New quaternary phosphonium salt as multi-site phase-transfer catalyst for various alkylation reactions

Article abstract of DOI:10.1007/s11164-016-2600-1

The present work describes the C-alkylation reactions of fluorene and curcumin catalyzed by a new phosphonium salt, benzene-1,3,5-triyltris(methylene))tris(triphenylphosphonium)bromide, as a multi-site phase-transfer catalyst (MPTC). The catalytic efficie

Full text of DOI:10.1007/s11164-016-2600-1

Res Chem Intermed
DOI 10.1007/s11164-016-2600-1
New quaternary phosphonium salt as multi-site phase-
transfer catalyst for various alkylation reactions
1
1
•
Kottala Vijaya Ponmuthu
1
•
Duraimurugan Kumaraguru
1
•
Jesin Beneto Arockiam
Murugesan Sepperumal
•
Sadhasivam Velu
1
Siva Ayyanar
1
•
Received: 1 January 2016 / Accepted: 31 May 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract The present work describes the C-alkylation reactions of fluorene and curcumin
catalyzed by a new phosphonium salt, benzene-1,3,5-triyltris(methylene))tris(triph-
enylphosphonium)bromide, as a multi-site phase-transfer catalyst (MPTC). The catalytic
efficiencies were found to be quite effective for di- and tetra-alkylation reactions with very
excellent yields under mild base and low concentrations of the catalyst. The synthesized
MPTC 3 have privileged catalytic activity compared to commercially available single-site
phase-transfer catalysts.
Keywords Multi-site phase-transfer catalysts Á Homogeneous catalysis Á Fluorene Á
Curcumin Á Tetraalkylation
Introduction
In most of the bi-phasic organic reactions which involve two immiscible solvents,
the reactants are not colliding with each other, and therefore cannot react very well.
In these cases, the use of phase-transfer catalysts (PTC) is inevitable; PTC increases
the rate of reaction which facilitates the migration of a reactant from one phase into
another phase where the reaction occurs [1, 2]. Many types of single-site PTC, such
as quaternary ammonium [3], phosphonium salt [4], crown ether [5], cryptands [6],
etc., have been intensively investigated due to their availability and easy reaction
work-up. Idoux et al. [7] first reported the soluble and insoluble multi-site phase-
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2600-1)
contains supplementary material, which is available to authorized users.
&
Siva Ayyanar
drasiva@gmail.com; ptcsiva@yahoo.co.in
1
Department of Inorganic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai, Tamilnadu 625 021, India
123

K. V. Ponmuthu et al.
transfer catalysts (MPTCs) containing three active phosphonium sites per molecule.
Keiji Maruoka and co-workers reported phosphonium salts as chiral phase-transfer
catalysts for various organic transformations [8]. Yildirim et al. [9] reported the
synthesis of a-aminonitriles catalyzed by montmorillonite K10 in the presence of
dicationic phosphonium salt in water under an ultrasonic effect . Enders et al. [10]
reported chiral quaternary phosphonium salts as organocatalysts. The main
advantage of MPTCs is that ithey have the ability to transfer a number of anionic
?
-
species (M Y ) from aqueous phase to organic phase. In contrast, a single-site
quaternary onium phase-transfer catalyst can transfer only one molecule of anionic
?
-
species, i.e., M Y from the aqueous phase, per cycle. In recent years, MPTC-
catalyzed alkylation reactions have gained considerable attention in organic
synthesis [11–15]. When a reaction is carried out in the presence of PTC in a
biphasic system, one can attain faster reactions together with higher chemical yields.
In addition, this will eliminate the need for expensive solvents because PTC will
dissolve all the reactants in one phase. PTC can be constructively used in green
chemistry because the usage of water is maximized, thus reducing the need for
organic solvents. In view of the above facts, we planned to synthesize a novel
MPTC, (benzene1,3,5triyltris(methylene))tris(triphenylphosphonium) bromide 3
(
Scheme 1). In our study, the catalytic efficiency of new MPTC was first examined
by -alkylation reactions in fluorene derivatives (Scheme 2). Many researchers have
reported using various phase-transfer catalysts, but the reaction time has been more
Scheme 1 Synthesis of phosphonium containing MPTC catalyst
Scheme 2 C-alkylation of fluorene derivatives 4
1
23

New quaternary phosphonium salt as multi-site…
Scheme 3 C and O-tetra alkylation of curcumin 7
than 12 h [16–26]; however, in the presence of MPTC 3 we got more yield in less
time under mild basic conditions at room temperature (30 °C). Secondly, the
efficiency of MPTC 3 was examined by the alkylation reaction of curcumin. The
study of curcumin derivatives has already been exploited and it has been reported
that it has antimicrobial [27], anti-inflammatory [28, 29] and anticancer activity
[
30–35]. Many researchers have synthesized curcumin-based derivatives, but the
method development was extremely complicated. Hence, we concentrated on
developing a simple methodology for the synthesis of curcumin derivatives. Apart
from this, the synthesis was considered to be eco-friendly because NaOH was used
as a base and the reaction was carried our at room temperature (30 °C). In this work,
for the first time we report the C-and O-alkylation of curcumin 7 (Scheme 3)
simultaneously under a mild concentration of base and MPTC conditions with very
good yield.
Experimental
Materials
All the chemicals were directly used for the synthesis without further purification
unless otherwise stated. Mesitylene, N-bromosuccinimide, triphenylphosphine,
4
4
-methylbenzylbromide,
4-nitrobenzylbromide,
4-bromobenzylbromide,
-cyanobenzylbromide, benzylbromide, allylbromide, curcumin, fluorene, and
benzoylperoxide were purchased from Sigma-Aldrich. Sodium hydroxide pellets
were purchased from Merck India. 2-Nitro fluorene, 1-bromooctane and 1-bromo-
hexane were purchased from Alfa Aesar. Solvents used for chromatography and
crystallization were of technical grade.
Analysis and instruments
1
13
Bruker (300 MHz) instruments were used to record H NMR and C NMR spectra.
Chemical shifts (d) are reported in parts per million (ppm) relative to residual
solvent peaks or trimethylsilane, and coupling constants are reported in Hertz (Hz).
NMR solvents were obtained from Merck. The spectra were recorded at room
123

K. V. Ponmuthu et al.
temperature. The multiplicities were denoted s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet. Silica gel-G plates (Merck) were used for TLC analysis
with a mixture of pet.ether and ethyl acetate as an eluent. Column chromatography
was carried out in silica gel (60–120 mesh size) using pet.ether and ethyl acetate as
an eluent.
Synthesis of 1,3,5-tris(bromomethyl)benzene (2)
Mesitylene 1 (8.6 g, 71.5 mmol), NBS (38.2 g, 214.6 mmol) and benzoyl peroxide
(
5.19 g, 21.4 mmol) and CCl (100 ml) were taken in a 150-ml RB flask. The
4
reaction mixture was refluxed for about 6 h at 70 °C. After completion of the
reaction time, the imide was removed by filtration and the solvent in the filtrate was
evaporated to give the pale yellow solid of 1,3,5-tribromomesitylene. Yield: 96 %.
1
13
m.p. 86–87 °C; H NMR (300 MHz, CDCl ) d: 7.35 (s, 3H), 4.45 (s, 6H); C NMR
3
(
75 MHz, CDCl )d: 139.00, 129.55, 32.19.
3
Synthesis of phosphonium salt of 1,3,5-tris(bromomethyl)benzene (3)
Triphenylphosphine (2.20 g, 8.4 mmol) was added into a stirred solution of 1,3,5-
tris(bromomethyl)benzene 2 (1 g, 2.8 mmol) in DCM (50 ml) and the reaction
mixture was stirred at RT for about 5 h. The reaction mass was then distilled off
1
under reduced pressure to get a white solid with 95 % yield. H NMR (300 MHz,
DMSO) d: 7.85 (t, J = 7.5 Hz, 10H), 7.66–7.60 (m, 20H), 7.50–7.44 (m, 15H), 6.69
1
3
(
s, 3H), 4.87 (d, J = 14 Hz, 6H); C NMR (75 MHz, DMSO) d: 139.32, 137.95,
37.81, 134.54, 134.37, 122.46, 121.33, 31.55.
1
General procedure for C-alkylation of fluorene derivatives (Scheme 2)
To a stirred solution of fluorene derivatives 4 in DMSO, 25 % aq. NaOH solution
was added dropwise over a period of 10 min under nitrogen atmosphere. Then, the
catalyst 3 was added, followed by alkyl bromide 5 into the reaction mixture and the
reaction mass was stirred at room temperature. After the completion of the reaction
based on the TLC, the reaction mass was poured into water and extracted with ethyl
acetate washed with brine, dried over sodium sulfate and concentrated under
reduced pressure. The crude product was then purified by silica-gel column
chromatography, eluting with n-hexane.
Synthesis of 2-nitro-9,9-dioctyl-9H-fluorene (6a)
To a stirred solution of 2-nitrofluorene 4a (1 g, 4.7 mmol) in DMSO, 25 % aq.
sodium hydroxide solution added dropwise over a period of 10 min under nitrogen
gas purging, then the catalyst 3 (10 mol %) was added, followed by 1-bromooctane
5
a (1.82 g, 9.4 mmol), then the reaction mass was stirred at room temperature.
Reaction completion was confirmed by TLC, then extracted with ethyl acetate,
washed with water, dried over sodium sulfate and evaporated under reduced
1
pressure, to produce a pale yellow viscous liquid with 90 % yield. H NMR
1
23

New quaternary phosphonium salt as multi-site…
(
300 MHz, CDCl ) d 8.26 (d, J = 6 Hz, 1H), 8.21 (s, 1H), 7.79 (d, J = 6 Hz, 2H),
3
7
.41 (s, 3H), 2.02 (t, J = 6 Hz, 4H), 1.20 – 1.03 (m, 24H), 0.81 (t, J = 4.5 Hz, 6H);
C NMR (75 MHz, CDCl ) d: 152.33, 151.98, 147.67, 147.14, 138.74, 129.28,
1
3
3
1
2
27.39, 123.28, 123.22, 121.21, 119.79, 118.25, 55.69, 40.06, 31.74, 29.87, 29.18,
9.16, 23.74, 22.58, 14.06.
Synthesis of 2-bromo-7-nitro-9,9-dioctyl-9H-fluorene (6b)
To a stirred solution of 2-bromo-7-nitro-fluorene 4b (1 g, 3.4 mmol) in DMSO,
2
5 % aq. sodium hydroxide solution added dropwise over a period of 10 min under
nitrogen gas purging, then catalyst 3 (10 mol %) was added and followed by
-bromooctane 5a (1.33 g, 6.8 mmol), then the reaction mass was stirred at room
1
temperature. Reaction completion was confirmed by TLC, then extracted with ethyl
acetate, washed with water, dried over sodium sulfate and evaporated under reduced
1
pressure, to obtain a white solid with 95 % yield. H NMR (300 MHz, CDCl ) d
3
8
.26-8.19 (m, 1H), 7.80-7.76 (m, 1H), 7.65 (d, J = 3 Hz, 1H), 7.58 (d, J = 27 Hz,
H), 7.53–7.37 (m, 1H), 2.07–1.95 (m, 4H), 1.25–1.05 (m, 24H), 0.82 (t,
1
13
J = 4.5 Hz, 6H); C NMR (75 MHz, CDCl ) d: 154.40, 151.63, 147.41, 146.46,
3
1
37.73, 130.74, 126.58, 123.44, 122.49, 119.92, 118.30, 118.24, 56.02, 39.95,
1.72, 29.78, 29.14, 23.70, 22.57, 14.05.
3
Synthesis of 2,7-dibromo-9,9-dioctyl-9H-fluorene (6c)
To a stirred solution of 2,7-dibromofluorene 4c (1 g, 3.0 mmol) in DMSO, 25 % aq.
sodium hydroxide solution added dropwise over a period of 10 min under nitrogen
gas purging, then the catalyst 3 (10 mol %) was added followed by 1-bromooctane
5
with ethyl acetate, washed with water, dried over sodium sulfate and evaporated
a (1.19 g, 6.1 mmol). Reaction completion was confirmed by TLC, then extracted
1
under reduced pressure, to obtain a white solid with 96 % yield. H NMR
(
300 MHz, CDCl ) d: 7.53–7.43 (m, 6H), 1.92–1.88 (m, 4H), 1.20–1.05 (m, 20H),
3
13
0
1
2
.85 (t, J = 6 Hz, 6H), 0.59 (d, J = 6 Hz, 4H); C NMR (75 MHz, DMSO) d:
52.54, 139.05, 130.14, 126.16, 121.47, 121.09, 55.67, 40.14, 31.75, 29.85, 29.16,
9.14, 23.61, 22.59, 14.07.
Synthesis of 9,9-dihexyl-9H-fluorene (6d)
To a stirred solution of fluorene 4d (1 g, 6.0 mmol) in DMSO, 25 % aq. sodium
hydroxide solution added dropwise over a period of 10 min under nitrogen gas
purging, then catalyst 3 (10 mol %) was added, followed by 1-bromohexane 5b
(
1.98 g, 12.0 mmol). Reaction completion was confirmed by TLC, then extracted
with ethyl acetate, washed with water, dried over sodium sulfate and evaporated
1
under reduced pressure, to obtain a colourless viscous liquid with 98 % yield. H
NMR (300 MHz, CDCl ) d: 7.88–7.86 (m, 2H), 7.53–7.43 (m, 6H), 2.19–2.14 (m,
3
1
H), 1.33–1.23 (m, 12H), 0.94 (t, J = 6 Hz, 6H), 0.85–0.78 (m, 4H); C NMR
3
4
(
75 MHz, CDCl ) d: 145.58, 136.25, 122.05, 121.79, 117.71, 114.72, 50.03, 35.66,
3
2
6.62, 24.90, 18.82, 17.69, 9.06.
123

K. V. Ponmuthu et al.
General Procedure for C- and O-tetraalkylation of curcumin (Scheme 3)
To a stirred solution of curcumin 7 in DCM, 25 % aq. NaOH solution added
dropwise, then the catalyst 3 was added, followed by aryl bromide 8, and the
reaction mass was stirred for 12 h at RT. The reaction mass was diluted with water
and extracted with DCM and the organic layer was washed with a saturated brine
solution, dried over Na SO and concentrated. The crude product was purified by
2
4
silica gel column chromatography using pet ether: ethyl acetate as an eluent.
Synthesis of (1E,6E)–1,7-bis(3-methoxy)-4-(benzyloxy)-phenyl)-4,4-
bis(benzyl)hepta-1,6–diene–3,5-dione (9a)
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol) in DCM solution, stirred for about 10 min, then the benzylbro-
mide 8a (0.18 g, 1.0 mmol) was added into the flask. The reaction mass was stirred
for 12 h at RT. The mass was diluted with water and extracted with DCM and the
organic layer was washed with a saturated brine solution, dried over Na SO and
2
4
concentrated. The crude product was purified by silica-gel column chromatography
using pet ether:ethylacetate (10 %) as an eluent. We obtained a yellow solid with
1
8
1
4 % yield. H NMR (300 MHz, CDCl d: 7.63 (d, J = 15 Hz, 2H), 7.38-7.08 (m,
3
)
1
4H), 6.49 (d, J = 15 Hz, 2H), 5.13 (s, 4H), 3.83 (s, 6H), 3.33 (s, 4H); C NMR
3
(
75 MHz, CDCl ) d: 196.32, 150.81, 149.74, 143.54, 136.57, 136.25, 130.41,
3
1
28.32, 120.00, 127.11, ‘23.38, 123.20, 121.03, 113.15, 110.58, 70.77, 70.07, 56.23,
7.75, 29.54.
3
Synthesis of (1E, 6E)–1,7-bis (3-methoxy)-4-(4-methylbenzyloxy)-phenyl)-4,4-
bis(4-methyl benzyl)hepta-1,6–diene–3,5-dione (9b)
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol)) in DCM solution, stirred for about 10 min, then the 4-methyl
benzylbromide 8b (0.20 g, 1.0 mmol) was added into the flask. The reaction mass
was stirred for 12 h at RT. The mass was diluted with water and extracted with
DCM and the organic layer was washed with a saturated brine solution, then dried
over Na SO and concentrated. The crude product was purified by silica gel column
2
4
chromatography using Pet.Ether:ethylacetate (10 %) as an eluent. We obtained a
1
yellow solid with 93 % yield. H NMR (300 MHz, CDCl ) d: 7.70 (d, J = 18 Hz,
3
2
J = 15 Hz, 2H), 5.16 (s, 4H), 3.89 (s, 6H), 3.37 (s, 4H), 2.36 (S, 6H), 2.28 (S, 6H);
H), 7.31 (d, J = 9 Hz, 5H), 7.18 (d, J = 9 Hz, 4H), 7.04–6.83 (m, 13H), 6.60 (d,
1
3
C NMR (75 MHz, CDCl ) d: 195.92, 149.81, 148.65, 142.58, 136.72, 135.04,
3
1
1
32.43, 132.35, 129.25, 128.25, 127.79, 126.44, 126.21, 122.41, 120.19, 112.26,
09.73, 69.66, 69.18, 55.03, 36.07, 20.13, 19.96.
1
23

New quaternary phosphonium salt as multi-site…
Synthesis of (1E,6E)-4,4-bis(4-bromobenzyl)-1,7-bis(4-(4-bromobenzyloxy)-
3
-methoxyphenyl)hepta-1,6-diene–3,5-dione (9c)
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol)) in DCM solution, stirred for about 10 min, then 4-bromo
benzylbromide 8c (0.27 g, 1.0 mmol) was added into the flask. The reaction mass
was stirred for 12 h at RT. The mass was diluted with water and extracted with
DCM and the organic layer was washed with a saturated brine solution, then dried
over Na SO and concentrated. The crude product was purified by silica-gel column
2
4
chromatography using pet ether:ethylacetate (10 %) as an eluent. We obtained a
1
yellow solid with 94 % Yield. H NMR (300 MHz, CDCl ) d: 7.67 (d, J = 15 Hz,
3
2
3
1
1
H), 7.49–7.26 (m, 13H), 6.95–6.80 (m, 9H), 6.44 (d, J = 15 Hz, 2H), 5.11 (s, 4H),
1
3
.87 (s, 6H), 3.27 (s, 4H); C NMR (75 MHz, CDCl ) d: 196.11, 150.55, 149.65,
3
44.11, 135.24, 131.98, 131.66, 131.13, 128.68, 127.39, 123.38, 121.89, 120.83,
20.71, 113.26, 110.64, 69.95, 69.56, 55.97, 37.20.
Synthesis of (1E,6E)–1,7-bis(3-methoxy-4-(4-nitrobenzyloxy)phenyl)hepta-
,6-diene-3,5-dione (9d)
1
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol)) in DCM solution, stirred for about 10 min, then the 4-nitro
benzylbromide 8d (0.23 g, 1.0 mmol) was added into the flask. The reaction mass
was stirred for 12 h at RT. The mass was diluted with water and extracted with
DCM and the organic layer was washed with a saturated brine solution, then dried
over Na SO and concentrated. The crude product was purified by silica gel column
2
4
chromatography using pet.ether:ethyl acetate (10 %) as an eluent. We obtained a
1
yellow solid with 85 % yield. H NMR (300 MHz, CDCl ) d: 8.29 (d, J = 9 Hz,
3
2
4
1
5
H), 8.22 (d, J = 6 Hz, 4H), 7.06–6.98 (m, 4H), 6.70 (d, J = 6 Hz, 2H), 4.85 (s,
13
H), 3.97 (s, 6H); C NMR (75 MHz, CDCl ) d: 191.32, 155.35, 151.50, 147.91,
3
46.92, 137.81, 130.57, 129.63, 127.34, 126.77, 123.48, 114.16, 108.58, 63.77,
5.89, 29.45.
´
Synthesis of 4,4-(2,2-bis((E)-3-(4-(4-cyanobenzyloxy(-3-methoxyphenyl)acryloyl)
propane-1,3-diyl)dibenzonitrile (9e)
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol)) in DCM solution, stirred for about 10 min, then the 4-cyano
benzylbromide 8e (0.21 g, 1.0 mmol) was added into the flask. The reaction mass
was stirred for 12 h at RT. The mass was diluted with water and extracted with
DCM and the organic layer was washed with a saturated brine solution, then dried
over Na SO and concentrated. The crude product was purified by silica gel column
2
4
chromatography using pet.ether:ethyl acetate (10 %) as an eluent. We obtained a
1
yellow solid with 95 % yield. H NMR (300 MHz, CDCl ) d: 7.74-7.47 (m, 15H),
3
123

K. V. Ponmuthu et al.
7
.15 (d, J = 9 Hz, 4H), 6.98 (d, J = 9 Hz, 2H), 6.90 (s, 2H), 6.77 (d, J = 9 Hz,
1
H), 6.44 (d, J = 15 Hz, 2H), 5.20 (s, 4H), 3.87 (s, 6H), 2.03 (s, 4H); C NMR
3
2
(
75 MHz, CDCl ) d: 195.48, 150.60, 149.82, 144.97, 141.69, 132.46, 131.93,
3
1
6
31.11, 127.40, 123.43, 120.49, 118.55, 113.89, 111.86, 111.06, 110.85, 69.75,
9.52, 56.11, 38.03.
Synthesis of (1E,6E)–4,4-diallyl-1,7-bis(4-(allyloxy)-3-
methoxyphenyl)hepta-1,6-diene-3,5-dione (9f)
An amount of 25 % sodium hydroxide solution (10 ml) was taken in a round-bottom
flask and phase-transfer catalyst 3 (10 mol %) was added, followed by curcumin 7
(
0.1 g, 0.27 mmol)) in DCM solution, stirred for about 10 min, then the
allylbromide 8f (0.13 g, 1.0 mmol) was added into the flask. The reaction mass
was stirred for 12 h at RT. The mass was diluted with water and extracted with
DCM and the organic layer was washed with a saturated brine solution, then dried
over Na SO and concentrated. The crude product was purified by silica gel column
2
4
chromatography using pet.ether:ethyl acetate (10 %) as an eluent. We obtained a
1
yellow solid with 96 % yield. H NMR (300 MHz, CDCl ) d: 7.68 (d, J = 15 Hz,
3
2
H), 7.11–7.00 (m, 4H), 6.82 (d, J = 9 Hz, 2H), 6.65 (d, J = 15 Hz, 2H),
.09–6.00 (m, 2H), 5.42–5.07 (m, 10H), 4.64-4.62 (m, 4H), 3.89 (s, 6H), 2.81 (d,
6
1
3
J = 6 Hz, 4H); C NMR (75 MHz, CDCl ) d: 195.23, 149.73, 148.57, 143.28,
3
1
31.55, 131.24, 126.30, 122.35, 118.64, 118.01, 117.27, 111.89, 109.70, 68.66,
6.80, 55.03, 33.42.
6
Results and discussion
The main objective of this study was on generating more than one catalytic active
site per molecule of catalyst in a simplified synthetic route. As discussed in the
‘‘Introduction’’, the importance of phase-transfer catalysts in various alkylation
reactions is that they accelerates the reaction manifolds, replace hazardous
chemicals and costly catalysts with simpler and better environmental performance
chemicals, wihle reducing the reaction time. Hence, we are interested in the
synthesis of the MPTC phosphonium salt of 1,3,5-tris(bromomethyl)benzene 3 from
mesitylene 1 (Scheme 1). The synthesized phosphonium salt was characterized by
1
13
H and C NMR.
Comparison of reactivity between the various single-site PTC and MPTC
The C- and O- alkylation of curcumin with 4-methylbenzyl bromide was chosen to
investigate the comparative relativities of various commercially available soluble
single-site PTC, i.e., triethylbenzylphosphonium bromide (TEBPB), triethylbenzy-
lammonium chloride (TEBAC), triethylbenzylammonium bromide (TEBAB),
tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC)
and newly synthesized phosphonium salts of 1,3,5-tris(bromomethyl)benzene
(
MPTC); all the reactions were carried out under identical reaction conditions.
1
23

New quaternary phosphonium salt as multi-site…
Table 1 Comparison of reactivity between the various single-site PTC and multi-site PTC 3
S. no
1
Name of the catalyst
TEBPB
Mole (%) Yield (%)
Products
10
10
10
26
17
21
2
3
TEBAC
TEBAB
4
TBAB
10
25
5
6
TBAC
10
10
23
93
MPTC 3
7
MPTC 3
3.3
92
All the reactions were carried out at room temperature (30 °C)
123

K. V. Ponmuthu et al.
MPTC 3 is almost fourfold more reactive than the commercially available single-
site PTCs and we also obtained the C- and O-alkylated products in the presence of
MPTC only (Table 1). This observation proves that the newly synthesized
phosphonium salt has three active sites, and that all the catalytic sites appear to
be co-operatively involved in the alkylation reaction, and hence the MPTC has an
?
-
ability to transfer a larger number of anionic species (M Y ) from the aqueous
phase to the organic phase.
The catalytic efficiency was carried out in the C-alkylation of fluorene
0
derivatives 4 with alkyl bromide 5 at 9,9 position (Scheme 2), and we obtained
more yield in a shorter time and mild basic conditions at room temperature (30 °C)
(Table 2, entries 1–4). Further, the catalytic efficiency of the new MPTC was
examined by the alkylation of curcumin 7 (Scheme 3). To the best of our
Table 2 Various alkylation reactions in the presence of MPTC 3
Isolated
Entry
Reactant
RX
Product
Time (h) Yield
(%)
1
C
8
H17Br
6
90
2
3
C
8
8
H
17Br
17Br
6
1
95
96
C
H
4
5
C
6
H
13Br
5
98
84
C
7
8
H
7
9
Br
Br
12
C
H
6
12
93
7 6 2
C H Br
7
8
12
12
94
85
7 6 2
C H BrNO
9
C
8
H
6
BrN
12
12
95
96
1
0
3 5
C H Br
All the reactions were carried out at room temperature (30 °C)
1
23

New quaternary phosphonium salt as multi-site…
knowledge, there has been no report for the alkylation of curcumin. Thus, we report
for the first time the C-and O-tetra alkylation of curcumin simultaneously under a
mild concentration of base and MPTC conditions (Table 2, entries 5–10), we
obtained a very good yield. The PTC 3 has three active sites which show effective
conversion of the corresponding product in a shorter time and very good yield
because the neighboring groups of the phosphonium sites are cooperatively
influencing the rate of formation of carbanion which can be interacted with the
electrophile (Scheme 4).
General mechanism for the C-alkylation reaction
The mechanism is involved in the C-alkylation of fluorene derivatives 4 and
-
?
alkylbromide 5 both in the organic phase. In the aqueous phase containing Q Br
-
PTC) and NaOH, the PTC has abstracted the OH from an aqueous phase to form a
(
?
-
?
-
Q OH which is hydrophobic in nature. Hence, the Q OH is transferred to the
organic phase, which can abstract a proton from 9th position of fluorene derivatives
4
. At the same time, the alkylhalide of the electrophile is also coming close to the
carbanion to give the corresponding alkylated product of fluorene 6 (Scheme 5)
36–38].
[
Scheme 4 The ion pair formation between MPTC 3 and substrates
Scheme 5 Mechanism involving C-alkylation of fluorene derivatives 4
123

K. V. Ponmuthu et al.
General mechanism for the simultaneous alkylation of Curcumin
The C- and O-alkylation of curcumin 7 appears to proceed by a two-step pathway.
The mode by the addition of substrate into the reaction flask appears to have a
significant role. Generally, in the alkylation of curcumin, MPTC 3 reacts first with
?
-
the base to form Q OH which further reacts with the substrate and generates the
anion of the substrate via the abstraction of protons, and later the addition of
arylbromide 8 leads to its dissociation into anions and cations, so that the cationic
species react with the carbanion of curcumin to form a C- and O-alkylated product
9
. So far, in the literature, two types of mechanisms have been frequently proposed
for phase-transfer catalyzed reactions, i.e., the extraction mechanism of Stark and
interfacial mechanism ofMakosza. Increased rates with increased organophilicity or
with larger symmetrical ammonium ions, and the independence of reaction rate with
respect to linear dependence of the reaction rate on the catalyst confirm that the
reaction should proceed via an extraction mechanism. An interfacial mechanism is
strongly dependent on stirring speed (rpm), maximum reactivity with relatively
hydrophilic triphenylphosphonium ions and fractional order with respect to the
catalyst, which are the parameters for the confirmation of the interfacial mechanism
(
Scheme 6).
Scheme 6 Plausible mechanism involving C and O-tetraalkylation of curcumin 7
1
23

New quaternary phosphonium salt as multi-site…
Conclusion
We have successfully synthesized new tri-site phase-transfer catalyst 3 which has
1
been thoroughly characterized by H and C NMR. The catalytic efficiencies were
13
0
measured by C-alkylation of fluorene derivatives 4 at the 9,9 position, which shows
very good yield under shorter time, normal atmospheric conditions, mild base and
low concentration of catalyst compared with previous reports. For the first time, we
report the C-and O-tetra alkylation of curcumin simultaneously under a mild
concentration of bases and MPTC conditions and we obtained very yields in shorter
times.
Acknowledgments We acknowledge the financial support of the Department of Science and
Technology, New Delhi, India (Grant No. SR/F/1584/2012-13), University Grants Commission, New
Delhi, India (Grant No.UGC No.41-215/2012 (SR) and Council of Scientific and Industrial Research,
New Delhi, India (Grant No. 01(2540)/11/EMR-II), DST-SERB, Extramural Major Research Project,
New Delhi, India (Grant No. EMR/2015/000969).
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