Synthesis and DFT Study of Newly Schiff Base and Fused Heterocyclic Compounds as Antibacterial Agent

Treatment of 2,3-di-(4-chlorophenyl) oxirane-2,3-dicarbonitriles(1) with nitrogen nucleophiles, e.g. N2H4, NH2OH afforded pyrazole 2, 1.2oxazole 3 derivatives respectively The 3-amino pyrazole-4-one derivatives 2 can be used as a key starting materials to synthesize some important Schiff base 4 and fused heterocyclic compounds e.g. Imidazolo-[4,5-c]pyrazole 5, Pyrazolo[3,4-e]1,2,4-triazine 6, pyrazol[1,2-a] 1,3,5-triazine 7, 8 and 9. The electromeric effect of the halogen atom in the aryl moieties can be controlled upon the rate of reaction and the yield of the product. The structures of synthesized new compounds were characterized by spectral data and screened for their antimicrobial activities against various bacteria and fungi strains. The heterocyclic compounds 7, 8 and 9 that contained bridgehead nitrogen gave an excellent result.&nbsp

Regioselective Green Synthesis and Antimicrobial properties of full fused non mixed Heterocyclic Systems

One pot synthesis and reaction of triazinthione and triazinohydrazide derivatives with different electrophilic reagents in ordered to synthesis of some interesting non-mixed heterocyclic compounds. Structures of thiazolotriazine, triazolotriazine, pyrimidinyltriazine, and triazinotriazine derivatives were established via spectroscopic data and elemental analysis. The synthesized compounds were screened for their antimicrobial activity

Ultrasonic and solvent free Synthesis of Regioselective Diastereomeric Adducts and Heterocyclic Products as antibacterial agent

Oxirane ring containing the carboxylic group in the α,β-position are useful intermediates in the synthesis of biologically active compounds. Epoxidation of 4-(4-acetylamino and/or bromophenyl)-4-oxo-but-2-enoic acids via ultrasound condition afforded α-oxirane carboxylic acid followed by regioselective diastereomeric adducts of camphor. The steric factor plays an important role in regioselectivity. Formation of oxirane and furan derivatives via ultrasonic condition was considered as key steps for synthesis of some important heterocyclic compounds. The structure of new synthesized compounds 2-9a,b were elucidated by elemental analysis and spectroscopic data. The antibacterial activity for the synthesized compounds was evaluated

Use of 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione in the Synthesis of Novel Quinazolinone Derivatives

The 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione 1 was synthesized and allowed to react with each of  p-methoxybenzaldehyde,  p-methoxyacetophenone and chloroacetyl chloride to produce the Schiff bases 2 and 3 and 2-chloro-N-(3-{5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1,3,4-thiadiazol-2-yl}-4-oxo-3,4-dihydroquinazolin-2-yl)acetamide 6, respectively. The products 2 and 3 were reacted with phenyl isothiocyanate to afford 4 and 5. Derivative 6 was reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol giving 7-9 respectively. In turn, the derivative 8 was reacted with α-bromoglucose tetraacetate affording product 8a whereas 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording derivative 9a. Moreover, the reactions of the derivative 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate gave derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1H-NMR and elemental analysis. Key words: Quinazolinyl thiazolidine, thioxodiazetidinyl quinazoline, piperazinyl quinazolinone, thiomorpholine and  triazinoquinazoline

Use of 2-Ethoxy(4H)-3,1-benzoxazin-4-one as a Precursor for Synthesis of Quinazoline and Quinazolinone Starting Materials

The interactions of 2-ethoxy(4H)-3,1-benzoxazin-4-one (1) with various nitrogen nucleophiles such as ammonium acetate,  hydrazine hydrate, ethanolamine, p-phenylenediamine, o-phenylenediamine, o-tolidine, dapsone, 2-aminophenol, 4-aminophenol, 4-aminobenzoic acid and 2-aminonicotinic acid have been discussed. The reactions of 2-thoxy-(3H)-quinazolin-4-one with ethyl chloroformate, phosphorus pentasulfide, chloroacetyl chloride and phosphorus oxychloride have also been investigated. Similar reactions of 2-ethoxy-4-chloroquinazoline with hydrazine hydrate and thiosemicarbazide have been introduced. Aminolysis of the 2-ethoxy group in some of the thiadiazoloquinazolinone derivatives has been attempted. The interactions of these aminolized derivatives and the 3-aminoquinazolinone with chloroacetyl chloride have been studied. All of the synthesized derivatives have been used in a wide range as starting materials for the synthesis of novel quinazoline and/or quinazolinones which have biological activity. The structures of all these products, obtained by heterocyclic ring opening and ring closure, were inferred by the IR, MS, 1H NMR spectral as well as elemental analyses. Keywords: Aminothiadiazole, Benzoxazin-4-one, N-nucleophile, quinazoline, quinazolin-4-one, thiosemicarbazide

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Microwave-assisted synthesis, antioxidant activity, docking simulation, and DFT analysis of different heterocyclic compounds

Abstract In this investigation, pressure microwave irradiation was used to clarify the activity of 1-(2-hydroxyphenyl)-3-(4-methylphenyl)prop-2-en-1-one (3) towards several active methylene derivatives utilized the pressurized microwave irradiation as green energy resource . Chalcone 3 was allowed to react with ethyl cyanoacetate, acetylacetone, and thioglycolic acid; respectively, at 70 °C with pressure under microwave reaction condition to afford the corresponding 2-hydroxyphenylcyanopyridone, 2-hydroxyphenyl acetylcyclohexanone, and thieno[2,3-c]chromen-4-one derivatives respectively. Moreover, the reaction of chalcone 3 with hydrogen peroxide with stirring affords the corresponding chromen-4-one derivative. All the synthesized compounds were confirmed through spectral tools such as FT-IR, 1HNMR, 13CNMR, and mass spectrum. Furthermore, the synthesized heterocycles were exhibited excellent antioxidant activity and comparable with vitamin C, where the presence of the OH group increases the scavenger radical inhibition. Furthermore, the biological activity of compound 12 was demonstrated through molecular docking stimulation using two proteins, PDBID: 1DH2 and PDBID: 3RP8, which showed that compound 12 possesses greater binding energy and a shorter bond length comparable with ascorbic acid. Also, the compounds were optimized through DFT/B3LYP/6-31G (d,p) basis set and identification of their physical descriptors, whereas the compound 12 was confirmed through X-Ray single structure with Hirsh field analysis of the compound to know the hydrogen electrostatic bond interaction, and correlated with the optimized structure by comparing their bond length, bond angle, FT-IR, and NMR, which gave excellent correlation

3-(4-Bromobenzoyl)prop-2-enoic acid as Precursor in Synthesis of Some Important Heterocyclic Compounds

Abstract The present work deals with the generation and synthesis of different heterocycles such as 2-pyrimidine thione, pyrane, pyridine and phthalazinone derivative via the treatment of 3-(4-bromobenzoyl)prop-2-enoic acid with thiourea, ethylcyanoacetate malononitrile& acetylacetone in presence of amm.acetate and/or piperidine respectively.Additionally, utility of 2-amino-3-cyano-4-carboxy-6-(4-bromophenyl)3,4-dihydropyridine (4) as a key starting material to synthesize some important heterocycles include fused pyrido-pyrimidine,fused pyrido-pyridazinopyrimidine and interesting diheterocyclic amines

Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents

A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data