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Synlett 2004(10): 1794-1798  
DOI: 10.1055/s-2004-829059
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Lewis Acid-Mediated Protocol for the Protection of Aryl Amines as their Boc-Derivatives

Giuseppe Bartoli*a, Marcella Boscoa, Manuela Locatellia, Enrico Marcantonib, Massimo Massaccesia, Paolo Melchiorrea, Letizia Sambri*a
a Dipartimento di Chimica Organica ‘A. Mangini’, v.le Risorgimento 4, 40136 Bologna, Italy
Fax: +39(051)2093654; e-Mail: giuseppe.bartoli@unibo.it; e-Mail: letizia.sambri@unibo.it;
b Dipartimento Scienze Chimiche, Università di Camerino, via S.Agostino 1, 62032 Camerino (Macerata), Italy
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Publikationsverlauf

Received 30 March 2004
Publikationsdatum:
01. Juli 2004 (online)

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Abstract

A new protocol of protection of poorly reactive aryl amines and functionalized amines with Boc2O in the presence of Zn(ClO4)2·6H2O as the catalyst is reported. The catalytic action of Zn(ClO4)2·6H2O is specific for the activation of the pyrocarbonates, thus acid sensitive functionalities and stereochemical configurations of the starting materials remain unaltered in the protection ­process.

Key words

protection - Lewis acid - zinc perchlorate - aryl amines - Boc-derivatives

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The reaction was also carried out by changing the Zn(II) counterion of the potentially explosive Zn(ClO4)2·6H2O using Zn(OAc)2. We obtained worse results, only a 60% conversion after 4.5 h in CH2Cl2 at r.t. was detected.

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Representative Experimental Procedure. Synthesis of tert -Butyl N -Phenylcarbamate ( 2a): To a round-bottom flask were added Zn(ClO4)2·6H2O (28 mg, 0.075 mmol), CH2Cl2 (2.25 mL), aniline (0.14 g, 1.50 mmol) and Boc2O (0.43 g, 1.95 mmol, 1.3 equiv). The reaction mixture was stirred at r.t. for 12 h. After addition of 5 mL of CH2Cl2, the solution was washed with H2O. The organic layer was dried over MgSO4 and concentrated at reduced pressure. The crude product was purified by column chromatography on silica gel. Compounds 2a, 2b, 2i, 2m, 4a, 4d and 4i are commercial products; 2c, [4] 2d [14] , 2e, [4] 2p [15] , 4c [16] , 4e [17] , 4g [18] and 4h [19] are known compounds. Spectroscopic data for selected examples follow. tert-Butyl N-[4-(Acetylamino)phenyl] Carbamate (2f): 1H NMR (300 MHz, CDCl3): δ = 1.51 (s, 9 H, t-Bu), 2.15 (s, 3 H, CH3), 6.50 (br s, 1 H, NH), 7.20 (br s, 1 H, NH), 7.26-7.35 (m, 2 H, Ph), 7.40-7.45 (m, 2 H, Ph). 13C NMR (100 MHz, CDCl3): δ = 23.7 (CH3), 26.9 (CH3), 79.8 (C), 116.3 (CH), 118.8 (CH), 133.3 (C), 134.3 (C), 152.7 (C), 168.4 (C). tert-Butyl N-(3-Sulfanylphenyl) Carbamate (2h): 1H NMR (300 MHz, CDCl3): δ = 1.51
(s, 9 H, t-Bu), 3.46 (s, 1 H, SH), 6.60 (br s, 1 H, NH), 6.90-6.95 (m, 1 H, Ph), 7.00-7.05 (m, 1 H, Ph), 7.05-7.10 (m, 1 H, Ph), 7.40 (br s, 1 H, Ph). 13C NMR (75 MHz, CDCl3):
δ = 28.3 (CH3), 80.7 (C), 115.5 (CH), 118.7 (CH), 123.6 (CH), 129.4 (CH), 131.8 (C), 138.9 (C), 152.5 (C). Diethyl (2S)-2-(4-[(tert-Butoxycarbonyl)amino] Benzoylamino) Pentanedioate (2l): [α] D = 13 (c 1.05, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.22 (t, 3 H, J HH = 7.1 Hz, CH3), 1.30 (t, 3 H, J HH = 7.2 Hz, CH3), 1.52 (s, 9 H, t-Bu), 2.05-2.60 (m, 4 H, 2 CH2), 4.10-4.20 (m, 2 H, CH2), 4.20-4.30 (m, 2 H, CH2), 4.75-4.80 (m, 1 H, CH), 6.80 (br s, 1 H, NH), 7.0 (br d, 1 H, J HH = 7.2 Hz, NH), 7.40-7.45 (m, 2 H, Ph), 7.75-7.80 (m, 2 H, Ph). 13C NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 14.1 (CH3), 27.1 (CH2), 28.2 (CH3), 30.5 (CH2), 52.3 (CH), 60.7 (CH2), 61.6 (CH2), 80.9 (C), 117.2 (CH), 127.6 (C), 128.2 (CH), 141.8 (C), 152.3 (C), 166.5 (C), 172.0 (C), 173.2 (C).