Kinetic study of the reactions of some 5-nitro-2-(4-nitrophenoxy)-3-x-thiophenes with aniline and 4-methoxyaniline in methanol

Article abstract of DOI:10.1135/cccc19991877

The rate constants of the title reactions have been measured at various amine concentrations. The second-order kinetic constant for the amino substitution increases in a hyperbolic way as a function of the nucleophile concentration. The k₃^Am/k_-1 ratio for each catalysed system is not a monotonic function of the X substituent. This result has been rationalized in the framework of the SB-GA (Specific Base-General Acid) mechanism of base catalysis.

Full text of DOI:10.1135/cccc19991877

Kinetic Study
1877
KINETIC STUDY OF THE REACTIONS OF SOME
5-NITRO-2-(4-NITROPHENOXY)-3-X-THIOPHENES WITH
ANILINE AND 4-METHOXYANILINE IN METHANOL
a
a
b1
Vincenzo FRENNA , Gabriella MACALUSO , Giovanni CONSIGLIO
,
b2
b3,
Susanna GUERNELLI and Domenico SPINELLI
*
a
Dipartimento di Chimica Organica “E. Paternò”, Viale delle Scienze Parco D’Orleans2,
I-90128 Palermo, Italy; e-mail: organica@unipa.it
b
Dipartimento di Chimica Organica “A. Mangini”, Via S. Donato 15, I-40127 Bologna, Italy;
1
2
3
e-mail: consigli@ms.fci.unibo.it, guernel@ms.fci.unibo.it, spinelli@alma.unibo.it
Received July 12, 1999
Accepted Septem ber 30, 1999
Dedicated to Professor Otto Exner on the occasion of his 75th birthday in recognition of his out-
standing contributions to physical organic chemistry and chemometrics.
Th e rate con stan ts of th e title reaction s h ave been m easured at various am in e con cen tra-
tion s. Th e secon d-order kin etic con stan t for th e am in o substitution in creases in a h yperbolic
way as a fun ction of th e n ucleoph ile con cen tration . Th e k3Am /k–1 ratio for each catalysed sys-
tem is n ot a m on oton ic fun ction of th e X substituen t. Th is result h as been ration alized in
th e fram ework of th e SB-GA (Specific Base-Gen eral Acid) m ech an ism of base catalysis.
Key w ord s: Arom atic n ucleoph ilic substitution s; Th ioph en es; Base catalysis; SB-GA m ech a-
n ism ; Reaction kin etics.
In recen t years we h ave th orough ly in vestigated th e m ech an ism of base ca-
talysis in arom atic n ucleoph ilic substitution s of n itro-activated th ioph en e
derivatives with prim ary an d secon dary am in es as n ucleoph iles, both in
m eth an ol an d in ben zen e1.
We n ow report on a kin etic study of th e reaction s of som e 5-n itro-2-
(4-n itroph en oxy)-3-X-th ioph en es with an ilin e an d 4-m eth oxyan ilin e in
m eth an ol, at 20 °C. Th e substrates used h ere as “ch em ical observers” h ave
an activatin g n itro group fixed at C-5 an d a variable substituen t at C-3,
wh ich represen ts an ortho-like position with respect to th e reaction cen tre
located at C-2.
Th e 3-X substituen ts ch osen , apart from X = H, are (i) th e sp2 groups
CONH2, CO2Me an d COMe with th e sam e geom etry aroun d th e carbon yl
carbon atom but with differen t “in tern al” an d “extern al” con jugative in ter-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1878
Frenna et al.:
action s an d differen t steric h in dran ce; (ii) th e m eth ylsulfon yl group
(SO2Me), a group with electron ic effects com parable with th ose of th e
COMe group but with a tetrah edral geom etry m uch m ore com pressive with
respect to th e adjacen t reaction cen tre; (iii) th e cyan o group (CN), a stron g
electron -with drawin g substituen t with a lin ear geom etry; an d (iv) th e
3-n itro group wh ich h as a plan ar geom etry but wh ose coplan arity with th e
arom atic rin g could be m ore or less preven ted by th e steric com pression s
occurrin g in th e reaction area.
Th e presen ce of an ortho-like substituen t n ear th e reaction cen tre can de-
term in e a differen t reaction path way in depen den ce on th ree m ain factors:
(a) th e activation degree of substrate; (b) th e prim ary an d/or secon dary ki-
n etic steric effects, as also related to th e structures of n ucleoph ile an d
n ucleofugal group; an d (c) th e possible an ch im eric assistan ce in decom posi-
tion of th e reaction in term ediate.
RESULTS AND DISCUSSION
Reaction Products
5-Nitro-2-(4-n itroph en oxy)-3-X-th ioph en es 1, on treatm en t with an ilin es in
m eth an ol, gave th e correspon din g an ilin o derivatives 2 an d 3 in h igh yields.
Th e relevan t ph ysical data are sh own in Tables I–III.
X
X
YC6H4NH3
4-NO2C6H4O
+
+
2 YC6H4NH2
OC6H4NO2-4
+
NHC6H4Y
O2N
O2N
S
S
2, 3
1
3: Y = 4-MeO
2: Y = H
a: X = H
b: X = CONH2
g: X = NO2
c: X = COOMe
d: X = COMe
e: X = SO2Me
f: X = CN
Kinetic Data
Th e apparen t secon d-order kin etic con stan ts, kA, for th e am in e substitution
reaction s of 1 in m eth an ol at 20 °C, at various am in e con cen tration s, in th e
presence of amine hydrochloride and at constant ionic strength (0.05 mol dm–3)
are given in Tables IV an d V.
In spection of th e data sh ows th at for both an ilin es, with th e exception of
th e reaction s in volvin g th e substrates with X = COMe an d X = NO2, kA in -
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1879
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Frenna et al.:
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1881
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1882
Frenna et al.:
TABLE IV
Apparen t kin etic con stan ts for th e reaction s of 5-n itro-2-(4-n itroph en oxy)-3-X-th ioph en es
with an ilin ea in m eth an ol at 20 °C
X = H
[An ilin e], m ol dm –3
kA, 10–6 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–6 dm 3 m ol–1 s–1
0.00505
0.232
0.202
1.30
0.0101
0.318
0.404
1.53
0.0253
0.409
0.606
1.64
0.0505
0.687
0.808
1.71
0.0758
0.891
1.01
0.101
1.05
1.73
X = CONH2
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
0.000606
1.60
0.00101
1.65
0.00152
1.70
0.00202
1.76
0.00306
1.84
0.00612
1.91
0.00756
2.00
0.00918
2.07
0.0122
2.15
0.0163
2.19
0.0204
2.25
0.0306
2.32
0.0510
2.38
0.102
2.44
0.204
2.47
0.306
2.48
0.408
2.49
0.510
2.49
X = CO2Me
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
0.000606
5.61
0.00101
5.83
0.00152
5.96
0.00202
6.09
0.00303
6.37
0.00606
6.70
0.00909
7.02
0.0121
7.36
0.0162
7.78
0.0202
8.22
0.0303
8.71
0.0505
9.27
0.101
10.00
0.202
0.303
10.5
10.7
0.404
0.505
10.8
10.8
X = CN
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
0.000606
1.48
0.00101
1.52
0.00152
1.55
0.00198
1.61
0.00297
1.66
0.00446
1.72
0.00594
1.78
0.00743
1.84
0.00891
1.91
0.0119
1.94
0.0158
1.97
0.0198
2.00
0.0297
2.04
0.0495
2.06
0.0990
2.09
0.198
2.11
0.297
2.11
0.396
2.11
X = SO2Me
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–4 dm 3 m ol–1 s–1
0.00122
0.636
0.00765
2.17
0.00204
0.961
0.00900
2.34
0.00300
1.35
0.00459
1.64
0.00600
1.82
0.0107
2.52
0.0120
2.70
0.0160
2.95
0.0200
3.13
0.0300
3.37
0.0500
3.66
0.100
3.90
0.200
4.04
0.300
4.10
0.400
4.10
0.500
4.12
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1883
TABLE IV
(Continued)
X = COMe
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
[An ilin e], m ol dm –3
kA, 10–3 dm 3 m ol–1 s–1
0.00202
2.28
0.00303
0.00404
2.30
0.00606
2.26
0.00808
2.28
2.25
0.0101
2.28
0.0152
2.26
0.0202
2.31
0.0303
2.25
0.0505
2.28
0.101
2.29
0.202
2.31
X = NO2
[An ilin e], m ol dm –3
kA, dm 3 m ol–1 s–1
0.000408
0.475
0.000612
0.480
0.000816
0.480
0.00102
0.478
0.00153
0.482
[An ilin e], m ol dm –3
kA, dm 3 m ol–1 s–1
0.00204
0.480
a
[An ilin e·HCl] + [NaCl] = 0.05 m ol dm –3
.
creases in a curvilin ear (h yperbolic) way as a fun ction of th e n ucleoph ile
con cen tration , at a con stan t buffer ratio, accordin g to Eq. (1).
kA = (k1k2 + k1kAm [Am ])/( k–1 + k2 + kAm [Am ])
(1)
Depen din g on th e catalysis m ech an ism followed, kAm is equal to k3Am /k–1
or to k3Am k4Am H /kAm k–1 (Sch em e 1).
−3
We will sh ow later on th at th e reaction s h ere in vestigated are gen eral
base-catalysed. In deed, due to th e ion ization equilibrium of th e am in es in
m eth an ol (Eq. (2)), two gen eral bases are in solution an d also catalysis with
th e m eth oxide ion sh ould in deed be observed.
Am + MeOH
Am H+ + MeO–
(2)
As a m atter of fact, sin ce th e ion ization con stan ts of an ilin e an d
4-m eth oxyan ilin e in m eth an ol are very low, th e m eth oxide ion con cen tra-
tion , un der th e experim en tal con dition s used, is too low to yield an y appre-
ciable con tribution to catalysis. Th e kin etic m easurem en ts carried out at a
con stan t an ilin e con cen tration an d a variable buffer ratio (Table VI) sup-
port th is con clusion .
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1884
Frenna et al.:
Equation (1) describes a depen den ce of kA on [Am ] wh ich is lin ear at low
con cen tration s {(k–1 + k2) >> kAm [Am ]; kA = k1k2/(k–1 + k2) + k1kAm [Am ]/(k–1
+
k2)}; th en curvilin ear (h yperbolic) an d fin ally sh ows a plateau correspon d-
in g to th e asym ptote of th e h yperbola, i.e., kA = k1, due to th e con dition
k
Am [Am ] >> (k–1 + k2).
X
X
k1
NH2C6H4Y
OC6H4NO2-4
OC6H4NO2-4
YC6H4NH2
O2N
O2N
S
S
k-1
1
+
XH
k2
X
YC6H4NH2
AmH
k-3
Am
NHC6H4Y
O2N
k3
Y = H, 4-OMe
S
2, 3
AmH
k4
X
AmH
K = k3Am/k-3
NHC6H4Y
OC6H4NO2-4
O2N
S
_
X
SCHEME 1
A n on -lin ear regression treatm en t of kin etic data by th e least-squares
m eth od, accordin g to Eq. (1) h as allowed to calculate th e values of k1, k2
an d of k3Am /k–1 ratio for each catalysed system ; th e values are reported in
Table VII.
A plot of th e logarith m ic relative kin etic con stan ts, log (k1,X/k1,H ) for th e
reaction s of com poun ds 1 with a given am in e versus σ– con stan ts of X sub-
stituen ts (Table VIII)2 sh ows an excellen t lin ear free en ergy correlation
(Table IX). Th e greater ρ value calculated for th e an ilin e as com pared with
th e 4-m eth oxyan ilin e reaction s apparen tly agrees with th e reactivity–selec-
tivity prin ciple3 but th e differen ce between th e ρ values is n ot statistically
sign ifican t.
Th e greater reactivity of 4-m eth oxyan ilin e with respect to an ilin e reflects,
alth ough on ly qualitatively, th e greater basicity of th e form er. In th e reac-
tion of decom position of th e zwitterion ic in term ediate givin g th e products,
th e k–1 reactivity order will be, of course, in verted, i.e., 4-m eth oxyan ilin e <
an ilin e. In oth er words, accordin g to th e Ham m on d postulate, for a given
substrate, th e tran sition state will be “early” for th e m ore reactive am in e.
Let us con sider th e structure of th e reaction in term ediate. On accoun t of
th e differen t geom etry of th e groups bon ded to tetrah edral carbon 2-atom ,
th e in teraction by h ydrogen bon din g between th e am m on ium n itrogen
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1885
TABLE V
Apparen t kin etic con stan ts for th e reaction s of 5-n itro-2-(4-n itroph en oxy)-3-X-th ioph en es
with 4-m eth oxyan ilin ea (con cen tration in m ol dm –3) in m eth an ol at 20 °C
X = H
[4-Meth oxyan ilin e]
kA, 10–5 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–5 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–5 dm 3 m ol–1 s–1
0.00495
0.651
0.149
2.09
0.00990
0.730
0.198
2.33
0.0248
0.899
0.297
2.60
0.0495
1.25
0.0743
1.52
0.0990
1.87
0.396
2.80
0.495
2.91
0.594
3.00
0.792
3.11
0.990
3.18
X = CONH2
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
0.00312
1.68
0.00520
1.73
0.00832
1.80
0.0125
1.86
0.0208
1.92
0.0312
1.97
0.0416
2.00
0.0541
2.02
0.0666
2.04
0.0790
2.05
0.0915
2.05
0.104
2.06
X = CO2Me
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
0.00510
5.61
0.0102
6.09
0.0163
6.56
0.0265
7.09
0.0326
7.30
0.0418
7.54
0.0510
7.75
0.0673
7.98
0.0816
8.11
0.102
8.25
X = CN
[4-Meth oxyan ilin e]
kA, dm 3 m ol–1 s–1
0.00125
0.0173
0.0312
0.0186
0.160
0.00312
0.0174
0.0416
0.0190
0.200
0.00520
0.0175
0.0541
0.0196
0.240
0.00832
0.0176
0.0666
0.0201
0.300
0.0125
0.0178
0.0790
0.0206
0.0208
0.0182
0.120
[4-Meth oxyan ilin e]
kA, dm 3 m ol–1 s–1
0.0208
[4-Meth oxyan ilin e]
kA, dm 3 m ol–1 s–1
0.0207
0.0209
0.0209
0.0210
X = SO2Me
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–3 dm 3 m ol–1 s–1
0.00312
1.82
0.00520
1.87
0.00832
1.94
0.0125
2.00
0.0208
2.14
0.0312
2.29
0.0416
2.42
0.0541
2.55
0.0666
2.66
0.0790
2.75
0.0915
2.83
0.104
2.90
X = COMe
[4-Meth oxyan ilin e]
kA, 10–2 dm 3 m ol–1 s–1
[4-Meth oxyan ilin e]
kA, 10–2 dm 3 m ol–1 s–1
0.00204
1.84
0.00306
1.80
0.00510
1.79
0.00734
1.80
0.0102
1.84
0.0143
1.87
0.0204
1.87
0.0306
1.87
X = NO2
[4-Meth oxyan ilin e]
kA, dm 3 m ol–1 s–1
0.000400
3.16
0.000500
3.18
0.000600
3.15
0.000700
3.14
0.000800
3.17
a
[4-Meth oxyan ilin e·HCl] + [NaCl] = 0.05 m ol dm –3
.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1886
Frenna et al.:
an d th e 3-X substituen t, th e so-called “built-in solvation ” (ref.4) presen ts
th ree typologies (4–6).
Z
O
S
Me
O
C
N
H
O
H
C
H
N
O2N
N
N
O2N
O2N
S
S
S
C6H4Y
C6H4Y
C6H4Y
L
L
L
H
H
H
4
5
6
L = OC6H4NO2-4; Z = NH2, OMe, Me
In th e decom position of th e reaction in term ediate in to th e reactan ts,
both th e in tram olecular h ydrogen bon din g between th e am m on ium pro-
ton an d 3-X group an d th e bon d between th e n ucleoph ile n itrogen atom
an d th e arom atic carbon atom are broken , as sh own , for exam ple, in 7. Th e
m ore n ucleoph ilic th e am in e is, th e stron ger th e n itrogen carbon bon d, th e
less acidic th e am m on ium h ydrogen an d th us th e weaker th e h ydrogen
bon din g. As far as th is latter bon d is con cern ed, th e tran sition state would
be “later” with th e m ore basic an ilin e. It appears th at th e effect depen din g
on th e n itrogen n ucleoph ilicity, wh ich , accordin g to Ham m on d’s postu-
late, would cause a given sequen ce of th e position s of tran sition state alon g
th e reaction co-ordin ate, is coun terbalan ced by th e h ydrogen bon din g ef-
fect. If it were th e on ly effect operatin g, it would give rise to th e exactly op-
posite sequen ce. Th us, for each substrate, th e n ucleoph ile variation does
n ot in volve a sign ifican t variation of th e position of th e tran sition state. In
oth er words, th e ran ge of tran sition states correspon din g to various substi-
tuted th ioph en e com poun ds does n ot ch an ge position on th e reaction co-
ordin ate with th e ch an gin g n ucleoph ile. Th is im plies th at th e selectivity, as
m easured by ρ, is virtually con stan t wh atever th e used am in e is.
Z
Z
C
C
O
H
O
H
δ
δ
δ
S
δ
S
N
N
O2N
O2N
C6H4Y
C6H4Y
L
L
H
H
7
8
δ
NH2
L = OC6H4NO2-4; Z = NH2, OMe, Me
C6H4Y
We h ave seen above th at, at varian ce with th e situation wh ere X = H,
CONH2, CO2Me, CN an d SO2Me, th e reaction s of com poun ds with X =
COMe an d NO2 are n ot catalysed. Sin ce on goin g from X = CO2Me to X =
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1887
CN, both k2/k–1 and kAm /k–1 ratios increase in parallel with k1 values (Table VII),
it is possible to estim ate th ese ratios for th e two substituen ts COCH3 an d
NO2. Such estim ates sh ow th at th e con dition kAm [Am ] >> (k–1 + k2) is ful-
filled even for th e lowest n ucleoph ile con cen tration used an d th us th e rele-
van t kA m easured represen t plateau values.
TABLE VI
Apparen t secon d-order kin etic con stan ts, kA, for th e reaction s of m eth yl 5-n itro-2-(4-n itro-
ph en oxy)th ioph en e-3-carboxylate with an ilin e in m eth an ol at 20 °C, as a fun ction of an ilin e
h ydroch loride con cen tration a
[An ilin e·HCl]
0.00100
7.14
0.00250
0.00500
7.13
0.0100
7.16
0.0200
7.15
kA, 10–4 dm 3 m ol–1 s–1
7.15
.
a
[An ilin e·HCl] + [NaCl] = 0.05 dm 3 m ol–1
TABLE VII
Lin ear regression an alysis of apparen t secon d-order kin etic con stan ts, kA, for th e reaction s of
5-n itro-2-(4-n itroph en oxy)-3-X-th ioph en es with an ilin e an d 4-m eth oxyan ilin e in m eth an ol
at 20 °C, accordin g to Eq. (1)
k1,
k3Am k–1
,
na
k2/k1
X
Am in e
dm 3 m ol–2 s–1
dm 6 m ol–2 s–1
H
an ilin e
1.90 10–6
2.51 10–4
4.18 10–4
1.11 10–3
2.13 10–3
2.28 10–3
4.79 10–1
3.59 10–5
2.11 10–3
3.99 10–3
9.05 10–3
2.19 10–2
1.84 10–2
3.16
0.0868
1.60
0
10.5
330
11
18
18
17
18
12
6
CONH2
SO2Me
CO2Me
CN
an ilin e
an ilin e
144
an ilin e
1.03
1.83
>>1
84.3
620
an ilin e
COMe
NO2
an ilin e
>>>1
>>>1
8.32
359
an ilin e
>>1
H
4-m eth oxyan ilin e
4-m eth oxyan ilin e
4-m eth oxyan ilin e
4-m eth oxyan ilin e
4-m eth oxyan ilin e
4-m eth oxyan ilin e
4-m eth oxyan ilin e
0.162
2.74
0.786
1.14
3.40
>>1
14
12
12
10
16
8
CONH2
SO2Me
CO2Me
CN
18.1
92.4
97.3
>>>1
>>>1
COMe
NO2
>>1
5
a
Num ber of data poin ts.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1888
Frenna et al.:
In order to get som e in sigh t in to th e catalysis m ech an ism , let us con sider
th e various kin etic coefficien ts in volved, i.e., k–1 an d kAm coefficien ts, as de-
term in ed by th e various 3-X substituen ts. As th e electron -with drawin g
power of th e 3-X substituen t in creases, on on e h an d th e stren gth of
in tram olecular h ydrogen bon din g also in creases on accoun t of th e h igh er
den sity of n egative ch arge on th e atom wh ich is th e acceptor of such a h y-
drogen bon din g; on th e oth er h an d, th e bon d between th e n ucleoph ilic n i-
trogen atom an d th e arom atic carbon atom becom es m ore difficult to be
broken . Both effects ten d to reduce th e k–1 value; th us ρ–1 sh ould be n ega-
tive.
As far as th e kAm step is con cern ed, it is con ven ien t to take in to con sider-
ation th e two catalysis m ech an ism s com m on ly accepted5.
In th e first m ech an ism 5, th e slow step in volves th e form ation of th e
tran sition state 8. With in creasin g electron -with drawin g power of th e X
substituen t, both th e basicity of th e oxygen atom (s) of th e 3-X group an d
th e acidity of th e h ydrogen atom in volved in th e built-in solvation in -
crease. Th erefore, th e two effects brough t about by th e X substituen t varia-
tion in crease th e stren gth of th e in tram olecular h ydrogen bon d. In th e
base-catalysed step it is n ot n ecessary to break th is bon d sin ce th e prim ary
am in e h as a secon d h ydrogen atom wh ich can be used to bon d th e base
catalyst. Th e in terven tion of a secon d m olecule of am in e determ in es th e
slow elim in ation of th e n on -h ydrogen bon ded proton . Sin ce an elec-
tron -with drawin g X substituen t in creases th e acidity of th is proton , as a
wh ole, in th is catalysis m ech an ism , ρA3 m > 0 sh ould be observed. Moreover,
sin ce th e effect of th e X substituen t on th e rate of proton elim in ation (k3Am
is presum ably lower th an th at on th e C–N bon d breakin g (k–1), on e sh ould
)
observe ρA3 m
<
ρ–1 . As a m atter of fact, it sh ould be (ρA3 m – ρ–1) > 0 with
th e im plication th at k3Am /k–1 sh ould in crease with in creasin g elec-
tron -with drawin g power of th e X substituen t.
In th e SB-GA m ech an ism 5 (Sch em e 1), th ere is a fast pre-equilibrium with
a tran sition state sim ilar to 8 wh ere a proton tran sfer from XH, to th e
am in e occurs (Eq. (3)).
K
XH + YC6H4NH2
X– + C6H4NH +3
(3)
For th is first reaction of th e SB-GA catalysis m ech an ism , on e sh ould ob-
serve ρK > 0. Th e subsequen t step, wh ich in volves th e gen eral acid-
catalysed detach m en t of th e leavin g group by th e con jugated acid of th e
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1889
am in e (tran sition state 9), is disfavoured by electron -with drawin g X sub-
stituen ts an d sh ould give ρ4 < 0. An exam in ation of data in Table VII sh ows
th at kAm /k–1 values are n ot a m on oton ic fun ction of th e X substituen t; th ey
decrease on goin g from X = CONH2 to X = CO2Me an d in crease on goin g
from X = CO2Me to X = NO2. Th is observation is in con trast with th at base
catalysis m ech an ism wh ich in volves proton tran sfer to th e base as th e
rate-determ in in g step (see above).
X
NHC6H4Y
δ
O2N
S
OC6H4NO2-4
H
9
δ
NH2C6H4Y
In con trast, th e tren d of kAm /k–1 values observed can be easily accoun ted
for in th e fram ework of th e SB-GA catalysis m ech an ism 5. In fact, it is evi-
den t th at th is tren d arises from a balan ce of electron ic effects of th e X
substituen t on th e two param eters kAm an d k–1. In th e SB-GA m ech an ism ,
th e kAm param eter correspon ds to Kk4. Sin ce th e decom position reaction of
XH in to th e products, con trolled by k4, an d th e decom position of XH in to
th e reactan ts are very sim ilar processes, it is probable th at k4 an d k–1 param -
eters ch an ge in a h om ogen eous an d regular way with ch an gin g X
substituen t. Moreover, sin ce it sh ould com ply with th e con dition k–1 >> Kk4
(oth erwise n o base catalysis would be observed), th e relation sh ip ρ–1
<
ρk + ρ4 h as to be satisfied an d, because of a m uch h igh er m obility of th e
am ine leaving group as com pared to 4-nitrophenoxy leaving group (k–1 >> k4),
also th e relation sh ip ρ–1
<
ρ4 .
As both ρ4 an d ρ–1 are n egative (see above), th e differen ce ρ4 – ρ–1 sh ould
be n egative, too. Th erefore, th e observation of k3Am /k–1 ratios, wh ich de-
crease on goin g from X = CONH2 to X = CO2Me, im plies th at th e ρK param -
eter sh ould be less th an ρ4 – ρ–1 . On th e oth er h an d, th e observation of
k3Am /k–1 ratios, wh ich in crease on goin g from X = CO2Me to X = CN an d to
X = NO2, would im ply th e con dition ρK > ρ4 – ρ–1 . In con clusion , two dif-
feren t ρK values correspon din g to th e two substituen t ran ges would be re-
quired.
We th in k th at th is dich otom y in th e beh aviour of th e various substrates
studied com es from th e h yper-ortho relation 6. Wh en th e 3-X substituen t h as
a relatively low con jugative effect, a preferen tial con jugative in teraction oc-
curs between th e reaction cen tre an d th e 5-n itro group. Th is preferen tial in -
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1890
Frenna et al.:
teraction causes a levellin g of electron ic effects exerted by th e X substituen t
on th e equilibrium XH + B
X– + BH+ an d a relatively low ρK value.
Wh en th e con jugation of th e reaction cen tre with th e 3-X substituen t be-
com es im portan t, it in terferes successfully with th e h yper-ortho relation an d
gives rise to a ρK value so m uch greater th an in th e precedin g case, as to
ch an ge th e sign of th e algebraic sum ρ4 + ρ3 – ρ–1. A positive sum produces
k
Am /k–1 ratios wh ich in crease with in creasin g electron -with drawin g power
of th e 5-X substituen t. Th is in terpretation of th e data obtain ed in th e pres-
en t work leads to stron g support for th e h ypoth esis th at th e catalysis ob-
served occurs via th e SB-GA m ech an ism .
Th e case for X = SO2Me is worth bein g con sidered separately. Th is substi-
tuen t h as m uch th e sam e substituen t con stan t as X = COMe (Table VIII) but
sh ows th e reactivity with both am in es lower th an th at of substrates with X =
CO2Me. Th is un expectedly low reactivity can be accoun ted for by a stron g
prim ary steric effect exerted by th is bulky substituen t an d, in addition , by a
greater difficulty th an with th e sp2 groups, to form th e h ydrogen bon din g
as sh own in 5. Th us data for SO2Me h ave to be excluded from th e Ham m ett
correlation (Table IX). On th e oth er h an d th e h yper-ortho relation deter-
m in es a com paratively m uch lesser value of th e k–1 con stan t for th is
TABLE VIII
Substituen t con stan ts
X
H
CONH2
0.57
CO2Me
0.67
CN
COMe
0.82
SO2Me
0.84
NO2
1.23
σ–
0.00
0.79
TABLE IX
Lin ear regression an alysisa of logarith m ic relative kin etic con stan ts [log (k1,X/k1,H)] for th e re-
action s of 5-n itro-2-(4-n itroph en oxy)-3-X-th ioph en es with an ilin e an d 4-m eth oxyan ilin e in
m eth an ol at 20 °C, accordin g to th e equation log (k1,X/k1,H) = ρσ–
No.
Am in e
ρ ± sρ
i ± si
r
nb
CL>(%)
1
2
An ilin e
4.30 ± 0.27
3.94 ± 0.31
–0.19 ± 0.21
–0.24 ± 0.24
0.992
0.988
6
6
99.9
99.9
4-Meth oxyan ilin e
a
ρ, reaction con stan t; i, in tercept of th e regression lin e with th e ordin ate σ = 0; sρ an d si,
stan dard deviation s of ρ an d i, respectively; r, correlation coefficien t; n, n um ber of data
b
poin ts; CL, con fiden ce level. Data for X = SO2Me h ave been excluded from th e correlation .
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Kinetic Study
1891
substituen t. As a con sequen ce, th e kAm /k–1 ratio for X = SO2Me does n ot lie
in th e sam e sequen ce as th at for th e oth er substituen ts.
For th e reaction s of 5-n itro-2-(4-n itroph en oxy)th ioph en e, very low k2/k–1
an d kAm /k–1 ratios are observed. Th is occurs because in th e tran sition states
pertain in g to th e reaction of th is substrate with th e two an ilin es, th ere is
n o built-in solvation (see above). In oth er words, th e powerful an ch im eric
assistan ce, wh ich for th e oth er ortho-substituted com poun ds reduces th e k–1
param eter th rough stabilisation of th e reaction in term ediate, is n ow m iss-
in g an d com paratively lower k2/k–1 an d kAm /k–1 ratios are, in deed, observed.
It is worth wh ile to recall th at th e correspon din g reaction s7 of 3-n itro-2-
(4-n itroph en oxy)th ioph en e are n ot catalysed suggestin g th at, th e activa-
tion bein g equal, th e position of th e activatin g n itro group with respect to
th e reaction cen tre is a crucial factor. In th is latter com poun d, in fact, th e
lack of com petition in th e con jugation with a 5-substituen t an d th e h yper-
ortho relation cause a stron g con jugative in teraction between th e reaction
cen tre an d th e 3-n itro group an d th e greatest possible electron den sity on
th e oxygen atom s of th is group. As a m atter of fact, th e stron gest possible
h ydrogen bon din g an d th e lowest k–1 value occur an d on th e basis of th e re-
lation sh ip k–1 << (k2 + kAm [Am ]), th e reaction s in volved are n ot catalysed.
EXPERIMENTAL
Eth ers 1 were prepared by th e gen eral m eth od of ref.7. An ilin e8, 4-m eth oxyan ilin e8 an d
m eth an ol9 were purified by th e reported m eth ods. Am in o derivatives 2 an d 3 were prepared
by th e gen eral m eth od of ref.10. Th e relevan t ph ysical data of 1–3 are sh own in Tables I–III.
Kinetics measurements. Th e kin etics were followed spectroph otom etrically as previously de-
scribed11. Th e con cen tration s used were 2 · 10–4–10–3 m ol dm –3 for substrates an d th ose re-
ported in Tables IV an d V for am in es. Th e wavelen gth an d log ε values for UV spectral
m easurem en ts are sh own in Tables II an d III. Optical den sity m easurem en ts were carried out
after dilution with acidified m eth an ol11
.
The authors thank MURST and CNR for financial support. Investigation supported by University of
Bologna (Funds for selected research topics).
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Collect. Czech. Chem. Commun. (Vol. 64) (1999)

1892
Frenna et al.:
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Collect. Czech. Chem. Commun. (Vol. 64) (1999)