Reactions of 1,ω-bis(2-bromopyridinium)alkanes with hydroxide ion in aqueous solutions

Article abstract of DOI:10.1002/(SICI)1099-1395(199801)11:1<25::AID-POC962>3.0.CO;2-E

The reaction of OH^- ion with 1,ω-bis(2-bromopyridinium)alkanes, where the reaction centers are separated by a varying number of methylene groups, was investigated to model the increased velocity of OH^- attack on premicellar aggregated N-alkylpyridinium compounds. 1,ω-Bis(2-bromopyridinium)aikanes (RPBr) [R = propane (I), butane (II), pentane (III), hexane (IV) and octane (V)] were synthesized and characterized by standard procedures. The kinetics of I-V with OH^- ion fitted two consecutive first-order reactions. The intermediate products, 1-(2-pyridone)-ω-(2-bromopyridinium)alkane, and also the final products 1,ω-bis(2-pyridone)alkanes, were isolated. Deuterium isotope effects, activation parameters and salt effects on the reaction rates suggest that OH^- attack is rate limiting and there is a through-space acceleration of the initial attack due to the proximity of the positive charges. These results place an upper limit of 20-fold for the electrostatic acceleration in OH^- attack in premicellar aggregates.

Full text of DOI:10.1002/(SICI)1099-1395(199801)11:1<25::AID-POC962>3.0.CO;2-E

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)
Reactions of 1,v-bis(2-bromopyridinium)alkanes with
hydroxide ion in aqueous solutions
1
2
1
1
3
Carmen Fernandez, Vicente G. Toscano, Hernan Chaimovich, Mario J. Politi * and Noboru Hioka
1
Departamento de Bioqu Âõ mica, Instituto de Qu õÂ mica da Universidade de S aÄ o Paulo, S aÄ o Paulo, SP, Brazil
Departamento de Qu õÂ mica Fundamental, Instituto de Qu õÂ mica da Universidade de S aÄ o Paulo, S aÄ o Paulo, SP, Brazil
Departamento de Qu õ mica, Funda cË aÄ o Universidade de Maring a , Maring a , Pr, Brazil
2
3
Received 18 September 1996; revised 17 February 1997; accepted 18 April 1997
�
ABSTRACT: The reaction of OH ion with 1,o-bis(2-bromopyridinium)alkanes, where the reaction centers are
�
separated by a varying number of methylene groups, was investigated to model the increased velocity of OH attack
on premicellar aggregated N-alkylpyridinium compounds. 1,o-Bis(2-bromopyridinium)alkanes (RPBr) [R = propane
(
I), butane (II), pentane (III), hexane (IV) and octane (V)] were synthesized and characterized by standard procedures.
�
The kinetics of I–V with OH ion fitted two consecutive first-order reactions. The intermediate products, 1-(2-
pyridone)-o-(2-bromopyridinium)alkane, and also the final products 1,o-bis(2-pyridone)alkanes, were isolated.
�
Deuterium isotope effects, activation parameters and salt effects on the reaction rates suggest that OH attack is rate
limiting and there is a through-space acceleration of the initial attack due to the proximity of the positive charges.
�
These results place an upper limit of 20-fold for the electrostatic acceleration in OH attack in premicellar aggregates.

1998 John Wiley & Sons, Ltd.
KEYWORDS: 1,o-bis(2-bromopyridinium)alkanes; hydroxide ion
4
INTRODUCTION
only 10 times higher than that in water. The reaction
2
product in the micelle, however, is exclusively pyridone.
In view of the above, we postulated that rate increase, and
preferred formation of pyridone observed for the reaction
of HPCN with OH below the CMC, are due to the
formation of premicellar aggregates of HPCN.
Aggregation often modifies, sometimes profoundly,
the mechanism or rate of thermal reactions.
supramolecular aggregate, such as a micelle formed by a
positively charged substrates, rate increases for reactions
with negatively charged ions (counterions), such as OH ,
arises from hydroxide ion concentration at the inter-
Surface electrostatic effects may also modify
the relative energy of initial and transition states in the
Below the CMC, however, the
size of aggregates is a matter of debate, although in some
systems detergent dimers have been demonstrated.
�
Reactions of OH with 4-cyano-N-alkylpyridinium ions
(RPCN) produce the corresponding pyridones (P) and
�
amides (A), by nucleophilic attack at either the CN group
or at C-4 of the pyridinium ring. For a series of RCPNs,
with R varying from methyl to dodecyl, the first-order
1
,2
2
�
5–12
rate constants for alkaline hydrolysis (k ), in excess OH ,
In a
�
3
are independent of RPCN concentration up to 1 Â 10
M
2
substrate. For 4-cyano-N-hexadecylpyridinium (HPCN),
however, the values of k and the P/A ratios increase with
�
�
6
2
[
HPCN] from concentrations as low as 1 Â 10 M.
HPCN is a detergent and its critical micelle concentration
CMC), measured by conductivity or fluorescence
11,12
face.
(
�
3
12,13
quenching, is ca 1 Â 10 M, well above the concentra-
surface of micelles.
�
tion where the reaction rate and products for OH ion
2
2,14–19
attack change with concentration. HPCN, and also other
RPCNs with R >butyl, are incorporated in hexadecyl-
Investigation of reaction rates in a detergent dimer should
contribute to our understanding of kinetic effects
observed in the premicellar region. However, the results
are difficult to interpret because the distribution of
aggregated species is unknown, and in dynamic equili-
brium, and the isolation of kinetic contributions of a
unique aggregate demands numerous assumptions and
complex fitting procedures.
2
,3
trimethylammonium halide (HTAX) micelles.
The
�
reaction rate of micellar-incorporated RPCN with OH
is orders of magnitude faster than the reaction in aqueous
2
,3
solution. As for many other bimolecular reactions, the
calculated second-order rate constant in the micelle is
*
Correspondence to: M. J. Politi, Departamento de Bioqu ´ı mica,
Instituto de Qu ´ı mica da Universidade de S a˜ o Paulo, S a˜ o Paulo, SP,
Brazil.
E-mail: mjpoliti@usp.br
Contract/grant sponsor: CNPq; Contract/grant sponsor: FAPESP;
Contract/grant sponsor: CAPES; Contract/grant sponsor: FINEP.
A simple model for a detergent dimer is a molecule
containing reactive groups linked by methylene spacers
of different lengths. Hydroxide ion attack on biscyano-
pyridiniums produces two intermediates and at least three

1998 John Wiley & Sons, Ltd.
CCC 0894–3230/98/010025–06 $17.50

2
6
C. FERNANDEZ ET AL.
and investigated the effect of the distance between the
pyridinium groups on reaction rates.
EXPERIMENTAL
Acetonitrile, 2-bromopyridine, 1,3-dibromopropane, 1,4-
dibromobutane, 1,5-dibromopentane, 1,6-dibromohex-
ane and 1,8-dibromooctane (Aldrich) were distilled
before use. All other reagents were of analytical grade
or better. Deionized, doubly glass-distilled water was
used throughout.
The bis(2-bromopyridinium)alkanes were synthesized
from the reaction of 2-bromopyridine with the corre-
sponding dibromoalkane. The reflux times were 13 h
Scheme 1
21
for 1,3-bis(2-bromopyridinium)propane dibromide (I),
1
4 h for 1,4-bis(2-bromopyridinium)butane dibromide
products; hence, to focus attention on the effect of the
distance between the two positive centers of the dimer on
the reaction rate, it is desirable to examine the reactivity
of compounds exhibiting simpler reaction pathways. The
(II), 20 h for 1,5-bis(2-bromopyridinium)pentane dibro-
mide (III), 60 h for 1,6-bis(2-bromopyridinium)hexane
dibromide (IV) and 120 h for 1,8-(2-bromopyridinium)-
octane dibromide (V). The products were recrystallized
twice from ethanol and vacuum dried at room tempera-
ture. Melting points (°C) and elemental analyses (%)
were as follows: I, m.p. 239–241, C, H, N exp. 28.19,
�
reaction of 2-bromo-N-alkylpyridiniums with OH
20
produces solely (the corresponding) 2-pyridone. In
�
the present study, we examined the reaction of OH ion
with a series of 1,!-(2-bromopyridinium)alkanes (RPBr)
3
.25, 5.05 and found 28.73, 3.08, 4.03; II, m.p. 256–258,
1
13
Table 1. UV, H NMR and C NMR of RPBR, bispyridones (RPP) and of the intermediate compound (RPBrP) for R = propane (XI)
a
ꢀmax (nm)
�
1
� 1
1
b
13
b
Compound
(e, l mol cm
H NMR
C NMR
RPBr (I)
277 (16 000)
2.47–2.63 (q, 2H)
28.65, 58.75
127.23, 134.71
138.24, 146.71
147.31
4
7
8
8
.81 (t, 4H)
.83–7.93 (m, 2H)
.22 (d, 4H)
.88 (d, 2H)
RPP (VI)
RPBr (V)
296 (11 200)
1.67–1.78 (m, 2H)
27.63, 47.15
109.06, 118.71
138.26, 141.81
163.35
25.0, 27.56
28.77, 62.94
126.75, 134.41
137.76, 145.82
147.02
3
6
7
.64 (t, 4H)
.11–6.22 (m, 4H)
.18–7.26 (m, 4H)
277.5 (15 600)
1.11 (m, 8H)
1
4
7
8
8
.69–1.76 (m, 4H)
.5 (t, 4H)
.7–7.78 (m, 2H)
.07 (d, 4H)
.71 (d, 2H)
RPP (X)
296
11 000)
3.31 (m, 4H)
4.24 (m, 4H)
24.93, 27.56
27.88, 50.09
109.01, 118.55
138.84, 141.76
163.64
(
4
6
9
.67 (m, 4H)
.96 (t, 4H)
.5–9.62 (m, 4H)
1
0.63–10.66 (m, 4H)
RPBrP (XI)
277 (8000)
96 (5600)
1.82 (q, 1H)
2.02 (q, 1H)
27.41, 28.34
47.27, 59.67
2
3.02–4.13 (m, 4H)
6.14–6.24 (m, 3H)
7.07–7.36 (m, 4H)
8.01–8.08 (m, 1H)
109.39, 118.95
127.05, 134.51
138.39, 141.94
142.24, 146.29
146.89, 164.48
a
ꢀ
max = absorption wavelength maxima.
b
Chemical shifts in ppm using TMS as the standard.

1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)

REDUCTION OF PYRIDINIUMALKANES WITH HYDROXIDE ION
27
Figure 1. Spectral time dependence for the alkaline hydrolysis of 1,3-bis(2-bromopyridinium) propane dibromide (I). Conditions:
�
3
� 5
[
NaOH] = 5 Â 10 M; [I] = 2 Â 10 M; temperature = 25°C. The time between the scans is 30 s
C, H, N exp. 31.61,3.03, 5.26 and found 30.86, 3.1, 4.88;
III, m.p. 207–209, C, H, N exp. 33.00, 3.32, 5.13 and
found 32.74, 3.36, 4.56; IV, m.p. 232–233, C, H, N exp.
assigned to the central methylene group of XI (Table 1).
The deshielding of the pyridinium protons indicates
partial stabilization of the positive charge of the ring.
This effect can be attributed to a conformation in which
both rings are in proximity. Preliminary energy mini-
mization calculations suggest the existence of a local
minimum where both rings are in proximity, as opposed
to RPBr where the central chain is fully extended. The
NMR data are in full agreement with the proposed
structure.
3
1
4
4.32, 3.60, 5.00 and found 34.44, 3.49, 4.78; V, m.p.
78–180, C, H, N exp. 36.77, 4.11, 4.76 and found 35.91,
2
2
.14, 4.49. The results of bromide titration were within
experimental error. Proton and carbon NMR spectra were
2
3
in accord with the structure. For I–V the molar
absorbances of the pyridinium substrates at 277 and
2
96 nm were 16 000 Æ 150 and 400 Æ 100, respec-
2
3
tively.
Reaction kinetics were followed at 296 nm in excess
�
The reaction products, isolated after complete reaction
OH at 25°C in a Beckman Model 70 spectrophotometer.
�
1
of I–V with OH , were isolated and characterized by H
1
3
and C NMR and UV spectrometry. All data were
consistent with the formation of the expected bispyridone
2
0
(Scheme 1).
RESULTS AND DISCUSSION
The intermediate 1-(2-pyridone)-3-(bromopyridi-
�
nium)propane (XI) was isolated in good yield from a
reaction mixture containing I. Aliquots of a reaction
The final products from the reaction of I and V with OH
ion, isolated in 90% yield from scaled-up reaction
mixtures, were the corresponding 1,!-bis(2-pyridone)-
alkanes (Scheme 1). The UV and NMR spectra of 1,3-
bis(2-pyridone)propane (VI) and 1,8-bis(2-pyridone)-
octane (X) were consistent with the proposed structures
�
mixture of I and OH , withdrawn at convenient times,
were acidified with 5 M acid and separated by thin-layer
23,24
chromatography (TLC) (0.5 M NaBr in methanol).
Compound XI was isolated by preparative TLC of a
1
13
23
scaled-up reaction mixture. The H and C NMR (D O)
(Table 1). The final products from the reaction of II–IV
with OH were not isolated, but the UV spectra were
2
�
and UV spectra were consistent with the structure shown
in Scheme 1. The multiplets between ꢁ1.82 and 2.02 were
those expected (not shown).

1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)

2
8
C. FERNANDEZ ET AL.
Figure 2. Experimental and simulation absorbance changes (ꢀ= 296 nm) for the alkaline hydrolysis of 1,3-bis(2-
bromopyridinium) propane dibromide (I). Conditions: (&) experimental, hydrogencarbonate buffer concentration = 20 mM,
�
5
� 5
� 3 � 1
� 4 � 1
s , P = 0.1834,
pH = 10.3, [I] = 1.7 Â 10 M; (solid line) simulation, [I] = 1.7 Â 10 M, k = 1.5 Â 10
s
, k = 1.5 Â 10
1
2
Q = 0.092, R = � 0.062 [see equation (1)]
�
The kinetics of the reaction of I–V with OH ion,
exemplified in Fig. 1 was followed spectrophotometri-
cally. The spectra of the reaction mixture of compounds
Several two-step reaction pathways yield kinetic fits to
25
equation (1). One particular reaction pathway, fast
�
OH attack on RPBr yielding a half-reacted pyridone,
�
�
I–V with OH exhibited an isosbestic point at 288 nm
followed by a slower OH attack on the intermediate, is
(
(
Fig. 1). First-order analysis of the change in absorbance
at 277 or 296 nm) with time did not fit the experimental
consistent with both the kinetic and structural data for this
reaction.
2
5
data. The variation of absorbance (Abs) with time (t)
This reaction pathway can be represented as
fitted the following equation (Fig. 2):
k1
k2
A�!B�!C
Abs ˆ P � Q expꢀ� Ft† ‡ R expꢀ� Gt†
ꢀ1†
where, A, B and C are the initial RPBr, intermediate
product and final pyridone, respectively (Scheme 1). In
where P, Q, F, R, and G are the fitting parameters.
�
Table 2. Rate constants for the reaction of compounds I±V with OH ion
�
1
3 a
pH
k (s  10 )
I
II
III
IV
V
1
1
1
1
1
1
1
1
1
0.3
k1
k2
k1
k2
k1
k2
k1
k2
k1
k2
k1
k2
k1
k2
k1
k2
k1
k2
1.74
0.19
2.85
0.33
6.27
0.74
11.3
1.47
47.3
0.74
0.12
0.97
0.19
2.35
0.47
4.15
0.85
17.6
3.01
32.1
5.76
54.9
0.47
0.1
0.27
0.07
0.44
0.13
1.00
0.32
1.79
0.58
6.90
1.68
13.3
3.58
23.5
6.66
50.5
0.16
0.05
0.26
0.09
0.72
0.27
1.07
0.47
4.02
1.39
10.1
3.21
14
5.37
31
0.6
1.0
1.3
1.8
2.1
2.3
2.7
3.0
0.56
0.14
1.37
0.37
2.22
0.65
10.3
2.22
17.6
4.3
33.8
7.85
78
22.3
115
34.2
4.9
87.8
9.34
154
16.4
425
47.9
620
73
10
122
27.3
208
43.2
18.1
81.2
28.4
13.1
83.5
26.4
a
�
1 2
k and k are the rate constants corresponding to the attack of OH ion on the substrate and half-reacted intermediate (Scheme 1). They were
calculated by a computer fit of the absorbance–time data with equation (1).

1998 John Wiley & Sons, Ltd. JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)

REDUCTION OF PYRIDINIUMALKANES WITH HYDROXIDE ION
29
�
Table 3. Second-order rate constants for the reaction of OH ion with N-ethyl-2-bromopyridinium (NEBP), compounds I±V (k )
12
and their respective intermediates (k )
22
Compound
a
Rate constant
NEBP
I
II
III
IV
V
�
�
1
� 1
� 1
k12 (l mol
k22 (l mol
s
s
)
)
0.4
—
7.0 Æ 0.8
2.6 Æ 0.5
1.5 Æ 0.4
1.06 Æ 0.2
0.7 Æ 0.1
1
0.8 Æ 0.1
0.5 Æ 0.06
0.4 Æ 0.06
0.31 Æ 0.04
0.25 Æ 0.02
a
�
Second-order rate constant for the reaction of NEBP with OH from Ref. 20.
Table 4. Secondary isotope effect of D O on the rate of
reaction of I with OD
The pH dependence of the rate constants for the two
kinetic transients (Scheme 1), obtained by computer
fitting of the data using equation (2), are presented in
Table 2. The slopes of the log k versus pH plots were
2
�
�
1
� 1
k1 (s
)
k2 (s )
a
a
NaOH/H O
0.11
0.13
0.011
0.013
2
1.0 Æ 0.02 for both k1 and k , indicating that both
2
NaOD/D O
�
2
reactions are first order in OH ion over this pH range.
a
�
�
The second-order rate constants for the reactions of I–V,
[
OD ] = [OH ] = 0.01 M.
�
and their respective intermediates, with OH (k and k ,
12
22
Scheme 1) are presented in Table 3. The second-order
�
�
excess or constant (buffer) OH , k and k are the
rate constant for OH attack on N-ethyl-2-bromo-
1
2
�
20
pseudo-first-order rate constants k [OH] and k [OH ],
pyridinium (NEBP) is included for comparison.
2
1
22
respectively. The corresponding equation describing the
variation of Abs with time for this reaction pathway
The moderate rate increase in both reaction steps,
�
using OD as a nucleophile in D O as a solvent (Table 4),
2
2
6
25
(Scheme 1) is
suggests that nucleophilic attack is rate limiting.
The Arrhenius plots were linear for both reaction steps
�
k1t
Abs ˆ A f"ꢀk � k † ‡ e ‰k ꢀ" � "† ‡ k ꢀ" � "†Š
from 10 to 60°C and the activation parameters, for the
0
c
2
1
2
a
c
1
b
a
�
reactions of I and NEBP with OH ion, are presented in
�
k2t
‡e
‰k ꢀ" � " †Šg
1
ꢀ2†
c
b
Table 5. The 10-fold difference between the rate
�
constants for attack of OH ion on I and on the
where A is the initial RPBr concentration and e , e and
intermediate is due to a favorable enthalpy of activation,
partially compensated for by an unfavorable activation
entropy (Table 5).
0
a
b
ec are the molar extinction coefficients of RPBr,
intermediate product and final bispyridone, respectively.
The fit of the experimental data to equation (1) is
exemplified in Fig. 2. The formation of a 1-(2-pyridone)-
Added salts decreased the reaction rate (Table 6). The
extrapolated value of k to zero salt concentration (linear
plot of log k against the square root of the ionic strength)
was similar for NaF and NaBr. The effect of salt on the
!-(bromopyridinium)alkane accounts for the single
isosbestic point in Figure 1. The final product, bispyr-
�
�
idone (Scheme 1), is formed by a slower attack of OH
rate constant for the attack of OH on I is larger than that
on the intermediate.
on the intermediate (Table 6). The (negative) salt effect
was expected since the reaction of dipositive ions, such as
I–V, with OH ion should be inhibited by salt and the
The isolation and characterization of the intermediate
and final products (see Experimental and Table 1)
demonstrate that the reaction pathway proposed in
Scheme 1 adequately describes the reaction of I–V with
�
effect should be larger for k than for k (Scheme 1) since
1
2
27
only the initial substrate is a dipositive ion.
�
OH and validates the use of a kinetic analysis using
The results on the kinetic effect of bis-positive double
reactive pyridinium ions are compatible with a simple
equation (2).
�
a
Table 5. Activation parameters for the reaction of I and NEBP with OH ion
Ea
DH‡
(kcal mol
DS‡
�
1
� 1
� 1 � 1
Reaction
(kcal mol
)
)
(cal mol
K )
�
b
OH ‡ I
12.5
15.4
15.8
11.9
14.8
15.2
� 13.4
c
�
Intermediate ‡ OH
� 8.1
� 8.3
d
�
NEBP ‡ OH
a
� 5
� 5
NaOH = 0.01 M, [I] = 1.7 Â 10 M.
b
c
d
[
NaOH] = 0.01 M, [I] = 1.7 Â 10 M.
See Scheme 1.
Data from Ref. 20.

1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)

3
0
C. FERNANDEZ ET AL.
�
Table 6. Effect of salts on the rate of reaction of I with OH
ion
premicellar aggregate is unlikely, we suggest that the
additional rate enhancement found in premicellar aggre-
gates of comparable pyridinium rings stems from ion
condensation in the aggregate.
�
1
� 1
Added Salt
Concentration (M)
k1 (s
)
k2 (s )
None
NaF
—
0.1
0.41
0.04
0.24
0.23
0.21
0.18
0.15
0.12
0.2
0.038
0.036
0.033
0.033
0.028
0.024
0.03
0
0
0
0
1
.2
.3
.4
.5
.0
Acknowledgments
This work was supported by the Brazilian grant agencies
CNPq, FAPESP, CAPES and FINEP.
NaBr
0.1
0.2
0.3
0.4
0.5
1.0
0.14
0.13
0.14
0.10
0.027
0.024
0.022
0.019
0.016
REFERENCES
0.087
1
2
. E. M. Kosower and J. W. Patton. Tetrahedron 22, 2081 (1966)
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1
051 (1989).
3
. M. J. Politi and H. Chaimovich. J. Phys. Org. Chem. 4, 207 (1991).
through-space electrostatic effect when analyzed as a
function of the average distance. For the short-chain
compounds the value of k22 is still larger than that of (the
reference) N-ethyl-substituted bromopyridinium (NEBP)
4. L. S. Romsted. in Surfactants in Solution, p. 1015. Plenum Press,
New York (1984).
. B. D. Anderson, R. A. Conradi and K. Johnson. J. Pharm. Sci. 72,
448 (1983).
5
6. S. Scheier, A. T. Amaral, A. S. Stachissini and M. L. Bianconi.
Bull. Magn. Reson. 8, 166 (1986).
. C. J. Suckling and A. A. Wilson. J. Chem. Soc., Perkin Trans. 2
1616 (1981).
(Table 3). The value of k22 decreases steadily with
7
increasing distance and for compound V k22 is about half
of that for NEBP (Table 3). The modest rate enhancement
for OH attack on I, when compared with the reaction of
8. S. O. Onyriuka, C. J. Suckling and A. A Wilson. J. Chem. Soc.
Faraday. Trans. 2 1103 (1983).
�
9
. C. N. Sukenik and J. K. Sutter. J. Org. Chem. 49, 1295 (1984).
the same nucleophile with the intermediate product, can
therefore be ascribed to a through-space electrostatic
effect on the reaction center. Therefore, the electrostatic
effect could be due to an increase in the stability of the
initial charge-transfer complex between the nucleophile
and the double positive charge on the reactivity at
reaction center.
1
0. D. A. Jaeger and D. Bolikai. J. Org. Chem. 51, 1350 (1986).
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1
2. (a) J. H. Fendler. Membrane Mimetic Chemistry. Wiley, New
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1
1
4. P. Mukerjee, K. J. Mysels and C. I. Dulin. J. Phys. Chem. 62, 1490
(
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1
1
1
1
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CONCLUSION
9
0 (1975).
We have shown that the reaction of hydroxide ion with
1
2
9. D. Eagland and F. Franks. Trans. Faraday Soc. 61, 2468 (1965).
0. H. A. Al-Lohedan, C. A. Bunton and L. S. Romsted. J. Org. Chem.
47, 3528 (1982).
1,!-bis(2-bromopyridinium)alkanes proceeds with a fast
initial formation of 1-(2-pyridone)-!-(2-bromopyri-
dinium)alkane, followed by a slower hydroxide attack
and final formation of 1,!-bis(2-pyridone)alkane. As the
number of methylene groups between the positively
charged 2-bromopyridinium rings increases from three to
six, the relative rates of initial attack approach that of
2
1. G. B. Barlin, J. A. Benbow. J. Chem. Soc., Perkin Trans. 2 790
(1974)
2
2. Q. Schales and S. S. Schales. J. Biol. Chem. 140, 879 (1941).
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Universidade de S a˜ ao Paulo (1991).
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25. R. B. Moodie. J. Chem. Res. (S), 144 1986
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McGraw-Hill, New York, (1981).
7. S. W. Benson. The Foundations of Chemical Kinetics. McGraw-
Hill New York, (1960).
2
�
reaction OH with 2-bromopyridinium ion. The rate
2
enhancement, attributed to a through-space charge effect,
reaches 20-fold for the propane derivative. Since a further
approximation of the charged reaction centers in a
2

1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 25–30 (1998)