Polystyrene supported: N -phenylpiperazine-Cu(II) complex: An efficient and reusable catalyst for KA2-coupling reactions under solvent-free conditions

Article abstract of DOI:10.1039/c5nj03272e

A new polystyrene supported N-phenylpiperazine-Cu(ii) complex 4c was found to be an efficient, simple, versatile catalyst for the selective multicomponent reaction of terminal alkynes, ketones, and secondary amines to give the corresponding propargylamine

Full text of DOI:10.1039/c5nj03272e

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PAPER
Polystyrene supported N-phenylpiperazine-Cu(II) complex: An
efficient and reusable catalyst for KA2-coupling reaction under
solvent-free conditions
Received 00th January 20xx,
Accepted 00th January 20xx
Pullaiah C. Perumgani,a Srinivas Keesara,*b Saiprathima Parvathaneni,a and Mohan Rao
Mandapati*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new polystyrene supported N-phenylpiperazine-Cu(II) complex 4c was found to be an efficient,
simple, versatile catalyst for the selective multicomponent reaction of terminal alkynes, ketones, and
secondary amines to give the corresponding propargylamines. The coupled products were formed in
excellent yields at low catalyst loadings (0.2 mol % of metal) under solvent free conditions at 110 °C.
Further, this heterogeneous catalyst showed excellent recyclability without any significant loss in its
activity upto five times.
developed CuBr catalyzed KA2 coupling reaction of aliphatic ketones
in toluene at 100 °C.9
Introduction.
Propargylamines are highly versatile intermediates in organic
synthesis1 and key structural elements in natural products and drug
molecules.2 In addition they have found broad application as
synthetic precursors of various nitrogen-heterocycles, such as
pyrrolidines, pyrroles and oxazoles.3 Furthermore some propargylic
amine derivatives were found to possess interesting biological
properties.4 The most direct generally applicable protocol to access
propargylamines is the multi-component coupling (MCC) of an
aldehyde, amine and alkyne in one pot, three component synthesis
referred as A3 coupling.5 This method has been widely investigated
as it circumvents isolation of imine intermediate compared to
ketones in MCC reaction.6
In d-block elements only Cu transition metal is more active for
MCC reactions of ketones but Chan et al. reported copper free
AuBr3 and M. H. Savari with ZnO for KA2 coupling of ketones.10–11
Moreover the reported homogeneous conditions require 5-20 mol
% of metal catalyst for efficient coupling and the recovery of the
catalyst is impossible. Ramon et al. has reported the first recyclable
heterogeneous catalyst Cu(OH)x–Fe3O4 (0.1 mol % of catalyst used)
for MCC reaction of 3-pentanone with phenylacetylene and
piperidine with considerably low yields and prolonged reaction
times.12 To till date, very few heterogeneous copper systems have
been reported for KA2 coupling reactions.12–14 To achieve the eco-
friendly protocol for KA2 reaction the primary goal is to develop an
economical, more benign recyclable catalyst, efficient even with
low catalytic loadings. Therefore making the process more viable
compared to homogeneous conditions. Thus there is a wide scope
for improvement of heterogeneous copper catalysts (HCC) for this
KA2 coupling transformations.
The three-component coupling with ketone–amine–alkyne is
known as KA2 coupling reaction and the use of ketones remains as a
synthetic challenge owing to its low reactivity. Due to the difficulty
of incorporating ketones, very few methods have been reported for
the propargylamine formation from ketones. This KA2 coupling
remains as green synthetic challenge viz to enhance the reactivity of
the substrates, yields, lowering the reaction times and catalytic
loadings with broad substrate scope. In view of this C. H. Larsen and
co-workers employed (Ti(OEt)4) as lewis acid to enhance the activity
of ketones7c and also described neat KA2 coupling reaction of acyclic
and cyclic aliphatic ketones under solvent free conditions.7 Vander
Eycken reported microwave-assisted Cu(I)-catalyzed one-pot
coupling of a ketone, an alkyne, and a primary amine.8 S. Ma et. al
Fig. 1 Polymer supported copper and palladium complexes (4a and
4b).
a.Indian Institute of Chemical Technology, Hyderabad-500607, India
b.School of Chemistry, University of Hyderabad, Hyderabad-500046, India
E-mail: mandapati@iict.res.in, Tel.: +91-40-27193181; Fax: +91-40-27160921
drsrinivaskeesara@yahoo.com
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(A)
The most significant advantage of heterogeneous catalysts is
recyclability and easy separation.15 Several heterogeneous catalysts
have been synthesized and applied for multi-component A3
coupling reactions.16 Polystyrene is the most popular polymeric
support used in the synthesis of heterogeneous catalysts because of
its low cost, ready availability, chemical inertness and facile
functionalization. A variety of polystyrene supported metal catalytic
systems were reported in many organic transformations.17
Recently, we have reported polystyrene-supported N,N-
dimethylethylenediamine with Cu and Pd complexes (4a and 4b in
figure. 1) as catalysts for Sonogashira, Suzuki and A3 coupling
reactions.18
Herein, we report polymer supported N-phenylpiperazine-Cu(II)
complex 4c as an efficient and highly reusable heterogeneous
catalyst for the synthesis of propargylamines from KA2 coupling
reaction under solvent free conditions. To the best of our
knowledge, this is the first report on the application of polymer
supported heterogeneous catalyst 4c for KA2 coupling reactions to
generate propargylamines.
(B)
Results and discussion
The synthesis of polymer-supported N-phenylpiperazine Cu(II)
complex 4c is systematically represented in Scheme 1. N-
phenylpiperazine functionalized polystyrene resin 3 was formed by
heating
a mixture of chloromethylated polystyrene and N-
phenylpiperazine in CH3CN at 70 °C for 48 h. This polymer-
supported N-phenylpiperazine 3 is insoluble in common organic
solvents. Reaction of polymer-bound N-phenylpiperazine with EtOH
and CuBr2 in 1 : 1 molar ratio for 24 h at 70 °C resulted in covalent
attachment of copper to give functionalized polymer. This complex
formation was confirmed by FT-IR analysis. In the FT-IR spectrum of
polymer-bound N-phenylpiperazine, the absence of sharp C−Cl peak
(due to CH2Cl groups) at 1263 cm−1 of starting polymer indicates the
introduction of nitrogen ligand on the polymer. In addition, the
stretching vibration of the Cu–N bond peaks observed at 531 cm−1
corresponds to the formation of polystyrene-supported N-
phenylpiperazine Cu(II) complex.19
Fig. 2 SEM image of chloromethylated polystyrene (A) and N-
phenylpiperazine-Cu(II) complex 4c (B).
The scanning electron micrograph (SEM) images of the
chloromethylated polystyrene and polymer supported N-
phenylpiperazine Cu(II) complex 4c shows the morphological
changes. The change in the morphology of polystyrene surface
indicates the formation of desired complex Fig. 2 (A and B). Energy
dispersive X-ray spectroscopy (EDX) analysis data for the polymer
anchored ligand and copper catalyst are given in Fig. 3 (I & II). The
EDX spectrum clearly shows the presence of copper metal in the
polymer complex. Thermal stability of the complex was investigated
by TGA (Fig. 4). The complex is stable up to 372 °C and above this
temperature it decomposes. The negligible weight loss below 200
°C is due to the physically adsorbed solvent molecules. The amount
of copper incorporated into the polymer was also determined by
inductively coupled plasma (ICP), which showed the value of 6.93%
(1.09 mmol/g).
Cl
NaI
Ph
N
NH
Ph
N
N
+
CH3CN, 70 °C
1
2
3
CuBr2
EtOH, 70 °C
To begin our study, we examined the MCC reaction of ketones,
amines and alkynes in the presence of polymer supported Cu(II)
complex 4c under a variety of reaction conditions. In order to
establish the optimum conditions, we have chosen cyclohexanone,
piperidine and phenylacetylene as model substrates (Table 1). The
effect of different organic solvents on the catalytic activity of
complex 4c has been studied (entries 1−11). From the above tested
Ph
N
N
Cu
Br Br
4c
Scheme 1 Synthesis of polymer-supported N-phenylpiperazine-
Cu(II) complex 4c.
2 | J. Name., 2012, 00, 1-3
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Table 1 Effect of solvent on the KA2 coupling reactiona
COMMUNICATION
(I)
Entry
1
Solvent
DCM
Time (h)
6
Yield (%)b
28
2
3
DCE
Dioxane
6
6
40
48
4
Toluene
6
91
5
6
THF
CH3CN
6
6
72
60
(II)
7
8
9
10
11
12
13
DMF
DMSO
MeOH
EtOH
Water
_
12
12
12
12
12
6
31
42
15
33
Nr
94
64c
54d
Nre
_
10
14
15
_
_
12
12
aReaction conditions: cyclohexanone (1.0 mmol), phenylac-
etylene (1.0 mmol), piperidine (1.0 mmol), catalyst 4c (0.2
b
c
mol % of Cu). Isolated yield. Reaction temperature 80 °C.
dReaction temperature 70 °C. eWithout catalyst. Nr = no
reaction.
solvents toluene showed excellent yield (91%) of KA2 coupling
product 8a (entry 4). Polar aprotic solvents gave low to moderate
yields (entries 5−8). No reacꢀon or poor yields was observed in case
of polar protic solvents like MeOH, EtOH and water (entries 9−11).
From the results, polar aprotic solvents affect the reaction more
than polar protic solvents. Next, we conducted solvent free MCC
reaction, and the desired product was obtained in excellent yield
(94%) in 6 h at 110 °C (entry 12). Further reducing the reaction
temperature and catalyst loading led to a low yield of product and
longer reaction times (entries 13 and 14). The KA2 coupling was
efficient at 110 °C and the catalytic activity of heterogeneous
copper complex is better in solvent free conditions. As expected no
product was observed in the absence of catalyst (entry 15). F.
Alonso reported KA2 coupling product 8a (77% yield) with 0.5 mol %
of CuNPs/TiO2-catalyst in dichloromethane at 70 °C for 24 h.13 Here
we employed only 0.2 mol % of copper for efficient KA2 coupling
reaction under solvent free conditions at 110 °C.
Fig. 3 EDX analysis of polystyrene-supported N-phenylpiperazine
ligand 3 (I) and N-phenylpiperazine-Cu(II) complex 4c (II).
35.00
100.0
15.1%
30.00
80.0
236.9Cel
25.00
28.53uV
20.00
15.00
10.00
5.00
60.0
40.0
20.0
0.0
440.6Cel
18.73uV
68.6%
124.8Cel
12.28uV
With the optimization conditions in hand, we examined the KA2
coupling reaction of cyclohexanone with phenylacetylene and
different secondary amines (Table 2). Six membered cyclic
secondary amines piperidine 6a and morpholine 6b both was
converted into the corresponding products 8a and 8b in excellent
yields (entries 1 and 2). Diamine groups consisted piperazine 6c
produced 1,4-bis-propargylamine product 8c in 90% yield under the
0.00
100.0
200.0
300.0
Temp Cel
400.0
500.0
Fig.
4
Thermogravimetric analysis of polymer supported N-
phenylpiperazine-Cu(II) complex 4c.
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Table 2 Synthesis of propargylamines via KA2 coupling reactionsa
Table 3 Synthesis of propargylamines via KA2 coupling reactions
piperazinea
Entry
Amine
Product
N
Yield(%)b
94
Ref.
10
Ph
1
8a
N
H
6a
O
Ph
O
2
3
N
98
10
8b
N
H
6b
Ph
H
N
N
N
90c
-
8c
N
H
6c
Ph
Ph
Ph
Ph
N
N
N
-
-
N
92
95
4
5
8d
N
H
6d
Ph
Ph
Ph
8e
Ph
8f
N
N
N
N
H
6e
6
7
89
88
14a
N
H
6f
10
Ph
N
H
N
6g
8g
a Reaction conditions: cyclohexanone (1.0 mmol), phenylacetylene (1.0 mmol),
amine (1.0 mmol), catalyst 4c (0.2 mol % of Cu). b Isolated yield. c Cyclohexa-
none (2.0 mmol) and phenylacetylene (2.0 mmol) were used.
mmol Zn).[14a] However, in presence of our catalyst 4c afforded
excellent yields of the same products 9a, 9b and 9f (92%, 94% and
92%) respectively (entries 1,2 and 6).
same reaction conditions by adding 2 equivalents of cyclohexanone
and phenylacetylene (entry 3). 4-substituted phenyl and benzyl
groups containing piperazine secondary amines 6d and 6e gave
excellent yields (92 and 95%) of 8d and 8e (entries 4 and 5).
Encouraged by the above results, further we extended the
Propargylamine 8f formed in 89% yield from 5-membered cyclic scope of the MCC reaction to cyclohexanone and N-
secondary amine pyrrolidine 6f (entry 6). Secondary N-dibutylamine phenylpiperazine with various alkynes (Table 4). Electron
6g afforded the corresponding coupling product 8g in 88% yield withdrawing like p-CF3O and p-Br substituted phenylacetylenes 7b
(entry 7).
and 7c afforded 86% and 89% yields of the corresponding products
(8h and 8i entries 1 and 2). 3-ethynylthiophene 7d and but-3-yn-1-
ylbenzene 7e gave the coupled products 8j and 8k in moderate to
good yields (entries 3 and 4). Ethynylcyclopentane 7f coupled
propargylamine product 8l was obtained in 91% yield (entry 5). The
reaction also extended to aliphatic acyclic terminal alkynes such as
1-hexyne 7g, 1-heptyne 7h, 1-octyne 7i and 1-decyne 7j which gave
the corresponding products 8m–8p in excellent yields (entries 6–9).
All the new tetrasubstituted propargylamine products 8h–8p of N-
phenylpiperazine and cyclohexanone were obtained in excellent
yields.
Next we extended the scope of this catalyst 4c for KA2 coupling
reaction of cyclopentanone 5b with phenylacetylene and variety of
secondary amines under the above optimized conditions (Table 3).
This proved to be an efficient catalytic method for KA2 coupling
reaction of cyclopentanone. All the amines reacted with
cyclopentanone and phenylacetylene to produce tetrasubstituted
propargylamine products 9a–g in excellent yields (80–95%, entries
1–7). M. H. Sarvari recently reported cyclopentanone coupled
products 9a, 9b and 9f in 90–95% yield with excess nano copper(I)
oxide–zinc oxide heterogeneous catalyst (0.073 mmol Cu and 0.033
4 | J. Name., 2012, 00, 1-3
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Table 4 KA2 coupling reaction of cyclohexanone with phenylacetyle-
ne and amine.
Fig. 5 Recyclability of catalyst 4c for propargylamine synthesis.
Scheme 2 Proposed catalytic pathway for KA2 coupling.
five recycles loss of 8% was observed, which shows the average
amount of leaching of copper per cycle is about 1.6%.
On the basis of the above described experiments we propose a
reaction mechanism which involves complexation of copper with
alkyne 7a and enamine 9 (generated in situ from ketone 5a and
amine 6a).8 This results in the formation of intermediate 10 and
intramolecular transfer of the alkyne moiety produces
corresponding propargylamine 8a with the regeneration of the
copper catalyst (Scheme 2).
The reusability of the heterogeneous catalyst is very important
for economic point of view and in industrial applications. Therefore
we have studied the reusability of the polymer supported catalyst
for KA2 coupling reactions of phenylacetylene with piperidine and
cyclohexanone. After the completion of the reaction, the catalyst
was easily separated from the reaction mixture by simple filtration,
washing with acetonitrile and drying for further use. The activity of
solid catalyst was not decreased considerably even after 5 cycles.
Conclusions
We have developed a highly efficient polymer supported N-
To find out the degree of leaching of the copper from the phenylpiperazine-copper complex-catalyzed KA2 coupling of ketone,
alkyne and amine in 1 : 1 : 1 ratio under solvent free conditions.
This method is simple and generates diverse range of
propargylamines in good to excellent yields of various substituted
amines and terminal alkynes with cyclohexanone and
cyclopentanone. This catalyst is superior in secondary amine
polymer supported N-phenylpiperazine, the catalyst was separated
by filtration and the copper content of the filtrate was determined
by ICP. During the course of multi-component coupling reactions,
only 0.2% of copper was lost into solution after the first run. After
a
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participating solvent-free KA2 coupling reactions compared to the 1,4-bis(1-(phenylethynyl)cyclohexyl)piperazine (8c): pale yellow
1
earlier reports. Moreover, the catalyst can be reused for
a
solid, mp 199-201 °C. H NMR (400 MHz, CDCl3, TMS) δ 7.45-7.43
reasonable number of consecutive cycles without a noticeable loss (m, 4H), 7.30-7.27 (m, 6H), 2.81 (s, 7H), 2.09 (d, J = 12.35 Hz, 4H),
of its catalytic activity. These advantages make this protocol more 1.75-1.70 (m, 4H), 1.67-1.59 (m, 6H), 1.53-1.47 (m, 4H), 1.25-1.22
viable from the cost and environmental point of view.
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 131.7, 128.1, 127.6, 123.6,
90.2, 86.6, 58.8, 46.6, 35.5, 29.6, 25.6, 22.9; HRMS: exact mass
calculated for C32H39N2 [M + H]+ = 451.3113, found m/z 451.3107.
Experimental
1-phenyl-4-(1-(phenylethynyl)cyclohexyl)piperazine (8d): white
1
solid, mp 155-157 °C. H NMR (400 MHz, CDCl3, TMS) δ 7.44-7.43
General information
(m, 2H), 7.28-7.25 (m, 5H), 6.95 (d, J = 8.69 Hz, 2H), 6.85 (t, J = 7.17
Hz, 1H), 3.25 (m, 4H), 2.91 (m, 4H), 2.12 (d, J = 12.20 Hz, 2H), 1.77-
1.74 (m, 2H), 1.69-1.62 (m, 4H), 1.55 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 151.3, 131.7, 129.0, 128.1, 127.7, 123.4, 119.5, 115.8, 89.8,
86.5, 58.7, 49.5, 46.1, 35.7, 25.6, 22.8; HRMS: exact mass calculated
for C24H29N2 [M + H]+ = 345.2331, found m/z 345.2306.
All materials were commercial reagent grade. Chloromethylated
polystyrene (1% cross linked, 200-400 mesh with 1.0-1.3 mmol/g)
was a product of Alfa-acer. Alkyne, ketone and amine compounds
were obtained from Aldrich. CuBr2 was procured from Merck and
used without further purification. All solvents were dried and
distilled by standard methods. Purification of products was carried
out by column chromatography using commercial grade silica gel
(60-120 mesh) using mixture of ethyl acetate and hexane as eluting
agent. The 1H NMR and 13C NMR spectra were obtained as solutions
in CDCl3 and TMS as the internal standard. IR spectra were obtained
using KBr pallets. ESI-MS spectra were determined on a LCQ ion
trap mass spectrometer equipped with an ESI source.
1-benzyl-4-(1-(phenylethynyl)cyclohexyl)piperazine (8e): pale
1
yellow solid, mp 96-97 °C. H NMR (400 MHz, CDCl3, TMS) δ 7.44-
7.42 (m, 2H), 7.33-7.25 (m, 8H), 3.52 (s, 2H), 2.76 (m, 4H), 2.53 (m,
4H), 2.07 (m, 2H), 1.73-1.69 (m, 2H), 1.66-1.58 (m, 3H), 1.51-1.45
(m, 2H), 1.25 (m, 1H),; 13C NMR (100 MHz, CDCl3) δ 137.9, 131.7,
129.2, 128.0, 127.6, 126.9, 123.5, 90.2, 86.3, 63.0, 58.6, 53.6, 46.0,
35.7, 25.6, 22.8; HRMS: exact mass calculated for C25H31N2 [M + H]+
= 359.2487, found m/z 359.2467.
Preparation of polymer supported N-phenylpiperazine (3)
1-phenyl-4-(1-((4-(trifluoromethoxy)phenyl)ethynyl)cyclohe-
1
To a 250-mL round bottom flask containing CH3CN (50 mL),
equipped with magnetic stirrer bar is added with chloromethylated
polystyrene (1 g, 1.2 mmol/g of Cl) and N-phenylpiperazine (5
mmol) and NaI (0.1 mmol). The reaction mixture was stirred for 48
h at 70 °C and was subsequently filtered and washed thoroughly
with CH3CN, dried in oven at 80 °C for 24 h.
xyl)piperazine (8h): pale yellow solid, mp 142-145 °C. H NMR (400
MHz, CDCl3, TMS) δ 7.46 (d, J = 8.85 Hz, 2H), 7.28-7.24 (m, 2H), 7.14
(d, J = 7.93 Hz, 2H), 6.95 (d, J = 7.93 Hz, 2H), 6.85 (t, J = 7.32 Hz, 1H),
3.24 (t, J = 5.03 Hz, 4H), 2.89 (t, J = 5.03 Hz, 4H), 2.11 (m, 2H), 1.77-
1.75 (m, 2H), 1.65-1.54 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 151.2,
148.5, 133.1, 129.0, 122.2, 120.7, 119.6, 115.8, 90.9, 85.1, 58.7,
49.5, 46.1, 35.6, 25.6, 22.7; HRMS: exact mass calculated for
C25H28ON2F3 [M + H]+ = 429.2154, found m/z 429.2122.
Preparation of polystyrene-supported Cu complex (4c)
1-(1-((4-bromophenyl)ethynyl)cyclohexyl)-4-phenylpiperazine
(8i): Pale yellow solid, mp: 169-171 °C. 1H NMR (400 MHz, CDCl3,
TMS) δ 7.42 (d, J = 8.55 Hz, 2H), 7.30-7.24 (m, 4H), 6.95 (d, J = 7.82
Hz, 2H), 6.85 (d, J = 7.33 Hz, 1H), 3.24 (t, J = 5.13 Hz, 4H), 2.88 (t, J =
To the EtOH solution polystyrene-supported N-phenylpiperazine
ligand (1 g ), and a solution of CuBr2 (0.5 g) in EtOH (10 mL) were
added, and the resulting mixture was allowed to stir at 70 oC for 24
h. This mixture was filtered and washed thoroughly with EtOH (3 ×
30 mL) and finally dried in vacuum at 80 oC for 24 h (Scheme 1).
5.01 Hz, 4H), 2.11 (m, 2H), 1.77-1.74 (m, 2H), 1.63-1.53 (m, 6H); 13
C
NMR (100 MHz, CDCl3) δ 151.1, 133.1, 131.3, 122.3, 121.8, 119.5,
115.8, 91.1, 85.4, 58.7, 49.5, 46.1, 35.5, 25.5, 22.7; HRMS: exact
mass calculated for C24H28N2Br [M + H]+ = 423.1426, found m/z =
423.1410.
General experimental procedure for KA2 coupling reaction
To a mixture of cyclohexanone (1.0 mmol), amine (1.0 mmol) and
phenylacetylene (1.0 mmol), catalyst 4c (20 mg, 0.02 mmol of Cu)
and the solution was stirred at 110 °C for 6 h. After the completion
of reaction (as monitored by TLC), the solvent EtOAc (10 mL) was
added and the catalyst was separated out by filtration and the
polymer was washed with acetonitrile. The Organic layer was dried
over anhydrous Na2SO4 and concentrated in vacuum. Then the
crude mixture was purified by column chromatography
(EtOAc/hexane) to afford the pure product. All the products were
confirmed from 1H and 13C NMR and Mass spectral analysis.
1-phenyl-4-(1-(thiophen-3-ylethynyl)cyclohexyl)piperazine (8j):
white solid, mp 165-167 °C. H NMR (400 MHz, CDCl3, TMS) δ 7.39
1
(m, 1H), 7.28-7.22 (m, 3H), 7.10 (m, 1H), 6.95 (d, J = 7.82 Hz, 2H),
6.84 (t, J = 7.33 Hz, 1H), 3.24 (t, J = 5.13 Hz, 4H), 2.89 (t, J = 5.13 Hz,
4H), 2.10 (m, 2H), 1.77-1.72 (m, 2H), 1.65-1.55 (m, 6H); 13C NMR
(100 MHz, CDCl3) δ 151.2, 130.1, 129.0, 127.9, 125.0, 122.3, 119.5,
115.8, 89.3, 81.3, 58.7, 49.5, 46.1, 35.7, 25.6, 22.7; HRMS: exact
mass calculated for C22H27N2S [M + H]+ = 351.1895, found m/z =
351.1873.
New compounds characterization data
6 | J. Name., 2012, 00, 1-3
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COMMUNICATION
1-phenyl-4-(1-(4-phenylbut-1-yn-1-yl)cyclohexyl)piperazine
115.8, 86.5, 79.6, 58.4, 49.4, 46.0, 35.8, 31.7, 29.6, 29.2, 29.0, 28.8,
(8k): pale yellow solid, mp 78-79 °C. 1H NMR (400 MHz, CDCl3, TMS) 25.6, 22.8, 22.6, 18.6, 14.0; HRMS: exact mass calculated for
δ
7.29-7.23 (m, 5H), 7.21-7.18 (m, 2H), 6.94 (d, J = 7.82 Hz, 2H), C26H41N2 [M + H]+ = 381.3252, found m/z = 381.3270.
6.84 (t, J = 7.33 Hz, 1H), 3.19 (t, J = 5.13 Hz, 4H), 2.83 (t, J = 4.73 Hz,
2H), 2.74 (t, J = 5.13 Hz, 4H), 2.53 (t, J = 7.45 Hz, 2H), 1.93 (m, 2H),
1.66-1.61 (m, 3H), 1.56-1.37 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
151.2, 140.7, 129.0, 128.5, 128.2, 126.0, 119.4, 115.8, 85.4, 80.6,
58.2, 49.4, 45.8, 35.6, 35.5, 25.6, 22.7, 20.7; HRMS: exact mass
calculated for C26H33N2 [M + H]+ = 373.2644, found m/z = 373.2625.
1,4-bis(1-(phenylethynyl)cyclopentyl)piperazine (9c): white
solid, mp 210-212 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.43-7.41
(m, 4H), 7.30-7.26 (m, 6H), 2.79 (s, 8H), 2.13-2.10 (m, 4H), 1.91-1.87
(m, 4H), 1.82-1.72 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 131.7,
128.0, 127.5, 123.6, 91.1, 85.4, 66.7, 49.3, 39.6, 23.3; HRMS: exact
mass calculated for C30H35N2 [M + H]+ = 423.2764, found m/z =
1-(1-(cyclopentylethynyl)cyclohexyl)-4-phenylpiperazine (8l): 423.2764.
white solid, mp 114-116 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.25
(t, J = 8.31 Hz, 2H), 6.94 (d, J = 7.82 Hz, 2H), 6.83 (t, J = 7.33 Hz, 1H),
1-phenyl-4-(1-(phenylethynyl)cyclopentyl)piperazine
(9d):
white solid, mp 143-145 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.42-
7.41 (m, 2H), 7.29-7.24 (m, 5H), 6.95 (d, J = 7.93 Hz, 2H), 6.84 (d, J =
7.32 Hz, 1H), 3.25 (t, J = 5.03, Hz, 4H), 2.88 (t, J = 5.03 Hz, 4H), 2.18-
2.15 (m, 2H), 1.93-1.91 (m, 2H), 1.83-1.77 (m, 4H); 13C NMR (100
MHz, CDCl3) δ 151.2, 131.6, 129.0, 128.1, 127.6, 123.4, 119.5, 115.8,
90.5, 85.6, 66.8, 49.3, 49.1, 39.6, 23.3; HRMS: exact mass calculated
for C23H27N2 [M + H]+ = 331.2174, found m/z = 331.2151.
3.22 (t, J = 5.25 Hz, 4H), 2.79 (t, J = 5.13, Hz, 4H), 2.68-2.61 (m, 1H),
1.97 (m, 2H), 1.90-1.84 (m, 2H), 1.74-1.65 (m, 5H), 1.62-1.52 (m,
7H), 1.42 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 151.2, 129.0, 119.3,
115.7, 91.2, 79.1, 58.2, 49.4, 45.9, 35.8, 34.4, 30.2, 25.7, 24.8, 22.9;
HRMS: exact mass calculated for C23H33N2 [M + H]+ = 337.2644,
found m/z = 337.2622.
1-(1-(hex-1-yn-1-yl)cyclohexyl)-4-phenylpiperazine (8m): pale
yellow solid, mp 101-102 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.25
(t, J = 8.68 Hz, 2H), 6.94 (d, J = 7.94 Hz, 2H), 6.84 (t, J = 7.33 Hz, 1H),
3.22 (t, J = 5.13 Hz, 4H), 2.80 (t, J = 5.13, Hz, 4H), 2.22 (t, J = 7.09 Hz,
2H), 1.97 (d, J = 12.47 Hz, 2H), 1.70-1.67 (m, 2H), 1.59 (m, 3H), 1.52-
1.39 (m, 7H), 0.91 (t, J = 7.21 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
151.3, 129.0, 119.4, 115.8, 86.3, 79.6, 58.3, 49.4, 45.9, 35.8, 31.3,
25.7, 22.8, 21.9, 18.3, 13.6; HRMS: exact mass calculated for
C22H33N2 [M + H]+ = 325.2644, found m/z = 325.2621.
1-benzyl-4-(1-(phenylethynyl)cyclopentyl)piperazine
(9e):
yellow solid, mp 81-83 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.43-
7.41 (m, 2H), 7.33-7.22 (m, 8H), 3.52 (s, 2H), 2.74 (t, J = 4.83 Hz, 4H),
2.53 (m, 4H), 2.13-2.09 (m, 2H), 1.90-1.86 (m, 2H), 1.82-1.69 (m,
4H); 13C NMR (100 MHz, CDCl3) δ 137.8, 131.6, 129.2, 128.0, 127.6,
126.9, 123.5, 90.9, 85.4, 66.7, 63.0, 53.2, 49.0, 39.6, 23.3; HRMS:
exact mass calculated for C24H29N2 [M + H]+ = 345.2331, found m/z =
345.2309.
1-(1-(hept-1-yn-1-yl)cyclohexyl)-4-phenylpiperazine (8n): Pale
1
N,N-dibutyl-1-(phenylethynyl)cyclopentanamine (9g): yellow
liquid. 1H NMR (400 MHz, CDCl3, TMS) δ 7.40 (d, J = 7.93 Hz, 2H),
7.30-7.23 (m, 3H), 2.61 (t, J = 8.08 Hz, 4H), 2.08 (m, 2H), 1.85-1.76
(m, 6H), 1.53-1.47 (m, 4H), 1.34-1.25 (m, 4H), 0.92 (t, J = 7.32 Hz,
6H); 13C NMR (100 MHz, CDCl3) δ 131.5, 128.1, 127.4, 124.0, 93.6,
83.4, 67.7, 53.0, 40.5, 32.4, 23.1, 20.7, 14.1; HRMS: exact mass
calculated for C21H32N [M + H]+ = 298.2535, found m/z = 298.2511.
yellow solid, mp: 87-89 °C. H NMR (400 MHz, CDCl3, TMS) δ 7.25
(t, J = 8.39 Hz, 2H), 6.94 (d, J = 7.78 Hz, 2H), 6.83 (t, J = 7.32 Hz, 1H),
3.21 (t, J = 5.18 Hz, 4H), 2.80 (t, J = 5.18, Hz, 4H), 2.21 (t, J = 7.17 Hz,
2H), 1.97 (m, 2H), 1.70-1.67 (m, 3H), 1.62-1.57 (m, 3H), 1.54-1.48
(m, 2H), 1.44-1.40 (m, 2H), 1.39-1.35 (m, 2H), 1.34-1.28 (m, 2H),
0.89 (t, J = 7.17 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.3, 129.0,
119.4, 115.8, 86.4, 79.7, 58.3, 49.5, 46.0, 35.8, 31.0, 28.9, 25.7,
22.8, 22.1, 18.6, 14.0; HRMS: exact mass calculated for C23H35N2 [M
+ H]+ = 339.2800, found m/z = 339.2777.
Acknowledgements
1-(1-(oct-1-yn-1-yl)cyclohexyl)-4-phenylpiperazine (8o): yellow
solid, mp 82-84 °C. 1H NMR (400 MHz, CDCl3, TMS) δ 7.25 (t, J =
8.80 Hz, 2H), 6.94 (d, J = 7.82 Hz, 2H), 6.83 (t, J = 7.33 Hz, 1H), 3.21
(t, J = 5.13 Hz, 4H), 2.81 (t, J = 5.13, Hz, 4H), 2.21 (t, J = 7.09 Hz, 2H),
1.98 (d, J = 12.34 Hz, 2H), 1.70-1.67 (m, 2H), 1.59 (m, 3H), 1.58-1.36
(m, 7H), 1.33-1.28 (m, 4H), 0.88 (t, J = 6.96 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 151.3, 129.0, 119.4, 115.8, 86.4, 79.7, 58.3, 49.5,
46.0, 35.8, 31.2, 29.1, 28.5, 25.7, 22.8, 22.5, 18.6, 14.0; HRMS: exact
mass calculated for C24H37N2 [M + H]+ = 353.2957, found m/z =
353.29367.
PCP and KS acknowledge UGC, New Delhi, for providing for
their JRF and Dr. D. S. Kothari postdoctoral research
fellowship.
Notes and references
1
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0.88 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 151.3, 129.0, 119.4,
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DOI: 10.1039/C5NJ03272E
COMMUNICATION
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DOI: 10.1039/C5NJ03272E
Polystyrene supported N-phenylpiperazine-Cu(II) complex: An efficient
and reusable catalyst for KA2-coupling reaction under solvent-free
conditions
Pullaiah C. Perumgani,a Srinivas Keesara,*b Saiprathima Parvathaneni,a and Mohan Rao
Mandapati*a
Propargylamines were synthesized in excellent yields from cyclohexanone and pentanone
with variety of secondary amines and alkynes by employing new polystyrene supported N-
phenylpiperazine-Cu(II) complex 4c.
O
R2
N
R
R1
80-95% yield
Catalyst 4c
110 o
R1
R2
+
N
N
N
H
C
Cu
R
O
Br
Br
R2
N
R
Catalyst 4c
R1
75-98% yield