Tosyl Chloride Research Articles

PhI(OAc)2-Promoted Site-Selective C-H Chlorination of (Hetero)arenes with p-Toluenesulfonyl Chloride.

An efficient and practical system for metal-free catalytic chlorination of (hetero)arenes by using readily available and inexpensive TsCl and PhI(OAc)2 is described. This newly developed protocol has been achieved by the nonsymmetric iodane generated by a combination of PhI(OAc)2 and TsCl. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and short reaction times make this method attractive for the late-stage chlorination of complex drug-like scaffolds.

One-Pot Synthesis of New Bipyridine and Yerpyridine Derivatives: Anti-proliferative Evaluation, DNA Flow Cytometry Analysis, and Molecular Docking Study

Some new bipyridine derivatives were synthesized using 2-oxo-4-(pyridin-3-yl)-6-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile 1a. While terpyridine derivatives were synthesized using 2-oxo-4-(pyridin-3-yl)-6-(pyridin-4-yl)-1,2-dihydropyridine-3-carbonitrile 1b as starting material. Alkylation of compounds 1a, b gave the alkyl derivatives 2a, b which converted into aceto hydrazides 3a,b. Treating the aceto hydrazides with ethyl cyanoacetate afforded 2'-(2-(3,5-dioxopyrazolidin-1-yl)-2-oxoethoxy)-6'-(thiophen-2-yl)-3,4'-bipyridine-3'-carbonitrile 4a and 6'-[2-(3,5-dioxopyrazolidin-1-yl)-2-oxoethoxy]-(3,4':2',4''-terpyridine)-5'-carbonitrile 4b. While treatment of 3a, b with ethyl benzoylacetate afforded the carboniltrile derivatives 2'-(2-oxo-2-(5-oxo-3-phenyl-4,5-dihydropyrazol-1-yl)ethoxy)-6'-(thiophen-2-yl)-3,4'-bipyridine-3'-carbonitrile 5a and 6'-[2-oxo-2-(5-oxo-3-phenyl-4,5-dihydropyrazol-1-yl)ethoxy]-(3,4':2',4''-terpyridine)-5' carbonitrile 5b. Treating compounds 3a, and b with two aromatic aldehydes (3,4-dihydroxy benzaldehyde, 4-chlorobenzaldehyde) afforded Schiff bases 6a-d. Finally, treatment of 3a, b with p-toluenesulfonyl chloride (Tosyl chloride) afforded the corresponding benzene sulfonohydrazide 7a, b. IR, 1HNMR, 13CNMR, MS, and elemental analysis confirmed the synthesized compounds. The anti-cancer activity of the compounds was investigated against the breast cancer (MCF-7) cell line. Compound 6b demonstrated the strongest cytotoxic activity among the tested compounds and it is more active than the reference drug 5-fluorouracil (5-FU), so that, it is subjected to further investigations, where its effect on the cell cycle distribution in the MCF-7 cell line, its ability to inhibit Topoisomerase II, the level of Caspase‐3/7 green flow cytometry assay was investigated. Also, Molecular operating environmental docking (MOE) has been studied and found that the inhibition efficiency could be organized as follows (S, Kcal/mol) values: 5b ˃ 6d ˃ 3a ˃ 3b ˃ 6b, while compound 5a did not show any interaction data belonging to the shaped complex with 1cca. Hence, most synthesized compounds can be used as anti-cancer and anti-oxidant agents.

Synthesis of Mesylated and Tosylated α-Hydroxy-Benzylphosphonates; Their Reactivity and Cytostatic Activity.

α-Hydroxyphosphonates and their acylated and phosphorylated derivatives may be of significant biological activity including cytotoxic effects. To extend the pool of the potentially bioactive species, new methane- and arenesulfonyloxyphosphonates were synthesized by the sulfonylation of differently substituted α-hydroxy-benzylphosphonates using methanesulfonyl chloride or p-toluenesulfonyl chloride at 25 °C in the presence of triethylamine in toluene. The new sulfonyl derivatives were obtained in 54-80% yields. In the case of the 4- or 2-methoxy substituent in the aromatic ring, surprisingly the corresponding α-chlorophosphonates were the exclusive products, whose formation was explained assuming a quinoid intermediate and supported by theoretical calculations. With a 3-methoxyphenyl substituent, the expected mesylation of the hydroxy group took place. Attempted alcoholyses of the diethyl α-methanesulfonyloxy-benzylphosphonates with different substituents in the benzyl ring at ∼140 °C in the presence of triethylamine under microwave irradiation left the P-function intact under the conditions applied, instead, the mesyloxy group was substituted by an alkoxy unit in a selective new reaction. The α-alkoxy-benzylphosphonates were isolated in 60-77% yields. While α-chloro- or α-bromo-benzylphosphonates proved to be rather inefficient in the Michaelis-Arbuzov reaction with triethyl phosphite, according to a new possibility, the α-methansulfonyloxy-benzylphosphonates underwent an efficient Arbuzov fission using the phosphite in excess at 135 °C. The arylmethylenebisphosphonates were obtained in yields of 76-81%. Bioactivity studies with the members of the phosphonate library revealed pronounced in vitro cytostatic effect of the α-hydroxy- and α-mesyloxy-3,5-di-tert-butylbenzylphosphonates on human breast carcinoma cell culture with IC50 values of 16.4 and 28.0 μM, respectively. The mesyloxy species was also cytostatic on melanoma cells (IC50 = 34.9).

A biorelevant test for tablets glycine sublingual in the «simulated saliva» dissolution medium

Introduction. Biorelevant dissolution media reconstitute the composition of the contents of the gastrointestinal tract. They are used as dissolution media in the evaluation of dissolution profiles of different dosage forms. Simulated biological fluids allow prediction of in vivo test results. The development of the composition of simulated salivary fluid allows the evaluation of drug properties under physiologically relevant conditions.Aim. Evaluation of the release of the drug product "glycine, sublingual tablets, 100 mg", domestically produced in Simulated Saliva 5 pH 6.8.Materials and methods. The preparations used for analysis were: «Glycine, sublingual tablets, 100 mg», domestically produced with valid expiration date. Comparative dissolution kinetics test was carried out on the dissolution test apparatus DT 6 (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Waters W1525 Binary HPLC Pump high-performance liquid chromatograph (Waters Corporation, USA) equipped with column and sample thermostat, degasser, autosampler and Waters 2487 Dual Absorbance Detector (Waters Corporation, USA). Detection was performed at a wavelength of 254 ± 2 nm after derivatization of the glycine molecule with 4-toluenesulfonyl chloride. A Grace Platinum C18-EPS 5 μm 4.6 × 250 mm Grace Platinum C18-EPS 5 μm 4.6 × 250 mm column (Grace, USA) and a Grace Platinum C18-EPS 5 μm 4.6 × 250 mm pre-column (Grace, USA) were used. The following software was used for the study: validated Microsoft Excel spreadsheet for calculating glycine release values.Results and discussion. The technique for quantitative determination of glycine was developed and validated under CDKT in purified water medium and Simulated Saliva 5 pH 6.8. The validated analytical range of the methodology was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The developed analytical technique was validated in the biopredictive in vitro test of glycine preparations. During the study in Simulated Saliva medium for drug formulations, more discriminative data were obtained, which were expressed as: different dissolution rate, curvature of the slope of the dissolution profile and time to reach the plateau in contrast to the dissolution medium purified water.Conclusion. The quantification technique was developed and validated for biopredictive tests of tablets "Glycine, sublingual tablets, 100 mg". The analytical range of the technique was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The results of the test in artificial saliva medium were more discriminatory.

Effect of m-PEG modification on the properties and structure of recombinant lipase from Aspergillus niger GZUF36

Natural lipase is challenging to meet industrial demands because of its low activity, poor stability, and intolerance to organic solvents. Our research aimed to improve the catalytic performance of the extracellular lipase from Aspergillus niger GZUF36 (PEXANL1) by modifying it with a molecular weight of 5000 monomethoxy polyethylene glycol (m-PEG5000) activated by p-toluenesulfonyl chloride (m-PEG5000-OTe). After modification of PEXANL1 with m-PEG5000-OTe (m-PEG5000-OTe@PEXANL1), the activity of m-PEG5000-OTe@PEXANL1 increased by 2.38-fold, its stability at high temperatures improved, and the optimal pH shifted towards the neutral region (pH 6). The effect of surfactants Triton X-100, Tween 20, Tween 80, and SDS on the enzyme activity of m-PEG5000-OTe@PEXANL1 was 118.44%, 124.28%, 120.40%, and 108.53%, respectively. They all activated the enzyme activity. Additionally, m-PEG5000-OTe@PEXANL enhanced its tolerance in organic solvents such as xylene and isopropanol. We analyzed the electrostatic interactions using Zeta potential and characterized the secondary structure using circular dichroism (CD) spectroscopy. The results indicated that the chemical modification led to structural changes in PEXANL1, enhancing its performance. The m-PEG5000-OTe@PEXANL1 may be used to synthesize healthy lipid 1, 3-diglyceride. That study laid the foundation for further industrial applications of PEXANL1 or other lipase by improving the catalytic performance of lipase through chemical modification.

Simple and Efficient Method for Mono‐ and Di‐Amination of Polypyridine N‐Oxides

AbstractHerein we report a simple synthetic route towards both known and novel aminated polypyridyl ligands. The use of tosyl chloride in combination with potassium phthalimide followed by hydrolysis allows for chemo–selective ortho–amination of (poly)pyridyl mono‐ and di‐N‐oxides with good to excellent yield. The reactions are scalable and reproducible while using inexpensive, commercially available reagents.

Novel Benzotriazole-β-lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.

Many people around the world suffer from malaria, especially in tropical or subtropical regions. While malaria medications have shown success in treating malaria, there is still a problem with resistance to these drugs. Herein, we designed and synthesized some structurally novel benzotriazole-β-lactams using 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid as a key intermediate. To synthesize the target molecules, the ketene-imine cycloaddition reaction was employed. First, The reaction of 1H-benzo[d][1,2,3]triazole with 2-bromoacetic acid in aqueous sodium hydroxide yielded 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid. Then, the treatment of 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid with tosyl chloride, triethyl amine, and Schiff base provided new β-lactams in good to moderate yields.The formation of all cycloadducts was confirmed by elemental analysis, FT-IR, NMR and mass spectral data. Moreover, X-ray crystallography was used to determine the relative stereochemistry of 4a compound. The in vitro antimalarial activity test was conducted for each compound against P. falciparum K1. The IC50 values ranged from 5.56 to 25.65 μM. A cytotoxicity profile of the compounds at 200 μM final concentration revealed suitable selectivity of the compounds for malaria treatment. Furthermore, the docking study was carried out for each compound into the P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site to analyze their possible binding orientation in the active site.

BENZAMINE DERIVATIVES: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY STUDY

: Our study is included the synthesis of a number of benzamide drivatives through two chemical processes. The first is the benzoylation of some aromatic amines containing a pyrimidine or a pyrazoline ring in their structures (A-G) using benzoyl chloride or p-chloronbenzoyl chloride in the presence of 1,4- dioxan as solvent productive (N1-N6, N13-N16) derivatives. The second is the tosylation of (N2-N6, N15) by p-toluene sulfonyl chloride in the presence of pyridine as catalyst and base at room temperature to produce (B1-B6 ) derivatives . The products have been characterized by IR, 1H-NMR ,13 C-NMR and mass spectroscpies and the physical properties of the products are recorded . The spectral data confirmed the validity of the benzamide derivatives. Also the work is included the study of antimicrobial activity of the synthesized compounds represented by determining the inhibition diameter zone (IZ), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) given by these compounds against the test organisms Staphylococcus aureas (Gr+ positive) and Escherichia coli (Grnegative). Furthermore, the results of MIC and MBC were compared with those of some common antibiotics such as tetracycline, ampicillin and streptomycin. This comparison showed that it is possible to use the synthesized derivatives as antimicrobials

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

AbstractIn this study, a novel series of sulfonate esters derived from 3‐hydroxyflavone was synthesized and their inhibitory effects on acetylcholinesterase (AChE), α‐glycosidase (AG), and carbonic anhydrase I and II (hCA I and II) enzymes were investigated using experimental and molecular docking analyses. The synthesis involved the reaction of 3‐hydroxyflavone with tosyl chloride, mesytl chloride, β‐naphthylsulfonyl chloride, and 8‐quinolinesulfonyl chloride. The characterization of each compound was confirmed by obtaining 1H NMR, 13C NMR and IR spectra. Furthermore, IC50 and Ki values for the synthesized compounds were calculated and compared to the clinical enzyme inhibitors. Our results showed that the synthesized compounds exhibited inhibition against the targeted enzymes, with Ki values ranging from 1.92 to 4.16 nM for AChE, 32.40 to 55.49 nM for AG, 9.45 to 65.53 nM for hCA I, and 76.62 to 163.33 nM for hCA II. The compound involved quinolinesulfonyl moiety demonstrated especially potent inhibition with IC50 values of 3.96 nM for AChE, 32.40 nM for AG, 9.50 nM for hCA I, and 76.62 nM for hCA II. The docking results aligned well with our experimental findings. The findings have promising implications for the development of novel inhibitors and drug discovery efforts in the future.

Synthesis, spectroscopic, DFT calculations, biological activity, SAR, and molecular docking studies of novel bioactive pyridine derivatives

Enaminonitrile pyridine derivative was used as a precursor for preparation of fourteen heterocyclic compounds using both conventional thermal and microwave techniques. Diverse organic reagents, such as chloroacetyl chloride, acetic anhydride, chloroacetic acid, carbon disulfide, p-toluene sulfonyl chloride, maleic anhydride, phthalic anhydride, were used. The chemical formulae and structures of isolated derivatives were obtained using different analytical and spectroscopic techniques such as IR, 1H-, 13C-NMR as well as mass spectrometry. The spectroscopic analyses revealed diverse structure arrangements for the products. Molecular structure optimization of certain compounds were performed by the density functional theory (DFT/B3LYP) method and the basis set 6–31 G with double zeta plus polarization (d,p). The antimicrobial inhibition and the antioxidant activity of the reported compounds were screened. Compounds 5, 6, 11 and 13 exhibited the highest antibacterial inhibition, while compound 8 gave the highest scavenging activity (IC50 43.39 µg/ml) against the DPPH radical. Structure–activity relationship of the reported compounds were correlated with the data of antibacterial and the antioxidant activity. The global reactivity descriptors were also correlated with the biological properties of compounds. The molecular docking studies of reported compounds were investigated, and the analysis showed that the docked compounds have highly negative values for the functional binding scores. The binding interaction was found to be correlated with the substituent fragments of the compounds.

A fast and accurate colorimetric assay for quantifying hippuric acid in human urine

Hippuric acid is an abundant metabolite in human urine. Urinary hippuric acid levels change with toxic exposure to aromatic compounds, consumption of fruits and vegetables, cancers, chronic kidney disease, schizophrenia and Crohn's disease. While urinary hippuric acid can be detected and quantified via mass spectrometry or nuclear magnetic resonance spectroscopy, a colorimetric assay would be preferable for a low-cost, point-of care clinical assay. Two colorimetric methods, that use p-dimethylaminobenzaldehyde (DMAB) or benzenesulfonyl chloride (PhSO2Cl), respectively, have been previously developed to detect hippuric acid but these assays have many limitations. We replaced PhSO2Cl with p-toluenesulfonyl chloride (p-TsCl), to create a simpler, faster and more accurate method that works with human urine. This modified colorimetric assay detects from 60 μM to 1000 μM hippuric acid in urine in 2 min. We also corrected for the effects of interfering compounds present in urine such that the assay works across many urine backgrounds. We validated this improved assay on multiple hippurate-spiked urine samples, observing an excellent correlation (R2 > 0.94) between observed and known hippurate concentrations. These data suggest that this colorimetric assay is accurate and should greatly facilitate the measurement of hippuric acid in urine to detect a variety of human conditions.

Novel cellulose derivative containing aminophenylacetic acid as sustainable adsorbent for removal of cationic and anionic dyes

The synthesis and characterization of a novel cellulose derivative as a potential sustainable adsorbent for cationic and anionic dyes are described through processing in ionic liquids. Cellulose was solubilized in ionic liquid with tosyl chloride to form tosyl cellulose which reacted with 4-aminophenylacetic acid through nucleophilic substitution mechanism. The new cellulose derivative was characterized and explored as an effective adsorbent for methylene blue (MB) and methyl orange (MO) removal, and the adsorption behaviors were investigated with various models. The adsorption behavior of the cellulose derivative followed Langmuir and pseudo-second-order models, and the maximum adsorption efficiency recorded 135 and 106 mg/g for MB and MO, respectively. There is possibility that the enhanced adsorption capacity of the cellulose derivative is due to the carboxylic and amino functional groups that provide sufficient active sites to enhance dye molecule affinity. The adsorption results demonstrate that the cellulose derivative containing aminophenylacetic acid was efficient adsorbent for removals of MB and MO.

A study of mono-, di- and tri-tosylated amines: An unexpected sulfonamide

2-Aminobenzylaniline was ditosylated and gave an unexpected product N,N-ditosylamino-2-benzylaminobenzene in which the primary amine had ditosylated, and the benzylamine was unreacted. The benzylamine, although more electron rich, is sterically crowded and less nucleophilic than the primary amine in this ditosylated system. Sterically crowded tosylamides were prepared by reacting o-phenylenediamine, p-phenylenediamine and 1,8-diaminonaphthalene with tosyl chloride.

Tosyl Chloride Mediated One Flask Facile Synthesis of 4-Arylmethylene-2-Phenyl-2- Oxazolin-5-Ones

Tosyl Chloride Mediated One Flask Facile Synthesis of 4-Arylmethylene-2-Phenyl-2- Oxazolin-5-Ones

Development, Validation and Approbation Analytical Method for the Quantitative Determination of Taurine by HPLC-UV Method in the Test of Comparative Dissolution Kinetics

Introduction. Taurine is a non-proteinogenic amino acid. The molecule is involved in lipid metabolism, adsorbs fat-soluble vitamins, and its conjugates with bile acids contribute to the emulsification of fats in the intestine. Drugs, which include a taurine molecule, have anti-cataract, cardiotonic, metabolic effects, and also stimulate regeneration. Among the dosage forms, where taurine acts as an active substance, there is a solid dosage form – film-coated tablets. One of the methods for assessing the quality of solid dosage forms is a comparative dissolution kinetics test. High-performance chromatography with ultraviolet detection is a widely used method for quantification within the dissolution test, however, for taurine, which does not contain chromophore groups in its structure, this method is not directly applicable. To solve this problem, one can apply the method of pre-column derivatization, because of which an fragment is introduced into the structure, providing a bathochromic shift in the UV spectrum of the starting compound.Aim. Development, validation and approbation analytical method for the quantitative determination of taurine by high-performance chromatography with ultraviolet detection as part of a test comparative kinetics dissolution of taurine tablets with a dosage of 250 and 500 mg.Materials and methods. The following preparations were used for the analysis: taurine tablets, film-coated 250 mg and 500 mg, domestic production with a valid expiration date. The comparative dissolution kinetics test was carried out on a DT 126 Light instrument for the "Dissolution" test (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Nexera-i LC-2040 high-performance liquid chromatograph (Shimadzu Corporation, Japan) equipped with a column and sample thermostat, a degasser, an autosampler, and an ultraviolet detector. Detection was carried out at a wavelength of 254 nm after derivatization of the taurine molecule with 4-toluenesulfonyl chloride. Were used a Shim-pack Velox C18 5 μm 4.6 × 150 mm column (Shimadzu Corporation, Japan) and a Shim-pack Velox C18 EXP Guard Column Cartridge 5 μm 4.6 × 5 mm (Shimadzu Corporation, Japan). Primary data were processed using LabSolutions Single LC software (Shimadzu Corporation, Japan).Results and discussion. The optimal conditions for taurine derivatization have been selected, and a method for the quantitative determination of taurine by HPLC-UV in test comparative kinetics dissolution in three dissolution media: 0.1M hydrochloric acid solution with pH 1.2, acetate buffer solution with pH 4.5, phosphate buffer solution with pH 6.8, as well as in the quality control medium – purified water has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics are within the acceptance criteria in 4 dissolution media. The analytical range of the method was 0.05–1.2 mg/mL and allows the developed method to be used for the quantitative determination of tablets with a dosage of 250 mg and 500 mg as part of the test comparative kinetics dissolution. The method was tested in 4 dissolution media, in all media, there was a complete release in both dosages (more than 85 % by 30 minutes).Conclusion. The method was tested in three dissolution media: 0.1 M hydrochloric acid solution with pH 1.2, acetate buffer solution with pH 4.5, phosphate buffer solution with pH 6.8, as well as in the quality control medium – purified water. In all media, there was a complete release in both dosages (more than 85 % by 30 minutes).

Synthesis, and Anticancer Evaluation of 4-[(Indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolone Derivatives via a Magnetic Aminated Starch Biocatalyst

An eco-friendly biocatalyst was constructed in three steps. In the first step, the tosylated starch (TsST) was synthesized by using a 4-toluenesulfonyl chloride. In the second step, the aminated starch was synthesized via the reaction of TsST with para-phenylenediamine. In the third step, the magnetic biocatalyst was fabricated by an in situ coprecipitation process from ferric and ferrous salts in the existence of aminated starch (AST). The biocatalyst was characterized by 1H NMR, EDX, FESEM, FTIR, VSM, and TGA analyses. The magnetic aminated starch (MAST) was used as a biocatalyst for the synthesis of 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolone derivatives. The various products were prepared in noteworthy yields (85–93%) in fast reaction times (35–80 min) without laborious work-up procedures. The anticancer evaluation of some 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolones derivatives was studied on the survival rate of breast cancer cell lines (MCF-7) and human fibroblast cells by using an MTT assay. Additionally, recovery of the biocatalyst was studied, and results showed that the MAST was easily isolated from the reaction flask and could be recycled for up to six consecutive cycles without meaningfully falling in its efficiency.

The physicochemical and thermophysical properties of sodium dodecyl sulfate: The influence of p-toluene sulfonyl chloride and temperature

In the present study, we report on the interaction between a hydrotrope, p-toluene sulfonyl chloride (p-TSC), and an anionic surfactant, sodium dodecyl sulfate (SDS) which has been performed using electrical conductivity, Fourier transform infrared (FTIR), 1H NMR, density, dynamic viscosity, and kinematic viscosity measurements. The effect of p-TSC on the micellization of SDS in non-aqueous (ethanol) medium at various temperatures (viz., 298.15, 303.15, 308.15, 313.15, 318.15, and 323.15 K) was investigated using the electrical conductivity method. The results show that the CMC value increases as the concentration of the hydrotrope is increased. It is noteworthy that at higher concentrations of hydrotrope, the trend of micelle formation is reversed (i.e., reverse micelles are formed). The thermodynamic parameters in micellization have also been evaluated. The FTIR and 1H NMR data reveal the physicochemical properties of the pure and mixed systems and confirm no covalent bond formation takes place. Density, dynamic viscosity, and kinematic viscosity of the pure as well as mixed systems at various temperatures were also reported.

A Simple and Modified One Pot Conversion of Carboxylic Acid to Ketone

Background: Ketone is one of the important functional groups in synthetic chemistry. For this reason, organic chemists focused on the synthesis of ketone starting from various functionalities since nineties. One of the method deals with the conversion of carboxylic acids to ketones in a one pot manner. We have recently reported a one pot transformation of carboxylic acid to ketone using TsCl or MsCl as an activator of carboxylc acid. In our previous reports, two equivalents of organometallic reagent have been used which may not be useful in medicinal chemistry. In this report, we have developed an alternative process for the transformation where only one equivalent of organometallic reagent has been employed. Objective: In present scenario, we are interested to develop a process for the transformation of carboxylic acid to ketone using one equivalent of an organometallic reagent. Methods: A carboxylic acid reacted with tosyl chloride in the presence of a sodium hydride to form a mixed anhydride. Here, the acidic proton was removed from the reaction mixture as hydrogen gas. This mixed anhydride was then treated with one equivalent of an organomagnesium reagent at -30°C to obtain the desired ketone. Results: Following the optimum conditions, a few commercially available carboxylic acids were treated with TsCl, followed by the treatment of phenyl magnesium and methyl magnesium bromide to obtain phenyl and methyl ketones, respectively, in good to excellent yields. Conclusion: A simple and modified one pot method for the conversion of carboxylic acids to ketone has been reported. In this developed process, one equivalent of the organomagnesium reagent has been used to obtain the desired ketone under the optimized reaction conditions.

A new entrant in ketene family: Generation of 2‐(3‐Oxo‐allyl)‐isoindole‐1,3‐dione and their [4+2] Cycloadditions with 1,3‐Diazabuta‐1,3‐dienes

AbstractThe manuscript describes a synthetic route for the formation of 5‐(methylisoindole‐1,3‐dione) pyrimidinones by [4+2] cycloaddition reactions of functionalized 1,3‐diazabuta‐1,3‐dienes with 2‐(3‐Oxo‐allyl)‐isoindole‐1,3‐dione generated in situ from phthaloylalanine and tosyl chloride using triethylamine as a base. The functionalized 5‐(methylisoindole‐1,3‐dione) pyrimidinones were further explored in the deprotection of amines to afford a variety of 5‐methylamino pyrimidinones. The synthesis of such functionalized pyrimidinones is significant as they have a wide range of pharmacological profiles and are valuable as organic synthons. Mechanistic insights are also proposed for the given synthetic methodology.

Synthesis, Structural Elucidation, and Biological Potential of Novel Sulfonamide Drugs

Sulfonamides are anti-microbial and anti-inflammatory agents used widely for the treatment of infections. The current research dealt with the synthesis of four sulfonamides formed by the reaction of p-toluenesulfonyl chloride with 4-amino phenyl acetic acid, 5-amino isophthalic acid, 4-piperidine carboxylic acid, and toluidine. The respective structures of sulfonamide drugs were verified by elemental analysis (CHNS), FT-IR spectroscopy, and thermogravimetry. The elemental analysis (CHNS) data conformed to the proposed chemical composition of the products 1-4. The FT-IR spectra verified the formation of sulfonamide drugs. Thermogravimetric analysis (TGA) of data in the range of 25-800oC showed that the evolved components and residues were in good agreement with the molecular skeletons of the products. The antibacterial potential of sulfonamide drugs was evaluated against bacterial strains using the disc diffusion method. The zones of inhibition were found to be larger against Escherichia coli as compared to Bacillus Subtilis. Cytotoxicity of products was in the acceptable range of 0.3-3.1%, as compared to triton X100. It indicates the safety of these products as future medicinal drugs for human beings.