Solvent-Free and Liquid-Phase Iodination of Thiophene Derivatives with Potassium Dichloroiodate Monohydrate

Abstract

Iodination of a series of benzene and thiophene derivatives by potassium dichloroiodate monohydrate was studied with and without a solvent. The liquid substrates tend to be more reactive in water while the solid substrates afford better yields in dichloromethane or under the solvent-free conditions. The 2-substituted thiophenes show good to excellent yields whereas the yield for 3-substituted and 3,4- or 2,4-disubstituted thiophenes and benzene derivatives are significantly lower. The mechanochemical reaction of 5-carbaldehyde-2,2′-bithiophene shows excellent yields, while 2,2′-bithiophene gives practical yields only in dichloromethane. In the case of thiophene and N-acetyl-p-toluidine, electrophilic iodination is accompanied by a small extent of chlorination.

Computational investigation of KICl2 iodination of thiophene and its electron‐poor derivatives

“…[25] These solvents were used experimentally in the iodination of thiophene, 3-bromothiophene, and thiophene-3-carbaldehyde. [17] The nature of all stationary points and transition states was verified by analytic computation of vibrational frequencies. Molecular partition functions were used in the computation of 298.15 K thermal contributions to Gibbs free energy employing the usual ideal-gas, rigid-rotator, and quasi-harmonic oscillator approximations.…”

“…[28] In all cases, the thermal contributions to the Gibbs free energy were also computed at the temperature used experimentally, 323.15 K, which gives a better yield. [17] 3 | RESULTS AND DISCUSSION…”

“…Potassium dichloroiodate (KICl 2 ) allows ICl to be generated in situ through its dissociation into ICl and KCl in solution, the former of which is the iodinating agent. [4,5,17] This dissociation proceeds until either all the KICl 2 has been dissociated, since ICl is being consumed promoting further KICl 2 dissociation, or no further iodination is possible or favorable, in which case an equilibrium between KICl 2 , ICl, and KCl is achieved. The free energies of dissociation of KICl 2 at 298.15 K and 323.15 K, different levels of theory, and solvents are presented in Table 1.…”

“…This high barrier is in agreement with the electrophilic attack being the rate-limiting step for the iodination process and is consistent with the long reaction times required experimentally (6 h with 30% and 20% mono-and di-iodination yield) and the barriers reported in previous computational studies for the iodination of aromatic compounds. [11,17] The electrophilic attack leads to a σ-complex containing a carbon-iodine bond and a positive charge in the thiophene ring. The CM5 atomic charges of the σ-complex reveal a change in the atomic charge of 0.10, -0.04, and 0.14 for the α and β carbons on the iodinated side of the thiophene ring and sulfur atom respective to the starting thiophene (Figure 2).…”

“…[12,13] There are a few experimental and computational studies on the effects the substrate and halogenating agent have on the energetics and reaction mechanism of the electrophilic halogenation of aromatic systems. [14][15][16][17] However, there are no computational studies on the electrophilic iodination of thiophene or its derivatives. Here we present the first computational study of the monoand di-iodination of thiophene and its electron-poor derivatives.…”