Selective Removal of N-Boc Protecting Group from Aromatic Amines Using Silica Gel-Supported Sodium Hydrogen Sulfate and HY-Zeolite as Heterogeneous Catalysts

Article abstract of DOI:10.1002/adsc.200303108

Silica gel-supported sodium hydrogen sulfate and HY-zeolite were found to be efficient catalysts for the selective removal of the N-Boc protecting group from aromatic amines keeping intact the aliphatic N-Boc amines. HY-zeolite was used as a reusable catalyst.

Full text of DOI:10.1002/adsc.200303108

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Selective Removal of N-Boc Protecting Group from Aromatic
Amines Using Silica Gel-Supported Sodium Hydrogen Sulfate
and HY-Zeolite as Heterogeneous Catalysts[1]
N. Ravindranath, C. Ramesh, M. Ravinder Reddy, Biswanath Das*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: ( ‡ 91)-40-7160512, e-mail: biswanathdas@yahoo.com
Received: May 29, 2003; Accepted: July 23, 2003
Abstract: Silica gel-supported sodium hydrogen
sulfate and HY-zeolite were found to be efficient
catalysts for the selective removal of the N-Boc
protecting group from aromatic amines keeping
Scheme 1.
intact the aliphatic N-Boc amines. HY-zeolite was
used as a reusable catalyst.
also remained unchanged. The electron-rich indole
Keywords: HY-zeolite; N-Boc aliphatic amines; N-
moiety was not at all affected during deprotection of
Boc aromatic amines; selective deprotection; silica
N-Boc-indoles due to the attack of the tert-butyl cation
gel-supported NaHSO4
(formed from the Boc group at the time of deprotection)
under the present experimental conditions. The struc-
tures of all the products were derived from their spectral
1
(IR, H NMR and MS) data and by direct comparison
Thetert-butoxycarbonyl (Boc) group is extensively used with authentic samples.
as a protecting group for amines and amino acids in
Both the catalysts, NaHSO4 ¥ SiO2 and HY-zeolite
organic synthesis.[2] This group is stable to mildly acidic acted as solid reagents under mild experimental con-
and basic conditions. There are a number of methods for ditions (see Experimental Section). They can be re-
removal of this group.[3] However, the reagents used in moved at ease from the reaction mixture after comple-
most of these methods work under homogeneous tion of reaction just by filtration. The first catalyst can
conditions. Recently silica gel under reduced pressure easily be prepared[6] from the readily available reagents,
[4]
[5]
and clay
have been used as solid reagents for NaHSO4 and silica gel (finer than 200 mesh) and the
removal of the N-Boc group from aromatic amines. In second catalyst is commercially available. In most of the
connection with our recent work on the application of earlier methods[3] the recovery of the catalyst for reuse
heterogeneous catalysts we have observed that silica was a problem but HY-zeolite can conveniently be
gel-supported sodium hydrogen sulfate (NaHSO4 ¥ recovered and reused.
SiO2) and HY-zeolite are efficient catalysts for the
selective deprotection of N-Boc aromatic amines.
In conclusion, we have applied two heterogeneous
catalysts, NaHSO4 ¥ SiO2 and HY-zeolite for selective
Several N-Boc aromatic and aliphatic amines were removal of Boc groups from aromatic amines. The
refluxed with HY-zeolite or NaHSO4 ¥ SiO2 in CH2Cl2 method is mild and the yields of the deprotected amines
(Table 1). Deprotected aromatic amines were obtained are very high. The great advantage is that one of the
in excellent yields while N-Boc aliphatic amines re- catalysts, HY-zeolite, can be recycled. We feel the
mained unchanged. This selectivity was also observed by present protocol will find practical application in
considering a starting molecule containing both aro- organic synthesis involving deprotection of N-Boc
matic and aliphatic N-Boc groups (entries 9 and 10). The aromatic amines.
product was found to be an aromatic amine having a
protected aliphatic amine group. To define the selectiv-
ity intermolecular competition experiments with mix-
ture of aromatic and aliphatic amines with N-Boc groups
Experimental Section
were also performed (entries 14 and 15). Deprotection
of aromatic amines was observed but N-Boc aliphatic
Deprotection of N-Boc Aromatic Amines
amines remained intact. Different acid-sensitive groups
like ether (entry 2), acetate (entry 5) and ester (entry 6) CH2Cl2 (15 mL) HY-zeolite (200 mg) (PQ Corporation , USA)
To a solution of Boc-protected aromatic amine (1 mmol) in
Adv. Synth. Catal. 2003, 345, 1207 1208
DOI: 10.1002/adsc.200303108
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1207

N. Ravindranath et al.
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Table 1. Deprotection of the N-Boc group from aromatic amines.[a]
filtrate was chromatographed over silica gel to get
the deprotected aromatic amine.
The recovered HY-zeolite was verified for three
times to catalyze the deprotection of Boc-protect-
ed aromatic amine (following the above-men-
tioned procedure) without loosing its efficiency.
The deprotected aromatic amine was obtained in
each case in almost identical yield.
Competitive Experiment
To a solution of N-Boc aromatic amine (1 mmol)
and N-Boc aliphatic amine (1 mmol) in CH2Cl2
(15 mL) HY-zeolite (200 mg) or NaHSO4 ¥ SiO2
(300 mg) was added and the mixture was refluxed
for 10 h. The mixture was filtered and concentrat-
ed. The residue was chromatographed over silica
gel to get the deprotected aromatic amine and the
unchanged N-Boc aliphatic amine.
Acknowledgements
The authors thank UGC and CSIR, New Delhi for
financial assistance.
References and Notes
[1] Part 19 in the series, ™Studies on Novel
Synthetic Methodologies∫, for part 18 see, C.
Ramesh, G. Mahender, N. Ravindranath, B.
Das, Tetrahedron 2003, 59, 1049. IICTCom-
munication No. 4585.
[2] a) T. W. Greene, P. G. M. Wut, in Protecting
Groups in Organic Synthesis, 2nd Edn., John
Wiley & Sons, Inc, New York, 1991; b) L. A.
Carpino, Acc. Chem. Res. 1973, 6, 193; c) M.
Bodanszky, in Principles ofpeptide chemistry ,
Springer Verlag, New York, 1984.
[3] D. S. Bose, V. Lakshminarayana, Synthesis
1999, 66 and references cited therein.
[4] T. Apelqvist, D. Wensbo, Tetrahedron Lett.
1996, 37, 1471.
[a]
All the products were characterized from their spectral data and by
comparison with authentic samples.
or NaHSO4 ¥ SiO2 (300 mg) was added and the mixture was
refluxed (time is indicated in Table 1). After completion of
reaction the mixture was cooled and filtered. The concentrated
[5] N. S. Shaikh, A. S. Gajare, V. H. Deshpande, A. V. Be-
dekar, Tetrahedron Lett. 2000, 41, 385.
[6] G. W. Breton, J. Org. Chem. 1997, 62, 8952.
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¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1207 1208