Methanolysis of 4-bromobenzenediazonium ions. Effects of acidity, [MeOH] and temperature on the formation and decomposition of diazo ethers that initiate homolytic dediazoniation

Article abstract of DOI:10.1039/b809521c

We have investigated the effects of solvent composition, acidity and temperature on the dediazoniation of 4-bromobenzenediazonium (4BrBD) ions in MeOH-H₂O mixtures by employing a combination of spectrometric and chromatographic techniques. The kinetic behaviour is quite complex; in the absence of MeOH, dediazoniations follow first-order kinetics with a half-life t_1/2 ? 3000 min (T = 45 °C), but addition of small concentrations of MeOH lead to more rapid but non-first-order kinetics, suggestive of a radical mechanism, with t_1/2 ? 125 min at 25% MeOH. Further increases in the MeOH concentration slow down the rate of dediazoniation and reactions progressively revert to first-order behaviour, and at percentages of MeOH higher than 90%, t_1/2 ? 1080 min. Analyses of reaction mixtures by HPLC indicate that three main dediazoniation products are formed depending on the particular experimental conditions. These are 4-bromophenol (ArOH), 4-bromoanisole (ArOMe), and bromobenzene (ArH). At acidities (defined as -log[HCl]) < 2, the main dediazoniation products are the substitution products ArOH and ArOMe but, upon decreasing the acidity, the reduction product ArH becomes predominant at the expense of ArOH and ArOMe, indicating that a turnover in the reaction mechanism takes place under acidic conditions. At any given MeOH content, the plot of k_obs or t_1/2 values against acidity is S-shaped, the inflexion point depending upon the MeOH concentration and the temperature. Similar S-shaped variations are found when plotting the dediazoniation product distribution against the acidity. The acid-dependence of the switch between the homolytic and heterolytic mechanisms suggests the homolytic dediazoniation proceeds via transient diazo ethers. The complex kinetic behaviour can be rationalized by assuming two competitive mechanisms: (i) the spontaneous heterolytic dediazoniation of 4BrBD, and (ii) an O-coupling mechanism in which the MeOH molecules capture ArN₂ ⁺ to yield a highly unstable Z-adduct which undergoes homolytic fragmentation initiating a radical process. Analyses of the effects of temperature on the equilibrium constant for the formation of the diazo ether and on the rate of splitting of the diazo ether allowed, for the first time, estimation of relevant thermodynamic parameters for the formation of diazo ethers under acidic conditions. The 2008 Royal Society of Chemistry.

Full text of DOI:10.1039/b809521c

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Methanolysis of 4-bromobenzenediazonium ions. Effects of acidity, [MeOH]
and temperature on the formation and decomposition of diazo ethers that
initiate homolytic dediazoniation
Alejandra Ferna´ndez-Alonso and Carlos Bravo-D´ıaz*
Received 5th June 2008, Accepted 7th July 2008
First published as an Advance Article on the web 5th September 2008
DOI: 10.1039/b809521c
We have investigated the effects of solvent composition, acidity and temperature on the dediazoniation
of 4-bromobenzenediazonium (4BrBD) ions in MeOH–H2O mixtures by employing a combination of
spectrometric and chromatographic techniques. The kinetic behaviour is quite complex; in the absence
of MeOH, dediazoniations follow first-order kinetics with a half-life t1/2 ª 3000 min (T = 45 ◦C), but
addition of small concentrations of MeOH lead to more rapid but non-first-order kinetics, suggestive of
a radical mechanism, with t1/2 ª 125 min at 25% MeOH. Further increases in the MeOH concentration
slow down the rate of dediazoniation and reactions progressively revert to first-order behaviour, and at
percentages of MeOH higher than 90%, t1/2 ª 1080 min. Analyses of reaction mixtures by HPLC
indicate that three main dediazoniation products are formed depending on the particular experimental
conditions. These are 4-bromophenol (ArOH), 4-bromoanisole (ArOMe), and bromobenzene (ArH).
At acidities (defined as -log[HCl]) < 2, the main dediazoniation products are the substitution products
ArOH and ArOMe but, upon decreasing the acidity, the reduction product ArH becomes predominant
at the expense of ArOH and ArOMe, indicating that a turnover in the reaction mechanism takes place
under acidic conditions. At any given MeOH content, the plot of kobs or t1/2 values against acidity is
S-shaped, the inflexion point depending upon the MeOH concentration and the temperature. Similar
S-shaped variations are found when plotting the dediazoniation product distribution against the acidity.
The acid-dependence of the switch between the homolytic and heterolytic mechanisms suggests the
homolytic dediazoniation proceeds via transient diazo ethers. The complex kinetic behaviour can be
rationalized by assuming two competitive mechanisms: (i) the spontaneous heterolytic dediazoniation
+
of 4BrBD, and (ii) an O-coupling mechanism in which the MeOH molecules capture ArN2 to yield a
highly unstable Z-adduct which undergoes homolytic fragmentation initiating a radical process.
Analyses of the effects of temperature on the equilibrium constant for the formation of the diazo ether
and on the rate of splitting of the diazo ether allowed, for the first time, estimation of relevant
thermodynamic parameters for the formation of diazo ethers under acidic conditions.
gations by other researchers.5–8 They assumed that the radical
pathway followed the propagation sequence postulated by DeTar
Introduction
In 1977, Bunnett published two papers1,2 focused on the ther-
molysis of arenediazonium ions, ArN2 , in acidic methanol
and Turetzky,9 Scheme 1, but could not find convincing evidence
for the nature of the initiation step and hypothesized a direct
electron transfer from the methanol to the arenediazonium ion,
step 1 in Scheme 1. The lack of convincing evidence for or
against the postulated initiation mechanism made the topic remain
a matter of debate for a long time because in such homolytic
dediazoniations no obvious reductants are employed.
+
seeking evidence to establish whether or not homolytic and
heterolytic dediazoniations proceed via a common intermediate.3
The phenomenon of interest was first described by DeTar
and Kosuge,4 who showed that substituted benzenediazo-
nium ions such as 4-bromobenzenediazonium, 4BrBD, and 4-
methoxybenzenediazonium ions decompose in acidic MeOH
under a N2 atmosphere yielding reduction products (mainly
bromobenzene and anisole, respectively), but in the presence of
O2 they decompose yielding the corresponding solvolytic products
(4-bromoanisole and 1,4-dimethoxybenzene, respectively).
On the basis of kinetic and product distribution measurements,
Bunnett and co-workers1,2 concluded that, in acidic methanol,
dediazoniations take place through competing ionic and radical
mechanisms, a conclusion substantiated in subsequent investi-
Scheme 1 Solvolytic dediazoniation mechanism proposed by Bunnett’s
group1,2 showing the initiation step 1, which was assumed to be an electron
transfer from the solvent to the arenediazonium ion, and the subsequent
propagation steps.
Universidad de Vigo, Facultad de Qu´ımica, Dpt. Qu´ımica F´ısica, 36200 Vigo,
Spain. E-mail: cbravo@uvigo.es; Fax: +34 986 812556; Tel: +34 986 812303
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In recent solvolytic dediazoniation work under acidic
conditions,10,11 we proposed an initiation mechanism based on the
formation of a transient O-diazo ether in a rapid pre-equilibrium
step followed by a homolytic bond cleavage that initiates a radical
mechanism, steps 1 and 2 in Scheme 2. The experimental basis for
our proposal was the finding of S-shaped variations in both kobs
and product formation with acidity for toluenediazonium10 and
4-nitrobenzenediazonium, 4NBD, ions11 and the results allowed
identification of the dual role played by the ROH molecules as
nucleophiles that (i) simply solvate the diazonium ions (allowing
them to undergo thermal heterolytic decomposition), and (ii) react
directly with arenediazonium ions to yield O-coupling adducts
in a highly unstable Z configuration, i.e. Z-diazo ethers. In
the second route, the Z-diazo-ethers then undergo homolytic
fragmentation initiating radical processes.5,6,8,10,12–14 Moreover, the
kinetic investigation of the methanolysis of 4NBD under acidic
conditions provided an excellent example of the influence of
solvent composition on the change from a heterolytic mechanism
to a homolytic one.11
(as opposed to methyl, for example) in the aromatic ring make
the arenediazonium ions prone to decompose through homolytic
pathways. For example, transient O-diazo ether derivatives were
detected in dediazoniation of 4NBD ions in the presence of
b-cyclodextrin17,18 or ascorbic acid;19 for both nucleophiles, the
adducts were detected experimentally and, in some instances,
isolated.20
As we shall show, the results obtained for the methanolysis of
4BrBD provide further support for a radical initiation mechanism
=
via formation of a transient diazo ether, Ar–N N–OMe, which
undergoes homolytic fragmentation yielding a bromophenyl rad-
ical (Ar∑) and the methoxy radical (∑MeO). Formation of the
O-adduct is dependent on the acidity, the MeOH concentration
and the temperature. At a given temperature and -log[HCl] > 2,
competitive homolytic and heterolytic mechanisms are observed
and the aryl radicals are able to abstract a hydrogen atom from
MeOH within the solvent cage leading to the formation of
the reduction product, bromobenzene. The formation of the O-
coupling adduct is exothermic, but the large negative entropic
term makes the Gibbs free energy for the equilibrium formation
of the diazo ether small but positive at normal temperatures. An
increase in the temperature does not favor diazo ether formation
even in reaction mixtures with a high MeOH content.
Results
Effects of the percentage of MeOH on the rate of
decomposition of 4BrBD
Scheme 2 Newly proposed solvolytic dediazoniation mechanism showing
an initiation step comprising the formation of a highly unstable diazo
ether in a rapid pre-equilibrium step that subsequently decomposes
homolytically initiating a radical process. The spontaneous decomposition
of ArN2+, which takes place through the rate-determining formation of
an aryl cation that further reacts with available nucleophiles (DN + AN
mechanism) is not shown for the sake of clarity.
The effect of solvent composition on the observed rate constant,
k
obs, was investigated by changing the percentage of MeOH in the
reaction mixture at different acidities (HCl, [H3O+] at least 10 times
greater than initial concentrations of substrate). In the absence
of MeOH, the thermal decomposition of 4BrBD in aqueous
acid solution is extremely slow but the reactions appeared to
follow first-order kinetics (results not shown) and a value of t1/2
ª
Here we report an extension to our solvolytic studies by
investigating the methanolysis of p-bromobenzenediazonium ions
(4BrBD) over the whole MeOH–H2O composition range at
different acidities and temperatures. Our aim is to confirm the
proposed initiation mechanism and to gain insights into the
energetics of diazo ether formation and decomposition. For this
purpose, a combination of spectrometric and chromatographic
techniques was employed.
3000 min was estimated at T = 45 ◦C (see Experimental section for
details). This remarkable thermal stability is consistent with that
of benzenediazonium ions bearing other electron-withdrawing
groups in the aromatic ring compared with that of those bearing
electron-donating groups.6,16,21
Addition of only small amounts of MeOH results in the UV
absorbance against time plots becoming S-shaped, Fig. 1, which
is clearly not compatible with simple first-order kinetics and
suggests intrusion of a radical process. Careful purification of
the diazonium salt (see Experimental section), and changes in the
batches of the MeOH employed to prepare the reaction mixtures
and of the MeOH supplier, did not result in significant changes in
the observed kinetic behavior, indicating that the results obtained
are not due to possible impurities in the MeOH.
Upon increasing further the percentage of MeOH, the reaction
profiles gradually became first order again with t1/2 ª 1080 min in
98% MeOH, i.e. t1/2 is about 3 times higher in 98% MeOH than in
pure water. All these observations are very similar to those found
for the methanolysis of 4NBD ions.10,11
4BrBD was chosen as a model arenediazonium ion for several
+
reasons; the most relevant are: I) 4BrBD is one of the ArN2 ions
employed in previous studies by DeTar et al.4 and Bunnett and co-
workers1,2 and II) because it is well recognized that substituents in
the aromatic ring of diazonium ions have important mechanistic
effects.5,6,15 For instance, electron-withdrawing substituents in the
4-position destabilize the aryl cation by induction more than
they destabilize the parent arenediazonium ions, and therefore its
spontaneous decomposition reaction is much slower than that of
the parent, or of arenediazonium ions bearing electron-releasing
groups such as Me.7,16 A Br- group in the 4 position (like 4-MeO-)
withdraws electrons by induction through the s bonds but has an
electron donating capability through resonance, which contrasts
with other electronegative groups such as 4-NO2, which has no
electron donating capability. Electron-withdrawing substituents
Because of the non-first-order behaviour obtained at interme-
diate MeOH percentages, but wishing to compare the effect of
the percentage of MeOH on the rate of the reaction, we report
half-lives, t1/2 values of which are plotted instead of kobs in Fig. 2.
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Fig. 1 Typical S-shaped kinetic plots obtained for the thermolysis of
4BrBD in a 25% (v : v) MeOH–H2O binary mixture at different acidities.
[4BrBD] ~ 1.3 ¥ 10-4 M, T = 45 ◦C.
Fig. 3 Effects of acidity on the methanolysis of 4BrBD in a 25 : 75 (●)
and in a 75 : 25 (ꢀ) MeOH/H2O (v : v) binary mixtures. [4BrBD] ~ 1.3 ¥
10-4 M, T = 45 ◦C.
becomes competitive), but the data obtained are suggestive of S-
shaped profiles.
The finding of S-shaped kinetic profiles is in keeping with
previous findings showing parallel variations of kobs or t1/2 with
the acidity in the ethanolyses10 and butanolyses22 of toluenedia-
zonium ions and in the methanolyses of 4NBD and attributed
to the formation of transient diazo ether intermediates from the
arenediazonium ions which then lead on to the reduction product
ArH, Scheme 2. Note the large variation of t1/2 in the -log[HCl] =
0–2 range compared to that in the 2–7 range, highlighting the
crucial role of the acidity in the formation of the diazo ethers,
whose formation seems to be important even under relatively high
acidic conditions (-log([HCl] ~ 1–2).
HPLC analyses of the reaction mixtures indicate that three main
dediazoniation products, ArH, ArOH, ArOMe were formed but
total yields were less than 100% in all runs as in previous 4BrBD
solvolytic dediazoniation works (see Experimental section). Fig. 4
shows the effects of acidity in the yields of the three main dediazo-
niation products, ArOH, ArH, and ArOMe, at two selected solvent
compositions. Fig. 4A shows that, at low percentages of MeOH,
the yield of ArOH drops very fast from ~70% at the highest acidity
to only 8% at -log[HCl] = 2, with a concomitant increase in the
yield of the reduction product (60% at -log[HCl] = 2). Thereafter,
however, the yield of ArOH is remarkably constant on changing
the acidity of the solution.
Fig. 4B displays the results at 75% MeOH showing the increase
in the yield of the reduction product ArH at the expense of the
substitution products ArOMe and ArOH. Note that the yield of
ArH becomes constant at -log[HCl] > 3 and that the yields of
ArOH and ArOMe are very similar in spite of the increase in
[MeOH].
Fig. 2 Variation of t1/2 with the percentage of MeOH for solvolyses of
4BrBD. [4BrBD] ~ 1.3 ¥ 10-4 M, [HCl] = 0.01 M, T = 45 ◦C. The inset is
a magnification of the 0–30% MeOH range.
As noted before, t1/2 ª 3000 min (T = 45 ◦C) in the absence of
MeOH, but addition of small amounts of MeOH speeds up the
reaction appreciably with t1/2 values decreasing to a minimum of
about t1/2 ª 125 min at 25% MeOH. Further addition of MeOH
causes t1/2 to increase smoothly up to about t1/2 ª1100 min at 98%
MeOH. The inset in Fig. 2 is an expansion of the results obtained
in the range 0–20% MeOH.
It may be worth noting that the ~ 24 fold decrease in t1/2 found
for 4BrBD, Fig. 2, is very similar to that observed for 4NBD, but
a larger [MeOH] is required; for 4NBD the minimum in t1/2 is
reached at ~ 9% MeOH.10,11
Effect of temperature on t1/2 and on the product distribution
Effect of acidity on t1/2 and on the product distribution
Fig. 5A and 5B show the effects of temperature on t1/2 for the
thermolysis of 4BrBD at different acidities in two selected MeOH :
H2O binary mixtures. Again, S-shaped kinetics are obtained at any
temperature and, at a given temperature, the largest variations in
t1/2 are obtained in the -log([HCl] = 0–2 acidity range.
The effects of acidity on t1/2 were investigated at selected per-
centages of MeOH, Fig. 3. In both cases, S-shaped profiles
were obtained, emphasizing the effect of acidity on the rate of
the reaction. It was not possible, however, to obtain complete
sigmoidal profiles at low percentages of MeOH because of the
much higher HCl concentrations needed, Fig. 3, and because of
the extremely low reactivity of 4BrBD (the thermal decomposition
To determine the effect of the temperature on product distri-
bution, the reaction mixtures at two solvent compositions and
different acidities were chromatographed after the reaction was
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Fig. 4 Effects of acidity on the product distribution for the methanolysis
Fig. 5 Effects of temperature and acidity on t1/2 for the methanolyses
of 4BrBD in 25% (A) and 75% (B) MeOH–H2O binary mixtures. ꢀ T =
ꢀ
of 4BrBD in 25 : 75 (A) and 75 : 25 (B) MeOH–H2O binary mixtures.
ArOH ꢁ ArOMe ● ArH. Experimental conditions as in Fig. 3.
◦
◦
◦
◦
45 C ꢁ T = 50 C ● T = 55 C T = 60 C. [4BrBD] = 1.37 ¥ 10-4 M.
ꢀ
complete, Fig. 6. At a given temperature, S-shaped variations in
the yields are observed on increasing the acidity and at a given
acidity temperature does not seem to have a major effect on the
product distribution.
is also consistent with reported results for other O-coupling
reactions,12,14,26,27 and was probed experimentally in reactions of
arenediazonium ions where geometric restrictions apply.17,28
From Scheme 2, eqn (1) can be derived where kHET and kHOM
are the rate constants for the spontaneous thermal heterolytic
decomposition of ArN2+ and the decomposition of the diazo ether,
respectively, with K standing for the equilibrium constant for diazo
ether formation shown in Scheme 2.
Discussion
S-shaped variations in kobs (or t1/2) with acidity such as those
shown in Fig. 3–6 are usually observed in reactions of acid–
base pairs where both forms are attainable and show different
reactivities.23 Only two specimens under our experimental con-
kHET[H+ ] + kHOMK[MeOH]
(1)
kobs
=
K[MeOH] +[H+ ]
+
ditions may undergo acid–base processes, the ArN2 ions and
MeOH. The pKa of MeOH is ~ 15 and the pKa value of 4BrBD
This equation is typical of processes where an S-shaped depen-
dence of kobs with -log[H+] is observed (where [H+] represents the
concentration of protonated solvent molecules). From eqn (1),
and by considering limits, we find that when [H+] >> K[MeOH],
has been reported to be ~ 11.1,24 so it appears unlikely that
ArN2 ions react with MeO- or with OH- ions, as in alkaline
+
medium,1,2 under our experimental conditions. We propose the
reaction mechanism shown in Scheme 2 which hypothesizes two
competitive mechanisms: (i) the thermal decomposition of the
kobs ª kHET, i.e., the reaction proceeds wholly through the DN
+
AN mechanism and only heterolytic products are obtained. On
the other hand, when [H+] << K[MeOH], kobs ª kHOM, i.e. the
reaction proceeds wholly through the O-diazo ether and formation
of reduction products is favored. The solid lines in Fig. 3–6 were
obtained by fitting the experimental data to eqn (1) by means of
a non-linear least-squares method provided by the GraFit 5.0.5
computer program and the average K values obtained are listed in
Table 1.
At a given temperature, the K values at 75% MeOH are lower
than those at 25% MeOH in keeping with previous findings
and confirming that increasing concentrations of MeOH have
opposing effects upon the formation of the diazo ether in this
+
solvated ArN2 ions through the heterolytic DN + AN mechanism
+
(not shown), and (ii) the formation of an adduct between ArN2
ions and MeOH in a rapid pre-equilibrium step followed by its
rate-determining homolysis, initiating a radical process.
Similar mechanisms have been employed to interpret the
reactivity of arenediazonium ions with a number of ascorbic
acid derivatives where the formation of a diazo ether interme-
diate was detected experimentally by employing electrochemical
methods19,25 and for the ethanolysis of toluenediazonium ions10
and methanolysis of 4-nitrobenzenediazonium ions.11 The as-
sumption of a rate-limiting decomposition of the diazo ether
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Fig. 6 Effects of T on product distribution for thermolysis of 4BrBD in a 25 : 75 (left) and in a 75 : 25 MeOH–H2O (right) mixtures. In the 25 : 75
MeOH–H2O mixture only traces of ArOMe were detected and for this reason the variation in its yield with acidity is not plotted. ꢀ T = 45 ◦C ꢁ T =
50 ◦C ● T = 55 ◦
C
T = 60 ◦C. Other conditions as in Fig. 5.
ꢀ
Table 1 Average values for the equilibrium constant K, determined by
fitting the data in Fig. 3–6 to eqn (1), and values for the enthalpy and
entropy of the formation of the diazo ether (step 1 in Scheme 2) determined
by means of eqn (2), (3)
the concentration of MeOH, and at 75% MeOH, an increase in K
of 1.5 fold is obtained on increasing the temperature from T = 40
to 60 ◦C.
The analysis of the variation of the K values with the tem-
perature allows one, for the first time, to gain insight into the
energetics of diazo ether formation, step 1 in Scheme 2. Fig. 7
T/◦C
45
50
55
60
MeOH : H2O (v : v)
102K
25 : 75
3.6
3.2
2.6
2.0
DH/kJ mol-1
DS/J mol-1 K-1
MeOH : H2O (v : v)
103K
-35
-137
75 : 25
3.4
2.1
1.7
0.9
DH/kJ mol-1
DS/J mol-1 K-1
-77
-288
concentration range: it is favored modestly by higher concen-
trations of MeOH through the mass action effect, but strongly
opposed by the medium effect on the equilibrium constant.
It is worth noting, however, that the variation of K with the
percentage of MeOH seems to be smaller than that found for the
methanolysis of 4NBD11 but larger than that for the ethanolysis
of toluenediazonium ions.10 At low percentages of MeOH, an
increase in the temperature does not seem to have a significant
effect on K but the effect seems to be more noticeable on increasing
Fig. 7 van’t Hoff plot according to eqn (2) for the equilibrium of
formation of the diazo ether, step 2 in Scheme 2. ● 25 : 75, ꢀ 75 : 25
MeOH : H2O (v : v). Data from Table 1.
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shows a typical van’t Hoff plot, according to eqn (2), illustrating
the linear variation found between -log K and 1/T at the two
methanol percentages investigated and from which the enthalpy
values shown in Table 1 were determined. Entropic terms, DS,
determined by employing eqn (3), are also displayed in Table 1.
Details on the assumptions and limitations on the use of eqn (2)
and (3) can be found elsewhere.29
evidence suggests, therefore, that in the present case there is
no conversion of the unstable Z-diazo ether to the much more
stable E-isomer, which would eventually undergo acid catalyzed
fragmentation,12,14,32 as was found for the methanolysis of 4NBD.11
In conclusion, we have been able to show that the methanolysis
of 4BrBD under acidic conditions takes place through two
competitive mechanisms where a MeOH molecule may act as
a nucleophile by simply solvating 4BrBD (allowing it to un-
dergo thermal heterolytic decomposition) or react directly with
4BrBD to yield an O-coupling adduct which undergoes homolytic
fragmentation. The formation of this adduct is favoured by
decreasing the acidity but suppressed by increasing [MeOH] and
the temperature.
Because large amounts of the reduction product ArH are
formed under relatively mild conditions, the results obtained here
also indicate a simple, effective and quick practical method for
replacing an aromatic amino group by hydrogen, representing
an improved alternative to the method proposed by Kornblum33
using hypophosphorous acid as reducing agent or that proposed
by Bravo-D´ıaz et al. using sodium dodecyl sulfate surfactants34 or
b-cyclodextrin.17
Formation of diazo ethers with neutral and anionic nucleophiles
in the course of dediazoniations has been described.17,19,20,25,35–37 In
most instances analyzed, the nucleophile must possess a charge,
such as OH-, CN-, RO- or ascorbate ions, and experimental
conditions are chosen so that substantial concentrations of the
anionic form of the nucleophile are present.14,19,25,31 However,
our results suggest that the formation of Z-diazoethers with
neutral nucleophiles is much more common than expected, and
further investigations to elucidate the role of substituents in the
aromatic ring and experimental conditions on the formation and
decomposition of diazo ethers are warranted.
È
˘
∂(logK)
∂(1/T )
DH = -2.3R
(2)
Í
Î
˙
˚
P
(3)
TDS = DH - DG
Data in Table 1 show that DH and DS are of the same sign,
and so work in opposite directions. Formation of the diazo ether
is exothermic yet has a positive standard free energy of formation
at any of the temperatures investigated. The Gibbs free energy DG
for the 75 : 25 mixture is higher than that for the 25 : 75 one,
highlighting the opposing effects of [MeOH]. Because DG > 0,
K = k1/k-1 < 1 and thus k1 < k-1. An increase in the temperature
increases kHOM, Fig. 8, and at any temperature kHOM must be higher
than k-1 since once the diazo ether is formed it splits homolytically
according to the steps indicated in Scheme 2.
Experimental section
Fig. 8 Variation of ln[t1/2(HOM)], which refers to the fitted value at low
acidity, eqn (1), for the methanolysis of 4BrBD with the reciprocal of the
temperature in a 25 : 75 (●) and a 75 : 25 (ꢀ) MeOH–H2O mixture.
[4BrBD] ~1.40 ¥ 10-4 M, -log[HCl] = 4.1.
Instrumentation
UV-VIS spectra and some kinetics experiments were followed on
an Agilent 8453 spectrophotometer equipped with a Julabo F12-
ED thermostatted cell carrier and attached to a computer for data
storage. Product analysis was carried out on a WATERS HPLC
system which included a model W600 pump, a W717 automatic
injector, a W2487 dual wavelength detector, and a computer for
control and data storage. Products were analyzed on a Microsorb-
MV C-18 (Rainin) reverse phase column (150 mm length, 3.9 mm
internal diameter, and 4 mm particle size) using a mobile phase of
45 : 55 v : v MeOH–H2O containing 10-4 M HCl. The injection
volume was 25 mL in all runs and the UV detector was set at
225 nm.
The analyses of the effects of temperature on kHET (or t1/2(HET))
and kHOM (or t1/2(HOM)) allowed us to estimate the values for
the activation energy of the heterolytic and homolytic pathways,
Fig. 8. The estimated value for the heterolytic process is in line
with those reported in the literature,30 Ea ª 100 kJ mol-1 and
those for the decomposition of the diazo ether in 25 : 75 (Ea =
(71 10) kJ mol-1) and 75 : 25 MeOH/H2O mixtures (Ea = (74
10) kJ mol-1) are very similar to each other but substantially lower
than that for the heterolytic process.
Previous studies on the formation of diazo ethers under alkaline
conditions suggest that diazo ethers are initially formed in a
highly unstable, kinetically controlled, Z-configuration which then
may undergo subsequent isomerization to the thermodynamically
stable E-isomers, which be in some instances can isolated,20 or
eventually may give rise to homolytic rupture of the bonds
providing the initiation of a radical process.14,19,25,31 This bond-
rotating mechanism to transform the Z- into the E-isomers
has been recently described for Sandmeyer hydroxylations and
chlorination reactions.31 All kinetic and product distribution
Materials
4-Bromobenzenediazonium (4BrBD) tetrafluoroborate (Aldrich,
96%) was purified three times from CH3CN–cold ether; it was
stored in the dark at low temperatures to minimize its de-
composition and was recrystallized periodically. 4-bromophenol
(ArOH), 4-bromoanisole (ArOMe), bromobenzene (ArH), were
from Across Organics and were used without further purification.
Other reagents were of maximum available purity from Panreac
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or Riedel de Ha¨en. Solution composition is expressed as percent
MeOH by volume. Molar concentrations were calculated by
ignoring the small excess volume of mixed solvents.38 All aqueous
solutions were prepared by using Milli-Q grade water.
low measurement of the initial amount of 4BrBD used. This
is unlikely to be the case because, in addition to the careful
purification of 4BrBD, different experiments and batches carried
out in different days gave similar results.
Yields less than 100% were already reported for the thermolysis
of 4BrBD in acidic MeOH in previous dediazoniation works1,2,4,27,40
and no clear explanation was provided in spite of the numerous
attempts to isolate minor products. Even in some of the most
recent dediazoniation studies, where the yields of 4BrBD solvolytic
reactions were determined by GC analyses,41 the computed total
yields are substantially less than 100% both in the presence
and absence of radical trapping agents such as iodoacetic acid.
Here we assumed, as Bunnett et al.1,2 did in the past, that
the low yields should be recognized as a systematic error on
computing total yields, which does not affect the kinetic results
(since dediazoniation products are formed competitively, see
experimental results) nor the variation in the yield of a given
dediazoniation product with acidity or temperature, thus not
affecting the main mechanistic conclusions that can be ruled out
from the experimental data.
Methods
Kinetic data were obtained spectrophotometrically and by
HPLC. Observed rate constants were obtained by fitting the
absorbance-time data for at least three half-lives to the integrated
first-order eqn (4) using a non-linear least squares method in those
cases where clean first-order kinetics were observed; otherwise,
t1/2 values are reported and defined as the time elapsed for the
absorbance or concentration of the reactant to decrease to half its
initial value, or for the yield of a product to increase to half its
final value.
Ê
ˆ
Mt - M •
M - M
ln
= -kobst
(4)
Á
˜
Ë
¯
0
•
Duplicate or triplicate experiments gave average deviations less
than 10%. Stock 4BrBD salt solutions were prepared by dissolving
it in the appropriate acidic (HCl) mixture to minimize diazotate
Acknowledgements
formation;39 solutions of final concentrations about 1 ¥ 10-3
M
We would like to thank Prof. H. Maskill for helpful discussions.
Financial support from the following institutions is acknowledged:
Xunta de Galicia (PGDIT06PXIB314249PR), Ministerio de Ed-
ucacio´n y Ciencia (CTQ2006-13969-BQU), Fondo Europeo para
el Desarrollo Regional (FEDER) and Universidad de Vigo.
and [HCl] = 3.6 ¥ 10-3 M were used generally immediately or
within 90 min with storage in an ice bath to minimize spontaneous
decomposition. Beer’s law plots (not shown) in aqueous and
methanolic solutions up to 2.00 ¥ 10-4 M were linear (cc. ≥ 0.999).
Spectrophotometric kinetic data were obtained by following the
+
disappearance of the absorbance of ArN2 at l = 292 nm.
Reactions were initiated by adding an aliquot (<100 mL) of the
+
Notes and references
ArN2 stock solution to the previously thermostatted reaction
mixture.
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Product analysis of reaction mixtures was by HPLC after
dediazoniation was complete. Preliminary HPLC experiments
showed that three main products are formed, ArOH, ArH, and
ArOMe. Linear (cc. >0.999) calibration curves for converting
HPLC peak areas, A, into concentrations were obtained for
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+
diazonium salt concentration, [ArN2 ]o, estimated by weight, i.e.
+
Y = 100[analyte]/[ArN2 ]o, as described elsewhere.1,14,15
Inasmuch as total yields were less than 100%, careful purifi-
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employed in the kinetic experiments was HPLC grade from
different suppliers and batches (and used as received), but
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to unidentified dediazoniation products. Large scale thermolysis
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minor by-products for easy identification and quantification but
all efforts were unsuccessful and no tangible amounts of other
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percentages of MeOH ranging 5–15%.
We found no easy explanation of the anomalous low total
yields found, which contrasts to the quantitative yields found
in other solvolytic dediazoniations under similar experimental
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4010 | Org. Biomol. Chem., 2008, 6, 4004–4011
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©