The synthesis of new 5-aminoisoxazoles by reaction of thiocarbamoylcyanoacetates with hydroxylamine

Article abstract of DOI:10.1007/s10593-008-0101-x

The reaction of thiocarbamoylcyanoacetates with hydroxylamine in ethanol under reflux conditions has provided a convenient method for the synthesis of 5-aminoisoxazoles.

Full text of DOI:10.1007/s10593-008-0101-x

Chemistry of Heterocyclic Compounds, Vol. 44, No. 6, 2008
THE SYNTHESIS OF NEW 5-AMINOISOXA-
ZOLES BY REACTION OF THIOCARBAMOYL-
CYANOACETATES WITH HYDROXYLAMINE
J. Khalafy, K. Akbari Dilmaghani, L. Soltani, and A. Poursattar-Marjani
The reaction of thiocarbamoylcyanoacetates with hydroxylamine in ethanol under reflux conditions has
provided a convenient method for the synthesis of 5-aminoisoxazoles.
Keywords: hydroxylamine, isothiocyanates, isoxazoles, thioxopropanoates.
Isoxazoles play an important role in biochemistry, organic chemistry, and bioorganic chemistry. The
biological activity of substituted isoxazoles [1] has made them a focus of medicinal chemistry over the years.
Isoxazoles are potent, selective agonists of human cloned dopamine D4 receptors [2] and exhibit GABAA
antagonistic [3], analgesic [3], anti-inflammatory [4], ulcerogenic [4], antifungal [5], antimicrobial [5], COX-2
inhibitory [6, 7], antinociceptive [8], and anticancer [9] activities.
Many synthetic methods have been employed in the synthesis of isoxazoles [10], including the reactions of
hydroxylamine with 1,3-dicarbonyl compounds [11], α,β-unsaturated carbonyl compounds [12], and α,β-
unsaturated nitriles [13]. The reaction of oxime-derived dianion and ester [14] or amide [15, 16] also provides
isoxazoles. [3+2] Cycloaddition reactions between alkynes and nitrile oxides have been also developed [17, 18].
However, these methods often require strong bases, strong mineral acids, and high temperatures, or provide poor
regioselectivity.
We have reported that the reaction of o-, m-, and p-substituted diethyl phenylthiocarbamoylmalonates
with hydroxylamine under reflux conditions gave o-, m-, and p-substituted 3-phenylaminoisoxazol-5(2H)-ones
[19-21].
X
S
CO2Et
NH2OH
H
NH
C
CH
CO2Et
HN
N
EtOH
O
EtO2C
O
X
X = H, 2-Me, 2-MeO, 3-Br, 4-Br, 3-Me, 4-Me, 4-CO2Et, 4-NO2
__________________________________________________________________________________________
Department of Chemistry, Faculty of Science, Urmia University, Urmia 57154, Iran; e-mail:
jkhalafi@yahoo.com, e-mail: j.khalafi@mail.urmia.ac.ir. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 6, pp. 907-912, June, 2008. Original article submitted July 28, 2007.
0009-3122/08/4406-0729©2008 Springer Science+Business Media, Inc.
729

The reaction of diethyl (2-ethoxycarbonylphenyl)thiocarbamoylmalonate with hydroxylamine under reflux
conditions gave ethyl 2,9-dioxo-4,9-dihydro-2H-isoxazolo[3,2-b]quinazoline-3-carboxylate by intramolecular
condensation [16].
Herein, we report a new and direct method for the synthesis of 5-aminoisoxazoles by the reaction of
thiocarbamoylcyanoacetates with hydroxylamine in ethanol under reflux conditions.
The reaction of aryl isothiocyanates 1a–e with sodium ethylcyanoacetate in ethanol at room temperature
gave the corresponding ethyl arylthiocarbamoyl- cyanoacetates 2a–e in high yield.
The reaction of thiocarbamoylcyanoacetates 2a–e with hydroxylamine by a modification of Worall [22]
procedures in aqueous ethanol under reflux conditions afforded the corresponding 5-aminoisoxazoles 3a–e.
H
ArN
CO2Et
NH2
CN
CN
ArNCS
1a–e
NH2OH
EtOH
N
ArNHCCCO2Et
NaCH
CO2Et
O
S
2a–e
3a–e
a Ar =Ph, b Ar = 2-BrC6H4, c Ar = 3-BrC6H4, d Ar = 4-BrC6H4, e Ar = 1-naphthyl
The mechanism of the reaction is shown in the following Scheme:
SH
S
H
CO2Et
CH
NH
N
NH2OH, EtOH
Ar
OH
Ar
N
H
EtO2C
C
CN
N
H
H
O
SH
H
H
N
N
N
N
Ar
Ar
O
–H2S
EtO2C
EtO2C
NH2
NH
We have reported [19–21] that the reaction of diethyl arylthiocarbamoylmalonate with hydroxylamine
under reflux conditions gave 3-arylamino- isoxazol-5(2H)-ones, but the reaction of ethyl 3-arylamino-2-cyano-
3-thioxopropanoates 2a–e with hydroxylamine under reflux conditions gave the corresponding 5-amino-
isoxazoles 3a–e in good yields. The formation of isoxazoles instead of isoxazolones may be due to the higher
electronegativity of cyano group, which in this case reacts with nucleophilic oximino group to form the
corresponding aminoisoxazoles.
The above results showed that the reaction of thiocarbamoylcyanoacetates with hydroxylamine provides a
synthetically useful method for obtaining 5-aminoisoxazoles in good yield.
EXPERIMENTAL
1H and 13C NMR spectra were recorded with a Bruker spectrometer (300 and 75 MHz, respectively).
The spectra were measured in CDCl3 (compounds 2a-e) or DMSO-d6 (compounds 3a–e) using TMS as the
730

internal standard. IR spectra were recorded on a Thermonicolet (Nexus 670) FT-infrared spectrometer, using
sodium chloride cells and measured as Nujol mulls or KBr disks. Mass spectra were recorded on a Finnigan
TSQ-70 spectrometer at 70 eV. Microanalyses were performed on a Leco Analyzer 932. Melting points were
determined on a Philip Harris C 4954718 apparatus and are uncorrected. All organic extracts were dried with
anhydrous sodium sulfate.
Ethyl 2-cyano-3-(phenylamino)-3-thioxopropanoate (2a). In a one-liter round-bottomed flask,
absolute ethanol (38 ml) was reacted with sodium (2.3 g, 0.1 mol) and after cooling to room temperature,
ethylcyanoacetate (11.3 g, 0.1 mol) was added. The reaction mixture was stirred at room temperature for 15 min.
Phenyl isothiocyanate (13.5 g, 0.1 mol) was added and the stirring was continued for a further 2 h, then water
(50 ml) was added to the reaction mixture. The aqueous layer was extracted with chloroform (30 ml) and then
acidified with diluted hydrochloric acid (10%) to maintain the pH at 3. The yellow precipitate was collected by
vacuum filtration, and recrystallization from n-hexane gave the desired product (21.8 g, 87%) as cream needles;
mp 120-121°C. FT-IR spectrum, ν, cm–1: 3169 (N–H), 2981, 2201, 1658 (C=O), 1587, 1545, 1492, 1453, 1375,
1356, 1261, 1171, 778, 693. 1H NMR spectrum, δ, ppm (J, Hz): 1.36 (3H, t, J = 7.2, CH3); 4.30 (2H, q, J = 7.2,
CH2); 4.72 (1H, s, CH); 7.27–7.50 (5H, m, Ar); 11.75 (1H, br. s, exchanged by D2O addition, NH). 13C NMR
spectrum, δ, ppm: 14.36, 61.06, 72.91, 126.12, 128.59, 129.76, 137.03, 167.78, 169.09. MS (EI), m/z (Irel, %):
248 [M]+ (3), 245 (100), 241 (45), 218 (19), 213 (26), 186 (29), 146 (13), 114 (17), 93 (12), 40 (10). Found, %:
C 57.80; H 4.72; N 11.49. C12H12N2O2S. Calculated, %: C 58.05; H 4.87; N 11.28.
Ethyl 3-(2-bromophenylamino)-2-cyano-3-thioxopropanoate (2b) was prepared as described for the 2a
derivative, using 2-bromophenyl isothiocyanate (21.4 g, 0.1 mol) and stirring for a further 4 h after addition of
2-bromophenyl isothiocyanate to give ethyl 3-(2-bromophenylamino)-2-cyano-3-thioxopropanoate (29 g, 88%)
as a yellow solid; mp 135-136°C. FT-IR spectrum, ν, cm–1: 3159 (N–H), 3070, 2204, 1655 (C=O), 1474, 1307,
1
1378, 1256, 1033, 769. H NMR spectrum, δ, ppm (J, Hz): 1.35 (3H, t, J = 7.2, CH3); 3.46 (1H, s, CH); 4.27
(2H, q, J = 7.2, CH2); 7.26-7.31 (2H, m, Ar); 7.41 (1H, dd, J = 7.2, J = 1.2, Ar); 7.71 (1H, dd, J = 8.1, J = 1.2,
Ar); 11.73 (1H, s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.33, 61.23, 73.84, 118.81,
121.61, 128.43, 129.20, 130.10, 133.81, 137.15, 167.49, 169.11. Found, %: C 44.34; H 3.46; N 8.31.
C12H11BrN2O2S. Calculated, %: C 44.05; H 3.39; N 8.56.
Ethyl 3-(3-bromophenylamino)-2-cyano-3-thioxopropanoate (2c) was prepared as described for the 2a
derivative, using 3-bromophenyl isothiocyanate (21.4 g, 0.1 mol) and stirring for a further 3 h after addition of
3-bromophenyl isothiocyanate to give the desired product (30 g, 91%) as yellow needles; mp 120-121°C. FT-IR
1
spectrum, ν, cm–1: 3150 (N−H), 3062, 2203, 1673 (C=O), 1474, 1376, 1259, 769, 695. H NMR spectrum, δ,
ppm (J, Hz): 1.36 (3H, t, J = 7.2, CH3); 3.51 (1H, s, CH); 4.27 (2H, q, J = 7.2, CH2); 7.23–7.63 (4H, m, Ar);
11.75 (1H, s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.31, 61.31, 63.07, 113.22, 123.04,
124.65, 129.06, 130.91, 131.56, 138.26, 165.68, 167.62. Found, %: C 44.29; H 3.54; N 8.32. C12H11BrN2O2S.
Calculated, %: C 44.05; H 3.39; N 8.56.
Ethyl 3-(4-bromophenylamino)-2-cyano-3-thioxopropanoate (2d) was prepared as described for the 2a
derivative, using 4-bromophenyl isothiocyanate (21.4 g, 0.1 mol) and stirring for a further 2 h after addition of
4-bromophenyl isothiocyanate to give ethyl 3-(4-bromophenylamino)-2-cyano-3-thioxopropanoate (27 g, 83%)
as yellow needles; mp 145-146°C. FT-IR spectrum, ν, cm–1: 3182 (N–H), 3069, 2973, 2200, 1671 (C=O), 1656,
1
1486, 1402, 1372, 1257, 1161, 1048, 768. H NMR spectrum, δ, ppm (J, Hz): 1.39 (3H, t, J = 7.2, CH3); 4.30
(2H, q, J = 7.2, CH2); 4.76 (1H, s, CH); 7.15 (2H, d, J = 7.5, Ar); 7.57 (2H, d, J = 7.5, Ar); 11.70 (1H, s,
exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.33, 61.23, 73.55, 118.83, 122.34, 127.64,
132.93, 136.03, 167.67, 168.78. MS (EI), m/z (Irel, %): 328 [M+2]+ (2), 326 [M]+, (2), 296 (96), 294 (100), 250
(59), 248 (59), 223 (31), 221 (32), 182 (28), 184 (28), 142 (41), 115 (18), 76 (15), 52 (10). Found, %: C 44.44;
H 3.48; N 8.69. C12H11BrN2O2S. Calculated, %: C 44.05; H 3.39; N 8.56.
731

Ethyl 2-cyano-3-(naphth-1-ylamino)-3-thioxopropanoate (2e) was prepared as described for the 2a
derivative, using 1-naphthyl isothiocyanate (18.5 g, 0.1 mol) and stirring for a further 5 h after addition of
1-naphthyl isothiocyanate to give the desired product (22.6 g, 79%) as yellow needles; mp 131-132°C. FT-IR
1
spectrum, ν, cm–1: 3400 (N–H), 2991, 2203, 1651 (C=O), 1570, 1375, 1277, 777. H NMR spectrum, δ, ppm
(J, Hz): 1.41 (3H, t, J = 7.2, CH3); 4.34 (2H, q, J = 7.2, CH2); 4.62 (1H, s, CH); 7.45-7.66 (4H, m, Ar); 7.89–
7.96 (3H, m, Ar); 11.98 (1H, br. s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.42, 61.14,
73.01, 119.04, 121.98, 125.07, 125.23, 127.25, 127.80, 128.60, 129.51, 129.58, 133.22, 134.36, 168.03, 170.64.
MS (EI), m/z (Irel, %): 298 [M]+, (14), 295 (100), 292 (64), 281 (24), 263 (29), 236 (16), 196 (13), 164 (19).
Found, %: C 64.30; H 4.83; N 9.10. C16H14N2O2S. Calculated, %: C 64.41; H 4.73; N 9.39.
Ethyl 5-amino-3-(phenylamino)isoxazole-4-carboxylate (3a). Potassium hydroxide (6 g, 0.1 mol) was
slowly added to a solution of hydroxylamine hydrochloride (7.08 g, 0.1 mol) in water (30 ml). Ethanol (80 ml)
was added and the resulting potassium chloride was filtered off. Propanoate 2a (2.47 g, 0.01 mol) was added to
the filtrate and the mixture was refluxed for 24 h, water (80 ml) was added to the reaction mixture and the white
precipitate was collected by vacuum filtration. The white solid was recrystallized from ethanol to give the
desired product (2.42 g, 97%) as white needles; mp 167-168°C. FT-IR spectrum, ν, cm–1: 3481 (N–H), 3268
(NH2), 1667 (C=O), 1654, 1606, 1559, 1120, 779, 746. 1H NMR spectrum, δ, ppm (J, Hz): 1.29 (3H, t, J = 7.2,
CH3); 4.24 (2H, q, J = 7.2, CH2); 6.94 (1H, t, J = 7.2, Ar); 7.30 (2H, t, J = 7.5, Ar); 7.44 (2H, d, J = 7.2, Ar);
7.79 (2H, br. s, exchanged by D2O addition, NH2); 8.10 (1H, s, exchanged by D2O addition, NH). 13C NMR
spectrum, δ, ppm: 14.87, 60.01, 77.09, 117.83, 121.47, 129.41, 140.33, 159.41, 163.52, 169.75 (C=O). Mass
spectrum (EI), m/z (Irel, %): 247 [M]+ (58), 246 (100), 201 (14), 200 (20), 159 (43), 157 (95), 131 (36), 129 (73),
102 (57), 90 (73), 78 (27), 77 (27), 65 (58). Found, %: C 58.11; H 5.67; N 16.70. C12H13N3O3. Calculated, %:
C 58.29; H 5.30; N 16.99.
Ethyl 5-amino-3-(2-bromophenylamino)isoxazole-4-carboxylate (3b) was prepared as described for
compound 3a, using ethyl propanoate 2b (3.27 g, 0.01 mol) and refluxing for 48 h, to give the desired product
(2.63 g, 80%) as white needles; mp 155-156°C. FT-IR spectrum, ν, cm–1: 3480 (N–H), 3281 (NH2), 1654
1
(C=O), 1599, 1584, 1555, 1458, 1442, 1129, 1022, 782, 742. H NMR spectrum, δ, ppm (J, Hz): 1.31 (3H, t,
J = 7.2, CH3); 4.29 (2H, q, J = 7.2, CH2); 6.90 (1H, td, J = 7.2, J = 1.5, Ar); 7.38 (1H, td, J = 8.1, J = 1.2, Ar);
7.63 (1H, dd, J = 7.8, J = 1.2, Ar); 7.90 (2H, br. s, exchanged by D2O addition, NH2), 8.06 (1H, dd, J = 8.6,
J = 1.5, Ar), 8.69 (1H, br. s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm: 14.86, 60.62, 77.21,
119.25, 122.32, 126.56, 128. 58, 132.29, 138.82, 157.75, 163.22, 172.34 (C=O). Found, %: C 44.43; H 3.67;
N 12.76. C12H12BrN3O3. Calculated, %: C 44.19; H 3.71; N 12.88.
Ethyl 5-amino-3-(3-bromophenylamino)isoxazole-4-carboxylate (3c) was prepared as described for
compound 3a, using compound 2c (3.27 g, 0.01 mol) and refluxing for 48 h, to give the desired product (2.9 g,
88%) as white needles; mp 160-161°C. FT-IR spectrum, ν, cm–1: 3481 (N–H), 3269 (NH2), 1650 (C=O), 1604,
1578, 1552, 1467, 1120, 773. 1H NMR spectrum, δ, ppm (J, Hz): 1.30 (3H, t, J = 7.2, CH3); 4.26 (2H, q, J = 7.2,
CH2); 7.10 (1H, br. d, J = 7.8, Ar); 7.24 (1H, t, J = 8.1, Ar); 7.41 (1H, d, J = 7.5, Ar); 7.80 (1H, s, Ar); 7.85 (2H,
s, exchanged by D2O addition, NH2); 8.23 (1H, s, exchanged by D2O addition, NH). 13C NMR spectrum, δ, ppm:
14.88, 60.07, 77.21, 117.05, 120.27, 122.29, 124.05, 131.22, 141.92, 159.17, 163.30, 169.86. Mass spectrum
(EI), m/z (Irel, %): 327 [M+2]+ (50), 325 [M+2]+ (50), 281 (10), 279 (10), 200 (16), 173 (20), 171 (21), 157
(100), 118 (14), 92 (27), 90 (88), 64 (39), 62 (40). Found, %: C 44.40; H 3.56; N 12.65. C12H12BrN3O3.
Calculated, %: C 44.19; H 3.71; N 12.88.
Ethyl 5-amino-3-(4-bromophenylamino)isoxazole-4-carboxylate (3d) was prepared as described for
compound 3a, using compound 2d (3.27 g, 0.01 mol) and refluxing for 48 h to give the desired product (2.6 g,
79%) as white needles; mp 160-161°C. FT-IR spectrum, ν, cm–1: 3469 (N–H), 3275 (NH2), 1667 (C=O), 1652,
1600, 1556, 1476, 1112, 781. 1H NMR spectrum, δ, ppm (J, Hz): 1.30 (3H, t, J = 7.2, CH3); 4.28 (2H, q, J = 7.2,
CH2); 7.25–7.56 (4H, m, Ar); 7.82 (2H, br. s, exchanged by D2O addition, NH2); 8.19 (1H, s, exchanged by D2O
addition, NH). 13C NMR spectrum, δ, ppm: 14.88, 60.04, 77.18, 112.91, 120.06, 132.02, 139.77, 159.24,
732

161.54, 169.85 (C=O). MS (EI), m/z (Irel, %): 327 [M+2]+ (6), 325 [M]+ (6), 199 (84), 198 (84), 197 (100), 169
(16), 118 (10), 98 (18), 90 (58), 44 (22). Found, %: C 44.31; H 3.63; N 12.50. C12H12BrN3O3. Calculated, %:
C 44.19; H 3.71; N 12.88.
Ethyl 5-amino-3-(naphth-1-ylamino)isoxazole-4-carboxylate (3e) was prepared as described for
compound 3a, using propanoate 2e (2.86 g, 0.01 mol) and refluxing for 48 h to give the desired product (1.78 g,
60%) as white needles; mp 138-139oC. FT-IR spectrum, ν, cm–1: 3310 (N–H), 3274 (NH2), 1651 (C=O), 1628,
1
1595, 1512, 1465, 1441, 1127, 786, 767. H NMR spectrum, δ, ppm (J, Hz): 1.50 (3H, t, J = 7.1, CH3); 4.52
(2H, q, J = 7.1, CH2); 7.19 (2H, s, exchanged by D2O addition, NH2); 7.52–7.71 (3H, m, Ar); 7.77 (1H, t,
J = 8.4, Ar); 7.86–7.97 (2H, m, Ar); 8.03 (1H, t, J = 8.4, Ar); 9.00 (1H, br. s, exchanged by D2O addition, NH).
13C NMR spectrum, δ, ppm: 14.43, 61.07, 112.98, 119.231, 122.30, 124.42, 127.65, 128.59, 132.29, 169.06
(C=O). MS (EI), m/z (Irel, %): 297 [M]+ (3), 269 (7), 199 (56), 185 (100), 158 (27), 114 (19), 79 (13), 40 (18).
Found, %: C 64.83; H 5.18; N 14.01. C16H15N3O3. Calculated, %: C 64.64; H 5.09; N 14.13.
The authors are grateful to Urmia University for financial support.
REFERENCES
1.
For a brief Review see: L. Carlsen, D. Dopp, H. Dopp, F. Duus, H. Hartmann, S. Lang-Fugmann,
B. Schulze, R. K. Smalley, and B. J. Wakefield, in: E. Schaumann (editor), Houben-Weyl, Methods in
Organic Chemistry; Georg Thieme Verlag, Stuttgart, Germany, 1992, Vol. E 8a, p. 45.
M. Rowley, H. B. Broughton, I. Collins, R. Baker, F. Emms, R. Marwood, S. Patel, and C. I. Ragan,
J. Med. Chem., 39, 1943 (1996).
B. Frolund, A. T. Jorgensen, L. Tagmose, T. B. Stensbol, H. T. Vestergaard, C. Engblom,
U. Kristiansen, C. Sanchez, P. Krogsgaard-Larsen, and T. Liljefors, J. Med. Chem., 45, 2454 (2002).
G. Daidone, D. Raffa, B. Maggio, F. Plescia, V. M. C. Cutuli, N. G. Mangano, and A. Caruso, Arch.
Pharm. Med. Chem., 332, 50 (1999).
2.
3.
4.
5.
K. Tomita, Y. Takahi, R. Ishizuka, S. Kamamura, M. Nakagawa, M. Ando, T. Nakanishi, and
T. Nakamura, H. Udaira, Ann. Sankyo Res. Lab., 1, 25 (1973); Chem. Abstr., 80, 120808 (1974).
J. J. Talley, Prog. Med. Chem., 13, 201 (1999).
6.
7.
8.
9.
J. J. Talley, D. L. Brown, J. S. Carter, M. J. Graneto, C. M. Koboldt, J. L. Masferrer, W. E. Perkins,
R. S. Rogers, A. F. Shaffer, Y. Y. Zhang, B. S. Zweifel, and K. Seibert, J. Med. Chem., 43, 775 (2000).
M. P. Giovannoni, C. Vergelli, C. Ghelardini, N. Galeotti, A. Bartolini, and V. Kal Piaz, J. Med. Chem.,
46, 1055 (2003).
W. T. Li, D. R. Hwang, C. P. Chen, C. W. Shen, C. L. Huang, T. W. Chen, C. H. Lin, Y. L. Chang,
Y. Y. Chang, Y. K. Lo, H. Y. Tseng, C. C. Lin, J. S. Song, H. C. Chen, S. J. Chen, S. H. Wu,
C. T. Chen, J. Med. Chem., 46, 1706 (2003).
10.
For a recent Review, see: B. J. Wakefield, in: E. Shaumann (editor), Science of Synthesis: Houben-Weyl
Methods of Molecular Transformations, Georg Thieme Verlag, Stuttgart, 2001, vol. 11, p. 229.
T. Bandiera, T, P. Grunanger, and F. M. Albini, J. Heterocycl. Chem., 29, 1423 (1992).
P. Cuadrado, A. M. Gonzalez-Nogal, and R. Valero, Tetrahedron, 58, 4975 (2002).
C. B. Vicentini, A. C. Verones, T. Poli, M. Guarneri, P. Giori, and V. Ferretti, J. Heterocycl. Chem., 27,
1481 (1990).
11.
12.
13.
14.
15.
16.
17.
Y. He and N. H. Lin, Synthesis, 9, 989 (1994).
G. N. Barber and R. A. Olofson, J. Org. Chem., 43, 3015 (1978).
T. J. Nitz, D. L. Volkots, D. J. Aldous, and R. C. Oglesby, J. Org. Chem., 59, 5828 (1994).
S. E. Denmark and J. M. Kallemeyn, J. Org. Chem., 70, 2839 (2005).
733

18.
V. Jaeger and P. A. Colinas, in: A. Padwa and W. H. Pearson (editors), Synthetic Applications of
1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles Natural Products, Chemistry of Heterocyclic
Compounds, Wiley, Hoboken, 2002, vol. 59, p. 361.
19.
20.
21.
J. Khalafy, A. R. Molla Ebrahimlo, R. Eisavi, and K. Akbari Dilmaghani, ARKIVOC, xiv, 59 (2005).
J. Khalafy, A. Poursattar Marjani, and A. R. Molla Ebrahimlo, J. Braz. Chem. Soc., 17, 570 (2006).
M. M. Baradarani, J. Khalafy, S. Khadivi, and A. Poursattar Marjani, ХГС, 751 (2008). [Chem.
Heterocycl. Comp., 44 (2008)].
22.
D. E. Worrall, J. Am. Chem. Soc., 45, 3092 (1923).
734