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Practical and Green Approach for N-Boc Protection of Amines Catalyzed by Indion 190 Resin
Practical and Green Approach for N-Boc Protection of Amines Catalyzed by Indion 190 Resin
Journal of the Korean Chemical Society. 2009. Aug, 53(4): 422-426
Copyright © 2009, The Korean Chemical Society
  • Received : March 10, 2009
  • Accepted : July 28, 2009
  • Published : August 20, 2009
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About the Authors
Atul Chaskar
Dipartimento Di Chimica,Materiali Ed Ingegneria Chimica "Giulio Natta" Politecnico Di Milano, Italy
Sampat Yewale
Department of Chemistry, Post graduate and Research centre, C. K. Thakur College, Navi Mumbai, Maharashtra, India-410206
Bhushan Langi
Department of Chemistry, Post graduate and Research centre, C. K. Thakur College, Navi Mumbai, Maharashtra, India-410206
Hrushikesh Deokar
Department of Chemistry, Post graduate and Research centre, C. K. Thakur College, Navi Mumbai, Maharashtra, India-410206

Abstract
An efficient, chemoselective and practical protocol for N -Boc protection of amines using di- tert -butoxypyrocarbonate (Boc) 2 O in presence of Indion 190 resin. Resin was easily separated from the reaction mixture by filtration and reused in subsequent reactions without any apparent loss of activity. Simple workup, mild condition, short reaction time and high yield are some of the striking features of the present process.
Keywords
INTRODUCTION
Protection and de-protection under mild reaction condition are crucial steps in organic synthesis. The protection of amines is an important step in synthetic organic chemistry. The tert -butoxycarbonyl (Boc) is widely used as a protecting group for amino functional group in organic synthesis. 1 - 6 Aryl amines protected in its Boc forms are important intermediates in organic synthesis. It has been used for the direct lithiation of aromatic rings and the preparation of unsymmetrical urea’s amongst others. 7 , 8 There are varieties of N -Boc protection strategies available in the literature. 9 , 10 N -Boc has gain importance, due to its resistance towards basic and nucleophilic stability as well as stability towards catalytic hydrogenation. 11 In recent years, various methods have been developed for the protection of amines in their N -Boc form, either in the presence of base (DMAP, 12 - 14 aq. NaOH, 15 , 16 NaHMDS 17 ) or Lewis acid catalyst such as Zr(ClO 4 ) 2 .6H 2 O, 18 ZrCl 4 , 19 LiClO 4 , 20 Yttria, Zirconia. 21 Bronsted acid ionic liquid, 22 thiourea, 23 and Iodine CsF 24 are also employed for N -Boc protection. However, despite the potential utility of these catalysts, many of these methodologies are associated with several shortcomings such as extended reaction time, 25 elevated temperatures, 26 tedious work-up, anhydrous organic solvents and nonrecyclability of the catalyst.
It is a need to develop an efficient and selective protecting reagent which can work under mild condition. By using solid catalyst Indion 190 resin, we have successfully carried out the N -Boc protection, which can be used for wide variety of substrates. We found that Indion 190 resin possesses unique properties such as physical and chemical stability, nontoxicity, noncorrosiveness, reusability, environmental compatibility and selectivity. Indion 190 resin can be handled easily and separated from the reaction mixture by simple filtration, washed with water, dried in oven and reused as per the experimental convenience. The recovered catalyst was consecutively reused several times without any variations in the yield of the product.
RESULTS AND DISCUSSION
Various catalysts such as BiCl 3 , CdCl 2 , triethylamine, PTSA, Bi (NO 3 ) 3 , CuCl 2 and Indion 190 resin were used for the reaction between aniline and (Boc) 2 O. The results obtained are summarized in 1 .
A wide range of structurally diverse aromatic, aliphatic and heterocyclic amines have been used during the reaction and the corresponding results of the reaction yield and time are listed in 2 .
It was observed that, when electron withdrawing group present along with amine group, reaction progresses slowly, but it is noteworthy that electron donating substituents on the aromatic ring enhance the rate of the reaction. This may be due to lone pair of electron of nitrogen of amine functional group which involves in the conjugation with electron withdrawing group and hence, it is not easily available for the reaction with (Boc) 2 O to form N -Boc protected amines. Further, presence of electron withdrawing group leads effect on the yield of the product, which was found to less compare to those formed in absence of same. Chemo selectivity of Indion 190 resin facilitates the reaction selectively with amino group in presence of other functional groups like -OH, -SH, etc, resulting in N -Boc product in high yield.
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N-Boc protection of amine
Effect of different catalyst on the yield and reaction time forN-Boc protection of aniline
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Effect of different catalyst on the yield and reaction time for N-Boc protection of aniline
Effect of nature of amines as well as presence of different functional group along with amine, on the Indion 190 catalyzedN-Boc protection of various amines
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Effect of nature of amines as well as presence of different functional group along with amine, on the Indion 190 catalyzed N-Boc protection of various amines
EXPERIMENTAL
All commercial reagents were used as received without purification and all solvents were of reagent grade. The reaction mixture was stirred in a round bottom flask magnetically and was monitored by TLC using on 0.25 mm E-Merck silica gel 60 F 254 precoated plates, which were visualized with UV light. Melting points were taken in open capillaries. The IR spectra were recorded on a Perkin-Elmer 257 spectrometer using KBr discs. 1 H NMR and 13 C NMR spectra in DMSO- d 6 were recorded on VXR-300 MHz using TMS as internal standard.
- General Experimental Procedure
Amine (0.01 mole) was added to the solution of (Boc) 2 O (0.01 mole), Indion 190 resin and t-butanol (15 mL) with constant stirring. After addition, the reaction mixture was heated at 50 ℃ till completion of the reaction. The reaction progress was monitored by TLC. After completion of the reaction, the catalyst was separated by filtration, washed with water, dried and reused. Evaporation of solvent imparts solid crude product. The product was purified by column chromatography, using ethyl acetatepetroleum ether (2:8) eluent. The physical and spectral data of known compounds are in agreement with those reported in the literature. 9 , 10 , 25
- Spectral data ofN-Boc amines
Entry 1 : IR (KBr) 3310, 3230, 1690, 1530, 1480, 1470, 1250 cm -1 ; 1 H NMR (DMSO- d 6 ) δ (ppm) 1.51 (s, 9 H), 6.98 (m, 1 H), 7.21 (m, 2 H), 7.35 (m, 2 H), 9.1 (s, 1 H, NH); 13 C NMR (DMSO- d 6 ) δ (ppm) 28.25, 79.96, 118.74, 122.34, 129.60, 136.64, 156.10; M.P. 134-136
Entry 2 : IR (KBr): 3315, 3200, 1580, 1540, 1520, 1490, 1410, 1260, 782, 650, 590 cm -1 ; 1 H NMR CDCl 3 (δ-ppm) 1.53 (s, 9 H), 7.25 (d, 1 H, J = 7.5 Hz), 8.56 (d, 1 H, J = 7.5 Hz), 8.11 (s, 1 H, NH); 13 C NMR CDCl 3 (δ-ppm) 28.73, 82.10, 118.20, 129.22, 142.10, 151.90, 152.10, 157.89; M.P. 159-161
Entry 3 : IR (KBr): 3610, 3325, 3250, 1590, 1570, 1520, 1490, 1470, 1255 cm -1 ; 1 H NMR DMSO- d 6 (δ-ppm) 1.49 (s, 9 H), 6.90 (d, 1 H, J = 7.0 Hz), 8.03 (d, 1 H, J = 7.0 Hz), 7.55 (m, 1 H), 8.52 (d, 1 H), 8.84 (d, 1 H), 8.64 (s, 1 H, OH), 10.17 (s, 1 H, NH); 13 C NMR DMSO- d 6 (δ-ppm) 28.25, 111.60, 113.10, 114.80, 120.86, 130.50, 134.27, 139.55, 149.23, 152.13, 158.19; M.P. 215-217
Entry 4 : IR (KBr): 3640, 3340, 3210, 1580, 1570, 1510, 1390, 1200 cm -1 ; 1 H NMR CDCl 3 (δ-ppm) 1.51 (s, 9 H), 6.39 (s, 1 H), 6.47 (d, 1 H, J = 7.5 Hz), 6.56 (d, 1 H, J = 7.5 Hz), 7.26 (s, 1 H, OH), 7.57 (s, 1 H, NH); 13 C NMR CDCl 3 (δ-ppm): 28.32, 84.12, 104.63, 112.80, 122, 124.10, 151.85, 157.60, 166.15; M.P. 147-149
CONCLUSION
In conclusion, Indion 190 resin was found to be an efficient catalyst for N -Boc protection of amines. The main advantages of the present synthetic protocols are mild reaction conditions, high chemo selectivity, ecofriendly recyclable catalyst and easy reaction work-up procedure. These advantages make the present method useful for large-scale operations.
Acknowledgements
The authors are grateful to Ion Exchange (India) Ltd, Mumbai for providing gift samples of Indion 190 resin and University Grant Commission, New Delhi for financial support. The authors are thankful to Dr. S. T. Gadade, Principal, C. K. Thakur College, for providing laboratory and other facilities.
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