Review
Progress in Reaction Kinetics and Mechanism, 2013, 38(1), 1 – 31
doi: 10.3184/146867812X13558462864799
The acid-catalysed benzidine rearrangements may
proceed via cation radicals formed by electron
transfer to a proton from a hydrazyl nitrogen
Andrew Mamantov
Office of Pollution Prevention and Toxics (7406M) US Environmental Protection Agency
Washington, DC 20460, US
E-mail: [email protected]
Abstract
The acid-catalysed benzidine rearrangements are proposed to proceed via
cation radical intermediates which arise by rapid electron transfer from a neutral
nitrogen of the hydrazyl moiety to a proton. Consequently, both the concerted
rearrangements, Table 1, benzidines, 4-methoxy-p-semidine formation, Eqns
(2), (3) and o,o'-biaryl-linked products, and non-concerted rearrangements,
Table 2, diphenyline, o-semidine, Eqns (5), (6) and perhaps 4-chloro-psemidine, may proceed via cation radical structures involving radical C – C
bond formations and homolytic N – N bond cleavages. This is contrary to the
current view of the Polar Transition State theory which postulates heterolytic
bond formations and cleavages, Schemes 1, 3 and 4. Mono-substituted and
4,4'-disubstituted hydrazobenzenes are proposed to undergo oxidation of the
most basic nitrogen as inferred from the estimated pKas as determined by
the SPARC program. This can explain why of the two possible o-semidine
rearrangement products, 2,N' and N,2'-linked, the observed major o-semidine
has the substituent para to the amino group, e.g. Eqn (5). However, if one of
the para substituents is a halogen, it is the nitrogen para to the halogen which
undergoes SET and oxidation. In these second-order acid reactions, this can
be explained by protonation of the most basic nitrogen followed by SET from
the hydrazyl nitrogen para to the halogen. In the case of 4,4'-disubstitution, the
hydrazobenzene may not lose its substituents readily and undergoes a rapid
one-electron reduction and consequent disproportionation reaction as shown
in Eqn (8). Thus the kinetics, first-order in hydrazoarene and the same kinetic
order in acid for both disproportionation and rearrangement, are explained.
KEYWORDS: benzidine rearrangements, disproportionation, single
electron transfer, homolysis, cation radicals
1
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Andrew Mamantov
1. INTRODUCTION
1.1 Rearrangements and disproportionation
The acid-catalysed benzidine rearrangements of aromatic hydrazo compounds
have baffled chemists since the rearrangement of hydrazobenzene was first
reported by Hofmann in 1863[1]. The rearrangements go through a seemingly
convoluted intramolecular mechanism which can yield diamino biaryls and
aminodiarylamines, e.g. Eqn (1). Both homolytic and heterolytic scissions
of the N – N bond had been proposed. Furthermore, in most cases, there is a
puzzling, accompanying disproportionation reaction [2 – 10].
(1)
The major rearrangement product if the hydrazoaromatic is not substituted in
the para position is the benzidine molecular framework. If there is substitution
in the para position, there is an increase in the formation of diphenyline,
o-benzidine, o-semidine and p-semidine products. Substitution in both para
positions shifts the reaction predominantly towards disproportionation.
With regard to the disproportionation reaction, the stoichiometry is shown in
Eqn (2).
ArNHNHAr → ArN = NAr + 2ArNH2
(2)
Two molecules of hydrazoarene yield one molecule of azoarene and two
molecules of arylamine. The kinetics of the disproportionation are always firstorder in hydrazoarene, while the disproportionation and the rearrangement
always have the same kinetic order in acid, whether it is first, second or mixed
order. Currently, the mechanisms of both reactions are written as either a one
(positively charged) or two (doubly positively charged) atom protonation, e.g.
Scheme 1.
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Acid-catalysed benzidine rearrangements
3
Scheme 1 PTS theory, second-order in acid protonation.
The conclusion is that there is an intermediate formed in a rate-determining step
and it is formed in a process which is kinetically identical to the rearrangement.
This intermediate then rapidly rearranges or rapidly oxidises a second
molecule of hydrazoarene to yield disproportionation. Consequently, the focus
of attention of the benzidine rearrangement shifted towards elucidating the
structure of this intermediate.
1.2 Previous theories
Banthorpe, Hughes, Cooper and Ingold postulated the polar transition
state theory (PTS) which suggested that the intermediate involved in
disproportionation has a quinonoid structure [2,3]. This structure also provides
a rationale for the rearranged products, Scheme 2. Four other possibilities which
have been proposed and reviewed [2 – 5] are the caged radical or caged radical
ion, Dewar’s π-complex theory [6], Lukashevich’s theory which postulates
that the hydrazo compound is not sufficiently basic to be diprotonated [8]
and the C-protonated theory, originally proposed by Hammick and Mason,
which postulates that one of the protonations occurs on carbon rather than
nitrogen [9]. Unlike the PTS theory, the benefit here is that a tetrahedral centre
is introduced, rendering the molecule more flexible, thereby enabling the
convolutions necessary for the rearrangements to occur. Dewar’s π-complex
theory proposed that in monoprotonated hydrazobenzene the N – N bond is
replaced by a delocalised π bond between the rings holding them together in
parallel planes in a relatively mobile configuration. This “π-complex” could
then collapse to yield the products. This theory, the caged radical or caged
radical ion, and Lukashevich’s theory are now regarded as unlikely.
1.3 Concerted and non-concerted Reactions
The studies of Shine et al., using nitrogen and carbon kinetic isotope
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Andrew Mamantov
Scheme 2Disproportionation mechanism, PTS theory. Reprinted by permission from
Macmillan Publishers Ltd [2].
effects (KIEs), have provided information concerning the concertedness
of the benzidine rearrangements and that the concerted reactions follow
the rules of orbital symmetry. Tables 1 and 2 show the concerted and nonconcerted reactions, respectively. It was found that the second-order proton
rearrangement of hydrazobenzene to benzidine was concerted whereas the
formation of diphenyline was non-concerted [11]. Benzidine formation can
be classified as an allowed [5,5] sigmatropic rearrangement while diphenyline
formation is a [3,5] sigmatropic rearrangement which also follows the
requirements of orbital symmetry and cannot be suprafacially concerted.
The other concerted reactions are the first-order proton [1,5] sigmatropic
rearrangement of 4-methoxyhydrazobenzene to p-semidine [12]; the first-order
proton [5,5] sigmatropic rearrangement of 2, 2'-dimethoxyhydrazobenzene to
3,3'-dimethoxybenzidine [13]; both the first-order and second-order proton [3,3]
sigmatropic rearrangements of 2,2'-hydrazonaphthalene [14] and N-2-naphthylN'-phenyl-hydrazine [15] to yield the o,o'-biaryl-linked diamines, 2,2'-diamino1,1'-binaphthyl and 1-(o-aminophenyl)-2-naphthylamine, respectively; the
second-order proton disproportionation reaction of 4, 4'-diiodohydrazobenzene
[16]; the second-order proton rearrangement of 4,4'-dichlorohydrazobenzene to
o-semidine may be a concerted [1,5] sigmatropic shift, but is not characterised
as such and is, therefore, suggested to be non-concerted [17]. The other nonconcerted rearrangements are the second-order proton [1,3] sigmatropic shift of
4,4'-dichlorohydrazobenzene [17], and also probably the first-order proton [1,3]
sigmatropic shift of 4-methoxyhydrazobenzene [12] to yield the corresponding
o-semidine products. The authors claim that the results rule out the possibility
of the rate-determining formation of a π-complex or radical/radical ion
intermediate in the disproportionation of 4,4'-diiodohydrazobenzene [16].
After the above 1980s work of Shine et al., interest in the mechanistic aspects
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Acid-catalysed benzidine rearrangements
Table 1 Concerted benzidine rearrangements
Starting hydrazoaromatic
Product
Ref.
of the rearrangements waned. There was a review commentary on Dewar’s
π-complex theory in 1989 [18] and some kinetic isotope work revisited in 1993
[19]. In 1997, Park’s report supported Shine’s proposals that the rearrangements
follow the patterns of sigmatropic processes [20] and there was one other Park
paper in 1998 with unsymmetrical hydrazoaromatics [21]. The latter work also
supported the concept that disproportionation is important in understanding
the rearrangements. Therefore, the current interpretation of the benzidine
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Andrew Mamantov
Table 2 Non-concerted benzidine rearrangements
Starting hydrazoaromatic
Product
a
May be concerted, but not characterised, see text.
Ref.
rearrangements and disproportionation basically represents the work up to the
1980s, that it occurs via a mono-or diprotonated quinonoid intermediate with
a polar transition state [2 – 5,17]. If the hydrazoaromatic is 4,4'-disubstituted, it
would be unable to lose its substituents readily and is postulated to be reduced
rapidly by a second molecule of hydrazo compound.
1.4 Renewed interest
While interest in the mechanistic aspects of the rearrangements declined in
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Acid-catalysed benzidine rearrangements
7
the last two decades, the products of the rearrangements may have relevance
for the synthesis of axially chiral biaryls [22,23]. The latter have gained
much prominence as scaffolds for asymmetric synthesis. In this regard,
binaphthyl systems have been much investigated concerning enantioselective
transformations [24]. The acid-catalysed benzidine rearrangements can yield
symmetrical biaryl skeletons. For example, 2,2'-hydrazonaphthalene rearranges
to 2,2'-diamino-1,1'-binaphthyl in almost 100% yield [14] and N-2-naphthylN'-phenylhydrazine rearranges to the corresponding naphthyl-phenyl biaryl
1-(o-aminophenyl)-2-naphthylamine in 99% yield [15]. This occurs under
mild conditions and the biaryls can then be used as platforms for asymmetric
syntheses. This is an advantage in comparison to some of the current methods
which utilise more harsh oxidative conditions or air sensitive compounds such
as Grignards, diaryl zinc and aryl lithium. The prominence of this field and
the developments below have given new relevance to the elucidation of the
mechanisms.
Synthetic aromatic azo dyes are widely used in the production of textiles, paints,
printing inks, food processing, reagents, biological stains, lasers, liquid crystal
displays, ink-jet printers and electro-optical devices. The textile industry is
one of the largest consumers of synthetic azo dyes. It has been estimated that
280,000 tons of textile dyes are discharged annually in industrial wastewaters
worldwide [25]. Consequently, there is concern about pollution due to improper
discharge of wastewater contaminated with azo dyes and their metabolites
such as the hydrazides and aromatic amines. This pollution can cause a variety
of environmental problems, toxic effects, mutagenicity and carcinogenicity
[26 – 29].
As a result, the US Environmental Protection Agency is regulating certain
azo dyes and is considering regulating additional azo dyes under the Toxic
Substances Control Act of 1976 because they may be metabolised to aromatic
amines which may be human carcinogens [30]. The European Union and
Canada have expressed similar concerns about the release of benzidine and its
congeners from azo dyes in consumer products. [31, 32].
The acid-catalysed benzidine rearrangement has been implicated in the
formation of benzidine by ingestion of azobenzene via hydrazobenzene in
the stomach [33]. Azobenzene is carcinogenic to rats and hydrazobenzene
is carcinogenic to rats and mice. It has been demonstrated that copper ion
can mediate oxidative DNA damage by hydrazobenzene, hydrazine and its
derivatives, and copper is present in mammalian cells. The mechanisms are
proposed to involve nitrogen hydrazyl radicals [26], but the intermediate may
actually be the nitrogen cation radical form of the hydrazyl moiety as proposed
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Andrew Mamantov
herein for the benzidine rearrangements.
Bioremediation of azo dyes in wastewater treatment is an important degradative
process [26]. The in vitro microbial degradation of azo dyes may involve
cytosolic flavin dependent azo reductases which shuttle electrons to azo dyes
via soluble flavins [29].
Accordingly, the mechanisms of the benzidine rearrangements are of renewed
interest.
2. ANALYSIS AND DISCUSSION
2.1 Mechanisms
At this stage, it is noted that most of the radical or radical ion intermediates which
have been previously postulated and excluded as candidates in rearrangement
and disproportionation are derived by the homolytic cleavage of a mono- or
diprotonated hydrazo bond. The exceptions to this are the cation radicals which
have been shown to be formed from tetraphenylhydrazine during the formation
of N,N'-diphenylbenzidine in trifluoroacetic acid [34] and uncatalysed
rearrangements in liquid sulfur dioxide [35]. Other tetra-and triarylhydrazines
may undergo loss of an electron from the hydrazyl moiety in the presence of
oxidizing agents, e.g. acids, to yield stable hydrazyl radicals or decomposition
products [36]. However, in the case of diaryl-substituted hydrazines, the known
oxidation of 9-hydrazo-acridine is apparently an unusual example of formation
of a stable hydrazyl radical which disproportionates slowly in the solid state
and rapidly in solution [37].
This is in line with the proposal given here that the benzidine rearrangements,
both concerted and non-concerted, and first, second and mixed order in
acid, proceed via cation radical intermediates which arise by a rapid electron
transfer from a neutral nitrogen of the hydrazyl moiety to the proton to yield
a hydrogen atom and a nitrogen cation radical whose charge and electron are
delocalised over the aromatic system. In the second-order in acid reactions, e.g.
the prototype benzidine rearrangement itself, the single electron transfer (SET)
may occur after protonation of the other hydrazyl nitrogen, Eqn (3).
It is further proposed that both the concerted rearrangements, i.e. benzidine,
4-methoxy-p-semidine and o,o'-binapthyl linked products, e.g. Eqns (3), (4),
and (7), respectively, and non-concerted rearrangements, i.e. o-semidine,
diphenyline, and 4-chloro-p-semidine which may be concerted, but is not
characterised as such, proceed via cation radical intermediates involving
radical C – C and C – N bond formations and homolytic N – N bond cleavages,
e.g. Eqns (5), (6) and (9). In the non-concerted reactions, N – N bond breaking
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Acid-catalysed benzidine rearrangements
9
is further along in the transition state in comparison to C – C bond making and
these appear to be dissociative processes.
(3)
This SET mechanism is in accord with experimental observations that the
rates are enhanced by electron-donating substituents and retarded by electronwithdrawing substituents [4].
The increase in rates due to increase in solvent polarity and addition of salts
are accounted for by the increase in polarity of the reacting system since the
electron transfer generates cation radical species.
2.1.1 Benzidine formation
Eqn (3) presents a rationale for the concerted two-proton benzidine
rearrangements. SET leads to cation radical formation, delocalisation,
homolytic synchronous N – N bond cleavage and 4,4'-carbon bond formation
between the two slightly bent rings which retain enough continuous p-orbital
overlap to account for the concertedness. The quinonoid intermediate is formed
which undergoes two tautomerisations and H-atom addition to the originally
oxidised nitrogen to yield benzidine. Similarly bent rings and rationale have
been proposed by Shine, but for heterolytic cleavage via the PTS theory. The
4,4'-linkage may be favoured because the para positions may have the largest
ring spin density [38,39]. The average measured kinetic isotope effects of
1.0222 for 15N, 1.0209 for 13C, 1.0284 for 14C via scintillation counting and 1.028
via combustion analyses support a concerted process for benzidine formation
[11]. This kinetic isotope work was revisited in 1993 and the results supported
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Andrew Mamantov
the conclusion that benzidine formation is concerted [19]. The kinetic isotope
effects, however, were smaller in magnitude for carbon, 1.0127 for 13C and
1.0121 for 14C. On the other hand, for nitrogen the kinetic isotope effects were
larger, 1.0410 for 15N.
Previously, in order to account for the second-order in acid and convoluted
benzidine rearrangement, Hammick and Mason proposed a C-protonated
intermediate [9]. This theory was revived by Allen [40], Webster [41], Lupes
[42] and Olah [43]. Allen and Lupes suggested ipso protonation of the carbon
directly adjacent to the protonated nitrogen. This suggestion has been regarded
as unreasonable [12]. On the other hand, Olah and co-workers favour the second
protonation to occur on the carbon attached to the nitrogen of the aromatic ring
distal to the protonated nitrogen. They propose that this protonation can occur
directly or alternatively by protonation of the second unprotonated nitrogen
followed by fast intramolecular transfer to the adjacent C-1 of the phenyl group.
The benefit of ipso protonation is that an sp2 carbon atom is converted to an
sp3, carbon yielding a more flexible ring thereby enabling the formation of
convoluted rearrangement products. However, the downside to ipso protonation
is that it disrupts the continuous array of p-orbitals which are probably required
to account for the concerted reaction.
Olah found NMR evidence, e.g. Eqn (3), structure e, of a di-C-protonated
quinonoidal ring-linked intermediate in super acid as proposed by Banthorpe,
Cooper, Hughes and Ingold, Scheme 2 [2,3]. The cation radical mechanism
presented herein can account for Olah’s experimental results, e.g. the nonobservance of deuterium incorporation into the aromatic rings.
2.1.2 Semidine formation
Eqn (4) is an example of a one-proton concerted p-semidine formation, X = OMe.
SET occurs from the less basic nitrogen which is inferred from the modelling
program called SPARC Performs Automated Reasoning in Chemistry (SPARC)
which provides estimated pKa values [44], Table 1, N = 0.58 versus N' = 0.63. As
discussed below in section 2.2 under PTS Theory, the less basic nitrogen is
para o the OMe group. This is somewhat surprising. Previously, it was assumed
that this nitrogen was the most basic. Hence, protonation of this nitrogen led
to complications in trying to explain results via heterolytic cleavage and the
PTS theory [4]. To explain the results, the transition state was represented by
protonation of the N' position as shown in Figure 1 [12]. In contrast, in Eqn
(4), there is homolytic N – N bond cleavage and N – C bond formation which
is concerted as determined by the average nitrogen and carbon kinetic isotope
effects of 1.0296 and 1.0390, respectively. Tautomerisation and H-atom addition
to the original nitrogen which underwent the SET completes the cycle.
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Acid-catalysed benzidine rearrangements
11
(4)
H
H
N
H
N
MeO
+
H
Figure 1 Second-order in acid formation of p-semidine. Reprinted with permission from
Journal of the American Chemical Society [12].
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Andrew Mamantov
Eqn (5), X = OMe, is an example of the one-proton non-concerted o-semidine
formation which is the major product. This time SET occurs from the most
basic nitrogen as inferred from SPARC estimated pKa values. Here, the average
nitrogen kinetic isotope effect of 1.0740 is much larger than the average nitrogen
kinetic isotope effect of 1.0296 for formation of p-semidine. A carbon kinetic
isotope effect could not be measured because of synthetic difficulties. Calculated
carbon and nitrogen kinetic isotope effects are 1.0367 and 1.0633, respectively,
which is indicative of a non-concerted process [12]. If X is electron withdrawing,
e.g. chlorine or nitro, diphenyline is also formed. Diphenyline is not reported if
X is methoxy.
(5)
2.1.3 Diphenyline formation
Eqn (6) is an example of the two-proton non-concerted formation of diphenyline
from hydrazobenzene.
The 15N, 13C and 14C labelling experiments gave kinetic isotope effects of
1.0633, 1.001 and 1.000, respectively, are supportive of a non-concerted process
[11]. This work was also revisited in 1993 and once again, within experimental
error, there was no 13C and 14C kinetic isotope effect. The 15N kinetic isotope
effect was 1.0367 [19]. The N – N homolytic bond cleavage is involved in the
rate-determining step, followed by C – C bond formation which is not part
of the rate-determining step in the transition state. Presumably, protonation
occurs first, followed by SET from the other nitrogen to the second proton to
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Acid-catalysed benzidine rearrangements
13
yield the delocalised aromatic cation radical. If SET occurred first, then the
second proton would have to protonate a presumably less basic nitrogen which
is adjacent to a partially positively charged nitrogen.
The estimated pKa of a singly protonated hydrazobenzene is 0.23 and that of
the doubly protonated molecule is – 7.30. Hence, it is highly unlikely that the
reaction would proceed via second-order in acid with both nitrogens protonated
as per the PTS theory.
(6)
2.1.4 O,O'-Biaryls and carbazole formation
With some exceptions, o-benzidine rearranged products are usually obtained in
trace quantities with hydrazobenzenes [4]. It has been suggested this is because
in the transition state the rings are slightly puckered, causing the ortho positions
to be pushed out from each other thereby inhibiting bonding between them [11].
The delocalised cation radical phenyl rings proposed in the SET mechanism
herein can be similarly bent and hence 2,2' bonding inhibited. In contrast, the
one-proton [3,3] sigmatropic rearrangement of 2,2'-hydrazonaphthalene [14],
Eqn (7), and two-proton catalysed N-2-napthyl-N'-phenylhydrazine [15] are
concerted reactions which undergo almost entirely o,o'-bonding with little
or no disproportionation. This may be because the extra ring in the naphthyl
system inhibits the puckering of the ring attached to the oxidised hydrazyl
nitrogen, thereby inhibiting the displacement of the ortho positions. It has
also been suggested that the ortho positions are simply closer together in the
naphthalene systems because the rings are less capable of “folding over” due to
steric considerations [5]. The inhibition to forming a bent napthyl cation radical
aromatic system can also explain the lack of observance of 2,4'-linked products
in the binaphthyl hydrazo compounds.
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Andrew Mamantov
While the reactions of these naphthalene systems are concerted, the N – N bond
breaking and C – C bond making proceed to different extents in the transition
states. It is unknown whether the high nitrogen and low carbon kinetic isotope
effects, 1.0904 and 1.0086, respectively, means that the N – N bond breaking
is further along in the transition state in comparison to C – C bond making
or the reverse; that C – C bond making is further advanced than N – N bond
breaking. Interestingly, the results of the acid-catalysed and neutral thermal
hydrazonaphthalene rearrangements are similar. In the latter, the N – N kinetic
isotope effect is 1.0611 and the C – C kinetic isotope effect is 1.0182 [14].
As shown in Eqn (7), the hydrazonaphthalenes give small yields of carbazole
(7)
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Acid-catalysed benzidine rearrangements
15
products. There is agreement that the carbazole is not formed from the o,o'bonding rearrangement product, but arises from a bifurcation in the pathway
after C – C bonding.
2.1.5 Disproportionation
Eqn (8) is a rationale for the puzzling disproportionation reaction.
The slow step in all the reactions is the formation of the quinonoidal
intermediates, e.g. structure 8a. If there are no substituents in the 4- and
4'-positions of the hydrazobenzene, e.g. Eqns (3) and (6), two tautomerisations
can yield the final product. This accounts for the first-order kinetics in
hydrazobenzene and the carbon and nitrogen kinetic isotope effects observed
by Shine et al. If, however, the hydrazobenzene is 4, 4'-disubstituted, it cannot
undergo the tautomerisations and instead undergoes a rapid intermolecular
one-electron reduction. In the last step, the aniline radical abstracts a hydrogen
from the hydrazyl radical to yield the second aniline and azo molecules. The
4,4'-diiodohydrazobenzene yielded about 100% disproportionation products
whereas the 2,2'-isomer yielded 100% benzidine product [2,16].
If the hydrazobenzene has only one para substituent, then formation of the
quinonoidal intermediate is still the slow step and disproportionation of the
intermediate is still rapid. In these cases, benzidine products have also not been
observed, but there are significant yields of diphenylines, o-semidines (2,N'
and N,2') and p-semidines along with disproportionation.
The second-order proton reaction of 4,4'-dichlorohydrazobenzene gave 11%
o-semidine, 12% p-semidine and 60% disproportionation. The results suggest
(8)
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Andrew Mamantov
that p-semidine formation, a 1,5 sigmatropic shift which, according to the
principles of orbital symmetry, may be concerted, is not characterised as such
because of a nitrogen kinetic isotope effect of 1.0162 and the absence of a carbon
kinetic isotope effect which was effectively unity. Formation of o-semidine, a
1,3 sigmatropic shift, cannot in principle be suprafacially concerted. This is
supported by the lack of a carbon kinetic isotope effect which was considered
to be unity and a nitrogen kinetic isotope effect of 1.0155.
As with the dichlorohydrazobenzene rearrangements, its disproportionation
reaction has the same kinetics, i.e. second-order in acid and first-order in
hydrazobenzene. Interestingly, the yield of azo product was not equal to just the
yield of p-chloroaniline products. It was equal to the sum of the p-chloroaniline
product and the yields of one or both of the semidines, but most likely the
p-semidine. Hence, the azo product is formed by both C – C bond cleavage
and by chloride displacement to yield p-semidine (or o-semidine), e.g. Eqn (9).
According to PTS theory, the formation of the semidine product is accounted
for by ejection of chloride cation, not the anion.
(9)
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Acid-catalysed benzidine rearrangements
17
In PTS theory, a quinonoidal intermediate is formed in a rate-determining step.
In subsequent steps, it rearranges to products or undergoes reductive cleavage
by a second molecule of hydrazoarene to yield disproportionation products,
azoarene and two aniline molecules, Scheme 2. However, the PTS theory,
unlike the SET mechanism proposed here, Eqn (8), lacks a detailed mechanistic
picture as to how the reduction occurs.
2.2 PTS theory and protonation
With regard to the PTS theory and its concept of mono- or diprotonation,
e.g. Scheme 1, of the hydrazo nitrogens to yield the corresponding monoor dications with first- or second-order acid reactions, respectively, the
only direct evidence of initial molecular protonation is the monoprotonated
hydrazobenzene monochloride prepared from hydrazobenzene with dry HCl
in ether [43]. The NMR spectrum indicated rapid proton exchange between
the two hydrazo nitrogens. The measured pKas of the hydrazoarenes are not
known. However, it is possible to get estimated micro and macro pKa values
via the SPARC program [44], shown in Tables 3 and 4. Table 3 has the available
estimated pKas for hydrazobenzene and the compounds listed in the tables of
ref. [2]. Table 4 has estimated pKas of representative compounds discussed in
refs [3 – 5] and [37] whose order in acid is not known. The micro pKa is the
microscopic dissociation constant of each ionisable atom in a molecule. The
macro pKa is the experimentally determined dissociation constant in a titration
experiment and can be obtained mathematically from combinations of the
micro pKas. The Ka1 dissociation constant corresponds to the monoprotonated
hydrazoarene yielding the neutral hydrazyl nitrogen species plus H+. The
Ka2 dissociation constant corresponds to the dicationic species wherein both
hydrazyl nitrogens are protonated to yield a monoprotonated cationic hydrazyl
nitrogen species plus H+.
Some analyses of protonations by perchloric acid in 60% aqueous dioxane of
the hydrazyl nitrogens are shown in Table 5. The first-order acid reactions of the
monosubstituted p-methoxyhydrazobenzene have been studied in a [H+] range
of 5.0 x 10 – 3 M to as low as 7.0 x 10 – 6 M and the o,o'-dimethoxyhydrazobenzene
in a [H+] range of 5.0 x 10 – 2 M to 1.0 x 10 – 4 M [2]. Examining the ratio of
unprotonated species to protonated species for the above monosubstituted
methoxy compound utilizing the macro pKa1 of 0.91 yields a ratio range of
25 (4% protonated) to 1.6 x 10 4 (6.3 x 10 – 3% protonated). Utilisation of the
micro pKa1 of 0.63 yields a ratio range of 46.8 (2.1% protonated) to 3.3 x 10 5
(3.0 x 10 – 4% protonated) whereas the more acidic N with pKa1 of 0.58 yields
ratio range of 52.5 (1.9% protonated) to 3.7 x 10 4 (2.6 x 10 – 3% protonated.
For the o,o'-dimethoxyhydrazobenzene using a macro pKa1 of 0.38 the ratio
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Andrew Mamantov
Table 3 SPARC pKas of hydrazobenzenes studied in ref. [2]
R,R' in Ph
Order
in H+
Micro pka1, N,N' a
H,H
2
2-MeO,2'-MeO
1
2-MeO,----
1,2
4-MeO,----
1
4-NHAc
1
2-F, 2'-F
2
2-Cl, 2'-Cl
2
Macro
pka1 b
Micro pka2,
0.23; 0.23 (0.84)
0.53
–7.30; –7.30
0.08; 0.08 (0.79)
0.38
–7.59; –7.59
0.01 (0.13); 0.75 (0.78)
0.82
–7.59; –6.85
0.58 (0.44); 0.63 (0.49)
0.91
–6.95; –6.90
–0.24 (0.17); 0.30 (0.59)
0.43
–7.76; –7.23
–1.74; –1.74
NA
–9.33; –9.33
–2.09; –2.09
NA
–9.68; –9.68
N,N' c
4-Cl, 4'-Cl
2
–0.94; –0.94
NA
–8.47; –8.47
4-Cl, ----
2
–0.58 (0.16); –0.13 (0.45)
0.00
–8.11; –7.66
2-Br, 2'-Br
1,2
–1.96; –1.96
NA
–9.57; –9.57
4-Br, 4'-Br
2
–0.99; –0.99
NA
–8.52; –8.52
2-I, 2'-I
1
–1.91; –1.91
NA
–9.55; –9.55
4-I, 4'-I
~ 2
–1.10; –1.10;
NA
–8.63; –8.63
2-Ph, 2'-Ph
2
0.41; 0.41
0.71
–7.27
4-Ph, ----
2
–0.23 (0.30); –0.15 (0.37)
0.11
–7.76; –7.50
4-NO2, ----
2
–5.45; –1.56
NA
–12.95; –8.49
1
–0.02; –0.02
0.28
–7.50; –7.50
1–2
0.11 (0.46); 0.22 (0.36)
0.47
–7.43; –7.27
1–2
0.85; 0.85
NA
–8.15, –8.15
1.1–2
–0.37 (0.26); –0.24 (0.35)
0.00
–7.90; –7.55
1-Nap, 1'-Nap d
1-Nap, Ph
d
2-Nap, 2'-Nap d
2-Nap, Ph d
Numbers in parenthesis correspond to maximum fraction of the micro species in solution at
25 ºC.
b
Macro pKa1 is the value obtained in titration experiment of monoprotonated hydrazo nitrogen.
c
pKa2 when both hydrazyl nitrogens protonated.
d
Compounds in ref. [3], Table 1.
NA = not available; Nap = naphthalene; Ph = phenyl.
a
range is 8.3 to 4.2 x 10 3 (12% to 24% protonated; H+ range of 5.0 x 10 – 2 M to
1.0 x 10 – 4 M) whereas using the micro pKa of 0.08 gives a ratio range of 16.6
to 8.3 x 10 3 (6% to 1.2 x 10 – 2% protonated). The second-order in acid reaction
of p-chlorohydrazobenzene has been studied in [H+] range of 0.07 to 1 M. The
micro pKa2s of the doubly protonated nitrogen species are – 8.11 (N) and – 7.66
(N'). Utilizing the pKa2 of the more acidic nitrogen N, – 8.11, yields a ratio range
of 1.9 x 10 9 to 1.3 x 10 8 (5.4 x 10 – 8% to 7.7 x 10 – 7% diprotonated). The point is
that while micro pre-equilibria may exist between the protons and hydrazo
nitrogens, it is certainly reasonable to question the concept that these firstwww.prkm.co.uk
19
Acid-catalysed benzidine rearrangements
order in acid benzidine reactions proceed via a monoprotonated cationic
nitrogen species when the ratios of unprotonated/protonated species are so
high in dilute acid range. Analogous reasoning applies to the second-order
in acid reactions. The percentage of diprotonation is extremely small which
renders the PTS theory open to question. In the preparation of hydrazobenzene
hydrochloride with dry HCl and hydrazobenzene in ether, the NMR spectrum
shows a monoprotonated hydrazobenzene indicative of rapid proton exchange
between – NH – and – NH2+ – . At – 78 °C in FSO3H – SO2(SO2ClF) or HF – SO2
[43] the diaminoquinonoidal intermediate postulated by Banthorpe, Cooper
Table 4 SPARC pKas of hydrazobenzenesa
R,R' in Ph
4-Me, 4'-Me2NH+
4-Me, 4'-OAc
4-Me, 4'-I
Micro pka1, N,N' b
Macro
pka1 c
Micro pka2, N,N' d
–0.10 (0.50); –0.82 (0.10)
–0.02
–7.63; –8.35
0.58 (0.70); 0.00 (0.18)
0.69
–7.52; –6.94
0.25 (0.63); –0.36 (0.15)
0.35
–7.27; –7.89
4-Me, 4'-Br
e
0.29 (0.63); –0.29 (0.17)
0.39
–7.24; –7.81
4-Me, 4'-Cl
e
0.31 (0.63); –0.26 (0.17)
0.41
–7.22; –7.78
0.38 (0.63); –0.10 (0.21)
0.51
–7.14; –7.63
4-Me, 4'-F
e
4-EtO, 4'-NMe2 NH
–0.21; –0.76
–0.10
–7.74; –8.28
4-EtO, 4'-Br
0.17 (0.22); –0.22 (0.55)
0.32
–7.35; –7.75
4-EtO, 4'-Me
0.88; 1.06
1.28
–6.47; –6.65
4-Me, 4'-Me f
0.99; 0.99
1.30
–6.53; –6.53
3-Me, 3'-Me g
0.52; 0.52
0.82
–7.01; –7.01
2-Me, 2'-Me h
+
0.49; 0.49
0.79
–7.12; –7.12
4-Me, ----
i
0.67 (0.53); 0.55 (0.40)
0.92
–6.85; 6.98
2-Me, ----
e
0.26 (0.35); 0.43 (0.52)
0.66
–7.30; –7.14
0.06 (0.14); 0.81 (0.78)
0.88
–7.52; –6.81
–12.73
NA
NA
2-OEt, ---- e
9Ac, 9Ac j
Compounds in ref. [3], acid order unknown.
Numbers in parentheses correspond to maximum fraction of monoprotonated hydrazyl
nitrogen micro species in solution at 25 ºC.
c
Macro pKa1 is value obtained in titration experiment of monoprotonated hydrazo nitrogen.
d
pKas when both hydrazyl nitrogens protonated.
e
Not in ref. [3] but presented for comparison.
f
Ref. [3], Table 1, 2nd order in acid.
g
Ref. [5].
h
Ref. [3], Table 1, 1st–2nd order in acid.
i
Refs [3,4].
j
Ref. [37].
a
b
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20
Andrew Mamantov
Table 5 Ratios of unprotonated to protonated hydrazobenzenes in acid range studieda
R,R' in Ph
4-MeO, H b
H+ Range (M)
Micro Ka1/H+
Macro Ka1/H+ and/or
Micro Ka2/H+
5 x 10 –3–7.0 x 10 –6
52.5–3.7 x 104 (N)
[1.9–2.6 x 10 –3% p] c
Macro Ka1/H+
25–1.6 x 104
[3.9–6.3 x 10 –3% p] c
46.8–3.3 x 104 (N')
[2.1–3.0 x 10 –3% p] c
2-MeO,
5 x 10 –2–1.0 x 10 –4
16.6–8.3 x 103 (N,N')
[5.7–1.2 x 10 –2% p] c
Macro Ka1/H+
8.3–4.2 x 103
[11–2.4 x 10 –4% p] c
1–0.07
3.8–55 (N)
[21–1.8% p] c
Macro Ka1/H+
1–14.5
[50–6.5% p]
Micro Ka2/H+
1.3 x 108–1.9 x 109 (N)
[7.7 x 10 –7–5.4 x 10 –8% p] c
2'-MeO b
4-Cl, H d
1.3–19.5 (N')
[43–4.9% p] c
4.6 x 107–6.6 x 108 (N')
[2.2 x 10 –6 –1.5 x 10 –7% p] c
H, H d
0.1 e
5.89 (N,N')
[14.5% p] c
Macro Ka1/H+
3.0
[25% p]c
Micro Ka2/H+
2.0 x 108 (N,N')
[5.0 x 10 –7% p] c
Perchloric acid in 60% aqueous dioxane, ref. [2].
First-order in acid.
c
Numbers in brackets correspond to % protonated (p).
d
Second-order in acid
e
0.1 M HCL in 75% aqueous ethanol: Shine, H.J., Henderson, G.N., Cu, A. and Schmid, P.
(1977) J. Am. Chem. Soc., 99, 3719.
a
b
and Ingold was observed by NMR, as well as the final benzidine product and
a small amount of diprotonated benzidine, but not a diprotonated hydrazo
intermediate. Since the first three intermediates were observed, it is surprising
that the diprotonated hydrazobenzene which leads to the intermediate
quinonoidal intermediate was not observed. Also interesting, hydrazobenzene
does not form the dihydrochloride salt in ether. Perhaps this is because the
monochloride precipitates out immediately after formation. However, in
SO2 solution saturated with HCl, hydrazobenzene does form the rearranged
benzidine product. Hence, there is no evidence that protonation of an atom is the
function of the second proton in formation of benzidine from hydrazobenzene.
Its function could be to undergo SET as postulated herein.
The second-order in acid rearrangements in equations shown here have
protonation occurring first. However, it may also be that SET occurs first,
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Acid-catalysed benzidine rearrangements
21
followed by protonation of the other nitrogen in the rearrangements of
hydrazobenzene whose kinetics were studied at 0 ºC in ~ 75% aqueous ethanol.
The existence of cation radicals has been discussed [34 – 37].
2.3 Rates
The benzidine rearrangements can occur by first-order and/or second-order in
acid and follow the rate law: – d(S)/dt = k2 [S][H+] + k3[S][H+]2.
Also, both reactions can occur concurrently resulting in mixed order in acid. At
low acidities, the second term becomes negligible and the reaction is first-order
in acid whereas at high acidities the first term can drop out.
The rates of the rearrangements are enhanced by electron-donating
substituents and retarded by electron-withdrawing ones [4]. To a degree,
this may be a reflection of the ease of oxidation of the nitrogen via electron
transfer and/or the stabilities of the intermediates. The former explanation
is in accord with the order of acidity required for the rearrangement of
variously substituted hydrazobenzenes. Generally, rearrangements of
hydrazobenzenes with electron-donating substituents proceed by a oneproton mechanism whereas electron-withdrawing substituents alter the
rearrangement resulting in a two-proton mechanism. It has been suggested
that the second proton is required to protonate the second nitrogen to
increase repulsion between the two hydrazyl nitrogens in order to effect
heterolysis as per PTS theory [2,4,5]. Similar reasoning may be applicable
in the SET oxidation of a neutral hydrazyl nitrogen to explain homolysis.
The rates are increased by the addition of salts. The increase in polarity of the
solvent system stabilises the developing cation radical species relative to the
reactant molecule.
In the R – NHNH – R' series where R, R' can be both naphthyl, naphthyl/phenyl,
both ortho tolyl, ortho tolyl/para tolyl, both phenyl, the decreasing rate of
rearrangement is:
Rate (one proton): both 1-naphthyl > 1-naphthyl/2-naphthyl > both
2-naphthyl > 2-naphthyl/phenyl > both 2-ortho tolyl.
Rate (two-proton): ortho-tolyl/para tolyl > 1-naphthyl/phenyl > both ortho
tolyl > 2-naphthyl/phenyl > phenyl.
In the hydrazotoluene series:
Rate (two-proton): para-toluene > meta-toluene > ortho-toluene > phenyl
In the first group, the one-proton rates can be explained by the greater ability
of the naphthyl group to stabilise an allylic form such as in Eqn (10), structure
b, without disrupting the aromaticity of the other ring.
Hence, the 1-naphthyl set is faster than the corresponding 2-naphthyl set
wherein the resonance structure requires a disruption of the other ring, Eqn (11),
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22
Andrew Mamantov
(10)
structure b. Even though the inferred nitrogen basicities of the R = R' = naphthyl
series is less than those of the mixed naphthyl/phenyl compounds wherein the
phenyl nitrogen portion has greater basicity and would be expected to undergo
oxidation easier, the naphthyl series have faster rates. It may be that the greater
cation radical charge delocalisation within the naphthyl rings lowers the
activation barrier to rearrangement sufficiently to make up for the difference
in basicities; e.g. compare R = R' = naphthyl with the mixed napthyl 1-napthyl/
phenyl, Table 1. A better stereochemical configuration for rearrangement of
the 1-naphthyl set could also be a contributing factor for their faster rate in
comparison to the 2-naphthyl set.
(11)
In the second group, the rates of the two-proton mixed naphthyl/phenyl sets
gave mixed results in comparison to the one-proton reactions. The ortho-tolyl/
para-tolyl pair is faster by an order of magnitude than the 1-naphthyl/phenyl
pair, and the ortho-tolyl/ortho-tolyl pair is faster than the 2-naphthyl/phenyl
pair. Perhaps in these cases, the greater basicity of the tolyl nitrogen and
consequent greater ease of oxidation overcomes the greater delocalisation and
ability of the cation radical in the naphthyl rings to yield the observed rates. As
expected, the two-proton reactions are faster than the one-proton reactions.
In the two-proton hydrazotoluene series, the rates parallel the inferred basicities
of the hydrazyl nitrogens. The ortho-tolyl is slower than the meta isomer
because it is less basic due to steric hindrance to protonation and/or solvation.
However, the ortho-tolyl isomer is more basic than the phenyl compound and
hence faster.
2.4 Product distribution
With unsymmetrical hydrazobenzenes, there are two possible ortho semidine
products, 2, N' linked or N, 2' linked. In the case of a mono-substituted
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23
Acid-catalysed benzidine rearrangements
hydrazobenzene, a single 4-substituent, whether electron donating or
withdrawing, generally results in a 2,N' o-semidine as a major product wherein
the substituent is para to the amino group. This result may apply to electron
donating groups OMe, OEt, Me, NHAc and electron withdrawing groups I,
Br, Cl, OAc, NMe2H+ [3,7] Ph and NO2 [2]. With electron withdrawing groups,
reaction yields an increase in 2,4'-diphenylines apparently at the expense of
2,N' linked o-semidines. The 4-OR groups and 4-NHAc are first-order acid
reactions [2,4] whereas the 4-Me [5] and 4-Cl [2,4,5] are second-order in acid.
Apparently, the orders in acid of 4-Br and 4-I have not been reported, but on the
basis of analogy to 4-Cl, they would be expected to be second-order in acid as
well as with electron withdrawing groups OAc and NMe2H+.
The major 2,N' linked o-semidine products in first-acid order reactions of singly
substituted 4-OMe, -OEt,and NHAc can be explained by SET from the most
basic hydrazyl nitrogen as inferred from the micro pKas of hydrazobenzenes
as determined by SPARC. Surprisingly, as seen in Table 3, the most basic
hydrazyl nitrogen in the electron donating para substituent series is distal
to the para group which is attached to ring A, i.e. the most basic nitrogen is
N', which is attached to ring B as per Ingold’s convention. Thus, these SET
mechanisms can yield 2,N' linkages which result in the observed o-semidines
as major products, e.g. Eqn (5). With the PTS theory, there are complications
explaining which nitrogen is protonated and the consequent representation of
the transition state [4]. Oxidation of the other less basic nitrogen, can result in
N,4' linked p-semidine and N,2' o-semidine products. The N,2' o-semidines
have been have been detected when modern chromatographic techniques are
used in the cases of 4-Cl and 4-OMe hydrazobenzenes [5]. See Table 6 and
Section 2.6 on Comparison of electron paths of PTS and SET theories.
In the 4,4'-disubstituted hydrazobenzenes, disproportionation is a major
product and a major rearrangement product is the o-semidine. In the case of
unsymmetrical 4,4'-disubstituted compounds, once again two o-semidines
Table 6 Rearrangement products of 4-chloro- and 4-methoxy hydrazobenzene obtained by
the Jacobson method [7]
Coupling pattern of products
4-chloro
4-methoxy
2,4'
~ 40
9
2,2'
0.5
~ 0.01
N,4'
14
11
2,N'
8
~ 65
N,2'
8
+
dispr.
28
13.75
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24
Andrew Mamantov
are possible, 2, N' and N,2'. The exclusive or major o-semidine is 2,N' linked
wherein the better electron donor is para to the amino group. The available
examples are 4-EtO, 4'-Me; 4-EtO, 4'-NMe2H+; 4-Me, 4'-I; 4-EtO, 4'-Br; 4-Me,
4'-OAc; 4-Me, 4'-NMe2H+ [3,7]. The order in acid of these compounds is not
known. The only member of this group where both substituents are electron
donating is 4-EtO, 4'-Me. It may be that this compound proceeds by a oneproton mechanism. However, 4,4'-dimethylhydrazobenzene is second-order in
acid [3]. The other members in the above group have a 4-electron donating
group and a 4'-electron withdrawing group. These compounds might proceed
by a two-proton mechanism.
For the 4-EtO, 4'-Me compound, as seen in Table 2, N' is more basic than N, pKa
1.06 versus 0.88. Thus N' is proposed to undergo SET to yield N' cation radical
which can go on to yield 2,N' linked o-semidine wherein the better electron
donor OEt group is para to the amino group. For the other compounds, as is the
case for the mono substituted examples, the presence of an electron withdrawing
group shifts the reaction to a two-proton mechanism. Rearrangement may occur
when the most basic nitrogen gets protonated followed by SET to a proton from
the other nitrogen to yield a nitrogen cation radical resulting in two adjacent
positively charged nitrogens whose repulsive energy provides the driving force
for homolysis. This is similar to the explanation in the PTS theory except here
it is a homolytic rather than a heterolytic cleavage. In the available examples,
the major products would be formed when the nitrogen para to the 4-R group
which is electron donating gets protonated whereas the other nitrogen, N', para
to the 4'-R group gets oxidised. This yields the observed major 2,N' linked
o-semidine. If the other nitrogen gets oxidised, N,2' o-semidine and N,4'
p-semidine products would be formed.
2.5 Deuterium studies
Both the first and second-order acid reactions are specific acid catalysed,
not general acid catalysed because neither proton addition or removal is rate
determining [4,5]. The Zucker-Hammett hypothesis has also been invoked
to support specific acid catalysis [45]. However, it has been noted that these
correlations are questionable because the results can also support general acid
catalysis [46].
The results for several compounds, both first and second acid order show
solvent isotope effects kD/kH between 2.1 and 4.8 [3]. This indicates that both
first and second acid order proton involvements occur in rapid equilibria prior
to the rearrangement step. In contrast, if the involvement of the catalysing
proton were rate-determining, reaction in D3O+ would cause rate retardation in
comparison to H3O+. However, if the concentrations of protonated or oxidised
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Acid-catalysed benzidine rearrangements
25
substrates are rate determining, reactions in D3O solutions should be faster
than in H3O+ solutions because D3O+ in D2O is a stronger acid than H3O+ in
H2O. The latter is what is observed, not rate retardation.
Isotope effects have also shown that ring deprotonation is not rate determining.
Substitution of deuterium for hydrogen in the rings of hydrazobenzene and
1,1'-hydrazonapthalene did not show primary isotope effects. Hence, ring
deprotonations are fast steps which occur after the slow rate determining step.
However, an inverse secondary deuterium isotope effect of 0.962 was found
when hydrazobenzene was deuterated in both para positions. This indicates
that C – C bond formation is part of the rate-limiting step which is ascribed
to formation of an sp3 para carbon from the sp2 form in the formation of the
quinonoidal intermediate in the transition state [11].
It has been demonstrated that hydrazo compounds which are ring deuterated
rearrange without deuterium loss or scrambling [3,47]. Also, deuterium is not
incorporated into the rings of hydrazobenzene when it rearranges in D2SO4
or SbF5/DF/SO2ClF [43]. All of these results are consistent with both the PTS
theory and the SET theory presented herein.
+
2.6 Comparison of electron paths of rearrangements of PTS and SET
theories
In SET it is clear that in para monosubstituted hydrazobenzenes, N,4'
p-semidine and N,2' o-semidine are formed via oxidation of the N nitrogen
whereas the 2,N' o-semidine is derived from oxidation of the other nitrogen,
N'. These two reaction paths compete with one another. In PTS theory, the
electron flow for the formation of these products is not clear. For 4-MeO (firstorder in acid) and 4-Cl (second-order in acid) the current representations for
formation of 2,N' o-semidine, N,4' p-semidine and 2,4' diphenyline all have the
heterolytic electron flow in direction away from the monosubstituted ring, from
N to N', because this way the PTS can be stabilised by electron donation by the
electrons of chlorine or oxygen on ring A, the monosubstituted ring, Schemes
3a and 4a [4,5]. On the other hand, originally it was proposed that for 4-MeO,
4-Cl and 4-NO2 cases, electron flow for p-semidine and diphenyline would be
toward the substituted ring whereas o-semidine (presumably 2,N') formation
would be in the opposite direction, from N to N', Schemes 3b,c and 4b,c [2].
Regarding the above, it is useful to compare the most currently available
yields of products for the 4-Cl and 4-MeO compounds shown in Table 6 [5].
The major product in the 4-MeO case is the 2,N' o-semidine (~ 65%) with a
trace of N,2' o-semidine whereas in 4-Cl example it is the 2,4' diphenyline
(~ 40%), equal amounts of 2,N' and N,2' o-semidines (8%) and slightly more
N,4' p-semidine (14%) than in 4-MeO case (11%). Hence diphenyline in the
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26
Andrew Mamantov
Scheme 3 Direction of electron flow in 4-methoxyhydrazobenzene in PTS theory
(a) [4,5], (b,c) [2].
4-Cl case increases at the expense of o-semidine in comparison with 4-MeO
example. Such a striking difference in major products is surprising in view
of the approximate similarity of transition states as currently represented in
PTS theory. It is also somewhat surprising to see equal amounts of the two
o-semidines in the 4-Cl case whereas in 4-MeO example N,2' o-semidine is
only a trace amount. These results can be explained if there are two different
reaction paths for N,4' p-semidine and diphenyline relative to 2,N' o-semidine
formation. As stated above, as originally postulated in PTS theory, this would
require electron flow in opposite directions [2]. Furthermore, it would also
require in a second-order in acid reaction that one of the transition states has
more than one positive charge on the N' nitrogen because it would not be able
to be stabilised by the electrons of the monosubstituted hetero atom on ring A,
Scheme 4c. This unfavourable situation does not exist in SET. In SET theory
for the first-order in acid 4-MeO case, the preponderance of SET would occur
from the most basic nitrogen yielding 2,N' o-semidine as major product. In the
second-order in acid 4-Cl case, preponderance of SET would occur from the N
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27
Acid-catalysed benzidine rearrangements
Scheme 4 Direction of electron
(a) [4,5] (b,c) [2].
flow
in
4-chlorohydrazobenzene
in
PTS
theory
nitrogen which is para to the chlorine. This results in a significant increase of
N,2' o-semidine and 2,4' diphenyline relative to the 4-MeO case.
Quantitative yields for 4-phenyl and 4-nitrophenylhydrazobenzene rearranged
products are not available. However, qualitative descriptors (+, ++, +++) for
these second-order acid reactions indicate a significant yield of 2,4' diphenyline
product (+++) in comparison to the 4-MeO example where diphenyline was
apparently not detected [2]. Hence, the former two cases also support the SET
theory with two possible reaction paths. In these two examples with electron
withdrawing substituents, it was not determined how much of the significant
yield of o-semidine (+++) was 2,N' versus N,2' linked product.
2.7 Cyclic voltammetry studies
One of the puzzles of the benzidine rearrangements is what compels the two
aryl rings to come together. It has been suggested that this is due to attractive
interaction between the rings in the polarised transition state [11]. Another
reason may come from the cyclic voltammetry studies of tetraalkylhydrazines
[48]. Some of these compounds have been found to undergo chemically
reversible one-electron electrochemical oxidations to yield radical cations. In
the neutral form, the interaction between the nitrogen lone pair electrons leads
to a conformation in which the dihedral angle Θ is about 90º, Figure 2a. Upon
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28
Andrew Mamantov
Figure 2 Dihedral angle Θ between N,N' electrons in conformations of tetraalkylhydrazine
structures (a) neutral form, Θ ~ 90º (b) radical cation, Θ ~ 0º.
oxidation, however, the preferred dihedral angle between nitrogen electrons is
about 0º, resulting in the postulated stabilizing “three-electron bond”, Figure
2b. This leads to flattening of the tetrahedral geometry at nitrogen and eclipsing
of the alkyl substituents. An analogous stabilizing three electron bond and
eclipsing of aryl substituents may occur in the benzidine rearrangements. This
could explain why the aryl rings are brought together. This would be followed
by the attractive interaction between them to yield the rearrangements.
3. Conclusion
The SET mechanism can account for both the chemistry of the benzidine
rearrangements and the details of the disproportionation reaction which is
lacking in the PTS theory. Tetra and triarylhydrazines are known to undergo
loss of an electron from the hydrazyl moiety in the presence of oxidizing agents
to yield stable hydrazyl radicals. The oxidation of 9-hydrazoacridine yields a
stable hydrazyl radical which disproportionates rapidly in solution.
The SPARC modelling program supports the concept that the function of one
of the protons in second-order reactions is other than the protonation of an
atom. It also supports the non-protonation of an atom in some cases in firstorder acid reactions.
The mechanism is in accord with: (1) the knowledge that the involvement
of the catalytic proton(s) is near the beginning of the reaction and is a low
energy process, whereas the loss of aromatic protons is an irreversible lowenergy process near the end of the reaction; (2) with the kinetics of the
disproportionation reaction which show that this mechanism occurs after
passage through the transition state. In this second late stage, the kinetics show
that there must be an intermediate which reacts with a second hydrazoaromatic
molecule in a fast reaction; (3) the accelerated rates of other cation radical
pericyclic reactions [49].
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Acid-catalysed benzidine rearrangements
29
The proposed mechanisms may also help: (1) clarify the biochemical degradation
of hydrazobenzene, hydrazine and its derivatives in mammalian cells which
have been shown to involve nitrogen hydrazyl radicals; and (2) provide some
guidance in the synthesis of axially chiral biaryls.
4. ACKNOWLEDGEMENT
The author thanks Professor H.J. Shine, Texas Tech. University, Lubbock, TX
for his review of some previous versions of manuscripts.
Portions presented at 22nd Reaction Mechanisms Conference, Pittsburgh, PA,
12 – 16 June,1988; 9th IUPAC Conference on Physical Organic Chemistry,
Regensburg, Germany, 21 – 26 August, 1988; 40th Southeast Regional
American Chemical Society Meeting, Atlanta, GA, 9 – 11 November, 1988;
197th National American Chemical Society Meeting, Dallas, TX, 9 – 14 April,
1989.
Disclaimer: The views and conclusions expressed in this paper are solely those
of the author and do not necessarily represent those of the US Environmental
Protection Agency.
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