Stacked Naphthyls and Weak Hydrogen-Bond Interactions Govern the Conformational Behavior of P-Resolved Cyclic Phosphonamides: A Combined Experimental and Computational Study

Abstract

P-Enantiomerically pure cyclic phosphonamides have been synthesized via a cyclization reaction of (S,S)-aminobenzylnaphthols with chloromethylphosphonic dichloride. The reaction is highly stereoselective and gives almost exclusively (S,S,SP)-cyclic phosphonamides in good yields. Analysis of the X-ray crystal structures shows clearly that the cyclization reaction forces the two naphthyl rings into a stable parallel displaced stacking assembly and indicates also the existence of intramolecular CH···π interactions and weak forms of intermolecular hydrogen bondings, involving the oxygen and the chlorine atoms. QM computations and NMR spectra in solution confirm the stacked molecular assembly as the preferred arrangement of the two naphthyl groups.

Structural insights into methyl- or methoxy-substituted 1-(α-aminobenzyl)-2-naphthol structures: the role of C—H...π interactions

“…These molecules were found to be isostructural, with the halogen atom not being involved in any peculiar binding interactions, while the C-HÁ Á Á interactions dominated the crystal packing. As a continuation of our work (Capozzi & Cardellicchio, 2017;Capozzi, Capitelli et al, 2014; on the synthesis and application of aminobenzylnaphthols, we decided to extend this class of molecules and investigate the effect of nonhalogen substituents on the phenyl groups, with a particular focus on methyl or methoxy groups. The methyl substituent was chosen because it is known to have almost the same molecular volume as a Cl atom.…”

“…Aminobenzylnaphthols 4 and 5 were synthesized according to a reported simple and straightforward procedure (Cardellicchio et al, 2012;Capozzi, Capitelli et al, 2014). Addition of ethanol to the crude reaction mixture, with subsequent digestion of the slurry with ultrasound, caused the precipitation of (S,S)-5 (35% yield).…”

“…Recently, some of us (Capozzi, Capitelli et al, 2014;Cardellicchio et al, 2012) applied the Betti reaction using chiral (R)-or (S)-arylethylamines ( Fig. 1) to obtain a library of chiral aminobenzylnaphthol compounds.…”

Synthesis and Computational Study of Semicroconaines and Nonsymmetric Croconaines

“…Mp > 300 °C. 2965, 2926, 2859, 1694, 1653, 1599, 1553, 1504, 1485, 1364, 1285, 1198thiazol-3-ium-2-yl)methylene)-3,4-dioxocyclopent-1-enolate (S7). Compound S7 was synthesized from 2-methyl-3-octyl-1,3-benzothiazol-3-ium iodide 7 (125 mg, 0.32 mmol) and croconic acid (54 mg, 0.38 mmol) in a mixture of water/ acetone (1:1) (5 mL) according to the general procedure.…”

Synthesis, Computational, and Anticancer In Vitro Investigations of Aminobenzylnaphthols Derived from 2-Naphtol, Benzaldehydes, and α-Aminoacids via the Betti Reaction

“…Aminobenzylnaphthols formed in this transformation, the so-called Betti bases, are a class of molecules found in many natural and synthetic compounds with a wide range of interesting activities and applications [13]. Betti base derivatives were tested as antitumor agents [14], sodium-and chloride-dependent neutral and basic amino acid transporter B(0+) (SLC6A14) blockers [13], antiyeast agents inhibiting Candida albicans growth [15], antitumor and antioxidants [16], and multidrug resistance (MDR) reversal agents [17].…”