7th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-7), http://www.mdpi.net/ecsoc-7, 1-30 November 2003

[A014]

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

Tel./fax: +48(22)5720643; E-mail: lskulski@farm.amwaw.edu.pl

___________________________________________________________________________________________________________________________

Abstract: By comparing our former and present results of numerous oxidative aromatic iodination experiments with using various brands of active MnO₂ as the oxidants, we would recommend the use of a Chemical Manganese Dioxide (Aldrich CMD; 90+% MnO₂) as the oxidant of choice, since it is satisfactorily pure and is notably less costly.

Keywords: Iodinated arenes, arenes, oxidative aromatic iodination, chemical manganese dioxide as oxidant

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Introduction

In our former paper [1] we reported some easy laboratory methods for the mono- or diiodination of several activated and deativated arenes, using either the self-prepared activated MnO₂ [2] or commercial KMnO₄ (Aldrich, 99+%) [3] as suitable oxidants to obtain either 62-89% or 73-87% yields, respectively, of the purified iodinated products. Starting our former iodination experiments with MnO₂, we had previously checked out experimentally various brands of this oxidant. An ordinary technical MnO₂ (Aldrich, 75% MnO₂) [3] was not applicable. The best iodination yields (vide supra) were attained with the activated MnO₂ freshly prepared by us prior to use [2]. An Activated Manganese Dioxide (Aldrich AMD, suitable for organic reactions, ca. 85% MnO₂) [3] gave lower iodination yields by ca. 5-10%. In this work, we checked out experimentally two brands of the so-called Chemical Manganese Dioxide (CMD), viz. (1) Wako CMD, min. 75% MnO₂ – its price in Europe is however ca. 10-12 times higher than that of Aldrich CMD [3, 4]; (2) Aldrich CMD, 90+% MnO₂[3]. CMD has been industrially produced mainly as dry batteries component [5], and is now available as an inexpensive, stable laboratory reagent for the oxidation of a wide variety of organic compounds.

In 1998, four Japanese papers were published [6-9] in which selective oxidations of various classes of organic compounds were reported, with using Wako CMD as the effective oxidant. The heterogeneous reactions carried out in hexane, CH₂Cl₂ or acetone, often proceeded in nearly quantitative yields under relatively mild conditions. Usually, a large excess of CMD was required for completion of the reactions smoothly. In some cases, Wako CMD proved to be much superior to usual AMD commercially available from Aldrich, Fluka, Merck, Nakarei and Wako companies [6]. These papers just prompted us to repeat our former iodination experiments [1], but with applying the said two CMD brands as the oxidants (see Experimental). However, in all our iodinating experiments, the both CMD oxidants were always dissolved in full (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 CMD applied were transferred in full into the iodinating reaction mixtures, and next they contaminated, more or less, the crude iodinated products. Apparently, Wako CMD is less concentrated and more contaminated than Aldrich CMD, what has been evidenced in our subsequent aromatic iodination experiments (vide infra).

Results and Conclusions

As previously [1], our novel iodination experiments proceeded as follows:

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): I₂ + Mn(IV) ® 2I⁺ + Mn(II). Presumably, only transient iodine(I) species, briefly denoted as I⁺ [10], were preponderantly acting there 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. H₂SO₄, to anhydrous AcOH/Ac₂O solvent mixtures cooled below 10 ^oC, the resulting reaction mixtures were stirred for 2 hours at 70 ^oC, and next they were poured into stirred excess aqueous Na₂SO₃ 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 mixture (in respect to that used for its monoiodination), the purified 1,4-diiodobenzene was obtained in only 41% yield (Table).

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, the following reaction stoichiometry was applied (Procedure 2): I₂ + 3Mn(IV) ® 2I³⁺ + 3Mn(II), which strongly favors the formation of more electrophilic transient iodine(III) species, briefly denoted as I³⁺ [10], acting there upon the reacted arenes to form some organic iodine(III) intermediates [10], ArISO₄ (not isolated). After adding all the reactants, viz. Wako CMD (used at first), powdered diiodine, a chosen arene, and an appropriate amount of concd H₂SO₄, to anhydrous AcOH/Ac₂O solvent mixtures cooled below 10 ^oC, the resulting reaction mixtures were stirred for 1-3 hours at 70 ^oC. After pouring the cooled reaction mixtures into stirred excess aqueous Na₂SO₃ solutions, the said organic iodine(III) intermediates were readily reduced to the corresponding iodoarenes, ArI. After more laborious isolation (cf. [1]) and purification 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 (Table).

Lower yields obtained generally in this work, with 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 troublesome purification of the dark-colored crude iodinated products, evidently more impure than those obtained in our former work [1].

Finally, we also carried out a number of analogous aromatic iodination reactions, covering benzene, three halobenzenes and seven deactivated arenes, but with using Aldrich CMD as the oxidant. The same Procedures 1 and 2 submitted in Experimental were applied. The final yields (46-90%) attained for the purified mono- and diiodinated products are given in Table (in square brackets). These yields are generally higher than those obtained with Wako CMD, and are comparable (or sometimes even higher) than those previously reported by us in the former paper [1]. It is also worthy to note 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 for purification.

Though the self-prepared AMD [2] is (mostly) somewhat more efficient in the oxidative aromatic iodination reactions than Aldrich CMD and Wako CMD commercial products [3, 4], but its tedious preparations are relatively expensive and time consuming. The most impure Wako CMD [4]gave the dark-colored and heavily contaminated crude iodinated products, which resulted in considerable losses during their troublesome isolations and purifications. So, we would recommend the application of the Aldrich CMD as the oxidant of choice in the oxidative aromatic iodination reactions, since it has a quite satisfactory activity, it is satisfactorily pure, and is notably less costly [3].

Experimental

General

Melting or boiling points in Table are uncorrected. The commercial reagents and solvents (Aldrich, Fluka) were used without purification. The both CMD brands (Wako, Aldrich) [3, 4] were not preheated or otherwise pretreated before 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 supported by their melting points (or boiling points) compared with those found in the literature (Table), as well as by mixed melting points with authentic specimens [1]. The structures were also corroborated by elemental microanalyses (Table). As previously [1], all the yields reported in Table were possibly optimized.

Procedure 1 (for the iodination of benzene and halobenzenes), with using Wako CMD:

Wako CMD (2.78 g; ca 24 mmol MnO₂; 20% excess) and powdered diiodine (5.08 g, 20 mmol; 0% excess) [for the diiodination of benzene: 5.59 g I₂, 22 mmol; 10% excess] were suspended in a stirred mixture of AcOH (40 ml) with Ac₂O (10 ml) cooled to 5-10 ^oC. Next, varied quantities (see Table 1) of concd (98%) H₂SO₄ were very slowly added dropwise with vigorous stirring while keeping the temperature at 5-10 ^oC (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, then the stirring was continued for 2 h at 70 ^oC. The anhydrous reaction mixtures were poured into ice-water (200 ml) containing previously dissolved Na₂SO₃ (1.0 g, 7.94 mmol) (under a fume hood). After ca 30 min, the precipitated oily or semi-solid crude products 1-5 were extracted with CHCl₃, the collected extracts were dried (MgSO₄), and filtered the solvent was distilled off, and the oily residues of compounds 1 and 5 were fractionated under vacuum (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 (Table).

Procedure 2 (for the iodination of deactivated arenes and some halobenzenes), with using Wako CMD:

Wako CMD (4.96 g; ca 43 mmol MnO₂; 43% excess) [for the monoiodination of halobenzenes, and for the diiodination of benzophenone: CMD (4.18 g; ca 36 mmol MnO₂; 20% excess)] and powdered diiodine (2.80 g, 11 mmol; 10% excess) were suspended in a stirred mixture of AcOH (40 ml) with Ac₂O (10 ml) cooled to 5-10 ^oC. Next, varied quantities (see Table) of concd (98%) H₂SO₄ were very slowly added dropwise with vigorous stirring while keeping the temperature at 5-10 ^oC (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 the stirring was continued for 1-3 h (Table) at 70 ^oC. The anhydrous reaction mixtures were poured into ice-water (200 ml) containing previously dissolved Na₂SO₃(5.0 g, 39.7 mmol) (under a fume hood). After 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 CHCl₃, but after removal of the solvent, this was recrystallized 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 the Soxhlet apparatus, the solvent was distilled off, and the residues were recrystallized from appropriate solvents (Table).

All our iodination experiments with using Aldrich CMD were similar to those submitted above. The crude iodinated products were however less contaminated, hence they were easier for purification. The final yields for the purified products are given in Table (in square brackets).

The yields for the purified iodinated products given in 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).

Table. Iodinated pure products prepared.

Substrate

Ar-H

Reaction

conditions ^a

Product (Arabic deno-

tation) Ar-I/ I-Ar-I

Yield

(%)

Analysis/I%

Calcd (Found)

Mp ^oC/solvent^b

(lit. mp) [11]

C₆H₆

1; 7.99

(150); 2

PhI (1)

[46]

62.23

(61.7)

bp. 80-82/27

(bp. 63-64/8; 188/760)

C₆H₆

1; 10.65

(200); 2

1,4-I₂C₆H₄ (2)

[61]

76.95

(77.2)

131-133/E

(129)

PhI

1; 13.32

(250); 2

1,4-I₂C₆H₄ (2)

76.95

(76.8)

131-133/E

(129)

PhI

2; 7.99

(150); 1

1,4-I₂C₆H₄ (2)

[73]

76.95

(76.9)

131-133/E

(129)

PhBr

1; 13.32

(250); 2

4-BrC₆H₄I (3)

[64]

44.86

(44.8)

90-91/E

(91-92)

PhBr

2; 7.99

(150); 1

4-BrC₆H₄I (3)

[91]

44.86

(44.7)

90-91/E

(91-92)

PhCl

1; 7.99

(150); 2

4-ClC₆H₄I (4)

[48]

53.22

(53.0)

54-56/E

(57)

PhCl

2; 5.33

(100); 1

4-ClC₆H₄I (4)

[46]

53.22

(53.1)

54-56/E

(57)

PhF

1; 5.33

(100); 2

4-FC₆H₄I (5)

[60]

57.18

(57.2)

bp. 82-84/38

(bp. 182-184/760)

PhCOOH

2; 10.65

(200); 2

3-IC₆H₄COOH (6)

[81]

51.17

(51.3)

189-191/C

(187-188)

PhCOOEt

2; 10.65

(200); 2

3-IC₆H₄COOEt (7)

45.97

(45.4)

bp. 158-164/26

(bp. 150.5/15)

4-MeC₆H₄COOH

2; 10.65

(200); 2

3-I-4-MeC₆H₃COOH (8)

[85]

48.43

(47.0)

211-212/C

(210-212)

PhCF₃

2; 18.64

(350); 3

3-IC₆H₄CF₃ (9)

[37]

46.65

(46.1)

bp. 73-76/25

(bp. 182-183/760)

PhNO₂

2; 26.63

(500); 3

3-IC₆H₄NO₂ (10)

[52]

50.96

(50.4)

bp. 161-164/24

(bp. 153/14; 38)

PhCONH₂

2; 23.97

(450); 3

3-IC₆H₄CONH₂ (11)

[77]

51.37

(51.9)

180-183/E

(186.5)

PhCOPh

2; 7.99 (150); 2

3-IC₆H₄COC₆H₄I-3' (12)

[47]

58.48

(58.1)

147-149/A

(152.5-153.5)

^a The following data are given: Procedure either 1 or 2; the amount [ml (mmol)] of concd (98%) H₂SO₄ added dropwise to the reaction mixture below 10 ^oC; the time (h) of the main iodination reaction proceeded at 70 ^oC.

^b Solvents used for recrystallization: A: Me₂CO; C: CCl₄; E: EtOH.

References and Notes

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.

3. Aldrich Catalogue Handbook of Fine Chemicals and Laboratory Equipment 2003-2004: (a) KMnO₄, 99+%, A. C. S. reagent, 14.90 €/500 g; (b) technical MnO₂, powder, < 5 micron, 75% MnO₂, 50.00 €/1 kg; (c) activated MnO₂, < 5 micron, ca. 85% MnO₂, 71.10 €/500 g, suitable for organic oxidations; (d) chemical MnO₂, 90+% MnO₂, < 10 micron, 21.90 €/500 g, suitable for use in batteries.

4. CMD suitable for use in dry batteries was available from Wako Chemicals GmbH (Nissantrasse 2, W-41468 Neuss, Germany); its price in 1999: 378.00 DM/500 g + freight cost 60.00 DM. Wako specification: Manganese(IV) Oxide, Chemicals Treated, 1st Grade (EP), assay: min. 75.0% MnO₂. The purchasers have informed us that their product should not be preheated or otherwise pretreated before reaction.

5. (a) Kirk-Othmer Concise Encyclopedia od Chemical Technology, 4^th Edition, Wiley-Interscience: New York, 1999, p. 1250; (b) Fatiadi, A. J. Synthesis 1976, 65-104 and 133-167.

6. Aoyama, T.; Sonoda, N.; Yamaguchi, M.; Toriyama, K.; Anzai, M.; Ando, A.; Schioiri, T. Synlett, 1998, 35-36. See also Refs. 4-8 therein for their former works, where Wako CMD was also applied.

7. Hirano, M.; Yakabe, S.; Hikamori, H.; Clark, J. H.; Morimoto, T J. Chem. Res. Synop., 1998, 308-309.

8. Hirano, M.; Yakabe, S.; Hikamori, H.; Clark, J. H.; Morimoto, T J. Chem. Res. Synop., 1998, 310-311.

9. Hirano, M.; Yakabe, S.; Hikamori, H.; Clark, J. H.; Morimoto, T J. Chem. Res. Synop., 1998, 770-771.

10. For more information on I⁺, I³⁺, and the organic iodine(III) intermediates, Ar-ISO₄, see our review: Skulski, L. Organic Iodine(I, III, and V) Chemistry: 10 Years of Development at the Medical University of Warsaw, Poland. Molecules 2000, 5, 1331-1351, see pp. 1336-1337. Avail. at URL: http://www.mdpi.org/molecules/papers/51201331.pdf

11. Dictionary of Organic Compounds, 6^th Ed.; Chapman & Hall: London, 1996.