Simplified approach to the regiospecific synthesis of trichloromethylpyrazolines using microwave irradiation

Article abstract of DOI:10.1080/00397910802162926

Twelve novel 3-alkyl[aryl]-1-carboxamides-5-trichloromethyl-5-hydroxy-4,5- dihydro-lH-pyrazole have been synthesized in good yields (72-90%) using environmentally benign microwave-induced techniques. The compounds were synthesized from the cyclocondensati

Full text of DOI:10.1080/00397910802162926

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Simplified Approach to the
Regiospecific Synthesis of
Trichloromethylpyrazolines
Using Microwave Irradiation
Marcos A. P. Martins a , Paulo Muraro a , Paulo Beck a
, Pablo Machado a , Clarissa P. Frizzo a , Nilo Zanatta
a & Helio G. Bonacorso a
a Department of Chemistry , Federal University of
Santa Maria , Santa Maria, Brazil
Published online: 30 Sep 2008.
To cite this article: Marcos A. P. Martins , Paulo Muraro , Paulo Beck , Pablo Machado ,
Clarissa P. Frizzo , Nilo Zanatta & Helio G. Bonacorso (2008) Simplified Approach to
the Regiospecific Synthesis of Trichloromethylpyrazolines Using Microwave Irradiation,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:20, 3465-3476, DOI: 10.1080/00397910802162926
To link to this article: http://dx.doi.org/10.1080/00397910802162926
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Synthetic Communications1, 38: 3465–3476, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802162926
Simplified Approach to the Regiospecific
Synthesis of Trichloromethylpyrazolines Using
Microwave Irradiation
Marcos A. P. Martins, Paulo Muraro, Paulo Beck,
Pablo Machado, Clarissa P. Frizzo, Nilo Zanatta, and
Helio G. Bonacorso
Department of Chemistry, Federal University of Santa Maria,
Santa Maria, Brazil
Abstract: Twelve novel 3-alkyl[aryl]-1-carboxamides-5-trichloromethyl-5-hydroxy-
4,5-dihydro-lH-pyrazole have been synthesized in good yields (72–90%)
using environmentally benign microwave-induced techniques. The compounds were
synthesized from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alkyl
[aryl]-2-ones [Cl3CC(O)C(R2) ¼ C(R1)OR, where R ¼ Me, Et; R1 ¼ H, Me, Et, Pr,
i-Pr, i-Bu, t-Bu, Ph, Ph-4-NO2, Ph-4-F, Ph-4-Cl, Ph-4-Br; and R2 ¼ H, Me] with
semicarbazide hydrochloride in the presence of pyridine and using methanol=water
(3:1 v=v) as the solvent. The advantages of using microwave irradiation, rather than
a conventional method, were demonstrated.
Keywords: Biological activity, enones, microwave irradiation, pyrazoles,
trichloromethyl compounds
INTRODUCTION
The pyrazole ring is known to be an important framework for a large
number of compounds possessing pharmaceutical and agrochemical
properties.[1–6] Numerous methods for the synthesis of these compounds
have been well documented in previous studies,[7,8] but the methods
Received December 26, 2007.
Address correspondence to Marcos A. P. Martins, Nu´cleo de Quımica de
´
Heterociclos (NUQUIMHE), Departamento de Quımica, Universidade Federal
´
de Santa Maria, Santa Maria 97105-900 RS, Brazil. E-mail: mmartins@base.
ufsm.br; www.ufsm.br/nuquimhe
3465

3466
M. A. P. Martins et al.
usually entail the synthesis of nonhalogenated pyrazoles, and there are
few methodologies for the preparation of trichloromethylated pyrazoles.
General methods for the preparation of these compounds involve reac-
tions of hydrazine derivatives with trichloromethylated precursors such
as 1-trichloromethylated 1,3-diketones,[9] trichloroacetyl acetylenes,[10]
b-alkoxyvinyl trichloromethyl ketones,[9,11] and b-trichloromethyl
enaminones.[12] Over the past few years, we have developed a general
procedure for preparing b-alkoxyvinyl halomethyl ketones from the b-
haloacetylation of enol ethers using functionalized acyl groups CX3CO
(with X ¼ F and Cl).[9,13] In addition, our research group has reported
the synthesis and importance of b-alkoxyvinyl trichloromethyl ketones
as versatile building blocks to be used in the construction of halo-
methyl-heterocyclic rings,[9,13–15] (e.g., isoxazoles, pyrazoles, pyrazolium
chlorides, pyrrolidinones, pyrimidines, pyrimidinones, pyridines, thiazolo
pyrimidinones, selenazoles, quinolines, and diazepines). In spite of the
importance of trichloromethylpyrazoles, improvements in methods for
their preparation have been quite limited in the literature in recent
years.[16] Developing concise and effective methodologies for preparing
combinatorial libraries of small molecules for drug discovery research
remains an important challenge. In this context, our research group
has recently reported the biological effect of novel trichloromethyl-
substituted pyrazoles in animal models of inflammation, fever, and
pain.[17] It was demonstrated that dihydropyrazoles 2b and 2h (Scheme 1)
caused rapid antipyresis and antinociception after their systemic adminis-
tration in mice.[17] The compounds demonstrated an antipyretic action
similar to that of dypirone, a classical nonsteroidal anti-inflammatory
drug (NSAID) and pyrazole compound. It was further ascertained
that the mechanisms of antinociception for 2b did not involve opioid
receptors but rather spinal 5-HT receptors and a2-adrenoceptors, which
Scheme 1.

Synthesis of Trichloromethylpyrazolines
3467
also happened when 2h induced antinociception.[17] In a more recent
study,[18] we have demonstrated that fluorinated analogs such as
5-trifluoromethyl-4,5-dihydro-1H-pyrazoles decreased pain-related beha-
vior during neurogenic and inflammatory phases of the formalin test in
mice when administered subcutaneously. In addition, the more active
analgesic compounds significantly decreased carrageenan-induced paw
edema in mice. These results suggest that these pyrazolines could be pro-
mising candidates for the future development of novel analgesic and anti-
inflammatory agents.
Microwave irradiation has been used to accelerate organic reactions
because of it is high heating efficiency, providing remarkable rate enhance-
ment and dramatic reduction in reaction times. Reactions that require
hours or even days by conventional heating can often be accomplished in
seconds or minutes by microwave heating.[19] In addition, there is increas-
ing interest in the medicinal chemistry community in technologies and con-
cepts that facilitate a more rapid synthesis and, consequently, the screening
of novel chemical substances to identify compounds with appropriate
pharmacological qualities.[20] In recent years, we have reported the applica-
tion of microwave irradiation for the synthesis of halomethyl-substituted
azoles.[21] Considering the pharmacological importance observed for
compounds 2b and 2h,[17] the aim of this study is to demonstrate the
advantages obtained by using microwave irradiation, as compared to the
conventional method reported[22] for the synthesis of a series of 5-trichloro-
methyl-4,5-dihydro-1H-1-pyrazole methyl esters 2 (Scheme 1).
RESULTS AND DISCUSSION
4-Methoxy-1,1,1-trichloro-3-alken-2-ones 1a–l were synthesized from the
reaction of trichloroacetyl chloride with enol ether or acetal in the
presence of pyridine, according to the methodology developed in our
laboratory.[22] The cyclocondensation reactions of enones 1 with semicar-
bazide hydrochloride were carried out at a molar ratio of 1:1:3, respec-
tively, in the presence of pyridine and using methanol=water (3:1 v=v)
as solvent (Scheme 1).
The solution was submitted to microwave irradiation (100 W)
for 4 min, at a temperature of 70 ꢀC and at 2.2 bar of pressure, to
produce 5-trichloromethyl-4,5-dihydro-1H-pyrazoles 2 with 72–90%
yields (Table 1). The new method for forming 5-trifluoromethyl-4,5-dihy-
dro-1H-pyrazoles 2 under microwave irradiation offers several advan-
tages, including faster reaction rates, fewer by products, and high
yields, while the conventional method entails moderate yields and a long
process (ca. 24 h).[22] Table 1 shows that the average yields of products

3468
M. A. P. Martins et al.
Table 1. Yieldsa and reaction conditions for microwave-assisted synthesis of 2a–l
Microwave methodb
Conventional methodc
Product
Reaction time (min)
Yield (%)
Reaction time (h)
Yield (%)
2a
2b
2c
2d
2e
2f
4
4
4
4
4
4
4
4
4
4
4
4
85
72
75
75
85
76
80
83
90
85
80
90
16
17
20
20
20
20
20
20
20
20
20
20
65
71
64
63
70
60
75
89
82
73
70
84
2g
2h
2i
2j
2k
2l
aYields of isolated products.
Reaction conditions: methanol=water (3:1 v=v), pyridine, 70 C, MW, 100 W,
b
ꢀ
2.2 bar.
cReaction conditions: methanol=water (3:1 v=v), 30–85 ꢀC(2a–b, 2h–i, 2l; see Ref. 22).
obtained by the microwave method are ca. 10% higher than those
obtained by the conventional method.[22] 1H and 13C NMR and mass
spectral data of all compounds are in full agreement with the proposed
structures (see the Experimental section).
The reaction time for the microwave method is the main advantage
of this method over other methods, where the average time ratio
between the two methods is 1:300.[22] Furthermore, the new method of
forming of 3-alkyl-5-hydroxy-5-trichloro-methyl-4,5-dihydro-1H-pyrazole-
1-carboxamides supplies a synthesis of compounds with promising
analgesic and antipyretic activities in mice. It also brings new structure
variations at the pyrazole ring, thus allowing for a future study of struc-
ture–activity relationships to obtain a pharmacological profile for this
species of compounds.
EXPERIMENTAL
Unless otherwise indicated, all common reagents and solvents were used
as obtained from commercial suppliers without further purification.
Yields listed are of isolated compounds. 1H, 13C, and spectra were
recorded on a Bruker DPX 400 spectrometer (1H at 400.13 MHz and

Synthesis of Trichloromethylpyrazolines
3469
13C at 100.63 MHz), 298 K, digital resolution of ꢁ0.01 ppm, 0.5 M, in
CDCl3-d6 using tetramethylsilane (TMS) as internal standard. All spectra
were acquired in a 5-mm tube, at natural abundance. Mass spectra were
registered in a HP 5973 mass spectrometer detector (MSD) connected
to an HP 6890 GC and interfaced by a Pentium PC. The GC was
equipped with a split–splitless, injector, auto sampler, and cross-linked
HP-5 capillary column (30 m and 0.32 mm of internal diameter), and
helium was used as the carrier gas. Melting points were determined with
an Electrothermal Mel-Temp 3.0 (Laboratory Devices Inc., USA). Ele-
mental analyses were performed on a Perkin-Elmer CHN elemental ana-
lyzer. Microwave irradiation was conducted in a multimode microwave
Ethos 1 (Milestone Inc.) with a twin magnetron wꢀith maximum delivered
power of 1300 W. The temperature was set to 70 C, and the irradiation
was automatically stopped at this temperature. The temperature and the
pressure were measured throughout with an ATC-400 CE and APC-55
detector, respectively.
Preparation of 1-Carboxamide-5-trichloromethyl-5-hydroxy-4,5-dihydro-
1H-pyrazole 2a (Microwave Method): Typical Procedure
A solution of 1a (2.0 mmol), semicarbazide hydrochloride (0.268 g,
2.4 mmol) in methanol=water 3:1 v=v (6 mL), and pyridine (2 mL) was
stirred for a few minutes. The mixture was irradiated in a microwave
Ethos 1 (Milestone Inc.) at 100 W and 2.2 bar of pressure for 4 min.
The multimode microwave has a twin magnetron withꢀ maximum
delivered power of 1300 W. The temperature was set to 70 C, and the
irradiation was automatically stopped at this temperature. The tempera-
ture and the pressure were measured throughout with ATC-400 CE and
APC-55 detectors, respectively. After cooling to room temperature, the
solution was extracted with chloroform (2 ꢂ 20 mL) and ethyl acetate
(2 ꢂ 20 mL). The organic layers were washed with distilled water
(2 ꢂ 20 mL) and dried with magnesium sulfate. The solvent was removed
in a rotatory evaporator, and 5-hydroxy-5-trichloromethyl-4,5-dihydro-1
H-1-carboxamidepyrazole 2a was obtained in high purity. When
necessary, products 2 were recrystallized from hexane.
1-Carboxamide-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole 2a
(Conventional Method) [22]: Typical Procedure
To a stirred solution of 1a (5.0 mmol) in methanol (6 mL), a solution
of semicarbazide hydrochloride (5.0 mmol) in water (2ꢀmL) was added
ꢀ
at 20–25 C. The mixture was stirred for 16 h at 50–55 C. The product

3470
M. A. P. Martins et al.
precipitated by the addition of cool water (15 mL) to the reaction. The
crystalline solids were filtered off and recrystallized from methanol.
Data
1-Carboxamide-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-
pyrazole (2a)
C5H6Cl3N3O2; mw 246.47; mp 129–130 ꢀC. 1H NMR (CDCl3, 400 MHz)
2
d (JH-H, Hz) 7.02 (d, 1H, H3), 3.32 (d, 1H, J ¼ 18, H4a), 3.65 (d, 1H,
2J ¼ 18, H4b). 13C NMR (CDCl3, 100 MHz) d 157.5 (C ¼ O), 145.4
(C3), 104.7 (CCl3), 99.0 (C5), 45.1 (C4). MS m=z (%) 128 (M þ, ꢃCCl3
16), 85 (100). Anal. calcd.: C, 24.37; H, 2.45; N, 17.05%. Found: C,
24.44; H, 2.60; N, 16.98%.
1-Carboxamide-5-trichloromethyl-3-methyl-5-hydroxy-4,5-dihydro-1H-
pyrazole (2b)
1
C6H8Cl3N3O2; mw 260.50; mp 141–143ꢀC. H NMR (CDCl3, 400 MHz)
2
2
d (JH-H, Hz) 3.26 (d, 1H, J ¼ 19, H4a), 3.51 (d, 1H, J ¼ 19, H4b), 2.00
(s, 3H, CH3). 13C NMR (CDCl3, 100 MHz) d 157.8 (C ¼ O), 155.5 (C3),
104.2 (CCl3), 100.5 (C5), 50.1 (C4), 15.6 (CH3). MS m=z (%) 142
(M þ, ꢃCCl3, 45), 117 (16), 99 (100), 82 (12). Anal. calcd.: C, 27.66, H,
3.10; N, 16.13%. Found: C, 27.75; H, 3.02; N, 16.65%.
1-Carboxamide-5-trichloromethyl-3-ethyl-5-hydroxy-4,5-dihydro-1H-
pyrazole (2c)
C7H10Cl3N3O2; mw 274.53; mp 127–128 ꢀC. 1H NMR (CDCl3, 400 MHz)
2
d (JH-H, Hz) 1.18 (t, 3H, CH3), 2.38 (q, 2H, CH2), 3.25 (d, 1H, J ¼ 19,
2
H4a), 3.52 (d, 1H, J ¼ 19, H4b), 2.00 (s, 3H, CH3). 13C NMR (CDCl3,
100 MHz) d 159.9 (C ¼ O), 157.9 (C3), 104.3 (CCl3), 100.3 (C5), 48.6
(C4), 23.3 (C8), 10.3 (C9). MS m=z (%) 156 (M þ, ꢃCCl3, 17), 113
(MHþ, ꢃCCl3, ꢃCONH2, 100), 85 (22). Anal. calcd.: C, 30.63; H,
3.67; N, 15.31%. Found: C, 30.48, H, 3.65, N, 15.24%.
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-propyl-4,5-dihydro-1H-
pyrazole (2d)
C8H12Cl3N3O2; mw 288.56; mp 95–97 ꢀC. 1H NMR (CDCl3, 400 MHz) d
(JH-H, Hz) 0.99 (t, 3H, CH3), 1.61–1.64 (m, 2H, CH2), 2.33 (t, 2H, CH2),

Synthesis of Trichloromethylpyrazolines
3471
3.23 (d, 1H, 2J ¼ 19, H4a), 3.52 (d, 1H, 2J ¼ 19, H4b). 13C NMR (CDCl3,
100 MHz) d 158.7 (C ¼ O), 158.1 (C3), 104.2 (CCl3), 100.1 (C5), 48.7
(C4), 31.6 (C8), 19.2 (C9), 13.5 (C10). MS m=z (%) 170 (M þ, ꢃCCl3,
25), 98 (14), 85 (44). Anal. calcd.: C, 33.30; H, 4.19; N, 14.56%. Found:
C, 33.15; H, 4.17; N, 14.50%.
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-(1-methylethyl)-4,5-
dihydro-1H-pyrazole (2e)
C8H12Cl3N3O2; mw 288.56; mp 92–95 ꢀC. 1H NMR (CDCl3, 400 MHz) d
(JH-H, Hz) 1.18 (d, 6H, 2CH3), 2.63–2.70 (m, 1H, CH), 3.24 (d, 1H,
2
2J ¼ 19, H4a), 3.55 (d, 1H, J ¼ 19, H4b). 13C NMR (CDCl3, 100 MHz)
d 163.1 (C ¼ O), 158.1 (C3), 104.3 (CCl3), 100.2 (C5), 46.7 (C4), 29.5
(C8), 19.5 (C9). MS m=z (%) 170 (M þ, ꢃCCl3, 19), 127 (MHþ, ꢃCCl3,
2, 100), 111 (8), 85 (65). Anal. calcd.: C, 33.30; H, 4.19; N, 14.56%.
Found: C, 33.10; H, 4.18; N, 14.45%.
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-(2-methylpropyl)-4,5-
dihydro-1H-pyrazole (2f)
C9H14Cl3N3O2; mw 302.59; mp 124–126 ꢀC. 1H NMR (CDCl3, 400 MHz)
d (JH-H, Hz) 0.99 (t, 6H, 2CH3), 1.92–2.02 (m, 1H, CH), 2.69 (d, 2H,
2
2
CH2), 3.23 (d, 1H, J ¼ 18, H4a), 3.53 (d, 1H, J ¼ 18, H4b). 13C NMR
(CDCl3, 100 MHz) d 157.9 (C ¼ O), 157.3 (C3), 104.4 (CCl3), 100.0
(C5), 48.7 (C4), 38.0 (C8), 25.3 (C9), 22.3 (C10). MS m=z (%) 184
(M þ, ꢃCCl3, 41), 141 (MHþ, ꢃCCl3, ꢃCONH2, 100), 125 (17), 85
(82). Anal. calcd: C, 35.73; H, 4.66; N, 13.89%. Found: C, 35.53, H,
4.62; N, 13.81%.
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-(1,1-dimethylethyl)-4,5-
dihydro-1H-pyrazole (2g)
C9H14Cl3N3O2; mw 302.59; mp 122–125 ꢀC. 1H NMR (CDCl3, 400 MHz)
2
d (JH-H, Hz) 1.20 (s, 9H, 3CH3), 3.27 (d, 1H, J ¼ 18, H4a), 3.60 (d, 1H,
2J ¼ 18, H4b). 13C NMR (CDCl3, 100 MHz) d 165.4 (C ¼ O), 158.2 (C3),
104.3 (CCl3), 100.5 (C5), 45.9 (C4), 34.1 (C8), 27.2 (C9). MS m=z (%) 184
(M þ, ꢃCCl3, 41), 141 (MHþ, ꢃCCl3, ꢃCONH2, 100), 125 (17), 85 (82),
57 (78). Anal. calcd.: C, 35.73; H, 4.66; N, 13.89%. Found: C, 35.57; H,
4.59; N, 13.78%.

3472
M. A. P. Martins et al.
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-
pyrazole (2h)
C11H10Cl3N3O2; mw 322.57; mp 158–160 ꢀC. 1H NMR (CDCl3,
2
2
400 MHz) d (JH-H, Hz) 3.77 (d, 1H, J ¼ 18, H4a), 3.94 (d, 1H, J ¼ 18,
H4b), 7.44–7.82 (5H, phenyl). 13C NMR (CDCl3, 100 MHz) d 157.6
(C ¼ O), 152.6 (C3), 104.6 (CCl3), 100.8 (C5), 46.3 (C4), 126.7, 128.7,
130.1, 130.5 (6 C, phenyl). Anal. calcd.: C, 40.96; H, 3.12; N, 13.03%.
Found: C, 40.94; H, 3.26; N, 13.37%.
1-Carboxamide-5-trichloromethyl-3-(4-fluorophenyl)-5-hydroxy-4,5-
dihydro-1H-pyrazole (2i)
C11H9Cl3FN3O2; mw 340.57; mp 184–186 ꢀC. 1H NMR (CDCl3,
2
2
400 MHz) d (JH-H, Hz) 3.71 (d, 1H, J ¼ 18, H4a), 3.98 (d, 1H, J ¼ 18,
H4b), 7.26–7.87 (m, 4H, aryl). 13C NMR (CDCl3, 100 MHz) d 152.3
(C ¼ O), 151.8 (C3), 103.3 (CCl3), 101.1 (C5), 46.8 (C4), 115.7, 127.0,
128.8, 163.2 (6C, aryl). MS m=z (%) 222 (M þ, ꢃCCl3), 236 (42), 191
(36), 163 (18), 147 (10), 120 (100), 101 (50). Anal. calcd.: C, 38.80; H,
2.66; N, 12.34%. Found: C, 38.58; H, 2.65; N, 12.27%.
1-Carboxamide-5-trichloromethyl-3-(4-chlorophenyl)-5-hydroxy-4,5-
dihydro-1H-pyrazole (2j)
1
ꢀ
C11H9Cl4N3O2; mw 357.02; mp 188–190 C. H NMR (CDCl3, 400 MHz)
d (JH-H, Hz) 3.89 (d, 1H, 2J¼ 18, H4a), 3.98 (d, 1H, 2J¼ 18, H4b), 7.42–7.68
(m, 4H, aryl). 13C NMR (CDCl3, 100 MHz) d 155.0 (C ¼ O), 153.8 (C3),
103.4 (CCl3), 100.7 (C5), 46.1 (C4), 127.9, 128.4, 129.1, 137.1 (6 C, aryl). MS
m=z (%) 194 (Mþ, ꢃCCl3, ꢃCONH2, 100), 163 (13), 137 (85), 101 (60). Anal.
calcd.: C, 37.01; H, 2.54; N, 11.77%. Found: C, 36.68; H, 2.50; N, 11.66%.
1-Carboxamide-5-trichloromethyl-3-(4-bromophenyl)-5-hydroxy-4,5-
dihydro-1H-pyrazole (2k)
C11H9Cl3BrN3O2; mw 401.47; mp 188–190 ꢀC. 1H NMR (CDCl3,
2
2
400 MHz) d (JH-H, Hz) 3.78 (d, 1H, J ¼ 18, H4a), 3.78 (d, 1H, J ¼ 18,
H4b), 7.70–7.73 (m, 4H, aryl). 13C NMR (CDCl3, 100 MHz) d 155.2
(C ¼ O), 151.8 (C3), 103.3 (CCl3), 101.1 (C5), 46.6 (C4), 123.9, 128.3,
129.4, 131.7 (6 C, aryl). MS m=z (%) 282 (Mþ, ꢃCCl3, 6), 253 (100),
225 (97), 183 (63), 157 (40), 102 (35). Anal. calcd.: C, 32.91; H, 2.26;
N, 10.47%. Found: C, 32.53; H, 2.34; N, 10.37%.

Synthesis of Trichloromethylpyrazolines
3473
1-Carboxamide-5-trichloromethyl-5-hydroxy-3-(4-nitrophenyl)-4,5-dihy-
dro-1H-pyrazole (2l)
C11H9Cl3N4O4; mw 367.56; mp 214–217 ꢀC. 1H NMR (CDCl3,
400 MHz): d (JH-H, Hz) 8.30 (s, 1H, OH), 8.28–8.15 (m, 4H, aryl), 7.30
2
2
(s, 2H, NH2), 4.10 (d, 1H, J ¼ 19, H4a), 3.80 (d, 1H, J ¼ 19, H4b).
13C NMR (CDCl3, 100 MHz) d 156.9 (C ¼ O), 150.4 (C3), 104.3
(CCl3), 101.4 (C5), 46.3 (C4), 123.8, 128.5, 132.4, 148.2 (6 C, aryl). Anal.
calcd.: C, 35.95; H, 2.47; N, 15.24%. Found: C, 36.12; H, 2.60; N,
15.17%.
ACKNOWLEDGMENTS
´
The authors thank the Conselho Nacional de Desenvolvimento Cientıfico
e Tecnologico (CNPq, Contract Nos. 46.0804=00–6 and 480067=01-5),
ꢀ
`
Fundac¸a˜o de Amparo a pesquisa do Estado do Rio Grande do Sul
(FAPERGS), and Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nıvel
´
Superior (CAPES) for financial support and fellowships. Also, the
´
authors thank E. M. D. Flores (Departamento de Quımica, Universidade
Federal de Santa Maria) for the providing the microwave equipment
ETHOS 1 (Milestone Inc.) for the compound synthesis.
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