Superactivity and dual reactivity of the system N-iodosuccinimide-H 2SO4 in the iodination of deactivated arenes

Article abstract of DOI:10.1134/S1070428007090035

Dissolution of N-iodosuccinimide in sulfuric acid gives rise to electrophilic iodine-containing species which are capable of successfully iodinating aromatic compounds with electron-withdrawing substituents in the temperature range from 0 to 20°C. The iodination in sulfuric acid is effected by both protonated N-iodosuccinimide and IOS(O)(OH⁺)OH intermediate.

Full text of DOI:10.1134/S1070428007090035

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ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 9, pp. 1278–1281. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.K. Chaikovskii, V.D. Filimonov, V.I. Skorokhodov, V.D. Ogorodnikov, 2007, published in Zhurnal Organicheskoi Khimii, 2007,
Vol. 43, No. 9, pp. 1285–1288.
Superactivity and Dual Reactivity
of the System N-Iodosuccinimide–H2SO4 in the Iodination
of Deactivated Arenes
V. K. Chaikovskiia, V. D. Filimonova, V. I. Skorokhodova, and V. D. Ogorodnikovb
a Tomsk Polytechnic University, pr. Lenina 30, Tomsk, 634050 Russia
e-mail: clg@mail.ru
b Institute of Petroleum Chemistry, Siberian Division, Russian Academy of Sciences, Tomsk, Russia
Received October 26, 2006
Abstract—Dissolution of N-iodosuccinimide in sulfuric acid gives rise to electrophilic iodine-containing
species which are capable of successfully iodinating aromatic compounds with electron-withdrawing substit-
uents in the temperature range from 0 to 20°C. The iodination in sulfuric acid is effected by both protonated
N-iodosuccinimide and IOS(O)(OH+)OH intermediate.
DOI: 10.1134/S1070428007090035
We previously found that superactive electrophilic
iodine capable of readily iodinating at 0°C strongly de-
activated arenes is formed in sulfuric acid from iodine
chloride and silver sulfate [1, 2] or from 2,4,6,8-tetra-
iodoglycoluril (1,3,4,6-tetraiodooctahydroimidazo-
[4,5-d]imidazole-2,5-dione) [3]. N-Iodosuccinimide
(NIS) has long been regarded as a weak iodinating
agent [4, 5] until Olah et al. [6, 7] have shown that NIS
in high-cost trifluoromethanesulfonic acid or in BF3–
H2O is capable of nitrating nitrobenzene and some
other deactivated arenes. Our preliminary results
showed that in the iodination of nitrobenzene expen-
sive trifluoromethanesulfonic acid can be successfully
replaced by accessible sulfuric acid [8]. The same
system (NIS–H2SO4) was used to effect selective
iodination of 4-chloro-2-nitrotoluene [9].
0°C into 3-iodobenzaldehyde (Ib), 3,3′-diiodobenzo-
phenone (IIb), and 3,3′-diiodobenzil (IIIb), respec-
tively. The syntheses of 2,7-diiodofluorenone (IVb)
and 2,7-diiodophenanthrenequinone (Vb) from fluor-
enone (IVa) and phenanthrenequinone (Va) were ac-
companied by tarring, but the complete transformation
of the initial compounds also required 30 min at 0°C.
The iodination of benzoic (VIa) and 4-fluorobenzoic
acids (VIIa) was slower than the iodination of alde-
hydes and ketones. The reason is not clear, but analo-
gous reduced reactivity of aromatic carboxylic acids
was observed by us previously in the iodination with
iodine(I) chloride in sulfuric acid [10].
The results of iodination strongly depend not only
on the electronic structure but also on the solubility of
substrates and other factors. For example, we failed to
selectively introduce one iodine atom into iodobenzene
(VIIIa) molecule or obtain hexaiodobenzene under the
given conditions. The iodination of VIIIa with a solu-
tion of 2 or 4 equiv of NIS in H2SO4 gave a complex
mixture of mono-, di-, tri-, and tetraiodobenzenes
(according to the GC–MS data). However, in the iodin-
ation of VIIIa with 10 equiv of NIS 1,2,4,5-tetraiodo-
benzene (VIIIb) was formed in 68% yield (Table 1).
No further iodination occurred, for tetraiodobenzene
VIIIb is almost insoluble in sulfuric acid (it com-
pletely separates from the solution once being formed).
The goal of the present work was to study in detail
preparative potential of the reagent obtained by disso-
lution of NIS in H2SO4 using deactivated aromatic
compounds as substrates and determine the nature of
electrophilic iodine-containing species generated in
that medium. Dissolution of NIS in 90% sulfuric acid
(d = 1.814 g/cm3) gave a stable dark brown solution
which exhibited enhanced iodinating power. It readily
reacted with many deactivated aromatic compounds at
0°C or at room temperature to give the corresponding
iodo-substituted derivatives (Table 1). Carbonyl com-
pounds, such as benzaldehyde (Ia), benzophenone
(IIa), and benzil (IIIa) were converted in 30 min at
4-Nitrotoluene (IXa) is poorly soluble in sulfuric
acid; therefore, only the dissolved part of substrate IXa
1278

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SUPERACTIVITY AND DUAL REACTIVITY OF THE SYSTEM
Table 1. Iodination of deactivated aromatic compounds with N-iodosuccinimide in sulfuric acid
1279
Tempera- Reaction
ture, °C time, min
Yield,
%
Substrate (no.)
Product
mp, °C (solvent); published data
00
00
00
030
030
030
3-Iodobenzaldehyde (Ib)
80 054–56 (EtOH); 57 [14]
Benzaldehyde (Ia)
Benzophenone (IIa)
Benzil (IIIa)
Bis(3-iodophenyl)methanone (IIb)
63 145–147(EtOH); 147–149 [17]
79 128–129 (EtOH); 128–129 [16]
1,2-Bis(3-iodophenyl)ethane-1,2-
dione (IIIb)
00
00
00
00
030
030
120
120
2,7-Diiodofluorenone (IVb)
35 205–206 (benzene); 205–206
[14]
Fluorenone (IVa)
Phenanthrenequinone
(Va)
2,7-Diiodophenanthrenequinone (Vb) 20 309–310 (toluene); 310 [14]
Benzoic acid (VIa)
3-Iodobenzoic acid (VIb)
42 185–186 (50% i-PrOH); 186–
187 [14]
4-Fluorobenzoic acid
4-Fluoro-3-iodobenzoic acid (VIIb)
73 173–174 (80% i-PrOH); 174–
(VIIa)
176 [3]
00
00
20
00
00
20
20
030
030
1,2,4,5-Tetraiodobenzene (VIIIb)
2-Iodo-4-nitrotoluene (IXb)
2,6-Diiodo-4-nitrotoluene (IXc)
4-Iodo-2-nitrotoluene (Xb)
3-Iodonitrobenzene (XIb)
68 250–253 (DMF); 254 [15]
55 055–57 (EtOH); 58 [14]
68 115–116 (EtOH); 117–118 [2]
41 058–59 (MeOH); 60–61 [14]
77 035–36 (EtOH); 36–37 [8]
79 035–36 (EtOH)
Iodobenzene (VIIIa)
4-Nitrotoluene (IXa)
080
2-Nitrotoluene (Xa)
Nitrobenzene (XIa)
060
090
020
12000
78 035–36 (EtOH)
undergoes iodination. As a result, the reaction mixture
contains the initial compound and monoiodination
product, 2-iodo-4-nitrotoluene (IXb), at comparable
concentrations; further iodination of compound IXb
gives 1,3-diiodo-2-methyl-5-nitrobenzene (IXc), and
both mono- and diiodo derivatives and initial nitro-
toluene IXa are present in solution. Nevertheless, we
found that the solubility problem can be partially
eliminated by using finely powdered substrate and
vigorously stirring the reaction mixture. In such a way
we succeeded in obtaining monoiodo derivative IXb in
55% yield (Table 1). Raising the temperature to 20°C
and using a solution of 4 equiv of NIS led to the
formation of only diiodo derivative IXc.
TLC data, the reaction of nitrobenzene (XIa) with
an equimolar amount of NIS at 20°C in 20 min resulted
in ~50% conversion of XIa into 3-iodonitrobenzene
(XIb), while iodination of the remaining substrate re-
quired ~19–20 h. An analogous pattern was observed
when the iodination was performed at 0°C. In this
case, ~50% conversion of nitrobenzene was attained in
1.5 h, but no transformation of XIa into XIb occurred
during the next 24 h. On the other hand, the iodination
of nitrobenzene (XIa) with 2 equiv of NIS was com-
plete in 1.5 h at 0°C and in 18–20 min at 20°C.
The 13C NMR spectrum of a solution of NIS in
H2SO4 at 20°C contained two carbonyl carbon signals
at δC 188.3 and 191.0 ppm with an intensity ratio of
55 : 45. These signals are displaced by 10.7 and
12.6 ppm downfield relative to the corresponding
signals of NIS and succinimide in DMSO-d6. There-
fore, the signal at δC 188.3 ppm was assigned to
protonated succinimide, and that at δC 191.0 ppm, to
protonated N-iodosuccinimide NIS-H+. We presumed
that NIS quickly loses more than half of iodine upon
dissolution in sulfuric acid; however, its complete
acidolysis to succinimide does not occur even on
storage over two days. These findings may be rational-
ized as shown in Scheme 1.
Liquid o-nitrotoluene (Xa) is better soluble in
sulfuric acid, and it is readily iodinated with NIS in
H2SO4 at 0°C. However, due to high reactivity of the
iodinating agent, a mixture of two monoiodo deriva-
tives and small amounts of diiodonitrotoluenes is
formed (GC–MS data). By recrystallization from
ethanol we isolated 41% of 4-iodo-2-nitrotoluene (Xb)
(Table 1).
While studying iodination of deactivated arenes
with NIS–H2SO4 we were the first to reveal two types
of reactivity of NIS in sulfuric acid. According to the
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CHAIKOVSKII et al.
1280
Scheme 1.
groups. In the latter case, the enthalpies of formation
of the monoprotonated structures are lower approxi-
mately by 84 kJ/mol than those of alternative struc-
tures (an analogous conclusion was recently drawn on
the basis of B3LYP/6-311G** quantum-chemical cal-
culations of protonated forms of N-chlorosuccinimide
[7]). Therefore, the structure IOS(O)(OH+)OH was se-
lected for the protonated form of acyl hypoiodite.
O
H2SO4
N
I
NIS–H+
+ HSO4
O
OH
N
H2SO4
As might be expected, protonation considerably
increases the electrophilicity of iodine. Electron defi-
ciency of the iodine atom in the above protonated
species changes in the same order as for the corre-
sponding neutral precursors. Protonation leads to ex-
tension of the heteroatom–iodine bonds, increases their
polarization, and reduces their order as compared to
neutral compounds.
The fact that IOS(O)(OH+)OH is a considerably
stronger electrophile than NIS-H+ is very consistent
with the observed dual reactivity of NIS in sulfuric
acid. According to the calculations, the more active
component of the reaction mixture is the product of
iodine transfer from N-iodosuccinimide to sulfuric
acid, IOS(O)(OH+)OH. The results of thermochemical
calculations for iodine exchange reactions of NIS and
NIS-H+ with sulfuric acid are given in Scheme 2. The
low positive values of ΔH and ΔG indicate that iodine
transfer to sulfuric acid is thermodynamically feasible;
they also conform to the above NMR data which
suggest that dissolution of NIS in sulfuric acid gives
rise to approximately equimolar amounts of protonated
forms of NIS (NIS-H+) and succinimide.
NIS
H
+
HOSO2OI
O
H2SO4
HOSO2OI
HOSO(OH+)OI
+ HSO4
Presumably, the dual reactivity of NIS in sulfuric
acid results from the presence of two types of electro-
philic iodinating species, protonated NIS and iodine(I)
hydrogen sulfate HOSO2OI or protonated form of the
latter. In order to estimate on a quantitative level the
reactivities of NIS and electrophilic iodine-containing
intermediates formed according to Scheme 1, we per-
formed their geometry optimization and calculated
their standard enthalpies of formation and Gibbs
energies in terms of the density functional theory
(DFT). The calculations were performed by the B3LYP
method [11] with extended 6-311G* basis set (10s9p5d
basis set for iodine atom [12]) in the natural bond
orbital (NBO) approximation using GAUSSIAN’98W
software [13]. The results are given in Table 2. Elec-
tron deficiency on the iodine atom (i.e., its electro-
philicity) strongly increases in going from NIS (0.273)
to the assumed hypoiodite-like intermediate HOSO2OI
(0.376). Polarization of the iodine–heteroatom bond
increases in the same order, while the order of that
bond decreases.
EXPERIMENTAL
The 13C NMR spectra were recorded on a Bruker
AC-300 spectrometer. The progress of reactions and
the purity of products were monitored by TLC on
Silufol UV-254 plates using benzene (I–V), hexane
(VIII), hexane–acetic acid (10:1) (VI, VII), or carbon
tetrachloride (IX–XI) as eluent; spots were visualized
under UV light.
Protonation of IOSO2OH and NIS may occur at
both heteroatoms directly attached to iodine and
double-bonded oxygen atoms of the S=O and C=O
Table 2. Charges on the iodine atom (qI) and heteroatom
attached thereto (qX), I–X bond lengths, their polarizations,
and Wiberg indices in iodine-containing electrophilic
species, calculated at the B3LYP/6-311G* NBO level
The iodination products were identified by com-
paring their spectral and analytical data with those of
authentic samples, as well as by measuring melting
points of mixed samples (no depression was observed).
N-Iodosuccinimide was synthesized by the procedure
described in [8].
Iodinating
species
Bond Bond polar- Wiberg
length, Å ization, % index
qI
qX
IOSO2OH 0.376 –0.575 2.065
IOSO2OH2+ 0.590 –0.553 2.119
73.78
81.25
69.41
73.09
0.742
0.588
0.797
0.765
Iodination of deactivated aromatic compounds
Ia–XIa with N-iodosuccinimide in sulfuric acid
(general procedure). Sulfuric acid (d = 1.814 g/cm3,
0.273 –0.598 2.065
0.444 –0.585 2.080
NIS
NIS-H+
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SUPERACTIVITY AND DUAL REACTIVITY OF THE SYSTEM
Scheme 2.
1281
NIS
+
+
H2SO4
+
HOSO2OI
ΔH = 19.7, ΔG = 19.6 kcal/mol
O
O
N
H
NIS–H+
H2SO4
+ HOSO2OI
ΔH = 37.2, ΔG = 36.4 kcal/mol
O
OH
N
H
5. Carreno, M.C., Carcia Ruano, J.L., Sanz, G., Tole-
do, M.A., and Urbano, A., Tetrahedron Lett., 1996,
vol. 37, p. 4081.
90%), 30 ml, was cooled to 0–5°C and added to 2.25 g
(10 mmol) of N-iodosuccinimide, and the mixture was
stirred for 20–30 min until it became homogeneous. To
effect monoiodination, 5 mmol of the corresponding
arene was added at 0 or 20°C (Table 1) to the resulting
dark brown solution, and the mixture was vigorously
stirred for 20–180 min. To introduce two iodine atoms
into the substrate molecule, its amount was reduced by
half. When the reaction was complete, the mixture was
poured into 100 ml of an ice–water mixture and treated
with a solution of Na2SO3. Compounds Ib, Xb, and
XIb were extracted into methylene chloride, the
extract was dried over CaCl2, the solvent was distilled
off, and the residue was recrystallized if necessary.
Compounds IIb, IIIb, VIb–VIIIb, IXb, and IXc were
filtered off, dried, and recrystallized from appropriate
solvent (Table 1). Compounds IVb and Vb were dis-
solved in benzene, the solution was filtered through
a layer of silica gel, and the solvent was distilled off
from the filtrate.
6. Olah, G.A., Wang, Q., Sandford, G., and Pra-
kash, G.K.S., J. Org. Chem., 1993, vol. 58, p. 3194.
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