Chemical Manganese Dioxide (CMD): Its application to the oxidative iodination of benzene, halobenzenes and some deactivated arenes

Article abstract of DOI:10.3390/90700595

After comparing our previous and newer results for numerous oxidative aromatic iodination experiments using various brands (of active MnO₂ as the oxidants, we recommend the use of a Chemical Manganese Dioxide (Aldrich CMD; 90+% (MnO₂) as the oxidant of choice, since it is satisfactorily pure and chemically active, and is notably less costly than other options.

Full text of DOI:10.3390/90700595

Molecules 2004, 9, 595-601
molecules
ISSN 1420-3049
http://www.mdpi.org
Chemical Manganese Dioxide (CMD): lts Application to the
Oxidative Iodination of Benzene, Halobenzenes and Some
†
Deactivated Arenes
Piotr Lulinski, Barbara Krassowska-Swiebocka and Lech Skulski*
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1
Banacha Street, PL 02-097 Warsaw, Poland.
†
This paper was presented at the Seventh Electronic Conference on Synthetic Organic Chemistry
(ECSOC-7, http://www.mdpi.net/ecsoc-7/), November, 1-30, 2003 (paper A014).
*
To whom correspondence should be addressed; E-mail: lskulski@farm.amwaw.edu.pl; Tel./Fax:
+48) 22-5720643
(
Received: 23 April 2004 / Accepted: 8 May 2004 / Published: 30 June 2004
Abstract: After comparing our previous and newer results for numerous oxidative
aromatic iodination experiments using various brands of active MnO
we recommend the use of a Chemical Manganese Dioxide (Aldrich CMD; 90+%
MnO ) as the oxidant of choice, since it is satisfactorily pure and chemically active, and
2
as the oxidants,
2
is notably less costly than other options.
Keywords: Iodinated arenas; arenas; oxidative aromatic iodination; chemical
manganese dioxide as oxidant.
Introduction
In a previous paper [1] we reported some easy laboratory methods for the mono- or diiodination of
several activated and deactivated arenes, using either freshly-prepared activated MnO [2] or
commercial KMnO (Aldrich, 99+%) [3] as suitable oxidants to obtain either 62-89% or 73-87%
2
4

Molecules 2004, 9
596
yields, respectively, of the corresponding purified iodinated products. Starting our earlier iodination
experiments with MnO , we had previously checked out various brands of this oxidant experimentally.
2
An ordinary technical grade MnO
2
(Aldrich, 75% MnO
2
) [3] was not usable. The best iodination yields
(
vide supra) were attained with activated MnO
2
freshly prepared by us prior to use [2]. An Activated
Manganese Dioxide (Aldrich AMD, suitable for organic reactions, ca. 85% MnO ) [3] gave lower
2
iodination yields by ca. 5-10%. In this work, we have experimentally checked out two brands of the
so-called Chemical Manganese Dioxide (CMD), viz. (1) Wako CMD, min. 75% MnO and (2)
2
Aldrich CMD, 90+% MnO [3]. CMD has been produced industrially mainly as a component of dry
2
batteries [4], and is now available as an inexpensive, stable laboratory reagent for the oxidation of a
wide variety of organic compounds, although the price of the Wako product in Europe is however ca.
1
0-12 times higher than that of the Aldrich CMD [3,5].
In 1998, four Japanese papers were published [6-9] in which selective oxidations of various classes
of organic compounds were reported, using Wako CMD as the effective oxidant. These heterogeneous
reactions, carried out in hexane, CH Cl or acetone, often proceeded in nearly quantitative yields under
2
2
relatively mild conditions. Usually, a large excess of CMD was required for smooth completion of the
reactions. In some cases, Wako CMD proved to be much superior to the usual AMDs commercially
available from the Aldrich, Fluka, Merck, Nakarei and Wako companies [6]. These papers prompted us
to repeat our earlier iodination experiments [1], but using the said two CMD brands as the oxidants
(
see Experimental). In all our iodination experiments, however, both the CMD oxidants were always
dissolved fully (or nearly so) in the anhydrous, strongly acidic reaction mixtures containing also
diiodine and a chosen arene to be oxidatively iodinated. Hence, all possible contaminants present in
the two CMDs used were transferred in full into the iodinating reaction mixtures, and they therefore
contaminated, more or less, the crude iodinated products. Apparently, Wako CMD is less concentrated
and more contaminated than Aldrich CMD, as has been shown in our subsequent aromatic iodination
experiments (vide infra).
Results and Discussion
As previously described [1], our novel iodination experiments proceed as follows:
1
. CMD/AcOH/Ac O/H SO
2
2
4
H-Ar-H + 1/2 or 1 I2
H-Ar-I or I-Ar-I
2
. excess aq. Na SO
2
3
For the monoiodination of benzene and four halobenzenes, using either Wako CMD or Aldrich
CMD as the oxidants, the following reaction stoichiometry was applied (Procedure 1):
+
I + Mn(IV) → 2I + Mn(II).
2
+
Presumably, only transient iodine(I) species, briefly denoted as I [10], preponderantly act upon the
reacted arenes to form the respective iodoarenes. After adding all the reactants, viz. Wako CMD (used
at first), powdered diiodine, a chosen arene, and an appropriate amount of concd. H
2
SO , to anhydrous
4
o
AcOH/Ac
2
O solvent mixtures cooled below 10 C, the resulting reaction mixtures were stirred for two

Molecules 2004, 9
597
o
hours at 70 C, and they were then poured into stirred excess aqueous Na
2
SO
3
solutions. After more
laborious isolation (cf. [1]) and purification of the crude iodination products, the purified iodoarenes
were obtained in only 40-56% yields. When we halved the amount of the benzene added to the reaction
mixtures (with respect to that used for its monoiodination), the purified 1,4-diiodobenzene was
obtained in only 41% yield (see Table).
Table. Iodinated pure products prepared.
o
b
Substrate
Ar-H
Reaction
conditions
1; 7.99
Product (Arabic
denotation) Ar-I/ I-Ar-I (%)
PhI (1)
Yield Analysis/I%
Mp C/solvent
a
Calcd (Found) (lit. mp) [11]
C
6
H
6
56
62.23
(61.7)
76.95
(77.2)
76.95
(76.8)
76.95
(76.9)
44.86
(44.8)
44.86
(44.7)
53.22
(53.0)
53.22
(53.1)
57.18
(57.2)
51.17
(51.3)
45.97
(45.4)
48.43
(48.0)
46.65
(46.1)
50.96
(50.4)
bp. 80-82/27 (bp. 63-
64 /8; 188/760)
131-133/E
(129)
131-133/E
(129)
131-133/E
(129)
90-91/E
(91-92)
90-91/E
(91-92)
54-56/E
(
150); 2
1; 10.65
200); 2
1; 13.32
250); 2
2; 7.99
150); 1
1; 13.32
250); 2
2; 7.99
150); 1
1; 7.99
150); 2
2; 5.33
100); 1
1; 5.33
100); 2
2; 10.65
200); 2
2; 10.65
[46]
41
[61]
42
C
6
H
6
1,4-I
2
C
6
4
H (2)
(
PhI
PhI
1,4-I C H (2)
2
6
4
(
1,4-I
2
C
6
H
4
(2)
57
[73]
48
(
PhBr
4-BrC H I (3)
6
4
(
[64]
53
[91]
40
PhBr
4-BrC
4-ClC
6
H
4
I (3)
I (4)
(
PhCl
6
H
4
(
[48]
41
[46]
50
(57)
PhCl
4-ClC H I (4)
54-56/E
6
4
(
(57)
PhF
4-FC H I (5)
bp. 82-84/38
(bp. 182-184/760)
189-191/C
(187-188)
bp. 158-164/26
(bp. 150.5/15)
211-212/C
(210-212)
bp. 73-76/25
(bp. 182-183/760)
bp. 161-164/24
(bp. 153/14; 38)
6
4
(
[60]
84
[81]
64
PhCOOH
PhCOOEt
3-IC H COOH (6)
6
4
(
3-IC H COOEt (7)
6
4
(
(
200); 2
4
-MeC H COOH 2; 10.65
3-I-4-MeC H COOH (8)
82
[85]
50
6
4
6
3
200); 2
PhCF3
PhNO2
2; 18.64
350); 3
2; 26.63
500); 3
3-IC H CF (9)
6
4
3
(
[37]
52
[52]
3-IC H NO (10)
6
4
2
(

Molecules 2004, 9
598
Table 1. Cont.
PhCONH
PhCOPh
2
2; 23.97
450); 3
2; 7.99
150); 2
3-IC
3-IC
6
6
H
4
4
CONH
2
(11)
70
[77]
59
51.37
(51.9)
58.48
(58.1)
180-183/E
(186.5)
147-149/A
(152.5-153.5)
(
H
6
COC H
4
I-3' (12)
(
[47]
a
The following data are given: Procedure (either 1 or 2); the amount [mL (mmol)] of
concd. (98%) H
time (h) of the main iodination reaction at 70 C.
Solvents used for recrystallization: A: Me
o
2
SO
4
added dropwise to the reaction mixture below 10 C; the reaction
o
b
2
CO; C: CCl ; E: EtOH.
4
For the monoiodination of six deactivated arenes and also three halobenzenes (used here for
comparison), using either Wako CMD or Aldrich CMD as the oxidants (in a threefold excess), the
following reaction stoichiometry was applied (Procedure 2):
3
+
I + 3Mn(IV) → 2I + 3Mn(II)
2
which strongly favors the formation of more electrophilic transient iodine(III) species, briefly denoted
3
+
as I [10], which act upon the reacted arenes to form some organic iodine(III) intermediates ArISO
not isolated) [10]. After adding all the reactants, viz. Wako CMD (used at first), powdered diiodine, a
4
(
chosen arene, and an appropriate amount of concd. H
cooled below 10 C, the resulting reaction mixtures were stirred for 1-3 hours at 70 C. After pouring
2
SO
4
, to anhydrous AcOH/Ac
2
O solvent mixtures
o
o
the cooled reaction mixtures into stirred excess aqueous Na
2
SO solutions, the said organic iodine(III)
3
intermediates were readily reduced to the corresponding iodoarenes, ArI. After more laborious
isolation (cf. [1]) and purifications of the crude iodination products, the purified monoiodinated arenes
were obtained in 41-84% yields. We also oxidatively diiodinated benzophenone to obtain, after
laborious isolation and purification, 3,3’-diiodobenzophenone in only 39% yield (see Table).
Lower yields obtained generally in this work when using Wako CMD as the oxidant (see Table and
cf.[1]), are mainly due to the fact that Wako CMD is apparently considerably contaminated. This
resulted in greater losses during the troublesome purification of the dark-colored crude iodinated
products, evidently more impure than those obtained in our earlier work [1].
Finally, we also carried out a number of analogous aromatic iodination reactions, covering
benzene, three halobenzenes and seven deactivated arenes, but using Aldrich CMD as the oxidant. The
same Procedures 1 and 2 described in Experimental were applied. The final yields attained for the
purified mono- and diiodinated products (46-90%) are given in Table (in square brackets). These
yields are usually higher than those obtained with Wako CMD, and are comparable (or sometimes
even higher) than those previously reported by us in the earlier paper [1]. It is also noteworthy that the
crude products isolated from the final reaction mixtures, when we used Aldrich CMD, were evidently
less contaminated (only slightly colored), and were easier to purify.

Molecules 2004, 9
599
Conclusions
Though the self-prepared AMD [2] is (mostly) somewhat more efficient in the oxidative aromatic
iodination reactions than either the commercial Aldrich CMD or Wako CMD products [3,5], its tedious
preparations are relatively expensive and time consuming. The more impure Wako CMD [5] gave
dark-colored and heavily contaminated crude iodinated products, which resulted in considerable losses
during their troublesome isolation and purification. Consequently, we would recommend the use of
Aldrich CMD as the oxidant of choice in these oxidative aromatic iodination reactions, since it has
quite satisfactory chemical reactivity and purity, and is notably less costly [3].
Experimental
General
Melting or boiling points given in the Table are uncorrected. The commercial reagents and solvents
(
Aldrich, Fluka) were used without purification. Both CMD brands (Wako, Aldrich) [3,5] were neither
preheated nor otherwise pretreated prior to their use the iodination reactions. Molecular iodine
diiodine) was finely powdered to facilitate its dissolution in the reaction mixtures. Elemental analyses
(
were carried out at the Institute of Organic Chemistry, The Polish Academy of Sciences, Warsaw,
Poland. After checking their purities and homogeneities by TLC, the structures of the purified
iodinated products, all known in the literature, were checked by comparison of their melting points (or
boiling points) with those reported in the literature (see Table), as well as by their mixed melting points
with authentic specimens [1]. The structures were also corroborated by elemental microanalyses (see
Table). As previously [1], all the yields reported in the Table represent potentially optimal values.
Procedure 1 for the iodination of benzene and halobenzenes using Wako CMD
Wako CMD (2.78 g; ca 24 mmol MnO
% excess) [for the diiodination of benzene: 5.59 g I
stirred mixture of AcOH (40 mL) and Ac
Table 1) of concd. (98%) H SO
2
; 20% excess) and powdered diiodine (5.08 g, 20 mmol;
0
2
, 22 mmol; 10% excess] were suspended in a
O (10 mL) cooled to 5-10 C. Next, varied quantities (see
o
2
2
4
o
were very slowly added dropwise with vigorous stirring while
keeping the temperature at 5-10 C (exothermic reactions). An appropriate arene (44 mmol; 10%
excess) [for the diiodination of benzene: 1.56 g benzene, 20 mmol, 0% excess] was added with stirring,
o
then the stirring was continued for 2 h at 70 C. The anhydrous reaction mixtures were poured into ice-
water (200 mL) containing previously dissolved Na SO (1.0 g, 7.94 mmol) (under a fume hood).
2
3
After ca. 30 min, the precipitated oily or semi-solid crude products 1-5 were extracted with CHCl , the
3
collected extracts were dried (MgSO ), filtered, and the solvent was distilled off, and the oily residues
4
of compounds 1 and 5 were fractionated under vacuum (see Table). The solidified in part residues of
compounds 2, 3 and 4 were triturated with ethanol, the precipitated solids were collected by filtration,
air-dried, and recrystallized from appropriate solvents (see Table).

Molecules 2004, 9
600
Procedure 2 for the iodination of deactivated arenes and some halobenzenes using Wako CMD
Wako CMD (4.96 g; ca 43 mmol MnO ; 43% excess) [for the monoiodination of halobenzenes,
2
and for the diiodination of benzophenone: CMD (4.18 g; ca 36 mmol MnO ; 20% excess)] and
2
powdered diiodine (2.80 g, 11 mmol; 10% excess) were suspended in a stirred mixture of AcOH (40
o
mL) and Ac O (10 mL) cooled to 5-10 C. Next, varied quantities (see Table) of concd. (98%) H SO
2
2
4
o
were very slowly added dropwise with vigorous stirring while keeping the temperature at 5-10 C
exothermic reactions). An appropriate arene (20 mmol; 0% excess) [for the diiodination of
(
benzophenone: 1.82 g benzophenone, 10 mmol; 0% excess] was added with stirring and this stirring
o
was continued for 1-3 h (see Table) at 70 C. The anhydrous reaction mixtures were poured into ice-
water (200 mL) containing previously dissolved Na SO (5.0 g, 39.7 mmol) (under a fume hood). After
2
3
ca 30 min, the precipitated oily crude products 7, 9 and 10, and the precipitated semi-solid crude
products 2, 3 and 4 were worked up as above in Procedure 1. The precipitated semi-solid crude
product 12 was also extracted with CHCl , but after removal of the solvent, this was recrystallized
3
from acetone. The precipitated solid crude products 6, 8 and 11 were collected by filtration, washed
with water, air-dried, extracted with boiling acetone in a Soxhlet apparatus, the solvent was distilled
off, and the residues were recrystallized from the appropriate solvents (see Table).
All our iodination experiments using Aldrich CMD were similar to those described above. The
crude iodinated products were however less contaminated, hence they were easier to purify. The final
yields for the purified products are also given in the Table (in square brackets). The yields for the
purified iodinated products given in the Table were calculated from the total amounts of those reagents
(
diiodine or arenes) which were used in the reactions in strictly stoichiometric quantities (0% excess).
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1
. Lulinski, P.; Skulski, L. Bull. Chem. Soc. Jpn., 1999, 72, 115-120.
2
. (a) Galecki, J. Preparatyka nieorganiczna; WNT: Warsaw, 1964, p. 439; (b) Karyakin, Yu. V.;
Angelov, I. I. Chistye khimicheskie reaktivy; Goskhimizdat: Moscow, 1955, p. 333.
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3
KMnO
MnO , 50.00 €/1 kg; (c) activated MnO
organic oxidations; (d) chemical MnO , 90+% MnO , < 10 micron, 21.90 €/500 g, suitable for use
4
, 99+%, A. C. S. reagent, 14.90 €/500 g; (b) technical MnO
2
, powder, < 5 micron, 75%
, 71.10 €/500 g, suitable for
2
2
, < 5 micron, ca. 85% MnO
2
2
2
in batteries.
th
4
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5
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Wako specification: Manganese(IV) Oxide, Chemicals Treated, 1st Grade (EP), assay: min. 75.0%
MnO
2
. The suppliers have informed us that their product should not be preheated or otherwise
pretreated before reaction.

Molecules 2004, 9
601
6
7
8
9
1
. Aoyama, T.; Sonoda, N.; Yamaguchi, M.; Toriyama, K.; Anzai, M.; Ando, A.; Schioiri, T. Synlett,
1
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3
3
7
+
3+
0. For more information on I , I , and the organic iodine(III) intermediates, Ar-ISO , see our review:
4
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th
1
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Sample Availability: Available from the authors.
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