Current Organic Chemistry, 2012, 16, 1485-1501 1485 Molecular Iodine: An Efficient and Versatile Reagent for Organic Synthesis Sunil U. Tekale a , Sushma S. Kauthale a , Satish A. Dake a , Swapnil R. Sarda b and Rajendra P. Pawar a * a Department of Chemistry, Deogiri College, Aurangabad-431005, Maharashtra, India b Department of Chemistry, J. E. S. College, Jalna-431203, Maharashtra, India Abstract: Molecular iodine has acquired an important role in organic synthesis due to its unique and powerful feature to catalyze organic transformations on account of its mild Lewis acidic character. The current review enlightens the versatile nature of the catalyst for nu- merous organic strategies including the synthesis of various heterocyclic compounds, iodination, protection- deprotection of functional groups etc. Keywords: Catalyst, Lewis acid, Molecular iodine, Organic transformations, Reagent etc. INTRODUCTION The element iodine was discovered by Bernard Courtois in 1811. Under standard conditions it is a bluish-black solid. Classi- cally iodine and its compounds were used in nutrition, medical applications and industrially in the production of acetic acid, certain polymers etc [1]. The elemental iodine dissolves easily in many organic solvents such as acetonitrile, chloroform, acetone, ethanol etc. Many cata- lysts or reagents such as ZnCl 2 , AlCl 3 , RuCl 3, TiCl 4 etc. have draw- backs like moisture sensitivity, environmentally hazardous nature, work for longer reaction time and furthermore some organic trans- formations requires the use of expensive metal salt as catalysts. However; molecular iodine is a non-metallic, non-toxic, inexpen- sive, environmentally benign and readily available catalyst. The mild Lewis acidity associated with the catalyst helps researchers to carry out various organic transformations to afford the correspond- ing products in excellent yields with high selectivity [2-4]. It is widely used for the synthesis of various heterocyclics, protection- deprotection of functional groups, Michael additions, Prins and related reactions etc. Many multi-component reactions can be car- ried out using this simple catalyst. The advantages of the catalyst include operational simplicity; inexpensive and its eco-friendly nature. Thus the major application of iodine as a catalyst in organic synthesis has received considerable attention due to powerful cata- lytic activity for various organic transformations and hence the processes catalyzed by molecular iodine can be extended for indus- trial applications. The present review focuses an overview of such transforma- tions. A comprehensive literature survey reveals that molecular iodine is a precious catalyst. It has been found to catalyze the following reactions: 1. Heterocyclic compound synthesis 2. Iodination of organic compounds 3. Protection-deprotection of functional groups 4. Michael additions *Address correspondence of this author at the Department of Chemistry, Deogiri College, Aurangabad-431005, Maharashtra, India; Tel: +91-(0240) 2334577; Fax: +91- 240-2487284; E-mail: rppawar@yahoo.com 5. Prins related reactions 6. Oxidation reactions 7. Miscellaneous reactions 8. Functionalization of alcohols by molecular iodine com- bined with other reagents (LTA / I 2, DIB/ I 2 etc): 1. MOLECULAR IODINE CATALYZED SYNTHESIS OF VARIOUS HETEROCYCLIC COMPOUNDS As well-known; organic chemistry is largely comprised of het- erocyclic compounds. Many nitrogen containing heterocyclic com- pounds are pharmacologically and biologically potent molecules having many interesting properties such as antibacterial, antifungal, anticancer, antidiabetic activities associated with them. These com- pounds include quinazolinones, quinoxaline, quinolines, imidazoles etc. Although many of the reported methods for the synthesis of these compounds involve the utility of various organometallic reagents, ionic liquid etc; some of the employed reagents may be toxic, workup procedure involved may be tedious and there may appear separation problem in many cases. Most of the nitrogen heterocycles involve substitution or con- densation of nitrogen nucleophiles with carbonyl compounds. Hence the present review focuses an attention on the construction of such heterocyclic compounds from their acyclic precursors using the simple molecular iodine. Metin Zora carried out the synthesis of ferrocenyl quinolines from ferrocenylimines and enolizable aldehydes in dioxane under reflux condition [5] (scheme 1). The synthesis of spiroorthcarbon- ates (scheme 2) using molecular iodine-catalyst was reported by M. Rahimizadeh [6]. The oxidative cyclocondensation of ortho-aminobenzamide and various aromatic aldehydes for the synthesis of quinazolin-4(3H)- ones (scheme 3) under mild reaction (room temperature) conditions using molecular iodine catalyst in absolute ethanol as the reaction medium was suggested by M. Bakavoli et al. [7]. Low toxicity, low-cost, short reaction time and high yield make this protocol an attractive process for the synthesis of quinazolinones. The hydroxyl group of the aldehydes was found to remain intact during the reac- tion to afford the corresponding products in excellent yield. Molecular iodine loaded on neutral alumina was used as an ef- ficient catalyst for the synthesis of flavones [8] under microwave conditions in excellent yield (scheme 4). This constitutes an impor- 1 5- /12 $58.00+.00 © 2012 Bentham Science Publishers