A Novel Naphthylmethyleneimino-Type Photocleavable Protecting Group for Primary Amines

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.

Key words

amines - protecting groups - carbamates - photochemistry - deprotection

References and Notes

• 1a Binkley RW. Flechtner TW. In Synthetic Organic Photochemistry   Horspool WM. Plenum; New York: 1984.  p.375 
• 1b Organic Photochemistry   Vol. 9:  Pillai VNR. Padwa A. Marcel Dekker; New York: 1987.  p.225 
• 2 Bochet CG. J. Chem. Soc., Perkin Trans. 1  2002,  125 
• 3 Yamada K. Sato M. Tanaka K. Wakabayashi A. Igarashi T. Sakurai T. J. Photochem. Photobiol., A  2006,  183:  205 
• 4a Abad A. Mellier D. Pete JP. Portella C. Tetrahedron Lett.  1971,  4555 
• 4b Amit B. Zehavi U. Patchornik A. J. Org. Chem.  1974,  39:  192 
• 4c Hanessian S. Masse R. Carbohydr. Res.  1977,  54:  142 
• 4d Pincock JA. Jurgens A. Tetrahedron Lett.  1979,  1029 
• 4e Yuan W. Fearon K. Gelb MH. J. Org. Chem.  1989,  54:  906 
• 4f Sundberg SA. Barrett RW. Pirrung M. Lu AL. Kiangsoontra B. Holmes CP. J. Am. Chem. Soc.  1995,  117:  12050 
• 4g Cameron JF. Willson CG. Frechet JMJ. J. Chem. Soc., Chem. Commun.  1995,  923 
• 4h Pirrung MC. Huang C.-Y. Tetrahedron Lett.  1995,  36:  5883 
• 4i Cameron JF. Willson CG. Frechet JMJ. J. Chem. Soc., Perkin Trans. 1  1997,  2429 
• 4j Papageorgiou G. Corrie JET. Tetrahedron  1997,  53:  3917 
• 4k Cossy J. Rakotoarisoa H. Tetrahedron Lett.  2000,  41:  2097 
• 4l Bochet CG. Tetrahedron Lett.  2000,  41:  6341 
• 4m Stutz A. Hobartner C. Pitsch S. Helv. Chim. Acta  2000,  83:  2477 
• 4n Du H. Boyd MK. Tetrahedron Lett.  2001,  42:  6645 
• 4o Schoenleber RO. Giese B. Synlett  2003,  501 
• 4p Bhushan KR. DeLisi C. Laursen RA. Tetrahedron Lett.  2003,  44:  8585 
• 5a Montgomery HJ. Perdicakis B. Fishlock D. Lajoie GA. Jervis E. Guillemette JG. Bioorg. Med. Chem.  2002,  10:  1919 
• 5b Perdicakis B. Montgomery HJ. Abbott GL. Fishlock D. Lajoie GA. Guillemette JG. Jervis E. Bioorg. Med. Chem.  2005,  13:  47 

6

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): ν_max = 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): ν_max = 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.

7

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%).

8

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).