Organobase catalysis using 1-(2-pyrimidyl)piperazine in micellar medium: An approach for better performance and reusability of organobase

Article abstract of DOI:10.1039/c5gc01966d

An organobase-surfactant micellar combined system was investigated for efficient and alkali/metal free base catalysis and to establish a simple method for separation and reuse of an organobase catalyst. Various aqueous organobase-surfactant micellar solutions were studied by using the Knoevenagel condensation of salicylaldehyde with active methylene compounds to 3-substituted coumarin as a model reaction. The 1-(2-pyrimidyl) piperazine (2-PP) was identified as a highly active organobase and its activity was further improved by using it in an aqueous solution of sodium dodecyl sulfate (SDS). The SDS micelles facilitate the reaction in water by solubilizing the 2-PP organobase and the reactants in their active forms. The reactant-SDS interactions in micelles play a significant role in promotion of the 2-PP catalyzed reaction. The SDS micellar medium not only promotes the 2-PP catalyzed reaction but also provides an easy and practicable protocol for the separation and reuse of the 2-PP organobase.

Full text of DOI:10.1039/c5gc01966d

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Organobase catalysis using 1-(2-pyrimidyl) piperazine in micellar medium: An
approach for better performance and reusability of organobase
1 1*
Manu Vashishtha, Manish Mishra and Dinesh O. Shah
1, 2
1
Department of Chemical Engineering & Shah-Schulman Center for Surface Science and
Nanotechnology, Faculty of Technology, Dharmsinh Desai University, College Road,
Nadiad – 387 001, Gujarat, India,
2
Department of Chemical Engineering and Department of Anesthesiology,
University of Florida, Gainesville, FL, USA 32608
*E-mail: manishorgch@gmail.com; Fax: +91 268 2520501; Tel.: +91 268 2520502
Abstract
An organobase-surfactant micellar combined system was investigated for efficient and alkali/
metal free base catalysis and to establish a simple method for separation and reuse of
organobase catalyst. Various aqueous organobase-surfactant micellar solutions were studied
by using Knoevenagel condensation of salicylaldehyde with active methylene compounds to
3-substituted coumarin as model reaction. The 1-(2-pyrimidyl) piperazine (2-PP) was
identified as a highly active organobase and its activity was further improved by using it in
aqueous solution of sodium dodecyl sulfate (SDS). The SDS micelles facilitate the reaction in
water by solubilizing the 2-PP organobase and the reactants in their active forms. The
reactants-SDS interactions in micelles play significant role in promotion of 2-PP catalyzed
reaction. The SDS micellar medium not only promotes the 2-PP catalyzed reaction but also
provide an easy and practicable protocol for separation and reuse of 2-PP organobase.
Keywords: Organobase; 1-(2-pyrimidyl) piperazine; surfactants; micelles; base catalysis;
Knoevenagel condensation; 3-substituted coumarins.
1

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1
. Introduction
There is a great demand for efficient and alkali/ metal free base catalytic system to be utilized in
the organic synthesis. In recent years, the organocatalysis has received much attention to
1
develop metal free and greener route for synthesis of important chemicals, especially for the
synthesis of biologically active compounds and intermediates. The cyclic organobases (Scheme
1d,1g-1j
1c,1k,1l
TBD,
1m
DBN, DABCO,
1f,1n
1
a) such as DBU,
etc. have been widely explored as non-
corrosive, environmentally benign and efficient homogeneous base catalyst for numerous
important organic transformations. These organobases have been of special interest for synthetic
organic chemistry due to their high basicity: the pKa values of TBD, DBU, DBN and DABCO
2
are 25.96, 24.34, 23.79 and 18.29, respectively. The basicity of guanidine derived bases is
higher than amines and amidine bases due to the formation of the number of canonical forms
after protonation. The organobase catalysts have been efficient under ambient condition and also
in water as solvent. They show excellent activity in homogeneous condition, but their difficult
separation and reusability limit their practical applicability. The TBD, a strong bi-cyclic
1
c
guanidine base, has been demonstrated to be efficient organobase catalyst for aldol reactions.
The polymer supported TBD catalysts were prepared for the easy separation and reusability.
3
The recovery of TBD from homogeneous reaction mixture has been reported by bubbling CO
2
in
the reaction mixture at the end of reaction producing a precipitate, which on heating at 130°C
1c
1g
under inert atmosphere gave TBD eliminating CO . Cota et al. reported the reusability of
2
DBU in base catalyzed aldol condensation reactions by removing the organic phase containing
the product from the aqueous phase (which contains dissolved DBU); however, they required
very high concentration of catalyst (DBU-H
activity.
2
O complex in 1/25 molar ratio) to achieve highest
The organic-aqueous biphasic reaction systems received much interest due to the use of water as
inexpensive and environmentally benign solvent and the recovery of water soluble catalyst from
2

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4
the reaction mass. The use of organobases in organic-aqueous biphasic reactions would be
promising for easy separation of organobases as they would be soluble in aqueous phase and
after reaction the aqueous phase can be easily separated. The presence of water in many
organocatalytic aldol reactions has been found to be useful as co-catalyst in promotion of the
5
reactions. However, the insolubility/ incompatibility of hydrophobic organic compounds in
,6
water has been found to be major constraint of water mediated or aqueous-organic biphasic
7
-10
reactions showing slow reaction rate.
Previously, we reported the potential of cationic
surfactants to overcome the problem of reagent(s) incompatibility in aqueous reactions showing
enhanced reaction rate and selectivity, and also for recovery and reuse of NaOH homogenous
11
catalyst. The reactions in a micellar solution are facilitated by micelles by generating huge
7
interfacial area between oil (reactants) and aqueous phase. This also provides advantages such
as solubilization/ localization of reactants in the micelles in special orientation and in active
form, and water soluble ionic species (e.g., catalyst) on the micellar surface making the reaction
11-13
faster and selective.
In continuation of our work on base catalysis using micellar systems, we
were interested in replacement of the NaOH base catalyst by an organobase to develop alkali
free micellar system for base catalysis. The organobase catalysis in an appropriate surfactant
solution could be an effective approach to have enhanced efficiency of organobase in the
aqueous medium as well as for easy separation of organobase for reuse.
The present work was aimed to study the catalytic potential of some important organobases in
aqueous surfactant micellar solution to develop an efficient, alkali/ metal free and green catalytic
system for base catalysis as well as to establish a simple protocol for recovery and reuse of
organobase. We studied five cyclic organobases (Scheme 1a) as well as some inorganic bases
2 3 3
(such as NaOH, KOH, Na CO and NaHCO ) as catalyst for base catalyzed Knoevenagel
condensation of salicylaldehyde and diethyl malonate (DEM) to 3-substituted (ester) coumarin
as a model reaction of aldol type reaction under neat, biphasic condition and in micellar
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solutions of different surfactants (anionic, cationic and nonionic; Scheme 1b). The 3-substituted
coumarins are bioactive compounds exhibiting numerous important pharmacological effects
such as analgesic, anti-arthritis, anti-inflammatory, anti-pyretic, anti-viral, anti-cancer,
14
anticoagulant, etc. We found that 1-(2-pyrimidyl) piperazine (2-PP; Scheme 1a) guanidine
base, which has not been studied for base catalysis, was highly active for organobase catalysis
among the studied organobase catalysts. In aqueous micellar solution of an appropriate
surfactant (anionic; SDS), the catalytic performance of 2-PP was observed to be significantly
improved. The SDS micelles solubilize the 2-PP organobase catalyst and reactants molecules in
water and bring them together for interaction. Furthermore, the favourable interactions between
SDS and the reactants in micelles (co-catalytic activity of surfactant) greatly help in catalysis of
the reaction. The spent 2-PP-SDS micellar solution could be easily recovered by filtration of
crystallized product for reuse.
(a)
H
N
(b)
N
N
O
S
O
O
Na
N
N
O
1
[
(
,8-Diazabicyclo
5.4.0]undec-7-ene
DBU)
1,5,7-Triazabicyclo
[4.4.0]dec-5-ene
(TBD)
Sodium dodecyl sulfate (SDS)
O
C
O
Na
N
N
N
Sodium dodecanoate (SDD)
O
N
C
O
Na
1
[
,5-Diazabicyclo
4.3.0]non-5-ene
1,4-Diazabicyclo
[2.2.2]octane
(DABCO)
Sodium hexadecanoate (SHD)
(
DBN)
CH
3
N
Br
N
CH
3
CH
Cetyl trimethylammonium bromide (CTAB)
3
N
N
HN
1-(2-Pyrimidyl) piperazine
(2-PP)
O
O
H
9
.5
tert.-octylphenoxypolyethoxyethanol (Triton X-100)
Scheme 1. Structure of different (a) organic bases and (b) surfactants used in the study.
2
. Experimental
.1. Materials
2
Salicylaldehyde (>99%), diethyl malonate (DEM; 98%), ethyl acetoacetate (EAA; 98%),
sodium hydroxide (99%), potassium hydroxide (99%), sodium bicarbonate (99%), sodium
4

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carbonate (99%), ethyl acetate (99%) and concentrated HCl (35%) were purchased from Merck,
India. Cetyl trimethylammonium bromide (CTAB; 98%), sodium dodecyl sulfate (SDS; 98%),
Triton X-100 (98%), and toluene (99%) were from S.D. Fine Chemicals, India. Sodium
dodecanoate (SDD; 99%), sodium hexadecanoate (SHD; 98.5%), DBU (99%), TBD (99%), 2-
PP (99%), DBN (99%) and DABCO (99%) were from Sigma Aldrich. All the chemicals were
used without any further purification. The double distilled milli-pore deionized water was used
in the reactions.
2.2. Experimental procedure
The catalytic activity of different bases was evaluated by carrying out Knoevenagel
condensation reactions of salicylaldehyde and DEM in solvent free condition (neat), in water
(
biphasic reaction) and in aqueous surfactant solutions. In the reaction tube of reaction station
12 Place Heated Carousel Reaction Station, RR99030, Radleys Discovery Technologies, UK),
(
5
mL of surfactant aqueous solution was taken and a mixture of salicylaldehyde (2.5 mmol) and
DEM (2.5 mmol) was added in the solution under stirring. The base (inorganic/organic) was
dissolved in the solution and the reaction mixture was stirred at required temperature for the
required period of time. The biphasic reaction (reaction in pure water) was carried out by first
dissolving the 2-PP in water (5 mL) followed by addition of reactants mixture in the solution.
The details of reaction conditions are also mentioned in the footnote of the tables and figures.
After completion of the reaction, the reaction mixture was neutralized with concentrated HCl
and diluted with excess of saturated NaCl solution to reduce the surfactant concentration below
the CMC (in case of micellar reactions). The organic phase was extracted with ethyl acetate (10
mL) and was analyzed by gas chromatography (Agilent 5975) having a HP-5 (60 meter, 250 µm
diameter) capillary column with a programmed oven temperature from 50 to 280°C, at 1 mL
-
1
min flow rate of N as carrier gas and FID detector. The conversion of DEM was calculated on
2
the basis of its weight percent as follows,
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Conversion (wt.%) of DEM = 100 X [Initial wt.% of DEM – Final wt.% of DEM]
Initial wt.% of DEM
The selectivity of the product (3-substututed coumarin) was calculated as below,
Selectivity (%) of 3-substututed coumarin = 100 [GC peak area % of 3-substututed coumarin]
Ʃ Total peak area for all the products
The products formed in the reactions were characterized by GC–MS analysis and the data were
matched with those reported in the literature. GC–MS analysis was carried out using gas
chromatograph mass spectrometer (Agilent 5975 GC/MSD with 7890A GC system) having HP-
5
capillary column of 60 m length and 250 µm diameter with a programmed oven temperature
−
1
from 50 to 280°C, at 1 mL min flow rate of He as carrier gas and ion source at 230°C.
To recover the surfactant-organobase aqueous solution after the completion of reaction for reuse
study, the stirring of reaction mixture was stopped and the solution was allowed for
crystallization. The micellar solution was separated by filtration and the surfactant-organobase
st
solution was reused for 1 cycle. In the spent surfactant-organobase solution, the mixture of
salicylaldehyde (2.5 mmol) and DEM (2.5 mmol) was added under stirring (700 rpm) and the
reaction was further carried out at 30°C for 6 h. The reaction mixture was worked up as
nd
previously described. For 2 and subsequent reaction cycle, the spent surfactant-organobase
solution was obtained by filtration of product crystals from reaction mixture of previous cycle
.
The spent organobase aqueous solution of biphasic reaction (surfactant free) was obtained by
phase separation and removing it from the top of the organic phase containing partially
crystallized product and unreacted reactants.
The UV-vis spectra of the reactants and 2-PP organobase in water and aqueous surfactant
solutions were recorded by using an Agilent, Carry 5000 spectrometer at room temperature. The
path length of the quartz cell used in this experiment was 1 cm. The UV absorptions were
studied by using separate solutions of base and both reactants (2-PP organobase: 0.18 mM;
6

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salicylaldehyde: 0.8 mM; DEM/ EAA: 2.4 mM) in water and in surfactant solutions. These
amounts were found to be completely soluble in the pure water (without surfactant) giving a
transparent solution, however, these concentrations of reactants and organobase (2-PP) were
1
different from those used in the catalysis experiments. The H NMR analyses of the reactants
mixture (salicylaldehyde and DEM/ EAA) and separately of 2-PP organobase in D O and
2
surfactant solutions (prepared in D
2
O) were carried out using a Bruker Avance III 500 MHz
O or
O or in
spectrometer. The reactants mixture (in 1:1 molar ratio; 10 µL) was solubilized in 1 mL D
2
surfactant solution in D
O. The 2-PP organobase solutions (0.18 mM) prepared in D
2 2
1
D O-surfactant solutions were used for H NMR analyses. The number of acquisitions was 32
2
1
for each sample. The H chemical shifts are reported in δ units (ppm) relative to that of
tetramethylsilane (TMS) as external standard.
3. Results and discussion
3.1. Catalytic activity of inorganic and organic bases in different reaction media
The control experiments (ESI; Table S1) showed that in pure water or in micellar solutions
without catalyst (inorganic/ organic base), there was no reaction between salicylaldehyde and
DEM/ EAA at room temperature as well as at 60°C. Initially, the reactions of salicylaldehyde
and DEM were carried out using 50 mol% of catalyst (inorganic/ organic base) in pure water
(biphasic reaction) and in 15 mM CTAB micellar solution at 30°C (Table 1; Entry 1 to 19). The
selectivity of the desired product (3-ethyl carboxylate coumarin) was 97-100% and in some
reactions, un-substituted coumarin was found as by-product, which could be probably formed
due to hydrolysis followed by decarboxylation of 3-substituted coumarin. From the results
(Table 1), this is evident that 2-pyrimidyl piperazine (2-PP) is highest in activity than inorganic
as well as other organobases giving highest conversion of DEM in water (95%) and in CTAB or
SDS micellar solutions (99%). The previously reported organobases such as DBU, TBD, DBN
and DABCO in either biphasic condition or micellar media gave lesser conversion than 2-PP.
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The higher activity of 2-PP as compared to other organobases may be due to the presence of two
basic functionalities in 2-PP molecule: guanidine moiety in aromatic system and secondary
amino group in piperazine ring.
The catalytic performance of 2-PP was further examined by reducing its molar amount (from 50
mol% to 10 mol%) in the neat, biphasic and micellar reactions (Table 1; Entry 20 to 28). The
biphasic reactions were performed to examine the performance of organobase without surfactant
1
and also to study the separation and reusability of the spent organobase catalyst. For
g
comparison, the reaction was also carried out using 10 mol% NaOH in CTAB micellar solution
1
1
(
previously studied system for aldol reactions) ; the reaction in NaOH-CTAB micellar solution
and even in neat condition resulted to very poor conversions (18% and 5%, respectively; Table
; Entry 27 and 28). In the biphasic reaction using 2-PP organobase, the conversion was found
1
to be decreased to 63% as compared to neat reaction using 2-PP (Table 1; Entry 20). The
reduced conversion in biphasic reaction may be due to immiscibility of aqueous phase
containing dissolved 2-PP and oil phase of reactants. In addition, the major concern was the
reusability of spent 2-PP aqueous solution recovered by phase separation from reaction mass,
which has been discussed in detail in section 3.3. The solvent free (neat) reaction using 2-PP
base resulted to 84% conversion (Table 1; Entry 21). In the neat condition, 2-PP organobase
would be completely soluble in the reaction mixture giving fairly good conversion, however, the
recovery of 2-PP from the reaction mass is tedious and requires post reaction work up.
8

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Table 1. Activity of various base catalysts for Knoevenagel condensation of salicylaldehyde
and DEM in different reaction media.
O
O
Base (inorganic/organic)
OEt
+
O
O
+
Neat/
EtO
OEt
O
O
OH
O
O
In water (5 mL)/
3
-ethyl carboxylate
coumarin
Unsubstiuted
coumarin
Salicylaldehyde
2.5 mmol)
DEM
(2.5 mmol)
In aq. surfactant solution
o
(
(15 mM; 5 mL), 30 C, 6 h
Entry
Catalyst
Conv. (wt.%)
of DEM
Selectivity (%) of
3-ethyl carboxylate
Un-substituted
coumarin
coumarin
98
99
1
2
3
4
5
6
7
8
9
NaOH-H
2
O
NaOH-CTAB
72
81
61
69
03
12
48
54
52
65
54
69
55
67
31
41
95
99
99
63
84
78
92
89
86
66
18
05
02
01
01
01
-
KOH-H O
2
99
99
KOH-CTAB
NaHCO -H O
100
100
100
100
99
3
2
NaHCO
Na CO
Na CO -CTAB
DBU-H
DBU-CTAB
TBD-H
3
-CTAB
-
-
-
01
01
01
01
01
01
-
2
3
-H2O
2
3
2
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
99
99
99
99
2
O
TBD-CTAB
DBN-H O
2
DBN-CTAB
DABCO-H O
99
100
99
2
DABCO-CTAB
O
01
01
02
03
01
01
01
01
01
01
01
-
2-PP-H
2-PP-CTAB
2-PP-SDS
2
99
98
97
99
99
99
99
99
2-PP-H
2
O
2-PP (neat)
2-PP-CTAB
2-PP-SDS
2-PP-SDD
2-PP-SHD
99
99
2-PP-Tx-100
NaOH-CTAB
NaOH (neat)
100
100
-
Entry 1 to 19: 50 mol% base; Entry 20 to 28: 10 mol% base
CTAB: cetyltrimethyl ammonium bromide; SDS: sodium dodecyl sulfate; SDD: sodium dodecanoate
̶
+
23COO Na ); SHD: sodium hexadecanoate (C15
̶
+
31COO Na ).
(C
11
H
H
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The reactions using 2-PP organobase in micellar solutions (CTAB, SDS, SDD, SHD, Tx-100;
5 mM) gave increased conversion (66% - 92%; Table 1; Entry 22 to 26) as compared to
1
biphasic reaction. The 2-PP-anionic surfactant (SDS, SDD and SHD) solutions gave higher
conversion (86% to 92%) as compared to 2-PP-cationic surfactant (CTAB; 78%) and non-
ionic surfactant (Tx-100; 66%) solutions showing higher activity of 2-PP-anionic surfactant
solutions. The surfactant molecules in aqueous medium would generate plenty of micelles as
the used concentration (15 mM) of the surfactants was far above the critical micellar
concentration (CMC) of all the surfactants. The micelles can facilitate the reactions in water
by solubilizing the hydrophobic reactants creating huge water-oil (organic reactants) interface
7
in the reaction medium. The ionic micelles are helpful in the aqueous reactions as they
accumulate the oppositely charged water soluble catalytic species at interface. The water
-
soluble organobase reacts with water and gets converted into protonated base and OH ions as
Brønsted base (Scheme 4). Thus the micelles can offer better interaction of water soluble
-
species (protonated base and OH ions) and reactants giving enhanced conversion in micellar
reactions. The selection of an appropriate surfactant is very important in 2-PP organobase
catalysis in micellar media, which is clearly evident from the catalysis results (Table 1; Entry
22 to 26). The surfactant’s nature (cationic/ anionic/ non-ionic) is playing crucial role in
enhancement of catalytic activity of 2-PP-micellar system. It was anticipation that anionic
micelles (SDS, SDD, SHD) might be solubilizing more number of positively charged
-
protonated 2-PP species along with OH ion as compared to cationic micelles (CTAB) and
therefore, 2-PP-anionic micellar systems showed higher activity. However, our investigations
(
discussed in the next section) showed that the co-catalytic activity of anionic surfactant
SDS) or surfactant-reactants interaction was greatly responsible for the promotion of the 2-
(
PP catalyzed micellar reaction. As SDS showed highest improvement in 2-PP catalysis and
has been widely employed as anionic surfactant in promotion of various catalytic reactions in
1
0

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1
5
water, we selected 2-PP-SDS system for detail investigation. The ionic surfactant’s micelles
play important role in micellar catalysis, especially when ionic species (catalyst and reaction
intermediates) are involved in the reaction; therefore, for comparison 2-PP-CTAB micellar
system was also studied.
2
2
-PP-SDS
-PP-CTAB
9
9
8
8
7
7
6
6
5
0
5
0
5
0
5
0
0
5
10 15 20 25 30 35 50 100
Surfactant concentration (mM)
150
200
Figure 1. Conversion of DEM in reactions in 2-PP-SDS and 2-PP-CTAB micellar solutions of
different surfactant concentrations [Reaction condition: 2.5 mmol salicylaldehyde, 2.5 mmol
DEM, 10 mol% 2-PP organobase, 5 mL aqueous SDS/CTAB surfactant solution , 30°C, 6 h].
The reaction kinetics of Knoevenagel condensation of salicylaldehyde and DEM in 2-PP-SDS
and 2-PP-CTAB micellar solutions at different surfactant concentrations (1 mM to 250 mM;
Figure 1) also shows the highest activity of 2-PP-SDS system. All the conversion values
reported in Figure 1 are within ±2% precision. Initially, the conversion of DEM increases with
increase in the concentration of both the surfactants (from 1 mM) and highest conversion (94%)
was obtained with 2-PP-SDS at 25 mM, and 2-PP-CTAB gave highest conversion (78%) at 15
mM. Further increase in the concentration of both the surfactants reduced the conversion of
DEM. Thus, the optimum concentration of CTAB and SDS showing highest activity in the
1
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reaction was found to be 15 mM and 25 mM, respectively. The gradual increase in conversion of
DEM with CTAB/ SDS concentration up to their optimum concentrations (15 mM/ 25 mM) can
be related to the increasing number of micelles in the solution solubilizing more reactants and 2-
PP (in protonated form) molecules in the micelles. The significant increased conversion in SDS
micellar solutions below CMC (1 mM and 5 mM; SDS CMC is 8 mM) as compared to biphasic
reaction is possible with the help of surfactant molecules, presumably in the form of submicellar
aggregates. In the SDS solutions below CMC, very likely there will be monomers and
submicellar aggregates. This has been reported that in the micellar reactions at below CMC, a
small number of surfactant monomers may aggregate with a substrate molecule to form a
catalytic micelle (substrate-induced micellization), which contributes in promotion of the
1
6
reaction. The successive decrease in conversion of DEM with increasing SDS or CTAB
concentration, above their optimum concentration (25 mM and 15 mM, respectively), may be
attributed to dilution of 2-PP molecules in the micelles slowing down the reaction rate. In
addition, the strong solubilization or binding of reactant(s) and/ or organobase molecules may
also be one of the reasons for showing reduced conversion at high surfactant concentrations. In
many micellar reactions, the decreased reaction rate at high surfactant concentration has been
1
6
ascribed to dissolution/ strong binding of reactant molecules in the micelles.
The 2-PP-SDS micellar system was also found to be effective in the synthesis of 3-acetyl
coumarin by Knoevenagel condensation of salicylaldehyde with EAA to 3-acetyl coumarin in
neat as well as in biphasic condition giving good conversion (93% and 90%, respectively, in 6 h)
and almost complete conversion in SDS micellar solution (Table 2). The significantly higher
conversion of EAA (90%) than DEM (63%) in even biphasic reaction can be attributed to higher
reactivity of EAA than DEM. The pKa values of EAA and DEM in dimethyl sulfoxide (DMSO)
1
are 14.4 and 16.4, respectively. It means that EAA is slightly more acidic than DEM i.e.,
7
deprotonation of EAA with the help of base catalyst to form its carbanion (enolate; which reacts
1
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with salicylaldehyde) would be easier than DEM, which might be making EAA more reactive in
this reaction giving its faster conversion than DEM.
Table 2. Knoevenagel condensation of salicylaldehyde and EAA to 3-acetyl coumarin using 2-
a
PP-SDS micellar solution.
O
O
CH3
10 mol % 2-PP
O
O
+
H C
3
OEt
Solvent free/
O
OH
Salicylaldehyde
O
5
ml Water/ aq. SDS
solution (15 mM),
EAA
(2.5 mmol)
3-acetyl coumarin
(
2.5 mmol)
3
0oC, 6 h
S. No.
Catalytic system
Conv. (wt.%) of
Selectivity (%) of 3-
acetyl coumarin
EAA
93
90
1
2
3
2-PP (neat)
100
100
100
2-PP-H
2
O
2-PP-SDS
>99
The activity of other organobases (DBU, TBD, DBN and DABCO) were also examined for the
reaction in aqueous SDS micellar solution (15 mM) using 10 mol% amount of organobases
(Table 3). But the 2-PP-SDS system showed highest activity in the reaction giving highest
conversion (92%). The room temperature (i.e., 30°C) and 10 mol% 2-PP base was found to be
optimum reaction temperature and catalyst amount giving substantial conversion (94%) of DEM
(ESI; Table S2 and S3).
Table 3. Catalytic activity of various bases in aqueous SDS micellar solution in Knoevenagel
a
condensation of salicylaldehyde and DEM.
Entry
Organobase-SDS
system
Conv. (wt.%)
of DEM
Selectivity (%) of
3-ethyl carboxylate
coumarin
Unsubstituted
coumarin
1
2
3
4
5
DBU-SDS
TBD-SDS
20
23
26
18
92
99
100
99
99
100
01
-
DBN-SDS
DABCO-SDS
2-PP-SDS
01
01
-
a
2
.5 mmol salicylaldehyde, 2.5 mmol DEM, 10 mol% base, 5 ml aq. SDS surfactant solution (15 mM), 30°C, 6
h.
1
3

Green Chemistry
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Numerous acid and base catalysts (homogeneous as well as heterogeneous) have been reported
for the Kneovenegal condensation of salicylaldehyde and its derivatives with active methylene
1
8
compounds to synthesize 3-substituted coumarins. The heterogeneous base catalysts such as
metal hydroxides and mixed oxides are known to be best owing to their easy separation and
reuse. However, the necessity of metal free processes, reusable catalyst, mild reaction conditions
and solvent free or green solvent mediated synthesis are major issues for viable application of
homogeneous and heterogeneous base catalysts. The solid acids and bases have been
demonstrated to be excellent catalysts for Kneovenegal condensation to synthesize of 3-
substituted coumarins owing to their advantageous features (easy separation and reusability),
18c-18h
18d,18f,18g,18i,18j
however, they require high temperature
and longer reaction time
. The 2-PP-
SDS micellar system was found to be comparable in activity for synthesis of 3-substituted
coumarins under ambient condition. Furthermore, the 2-PP-SDS system offers a metal free and
green catalytic route for synthesis of biologically active compounds. This study may further
explore the wide application of the 2-PP-micellar system in base catalysis and in particular this
catalytic system may be of great interest for the synthesis reactions reported with various
1
organobases in homogeneous/ biphasic conditions, inorganic base-surfactant micellar
11,19
and
20
organobase-surfactant micellar solutions.
3.2. Role of surfactant’s nature (SDS vs. CTAB) on activity of 2-PP-micellar system
The catalysis study (Table 1 and Figure 1) revealed the higher activity of 2-PP-SDS micellar
system than 2-PP-CTAB. This result indicates that the nature of surfactant (cationic/ anionic)
plays crucial role in promotion of 2-PP catalyzed reaction. Recently, it was shown by NMR
2
studies of DBU-H O systems, that the nitrogen atom of DBU (Lewis base) gets protonated by
water molecule forming a second resonance structure (positively charged protonated DBU
1
g
species) with hydroxyl ion (Scheme 4a), which behaves like a Brønsted base catalyst.
1
4

Page 15 of 38
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Similarly, the 2-PP molecule (both aromatic guanidine moiety and piperazine secondary amino
group) can also get protonated with water molecules in aqueous medium giving a positively
-
charged protonated 2-PP species and associated hydroxyl ions (OH ) Brønsted base (Scheme
1
b). The protonation of 2-PP molecules in aqueous medium was revealed by comparing the H
4
NMR spectra of 2-PP in CDCl and D O solvents (Figure 3; i & ii). In D O, the upfield shifting
3
2
2
th
of the resonance signals for protons at 4 and 6 positions of pyrimidyl ring, the downfield
th
th
shifting of the resonance signals for proton at 5 position of pyrimidyl ring, and the upfield
shifting of the resonance signals for all protons at piperazine ring are indication of protonation
1
of pyrimidyl ring of 2-PP (Scheme 4b). The H NMR results (Figure 3; i & ii) can be explained
by using resonating structures of guanidine moiety of protonated 2-PP species given in Scheme
th
th
5
: structures IV & V exhibit reduced π-electrons density at 4 and 6 positions of pyrimidyl ring
of protonated 2-PP showing shielding (upfield shifting) of their protons; comparatively higher
th
electron density over 5 carbon of pyrimidyl ring will cause deshielding (downfield shifting) of
its proton; and protonation of pyrimidyl ring or its dearomatization as well as protonation of
piperazine secondary amino group would show shielding effect on all protons of piperazine ring
1g
2
causing upfield shifting. Cota et al. also observed in NMR studies of DBU-H O complexes
that the protonation of DBU leads to a shielding of the carbon atoms directly linked to the basic
nitrogen atom.
1
5

Green Chemistry
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N
N
a.
b.
2
+ H O
OH
N
N
N
H
DBU
Protonated DBU
N
+
2H O
2
OH
N
H
N
N
N
OH H N
HN
2
2
-PP
Protonated 2-PP species
1
Scheme 4. Reaction of Lewis bases (a) DBU and (b) 2-PP with water forming their respective
g
protonated species and hydroxyl ion.
H
N
H
N
H
N
H
N
H
N
H
N
H
N
H
N
H O OH N
N
N
N
N
OH
N
N
N
2
OH
OH
OH
N
OH
N
2
N
H
H
or OH
H
H
H
1
3
H
N
N
N
H
N
N
N
N
N
N
N
N
N
N
6
4
5
I
II
III
IV
V
VI
+
-
2
-PP
2-PPH .OH
Scheme 5. Resonating structures of guanidine moiety of protonated 2-PP species.
The comparative study on binding/ solubilization of procaine drug (amine.HCl salt) with SDS,
21
CTAB and triton X-100 micelles has demonstrated the higher binding affinity of procaine to
SDS than CTAB and triton X-100 owing to the strong electrostatic and hydrophobic interactions
between procaine molecules with SDS micelles. Therefore, it was anticipation that higher
activity of 2-PP-SDS micellar solution should be related to higher binding/ solubilization of
-
protonated 2-PP species in SDS micelles providing more OH ions in micellar phase for reaction.
To understand the promotional effect of SDS in the micellar reaction, the solubilization behavior
and interaction of both types of micelles (SDS and CTAB) for 2-PP and reactants were studied
1
by using UV and H NMR spectroscopic techniques.
3
.2.1.Characterization of 2-PP organobase-surfactant solutions
The UV absorption spectra of 2-PP in CTAB and SDS solutions at different concentrations
Figure 2) clearly depict the solubilization/ association of 2-PP molecules in both the micellar
(
1
6

Page 17 of 38
Green Chemistry
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structures (cationic and anionic) showing gradual increase in the intensity and blue shift of the
2
2
1
peak (for 2-PP; λmax: 243 nm) with surfactant concentration. The H NMR study has been
widely used for probing the solubilization and binding location of aromatic compounds in
micelles by observing the aromatic ring induced changes in the chemical shifts of the
23
surfactant. We also observed the aromatic solute induced shift effect by solubilized 2-PP
species on SDS and CTAB molecules showing upfield shifting of the signals for different
protons of SDS and CTAB (see ESI; Table S4 & S5), which indicates the inclusion of 2-PP
species in SDS and CTAB micelles. For CTAB, the major shift for the alkyl chain protons
occurs near the head group, whereas in SDS the protons around the middle of the chain are
shifted significantly indicating deeper penetration of solubilizate in SDS micelles as compared
2
3b
to CTAB micelles. Our observation was in line of a previous reports showing the deeper
penetration of even a charged solubilizate (i.e., 2-PP species) in SDS micelles. This behavior of
SDS has been explained as bending of the alkyl chain of the surfactant toward the aromatic parts
23b
of the solubilizate.
2.75
2.50
2.25
2.00
1.75
1.50
1.25
1.00
0.75
0.50
0.25
0.00
Water
mM CTAB
15mM CTAB
5mM CTAB
50mM CTAB
3.00
2.75
Water
5 mM SDS
(a)
(b)
5
1
2
5
5 mM SDS
5 mM SDS
0 mM SDS
2
2
2
2
1
1
1
1
0
0
0
.50
.25
.00
.75
.50
.25
.00
.75
.50
.25
0.00
2
50
300
Wavelength (nm)
350
250
300
Wavelength (nm)
350
Figure 2. UV absorption spectra of 2-PP in aqueous solutions of (a) CTAB and (b) SDS
micellar solutions at different concentrations (0, 5, 15, 25, 50 mM; 2-PP concentration: 0.18
mM).
1
7

Green Chemistry
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H
H
H
N
N
N
N
N
N
N
H
N
H
(iv)
(iv)
(
iii)
(iii)
(ii)
(
ii)
(i)
(i)
8.45
8.40
8.35
Chemical shift (ppm)
8.30
8.25 6.75
6.70 6.65
Chemical shift (ppm)
6.60
6.55
N
N
N
N
H
N
H
H
N
H
H
H
H
H
N
H
N
H
(iv)
(iv)
(iii)
(iii)
(ii)
(ii)
(i)
(i)
3
.90 3.85 3.80 3.75 3.70 3.65 3.60 3.05
Chemical Shift (ppm)
3.00
Chemical shift (ppm)
2.95
2.90
2.85
1
3 2
Figure 3. H NMR chemical shifts of different protons of 2-PP in (i) CDCl , (ii) D O, (iii) 25
mM CTAB and (iv) 25 mM SDS aqueous solutions.
The solubilization of 2-PP in CTAB and SDS micelles as protonated 2-PP species is also evident
1
from H NMR spectrum of 2-PP in micellar solutions showing resemblance with the spectrum in
2 2
D O (Figure 3; iii & iv). However, some spectral differences of 2-PP in micellar and D O
1
8

Page 19 of 38
Green Chemistry
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solutions can be seen, which are possibly due to presence of 2-PP species in micellar
environment. In SDS solution, the slight upfield shifting of the signals for protons of pyrimidyl
ring indicates orientation of pyrimidyl group towards core i.e., in non-polar environment, and
the slight downfield shifting of the signals for protons of piperazine ring presents its projection
1
towards micellar surface (i.e., polar/ ionic environment). The H NMR results (Figure 3; iii &
iv) also indicate stronger hydrophobic interaction of pyrimidyl group of 2-PP species with SDS
alkyl chain relative to CTAB showing upfield shifting of pyrimidyl protons in SDS solution.
The protonated 2-PP species can be localized in the SDS micelles by ionic interaction with
sulfate head group of SDS molecules and hydrophobic interaction with surfactant alkyl group. In
CTAB micelles, 2-PP species can reside interacting with CTAB head group through the lone
23a
1
pair of electrons of nitrogen atoms and by hydrophobic interaction. From UV and H NMR
studies, it can be concluded that 2-PP is solubilized in protonated form in the micelles of both
cationic and anionic surfactants (CTAB and SDS) as shown in Scheme 6.
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
_
=
=
SDS/ CTAB
OH
_
H
_
_
_
N
_
_
_
_
OH
H N
2
N
_
_
_
N
Protonated 2-PP species
_
_
Water
_
_
_
_
Scheme 6. Solubilization of protonated 2-PP species in SDS/ CTAB micelles.
3.2.2.Micellar solubilization and reactant(s)-surfactant interactions: Co-catalytic activity
of SDS
From spectroscopic characterization of 2-PP-surfactant solutions, the role of SDS in 2-PP-SDS
systems for promotion of the micellar reaction could not be rationalized as both micellar systems
1
9

Green Chemistry
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exhibit excellent solubilization behavior for 2-PP as catalytically active species i.e., protonated
1
1a
2
-PP. In our previous study, we observed the co-catalytic activity of surfactant molecules
(CTAB) in micelles to activate the reacting molecules by favorable surfactant-reactant
interactions, which was found to be much supportive in the micellar reaction. In addition to
1
monitoring micellar solubilization of reaction components, H NMR can also be used for
studying the reaction reactant(s)-surfactant interactions in micelles. The salicylaldehyde
molecules may exist in two structural forms (SAL-I & SAL-II) depending upon the nature of
environment (Scheme 7): in SAL-I, the phenolic –OH group is in intermolecular hydrogen
bonding with solvent molecules (usually in a polar solvent) and in SAL-II, the phenolic –OH has
24
1
intramolecular hydrogen bonding with aldehyde group within the molecule. The H NMR
spectrum of salicylaldehyde in D O indicates the presence of SAL-I in surfactant free solution
2
showing an intense resonance signal for proton b at 9.54 ppm (Figure 4i). A weak signal at ~5.4
ppm can be assigned for proton b' of phenolic –OH group indicating the presence of SAL-II in
minor proportion. The signals for aromatic protons (c, d, e and f protons) of salicylaldehyde can
be seen in the range of 6.9 ppm to 7.8 ppm (4 signals; two doublets and two triplets; Figure 4i).
a
H
a
H
O
O b'
H
b
OH
f
f
H
H
O
e
H
c
H
e
H
c
H
d
H
d
H
SAL-I
SAL-II
Scheme 7. Different types of protons in SAL-I and SAL-II forms of salicylaldehyde.
2
0

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(v)
(iv)
(iii)
(ii)
a
b
e
d
f
c
b'
(i)
10.0
9.9
9.8
9.7
9.6
9.5
7.8
7.5
7.2
6.9 5.60
5.55
5.50
5.45
Chemical shift (ppm)
Chemical shift (ppm)
Chemical shift (ppm)
Figure 4. Chemical shifts for different protons of salicylaldehyde in D O and in CTAB
2
solutions of different concentrations [i. D
CTAB, v. 100 mM CTAB].
2
O, ii. 1 mM CTAB, iii. 25 mM CTAB, iv. 50 mM
(viii)
(vii)
(vi)
(v)
(iv)
(iii)
b''
(ii)
a
b
d
b'
f
e
c
(i)
10.0
9.5
7.5
Chemical shift(ppm)
7.0
5.60
5.55
5.50
5.45
Chemical shift (ppm)
Chemical shift (ppm)
Figure 5. Chemical shifts for different protons of salicylaldehyde in D
2
O and in SDS solutions
of different concentrations [i. D O, ii. 1 mM SDS, iii. 5 mM SDS, iv. 10 mM SDS, v. 15 mM
2
SDS, vi. 25 mM SDS, vii. 50 mM SDS, viii. 100 mM SDS].
2
1

Green Chemistry
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1
2
The H NMR spectra of pure SDS and CTAB in D O (25 mM) and their chemical shifts are
given in ESI (Figure S1 & S2; Table S4-S7). As compared to pure surfactants (SDS or CTAB;
at 25 mM), there was upfield shifting for the protons of both the surfactants in the presence of
reactants (see ESI; Table S6 & S7), which is probably due to the hydrophobic effect and
23
aromatic ring induced shifts effect of solubilized reactants. This indicates the existence of
solubilized reactants in CTAB and SDS micelles. However, the significantly higher upfield
shifting for the protons around the middle of the chain of SDS (see ESI; Table S6) reveals the
deeper penetration of reactant molecules (salicylaldehyde) in SDS micelles. The significant
upfield shifting for the protons near the head group of CTAB indicates the presence of reactant
1
molecules near the head group of CTAB micelles (see ESI; Table S7). The H NMR spectra of
salicylaldehyde in CTAB and SDS solutions (Figure 4 and 5) also show its solubilization and
interaction in the micelles. The remarkable spectral changes and shifting of different signals for
salicylaldehyde in even below CMC (Figure 5ii & 5iii) was noticed, which can be attributed to
the formation of salicylaldehyde-surfactant combined aggregations. Brinchi et al. reported the
acceleration of reactions in cationic surfactant solutions at or below CMC (in premicellar
solutions) due to either complexation of the substrate with surfactant monomers or pre-micelles
1
6b
or to substrate induced formation of micelles. The gradual upfield shifting of the signals of
salicylaldehyde (except a and b protons in CTAB solution) on increasing surfactant
concentration is indication of salicylaldehyde solubilization in both CTAB and SDS micelles.
The downfield shifting of signals a and b of salicylaldehyde with CTAB concentration may arise
from ionic interaction of aldehydic and phenolic –OH groups of salicylaldehyde with CTAB
1
1a
head group. On increasing CTAB concentration, the resonance signal b was observed to be
decreasing in intensity, which completely disappeared in 100 mM CTAB solution, and the
signal b' increased in intensity with upfield shifting. These spectral changes can be related to the
existence of salicylaldehyde molecules as SAL-II in CTAB micelles (hydrophobic core). In 100
2
2

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mM CTAB solution, the significant downfield shifting of a and b' indicates the localization of
salicylaldehyde molecules in polar part of micelles, i.e., Stern layer, interacting with CTAB head
11a
group through of carbonyl group. The gradual upfield shifting of signals for different protons
(b', c, d, e and f) in CTAB solutions with 1-50 mM concentration and then downfield shifting
(which is more significant for aldehydic proton) at 100 mM represents the movement of
salicylaldehyde molecules from core of micellar phase to micellar surface and its localization at
1
1a
micellar surface (Stern layer) at high surfactant concentration. In our previous study, we
proposed the localization of aldehyde molecules (benzaldehyde) at interface/ in Stern layer of
micellar phase in CTAB solution at high concentrations due to elongation of micelles and the
ionic interaction between aldehyde group and CTAB head group. In SDS solution, some
significant spectral changes such as disappearance of the signal b, and appearance of the signal
b' and a new signal b'' on increasing SDS concentration was observed (Figure 5). The new
upfield resonance signal b'' might have originated due to interaction of b' type proton of
phenolic –OH group of solubilized salicylaldehyde molecules with SDS head group (through
sulfate ion group) as shown in Scheme 8. The b'' type proton, interacting with sulfate group of
SDS would resonate at higher frequency due to shielding effect of electron rich (negatively
charged) sulfate group.
2
3

Green Chemistry
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4
.5
(a)
0
5mM
(b)
Inpurewater
In100mMSDS
Inaq.NaOH
3
.0
3.0
2.5
2.0
1.5
1.0
0.5
0.0
4.0
3.5
2
50mM
0 mM
2
5mM
50mM
00mM
50mM
3.0
2.5
2.5
250 mM
2.0
1.5
1.0
0.5
1
0
mM
2
2.0
0.0
300
350 400
Wavelength(nm)
450
0
5
1.5
mM
1
5mM
5mM
35mM
0mM
00mM
150mM
00mM
50mM
2
1.0
5
1
0.5
2
2
0.0
300
350 400
Wavelength(nm)
450
300
350
Wavelength(nm)
400
450
Figure 6. UV absorption spectra of salicylaldehyde in (a) CTAB and (b) SDS solutions (inset:
UV absorption spectra of salicylaldehyde in pure water, 100 mM SDS and 0.5 M NaOH
aqueous solutions; salicylaldehyde concentration: 0.8 mM).
The UV absorption spectra of salicylaldehyde in CTAB solutions (Figure 6a) indicate its
solubilization (localization) in micellar phase showing gradual increase in the peak intensity
(~324.5 nm) with surfactant concentration. Interestingly, the spectra of salicylaldehyde in SDS
solutions (Figure 6b) showed an additional band at higher wave length (~376.5 nm) on
1
increasing the surfactant concentration. This result supports H NMR result showing the
interaction of salicylaldehyde molecules solubilized in micelles with SDS molecules. The new
band was presumed to be originated from the interaction of salicylaldehyde through its hydroxyl
(
–OH group) hydrogen atom with head group of SDS molecules forming a phenolate type
species as shown in Scheme 8. This was confirmed from the presence of a similar band (at
376.5 nm) in UV spectrum of salicylaldehyde in aqueous NaOH solution (0.5 M) (Figure 6b;
~
inset), which will have phenolate ion (sodium phenolate) of salicylaldehyde. The phenolate ion
of salicylaldehyde can have electronic transition at significantly lower wave length. It was
observed that the salicylaldehyde-SDS solution (150-250 mM) resembles the color (yellow) of
aqueous NaOH solution of salicylaldehyde and the color intensity gradually increases as SDS
2
4

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concentration increases from 1 mM to 250 mM (Figure 7). From the spectroscopy studies, it can
be concluded that salicylaldehyde molecules are simply solubilized (as SAL-II) in CTAB
micelles, and in SDS micelles salicylaldehyde molecules are solubilized as their phenolate
species (Scheme 8) interacting with SDS head group.
+
δ
Hb"
Na
O
O
S
O
S
Na
−
O
δ
O
O
O
O
O
Hc
O
Ha
C12H23
C12H23
Hf
Hd
He
Scheme 8. Interactions between salicylaldehyde and SDS molecules in SDS micellar
solution.
Figure 7. Color of different solutions of salicylaldehyde in (i) aqueous NaOH, (ii) pure water,
(
iii) 1 mM SDS, (iv) 5 mM SDS, (v) 10 mM SDS, (vi) 15 mM SDS, (vii) 25 mM SDS, (viii) 35
mM SDS, (ix) 50 mM SDS, (x) 100 mM SDS, (xi) 150 mM SDS, (xii) 200 mM SDS and (xiii)
50 mM SDS [salicylaldehyde concentration in all the solutions was 0.8 mM].
2
2
5

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1
Similarly, H NMR spectra of DEM in CTAB and SDS solutions revealed its solubilization in
both CTAB and SDS micelles showing upfield shifting of resonance signals for different
protons of DEM (Figure 8 and 9). The slight shifting of different signals for DEM in dilute SDS
micellar solutions (below CMC; 9ii & 9iii) can be attributed to the formation of DEM-surfactant
combined micellar aggregates. Interestingly SDS micelles showed strong influence over
2
solubilized DEM; the signals for methylene protons (-CH -) of DEM were disappeared in
spectra on increasing SDS concentration (Figure 9). The disappearance of the signals for
methylene protons could be possible due to interaction of methylene protons (being acidic in
nature) of DEM with SDS head group (sulfate ion) of SDS molecules in micelles (Scheme 9),
which might have exchanged by deuterium ions in the D O solution. Similar results were also
2
obtained with EAA; the disappearance of its methylene protons in SDS solutions with increasing
concentration (see ESI, Figure S3). The disappearance of the methylene protons of both the
1
methylene active compounds was also observed in H NMR spectra of DEM and EAA in the
sodium sulfate solution (25 mM in D O; see ESI, Figure S4) proving that the sulfate group of
2
SDS is the site for the interaction with methylene protons.
a
b
(CO-O-CH
c
CH
2
2
3 2
-CH )
v
iv
iii
ii
b
a
c
i
4
.32
4.24
4.16
3.60
3.54
3.48
1.32
1.26
1.20
Chemical shift (ppm)
2
Figure 8. Chemical shifts for different protons of DEM in D O and in CTAB solutions of
different concentrations (i. D O, ii. 1 mM CTAB, iii. 25 mM CTAB, iv. 50 mM CTAB, v. 100
2
mM CTAB).
2
6

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a
b
c
viii
vii
CH
2
2 3 2
(CO-O-CH -CH )
vi
v
iv
iii
ii
i
a
c
b
4
.27
4.20
3.69
3.60
3.51
1.33
1.26
1.19
Chemical shift (ppm)
1
Figure 9. H NMR spectra of DEM in D O and in SDS solutions of different concentrations
2
[
(i) D O, (ii) 1 mM SDS, (iii) 5 mM SDS, (iv) 10 mM SDS, (v) 15 mM SDS, (vi) 25 mM
2
SDS, (vii) 50 mM SDS, (viii) 100 mM SDS].
OEt
OEt
H
OEt
OEt
Na
O
Na
O
−
δ
−
δ
O
S
O
O
O
C
H
O
Na
O
O
S
C
O
+δ
+δ
Na
O
+δ
H
Na
H
O
Na
O
S
O
S
O
O
S
O
S
O
O O
O
and/ or
O
O O
C H
2 23
1
C H
2 23
1
O
O
O
C
O
C H
1
C H
12
H
23
C H
12 23
2
23
12 23
Scheme 9. Interactions of DEM molecule with SDS molecules in SDS micellar solution.
2
7

Green Chemistry
Page 28 of 38
View Article Online
DOI: 10.1039/C5GC01966D
2
.0
5.0
4.5
Inwater
In200mMSDS
Inaq.NaOH
2
.0
(b)
(a)
0
5
4
.0
.5
3.0
.5
.0
.5
1.0
.5
.0
mM
5mM
5mM
35mM
0mM
00 mM
00mM
50mM
3
1
2
2
2
1.5
1.5
1.0
1
5
0
1
0
2
250
300
Wavelength(nm)
350
400
2
1.0
0
5
mM
15mM
5mM
5 mM
50 mM
00 mM
200mM
50mM
2
50 mM
2
2
50 mM
3
0.5
0.5
0
mM
1
0
mM
2
0.0
0.0
200
250
300
Wavelength(nm)
350
400
450
200
250
300
350
Wavelength(nm)
Figure 10. UV absorption spectra of EAA in (a) CTAB and (b) SDS solutions (inset: spectra of
EAA in pure water, 200 mM SDS and 0.5 M NaOH aqueous solutions; DEM concentration: 2.4
mM).
The UV absorption spectra of EAA (Figure 10; EAA was used because of its better UV
absorbance than DEM) confirms its solubilization in both types of micelles but strong
interaction with SDS micelles showing emergence of an additional broad band at higher wave
length with surfactant concentration. The interaction of the methylene group of EAA with SDS
head group (Scheme 9) will result to their enolate type species bonded (by ionic interaction)
with SDS molecules, which will cause the electronic transition at higher wave length. This was
confirmed by analyzing EAA in aqueous NaOH solution, which would form sodium salt of its
25
enolate ion. The UV absorption spectrum of this solution exhibits almost a similar band
(Figure 10b; inset) as there was a new band in the spectrum of EAA-SDS solution indicating the
possibility of the formation of enolate species in SDS solution as a result of the interaction.
1
From the H NMR and UV spectroscopy studies of catalyst-micellar and reactants-micellar
solutions, it was found that both 2-PP-SDS and 2-PP-CTAB micellar systems contain
solubilized 2-PP species (protonated form) and both the reactant molecules (salicylaldehyde
2
8

Page 29 of 38
Green Chemistry
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DOI: 10.1039/C5GC01966D
and DEM/ EAA) are solubilized in both CTAB and SDS micellar structures. However, SDS
micelles solubilize both the reactants in their active forms (i.e., as phenolate of salicylaldehyde
and enolate of DEM/ EAA) required for the reaction. The hydroxyl ions of protonated 2-PP
species solubilized in SDS micelles can easily remove the protons from thus solubilized
salicylaldehyde and DEM/ EAA molecules to produce phenolate and enolate reaction
intermediates, respectively. The phenolate and enolate intermediates react (aldol condensation
followed by transesterification) to form 3-substituted coumarin product. The solubilization of
reactant molecules by SDS micelles in their active forms is the major cause for higher activity of
2-PP-SDS micellar system than 2-PP-CTAB in this reaction. Thus, we found that in addition to
solubilization of the reactants and catalyst by SDS micelles, SDS molecules in micelles also
show co-catalytic activity to facilitate the reaction. The present study also discloses that SDS
micellar solution can be explored as an effective reaction medium for activation of phenolic
substrates and methylene active compounds in many reactions.
11a,11c
In our previous studies on NaOH-CTAB catalytic systems,
the activity of NaOH-CTAB
micellar solutions (i.e., substrate conversion) was observed to be increasing with surfactant
concentration (even up to 200 mM) and the highest activity was achieved at high surfactant
concentration (~150 mM) and with equivalent moles of NaOH. With 2-PP-SDS or 2-PP-CTAB,
the highest activity was observed at comparatively lesser surfactant concentration (25 mM and
15 mM, respectively; Figure 1) and at 10 mol% amount of 2-PP base. Above the optimum
surfactant concentration, the activity of 2-PP-micellar solutions decreases with surfactant
concentration (Figure 1), which may be due to decreased concentration of solubilized 2-PP
species in the micelles and/ or strong binding of 2-PP species and reactants in the micelles.
-
Contrary to 2-PP-SDS or 2-PP-CTAB, NaOH-CTAB system has free OH ions on the micellar
surface, which can be exchanged from one micelle to other micelle, and thus on increasing the
number of micelles (i.e., surfactant concentration) new micelles do not have deficiency of
2
9