2,4,6-Tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine as a New Recyclable Hypervalent Iodine(III) Reagent for Chlorination and Oxidation Reactions

Abstract

The synthesis of 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine, as a new recyclable nonpolymeric analogue of (dichloroiodo)benzene, is achieved in two steps using 2,4,6-trichloro-1,3,5-triazine and 4-iodophenol. The application of 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine for the chlorination reaction of various activated arenes, olefin, and 1,3-diketone is demonstrated. The reagent 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine can be applied also for the oxidative synthesis of 1,3,4-oxadiazoles and 1,2,4-thiadiazoles under mild conditions in excellent yields. The recyclability of the 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine was possible owing to the facile recovery and reuse of the coproduced 2,4,6-tris(4-iodophenoxy)-1,3,5-triazine from the reaction mixture due to its practical insolubility in methanol.

Key words

oxidation - hypervalent iodine reagent - (dichloro­iodo)benzene - 1,3,5-triazine - chlorination

• References and Notes


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• 16 Synthesis of 2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine (8) 2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine was dissolved in CHCl₃, and chlorine gas was passed through this solution at 0 °C with stirring for 2 h. 2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine precipitated out as yellow, stable, micro-crystalline solid. The reaction mixture was kept under refrigeration for 24 h, then filtered and washed with CHCl₃ to produce 8 in 94% yield. Yellow solid, mp 232–234 °C. IR (neat): ν = 1586, 1561, 1479, 1380, 1360, 1212, 1176, 1002, 838, 807, 749 cm^–1.
• 17 General Procedure for Nuclear Chlorination of Arenes Reagent 8 (0.5 mmol) was added to a stirred solution of the appropiate activated arene (1 mmol) in CH₂Cl₂ (3 mL). The reaction mixture was stirred at r.t. for the period of time given in Table 1, and progress of reaction was monitored by TLC. When the substrate was consumed, the CH₂Cl₂ was evaporated under reduced pressure. MeOH was added to the reaction mass, and the white precipitate was isolated by filtration. The residue was washed several times with small aliquote of MeOH and air-dried to recover 2,4,6-tris(4-iodophenoxy)-1,3,5-triazine in 93% yield. The filtrate was concentrated in vacuo to afford the crude product which was purified by column chromatography on silica gel using PE–EtOAc (9:1) as eluent to give the chlorinated product in excellent purity.
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• 21 General Experimental Procedure for the Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles 15 from Aldehyde N-Acylhydrazones 14 2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine (8, 0.4 mmol) was added to a stirred solution of the appropriate aldehyde N-acylhydrazone (1 mmol) in CH₂Cl₂ at r.t. The progress of the reaction was monitored by TLC, and the reaction was complete within 2–6 h. After completion, the solvent was removed in vacuo followed by addition of MeOH to precipitate out triiodide 11. The resulting heterogeneous solution was filtered to recover 11 which was subsequently subjected to chlorination at 0 °C in CHCl₃ to form 8. The filtrate, meanwhile, was concentrated in vacuo to afford the crude product which was purified by column chromatography on silica gel using PE–EtOAc (9:1) as eluent to give 2,5-disubstituted 1,3,4-oxadiazoles in excellent purity.
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• 23 The same reaction in CH₂Cl₂ resulted in the formation of few other side products as revealed by TLC.
• 24 General Procedure for 1,2,4-Thiazoles 17 2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine (8, 0.947 g, 1 mmol) was added to a stirred solution of appropriate thiobenzamide (3 mmol) in MeOH at r.t. The progress of the reaction was monitored by TLC, and the reaction was complete within 2 h. After completion of reaction, the mixture was filtered, and the resulting white precipitate was washed several times with MeOH to recover 11 which was subsequently subjected to chlorination at 0 °C in CHCl₃ to form 8. The original filtrate was concentrated in vacuo to afford the crude product which was purified by column chromatography on silica gel using PE–EtOAc (9:1) as eluent to give the substituted 1,2,4-thiazole in excellent purity.
• 25 The measured solubilities of the coproduced triiodide 11, a reduced form of the 2,4,6-tris[(4-dichloroiodo)phenoxy]-1,3,5-triazine (8) reagent, in several (mixed) solvents at 25 °C are as follows: 0.02 mg·mL^–1 (MeOH); 0.02 mg·mL^–1 (i-PrOH); 0.2 mg·mL^–1 (MeCN); 4.1 mg·mL^–1 (EtOAc); 4.3 mg·mL^–1 (acetone); 0.04 mg·mL^–1 (MeOH–EtOAc = 10:1); 0.06 mg·mL^–1 (MeOH–EtOAc = 5:1); 0.6 mg·mL^–1 (MeOH–EtOAc = 1:1).