Metal free green protocol for the synthesis of bis-spiro piperidine and pyrimidine derivatives

Article abstract of DOI:10.1007/s11164-018-3310-7

Abstract: A highly efficient one-pot three-component synthesis of bis-spiro piperidine and pyrimidine derivatives has been reported by performing the reaction of formaldehyde, aromatic aniline and 1,3-dicarbonyl compounds. This reaction was carried out at room temperature in 2,2,2-trifluoroethanol (TFE) as a recyclable reaction medium under the metal free condition. The strong hydrogen donor ability and acidic property of TFE plays a key role in accelerating the rate of reaction and initiates the reaction smoothly. The advantageous features of this method are a mild reaction condition, no column chromatographic purification, and high yield of products and recyclability of TFE. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-018-3310-7

Res Chem Intermed
https://doi.org/10.1007/s11164-018-3310-7
Metal free green protocol for the synthesis of bis‑spiro
piperidine and pyrimidine derivatives
Audumbar Patil1 · Rajashri Salunkhe1
Received: 5 December 2017 / Accepted: 23 January 2018
© Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract A highly efcient one-pot three-component synthesis of bis-spiro piper-
idine and pyrimidine derivatives has been reported by performing the reaction of
formaldehyde, aromatic aniline and 1,3-dicarbonyl compounds. This reaction was
carried out at room temperature in 2,2,2-trifuoroethanol (TFE) as a recyclable reac-
tion medium under the metal free condition. The strong hydrogen donor ability and
acidic property of TFE plays a key role in accelerating the rate of reaction and ini-
tiates the reaction smoothly. The advantageous features of this method are a mild
reaction condition, no column chromatographic purifcation, and high yield of prod-
ucts and recyclability of TFE.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/
s11164-018-3310-7) contains supplementary material, which is available to authorized users.
*
Rajashri Salunkhe
rsschem1@gmail.com
1
Department of Chemistry, Shivaji University, Kolhapur 416004, India
1 3

A. Patil, R. Salunkhe
Graphical Abstract
R
R
O
N
O
N
O
O
N
O
O
R
O
O
O
NH2
R
O
O
H
H
Trifluroethanol
O
R
R
N
O
N
O
O
O
N
OO
O
R
Keywords 2,2,2-Trifuoroethanol · Bis-spiro piperidine · 1,3-Diaryl-
hexahydropyrimidine · Multicomponent reaction · Green synthesis · Reusability
Introduction
Recently fuorinated alcohols are widely used as a new class of novel solvents,
co-solvent as a medium for organic synthesis and various catalytic processes [1].
Fluorinated alcohols possess interesting physicochemical properties, such as high
hydrogen bonding donor ability, non-volatility, non-fammability, high polarity, high
ionizing power and low nucleophilicity [2–4]. In fuorinated alcohols particularly
TFE is gaining more interest in organic synthesis because the reactions carried out
in TFE are selective with easy isolation of product and recovery of TFE by distil-
lation [5]. Due to its strong hydrogen bonding ability and high acidic character of
TFE, it is advantageous to study bond cleavage and bond formation reaction in syn-
thesis [5–14]. The electron-withdrawing character of CF3 confers the high acidity to
the hydrogen of the hydroxyl group, and this is benefcial to carry out the reaction
1 3

Metal free green protocol for the synthesis of bis‑spiro…
in the absence of promoting agents, reactions that usually require the aid of Lewis
acids or catalysts.
In multicomponent reactions several bonds form in a single operation and are
attracting increasing attention as one of the most powerful emerging synthetic tools
for the creation of molecular diversity and complexity [15–19]. This has several
advantages over the classical step-by-step method. One of the important reactions in
the feld of multicomponent reactions is the condensation of anilines with 1,3-dicar-
bonyl compounds and formaldehyde without catalyst to the formation of 3,5-dispiro-
substituted piperidines and pyrimidine [20]. These scafolds are of remarkable inter-
est in recent years due to distinct pharmacological and therapeutic activities [21,
22]. Diferent N-substituted hexahydropyrimidines are synthetic intermediates for
spermidine-nitroimidazole drugs for the treatment of A549 lung carcinoma. Piperi-
dines and the pyrimidine nucleus found in a number of naturally occurring alkaloids
and synthetic compound have interesting biological and pharmacological properties
[23].
Compounds containing this scafold give antihypertensive [24], antimyco-bac-
terial [25], and anticonvulsant, anti-infammatory, antimalarial, antimicrobial and
anti-HIV activities [26–29]. Spiro compounds have cyclic structure, fused at the
central carbon and, due to their interesting conformational structures, they are found
in biologically active compounds Fig. 1a–e).
Only few reports on the synthesis of bis-spiro substituted piperidine and pyrimi-
dine are available in the literature, which includes use of FeCl3 in DCM [30],
In(OTf)3 in DCM [31], silica supported tungstic acid in DCM [32], silica supported
copper catalyst in DCM [33], acetic acid [34], p-TSA in DMSO [35], iron trifuoro-
acetate in aq. SDS [36], cerium supported chitosan in PEG-200 [37] and super par-
amagnetic iron oxide (Fe3O4) at 80 °C [38] and copper ferrite nanocatalysts [39].
Some of these catalysts are homogenous and difcult to separate out after reaction
completion. In all reported methods mostly hazardous and volatile solvents are used,
O
NH
S
N
NH
N
R
A
B
O
O
S
O
NH
NH
O
N
N
R
R
D
C
E
Fig. 1 Bioactive bis-spiro piperidine skeletons
1 3

A. Patil, R. Salunkhe
and they are highly harmful to the environment and also have long reaction times.
To minimize these drawbacks and to reduce the environmental impact from the use
of toxic solvents in organic synthesis, we have employed TFE as a green solvent as a
reaction medium. Recently, TFE has presented a great importance in organic synthe-
sis due to its green character, strong hydrogen bonding capacity and acidic nature.
To the best of our knowledge, there has been no report on the TFE as a reaction
medium as well as catalyst for the synthesis of bis-spiro piperidine and 1,3-diaryl-
hexahydro pyrimidine derivatives. We have reported efcient and practical synthesis
of bis-spiro derivatives by reacting aniline, formaldehyde and 1,3-dicarbonyl com-
pound by using TFE as reusable reaction medium at room temperature.
Experimental
General
The various substrates used in the present study were purchased from both Sigma-
Aldrich and Alfa Aesar and, used without any further purifcation. TLC was car-
ried out using silica gel G 60 F254 plates (Merck). The melting points of products
were measured in open capillary tubes and are uncorrected. 1H NMR, 13C NMR and
DEPT-135 spectra were recorded on a Brucker-Advance 300 and 75 MHz spectrom-
eter using TMS as an internal standard and CDCl3/DMSO-d6 as a solvent.
General procedure for the synthesis of bis‑spiro pyrimidine
In a reaction fask, was stirred a solution of formaldehyde (3 mmol) 1,3 dicarbonyl
compound (1 mmol) and aniline (2 mmol) in a 5 mL of TFE at room temperature
for the stipulated time given in Tables 4 and 5. The reaction progress was moni-
tored by thin layer chromatography (TLC). After the completion of a reaction, the
solid obtained was fltered, and the TFE was separated by distillation of fltrate. The
synthesized product was identifed by comparing the physical and spectral data (1H
NMR, 13C NMR, MS and IR) with those of the compounds reported in the literature.
General procedure for the synthesis of bis‑spiro piperidine
In a reaction fask, was stirred a solution of formaldehyde (3 mmol) 1,3 dicarbonyl
compound (2 mmol) and aniline (1 mmol) in a 5 mL of TFE at room temperature
for the stipulated time given in Tables 2 and 3. The reaction progress was monitored
by thin layer chromatography (TLC). After the completion of a reaction, the solid
obtained was fltered, and the TFE was separated by distillation. The synthesized
product was identifed by comparing the physical and spectral data (1H NMR, 13C
NMR, MS and IR) with those of the compounds reported in the literature.
1 3

Metal free green protocol for the synthesis of bis‑spiro…
Spectral data of representative compounds
(15‑(Phenyl)‑3,3,11,11‑tetramethyl‑15–azadispiro[5.1.5.3]hexa‑
decne‑1,5,9,13‑tetrone (4a) Yellow solid mp: 194–198 °C (lit. 195–198 °C) [ref.
37]; IR (KBr, vmax/cm−1): 2970, 1735, 1725, 1710, 1695, 1595, 1255, 1222, 1162
1
and 1078. H NMR (300 MHz, CDCl3 δ ppm): 1.06 (12H, s, CH3), 2.30 (2H, s,
CH2), 2.52 (4H, d, J = 13.5 Hz, COCH2), 2.83 (4H, d, COCH2), 3.69 (4H, s, NCH2),
7.00–7.31 (5H, m, ArH); 13C NMR (75 MHz, CDCl3, δ ppm): 28.12, 28.21,30.55,
32.38, 51.20, 65.73, 118.80, 121.60, 129.20, 151.90, 205.80; MS (m/z): 409 (M+).
(15‑(4‑Chlorophenyl)‑3,3,11,11‑tetramethyl‑15–azadispiro[5.1.5.3]hexa‑
decne‑1,5,9,13‑tetrone (4h) White solid mp: 216–218 °C (lit. 216–218 °C) [ref.
35]; IR (KBr, vmax/cm−1): 2966, 2920, 2865, 2830,1730, 1720,1705,1690,159
1
0,1461,1248,1159, 826, 675 and 520. H NMR (300 MHz, CDCl3, δ ppm): 1.08
(12H, s, CH3), 2.55 (2H, s, CH2), 2.70 (4H, d, J = 13.5 Hz, COCH2), 2.92 (4H, d,
J = 13.5 Hz, COCH2), 3.54 (4H, s, NCH2), 7.10 (2H, d, J = 8 Hz, ArH), 7.31(2H,
d, J = 8 Hz, ArH); 13C NMR (75 MHz, CDCl3, δ ppm): 28.2, 28.4, 30.7, 32.2, 51.2,
54.2, 65.4, 113.4, 120.4, 131.2, 150.4 and 205.6;. MS (m/z): 443(M+).
(15‑(4‑Nitro‑phenyl)‑3,3,11,11‑tetramethyl‑15–azadispiro[5.1.5.3]hexa‑
decne‑1,5,9,13‑tetrone (4g) Yellow solid mp: 222–226 °C (lit. 222–224 °C) [ref.
35]; IR (KBr, vmax/cm−1): 2956, 2928, 2870, 1730, 1722, 1595, 1498, 1328, 1280,
1
1222, 1112, 948, 826,753, 660 and 505; H NMR (300 MHz, DMSO-d6, δ ppm):
0.93 (12H, s, CH3), 2.60 (2H, s, CH2), 2.70 (4H, d, J = 13.5 Hz, COCH2), 2.92 (4H,
d, J = 13.5 Hz, COCH2), 3.78 (4H, s, NCH2), 7.20 (2H, d, J = 8.6 Hz,2H ArH),
8.01(2H, d, J = 8.6 Hz,2H ArH); 13C NMR (75 MHz, DMSO-d6, δ ppm): 28.1,
28.5, 31.2, 32.4, 49.5, 51.2, 65.9, 114.5, 125.9, 137.5, 154.8 and 205.9; MS (m/z):
454(M+).
1′‑phenyldispiro[indane‑1,3‑dione‑2,3′‑piperidine‑5′,2″‑indane‑1,3‑dione
(6a) brown solid mp: 256–258 °C (lit. 257–258 °C) [ref. 38]; IR (KBr, vmax/cm−1):
2960, 2870, 1726, 1708, 1669 and 1339; 1H NMR (300 MHz, CDCl3, δ ppm): 2.56
(2H, s, CH2), 3.4 (4H, s, CH2–N–CH2), 6.90–7.10 (5H, m), 7.57–7.86 (8H, m); 13
C
NMR (75 MHz, CDCl3, δ ppm): 19.6, 53.5, 65.4, 114.4, 119.6, 128.7, 129.7, 133.1,
141.1, 149.6 and 202.8; MS (m/z): 421 (M+).
1′‑(4‑methoxyphenyl)dispiro[indane‑1,3‑dione‑2,3′‑piperidine‑5′,2″‑indane‑1,
3‑dione (6b) brown solid mp: 258–260 °C (lit. 259–260 °C) [ref. 38]; IR (KBr,
1
vmax/cm−1): 3010, 2942, 1778, 1705, 1558 and 1360; H NMR (300 MHz, CDCl3,
δ ppm): 2.70 (2H, s, CH2), 3.6 (4H, s, CH2–N–CH2), 4.3(3H, s, OCH3), 6.86 (2H,
d, J = 7.2 Hz), 6.96 (2H, d, J = 7.2 Hz), 7.52–7.97 (8H, m); 13C NMR (75 MHz,
CDCl3, δ ppm):20.8, 53.5, 58.9, 118.3, 118.9, 125.8, 126.2, 128.4, 131.8, 132.8,
134.1, 134.9, 142.9, 148.1, 152.1 and 204.4; MS (m/z): 452 (M+).
1 3

A. Patil, R. Salunkhe
2‑(2,4‑Di‑phenyl‑2,4‑diazaspiro‑6‑yl)‑indane‑1,3‑dione (7a) White solid mp:
122 °C (lit. 122–124 °C) [ref. 31]; IR (KBr, vmax/cm−1): 3120, 2960, 2890, 1708,
1589, 1450, 1440, 1373, 1256,1228,1024, 928 and 760; 1H NMR (300 MHz, CDCl3,
δ ppm): 3.65 (4H, m, CH2), 5.01 (2H, s), 6.70–7.08 (10H, m), 7.60–7.78 (4H, m);
13C NMR (75 MHz, CDCl3, δ ppm): 56.7, 76.2, 80.4, 114.9, 118.3, 128.9, 129.7,
141.2 and 194.4; MS (m/z): 368 (M+).
2,4‑di‑p‑Tolyl‑2,4‑diazaspiro[5.5]undecan‑7‑one (9c) White solid mp: 122–
124 °C (lit. 124–126 °C) [ref. 32]; IR (KBr, vmax/cm−1): 3110, 2940, 1718, 1556,
1
1360, 1440, 1260,1220 and 820; H NMR (300 MHz, CDCl3, δ ppm): 1.58–1.60
(4H, m, CH2), 2.95 (4H, t, J = 7.5 Hz CH2), 2.48 (6H, s, CH3), 2.50 (2H, s,
CH2), 3.38 (2H, s, CH2), 3.56 (2H, s, CH2), 6.93 (4H, d, J = 7.2 Hz), 7.22 (4H, d,
J = 8.1 Hz); 13C NMR (75 MHz, CDCl3, δ ppm):22.4, 22.9, 26.4, 29.5, 33.4, 40.1,
48.5, 54.5, 70.4, 118.4, 129.7, 148.8 and 206.4; MS (m/z): 348 (M+).
2,4‑Bis‑(4‑chlorophenyl)‑2,4‑diazaspiro[5.5]undecan‑7‑one(9h) White
solid
mp: 158–160 °C (lit. 160–162 °C) [ref. 32]; IR (KBr, vmax/cm−1): 3112, 2910, 1715,
1
1580, 1360, 1240, 1223 and 840; H NMR (300 MHz, CDCl3, δ ppm): 1.55–1.80
(4H, m, CH2), 3.05 (4H, t, J = 7.2 Hz CH2), 4.3 (4H, s), 4.8 (2H, s), 7.02 (4H, d,
J = 7.2 Hz), 7.18 (4H, d, J = 8.2 Hz); 13C NMR (75 MHz, CDCl3, δ ppm):19.2,
26.4, 30.2, 38.4, 47.7, 52.3, 65.8, 121.2, 128.2, 129.3, 148.4 and 205.5; MS (m/z):
389 (M+).
Result and discussion
Initially to optimize the suitable reaction condition for the synthesis of 15-(4-nitro-
phenyl)-3,3,11,11-tetramethyl-15-azadispiro[5.1.5.3]hexadecane-1,5,9,13-tetrone,
we carried out the reaction of dimedone 1, formaldehyde 2, 4-nitroaniline 3,
(Scheme 1) as a model reaction in diferent solvents. The results of solvent study at
room temperature are displayed in Table 1.
NO2
NO2
O
O
O
Solvent
r.t.
O
N
O
3
2
+
+ 1
H
H
NH2
O
O
1
2
3
4a
Scheme 1 Catalyst free synthesis of bis-spiro substituted piperidine
1 3

Metal free green protocol for the synthesis of bis‑spiro…
Table 1 Optimization of
Entry
Solvent
Condition
Time (h)
Yield b(%)
one-pot reaction under various
solvents at room temperaturea
1
2
3
4
5
6
7
8
–
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
48
48
12
12
12
24
12
12
12
3
–
–
Water
Ethanol
Methanol
PEG-400
Acetonitrile
DCM
Chloroform
Toluene
Trifuoroethanol
Acetic acid
THF
53
55
50
44
36
40
38
92
80
42
56
9
10
11
12
13
10
20
12
DMSO
aReaction condition: 4-nitroaniline (1 mmol), formaldehyde
(3 mmol) and dimedone (2 mmol) in diferent solvents (5 mL) at
room temperature
bYield of isolated product
Initially the reaction was carried out without any solvent and catalyst at room
temperature, after 24 h there was no product formation. We have studied the efect
of diferent solvents on a reaction and observed that some of the solvents give lower
yields with long reaction time but surprisingly observed that TFE gives excellent
yield with high purity, short reaction time (entry 10) without use of any catalyst and
at room temperature. It is due to the electron-withdrawing character of CF3 which
confers the high acidity to the hydrogen of the hydroxyl group, a high ionization
constant and a very strong hydrogen bonding capability, which makes it is a superior
reaction medium without any catalyst (Scheme 2).
After the optimization of solvents, the scope and importance of this reaction
was explored for various substituted aromatic amines and 1, 3-dicarbonyl com-
pounds with diferent proportions. We have used 2 mmol of carbonyl compound
and 1 mmol of amine to give bis-spiro piperidine derivative, whereas 1 mmol
R
NH2
O
O
O
N
O
O
Trifluoroethanol
r.t. 3-3.5 h
2
3
+
+
H
H
R
3
O
O
1
2
4a-j
Scheme 2 Synthesis of bis-spiro piperidines by using optimized reaction conditions
1 3

A. Patil, R. Salunkhe
Table 2 Bis-spiro piperidines
Entry no.
Amines
Product
Time (h)
Yieldb (%)
derivativesa
1
2
3
4
5
6
7
8
9
4-H
4a
4b
4c
4d
4e
4f
4g
4h
4i
3
86
88
85
83
88
90
92
89
90
87
4-OCH3
4-CH3
3- CH3
2-NO2
3-NO2
4-NO2
4-Cl
3.5
3.5
3.5
3.5
3
3
3
3
3
4-F
4-Br
10
4j
aReaction condition: dimedone (2 mmol) formaldehyde (3 mmol)
and aniline (1 mmol) solvent (5 mL) Trifuoroethanol
bIsolated yield
R
NH2
O
Trifluoroethanol
r.t. 3-3.5 h
N
O
O
O
2
+
3
+
H
H
O
R
OO
2
3
5
6a-j
Scheme 3 Synthesis of bis-spiro piperidines
carbonyl compound and 2 mmol amine gives spiro pyrimidine derivatives. In
all amines, those substituted with electron-donating and electron-withdrawing
groups undergo the smooth reaction and gave excellent yield. The results are
summarised briefy in Table 2.
We have changed the dicarbonyl compound such as indane 1,3 dione in place
of dimedone and get a good result (Scheme 3) which is shown in Table 3.
Synthesis of spiro pyrimidine derivatives by reaction of Indane 1,3 dione and
cyclohexanone (1 mmol) aniline (2 mmol) and formaldehyde (3 mmol) under
optimised reaction conditions (Schemes 4, 5, Tables 4, 5).
Next, we have investigated the recyclability of TFE. After the completion of
a reaction as indicated by TLC, solid product obtained was fltered and the TFE
was separated by distillation of fltrate. The obtained TFE after distillation was
used for the next catalytic cycle, and it was observed that it could be reused for
fve cycles with slight decrease in yield of the product.
1 3

Metal free green protocol for the synthesis of bis‑spiro…
Table 3 Synthesis of bis-spiro
Entry no.
Amines
Product
Time (h)
Yieldb (%)
piperidines derivativesa
1
2
3
4
5
6
7
8
9
4-H
6a
6b
6c
6d
6e
6f
6g
6h
6i
3
85
88
84
82
86
88
92
86
90
87
4-OCH3
4-CH3
3-CH3
2-NO2
3-NO2
4-NO2
4-Cl
3.5
3.5
3.5
3.5
3
3
3
3
3
4-F
4-Br
10
6j
aReaction condition: Indane 1,3 dione (2 mmol) formaldehyde
(3 mmol) and aniline (1 mmol) solvent (5 mL) Trifuoroethanol
bIsolated yield
R
NH2
O
O
N
O
Trifluoroethanol
r.t. 3-3.5 h
+
2
3
+
H
H
N
O
R
3
O
R
2
5
7a-j
Scheme 4 Synthesis of spiro pyrimidine derivatives
R
O
NH2
O
O
N
N
Trifluoroethanol
r.t. 3-3.5 h
+
2
3
+
H
H
R
3
R
8
2
9a-j
Scheme 5 Synthesis of spiro pyrimidine derivatives
1 3

A. Patil, R. Salunkhe
Table 4 Synthesis of spiro
Entry no.
Amines
Product
Time (h)
Yieldb (%)
pyrimidine derivativesa
1
2
3
4
5
6
7
8
9
4-H
7a
7b
7c
7d
7e
7f
7g
7h
7i
3
82
86
83
81
84
87
92
87
89
85
4-OCH3
4-CH3
3-CH3
2-NO2
3-NO2
4-NO2
4-Cl
3.5
3.5
3.5
3.5
3
3
3
3
3
4-F
4-Br
10
7j
aReaction condition: Indane 1,3 dione (1 mmol) formaldehyde
(3 mmol) and aniline (2 mmol) solvent (5 mL) Trifuoroethanol
bIsolated yield
Table 5 Synthesis of spiro
Entry no.
Amines
Product
Time (h)
Yieldb (%)
pyrimidine derivativesa
1
2
3
4
5
6
7
8
9
4-H
9a
9b
9c
9d
9e
9f
9g
9h
9i
3
84
88
85
83
86
88
91
88
89
86
4-OCH3
4-CH3
3-CH3
2-NO2
3-NO2
4-NO2
4-Cl
3.5
3.5
3.5
3.5
3
3
3
3
3
4-F
4-Br
10
9j
aReaction condition: cyclohexanone (1 mmol) formaldehyde
(3 mmol) and aniline (2 mmol) solvent (5 mL) Trifuoroethanol
bIsolated yield
Reaction mechanism
The possible reaction mechanism of synthesis of bis-spiro compounds is outlined in
Scheme 6. Initially, when TFE reacts with dimedone 1 and forms enol 4, it undergoes
reaction with formaldehyde 2 through Knoevenagel condensation to form the α,β-
unsaturated carbonyl compound 5. The reaction mechanism proceeds through Kno-
evenagel condensation followed by Michael addition and Mannich reaction. Another
1 3

Metal free green protocol for the synthesis of bis‑spiro…
O
R
HO-CH2-CF3
O
..
OH
H-OCH2CF3
O
N
O
O
1
K
2
H
H
n
4
o
O
v
e
n
9
O
O
g
e
l
H
H
R
O
O
5
+
N O
O
..
O
O
Ph
..
OH
O
O
O
8
O
O
O
H
H
H
OCH2-CF3
H
..
6
NH2
H
N
O
+
H
H
R
3
R
7
Scheme 6 Plausible reaction mechanism for the synthesis of spiro piperidine derivative
molecule of dimedone, i.e., the enol form attacks as a nucleophile on α,β-unsaturated
carbonyl compound to produce intermediate 6. Simultaneously the condensation of
another molecule of formaldehyde reacts with aniline 3 to give imine intermediate 7.
Which in reaction with intermediate 6 produced adduct 8 through the Mannich reaction
followed by intramolecular cyclization providing bis-spiro piperidine derivative 9.
Conclusion
In summary we have developed a more efcient method for the synthesis of bis-
spiro piperidine and pyrimidine derivatives. This method is simple, having less reac-
tion time, excellent yield, and an economical and environmentally friendly benign
scafold at room temperature. The importance of this protocol is easy availability
of starting material, simple working procedure and mild reaction conditions. The
reusability of TFE as a reaction medium is an important advantage for a commercial
utility.
Acknowledgements We gratefully acknowledge the fnancial support from the Department of Science
and Technology and University Grants Commission, New Delhi, India.
1 3

A. Patil, R. Salunkhe
References
1. I.T. Horvath, P.T. Anastas, Chem. Rev. 107, 2167 (2007)
2. A. Dandia, R. Sigh, J. Joshi, S. Kumari, J. Fluor. Chem. 156, 238 (2013)
3. H. Alinezhad, M. Taibakhsh, M. Zare, J. Fluor. Chem. 132, 995 (2011)
4. M. Daryabhari, S. Khaksar, J. Mol. Liq. 198, 263 (2014)
5. S. Rostanmia, E. Doustkhah, Tetrahedron Lett. 55, 2508 (2014)
6. K. De, J. Legros, B. Crousse, D. Bonnet-Delpon, J. Org. Chem. 74, 6260 (2009)
7. S. Rashmi, N. Sandhya, B. Raghava, M. Kumara, K. Mantelingu, K. Rangappa, Synth. Commun.
43, 424 (2012)
8. E. Doustkhah, S. Rostamnia, A. Hassankhani, J. Porous Mater. 23, 549 (2016)
9. S. Rostamnia, E. Doustkhah, Synlett 26(10), 1345 (2015)
10. S. Khaksar, J. Fluor. Chem. 172, 51 (2015)
11. S. Rostamnia, E. Doustkhah, A. Nuri, J. Fluor. Chem. 153, 1 (2013)
12. S. Rostamnia, E. Doustkhah, K. Bahrami, S. Amini, J. Mol. Liq. 207, 334 (2015)
13. S. Rostamnia, A. Zabardasti, J. Fluor. Chem. 144, 69 (2012)
14. I. Shuklov, N. Durrovina, A. Borner, Synthesis 19, 2925 (2007)
15. R. Cioc, E. Ruitzer, R. Orru, Green Chem. 16, 2958 (2014)
16. X. Xin, Y. Wang, S. Kumar, X. Liu, Y. Lin, D. Dong, Org. Biomol. Chem. 8, 3078 (2010)
17. A. Jadhav, S. Balve, K. Lim, Y. Jeong, Tetrahedron 73, 2806 (2017)
18. R. Ghahremanzadeh, G. Shakibaei, S. Ahadi, A. Bazgir, J. Comb. Chem. 12, 191 (2010)
19. J. Li, N. Wu, Y. Tian, J. Zhang, S. Wu, A.C.S. Med, Chem. Lett. 4, 806 (2013)
20. N. Kozlov, A. Kadutskii, Tetrahedron Lett. 49, 3875 (2008)
21. L. Ye, Y. Tian, Z. Li, H. Jin, Z. Zhu, S. Wan, J. Zhang, P. Yu, J. Zhang, S. Wu, Eur. J. Med. Chem.
50, 370 (2012)
22. S. Padvi, Y. Tayde, Y. Wagh, D. Dalal, Chin. Chem. Lett. 2, 714 (2016)
23. J. Vieges, S. Bolzani, M. Furlan, J. Barreiro, C. Young, D. Tomazela, N. Eberlin, J. Nat. Prod. 67,
908 (2004)
24. H. Bin, M. Crider, A. Stables, Eur. J. Med. Chem. 36, 265 (2001)
25. R. Kumar, S. Perumal, P. Senthilkumar, P. Yogeeswari, D. Sriram, J. Med. Chem. 51, 5731 (2008)
26. M. Mishra, S. Pandey, V. Pandey, J. Pandey, R. Tripathi, R.P. Tripathi, Bioorg. Med. Chem. 17, 625
(2009)
27. R. Weis, K. Schweiger, J. Faist, E. Rajkovic, A. Kungl, W. Fabin, W. Schunack, W. Seebacher,
Bioorg. Med. Chem. 16, 10326 (2008)
28. S. Petit, J. Nallet, M. Guillard, J. Dreux, R. Chermat, M. Poncelet, C. Bulach, P. Simon, C. Fontaine,
M. Barthelmebs, Eur. J. Med. Chem. 26, 19 (1991)
29. Y. Zhou, V. Gregor, B. Ayida, G. Winters, Z. Sun, D. Murphy, G. Haley, D. Bailey, J. Froelich, S.
Fish, S. Webber, D. Wall, Bioorg. Med. Chem. Lett. 17, 1206 (2007)
30. C. Mukhopadhyay, S. Rana, R.J. Butcher, Tetrahedron Lett. 52, 4153 (2011)
31. A. Dandia, A. Jain, S. Sharma, Tetrahedron Lett. 53, 5270 (2012)
32. A.B. Atar, Y.T. Jeong, Tetrahedron Lett. 54, 1302 (2013)
33. S. Ray, S. Bhaumik, B. Banerjee, P. Manna, C. Mukhopadhyay, Monatsh. Chem. Chem. Mon. 146,
1881 (2015)
34. M. Mousavi, H. Gharari, M. Maghsoodiou, N. Hazeri, Res. Chem. Intermed. 42, 3875 (2016)
35. P. Chidurla, V. Jetti, J. Meshram, J. Heterocycl. Chem. 53, 389 (2016)
36. T. Lohar, S. Jadhav, A. Kumbhar, A. Mane, R. Salunkhe, Res. Chem. Intermed. 42, 5329 (2016)
37. N. Ahmed, Z. Siddiqui, A.C.S. Sustain, Chem. Eng. 3, 1701 (2015)
38. F. Janati, M. Heravi, A. Mirshokraie, J. Chem. 2013, 1 (2013)
39. A. Dandia, A. Jain, S. Sharma, RSC Adv. 3, 2924 (2013)
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