The remarkable effect of 7-amino substituents on the reactivity of 4-nitrobenzofurazans with nucleophiles

Article abstract of DOI:10.1139/v05-116

The reactions of four 4-nitrobenzofurazans (4a-4d) substituted at the 7 position with (a) N-ethyl, (b) N-butyl, (c) piperidino, or (d) pyrrolidino groups have been examined with sulfite ions and with hydroxide ions in water-DMSO (80:20, v/v). Addition of

Full text of DOI:10.1139/v05-116

1
222
The remarkable effect of 7-amino substituents on
the reactivity of 4-nitrobenzofurazans with
1
nucleophiles
Michael R. Crampton, Chukwuemeka Isanbor, and Thomas C. Willett
Abstract: The reactions of four 4-nitrobenzofurazans (4a–4d) substituted at the 7 position with (a) N-ethyl, (b) N-
butyl, (c) piperidino, or (d) pyrrolidino groups have been examined with sulfite ions and with hydroxide ions in water–
5
DMSO (80:20, v/v). Addition of sulfite at the 5 position gives σ adducts with equilibrium constants ca. 10 lower than
that for the formation of the corresponding adduct from 4-nitrobenzofurazan. These reductions are attributed to the sta-
bilization of the parent molecules 4a–4d by conjugative interaction between the 4 and 7 substituents. In alkaline solu-
tion, 4a and 4b yield the conjugate bases while 4c and 4d suffer nucleophilic substitution to give 7-hydroxy-4-
nitrobenzofurazan. Reactivity here is relatively high because of the iminium ion character of the substrates.
Key words: benzofurazans, σ adducts, nucleophilic reactivity, substitution.
Résumé : Opérant dans un milieu eau–DMSO (80:20, v/v), on a étudié les réactions des ions sulfites et des ions hy-
droxydes avec quatre 4-nitrobenzofurazanes (4a–4d) substitués en position 7 par (a) N-éthyle; (b) N-butyle; (c) pipéri-
dino ou (d) des groupes pyrrolidino. L’addition de l’ion sulfite en position 5 conduit à des adduits σ dont les
5
constantes d’équilibre sont 10 fois plus lentes que celles des formations des adduits correspondants à partir du 4-
nitrobenzofurazane. On attribue ces réductions à la stabilisation des molécules parentes 4a–4d par une interaction de
conjugaison entre les substituants dans les positions 4 et 7. En solution alcaline, les composés 4a et 4b conduisent à la
formation des bases conjuguées alors que les composés 4c et 4d subissent des réactions de substitution nucléophile qui
conduisent à la formation de 7-hydroxy-4-nitrobenzofurazanes. Dans ces cas, la réactivité est relativement grande en
raison du caractère d’ion iminium des substrats.
Mots clés : benzofurazanes, adduits σ, réactivité nucléophile, substitution.
[
Traduit par la Rédaction] Crampton et al. 1227
Introduction
the pK values (3) corresponding to the covalent reaction
with water are 3.75 for DNBF and 13.43 of TNB, showing a
rather larger difference than the E values.
a
There is current interest in quantitatively measuring reac-
tivity in nucleophile–electrophile combination reactions.
Mayr and co-workers (1, 2) have investigated a wide-range
of carbon–carbon bond forming reactions. There is also in-
formation available on the reactivities of both aromatic and
heteroaromatic electron-deficient molecules with neutral and
anionic nucleophiles (3, 4). Thus, Terrier, Buncel, and co-
workers (5) were recently able to assign electrophilicity val-
ues (E) of –5.13 for 4,6-dinitrobenzofuroxan (DNBF), an ex-
cellent electrophile, and –13.10 for 1,3,5-trinitrobenzene
In thermodynamic terms the stabilities of σ adducts formed
by the reaction at the 5 position of 4-nitrobenzofurazan (1)
are generally comparable with those of the corresponding σ
adducts from TNB. However, there are significant differ-
ences depending on the nature of the nucleophile and the
solvent. Thus, for the reaction with methoxide ions in meth-
3
–1
anol, values of equilibrium constants are 141 dm mol for
3
–1
1
(6) and 23 dm mol for TNB (7). For reaction with
aliphatic amines in dimethyl sulfoxide (DMSO), values of
equilibrium constants are ca. 100 times lower for 1 than for
TNB (8, 9). Interestingly, for reactions with sulfite ions (10)
(
TNB), a weaker electrophile. These values were obtained in
reactions with carbon nucleophiles in acetonitrile. The rela-
tive electrophilicities may be expected to show some de-
pendence on the type of nucleophile and the solvent. Thus,
3
4
or hydroxide ions (11) in water, values are 10 –10 times
larger for 1 than for TNB. These differences may be largely
due to the effects of solvation. Thus, 2 with a localized nega-
tive charge will be well-solvated by water, while 3 with a
more delocalized charge will be stabilized by DMSO.
Received 15 December 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 30 September
2
005.
2
M.R. Crampton and T.C. Willett. Chemistry Department,
Durham University, Durham, DH1 3LE, UK.
C. Isanbor. Department of Chemistry, University of Lagos,
Lagos, Nigeria.
N
O
N
1This article is part of a Special Issue dedicated to organic
reaction mechanisms.
Corresponding author (e-mail: m.r.crampton@durham.ac.uk).
NO2
2
1
Can. J. Chem. 83: 1222–1227 (2005)
doi: 10.1139/V05-116
© 2005 NRC Canada

Crampton et al.
1223
Table 1. Spectroscopic data for parent molecules, σ adducts, and products.
1H NMR data (δ)a
UV absorbanceb
3
–1
–1
Compound
H-5
H-6
J56
8.8
8.8
9.4
9.0
6.2
Other
λmax (nm)
ε (dm mol cm )
4
4
4
4
4
5
5
5
6
a
b
c
d
a
b
c
8.53
8.49
8.44
8.46
5.34
5.31
5.36
7.62
6.40
6.40
6.64
6.27
5.23
5.19
5.73
6.42
6.20
6.44
6.20
6.08
9.54 (NH), 3.51 (2H), 1.28 (3H)
9.55 (NH), 3.46 (2H), 1.65 (2H), 1.39 (2H), 0.92 (3H)
4.16 (4H), 1.76 (6H)
4.19 (2H), 3.69 (2H), 2.10 (4H)
3.05 (2H), 1.15 (3H)
2.99, 2.51 (2H), 1.61, 1.55 (2H), 1.29 (2H), 0.83 (3H)
3.05 (2H), 2.84 (2H), 1.57 (4H), 1.46 (2H)
3.58 (2H), 1.23 (3H)
482
484
510
502
315
310
327
393
2.6 × 10
2.8 × 10
2.6 × 10
3.0 × 10
1.2 × 10
1.0 × 10
1.1 × 10
2.0 × 10
4
4
4
4
4
6.2
5.8
4
c
c
c
c
4
a
10.5
10.5
10.8
10.8
9.7
7
.50
7.60
.50
8.42
3.90 (2H), 1.29 (3H)
3.55 (2H), 1.60 (2H), 1.31 (2H), 0.83 (3H)
3.90 (2H), 1.65 (2H), 1.31 (2H), 0.83 (3H)
6
8
b
392
466
2.2 × 104
2.7 × 104
7
a
2
2
Values for parent molecules 4a–4d are in [ H ]-DMSO. All other values are in D O–[ H ]-DMSO (80:20, v/v).
In water–DMSO (80:20, v/v).
6
2
6
b
c
Values for the conformational isomers, see text.
H
Bu
H
H
NR2
Et
N
N
O N
NO2
N
N
2
N
N
N
N
O
H
O
O
–
O3S
–
NO2
NO2
NO2
NO2
2
3
4a
4b
Here, we are concerned with the reactivities of 1 and its 7-
substituted derivatives in σ-adduct formation; in particular,
the effect of an amino group or substituted amino group at
the 7 position.
One source of interest in 4-nitrobenzofurazans is their po-
tential to act as in vitro inhibitors of nucleic acid and protein
biosynthesis in animal cells (12–15). Also, the fluorescence
characteristics of 7-amino derivatives have been studied (16–
N
N
N
N
N
O
O
N
NO2
NO2
1
(
8) and their use as fluorescent probes has been investigated
19).
Here, results are reported for the reaction of compounds
a–4d with sulfite and with hydroxide ions in largely aque-
4c
4d
4
Scheme 1.
R'
ous media. There is evidence for strong conjugation between
the groups at the 4 and 7 positions, which stabilizes the par-
ent molecules.
R
R'
R
N
N
N
N
N
N
+ SO32–
O
O
Results and discussion
H
–
O3S
Most measurements relate to a solvent system of water–
DMSO (80:20, v/v). This system was chosen because of the
low solubilities (<5 × 10–5 mol dm ) of 4b–4d in water. The
solubility of 4a in water was higher, therefore, measure-
ments were made both in water–DMSO (80:20) and in wa-
ter, allowing a comparison of the solvent systems.
NO2
NO2–
–3
4
5
The coupling constant J56 is reduced from ca. 9 Hz in the
parent to ca. 6 Hz, consistent with the change in hybridiza-
tion at C-5. Since the shifts of H-5 and H-6 are similar, the
assignments may be reversed. Due to the low solubility of
4d and the low equilibrium constant for adduct formation,
useful spectra could not be obtained for 5d.
Reaction with sulfite
Spectroscopic results for the parent molecules in DMSO
and for the products of the reaction with sulfite in water–
1
DMSO (80:20) are in Table 1. The H NMR spectra are con-
sistent with sulfite addition at the 5 position to give 5 as
shown in Scheme 1. H-5 shows a large shift to lower fre-
quency (ca. δ 5.3) on adduct formation, while H-6 shows a
smaller shift.
The spectra of the adducts were unchanged after several
days and there was no evidence for sulfite attack at the 7 po-
sition. However, after a week, spectra of 4a showed small
bands at δ 8.42 and 6.08, characteristic of the anion of 7-
©
2005 NRC Canada

1
224
Can. J. Chem. Vol. 83, 2005
Scheme 2.
R'
R'
H
R'
N
N
N
N
N
N
N
N
N
–
O
+ HO
O
+
O + H O
2
–
–
NO2
a, 4b
NO2
NO2
4
6a, 6b
a
Table 2. Kinetic and equilibrium results for reaction of 4c with
sulfite in water–DMSO (80:20, v/v) at 25 °C.
Table 3. Summary of kinetic and equilibrium data for reactions
with sulfite ions in water–DMSO (80:20, v/v) at 25 °C.
SO 2–]
k
k
b
Abs
(510 nm)
K5c
(dm mol )
[
(
k5
k–5
(s )
K5
3
obs
–1
calcd
–1
10 mol dm–3)
–
4
(s )
(s )
3
–1
3
–1 –1
–1
3
–1
Compound
(dm mol s )
(dm mol )
4aa
4a
4b
4c
170
180
154
87
64
3.3 × 10
4.5
1.9
2.1
0.17
19
38
95
73
510
3.4
0
8
—
—
1.27
0.90
0.79
0.71
0.64
0.41
0.32
0.21
0.15
0.11
—
.0
0.24
0.28
0.31
0.33
0.50
0.71
0.93
1.42
1.98
0.24
0.27
0.31
0.34
0.52
0.69
1.04
1.48
1.91
510
505
490
490
520
500
508
500
525
1
1
2
4
6
2.0
6.0
0.0
0.0
0.0
00
50
00
4d
a,b
4
6
1
0.020
125
1.65 × 10
290
a,c
4
TNB
3.5 × 10
1
1
2
a
Measurements in water.
Data from ref. 10.
b
c
Data from ref. 20 for the reaction at unsubstituted ring positions in
,3,5-trinitrobenzene. Data have not been statistically corrected.
1
Note: Abs = Absorbance.
a
b
c
–5
–3
Concentration (5 × 10 mol dm ).
Calculated from eq. [1] with k = 87 dm mol
Calculated as ((1.27 – Abs)/Abs) × (1/[SO3 ]).
3
–1 –1
–1
s
and k–5 = 0.17 s .
5
2–
rium constant for reaction with hydroxide at the 5 position is
3
–1
2
700 dm mol . However, this behaviour is not unexpected
in light of the results with sulfite, which show that values of
hydroxy-4-nitrobenzofurazan (8). Presumably in the sulfite
solutions, which are weakly alkaline, hydrolysis occurs very
slowly. The failure to observe sulfite attack at the 7 position
of 4a–4d is presumably steric in origin. It is known that in 1
itself, attack at the 5 position is followed by a slow
isomerization to give the adduct at the 7 position.
Rate and equilibrium measurements for the formation of
adducts 4a–4d were made spectrophotometrically in solu-
tions where the sulfite concentration was in large excess of
the substrate concentration. In these conditions, a single,
first-order process was observed, and rate constants were de-
termined by the stopped-flow method.
K are many orders of magnitude lower for 4 than for 1.
5
1
The H NMR spectra of 4a and 4b in the presence of hy-
droxide are reported in Table 1 and indicate deprotonation to
give the respective conjugate bases 6a and 6b as shown in
Scheme 2.
Interestingly, the spectra in each case are compatible with
the formation of two conformational isomers as indicated in
the scheme. For 6a, bands for H-5 and H-6 are observed at δ
7
.62 and 6.42, J = 10.5 Hz, for the major isomer, and δ 7.50
and 6.20, J = 10.5 Hz, for the minor isomer. For 6a, the ratio
of isomers is 3:1 and for 6b it is 4:1. Very slow displace-
ment of the 7 substituents is observed so that after 1 week,
bands are present due to the anion 8.
Plots of kobs vs. sulfite concentration were linear with a
positive intercept on the y axis, according to eq. [1], allow-
ing the determination of values of k and k . Specific results
Deprotonation of 4a and 4b is accompanied by changes in
5
–5
the UV–vis spectra. In the case of 4b, λ
is 484 nm in the
parent and 392 nm in the anion. These changes were used to
max
for the reaction of 4c are in Table 2. Values of the equilib-
rium constant K5 calculated as k /k were in excellent
5
–5
measure the pK values. An example calculation, in Table 4,
a
agreement with those determined using equilibrium
absorbance values. Results are collected in Table 3. We will
delay the detailed discussion, but note that the adducts
yields a pK value of 10.15 ± 0.02 for 4b in water–DMSO
a
(
80:20). Values for 4a were 10.14 ± 0.05 in solvent (80:20)
5
and 10.02 ± 0.02 in water.
formed from 4 have stabilities ca. 10 times lower than the
In the presence of hydroxide, 4c and 4d were irreversibly
corresponding adduct from 1.
converted to the anion (8) of 7-hydroxy-4-nitrobenzofurazan,
[
1]
kobs = k [SO32–] + k–5
which was identified from its H NMR and UV–vis spectra
1
5
(
11). Kinetic measurements were made, at λ
for the par-
max
Reaction with hydroxide
ent, with hydroxide concentrations in large excess and in the
–
3
There is no spectroscopic evidence for σ-adduct formation
range 0.05–0.20 mol dm . First-order kinetics were ob-
tained, and plots of the rate constant vs. hydroxide concen-
tration, which were linear with a zero intercept yielded
values of the second-order rate constants. The reaction is
likely (3, 4) to proceed by the addition–elimination mecha-
from 4a–4d and hydroxide ions in solutions containing up to
–
3
1
mol dm hydroxide in water–DMSO (80:20, v/v). Hence,
3
–1
we may estimate that K < 0.1 dm mol . This contrasts
5
with the behaviour of 1 where the value (11) of the equilib-
©
2005 NRC Canada

Crampton et al.
1225
Scheme 3.
R
R'
R
N
O
R'
N
OH
N
N
N
N
N
N
k7
–
O
O
+ NHRR'
+
HO
O
–
–
NO2
c, 4d
NO2
NO2
4
7
8
a
When comparing values of rate and equilibrium constants,
it must be noted that here values generally refer to water–
DMSO (80:20, v/v), corresponding to a mol fraction of
0.059 in DMSO. The comparisons with other compounds are
generally made with results obtained in water. Nevertheless,
the proportion of DMSO is small so that effects are likely to
be small. Thus, the results in Table 3 for sulfite addition to
Table 4. Calculation of the pK values for 4b in water–DMSO
a
(
80:20, v/v) at 25 °C.
pHb
Abs (484 nm)
pK c
a
7
9
9
9
0.18
0.35
0.71
0.91
1.20
.0
1.36
—
.63
.80
.96
1.070
0.983
0.852
0.207
0.599
0.403
0.293
0.225
0.125
10.14
10.16
10.17
10.13
10.14
10.17
10.11
10.15
—
4
a indicate an increase in the value of K by a factor of 2.5
5
on going from water to the mixed solvent. This is in line
with other results showing increases in stability for the σ ad-
ducts as the proportion of DMSO in the solvent is increased
1
1
1
1
1
(
3, 4, 10).
One effect of the conjugative stabilization shown in 9 is to
dramatically decrease values of equilibrium constants for σ-
adduct formation at the 5 position. In the case of sulfite ad-
0
.3 NaOH
Note: Abs = Absorbance.
Concentration is 5 × 10 mol dm .
Borax buffers.
a
b
c
–5
–3
dition, the results in Table 3 show that values of K are re-
5
5
duced by factors of ca. 10 relative to the value for the
Calculated as pH + log(Abs – 0.125)/(1.36 – Abs).
reaction of 1. Values of k are decreased and values of k
5
–5
are increased. The overall effect is notably bigger for the
pyrrolidino derivative (4d) than for the piperidino analogue
(4c). Related differences between these amines have been re-
ported previously (21–23) and may be attributed to the par-
ticular stability of the resonance form 9 in the pyrrolidino
derivative.
nism shown in Scheme 3. There was no evidence for the ac-
cumulation of the reaction intermediates 7c and 7d so that
the measured second-order rate constants are likely to repre-
sent the values for k for nucleophilic attack at the 7 posi-
7
3
–1 –1
tion. Values obtained were 0.91 ± 0.05 dm mol
and 0.71 ± 0.04 dm mol
compared to a value (11) of 0.2 ± 0.1 dm mol
s
for 4c
3
–1 –1
s
for 4d. These values may be
It is of interest to contrast the effects of an amino substi-
tuted in the 4-nitrobenzofurazans with related effects in
1,3,5-trinitrobenzene derivatives. Thus, the values of the
equilibrium constants for the formation of the sulfite adducts
3
–1 –1
s
for hy-
droxide attack at the 7 position of 1.
4
4
3
Comparisons
10, 11, and 12 are (24) 250, 5.4 × 10 , and 5.4 × 10 dm
–
1
Our results provide evidence for a strong conjugation be-
tween the 4-nitro and 7-amino substituents as indicated in 9.
The UV–vis absorbance maxima in 4a–4d are at 482–510 nm,
mol , respectively. Here, the effect of an N-methyl or N,N-
dimethyl substituent is to enhance the stability of the adduct
by a factor >100. It is likely that the difference in behaviour
in the two systems is largely steric in origin. Hence, in the
parent amino-trinitrobenzenes, it is not possible to achieve
the degree of planarity required for strong conjugative inter-
action. The lower aromaticity in the benzofurazans relative
to the benzene derivatives (4) may also favour conjugative
interaction as shown in 9.
showing a strong bathochromic shift relative to 1 where λ
max
is 327 nm. A similar, but much weaker, conjugative effect
has been noted in 7-methoxy-4-nitrobenzofurazan (10)
1
where λ
is 383 nm. It is interesting that in the H NMR
max
spectrum of 4d, the pyrrolidino derivative, the two pairs of
α-CH hydrogens show discrete spin-coupled bands at δ 4.19
2
and 3.69, indicative of the double bond character in the
carbon–nitrogen bond.
σ-Adduct formation at the 5 position of 4 results in the
loss of conjugation between the 4 and 7 substituents, and
R'
R'
R
R
N
N
Me
H
Me
Me
H
N
N
N
N
N
N
O N
O N
O N
2
2
NO2
H
2
NO2
NO2
O
O
H
H
H
–
–
–
SO3
SO
3
SO3
–
NO2
NO2
NO2
NO2
NO2
9
10
1
1
12
©
2005 NRC Canada

1
226
Can. J. Chem. Vol. 83, 2005
hence, is relatively disfavoured. However, ionization
Scheme 2) is not similarly disadvantaged. Thus, the pKa
values of ca. 10 found for 4a and 4b may be compared (3, 4,
5, 26) with corresponding values of ca. 13 for picramide
and N-alkylpicramides (13). In a related fashion, the acidity
in water–DMSO (20:80, v/v) of 7-anilino-4-nitrobenzo-
phosphate, were measured using a Jenway 3020 pH meter,
calibrated using aqueous buffers. All other materials and sol-
vents were the purest available commercial specimens.
(
1
2
H NMR spectra were measured using Bruker Ultrashield
400 MHz or Varian Inova 500 MHz spectrometers. Parent
2
molecules were dissolved in [ H ]-DMSO. Measurements in
6
furazan (14, pK 7.68) has been found (27) to be higher than
solutions containing sodium sulfite or sodium deuteroxide
were made in water–DMSO (80:20, v/v) using deuteriated
solvents. Parent concentrations were in the range 0.005–
a
that of 2,4,6-trinitrodiphenylamine (pK 8.20).
a
–
3
0
.01 mol dm with the nucleophile concentration (ca.
R
H
Ph
H
–
3
N
N
0.1 mol dm ) in large excess. UV–vis spectra and kinetic
measurements were made at 25 °C with a PerkinElmer
Lambda 2 spectrophotometer, a Shimadzu UV-2101 PC
spectrophotometer, or an Applied Photophysics SX-17 MV
stopped-flow instrument. Reported rate constants are the
mean of several determinations and are precise to ±5ꢀ.
O N
2
NO2
N
N
O
NO2
NO2
1
3
14
Acknowledgement
The high reactivity of 4c and 4d towards hydrolysis
Scheme 3) may be attributed to the contribution of the reso-
We thank the Royal Society, London, for financial assis-
tance to allow C. Isanbor to visit Durham.
(
nance from 9 to the structure. This gives the carbon–nitrogen
bond iminium ion character, hence explaining (28) the reac-
tivity towards the attack of hydroxide. The values obtained
References
3
–1 –1
for k of ca. 1 dm mol
s may be compared (29) with val-
7
1
2
3
. H. Mayr, B. Kempf, and A.R. Ofial. Acc. Chem. Res. 36, 66
2003).
. B. Kempf, N. Hampel, A.R. Ofial, and H. Mayr. Chem. Eur. J.
, 1 (2003).
. E. Buncel, M.R. Crampton, M.J. Strauss, and F. Terrier. Elec-
tron deficient aromatic- and heteroaromatic-base interactions.
Elsevier, Amsterdam. 1984.
3
–1 –1
ues of 0.0031 and 0.015 dm mol
attack of hydroxide on 1-piperidino- and 1-pyrrollidino-
,4,6-trinitrobenzene, respectively. It is interesting that in al-
s
for the corresponding
(
2
9
kaline solutions, 4a and 4b, where anion formation predomi-
nates, are very slowly hydrolysed. This is likely to involve
hydroxide attack on low concentrations of the parent mole-
cules. As in previous work (10), there is no evidence for an
attack of sulfite at the 7 position of 4-nitro-7 substituted
benzofurazans, presumably owing to unfavourable steric in-
teractions.
4
. F. Terrier. Nucleophilic aromatic displacement. VCH, New
York. 1991.
5. F. Terrier, S. Lakhdar, R. Goument, T. Boubaker, and E.
Buncel. Chem. Commun. 22, 2586 (2004).
6
. F. Terrier, A.-P. Chatrousse, and F. Millot. J. Org. Chem. 45,
666 (1980).
. C.F. Bernasconi. J. Am. Chem. Soc. 72, 4682 (1970).
2
Experimental
7
Compounds 4a–4d were prepared from 7-chloro-4-nitro-
benzofurazan by reaction with 4 equiv. of the appropriate
amine in DMSO. Mixtures were stirred for 5 h at room tem-
perature and quenched in ice-cold dilute hydrochloric acid.
The precipitates were filtered, washed with water and etha-
8. M.R. Crampton, J. Delaney, and L.C. Rabbitt. J. Chem. Soc.
Perkin Trans. 2, 2473 (1999).
9. L.C. Rabbitt. Ph.D. thesis, University of Durham, Durham,
UK. 2000.
10. M.R. Crampton, L.M. Pearce, and L.C. Rabbitt. J. Chem. Soc.
Perkin Trans. 2, 257 (2002).
1. M.R. Crampton, R.E.A. Lunn, and D. Lucas. Org. Biomol.
1
nol, and recrystallized from ethanol. H NMR spectra are re-
1
ported in Table 1, and indicated the absence of impurities.
+
Chem. 1, 3438 (2003).
12. P.B. Ghosh, B. Ternai, and M.W. Whitehouse. J. Med. Chem.
4
(
a: mp 164 °C. MS (ES ) m/z 209 corresponds to C H N O
8
9
4
3
+
+
M + H ). 4b: mp 90 °C. MS (ES ) m/z 237 corresponds to
C H N O (M + H ). 4c: mp 166 °C. MS (ES ) m/z 249
+
+
11, 305 (1968).
1
0
13
4
3
+
13. P.B. Ghosh, B. Ternai, and M.W. Whitehouse. J. Med. Chem.
15, 255 (1972).
corresponds to C H N O (M + H ). 4d: mp 210 °C. MS
1
1
13
4
3
+
+
(
ES ) m/z 235 corresponds to C H N O (M + H ).
10 11 4 3
1
4. M.W. Whitehouse and P.B. Ghosh. Biochem. Pharmacol. 17,
58 (1968).
5. B.S. Baines, G. Allen, and K. Brocklehurst. Biochem. J. 163,
89 (1977).
Sulfite solutions were prepared from AnalaR sodium sul-
1
fite. To check that no depletion of sulfite concentration oc-
curred because of hydrolysis when making kinetic and
equilibrium measurements, measurements were also made in
solutions buffered at pH 8.3 using mixtures of sodium sulfite
and sodium hydrogen sulfite. The values of rate and equilib-
rium constants obtained were identical, within experimental
error, to those obtained in unbuffered solutions with the
same sulfite concentration. Solutions of known hydroxide
concentration were made by dilution of AnalaR sodium hy-
droxide solution. The pH values of buffer solutions, borax or
1
1
1
1
1
6. T. Hiratsuka and T. Kato. J. Biol. Chem. 262, 6318 (1987).
7. A. Chattopadhyay. Chem. Phys. Liquids, 53, 1 (1990).
8. S. Uchiyama, T. Santa, and K. Imai. J. Chem. Soc. Perkin
Trans. 2, 2525 (1999).
9. J.M. Boon, R. Shukla, B.D. Smith, G. Licini, and P. Scrimin.
Chem. Commun. 260 (2002).
1
20 C.F. Bernasconi and R.G. Bergstrom. J. Am. Chem. Soc. 95,
3603 (1973).
©
2005 NRC Canada

Crampton et al.
1227
2
2
2
1. J.F. Bunnett, S. Sekiguchi, and L.A. Smith. J. Am. Chem. Soc.
03, 4865 (1981).
2. S. Sekiguchi and J.F. Bunnett. J. Am. Chem. Soc. 103, 4871
1981).
3. S. Sekiguchi, T. Suzuki, and M. Hosokawa. J. Chem. Soc.
Perkin Trans. 2, 1783 (1989).
26. M.R. Crampton and B. Gibson. J. Chem. Soc. Perkin Trans. 2,
752 (1980).
27. J.-C. Halle, M. Mokhtari, P. Soulie, and M.-J. Pouet. Can. J.
Chem. 75, 1246 (1997).
28. E.H. Cordes and W.P. Jencks. J. Am. Chem. Soc. 84, 832
(1962).
1
(
2
2
4. M.R. Crampton. J. Chem. Soc. B, 1341 (1967).
5. V. Gold and C.H. Rochester. J. Chem. Soc. 1727 (1964).
29. E.I. Bujan, V. Remedi, and R.H. de Rossi. J. Chem. Soc.
Perkin Trans 2, 969 (2000).
©
2005 NRC Canada