Direct N-heterocyclization of hydrazines to access styrylated pyrazoles: synthesis of 1,3,5-trisubstituted pyrazoles and dihydropyrazoles

Article abstract of DOI:10.1039/c8ra04550j

A microwave-assisted method has been developed for the synthesis of tri-substituted pyrazoles via direct N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using any base or additives. Most importantly, the synthesis of 1-aryl-5-phenyl-3-styryl-1H-pyrazoles was achieved in a single step using hydrochloride salt of various phenylhydrazines and this is the first report for direct construction of these molecules. The reaction medium and microwave conditions play a critical role for their selective product formation during the reaction. The present reaction explored the usage of metal-diketonic complexes as reaction substrates providing acetylacetone and dibenzylideneacetone moieties to directly participate in cyclization with hydrazines to form the corresponding pyrazoles in excellent yields. The present protocol introduces the important N-heterocyclic moieties in the final structures, giving the reaction great applications from a medicinal chemistry perspective, particularly in the late stage modification strategies in drug discovery.

Full text of DOI:10.1039/c8ra04550j

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Direct N-heterocyclization of hydrazines to access
styrylated pyrazoles: synthesis of 1,3,5-
Cite this: RSC Adv., 2018, 8, 26523
trisubstituted pyrazoles and dihydropyrazoles†
Vunnam Venkateswarlu,‡ab Jaspreet Kour,‡ab K. A. Aravinda Kumar,a
Praveen Kumar Verma,a G. Lakshma Reddy,ab Yaseen Hussain,ab Aliya Tabassum,a
Shilpi Balgotra,ab Sorav Gupta,ab Abhinandan D. Hudwekar,ab Ram A. Vishwakarmaa
ab
*
and Sanghapal D. Sawant
A microwave-assisted method has been developed for the synthesis of tri-substituted pyrazoles via direct
N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using
any base or additives. Most importantly, the synthesis of 1-aryl-5-phenyl-3-styryl-1H-pyrazoles was
achieved in a single step using hydrochloride salt of various phenylhydrazines and this is the first report
for direct construction of these molecules. The reaction medium and microwave conditions play
a critical role for their selective product formation during the reaction. The present reaction explored the
usage of metal-diketonic complexes as reaction substrates providing acetylacetone and
dibenzylideneacetone moieties to directly participate in cyclization with hydrazines to form the
corresponding pyrazoles in excellent yields. The present protocol introduces the important N-
heterocyclic moieties in the final structures, giving the reaction great applications from a medicinal
chemistry perspective, particularly in the late stage modification strategies in drug discovery.
Received 28th May 2018
Accepted 2nd July 2018
DOI: 10.1039/c8ra04550j
rsc.li/rsc-advances
synthesized by cyclocondensation of hydrazines with diketones
under acidic conditions,10 aromatization of pyrazolines11 and
intramolecular coupling of hydrazones.12
1. Introduction
Pyrazoles are very important functional moieties having extensive
applications in pharmaceuticals,1 agriculture,2 supramolecular
chemistry,3 polymers,4 liquid crystals,5 ligands in catalysis6 and
many others. Despite the intricacy in N–N bond formations, these
are widely present in nature7 such as in withasomnine, pyr-
azofurin, formycin A and B, nostocine A, uviol A–E, and
pyrazole-3(5)-carboxylic acid and show remarkable biological
potential. 1,3,5-Trisubstituted pyrazoles constitute a number of
drugs,1i,8 including sildenal (inhibits phosphodiesterase), cele-
coxib (selective COX-2 inhibitor used for inammation and
arthritis), rimonabant (inverse agonist for cannabinoid receptor
CB1 and anti-obesity drug) and difenamizole (analgesic). In
recent times, these are one of the privileged scaffolds in drug
discovery and are extensively targeted by synthetic chemists. A
number of methods have been developed to construct pyrazole
scaffolds.9 Traditionally, 1,3,5-trisubstituted pyrazoles are
aMedicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal
Road, Jammu-180001, India. E-mail: sdsawant@iim.res.in; sdsawant@iiim.ac.in;
Fax: +91 191 2586333; Tel: +91 191 2585222
bAcademy of Scientic and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Ra
Marg, New Delhi 110001, India
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra04550j
‡ Equal contribution as rst author.
Scheme 1 Synthesis of pyrazoles and dihydropyrazoles.
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Table 1 Optimization of conditions for formation of styryl pyrazolesa
Recently, pyrazoles have been synthesized from imine
hydrazine precursors (I, II) by cyclization using metal catalyst
and oxidants or base13 and from addition of hydrazones by a-
bromo ketones using light irradiation.14
Among 1,3,5-trisubstituted pyrazoles, the synthesis of 1-aryl-5-
phenyl-3-styryl-1H-pyrazoles require pre-installed pyrazolines (III)
as a substrate15 for further oxidation to pyrazoles (Scheme 1). To
date, we could not come across any report in our thorough
literature search for the direct synthesis of 1-aryl-5-phenyl-3-
styryl-1H-pyrazoles (IV) in one step. The electrocyclization of
dibenzylideneacetones with hydrazines leads to the synthesis of
pyrazolines (III) in the presence of a catalyst (Scheme 1).16 Metal-
acetylacetonates [M(acac)2] and metal-dibenzylideneacetones
[M2(dba)3 or M(dba)2] are very powerful reagents in organic
synthesis and catalysis. However, these metal complexes have not
been used till date as a partner substrate for the construction of
pyrazoles. As envisioned, herein, we disclose a general method
for N-heterocyclization of different arylhydrazines with metal-
diketonic complexes to access 1,3,5-trisubstituted pyrazoles,
namely, 1-aryl-5-phenyl-3-styryl-1H-pyrazoles (IV), 3,5-dimethyl-N-
aryl-1H-pyrazoles (V), 3,5-dimethyl-N-sulfonyl aryl-1H-pyrazoles
(VI) and 1,3-diphenyl-5-styryl-4,5-dihydro-1H-pyrazole (III), under
neutral conditions using microwave irradiations (Scheme 1).
Yieldb [%]
Entry
Solvent
MW (watts)
A
B
1
2
3
4
5
6
7
8
9c
H2O
DMSO
DMF
MeOH
PEG-200
CHCl3
THF
Toluene
H2O
50
50
50
50
50
50
50
50
50
30
80
0
20
5
15
20
10
5
25
5
10
10
8
0
6
0
89
a
Reaction conditions: phenyl hydrazine hydrochloride (1.0 mmol),
Pd2(dba)3 (0.5 equiv.), solvent (1 mL), MW (watts), 100ꢀC, for 5 min.
Isolated yields. c Reaction with phenyl hydrazine (no HCl salt).
b
To obtain the dihydropyrazole product, reaction of Pd2(dba)3
was carried out with various substituted phenylhydrazines in
H2O. The reaction of triuoromethoxy, nitrile and halides (F, Cl,
Br) substituted phenyl hydrazines afforded the corresponding
dihydropyrazoles in good yields (Table 2, 2l–2s). Also, phenyl-
hydrazine gave the desired product in high yield (Table 2, 2t).
Following this, we thought to explore the scope of the current
2. Results and discussion
To investigate the optimized conditions for the synthesis of
styryl substituted pyrazoles (A), we choose phenyl hydrazine
hydrochloride as a model substrate. The reaction of model
substrate with Pd2(dba)3 was performed in different solvents
ꢀ
under microwave irradiation at 100 C and 50 watt for 5 min
Table 2 Synthesis of pyrazoles and dihydropyrazolesabcd
(Table 1). Reaction with phenylhydrazine hydrochloride in H2O
gave both pyrazole as well as dihydropyrazole in approximately
equal amounts (Table 1, entry 1). However, interestingly, in the
case of phenyl hydrazine substrate (without hydrochloride salt),
the reaction gave styryl-substituted dihydropyrazole (B) as the
major product (Table 1, entry 9). DMSO afforded the desired
styryl-substituted pyrazole in high yield (Table 1, entry 2). In
case of DMF, the reaction did not give pyrazole (A) product, but
only 10% of dihydropyrazole (B) was observed (Table 1, entry 3).
Reaction in CHCl3 and toluene selectively provided the pyr-
azole (A) product. However, very less conversion was observed
(Table 1, entries 6 and 8). Other solvents such as MeOH, PEG-
200 and THF also did not provide promising yields and selec-
tivity of the desired pyrazole (A) product (Table 1, entries 4, 5
and 7).
Thereaer, we investigated the scope for an important
nding in the present report, i.e. direct synthesis of 1-aryl-5-
phenyl-3-styryl-1H-pyrazoles from the reaction of phenyl
hydrazine hydrochlorides (Table 2). The reaction of tri-
uoromethoxy, nitrile, methoxy and triuoro methyl-
substituted hydrazines afforded 1-aryl-5-phenyl-3-styryl-1H-pyr-
azoles in good yields (Table 2, 2a–2d) with Pd2(dba)3 using
DMSO as a solvent instead of H2O. Halogenated (Cl, F, Br)
phenylhydrazines also gave the desired product in high yields
(Table 2, 2e–2j). The reaction of phenylhydrazine hydrochloride
proceeded well under optimised conditions (Table 2, 2k).
a
Reaction conditions: hydrazine (1.0 mmol), Pd(dba)3 (0.5 equiv.), MW
(50 watts), 100 ꢀC, for 5 min. b Isolated yields. c DMSO (1 mL) was used
as solvent for synthesis of pyrazoles (5a–5k). d H2O (1 mL) was used as
e
solvent for synthesis of dihydropyrazoles (5l–5t).
parenthesis are with Pd(dba)2 (0.5 equiv.).
Yields in
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Scheme 2 Formation of pyrazole and/or other products (azobenzene and biphenyl) using phenylhydrazine and M(acac)2 in DMSO.
methodology for other metal complexes that could be used as the amount drastically, the yield of the product greatly reduced
coupling partners. Initially, the reaction of phenyl hydrazine (Table 3, entries 14 and 15). The increase in microwave (MW)
with Cu(acac)2 in DMSO was performed to optimize the condi- power did not inuence the yields per time of the present
tions under microwave irradiation (Scheme 2).
reaction (Table 3, entries 17 and 18).
To extend the scope of various substituted pyrazoles, we
The present reaction was explored for the synthesis of
screened different solvents with the Cu(acac)2 on model various 1,3,5-trisubstituted pyrazoles. Different types of func-
substrates (Table 3, entries 1–8) and among them, H2O (96%), tional groups were tolerated under the present reaction condi-
DMSO (89%) and THF (90%) provided the desired 3,5-dimethyl- tions. The reaction of phenyl hydrazine gave the desired
1-phenyl-1H-pyrazole (C) in high yields. In case of DMF and pyrazole in 96% yield (Table 4, 3a). Halogen bearing phenyl
toluene, azobenzene (D) was observed as the major (>90%) hydrazines proceeded well and afforded the corresponding
product (Table 3, entries 3 and 8). Undoubtedly, an ideal solvent 1,3,5-trisubstituted pyrazoles in high yields (Table 4, 3b–3j).
H2O was selected for further study. Furthermore, the reaction Nitrile, nitro, methoxy, methyl and methylenedioxy accommo-
with different metal (Cu, Co, Pd, Ni, Cr, Mn)-diketones were also dated phenyl hydrazines also gave the corresponding pyrazoles
explored; the results showed the formation of the desired pyr- in excellent yields (Table 4, 3k–3p). The labile ester group
azole in good to excellent yields (63–96%). To our delight, remained intact in the nal product during the reaction (Table
Cu(acac)2 showed the best results (Table 3, entries 1 and 9–13).
The required minimum amount of Cu(acac)2 for the reaction
was also optimized (Table 3, entries 1 and 14–16). On
Table 4 Synthesis of 1,3,5-trisubstituted pyrazolesab
decreasing the amount to 0.5 equiv., yield of the product was
not affected (Table 3, entry 17). However, on further decreasing
Table 3 Optimization of conditions for 3,5-dimethyl substituted
pyrazolea
Entry
M(acac)2 (equiv.)
Solvent
MW (watts)
Yieldb [%]
1
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Cu(acac)2 (1)
Co(acac)2 (1)
Pd(acac)2 (1)
Ni(acac)2 (1)
Cr(acac)2 (1)
Mn(acac)2 (1)
Cu(acac)2 (0.05)
Cu(acac)2 (0.25)
Cu(acac)2 (0.5)
Cu(acac)2 (0.05)
Cu(acac)2 (1)
H2O
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
100
100
96
86
0
35
63
52
90
6
89
88
72
65
63
9
45
96
95
96
2
DMSO
DMF
MeOH
PEG-200
CHCl3
THF
Toluene
H2O
H2O
H2O
H2O
H2O
H2O
3c
4
5
6
7
8d
9
10
11
12
13
14
15
16
17
18
H2O
H2O
H2O
H2O
a
Reaction conditions: phenyl hydrazine (1.0 mmol), M(acac)2 (equiv.),
b
solvent (1 mL), MW (watts), 100 ꢀC, for 5 min. Isolated yields.
c
a
Azobenzene (40%) and biphenyl (60%) were formed as major
Reaction conditions: hydrazine (1.0 mmol), Cu(acac)2 (0.5 equiv.), H2O
(1 mL), MW (50 watts), 100 ꢀC, for 5 min. b Isolated yields.
products. d Azobenzene was formed as major product (96%).
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Table 5 Synthesis of 3,5-dimethyl-N-sulfonyl aryl-1H-pyrazolesab
3. Conclusions
In conclusion, we have developed a new method for direct N-
heterocyclization of hydrazines with metal-diketones for the
synthesis of various trisubstituted pyrazoles under microwave
irradiation offering excellent yields. The synthesis of 1-aryl-5-
phenyl-3-styryl-1H-pyrazoles was achieved in a single step,
which is the most important nding in the present method. In
addition to the various substituted phenyl hydrazines, this
method was also applicable to various sulfonyl hydrazines,
which are very important functional moieties in drug discovery.
To ascribe the late stage modication importance of the present
methodology, pyrazole analogue of sildenal was also prepared.
Bringing N-heterocyclic moieties, pyrazoles, in the nal struc-
ture in a single step, the present method could have great
importance in medicinal chemistry or drug discovery.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
a
Reaction conditions: sulfonylhydrazine (1.0 mmol), Cu(acac)2 (0.5
equiv.), H2O (1 mL), MW (50 watts), 100 ꢀC, for 5 min. b Isolated yields.
The funding support from CSIR-India funded project HCP0008
and BSC0108 is gratefully acknowledged. SG thanks UGC for
award of Senior Research Fellowship, PKV is thankful to DST-
SERB for the Fast-track Young Scientist Grant. SDS thanks
CSIR for the award of Raman Research Fellowship. IIIM
communication No. IIIM/2148/2018.
Notes and references
Fig.
1 Direct application of method in preparation of pyrazole
1 (a) C. E. Mowbray, C. Burt, R. Corbau, S. Gayton, M. Hawes,
M. Perros, I. Tran, D. A. Price, F. J. Quinton, M. D. Selby,
P. A. Stupple, R. Webster and A. Wood, Bioorg. Med. Chem.
Lett., 2009, 19, 5857; (b) P. G. Wyatt, A. J. Woodhead,
V. Berdini, J. Boulstridge, M. G. Carr, D. M. Cross,
D. J. Davis, L. A. Devine, T. R. Early, R. E. Feltell,
E. J. Lewis, R. L. MsMenamin, E. F. Navarro, M. A. O'Brien,
M. O'Reilly, M. Reule, G. Saxty, L. A. Seavers, D. M. Smith,
M. Squires, G. Trewartha, M. T. Walker and
A. J. A. Woolford, J. Med. Chem., 2008, 51, 4986; (c)
P. Wickens, H. Kluender, J. Dixon, C. Brennan, F. Achebe,
A. Bacchiocchi, D. Bankston, D. Bierer, M. Brands,
D. Braun, M. S. Brown, C. Y. Chuang, J. Dumas, I. Enyedy,
G. Holena, Z. Hong, T. Housley, B. Jones, U. Khire,
C. Kreiman, E. Kumarasinghe, T. Lowinger, R. Ott-Morgan,
L. Perkins, B. Phillips, R. Schoenleber, W. J. Scott,
R. Sheeler, A. Redman, X. Sun, I. Taylor, L. Wang,
S. Wilhelm, X. Zhang, M. Zhang, E. Sullivan, C. Carter,
M. Miglarese and J. Levy, Bioorg. Med. Chem. Lett., 2007,
17, 4378; (d) T. de Paulis, K. Hemstapat, Y. Chen, Y. Zhang,
S. Saleh, D. Alagille, R. M. Baldwin, G. D. Tamagnan and
P. J. Conn, J. Med. Chem., 2006, 49, 3332; (e) A. A. Bekhit
and T. Abdel-Aziem, Bioorg. Med. Chem., 2004, 12, 1935; (f)
A. Tanitame, Y. Oyamada, K. Ofuji, M. Fujimoto, K. Suzuki,
T. Ueda, H. Terauchi, M. Kawasaki, K. Nagai, M. Wachi
analogue of sildenafil.
4, 3q). The reaction of hydrazine having the heterocyclic ring
system, i.e., 2-hydrazinopyridine, afforded the corresponding
pyrazole product in high yield (Table 4, 3r).
Next, with the thought of further expanding the scope of the
reaction, we moved our attention towards applying the meth-
odology on sulfonyl hydrazines. The reaction with various
substituted aryl sulfonylhydrazines such as methyl, methoxyl,
halides, triuoromethyl, triuoromethoxyl, nitrile, and naph-
thalene substituted sulfonyl hydrazines gave the corresponding
arylsulfonyl pyrazoles in excellent yields (Table 5, 5a–5m).
As an extension of the present method, a typical example of
alkyl-hydrazine, i.e., phenethylhydrazine hydrochloride, was
reacted under the optimized conditions, in which the desired
product 3,5-dimethyl-1-phenethyl-1H-pyrazole (see ESI†) was
obtained in trace amount.
The present protocol was applied in some complex molecules
to elaborate the commercial importance in late stage modica-
tions. In continuation to our ongoing project for the synthesis of
selective PDE5 inhibitors,17 the pyrazole-bearing analogue with
different heterocyclic moiety in the native structure of sildenal
(Fig. 1) was prepared only to show the utility of method in late
stage modications of important drug scaffolds.
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and J. I. Yamagishi, Bioorg. Med. Chem., 2004, 12, 5515; (g)
RSC Advances
J. A. S. Cavaleiro and J. Elguero, Eur. J. Org. Chem., 2004,
117, 4348; (c) S. T. Heller and S. R. Natarajan, Org. Lett.,
2006, 8, 2675; (d) E. Vickerstaffe, B. H. Warrington,
M. Ladlow and S. V. J. Ley, Comb. Chem., 2004, 6, 332; (e)
S. K. Singh, M. Srinivasa Reddy, S. Shivaramakrishna,
D. Kavitha, R. Vasudev, J. M. Babu, A. Sivalakshmidevi and
Y. Rao, Tetrahedron Lett., 2004, 45, 7679; (f) V. Polshettiwar
and R. S. Varma, Tetrahedron, 2010, 66, 1091; (g)
A. DeAngelis, D. H. Wang and S. L. Buchwald, Angew.
Chem., Int. Ed., 2013, 52, 3434; (h) W. Jin, H. F. Yu and
Z. K. Yu, Tetrahedron Lett., 2011, 52, 5884.
K. M. Kasiotis, E. N. Tzanetou and S. A. Haroutounian,
Front. Chem., 2014, 2, 78; (h) A. Balbi, M. Anzaldi,
C. Maccio, C. Aiello, M. Mazzei, R. Gangemi, P. Castagnola,
M. Miele, C. Rosano and M. Viale, Eur. J. Med. Chem., 2011,
46, 5293; (i) M. F. Khan, M. M. Alam, G. Verma, W. Akhtar,
M. Akhter and M. Shaquiquzzaman, Eur. J. Med. Chem.,
2016, 120, 170.
2 (a) F. Giornal, S. Pazenok, L. Rodefeld, N. Lui, J. P. Vors and
F. R. Leroux, J. Fluorine Chem., 2013, 152, 2; (b) J. Jaunzems
and M. Braun, Org. Process Res. Dev., 2014, 18, 1055; (c)
P. Lei, X. Zhang, Y. Xu, G. Xu, X. Liu, X. Yang, X. Zhang 11 (a) M. Zolgol, D. Azarifar and B. Maleki, Tetrahedron Lett.,
and Y. Ling, Chem. Cent. J., 2016, 10, 40.
2004, 45, 2181; (b) L. Chai, Y. Zhao, Q. Sheng and
Z. Q. Liu, Tetrahedron Lett., 2006, 47, 9283; (c) G. Su,
W. T. Wu, J. T. Wang and L. M. Wu, Chin. Chem. Lett.,
2008, 19, 1013; (d) N. Nakamichi, Y. Kawashita and
M. Hayashi, Org. Lett., 2002, 4, 3955; (e) Y. Kawashita and
M. Hayashi, Molecules, 2009, 14, 3073; (f) G. S. Ananthnag,
A. Adhikari and M. S. Balakrishna, Catal. Commun., 2014,
43, 240.
3 (a) M. A. Halcrow, Dalton Trans., 2009, 2059; (b) J. Perez and
L. Riera, Eur. J. Inorg. Chem., 2009, 2009, 4913; (c)
I. R. Fernando, S. Jianrattanasawat, N. Daskalakis,
K. D. Demadis and G. Mezei, CrystEngComm, 2012, 14, 908;
(d) M. Ishida, H. Fujimoto, T. Morimoto, S. Mori,
M. Toganoh, S. Shimizu and H. Furuta, Supramol. Chem.,
2017, 29, 8.
4 (a) V. Mukundam, A. Kumar, K. Dhanunjayarao, A. Ravi, 12 (a) T. H. Zhang and W. L. Bao, J. Org. Chem., 2013, 78, 1317;
S. Peruncheralathan and K. Venkatasubbaiah, Polym.
Chem., 2015, 6, 7764; (b) S. Carlotto, M. Casarin, A. Lanza,
F. Nestola, L. Pandolfo, C. Pettinari and R. Scatena, Cryst.
Growth Des., 2015, 15, 5910.
5 (a) M. Viciano-Chumillas, S. Tanase, L. Jos de Jongh and
J. Reedijk, Eur. J. Inorg. Chem., 2010, 2010, 3403; (b)
J. Olguin and S. Brooker, Coord. Chem. Rev., 2011, 255, 203.
6 (a) B. H. Pearce, H. F. Ogutu and R. C. Luckay, Eur. J. Inorg.
Chem., 2017, 1189; (b) F. Estevan, P. Hirva, A. Ofori,
M. Sanau, T. Spec and M. Ubeda, Inorg. Chem., 2016, 55,
(b) J. T. Hu, S. Chen, Y. H. Sun, J. Yang and Y. Rao, Org. Lett.,
2012, 14, 5030; (c) X. W. Li, L. He, H. J. Chen, W. Q. Wu and
H. F. Jiang, J. Org. Chem., 2013, 78, 3636; (d) G. W. Zhang,
Y. Zhao and H. B. Ge, Angew. Chem., Int. Ed., 2013, 52,
2559; (e) M. Zora and A. Kivrak, J. Org. Chem., 2011, 76,
9379; (f) P. Liu, Y. M. Pan, Y. L. Xu and H. S. Wang, Org.
Biomol. Chem., 2012, 10, 4696; (g) Z. L. Li, J. H. Liu,
Z. W. Huang, Y. Yang, C. G. Xia and F. W. Li, ACS Catal.,
2013, 3, 839; (h) P. Rai, M. Srivastava, J. Singh and J. Singh,
RSC Adv., 2014, 4, 779.
2101; (c) W. D. Bailey, L. Luconi, A. Rossin, D. Yakhvarov, 13 (a) J. Hu, S. Chen, Y. Sun, J. Yang and R. Yu, Org. Lett., 2012,
S. E. Flowers, W. Kaminsky, R. A. Kemp, G. Giambastiani
and K. I. Goldberg, Organometallics, 2015, 34, 3998.
7 V. Kumar, K. Kaur, G. K. Gupta and A. K. Sharma, Eur. J. Med.
Chem., 2013, 69, 735.
8 A. Ansari, A. Ali, M. Asif and Shamsuzzaman, New J. Chem.,
2017, 41, 16.
14, 5030; (b) T. Zhang and W. Bao, J. Org. Chem., 2013, 78,
1317; (c) X. Li, H. Li, H. Chen, W. Wu and H. Jiang, J. Org.
Chem., 2013, 78, 3636.
14 X. W. Fan, T. Lei, C. Zhou, Q. Y. Meng, B. Chen, C. H. Tung
and L. Z. Wu, J. Org. Chem., 2016, 81, 7127.
15 S. Naik and V. Desai, Green Sustainable Chem., 2013, 3, 1.
9 (a) M. Suri, T. Jousseaume, J. J. Neumann and F. Glorius, 16 (a) K. N. V. C. Lakshmi, M. Venkatesh, J. Hareesh, B. S. Raju
Green Chem., 2012, 14, 2193; (b) P. Prasanna, S. Perumal
and B. Anupama, Pharma Chem., 2016, 8, 122; (b)
Z. Daneshfar and A. Rostami, RSC Adv., 2015, 5, 104695; (c)
V. N. Pathak, R. Joshi, J. Sharma, N. Gupta and V. M. Rao,
Phosphorus, Sulfur Silicon, 2009, 184, 1854.
´
and J. C. Menendez, Green Chem., 2013, 15, 1292; (c)
Q. Wang, Z. Zhang, Z. Du, H. Hua and S. Chen, Green
Chem., 2013, 15, 1048; (d) F. Li, J. Nie, L. Sun, Y. Zheng
and J. A. Ma, Angew. Chem., Int. Ed., 2013, 52, 6255; (e) 17 (a) S. D. Sawant, G. L. Reddy, M. I. Dar, M. Srinivas, G. Gupta,
R. Harigae, K. Moriyama and H. Togo, J. Org. Chem., 2014,
79, 2049; (f) S. Dadiboyena and A. Nefzi, Eur. J. Med. Chem.,
P. K. Sahu, P. Mahajan, A. Nargotra, S. Singh, S. C. Sharma,
M. Tikoo, G. Singh, R. A. Vishwakarma and S. H. Syed,
Bioorg. Med. Chem., 2015, 23, 2121; (b) S. D. Sawant,
G. L. Reddy, M. Srinivas, S. S. Hussain, M. I. Dar,
A. Nargotra, P. Mahajan and R. A. Vishwakarma, WO 2015/
114647 A1, 2015.
´
´
2011, 46, 5258; (g) S. Fustero, M. Sanchez-Rosello, P. Barrio
´
and A. Simon-Fuentes, Chem. Rev., 2011, 111, 6984; (h)
J. L. Tang, L. Ming and X. M. Zhao, J. Heterocyclic Chem.,
2016, 53, 1367–1370.
10 (a) L. Knorr, Ber. Dtsch. Chem. Ges, 1883, 16, 2587; (b)
V. L. M. Silva, A. M. S. Silva, D. C. G. A. Pinto,
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