The traditional chlorination reaction of α-aminoacids with PCl5 was elucidated by means of spectroscopic and DFT studies. Thus [NH2(CH2)3CHC(O)Cl][Cl], 1, and [RCH(NH3)C(O)Cl][Cl] (R = H, 3; R = CH3, 4; R = CH2Ph, 5; R = CH2CHMe2, 6) were obtained in high yields from equimolar amounts of PCl5 and L-proline, glycine, L-alanine, L-phenylalanine and L-leucine, respectively. Compounds 3–6 resulted to be stable at room temperature under nitrogen atmosphere, whereas 1 rapidly degraded under the same conditions, both in the solid state and in solution. The 1:2 molar reaction of PCl5 with L-proline selectively afforded the salt [NH2(CH2)3CHC(O)Cl][PCl6], 2, showing better inertness than the homologous 1. The slow degradation reaction of 2 may represent a strategy for the clean synthesis of the L-proline-derived 2,5-diketopiperazine, which was recovered in ca. 60% yield from a dichloromethane solution stirred at room temperature for several days and purged with nitrogen gas in order to remove the released HCl. Compounds 1–6 were characterized by elemental analysis and IR spectroscopy, and by NMR spectroscopy in the cases of soluble 1 and 2. Furthermore, the structures of 1–6 were computationally optimized by means of DFT functionals. According to the spectroscopic and DFT outcomes, 1–6 exist in solution as tight ion pairs featured by NH⋯Cl cation–anion interactions, leading to possible HCl formation and consequent condensation reactions. The less stability observed for 1–2 respect to 3–6 should be associated with the relatively high ΔG value of the condensation step.

Revisitation of the PCl5-chlorination reaction of a-amino acids: Spectroscopic and DFT insights, and synthesis of the L-proline-derived 2,5-diketopiperazine

MARCHETTI, FABIO;PAMPALONI, GUIDO
2015

Abstract

The traditional chlorination reaction of α-aminoacids with PCl5 was elucidated by means of spectroscopic and DFT studies. Thus [NH2(CH2)3CHC(O)Cl][Cl], 1, and [RCH(NH3)C(O)Cl][Cl] (R = H, 3; R = CH3, 4; R = CH2Ph, 5; R = CH2CHMe2, 6) were obtained in high yields from equimolar amounts of PCl5 and L-proline, glycine, L-alanine, L-phenylalanine and L-leucine, respectively. Compounds 3–6 resulted to be stable at room temperature under nitrogen atmosphere, whereas 1 rapidly degraded under the same conditions, both in the solid state and in solution. The 1:2 molar reaction of PCl5 with L-proline selectively afforded the salt [NH2(CH2)3CHC(O)Cl][PCl6], 2, showing better inertness than the homologous 1. The slow degradation reaction of 2 may represent a strategy for the clean synthesis of the L-proline-derived 2,5-diketopiperazine, which was recovered in ca. 60% yield from a dichloromethane solution stirred at room temperature for several days and purged with nitrogen gas in order to remove the released HCl. Compounds 1–6 were characterized by elemental analysis and IR spectroscopy, and by NMR spectroscopy in the cases of soluble 1 and 2. Furthermore, the structures of 1–6 were computationally optimized by means of DFT functionals. According to the spectroscopic and DFT outcomes, 1–6 exist in solution as tight ion pairs featured by NH⋯Cl cation–anion interactions, leading to possible HCl formation and consequent condensation reactions. The less stability observed for 1–2 respect to 3–6 should be associated with the relatively high ΔG value of the condensation step.
Marco, Bortoluzzi; Marchetti, Fabio; Maria G., Murrali; Pampaloni, Guido
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/659267
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