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17 protocols using melting point b 540

1

Synthesis and Characterization of Pyrazolones

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All reagents were of analytical
grade, obtained from commercial suppliers, and used without further
purification. All pyrazolones were prepared according to previously
reported procedures.26 (link)−28 (link) Melting points were measured in an open capillary
using Büchi melting point B-540 apparatus and are uncorrected. 1H NMR and 13C NMR spectra were recorded on 400 and 100
MHz spectrometers, respectively, using tetramethylsilane
as internal standard. The 19F NMR spectra were obtained
using a 400 spectrometer (376 MHz). DMSO-d6 was used as the NMR solvents. High-resolution mass spectra (HRMS)
were acquired in the electron ionization (EI) mode using a time-of-flight
mass analyzer. Silica gel (300–400 mesh size) was used for
column chromatography. Thin-layer chromatography (TLC) analysis of
reaction mixtures was performed using silica gel plates.
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2

Melting Point Analysis of MIX-F

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The melting temperature range was determined by placing randomly selected aliquots of MIX-F into a capillary glass and analysing them by a Büchi Melting Point B-540 instrument (Flawil, Switzerland). Samples were placed into the instrument at room temperature, and then a heating rate of 5 °C/min was applied until complete melting. Similarly, the melting point of each single component were determined. The analyses were performed in triplicate, and results are reported as means ± SE (n = 3).
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3

Synthesis of 2-Fluorobenzaldehyde Derivatives

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The predominance of the materials
used in this work was commercially available from Acros, Merck, and
Aldrich. The starting compounds 1a1n were prepared by a reaction of 2-fluorobenzaldehyde and substituted
phenol or thiophenol compounds. The whole new products were described
by IR, 1H-NMR, 13C-NMR, GC–MS, and elemental
analysis. The reactions were observed using TLC by silica gel plates
and the products were made pure by column chromatography systems on
silica gel (Merck; 230–400 mesh), eluting with hexane–ethyl
acetate (v/v 9:1). GC–MS were recorded on a Shimadzu QP2010
Plus. The IR spectra were recorded on a Mattson 1000 spectrometer.
The NMR spectra were recorded at 500 or 400 MHz for 1H
and 125 or 101 MHz for 13C using Me4Si as the
internal standard in CDCl3. Melting points were measured
using Büchi Melting Point B-540.
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4

NMR Spectroscopy Data Reporting Protocol

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The 1H and 13C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Avance spectrometer 400 at 400 MHz and 100 MHz, respectively. Chemical shifts are given in ppm (δ) referenced to CDCl3 with 7.26 for 1H and 77.10 for 13C, and to d6-DMSO with 2.50 for 1H and 39.5 for 13C. In the case of multiplet, signals are reported as intervals and abbreviated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Coupling constants are expressed in hertz. High-resolution mass spectra (HRMS) were recorded on a BRUKER VPEXII spectrometer with ESI mode unless otherwise stated. Melting point was measured by BUCHI Melting Point B-540. The progress of the reactions was monitored by thin-layer chromatography on a glass plate coated with silica gel with fluorescent indicator (GF254). Column chromatography was performed on silica gel (200–300 mesh).
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5

Synthetic Procedures for Organic Compounds

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The chemicals were purchased from commercial sources (Sigma Aldrich, Acros Organics, TCI, Merck). Commercial grade reagents were used without further purification. Reactions were monitored by means of thin layer chromatography plates coated with 0.2 mm Silica Gel 60 F254 (Merck). TLC plates were visualized by UV irradiation (254 nm). The products were purified by crystallization, by means of column chromatography employing Silica Gel 60 (Merck). All melting points were determined on Melting Point B-540 apparatus (Buchi, Germany) and are uncorrected. NMR spectra were measured in CDCl3 solutions on a Bruker Avance 300 or 500 MHz apparatus. The chemical shifts δ are given in ppm, relating to chemical shift of the solvent. The coupling constants (J) are reported in hertz (Hz). Elemental analysis (C, H, N) was performed on a Thermo Scientific Flash 2000 Organic elemental analyser.
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6

Analytical Characterization of Organic Compounds

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The reagents were purchased from Merck Life Science S.r.l. and Biosynth Carbosynth®. Melting points were evaluated on a Buchi Melting Point B-540 instrument. They are uncorrected and were evaluated on chromatographically purified or recrystallized compounds. The reactions were controlled by thin layer chromatography (TLC), using Merck silica gel 60 F254 plates preloaded with fluorescent indicator and visualized with UV light (254 nm). Silica gel column (Kieselgel 60) was employed for preparative chromatographic purifications. Na2SO4 was used to dry all the solutions which were concentrated with a Buchi R-114 rotary evaporator at low pressure. Homogeneity of the products was evaluated by analytical reversed-phase HPLC (RP-HPLC) on a Shimadzu-10 ADsp HPLC system by means of a Phenomenex Kinetex XB-C18 column, 5 μm, 4.6 × 250 mm and applying the gradient of acetonitrile (CH3CN) in 0.1% aqueous trifluoroacetic acid (TFA), from 0% to 100% in 25 min, at a flow rate of 1 mL/min. Analytical RP-HPLC indicated a purity > 98%. 1H and 13C NMR spectra were recorded on Varian Mercury Plus 400 MHz instrument in dimethyl sulfoxide (DMSO‑d6). Chemical shifts are described in ppm, while peak patterns are reported using the abbreviations: m (multiplet), t (triplet), d (doublet), s (singlet). API 2000 Applied Biosystem mass spectrometer was used to determine mass spectra of the final products.
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7

Synthetic Characterization of Novel Compounds

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Reagent grade chemicals and analytical grade solvents were procured from Sigma-Aldrich and used for the synthesis, characterization and biological screening of title compounds. The analytical reagent [AR] grade solvents were purified by literature methods33 . TLC monitoring was performed on alumina supported silica gel 60 F254 plates (Merck, Darmstadt, Germany) and visualized under UV light. All 1H (400 MHz) and 13C NMR (400 MHz) spectra were recorded on Bruker NMR spectrometer. Chemical shifts were reported in ppm (δ) with reference to TMS (internal standard) using CDCl3, DMSO-d6 and TFA as solvents. Coupling constant (J) values were given in Hertz and the multiplicities were designated as br, broad; s, singlet; d, doublet; t, triplet; m, multiplet. Molecular weights of the synthesized compounds were checked by SHIMADZU LCMS-2020 series in ESI mode. Melting points were recorded in capillaries and on Buchi Melting Point B-540 and are uncorrected. IR data was recorded on Perkin Elmer Spectrum 100. Column chromatography was performed with 100–200 mesh silica.
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8

Assessing Wax Mixture Melting Points for Biocompatible Capsules

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Firstly, the melting point of different lanolin/cetyl alcohol mixtures was assessed (Fig. 1). Lanolin and cetyl alcohol were used as a wax coating because of their high biocompatibility, their wide usage as pharmaceutical excipients, and their food excipient status. Lanolin contains mainly (hydroxy-)sterol esters and wax esters, triterpene esters, and small amounts of dihydroxy wax esters, free sterols, free alcohols, and branched fatty acids [31 (link)]. To determine the melting point of different lanolin/cetyl alcohol wax mixtures, lanolin and cetyl alcohol were heated to 70 °C in a water bath and mixed in different proportions, and the resultant wax mixtures were added to melting point tubes. Once the wax mixtures were cooled down, a controlled temperature increase in a melting point apparatus (Melting Point B-540, Buchi Labortechnik, Flawil, Switzerland) allowed the precise determination of their melting range.

Schematic depiction of the workflow yielding wax-coated capsules. Firstly, different lanolin/cetyl alcohol mixtures are analysed in terms of melting point. Secondly, empty capsules are filled with a lyophilised gadolinium-based contrast agent and a filling agent (barium sulphate). Thirdly, the capsules are coated with the wax mixture (yellow)

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9

Characterization of Organic Compounds

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Melting points were determined with a Büchi Melting Point B-540 apparatus. 1H NMR and 13C NMR spectra were recorded on Brucker ARX 250, Brucker DRX 300 or Brucker DRX 500 spectrometers by using CDCl3, if not otherwise indicated. Chemical shifts (δ) are expressed in ppm relative to TMS. Multiplicity is indicated as s (singlet), d (doublet), t (triplet) and m (multiplet). Har stands for an aromatic proton in 1H NMR. CIV indicates a quaternary carbon in the 13C NMR assignation. J values are given in Hz. 19F NMR was performed using 1,2-difluorobenzene as external standard (δ= −139.0 ppm). Electron Impact (EI) mass spectra were recorded at 70 eV on Jeol JMS-700 and Finnigan TSQ 700 spectrometers at the Institut für Organische Chemie der Ruprecht-Karls Universität Heidelberg. Elemental analyses were carried out in the Mikroanalytisches Laboratorium der Chemischen Fakultät der Ruprecht-Karls Universität Heidelberg. Analytical thin layer chromatography (TLC) was performed on pre-coated silica gel plates Polygram® SIL G/UV254 and silica gel G60 from Macherey-Nagel (230–400 mesh) was used for flash column chromatography.
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10

Melting Point Measurement of Salts

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The melting points of the obtained salts were measured using a Melting Point B-540 (Büchi, Bretten, Germany) apparatus. The device was performed using reference materials with defined melting points (vanillin—81.7 °C, phenacetin—134.8 °C and caffeine—234.0 °C). The heating rate of the tested samples was equal to 5 °C/min. The melting point was visually determined for each sample.
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