A Novel Aromatic Iodination Method, with Sodium Periodate Used as the Only Iodinating Reagent

Abstract

Benzene, halobenzenes and some deactivated arenes readily reacted in anhydrous NaIO₄/AcOH/Ac₂O/concd. H₂SO₄ mixtures to afford, after quenching with excess aqueous Na₂SO₃ solution (a reducing agent), purified iodinated products in 27-88% yields. This novel method of aromatic iodination is simple, fairly effective and environmentally safe.

Introduction

Only inorganic iodine(VII) derivatives are known and up to now not a single organoiodine(VII) compound has been synthesized and investigated [1,2]. The few reported attempts to synthesize periodylarenes, ArIO₃, ended in failure. Willgerodt [3] oxidized iodylbenzene, PhIO₂, with a hot 30% solution of perchloric acid, expecting to obtain periodylbenzene (“Superjodobenzol” or “Phenyljodtrioxyd”), PhIO₃, but he obtained instead some white explosive crystals, probably an aromatic iodonium salt, Ph₂I⁺ClO₄^-. Lewitt and Iglesias [4] attempted to prepare PhIO₃ by adding benzene dropwise to a chilled solution of H₅IO₆ in concd. H₂SO₄, but reported obtaining only a 48% yield of periodobenzene, C₆I₆; they observed, however, that the initially colorless H₅IO₆/concd. H₂SO₄ solution, after adding the benzene, turned first green, then red, and finally light yellow, as the yellow-tan C₆I₆ gradually precipitated out. They remarked that the first formed green intermediate (presumably PhIO₃) and the next red one should be further studied, and invited any investigators interested in this unusual reaction to pursue this avenue of research. Mattern [5] improved the above protocol for preparing either C₆I₆ (45%) or 1,2,4,5-C₆H₂I₄ (60%) from benzene, but he made no attempt to study the green and red intermediates observed by Levitt and Iglesias [4]. Similarly, nobody has succeeded in preparing and investigating any single organobromine(VII) compound, while in contrast, the stable and unusually resistant to reduction perchloryl aromatics, ArClO₃, have been known since 1958 [6].

Results and Discussion

As a continuation of our systematic studies on effective aromatic iodination reactions, which are related in detail in our two latest reviews [7,8], we recently decided to use sodium periodate NaIO₄, alone, as an iodinating reagent. The reactions were carried out in anhydrous acetic acid/acetic anhydride solvent mixtures containing NaIO₄ and a chosen arene (Table 1), and then strongly acidified with varied amounts (see Table 1) of concd. (95%) sulfuric acid. We expected that the following subsequent reactions would probably proceed in the acidified reaction mixtures, viz.:

(1)

(2)

(3)

(4)

where: [IO₃]⁺ represents hypothetical transient periodyl cations and [ArIO₃], the non isolable (vide infra), hypothetical periodyl intermediates. We must admit that in spite of our numerous attempts, we could not isolate from the final reaction mixtures any such ArIO₃ intermediates. In fact, after the addition of excess concd. hydrochloric acid to the cooled final reaction mixtures, we sometimes isolated the well-known [1,2,3,7] (dichloroiodo)arenes, ArICl₂, in moderate yields, e.g. methyl 3-(dichloroiodo)benzoate, m.p. 108-109 °C (dec.), lit. [12] m.p. 104-105 °C (dec.), was isolated in 35% crude yield. These results suggest that the desirable aromatic iodine(VII) compounds must be obtained by a different route [9].

Table 1.

Iodinated Pure Products Prepared and Volumes of Concd. H₂SO₄ Added.

Substrate	Product	Yield/%	Concd H2SO4a) mL/mmol	Analysis/I% Calcd (Found)	Mp or Bp/°C/solvent b) (Lit [12] mp or bp/°C)
C6H6	1,4-I2C6H4	52	2.13/40	76.95 (76.7)	125-127/E (129)
PhI	1,4-I2C6H4	69	4.26/80	76.95 (76.9)	126-128/E (129)
PhBr	4-BrC6H4I	66	4.26/80	44.86 (44.8)	89-91/E (91-92)
PhCl	4-ClC6H4I	27	5.33/100	53.22 (52.7)	54-55/E (57)
PhCOOH	3-IC6H4COOH	82	6.39/120	51.17 (51.0)	190-191/C (187-188)
PhCOOMe	3-IC6H4COOMe	82	6.39/120	48.43 (48.4)	46-48/EW (54-55)
PhCOOEt	3-IC6H4COOEt	57	7.46/140	45.97 (45.9)	bp 180-181/69 (bp 150.5/15)
4-MeC6H4COOH	3-I-4-MeC6H3COOH	88	6.39/120	48.43 (48.3)	209-211/C (210-212)
4-ClC6H4COOH	3-I-4-ClC6H3COOH	60	7.46/140	44.93 (44.5)	214-216/EW (216-217)
4-MeC6H4NO2	3-I-4-MeC6H4NO2	73	6.39/120	48.25 (47.8)	52-53/E (61)
PhCONH2	3-IC6H4CONH2	61	12.78/240	51.37 (51.0)	184-185/E (186.5)
PhCN	3-IC6H4CONH2	59	13.85/260	51.37 (51.1)	183-184/E (186.5)
PhCF3	3-IC6H4CF3	45	8.52/160	46.65 (46.2)	bp 70-72/40 (bp 182-183/760)

a) The amount of concd H₂SO₄ added dropwise to each of the cooled and stirred reaction mixtures.

b) Solvents used for recrystallization: C: CHCl₃; E: EtOH; EW: EtOH:H₂O (1:1 v/v ).

The aforesaid reaction mixtures were stirred at a temperature not exceeding 40 °C for 2 hours, then the temperature was slowly increased (over 30 min) to 60-70 °C, and the mixtures were finally stirred at this temperature for a further 40-50 min (at higher temperatures, the evolution of the iodine vapors and the appearance of some crystals were observed). During these reactions we did not observe any transient green or red colorations. After cooling, the final reaction mixtures were poured into ice-water containing a previously dissolved excess of Na₂SO₃ (a reducing agent) to obtain the expected iodoarenes, ArI, viz.

(5)

Activated arenes, e.g. anisole, acetanilide, and N,N-dimethylaniline, were easily oxidized under the given reaction conditions to form some tarry products, while nitrobenzene was unaffected, and was recovered as such after completing the reactions shown in Eqs. 1-5. Benzene was deliberately diiodinated to afford pure 1,4-diiodobenzene in 52% yield. Benzonitrile, after completing all the reactions, gave only pure 3-iodobenzamide in 59% yield; cf. our former paper [10]. Halobenzenes and the nine deactivated arenes shown in Table 1 gave the purified monoiodinated products in 27-88% yields. Their purities and homogeneities were checked by TLC and the corresponding melting/boiling points were all close to those reported in the literature. The proposed chemical structures were also supported by elemental analyses (%I), and comparison of the ¹H- and ¹³C-NMR solution spectra (not shown here) with the corresponding spectra of authentic specimens [11].

Conclusions

We present in this short paper a quite novel approach to aromatic iodination, which allows one to effectively obtain iodoarenes from benzene, halobenzenes and some moderately deactivated arenes. The protonated transient meta-periodic acid, O₄I⁺H₂ (formed from the reagent grade NaIO₄, which is sufficiently soluble in warm anhydrous and strongly acidic solutions, Eq. 1) was the sole iodinating agent present, capable of forming the stable C-I bond in the starting arenes. We failed however to isolate the expected aromatic iodine(VII) intermediates.

Experimental

General

All the reagents and solvents were commercial materials (Aldrich) and were used without further purification. The melting/boiling points of pure iodinated products (Table 1) are uncorrected. Elemental microanalyses (%I) were performed at the Institute of Organic Chemistry, the Polish Academy of Sciences in Warsaw. ¹H- and ¹³C-NMR spectra (not shown here) were recorded at the Medical University of Warsaw, at room temperature, with a Brucker Avance DMX 400 MHz spectrometer in CDCl₃ solutions, and with TMS added as an internal standard.

Optimized Preparations of Iodoarenes from Arenes

Powdered NaIO₄ (3.51 g, 16.4 mmol; 2.5% excess) [for the iodination of halobenzenes: 3.42 g NaIO₄ (16 mmol; 0% excess), and for the preparation of 1,4-diiodobenzene from benzene: 3.60 g NaIO₄ (16.8 mmol; 5% excess)] was suspended with stirring in a mixture made up of glacial AcOH (15 mL) and Ac₂O (10 mL) cooled to 10 °C. A chosen arene (16 mmol, 0% excess) [for the iodination of halobenzenes: 16.8 mmol; 5% excess, and for the preparation of 1,4-diiodobenzene from benzene: 8 mmol; 0% excess] was added dropwise or portionwise. Still keeping the temperature at ca 10 °C, a given volume (see Table 1) of concd. (95%) H₂SO₄ was slowly added dropwise. The resulting reaction mixture was stirred at temperatures not exceeding 40 °C for 2 hours, then the temperature of the reaction mixture was slowly increased (within 30 min) to 60-70 °C, and the mixture was stirred at this temperature for a further 40-50 min. After cooling to r.t., the final reaction mixture was poured into stirred ice-water (150 g) containing previously dissolved Na₂SO₃ (4 g). The oily crude products were extracted with CHCl₃ (3 x 20 mL), the combined extracts were dried over anhydrous MgSO₄, filtered, the solvent was distilled off, and the oily residues were fractionated under reduced pressure. The solid crude products were collected by filtration, washed well with cold water, air-dried in the dark, and recrystallized from appropriate organic solvents to afford the purified iodinated products (Table 1). The yields given for pure products were calculated from the total amounts of those reagents (ArH or NaIO₄) which were used in the reactions in strictly stoichiometric quantities (0% excess).