Selective and effective oxone-catalysed α -iodination of ketones and 1,3-dicarbonyl compounds in the solid state

Selective α -iodination of ketones and 1,3-dicarbonyl compounds was accomplished in the solid state within a very short reaction time with excellent yields using elemental iodine and Oxone as the catalyst, by grinding in a mortar.


Introduction
Iodo-functionalized organic molecules are versatile intermediates in synthetic organic chemistry, based on their ability to form carbon-carbon bonds and to undergo iodine-metal exchange reactions. 1Moreover, a considerable number of iodo-substituted molecules possess biological activity and their properties have attracted considerable attention in the medicinal field. 2 Among the variety of methods known for the introduction of iodine atom into a molecule, the most conventional is the use of an oxidizing agent with iodides, iodine or I + -generating reagents as the source of the iodine atom. 3Few solvent free iodination methods with microwave irradiation have been reported. 4

Results and Discussion
In this communication, we report an efficient solvent-free selective α-iodination of ketones and 1,3-diketones, using elemental iodine and a catalytic amount of Oxone, by grinding in a mortar (Scheme 1).There was no requirement for any additives.Oxone is a stable ternary composite of KHSO 5 /KHSO 4 and K 2 SO 4 in 2:1:1 molar ratio and its utility has been established for a variety of organic reactions. 5Although aromatic iodination using an equimolar amount of oxone and NH 4 I in methanol, at room temperature, has been reported, 6 there are no reports of selective αiodination of 1,3-dicarbonyl compounds or ketones, using molecular iodine and catalytic Oxone.
For the current study, methyl acetoacetate 1a was taken as the model substrate.Methyl acetoacetate (1 equiv) was mixed with Oxone (0.1 equiv) and molecular iodine (0.5 equiv) and the mixture was ground in a mortar for 1 min.The crude reaction mixture was filtered, dried and analyzed without any further purification.The reaction furnished selectively α-monoiodinated methyl acetoacetate 1b in excellent yield without the formation of any side products.This result encouraged us to examine other 1,3−dicarbonyl compounds (Table 1).a Isolated yield Τhe β-keto esters 2a -6a reacted smoothly to give α-monoiodinated β-ketoesters.Similarly, the cyclic β-keto ester 7a also gave the iodinated product 7b.Reaction of β-keto ester 8a, which possesses both the active methylene hydrogens together with a carbon-carbon double bond, suffered only α-iodination, without affecting the double bond.
Examination of 1,3-diketones 9a -12a showed them also to give mono α-iodinated products in good yields.We note that a 13 C carbonyl signal for compound 12b could not be seen, perhaps due to rapid keto-enol tautomerism.The structure of compound 12b was confirmed by a single crystal X-ray diffraction study (Figure 1). Figure 1.ORTEP plot of α-monoiodo dimedone 12b with atom numbering scheme Literature reports 7 reveal the difficulty in iodinating dialkyl malonates.We succeeded in iodinating diethyl malonate 13a to produce the mono-iodo derivative by increasing the amount of catalyst from 0.1 equiv to 0.25 equiv.

Table 2. α-Iodination of diketones
Entry Substrate (a)  Products As metal persulfates are known 9 to be activated for oxidation reactions on heating, we suggest that the oxidation of iodine probably involves oxidation induced by the heat and pressure generated in the mortar.
In conclusion, the major advantages of the new method are the introduction of an iodine atom into organic molecules in the absence of an organic co-solvent, complete consumption of iodine, lack of work-up and purification procedure along with the requirement for only a short reaction time.Moreover since iodinated compounds have a tendency to decompose on purification by column chromatography, our procedure overcomes this problem as only monoiodinated products were obtained exclusively.

Experimental Section
General Procedure.Chemicals were purchased from Fluka, Merck, and Aldrich chemical companies.Some of the β-ketoesters were prepared by reported procedures.Some of the products were characterized by comparison of their spectral (IR, UV, 1 H NMR, and 13 C NMR) and physical data with the authentic samples.
Typical experimental procedure.Typical experimental procedure: The substrate (1 mmol) was mixed with iodine (0.5 equiv) and Oxone (0.1 equiv) in a mortar and the mixture ground for 1 min.After completion of the reaction as indicated by TLC, the reaction mixture was transferred to a filter paper and extracted with dichloromethane.The extract was evaporated to dryness and the residue analysed without further purification.