Expedient synthesis of pyrazoles substituted with amino, hydroxyl and thioamide groups

Article abstract of DOI:10.1016/j.tetlet.2008.03.046

The reaction of α,β-acetylenic γ-hydroxy nitriles with thiosemicarbazide, under mild conditions (rt, no catalyst, in 1:1 aqueous ethanol, 4-14 h), proceeds chemo-, regio- and stereoselectively to give atypically so far inaccessible tri-functionalized (ami

Full text of DOI:10.1016/j.tetlet.2008.03.046

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3104–3107
Expedient synthesis of pyrazoles substituted
with amino, hydroxyl and thioamide groups
a,
a
a
*
Boris A. Trofimov , Anastasiya G. Mal’kina , Angela P. Borisova ,
Valentina V. Nosyreva a, Olesya A. Shemyakina a, Olga N. Kazheva b,
Gennadii V. Shilov b, Oleg A. Dyachenko b
a A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia
b Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Academician Semenov Str., 142432 Chernogolovka, Russia
Received 30 January 2008; revised 28 February 2008; accepted 7 March 2008
Available online 18 March 2008
Abstract
The reaction of a,b-acetylenic c-hydroxy nitriles with thiosemicarbazide, under mild conditions (rt, no catalyst, in 1:1 aqueous
ethanol, 4–14 h), proceeds chemo-, regio- and stereoselectively to give atypically so far inaccessible tri-functionalized (amino, hydroxyl
and thioamide groups) pyrazoles in 53–91% yields. The hydroxyl function is easily protected by using the corresponding acetals of the
starting acetylenic hydroxy nitriles.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: a,b-Acetylenic c-hydroxy nitriles; Thiosemicarbazide; Pyrazoles; Nucleophilic addition/cyclization; X-ray crystal structure
Pyrazoles are important compounds in the pharmaceuti-
cal industry as the pyrazole motif forms the core structure
of numerous biologically active compounds.1 Pyrazole
derivatives have been used as analgesic,2 antiinflamma-
tory,3 antipyretic,4 antidepressant,5 antibacterial,6 antimi-
crobial,7 anticonvulsant and antifilarial agents,8 and for
the treatment of rheumatoid arthritis.9 They are also
applied as herbicides,10 fungicides,11 insecticides12 and
dyestuffs13 in sunscreen materials,14 and as analytical
reagents.15
azoles. For example, in the usual route to pyrazoles, the
reaction of hydrazines with 1,3-dicarbonyl compounds
results, as a rule, in a mixture of regioisomers.1b,17 Also,
the syntheses of substituted pyrazoles by the reaction of
hydrazones with electron-deficient alkynes are non-
regioselective.18
In this Letter, we report on the regioselective synthesis
of 5-amino-3-hydroxyalkyl-1-aminothiocarbonyl-pyrazoles
2 (in 53–91% yields) by the cyclization of a,b-acetylenic
c-hydroxy nitriles 1a–d with thiosemicarbazide.19
Hence, numerous methods for the preparation of pyra-
zoles have been developed. However, the regioselective syn-
thesis of densely functionalized pyrazoles still remains a
significant challenge for organic chemists. Thus, a new
expedient method for the regioselective synthesis of the
functionalized pyrazole derivatives would be an important
contribution to pyrazole chemistry.1b,16 Hydrazines, as
starting materials, are employed for the synthesis of pyr-
The structural assignment proved to be a difficult task.
Indeed, a number of alternative structures with the same
composition and mass as well as similar spectra (IR,
NMR and UV) could be expected to be formed (Table 1).
For an unambiguous structure assignment, we per-
formed an X-ray analysis of a single crystal of product
2d, which proved to be 5-amino-3-(1-hydroxycyclohexyl)-
1H-pyrazole-1-carbothioamide20 (Fig. 1).
The pyrazole ring is planar, with the maximum devia-
tion of the C(4) and C(5) atoms out of the plane being
0.006 A. The dihedral angle between the pyrazole ring
*
Corresponding author. Tel.: +7 395 2 51 19 26; fax: +7 395 2 41 93 46.
E-mail address: boris_trofimov@irioch.irk.ru (B. A. Trofimov).
˚
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.046

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3104–3107
3105
Table 1
The synthesis of 5-amino-3-(1-hydroxyalkyl)-1H-pyrazole-1-carbothioamidesa
R2
R1
HO
N
R2
H
N
NH2
R1
CN
+
H2N
H2N
N
OH
S
1a-d
NH2
S
2a-d
R1
R2
Product
Time (h)
Yield (%)
Me
Me
Me
Et
2a
2b
2c
2d
4
5
14
14
91
73
53
68
Cyclopentyl
Cyclohexyl
a
The reaction proceeds in aqueous ethanol (1:1 vol) at room temperature.
Fig. 1. The X-ray structure of 5-amino-3-(1-hydroxycyclohexyl)-1H-
pyrazole-1-carbothioamide 2d.
plane and the SC(7)N(8) plane is 168.2°. In the crystal,
all the molecules are directed by thioamide functions to
each other and are linked by hydrogen bonds
˚
˚
[Sꢀ ꢀ ꢀH(8B)—2.61(3) A, Oꢀ ꢀ ꢀH(8A)—2.23(3) A, N(2)ꢀ ꢀ ꢀ
˚
˚
H(6A)—2.54(3) A, N(6)ꢀ ꢀ ꢀH(O)—2.50(3) A; Van der
21
Fig. 2. The supramolecular crystal structure of 5-amino-3-(1-hydroxy-
cyclohexyl)-1H-pyrazole-1-carbothioamide 2d (hydrogen atoms are not
shown).
˚
˚
Waals radii are Sꢀ ꢀ ꢀH—3.15 A, Oꢀ ꢀ ꢀH—2.7 A, Nꢀ ꢀ ꢀH—
˚
2.8 A]. Thus, a supramolecular structure exists in the
solid state (Figs. 2 and 3).
In the IR spectra of pyrazoles 2a–d (dilute CCl4 solu-
tions, c = 1 ꢁ 10ꢂ1 M, d = 0.5–200 mm) four absorption
bands were present at ca. 3510, 3478, 3356 and
3271 cmꢂ1, which are assigned to the OH (non-associated)
and NH2 (non-associated and associated) groups,
respectively.22
1
In the H NMR spectra of compounds 2, the proton of
the pyrazole ring occurred as a singlet at d 5.43–5.49 ppm.
The NH2 group at the pyrazole C-5 appeared as a broad
singlet at d 7.07–7.11 ppm, while the NH2 group of the thi-
oamide function appeared as two broad singlets at 8.88–
9.00 ppm and 8.37–8.45 ppm. The 13C NMR spectra corre-
sponded with the structures of pyrazoles 2.22
The present cyclization reaction is unexpected. Indeed, it
is known that thiosemicarbazide attacks electron-deficient
acetylenes (dimethyl acetylenedicarboxylate) initially
through the sulfur (as shown for substituted thiosemicarb-
azides: 4-methyl- and 4-allylthiosemicarbazide).23 Also
Fig. 3. Fragments of the supramolecular network of 5-amino-3-(1-
hydroxycyclohexyl)-1H-pyrazole-1-carbothioamide 2d (hydrogen atoms
of cyclohexane are not shown).

3106
B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3104–3107
reported are examples of thiosemicarbazide addition to tri-
ple bonds through the amino group.24,25 In a short note,24
it was reported, that the reaction of 1,3-diphenyl-2-propyn-
1-one with 1-phenylthiosemicarbazide gave 1,3,5-tri-
phenylpyrazole (characterized by mp and IR spectroscopy).
Meanwhile, the addition of thiosemicarbazide to cyano-
acetylene stopped after the first step to afford the open-
chain adduct.25
The formation of pyrazoles 2a–d is likely to start with
the addition of the hydrazide amino group to the triple
bond of 1 to form intermediate A, which cyclizes through
the cyano group to furnish iminodihydropyrazole B.
Finally, a prototropic shift yields pyrazoles 2.
References and notes
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Heterocycl. Syst. 2002, 6, 52–98; (b) Deng, X.; Mani, N. S. Org. Lett.
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¨
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V. Pharm. Chem. J. 2006, 40, 373–376.
R2
R1
NH
H
N
R2
R1
NH2
HO
N
HO
5. Bailey, D. M.; Hansen, P. E.; Hlavac, A. G.; Baizman, E. R.; Pearl, J.;
Defelice, A. F.; Feigenson, M. E. J. Med. Chem. 1985, 28, 256–260.
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Arch. Pharm. 2006, 339, 291–298.
H2N
S
1a-d
NC
HN
NH
2a-d
HN
H2N
S
S
NH2
7. Wardakhan, W. W.; Louca, N. A. J. Chil. Chem. Soc. 2007, 52, 1145–
1149.
A
B
8. Chauhan, P. M. S.; Singh, S.; Chatterjee, R. K. Indian J. Chem., Sect.
B 1993, 32, 858–861.
9. (a) Kurowski, M.; Dunky, A.; Geddawi, M. Eur. J. Clin. Pharmacol.
1986, 31, 307–311; (b) Leenen, F. H. H.; Smith, D. L.; Unger, W. P.
Br. J. Clin. Pharmacol. 1988, 26, 481–485.
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(b) Vicentini, C. B.; Guccione, S.; Giurato, L.; Ciaccio, R.;
Mares, D.; Forlani, G. J. Agric. Food Chem. 2005, 53, 3848–
3855.
The synthetic value of this cyclization can be enlarged
by the protection of the hydroxyl function in the pyrazoles
formed. This was realized by employing the corresponding
acetals of type 3 instead of alcohols 1a–d. Such acetals are
readily prepared by the electrophilic addition of the
hydroxy derivatives 1a–d to vinyl ethers.26
Me
HCl
11. (a) Chen, H.; Li, Z.; Han, Y. J. Agric. Food Chem. 2000, 48, 5312–
5315; (b) Vors, J.-P.; Gerbaud, V.; Gabas, N.; Canselier, J. P.;
Jagerovic, N.; Jimeno, M. L.; Elguero, J. Tetrahedron 2003, 59, 555–
560.
12. (a) Finkelstein, B. L.; Strock, C. J. Pestic. Sci. 1997, 50, 324–328; (b)
Shiga, Y.; Okada, I.; Takizawa, E.; Fukuchi, T. J. Pestic. Sci. 2003,
28, 313–314.
13. Fahmy, S. M.; Badran, A. H.; Elnagdi, M. H. J. Chem. Tech. B:
Technol. 1980, 30, 390–395; Chem. Abstr. 1981, 94, 48804.
14. Garcia, H.; Iborra, S.; Miranda, M. A.; Morera, I. M.; Primo, J.
Heterocycles 1991, 32, 1745–1755.
15. Busev, A. I.; Akimov, V. K.; Gusev, S. I. Russ. Chem. Rev. (Engl.
Transl.) 1965, 34, 237–249; Chem. Abstr. 1965, 62, 15395.
16. (a) Elguero, J. In Comprehensive Heterocyclic Chemistry; Katritzky,
A. R., Rees, C. W., Eds.; Pergamon Press: Oxford, 1984; Vol. 5, pp
167–303; (b) Elguero, J. In Comprehensive Heterocyclic Chemistry;
Shinkai, I., Katritzky, A. R., Rees, C. W., Scriven, E. F., Eds.;
Pergamon Press: Oxford, 1996; Vol. 3, pp 1–75, 817–932; (c) Makino,
K.; Kim, H. S.; Kurasava, Y. J. Heterocycl. Chem. 1998, 35, 489–497.
and references cited therein.
Me
CN
OBu- n
Bu-n
1a
+
O
30 o C, 3 h
O
Me
3
Acetal 3 reacted with thiosemicarbazide to give pyrazole
4, with a protected hydroxyl function, in 40% isolated yield
(not optimized).
Me
O
O
H
N
Bu-n
NH2
H2O/EtOH (1:1 vol)
r.t., 14 h
Me Me
3
+
H2N
H2N
N
N
S
S
NH2
4
Thus, chemo-, regio- and stereoselective addition of thi-
osemicarbazide to a,b-acetylenic c-hydroxy nitriles and
their acetal derivatives yields an expedient route to previ-
ously inaccessible densely functionalized (amino, hydroxyl,
acetal and thioamide groups) pyrazoles, which are the
promising substrates for drug design.
17. (a) Miller, R. D.; Reiser, O. J. Heterocycl. Chem. 1993, 30, 755–763;
(b) Bishop, B. C.; Brands, K. M. J.; Gibb, A. D.; Kennedy, D. J.
Synthesis 2004, 43–52; (c) Wang, Z.-X.; Qin, H.-L. Green Chem. 2004,
6, 90–92; (d) Norris, T.; Colon-Cruz, R.; Ripin, D. H. B. Org. Biomol.
Chem. 2005, 3, 1844–1849.
18. (a) Saxena, M. K.; Gudi, M. N.; George, M. V. Tetrahedron 1973, 29,
101–105; (b) Bardakos, V.; Sucrow, W.; Fehlauer, A. Chem. Ber.
1975, 108, 2161–2170; (c) Baumes, R.; Jacquier, R.; Tarrago, G. Bull.
Soc. Chim. Fr. 1976, 260–264.
Acknowledgements
19. The reaction was monitored by TLC on Al2O3 with chloroform–
benzene–ethanol (20:4:1) used as an eluent. Thiosemicarbazide
recrystallized from water was employed, mp 183–184 °C. The starting
a,b-acetylenic c-hydroxy nitriles 1a–d were synthesized from bromo
This work was supported by the Russian Foundation of
Basic Research (Grant No. 08-03-00156) and Integration
Project No. 54.

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3104–3107
3107
derivatives of acetylenic alcohols and CuCN in DMF.27 Nitriles 1a–d
are stable compounds and can be stored at ꢂ5 to ꢂ8 °C for longer
than one year without visible decomposition.
(KBr): 3522, 3398, 3337, 3287, 3250, 3168, 2964, 2934, 2871, 1615,
1556, 1491, 1451, 1423, 1363, 1328, 1292, 1215, 1179, 1096, 1073,
1039, 1006, 905, 886, 870, 756, 707, 652, 625, 554, 463 cmꢂ1. Anal.
Calcd for C9H14N4OS: C, 47.77; H, 6.24; N, 24.76; S, 14.17. Found:
C, 47.69; H, 6.43; N, 24.88; S, 14.55.
20. Crystal and experimental data: C10H16N4OS, M = 240.33, mono-
˚
˚
˚
clinic, P21/n, a = 10.487(2) A, b = 10.164(2) A, c = 11.765(2) A,
b = 107.14(3)°, V = 1198.3(4) A , Z = 4, Dcalcd = 1.33 g cmꢂ3
,
5-Amino-3-(1-hydroxycyclohexyl)-1H-pyrazole-1-carbothioamide
(2d): mp 142–144 °C. 1H NMR [(CD3)2CO, 400.13 MHz]: d 8.93 (s,
1H, NH), 8.37 (s, 1H, NH), 7.07 (s, 2H, NH2), 5.47 (s, 1H, @CH),
3.69 (s, 1H, OH), 1.76–1.49 (m, 10H, CH2). 13C NMR [(CD3)2CO,
101.61 MHz]: d 179.95 (S@C–NH2), 162.63 (H2N–C@CH), 153.28
(–N@C–CH@), 86.69 (@CH), 70.44, 38.29, 26.30, 22.48 (C-cyclo-
hexyl). IR (KBr): 3512, 3387, 3343, 3267, 3249, 3171, 3152, 2940,
2912, 2850, 1612, 1555, 1487, 1449, 1422, 1362, 1342, 1259, 1250,
1191, 1178, 1137, 1127, 1079, 1035, 970, 905, 872, 840, 755, 719, 664,
638, 596, 495, 462, 449 cmꢂ1. UV (ethanol): 243 (lge = 3.98), 275
(lge = 4.23), 317 (lge = 3.24) nm. Anal. Calcd for C10H16N4OS: C,
49.98; H, 6.71; N, 23.31; S, 13.34. Found: C, 50.19; H, 6.90; N, 23.61;
S, 13.53.
3
˚
l = 0.256 mmꢂ1, reflections observed/independent 2475/1906, 194
parameters refined, R = 0.067 for 860 reflections with [F0 > 4r(F0)].
X-ray diffraction was carried out on an Enraf Nonius diffractometer
at room temperature (x/2h-scanning, Mo-Ka radiation, graphite
monochromator). The crystal structure was solved by direct methods
followed by Fourier synthesis using SHELXS-97.28 All the non-
hydrogen atoms were refined using full-matrix anisotropic approxi-
mation using SHELXL-97.28 The coordinates of the hydrogen atoms
were defined experimentally and refined isotropically. Crystallo-
graphic data (excluding structure factors) for the structure in this
paper have been deposited with the Cambridge Crystallographic Data
Centre as Supplementary Publication Number CCDC 675539. Copies
of the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK; (fax: +44 (0)1223 336033;
or e-mail: deposit@ccdc.cam.ac.uk).
23. Lown, J. W.; Ma, J. S. N. Can. J. Chem. 1967, 45, 953–
967.
24. Nakhmanovich, A. S.; Glotova, T. E. Khim. Geterotsikl. Soed. 1985,
1136–1137 (Russian).
25. Murahashi, S.; Ryutani, B.; Shuto, Y. J. Chem. Soc. Japan, Pure
Chem. Sect. 1957, 78, 324–333.
21. Batsanov, S. S. Russ. J. Inorg. Chem. 1991, 36, 3015–3037.
22. General procedure for the synthesis of pyrazoles: A solution of
thiosemicarbazide (0.23 g, 2.5 mmol) in water (4 mL) and ethanol
(2 mL) was heated to 43–45 °C, then a solution of hydroxylalkyne-
nitrile (2.5 mmol) 1 in ethanol (2 mL) was slowly added (15 min). The
mixture was stirred for 4–14 h at 20–25 °C, after which the majority of
the solvent was removed in vacuum. The residue was passed through
an Al2O3 column (4–5 cm, chloroform–benzene–ethanol as an eluent,
20:4:1). After the removal of the solvents, the crude product was
washed consecutively with diethyl ether and hexane, then dried in
vacuum to give compounds 2a–d.
26. The acetal, 4-(1-butoxyethoxy)-4-methyl-2-pentynenitrile, 3 was syn-
thesized as follows: to a solution of butyl vinyl ether (10 mL) and
nitrile 1a (3.27 g, 30 mmol), a saturated solution of HCl in dry
dioxane (0.06 g) was added. The reaction mixture was heated to 30 °C
and the mixture was stirred for 3 h. After neutralization with K2CO3,
the reaction mixture was distilled under vacuum to give 3.76 g (60%)
25
of acetal 3, bp 88–92 °C (1 mmHg), ½nꢃD 1.4415. 1H NMR [(CD3)2CO,
400.13 MHz]: d 5.04 (q, 1H, OCHO, 3J = 5.44 Hz), 3.47 (m, 2H,
OCH2), 1.56 (s, 3H, CH3), 1.52 (s, 3H, CH3), 1.49 (m, 2H, CH2), 1.36
(m, 2H, CH2), 1.25 (d, 3H, OCHCH3O, 3J = 5.12 Hz), 0.89 (t, 3H,
CH3, 3J = 7.29 Hz). 13C NMR [(CD3)2CO, 101.61 MHz]: d 105.46
(CN), 97.62 [OCH(CH3)O], 89.07 („CC), 70.55 („CC), 64.85
(OCH2), 58.08 („CCN), 32.62 (CH2), 28.70 [(CH3)2C], 21.67
(OCCH3), 20.09 (CH2CH3), 14.03 (CH3). IR (KBr): 2975, 2950,
2930, 2863, 2292, 2265, 1460, 1450, 1373, 1360, 1333, 1227, 1155,
1115, 1065, 1020, 1010, 970, 905, 890, 825, 735, 600, 487 cmꢂ1. Anal.
Calcd for C12H19NO2: C, 68.87; H, 9.15; N, 6.69. Found: C, 68.80; H,
8.94; N, 6.72.
5-Amino-3-(1-hydroxy-1-methylethyl)-1H-pyrazole-1-carbothioamide
(2a): mp 132–134 °C. 1H NMR [(CD3)2CO, 400.13 MHz]: d 8.95 (s,
1H, NH), 8.42 (s, 1H, NH), 7.11 (s, 2H, NH2), 5.48 (s, 1H, @CH),
4.03 (br s, 1H, OH), 1.43 (s, 6H, CH3). 13C NMR [(CD3)2CO,
101.61 MHz]: d 179.95 (S@C–NH2), 162.55 (H2N–C@CH), 153.33
(–N@C–CH@), 86.64 (@CH), 69.53 [C(CH3)2], 30.38 [(CH3)2C]. IR
(KBr): 3381, 3276, 3242, 3140, 2980, 1620, 1600, 1560, 1490, 1460,
1370, 1330, 1220, 1170, 1130, 1090, 1040, 980, 940, 880, 840, 760, 720,
680, 620, 550 cmꢂ1. UV (ethanol): 242 (lge = 4.08), 275 (lge = 4.26),
317 (lge = 3.41) nm. Anal. Calcd for C7H12N4OS: C, 41.98; H, 6.04;
N, 27.98; S, 16.01. Found: C, 42.24; H, 6.20; N, 27.65; S, 15.98.
5-Amino-3-(1-hydroxy-1-methylpropyl)-1H-pyrazole-1-carbothioa-
mide (2b): mp 120–122 °C. 1H NMR [(CD3)2CO, 400.13 MHz]: d 9.00
(s, 1H, NH), 8.45 (s, 1H, NH), 7.13 (s, 2H, NH2), 5.43 (s, 1H, @CH),
3.93 (br s, 1H, OH), 1.70, 1.69 (dq, 2H, CH2, J = 7.26 Hz), 1.37 (s,
3H, CH3), 0.80 (t, 3H, CH3, J = 7.53 Hz). 13C NMR [(CD3)2CO,
101.61 MHz]: d 178.54 (S@C–NH2), 160.07 (H2N–C@CH), 151.89
(–N@C–CH@), 86.70 (@CH), 72.18 (C2H5–C–CH3), 35.06 (CH2–
CH3), 27.84 (CH3), 7.91 (CH2–CH3). IR (KBr): 3395, 3276, 3161,
2971, 2932, 2878, 1615, 1557, 1494, 1461, 1416, 1368, 1335, 1201,
5-Amino-3-[1-(1-butoxyethoxy)-1-methylethyl]-1H-pyrazole-1-carbo-
thioamide (4): 1H NMR [(CD3)2CO, 400.13 MHz]: d 8.88 (s, 1H,
NH), 8.45 (s, 1H, NH), 7.11 (s, 2H, NH2), 5.45 (s, 1H, @CH), 4.73 [q,
1H, OCH(CH3)O, 3J = 5.37 Hz], 3.32 (m, 2H, OCH2), 1.52 (s, 6H,
CH3), 1.42–1.31 (m, 4H, CH2), 1.13 [d, 3H, OCH(CH3)O,
3J = 5.37 Hz], 0.86 (t, 3H, CH3, 3J = 7.30 Hz). 13C NMR
[(CD3)2CO, 101.61 MHz]:
d 179.85 (S@C–NH2), 159.22 (H2N–
C@CH), 153.26 (–N@CCH@), 95.74 [OCH(CH3)O], 87.50 (@CH),
74.54 [C(CH3)2], 67.47 (OCH2), 32.71 (CH2), 26.35 [(CH3)2C], 21.71
(OCCH3), 19.97 (CH2CH3), 14.14 (CH3). IR (KBr): 3401, 3279, 3161,
2958, 2932, 2871, 1617, 1561, 1492, 1467, 1381, 1348, 1232, 1150,
1121, 1084, 976, 916, 888, 759, 729, 629, 567 cmꢂ1. Anal. Calcd for
C13H24N4O2S: C, 51.98; H, 8.05; N, 18.30; S, 10.67. Found: C, 52.24;
H, 8.23; N, 18.47; S, 10.98.
1168, 1106, 1037, 999, 976, 917, 899, 846,758, 723, 627, 595, 552 cmꢂ1
.
Anal. Calcd for C8H14N4OS: C, 44.84; H, 6.59; N, 26.15; S, 14.66.
Found: C, 45.13; H, 6.44; N, 26.35; S, 14.96.
5-Amino-3-(1-hydroxycyclopentyl)-1H-pyrazole-1-carbothioamide
(2c): mp 122–124 °C. 1H NMR [(CD3)2CO, 400.13 MHz]: d 8.95 (s,
1H, NH), 8.40 (s, 1H, NH), 7.11 (s, 2H, NH2), 5.49 (s, 1H, @CH),
3.90 (s, 1H, OH), 1.98–1.63 (m, 8H, CH2). 13C NMR [(CD3)2CO,
101.61 MHz]: d 179.71 (S@C–NH2), 161.25 (H2N–C@CH), 153.18
(–N@C–CH@), 87.15 (@CH), 80.02, 41.36, 24.50 (C-cyclopentyl). IR
27. Trofimov, B. A.; Andriyankova, L. V.; Shaikhudinova, S. I.;
Kazantseva, T. I.; Mal’kina, A. G.; Zhivet’ev, S. A.; Afonin, A. V.
Synthesis 2002, 853–855.
28. Sheldrick, G. M. SHELXS 97; University of Gottingen: Germany,
1997.