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

Abstract

The traditional chlorination reaction of α-aminoacids with PCl 5 was elucidated by means of spectroscopic and DFT studies. Thus [NH 2 (CH 2 ) 3 CHC(O)Cl]Cl, 1, and [RCH (NH 3

Synthesis of new Amides based on N-Phthaloyl-α-Amino Acids

“…To bypass this barrier in the synthesis of N-phthaloyl amino acid amides, the carboxyl group had to be activated in an alternative way. In this case, acyl chloride of N-phthaloyl amino acids 3a-g were obtained using known methods [16,35] and were used for 6a-g synthesis of targeted amides without excessive The reaction was carried out by stirring from 0°C to room temperature, and by processing the corresponding amides were isolated in pure form at 6a-g (Scheme 3). We also repeated the acylation process for all compounds by converting the solvent to non-polar benzene, the proton acceptor to pyridine.…”

“…H NMR (400 MHz, TFA + CD3COOD, δ, ppm, J/Hz): 2.43 (2H t, J = 6.9, CH2-α), 3.23 (2H, q, J = 6.5, CH2-β),3.45 (3H, s, OCH3),3.48 (3H, s, OCH3), 4.15 (2H, s, CH2-2a),6.40 (1H, dd, J = 8.2, 1.9, ArH-6),6.43 (1H, d, J = 1.9, ArH-2), 6.46 (1H, d, J = 8.2, ArH-5),6.90 (1H, br.t, J = 5.9, NH), 7.42-7.45 (2H, m, H-phthalimid), 7.50-7.53 (2H, m, Hphthalimid). 13C NMR (100 MHz, TFA + CD3COOD, δ, ppm) 35…”

The reactions of α-amino acids and α-amino acid esters with high valent transition metal halides: synthesis of coordination complexes, activation processes and stabilization of α-ammonium acylchloride cations

“…On the other hand, in the case of the L-proline derivative (secondary N), both Cl À and [PCl 6 ] À salts undergo quick degradation at room temperature, due to HCl release and subsequent condensation reactions. 29 Furthermore, the reactions of PCl 5 with L-N,N-dimethylphenylalanine (tertiary N), sarcosine (secondary N) and L-methionine (thioether group), in CH 2 Cl 2 , proceed with the formation of complicated mixtures of products ( 1 H and 31 P NMR spectroscopy). Thus, the L-N,Ndimethylphenylalanine and L-methionine acylchloride derivatives have not been known heretofore, while the highly moisture sensitive [NH(Me)CH 2 COCl][WOCl 5 ] has been recently obtained by ourselves from sarcosine/WCl 6 .…”

“…When a dichloromethane 1 : 1 molar mixture of PCl 5 and NbCl 5 was treated with L-N,N-dimethylphenylalanine or sarcosine, 31 the subsequent 31 P NMR analysis on the reaction solution evidenced the presence of POCl 3 as prevalent phosphorous species [singlet at 6.2 ppm (from PCl 5 /NbCl 5 /L-N,N-dimethylphenylalanine) and 5.6 ppm (from PCl 5 /NbCl 5 /sarcosine), respectively]. 13b, 29,32 The corresponding [NbCl 6 ] À a-ammonium acylchloride salts, 5a-b, were isolated at room temperature in 40-50% yields (Scheme 7). The presence of [NbCl 6 ] À in 5a-b was unambiguously detected by a typical 93 Nb NMR resonance around 0 ppm.…”

MoCl5 as an effective chlorinating agent towards α-amino acids: synthesis of α-ammonium-acylchloride salts and α-amino-acylchloride complexes

“…6 According to the Fischer procedure, 6a,7 the combination of PCl 5 with α-amino acids in chlorinated solvents leads to the corresponding α-ammonium-acylchloride derivatives, in the form of either [Cl] − or [PCl 6 ] − salts depending on the PCl 5 / amino acid ratio. 8 The products are generally fairly-stable at room temperature, when they contain a primary ammonium group. Increasing the degree of N-substitution may favour HCl elimination and subsequent condensation reactions; moreover, outcomes alternative to the formation of the acylchloride function become operative in the case of N-trisubstituted α-amino acids.…”