208 * To whom all correspondence should be sent: E-mail: vkurteva@orgchm.bas.bg © 2015 Bulgarian Academy of Sciences, Union of Chemists in Bulgaria Bulgarian Chemical Communications, Volume 47, Number 1 (pp. 208–220) 2015 Novel 13-membered cyclic dioxatetraaza scaffolds – synthesis, solution and solid state characterization A. A. Petrova 1 , S. M. Angelova 1 , I. A. Nikolchina 1 , R. I. Russev 2 , V. B. Kurteva 1 *, B. L. Shivachev 2 *, R. P. Nikolova 2 1 Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 9, 1113 Sofia, Bulgaria 2 Institute of Mineralogy and Crystallography “Acad. Ivan Kostov”, Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 107, 1113 Sofia, Bulgaria Received December, 2014; Revised January, 2015 A series of three novel ligands with 1,4,8,11-tetraazacyclotridecine-2,10-dione skeleton, possessing relatively hindered amine fragment and variable substitution pattern at the aryl group in the amide moiety, was designed and obtained via an improved synthetic protocol. The macrocycles were analysed by NMR spectra in solution and by single crystal and powder XRD in solid state. The 13-membered ring conformation was discussed and compared with literature data. Key words: 1,4,8,11-tetraazacyclotridecine-2,10-diones, NMR, single crystal XRD, powder XRD INTRODUCTION Macrocyclic polyfunctional molecules are of growing interest as they are widely applied as scaf- folds in the combinatorial synthesis of artificial receptors for ions with medical and environmental potential [1–16]. Among the broad variety of syn- thetic macrocycles [17–26], polyaza ligands have received special attention due to their outstand- ing coordination abilities [27–34]. In particular, dioxаtetraaza macrocycles possess unique proper- ties due to their dual features between oligopeptides and saturated cyclic amines. The characteristics of the amide group and the hydrogen-bonding capabil- ity of both NH and C=O moieties [35] determine the amino acid like ligands’ properties. The latter insti- gated the extraordinary research in supramolecular chemistry in last decades on the amide-based recep- tors for molecule and ion recognition [36–49]. The most widely studied dioxаtetraaza macrocy- cles are built of o-phenylene diamine amide frag- ment and saturated amine unit. The usual protocol for their construction is based on subsequent acyla- tion of o-phenylene diamine and reaction with bis- amine. Among the latter, unsubstituted ethylene and propylene α,ω-diamines are commonly used [42, 46, 49]. The corresponding 12- and 13-membered cy- clic products are isolated in low to moderate yields and studied as ligands for metal complexes. Herein, we report on the synthesis of three new 13-membered cyclic dioxаtetraaza ligands, conven- ient scaffolds for synthetic protein surface receptors, via improved protocol and their characterization in solution and solid state. EXPERIMENTAL Synthesis All reagents were purchased from Aldrich, Merck and Fluka and were used without any further purification. Fluka silica gel/TLC-cards 60778 with fluorescent indicator 254 nm were used for TLC chromatography and R f -values determination. The melting points were determined in capillary tubes on SRS MPA100 OptiMelt (Sunnyvale, CA, USA) automated melting point system with heating rate 1 °C/min. The NMR spectra were recorded on a Bruker Avance II+ 600 spectrometer (Rheinstetten, Germany) at 25 °C; the chemical shifts were quoted in ppm in δ-values against tetramethylsilane (TMS) as an internal standard and the coupling constants were calculated in Hz. The assignment of the sig-