The influence of some steric and electron effects on the mechanism of aromatic nucleophilic substitution (SNAr) reactions in nonpolar solvent

Article abstract of DOI:10.1002/kin.20109

Kinetic studies are reported for the reactions with aniline in benzene of a series of X-phenyl 2,4,6-trinitrophenyl ethers [X = H; 2-, 3-, 4-CH ₃; 2,4-, or 2,6-(CH₃)₂] 1a-f, and the results compared with those of the corre

Full text of DOI:10.1002/kin.20109

The Influence of Some
Steric and Electron Effects
on the Mechanism of
Aromatic Nucleophilic
Substitution (SNAr)
Reactions in Nonpolar
Solvent
THOMAS A. EMOKPAE, NKECHI V. ATASIE
Chemistry Department, Faculty of Science, University of Lagos, Akoka Lagos, Nigeria
Received 14 May 2004; accepted 19 April 2005
DOI 10.1002/kin.20109
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Kinetic studies are reported for the reactions with aniline in benzene of a series
of X-phenyl 2,4,6-trinitrophenyl ethers [X = H; 2-, 3-, 4-CH3; 2,4-, or 2,6-(CH3)2] 1a–f, and the
results compared with those of the corresponding nitro derivatives. In the methyl series, kinetic
data show that increasing substitution reduces drastically the rates of reactions indicative of
the operation of some kind of steric effect. The unfavorable steric congestion at the reaction
center appears to be unimportant in determining the kinetic order of the reactions. In general,
the second-order rate constants kA depend linearly on the square of nucleophile concentra-
tion. The change in the kinetic form observed in the nitro derivatives may be largely due to the
electron-withdrawing effect of the group. With the 2,6-dinitro derivative, however, the uncat-
alyzed pathway k2 takes all the reaction flux. Steric hindrance to intermolecular proton transfer
from base to the ethereal oxygen of the intermediate is sufficient to make the base-catalyzed
pathway insignificant relative to the k2 pathway. ꢀ 2005 Wiley Periodicals, Inc. Int J Chem Kinet
C
37: 744–750, 2005
INTRODUCTION
reactions, and in most cases they have been well
substantiated experimentally. However, the effects of
Bernasconi [1] has discussed the various factors re-
ortho-substituents in such reactions are complex. In
sponsible for the incidence of base catalysis in SNAr
the process of obtaining additional data which would
provide further evidence for the cyclic transition state
mechanism for reactions in nonpolar aprotic solvents,
Banjoko and Ezeani [2] have shown for the reactions in
Correspondence to: Thomas A. Emokpae; e-mail: temokpae@
yahoo.com.
2005 Wiley Periodicals, Inc.
c
ꢀ

INFLUENCE OF STERIC AND ELECTRON EFFECTS ON SNAr REACTIONS
745
benzene of aniline with 2,4,6-trinitrodiphenyl ether and
EXPERIMENTAL
derivatives containing a nitro group in the 2-, 3-, and
4-positions of the leaving group that the second-order
rate constant kA had a linear dependence on [aniline]2.
A similar dependence on nucleophile concentration for
the 4-nitro derivative was obtained by Emokpae et al.
[3] when the nucleophile was the secondary amine, N-
methylaniline. Banjoko and Ezeani [2] also observed
that with exception of the 2ꢁ,6ꢁ-dinitro isomer, when
the leaving group contained two nitro groups, kA had a
linear dependence on the aniline concentration, i.e. the
transition state for the decomposition of the intermedi-
atetoproductsonlycontainedtwomoleculesofaniline.
The 2ꢁ,6ꢁ-dinitro derivative was not base catalyzed and
so was first order in both substrate and nucleophile.
The lack of catalysis observed in the 2ꢁ6ꢁ-dinitro iso-
mer was attributed to an interplay of electronic effects
and steric compressions in the δ-complex.
In order to better assess the role played by these
effects on the uncatalytic behavior of the 2ꢁ,6ꢁ-dinitro
isomer, the investigations of the nitro series 2b–f have
been extended to a series of mono- and di-methyl-
substituted phenyl-2,4,6-trinitrophenyl ethers 1a–f.
Capon and Chapman [4] have shown that while the
polar effect of a methyl group is small, the steric effect
of an ortho-methyl group is appreciable. The electronic
effects of methyl substituents as reflected in the values
of the pKa of the corresponding phenols in water [5]
(Table I) are almost identical. In benzene, the differ-
ences between the values of the pKa are not likely
to be magnified. The nucleofugalities of the leaving
groups will therefore be nearly identical. Similarity in
the kinetic form of the reactions of 1a–f would show
that steric effects are relatively insignificant while a
change in the kinetic order would indicate the impor-
tance of steric effects in determining the kinetic form
of the reactions of mono- and di-methyl-substituted
phenyl-2,4-6-trinitrophenyl ethers with aniline in ben-
zene. The results, unlike those of the nitro series 2a–f,
show that there is no dramatic change in the behavior
from the 2,6-dimethyl derivative. Although steric ef-
fects certainly caused rate decreases in the reactions of
methyl-substituted trinitrophenyl ethers 1a–f with ani-
lineinbenzene, therewasnochangeinthekineticorder.
The plots of kA/[amine] versus [aniline] were all linear.
Diphenyl ethers 1a–f were prepared by the reaction of
picryl chloride with 1 equivalent of base in the pres-
ence of an excess of the appropriate phenol in aqueous
ethanol. Recrystallization was from ethanol. The reac-
tion product, 2,4,6-trinitrodiphenylamine V was pre-
pared by reaction of picryl chloride with excess ani-
line in ethanol. All substrates had m.p.s in satisfactory
agreementwithpublishedvalues[2,6,7]. Thedetailsfor
the purification of aniline and the spectroscopic deter-
mination of the rate constants have already been given
[2,3,6].
RESULTS AND DISCUSSION
Aniline reacted with the substrates in benzene to
give the expected N-(2,4,6- trinitrophenyl) aniline in
quantitative yield. With concentration of aniline (0.1–
0.8 mol dm−3) in large excess of the concentration of
the diphenyl ethers, (10−4 mol dm−3), excellent first-
order kinetics were observed; the reactions proved to be
first order in the substrates, and division of the pseudo-
first-order rate coefficients kobs by the appropriate con-
centration of aniline gave second-order rate constants
kA. The data are gathered in Table II.
The Methyl Series, 1a–f
The values of the second-order rate coefficient kA in-
creased rapidly with aniline concentration. A typical
plot, in this case for the 2,4-dimethylphenyl substrate,
of kA versus aniline concentration is given in Fig. 1. It
shows a line with an upward curvature and with inter-
cept on the y-axis statistically indistinguishable from
zero. This indicates that the contribution of k2, the un-
catalyzed pathway, is insignificant. Similar plots were
obtained for all the other methyl substrates. Plots (not
shown) of the quotient kA/[aniline] against aniline con-
centration however were linear (correlation coefficient
>0.9990) consistent with reactions being third order in
the rate law.
The kinetic data are analyzed in terms of Scheme 1.
The reactions are expected to proceed through three
routes: (a) an uncatalyzed pathway involving the
Table I pK a Values of the Substituted Phenols in Water for the X-phenyl 2,4,6-trinitrophenyl ethers [X = H; 2-, 3-,
4-CH3; 2,4-, 2,6-(CH3)2] 1a–f and [X = 2-, 3-, 4-NO2; 2,4-, 2,6-(NO2)2] 2b–f
1a
1b
1c
1d
1e
1f
2b
2c
2d
2e
2f
10.00
10.28
10.08
10.14
10.40
10.60
7.23
7.10
7.15
4.11
3.15

746
EMOKPAE AND ATASIE
Table II Kinetic Results for the Reactions of X-phenyl-2,4,6-trinitrophenyl Ethers (X = 4-H,2-, 3-, 4-CH3, 2,4-,
2,6-(CH3)2) 1a–f with Aniline in Benzene at 30◦C
kA (×10−4 dm3 mol−1 s−1
)
[Aniline] (mol dm−3
)
4-H
2-CH3
3-CH3
4-CH3
2,4-CH3
2,6-CH3
0.0115
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.50
0.60
0.65
0.70
0.80
1.60
3.15
5.0
7.63
10.85
14.63
1.96
3.9
6.95
10.44
14.80
20.0
5.3
8.3
13.0
18.0
23.5
30.0
1.75
0.60
2.61
3.72
5.11
1.02
1.48
2.08
0.0191
0.0294
0.042
0.0497
0.057
6.73
8.53
2.80
3.65
formation of a four-membered ring (II), (b) a catalytic
route involving the formation of a six-membered ring
(III) due to the participation of one molecule of amine,
and (c) a catalytic route involving the formation of a
eight-membered ring (IV) due to the participation of
two amine molecules.
zero. Since k1 measures the rate of monomer attack, it is
reasonable to assume that its value is not negligible; so
most probably k2 is zero i.e. the uncatalyzed pathway,
route (a) is unimportant. With this assumption, Eq. (1)
simplifies to Eq. (2)
k1k3[B] + k1k4[B]2
The assumption that these intermediates may be
treated as steady-state intermediates leads to Eq. (1)
kA =
(2)
k
−1 + k3[B] + k4[B]2
k1k2 + k1k3[B] + k1k4[B]2
Our results which provide evidence for base catalysis
indicate that the condition k ꢂ k3[B] + k4[B]2 ap-
kA =
(1)
−1
k
−1 + k2 + k3[B] + k4[B]2
plies so that Eq. (2) reduces to Eqs. (3) and (4)
From Fig. 1, it can be seen that kA = 0 at null base
concentrations, the k1k2/k−1 + k2 must therefore be
k1k3[B] k1k4[B]2
kA
=
=
+
(3)
(4)
k
k
−1
−1
kA
[B]
k1k3
k1k4[B]
+
= kꢁ + kꢁꢁ[B]
k
k
−1
−1
Equation (4) agrees with the experimental results of the
linear dependence of kA/[B] on [B] observed for all the
reactions.
Nitro Series, 2b–f
For the mononitro derivatives, the behavior was quali-
tatively similar to that for the methyl isomers; values of
k2 were negligibly small, and data in Tables III conform
to Eqs. (1) and (4). Banjoko and Ezeani [2] had shown
that the plot of kA versus aniline concentration for 2e,
the 2,4-dinitro derivative gave an excellent straight line.
The sizable intercept on the y-axis represents reaction
by uncatalyzed pathway, while the positive slope in-
dicates the presence of a base-catalyzed route. For 2f,
the 2,6-derivative, the values of kA were independent
of aniline concentration; the reaction was therefore not
base catalyzed.
Figure 1 Plot of kA vs. [aniline] in benzene at 30◦C for
the reaction of 2,4-dimethylphenyl-2,4,6-trinitrophenyl ether
(1e) with aniline.

INFLUENCE OF STERIC AND ELECTRON EFFECTS ON SNAr REACTIONS
747
Scheme 1
Table III Kinetic Results for the Reactions of X-phenyl-2,4,6-trinitrophenyl Ethers (X = 4-H; 2-, 3-, 4-NO2, 2,4-,
2,6-(NO2)2) with Aniline in Benzene at 30◦C
kA (10−4 dm3 mol−1 s−1
3-NO2
4-NOa2
)
[Aniline] (mol dm−3
)
4-Ha
2-NOb2
2,4-NOb2
2,6-NOb2
99.6
99.6
99.6
99.6
0.01
0.02
0.03
0.04
0.05
0.06
0.08
0.10
0.12
0.15
0.18
0.20
0.25
0.30
0.35
0.40
4.45
8.25
12.0
2.05
33.0
15.75
4.0
5.0
53.3
81.4
16.5
24.0
36.0
50.3
62.0
18.0
25.0
39.0
55.0
68.0
5.3
8.3
13.0
18.0
23.5
30.0
a Data from present work.
b Data from [2].

748
EMOKPAE AND ATASIE
intramolecular proton transfer that the highest possi-
bility for proton transfer would occur when the cyclic
transition state involved could accommodate a linear
arrangement of donor–proton–acceptor of appropriate
length. This easily occurs when the ring size is eight.
Most of the conceptual difficulties associated with the
cyclic intermediates in SNAr reactions pertain to catal-
yses by tertiary amines because of the unlikelihood of
the formation of three hydrogen bonds in a single step.
There is now evidence for bifurcated hydrogen bonds
in both small crystal structures [20,21] and if formation
of hydrogen bonds of weak to moderate strength is an
electrostatic phenomenon, they should also exist in so-
lution of solutes in solvents of low relative permittivity.
Hirst has recently advanced convincing reasons that if
three-centered hydrogen bonding is allowed, then the
distinction between cyclic and homo-/heteroconjugate
mechanisms becomes blurred [22]. For the present re-
actions, we prefer to interpret our results in terms of
the cyclic state mechanism.
Base Catalysis
The origin of the upward curvature of the plot of kA
against base concentration has generated a lot of inter-
est and active discussion. Initially this was ascribed to
“unspecific solvent effects,” but more recently three
major explanations of the abnormal behavior have
been given and they have enjoyed varied degree of
acceptances:
(i) Dimer mechanism: Nudelman and Palleros [8–
10] have suggested association of the nucleophile
with the base prior to attack on the substrate fol-
lowed by the base-catalyzed decomposition of
the intermediate.
(ii) The cyclic transition state mechanism modified
by Banjoko et al. [2,11,12] in which there is an
initial attack of an amine molecule on the sub-
strate followed by the decomposition of the re-
sulting intermediate via on eight-membered ring
involving three molecules of the amine.
(iii) Homo/heteroconjugate mechanism: Ayediran
et al. [13] have proposed that because of the
low relative permittivity of aprotic solvents and
the consequent range of electrostatic forces, ag-
gregates are formed within which mechanisms
such as those proposed by Bunnett and Davies
[14] can operate. They explained [15] the up-
ward curving plots as due to electrophilic cataly-
sisoftheexpulsionoftheleavinggroupbyhomo-
and hetero-conjugate acid of the nucleophile. It
was stressed [16] however that because of the
range of electrostatic forces and the importance
of hydrogen bonding in these solvents, several
mechanisms could operate, the relative impor-
tance of which would depend not only on the en-
tities employed, but also on their concentration.
Recently, the mechanism was strongly supported
by Jain et al. [17] in their investigation of ammol-
ysis reactions of o-aryl oximes with aliphatic pri-
mary and secondary amines in benzene. Akinyele
et al. [18] had given plausible mechanism for
the formation of cyclic transition state for aro-
matic nucleophilic substitution reactions in all
solvents of low relative permittivity. The concept
was developed by Emokpae et al. [3] to rational-
ize reactions proceeding through cyclic transition
states containing either two or three molecules of
amines.
COMPARISON
Since the reactions of 1a–f have the same kinetic form,
we can assess the relative rates of their reactions. Com-
parison of the second-order rate constants kA under the
same experimental conditions shows that the reactivity
of the substrates decreases in the order
1a > 1d > 1c > 1b > 1e > 1f.
This can be rationalized in terms of the nucleofugal-
ity of the leaving groups. The expulsion of the leaving
group involves the breaking of the C O bond in the
zwitterionicintermediateZwhichthengeneratesaneg-
ative charge on the oxygen atom of the phenoxide ion.
The departure of the nucleofuge would be facilitated if
it is stabilized by delocalization of the negative toward
the benzene ring of the phenoxide ion through conju-
gation. This is certainly aided by substituents which
are election withdrawing and retarded by those that are
election donating. All the mono- and di-methyl substi-
tuted groups decreased the nucleofugality of the leav-
ing group and consequently reduced the rates of the
reactions. Specifically, a 4-methyl group in the nucle-
ofuge decreased the rate constant by a factor of 1.2,
while a 2-methyl group gave a 10-fold reduction. The
2,6-dimethyl group also reduced the rate constant by
a factor of ca. 1600. While the effect of the 2-methyl
group may be regarded as small, that of 2,6-dimethyl
group is enormous, indicative of the operation of some
kind of steric effect. This was reinforced recently by
X-ray crystal structures of 1a, 1f, and 2f which provide
evidence of steric crowding around the 1-position of
An eight-membered transition state is more effective
in removing the nucleofuge than a six-membered tran-
sition state. This was confirmed by Gandour [19] who
showed from the study of structural requirements for

INFLUENCE OF STERIC AND ELECTRON EFFECTS ON SNAr REACTIONS
749
these molecules [23]. Our kinetic data, however, show
thatthisunfavorablestericcrowdingatthereactioncen-
ter does not change the kinetic order. It only reduces the
rates of the reactions. It is worth noting that in acetoni-
trile [23] such increase crowding at the reaction center
did not sterically inhibit attack by the nucleophile, and
an “early” transition state was suggested.
In reactions in which the decomposition of the in-
termediates to reactants is rate limiting, steric effects
may in principle be reflected in all elementary rate con-
stants in Scheme 1. There are various sources of these
effects. The first is steric compression in the interme-
diate between the amine and the aromatic ring plus
ortho-substituents. On reverting to reactants, the steric
strain is partially released since the transition state is
moved from the para- to the ortho-position in the nu-
cleophile. This change in the rate-limiting step for the
same reactions brought about changing the steric prop-
erties of the nucleophile was recently confirmed by the
determination of leaving group fluorine kinetic isotope
effects [FK1Es]. The large FKIE [1.0119 0.0037] for
2-methylaniline suggests rate-limiting leaving group
departure for the sterically more hindered nucleophile,
whereas the insignificant FKIE (1.0005 0.0030] for
the less sterically hindered 4-methyl aniline indicates
rate-limiting addition of the nucleophile [29]. Interest-
ingly, the reaction of 1-bromo 3,5-dinitrobenzene with
2-methyaniline in dimethyl sulfoxide was not base cat-
alyzed. The introduction of a 6-bromo-substituent into
1-fluoro 2,4-dinitrobenzene caused the mechanism of
its reactions with 2-methylaniline to revert to a rate-
determining formation of zwitterions [28].
The kinetic data for the series 1a–f are different
from those of the 2b–f. The nitro group enhances the
departure ability of the leaving group by facilitating
delocalization of negative charge due to its electron-
withdrawing effect. In the nitro series 2b–f, there was
a change in the kinetic form for the reactions of aniline
with ethers containing unsubstituted or mono nitro sub-
stituted leaving groups from a third-order dependence
on aniline concentration to a second-order dependence
for leaving groups containing 2,4-, 3,4-, and 2,5-dinitro
groupto kA = k1 forthe2,6-dinitrophenoxygroup. The
change was ascribed to changes in the transition states
for the decomposition of the intermediate from eight- to
six- to four-membered rings (containing two, one, and
no molecules of aniline respectively) brought about by
increases in the leaving group ability of the nucleofuge.
Thisisreadilyexplicableastheintroductionofasecond
nitro group will reduce the basicity of the ethereal oxy-
gen in the zwitterionic intermediate Z and decrease the
population of species hydrogen bonded to it and thus
the livelihood of the attainment of a third molecule of
the nucleophile. The favorable electronic effect of the
nitro groups therefore outweighs their adverse steric
effect.
“looser” than the intermediate. This enhances k and
−1
therefore decreases k2/k−1. The transition state for the
decomposition Z to reactants is the same as for its for-
mation, and according to the Hammond postulate it is
structurally close to the intermediate. Steric compres-
sions will therefore be expected in the transition state,
and these should be manifested in a reduction in k1.
A second is due to the fact that when the leaving group
X leaves the intermediate, the incoming group must
move from the “tetrahedral” position to a position in
theplaneofthebenzenering. Anyinterferencewiththis
motion by other groups in the molecule would lead to
a reduction in k2 and k3. Other related effects that may
cause reduction in the values of k2 and k3 have been dis-
cussed exhaustively by Bernasconi and de Rossi [24].
Despite these factors which reduce k2/k or k3/k
,
−1
−1
the role of steric effects in bringing about the inci-
dence of base catalysis is not clear-cut. They are only a
few unambiguous examples of steric effect influencing
the occurrence of base catalysis. The reaction of 2,4-
dinitrodiphenyl ether with pyrrolidine which was in-
sensitive to catalysis by NaOH [25] responded linearly
to catalysis by NaOH when the substrate was changed
tothe6-methylderivative[26]. Similarly, inacetonitrile
and in dimethyl sulfoxide, the introduction of 6-methyl
group changed the kinetic form of the reaction of 2,4-
dinitrophenyl phenyl ether with n-butylamine from an
uncatalyzed one to one in which there was a linear de-
pendence of the rate constant kA on nucleophile con-
centration [27]. Another example where change in the
rate-limiting step was induced by the steric effect of
an ortho-methyl group was the reactions of substituted
aniline with 2,4-dinitrofluorobenzene in dimethyl sul-
foxide [28]. The introduction of 2-methyl group into
aniline changed the kinetic form of the reaction from
an uncatalyzed one to one in which there was a curvilin-
ear dependence of the rate constant kA on nucleophile
concentration. The rate of the reaction was reduced to
a factor of ca. 200 when the methyl substituent was
With 2f, the 2,6-dinitro derivative, the steric hin-
drance to intermolecular proton transfer from the base
to the ethereal oxygen in the intermediate is sufficient
to make the base-catalyzed pathway insignificant rela-
tive to the k2 pathway. There is general agreement that
in aprotic solvent such as cyclohexane and benzene,
the uncatalyzed decomposition of the intermediate to
products takes place unimolecularly via a hydrogen-
bonded intermediate (Fig. 2). Since this involves in-
tramolecular proton transfer, steric effects are unlikely
to be important. In acetonitrile, the reaction of 2f, the
2,6-dinitro derivative was also not catalyzed by the nu-
cleophile [23].

750
EMOKPAE AND ATASIE
5. Kortum, G.; Vogel, W.; Andrussow, K. Dissociation
Constants of Organic Acids in Aqueous Solution; But-
terworths: London, 1961.
6. Isanbor, C.; Emokpae, T. A.; Crampton, M. R. J Chem
Soc, Perkin Trans 2 2002, 2019.
7. Okon, K. Rocz Chem 1958, 32, 213.
8. Palleros, D.; Nudelman, N. S. J Chem Soc, Perkin Trans
2 1985, 479.
9. Nudelman, N. S.; Palleros, D. J Org Chem 1983, 48,
1607.
Figure 2 Hydrogen bonding in the uncatalyzed decompo-
sition of the intermediate to products.
10. Nudelman, N. S.; Palleros, D. J Org Chem 1983, 48,
1613.
11. Banjoko, O.; Ezeani, C. J Chem Soc, Perkin Trans 2
1982, 1357.
CONCLUSION
Our results reveal that steric crowding at the reaction
center does not play a major role in the determination of
the kinetic order of the reactions of aniline with methyl-
substituted trinitrodiphenyl ethers in nonpolar aprotic
solvent. It however retards the rates of such reactions.
The change in the kinetic form observed in the nitro
derivatives must have arisen from the basicity of the
phenolic-leavinggroup. Itisonlywith2eand2fderived
from the least phenoxides that the uncatalyzed reaction
could compete with the base-catalyzed pathway. With
the 2,6-dinitro derivative, the main reaction flux occurs
through the uncatalyzed pathway. Steric hindrance to
intermolecular proton transfer from base to the ethe-
real oxygen is sufficient to make the base-catalyzed
pathway insignificant relative to the k2 pathway.
12. Banjoko, O.; Otiono, C. J Chem Soc, Perkin Trans 2
1986, 531.
13. Ayediran, D.; Bamkole, T. O.; Hirst, J.; Onyido, I. J
Chem Soc, Perkin Trans 2 1977, 597.
14. Bunnett, J. F.; Davies, G. T. J Am Chem Soc 1960, 82,
665.
15. Bamkole, T. O.; Hirst, J.; Onyido, I. J Chem Soc, Perkin
Trans 2 1982, 889.
16. Hirst, J.; Onuoha, G. N.; Onyido, I. J Chem Soc, Perkin
Trans 2 1988, 971.
17. Jain, A. K.; Singh, P.; Sahoo, B. B. J Phys Org Chem
1996, 9, 770.
18. Akinyele, E. T.; Hirst. J.; Onyido, I. J Phys Org Chem
1990, 3, 41.
19. Grandour, R. H. Tetrahedron Lett 1974, 3, 295.
20. Jeffrey, G. A. An Introduction to Hydrogen Bonding;
Oxford University Press: Oxford, UK, 1997.
21. Aakeroy, C. B.; Seddon, K. R. Chem Rev 1993, 397.
22. Hirst, J. J Phys Org Chem 1994, 7, 68.
23. Crampton, M. R.; Emokpae, T. A.; Howard, J. A. K.;
Isanbor, C.; Mondal, R. J Phys Org Chem 2004, 17, 65.
24. Bernasconi, C. F.; de Rossi, R. H. J Org Chem 1976, 41,
44.
We thank Dr. Chukwuemeka Isanbor for helpful discussions.
BIBLIOGRAPHY
1. Bernasconi, C. F. MTP Int Rev Sci Org Ser 1 1973, 3,
33.
2. Banjoko, O.; Ezeani, C. J Chem Soc, Perkin Trans 2
1986, 531.
3. Emokpae, T. A.; Uwakwe, P. U.; Hirst, J. J Chem Soc,
Perkin Trans 2 1990, 2191.
4. Capon, B.; Chapman, N. B. J Chem Soc 1957, 6001.
25. Bunnett, J. F.; Herman, D. H. Biochemistry 1970, 9, 816.
26. Bunnett, J. F.; Sekiguchi, S.; Smith, L. A. J Am Chem
Soc 1981, 103, 4865.
27. Emokpae, T. A.; Uwakwe, P. U.; Hirst, J. J Chem Soc,
Perkin Trans 2 1993, 125.
28. Hirst, J.; Onyido I. J Phys Org Chem 1991, 4, 367.
29. Persson, J.; Matsson O. J Org Chem 1998, 63, 9348.