A versatile method for the protection of carbonyl compounds by camphorsulfonic acid
The article by Dr. Bimal Krishna Banik et al. is published in Current Organocatalysis, 2018
Because of the nucleophilic character of the carbonyl groups, significant attention has been drawn to the chemistry of molecules that have aldehyde and keto functionalities. These reactions have become fascinating because carbonyl groups react with diverse reagents under catalytic and non-catalytic conditions. One of the most common reactions of the carbonyl groups is to mask their reactivity depending upon the requirement in the synthesis of molecules. For this reason, methods have been identified for the protection of carbonyl groups.
Acetal, 1-3-dioxalane, mixed ketal, and thioketal are extremely useful compounds and these are derived from carbonyl compounds. Many of these methods require acidic catalysts for effective completion of the process. An efficient and general method for the protection of carbonyl groups is required. However, there are some shortcomings of the available procedures. A few methods require high temperature and stoichiometric amount of reagents. Importantly, none of the existing methods are general. We have discovered a new iodine-catalyzed acetalization and thioketalization chemoselective procedure of aldehydes and ketones. In continuation of this study, we have developed an expeditious camphorsulfonic acid-catalyzed protection method of carbonyl groups.
In general, acetal and ketal is prepared with acids using trialkyl orthoformate or alcohol. Selective ketalization is performed with lanthanides and metal-catalysts. However, lanthanides-catalyzed reactions do not work with all types of carbonyl compounds. Our studies have identified camphorsulfonic acid as a suitable catalyst for the protection of different types of carbonyl compounds. This procedure has been used for the preparation of 1,3-dioxalones and the reaction proceeds successfully regardless of the nature of the aldehydes and ketones.
The protection of carbonyl compounds as thioketals has been investigated in the presence of acids, magnesium or zinc triflates, titanium tetrachloride, Nafion-H and lanthanum chloride. Chemoselectivity has been observed with Amberlyst-15 catalyst, silica gel-thionyl chloride, indium trichloride and ceric ammonium nitrate. We have discovered that thioketalization of carbonyl compounds work well with camphorsulfonic acid as catalyst.
As a result of the successes of this current method, synthesis of mixed ketals has been performed in good yield. In contrast to acetal, ketal and thioketal methods, the mixed ketal method of carbonyl compounds is found to be slower.
Camphorsulfonic acid-catalyzed procedure has been applied to transketalization. This procedure has required mixing acetal and ethane thiol or ethylene glycol in the presence of camphorsulfonic acid. Transketalization has proceeded well and good yields of the products are obtained.
The mechanistic course of camphorsulfonic acid-catalyzed protection method of carbonyl compounds in diverse forms deserves attention. It is believed that the pathways for all of these products follow a generate route. The nucleophilic character of the carbonyl compounds has promoted a protonation as the first step of the reaction and then a second nucleophilic process by the oxygen of glycol (or sulfur depending upon the substrates) is anticipated to generate unstable species. This intermediate retains the protective reagents attached to the carbonyl functional group. The negatively charged anion which is formed in the reaction has served as a basic unit and has the capability of removing a proton. An additional protonation, nucleophilic reaction by the hydroxyl group (or sulfur) and subsequent deprotonation has occurred through a series of processes. The end results become successful protection of the carbonyl compounds as individuals, acetal, ketal, thioketal, mixed ketal and trans ketal. This process is extremely simple, general, high yielding, environmentally friendly, and economical. Considering the nature of this method, this process may find applications in the synthesis of diverse organic compounds.
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About the Author:
Ram Naresh Yadav1, 2 and Bimal Krishna Banik*1, §
1Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78539, USA;
§Current Address: Community Health System of South Texas, 3135 S. Sugar Road, Edinburg, TX 78539, USA;
2Department of Chemistry, Faculty of Engineering & Technology, Veer Bhadur Singh Purvanchal University, Jaunpur-222003 (UP) INDIA.
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