Synlett 2007(9): 1436-1440  
DOI: 10.1055/s-2007-980370
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Naphthylmethyleneimino-Type Photocleavable Protecting Group for Primary Amines

Tetsutaro Igarashi, Masaru Shimokawa, Miyuki Iwasaki, Kensaku Nagata, Masato Fujii, Tadamitsu Sakurai*
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, Kanagawa-ku, Yokohama 221-8686, Japan
Fax: +81(45)4917915; e-Mail: sakurt01@kanagawa-u.ac.jp;
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Publikationsverlauf

Received 18 December 2006
Publikationsdatum:
23. Mai 2007 (online)

Abstract

A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties.

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Typical Experimental Procedures for the Synthesis of Compounds 1, and Physical Data of Selected Compounds O-(4-Nitrophenyl)-N-(4-tolyl)carbamate and O-(1-naphthylmethyleneimino)-N-(4-tolyl)carbamate (1h), chosen as typical carbamate derivatives, were prepared according to the following procedures.
O-(4-Nitrophenyl)-N-(4-tolyl)carbamate: 4-Toluidine (1.1 g, 10 mmol) and pyridine (0.80 g, 10 mmol) were dissolved in 10 mL CH2Cl2 at r.t.. 4-Nitrophenyl chloroformate (2.1 g, 10 mmol) was dissolved in 5 mL CH2Cl2 and added dropwise to the 4-toluidine solution with stirring at r.t. After 30 min, the reaction mixture was concentrated to dryness in vacuo and the remaining crystalline solid was reprecipitated with CHCl3-hexane to give quantitatively O-(4-nitrophenyl)-N-(4-tolyl)carbamate as a precursor of 1h; mp 137.0-138.0 °C. IR (KBr): νmax = 3337, 1709, 1537, 1346 cm-1. 1H NMR (500 MHz, DMSO-d 6): δ = 2.26 (3 H, s), 7.15 (2 H, d, J = 8.3 Hz), 7.40 (2 H, d, J = 8.3 Hz), 7.53 (2 H, d, J = 9.2 Hz), 8.30 (2 H, d, J = 9.2 Hz), 10.35 (1 H, s). 13C NMR (125 MHz, DMSO-d 6): δ = 20.4, 118.7 (2 C), 122.9 (2 C), 125.2 (2 C), 129.3 (2 C), 132.3, 135.5, 144.5, 150.5, 155.6. Anal. Calcd for C14H12N2O4: C, 61.76; H, 4.44; N, 10.29. Found: C, 61.91; H, 4.49; N, 10.24.
Compound 1h: 1-Naphthaldehyde oxime (0.86 g, 5.0 mmol) and Et3N (0.50 g, 5.0 mmol) were dissolved in 20 mL CH2Cl2 at r.t. To the 1-naphthaldehyde oxime solution was added slowly O-(4-nitrophenyl)-N-(4-tolyl)carbamate (1.4 g, 5.0 mmol) dissolved in 5 mL CH2Cl2 and the resulting reaction mixture was allowed to stand for 60 min at r.t. After 50 mL CHCl3 was added, the solution was washed with 1 M NaHCO3 solution (2 × 100 mL), H2O (2 × 100 mL) and then sat. NaCl solution (2 × 100 mL). The organic layer was separated, dried over MgSO4, filtered and the solvent was removed in vacuo. The residual solid obtained was reprecipitated with CHCl3-hexane to afford analytical grade 1h in a 80% yield; mp 135.0-136.0 °C. IR (KBr): νmax = 3292, 1726, 1603 cm-1. 1H NMR (500 MHz, DMSO-d 6): δ = 2.27 (3 H, s), 7.15 (2 H, d, J = 8.2 Hz), 7.45 (2 H, d, J = 8.2 Hz), 7.63-7.67 (2 H, m), 7.70 (1 H, dd, J = 6.9, 7.9 Hz), 8.04 (1 H, d, J = 6.9 Hz), 8.06 (1 H, d, J = 8.6 Hz), 8.14 (1 H, d, J = 7.9 Hz), 8.81 (1 H, d, J = 8.6 Hz), 9.20 (1 H, s), 9.89 (1 H, s). 13C NMR (125 MHz, DMSO-d 6): δ = 20.4, 119.2 (2 C), 125.0, 125.5, 126.4, 126.6, 127.8, 128.8, 129.3 (2 C), 130.0, 130.1, 132.0, 132.1, 133.4, 135.8, 151.9, 155.2. Anal. Calcd for C19H16N2O2: C, 74.98; H, 5.30; N, 9.20. Found: C, 74.96; H, 5.42; N, 9.32.

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Typical Experimental Procedure for the Photo-deprotection of Compounds 1 Analytical grade 1h (49 mg, 0.16 mmol) was dissolved in 50 mL MeCN at r.t. and the resulting solution was transferred into a Pyrex glass vessel. External irradiation was made at r.t. (25-30 °C) under an Ar atmosphere with Pyrex filtered light (λ > 280 nm) from a 450 W high-pressure Hg lamp mounted in a home-made lamp house. After the 2 h irradiation, TFA (91 mg, 0.80 mmol) was added to the irradiated solution and the resulting mixture was concentrated to dryness in vacuo. The residue obtained was dissolved in EtOAc and then subjected to column chromatography over silica gel (230 mesh) with an EtOAc eluent, which enabled the isolation of 4-methylanilinium trifluoroacetate (78%) and 1-cyanonaphthalene (82%).

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Control Experiments Analytical-grade 1h (49 mg, 0.16 mmol) and TFA (91 mg, 0.80 mmol) were dissolved in 50 mL MeCN and the resulting solution was allowed to stand for 5 h at r.t. After the solution was concentrated to dryness in vacuo, the remaining crystalline solid was dissolved in 1 mL DMSO-d 6 and subjected to 1H NMR analysis. This analysis showed the negligible decomposition of 1h. The same result was obtained also in the presence of a fivefold molar excess of Et3N (81 mg, 0.80 mmol).