Dediazoniation of 4-nitrobenzenediazonium ions in acidic MeOH/H 2O mixtures: Role of acidity and MeOH concentration on the formation of transient diazo ethers that initiate homolytic dediazoniation

Article abstract of DOI:10.1002/ejoc.200500946

We have investigated the dediazoniation of 4-nitrobenzene-diazonium (4NBD) ions in MeOH/H₂O mixtures under acidic conditions at 50°C employing a combination of spectrophotometric and chromatographic techniques. The kinetic behaviour is quite co

Full text of DOI:10.1002/ejoc.200500946

FULL PAPER
DOI: 10.1002/ejoc.200500946
Dediazoniation of 4-Nitrobenzenediazonium Ions in Acidic MeOH/H2O
Mixtures: Role of Acidity and MeOH Concentration on the Formation of
Transient Diazo Ethers that Initiate Homolytic Dediazoniation
Roman Pazo-Llorente,[a] Howard Maskill,[b] Carlos Bravo-Diaz,*[a] and
Elisa Gonzalez-Romero[c]
Keywords: Arenediazonium ions / Dediazoniation / Solvolysis / Alcohols / Kinetics
We have investigated the dediazoniation of 4-nitrobenzene-
diazonium (4NBD) ions in MeOH/H2O mixtures under acidic
MeOH, both ArH (60%) and ArOMe (40%) are obtained.
The observed rate constants, kobsd., or half-lives, t1/2, are the
conditions at 50 °C employing a combination of spectropho- same regardless of whether they are determined by monitor-
tometric and chromatographic techniques. The kinetic be-
haviour is quite complex; in the absence of MeOH, the de-
ing product formation (by a well-established product
derivatization protocol followed by HPLC measurements) or
reactant decomposition (obtained UV spectrophotometri-
cally). At any given MeOH content, the plot of kobsd. or t1/2
values against the acidity (defined as –log[HCl]) is S-shaped,
the inflexion point depending upon the MeOH concentra-
tion. The complex behaviour can be accounted for by two
competitive mechanisms, and whichever is dominant de-
pends upon the acidity and the composition of the aqueous
methanol solvent. Furthermore, the acid-dependence of the
switch between the homolytic and heterolytic mechanisms
suggests the homolytic dediazoniation proceeds via transient
diazo ethers. Thus, the MeOH molecules react with ArN2+ to
yield an O-coupling adduct in a highly unstable Z configura-
tion, i.e. a (Z)-diazo ether. Subsequently, this undergoes
homolytic fragmentation which initiates a radical process. In
diazoniations follow first-order kinetics with a half-life t1/2
=
1383 min, but the addition of small concentrations of MeOH
lead to more rapid but non-first-order kinetics, suggestive of
a radical mechanism, with t1/2 Ϸ 6 min at 10% MeOH. Fur-
ther increases in the MeOH concentration slow down the rate
of dediazoniation and reactions progressively revert to first-
order behaviour, with clean first-order kinetics at percent-
ages of MeOH higher than 90% (t1/2 Ϸ 77 min). The analyses
of the reaction mixtures by HPLC indicate up to four de-
diazoniation products depending on the particular experi-
mental conditions. These are 4-nitrophenol (ArOH), 4-nitro-
anisole (ArOMe), nitrobenzene (ArH), and 4,4Ј-dinitrobi-
phenyl (DNB), this last product being detected only at MeOH
percentages in the range 0.5–15%. In the absence of MeOH,
ArOH is the only product and formed in quantitative yield;
however, at only 20% MeOH, ArOH is down to less than
10% and the reduction product, ArH, is obtained in more
than 90%. Upon increasing the MeOH content further, the
formation of ArOMe becomes competitive and, at 99%
+
the polar alternative, the methanol simply solvates the ArN2
ions, allowing them to undergo thermal heterolysis, i.e. a DN
+ AN mechanism via the aryl cation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
take place by a heterolytic pathway, Scheme 1 (A), charac-
terized by the intermediacy of aryl cations in a DN + AN
mechanism,[4–9] or by a homolytic pathway involving aryl
Introduction
Arenediazonium ions, ArN2+, are among the most useful radicals,[4,5,10] Scheme 1 (B). In addition to the well-known
reagents in aromatic organic chemistry because the versatile applications in synthetic and azo-dye chemistry, new and
diazonium group can be readily replaced by numerous interesting applications of arenediazonium salts are emerg-
other groups.[1–4] This so-called dediazoniation reaction can ing, e.g. they are currently being used to modify carbon
[a] Universidad de Vigo, Facultad de Química, Dpto. Química
Física,
Fax: +986-812556
E-mail: cbravo@uvigo.es
[b] Chemistry Department, University of Newcastle,
Newcastle upon Tyne, NE1 7RU, UK
[c] Universidad de Vigo, Facultad de Química, Dpto. Química An-
Scheme 1. Basic representation of the dediazoniation mechanisms:
(A) heterolytic, i.e. DN + AN; (B) homolytic.
alítica y Alimentaria,
36200 Vigo, Spain
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R. Pazo-Llorente, H. Maskill, C. Bravo-Diaz, E. Gonzalez-Romero
Changes in the concentration of electrolytes (e.g., Cl–,
FULL PAPER
surfaces,[11] to probe interfacial compositions of colloidal
aggregates,[12] and to assess the distribution of polar mole- CuCl2, or H3O+) have a negligible effect on the rate con-
cules in emulsions.[13] However, their use is not without po- stant and the dediazoniation product distribution of tol-
tential hazard; under some conditions, some may be dan- uenediazonium ions.[23] In contrast, dediazoniation rate
gerously thermally unstable[2] and the role of some in car- constants and the product distribution for 4NBD decompo-
cinogenic and mutagenic processes is being explored.[14]
sition are significantly modified; for example, CuCl2 cata-
+
ArN2 ions may function readily as Lewis acids, the β- lyzes 4NBD decomposition and leads to the formation of
nitrogen being the site of electrophilic reactivity, to give co- large amounts of p-chloronitrobenzene at the expense of 4-
valently bonded adducts, ArN2–Nu, with Lewis bases (nu- nitrophenol.[22] Electron-withdrawing substituents (as op-
cleophiles), Nu– (or NuH, followed by loss of a proton).[4,5] posed to methyl, for example) in the aromatic ring make
Typical examples of these reactions are the formation of the arenediazonium ions prone to decompose through
azo dyes, where N- and C-coupling reactions take place; but homolytic pathways and to form transient O-diazo ether
other atoms such as oxygen, sulfur, and phosphorus may derivatives in the presence of β-cyclodextrin[24,25] or ascor-
also be involved leading to the so-called O-, S-, and P-coup- bic acid;[15] for both nucleophiles, the adducts were detected
ling reactions.[4,5] Coupling with oxygen has been mostly experimentally and, in some instances, isolated.[26]
observed under experimental conditions allowing appreci-
able concentrations of the anionic forms of the nucleo-
–
philes, e.g. when OH–, RCO2 , RN2O–, RO–, or ascorbate
Results
ions are present in the reaction mixture.[15–17]
The addition of arenediazonium cations to alkoxide and
1. Effects of the Percentage of MeOH on the Rate of
Decomposition of 4NBD
phenoxide anions is an O-coupling reaction that has been
well investigated.[4,5] Bunnett and co-workers postulated
The effect of solvent composition on the observed rate
constant, kobsd., in the presence of 0.001  HCl (which is
at least 10 times greater than the initial concentrations of
substrate) was investigated by changing the percentage of
MeOH in the reaction mixture. In the absence of MeOH,
that, in alkaline methanolic solutions, the reaction takes
place through the kinetically controlled formation of a
highly unstable (Z)-diazo ether that can either isomerize to
yield the thermodynamically stable (E)-diazo ether, or un-
dergo homolytic scission leading to reduction prod-
ucts.[18,19] Under acidic conditions, the same researchers
postulated that hydrodediazoniations take place by direct
electron transfer from the solvent to the arenediazonium
ion;[18] however, no convincing evidence for this, or other
mechanistic alternatives, was provided and the initiation
process of solvent-induced hydrodediazoniations has re-
mained a matter of debate for a long time because no obvi-
ous reductants were employed in those experiments.[4,10]
In recent solvolytic dediazoniation work,[20] we found S-
shaped variations in both kobsd. and product formation with
acidity for toluenediazonium ions. The results allowed us to
conclude that the initiation pathways of the solvent-induced
homolytic dediazoniations is not an electron transfer from
the solvent but proceeds through the formation of a tran-
sient O-diazo ether in a rapid preequilibrium step which
decomposes homolytically initiating a radical mechanism.
Here, we report an extension to our solvolytic studies by
a detailed investigation of the methanolyses of p-nitro-
benzenediazonium ions (4NBD) in the whole MeOH/H2O
composition range at different acidities to probe further the
proposed initiation mechanism. For this purpose, spectro-
photometric and chromatographic techniques were em-
ployed. 4NBD was chosen because it is well recognized that
substituents in the aromatic ring of diazonium ions have
important mechanistic effects.[7,8,21] For instance, electron-
withdrawing substituents in the 4-position destabilize the
aryl cation by induction more than they destabilize the par-
ent arenediazonium ions, and therefore its spontaneous de-
composition reaction is much slower than that of the par-
ent, or of arenediazonium ions bearing electron-releasing
groups such as Me.[22,23]
Figure 1. Variation of the absorbance at λ = 260 nm with time in
different MeOH/H2O mixtures. [4NBD]o Ϸ 1·10–4 , [HCl] =
10–3 , T = 50 °C.
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Dediazoniation of 4-Nitrobenzenediazonium Ions
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Figure 2. Variation of t1/2 with the percentage of MeOH for solvolyses of 4NBD. Experimental conditions are as in Figure 1.
the thermal decomposition of 4NBD follows clean first-or- in 98% MeOH than in pure water. It is worth noting that
der kinetics for more than three half-lives, as previously re- the kobsd. value obtained in 99.5% MeOH is in excellent
ported, with kobsd. = 8.26·10–6 s–1.[22,27] Surprisingly, ad- agreement with a literature value obtained in acidic MeOH
dition of only small amounts of MeOH results in the UV under N2,[28] kobsd. = 1.54·10–4 s–1.
absorbance against time plots becoming S-shaped (Fig-
Because of the non-first-order behaviour obtained at in-
ure 1), which is clearly not compatible with simple first- termediate MeOH percentages, but wishing to compare the
order kinetics and suggests intrusion of a radical process. effect of the percentage of MeOH on the rate of the reac-
Careful purification of the diazonium salt, and changes in tion, we report half-lives values (t1/2) that are plotted in-
the batches of the MeOH employed to prepare the reaction stead of kobsd. in Figure 2. In aqueous acid solution, in the
mixtures and of the MeOH supplier, did not result in sig- absence of MeOH, t1/2 Ϸ 1383 min (not included in Fig-
nificant changes in the observed kinetic behavior, indicating ure 2), consistent with remarkable thermal stability of
that the results obtained are not due to possible impurities 4NBD compared with other arenediazonium ions,[7,22,28]
in the MeOH.
but addition of small amounts of MeOH speeds up the re-
Interestingly, upon increasing further the percentage of action appreciably with t1/2 values decreasing to a minimum
MeOH, the reaction profiles gradually became first order of about t1/2 = 6 min at 10% MeOH. Further addition of
again; at percentages higher than 90% MeOH, clean first- MeOH causes t1/2 to increase smoothly up to about t1/2
=
order kinetics are again obtained, with kobsd. = 1.5·10–4 s–1 77 min at 99.7% MeOH. The inset in Figure 2 is an expan-
in 98% MeOH, Figure 1, i.e. kobsd. is about 18 times higher sion of the results obtained in the range 0–20% MeOH.
Figure 3. Changes in the percentages of products with time determined by HPLC: (A) 0.5% MeOH; (B) 99.97% MeOH. Other conditions
are as in Figure 1.
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R. Pazo-Llorente, H. Maskill, C. Bravo-Diaz, E. Gonzalez-Romero
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2. Kinetics of Product Formation
The observed rate constants for the product formation
were obtained chromatographically by following a pub-
lished procedure[29] at selected percentages of MeOH. Fig-
ure 3 includes representative plots showing the formation of
products with time at 0.5% MeOH (Figure 3, A) and 99.7%
MeOH (Figure 3, B). At 0.5% MeOH, HPLC chromato-
grams (not shown) showed signals for three anticipated
products (ArOH, ArH, and ArOMe) plus one due to a
compound subsequently shown to be 4,4Ј-dinitrobiphenyl,
DNB; see Exp. Sect. for peak identification. At 99.7%
MeOH, only peaks for ArOMe, ArOH, and ArH were de-
tected, ArOMe and ArH being the major ones.
At 0.5% MeOH (Figure 3, A) the product formation
does not follow first-order kinetics; S-shaped curves are ob-
tained with a t1/2 value of 60 min for the formation of either
ArOH or ArH (or the total). The change with time of the
chromatographic signal due to DNB (not shown) follows a
similar profile with the same t1/2 as that for the other prod-
ucts (Figure 3, A). Note that the t1/2 value obtained for
product formation is identical with that obtained spectro-
photometrically for ArN2+ loss, Figure 2. At 99.7% MeOH
(Figure 3, B) formation of products follows clean first-order
behaviour and only two out of three dediazoniation prod-
ucts, ArH and ArOMe, are formed in appreciable quanti-
ties; conversion to these products is essentially quantitative.
The observed rate constant for ArH formation is the same,
within experimental error, to that for ArOMe formation,
Figure 4. Variation in t1/2 with acidity, defined as –log[HCl], at dif-
ferent percentages of MeOH: (A) 95%; (B) 80%; (C) 5%. Other
experimental conditions are as in Figure 1. Solid lines were ob-
tained by fitting the data to a titration curve of the Henderson–
Hasselbach type.
the average value kobsd.
= =
(1.6 0.1)·10–4 s–1 (t1/2
4313 332 s) being in excellent agreement with that re-
ported by Kuokkanen for reaction under N2,[28] and with
+
that obtained for ArN2 loss obtained spectrophotometri-
cally, Figure 1, B and Figure 2.
HPLC kinetics results thus show that homolytic and het-
erolytic products are formed with rate constants the same
as for disappearance of 4NBD ions, strongly suggesting
competitive mechanisms.
Scheme 2. Proposed competitive heterolytic and homolytic dedi-
azoniation mechanisms.
3. Effects of Acidity on the Rate of the Reaction
4. Effects of Solvent Composition on Dediazoniation
Product Distribution
The effects of acidity on kobsd. or t1/2 were investigated at
different percentages of MeOH, Figure 4. At high percent-
ages of MeOH, S-shaped profiles are obtained, indicating
The effect of solvent composition on the product distri-
that the acidity of the reaction has a significant effect on bution was investigated by measuring the product yields at
the reaction mechanism. It was not possible, however, to different percentages of MeOH when dediazoniation was
obtain a complete sigmoidal profile at low percentages of complete. Up to four dediazoniation products, ArH, ArOH,
MeOH because of the much higher HCl concentrations ArOMe, and DNB were detected, and conversion to prod-
needed (Figure 4, C), but the data obtained are suggestive ucts is quantitative. Because DNB is only formed at low
of a similar S-shaped profile. Parallel variations were ob- percentages of MeOH, its yield is not shown in Figure 5 for
served in the ethanolyses[20] and butanolyses[30] of toluene- the sake of clarity, nor included in the “total yield”.
diazonium ions and attributed to the formation of a tran-
Figure 5 shows the variations in the yields of the three
sient diazo ether intermediate from the arenediazonium main dediazoniation products, ArOH, ArH, and ArOMe,
ions which then leads on to the reduction product ArH, with solvent composition. The yield of ArOH drops very
Scheme 2.
fast from virtually 100% to only 8% at 15% MeOH, with
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Dediazoniation of 4-Nitrobenzenediazonium Ions
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Figure 5. Variation in the product distribution with the percentage of MeOH for the methanolysis of 4NBD: ᭺; Ar–OH: ᭹; Ar–H: ᭿;
Ar–OMe: ᮀ, total. Inset: amplification of the results at low percentages of MeOH; note that, under these conditions, 4,4Ј-dinitrobiphenyl
is also formed (but not shown here). See text and Exp. Sect. for product identification and HPLC details; other conditions are as in
Figure 1.
a concomitant increase in the yield of the reduction product yield Ar–H derivatives.[4,5,33,34] The source of electrons in
(90% at 15% MeOH) and DNB. Thereafter, however, the solvolytic dediazoniations has been reported to be the sol-
yield of ArOH is remarkably constant. Figure 5 also shows vent.[7,8,10,35] However, in contrast to other dediazoniations,
that the variation in the yield of ArOMe with MeOH con- no obvious reductants are employed in these experiments
centration, increasing from about 40% MeOH, is princi- to initiate the radical process and hence the mechanism and
pally at the expense of the reduction product, ArH. At per- nature of the initiation step has been a matter of debate for
centages of MeOH close to 100%, about 60% of ArH and a long time.[4,9,10,19,34]
We recently proposed[20,30] that the initiation process of
the homolytic pathway follows the formation of a highly
unstable transient diazo ether and is not by a direct electron
transfer from the solvent (EtOH) to the arenediazonium
ion.[19,33] The S-shaped variations in kobsd. with –log[HCl]
shown in Figure 4 are consistent with such a hypothesis be-
cause they are suggestive of reactions of acid–base conju-
gate pairs where both forms are attainable but show dif-
ferent reactivities, i.e., two competitive mechanisms as
shown in Scheme 2. These comprise the thermal heterolytic
40% of ArOMe are obtained, in agreement with previous
results obtained by De Tar and Kosuge.[31]
Discussion
Solvolytic dediazoniation studies in a variety of sol-
vents[4,5,10] indicate that MeOH, EtOH, and DMSO are
usually borderline solvents where both homolytic and het-
erolytic mechanisms can be observed simultaneously de-
pending on experimental conditions and the nature of sub-
stituents in the arenediazonium ions. Previous studies on
the methanolyses of 4-toluenediazonium ions under experi-
mental conditions similar to those employed in this work
indicate that reactions are first order throughout the whole
composition range,[23,32] with kobsd. values increasing 2–3
fold on going from 0 to 100% MeOH. And, although the
reduction product (toluene) was detected, its yield was re-
ported to be less than 10% indicating that heterolysis is the
predominant mechanism.
+
decomposition of solvated ArN2 ions by the DN + AN
mechanism and a rate-determining fragmentation of a tran-
+
sient diazo ether (ArN2OMe) formed from ArN2 ions and
MeOH molecules in a solvation shell in a rapid pre-equilib-
rium step. Under our experimental conditions, only two
species may undergo acid-base processes, MeOH (pKa Ϸ
+
15) and the ArN2 ions, which may give rise to the diazoic
acid, Ar–N=N–OH; pKa values for 4NBD have been re-
+
ported to be ca. 6.3,[24,36] so it appears unlikely that ArN2
ions react with MeO– or with OH– ions under the present
conditions, as they do in alkaline media.[18,19,33]
Earlier reports of solvolytic investigations with electron-
withdrawing substituents pointed out that reactions in
alcohols such as EtOH and trifluoroethanol (TFE) are
Similar mechanisms have been employed to interpret the
qualitatively different from those in more ionizing media reactivity of arenediazonium ions with a number of ascor-
(although TFE is actually a fairly ionizing medium) because bic acid derivatives where the formation of a diazo ether
of the appreciable amounts of hydrodediazoniation prod- intermediate was detected experimentally by employing
ucts formed.[7,8,21,22,27] Many investigators have sought to electrochemical methods.[15,17] The assumption of a rate-
determine the mechanisms by which the diazonium group limiting decomposition of the diazo ether is also consistent
is replaced by hydrogen in solvolytic dediazoniations to with reported results for other O-coupling reactions,[4,5,18,37]
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and was probed experimentally in reactions of arene- ionic mechanism becomes competitive with the radical one
diazonium ions where geometric restrictions apply.[24,38] leading to the results shown in Figure 3 (B) and Figure 5.
From Scheme 2, Equation (1) can be derived where kHET
We thus propose that the initiation step in homolytic de-
and kHOM are the rate constants for the spontaneous ther- diazoniations induced by the solvent is the unimolecular
+
mal heterolytic decomposition of ArN2 and that for the decomposition of the transient diazo ether, yielding Ar· and
decomposition of the diazo ether, respectively, and K1 = K ·OMe; the experimental observations can then be rational-
[MeOH] with K standing for the equilibrium constant for ized by adapting the currently assumed radical propagation
diazo ether formation shown in Scheme 2.
mechanism[8,19,33,39] by including as the initiation step the
homolytic fragmentation of the transient diazo ether,
Scheme 3.
This equation is typical of processes where an S-shaped
dependence of kobsd. with –log[H+] is observed (where [H+]
represents the concentration of protonated solvent mole-
cules). From Equation (1), and by considering limits, we
find that when [H+] ϾϾ K1, kobsd. Ϸ kHET, i.e., the reaction
proceeds wholly through the DN + AN mechanism and only
heterolytic products are obtained. On the other hand, when
[H+] ϽϽ K1, kobsd. Ϸ kHOM, i.e. the reaction proceeds
wholly through the O-diazo ether and formation of re-
duction products is favoured. Solid lines in Figure 4 (A) and
Figure 4 (B) were obtained by fitting the data to a titration
curve of the Henderson–Hasselbach type, from where val-
ues of pK1 = 4.18 (95% MeOH) and 2.2 (80% MeOH) can
be obtained. Fitting parameters are listed in Table 1. Thus,
increasing concentrations of MeOH have opposing effects
upon the formation of the diazo ether in this concentration
range: it is favoured modestly by higher concentrations of
MeOH through the mass action effect, but strongly op-
posed by the medium effect on the equilibrium constant. It
was not possible to determine pK1 values at low MeOH
content, see Figure 4 (C), but the data suggest that the in-
flexion point should be reached at [HCl] Ͼ 1 . Variations
in pK1 values with the percentage of alcohol were pre-
viously observed[20] but were not as large as in the present
case.
Scheme 3. Proposed radical mechanism for the homolytic reaction
of arenediazonium ions with alcohols.
Once the aryl radical is formed after homolytic fragmen-
tation of the transient diazo ether in steps 1–2, the Ar· radi-
cals partitions between competing product-forming routes.
At low percentages of MeOH, an aryl radical reacts with
another aryl radical to yield 4,4Ј-dinitrobiphenyl, step 5, as
was found experimentally, and the reaction terminates. At
higher MeOH concentrations, when MeOH becomes an im-
portant part of the solvation shell, the aryl radical reacts
with a MeOH molecule within the solvent cage by ab-
stracting a hydrogen atom, and this is followed by dispro-
portionation of the hydroxymethyl radicals to yield form-
aldehyde as a final by-product in this termination route.
+
It was reported[8] that, in ethanolyses of ArN2 ions
bearing electron-withdrawing substituents, hydrodediazoni-
ations are invariably accompanied by the formation of some
aryl ethyl ether in spite of the very large difference between
the homolytic and heterolytic rate constants. To rationalize
this observation, it was proposed that the ethyl ethers may
be formed by the product-forming path 6 in Scheme 3,
which competes with the main hydrodediazoniation path.
Evidence coming from different directions suggests that this
is not a major pathway for the formation of ArOMe under
our experimental conditions, although it cannot be com-
pletely ruled out. At percentages between 5–60% MeOH,
the homolytic pathway is predominant because of the very
Table 1. Kinetic parameters obtained by fitting the data in Figure 4
(A) and Figure 4 (B) to a modified Henderson–Hasselbach equa-
tion. The parameters t1/2 (HET) and t1/2 (HOM) refer to the fitted
values at high and low acidity, respectively; t1/2 values at 95%
MeOH were determined from the first-order rate constants for the
sake of comparisons.
% MeOH
pK1
t1/2 (HET) [s]
t1/2 (HOM) [s]
95
80
4.18
2.20
1824
1375
3648
15687
It appears evident, therefore, that the formation of the low t1/2 values compared to that in absence of MeOH, Fig-
transient diazo ethers depends on both pH and MeOH con- ure 2, and because only ArH is obtained in significant
centration, and that at low percentages of MeOH the diazo yields, Figure 5. It follows, therefore, that if ArOMe is being
ether is formed because of the low acidities employed (i.e., formed by the homolytic pathway 6 in Scheme 3, appreci-
the high K1 value for the formation of the transient diazo able yields should have been detected within this MeOH
ether) and the reaction proceeds through a radical mecha- range but were not.
nism. In contrast, its formation is not so favoured at high
As discussed before, in aqueous acid solution in the ab-
percentages of MeOH in spite of the much higher MeOH sence of MeOH, the thermal decomposition of 4NBD is
concentrations present in the reaction mixture; in these situ- very slow, t1/2 = 1383 min, but addition of even low concen-
ations, MeOH molecules simply solvate ArN2+ ions and the trations of MeOH increases the overall rate because of the
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Dediazoniation of 4-Nitrobenzenediazonium Ions
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intervention of the homolytic route via the formation of the nucleophiles competing with water for stabilized carbo-
transient diazo ether and its subsequent fragmentation. At cations[42,43] and is consistent with the reactivity-selectivity
percentages of MeOH higher than 20%, the observed t1/2 principle, Scheme 1 (A), i.e., rate-determining formation of
increases again, i.e. the reaction becomes slower, although a highly reactive electrophilic intermediate.
there are two opposing effects. On the one hand, the equi-
librium constant for formation of the transient diazo ether
decreases but, on the other hand, the mass action effect will
promote formation of the diazo ether. Results in Table 1
show that observed t1/2 values for the heterolytic pathway
[i.e., when [H+] ϾϾ K1, Equation (1)] increase upon increas-
ing the MeOH content of the solution, as is found with
other arenediazonium ions, for example, the methyl deriva-
tives,[7–9] but observed t1/2 values for the homolytic pathway
(i.e., when [H+] ϽϽ K1) decrease upon increasing the per-
centage of MeOH. So, the heterolytic pathway becomes in-
creasingly more competitive with respect to the homolytic
one and because this happens at high [MeOH], larger
amounts of ArOMe than ArOH are expected and are ob-
served, see Figure 5.
Conclusions
In conclusion, we have been able to rationalize the com-
plicated behaviour found for the aqueous methanolysis of
4-nitrobenzenediazonium ions under acidic conditions. The
reaction provides an excellent example of the influence of
solvent composition on the change from a heterolytic
mechanism to a homolytic one. In the present case, this
change can be accommodated by a mechanism in which a
solvent molecule acts either as a nucleophile that simply
solvates the diazonium ions (allowing them to undergo
thermal heterolytic decomposition), or it may react directly
with them to yield O-coupling adducts in a highly unstable
Z configuration, i.e. (Z)-diazo ethers (which then undergo
homolytic fragmentation initiating radical processes). In the
present case, it appears therefore, that there is no conversion
of the unstable (Z)-diazo ether to the much more stable
E isomer, which would eventually undergo acid-catalyzed
fragmentation.[4–9] The proposed mechanism accounts for
the kinetic parameters, the reduction product formation,
the ether formation, the rate-enhancing effect of electron-
withdrawing substituents in the aromatic ring and the non-
first-order kinetics observed at intermediate percentages of
MeOH because at low-moderate MeOH percentages, the
According to Scheme 2, kobsd. is given by Equation (1),
and the ratio of yields of homolytic to heterolytic products
is given by Equation (2).[40]
Hence, if one assumes that ArOH and ArOMe are
formed exclusively by the heterolytic route, the ratio of the
total yields of homolytic products to the heterolytic ones is
+
rate of disappearance of ArN2 depends on the concentra-
Y
HOM/YHET Ϸ 2.9 at 95% MeOH (HPLC data not shown).
tion of methoxy radicals and, at low percentages of MeOH,
on the concentration of Ar radicals (path 4 and 6 in
Scheme 3).
From Figure 4 (A), pK1 = 4.18 and from Equation (2) with
[H3O+] = 10–3 , it follows that kHOM/kHET Ϸ 44. By taking
into consideration Equation (1), one can obtain values for
the homolytic and heterolytic rate constants at 95% MeOH,
kHET = 3.3·10–5 s–1 and kHOM = 1.4·10–3 s–1. The deter-
mined kHET value represents an increase of 4–fold on going
from water, i.e., absence of MeOH, to 95% MeOH, an in-
crease higher than that observed for other arenediazonium
ions in acidic aqueous methanol mixtures, where increases
in kHET of about twofold were reported.[23] For the ionic
mechanism, Scheme 1 (A), a rate-limiting nucleophilic at-
tack that would lead to a much stronger dependence of
kHET with solvent composition than that observed; our data
are thus consistent with an ionic mechanism in which the
rate-limiting step is the formation of a highly unstable aryl
cation, Scheme 1 (A), in agreement with the previous re-
ports based on the behavior of other ArN2+ ions in alcohol-
water mixtures.[7–9]
Focusing on the ionic mechanism, data in Figure 5 indi-
cate that, at approximately 80% MeOH/H2O, yields of
ArOH and ArOMe are the same. Therefore, the selectivity
of the electrophilic intermediate in the reaction towards
water and MeOH as competing nucleophiles is given by
SWMeOH = [H2O]/[MeOH] = 0.56, a value very similar to
those found from reactions of other arenediazonium ions
with different non-ionic nucleophiles.[12,41] Such a value is
A preliminary analysis of the pK1 values found in this
work, together with those previously reported,[20] appears
to suggest that the formation of the O adducts depends on
the nature of the alcohol employed as well as on alcohol
concentration, the acidity of the medium, and the nature of
the substituent in the benzene ring of the diazonium ions.
Further investigations into the formation of diazo ethers
are in progress and will be the subject of future reports.
Finally, it is worth noting that the results obtained here
indicate a simple, effective, and quick practical method for
replacing an aromatic primary amino group by hydrogen.
It represents an improved alternative to the method using
hypophosphorous acid as reducing agent proposed by
Kornblum.[44] Because arenediazonium salts can be pre-
pared easily from readily available aromatic primary
amines, these deamination processes involving reductive re-
moval of the primary amine groups are particularly useful
in synthetic aromatic chemistry because of the strong di-
recting effects associated with amine substituents.[45,46]
Experimental Section
Instrumentation: UV/Vis spectra and some kinetics experiments
orders of magnitude lower than those observed for anionic were followed with
a
Beckman DU-640 spectrophotometer
Eur. J. Org. Chem. 2006, 2201–2209
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2207

R. Pazo-Llorente, H. Maskill, C. Bravo-Diaz, E. Gonzalez-Romero
FULL PAPER
equipped with a thermostatted cell carrier and attached to a com-
puter for data storage. Product analysis was carried out with a
WATERS HPLC system which included a model 560 pump, a 717
automatic injector, a 2487 dual-wavelength detector, and a com-
puter for control and data storage. Products were analysed with a
Microsorb-MV C-18 (Rainin) reverse-phase column (25 cm length,
4.6 mm internal diameter, and 5 µm particle size) using a mobile
phase of 70:30 v/v MeOH/H2O containing 10–4  HCl. The injec-
tion volume was 25 µL in all runs and the UV detector was set at
220 and 280 nm.
centration, [ArN2+]o, estimated by weight, i.e. Y = 100[Analyte]ϱ/
[ArN2+]o, as described elsewhere.[9,20,33]
At low percentages of MeOH, an unanticipated product was de-
tected. To identify it, dediazoniation was performed at 50 °C on a
large scale in a 0.5% MeOH/H2O reaction mixture containing
[HCl] = 1 mM. The reaction products were extracted with diethyl
ether and the solvent was evaporated under reduced pressure. The
residue was then dissolved in CH2Cl2 and chromatographed on a
silica gel column (43–63 u, 60 Å). The isolated target compound
was identified by 1H NMR, 13C NMR as 4,4Ј-dinitrobiphenyl, and
the chemical shifts of the hydrogen atoms were positively correlated
with those of the directly bonded carbon atoms by HSQC. 1H
NMR (400 MHz, CDCl3): δ = 6.93 (d, J = 9.1 Hz, 4 H, H2, H2Ј,
H6, H6Ј), 8.14 (d, J = 9.1 Hz, 4 H, H3, H3Ј, H5, H5Ј) PPM. 13C
NMR (100 MHz, CDCl3): δ = 115.7 (d, C3, C3Ј, C5, C5Ј), 126.3
(d, C2, C2Ј, C6, C6Ј), 141.1 (s, C4, C4Ј), 162.0 (s, C1, C1Ј) PPM.
Materials: 4-Nitrobenzenediazonium (4NBD) tetrafluoroborate
was prepared under non-aqueous conditions as described else-
where,[47] and recrystallized three times from CH3CN/cold diethyl
ether; it was stored in the dark at low temperatures to minimize its
decomposition and was recrystallized periodically. 4-Nitrophenol
(ArOH), 4-nitroanisole (ArOMe), nitrobenzene (ArH), and other
reagents including those used in the preparation of arenediazonium
salts (as tetrafluoroborates) were of maximum available purity and
were used without further purification. The MeOH employed in
the kinetic experiments was HPLC grade and was used as received.
Solution composition is expressed as percent MeOH by volume.
Molar concentrations were calculated by ignoring the small excess
volume of mixed solvents.[48] All aqueous solutions were prepared
by using Milli-Q grade water.
Acknowledgments
Financial support from the following institutions is acknowledged:
MCyT(BQU2003-04775-C02), FEDER, Xunta de Galicia
(PGDIT03TAL30101PR), and Universidad de Vigo. R. P-L.
thanks Xunta de Galicia and Universidad de Vigo for a research
contract.
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 Equation (3) using a non-linear least-squares method in
those cases where clean first-order kinetics were observed; other-
wise, 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.
[1] D. S. Wulfman, Synthetic Applications of Diazonium Ions, in
The Chemistry of Diazonium and Diazo Compounds (Eds.: S.
Patai), John Wiley & Sons, 1978.
[2] K. H. Saunders, R. L. M. Allen, Aromatic Diazo Compounds,
Edward Arnold, Baltimore, MD, 1985.
[3] H. Zollinger, Color Chemistry, VCH, 1991.
[4] H. Zollinger, Diazo Chemistry I, Aromatic and Heteroaromatic
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[5] A. F. Hegarty, Kinetics and Mechanisms of Reactions Involv-
ing Diazonium and Diazo Groups, in The Chemistry of Diazo-
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NY, 1978.
[6] A. Chauduri, J. A. Loughlin, L. S. Romsted, J. Yao, J. Am.
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[8] P. S. J. Canning, H. Maskill, K. Mcrudden, B. Sexton, Bull.
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[10] C. Galli, Chem. Rev. 1988, 88, 765.
[11] J. Pinson, F. Podvorika, Chem. Soc. Rev. 2005, 34, 429.
[12] L. S. Romsted, Interfacial Compositions of Surfactant As-
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Method and Applications, in Reactions and Synthethis in Sur-
factant Systems (Ed.: J. Texter), Marcel Dekker, New York,
2001.
[13] K. Gunaseelan, L. S. Romsted, E. González-Romero, C. Bravo-
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[14] J. H. Powell, P. M. Gannet, J. Environ. Pathol. Toxicol. Oncol.
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All kinetics runs were at 50 °C. Duplicate or triplicate experiments
gave average deviations less than 7%. Stock 4NBD salt solutions
were prepared by dissolving it in the appropriate acidic (HCl) mix-
ture to minimize diazotate formation;[49] solutions of final concen-
trations about 1·10–3  and [HCl] = 3.6·10–3  were used generally
immediately or within 90 min with storage in an ice bath to mini-
mize decomposition. Beer’s law plots (not shown) in aqueous and
methanolic solutions up to 2.00·10–4  were linear (cc. Ն 0.999).
Spectrophotometric kinetic data were obtained by following the
+
disappearance of the absorbance of ArN2 at λ = 260 nm. Reac-
+
tions were initiated by adding an aliquot (Ͻ 100 µL) of the ArN2
stock solution to the previously thermostatted reaction mixture.
HPLC kinetic data were obtained by following a well-established
derivatization protocol that exploits the rapid reaction between
4NBD and a coupling agent to yield an azo dye as described else-
where.[29,47]
[15] U. Costas-Costas, E. Gonzalez-Romero, C. Bravo Díaz, Helv.
Chim. Acta 2001, 84, 632.
[16] P. Hanson, J. R. Jones, A. B. Taylor, P. H. Walton, A. W.
Timms, J. Chem. Soc., Perkin Trans. 2 2002, 1135.
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[18] J. F. Bunnet, H. Takayama, J. Org. Chem. 1968, 33, 1924.
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643.
Product analysis of reaction mixtures was by HPLC after de-
diazoniation was complete. Preliminary HPLC experiments showed
that three main products are formed, ArOH, ArH, and ArOMe.
Linear (cc. Ͼ0.999) calibration curves for converting HPLC peak
areas, A, into concentrations were obtained for these products by
employing commercial samples. Percentage of formation, Y, of de-
diazoniation products were obtained from the dediazoniation prod-
uct concentration, [Analyte]ϱ, and the initial diazonium salt con-
[20] R. Pazo-Llorente, C. Bravo-Díaz, E. González-Romero, Eur. J.
Org. Chem. 2004, 3221.
2208
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Eur. J. Org. Chem. 2006, 2201–2209

Dediazoniation of 4-Nitrobenzenediazonium Ions
FULL PAPER
[21] S. J. Canning, K. McCruden, H. Maskill, B. Sexton, Chem.
Commun. 1998, 1971.
from the solvent to the arenediazonium ions (see refs.[4,5,31,33]),
Scheme 1, and hence kobsd. = kHET + kHOM, and kHET/kHOM
=
[22] C. Bravo-Diaz, L. S. Romsted, M. Harbowy, M. E. Romero-
Nieto, E. Gonzalez-Romero, J. Phys. Org. Chem. 1999, 12, 130.
[23] R. Pazo-Llorente, E. González-Romero, C. Bravo-Díaz, Int. J.
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[24] E. González-Romero, B. Malvido-Hermelo, C. Bravo-Díaz,
Langmuir 2002, 18, 46.
(yields of heterolytic products)/(yields of homolytic products),
see for example: J. H. Espenson, Chemical kinetics and reaction
mechanisms, 2nd ed., Mc-Graw-Hill, NY, 1995; however, our
data clearly show that the product yields depends on both the
acidity and MeOH concentration, i.e., Scheme 2, and hence the
above relationships are no longer valid.
[25] C. Bravo-Díaz, E. González-Romero, Langmuir 2005, 21, 4888.
[26] M. P. Doyle, C. L. Nesloney, M. S. Shanklin, C. A. Marsh,
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[30] M. J. Pastoriza-Gallego, C. Bravo-Díaz, E. González-Romero,
Langmuir 2005, 21, 2675.
[41]
C. Bravo-Díaz, E. González-Romero, “Reactivity of Arene-
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[43]
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[33] J. F. Bunnet, C. Yijima, J. Org. Chem. 1977, 42, 639.
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[48] H. Yamamoto, K. Ichikawa, J. Tokunaga, J. Chem. Eng. Data
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Received: December 2, 2005
Published Online: March 6, 2006
Eur. J. Org. Chem. 2006, 2201–2209
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2209