Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

Article abstract of DOI:10.3762/bjoc.9.173

A method for the synthesis of N-aryl-C-nitroazoles is presented. A coupling reaction between variously substituted arylboronic acids and 3(5)-nitro-1H-pyrazole catalyzed by copper salt has been carried out in methanol in the presence of sodium hydroxide t

Full text of DOI:10.3762/bjoc.9.173

Coupling of C-nitro-NH-azoles with arylboronic acids.
A route to N-aryl-C-nitroazoles
Marta K. Kurpet*1, Aleksandra Dąbrowska1, Małgorzata M. Jarosz1,
Katarzyna Kajewska-Kania1, Nikodem Kuźnik1 and Jerzy W. Suwiński2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 1517–1525.
1Department of Organic Chemistry, Bioorganic Chemistry and
Biotechnology, Silesian University of Technology, Krzywoustego 4,
Gliwice 44-100, Poland and 2Centre of Polymer and Carbon
Materials, Polish Academy of Sciences, M. Curie-Skłodowskiej 34,
Zabrze 41-819, Poland
doi:10.3762/bjoc.9.173
Received: 11 May 2013
Accepted: 28 June 2013
Published: 30 July 2013
Email:
Associate Editor: J. P. Wolfe
Marta K. Kurpet* - marta.kurpet@polsl.pl
© 2013 Kurpet et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
arylboronic acids; C-nitroazoles; coupling; N-arylation;
N-aryl-C-nitroazoles
Abstract
A method for the synthesis of N-aryl-C-nitroazoles is presented. A coupling reaction between variously substituted arylboronic
acids and 3(5)-nitro-1H-pyrazole catalyzed by copper salt has been carried out in methanol in the presence of sodium hydroxide to
afford the desired N-aryl-C-nitroazoles in good yields. This synthetic route has also been successfully applied to obtain N-phenyl
derivatives of 4-nitropyrazole, 2-nitroimidazole, 4(5)-nitroimidazole and 3-nitro-1,2,4-triazole.
Introduction
The nitroazoles constitute a class of compounds with a broad suffer from mutagenic and carcinogenic properties [9]. There-
spectrum of useful properties. They have found applications in fore the efforts of several research groups are focused on
agrochemicals as plant-growth regulators [1], herbicides or finding new compounds bearing C-nitroazole rings in their
insecticides [2], in veterinary science [3], and as propellants and structure but exhibiting a less toxic effect.
precursors of energetic materials [4]. Special attention has been
paid to the development of their application in medicine where Recent studies on biologically active derivatives of nitroazoles
so far they are used as antiprotozoal, antifungal, and antibacte- led to the synthesis and wide investigation of antibacterial and
rial drugs [5,6], as hypoxic cell sensitizers in radiation therapy antiprotozoal 4-nitroimidazoles functionalized with an aryl
of cancer [7], or as antiphlogistic drugs [8]. Many derivatives of substituent on the ring nitrogen atom. Many of these com-
C-nitroazoles, particularly N-alkylnitroimidazoles being the pounds exhibit a potent and selective anti-trypanosomal activity
most often repeating subunit in biologically active compounds, with relatively low mutagenic characteristics as well as geno-
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toxic risk [10] and show promising antitubercular properties pounds for inhibiting phosphate transport [32], and are
[11]. This opens an opportunity to look for new N-aryl-C- described as being useful for the treatment of cognitive-deficit-
nitroazoles with the desired biological activity. Very recently, associated psychiatric, neurodegenerative and neurological
we reviewed the syntheses of N-phenyl-C-nitroazoles [12], and disorders [33].
syntheses of their derivatives will be reviewed soon. The range
of methods of N-aryl-C-nitroazoles synthesis includes nitration Only four papers describe the synthesis of 3-nitro-1-phenyl-1H-
[13], ring closure [14,15], degenerated ANRORC reactions pyrazole. It may be a product of oxidation of 3-amino-1-phenyl-
[16], transformation of other cyclic molecules [17], oxidation of 1H-pyrazole [18], a product of coupling of diaryliodonium salts
aminoazoles [18], and introduction of an aryl substituent at the with 3-nitro-1H-pyrazole [20], a product of Ullman phenyla-
ring nitrogen atom in starting nitroazole [19,20]. Many of these tion of 3-nitro-1H-pyrazole [34], or a byproduct in the syn-
methods suffer due to the inconvenient conditions of reactions, thesis of 1-phenyl-4-amino-5-methylaminopyridazin-6-one [17]
lack of selectivity, or low yields of the products. Therefore, (Scheme 1).
there is a need for the development of a new, simple synthetic
route, applicable to a wide range of C-nitro-NH-azoles.
Although these works describe 3-nitro-1-phenyl-1H-pyrazole
(3a) as the product of the reaction, different physical properties
Since 1998 when Chan and Lam [21,22] described a novel are specified below.
method for the formation of C–N bonds through the copper-
catalyzed coupling of NH-containing substrates such as amines, Despite, we obtained 3-nitro-1-phenyl-1H-pyrazole (3a), for
amides, imides or heterocycles with boronic acids, the method which the spectra determined in chloroform-d were in excellent
has become a powerful synthetic route for N-arylation. Many agreement with those presented by Chertkov et al. for their
investigations concerning the influence of the amount and kind product [20], the melting points differed from each other by
of a catalyst, type of solvent, temperature, the presence of a almost 30 °C.
base, and other reaction conditions, have carried out [23-27].
The melting point of the product synthesized by us is 98–99 °C,
We were interested in developing an easy and effective method which is consistent with results obtained by Coburn [18],
for the synthesis of N-aryl-C-nitroazoles that would allow us to who oxidized 3-amino-1-phenyl-1H-pyrazole (Scheme 1,
obtain a broad range of the desired products bearing both chem- method A), while Chertkov et al. determined a value of 127 °C
ically and electronically varying substituents on the benzene (Scheme 1, method B), which on the other hand fits with the
ring. The presence of the nitro group (a strong electron-with- data published by Predvoditeleva [17] (Scheme 1, method D).
drawing substituent) in the azole entails the adjustment of the
conditions of N-arylation reaction.
The presence of tautomeric forms of 3(5)-nitro-1H-pyrazole
(1a) and the discrepancy in the melting point of our product and
Besides a very recently published approach involving N-aryl- the recently described one, led us to look carefully into its struc-
ation of nitroazoles with diaryliodonium salts [20], already ture and to investigate the possibility of formation of other
described methods utilize arylboronic acids and substituted isomers.
C-nitroazole coupling, applying the conditions described for the
Chan–Lam reaction. This involves the use of chlorinated The analysis of 13C NMR spectra of our products shows that
solvents, pyridine as base, and prolonged reaction times to there are characteristic signals, which can be assigned to carbon
obtain high yields of the product [28,29]. No detailed investi- atoms in the 3-nitro-pyrazole rings: about 103–105 ppm for
gation on the influence of the conditions on the yield of the C4-Py, 129–132 ppm for C5-Py and 156–157 ppm for C3-Py.
product has been presented.
These results are consistent with the analysis of regioisomers of
1-substituted-C-nitropyrazoles presented by Larina and Lopyrev
in their review on nitroazoles [35]. Table 1 contains exempli-
Results and Discussion
The group of products that we mainly describe is the 1-aryl fied structures of 3-nitro-, 4-nitro- and 5-nitropyrazole deriva-
derivatives of 3(5)-nitro-1H-pyrazole (1a). This is still a barely tives and shows the differences in chemical shifts of carbon
investigated group of compounds that can have attractive atoms in particular isomers. The examples do not include the
properties. Some recent reports describe them as new glucagon 1-aryl substituent, which is present in our product, but general
receptor antagonists [28] and compounds having insectidal trends in chemical shifts can be observed. The C–NO2 signal in
properties [30]. They are a substructure of compounds 5-nitropyrazole is shifted by about 10 ppm downfield in com-
being inhibitors of cannabinoid receptor 1 [31], they can be parison to the C–NO2 signal in 3-nitropyrazole, what agrees
used as intermediate products, e.g., in the synthesis of com- with spectra recorded by us.
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Beilstein J. Org. Chem. 2013, 9, 1517–1525.
Scheme 1: Methods of synthesis of 3-nitro-1-phenyl-1H-pyrazole (3a) described in the literature.
Additionally, in order to confirm the structure we used X-ray At the very beginning we decided to perform several experi-
analysis for one of our products. The analyzed crystal of ments that would allow us to establish the necessity of the pres-
3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-nitro-1H-pyrazole ence of a catalyst, air and a base in the reaction system
(3k) was a monocrystal recrystallized from diethyl ether (Table 2). The initial conditions of the reaction were based on
(Figure 1). It forms a monoclinic unit cell with two symmetry- those published by Lan et al. [24] for coupling imidazole with
related pairs of molecules. The molecule is relatively flat, with phenylboronic acid. Most reports on the Chan–Lam coupling
the benzene ring slightly twisted out from the pyrazole plane reaction underline the demand of air introduction into the
19.60° (27), while the nitro-substituent is almost coplanar with reaction mixture to provide high yields of the products
pyrazole root 8.06° (90). Such a structure enables efficient over- [22,24,36,37]. The plausible mechanism of this catalytic reac-
lapping of π orbitals resulting in high conjugation.
tion was proposed by Evans [38] and described for N-nucleo-
philes by Collman [39]. It involves several steps: transmetalla-
Based on the agreement of our NMR spectra with those tion of boronic acid with a catalyst, coordination of the azole
presented and thoroughly analyzed by Chertkov et al., as well as molecule to the Cu(II) species followed by oxidation of
on our X-ray analysis, the substitution of the nitro-group in the copper(II) into copper(III) in the presence of oxygen, and then
3-position of the 1H-pyrazole moiety was confirmed.
reductive elimination releasing the product and Cu(I) complex.
A regeneration of the catalyst takes place in the presence of
Our screening of the conditions involved the factors influ- oxygen reproducing the Cu(II) cation.
encing the chemical yield of reaction, including the solvent/base
system, the type of catalyst, and the stoichiometry of the In the case of the application of Cu(I) salts, for which our
reagents. 3-Nitro-1H-pyrazole (1a) and phenylboronic acid (2a) preliminary studies were carried out, the presence of air proved
were used as model substrates to optimize the reaction condi- to be obligatory. Attempts to perform the reaction without air
tions (Scheme 2).
resulted in no or only trace amounts of product being detected
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Beilstein J. Org. Chem. 2013, 9, 1517–1525.
Table 1: 13C NMR chemical shifts (ppm) of C-nitropyrazoles [35].
Table 2: The influence of the presence of air, a base and a catalyst on
the yield of 3-nitro-1-phenyl-1H-pyrazole (3a).a
Substituents in
nitropyrazole ring
13C NMR chemical shifts (ppm) for
nitropyrazoles
Entry
Catalyst
Base
Air
Yieldb
R1
R3
R4
R5
C3
C4
C5
solvent
1
CuI
CuI
no
noe
+
0%
trace
trace
64%
56%
69%
0%
2c
no
3d
CuI
NaOH
NaOH
NaOH
NaOH
NaOH
noe
+
4c,d
5d
CuI
CuCl2
CuCl2
–
noe
+
6c,d
7c,d
H
–
–
–
H
H
H
H
H
H
155.70 103.24 132.80 CD3OD
154.90 102.70 134.50 DMSO-d6
152.96 102.17 132.80 DMSO-d6
+
CH3
NH2
aConditions: 2 mmol of 2a, 2.4 mmol of 1a, 10 mol % of catalyst,
methanol, reflux. The progress of the reaction was controlled by TLC.
bIsolated yields. cAir was bubbled through solution. dIn the presence of
2.4 mmol of NaOH. eNo bubbling of air through solution.
H
H
H
H
–
–
–
H
H
H
132.41 136.00 132.44 DMSO-d6
135.00 134.90 130.60 DMSO-d6
132.96 133.33 128.32 DMSO-d6
CH3
NH2
Scheme 2: Cross coupling of 3-nitro-1H-pyrazole (1a) with phenyl-
boronic acid (2a).
CH3
NH2
H
H
H
H
–
–
137.60 106.30 145.80 DMSO-d6
133.60 104.72 142.26 DMSO-d6
are in agreement with those obtained by Strijdonck [40] who
carried out copper-catalyzed coupling under anaerobic condi-
tions. The mechanism of this reaction is still a matter of
research. The reaction does not take place without a base
(Table 2, entry 2) or in the absence of copper catalyst (Table 2,
entry 7).
A parameter influencing chemical yields to a greater extent
was the applied solvent/base system. Sodium hydroxide
(pKa = 15.7) [41] and triethylamine (Et3N) (pKa = 10.9) [42] in
dichloromethane, acetonitrile, dimethylformamide, tetrahydro-
furan and methanol were investigated. Dichloromethane, being
the most often reported solvent for coupling [21-23,36], turned
out to be the least appropriate in the case of C-nitroazoles.
Yields of the product obtained were then 3% and 8% in the
presence of Et3N and NaOH, respectively (Table 3, entries 1,2).
Even prolonged time did not improve the yield (Table 3, entry
3). Better results were obtained for more polar solvents (aceto-
nitrile, dimethylformamide, tetrahydrofuran, methanol) inde-
pendently on a base (Table 3, entries 4–11). The most efficient
combinations were dimethylformamide/sodium hydroxide and
methanol/sodium hydroxide. Methanol was the solvent of
choice due to higher yields and convenience of workup and
purification of the product.
Figure 1: X-ray structure of 3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-
nitro-1H-pyrazole (3k) with 60% probability ellipsoids.
on the TLC plate (Table 2, entries 1 and 3). Our further experi-
ments carried out in the presence of Cu(II) salt revealed that the
air does not seem to be necessarily introduced for the reaction
to take place (Table 2, entry 5). However, bubbling air through
the reaction mixture improved the yield (Table 2, entry 6), indi-
cating its possible impact on the catalytic cycle. These results
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Table 3: Influence of the solvent/base system on the yield of 3a.a
Table 4: The influence of copper catalyst on the yield of 3a.a
Entry
Solvent
Base
Time [h]
Yieldb
Entry
Catalyst
Yieldb
1
2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CH3CN
DMF
NaOH
Et3N
11
10
20
11
11
9
8 %
3%
1
2
3
4
5
6
7
8
CuI
CuCl
63%
66%
58%
trace
69%
66%
66%
53%
3
NaOH
NaOH
Et3N
8%
CuBr
4
48%
40%
56%
40%
48%
37%
64%
26%
25%
63%
CuO
5
CuCl2
6
NaOH
Et3N
Cu(OAc)2·H2O
CuSO4
Cu(acac)2
7
DMF
11
10
11
10
11
13
12
8
THF
NaOH
Et3N
9
THF
aConditions: 2 mmol of 2a, 2.4 mmol of 1a, 10% mol of a catalyst,
2.4 mmol of NaOH, methanol, reflux, 10 h, air bubbled through solu-
tion. The progress of the reaction was controlled by TLC. bIsolated
yields.
10
11
12
13
CH3OH
CH3OH
CH3OH
CH3OH
NaOH
Et3N
K2CO3
DBU
aConditions: 2 mmol of 2a, 2.4 mmol of 1a, 10 mol % of CuI, 2.4 mmol
of base, methanol, reflux, air bubbled through solution. The progress of
the reaction was controlled by TLC. bIsolated yields.
previous experiments confirmed, it is not required for Cu(II)
salts, although it provides higher yields of the product.
It turned out that the ratio of reagents has an important influ-
In order to complete the research on the solvent/base system, ence on the chemical yield of 3-nitro-1-phenyl-1H-pyrazole. A
the coupling reaction was carried out in methanol in the pres- ratio of arylboronic acid to 3-nitro-1H-pyrazole to the base of
ence of other bases such as potassium carbonate (pKa = 10.33) 2.6:1.6:1.6 seems to be optimal. This gave the highest (up to
[43] and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, pKa = 12) 82%) yield of the product. A series of experiments, when either
[44] (Table 3, entries 12,13). Although the pKa values were an excess of azole or a base over other reagents was used,
determined in water, they are usually in good agreement in resulted in decreased yields. Nevertheless, the base should be
other polar solvents scales [45]. Not surprisingly, the differ- used in stoichiometric proportion to the azole. Both increasing
ences in pKa values of the bases are reflected in the results and decreasing the proportion led to lower yield of the product.
obtained. Very strong bases (DBU, NaOH) are needed for the
reaction to take place. Although the reaction with DBU yielded With an efficient N-arylating system for phenylboronic acid, we
a similar amount of product as NaOH, the latter was chosen as expanded the scope of this reaction by exploring a variety of
being of lower toxicity, easier to process and environmentally boronic acids with different substitution patterns. The investi-
friendly.
gated compounds brought such substituents as F, Cl, CH3,
OCH3, OCF3, and NO2 (Scheme 3). The results show that an
Next the catalytic activity of the copper salts was screened. electron-donating character of a substituent (Table 5, entries
Most known reports concerning N-arylation focus on Cu(OAc)2 7–10) allows higher yields of the products to be obtained than
salt [21,22], complexes of Cu(II) with different ligands [23,36], with electron-withdrawing groups (Table 5, entries 2–6 and
and heterocyclic copper-based catalysts [25,37]. Basically, entries 11–14).
easily available simple copper(I) and copper(II) compounds,
mostly salts, were investigated. The yields obtained for Cu(I)
salts (Table 4, entries 1–3) were slightly lower than those
achieved for Cu(II) salts (Table 4, entries 5–8). However, the
differences are small, and it can be assumed that under the reac-
tion conditions applied the choice between Cu(I) and Cu(II) is
not crucial, considering the yield of 3-nitro-1-phenyl-1H-pyra-
zole. Also the effect of the counterion seems to be insignificant.
Among the investigated compounds only CuO was ineffective
as a catalyst and gave only trace amounts of the product as
detected on the TLC plate. This implies the need to consider
another factor. The use of Cu(I) species obligates the introduc-
Scheme 3: Cross coupling of 1a with arylboronic acids 2a–n.
tion of air into the reaction mixture during the reaction. As our
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Beilstein J. Org. Chem. 2013, 9, 1517–1525.
Table 5: Coupling of 1a with arylboronic acids 2a–n.a
Table 5: Coupling of 1a with arylboronic acids 2a–n.a (continued)
Entry
1
Boronic acid
Product
Time [h]
18
Yieldb
82%
10
11
3j
13
15
86%
66%
3a
2j
2a
3k
2
3b
11
64%
2k
2l
2b
2c
2d
12
13
3l
15
31
64%
62%
3
4
3c
3d
11
25
58%
50%
3m
2m
14
3n
30
65%
5
3e
16
67%
2n
2e
aConditions: 2.6 mmol of arylboronic acid 2a–n, 1.6 mmol of 1a,
10 mol % of a catalyst, 1.6 mmol of NaOH, methanol, reflux, air
bubbled through the solution. The progress of the reaction was moni-
tored by TLC. bIsolated yields.
6
7
8
3f
3g
3h
8
8
44%
74%
86%
2f
The yields also vary with the location of the substituent on the
benzene ring. Ortho- and meta-substituted phenylboronic acids
gave in most cases lower yields in comparison to para-substi-
tuted ones (Table 5, entries 2,3,5–8,11–14). This might be a
result of steric hindrance around the reaction center in the
catalytic cycle.
2g
Applicability of the synthetic procedure to the preparation of
various N-aryl-C-nitroazoles was also investigated. For this
purpose the cross coupling of phenylboronic acid with a
series of C-nitro-NH-azoles such as: 3(5)-nitropyrazole (1a)
(pKa = 9.81) [46], 4-nitropyrazole (1b) (pKa = 9.67) [46],
4(5)-nitroimidazole (1c) (pKa = 8.93) [47], 3-nitro-1,2,4-
triazole (1d) (pKa = 6.05) [48] and 2-nitroimidazole (1e)
(pKa = 7.15 in CH3OH/H2O 1:1) [49] (Scheme 4, Table 6) was
carried out. The results show that this method allows N-aryl
derivatives of C-nitroazoles to be obtained within a wide pKa
range.
14
2h
9
3i
20
80%
2i
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Beilstein J. Org. Chem. 2013, 9, 1517–1525.
Table 6: Cross coupling of C-nitro-NH-azoles 1a–e with 2a.a
Entry
C-nitro-NH-azole
Product
Time [h]
18
Yieldb
82%
1
3a
1a
1b
1c
2
3
15
18
53%
86%
3o
3p
3r
4
5
16
9
50%
40%
1d
1e
3s
aConditions: 2.6 mmol of 2a, 1.6 mmol of C-nitroazole 1a–e, 10 mol % of a catalyst, 1.6 mmol of NaOH, methanol, reflux, air bubbled through the
solution. The progress of the reaction was controlled by TLC. bIsolated yields.
copper salts. The reaction takes place in a protic solvent
containing a base, both of which are necessary for providing
good yields of the products. The method represents an impor-
tant supplement to the synthetic methodologies for the prepar-
ation of N-aryl-C-nitroazoles and can be successfully applied to
the synthesis of a series of diverse C-nitroazoles functionalized
Scheme 4: Cross coupling of C-nitro-NH-azoles 1a–d with phenyl-
boronic acid (2a).
with an aryl substituent on a ring nitrogen atom.
Supporting Information
Comparing our results presented here with those reported very
recently by V. A. Chertkov et al. [20], it appears that both
Supporting Information File 1
methods are regioselective and lead to syntheses of N-aryl-C-
nitroazoles in moderate to high yields. Arylboronic acids are
more easily available than diaryliodonium salts, and thus the
scope of our approach seems to be wider. The much milder
reaction conditions presented in this paper make this route more
valuable.
Experimental procedures and characterization of products.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-173-S1.pdf]
Supporting Information File 2
Crystallographic information file (structure of
3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-nitro-
1H-pyrazole).
Conclusion
In conclusion, we have developed an efficient and simple
method for the cross coupling of arylboronic acids with C-nitro-
NH-azoles in the presence of a catalytic amount of simple
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-173-S2.cif]
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Beilstein J. Org. Chem. 2013, 9, 1517–1525.
21.Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winteres, M. P.
Tetrahedron Lett. 1998, 39, 2933–2936.
Acknowledgements
This work was supported by the European Community from the
doi:10.1016/S0040-4039(98)00503-6
European Social Fund within the RFSD 2 project.
22.Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.;
Chan, D. M. T.; Combs, A. Tetrahedron Lett. 1998, 39, 2941–2944.
doi:10.1016/S0040-4039(98)00504-8
References
23.Collman, J. P.; Zhong, M. Org. Lett. 2000, 2, 1233–1236.
doi:10.1021/ol000033j
1. Wang, S.; Sun, H.; Nikolovsksa-Colska, Z.; Yang, C.-Y.; Xu, L.;
Saito, N. G.; Chen, J. Conformationally constrained smac mimetics and
the uses thereof. U.S. Patent 7,674,787, March 9, 2010.
2. Dereu, N.; Welter, A.; Ghyczy, M. Herbicidally active 1-substituted
2,4(5)-diisopropyl 5(4)-nitroimidazoles. German Patent 3,247,648, June
28, 1984.
24.Lan, J.-B.; Chen, L.; Yu, X.-Q.; You, J.-S.; Xie, R.-G. Chem. Commun.
2004, 188–189. doi:10.1039/b307734a
25.Kantam, M. L.; Venkanna, G. T.; Sridhar, C.; Sreedhar, B.;
Choudary, B. M. J. Org. Chem. 2006, 71, 9522–9524.
doi:10.1021/jo0614036
3. Girard, M.; Clairmont, F.; Maneckjee, A.; Mousseau, N.; Dawson, B. A.;
Whitehouse, L. W. Can. J. Chem. 1993, 71, 1349–1352.
doi:10.1139/v93-174
26.Chen, S.; Huang, H.; Liu, X.; Shen, J.; Jiang, H.; Liu, H.
J. Comb. Chem. 2008, 10, 358–360. doi:10.1021/cc8000053
27.Reddy, K. R.; Kumar, N. S.; Sreedhar, B.; Kantam, M. L.
J. Mol. Catal. A 2006, 252, 136–141.
4. Spear, R. J. Aust. J. Chem. 1984, 37, 2453–2468.
doi:10.1071/CH9842453
doi:10.1016/j.molcata.2006.02.053
5. Grimmet, M. R. Imidazoles and their Benzo Derivatives: (iii) Synthesis
and Applications. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R.; Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 5,
pp 469–498.
28.Filipski, K. J.; Bian, J.; Ebner, D. C.; Lee, E. C. Y.; Li, J.-C.;
Sammons, M. F.; Wright, S. W.; Stevens, B. D.; Didiuk, M. T.; Tu, M.;
Perreault, C.; Brown, J.; Atkinson, K.; Tan, B.; Salatto, C. T.;
Litchfield, J.; Pfefferkorn, J. A.; Guzman-Perez, A.
6. Potts, K. T. Chem. Rev. 1961, 61, 87–127. doi:10.1021/cr60210a001
7. Davis, D. P.; Kirk, K. L.; Cohen, L. A. J. Heterocycl. Chem. 1982, 19,
253–256. doi:10.1002/jhet.5570190206
Bioorg. Med. Chem. Lett. 2012, 22, 415–420.
doi:10.1016/j.bmcl.2011.10.113
29.Berk, S. C.; Close, J.; Hamblett, C.; Heidebrecht, R. W.; Kattar, S. D.;
Kliman, L. T.; Mampreian, D. M.; Methot, J. L.; Miller, T.; Sloman, D. L.;
Stanton, M. G.; Tempest, P.; Zabierek, A. A. Spirocyclic compounds.
U.S. Patent 7,544,695, June 9, 2009.
8. Makarova, N. G.; Anisimova, N. A.; Berkova, G. A.; Deiko, L. I.;
Berestovitskaya, V. M. Russ. J. Org. Chem. 2005, 41, 941–943.
doi:10.1007/s11178-005-0272-1
9. Larina, L.; Lopyrev, V. Application of Nitroazoles. Nitroazoles:
Synthesis, Structure and Applications; Topics in Applied Chemistry;
Springer Verlag: New York, NY, USA, 2009; pp 407–432.
doi:10.1007/978-0-387-98070-6_4
30.Goergens, U.; Mihara, J.; Murata, T.; Shibuya, K.; Shimojo, E.;
Yamazaki, D.; Yoneta, Y. Insecticidal aryl pyrrolidines. WO Patent
Application 2008/128711 A1, Oct 30, 2008.
31.Choi, H.-S.; Ellis, A. D.; He, X.; Liu, H.; Nguyen, N. T.; Wang, Z.;
Woodmansee, D.; Wu, B.; Yang, K. Compounds and compositions as
inhibitors of cannabinoid receptor 1 activity. WO Patent Application
2006/047516 A2, May 4, 2006.
And references cited therein.
10.Bourdin Trunz, B.; Jędrysiak, R.; Tweats, D.; Brun, R.; Kaiser, M.;
Suwiński, J.; Torreele, E. Eur. J. Med. Chem. 2011, 46, 1524–1535.
doi:10.1016/j.ejmech.2011.01.071
32.Lewis, J. G.; Jacobs, J. W.; Reich, N.; Leadbetter, R.; Bell, N.;
Chang, H.-T.; Chen, T.; Navre, M.; Charmot, D.; Carreras, Ch.;
Labonte, E. Compounds and methods for inhibiting phosphate
transport. WO Patent Application 2012/006473 A1, Jan 12, 2012.
33.Dounay, A. B.; Mcallister, L. A.; Parikh, V. D.; Rong, S.; Verhoest, P. R.
Kat II inhibitors. WO Patent Application 2012/073143 A1, June 17,
2012.
11.Walczak, K.; Gondela, A.; Suwiński, J. Eur. J. Med. Chem. 2004, 39,
849–853. doi:10.1016/j.ejmech.2004.06.014
12.Kurpet, M.; Jędrysiak, R.; Suwiński, J. Chem. Heterocycl. Compd.
2013, 48, 1737–1750. doi:10.1007/s10593-013-1205-5
13.Grimmett, M. R.; Hartshorn, S. R.; Schofield, K.; Weston, J. B.
J. Chem. Soc., Perkin Trans. 2 1972, 1654–1660.
doi:10.1039/P29720001654
34.Grimmett, M. R.; Lim, K. H. R.; Weavers, R. T. Aust. J. Chem. 1979,
32, 2203–2213. doi:10.1071/CH9792203
14.Pocar, D.; Maiorana, S.; Dalla Croce, P. Gazz. Chim. Ital. 1968, 98,
949–957.
35.Larina, L.; Lopyrev, V. Application of Nitroazoles. Nitroazoles:
Synthesis, Structure and Applications; Topics in Applied Chemistry;
Springer: New York, NY, USA, 2009; pp 182–199.
doi:10.1007/978-0-387-98070-6
15.Nishiwaki, N.; Ogihara, T.; Takami, T.; Tamura, M.; Ariga, M.
J. Org. Chem. 2004, 69, 8382–8386. doi:10.1021/jo0488513
16.Jędrysiak, R.; Sawicki, M.; Wagner, P.; Suwiński, J. ARKIVOC 2007, vi,
103–111.
And references cited therein.
17.Predvoditeleva, G. S.; Kartseva, T. V.; Shchukina, M. N.
Pharm. Chem. J. 1974, 8, 525–527. doi:10.1007/BF00760681
18.Coburn, M. D. J. Heterocycl. Chem. 1970, 7, 455–456.
doi:10.1002/jhet.5570070242
36.Collman, J. P.; Zhong, M.; Zhang, C.; Costanzo, S. J. Org. Chem.
2001, 66, 7892–7897. doi:10.1021/jo010615u
37.Kantam, M. L.; Prakash, B. V.; Reddy, Ch. V. J. Mol. Catal. A 2005,
241, 162–165. doi:10.1016/j.molcata.2005.07.015
19.Chauzov, V. A.; Parchinsky, V. Z.; Sinelshchikova, E. V.;
Petrosyan, V. A. Russ. Chem. Bull. 2001, 50, 1274–1279.
doi:10.1023/A:1014023310543
38.Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39,
2937–2940. doi:10.1016/S0040-4039(98)00502-4
39.Collman, J. P.; Zhong, M.; Zeng, L.; Costanzo, S. J. Org. Chem. 2001,
66, 1528–1531. doi:10.1021/jo0016780
20.Chertkov, V. A.; Shestakova, A. K.; Davydov, D. V.
Khim. Geterotsikl. Soedin. 2011, 1, 63–74.
40.van Berkel, S. S.; van den Hoogenband, A.; Terpstra, J. W.; Tromp, M.;
van Leeuwen, P. W. N. M.; van Strijdonck, G. P. F. Tetrahedron Lett.
2004, 45, 7659–7662. doi:10.1016/j.tetlet.2004.08.094
Chem. Heterocycl. Compd. 2001, 47, 45–54.
doi:10.1007/s10593-011-0718-z
1524

Beilstein J. Org. Chem. 2013, 9, 1517–1525.
41.Smith, M. B.; March, J. March’s Advanced Organic Chemistry:
Reactions, Mechanisms, and Structure, 6th ed.; John Wiley & Sons:
Hoboken, NJ, USA, 2007; p 362.
42.Faltin, C.; Fleming, E. M.; Connon, S. J. J. Org. Chem. 2004, 69,
6496–6499. doi:10.1021/jo0490907
43.Reeves, R. R. Recovery of alcohols. U.S. Patent 4,594,466, June 10,
1986.
44.Granitza, D.; Beyermann, M.; Wenschuh, H.; Haber, H.; Carpino, L. A.;
Truran, G. A.; Bienert, M. J. Chem. Soc., Chem. Commun. 1995,
2223–2224.
45.Boncel, S.; Saletra, K.; Hefczyc, B.; Walczak, K. Z.
Beilstein J. Org. Chem. 2011, 7, 173–178. doi:10.3762/bjoc.7.24
46.Kanishchev, M. I.; Korneeva, N. V.; Shevelev, S. A.; Fainzil'berg, A. A.
Chem. Heterocycl. Compd. 1988, 24, 353–370.
doi:10.1007/BF00478852
47.Li, W.; Norris, B. C.; Snodgrass, P.; Prasad, K.; Stockett, A. S.;
Pryamitsyn, V.; Ganesan, V.; Bielawski, C. W.; Manthiram, A.
J. Phys. Chem. B 2009, 113, 10063–10067. doi:10.1021/jp904192t
48.Kofman, T. P.; Kartseva, G. Yu. Russ. J. Org. Chem. 2001, 37,
707–716. doi:10.1023/A:1012460103654
49.Gallo, G. G.; Pasqualucci, C. R.; Radaelli, P.; Lancini, G. C.
J. Org. Chem. 1964, 29, 862–865. doi:10.1021/jo01027a023
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