2.46 (s, 3 H, CH3), 6.91 (s, 1 Hisoxazole), 7.20 (m, 2 Harom), 7.54
(s, 1 Harom), 10.33 (s, 1 H, NH).
13C NMR (125 MHz, acetone-d6): δ = 20.64 (CH3), 98.73
(CHisoxazole), 125.89 (2 CHarom), 129.93 (2 CHarom), 124.21, 141.25,
156.73, 158.20 (4 Cq), 171.15 (C=O).
13C NMR (125 MHz, CDCl3): δ = 18.89 (CH3), 21.51 (CH3), 21.60
(CH3), 102.88 (CHisoxazole), 129.57 (CHarom), 132.12 (CHarom),
132.20 (CHarom), 126.24, 134.01, 136.69, 156.96, 157.24 (5 Cq),
168.89 (C=O), 172.65 (C=O).
Anal. Calcd for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84. Found: C,
60.87; H, 4.93; N, 12.75.
Anal. Calcd for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21. Found: C,
61.57; H, 5.38; N, 10.32.
5-(2,5-Dimethylphenyl)isoxazole-3-hydroxamic Acid (3)
Yield: 1.74 g (75%); white solid; mp 149–151 °C.
Rearrangement of 5-Arylisoxazole-3-hydroxamic Acids and
Their O-Acetyl Derivatives into 3,4-Substituted 1,2,5-Oxadia-
zoles 16–18; General Procedures
IR (KBr): 3363, 3159, 2922, 2869, 1689, 1660, 1568, 1531, 1509,
1443, 1425, 1376, 1262, 1137, 1042, 1001, 957, 873, 854, 814 cm–1.
1H NMR (500 MHz, acetone-d6): δ = 2.36 (s, 3 H, CH3), 2.46 C (s,
3 H, CH3), 6.95 (s, 1 Hisoxazole), 7.26 (m, 2 Harom), 7.58 (s, 1 Harom),
8.73 (s, 1 H, OH), 10.92 (s, 1 H, NH).
13C NMR (125 MHz, CDCl3): δ = 21.13 (CH3), 21.29 (CH3), 103.18
(CHisoxazole), 129.97 (CHarom), 132.48 (CHarom), 132.68 (CHarom),
127.29, 134.46, 137.20, 157.75, 158.95 (5 Cq), 172.24 (C=O).
Method A: The corresponding 5-arylisoxazole-3-hydroxamic acid
1–3 (5 mmol) was added to a solution of KOH (0.84 g, 15 mmol) in
H2O (30 mL), and the mixture was stirred at 55–60 °C for 7 h. The
reaction mixture was diluted with H2O (200 mL), extracted with
CH2Cl2 (50 mL), and the extract dried (CaCl2). The solvent was re-
moved under reduced pressure and the residue was purified by re-
crystallization from a mixture CH2Cl2–hexane (1:3).
Method B: The corresponding O-acetyl-5-arylisoxazole-3-hy-
droxamic acid 4–6 (5 mmol) was added to a solution of KOH (1.4
g, 25 mmol) in H2O (40 mL), and the mixture was stirred at 55 °C
for 9 h. The reaction mixture was diluted with H2O (300 mL), acid-
ified with 4 M HCl to pH 6, extracted with CH2Cl2 (50 mL), and the
extract dried (CaCl2). The solvent was removed under reduced pres-
sure and the residue was purified by recrystallization from a mixture
CH2Cl2–hexane (1:3).
Anal. Calcd for C12H12N2O3: C, 62.06; H, 5.21; N, 12.06. Found: C,
62.23; H, 5.44; N, 12.18.
O-Acetyl Derivatives of 5-Arylisoxazole-3-hydroxamic Acids 4–
6; General Procedure
AcCl (0.86 g, 11 mmol) was slowly added dropwise at r.t. to a
stirred solution of the corresponding 5-arylisoxazole-3-hydroxamic
acid 1–3 (10 mmol) in anhyd pyridine (10 mL). After completion of
the addition, the reaction mixture was stirred at 50–55 °C for 3 h.
The mixture was cooled to r.t. and diluted with H2O (100 mL). The
product was extracted with CHCl3 (40 mL), the extract was dried
(CaCl2), and concentrated up to 10 mL. Then 50 mL of hexane was
added and precipitate was filtered and dried in vacuo.
2-(4-Hydroxy-1,2,5-oxadiazol-3-yl)-1-phenylethanone (16)
Yield: 1.43 g (70%, method A); 1.10 g (54%, method B); white sol-
id; mp 83–85 °C.
IR (KBr): 3353, 2921, 1693, 1597, 1582, 1548, 1450, 1385, 1330,
1216, 1182, 1002, 929 cm–1.
1H NMR (500 MHz, CDCl3): δ = 4.43 (s, 2 H, CH2), 7.47 (m, 3
N-Acetoxy-5-phenylisoxazole-3-carboxamide (4)
Yield: 2.04 g (83%); white solid; mp 143–145 °C.
Harom), 7.92 (m, 2 Harom), 9.50 (s, 1 H, OH)
IR (KBr): 3208, 3128, 2936, 1795, 1705, 1609, 1590, 1572, 1519,
1497, 1448, 1370, 1253, 1185, 1048, 1004, 947, 880, 765, 689 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H, CH3), 7.00 (s, 1
13C NMR (125 MHz, CDCl3): δ = 32.52 (CH2), 128.35 (2 CHarom),
128.73 (CHarom), 129.97 (CHarom), 134.97, 143.03, 163.05 (3 Cq),
194.28 (C=O).
Hisoxazole), 7.47 (m, 3 Harom), 7.77 (m, 2 Harom), 9.96 (s, 1 H, NH).
Anal. Calcd for C10H8N2O3: C, 58.82; H, 3.95; N, 13.72. Found: C,
59.11; H, 4.27; N, 13.88.
13C NMR (125 MHz, CDCl3): δ = 18.30 (CH3), 99.47 (CHisoxazole),
126.11 (2 CHarom), 129.31 (2 CHarom), 131.12 (CHarom), 126.47,
156.60, 156.83 (3 Cq), 168.33 (C=O), 171.97 (C=O).
2-(4-Hydroxy-1,2,5-oxadiazol-3-yl)-1-(p-tolyl)ethanone (17)
Yield: 1.55 g (71%, method A); 1.31 g (60%, method B); white sol-
id; mp 93–95 °C.
© Georg Thieme Verlag Stuttgart · New York
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264
V. I. Potkin et al.
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IR (KBr): 3220, 3951, 2922, 1685, 1606, 1574, 1552, 1519, 1444,
1407, 1397, 1330, 1225, 1185, 1008, 929 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.43 (s, 3 H, CH3), 4.51 (s, 2 H,
CH2), 7.27 (d, J = 8.0 Hz, 2 Harom), 8.00 (d, J = 8.0 Hz, 2 Harom), 9.96
(s, 1 H, OH).
13C NMR (125 MHz, CDCl3): δ = 21.91 (CH3), 32.92 (CH2), 129.37
(2 CHarom), 130.41 (2 CHarom), 126.64, 132.83, 144.88, 163.35 (4
Cq), 194.67 (C=O).
References
(1) (a) Modern Heterocyclic Chemistry; Alvarez-Builla, J.;
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Zubenko, Yu. S.; Chernov, A. N.; Talabaev, M. V.;
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Anal. Calcd for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84. Found: C,
60.76; H, 4.87; N, 12.91.
1-(2,5-Dimethylphenyl)-2-(4-hydroxy-1,2,5-oxadiazol-3-yl)eth-
anone (18)
Yield: 1.76 g (76%, method A); 1.44 g (62%, method B); white sol-
id; mp 100–102 °C.
IR (KBr): 3238, 2976, 2921, 1668, 1599, 1566, 1541, 1495, 1386,
1338, 1231, 1176, 1009, 980 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.42 (s, 3 H, CH3), 2.52 (s, 3 H,
CH3), 4.53 (s, 2 H, CH2), 7.22 (d, J = 8.0 Hz, 1 Harom), 7.31 (d,
J = 8.0 Hz, 1 Harom), 7.65 (s, 1 Harom), 10.40 (s, 1 H, OH).
13C NMR (125 MHz, CDCl3): δ = 21.08 (CH3), 21.54 (CH3), 35.38
(CH2), 130.31 (CHarom), 132.70 (CHarom), 135.10 (CHarom), 134.16,
135.95, 137.14, 143.22, 163.11 (5 Cq), 198.41 (C=O).
Anal. Calcd for C12H12N2O3: C, 62.06; H, 5.21; N, 12.06. Found: C,
62.15; H, 5.34; N, 12.11.
X-ray Crystal Structure Analysis9
X-ray data of 18 were collected on a diffractometer Nicolet R3m at
293(2) K. The crystal structure was solved by direct methods using
the program SIR2004.10 The structure was refined with the program
SHELXL.11 All non-hydrogen atoms were refined anisotropically.
The hydrogen atoms were placed in calculated positions and refined
in ‘riding’ model approximation, with Uiso(H) = 1.5Ueq(C,O) for the
methyl and hydroxy groups, and Uiso(H) = 1.2Ueq(C) for others. The
package PLATON12 was used for molecular graphics.
(8) Allen, F. H. Acta Crystallogr., Sect B 2002, 58, 380.
(9) CCDC 903835 contains the supplementary crystallographic
data for 18. These data can be obtained via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, free of
charge or from the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; e-mail:
deposit@ccdc.cam.ac.uk or fax: +44(1223)336033.
(10) Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.;
Cascarano, G. L.; De Caro, L.; Giacovazzo, C.; Polidori, G.;
Spagna, R. J. Appl. Crystallogr. 2005, 38, 381.
Acknowledgment
We thank the Belarusian Republican Foundation for Basic Research
(X10Az-001) for financial support of this work.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
(11) Sheldrick, G. M. Acta Crystallogr., Sect A 2008, 64, 112.
(12) Spek, A. L. Acta Crystallogr., Sect. D. 2009, 65, 148.
nnfomartit
Synthesis 2013, 45, 260–264
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