Synthesis of dimeric pyridinium bromide under silica supported approach

Article abstract of DOI:10.1080/00397911.2020.1733611

Synthesis of dimeric substituted ester derivative of pyridinium salt with flexible linker units under conventional/silica supported approach. Solid-phase approach is much superior to the conventional method due to nontoxic, solvent free, easy work up proc

Full text of DOI:10.1080/00397911.2020.1733611

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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Synthesis of dimeric pyridinium bromide under
silica supported approach
Ramalingam Tamilarasan, Sadaiyan Govindaraj & Kilivelu Ganesan
To cite this article: Ramalingam Tamilarasan, Sadaiyan Govindaraj & Kilivelu Ganesan
(2020): Synthesis of dimeric pyridinium bromide under silica supported approach, Synthetic
Communications, DOI: 10.1080/00397911.2020.1733611
To link to this article: https://doi.org/10.1080/00397911.2020.1733611
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https://doi.org/10.1080/00397911.2020.1733611
Synthesis of dimeric pyridinium bromide under silica
supported approach
Ramalingam Tamilarasana, Sadaiyan Govindarajb, and Kilivelu Ganesanb
aDepartment of Chemistry, Vel Tech Multi Tech Dr. Rangarajan Dr. Sakunthala Engineering College,
b
Chennai, India; PG & Research Department of Chemistry, Presidency College (Autonomous),
Chennai, India
ABSTRACT
ARTICLE HISTORY
Received 2 December 2019
Synthesis of dimeric substituted ester derivative of pyridinium salt
with flexible linker units under conventional/silica supported
approach. Solid-phase approach is much superior to the conven-
tional method due to nontoxic, solvent free, easy work up proced-
ure, and lesser reaction period. Synthesized dimeric ester derivative
of pyridinium salts is showed excellent catalytic response for the
preparation of oxizinone derivatives under conventional/approach.
KEYWORDS
Anion exchange; dimeric
ester derivative; optimum
concentration; oxazinone;
solid phase
GRAPHICAL ABSTRACT
Water insoluble
organic reactant
Water soluble
Zwitter ion
Introduction
Ionic liquids consist of an organic cation (pyridinium, pyrrolidinium, imidazolium) and
inorganic or organic anions which shows ionic conductivity, high polarizing nature,
non-volatility, higher chemical, and thermal stability.[1] Ionic liquids exhibit a number
of biological applications such as an adhesive, antifouling reagent, antiseptic, biocide,
and disinfectant.[2–5] Pyridinium containing amide-based poly (ionic liquids) are used
to calculate the interaction and separation of CO2 and methane gas by theoretical
model.[6] Various concentration of anthracene-based dimeric substituted pyridinium
chloride is acted as fluorescence sensing probe and showed significant response with
H2PO4À ion.[7] Brønsted acid-surfactant mixed catalyst acted as a potential catalyst to
enhance one-pot three components Mannich reaction (BrÀ, HSO4À, H2PO4À, TosÀ),
CONTACT Kilivelu Ganesan
kiliveluganesan@yahoo.co.in
PG & Research Department of Chemistry, Presidency
College (Autonomous), Chennai, India.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

2
R. TAMILARASAN ET AL.
various counter anions containing ionic liquids are used. Among these anions, the TosÀ
ion showed better catalytic response than the others due to bulkier.[8] Multicomponent
one-pot reaction has been attracted much interest in the area of synthetic organic chem-
istry to generate more derivatives in combinatorial drug discovery.[9,10] b-Amino car-
bonyl derivatives are prepared from one-pot multicomponent reaction which is
catalyzed by acid–ionic polymer bearing imidazolium trifluoromethane sulfonate.[11]
Didecyldimethyl ammonium cation with different organic anion are showed dual bio-
logical responses such as antimicrobial and sweetener.[12] Herein, we wish to report the
synthesis of ester derivative of pyridinium salt under the conventional/greener approach
and its catalytic application.
Results and discussion
Synthesis of ester derivative pyridine 1 from pyridine 2, 6-dicarbonyl dichloride (1.0
equiv.; 1.47 Â 10À2 mmol) and 2-naphthol (2.05 equiv.; 3.014 Â 10À2 mmol) along with
anhydrous K2CO3 (2.0 equiv.; 3.014 Â 10À2 mmol) in the presence of 30 mL of dry DMF
at 60 ꢀC for 5 min. to give ester derivative pyridine 1 in 98% yield. N-alkylation is car-
ried out by treating 2.05 equiv. of ester derivative pyridine 1 (2.673 Â 10À3 mmol) and
1, 5-dibromopentane/m-xylenedibromide (1.00 equiv.; 1.304 Â 10À3 mmol) in the pres-
ence of 20 mL dry CH3CN under refluxing condition for 13–16 h to give N-alkylated
substituted pyridinium bromide 2/3 in quantitative yield.
Same N-alkylation reaction is tried under solvent free silica supported reaction using
Muffle furnace at 100 ꢀC. Solid-phase silica-supported approach is much superior to
conventional due to its lesser reaction period, higher yield, solvent-free, and environ-
mental friendly approach. Solvent-free silica-supported reactions are nearly 15 times
faster than the conventional method. M-Xylenedibromide reacts much faster than 1, 5-
dibromopentane during N-alkylation reaction. In general, ionic liquids will show
different physical and chemical properties based on counter anions. So anion exchange
reaction is very important to study their various physical and chemical properties.
Anion exchange reaction is carried out with different counter anion containing inor-
ganic salts such as KPF6, NaBF4, and LiCF3SO3 in 20 mL of deionized water under
room temperature with stirring for 2 h to give anion exchange products of 2/3(b–d) in
80–94% of yield (Scheme 1).
Catalytic activity
Flexible dimeric pyridinium salts are prepared from easily available starting materials
under conventional and solid-phase solvent-free Muffle furnace method. One-pot multi-
component reaction is tried in the presence of various concentrations of our catalyst
with/without solvent (Scheme 2).
Substituted dimeric pyridinium bromide 3 is showed excellent catalytic activity for
the preparation of oxizinone derivative than the others. To optimize the catalyst con-
centration of m-xylene core moiety containing dimeric pyridinium bromide, the reac-
tions are repeated with various concentrations such as 1.8135 Â 10À2 mmol,
3.627 Â 10À2 mmol, and 5.440 Â 10À2 mmol for one-pot preparation of substituted

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3
O
O
O
O
N
Cl
Cl
O
O
O
N
CR
N
O
O
O
O
K2CO3/
DMF
Br-
Br-
Di
O
O
O
+
bromide:
O
N
MR
Br-
HO
N
600C, 5min,
98%
O
O
O
O
O
N
O
O
2
Br-
3
1
MX /H2O, rt,
2h, 94-96%
MX= KPF6,
NaBF4;
Dibromide:
LiCF3SO3
O
O
O
O
Br
N
Br
Br
O
O
N
Br
X-
O
X-
O
O
O
X-
N
Conventional route (CR): CH3CN:MeOH, 80 0C,
ref., 13-16 h, 86-88%;
O
O
O
Muffle furnace route (MR): 100 0C, 40-60 min., 90-92%;
O
N
O
O
X-
2/ 3(b-d)
Scheme 1. Synthesis of substituted ester derivative of pyridinium salts under multiple approach.
CHO
CA
O
OH
O
catalyst
H2N
NH2
N
H
O
R
R
SSA
R= -OH, -OCH3 , -H, -p-NO2 ,- m-NO2
4(a-e)
Scheme 2. Synthesis of substituted oxazinone derivatives under multiple approach. Reagent and con-
ditions: Conventional approach (CA): CH3CN/ 3a, ref, 03–120 min, 80–96%; Solid supported approach
(SSA): Muffule furnace, 100 ꢀC, 20–45 min., 84–98%
oxazinone derivatives. While increasing the catalyst concentration from
5.440 Â 10À2 mmol into 7.254 Â 10À2 mmol, there is no appreciable change in the per-
centage of yield and reaction time.
Plausible mechanism for preparation of oxazinone using flexible dimeric pyridinium
bromide

4
R. TAMILARASAN ET AL.
Various substituted oxazinone derivatives are prepared under conventional/solid-
phase approach; reactions are repeated with different concentrations. The results are
summarized in Tables 1 and 2; MgFe2O4 and SiO2–SO3H catalyst are used to prepare
benzthioxazione under microwave-assisted solvent-free approach. Reaction time and
percentage of yield are appreciable but expensive catalyst as well as base sensitive cata-
lyst.[13] Oxazinone derivatives are prepared under 200 mg of Amberlite IRA-400 Cl cata-
lyst which required more than 2 h for reaction completion.[14] Whereas only 60 mg of
flexible/m-xylene bridged dimeric pyridinium salt under silica-supported approach
required for just 20 min. for completion. Hence catalyst is potential due to its shorter
reaction time, solvent-free higher yield, and environmental friendliness.
We have recycled upon fourth cycles and used for the preparation of 1, 2-dihydro-1-
(4-hydroxyphenyl) naphtho [1, 2-e][1, 3]oxazin-3-one 4a under same reaction condi-
tion; even after fourth cycles the product obtained was as observed in excellent to good
yield which is shown in Table 3.
Conclusions
Dimeric ester derivative of pyridinium salts are prepared under conventional/silica-sup-
ported Muffle furnace reaction condition. Muffle furnace approach is nearly fifteen
times faster than the conventional method. We have tried with various concentrations
of our catalyst for the preparation of oxazine-3-one derivatives. Bromide counter anion
containing dimeric ester derivative of pyridinium salts showed excellent catalytic

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R. TAMILARASAN ET AL.

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7
Table 3. Study of catalyst re-useable efficiency up to fourth cycles.
1st cycle
2nd cycle
3rd cycle
4th cycle
CA
SSA
CA
SSA
CA
SSA
CA
SSA
S. No
Catalyst
T
Y
T
Y
T
Y
T
Y
T
Y
T
Y
T
Y
T
Y
1
2
3
4
3a
3b
3c
3d
40
50
60
65
93
92
91
90
16
20
25
08
95
93
92
90
40
50
60
65
89
88
86
86
16
20
25
08
92
90
88
88
40
50
60
65
89
88
86
86
16
20
25
08
92
90
88
88
40
50
60
65
93
92
91
90
16
20
25
08
90
89
86
86
T: Time in minutes; Y: percentage of yield.
response than the others; due to bigger size of anion which is away from cation so
effective binding is possible. Hence, bromide counter anion containing dimeric ester
derivative of pyridinium cation could perform as a better Lewis character. We have pre-
pared two different linker units containing dimeric pyridinium salt. m-Xylene bridged
dimeric pyridinium salts are showed excellent catalytic response than the flexible pent-
ane moiety due to more flexibility which shows lesser Lewis character. We observed
that 5.440 Â 10À2 mmol concentration of m-xylene bridged dimeric pyridinium bromide
3a is the optimum catalytic concentration for the preparation of oxazinone derivatives.
General experimental conditions
Preparation of bis (2-naphthyl) pyridine-2, 6-dicarboxylate 1: 3.0 g of pyridine-2, 6-
dicarboyl dichloride (1.47 Â 10À2 mmol; 1.0 equiv.) is mixed with 4.3 g of naphthalen-2-
ol (3.014 Â 10À2 mmol; 2.0 equiv.) and 4.1 g of K2CO3 dissolved (3.014 Â 10À2 mmol; 2.0
equiv.) in the presence of 50 mL of N, N-dimethylformamide (DMF) at room tempera-
ture stirring for 5 min. to give compound 1 in quantitative yield. Yield: 3.4 g, (98%);
1
Liquid; H NMR: (400 MHz, DMSO-d6) d: 6.43–6.94 (m, 8H), 7.32 (s, 2H), 7.65–7.87
(m, 4H), 8.42–8.58 (m, 3H); 13C NMR: (100 MHz, DMSO-d6) d: 117.8, 124.0, 126.6,
126.9, 128.2, 129.3, 131.1,134.9, 140.0, 147.9 and 156.5; MS (FAB): m/z 419.43; Anal.
Calcd for: C27H17NO4: C: 77.32: H: 4.09: N: 3.34; Found: C: 77.26: H: 3.94: N: 3.26.
General procedure for N-alkylation reaction: Bis (2-naphthyl) pyridine-2, 6-dicar-
boxylate 1 (2.328 Â 10À3 mmol; 2.05 equiv.) is treated with 1, 5-dibromopentane/m-xyle-
nedibromide (1.304 Â 10À3 mmol; 1.0 equiv.) in the presence of 20 mL dry acetonitrile
under refluxing condition for 13–16 h to give N-alkylated product of compound 2a/3a.
Bis-2, 6-(dicarboyl) bis (naphthalene-2-yl naphthalene-3-yl dipyridinium 1, 5 (pent-
ane) bromide 2a: Yield: 1.27 g (86%); Liquid; 1H NMR: (400 MHz, DMSO-d6) d:
2.50–2.58 (q, 2H), 2.80–2.92 (q, 4H), 4.40–4.48 (t, 4H), 6.22–6.75 (m, 16H), 7.12 (s,
4H), 7.23–7.37 (m, 8H), 7.40–8.64 (m, 6H); 13C NMR: (100 MHz, DMSO-d6) d: 26.6,
31.7, 35.3, 117.8, 124.0, 126.6, 126.9, 128.2, 129.3, 131.1, 134.9, 140.0, 147.9 and 156.5;
MS (FAB): m/z 1068.8; Anal. Calcd for: C59H44Br2N2O8: C: 66.30: H: 4.15: N: 2.62;
Found: C: 66.24: H: 4.08: N: 2.58
General procedure for anion exchange reaction was carried out from flexible dimeric pyri-
dinium bromide 2a/3a (2.65 Â 10À4 mmol; 1.0 equiv.) is treated with various counter anion
containing inorganic salt such as NaBF4, K4PF6, and LiCF3SO3 (5.44 Â 10À4 mmol; 2.05
equiv.) is dissolved in 20mL of deionized water at room temperature with stirring for 2 h to
give anion exchange product of compound 2/3(b–d) in 90–97% yield. Metallic bromide and

8
R. TAMILARASAN ET AL.
flexible dimeric pyridinium salts are soluble in water, so separation is not easier. Under these
circumstance, Soxhlet extraction is used in for purification dry THF for 1 h refluxtion.
Anion exchanged reaction is confirmed by aqueous AgNO3 solution.
Bis-2, 6-(dicarboyl) bis (naphthalene-2-yl naphthalene-3-yl dipyridinium 1, 5 (pent-
1
ane) hexafluorophosphate 2 b: Yield: 0.28 g, (91%); Liquid; H NMR: (400 MHz, DMSO-
d6) d: 2.48–2.56 (q, 2H), 2.78–2.90 (q, 4H), 4.38–4.46 (t, 4H), 6.20–6.73 (m, 16H), 7.10
(s, 4H), 7.21–7.35 (m, 8H), 7.38–8.62 (m, 6H); 13C NMR: (100 MHz, DMSO-d6) d: 26.4,
31.5, 35.1, 117.6, 123.8, 126.4, 126.7, 128.0, 129.1, 130.0, 134.7, 139.8, 147.7 and 156.3;
MS (FAB): m/z 1198.92; Anal. Calcd for: C59H44F12N2O8P2: C: 59.11: H: 3.70: N: 2.34;
Found: C: 59.05: H: 3.66: N: 2.28.
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