Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9, 1764-1775 2025 Publisher: Learning Gate DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate © 2025 by the authors; licensee Learning Gate History: Received: 7 July 2025; Revised: 19 August 2025; Accepted: 22 August 2025; Published: 26 September 2025 * Correspondence: nurasar.82@korkyt.kz Synthesis of new asymmetrical frame phosphonates based on Sesamol A. Zalaltdinova1, N. Appazov2*, Yu. Sadykova1, A. Gazizov1, A. Burilov1 1Laboratory of Elementorganic Compounds, Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 420088, Kazan, Russia; zalaltdinova.alena@iopc.ru (A.Z.), sadykova@iopc.ru (Y.U.S.), agazizov@iopc.ru (A.G.), burilov@iopc.ru (A.B.). 2Department of Engineering Technology, Korkyt Ata Kyzylorda University, 120014, Kyzylorda, Kazakhstan; nurasar.82@korkyt.kz (N.A). Abstract: A method for synthesizing new asymmetrical frame phosphonates is proposed, based on the reaction of dichlorophosphonate with an equimolar mixture of two different phenols in toluene, in the presence of trifluoroacetic acid. The reaction of sesamol with resorcinol (or 2-methylresorcinol or pyrogallol) and 2-ethoxyvinyl dichlorophosphonate yielded an unexpected result—a crystalline product with good solubility in dimethyl sulfoxide, representing an inseparable mixture of asymmetrical and symmetrical frame phosphonates based on sesamol. Due to their similar chromatographic mobility, it was not possible to isolate the individual compounds. A similar outcome was observed when 2- ethoxyvinyl dichlorophosphonate reacted with a mixture of sesamol and 2,4-dimethylresorcinol: a mixture of symmetrical and asymmetrical frame phosphonates was formed, with the symmetrical product derived from 2,4-dimethylresorcinol. This synthetic outcome can be explained by the higher reactivity of 2,4-dimethylresorcinol compared to sesamol. Ultimately, in both reactions, the symmetrical frame phosphonate based on sesamol was formed and subsequently isolated in its pure form. The validity of the obtained results is supported by modern physicochemical analytical methods, including mass spectrometry (MALDI-TOF), IR spectroscopy, ¹H, ¹³C, and ³¹P NMR spectroscopy, elemental analysis, and X-ray crystallography. Keywords: 2-ethoxyvinyl dichlorophosphonate, Asymmetrical frame phosphonates, Equimolar mixture, Phenols, Resorcinol, Sesamol. 1. Introduction The chemistry of three-dimensional, spatially organized structures has been developing particularly actively in recent years, largely due to the creation of new efficient and selective heterogeneous and homogeneous catalysts. These catalysts contribute to the development of energy-saving technologies and the advancement of "green" chemistry [1-3]. Phosphorus-containing cage compounds with endocyclic phosphorus-carbon bonds exhibit unusual reactivity and physicochemical properties, making them promising both for fundamental research and practical applications [4-6]. A prominent example of such phosphorus-containing cage compounds is derivatives of 7-phospha-1,3,5-triazaadamantane, which are widely used as ligands in metal complexes involved in various homogeneous catalytic reactions. Moreover, their areneruthenium complexes (RAPTA-C, RAPTA-B) exhibit pronounced antitumor properties with low overall toxicity and are considered promising antimetastatic agents [7, 8]. Previously, we developed a simple new "one-pot" synthesis method for a class of phosphorus- containing cage compounds with two endocyclic phosphorus-oxygen bonds and one endocyclic phosphorus-carbon bond, previously unknown in the literature. This method is based on a novel cascade reaction of 2-ethoxyvinyl dichlorophosphonate with various phenols. It is worth noting that the proposed approach allows only the synthesis of symmetrical cage compounds [9, 10]. Asymmetrical cage phosphonates — a new class of phosphorus-organic compounds – were obtained by us relatively https://orcid.org/0000-0002-4822-7330 https://orcid.org/0000-0001-8765-3386 https://orcid.org/0000-0003-2093-2860 https://orcid.org/0000-0001-9899-9606 https://orcid.org/0000-0003-2938-7352 1765 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate recently as a result of a new reaction of oxaphosphinines with various phenols followed by their cyclization [11, 12]. Expanding on these studies, the present article introduces a new method for the synthesis of asymmetrical cage phosphonates based on a naturally occurring phenol, namely sesamol (3,4- methylenedioxyphenol). Due to its pharmacological activity, sesamol is a component of various highly effective biologically active substances [13-15]. 2. Material and Methods NMR spectra were recorded using high-resolution pulsed NMR spectrometers: Bruker Avance-400 (^1H – 399.93 MHz; ^13C – 100.57 MHz; ^31P – 161.90 MHz), Bruker Avance-500 (^1H – 500.13 MHz; ^13C – 125.76 MHz; ^31P – 202.46 MHz), and Bruker Avance-600 (^1H – 600.13 MHz; ^13C – 150.92 MHz; ^31P – 242.94 MHz), in d₆-DMSO (at 45 °C) or CDCl₃ (at 25 °C) solvents. Chemical shifts for protons and carbon atoms were referenced to the residual signals of the corresponding solvents (d₆- DMSO or CDCl₃), with the δ scale calibrated against TMS used as the internal standard. Chemical shifts for phosphorus (^31P) were measured relative to an external standard — a solution of H₃PO₄. The following parameters were used for two-dimensional correlation NMR experiments: ¹H–¹³C HSQC – optimized for ¹JCH = 165 Hz; ¹H–¹³C HMBC – for ¹JCH = 165 Hz and ³JCH = 8 Hz; ¹H–³¹P HMBC – for J = 8 Hz. IR spectra were recorded using a Bruker Vector-22 FT-IR spectrometer in the range of 400–4000 cm⁻¹. The samples were prepared as KBr pellets. Mass spectra were obtained using matrix-assisted laser desorption/ionization (MALDI) on an UltraFlex III TOF/TOF mass spectrometer (Bruker Daltonics). Measurements were conducted in positive ion mode (detection of positively charged ions) in the m/z range of 100–5000, using a Nd:YAG laser (λ = 355 nm). Plastic and metal substrates were used as targets. 2,5-Dihydroxybenzoic acid (DHB) and para-nitroaniline (p-NA) served as matrices. Elemental analysis (C, H, N content) was performed using a high-temperature dual-reactor analyzer Carlo-Erba EA 1108. Halogens were determined using the Schöninger method, and phosphorus was quantitatively determined via pyrolysis in an oxygen stream. X-ray structural analysis of the compounds was performed using equipment from the Shared Research Center for Physical Methods of Investigating Substances and Materials at the N. S. Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences. Structure determination was carried out using the direct method with the SIR program [16] and the refined structural model was obtained using the SHELXL–97 program [17] in both isotropic and anisotropic approximations. Calculations were carried out using the WinGX [18] and APEX2[19] software packages. Hydrogen atom coordinates were calculated based on stereochemical considerations and refined using the "riding" model. Intermolecular interactions were analyzed using the PLATON program [20]. General Method for Synthesizing Cage Phosphonates 4a–c and 5. A mixture of 0.73 g (5.3 mmol) sesamol, 0.58 g (5.3 mmol) resorcinol (or 0.66 g (5.3 mmol) 2-methylresorcinol, 0.67 g (5.3 mmol) pyrogallol, or 0.66 g (5.3 mmol) 2,4-dimethylresorcinol) and 0.6 g (5.3 mmol) trifluoroacetic acid in 30 mL of boiling toluene was treated dropwise with 1 g (5.3 mmol) of 2-ethoxyvinyl dichlorophosphonate in 5 mL of toluene. The reaction mixture was refluxed for 12 hours. The resulting precipitate was filtered, washed initially with distilled water, then with acetone, and dried under vacuum to constant weight, yielding a mixture of cage phosphonates. The filtrate was evaporated under vacuum, and the resulting solid was washed with diethyl ether, filtered, and dried under vacuum to constant weight. This gave 0.97–1.05 g (53–57%) of the symmetrical cage phosphonate 5 based on sesamol. 3-Hydroxy-13H-6,13-methano[1,3]dioxolo[4',5':4,5]benzo[1,2-d]benzo[g] [1,3,2]dioxaphosphocin 6-oxide (4a) and 13H-6,13-methano[1,3] dioxolo[4',5':4,5] benzo[1,2- d][1,3]dioxolo[4',5':4,5]benzo[1,2-g][1,3,2]dioxaphosphocin 6-oxide (5) 1766 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate A fine white powder, m.p. >300 °C. 31Р NMR (242.94 MHz, d6-DMSO, δ, ppm): 13.7 and 13.9. 1Н NMR (600.13 MHz, d6- DMSO, δ, ppm, J/Hz): 2.63 (dd., 4Н, 2JРН=14.4, 3JНН=3.7, СН2Р), 4.58 (dt, 2Н, 3JНН=3.8, 3JРН=35.8, PCH2CH), 5.93 (с, 1Н, Н-10), 5.94 (s, 2Н, Н-2*), 6.00 (s, 1Н, Н-10), 6.01 (s, 2Н, Н-10*), 6.40 (d, 1Н, 4JНН=2.3, Н-4), 6.48 (dd., 1Н, 3JНН=8.4, 4JНН=2.3, Н-2), 6.72 (s, 1Н, Н-8), 6.73 (s, 2Н, Н-4*,8*), 7.07 (s, 1Н, Н-12), 7.13 (s, 2Н, Н-12*,14*), 7.29 (d, 1Н, 3JНН=8.4, Н-1), 9.69 (s, 1Н, ОН). IR spectrum (KBr pellet, ν/cm⁻¹): 1242 (P=O), 1624 (С=СAr), 3237 (OH). Mass spectrum (MALDI-TOF, m/z): 341 [M+Na]+. 13H-6,13-Methano[1,3]dioxolo[4',5':4,5]benzo[1,2- d][1,3]dioxolo[4',5':4,5]benzo[1,2-g][1,3,2]dioxaphosphocin 6- oxide (5) Yield: 0.97–1.05 g (53–57%), white powder, m.p. > 300 °C. 31Р NMR (242.94 MHz, d6- DMSO, δ, ppm): 13.8. 1Н NMR (600.13 MHz, d6- DMSO, δ, ppm, J/Hz): 2.64 (dd, 2Н, 2JРН=16.2, 3JНН=3.8, СН2Р), 4.55 (dt, 1Н, 3JНН=3.8, 3JРН=35.1, PCH2CH), 5.94 (s, 2Н, Н- 2), 6.01 (s, 2Н, Н-10), 6.73 (s, 2Н, Н- 4,8), 7.13 (s, 2Н, Н-12,14). 13С NMR (150.92 MHz, d6- DMSO, δ, ppm, J/Hz): 19.8 (d, 1JРС=111.1, PCH2), 39.7 (d, 2JРС=20.8, PCH2CH), 100.8 (d, 3JРС=8.3, С-4,8), 102.2 (s, С-2,10), 107.8 (s, С-12,14) 120.8 (d, 2JРС=10.9, С-4’,7’), 144.0 (s, С-3’,8’), 145.3 (d, 3JРС=7.6, С-12’,13’), 147.5 (s, C-11’,14’). IR Spectrum (KBr pellet, ν/cm⁻¹): 1292 (P=O), 1634 (С=СAr). Found (%): С 55.30, Н 3,07, Р 8,95. С16H11О7Р. Calculated (%):С 55.49, Н 3.17, Р 8.97. Mass Spectrum (MALDI-TOF, m/z): 346 [M]+, 347 [M+H]+, 369 [M+Na]+, 385 [M+K]+. 3-Hydroxy-4-methyl-13H-6,13-methano[1,3]dioxolo[4',5':4,5]benzo[1,2- d]benzo[g][1,3,2]dioxaphosphocin 6-oxide (4b) and 13H-6,13-methano[1,3]dioxolo[4',5':4,5]benzo[1,2-d][1,3]dioxolo[4',5':4,5]benzo[1,2- g][1,3,2]dioxaphosphocin 6-oxide (5) White powder, m.p. > 300 °C. 31Р NMR (161.90 MHz, d6- DMSO, δ, м.д.): 13.6 and 13.8. 1Н NMR (399.93 MHz, d6- DMSO, δ, ppm, J/Hz): 1.98 (s, 3Н, СН3), 2.60 (m, 4Н, СН2Р), 4.56 (dt, 2Н, 3JНН=5.5, 3JРН=38.2, PCH2CH), 5.92 (s, 1Н, Н-10), 5.94 (s, 2Н, Н-2*), 6.00 (s, 1Н, Н-10), 6.01 (s, 2Н, Н-10*), 6.51 (dd, 1Н, 3JНН=8.4, 4JНН=5.9, Н-2), 6.71 (s, 1Н, Н-8), 6.73 (s, 2Н, Н-4*,8*), 7.03 (s, 2Н, Н-12*,14*), 7.04 (s, 1Н, Н-12), 7.11 (d, 1Н, 3JНН=8.4, Н-1), 9.53 (s, 1Н, ОН). IR Spectrum (KBr pellet, ν/cm⁻¹): 1267 (P=O), 1614 (С=СAr), 2926 (СH3), 3229 (OH). Mass spectrum (MALDI-TOF, m/z): 355 [M+Na]+, 371 [M+K]+. 1767 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate 3,4-Dihydroxy-13H-6,13-methano[1,3]dioxolo[4',5':4,5]benzo[1,2- d]benzo[g][1,3,2]dioxaphosphocin 6-oxide (4c) and 13H-6,13-methano[ 1,3]dioxolo[4',5':4,5] benzo[1,2-d] [1,3]dioxolo[4',5':4,5] benzo[1,2- g][1,3,2]dioxaphosphocin 6-oxide (5) White powder, m.p. > 300 °C. 31Р NMR (161.90 MHz, d6- DMSO, δ, ppm): 13.6 and 13.8. 1Н NMR (399.93 MHz, d6- DMSO, δ, ppm, J/Hz): 2.63 (m, 4Н, 3JНН=3.8, 2JРН=16.1, СН2Р), 4.55 (dt, 2Н, 3JНН=4.1, 3JРН=35.1, PCH2CH), 5.92 (s, 1Н, Н-10), 5.94 (s, 2Н, Н-2*), 6.00 (s, 1Н, Н-10), 6.01 (s, 2Н, Н-10*), 6.46 (d, 1Н, 3JНН=8.3, Н-2), 6.72 (s, 1Н, Н-8), 6.73 (s, 2Н, Н-4*,8*), 7.74 (d, 1Н, 3JНН=8.3, Н-1), 7.04 (s, 1Н, Н-12), 7.13 (s, 2Н, Н-12*,14*), 8.86 (s, 1Н, ОН), 9.22 (s, 1Н, ОН). IR spectrum (KBr pellet, ν/cm⁻¹): 1246 (P=O), 1636 (С=СAr), 3424 (OH). Mass spectrum (MALDI-TOF, m/z): 357 [M+Na]+, 369 [M*+Na]+, 385 [M*+K]+. 3-Hydroxy-2,4-dimethyl-13H-6,13- methano[1,3]dioxolo[4',5':4,5]benzo[1,2- d]benzo[g][1,3,2]dioxaphosphocin 6-oxide (7) and 3,9- Dihydroxy-2,4,8,10-tetramethyl-12H-6,12- methanodibenzo[d,g][1,3,2]dioxaphosphocin 6-oxide (8). White powder, m.p. > 300 °C. 31Р NMR (242.94 МHz, d6- DMSO, δ, ppm): 13.8 and 14.1. 1Н NMR (399.93 МHz, d6-DMSO, δ, ppm, J/Hz): 2.02-2.08 (s, 18Н, СН3), 2.60 (d, 4Н, 2JРН=17.0, СН2Р), 4.49 (m, 2Н, 3JНН=3.9, 3JРН=31.6, PCH2CH), 5.92 (s, 1Н, Н-10), 6.00 (s, 1Н, Н-10), 6.72 (s, 1Н, Н-8), 6.97 (s, 1Н, Н-1), 7.05 (s, 2Н, Н-1*,11*), 7.06 (s, 1Н, Н-12), 8.50 (s, 1Н, ОН), 8.54 (s, 2Н, ОН). IR spectrum (KBr pellet, ν/cm⁻¹): 1276 (P=O), 1617 (С=СAr), 2923 (СH3), 3574 (OH). Mass spectrum (MALDI-TOF, m/z): 347 [M+Н]+, 369 [M+Na]+, 385 [M+K]+, 715 [2M+Na]+. 2-Hydroxy-15H-8,15-methano[1,3]dioxolo[4',5':4,5]benzo[1,2-d]naphtho[1,2- g][1,3,2]dioxaphosphocin 8-oxide (10). To a boiling solution of 0.73 g (5.3 mmol) of sesamol, 0.85 g (5.3 mmol) of 2,7-naphthalenediol, and 0.6 g (5.3 mmol) of trifluoroacetic acid in 30 mL of toluene, a solution of 1.0 g (5.3 mmol) of 2- ethoxyvinyl dichlorophosphonate in 5 mL of toluene was added dropwise. The reaction mixture was refluxed for 10 hours. The resulting precipitate was filtered off, washed first with distilled water and then repeatedly with acetone, and dried under vacuum to constant weight, yielding the cage phosphonate 10. The filtrate was evaporated under reduced pressure, and the resulting solid was washed with diethyl ether, filtered, and dried under vacuum to constant weight. As a result, 1.03 g (56%) of the symmetrical cage phosphonate 10 based on sesamol was obtained. 1768 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate Yield: 0.68 g (35%), white powder, m.p. > 300 °C. 31Р NMR (242.94 MHz, d6-DMSO, δ, ppm): 15.1. 1Н NMR (600.13 МHz, d6-DMSO, δ, ppm, J/Hz): 2.76 (m, 2Н, СН2Р), 5.31 (dt, 1Н, 3JНН=4.0, 3JРН=34.5, PCH2CH), 5.88 (s, 1Н, Н-12), 6.02 (s, 1Н, Н-12), 6.77 (s, 1Н, Н-10), 7.00 (d, 1Н, 3JНН=8.8, Н-6), 7.05 (dd, 1Н, 3JНН=8.8, 4JНН=1.8, Н-3), 7.17 (s, 1Н, Н-14), 7.71 (s, 1Н, Н-1), 7.72 (d, 1Н, 3JНН=8.8, Н-5), 7.77 (d, 1Н, 3JНН=8.8, Н-4), 10.02 (s, 1Н, ОН). 13С NMR (150.92 МHz, d6-DMSO, δ, ppm, J/Hz): 20.4 (d, 1JСP=111.0, PCH2); 35.8 (d, 2JСP=10.0, PCH2CH); 101.0 (d, 3JСР=8.4, С-10), 102.3 (s, С-12), 105.9 (s, С-1), 107.6 (s, С-14), 116.0 (d, 3JСP=7.7, С-6), 117.9 (s, С-3), 119.4 (d, 3JСP=10.1, С-15’), 119.8 (d, 2JСP=10.5, С- 14'), 125.4 (s, C-4’), 130.0 (s, C-5), 131.1 (s, C-4), 132.0 (s, C-1’), 143.7 (s, C-10’), 146.0 (d, 3JСP=7.0, С-9’), 147.6 (s, C-13’), 149.5 (d, 2JСP=7.9, С-6’), 157.4 (s, C-2). IR spectrum, (KBr pellet, ν/cm⁻¹): 1234 (P=O), 1623 (С=СAr), 3314 (OH). Found (%): С 61.92, Н 3.48, Р 8.34. С19H13О6Р. Calculated (%): С 61.97, Н 3.56, Р 8.41. Mасс-спектр (MALDI-TOF, m/z): 369 [M+Н]+, 391 [M+Na]+. 3. Results and Discussion The synthesis was carried out according to our previously developed method for obtaining asymmetric cage phosphonates, which is based on the reaction of dichlorophosphonate 1 with an equimolar mixture of two different phenols in toluene in the presence of trifluoroacetic acid [11, 12]. In the first stage, we performed the reaction of a mixture of sesamol 2 with resorcinol 3a (or 2- methylresorcinol (3b) or pyrogallol (3c)) and 2-ethoxyvinyl dichlorophosphonate 1 (Scheme 1). As a result, an unexpected outcome was obtained: the product formed as crystals with good solubility in DMSO, representing an inseparable mixture of the asymmetric cage phosphonate 4a–c and the symmetric cage phosphonate based on sesamol 5. It turned out that these compounds possess very similar chromatographic mobility, and we were unable to isolate them as individual substances. The structure and composition of the cage phosphonate mixture 4a–c and 5 were determined based on ^31P NMR, ^1H NMR, IR spectroscopy, and elemental analysis. Scheme 1 In the ³¹P NMR spectra of the cage phosphonate mixture 4a–c and 5, two signals were observed with phosphorus chemical shifts in the region of 13–14 ppm. In the ¹H NMR spectrum, the signals of the methylene protons adjacent to the phosphorus atom (H-14 and H-14*) appear as a multiplet at δ 2.63 ppm (³Jₙₙ = 3.8 Hz, ²Jₚₙ = 16.1 Hz), while the methine protons (H-13 and H-13*) appear as doublets of triplets at δ 4.55 ppm (³Jₙₙ = 4.1 Hz, ²Jₚₙ = 35.1 Hz). The assignment of the remaining proton signals was made based on their multiplicity and integral intensity. 1769 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate It is important to note that, in addition to the cage phosphonate mixture 4a–c and 5, we were able to isolate the symmetric sesamol-based cage phosphonate 5 as an individual compound. It forms white crystals with good solubility in DMSO. The structure and composition of the sesamol-derived cage phosphonate 5 were confirmed by 31Р-, 1Н-, 13С- NMR spectroscopy, IR spectroscopy, elemental analysis, and MALDI mass spectrometry. In the 31Р NMR phosphonate 5 displays a single signal at δ 13.8 ppm. In the 1H NMR spectrum, the methylene protons adjacent to phosphorus appear as a doublet of doublets at δ 2.64 ppm (3JНН 3.8 Hz, 2JРН 16.2 Hz), and the methine proton appears as a doublet of triplets at δ 4.52–4.59 ppm (3JНН 3.8 Hz, 3JРН 35.1 Hz). The signals of the dioxymethylene group protons are observed as two singlets at δ 5.94 ppm and 6.01 ppm, while the sesamol fragment protons are seen as two singlets at δ 6.73 ppm and 7.13 ppm. In the 13C-(1H) NMR spectrum contains characteristic carbon signals: С-14 (δС 19.8 ppm, 1JРС 111.1 Hz), С-13 (δС 39.7 ppm, 2JРС 20.8 Hz), С-4,8 (δС 100.8 ppm, 3JРС 8.3 Hz), C-4’,7’ (δС 120.8 ppm, 3JРС 10.9 Hz), C-12’,13’ (δС 145.3 ppm, 3JРС 7.6 Hz), these carbons exhibit spin–spin coupling with the phosphorus nucleus and appear as doublets. The assignment of the aromatic carbon signals was based on their multiplicity and integral intensity. In the MALDI-TOF mass spectrum, molecular ion peaks were recorded at m/z 346 [M]+, 347 [M+H]+, 369 [M+Na]+, and 385 [M+K]+, corresponding to the sesamol-based cage phosphonate 5. The reaction of 2-ethoxyvinyl dichlorophosphonate 1 with a mixture of sesamol 2 and 2,4- dimethylresorcinol 6 proceeds under analogous conditions (Scheme 2). In this case, the formation of a mixture of the symmetric cage phosphonate 8 and the asymmetric cage phosphonate 7 is also observed, with the only difference being that the symmetric cage phosphonate 8 is derived from 2,4- dimethylresorcinol. This synthetic outcome can be attributed to the higher reactivity of the 2,4- dimethylresorcinol molecule compared to sesamol. As in the previous reaction, we also observe the formation of the symmetric sesamol-based cage phosphonate 5, independently of the product mixture, which can subsequently be isolated as an individual compound. Scheme 2 The structure and composition of the cage phosphonate mixture 7 and 8 were established based on data from ^31P and ^1H NMR spectroscopy, IR spectroscopy, and elemental analysis. The mixture of cage phosphonates 7 and 8 forms white crystals with good solubility in DMSO. In the ³¹P NMR spectrum of the cage phosphonate mixture 7 and 8, two signals corresponding to phosphorus atoms are observed at δ 13.8 and 14.1 ppm. In the ^1H NMR spectrum, signals from methyl 1770 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate group protons appear as singlets in the high-field region at δ 2.02–2.08 ppm. The methylene protons (H-14 and H-13*) adjacent to the phosphorus atom appear as a doublet at δ 2.60 ppm (2JРН=17.0 Гц); the signals of the methine protons (H-13 and H-12*) appear as a multiplet at δ 4.49 ppm. (3JНН 3.9 Гц, 3JРН 31.6 Гц). The aromatic proton signals appear in the ^1H NMR spectrum as singlets in the region of δ 5.92–7.06 ppm. The structure of cage phosphonates 7 and 8 was further confirmed by X-ray crystallographic analysis. The crystals obtained from the synthesis represent a cocrystal of compounds 7 and 8 in a 1:1 ratio (Figure 1). Compound 8, despite its chemically symmetric structure, is not entirely symmetric geometrically. The bond lengths between the phosphorus atom and the oxygen atoms O1 and O2 are 1.574(5) Å and 1.595(6) Å, respectively, while the bond length to O3 is 1.461(6) Å. Compound 7, which is chemically nonequivalent to compound 8, exhibits very similar geometry. The phosphorus–oxygen bond lengths are 1.596(5) Å and 1.587(6) Å, respectively, and the length of the P=O double bond is 1.468(6) Å. Figure 1. Molecular structure of compounds 7 and 8 in the cocrystal. The angles between the planes of the bicyclic fragments are 81.52° in the symmetric compound 8 and 74.20° in the asymmetric compound 7. The molecular packing in the cocrystal of compounds 8 and 7 is shown in Figure 2. 1771 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate Figure 2. Molecular packing in the 7/8 cocrystal. The molecules of compounds 7 and 8 are connected in the crystal by classical hydrogen bonds between the hydroxyl group of one molecule and the phosphoryl oxygen atom of another, resulting in infinite zigzag chains, which are further linked into a three-dimensional network through weaker C– H…π and π…π interactions. The 7/8 cocrystals are monoclinic, with space group Cc. Unit cell parameters: a=9.3130(3)Å, b=13.3105(5)Å, c=25.1206(9) Å, β=90.857(2)˚, V=3113.62(19)Å3. Expanding the synthetic scope of this reaction, we carried out the reaction of 2-ethoxyvinyl dichlorophosphonate 1 with sesamol 2 and 2,7-naphthalenediol 9 in boiling toluene in the presence of trifluoroacetic acid (Scheme 3). As a result, a new representative of the class of asymmetric cage phosphonates based on sesamol, compound 10, was obtained and successfully isolated as an individual substance. As in the previously described reactions, the formation of the symmetric sesamol-based cage phosphonate 5 was also observed. Scheme 3 The structure and composition of the new asymmetric cage phosphonate 10 were confirmed by ¹H, ³¹P и ¹³C NMR spectroscopy, IR spectroscopy, MALDI mass spectrometry, and elemental analysis. 1772 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate In the 31Р NMR spectrum of cage phosphonate 10, shown in Figure 3, a single signal is observed with a phosphorus chemical shift at approximately δ 15 ppm. In the 1Н NMR spectrum of compound 10 (figure 3), the methylene protons in the α-position to the phosphorus atom (H-16) appear as a multiplet at δ 2.76 ppm, while the methine proton (H-15) appears as a doublet of triplets at δ 5.31 ppm (3JНН 4.0 Hz, 3JРН 34.5 Hz). The naphthalene ring protons are represented in the 1Н NMR spectrum as follows a doublet of doublets at δ 7.05 ppm (Н-3, 3JНН=8.8 Hz, 4JНН=1.8 Hz), doublets at δ 7.00 ppm (Н-6, 3JНН 8.8 Hz), δ 7.72 ppm (Н-5, 3JНН 8.8 Hz), and δ 7.77 ppm (Н-4,3JНН 8.8 Hz), as well as a singlet at δ 7.71 ppm (Н-1). The protons of the dioxobenzene fragment (H-10, H-12, H-14) are observed as singlets. In the 13C NMR spectrum of the asymmetric cage phosphonate 10 (shown in Figure 4), carbon atoms C-16 (δС 20.4 ppm, 1JРС 111.0 Hz) and С-15 (δС 35.8 ppm, 2JРС 10.0 Hz), show spin–spin coupling with the phosphorus atom and appear as doublets. In thearomatic region of the 13C NMR spectrum the following carbon atoms also appear as doublets due to phosphorus coupling: С-10 (δС 101.0 ppm, 3JРС 8.4 Hz), С-6 (δС 116.0 ppm, 3JРС 7.7 Hz), С-15’ (δС 119.4 ppm, 3JРС 10.1 Hz), С-14’ (δС 119.8 ppm, 2JРС 10.5 Hz), С-9’ (δС 146.0 ppm, 3JРС 7.0 Hz) and С-6’ (δС 149.5 ppm, 2JРС 7.9 Hz) appears as doublets. The assignment of the remaining aromatic carbon signals was made based on their multiplicity and integral intensity. In the MALDI-TOF mass spectrum, molecular ion peaks were recorded at m/z 369 [M+H]+ and 391 [M+Na]+, consistent with the molecular composition of asymmetric cage phosphonate 10. Figure 3. –1Н NMR spectrum (600.13 MHz, d₆-DMSO) of the compound 10. 1773 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate Figure 4. –13C-(1Н) NMR spectrum (150.92 MHz, d₆-DMSO) of the compound 10. Thus, as a result of the conducted study, we have developed a method for the synthesis of asymmetric cage phosphonates based on sesamol. The first representative of this class was obtained, and a molecular mixture of symmetric and asymmetric cage phosphonates was characterized using X-ray crystallographic analysis (XRD). 4. Conclusions Thus, as a result of the reaction of a mixture of sesamol with resorcinol (or 2-methylresorcinol or pyrogallol) with 2-ethoxyvinyl dichlorophosphonate, an unexpected outcome was obtained—a crystalline product with good solubility in dimethyl sulfoxide, representing an inseparable mixture of asymmetric cage phosphonate and symmetric cage phosphonate based on sesamol. In the reaction of 2-ethoxyvinyl dichlorophosphonate with a mixture of sesamol and 2,4- dimethylresorcinol, the formation of a mixture of symmetric and asymmetric cage phosphonates was also observed, with the only difference being that the symmetric phosphonate was derived from 2,4- dimethylresorcinol. Ultimately, the formation of the symmetric sesamol-based cage phosphonate was observed in all cases, occurring independently of the product mixture and allowing for its isolation as an individual compound. 1774 Edelweiss Applied Science and Technology ISSN: 2576-8484 Vol. 9, No. 9: 1764-1775, 2025 DOI: 10.55214/2576-8484.v9i9.10213 © 2025 by the authors; licensee Learning Gate Funding: The research was funded by the Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant Number: AP19677249). The X-ray diffraction data of the compounds were obtained at the Laboratory of Diffraction Research Methods of the A.E. Arbuzov Institute of Organic and Physical Chemistry, a branch of the Kazan Scientific Center of the Russian Academy of Sciences, within the framework of the state assignment funding of the Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences". Transparency: The authors confirm that the manuscript is an honest, accurate, and transparent account of the study; that no vital features of the study have been omitted; and that any discrepancies from the study as planned have been explained. This study followed all ethical practices during writing. Acknowledgments: The authors express their gratitude to the Shared Spectral-Analytical Center for the Study of Structure, Composition, and Properties of Substances and Materials of the Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences" for technical support in conducting the research. Copyright: © 2025 by the authors. This open-access article is distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). References [1] N. Natarajan, E. Brenner, D. Sémeril, D. Matt, and J. 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