Evaluation of the reactivity and regioselectivity of superelectrophilic iodinating systems

Article abstract of DOI:10.1134/S1070428009090073

Iodination of o-nitrotoluene in H₂SO₄ or CF ₃SO₃H at 0°C with compounds having a nitrogen-iodine bond leads to the formation of isomeric mono- and diiodo derivatives whose ratio differs from the statistical value. The reaction of nitrobenzene with 2 equiv of N-I reagents in trifluoromethanesulfonic acid at 0°C takes less than 1 min and yields 79-85% of m-iodonitrobenzene. The electrophilic reactivity of the iodinating agents was estimated by quantum-chemical methods.

Full text of DOI:10.1134/S1070428009090073

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 9, pp. 1349–1352. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.K. Chaikovskii, V.D. Filimonov, A.A. Funk, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 9,
pp. 1364–1367.
Evaluation of the Reactivity and Regioselectivity
of Superelectrophilic Iodinating Systems
V. K. Chaikovskii, V. D. Filimonov, and A. A. Funk
Tomsk Polytechnical University, pr. Lenina 30, Tomsk, 634050 Russia
e-mail: clg@mail.ru
Received November 12, 2008
Abstract—Iodination of o-nitrotoluene in H2SO4 or CF3SO3H at 0°C with compounds having a nitrogen–
iodine bond leads to the formation of isomeric mono- and diiodo derivatives whose ratio differs from the
statistical value. The reaction of nitrobenzene with 2 equiv of N–I reagents in trifluoromethanesulfonic acid at
0°C takes less than 1 min and yields 79–85% of m-iodonitrobenzene. The electrophilic reactivity of the iodinat-
ing agents was estimated by quantum-chemical methods.
DOI: 10.1134/S1070428009090073
The rate of electrophilic substitution reactions in
the aromatic series and isomeric composition of the
products are largely determined by the electrophile
nature. In keeping with the Brown selectivity relation-
ship, stronger electrophiles exhibit lower intramolec-
ular selectivity in substitution reactions in the benzene
ring [1]. The most reactive electrophiles give rise to
a mixture of regioisomers whose ratio approaches sta-
tistical value. In the iodination with common iodinat-
ing systems, the reactivity and selectivity may be eval-
uated using the reaction with toluene as an example
[2]. However, the procedure based on determination of
the ratio of o- and p-iodotoluenes cannot be applied to
reactions with superelectrophilic iodinating systems
[3–6], which lead to the formation of a mixture of
polyiodotoluenes containing mostly tri- and tetraiodo
derivatives. Therefore, to estimate the selectivity of
superelectrophilic iodinating systems we compared the
compositions of products formed in the iodination of
o-nitrotoluene (I) with reagents generated by dissolu-
tion of 1,3,4,6-tetraiodoglycoluril (TIG), 1,3-diiodo-
5,5-dimethylhydantoin (DIH), and N-iodosuccinimide
(NIS) in sulfuric acid [3, 5, 6] (Scheme 1).
Traditional methods for the determination of the
reactivity and regioselectivity of iodinating systems by
analysis of the iodination products of nitroarene I can-
not be used, for nitrotoluenes do not undergo iodina-
tion by common methods at 0°C. Detailed GC–MS
study on the products of reactions of compound I with
TIG–H2SO4, DIH–H2SO4, and NIS–H2SO4 showed
(Table 1) that the use of stoichiometric amounts of the
reagents (calculated on the active iodine) does not en-
sure complete conversion of I (Table 1, run nos. 1–3),
and 30–35% of the initial compound remains un-
changed.
A similar conversion of other substrates at the same
reagent-to-substrate ratio was noted by us previously
[3–6]. Approximately similar selectivities were ob-
served in the iodination with TIG–H2SO4 and DIH–
H2SO4. In the reaction with N-iodosuccinimide, the
fraction of 4-iodo-2-nitrotoluene (II) was slightly
larger than the fraction of 6-iodo-2-nitrotoluene (III),
but the substrate conversion was lower.
The reactions in the presence of 2 equiv of the
iodinating agents (Table 1, run nos. 4–6) are character-
ized by appreciably reduced para-selectivity. However,
Scheme 1.
NO2
NO2
NO2
N–I reagent, 0°C
H2SO4 or CF3SO3H
Me
Me
Me
I
+
I
I
II
III
1349

CHAIKOVSKII et al.
Table 1. Iodination of o-nitrotoluene (I) in sulfuric acid (d = 1.814 g/cm3) at 0°C
1350
Run no.
Reagent
Molar ratio I–reagent Reaction time, min Product ratio II:III, % Unreacted substrate I, %
1
2
3
4
5
6
TIG–H2SO4
DIH–H2SO4
NIS–H2SO4
TIG–H2SO4
DIH–H2SO4
NIS–H2SO4
00.1:0.25
.01:0.5
1:1
60
60
60
30
30
30
14:86
14:86
12:88
19:81
23:77
a22:65a
30
32
35
00
00
00
.01:0.5
1:1
1:2
a
In addition, five isomeric diiodonitrotoluenes and one triiodonitrotoluene were detected.
Table 2. Iodination of o-nitrotoluene (I) with the system NIS–H2SO4 at 0°C (substrate–reagent ratio 1:2)
Retention
time, min
Fraction,
%
Iodination product
Mass spectrum, m/z (Irel, %)
6-Iodo-2-nitrotoluene (III)
14.54
263 [M]+ (39), 246 (100), 218 (8), 127 (4), 119 (23) 90 (60), 78 (5),
22.0
65.0
09.9
02.9
63 (21), 39 (2)
4-Iodo-2-nitrotoluene (II)
14.74
18.67
18.46
18.89
19.19
19.27
22.60
263 [M]+ (41), 246 (100), 218 (11), 127 (5), 119 (14), 89 (35), 63
(16), 39 (3)
4,6-Diiodo-2-nitrotoluene
389 [M]+ (48), 372 (100), 344 (21), 245 (20), 216 (43), 189 (5), 127
(9), 105 (11), 89 (82), 63 (35), 39 (9)
389 [M]+ (100), 372 (81), 343 (4), 245 (71), 216 (68), 189(4), 165
(3), 127 (13), 105 (9), 89 (82), 63 (46), 39 (11)
389 [M]+ (100), 372 (48), 343 (9), 254 (12), 245 (21), 216(60), 127
(17), 118 (21), 89 (86), 63 (50), 50 (11), 39 (8)
389 [M]+ (90), 372 (100), 344 (8), 254 (7), 245 (35), 216(40), 189
(6), 127 (11), 105 (14), 89 (95), 63 (47), 39 (12)
389 [M]+ (76), 372 (100), 343 (10), 245 (39), 216 (44), 189 (4), 127
Diiodo-2-nitrotoluenes
(4 isomers)
(9), 105 (10), 89 (74), 63 (35), 39 (8)
515 [M]+ (100), 498 (50), 485 (10), 371 (14), 342 (51), 244 (38),
Triiodo-2-nitrotoluene
00.2
215 (81), 165 (14), 127 (19), 88 (49), 62 (26), 44(4)
in the iodination with TIG–H2SO4 and DIH–H2SO4
only monoiodo derivatives were detected, whereas the
system NIS–H2SO4 gave rise to a mixture of mono-
iodination products, five isomeric diiodonitrotoluenes
(overall yield ~13%), and traces of triiodonitrotoluene
(Table 2). As might be expected, replacement of sul-
furic acid by considerably stronger trifluoromethane-
sulfonic acid resulted in slightly reduced regioselec-
tivity (Table 3). Furthermore, despite the presence of
excess iodinating agent (2 equiv), neither di- nor poly-
iodo derivatives were detected by GC–MS in the
reaction mixtures obtained in trifluoromethanesulfonic
acid, and even up to 3% of initial o-nitrotoluene I re-
mained unchanged.
IV and some other deactivated aromatic compounds
with N-iodosuccinimide in trifluoromethanesulfonic
acid was performed at 20°C, and the yield of 3-iodo-
nitrobenzene (V) was 86% in 2 h. We tried to re-
produce the results reported in [7] and found that the
reaction with stoichiometric amounts of the reactants
(IV:NIS = 1:1) takes less than 1 min even at 0°C, but
the substrate conversion is no more than 61–65%. By
carrying out the reaction at 20°C for 5 and 20 h we
succeeded in attaining no more than 65% conversion
of arene IV into 3-iodonitrobenzene (V) (GC–MS
data). However, the use of 2 equiv of NIS, as well as of
TIG and DIH, ensured complete conversion of IV into
iodo derivative V in a few seconds, i.e., in this case
the process may be regarded as a “test-tube” reaction
(Table 4).
The iodination of I was carried out over a period of
15 min; however, it turned out that the process was
considerably faster. Initially, we relied upon the data of
[7], according to which the iodination of nitrobenzene
Moreover, the reaction took less than 1 min at 0°C,
and the yield of V ranged from 79 to 85%, depending
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

EVALUATION OF THE REACTIVITY AND REGIOSELECTIVITY
Table 3. Iodination of o-nitrotoluene (I) in trifluoromethanesulfonic acid at 0°C
1351
Run no.
Reagent
Molar ratio I–reagent Reaction time, min Product ratio II:III, % Unreacted substrate I, %
1
2
3
TIG–CF3SO3H
DIH–CF3SO3H
NIS–CF3SO3H
.01:0.5
1:1
15
15
15
25:72
22:76
27:71
3
2
2
1:2
Table 4. Iodination of nitrobenzene (IV) in trifluoromethanesulfonic acid
Reagent
Molar ratio IV–reagent
Reaction time
Temperature, °C
Yield of V, %
NIS–CF3SO3H
NIS–CF3SO3H
NIS–CF3SO3H
NIS–CF3SO3H
TIG–CF3SO3H
DIH–CF3SO3H
1:2
1:2
<1 min<
1 min
1 min
20 h
20
00
00
20
00
00
a83a
a85a
61
1:1
1:1
65
1:1
1 min
1 min
a79a
a82a
0.1:0.5
a
Preparative yield.
on the iodinating agent (Table 4). As far as we know,
this is the best result in the iodination of deactivated
arenes, in particular of nitrobenzene (IV).
confirm that hypoiodites derived from the stronger
acid exhibit stronger electrophilicity and that species
like I3+An− (where An− is the corresponding acid anion)
are considerably more electrophilic than reagents
like I+An−.
We previously showed, first by theoretical methods
[8] and then experimentally [9], that disproportionation
of hypoiodite I+HSO3− generated upon dissolution of
N-iodo reagents (NIS, TIG, and DIH) in sulfuric acid
could give rise to I3+HSO4–. Presumably, I+3 could also be
generated from I+CF3SO3− which is likely to arise upon
dissolution of NIS [7], as well as of TIG and DIH, in
CF3SO3H. We believe that just I3+ F3CSO3− should
exhibit the highest electrophilicity in the examined
systems. With a view to compare the electrophilities of
reactive species that could be involved in the iodina-
tion process, the structures of I+HSO3− and I3+HSO3−, as
well as of I+ F3CSO3− and I3+F3CSO3−, were optimized at
the NBO RHF/6-311G(d) level of theory in the gas
phase; Table 5), and their global electrophilicities (ω)
[10] were determined.
EXPERIMENTAL
The progress of reactions was monitored by thin-
layer chromatography using Sorbfil plates and carbon
tetrachloride as eluent; spots were visualized under UV
light. Initial o-nitrotoluene (I) and nitrobenzene (V)
were distilled under reduced pressure and analyzed by
GLC. Sulfuric acid of chemically pure grade and tri-
fluoromethanesulfonic acid (from Angarsk Electrolysis
Table 5. Ionization potentials (IP), electron affinities (EA),
global electrophilicities (ω), and charges on the iodine atoms
[q(I)] in iodinating agents, calculated for the gas phase at the
RHF/6-311G(d) level using natural bond orbital (NBO)
approximationa
According to the B3LYP/6-311G(d) calculations
[8], the I3+ cation has a trigonal structure with an I–I–I
bond angle of 107.8°. Our calculations gave a value of
103.3° for I3+, and the corresponding angles in I3+HSO4−
and I3+ CF3SO3− were estimated at 96.1 and 96.6°,
respectively. These values are typical of multivalent
iodine compounds [11] and complexes like I3+ AlCl4−
and I3+ AsF6− [12]. The lowest unoccupied molecular
orbital in the examined species is localized on the I–I–I
fragment; this means that their electrophilicity is re-
lated mainly to central iodine atom. The data in Table 5
Iodinating
agent
IP = −EHOMO EA = −ELUMO q(I)
ω, eV
I3+
14.930
11.342
10.804
11.546
11.082
6.437
0.570
2.416
0.908
2.489
0.503 6.720
0.482 1.647
0.738 2.604
0.507 1.823
0.707 2.679
IHSO4
I3+HSO4−
CF3SO3I
I3+CF3SO3−
a
Imaginary frequency 66.4 cm−1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

CHAIKOVSKII et al.
1352
and Chemical Complex) containing no less than
99.5% of the main substance were used.
off, and the residue (3-iodonitrobenzene) was recrys-
tallized from ethanol. Yield 0.99–1.1 g (79–85 %),
mp 35–36°C.
Gas chromatographic–mass spectrometric analysis
was performed on a Trace DSQ instrument (Thermo-
electron Corp.); Xcalibur 1.4 software; BPX5 capillary
column, 25 m; injector temperature 280°C; oven tem-
perature programming from 70 to 250°C at a rate of
15 deg/min; a.m.u. range 33–500. Quantum-chemical
calculations were performed using GAUSSIAN’98W
software.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009