Kinetics of the reaction of phenyl picrates with phenoxide ions in water. Concerted or stepwise?

Article abstract of DOI:10.1002/poc.3172

A kinetic study is reported of the exchange reactions of substituted phenoxide ions with some ring-substituted 2,4,6-trinitrophenyl ethers in water. The βronsted diagrams formed by plotting log k, where k is the second-order rate constant for reaction, ve

Full text of DOI:10.1002/poc.3172

Special Issue Article
Received: 2 April 2013,
Revised: 13 May 2013,
Accepted: 11 June 2013,
Published online in Wiley Online Library: 27 August 2013
(wileyonlinelibrary.com) DOI: 10.1002/poc.3172
Kinetics of the reaction of phenyl picrates with
phenoxide ions in water. Concerted or
stepwise?†‡
Michael R. Cramptona* and Ian A. Robothama
A kinetic study is reported of the exchange reactions of substituted phenoxide ions with some ring-substituted
2,4,6-trinitrophenyl ethers in water. The βrønsted diagrams formed by plotting log k, where k is the second-order
rate constant for reaction, versus pKa show a distinct change in slope when ΔpKa = 0 (ΔpKa being the difference in
pKa values of the leaving group and nucleophile). This is consistent with a two-step process involving a discrete
σ-adduct intermediate rather than a concerted process. From the measured β values for forward and reverse
processes, the overall effective charge map has been constructed. Copyright © 2013 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: βrønsted equation; effective charge map; intermediates; nitro-compounds; nucleophilic aromatic substitution
There is considerable evidence that most reactions proceeding by the
SNAr mechanism of nucleophilic aromatic substitution involve an inter-
mediate sitting in a potential energy well. The two-step Addition–Elimi-
nation mechanism postulated by Bunnett[1] is well documented in the
literature.[2] The successful identification by NMR of intermediates such
as (1), known as Meisenheimer Complexes or σ-adducts, on the substitu-
tion pathway offers significant support to the proposed mechanism.[3–5]
Also, detailed kinetic studies of leaving group effects and base catalysis
can only be understood in terms of the presence of intermediates.[6]
is replaced by a transition state.[9] A linear βrønsted plot of
log k, where k represents the second-order rate constant for
displacement, versus pKa values was observed. The pKa values
are for the parent phenols from which the nucleophiles are
derived. The linearity of the plot extended to pKa values both
above and below that of the leaving group, 4-nitrophenol,
and this linearity is evidence for a concerted process.
In fact, there is good evidence that several nucleophilic substi-
tutions on esters and other acyl compounds, including the
reaction of 4-nitrophenyl acetate with aryloxide ions,[10] are con-
certed one-step processes.[11,12] However, the reaction of
4-nitrophenoxy derivatives of Fischer carbenes with aryloxide
ions has been shown to proceed by a stepwise mechanism.[13]
Here, we report a kinetic study of the reactions, in aqueous
solution, of some ring-substituted 2,4,6-trinitrophenyl ethers,
2, with a series of substituted phenoxide ions, 3. The
βrønsted diagrams formed when plotting log k versus pKa
show a distinct change in slope when ΔpKa = 0 (ΔpKa being
the difference in pKa values of the leaving group and nucleo-
phile). This is consistent with a two-step process involving a
discrete σ-adduct intermediate 4 as shown in Eqn (2). From
the measured β value for both forward and reverse processes,
the effective charges have been determined, and the overall
effective charge map constructed.[14]
An alternative mechanism for nucleophilic aromatic substitution is
one that involves a concerted pathway in which there is a single transi-
tion state, i.e. transformation from a two-step to a one-step process,
without the presence of an intermediate. Evidence for this pathway
comes from kinetic studies of the displacement of the 4-nitrophenoxide
ion from 2-(4-nitrophenoxy)-4,6-dimethoxy-1,3,5-triazine by substituted
phenoxide ions in aqueous solution,[7,8] Eqn (1). Here, the possible inter-
mediate is regarded as being so unstable that it
* Correspondence to: Michael R. Crampton, Chemistry Department, Durham
University, Durham, DH1 3LE, UK
E-mail: m.r.crampton@durham.ac.uk
†
This article is published in Journal of Physical Organic Chemistry as a special
issue: In Memoriam, edited by Michael Page (University of Huddersfield, Chem-
istry, Queensgate, Huddersfield, HD1 3DH,United Kingdom).
‡
This paper is in memory of Professor Rory More O'Ferrall, a fine chemist and a
gentleman.
a M. R. Crampton, I. A. Robotham
Chemistry Department, Durham University, Durham, DH1 3LE, UK
J. Phys. Org. Chem. 2013, 26 1084–1089
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KINETICS OF THE REACTION OF PHENYL PICRATES WITH PHENOXIDE IONS IN WATER.A CONCERTED OR STEPWISE?
RESULTS AND DISCUSSION
The rate constants for reaction of various ring-substituted
phenoxide ions, in phenol/phenoxide buffers, with five different
phenyl-2,4,6-trinitrophenyl ethers, 2(a–e), were measured in aque-
ous solution at 25 °C. The addition of dioxan (5–10%, v/v) was re-
quired to aid solubility, but the dioxan proportion was kept
constant for each substrate. A series of buffer solutions was pre-
pared with various phenoxide concentrations but at constant pH,
and with ionic strength maintained at 0.1 mol dm–3 with sodium
chloride. Reactions were initiated by addition of the substrate solu-
tion to a prepared sample in the thermostatted cell compartment
of a conventional spectrophotometer. For faster reactions,
stopped-flow spectrophotometry was used, and for very slow
reactions, a sampling technique (experimental section) was
used. Reactions were monitored by the appearance of the
appropriate leaving group, e.g. 4-nitrophenoxide from 2(a),
at a wavelength between 360 and 400 nm. Typical data are
in Fig. 6 (supplementary information). There was no evidence
for the accumulation of either intermediates, or of other
adducts not on the reaction pathway[2,4,5] during these
processes. All kinetic measurements were made under
first-order conditions with the buffer concentration
(PhOH/PhO–) in large excess of the substrate concentration
(2 × 10–5 mol dm–3). A typical trace is shown in Fig. 7
Figure 1. Dependence of kobs on phenoxide concentration for the reactions of
2(a) with phenoxide, 4-bromophenoxide and 2-chloro-4-methylphenoxide ions
(supplementary information). First-order rate constants, kobs
,
were calculated with correlation coefficients 0.992–0.999 by
standard techniques.
At constant pH, values of kobs were found to increase linearly
with the phenoxide concentration as shown in Fig. 1. The
gradients of these plots give the values of the second-order
rate constants, ks, for the forward reaction shown in Eqn (2).
Generally, buffer ratios PhOH/PhO– were kept close to 1:1.
Changing the buffer ratio to 2:1 did not affect the values
obtained for ks, within experimental error, indicating that
interference from hydroxide ions was not a problem. Data for
reactions of 2(a), leaving group[15] pKa 7.12, are in Table 1.
Table 1. Kinetic dataa for the reactions of 2(a) with substituted phenoxide ions at 25 °C
b
Substituents in 3
pKa
ks/dm3 mol–1 s–1
pH
[3]/10–2 mol dm–3
kobs/s–1
0.3–7.5
0.07–1.5
0.17–1.1
0.4–1.0
0.2–1.0
0.1–0.3
(3–9) × 10–2
(1–3) × 10ꢀ2
(2–4) × 10–3
(2–7) × 10–4
(5–12) × 10–4
(1–3) × 10–5
1 × 10–5
4-MeO
10.3
9.81
370
73
71
52
44
2
1
1
1
1
10.19
10.0
9.6
0.1–2.0
0.05–1.5
0.5–3.0
0.7–2.0
0.5–2.0
0.7–2.0
0.7–2.0
0.7–2.0
0.7–2.0
0.3–1.8
0.3–1.5
10–30
4-H
4-Hc
9.81
9.26
9.21
8.68
8.32
7.80
7.22
6.93
6.58
5.41
5.33
4-Cl
4-Br
2-Cl, 4-Me
2-Cl
4-CN
9.37
9.21
9.40
9.20
7.92
7.15
7.23
8.03
6.33
5.91
13.6 0.2
4.5 0.4
1.28 0.01
2-CN
0.22 7 × 10–3
(3.6 0.5) × 10–2
(5.7 0.8) × 10–2
(8.3 2) × 10–5
< 4.0 × 10–5
2,3,5-trifluoro
2,3,5-trichloro
2,3,5,6-tetrafluorod
pentafluorod
10–30
aMeasurements at 400 nm
bFrom ref. 8 and 16.
cApproximately 2:1 buffer ratio [PhOH]:[PhO–].
dMeasured using the sampling method.
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M. R. CRAMPTON AND I. A. ROBOTHAM
Table 2. Kinetic dataa for the reaction of 2(b) with substituted phenoxide ions at 25 °C
ks/dm3 mol–1 s–1
pH
[3]/10–2 mol dm–3
kobs/s–1
b
Substituents in 3
pKa
4-MeO
4-H
2-Cl, 4-Me
2-Cl
2-CN
10.3
9.81
1280 20
10.04
9.9
0.1–0.5
0.2–1.4
0.7–2.0
0.7–2.0
0.7–1.7
0.3–1.5
0.5–2.5
1–8
0.6–3.5
0.5–1.5
260
76
1
1
8.68
8.32
7.22
6.58
5.41
9.26
8.68
6.92
8.22
6.33
23.5 0.7
3.10 0.05
1.20 0.08
0.015 0.001
(2–5) × 10ꢀ1
(2–5) × 10–2
(2–19) × 10–3
(1–4) × 10–4
2,3,5-Trichloro
2,3,5,6-Tetrafluoro
aMeasurements at 400 nm.
bFrom ref. 8 and 16.
Results for the reaction of 2(b) with seven ring-substituted
phenoxide ions are in Table 2.
βrønsted plots for these reactions and for the related reac-
tions of 2(c) are shown in Fig. 2. For compounds 2(a) and 2(c),
the plots show two intersecting linear correlations consistent
with a two-step mechanism involving a σ-adduct intermediate, 4.
As predicted, the break in linearity occurs at the pKa of
the leaving group,[15] 7.12 for 4-nitrophenol and 8.19 for
3-nitrophenol. For 2(b) the pKa value[15] of 5.4 of the leaving
group, 3,4-dinitrophenol, is below that of most of the
accessible phenol nucleophiles so that a precise break in the
plot is not observed.
(b)
(a)
(c)
Figure 2. (i) and 2(ii) βrønsted plots for the reaction of 2(a), (b) and (c) with phenoxide ions. The vertical arrows correspond to the pKa values of the
appropriate leaving group
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KINETICS OF THE REACTION OF PHENYL PICRATES WITH PHENOXIDE IONS IN WATER.A CONCERTED OR STEPWISE?
Table 3. Summary of β values
Substrate
Nucleophile
Various
β1
β1+β2–β
Δβ
–β
ꢀ2
ꢀ1
2(a)
0.93 0.08
1.88 0.08
0.95
-
2(b)
Various
0.83 0.06
-
-
-
2(c)
Various
0.89 0.10
1.98 0.06
1.09
-
Various
Various
phenoxide
4-chlorophenoxide
-
-
-
-
-
-
0.18 0.03
0.21 0.04
The reverse process
k1:k2
ꢀ1 þ k2
It is possible to obtain additional information by measuring rate
constants for reaction of single phenolic nucleophiles with a
range of ring-substituted phenyl 2,4,6-trinitrophenyl ethers.
Measurements were made for reaction of phenoxide ions in
phenol/phenoxide buffers at constant pH with substrates 2(a),
(b),(d),(e). The wavelengths chosen were appropriate for the
anionic form of the leaving group. For solubility reasons, all
measurements were made in 15% (v/v) dioxan-water and with
ionic strength maintained at 0.1 mol dm–3. Under first-order
conditions, plots of kobs versus phenoxide concentration, Fig. 3,
were linear, and the slopes gave values for k–s, the second-
order rate constants for the reverse reaction. A second set of
results was obtained for reactions with 4-chlorophenoxide ions
in buffers with 4-chlorophenol.
ks ¼
(3)
k
ks ¼ k1
ks ¼ K1k2
(4)
(5)
(6)
(7)
log ks ¼ β1pKa þ C1
log ks ¼ ðβ1 þ β2–β–1ÞpKa þ C12
relationships in Eqns (6) and (7). Values obtained, from Fig. 2,
for the βrønsted exponents are in Table 3.
Ideally, for the reverse process, it would be appropriate to study
reactions with the leaving groups used in the forward reaction, i.e.
4-nitrophenoxide, 3-nitrophenoxide and 3,4-dinitrophenoxide.
Due to the poor reactivity of these species acting as nucleophiles,
this was not possible. The approach used was to measure rate
constants with the more reactive nucleophiles phenoxide and
4-chlorophenoxide. The linear plots obtained in Fig. 4 show that
here the condition of Eqn (8) applies leading to the βrønsted
relation in Eqn (9).
βrønsted plots of log k–s versus the pKa values[15,17] of the
leaving groups are shown in Fig. 4. As expected, straight lines,
with no break, are obtained since the pKa values associated with
the nucleophiles phenol, pKa 9.81 and 4-chlorophenol, pKa 9.26
are higher than those of the leaving groups.
Kinetic analysis
The results are consistent for the reaction given in Eqn (2)
with (4) being treated as a steady-state intermediate. This
leads to Eqn (3). The two limiting conditions corresponding
to rate-limiting nucleophilic attack, k2 > kꢀ1, and rate-limiting
expulsion of the leaving group, kꢀ1 > k2, lead, respectively, to
Eqns (4) and (5) with the related βrønsted
k–s ¼ k–2
log k–s ¼ β–2pKa þ C2
(8)
(9)
Values for βꢀ2, from Fig. 4, are in Table 3. Using the information
obtained, the effective charge map[14,18–20] shown in Fig. 5
Figure 4. βrønsted plots for reactions of 2(a), (b), (d), (e) with
phenoxide and 4-chlorophenoxide ions. pKa values are for the
leaving groups
Figure 3. Variation of kobs with phenoxide concentration in the
reactions with 2(a), (b), (d) and (e) in phenol/phenoxide buffers
J. Phys. Org. Chem. 2013, 26 1084–1089
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M. R. CRAMPTON AND I. A. ROBOTHAM
Figure 5. Effective charge map for reaction of 3'-nitrophenyl-2,4,6-trinitrophenyl ether and for the associated transition states
involving displacement of the 3-nitrophenoxide ion may be
constructed. Effective charge distribution for the two transition
states is included. The values determined for Leffler's α-parameter,
Eqn (10), in this case 0.50 0.06, are expected to be identical for
formation of an intermediate from reactant
which is consistent with a substantial difference in effective
charge on the reacting oxygen atoms on going from the
intermediate to the transition states corresponding to the k
ꢀ2
and k2 processes. A value of zero is expected for Δβ for a
concerted process.
The value of 0.85 obtained for β1 indicates that bond
formation is well advanced in the transition state for formation
of the intermediate. That this value is higher than those,
0.5–0.7, normally associated[2] with nucleophilic substitu-
tions may beattributed to the strongly electron-withdrawing
effect of the trinitrobenzene ring. Values of β close to or
higher than one have been attributed to the intervention of
an SET pathway[21,22] for substitution but there is no evidence
that this applies here.
β1
βeqð1Þ
βꢀ2
α ¼
¼ ꢀ
(10)
βeqð2Þ
or product in a symmetrical reaction.
The significant amount of effective charge, –2.42, distributed
within the trinitro-substituted moiety of the intermediate may
be attributed to the strongly electron withdrawal, effect of the
nitro-groups and their excellent solvation in water. For compari-
son, Williams and co-workers have reported an effective charge
of ꢀ1.42 within the triazine ring of the intermediate 5 formed
from reaction of substituted pyridines and the 1'(2,6-diphenoxy-
EXPERIMENTAL
Phenyl 2,4,6-trinitrophenyl ethers 2(a)–(e) were prepared by the reaction
of picryl chloride with the appropriate phenoxide in water. The relevant
phenol (0.013 mol. equiv) with sodium hydroxide (0.01 mol, 0.4 g) in
water (15 cm3) was stirred for 15 min to give a solution after which picryl
chloride (0.008 mol, 2 g) was gradually added over 30 min. The mixture
was stirred and heated at 45 °C for 8 h, or in the case of 2(b) for 24 h.
After cooling, a further 30 cm3 of water was added to dissolve any
remaining sodium chloride or picric acid impurities. The precipitate
produced was separated by filtration, washed with ethanol and
recrystallised from ethanol. 1H NMR data, measured with a Varian Gemini
400 instrument, and melting points are in Table 4.
1,3,5-triazin-2-yl) pyridinium cation in water. Evidence for a
stepwise process is confirmed by the value of Δβ, 1.05 0.05,
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KINETICS OF THE REACTION OF PHENYL PICRATES WITH PHENOXIDE IONS IN WATER.A CONCERTED OR STEPWISE?
Table 4. Data for phenyl 2,4,6-trinitrophenyl ethers
Compound
m.p.
163
lit m.p.
157[23]
1H NMR results in DMSO-d6
2(a)
9.32(s) 8.30(d, J = 9.0 Hz)
7.35(d, J = 9.0 Hz)
9.37(s) 8.40(d, J = 9.1 Hz)
8.07(d, J = 2.9 Hz)
7.70(dd, J = 9.1 and 2.9 Hz)
9.29(s) 8.05(dd, J = 8.4 and 3.0 Hz)
7.90(t, J = 3.0 Hz)
2(b)
2(c)
203
172
202[24]
174[25]
7.71(t, J = 8.4 Hz)
7.62(dd, J = 8.4 and 3.0 Hz)
9.29(s) 9.94(s)
7.94(d, J = 8.8 Hz)
7.30(d, J = 8.8 Hz)
9.28(s) 9.95(s)
2(d)
2(e)
127
65
128[26]
7.74(d, J = 7.8 Hz)
7.64(t, J = 7.8 Hz)
7.50(m)
concentrations present in the phenol/phenoxide buffers, reactions with
hydroxide will not interfere significantly.
Phenols were the purest available commercial specimens. Buffer solu-
tions were prepared by addition of measured quantities of carbonate free
sodium hydroxide solution to the appropriate phenol. pH values were
measured using a Jenway 3020 pH meter (accurate to 0.02 pH units).
UV/visible spectra were measured using Shimadzu UV-2101 PC or Perkin-
Elmer Lambda 2/12 instruments, which were also used for kinetic measure-
ments. For the faster reactions, either an Applied Photophysics SX-17 MV
or a Hi-Tech SF-3 stopped-flow spectrometer was used.
Kinetic measurements were made by following the appearance of the
appropriate leaving group in its anionic form. For phenols with very low
reactivity, such as tetra- or penta-halogenated phenols, measurements
were made at pH values lower than the pKa value of the leaving group.
Here, a sampling technique was used where 1 cm3 of reaction solution
was removed and added to 1 cm3 of sodium carbonate solution in a
cuvette. Absorbances were measured immediately, before further
reaction could occur. This technique restores the pH to a value above
that of the pKa of the leaving group ensuring conversion to the anionic
form. These reactions were typically followed over several days.
All measurements were made at 25° and with ionic strength
maintained at 0.1 mol dm–3 with sodium chloride.
REFERENCES
[1] J. F. Bunnett, R. E. Zahler, Chem. Rev. 1951, 49, 273.
[2] F. Terrier, Nucleophilic Aromatic Displacement, V.C.H., N.Y., 1991.
[3] C. A. Fyfe, S. W. H. Damji, A. Koll, J. Am. Chem. Soc. 1979, 101, 951.
[4] M. R. Crampton, Adv. Phys. Org. Chem. 1969, 7, 211.
[5] M. J. Strauss, Chem. Rev. 1970, 70, 667.
[6] C. F. Bernasconi, MTP Int. Rev. Sci. Org. Chem. Ser 1 1973, 3, 33.
[7] A. H. M. Renfrew, J. A. Taylor, J. M. J. Whitmore, A. Williams, J. Chem.
Soc., Perkin Trans, 2 1993, 1703.
[8] A. H. M. Renfrew, D. Rettura, J. A. Taylor, J. M. J. Whitmore, A. Williams,
J. Am. Chem. Soc. 1995, 117, 5484.
[9] W. P. Jencks, Acc. Chem. Res. 1980, 13, 161.
[10] S. Ba-Saif, A. K. Luthra, A. Williams, J. Am. Chem. Soc. 1987, 109, 6362.
[11] S. Ba-Saif, A. K. Luthra, A. Williams, J. Am. Chem. Soc. 1989, 111, 2647.
[12] D. Stefanidis, S. Cho, S. Dhe-Pagenon, W. P. Jencks, J. Am. Chem. Soc.
1993, 115, 1650.
[13] C. F. Bernasconi, M. E. Z. Michoff, R. H. de Rossi, A. M. Granados,
J. Org. Chem. 2007, 72, 1285.
[14] M. Page and A. Williams, Organic and Bio-organic Mechanisms,
Longman, Harlow, Essex, UK 1997.
[15] E. P. Serjeant, B. Dempsey, IUPAC data series 23, Pergamon Press,
Oxford, UK 1979.
[16] D. Stefanidis, S. Cho, S. Dhe-Paganon, W. P. Jencks, J. Am. Chem. Soc.
1993, 115, 1650.
[17] I.-H. Um, J.-Y. Lee, S.-H. Ko, S.-K. Bae, J. Org. Chem. 2006, 71, 5800.
[18] A. Williams, Acc. Chem. Res. 1984, 17, 425.
[19] A. Williams, Free Energy Relationships in Organic and Bio Organic
Chemistry, RSC: London 2003.
[20] N. R. Cullum, A. H. M. Renfrew, D. Rettura, J. A. Taylor, J. M. J. Whitmore,
A. M. Williams, J. Am. Chem. Soc. 1978, 100, 5530.
[21] F. Terrier, M. Mokhtari, R. Goumont, J.-C. Halle, E. Buncel, Org.
Biomol. Chem. 2003, 1, 1757.
[22] I. Imaoui, T. Boubaker, R, Goumont, Int. J. Chem. Kinet. 2013, 45, 152.
[23] C. Willgerodt, E. Huetlin, Chem. Ber. 1884, 17, 1766.
[24] O. Banjoko, C. Ezeani, J. Chem. Soc., Perkin Trans. 2 1986, 4, 531.
[25] K. Okon, Rocz. Chem. 1958, 32, 213.
Reactions with hydroxide ions
In order to confirm that interferences from reaction of substrates with
hydroxide ions were minimal, rate constants were measured for the
direct reaction of 2(a) and 2(b) with sodium hydroxide in water. For 2
(a), the UV/visible spectra of the products showed a maximum at 396
nm and were consistent with the formation of picrate ions and
4-nitrophenoxide. There was no evidence for the formation of intermedi-
ates in spectroscopically observable concentrations. Nor was there
evidence, at the low hydroxide concentration (1–5 × 10–3 mol dm–3
)
used, for hydroxide attack at the 3-position which has been observed
in related systems.[27] Hence, the reaction is interpreted as
rate-determining nucleophilic attack by hydroxide. First-order rate con-
stants, kobs, were measured with [OH–] > > [2a] or [2b] and were found
to increase linearly with hydroxide concentrations. Values obtained for
the second-order rate constant, kOH, were 3.5 dm3 mol–1 s–1 for 2(a) in
5% (v/v) dioxan-water and 3.9 dm3 mol–1 s–1 for 2(b) in 15% (v/v)
dioxan-water. These values indicate that at the very low hydroxide
[26] K. H. Slotta, K. H. Soremba, Chem. Ber. 1935, 68, 2059.
[27] R. Chamberlin, M. R. Crampton, R. L. Knight, J. Chem. Res. (s)
1993, 444.
J. Phys. Org. Chem. 2013, 26 1084–1089
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