A protic ionic liquid catalyzed strategy for selective hydrolytic cleavage of tert-butyloxycarbonyl amine (N-Boc)† Swapan Majumdar, * a Jhinuk De, a Ankita Chakraborty, a Dipanwita Roy b and Dilip K. Maiti b A simple, mild and efficient strategy for selective hydrolytic cleavage of the N-tert-butyloxycarbonyl (Boc) group is devised using a protic ionic liquid as an efficient catalyst. The deprotection reaction proceeded well for N-Boc protected aromatic, heteroaromatic, aliphatic compounds, and chiral amino acid esters and peptides. A wide range of labile protecting groups such as tert-butyl ester, tert-butyl ether, benzyloxycarbonyl (Cbz), TBDMS, O-Boc and S-Boc remained unaf- fected under the reaction conditions. Due to environmental and economic issues as well as legisla- tion, chemistry is driven to reduce waste, and reuse and recycle materials in order to meet the principles of green chemistry. 1 Thus the development of an environmentally benign, efficient and simple methodology for a fundamental organic trans- formation is in great demand. The protection and deprotection of functional groups is a common feature to synthesize multi- functionalized molecules in target oriented syntheses. 2 The choice of a suitable protecting group is oen crucial in the context of simplifying the procedure, achieving the highest yield of the desired product, easy workup and separation. The protection of amines plays pivotal role in the synthetic organic chemistry. For instance, the N-Boc group is extensively used as a protecting group of amines in organic synthesis and amino acids in peptide and nucleoside chemistry. Consequently, a number of methods were developed for cleavage of the N-Boc group using strong acids, 3 Lewis acids 4 and microwave assisted neutral conditions 5 to liberate the parent amine. In some cases, basic conditions 6 such as aq. Na 2 CO 3 , Cs 2 CO 3 –imidazole and NaO t Bu have been employed. The heterogeneous catalysis promoted N-Boc deprotection using sulfonic acid resin, 7a montmorillonite K10, 7b silica, 7c heteropolyacids, 7d HY-zeolite 7e are also reported. However, most of the reported strategies suffer from serious drawbacks such as (i) longer reaction time, (ii) high temperature, (iii) low yield of products and (iv) exploiting expensive catalysts. Moreover, preparations of some of the catalysts are very tedious. Thus, organic synthesis professionals of industries and academia seek simple, efficient and milder methods for deprotection of this most frequently used protecting group, which should be selective enough for preserving the other functionalities in the molecule. G. Wang et al. (2009) reported 8 a special and efficient “green”, catalyst- free, N-Boc deprotection in supercritical water under pressure. In their methodology, both aromatic and aliphatic N-Boc amines can be converted into the corresponding amines in high yields within 2–16 h, using distilled and deionized water (20 mL mmol 1 ) at 150  C. J. Wang and his colleagues (2009) described 9 a selective N-Boc deprotection method using boiling water as a reaction medium. In spite of the potentiality of these green methods, their major limitation is the use of sophisticated and costly technology, incompatibility of the deprotection reaction with ester functionality and longer reaction time. As an inex- pensive and readily available reagent, imidazolium based protic ionic liquid has attracted considerable interest due to its less hazardous nature and efficiency in various organic trans- formations. 10 We have reported earlier an efficient method 11a for the tert-butyloxycarbonylation of amines, amino acids/esters, alcohols and a green strategy for the selective hydrolytic cleavage of acetals and ketals 11b using protic ionic liquid as an effective catalyst. In this communication, we disclose the effi- cacy of a protic ionic liquid as a catalyst for the selective deprotection of N-Boc group of a wide range of achiral and chiral compounds. In our initial experiments we choose readily available N-Boc aniline as a model substrate and, the results for development and optimization of the deprotection studies is displayed in Table 1. On treatment of the N-Boc aniline (1 mmol) with 1 mmol of Bronsted acid ionic liquid (I or II) in water–dioxane (1 : 1) at 30  C, the deprotection did not take place (Table 1, entry 1). However on rising the temperature to 70–72  C a Department of Chemistry, Tripura University, Suryamaninagar, 799 022, India. E-mail: smajumdar@tripurauniv.in; Fax: +91-381-2374802; Tel: +91-381-237-9070 b Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700 009, India † Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra13419b Cite this: RSC Adv. , 2015, 5, 3200 Received 29th October 2014 Accepted 4th December 2014 DOI: 10.1039/c4ra13419b www.rsc.org/advances 3200 | RSC Adv. , 2015, 5, 3200–3205 This journal is © The Royal Society of Chemistry 2015 RSC Advances COMMUNICATION