The study of reactions of α-chlorocinnamonitriles with hydroxylamine

Article abstract of DOI:10.1007/s11172-006-0029-1

The E-isomers of α-chlorocinnamonitriles react with hydroxylamine to give a mixture of isomeric aminoisoxazoles, while the Z-isomers yield 3-aryl-2-chloroacrylamide oximes.

Full text of DOI:10.1007/s11172-006-0029-1

1
728
Russian Chemical Bulletin, International Edition, Vol. 54, No. 7, pp. 1728—1732, July, 2005
The study of reactions of αꢀchlorocinnamonitriles with hydroxylamine
V. G. Nenajdenko,aꢀ I. V. Golubinskii, O. N. Lenkova, A. V. Shastin, and E. S. Balenkova
a
a
b
a
aDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 932 8846. Eꢀmail: nen@acylium.chem.msu.ru
Institute of Problems of Chemical Physics, Russian Academy of Sciences,
b
1
42432 Chernogolovka, Moscow Region, Russian Federation.
Eꢀmail: shastin@icp.ac.ru
The Eꢀisomers of αꢀchlorocinnamonitriles react with hydroxylamine to give a mixture of
isomeric aminoisoxazoles, while the Zꢀisomers yield 3ꢀarylꢀ2ꢀchloroacrylamide oximes.
Key words: 3ꢀarylꢀ2ꢀchloroacrylamide oximes, aminoisoxazoles, αꢀchlorocinnamonitriles,
hydroxylamine, catalytic olefination.
αꢀChlorocinnamonitriles 1, which are easily obtained
(2ꢀfuryl)acrylonitrile in the presence of sodium ethoxide.
The use of Nꢀhydroxyurea increased the yield compared
to hydroxylamine but had no effect on the regiochemistry
of the reaction. The reaction can be complicated by side
processes such as nucleophilic addition of the ethoxy
group at the double bond followed by elimination of the
1
by earlier developed catalytic olefination, are convenient
starting materials for the synthesis of various heterocyclic
2
compounds. In the present work, we studied reactions of
nitriles 1 with hydroxylamine. Since NH OH contains
2
two different nucleophilic centers, the resulting isomeric
adducts (in particular, aminoisoxazoles) can contain the
amino group in position 3 or 5.
1
4
halogen.
In the present work, we studied reactions of hydroxylꢀ
amine with some αꢀchlorocinnamonitriles 1a—g prepared
by catalytic olefination.
2ꢀChloroꢀ3ꢀ(4ꢀchlorophenyl)acrylonitrile (1a) as a
mixture of two diastereomers (E : Z = 4 : 1) was chosen as
a model compound. It was found that in the reaction of
Isoxazoles are valuable organic compounds widely used
3
,4
in medicinal chemistry. Known routes to 5ꢀaminoꢀ3ꢀ
arylisoxazoles involve reactions of hydroxylamine with
αꢀcyano ketones.5—7 The reactions of olefins with NOCl
followed by treatment with cyanides should also be menꢀ
tioned; however, this method is not regioselective for
compound 1a with NH OH•HCl in boiling ethanol in
2
8
nonsymmetrical olefins. Another method for the syntheꢀ
the presence of potassium carbonate, the diastereomeric
nitriles behave differently (TLC data). It turned out that
the Zꢀisomer reacts significantly more rapidly than the
Eꢀisomer, yielding several products.
sis of 5ꢀaminoꢀ3ꢀarylisoxazoles is based on reactions of
αꢀbromo ketoximes with sodium cyanide in aqueous
9
methanol. A mixture of isomeric aminoisoxazoles was
obtained earlier1 in reactions of 3ꢀarylpropꢀ2ꢀynenitriles
0
In subsequent reactions with the individual isomers of
the model nitrile (which were separated off by column
chromatography), we found that the Zꢀisomer reacts with
hydroxylamine even at room temperature within 20 to
30 min to give a single product, namely, earlier unknown
2ꢀchloroꢀ3ꢀ(4ꢀchlorophenyl)propꢀ2ꢀenamide oxime (2a).
This compound is formed when hydroxylamine adds to
the nitrile fragment of the substrate. The reaction proved
to be of the general character and the corresponding
amides of hydroximic acids were also obtained in high
yields from other Zꢀisomeric nitriles (Scheme 1, Table 1).
It should be noted that the resulting products undergo
no subsequent in situ transformations: their intramolecuꢀ
lar cyclization into 3ꢀaminoꢀ5ꢀarylisoxazoles did not ocꢀ
cur even when the reaction mixture was refluxed for a
and βꢀbromocinnamonitriles with hydroxylamine.
The dual reactivity of hydroxylamine is exhibited in its
reactions with αꢀbromoꢀβꢀglycosylꢀα,βꢀunsaturated niꢀ
triles and ketones to give derivatives of isoxazole or
isoxazoline, respectively. The site of primary nucleophilic
attack can be located from the positions of substituents in
the resulting heterocycle. In addition to an activated
double bond, the N atom of hydroxylamine is usually
more nucleophilic and the major reaction products
are the corresponding 5ꢀaminoisoxazoles. Interestingly,
the use of Nꢀhydroxyurea selectively leads to isomeric
1—13
3
ꢀaminoisoxazole.1
Aminoisoxazoles containing a furan fragment were obꢀ
tained by reactions of Nꢀhydroxyurea with αꢀhaloꢀβꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1678—1682, July, 2005.
066ꢀ5285/05/5407ꢀ1728 © 2005 Springer Science+Business Media, Inc.
1

Reactions of αꢀClꢀcinnamonitriles with NH OH
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
1729
2
Scheme 1
Table 2. Yields and ratios of isomeric aminoarylisoxazoles
Products
Ar
Total yield of
Ratio
3
and 4 (%)
of 3 : 4
3
3
3
3
3
3
3
a, 4a
b, 4b
c, 4c
d, 4d
e, 4e
f, 4f
4ꢀClꢀC H
86
75
64
73
52
80
56
2 : 1
6
4
2ꢀNaphthyl
4ꢀMeꢀC H
1.6 : 1
1 : 1.2
1 : 1.1
1 : 1.5
1.8 : 1
1.1 : 1
6
4
4ꢀMeOꢀC H
6
4
4ꢀO NꢀC H
4
2
6
4ꢀBrꢀC H
6
4
Table 1. Synthesis of 3ꢀarylꢀ2ꢀchloroacrylamide oximes
g, 4g
4ꢀMe NꢀC H
2 6 4
Comꢀ
pound
Ar
Yield
(%)
Scheme 2
2
2
2
2
2
2
2
a
b
c
d
e
f
4ꢀClꢀC H
79
74
84
82
67
81
63
6
4
2ꢀNaphthyl
4ꢀMeꢀC H
6
4
4ꢀMeOꢀC H
6
4
4ꢀO NꢀC H
2
6
4ꢀBrꢀC H
6
4
g
4ꢀMe NꢀC H
2 6 4
long period of time. Reactions of hydroxylamine with
nitriles leading to the corresponding amide oximes have
been documented;15 at the same time, reactions of hydrꢀ
oxylamine and its derivatives with acrylonitriles usually
occur at the activated double bond rather than the cyano
group.1
6
The Eꢀisomers of αꢀchlorocinnamonitriles do not reꢀ
act with hydroxylamine without refluxing. The initial
Michael attack of hydroxylamine on the substrate is folꢀ
lowed by cyclization of the resulting adduct to give a
mixture of the corresponding 5ꢀaminoꢀ3ꢀarylisoxazoles
3
a—g and 3ꢀaminoꢀ5ꢀarylisoxazoles 4a—g (Scheme 2,
Table 2).
It is known that the selectivity of a chemical reaction
Eꢀisomer. At the same time, the charge at the cyano
C atom is higher for the Eꢀisomer; however, its orbital
coefficient is somewhat lower than that for the Zꢀisomer.
If the reaction were controlled by orbital interactions, a
predominant attack of the nucleophile on the double bond
could be expected for either isomer. The charge control
would make an attack on the cyano group preferred and
the Eꢀisomer should be more reactive. The fact that the
calculated and experimental data do not correlate can
suggest that the reactions of isomeric nitriles are conꢀ
trolled not only by orbital or charge interactions. Apparꢀ
ently, the steric accessibility of a specific reactive site is
is determined by a combination of steric and electronic
factors. To compare the reactivities of the electrophilic
sites in the starting nitriles and to explain the observed
chemiselectivity, we performed quantumꢀmechanical calꢀ
culations at the MP2 level for the Eꢀ and Zꢀisomers. The
calculated LUMO coefficients and charges at the C and
N atoms in the fragment of the unsaturated nitrile are
given in Table 3.
Both the orbital coefficient and the charge at the C(3)
atom for the Zꢀisomer are higher than those for the
Table 3. MP2ꢀcalculated charges and LUMO coefficients
Isoꢀ
mer
C(3)
LUMO
C(2)
LUMO
C(1)
LUMO
N
Charge
Charge
Charge
Charge
LUMO
Eꢀ1a
Zꢀ1a
0.086
0.087
0.317
0.338
–0.111
–0.098
0.291
0.293
0.193
0.173
0.036
0.042
–0.277
–0.274
0.107
0.128

1730
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
Nenajdenko et al.
2 H, NH2). 13C NMR (DMSOꢀd6), δ: 149.91 (CNH2); 133.11,
substantial in this case. In the Zꢀisomer, the more reactive
cyano group is not shielded by the aryl substituent and
hydroxylamine attacks the site bearing the highest posiꢀ
tive charge to give amide oximes. In the Eꢀisomer, the
cyano group is shielded by the aromatic substituent and
hydroxylamine reacts with the less reactive but more acꢀ
cessible double bond to yield isomeric isoxazoles.
1
32.91, 131.28, 128.52, 125.87, 124.88 (CCl).
ꢀChloroꢀ3ꢀ(2ꢀnaphthyl)propꢀ2ꢀenamide oxime (2b). The
yield was 74%, colorless crystals, m.p. 142—144 °C, R 0.59
2
f
(
CH Cl —EtOAc, 2 : 1). Found (%): C, 63.35; H, 4.33.
2 2
1
C H ClN O. Calculated (%): C, 63.29; H, 4.49. H NMR
13
11
2
(
DMSOꢀd ), δ: 10.13 (br.s, 1 H, OH); 8.26 (s, 1 H, H arom.);
6
7
7
.95—7.83 (m, 4 H, H arom.); 7.55—7.51 (m, 2 H, H arom.);
13
.48 (s, 1 H, CH); 5.83 (br.s, 2 H, NH2). C NMR (DMSOꢀd ),
6
δ: 150.02, 132.66, 132.54, 131.65, 129.17, 128.26, 127.78, 127.51,
27.00, 126.92, 126.84, 126.53, 124.44.
ꢀChloroꢀ3ꢀ(4ꢀmethylphenyl)propꢀ2ꢀenamide oxime (2c). The
yield was 84%, colorless crystals, m.p. 124—126 °C, R 0.59
1
2
f
(
CH Cl —EtOAc, 2 : 1). Found (%): C, 56.91; H, 5.24.
2 2
1
C H ClN O. Calculated (%): C, 57.01; H, 5.26. H NMR
10
11
2
Thus, we studied the reactions of αꢀchlorocinnamoꢀ
nitriles with hydroxylamine and demonstrated that the
Zꢀisomers react to give amides of hydroximic acids, while
the Eꢀisomers yield mixtures of isomeric isoxazoles. We
developed the methods for the preparation of earlier unꢀ
known 3ꢀarylꢀ2ꢀchloropropꢀ2ꢀenamide oximes and new
(
7
DMSOꢀd ), δ: 10.03 (br.s, 1 H, OH); 7.25 (s, 1 H, CH); 7.62,
6
.22 (both d, 2 H each, H arom., J = 8.2 Hz); 5.73 (br.s, 2 H,
13
NH ); 2.31 (s, 3 H, Me). C NMR (DMSOꢀd ), δ: 150.01,
2
6
138.17, 131.22, 129.54, 129.02, 126.87, 123.15, 20.93 (Me).
ꢀChloroꢀ3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenamide oxime (2d).
The yield was 82%, colorless crystals, m.p. 142—144 °C, R 0.49
2
f
(
CH Cl —EtOAc, 2 : 1). Found (%): C, 52.52; H, 4.76.
2 2
3
ꢀaminoꢀ5ꢀarylisoxazoles, which can find wide use in orꢀ
1
C H ClN O . Calculated (%): C, 52.99; H, 4.89. H NMR
(
H arom., J = 8.8 Hz); 7.22 (s, 1 H, CH); 5.70 (br.s, 2 H, NH );
3
1
10
11
2
2
ganic synthesis. Based on our quantumꢀchemical data,
we discussed possible reasons for the different reactivities
of the Zꢀ and Eꢀisomers.
DMSOꢀd ), δ: 9.98 (s, 1 H, OH); 7.71, 6.98 (both d, 2 H each,
6
2
13
.78 (s, 3 H, Me). C NMR (DMSOꢀd ), δ: 159.33, 150.11,
6
31.19, 126.49, 121.70, 113.89, 99.51, 55.17 (Me).
2
ꢀChloroꢀ3ꢀ(4ꢀnitrophenyl)propꢀ2ꢀenamide oxime (2e). The
Experimental
yield was 67%, yellow crystals, m.p. 186—187°C, R 0.52
f
(
CH Cl —EtOAc, 2 : 1). Found (%): C, 45.11; H, 3.46.
2 2
1
Quantumꢀchemical calculations were performed with the
C H ClN O . Calculated (%): C, 44.74; H, 3.34. H NMR
9 8 3 3
1
7,18
PRIRODA program.
The ccꢀpVDZm basis set was used. This
(DMSOꢀd ), δ: 10.26 (s, 1 H, OH); 8.27, 7.95 (both d, 2 H each,
6
basis set was derived from Dunning´s well known correlation
consistent basis set ccꢀpVDZ with retention of the number of
basis functions but a different contraction scheme: {5,6/2} for H,
H arom., J = 8.8 Hz); 7.45 (s, 1 H, CH); 5.85 (br.s, 2 H, NH ).
2
1
3
C NMR (DMSOꢀd ), δ: 149.55, 146.54, 140.69, 130.51,
6
127.64, 125.18, 123.48.
{
8,9,10/5,6/2} for C, N, and O, and {11,12,13,14/8,9,10/2}
3ꢀ(4ꢀBromophenyl)ꢀ2ꢀchloropropꢀ2ꢀenamide oxime (2f). The
for Cl. The Mulliken population analysis was used.
yield was 81%, colorless crystals, m.p. 126—128 °C, R 0.56
f
IR spectra were recorded on a URꢀ20 spectrophotometer
(CH Cl —EtOAc, 2 : 1). Found (%): C, 39.19; H, 3.12.
C H BrClN O. Calculated (%): C, 39.23; H, 2.93. H NMR
9 8 2
2
2
1
13
1
(
Nujol). H and C NMR spectra were recorded on a Varian
1
13
VXRꢀ400 spectrometer (400 and 100 MHz for H and C, reꢀ
spectively) in CDCl and DMSOꢀd with Me Si as the internal
(DMSOꢀd ), δ: 10.12 (s, 1 H, OH); 7.63 (m, 4 H, H arom.);
6
13
7.28 (s, 1 H, CH); 5.77 (br.s, 2 H, NH2). C NMR (DMSOꢀd ),
3
6
4
6
standard. TLC analysis was carried out on Merck 60 F254 plates.
Column chromatography was performed on Merck silica gel
δ: 149.76, 133.22, 131.43, 131.37, 125.83, 124.87, 121.65.
2ꢀChloroꢀ3ꢀ(4ꢀdimethylaminophenyl)propꢀ2ꢀenamide oxime
(2g). The yield was 63%, yellow crystals, m.p. 171—172 °C,
R 0.44 (CH Cl —EtOAc, 2 : 1). Found (%): C, 54.50; H, 5.60.
(
63—200 mesh).
Compounds 1a—g were prepared as described earlier.1
Synthesis of 3ꢀarylꢀ2ꢀchloroacrylamide oximes (2) (general
f
2
2
1
C H ClN O. Calculated (%): C, 55.12; H, 5.89. H NMR
1
1
14
3
procedure). A solution of the Zꢀisomer of αꢀchlorocinnamonitrile
1 mmol), hydroxylamine hydrochloride (0.14 g, 2 mmol), and
anhydrous potassium carbonate (0.28 g, 2 mmol) in ethanol
(DMSOꢀd ), δ: 9.88 (s, 1 H, OH); 7.63, 6.72 (both d, 2 H each,
6
(
H arom., J = 8.8 Hz); 7.12 (s, 1 H, CH); 5.63 (br.s, 2 H, NH );
2
13
2.94 (s, 6 H, NMe ). C NMR (DMSOꢀd ), δ: 150.40, 150.13,
2
6
(
(
5 mL) was stirred at room temperature for 1 h. Then water
20 mL) was added. The product was filtered off, washed with
131.01, 126.95, 121.38, 118.82, 111.50, 39.65 (NMe ).
2
Synthesis of aminoarylisoxazoles 3 and 4 (general procedure).
A solution of the Eꢀisomer of 3ꢀarylꢀ2ꢀchloroacrylonitrile
(1 mmol) and hydroxylamine hydrochloride (0.14 g, 2 mmol) in
ethanol (5 mL) was mixed with a solution of KOH (0.22 g,
4 mmol) in water (1 mL). The reaction mixture was refluxed for
4 h and diluted with water (20 mL). The product was extracted
with methylene chloride (3×10 mL). The solvent was removed
and isomeric isoxazoles were separated off by column chromaꢀ
tography with CH Cl —MeCN (10 : 1) as the eluent.
water (5 mL), and dried. When needed, the target amide can be
recrystallized from ethanol.
The IR spectra of all compounds 2a—g contain bands of
–
1
–1
NH (3340—3450 cm ) and OH groups (3150—3240 cm ).
2
2
ꢀChloroꢀ3ꢀ(4ꢀchlorophenyl)propꢀ2ꢀenamide oxime (2a). The
yield was 79%, colorless crystals, m.p. 120—121 °C, R 0.57
(
C H Cl N O. Calculated (%): C, 46.78; H, 3.49. H NMR
f
CH Cl —EtOAc, 2 : 1). Found (%): C, 46.63; H, 3.48.
2 2
1
9
8
2
2
2
2
(
2
DMSOꢀd ), δ: 10.12 (br.s, 1 H, OH); 7.73, 7.48 (both d,
H each, H arom., J = 8.6 Hz); 7.30 (s, 1 H, CH); 5.78 (br.s,
The IR spectra of all compounds 3a—g contain bands of an
6
–
1
NH group (3400—3440 cm ).
2

Reactions of αꢀClꢀcinnamonitriles with NH OH
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
1731
2
5
ꢀAminoꢀ3ꢀ(4ꢀchlorophenyl)isoxazole (3a). The yield
10 : 1). Found (%): C, 53.08; H, 3.59. C H N O . Calcuꢀ
9 7 3 3
1
was 57%, light yellow crystals, m.p. 165—166 °C (cf. Ref. 7:
65—167 °C), R 0.55 (CH Cl —MeCN, 10 : 1). H NMR
CDCl —DMSOꢀd ), δ: 7.57, 7.29 (both d, 2 H each, H arom.,
lated (%): C, 52.69; H, 3.44. H NMR (CDCl ), δ: 8.30, 7.66
3
1
1
(
(both d, 2 H each, H arom., J = 8.8 Hz); 6.27 (s, 1 H, CH); 4.11
f
2
2
13
(s, 2 H, NH2). C NMR (DMSOꢀd ), δ: 166.37, 164.59, 140.73,
3
6
6
J = 8.8 Hz); 5.58 (s, 2 H, NH ); 5.25 (s, 1 H, CH).
129.01, 126.96, 124.30, 119.70, 92.59.
2
3
ꢀAminoꢀ5ꢀ(4ꢀchlorophenyl)isoxazole (4a). The yield
was 29%, colorless crystals, m.p. 137—138 °C (cf. Ref. 19:
41—142 °C), R 0.39 (CH Cl —MeCN, 10 : 1). Found (%):
5ꢀAminoꢀ3ꢀ(4ꢀbromophenyl)isoxazole (3f). The yield
was 51%, colorless crystals, m.p. 164—166 °C (cf. Ref. 9:
1
1
164—166 °C), R 0.56 (CH Cl —MeCN, 10 : 1). H NMR
f
2
2
f
2
2
C, 54.71; H, 3.81. C H ClN O. Calculated (%): C, 55.54;
(CDCl —DMSOꢀd ), δ: 7.51, 7.45 (both d, 2 H each, H arom.,
9
7
2
3 6
1
H, 3.63. H NMR (CDCl ), δ: 7.63, 7.40 (both d, 2 H each,
J = 8.8 Hz); 5.41 (s, 2 H, NH ); 5.27 (s, 1 H, CH).
3
2
H arom., J = 8.6 Hz); 6.06 (s, 1 H, CH); 4.01 (s, 2 H, NH ).
3ꢀAminoꢀ5ꢀ(4ꢀbromophenyl)isoxazole (4f). The yield
was 29%, colorless crystals, m.p. 150—151 °C (cf. Ref. 11:
147—149 °C), R 0.39 (CH Cl —MeCN, 10 : 1). Found (%):
2
1
3
C NMR (DMSOꢀd ), δ: 166.00, 164.64, 134.43, 129.10,
6
1
27.02, 126.40, 93.36.
f
2
2
5
ꢀAminoꢀ3ꢀ(2ꢀnaphthyl)isoxazole (3b). The yield was 46%,
C, 45.21; H, 2.75. C H BrN O. Calculated (%): C, 45.22;
9 7 2
1
light yellow crystals, m.p. 153—154 °C (cf. Ref. 9: 126—128 °C),
R 0.55 (CH Cl —MeCN, 10 : 1). H NMR (CDCl ), δ: 8.16 (s,
H, H arom.); 7.83—7.92 (m, 4 H, H arom.); 7.48—7.53 (m,
H, H arom.); 5.56 (s, 1 H, CH); 4.59 (s, 2 H, NH ).
H, 2.95. H NMR (CDCl ), δ: 7.71, 7.68 (both d, 2 H each,
3
1
H arom., J = 8.8 Hz); 6.37 (s, 1 H, CH); 5.68 (s, 2 H, NH ).
f
2
2
3
2
1
3
1
2
C NMR (DMSOꢀd ), δ: 166.03, 164.61, 131.97, 127.18,
6
126.69, 123.11, 93.37.
2
3
ꢀAminoꢀ5ꢀ(2ꢀnaphthyl)isoxazole (4b). The yield was 29%,
5ꢀAminoꢀ3ꢀ(4ꢀdimethylaminophenyl)isoxazole (3g). The yield
colorless crystals, m.p. 177—178 °C, R 0.40 (CH Cl —MeCN,
was 29%, light yellow crystals, m.p. 185—187 °C, R 0.40
f
2
2
f
1
0 : 1). Found (%): C, 73.48; H, 5.07. C H N O. Calcuꢀ
(CH Cl —MeCN, 10 : 1). Found (%): C, 64.84; H, 6.48.
C H N O. Calculated (%): C, 65.01; H, 6.45. H NMR
11 13 3
13
10
2
2
2
1
1
lated (%): C, 74.27; H, 4.79. H NMR (CDCl ), δ: 8.23 (s, 1 H,
3
H arom.); 7.91—7.83 (m, 3 H, H arom.); 7.76—7.73 (m, 1 H,
H arom.); 7.55—7.50 (m, 2 H, H arom.); 6.20 (s, 1 H, CH); 4.07
(CDCl ), δ: 7.61, 6.74 (both d, 2 H each, H arom., J = 9.0 Hz);
3
5.39 (s, 1 H, CH); 4.43 (s, 2 H, NH ); 3.01 (s, 6 H, NMe ).
2
2
13
13
(
s, 2 H, NH ). C NMR (DMSOꢀd ), δ: 167.11, 164.65, 133.22,
C NMR (DMSOꢀd ), δ: 170.40, 162.50, 150.99, 127.06,
6
2
6
1
1
32.70, 128.67, 128.50, 127.70, 127.15, 126.88, 124.91, 124.47,
22.81, 93.26.
117.30, 111.83, 74.61, 39.83.
3ꢀAminoꢀ5ꢀ(4ꢀdimethylaminophenyl)isoxazole (4g). The yield
5
ꢀAminoꢀ3ꢀ(4ꢀmethylphenyl)isoxazole (3c). The yield
was 27%, light yellow crystals, m.p. 174—176 °C, R 0.29
f
was 29%, colorless crystals, m.p. 149—150 °C (cf. Ref. 9:
(CH Cl —MeCN, 10 : 1). Found (%): C, 63.19; H, 6.68.
2
2
1
1
49—151 °C), R 0.55 (CH Cl —MeCN, 10 : 1). H NMR
C11H13N O•1/3H O. Calculated (%): C, 63.14; H, 6.58.
3 2
f
2
2
1
(
CDCl ), δ: 7.62, 7.24 (both d, 2 H each, H arom., J = 8.3 Hz);
H NMR (CDCl ), δ: 7.59, 6.71 (both d, 2 H each, H arom., J =
3
3
5
.42 (s, 1 H, CH); 4.56 (s, 2 H, NH ); 2.39 (s, 3 H, Me).
9.0 Hz); 5.89 (s, 1 H, CH); 3.93 (s, 2 H, NH ); 3.03 (s, 6 H,
2
2
1
3
3
ꢀAminoꢀ5ꢀ(4ꢀmethylphenyl)isoxazole (4c). The yield
NMe ). C NMR (DMSOꢀd ), δ: 168.08, 164.47, 150.99,
2
6
was 35%, colorless crystals, m.p. 152—153 °C, Rf 0.40
126.35, 115.21, 111.78, 89.56, 39.70.
(
C
1
CH Cl —MeCN, 10 : 1). Found (%): C, 66.00; H, 5.84.
2 2
10H10N O•0.5H O. Calculated (%): C, 65.56; H, 6.05.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ
32052a) and the Foundation for Assistance to Domestic
Science.
2
2
H NMR (CDCl ), δ: 7.61, 7.25 (both d, 2 H each, H arom., J =
3
8
.2 Hz); 6.04 (s, 1 H, CH); 3.99 (s, 2 H, NH ); 2.40 (s, 3 H,
2
13
Me). C NMR (DMSOꢀd ), δ: 167.25, 164.51, 139.54, 129.52,
6
1
25.16, 124.93, 92.10, 20.92.
ꢀAminoꢀ3ꢀ(4ꢀmethoxyphenyl)isoxazole (3d). The yield
was 35%, colorless crystals, m.p. 136—137 °C (cf. Ref. 9:
5
References
1
1
36—138 °C), R 0.44 (CH Cl —MeCN, 10 : 1). H NMR
f 2 2
(
CDCl —DMSOꢀd ), δ: 7.57, 6.85 (both d, 2 H each, H arom.,
3 6
1. V. G. Nenajdenko, A. V. Shastin, I. V. Golubinskii,
O. N. Lenkova, and E. S. Balenkova, Izv. Akad. Nauk,
Ser. Khim., 2004, 218 [Russ. Chem. Bull., Int. Ed., 2004,
J = 8.8 Hz); 5.26 (s, 1 H, CH); 5.14 (s, 2 H, NH ); 3.75 (s,
2
3
H, MeO).
ꢀAminoꢀ5ꢀ(4ꢀmethoxyphenyl)isoxazole (4d). The yield
was 38%, colorless crystals, m.p. 176—177 °C (cf. Ref. 11:
71—172 °C), R 0.35 (CH Cl —MeCN, 10 : 1). Found (%):
3
5
3, 228].
2
. V. G. Nenajdenko, I. V. Golubinskii, O. N. Lenkova, A. V.
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1
f
2
2
C, 62.44; H, 5.27. C H N O . Calculated (%): C, 63.15;
H, 5.30. H NMR (CDCl ), δ: 7.66, 6.96 (both d, 2 H each,
H arom., J = 8.8 Hz); 5.97 (s, 1 H, CH); 3.99 (s, 2 H, NH );
3
1
0
10
2
2
1
3
3. D. L. Flynn, T. R. Belliotti, A. M. Boctor, D. T. Conor,
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2
.86 (s, 3 H, MeO). 13C NMR (DMSOꢀd ), δ: 167.17, 164.53,
6
1
60.37, 126.87, 120.34, 114.39, 91.28, 55.26.
5
ꢀAminoꢀ3ꢀ(4ꢀnitrophenyl)isoxazole (3e). The yield was 21%,
yellow crystals, m.p. 163—165 °C (cf. Ref. 9: 163—165 °C),
R 0.40 (CH Cl —MeCN, 10 : 1). H NMR (CDCl ), δ: 8.33,
7
4
1
f
2
2
3
.89 (both d, 2 H each, H arom., J = 9.0 Hz); 5.31 (s, 1 H, CH);
.01 (s, 2 H, NH ).
2
3
ꢀAminoꢀ5ꢀ(4ꢀnitrophenyl)isoxazole (4e). The yield was 31%,
8. M. Dines and M. L. Sheinbaum, Tetrahedron Lett.,
1969, 4817.
yellow crystals, m.p. 136—137 °C, R 0.28 (CH Cl —MeCN,
f
2
2

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1
1
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6, 1310.
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1
1
2. J. M. Tronchet, O. Martin, A. Grouiller, and N. Sarda,
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Received January 11, 2005;
in revised form June 16, 2005
1
984, 3, 93.