Solvent-free route to β-enamino dichloromethyl ketones and application in the synthesis of novel 5-dichloromethyl-1H-pyrazoles

Article abstract of DOI:10.1002/jhet.227

(Chemical Equation Presented) An efficient procedure to prepare a series of five 4-amino-1,1-dichloro-3-penten-2-ones [CHCl₂C(O)CH=C(Me)NR ¹R², where R¹/R² = H/Ph, H/Bn, H/CH₂CH₂

Full text of DOI:10.1002/jhet.227

November 2009
Solvent-free Route to b-Enamino Dichloromethyl Ketones
and Application in the Synthesis of Novel
5-Dichloromethyl-1H-pyrazoles
1247
Marcos A. P. Martins,a* Rodrigo L. Peres,a Clarissa P. Frizzo,a
Elisandra Scapin,b Dayse N. Moreira,a Gabriela F. Fiss,a Nilo Zanatta,a
and Helio G. Bonacorsoa
a
´
´ ´
Nucleo de Quımica de Heterociclos, Departamento de Quımica, Universidade Federal de Santa
Maria, 97105-900, Santa Maria, RS, Brazil
Laboratorio de Quımica, Coordenac¸a˜o de Engenharia Ambiental, Universidade Federal do
b
´
´
Tocantins, 109 Norte, Palmas, TO, Brazil
*E-mail: mmartins@base.ufsm.br
Received April 1, 2008
DOI 10.1002/jhet.227
Published online 6 November 2009 in Wiley InterScience (www.interscience.wiley.com).
An efficient procedure to prepare
a
series of five 4-amino-1,1-dichloro-3-penten-2-ones
H/Ph, H/Bn, H/CH2CH2OH, A(CH2)4A,
[CHCl2C(O)CH¼¼C(Me)NR1R2, where R1/R2
¼
A(CH2)2O(CH2)2] from the solvent-free reaction of 1,1-dichloro-4-methoxy-3-penten-2-one with pri-
mary and secondary amines is reported. 1,1-Dichloro-4-methoxy-3-penten-2-one was reacted with hy-
drazine hydrochloride, phenylhydrazine hydrochloride and semicarbazide hydrochloride to obtain 5-
dichloromethyl-3-methylpyrazoles. Aminoguanidine hydrochloride and 1,2-dimethylhydrazine dihydro-
chloride were also reacted with 1,1-dichloro-4-methoxy-3-penten-2-one to obtain 5-dichloromethyl-3-
methylpyrazoline and 5-dichloromethyl-1,2,3-trimethyl pyrazolium chloride, respectively. All cyclocon-
densation reactions were performed in one-pot procedures.
J. Heterocyclic Chem., 46, 1247 (2009).
INTRODUCTION
numerous methods have been developed, regioselective
synthesis of the pyrazole ring remains a significant chal-
lenge for organic chemists. For example, the prevalent
method of reacting hydrazines with 1,3-dicarbonyl com-
pounds often results in a mixture of regioisomers when
the reactivity of the two carbonyl groups is not drasti-
cally different. A modification of this method, replacing
1,3-dicarbonyl compounds with a,b-unsaturated ketones
Substituted pyrazoles are important synthetic targets
in the pharmaceutical industry because the pyrazole
motif makes up the core structure of numerous biologi-
cally active compounds, including blockbuster drugs
such as Celecoxib [1] and Sildenafil [2]. Specifically, 5-
hydroxy-4,5-dihydro-1H-pyrazoles are known to possess
anti-inflammatory and analgesic activity [3,4]. Although
C
V
2009 HeteroCorporation

1248
M. A. P. Martins, R. L. Peres, C. P. Frizzo, E. Scapin, D. N. Moreira, G. F. Fiss, N. Zanatta,
and H. G. Bonacorso
Vol 46
Scheme 1. i: NHR1R2, 0–25ꢀC, 5 min.
reaction of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with
primary and secondary amines. In addition, we have
studied the cyclocondensation reaction of dichloro-
methyl substituted a,b-unsaturated ketone with hydra-
zines in environmentally favorable conditions.
RESULTS AND DISCUSSION
The starting material, 1,1-dichloro-4-methoxy-3-
penten-2-one 1, was synthesized from the reaction of 2-
methoxypropene with dichloroacetyl chloride, by meth-
odologies developed in our laboratories [6,20,21]. The
synthetic method used to obtain b-enamino dichloro-
methyl ketones presented in this article was based on
the solvent-free reaction of 1,1-dihalo-4-methoxy-3-
penten-2-one with amines. The typical experiment was
carried out through the addition of the appropriate amine
to 1,1-dichloro-4-methoxy-3-penten-2-one 1 at 0ꢀC, fol-
lowed by stirring the reaction mixture at room tempera-
ture for 5 min (Scheme 1). The structures of the synthe-
sized compounds were analyzed by H, and 13C NMR
1
or esters affords products with higher regioselectivity
[5]. Over the last twenty years, our research group has
developed a general procedure for preparing b-alkoxy-
vinyl halomethyl ketones from the b-haloacetylation of
enol ethers using functionalized acyl groups RCO (with
R ¼ CF3, CCl3 and CHCl2) [6,7], and demonstrated
their importance in the construction of halomethyl-heter-
ocyclic rings [6–11]. Our results have shown that the
reaction of b-alkoxyvinyl trihalomethyl ketones and
hydrazines generally produces highly regioselective 5-
hydroxy-4,5-dihydro-1H-pyrazoles. Although trihalo-
methyl pyrazolium chlorides have been synthesized by
the cyclocondensation reaction of 4-alkoxy-1,1,1-tri-
chloro-3-alken-2-ones with 1,2-dimethylhydrazine [12],
they remain rare in the literature. The reactivity of b-
alkoxyvinyl dichloromethyl ketones with amines to
obtain enaminones and reactions with different hydra-
zines in an attempt to obtain the respective 5-dichloro-
methylpyrazoles and 5-dichloromethylpyrazolium has
not yet been studied. There is only one report in the lit-
erature concerning the reactivity of these compounds
with hydroxylamine, and scarce reports on their reaction
with amines [13].
spectroscopy and GC-MS spectrometry. Data are
reported in the Experimental Section. In every case, the
stereochemistry of the 1,1-dichloro-4-methyl-aminopent-
3-en-2-ones 2a–e (Scheme 1) was determined based on
1H NMR spectroscopy. The chemical shift of the enam-
ino hydrogen (NH) was observed at 10–12 ppm, which
further confirms the Z-configuration for the enaminones
2a–c. This configuration is stabilized by the intramolec-
ular hydrogen bond between the NH and the carbonyl
oxygen [13,18]. The E-configuration of enaminones 2d–
e was determined by X-ray diffraction. The proposed
structure of enaminone 2e is illustrated in Figure 1.
When the results were compared with those obtained
from the same reaction carried out in ionic liquid, the
yields (81–88%) and reaction times were similar [13].
For compounds with a trichloromethyl substituent syn-
thesized by this method, the yields were slightly better
[18]. Consequently, it was demonstrated that 1,1-
dichloro-4-methoxy-3-penten-2-one reacted in good
yields with primary and secondary amines in solvent-
free conditions.
In the last few years, our research group has been
interested in developing environmental alternatives to
obtain heterocyclic building blocks and heterocycles.
More recently, we have employed ionic liquids for this
objective [13–17]. We have also developed synthetic
methods under solvent-free conditions to obtain enami-
nones [13,18] and 5-hydroxy-4,5-dihydro-1H-pyrazoles
[19]. Considering our interest in new and green routes
in organic synthesis, we have investigated the synthesis
of b-enamino dichloromethyl ketones by the solvent-free
Figure 1. ORTEP of (E)-1,1-dichloro-4-morpholin-4-yl-3-penten-2-
one (2e).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Solvent-free Route to b-Enamino Dichloromethyl Ketones and Application
in the Synthesis of Novel 5-Dichloromethyl-1H-pyrazoles
1249
Scheme 2.
75ꢀC, 24 h.
R ¼ H (83%), Ph (68%), C(O)NH2 (56%), i: EtOH,
Scheme 4.
60%.
i: MeNHNHMe ꢂ 2HCl, EtOH/HCl 1:1, 75ꢀC, 24h,
The second part of this study involved the reactivity
of 1,1-dichloro-4-methoxy-3-penten-2-one with hydra-
zines. When 1,1-dichloro-4-methoxy-3-penten-2-one
reacted with hydrazine hydrochoride, phenylhydrazine
hydrochloride and semicarbazide hydrochloride, the 5-
dichloromethyl-3-methylpyrazoles 3–5 (Scheme 2) were
obtained. In accordance with previous results published
by us, the formation of compound 5 was expected under
the conditions used in the present study (refluxing etha-
nol for 24 h) [22]. On the other hand, the formation of
compound 4 with high regioselectivity was unexpected,
considering that the reaction of 1,1,1-trihalo-4-methoxy-
3-penten-2-ones with phenyl hydrazine resulted in a
mixture of isomers when the reaction was carried out in
a microwave oven [23]. More surprising was the dehy-
drated product obtained from the reaction of 1,1-
dichloro-4-methoxy-3-penten-2-one with semicarbazide
hydrochloride. This result is especially surprising con-
sidering the reaction conditions employed in this study
because, for the reaction of trihalomethyl precursors the
dehydrated product is only obtained after heating 5-
trihalomethyl-5-hydroxy-4,5-dihydro-1H-pyrazole with
concentrated sulphuric acid [24]. The yields and reaction
conditions are summarized in Scheme 2.
ence of hydrochloric acid as a catalyst and ethanol as
solvent. The reaction mixture was stirred at reflux tem-
perature for 24 h. There is little information on the syn-
thesis of these compounds using cyclocondensation
methods such as the reaction of a b-diketone derivative
with 1,2-dialkylhydrazines [26]. In addition, the most
important route to synthesis of 1,2-dialkylpyrazolium
salts is the N-alkylation of pyrazoles [27].
In conclusion, this article has demonstrated that 1,1-
dichloro-4-methoxy-3-penten-2-one reacted with amines
in solvent-free conditions to result in enaminones in
good yields. In addition, they were reacted with hydra-
zines under mild reaction conditions furnishing products
with high regioselectivity and in some cases led to
unexpected products. Thus, we have demonstrated that
the presence of the dichloromethyl group is a determin-
ing factor in the regiochemistry of the reaction because
it provides a good deal of stability for the intermediate
5-dicloromethyl-5-hydroxy-4,5-dihydropyrazole, which
contributes for high regioselectivity.
EXPERIMENTAL
Another dinucleophile evaluated was aminoguanidine
hydrochloride, which led to 5-dicloromethyl-5-hydroxy-
4,5-dihydropyrazoles 6 (Scheme 3), the expected prod-
uct under the reaction conditions used [25]. The pair of
General procedures. Unless otherwise indicated, all com-
mon reagents and solvents were used as obtained from com-
mercial suppliers without further purification. 1H and 13C
NMR spectra were recorded on a Bruker DPX 400 spectrome-
ter (1H at 400.13 MHz and 13C at 100.61 MHz) 298 K, digital
resolution of 60.01 ppm, with 0.1 mol Lꢁ1 solution in CDCl3,
DMSO-d6or H2D/C6D6 as solvent. All spectra were registered
in a 5 mm tube, at a natural abundance. Mass spectra were
registered in a HP 5973 MSD connected to a HP 6890 GC and
interfaced by a Pentium PC. The CG was equipped with a
split–splitless, injector, auto sampler, cross-linked HP-5 capil-
lary column (30 m, 0.32 mm of internal diameter), and helium
was used as the carrier gas.
Synthesis of 4-amino-1,1-dichloro-3-penten-2-ones (2a–e).
The appropriate amine (2 mmol) was added to 1,1-dichloro-4-
methoxy-3-penten-2-one 1 (2 mmol) at 0ꢀC. The reaction mix-
ture was stirred at room temperature for 5 min. The residue
was extracted with dichloromethane, dried over anhydrous
(MgSO4), filtered, and the solvent was removed under reduced
pressure. The crude product 2e was obtained with good purity,
and the solids’ products 2a–d were recrystallized from hexane/
ethyl acetate 9:1 as solvent.
1
doublets (H4) for geminal protons observed in H NMR
spectra appeared at 3.4 and 3.6 ppm, with J ¼ 19.5 Hz,
which is typical spectroscopic data for 4,5-dihydropyra-
zoles [17,19,25]. Compound 6 is stable and was not con-
verted to the corresponding pyrazole derivative.
In the same context, 5-dichloromethyl-1,2,3-trimethyl
pyrazolium chloride 7 (Scheme 4) was formed from the
reaction of 1,1-dichloro-4-methoxy-3-penten-2-one
with 1,2-dimethylhydrazine dihydrochloride in the pres-
1
Scheme 3. i: NH2C(NH)NH2 ꢂ 2HCl, EtOH, 75ꢀC, 24h, 58%.
Synthesis of 5-dichloromethyl-3-methylpyrazoles (3–5)
and 5-dichloromethyl-3-methylpyrazoline (6). The appropri-
ate hydrazine (2 mmol) was added to a solution of 1,1-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1250
M. A. P. Martins, R. L. Peres, C. P. Frizzo, E. Scapin, D. N. Moreira, G. F. Fiss, N. Zanatta,
and H. G. Bonacorso
Vol 46
dichloro-4-methoxy-3-penten-2-one 1 (2 mmol) in ethanol
(2 mL) at room temperature. The reaction mixture was stirred
at reflux temperature for 24 h. The residue was extracted with
dichloromethane, dried (MgSO4), filtered, and the solvent was
removed under reduced pressure. The crude product 4 was
obtained with good purity, and the solids products 3 and 5–6
were recrystallized from ethanol as solvent.
Synthesis of 5-dichloromethyl-1,2,3-trimethyl pyrazolium
chloride (7). 1,2-dimethylhydrazine dihydrochloride (2 mmol)
and 36% hydrochloric acid (2 mL) were added to a solution of
1,1-dichloro-4-methoxypent-3-en-2-one 1 (2 mmol) in ethanol
(2 mL) at room temperature. The reaction mixture was stirred at
reflux temperature for 24 and the byproducts were extracted with
dichloromethane. The product 7 was obtained in good purity
from the aqueous phase after evaporation of water under vacuum.
(Z) 1,1-Dichloro-4-phenylaminopent-3-en-2-one (2a). C11H11
Cl2NO Mol. Wt.: 244.12 (83%); mp 63–65ꢀC; 1H NMR (200
MHz, CDCl3) d 2.08 (s, 3H, H5), 5.56 (s, 1H, H3), 5.90 (s,
1H, H1), 7.20–7.40 (m, 5H, Ph), 12.32 (s, 1H, NH); 13C NMR
(50 MHz, CDCl3) d 20.1 (C5), 70.3 (C3), 91.0 (C1), 124.9,
126.7, 129.2, 137.3, 165.9 (C4), 184.6 (C2); m/z 243 (Mþ,
31%), 160 (100), 144 (43), 77 (64).
10.8 (CH3), 69.0 (CHCl2), 105.6 (C4), 142.9 (C5), 143.0 (C3);
m/z 164.1 (Mþ, 13%), 149.1 (100), 109.1 (22).
5-Dichloromethyl-3-methyl-1-phenyl-1H-pyrazole (4). C11
H10Cl2N2 Mol. Wt.: 241.12 (68%); oil; 1H NMR (400 MHz,
CDCl3) d 2.35 (s, 3H, CH3), 6.57 (s, 1H, CH), 6.65 (s, 1H,
CHCl2), 7.43–7.52 (m, 5H, Ph); 13C NMR (100 MHz, CDCl3)
d 13.4 (CH3), 61.1 (CHCl2), 107.5 (C4), 125.9, 128.9, 129.4,
138.3, 142.3 (C5), 149.5 (C3); m/z 240 (Mþ, 36%), 205.1 (73),
169.1 (100).
1-Carboxamide-5-dichloromethyl-3-methyl-1H-pyrazole (5).
C6H7Cl2N3O Mol. Wt.: 208.05 (46%); mp 110–111ꢀC; 1H
NMR (400 MHz, DMSO-d6) d 2.22 (s, 3H, CH3), 6.41 (s, 1H,
CH), 7.76 (s, 1H, CHCl2); 13C NMR (100 MHz, DMSO-d6) d
14.2 (CH3), 64.3 (CHCl2), 107.3 (C4), 145.2 (C5), 151.7 (C3),
152.6 [C(O)NH2]; m/z 207 (Mþ, 84%), 191 (38), 161 (62),
133 (100), 115 (85).
1-Carboximidamide-5-dichloromethyl-5-hydroxy-3-methyl-
4,5-dihydro-1H-pyrazole (6). C6H10Cl2N4O Mol. Wt.: 225.08
(58%); mp 68–70ꢀC; 1H NMR (200 MHz, DMSO-d6) d 2.08
(m, 3H, CH3), 3.61 (d, J ¼ 19.6 Hz, 1H, H4a), 3.38 (d, J ¼
19.4 Hz, 1H, H4b), 7.89 (s, 1H, CHCl2), 9.01 (br s, 3H, 3 ꢃ
NH); 13C NMR (50 MHz, DMSO-d6) d 15.7 (CH3), 47.2 (C4),
73.0 (CHCl2), 96.7 (C5), 152.5 (C3), 158.7 [C(NH)NH2].
5-Dichloromethyl-1,2,3-trimethyl pyrazolium chloride
(Z) 4-Benzylamino-1,1-dichloropent-3-en-2-one (2b). C12H13
Cl2NO Mol. Wt.: 258.15 (68%); mp 72–74ꢀC; 1H NMR (200
MHz, CDCl3) d 2.07 (s, 3H, H5), 4.50 (d, J ¼ 5.9 Hz, 2H,
CH2), 5.41 (s, 1H, H3), 5.85 (s, 1H, H1), 7.30–7.40 (m, 5H,
Ph), 11.11 (br s, 1H, NH); 13C NMR (50 MHz, CDCl3) d 19.3
(C5), 47.2 (CH2), 70.4 (C3), 80.7 (C1), 126.8, 127.7, 128.8,
136.3, 168.0 (C4), 183.8 (C2); m/z 257 (Mþ, 24%), 174 (98),
91 (100), 65 (49).
1
(7). C7H11Cl3N2 Mol. Wt.: 229.54 (60%); mp 112–113ꢀC; H
NMR (200 MHz, H2O/C6D6) d 2.73 (s, 3H, CH3), 4.22 (s, 3H,
CH3), 4.34 (s, 3H, CH3), 7.19 (s, 1H, CH), 7.58 (s, 1H,
CHCl2); 13C NMR (50 MHz, H2O/C6D6) d 11.9 (CH3), 34.2
(CH3), 35.4 (CH3), 59.9 (CHCl2), 107.5 (C4), 145.4 (C5),
147.6 (C3); m/z 193 (M–Cl, 59%), 156 (100), 129 (39).
(Z) 1,1-Dichloro-4-(2-hydroxyethylamino)-pent-3-en-2-one
(2c). C7H11Cl2NO2 Mol. Wt.: 212.07 (78%); mp 70–72ꢀC; H
1
Acknowledgments. The authors thank the Conselho Nacional
NMR (200 MHz, CDCl3) d 2.09 (s, 3H, H5), 3.50 (t, J ¼ 5.6 Hz,
2H, CH2), 3.80 (t, J ¼ 5.2 Hz, 2H, CH2), 5.36 (s, 1H, H3), 5.84
(s, 1H, H1), 10.96 (s, 1H, NH); 13C NMR (50 MHz, CDCl3) d
19.6 (C5), 45.7 (CH2), 60.9 (CH2), 70.6 (C3), 89.8 (C1), 168.9
(C4), 183.3 (C2); m/z 211 (Mþ, 15%), 128 (100), 82 (24).
(E) 1,1-Dichloro-4-(pyrrolidin-1-yl)-pent-3-en-2-one (2d).
C9H13Cl2NO Mol. Wt.: 222.11 (60%); mp 112–113ꢀC; 1H
NMR (200 MHz, CDCl3) d 1.94–2.12 (m, 4H, 2 ꢃ CH2), 2.57
(s, 3H, H5), 3.39 (t, J ¼ 6.1 Hz, 2H, CH2), 3.52 (t, J ¼ 5.9
Hz, 2H, CH2), 5.25 (s, 1H, H3), 5.80 (s, 1H, H1); 13C NMR
(50 MHz, CDCl3) d 17.9 (C5), 24.6 (CH2), 24.9 (CH2), 48.5
(CH2), 48.7 (CH2), 72.5 (C3), 87.8 (C1), 164.6 (C4), 182.6
(C2); m/z 221 (Mþ, 25%), 138 (100), 70 (37).
´
de Desenvolvimento Cientıfico e Tecnologico em Pesquisa
(CNPq/PADCT) and the Fundac¸a˜o de Amparo a Pesquisa do
Estado do Rio Grande do Sul (FAPERGS) for financial support.
The fellowships from CNPq, CAPES, and FAPERGS are also
acknowledged.
´
`
REFERENCES AND NOTES
[1] Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter,
J. S.; Collins, P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha,
J. W.; Miyashiro, J. M.; Rogers, R. S.; Rogier, D. J.; Yu, S. S.; Ander-
son, G. D.; Burton, E. G.; Cogburn, J. N.; Gregory, S. A.; Koboldt,
C. M.; Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.;
Isakson, P. C. J Med Chem 1997, 40, 1347.
(E) 1,1-Dichloro-4-(morpholin-4-yl)-pent-3-en-2-one (2e).
1
C7H11Cl2NO Mol. Wt.: 238.11 (85%) Mp 96–98ꢀC; H NMR
[2] Terrett, N. K.; Bell, A. S.; Brown, D.; Ellis, P. Bioorg Med
Chem Lett 1996, 6, 1819.
(CDCl3, 400 MHz): d 2.56 (s, CH3), 3.51 (qua, 2 ꢃ CH2),
3.76 (qua, 2 ꢃ CH2), 5.53 (s, CH), 5.79 (s, CH); 13C NMR
(CDCl3, 100 MHz): d 16.1 (CH3), 46.5 (CH2), 66.1 (CH2),
72.4 (C), 88.7 (CH), 165.9 (CH), 184.4 (C¼¼O); m/z 237 (Mþ,
6%), 154 (100), 55 (33), 96 (22), 174 (12), 126 (7), 202 (5).
Crystallographic data for 2e were deposited at the Cambridge
Crystallographic Data Center (CCDC 649396). Copies of the
data can be obtained, free of charge, on application to CCDC
12 Union Road, Cambridge CB2 1EZ, UK (Fax: 44-1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk).
5-Dichloromethyl-3-methyl-1H-pyrazole (3). C5H6Cl2N2
Mol. Wt.: 165.02 (83%); mp 89–90ꢀC; 1H NMR (400 MHz,
CDCl3) d 2.30 (s, 3H, CH3), 6.28 (s, 1H, CH), 6.74 (s, 1H,
CHCl2), 8.15 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3) d
[3] de Souza, F. R.; Fighera, M. R.; Lima, T. T. F.; de Bas-
tiani, J.; Barcellos, I. B.; Almeida, C. E.; Oliveira, M. R.; Bonacorso,
H. G.; Flores, A. E. Pharm Biochem Behavior 2001, 68, 525.
[4] (a) Milano, J.; Oliveira, S. M.; Rossato, M. F.; Sauzem, P.
D.; Machado, P.; Beck, P.; Zanatta, N.; Martins, M. A. P.; Mello, C.
F.; Rubin, M. A.; J. Ferreira, Bonacorso, H. G. Europ J Pharmacol
2008, 581, 86; (b) Makino, K.; Kim, H. S.; Kurasawa, Y. J Heterocycl
Chem 1998, 35, 489 and references therein.
[5] (a) Norris, T.; Colon-Cruz, R.; Ripin, D. H. B. Org Biomol
Chem 2005, 3, 1844; (b) Bishop, B. C.; Brands, K. M. J.; Gibb, A. D.;
Kennedy, D. J. Synthesis 2004, 43; (c) Miller, R. D.; Reiser, O. J Het-
erocycl Chem 1993, 30, 755.
[6] Colla, A.; Clar, G.; Martins, M. A. P.; Krimmer, S.; Fi-
scher, P. Synthesis 1991, 483.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Solvent-free Route to b-Enamino Dichloromethyl Ketones and Application
in the Synthesis of Novel 5-Dichloromethyl-1H-pyrazoles
1251
[7] Martins, M. A. P.; Cunico, W.; Pereira, C. M. P.; Sinhorin,
[19] Martins, M. A. P.; Beck, P.; Machado, P.; Brondani, S.;
Moura, S.; Zanatta, N.; Bonacorso, H. G.; Flores, A. F. C. J Braz
Chem Soc 2006, 17, 408.
A. P.; Flores, A. F. C.; Bonacorso, H. G.; Zanatta, N. Curr Org Chem
2004, 1, 391.
[8] Druzhinin, S. V.; Balenkova, E. S.; Nenajdenko, V. G. Tet-
rahedron 2007, 63, 7753.
[20] Hojo, M.; Masuda, R.; Okada, E. Synthesis 1986, 12,
1013.
[9] Elguero, J. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Sci-
ence: New York, 1996; Vol. 3, pp 817–932.
[21] Martins, M. A. P.; Zoch, A. N.; Flores, A. F. C.;
Clar, G.; Zanatta, N.; Bonacorso, H. G. J Heterocycl Chem 1995, 32,
739.
[10] Nenajdenko, V. G.; Sanin, A. V.; Balenkova, E. S. Mole-
cules 1997, 2, 186.
[22] (a) Braibante, M. E. F.; Clar, G.; Martins, M. A. P. J Heter-
ocycl Chem 1993, 30, 1159; (b) Martins, M. A. P.; Freitag, R.;
Zanatta, N. Synthesis 1995, 1491.
[11] Tietze, F.; Meier, H.; Voss, E. Synthesis 1988, 274.
[12] Martins, M. A. P.; Pereira, C. M. P.; Sinhorin, A. P.; Bas-
tos, G. P.; Zimmermann, N. E. K.; Rosa, A.; Bonacorso, H. G.;
Zanatta, N. Synth Commun 2002, 32, 419.
[23] (a) Martins, M. A. P.; Pereira, C. M. P.; Moura, S.; Frizzo,
C. P.; Beck, P.; Zanatta, N.; Bonacorso, H. G.; Flores, A. F. C. J Het-
erocycl Chem 2007, 44, 1195; (b) Martins, M. A. P.; Pereira, C. M.
P.; Zimmermann, N. E. K.; Cunico, W.; Moura, S.; Beck, P.; Zanatta,
N.; Bonacorso, H. G. J Fluorine Chem 2003, 123, 261; (c) Moura S.;
Flores, A. F. C.; Favero, R. P.; Pinto, E.; Machado, P.; Martins M. A.
P. Lett Org Chem 2008, 5, 91.
[13] Martins, M. A. P.; Guarda, E. A.; Frizzo, C. P.; Marzari,
M. R. B.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Monatsh
Chem 2008, 139, 1321.
[14] Martins, M. A. P.; Guarda, E. A.; Frizzo, C. P.; Scapin, E.;
Beck, P.; Costa, A. C.; Zanatta, N.; Bonacorso, H. G. J Mol Catal A:
Chem 2006, 266, 100.
[24] (a) Bonacorso, H. G.; Oliveira, M. R.; Wentz, A. P.; Was-
¨
towski, A. D.; Oliveira, A. B.; Hoerner, M.; Zanatta, N.; Martins, M.
[15] Martins, M. A. P.; Guarda, E. A.; Frizzo, C. P.; Moreira, D.
N.; Marzari, M. R. B.; Zanatta, N.; Bonacorso, H. G. Catal Lett 2009,
130, 93.
A. P. Tetrahedron 1999, 55, 345; (b) Bonacorso, H. G.; Wastowski, A.
D.; Zanatta, N.; Martins, M. A. P.; Naue, J. A. J Fluorine Chem 1998,
92, 23.
[16] Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Rosa, F.
A.; Marzari, M. R. B.; Zanatta, N.; Bonacorso, H. G. Cat Commun
2008, 9, 1375.
[25] Bonacorso, H. G.; Wentz, A. P.; Zanatta, N.; Martins, M.
A. P. Synthesis 2001, 1505.
[26] (a) Martins, M. A. P.; Blanco, R. F.; Pereira, C. M. P.;
Beck, P.; Brondani, S.; Cunico, W.; Zimmermann, N. E. K.; Bona-
corso, H. G.; Zanatta, N. J Fluorine Chem 2002, 118, 69; (b) Tang,
X.-Q.; Hu, C.-M. J Fluorine Chem 1995, 73, 129.
[17] Martins, M. A. P.; Moreira, D. N.; Frizzo, C. P.; Longhi,
K.; Zanatta, N.; Bonacorso, H. G. J. Braz Chem Soc 2008, 19, 1361.
[18] Martins, M. A. P.; Peres, R. L.; Fiss, G. F.; Dimer, F. A.;
Mayer, R.; Frizzo, C. P.; Marzari, M. R. B.; Zanatta, N.; Bonacorso,
H. G. J. Braz Chem Soc 2007, 18, 1486.
´ ´
[27] Diez-Barra, H.; de La Hoz, A.; Sanchez-Miguallon, A.;
Elguero, J. J Heterocycl Chem 1999, 36, 889.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet