[E006]
Microwave-Accelerated Iodination of Some Aromatic Amines, Using a Urea-Hydrogen Peroxide (UHP) Addition Compound as the Oxidant
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University, PL 02-097 Warsaw, Poland, 1 Banacha Street
E-mail: [email protected]; Tel./Fax: +(4822)5720643
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Abstract: A fast and simple method for the oxidative iodination of some aromatic amines, under microwave irradiation, is reported, using diiodine and Urea-Hydrogen Peroxide (UHP) addition compound as the oxidant. The reactions were carried out in boiling CHCl3 under a reflux condenser, within 10 minutes, to afford the purified monoiodinated products in 40-80% yields.
Keywords: Iodinated arylamines, urea-hydrogen peroxide as oxidant, microwave irradiation
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Khalaj with co-workers [1] have recently iodinated N-succinyl-4-[3,3-(1,4-butanediyl)-triazene]benzonate with the in situ generated trimethylsilyl iodide (formed there from trimethylsilyl chloride and common Na127I in dry acetonitrile) at 75 ºC for 45 minutes. After its isolation and purification, N-succimidyl-4-iodobenzoate was prepared in 90% yield. The activation of this reaction by exposure to microwave irradiation (in a domestic oven at 2450 MHz for 8 minutes) afforded the some pure monoiodinated product in 87% yield; by small scale preparations under the same microwave assisted conditions, but with using the radioactive Na125I, the corresponding labelled aromatic iodide was obtained in 81% radiochemical yield. It is seen that this iodinating method [1] by no means belongs to the class of microwave assisted oxidative iodination reactions of aromatics, which are reported in the present communication – for the first time as far as we know. The use of microwave irradiation to simplify and improve classic organic reactions has become a very popular method [2-4], because it often leads to higher yields, cleaner reactions and shorter reaction times.
In our laboratory, we have recently developed a novel (classic) method [5] for the oxidative iodination of several aromatic amines, carrying out the reactions in neat ethyl acetate (at room temperature within 30 minutes, next at 45 ºC for 2-3 hours), with the use of UHP as an effective oxidant. So far, we have attained the following yields for the purified products: 4-IC6H4NH2 (64%), 4-IC6H4NHMe (41%), 4-IC6H4NMe2 (85%), 4-IC6H4NEt2 (60%), 4-I-2-MeC6H3NH2 (92%), 2-I-5-MeC6H3NH2 (62%), 2,4-I2C6H3NH2 (58%) and 2-Cl-4-IC6H3NH2 (55%). All these reactions obeyed the following stoichiometry: 2ArH + I2 + H2O2 → 2ArI + 2H2O.
In this work, we have attempted to accelerate the aforementioned reactions with microwave irradiation, under a reflux condenser attached from outside. We have established that better results are attained by changing ethyl acetate (b.p. 77 ºC) to chloroform (b.p. 61 ºC) or, sometimes, dichloromethane (b.p. 42 ºC) used as the solvents of choice. The reactions were complete after ca. 10 minutes. After pouring the reaction mixtures into vigorously stirred excess aq. Na2SO3 solutions, the organic layers were separated, dried over Na2SO4, the solvent was distilled off, and the residues were recrystallized from hexane or ethanol (only 4-IC6H4NMe2). The purified products were checked chromatographically (TLC) to establish their homogeneity, next they were microanalyzed (%I). Their melting points (uncorrected) were very close to those obtained with the classic method [5]. By comparing our novel results (Table 1) with those previously obtained with the classic method (vide supra) it is seen that the microwave assisted iodination reactions afforded lower yields, though the former reaction times were considerably shorthened to only 10 minutes. In our opinion, it is worthy to further study various aromatic iodination reactions irradiated with microwaves. The results would probably be better with the use of focused microwave irradiation, what is not attainable in our laboratory.
Table 1. Final yields of the monoiodinated aromatic amines (after purification) and their melting points (uncorrected).
|
Iodinated product |
Yield (%) |
Melting point (ºC) |
Lit.[6] m.p.(ºC) |
|
4-IC6H4NMe2 |
80 |
80-81 |
82 |
|
4-IC6H4NH2 |
58 |
62-63 |
63-65 |
|
4-I-2-MeC6H3NH2 |
60 |
87-88 |
88, 91-92 |
|
2,4-I2C6H3NH2 a) |
50 |
95-96 |
95-96 |
|
2-Cl-4-IC6H3NH2 |
50 |
71-72 |
68, 70-73 |
|
4-Br-2-IC6H3NH2 |
40 |
69-70 |
70-71 |
a) Synthesized from 4-IC6H4NH2
Our microwave experiments were performed using a microwave oven purchased from „Plazmatronika” (Wroclaw, Poland). The microwave reactor, working at 2450 MHz, consists of a multimode microwave power delivery system with an operator selectable power output between 0 and 750 W, a tube allowing to attach an outer reflux condenser, and a magnetic stirrer. The reactions were carried out in glass vessels (200 ml). The temperature of the content of the vessel was monitored using a calibrated infrared temperature control mounted under the reaction vessel. All our experiments were performed using the stirring option, whereby the contents of the vessels were stirred by means of a rotating magnetic plate located below the floor of the microwave cavity and a teflon-coated magnetic stirring bar in the vessel. All chemicals were of reagent grade (Aldrich, Fluka), and were used without purification.
1.53 g UHP (16.5 mmol; 10% excess) and 3.81 g of finely powdered diiodine (15 mmol; 0% excess) were suspended in CHCl3 (50 mL). Then, 30 mmol (0% excess) of an appropriate arylamine was added, the mixture was put into the microwave cavity, a reflux condenser was attached, and the magnetic stirring was switched on. A chosen power output was used (500 to 750 W) to secure a slight, uninterrupted boil of the solvent. After 10 minutes, the reaction mixtures were cooled to room temperature. Next, they were poured into vigorously stirred aq. Na2SO3 solutions (5 g Na2SO3 in 50 mL of water). The organic layers were separated, dried over anhydr. Na2SO4, filtered, and the solvent was distilled off. The residues were cooled, if they were oily, to be solidified, and next they were recrystallized from hexane, except for 4-IC6H4NMe2 recrystallized from EtOH. The final results are shown in Table 1. The purities and homogeneities of the purified products were checked by TLC and microanalyses (%I). The (uncorrected) m.ps. were very close to those found in our former work [5].
References
[1] Khalaj, A.; Beiki, D., Rafiee, H.; Najafi, R. J. Labelled Cpd. Radiopharm. 2001, 44, 235.
[2] Microwave-Enhanced Chemistry Fundamentals, Sample Preparation and Applications. Kingston, H.M.; Haswell, S.J., Eds.; American Chemical Society: Washington, D.C., 1997.
[3] Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199. A review.
[4] Lindstroem, P.; Tierney, J.; Whathey, B.; Westman, J. Tetrahedron 2001, 57, 9225. A review.
[5] Lulinski, P.; Kryska, A.; Skulski, L. unpublished results, communicated at the Internation Symposium on Frontiers in Molecular Science 2002, July 14-18, Qingdao, China; see Proceedings, p. 23.
[6] Dictionary of Organic Compounds. 6th ed.; Chapman & Hall: London 1996.