Kinetic Study of the Pyridine-Catalyzed Selenolactonization of 4-Pentenoic Acid

Article abstract of DOI:10.1007/s10562-020-03107-0

Abstract: The kinetics and mechanism of the pyridine-catalyzed cyclofunctionalization of 4-pentenoic acid by means of PhSeX (X = Cl, Br) have been investigated spectrophotometrically, under pseudo-first order reaction conditions. The influence of the reac

Full text of DOI:10.1007/s10562-020-03107-0

Catalysis Letters
https://doi.org/10.1007/s10562-020-03107-0
Kinetic Study of the Pyridine‑Catalyzed Selenolactonization
of 4‑Pentenoic Acid
1
2
2
Marina D. Kostić · Kristina Mihajlović · Vera M. Divac
Received: 1 November 2019 / Accepted: 15 January 2020
©
Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
The kinetics and mechanism of the pyridine-catalyzed cyclofunctionalization of 4-pentenoic acid by means of PhSeX (X =Cl,
Br) have been investigated spectrophotometrically, under pseudo-ꢀrst order reaction conditions. The inꢁuence of the reaction
temperature, the type of cyclization reagent and used catalyst on the reaction rate and mechanism was examined. The obtained
data have showed that rate constants go on increasing as the temperatures go up and with use of PhSeCl as reagent. Also, the
reaction rate is directly depended on the type of the catalyst used—stronger bases with higher tendency for hydrogen bond
formation (DN) are promoting reaction in more eꢂcient way.
Graphic Abstract
O
O
PhSeX (X = Cl, Br)
HO
O
SePh
N
catalyst
Keywords Kinetics · Lactone · Pyridine · Selenium
1
Introduction
Gama lactones present a unique class of organic compounds
due to their presence as key structural units in numerous bio-
logically active molecules, as well as due to their potential
to serve as building blocks for the total synthesis of natu-
ral products [1]. The gamma-lactone motif has been pre-
sent in more than one third of natural products. Moreover,
its presence in the core of the fungal, marine or bacterial
sourced-biomolecules is distinctive for the wide range of
expressed biological activities [2–4]. Therefore, modern
science is setting an imperative in front of organic chem-
ists for development of new and improvement of existing
methodologies for the selective synthesis of gamma lactone
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-020-03107-0) contains
supplementary material, which is available to authorized users.
*
Marina D. Kostić
mrvovic@kg.ac.rs
1
Department of Science, Institute for Information
Technologies, University of Kragujevac, Jovana Cvijića bb,
Kragujevac, Serbia
2
Department of Chemistry, Faculty of Science, University
of Kragujevac, Radoja Domanovica 12, Kragujevac, Serbia
Vol.:(0
1
123456789)
3

M. D. Kostić et al.
Scheme 1 Mechanistic survey of the selenolactonization of 4-pentenoic acid. The eꢃect of the pyridine as catalyst in selonalactonization
molecules. Under these circumstances, a lot of eꢃective
methods for the lactone ring have arisen in literature [5–10].
One of the commonly utilized approaches is the cyclofunc-
tionalization of the alkenoic acids [11–15]. Depending on
the substrate substitution pattern, type of reagent used or
presence of external catalyst, a great structural variety of
the target lactone molecules can be achieved. The applica-
tion of the organoselenium-based molecules as reagents for
cyclofunctionalization of alkenoic acids has many advan-
tages which are reꢁected in high regioselectivity, acceptable
yields of lactone products and easy manipulation with the
organoselenium part in side chain of lactone ring [16–18].
From these reasons, organoselenium-induced selenolactoni-
zations have been utilized in total synthesis of the natural
products containing lactone-ring in structure. Despite the
synthetic utility of the organoselenium-based lactonization
of unsaturated acids, the literature survey still suꢃers from
the moderate number of mechanistic reports for these reac-
tions. The examination of the reaction transformations at the
mechanistic level is important due to the possibility for the
process optimization and improvement in the term of yields,
selectivity and reaction rates.
Our group has been involved in long-term kinetic studies
of the related cyclofunctionalization of unsaturated alco-
hols by organoselenium reagents in the presence of diꢃerent
Lewis bases and acids as catalysts [19–27]. In an extension
of our previous studies and on the base of our earlier ꢀnd-
ings, herein we are presenting results of mechanistic and
kinetic study of the cyclofunctionalization of the 4-pentenoic
acid by PhSeCl and PhSeBr, in the presence of the pyridine
as catalysts.
1
3

Kinetic Study of the Pyridine-Catalyzed Selenolactonization of 4-Pentenoic Acid
2
Results and Discussion
which can be captured by the COOH group to afford
desired lactone (Scheme 1).
The reaction between 4-pentenoic acid 1 and PhSeX
For more detailed insight into kinetic and mechanistic
aspects of the pyridine-mediated phenylselenolactoniza-
tion of the 4-pentenoic acid, we performed kinetic investi-
gation using conventional UV–Vis method [30]. The study
has involved the investigation of the inꢁuence of the tem-
perature variation, as well as variation of the cyclization
reagent (PhSeCl or PhSeBr) on the reaction rates. In addi-
tion, activation parameters of the reaction—entropy and
enthalpy of activation have been determined.
(
X = Cl, Br) is resulting in formation of basic example of
seleno-functionalized gamma-lactone 2 (Scheme 1). The
typical reaction mechanism of these reactions involves: a)
electrophilic addition of the electrophilic reagent PhSeX
(
X = Cl, Br) on double bond of 4-pentenoic acid 1, which
has formation of positively charged selenonium cation I
as intermediate for result. This step activates C–C bond
for the subsequent nucleophilic attack of the oxygen from
COOH group and formation of protonated salt II. Finally,
fast removal of the proton attached to the oxygen atom
releases the ꢀnal lactone product 2. Due to the presence of
halide anion from PhSeX reagent (Cl or Br), the reaction
can also follow second pathway and formation of addi-
tion product 3 can occur. In order to prevent side reac-
tion, as well as to increase nucleophilicity of the oxygen
in carboxylic group, the presence of catalyst is necessary.
It is well known that the bases (such as pyridine, trieth-
The reactions were processed under pseudo-ꢀrst order
conditions, at three diꢃerent temperatures (288, 298 and
308 K), in THF as solvent. The temperature of all reacting
solutions was controlled at ± 0.1 °C. Rate constants have
been obtained by spectrophotometrically monitoring of the
decay of the absorbance of the 4-pentenoic acid at suit-
able wavelength (Fig. 1). Kinetic runs were performed by
adding adequate amounts of reagent and catalyst solution
to a 4-pentenoic acid solution contained in spectrometer
cuvettes that has been allowed to reach temperature equi-
librium with the spectrometer cell compartment. The data
obtained suited to the pseudo-ꢀrst order rate law well and
ylamine, NaHCO ) in this type of chemical transforma-
3
tions could prevent prolonged reaction time and excess of
reagent used. This feature can be attributed to the diꢃer-
ent ways in which base could act in selenolactonization
reaction: bases have ability to abstract hydrogen from the
carboxylic group and, on that way, to increase nucleophilic
power of oxygen from COOH group for the attack on the
activated C–C bond in seleniranium cation (Scheme 1).
The newest researches [28, 29] have indicated that Lewis
bases increase electrophilicity of the weak electrophilic
PhSeX reagents, by the coordination of Lewis base donor
to PhSeX electrophile and net polarization of the obtained
Lewis acid–base adduct. The result of this process is for-
mation of the highly electrophilic selenonium cation,
Pyridine + PhSeCl
0
.4
.35
.3
0
0
0
0
288 K
298 K
308 K
0
.25
0.2
.15
0
.1
.05
0
0
0.1
0.2
1
0.3
0.4
0.5
0.6
03[4-Pentenoic acid]
Pyridine + PhSeBr
0
0
0
0
.0035
.003
.0025
.002
.0015
.001
0
2
88 K
298 K
08 K
3
0
0
.0005
0
0
0.001
0.002
0.003
0.004
0.005
0.006
1
03[4-Pentenoic acid]
Fig. 1 Kinetic traces for the reaction between PhSeCl and 4-pente-
Fig. 2 Observed rate constants for the pseudo-ꢀrst order reaction as
noic acid, in the presence of pyridine, at 308 K (λ=250 nm)
a function of 4-pentenoic acid concentration at diꢃerent temperatures
1
3

M. D. Kostić et al.
Table 1 Rate constants and activation parameters for the phenylselenolactonization of 4-pentenoic acid with PhSeCl and PhSeBr in the presence
of pyridine
T (K)
PhSeCl+Pyridine
PhSeBr+Pyridine
k2 (M−1 s−1
)
k1 (s−1)
∆H (kJM−1)
#
∆S (JK M−1
#
−1
)
k2 (M−1 s−1
)
k1 (s−1)
∆H (kJM−1)
#
∆S (JK M−1
)
#
−1
288
298
308
0.42± 0.03
0.52± 0.06
0.70± 0.02
/
/
/
16± 2
− 210± 7
0.29± 0.01
0.36± 0.02
0.45± 0.03
/
/
/
14± 1
− 223± 2
Table 2 Comparison between rate constants for the reaction of 4-pentenoic acid selenocyclofuntionalization by means of PhSeX (X=Cl, Br), in
the presence of pyridine and trimethylamine as catalysts
T
PhSeCl+Pyridine
PhSeCl+Et N[25]
PhSeBr+Pyridine
PhSeBr+Et N[25]
3
3
3
2
2
08
98
88
0.70± 0.02
0.52± 0.06
0.42± 0.03
1.36± 0.06
0.92± 0.04
0.64± 0.02
0.45± 0.03
0.36± 0.02
0.29± 0.01
0.84± 0.02
0.6± 0.03
0.44± 0.02
observed pseudo-ꢀrst order constants are determined by
demonstrated the rate constants almost two times higher
in the case of triethylamine. This can be explained by the
fact that triethylamine is stronger base than pyridine (pKa
least squares ꢀtting of an exponential function.
Observed pseudo-first order constants, k
, are
obsd
described by the following equation, where the values
(Et N)=10.75; pKa (Py)=5.25), and also has higher donor
3
of the k constants correspond to the rate of the forward
number (DN (Et N)=61; DN (Py)=33.1). These two fea-
2
3
reaction—cyclofunctionalization, while the k constants
tures are responsible for the activation of the electrophilic
PhSeX reagent toward formation of the selenonium cation,
or for the activation of the COOH group for the nuclephilic
attack on the selenonium cation.
1
describe the eꢃect of the side reaction (addition of the
electrophile organoselenium reagent to the double bond,
formation of the product 3 in Scheme 1). k values are
2
calculated from the slopes of the plots k
vs. 4-pentenoic
By the ꢀtting values for rate constants to the Eyring equa-
tion, the activation parameters have been obtained (Fig. 3).
Their values are presented in Table 1. Variation in the rea-
gent type and catalyst used is not inꢁuencing the reaction
mechanism, and the negative values for entropy of activation
obsd
acid concentration, while k values have been derived from
1
the intercepts in the same plots (Fig. 2, Table 1).
ꢀ
ꢁ
k
= k + k 4 − pentenoic acid
2
obsd
1
values are supporting S 2 mechanism of the OH nucleo-
N
philic attack on the selenonium cation.
Kinetic parameters derived from this equation (Table 1)
ꢀ
ꢁ
ꢂ
ꢀ
ꢁ
ꢃ
have demonstrated dependence of the reaction rate on the
reaction temperature, as well as dependence on electrophilic
source used. In all investigated reactions, reaction rates
increase with an increase in reaction temperature. In addi-
tion, all tested cases have showed increasing tendency for
rate constants for PhSeCl as reagent, in comparison to the
PhSeBr where rate of reactions was lower. The eꢃect of the
k
ΔH≠
k
ΔS≠
2
2
ln
= −
+ ln
+
T
RT
T
R
-
6.5
side reaction, which is described by the k constants, is neg-
1
0
.0032 0.00325 0.0033 0.00335 0.0034 0.00345 0.0035
ligible in comparison to the forward reaction and therefore,
these values are not showed in Table 1. Comparison of the
rate constants obtained in this study with analogues values
for the reactions where triethylamine was used as catalyst
-6.6
6.7
-6.8
-1
T (K)
-
[
26] (Table 2), has revealed that triethylamine has stronger
-6.9
potential for rate increasing than pyridine. Although these
two catalysts are acting in quite similar way in synthetic
investigation (the presence of both catalysts are increasing
yields of the lactone up to 100%), kinetic investigation has
-7
Fig. 3 Eyring equation plot for the reaction between 4-pentenoic acid
and PhSeBr in the presence of pyridine
1
3

Kinetic Study of the Pyridine-Catalyzed Selenolactonization of 4-Pentenoic Acid
3
Conclusion
All kinetic runs were ꢀtted as single exponential func-
tion. The obtained pseudo-ꢀrst order rate constants present
average value from two to ꢀve independent kinetic runs
using Microsoft Excel and Origin 6.1.
The kinetics and the mechanism of the pyridine-catalyzed
selenolactonization of the 4-pentenoic acid have been
reviewed. The achieved results in the kinetic study have
revealed that reaction rates depend on the reaction tempera-
ture (increasing rate constants with an increase in tempera-
ture), as well as on the type of the organoselenium reagent
used (PhSeCl is more reactive than PhSeBr). In addition, this
study has conꢀrmed tight relation between catalyst basicity
and ability for formation of hydrogen bond and values of
rate constants. Stronger bases with better ability for proton
abstraction (DN) are promoting reaction in more eꢂcient
way. The variation in reagent and catalyst used is not inꢁu-
encing change in reaction mechanism.
Acknowledgements This work was funded by the Ministry of Edu-
cation, Science and Technological Development of the Republic of
Serbia (Grant: 172011). This research is part of the thematic multi-
disciplinary network SeS Redox and Catalysis.
Compliance with Ethical Standards
Conflict of interest The authors declare that they have no conꢁict
of interest.
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