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4-(N-Boc-amino)-1Н-1,2,3-triazolecarbothioamides, obtained by a sequential treatment of 4-(N-Boc-amino)-1Н-1,2,3-triazoles with n-BuLi and alkyl isothiocyanates at –78÷–60°C, reacted with ethyl bromoacetate, forming the respective 4-(N-Boc-amino)-5-thioimidates, which underwent intramolecular cyclocondensation upon treatment in saturated НCl solution in dioxane, producing 8-(alkylimino)-4,8-dihydro-1Н-[1,2,3]triazolo[4,5-e][1,4]thiazepin-5(6Н)-ones.

The reaction of alkyl 2-(bromozinc)acylates, obtained from ethyl bromoacetate (or butyl 2-bromobutanoate, or butyl 2-bromo-2-methylpropanoate) under the action of zinc, with N-chloro- or N-bromodiethylamine in tetrahydrofuran at 20–25°C under argon for 2 h resulted in the formation of diethyl succinate (or dibutyl 2,3-diethyl succinate, or dibutyl tetramethyl succinate) and diethylamine instead of the expected products of the nucleophilic substitution of the halogen with the 2-alkoxycarbonylalkyl residue. An anion-radical reaction mechanism was proposed.

Camphor thiosemicarbazone 1 was utilized in the synthesis of new thiazolidinones. Thus, the reaction of 1 with ethyl bromoacetate, dimethyl acetylenedicarboxylate and maleic anhydride afforded the corresponding thiazolidinone 2, thiazolidinylidene acetate 3 and thiazolidinyl acetic acid 4, respectively. The acid 4 underwent esterification to afford the ester 5. Treatment of compounds 2, 3 and 5 with appropriate reagents afforded the newly camphor thiazolidinone derivatives 6a,b–14a,b. The elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectra confirm the chemical structure of the new thiazolidinones. The potential use of some selected derivatives as antibacterial and antifungal agents was investigated and gave promising results.

The reaction of substituted 4,4-diphenyl-3,4(1,4)-dihydroquinazolines with various alkylating agents in DMSO–KOH leads (depending on the structure of the alkylating agent) to the formation of the corresponding N1-monoalkyl-substituted 1,4-dihydroquinazolines or, in the reaction with ethyl bromoacetate, to N-{[5-bromo-2-(methylamino)phenyl]diphenylmethyl}benzamide with opening of the heterocyclic ring. The molecular structures of 1-ethyl-2,4,4-triphenyl-1,4-dihydroquinazoline and 1-ethyl-2-(7-methoxy-1,3-benzodioxol-5-yl)-4,4-diphenyl-1,4-dihydroquinazoline were investigated and proven by X-ray structural analysis.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a DNA repair enzyme that plays a key role in repairing damage caused by various antitumor drugs. It is a promising target in medicinal chemistry for the creation of cancer adjuvant therapy. Inhibition of this enzyme together with the use of anticancer chemotherapy enhances the effect of the latter. The natural mutant of TDP1, TDP1(H493R), causes severe neurodegenerative disease spinocerebellar ataxia syndrome with axonal neuropathy (SCAN1). Inhibition of TDP1(H493R) appears to be useful in containment the progression of the disease. A library of compounds was synthesized starting from dehydroabietylamine including heterocyclic pharmacophore groups in the core. To obtain the desired products, the starting dehydroabietylamine was introduced sequentially in reaction with isothiocyanate and ethyl bromoacetate. Different classes of heterocyclic derivatives-2-iminothiazolidin-4-ons and 2-thioxoimidazolidin-4-ones-were obtained depending on the addition order of reagents. 2-Iminothiazolidin-4-thiones were obtained from 2-iminothiazolidin-4-ones under the action of the Lawesson's reagent. Effective TDP1 inhibitors were found among the obtained compounds that work in submicromolar concentrations. The inhibitor of TDP1(H493R) was also detected.

Some new sulfathiazole derivatives were synthesized. The sulfathiazole starting material was reacted with ethyl bromoacetate and gave unpredictably an ester product 2. The substitution occurred selectively at the tautomeric proton of the NH thiazolyl nitrogen rather than the aromatic NH2 protons. The ester was further hydrazinolysed followed by condensation with several aldehydes to establish hydrazones (4a-h). Hantzesch thiazole synthesis was also applied to build antimicrobial agents containing multi-thiazole moieties. The structures of the synthesized compounds were confirmed by 1H, 13C, 2D 1H NMR, MS, and microanalyses. The synthesized compounds were tested for their antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungi strains. Some of the investigated compounds showed prominent high potency. The docking study revealed the mode of action between the modified sulfathiazole ligands and the binding site of DHPS.

Modular gram-scale syntheses of the trimethyl ethers of lamellarins G (6) and D (7) were achieved from readily accessible precursors in the highest overall yields reported to date (6, six steps, 82%; 7, seven steps, 86%). A novel demethylative lactonization between an aryl methyl ether and a neighboring carboxylic acid was developed for creating the chromenone unit of the targets to avoid the need for additional protection and deprotection steps. The central pyrrole core was constructed in a late-stage [4 + 1] condensation between ethyl bromoacetate and an enaminone possessing the remaining components of the lamellarin skeleton. Exhaustive demethylation of both permethyl ethers 6 and 7 gave the polyphenolic natural lamellarins A4 (3) and H (5), respectively.

demirci, serpil/0000-0002-6579-4273 WOS: 000489305700012 This study was designed to synthesize hybridizing molecules starting from compound of 6-(4-phenyl-piperazin-1-yl)pyridine-3-ylamine by enhancing its biological activity with other heterocycles and to determine anticancer activity of the resulting compounds. To this end, 6-(4-phenylpiperazin-1-yl)pyridin-3-ylamine (4) was used as the leading compound, which is known to exert anticancer activities. The synthesis of the leading compound was carried out using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method with the reaction of N-phenylpiperazine (2) and 2-chloro-5-nitropyridine. 6-(4-phenylpiperazin-1-yl)pyridin-3-ylamine (4) was converted to compound 5, an active intermediate compound, by substitution of one of the amine hydrogens with ethyl bromoacetate. The resulting ester product (5) followed by the hydrazidation (6) was added arylisocyanate to obtain the active intermediate (8). Then, by a series of substitution through cyclization and condensation reactions, thiazolidinone (9), 1,3,4-oxadiazole (7), and 1,2,4-triazole (10) were synthesized. Novel Mannich bases (11a-11f and 12a-12f) were obtained using oxazole (7) and triazole (10) hetero rings with primer or secondary amine compounds. The characterization of the compounds was completed using FT IR, H-1-NMR, C-13-NMR, HRMS spectroscopic methods and elemental analysis technique. The chemicals, then, were tested for their anticancer activities against prostate cancer cell lines PC3 [ATCC, CRL-1435], LNCaP [ATCC, CRL-1740], and DU145 [ATCC, HTB-81]. The results revealed that the Mannich bases exhibited moderate cytotoxic activity against cancer cells tested. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Z932] The support provided by Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 116Z932) is gratefully acknowledged. We thank to Selami Demirci for his help in paper editing.

A new olefination protocol utilizing ethyl bromoacetate was highlighted, in which magnesium enolate of the ester coupled with C20 dialdehyde 6, and double eliminations of the protected hydroxyl groups and bromine atoms of the coupling bromohydrin product, efficiently produced norbixin 1 after concomitant hydrolysis of the ester. A new (C7 + C10 + C7) disconnection approach was demonstrated for the synthesis of norbixin ethyl ester 2 by the Julia–Kocienski olefination of novel C7 benzothiazolyl-sulfone 11 and C10 2,7-dimethyl-2,4,6-octatrienedial (12).

International audience; The pyrolysis of a halogenated ester, methyl chloroacetate (MC), under dilute atmosphere and quasi-atmospheric pressure was studied at temperatures from 473 to 1048 K using an alumina tubular reactor. MC was chosen as a surrogate to model the thermal decomposition of ethyl bromoacetate, a chemical warfare agent. A maximum MC conversion of 99.8% was observed at a residence time of 2 s, a temperature of 1048 K, and an inlet mole fraction of 0.01. The following products were quantified: CO, CO2, HCl, methane, ethylene, ethane, propene, chloromethane, dichloromethane, vinyl chloride, chloroethane, and dichloroethane. For the first time, a detailed kinetic model of MC pyrolysis was developed and gave a good prediction of the global reactivity and the formation of most of the major products. Flow rate and sensitivity analyses were made to highlight the different pathways of decomposition during the MC pyrolysis. In a first attempt to extrapolate the results obtained with methyl chloroacetate to ethyl bromoacetate, simulations were run with a modified version of the model developed in this study taking into account the differences in bond dissociation energies induced by the change of the chlorine atom by a bromine one.

The reaction of pyrazolo[1,5-a]pyrazine-4(5H)ones with phosphorus tribromoxide in boiling benzene yielded 4-bromopyrazolo[1,5-a]pyrazines, and the thionation with phosphorus pentasulfide in pyridine at 90 °C led to pyrazolo[1,5-a]pyrazine-4(5H)thiones. The synthesized bromine derivatives are electrophilic, and thiones are nucleophilic substrates. Their subsequent structural modification in the first case was carried out by interaction with thiophenols, and in the second case was conducted with functional halogenoalkanes. It was shown that bromides react with substituted thiophenols in dimethylformamide in the presence of potassium carbonate at 90 °C to form 4-arylthiopyrazolo[1,5-a]pyrazines with yields of 65–83 %. 4-S-methyl-functionalized derivatives of pyrazole[1,5-a]pyrazines with yields of 60–78 % were easily obtained by the alkylation of pyrazole[1,5-a]pyrazin-4(5H)thiones with a-bromoketones, bromoacetic acid, ethyl bromoacetate and bromoacetonitrile in the K2CO3—DMF system at room temperature. The composition of all synthesized compounds is in agreement with the results of elemental analysis and mass spectra. Their structure is confirmed by NMR 1H and 13C spectra. In particular, in the NMR 1H spectra of 4-arylthiopyrazolo[1,5-a]pyrazines, in addition to the characteristic signals of the pyrazole and pyrazine nuclei, signals of protons of thioaryl substituents are present in the range of 7.04 –8.05 ppm, and in NMR spectra of the 1H 4-S-methylfunctionalized derivatives of pyrazole[1,5-a]pyrazines signals of exocyclic methylene protons are present at 4.11– 5.02 ppm. Promising derivatives with antibacterial activity against the test cultures S. aureus (MIC = 7.8 g/mL), M. luteum (MIC = 3.9 g/mL), and antifungal activity against the test culture of fungus A. niger (MIC = 7.8 g/mL) were determined among 4-S-substituted pyrazole[1,5-a]pyrazines as a result of studies of the antimicrobial activity.

The syntheses of Cu, Fe and Mn doped nanocrystalline MgO was carried out using alkali leached hydrothermal technique. The synergistic effect of transition metals (Cu, Fe and Mn) doping, particle size and nano-scale morphology on surface basicity enhancement was established in one pot Wittig reaction. The doped and undoped nanocrystalline MgO catalysts are characterized by XRD, UV-DRS, FT-IR, FESEM, EDS and XPS techniques. XRD study revealed formation of pure cubic phase of undoped and up to 1 wt% Cu, Fe and Mn doped MgO. The FESEM photographs of transition metal doped MgO indicated the formation of prismatic hexagonal nano plates and nanosheets with thickness in the range 20–70 nm. The catalytic activity of synthesized catalysts was investigated in one pot Wittig reaction of benzaldehyde, triphenylphosphine and ethyl bromoacetate at room temperature in DMF solvent. The Mn doped nanocrystalline MgO catalyst shows 98% yield under optimized reaction conditions. Enhancement of surface basicity due to doping of Mn in MgO was ascertained by UV-DRS and XPS study. The characterization of Wittig product ethyl cinnamate was carried out using HR-MS, 1H NMR, 13C NMR. The 1H NMR evaluates 95:5% E/Z ratio of ethyl cinnmate. Reported methodology is eco-friendly and easy to scale up.

Aroylation of m-xylene by phthalic anhydride under Friedel craft’s reaction conditions to afford the corresponding o-aroylbenzoic acid derivative 2, which followed by cyclization reaction with hydroxylamine hydrochloride to produce the correlating benzoxazinone derivative 3, which was utilized as a precursor for the formation of some novel phthalazinone derivatives 4 ˗ 6. This transformation was achieved by interactions with thiosemicarbazide, thiocarbohydrazide, and hydrazine monohydrate and/or ammonium acetate under suitable conditions. 4-Substituted-1(2H)- phthalazinone derivative 6, which undergoes N-alkylation using ethyl bromoacetate to produce the phthalazinone acetic acid ethyl ester derivative 7, that followed by the interaction with hydrazine monohydrate to afford the phthalazinone acetic acid hydrazide derivative 8. The latter product was conducted with different aromatic acid compounds in presence of POCl3, to give the correlating oxadiazoles 9, 10. The chemical structures of all the synthesized compounds are confirmed using physical and spectral data analyses like FT- IR, 1H-NMR, and mass spectroscopy.

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.

The two isotopomers of teriflunomide were synthesized starting from isotopically stable-labeled stocks of [13 C]potassium cyanide and [1-13 C]ethyl bromoacetate. The two 13 C-labeled compounds 1a, b were applied in several NMR studies to study the E/Z ratio in different matrices. In a solution, such as dimethyl sulfoxide (DMSO), a dynamic equilibrium between E/Z-isomers (ratio of 8:92) was determined by initial 13 C-carbon NMR experiments. To get insights into the E/Z ratio of teriflunomide under in vivo conditions, advanced heteronuclear NMR (heteronuclear Overhauser effect spectroscopy [HOESY]) in D2 O and mixtures of D2 O/plasma were performed. Whereas NMR experiments in mixtures of water and plasma failed owing to extreme line broadening, NMR spectra in water at pH 7.4 showed only the Z-isomer.

Microwave synthesis for a new series of triazolo[3,4-b]thiadiazines and triazolo[3,4-b]thiadiazoles was described. Thus, intermolecular cyclization of triazole 1 with ethyl bromoacetate, chloroacetyl chloride or different α-bromoketones under both conventional and microwave conditions afforded triazolo[3,4-b]thiadiazine derivatives in a good yield. The best results (reaction time and yield) were obtained from microwave condition. However, triazolo[3,4-b]thiadiazole derivatives were obtained via cyclization of triazole 1 with aryl isothiocyanate, ethyl chloroformate or α,α-dibromodimedone without catalyst or in the presence of sodium methoxide and triethylamine, respectively. An attempt to synthesize triazolo[3,4-b]thiadiazine derivatives from reaction of compound 1 with a variety of acetamides was failed; the obtained products are S-alkylated triazoles. Triazolo[3,4-b]thiadiazine 9b and triazolo[3,4-b]thiadiazoles 3a,b, 10 and 12, and triazol-3-ylsulfanyl acetamide derivative 14a have significant results against Escherichia coli, Pseudomonas aeruginosa as gm (–ve) bacteria and Staphylococcus aureus, Bacillus subtilis as gm (+ve) bacteria) and Candida albicans and Aspergillus flavus as pathogenic fungi.

Novel 1-(3-(4-bromophenyl)-5-methyl-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethan-1-one 1 was synthesized through a one-step reaction and allowed to react with ethyl bromoacetate followed by hydrazine hydrate to produce 1-(1-(4-bromophenyl)-2-hydrazinyl-4-methyl-1H-imidazol-5-yl)ethan-1-one (4), which was subjected to various cyclization reactions in the presence of carbon disulfide, benzoyl chloride, acetic anhydride, triethyl orthoformate, phenyl isothiocyanate, and potassium thiocyanate to obtain imidazolotriazoles 6–11. Moreover, imidazole-pyrazole hybrids 12–14 were obtained upon treatment of 2-hydrazino-imidazole derivative 4 with different active methylene compounds, namely, diethyl malonate, ethyl cyanoacetate, and acetylacetone. Finally, imidazolotriazines 15–17 and imidazole-pyrrole hybrid 18 and 19 were prepared by heating derivative 4 in the presence of diethyl oxalate, bromoacetic acid, 1,2-dichloroethane, maleic anhydride, and phthalic anhydride. All newly prepared derivatives containing an imidazole nucleus were evaluated against Escherichia coli (Gram-negative bacteria, NCTC-10416), Staphylococcus aureus (Gram-positive bacteria, NCTC-7447), and Candida albicans (fungi; NCCLS 11). Compounds 16, 6, 12 and 18 presented excellent antimicrobial potency against Gram-positive bacteria which were 1.64%, 3.28%, 9.84%, and 16.39% higher than that of the common reference drug streptomycin, respectively. Furthermore, compounds 6, 12, 15, 16, and 18 showed excellent antimicrobial activities against Gram-negative bacteria, outperforming streptomycin by 38.77%, 30.61%, 67.35%, 48.98%, and 24.49%, respectively. Finally, compound 13 exhibited an excellent antifungal performance, which was 6.94% higher than that of the common reference drug griseofulvin.

The present work refers to the synthesis of novel dialkylacylphosphonylhydrazones that occurs in three reaction steps: the first one is the synthesis of different dialkyl acetate phosphonoacetates obtained by the reaction of ethyl bromoacetate with the trialkyl phosphite of interest. The second one is the synthesis of acetic diethoxyphosphonylhydrazines which is from the reaction between the synthesized dialkyl phosphonoacetates and hydrazine. The third and final steps is the condensation of acetic diethoxyphosphonylhydrazides with different heterocyclic aldehydes. In total, 17 unpublished compounds, namely 1 to 17 ( Table 1 ) were obtained with a diastereoisomeric mixture of the preferential conformation E and all the compounds were characterized by 1-H and 13-C and 31-P NMR, infrared (IR) and mass spectroscopy (MS). This work presents the characterization data of these compounds.

Intramolecular cyclization of 2-{[(4-methyl(or 4,6- and 4,8-dimethyl)quinolin-2-yl)sulfanyl]-acetyl}-N-phenylhydrazine-1-carbothioamides in alkaline and acidic media afforded {[(4-methyl(or 4,6- and 4,8-dimethyl)quinolin-2-yl)sulfanyl]acetyl}-substituted 1,2,4-triazoles and 1,3,4-thiadiazoles. The reaction of these compounds with ethyl bromoacetate gave thiazolidinone derivatives.

In present work, new esters with a thioxoimidazoquinazoline ring were obtained in a reaction of 1-phenyl-2H,6H-3-thioxoimidazo[1,5-c]quinazolin-5-one with ethyl bromoacetate. The obtained esters - 2-(ethoxycarbonylmethyl)-1-phenyl-6H-3-thioxoimidazo[1,5-c]quinazoline-5-one and 2,6-bis(ethoxycarbonylmethyl)-1-phenyl-3-thioxoimidazo[1,5-c]quinazoline-5-one, were isolated at high yield and characterized by instrumental methods: elemental analysis, IR, 1H and 13C NMR, UV and MS-ESI spectroscopies. 2-(ethoxycarbonylmethyl)-1-phenyl-6H-3-thioxoimidazo[1,5-c]quinazolin-5-one is formed as the only product of the equimolar reaction. Quantum-mechanical modelling carried out with the use of the DFT method explained the substitution course. Moreover, the quantum calculations and the spectroscopic analysis exclude the presence of a product with ester group linked via sulfur atom. It was calculated that 99.96% of the monoester is formed at position No. 2. The reason for the reaction's chemoselectivity is the distribution of electron density in the 1-phenyl-2H, 6H-3-thioxoimidazo[1,5-c]quinazolin-5-one molecule. Only the second mole of ethyl bromoacetate reacts with nitrogen atom No. 6, and diester is formed. Quantum-mechanical calculations allowed to determine the composition of 2-(ethoxycarbonylmethyl)-1-phenyl-6H-3-thioxoimidazo[1,5-c]quinazoline-5-one and 2,6-bis(ethoxycarbonylmethyl)-1-phenyl-3-thioxoimidazo[1,5-c]quinazoline-5-one conformers. Furthermore, the conformer compositions of mono and diesters of 1-phenyl-2H,6H-3-thioxoimidazo[1,5-c]quinazolin-5-one were compared with those ones of 1-phenyl-2H,6H-imidazo[1,5-c]quinazoline-3,5-dione.

Tetra- and octa-phosphinanyl-ortho-methyl-tetra-C-naphthyl-resorcinarenes were alkylated with haloalkanes and ethyl bromoacetate. In all cases, the reactions followed the Michaelis-Arbuzov pathway to give phosphonates with haloalkyl groups at the periphery of the molecule. The O-alkylation of tetra-phosphato-ortho-methyl-tetra-C-naphthyl-resorcinarene with ethyl bromoacetate afforded a derivative with different functional sites at the horizontal and vertical benzene rings of the macrocycle, that is, phosphate and ethyl acetate sites, respectively. The exhaustive O-alkylation of ortho-methyl-tetra-C-naphthyl-resorcinarene afforded the octa(ethyl acetate) derivative, which was quantitatively transformed into the corresponding acid and amide.

In this study, we described the synthesis of the derivatives of thiosemicarbazide, dicarboximide, 1,2,4-triazole-5-thione and 4-oxo-1,3-thiazolidine. Two different dicarboxylic acid anhydrides reacted with 4-substituted-3-thiosemicarbazide, and derivatives of thiosemicarbazide and dicarboximide were obtained. Next, cyclization reaction of dicarboximide derivatives in alkaline media was used to prepare 1,2,4-triazole-5-thione. The 4-oxo-1,3-thiazolidine was synthesized by the reaction of dicarboximide with ethyl bromoacetate. All obtained derivatives were analysed by 1H and 13C NMR spectra, and for one compound, the X-ray crystallography was done. Antimicrobial, antiviral and in vitro evaluations of cytotoxicity were examined. According to the preliminary antiviral screening, compounds 3 and 4 presented the antiviral activity against HSV-1 and CVB3. Additionally, compound 3 shows selective in vitro toxic effect against human epithelial cells FaDu, without affecting normal animal cell line (Vero). The same derivatives 3 and 4 also displayed a wide spectrum of antimicrobial activity against reference microorganisms and indicated both antibacterial and antifungal potential activities.

A series of novel sulphonamide derivatives was obtained from sulphanilamide which was N4-alkylated with ethyl bromoacetate followed by reaction with hydrazine hydrate. The hydrazide obtained was further reacted with various aromatic aldehydes. The novel sulphonamides were characterised by infrared, mass spectrometry, 1H- and 13C-NMR and purity was determined by high-performance liquid chromatography (HPLC). Human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and II and Mycobacterium tuberculosis β-CA encoded by the gene Rv3273 (mtCA 3) inhibition activity was investigated with the synthesised compounds which showed promising inhibition. The KIs were in the range of 54.6 nM–1.8 µM against hCA I, in the range of 32.1 nM–5.5 µM against hCA II and of 127 nM–2.12 µM against mtCA 3.

Thiazolidine and thiazolidinone derivatives containing a quinoline fragment have been synthesized by heterocyclizations of 4-(2-hydroxy-4-methylquinolin-3-yl)butan-2-one thiosemicarbazones with bromoacetophenone and ethyl bromoacetate.