Sodium Methoxide In Methanol Research Articles

Regioselective synthesis of new imidazo[4,5‐e][1,3]thiazino[2,3‐c][1,2,4]triazines via reaction of imidazo[4,5‐e][1,2,4]triazinethiones with ethyl phenylpropiolate

AbstractA method for the regioselective synthesis of imidazo[4,5‐e][1,3]thiazino[2,3‐c][1,2,4]triazine derivatives has been developed by the reaction of imidazotriazinethiones with ethyl phenylpropiolate upon treatment with potassium carbonate or sodium methoxide in methanol. The synthesis was accomplished by Michael‐type addition of the imidazotriazinethiones to the triple bond of ethyl phenylpropiolate followed by subsequent intramolecular cyclization.

Adaptation of Zemplén's conditions for a simple and highly selective approach to methyl 1,2−trans glycosides

1,2-trans methyl glycosides can be readily obtained from peracetylated sugars through their initial conversion into glycosyl iodide donors and subsequent exposure of these latter to a slight excess of sodium methoxide in methanol. Under these conditions a varied set of mono- and disaccharide precursors afforded the corresponding 1,2-trans glycosides with concomitant de-O-acetylation in satisfying yields (in the range 59–81%). A similar approach also proved effective when using GlcNAc glycosyl chloride as the donor.

Tert-Butyl (E)-3-oxo-2-(3-oxoisobenzofuran-1(3H)-ylidene)butanoate

Non-fullerene acceptors have recently attracted much attention as components of organic solar cells. 1H-indene-1,3(2H)-dione is a key compound for the synthesis of the end-capping component of non-fullerene acceptors. In this communication, an intermediate for the synthesis of this compound, tert-butyl (E)-3-oxo-2-(3-oxoisobenzofuran-1(3H)-ylidene)butanoate, was prepared by the reaction between phthalic anhydride and tert-butyl acetoacetate. Further treatment with sodium methoxide in methanol led to the formation of 1H-indene-1,3(2H)-dione in a high yield. The structure of the newly synthesized compound was established by means of elemental analysis, high-resolution mass spectrometry, 1H, 13C NMR, IR spectroscopy, mass spectrometry and X-ray analysis.

Exploration of Dihydrothieno[2,3-c] Isoquinolines As Luminescent Materials and Corrosion Inhibitors.

The reaction of the starting compound, 7-acetyl-4-cyano-1,6-dimethyl-8-phenyl-7,8-dihydroisoquinoline-3(2H)-thione, with some N-aryl-2-chloroacetamides or chloroacetonitrile, in the presence of sodium acetate trihydrate, gave the corresponding substituted 3-methylsulfanyl-7-acetyl-4-cyano-1,6-dimethyl-8-phenyl-7,8-dihydroisoquinolines. Upon heating of the latter compounds with sodium methoxide in methanol, they underwent intramolecular Thorpe-Zeigler cyclization, affording the target isomers 1-amino-2-(substituted)-5,8-dimethyl-6-phenyl-6,7-dihydrothieno[2,3-c]isoquinolines (DHTIQs). The chemical structures of all produced substances were characterized by elemental and spectral analyses. The photophysical characteristics of the produced DHTIIQs (He1-Ph-Cl, He2-Ph-CH3, He3-Ph, and He4-CN) have been investigated as luminous compounds. Potentiodynamic, surface morphology, and theoretical calculations were used to study the behavior of the synthesized DHTIQs as corrosion inhibitors on mild steel in a 1.0 M sulfuric acid solution.

Regioselective synthesis and theoretical calculations of Bis(pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidines) linked to benzofuran units via piperazine spacer: A DFT, MM2, and MMFF94 study

• A novel bis(3-amino-1 H -pyrazolo[3,4- b ]pyridine) is prepared in a good yield. • A regioselective synthesis of new series of piperazine-linked bis(pyrimidines) hybrids is performed. • The new structures were elucidated by elemental and spectral analyses. • DFT and Fukui indices calculations are used to provide additional evidence for the proposed structures. • MM2, and MMFF94 minimization are used to investigate the plausible formation mechanism of the bis(pyrimidines) . Bis(enaminone), linked to benzofuran units via piperazine spacer, was prepared and used as a key intermediate in this study. It reacted for 8 h at reflux with two equivalents of 2-cyanothioacetamide in dioxane in the presence of TEA to give the corresponding bis(pyridine-2(1 H )-thione) derivative. The previous compound was reacted with two equivalents of iodomethane in methanolic sodium methoxide solution at reflux for 1 h to yield the corresponding bis(2-methylthiopyridine) derivative. Boiling of the prior compound with hydrazine hydrate in pyridine at reflux for 12 h gave the precursor bis(3-amino-1 H -pyrazolo[3,4- b ]pyridine) derivative in a good yield. Next, a regioselective protocol was conducted for the synthesis of a diverse series of the target bis(pyrido[2′,3′:3,4]pyrazolo[1,5- a ]pyrimidine) derivatives in good to excellent yields. The protocol involved the reaction of bis(3-amino-1 H -pyrazolo[3,4- b ]pyridine) with two equivalents of prop-2-en-1-ones in DMF in the presence of two equivalents of barium hydroxide at reflux for 5–7 h. To gain a better understanding of the regioselectivity observed in these reactions, DFT calculations were performed using B3LYP method and 6-31+G(d,p) basis set. The favored mechanism and the experimental regioselectivity of this reaction were explained by calculations of activation energy, natural atomic charge, Fukui indexes derived from density functional theory, MM2, and MMFF94 calculations. The current study demonstrated that using the previous computational tools, the regioselectivity of the applied reaction protocol could be correctly predicted.

Выявление фальсификации говяжьих полуфабрикатов куриным фаршем механической обвалки на примере пельменей

Human nutrition is an important factor affecting human health. Counterfeiting is one of the most pressing problems in the market, which worries manufacturers, sellers and consumers. There are a variety of product counterfeiting: substitution of expensive food products for cheaper ones, manufacturing of products with low nutritional value, deterioration of the recipe and plagiarism of the brand. It is also necessary to observe the correct labeling of the product, as this enables the consumer to meet his requirements when choosing a product. This article presents the results of our own research revealing the falsification of semi-finished beef products with mechanically deboned minced chicken using the example of dumplings. In the analysis, four fatty acids were selected for the presence or absence of chicken fat in ground beef. The determination of fatty acids was carried out by gas chromatography. Gas chromatographic analysis is considered to be effective for identifying food products due to its high degree of sensitivity, speed and simplicity. Sample preparation stages included the use of sodium methoxide in methanol with a molar concentration of 2 mol/dm3. Gas chromatographic analysis was carried out on a flame ionization detector with a quartz capillary column. For simplicity, reduction of sample preparation time and better results, the samples were filtered under vacuum at atmospheric pressure, which significantly accelerated the filtration process. The analysis of the test sample was carried out in an automatic mode according to the specified program of the chromatograph. Myristic, palmitoleic, margaric, stearic, linoleic, and arachidic acids were chosen as “labels” of fatty acids. It has been shown that even an insignificant addition of one type of impurity of another to meat leads to a change in the fatty acid composition of the product.

Nitroalkene ring closure route to carbon-linked scaffolds for mimicking α-d-mannopyranosyl natural linkage

Controlled treatment of 3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-nitro-d-manno-hept-1-enitol with sodium methoxide in methanol was stopped by decationization at a point providing about equimolar mixture of α-d-mannopyranosyl and β-d-mannopyranosyl nitromethanes, from which the target α-anomer was isolated by chemisorption chromatography on a cation exchange resin in the Ba2+ form in a 36% yield. Direct reduction of the above mixture with ferrous hydroxide in situ to the corresponding amines, followed by the selective N-acetylation and the analogical chromatographic separation of both pertinent isomers with their stable ring structures gave N-acetyl-C-α-d-mannopyranosyl-methylamine. Alternative stopping of the initial ring forming reaction with acidified methanol at the above given product ratio initiated a subsequent Nef reaction and α-d-mannopyranosyl methanal dimethyl acetal was then chromatographically separated from its β-isomer on an anion exchange resin in the OH− form. Activations of two latter C-α-d-mannopyranosyl scaffolds by acid hydrolysis into respective reactive free amine or aldehyde forms were developed as well. Detailed reinvestigation of the classical method of preparation of d-mannosyl nitromethanes by thermal dehydration of a 1-deoxy-1-nitroalditol derived from d-mannose showed a maximum occurrence of only 18% of the required α-d-mannopyranosyl anomer.

Novel Synthesis of β-Keto Cycloacetals via Organoboranes

(Z)-1-Bromo-1-alkenylboronate esters were easily synthesized from the hydroboration of terminal alkynes with dibromoborane dimethyl complex under nitrogen atmosphere followed by treatment with propne-1,3-diol. These boronate esters are readily reacted with 1,3-dioxan-2-ylethyl)magnesium bromide in ether and tetrahydrofuran at -78 ºC for 1 h. The resulting "ate" complex upon addition of sodium methoxide in methanol undergo intramolecular nucleophilic substitution reactions to produce the corresponding (E)-alkenylboronate esters containing (1,3-dioxan-2-ylethyl) moiety in 70-82% isolated yields. The resulting intermediates are oxidized with sodium acetate and hydrogen peroxide to provide the corresponding β-keto cycloacetals in good yields (68-84%).

Pyrolysis of derivatives of technical mixtures of polychlorinated biphenyls

Thermal stability and gas phase composition of the most common technical mixtures of polychlorinated biphenyls “Sovol” and “Trichlorobiphenyl” were studied by simultaneous thermal analysis and mass spectrometry compared to their derivatives synthesized by the interaction of these mixtures with sodium methoxide in dimethyl sulfoxide and methanol. For the first time it was established that derivatives of polychlorinated biphenyls are less thermostable compounds as compared with the initial products and under pyrolysis they undergo not only evaporation stages, but also decomposition processes to the simplest volatile substances. Thermal destruction of derivatives is characterized by a decrease in the level of emission of hazardous compounds and requires less energy.

Thermodynamic Modeling of the Stage of Polychlorinated Biphenyls Preparation to Thermal Decomposition

The reaction of Sovol (technical mixture of polychlorinated biphenyls) with sodium methoxide in dimethyl sulfoxide and methanol has been studied using the thermodynamic modeling method. The optimal process conditions have been elaborated: 1 atm, 115°C, 0.25 mol of dimethyl sulfoxide, 0.085 mol of methanol, the polychlorinated biphenyls: sodium methoxide molar ratio = 1: 4. Experimental data on the interaction of the polychlorinated biphenyls with sodium methoxide under the theoretically determined conditions have revealed a range of positive effects: savings of the reactants, complete conversion, and the formation of potentially less toxic compounds. The studied interaction can serve as a stage for the pretreatment of toxic polychlorinated biphenyls for the pyrolytic destruction.

Synthesis and Spectral Characterization of Impurities of a COX‐2 Selective Drug, Celecoxib

Celecoxib and its impurities. Rheumatoid arthritis is one of the omnipresent autoimmune disorders which leads to bone damage, skeletal disorders, and disability.1 Celecoxib (1) the brand name Celebrex, is a selective cyclooxygenase (COX)-2 inhibitor (coxib) used for treatment of osteoarthritis, rheumatoid arthritis approved by the FDA.2 Coxibs were developed to provide anti-inflammatory/analgesic activity similar to that of nonselective non-steroidal anti-inflammatory drugs (NSAIDs), but without gastrointestinal toxicity resulting from COX-1 inhibition.3 Impurities are the unwanted chemical entities that are formed during the process of synthesizing active pharmaceutical ingredients (APIs) or during formulation of the drug. Even in trace amounts the existence of the impurities may affect the efficacy and safety of the drug. As per guideline on impurities by International Conference on Harmonization (ICH), it is mandatory to identify and characterize all the impurities which are present 0.10% or more.4 As a part of our continuing research on synthesis of pharmaceutically important molecules, we aimed at synthesis of process impurities of celecoxib.5 During the HPLC analysis of crude celecoxib, two main impurities have been detected in the range of 0.01-0.15%, which originated from the manufacturing process of API. Initial analysis of HPLC and previous reports suggested that the impurities are the regioisomers of the celecoxib. Few reports are present in literature; however, these methods involve multistep synthesis with low yields and HPLC methods to identify these impurities are scarce.6 The synthetic strategy which is widely used to synthesize the diarylpyrazole ring of celecoxib as follows, the condensation reaction between hydrazine 7 with 1,3-dicarbonyl compound 6 produce 1 (Scheme 1). One of the demerits of this route was the formation of regioisomeric impurities.7 Impurity A 2, regioisomer is believed to originate from a starting material 1,3 dicarbonyl compound 8 (Scheme 2).8 Whereas the impurity B 3, formed due to reaction of 1,3 diketone 6 with traces of the water present in the reaction mixture, afforded hydrate 9, which underwent condensation with hydrazine 7 resulting the impurity B 3 (Scheme 2).9 After identifying the cause for the formation of these impurities, we set out our goals to synthesize these molecules. Synthesis of impurity A 2 was achieved by using a twostep straight forward strategy (Scheme 3). Initially isopropyl trifluoroacetate 10 was reacted with 3′-methylacetophenone 11 in toluene with sodium methoxide as a base to afford 4,4,4-trifluoro-1-(m-tolyl)butane-1,3-dione, 8 with a good yield (87%). Further, 8 was added to 4-hydrazinobenzenesulfonamide hydrochloride 7 in ethyl acetate, the impurity A 2 was obtained as white solid (5.15 g) with an excellent yield of 92.0%. Impurity B was synthesized in a single step by using mild condition (Scheme 4). To a solution of (E)-4,4,4-trifluoro-1-(p-tolyl)but-2-en-1-one 12 and 4-hydrazinobenzenesulfonamide hydrochloride 7 in DMF sodium methoxide in methanol was added. After the addition, reaction mixture was heated to 100 °C till the starting materials are consumed. The impurity B 3 was isolated and purified by column chromatography as an off-white solid (120 mg, 22.5%) with high purity. 19F NMR confirms that the impurities were regio-isomers of celecoxib (see supporting information). The HPLC analysis of crude celecoxib drug in our method showed the targeted impurities were present in trace amounts which were taken up for further HPLC analysis. In the initial analysis, crude celecoxib drug has the assay of 99.12% at retention time of 20.21 min, whereas the impurity A and impurity B were observed at retention times 18.80 and 21.66 min, respectively (Figure 1). HPLC analysis of the impurities synthesized were matched with the impurities in the drug, the synthesized molecules were highly pure with assay of 98.63% and 98.30% for impurity A and impurity B, respectively. In summary, the origins for the formation of these impurities A & B during process development were hypothesized, synthesized and characterized in this report; which were obtained with the overall yield of 80% and 23%, respectively. A robust HPLC method also has been developed to calculate the assay of these impurities as 98.6% and 98.3%. This work was supported by the National Research Foundation of Korea grants funded by the Korea Government (MSIP) (MRC 2017R1A5A2015541, and Basic Science Research Program 2017R1D1A1B03) and the International Science and Business Belt Program through the Ministry of Science, ICT and Future Planning (2017K000490). This work was also supported by Post-doctoral Fellowship program funded by the Ministry of Education of the Republic of Korea through the Chungbuk National University in 2018 (M. V). Experimental section along with 1H, 13C, 19F NMR, HRMS, and HPLC spectral data are available at the online version of this communication. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Synthesis and Biological Activity of 5-Aryl-N-{4-[(1,3-thiazol-2-yl)sulfamoyl]phenyl}-1-phenyl-1H-pyrazole-3-carboxamides and Their Salts

The reaction of 4-aryl-2-hydroxy-4-oxo-N-{4-[(1,3-thiazol-2-yl)sulfamoyl]phenyl}but-2-enamides with phenylhydrazine in glacial acetic acid afforded 5-aryl-N-{4-[(1,3-thiazol-2-yl)sulfamoyl]phenyl}-1-phenyl-1H-pyrazole-3-carboxamides. Treatment of the latter with an equimolar amount of silver nitrate in ethanol–DMF (2:1) gave the corresponding silver salts, while 5-aryl-N-{4-[(1,3-thiazol-2-yl)sulfamoyl]phenyl}-1-phenyl-1H-pyrazole-3-carboxamide sodium salts were obtained by reaction with sodium methoxide in methanol–DMF (1:1). The synthesized compounds were tested for analgesic, anti-inflammatory, and antimicrobial activities.

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.

Synthesis and Characterisation of Indium(III) Bis-Thiosemicarbazone Complexes: 18F Incorporation for PET Imaging

Several structurally related indium chlorido complexes of bis-thiosemicarbazones were prepared, starting from the appropriately substituted bis-thiosemicarbazones, using sodium methoxide in methanol. Detailed NMR studies were conducted to assign the structure including COSY, HSQC, and HMBC techniques. The structures of all indium complexes were solved using single crystal X-ray diffraction. The chlorido ligand was present at the apex of the square pyramidal coordination sphere in all indium complexes. In some complexes, an intermolecular hydrogen bond was present between the chlorine atom and an NH group. Three different indium chlorido complexes were converted into the corresponding fluorido-derivative by a simple halide exchange method using K18F. These novel complexes, containing the positron emitting isotope 18F, may have potential applications in positron emission tomography (PET).

Nucleosides 10: Synthesis of New Derivatives of Pyrimidine and Fused Pyrimidine Nucleosides of Expected Biological Activity

Pyrimidines, such as 6-amino-2-thio and 2-methylthiouracils and fused pyrimidines, such as thienopyrimidines reacted with 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose to get new derivatives of the corresponding nucleosides. The obtained protected nucleosides were deprotected by methanolic sodium methoxide to get the corresponding free uracil and thienopyrimidine nucleosides. The new nucleosides formed were tested for biological activity against some of microorganism (some fungi and bacteria species). Some of the tested products showed moderate activity and the results were reported.

2-Azido-1,3,4-thiadiazoles, 2-Azido-1,3-thiazoles, and Aryl Azides in the Synthesis of 1,2,3-Triazole-4-carboxylic Acids and Their Derivatives

Diazotization of 2-amino-1,3,4-thiadiazoles gave 1,3,4-thiadiazole-2-diazonium sulfates which were converted to 2-azido-1,3,4-thiadiazoles. The latter reacted with ethyl acetoacetate in the presence of sodium methoxide in methanol to produce 1-(5-R1-1,3,4-thiadiazol-2-yl)-5-R2-1H-1,2,3-triazole-4-carboxylic acid derivatives. The reactions of 2-azido-5-methyl-1,3,4-thiadiazole and 2-azido-1,3-thiazole with ethyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate led to the formation of 1,2,3-triazole ring under milder conditions (K2CO3, DMSO). Various 1,2,3-triazole-4-carboxylic acid derivatives were synthesized.

Synthesis of new functionalized hydroxy‐ and aminomethylphosphinates with indan moieties

AbstractThe convenient synthesis of new functionalized organophosphorus acids and their derivatives containing indan moieties was developed. The regioselective radical addition of bis(trimethylsiloxy)phosphine to indene proceeds to give rise to 2‐indanylphosphonite as key compound for preparation of above acids with bicyclic substituents. Azobis(isobutyronitrile) (AIBN) in the conditions of its thermolysis was used as effective initiator of the addition reaction. The further treatment of organophosphorus acids trimethylsilyl esters with the methanolic sodium methoxide solution resulted in the water‐soluble sodium salts of the corresponding acids.

Synthesis and antiproliferative activity of flavonoid triazolyl glycosides

Abstract Sixteen flavonoid triazolyl glycosides 4–19 were synthesized in good yields via Cu(I)-catalyzed azide-alkyne cycloadditions of terminal alkynes of flavonoids 1–3 with acetylated sugar azides followed by deacetylation with sodium methoxide in anhydrous methanol. The antiproliferative activity of the synthesized compounds against three human cancer cell lines (Hela, HCC1954 and SK-OV-3) in vitro was evaluated. Flavonoids 1, 2 and flavonoid triazolyl glycosides 7, 12, 17 exhibit potent antiproliferative activity against these cancer cell lines.

First Time Determination of Important Catalyst Sodium Methoxide Used in Biodiesel by Colorimetric Method.

A simple and selective spectrophotometric method has been developed for the first time for the determination of sodium methoxide in methanol solution in the presence of sodium hydroxide. The developed method involves the formation of a pink species by the reaction between sodium methoxide and α-santonin. The pink compound formed shows absorbance maximum at 513 nm. N, N-Dimethylformamide and methanol were used as solvents, and the reaction was performed at different temperatures and 25 °C was selected for further experiments. The pink compound formed was dried and then was studied using FTIR and mass spectrometry. The calibration curve was constructed from 0.10 to 0.30% (m/v) sodium methoxide in methanol, and the standard deviation is 0.010%. Similarly, the relative standard deviations of 28%, 26%, and 24% solutions of sodium methoxide were obtained in the range of 0.4 to 1.9%. The correlation coefficient of the analytical curve r = 0.9997; the limit of detection, LOD, is ca. 1.1 × 10-3 % w/w; and the limit of quantification, LOQ, is ca. 3.2 × 10-3 % w/w. The results of analysis were validated statistically.

Sodium Methoxide Catalyzed Depolymerization of Waste Polyethylene Terephthalate Under Microwave Irradiation

Chemical recycling of polyethylene terephthalate (PET) to produce terephthalic acid (TPA) was studied using in situ hydrolysis with sodium methoxide in methanol and dimethyl sulfoxide (DMSO) as solvent under microwave irradiation. The microwave-assisted reaction was carried out at different temperatures, and reaction time between 5 to 30 min. High degrees of depolymerization were examined at temperature near 70°C at microwave power 300 W. The reaction was carried out in a sealed microwave reactor in which the time and temperature were controlled and recorded. The products were mainly monomers such as TPA and ethylene glycol (EG) which were isolated and purified for further analysis. Monomethyl terephthalate, dimethyl terephthalate, and terephthalic acid were formed initially then converted to TPA as a single monomer product. Purified, TPA was analyzed and identified by NMR, TGA, DSC and FTIR. It was observed that the reaction greatly depends on the amount of sodium methoxide, the volume of methanol and DMSO used, the reaction time, and temperature. Compared to conventional heating methods, the time needed to achieve complete degradation of PET was significantly reduced to 5 min by using microwave irradiation and sodium methoxide catalyst. This has led to substantial saving in energy and cost supporting the conclusion that this proposed recycling process is very beneficial for the recycling of PET wastes.