DOCSLIB.ORG

Thiazole Cores As Organic Fluorophore Units

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thiazole Cores As Organic Fluorophore Units 116 T HIAZOLE CORE S AS ORGANIC FLUOROPHORE UNITS: SYNTHESIS AND FLUORESCENCE DOI: http://dx.medra.org/ 10.17374/targets.2020.23.116 Nataliya P. Belskaya * a,b , Irena Kostova c , Zhijin Fan d a Ural Federal University, Mira str. 19, 620002 Ekaterinburg, Russia b Institut e of Organic Synthesis, Ural Branch of Academy of Science , 620219 E katerinburg, Russia c Department of Chemistry, Faculty of Pharmacy, Medical University , Dunav s tr. 2, 1000 Sofia, Bulgaria d State Key Laboratory of Elemento - Organic Chemistry, College of Chemis try, Nankai University, 30 0 071 Tianjin, PR China , Collaborative Innovation Center of Chemical Science and Engineering ( Tianjin ) , Nankai University, 300071 Tianjin , P . R . China (e - mail: [email protected] ) Abstract. M ethods for the synthesis of thiazole s , which display ph otoph y sical properties, are present ed and analy z ed . T he scope and limitation s of well - known pathways used to construct th is heterocyclic core , and the introduction of funct ional groups, substituents , and linear linkers to tune the fluorescence , are described . R elationships between structure and photoph y sical properties , and applications as photoswitches and in i on recognition, are also discussed . Contents 1. Introduction 2. Synthesis of fluorescent thiazoles 2.1 . M ain approaches to thiazole core construction 2.1.1. Erlenmeyer method for thiazole ring construction 2.1.2. Different methods for thiazole ring construction 2.2 . Modification of the thiazole core 2.2.1. Aryl/heteroarylation of the thiazole ring 2.2.2. Alkylation of hydroxythiazoles 2.2.3. Introduction of substituents containing C=C, С=N, and N=N bonds 2. 3 . Complexation of thiazole derivatives 3. Photophysical properties 3.1 . 4 - Hydroxythiazoles as chromophores and fluorophores 3.2 . Photophysical properties of 2 - and 5 - aminothiazoles 3.3 . Thiazoles with flexible conjugated systems 4. Photoswitches base d o n 1,3 - thiazole derivatives 5. Cation sensors 6. pH - sensitive thiazole fluorescence 7. Conclusion s Acknowledgement s References 1. Introduction T hiazole structures exhibit interesting properties that have attract ed research attention o wing to the ir abundance and potential as building blocks in the development of lead molecules , new drug candidates and biologically active compounds . 1 - 5 In the last decade , thiazoles have been applied as fluorescent dyes. 6 The thiazole heterocyclic core is key to several natural products, such as luciferin , a compound responsible for bioluminescen ce in the firefly (Lampyridae) (Figure 1) . 7 Figure 1. Structure of f irefly l uciferin and o xyluciferin . 117 Owing to the expansion of material s science in the last decade , the design of novel thiazole derivatives for application s in this field has received increasing research interest. In this chapter, we report current progress in the development of fluorophores containing thiazole core s, their properties , and the ir main application s, covering the period 2009 - 2019. 2. S ynthesis of fluorescent thiazoles These new thiazoles with substituents necessary to afford meaningful fluorescence can be obtained using different pathways. One pathway involves preparing the heterocyclic core from starting reagents in which all additional groups are already present . Another pathway decorate s the prepared thiazole with various functionalities according to the demands of the subsequent application. We hav e limited this survey to thiazoles that have exhibited photophysical properties. Fluorophore design with unique characteristics is guided by several definite rules and recommendations and usual requires introducing specific substituents, functionalities, c hains, cyclic and heterocyclic fragments, multiple bonds, and tailored constructions that provide molecules with the necessary electronic density However, in addition to the nature and strength of the electronic properties of substituents , their location in the molecule is also important . Furthermore , the design of new fluorophores must account for molecule structure symmetry , which significantly a ffect s the substance optic properties. 2.1. M ain approaches to thiazole core construction The most general and wide ly used method for construct ing thiazole cycle s is based on the condensation reaction of thi o carbamoyl compounds with - halogenocarbo nyl derivatives ( Hantzsch synthesis ) 1 at room temperature or by heat ing in solvent (EtOH, DMF, acetone, acetic acid , toluene ) in the presence of a catalytic amount of base (TEA, NaOAc, DIEA ) or without any additive . Th is synthesis does not usually require severe conditions or expensive catalysts or reagents. Furthermore , various compounds can be obtained , with the electronic structures controlled and tuned by varying the electronic nature and spatial parameters of the substituents. Employing this synthetic method (Scheme 1) , various 2,4 - di substituted and 2,4,5 - trisubstituted thiazoles have been synthesized in good yields. 8 - 2 7 Scheme 1 . Classical Hantzsch thiazole synthesis . This r eaction has a large scope , with a romatic - halo carbon y l compounds and many different heterocyclic derivatives often used as electrophilic reagent s . 1 0,13,14,16,17,19,25 - 27 For example, a library of 4 - het ero arylthiazoles 6 has been synthesized with good yields , as shown in Scheme 2 . Scheme 2 . Synthes is of 4 - het ero aryl thiazole s 6 . Furthermore , various heterocyclic thioamides 7 can be used in this reaction (Scheme 3) . 12,15 - 20,22 ,26,27 New thiazole derivatives 12 and 13 ( Scheme 4 ) with conjugated system including flexible groups containing enamine (NH – CH=C – ) or aza - enamine (NH – N=C – ) chains on the C2 ring atom were synthesized by heating in DMF. 21 - 24 118 Scheme 3 . Synthesis of 2 - het ero arylthiazoles 9 . Scheme 4 . Synthesis of enamine and aza - enamine thiazoles 1 2 and 1 3 . 3 - A ryl - 2 - (thiazol - 2 - yl)acrylonitriles 1 6 were also synthesiz ed using the Hantzsch thiazole synthesis, in which thioacetamides 1 4 were condensed with the corresponding - halocarbon yl compounds 1 5 in DMF or ethanol (Scheme 5 ) . 25 Scheme 5 . Synthesis of thiazoles 1 6 . 4,4 ' - Bis - thia z ole 19 and its isomeric form 2,2 ' - bisthiazole 2 3 were synthesized in good yield s by the Hantzsch reaction of 2 - hydroxythiobenzamide 1 7 with 1,4 - dibromo - 2,3 - butan e dione 18 and dithiooxamide 21 with 2 - bromo - 2 - methoxyacethophenone 2 0 , respectively, in refluxing ethanol (Scheme 6 ) . 28 Scheme 6 . Synthesis of bisthiazole s 19 and 2 3 . Thiourea has also been explored as a nucleophilic partner with haloketones to give 2 - amino thiazole. 2 9 - 3 6 2 - A mino - 4 - aryl thiazole derivatives 25 have been synthesized in a solution of - bromoarylethanones 2 and thiourea 2 4 using different conditions (Scheme 7 ). 30 - 3 3 Several studies have reported multicomponent one - pot implementations of the Hantzsch reaction. Styrenes 26 reacted with N - bromosuccinimide (NBS) and carbothioamide to afford the corresponding 2,4 - disubstituted and 2,4,5 - trisubstituted thiazoles 29 (Scheme 8). 37 The reaction mechanism involved the formation of bromohydrin 27 followed by NBS - mediated oxidation and in - situ formation of phenacyl 119 bromide 28 , which then underwent condensation with a carbothioamide to form thiazoles 29 with good and high yields (Scheme 8 ) . 37 Scheme 7 . Synthesis of 2 - aminothiazoles 25 . Scheme 8 . NBS - assisted o ne - p ot synthesis of substituted thiazoles from styrenes in water . In a one - pot procedure using available arylalkyl ketones 3 0 , NBS , and thiourea , citric acid was employed as catalyst for t he synthesis of 2 - amino - 4 - aryl thiazoles 3 2 via - bromination with subsequent C – S and C – N bond formations (Scheme 9) . 38 Scheme 9 . One - pot s ynthesis of 2 - amino - 4 - aryl substituted thiazoles. A m ultistep synthesis was developed to obtain n ovel push - pull dye 35 , which contains a benzimidazole fluorophore and thiazole unit. D ye 3 5 was polar and showed poor solubility (Scheme 10). 39 - 4 3 Scheme 1 0 . Synthesis of ( benzoimidazol - 2 - yl)thiazole 3 5 . Coumarin and pyran - 2 - оne derivatives form an important class of oxygen - containing heterocyclic compounds with interesting photophysical, photochemical, and fluorescent properties. Therefore, many heterocyclic systems incorporating these oxygen - containing and thiazole cycles, have been synthesized . 44 - 46 A multi component reaction strategy was used to synthesize the desired series of coumarinyl thiazoles 39 . 46 First, 3 - (2 - bromoacetyl) - 2 H - chromen - 2 - one 3 7 was readily synthesized by the base - catalyzed condensation of salicylaldehyde with ethyl acetoacetate, followed by bromination ( Scheme 11) . 46 I ntermediate 37 was then treated with differently substituted acetophenones 38 and thiosemicarbazide in one - pot i n the presence of glacial acetic acid as catalyst to obtain compounds 39 in 63 - 78% yields. 120 Scheme 1 1 . Synthetic route toward coumarinyl thiazole analogues 3 9 via a one - pot reaction . Systems containing both thiazole and pyrazole cycles were synthesized by using thiosemicarbazide as the thiocarbamoyl nucleophilic center. 44 - 49 A novel series of pyran - and coumarin - substituted thiazolyl - pyrazole - chromen - 2 - one derivatives 41 were efficiently synthesized through a co nvenient one - pot multicomponent transformation using the Hantzsch thiazole and Knorr pyrazole syntheses (Scheme 12). 44 Scheme 1 2 . Synthesis of multiheterocycle thiazolyl
Load more

Recommended publications
  • Study of Antibacterial Effect of Novel Thiazole, Imidazole, and Tetrahydropyrimidine Derivatives Against Listeria Monocytogenes
    ORIGINAL ARTICLE Study of Antibacterial Effect of Novel Thiazole, Imidazole, and Tetrahydropyrimidine Derivatives against Listeria Monocytogenes Behzad Ghasemi,1* Hamid Beyzaei,2 Hadi Hashemi3 1Department of Pathobiology, Faculty of Veterinary, University of Zabol, Zabol, Iran. 2Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran. 3Department of Clinical Sciences, Faculty of Veterinary, University of Zabol, Zabol, Iran. ABSTRACT Purpose: In this study, we have focused on antibacterial effect of newly synthesized thiazole, imidazole, and tetrahydropyrimidine derivatives in Iran on listeria monocytogenes. Materials and Methods: For evaluation of antibacterial effect, the disk diffusion method was applied to measure the growth inhibition zone diameter and broth micro dilution was performed to determine the minimum inhibitory concentration. Results: Assessing the antibacterial effect showed that only thiazole derivative 6d had inhibitory effect on listeria monocytogenes and the other thiazole, imidazole and tetrahydropyrimidine derivatives lacked any inhibitory clue on this organism. The inhibitory effect of thiazole derivative 6d was shown by minimum inhibitory concentration = 64 and growth inhibition zone diameter = 23 ± 0.1. In antibiogram test, also the most susceptibility was recorded for gentamicin and penicillin with minimum inhibitory concentration = 1 µg/mL. Conclusion: The antibacterial effect of thiazole, imidazole and tetrahydropyrimidine derivatives differs from each other and cross connections such as linkage of oxygen to thiazole ring in derivative 6d, could reinforce this effect. By proving the in vitro antibacterial effect of the novel thiazole derivative on listeria monocytogenes, to more recognize this compound, next step is determining the toxicity and therapeutic effects in laboratory animals. Keywords: listeriosis; drug therapy; treatment outcome; antifungal agents; chemistry; pharmacology.
    [Show full text]
  • Synthesis of New Thiazole and Thiazolyl Derivatives of Medicinal Significant-A Short Review
    MOJ Bioorganic & Organic Chemistry Mini Review Open Access Synthesis of new thiazole and thiazolyl derivatives of medicinal significant-a short review Abstract Volume 2 Issue 2 - 2018 In the field of therapeutic science, thiazoles are of extraordinary importance, because of their potent and significant biological activities. Likewise thiazole and their Weiam Hussein,1 Gülhan Turan- derivatives are found in various powerful naturally and biologically active compounds Zitouni2 which possess a broad spectrum of biological activity therefore, synthesis of this 1Department of Pharmaceutical Chemistry, Aden University, compound is of remarkable concern. This review primarily focuses on the updated Yemen research papers reported in literature for the synthesis of thiazole and thiazolyl 2Department of Pharmaceutical Chemistry, Anadolu University, compounds. Turkey Keywords: thiazoles, thiazolyl, synthetic procedures, biological activity Correspondence: Weiam Hussein, Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir, Turkey, Tel +905074929053, Email [email protected] Received: February 23, 2018| Published: March 12, 2018 Introduction Kaplancikli et al. 11 reported a simple and three steps-reaction procedure for the synthesis of new benzimidazole-thiazole derivatives. The synthesis of heterocyclic rings has been a fascinating field 4-(1H-benzimidazol-1-yl)benzaldehyde was prepared by reacting in therapeutic science. Various heterocyclic compounds containing 1H-benzimidazole and 4-fluorobenzaldehyde under microwave nitrogen and sulfur have flexible frameworks for drugs development irradiation, then, the reaction between 4-(1H-benzimidazol- and design.1 Thiazole is one of the most intensively studied classes of 1-yl)benzaldehyde and hydrazine carbothioamide gave as a aromatic five-membered heterocyclics. It was first defined by Hantzschresult 2-(4-(1H-benzimidazol-1-yl)benzylidene)hydrazine-1- and Weber in 1887.
    [Show full text]
  • In Vitroo and in Vivo Pharmacology of 4-Substituted
    IN VITROO AND IN VIVO PHARMACOLOGY OF 4-SUBSTITUTED METHOXYBENZOYL-ARYL-THIAZOLES (SMART) AND 2- ARYLTHIAZOLIDINE-4-CARBOXYLIC ACID AMIDES (ATCAA) Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Chien-Ming Li, M.S. Graduate Program in Pharmacy The Ohio State University 2010 Dissertation Committee: Dr. James T. Dalton, Advisor Dr. Robert W. Brueggemeier Dr. Thomas D. Schmittgen Dr. Mitch A. Phelps Copyright by Chien-Ming Li 2010 ABSTRACT Formation of microtubules is a dynamic process that involves polymerization and depolymerization of the αβ-tubulin heterodimers. Drugs that enhance or inhibit tubulin polymerization can destroy this dynamic process, arresting cells in the G2/M phase of the cell cycle. Although drugs that target tubulin generally demonstrate cytotoxic potency in sub-nanomolar range, resistance due to drug efflux is a common phenomenon among the antitubulin agents. We recently reported a class of 4-Substituted Methoxybenzoyl-Aryl- Thiazoles (SMART), which exhibited great in vitro and in vivo potency. SMART compounds effectively inhibited tubulin polymerization in dose dependent manner, suggesting that SMART compounds may bind to tubulin and subsequently hamper the polymerization. To date the only method to determine the binding of inhibitor to tubulin has been competitive radioligand binding assays. We developed a novel non-radioactive mass spectrometry (MS) binding assay to study the tubulin binding of colchicine, vinblastine and paclitaxel. The method involves a very simple step of separating the unbound ligand from macromolecules using ultrafiltration. The unbound ligand in the filtrate can be accurately determined using a highly sensitive and specific LC-MS/MS method.
    [Show full text]
  • Heterocyclic Chemistrychemistry
    HeterocyclicHeterocyclic ChemistryChemistry Professor J. Stephen Clark Room C4-04 Email: [email protected] 2011 –2012 1 http://www.chem.gla.ac.uk/staff/stephenc/UndergraduateTeaching.html Recommended Reading • Heterocyclic Chemistry – J. A. Joule, K. Mills and G. F. Smith • Heterocyclic Chemistry (Oxford Primer Series) – T. Gilchrist • Aromatic Heterocyclic Chemistry – D. T. Davies 2 Course Summary Introduction • Definition of terms and classification of heterocycles • Functional group chemistry: imines, enamines, acetals, enols, and sulfur-containing groups Intermediates used for the construction of aromatic heterocycles • Synthesis of aromatic heterocycles • Carbon–heteroatom bond formation and choice of oxidation state • Examples of commonly used strategies for heterocycle synthesis Pyridines • General properties, electronic structure • Synthesis of pyridines • Electrophilic substitution of pyridines • Nucleophilic substitution of pyridines • Metallation of pyridines Pyridine derivatives • Structure and reactivity of oxy-pyridines, alkyl pyridines, pyridinium salts, and pyridine N-oxides Quinolines and isoquinolines • General properties and reactivity compared to pyridine • Electrophilic and nucleophilic substitution quinolines and isoquinolines 3 • General methods used for the synthesis of quinolines and isoquinolines Course Summary (cont) Five-membered aromatic heterocycles • General properties, structure and reactivity of pyrroles, furans and thiophenes • Methods and strategies for the synthesis of five-membered heteroaromatics
    [Show full text]
  • Thiazole Analogues of the Marine Alkaloid Nortopsentin As Inhibitors of Bacterial Biofilm Formation
    molecules Article Thiazole Analogues of the Marine Alkaloid Nortopsentin as Inhibitors of Bacterial Biofilm Formation Anna Carbone †,‡, Stella Cascioferro † , Barbara Parrino, Daniela Carbone , Camilla Pecoraro, Domenico Schillaci , Maria Grazia Cusimano, Girolamo Cirrincione and Patrizia Diana * Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy; [email protected] (A.C.); [email protected] (S.C.); [email protected] (B.P.); [email protected] (D.C.); [email protected] (C.P.); [email protected] (D.S.); [email protected] (M.G.C.); [email protected] (G.C.) * Correspondence: [email protected] † Present address: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132 Genova, Italy. ‡ These authors contributed equally to this work. Abstract: Anti-virulence strategy is currently considered a promising approach to overcome the global threat of the antibiotic resistance. Among different bacterial virulence factors, the biofilm formation is recognized as one of the most relevant. Considering the high and growing percentage of multi-drug resistant infections that are biofilm-mediated, new therapeutic agents capable of counteracting the formation of biofilms are urgently required. In this scenario, a new series of 18 thiazole derivatives was efficiently synthesized and evaluated for its ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923 and S. aureus ATCC 6538 and the Gram-negative strain Pseudomonas aeruginosa ATCC 15442. Most of the new compounds showed a marked selectivity against the Gram-positive strains. Remarkably, Citation: Carbone, A.; Cascioferro, S.; five compounds exhibited BIC50 values against S.
    [Show full text]
  • Dissociation Constants of Organic Acids and Bases
    DISSOCIATION CONSTANTS OF ORGANIC ACIDS AND BASES This table lists the dissociation (ionization) constants of over pKa + pKb = pKwater = 14.00 (at 25°C) 1070 organic acids, bases, and amphoteric compounds. All data apply to dilute aqueous solutions and are presented as values of Compounds are listed by molecular formula in Hill order. pKa, which is defined as the negative of the logarithm of the equi- librium constant K for the reaction a References HA H+ + A- 1. Perrin, D. D., Dissociation Constants of Organic Bases in Aqueous i.e., Solution, Butterworths, London, 1965; Supplement, 1972. 2. Serjeant, E. P., and Dempsey, B., Ionization Constants of Organic Acids + - Ka = [H ][A ]/[HA] in Aqueous Solution, Pergamon, Oxford, 1979. 3. Albert, A., “Ionization Constants of Heterocyclic Substances”, in where [H+], etc. represent the concentrations of the respective Katritzky, A. R., Ed., Physical Methods in Heterocyclic Chemistry, - species in mol/L. It follows that pKa = pH + log[HA] – log[A ], so Academic Press, New York, 1963. 4. Sober, H.A., Ed., CRC Handbook of Biochemistry, CRC Press, Boca that a solution with 50% dissociation has pH equal to the pKa of the acid. Raton, FL, 1968. 5. Perrin, D. D., Dempsey, B., and Serjeant, E. P., pK Prediction for Data for bases are presented as pK values for the conjugate acid, a a Organic Acids and Bases, Chapman and Hall, London, 1981. i.e., for the reaction 6. Albert, A., and Serjeant, E. P., The Determination of Ionization + + Constants, Third Edition, Chapman and Hall, London, 1984. BH H + B 7. Budavari, S., Ed., The Merck Index, Twelth Edition, Merck & Co., Whitehouse Station, NJ, 1996.
    [Show full text]
  • Synthesis, Reactions and Medicinal Uses of Following Compounds/ Derivatives
    COURSE: B. PHARMACY, 4 Sem Module-4: SYNTHESIS, REACTIONS AND MEDICINAL USES OF FOLLOWING COMPOUNDS/ DERIVATIVES Module-4 Learning Material Learning Material Course: B. Pharmacy 4th Sem MODULE-4: SYNTHESIS, REACTIONS AND MEDICINAL USES OF FOLLOWING COMPOUNDS/ DERIVATIVES Ms. Baljeet Kaur, Assistant Professor A.S.B.A.S.J.S.M College of Pharmacy, Bela, Ropar 140111 ASBASJSM COLLEGE OF PHARMACY, BELA, ROPAR Page 1 COURSE: B. PHARMACY, 4 Sem Module-4: SYNTHESIS, REACTIONS AND MEDICINAL USES OF FOLLOWING COMPOUNDS/ DERIVATIVES PYRAZOLE: Pyrazoles are the derivatives of a five-membered heterocyclic ring system called pyrazole. Pyrazole consists of two nitrogen atoms at 1 and 2 positions of the cyclic system. N N H Physical Properties: 1. Pyrazole is a colourless solid. 2. It possesses a pleasant smell. 3. Pyrazole is soluble in water. 4. Pyrazole exhibits tautomerism. 5. Pyrazole has aromatic properties. N NH N N H Synthesis 1. From 1,3-dicarbonyl compounds- 1,3-Dicarbonylcompounds react with hydrazine or hudroxylamine and gives pyrazoles. CH3 O 4 3 O - -H2O NH HSO4 C NH2 3 5 H3C C C N 2 H H3C 2 CH3 N H Acetylacetone 1 3,5-Dimethylpyrazole 2. From 1,3-di polar compounds- Pyrazole derivatives can also be prepared by adding a diazo compound to an acetylenic derivative. C6H5 COOCH3 C N2CH-COOCH3 C6H5 C COOCH3 H3COOC N Methyldiazo acetate N Methylphenyl propiolate H 3,5-Dicarbomethoxy-4-phenylpyrazole Chemical Properties: 1. Oxidation: Pyrazole is resistant to oxidizing agents but the side chain may be oxidized to carboxylic acid group in presence of potassium permanganate.
    [Show full text]
  • Essentials of Heterocyclic Chemistry-I Heterocyclic Chemistry
    Baran, Richter Essentials of Heterocyclic Chemistry-I Heterocyclic Chemistry 5 4 Deprotonation of N–H, Deprotonation of C–H, Deprotonation of Conjugate Acid 3 4 3 4 5 4 3 5 6 6 3 3 4 6 2 2 N 4 4 3 4 3 4 3 3 5 5 2 3 5 4 N HN 5 2 N N 7 2 7 N N 5 2 5 2 7 2 2 1 1 N NH H H 8 1 8 N 6 4 N 5 1 2 6 3 4 N 1 6 3 1 8 N 2-Pyrazoline Pyrazolidine H N 9 1 1 5 N 1 Quinazoline N 7 7 H Cinnoline 1 Pyrrolidine H 2 5 2 5 4 5 4 4 Isoindole 3H-Indole 6 Pyrazole N 3 4 Pyrimidine N pK : 11.3,44 Carbazole N 1 6 6 3 N 3 5 1 a N N 3 5 H 4 7 H pKa: 19.8, 35.9 N N pKa: 1.3 pKa: 19.9 8 3 Pyrrole 1 5 7 2 7 N 2 3 4 3 4 3 4 7 Indole 2 N 6 2 6 2 N N pK : 23.0, 39.5 2 8 1 8 1 N N a 6 pKa: 21.0, 38.1 1 1 2 5 2 5 2 5 6 N N 1 4 Pteridine 4 4 7 Phthalazine 1,2,4-Triazine 1,3,5-Triazine N 1 N 1 N 1 5 3 H N H H 3 5 pK : <0 pK : <0 3 5 Indoline H a a 3-Pyrroline 2H-Pyrrole 2-Pyrroline Indolizine 4 5 4 4 pKa: 4.9 2 6 N N 4 5 6 3 N 6 N 3 5 6 3 N 5 2 N 1 3 7 2 1 4 4 3 4 3 4 3 4 3 3 N 4 4 2 6 5 5 5 Pyrazine 7 2 6 Pyridazine 2 3 5 3 5 N 2 8 N 1 2 2 1 8 N 2 5 O 2 5 pKa: 0.6 H 1 1 N10 9 7 H pKa: 2.3 O 6 6 2 6 2 6 6 S Piperazine 1 O 1 O S 1 1 Quinoxaline 1H-Indazole 7 7 1 1 O1 7 Phenazine Furan Thiophene Benzofuran Isobenzofuran 2H-Pyran 4H-Pyran Benzo[b]thiophene Effects of Substitution on Pyridine Basicity: pKa: 35.6 pKa: 33.0 pKa: 33.2 pKa: 32.4 t 4 Me Bu NH2 NHAc OMe SMe Cl Ph vinyl CN NO2 CH(OH)2 4 8 5 4 9 1 3 2-position 6.0 5.8 6.9 4.1 3.3 3.6 0.7 4.5 4.8 –0.3 –2.6 3.8 6 3 3 5 7 4 8 2 3 5 2 3-position 5.7 5.9 6.1 4.5 4.9 4.4 2.8 4.8 4.8 1.4 0.6 3.8 4 2 6 7 7 3 N2 N 1 4-position
    [Show full text]
  • An Overview of the Synthesis and Antimicrobial, Antiprotozoal, and Antitumor Activity of Thiazole and Bisthiazole Derivatives
    molecules Review An Overview of the Synthesis and Antimicrobial, Antiprotozoal, and Antitumor Activity of Thiazole and Bisthiazole Derivatives 1,2 1, 3 1 Anca-Maria Borcea , Ioana Ionut, *, Ovidiu Cris, an and Ovidiu Oniga 1 Department of Pharmaceutical Chemistry, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, 41 Victor Babes, Street, 400012 Cluj-Napoca, Romania; [email protected] (A.-M.B.); [email protected] (O.O.) 2 Preclinic Department, Pharmacy Specialization, Faculty of Medicine, Lucian Blaga University of Sibiu, 2A Lucian Blaga Street, 550169 Sibiu, Romania 3 Department of Organic Chemistry, “Iuliu Hat, ieganu” University of Medicine and Pharmacy, 41 Victor Babes, Street, 400012 Cluj-Napoca, Romania; [email protected] * Correspondence: [email protected]; Tel.: +40-747-507-629 Abstract: Thiazole, a five-membered heteroaromatic ring, is an important scaffold of a large number of synthetic compounds. Its diverse pharmacological activity is reflected in many clinically approved thiazole-containing molecules, with an extensive range of biological activities, such as antibacterial, antifungal, antiviral, antihelmintic, antitumor, and anti-inflammatory effects. Due to its significance in the field of medicinal chemistry, numerous biologically active thiazole and bisthiazole deriva- tives have been reported in the scientific literature. The current review provides an overview of different methods for the synthesis of thiazole and bisthiazole derivatives and describes various com- pounds bearing a thiazole and bisthiazole moiety possessing antibacterial, antifungal, antiprotozoal, and antitumor activity, encouraging further research on the discovery of thiazole-containing drugs. Citation: Borcea, A.-M.; Ionut,, I.; Cris, an, O.; Oniga, O. An Overview of the Synthesis and Antimicrobial, Keywords: thiazole; bisthiazole; synthesis; derivatives; biological activity Antiprotozoal, and Antitumor Activity of Thiazole and Bisthiazole Derivatives.
    [Show full text]
  • Design, Synthesis and Docking Studies of Novel Thiazole Derivatives Incorporating Pyridine Moiety and Assessment As Antimicrobial Agents Rizk E
    www.nature.com/scientificreports OPEN Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents Rizk E. Khidre 1,2,3* & Ibrahim Ali M. Radini1,3 A novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine- 3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N’- arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between − 6.4 and − 9.2 kcal/mol and they were screened for their antimicrobial activities. Compound 13a shown good antibacterial activities with MIC ranged from 93.7–46.9 μg/mL, in addition, it shown good antifungal activities with MIC ranged from 7.8 and 5.8 μg/mL. Tiazoles are present in numerous natural products e.g. epithilone, thiostrepton, thiamine pyrophosphate (TPP), carboxylase vitamin B1, and penicillin1. Tiazoles have diverse applications in drug development for treatment allergies2, infammation3, HIV infections4, hypertension5, bacterial infections 6, hypnotics7, schizophrenia8, and pain9, as novel inhibitors of bacterial DNA gyrase B10, and as fbrinogen receptor antagonists with antithrom- botic activity11. Tey exhibited fabulous pharmaceutical activities for instance antifungal 12, antimicrobial13–15, anti-infammatory16,17, analgesic18, and anti-cancer19,20, anticonvulsant activities 21. Tere are several commercial drugs contain thiazole moiety (Fig. 1). Pyridines are an important class of heterocyclic compounds because they occur in many natural compounds that have biological activity such as vitamin B3 (niacin) and vitamin B6 (pyridoxin) and natural alkaloids 22.
    [Show full text]
  • Thiazole Via Direct Electrophilic Aromatic Substitution Vladimir Benin University of Dayton, [email protected]
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Dayton University of Dayton eCommons Chemistry Faculty Publications Department of Chemistry 5-2008 Preparation of Halogenated Derivatives of Thiazolo[5,4-d]thiazole via Direct Electrophilic Aromatic Substitution Vladimir Benin University of Dayton, [email protected] Alan T. Yeates Air Force Research Laboratory Douglas Dudis Air Force Research Laboratory Follow this and additional works at: https://ecommons.udayton.edu/chm_fac_pub Part of the Analytical Chemistry Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Chemical and Pharmacologic Phenomena Commons, Environmental Chemistry Commons, Inorganic Chemistry Commons, Materials Chemistry Commons, Medical Biochemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons, Other Chemistry Commons, and the Physical Chemistry Commons eCommons Citation Benin, Vladimir; Yeates, Alan T.; and Dudis, Douglas, "Preparation of Halogenated Derivatives of Thiazolo[5,4-d]thiazole via Direct Electrophilic Aromatic Substitution" (2008). Chemistry Faculty Publications. 11. https://ecommons.udayton.edu/chm_fac_pub/11 This Article is brought to you for free and open access by the Department of Chemistry at eCommons. It has been accepted for inclusion in Chemistry Faculty Publications by an authorized administrator of eCommons. For more information, please contact [email protected], [email protected]. Jan 2008 Preparation of Halogenated Derivatives of Thiazolo[5,4-d]thiazole 1 via Direct Electrophilic Aromatic Substitution Vladimir Benin* [a], Alan T. Yeates [b], Douglas Dudis [b] [a]Department of Chemistry, University of Dayton, Dayton, OH 45469-2357 [b]Air Force Research Laboratory, Materials and Manufacturing Directorate, Wright-Patterson Air Force Base, Dayton, OH 45433-7750 Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives.
    [Show full text]
  • Enthalpies of Vaporization of Organic and Organometallic Compounds, 1880–2002
    Enthalpies of Vaporization of Organic and Organometallic Compounds, 1880–2002 James S. Chickosa… Department of Chemistry, University of Missouri-St. Louis, St. Louis, Missouri 63121 William E. Acree, Jr.b… Department of Chemistry, University of North Texas, Denton, Texas 76203 ͑Received 17 June 2002; accepted 17 October 2002; published 21 April 2003͒ A compendium of vaporization enthalpies published within the period 1910–2002 is reported. A brief review of temperature adjustments of vaporization enthalpies from temperature of measurement to the standard reference temperature, 298.15 K, is included as are recently suggested reference materials. Vaporization enthalpies are included for organic, organo-metallic, and a few inorganic compounds. This compendium is the third in a series focusing on phase change enthalpies. Previous compendia focused on fusion and sublimation enthalpies. Sufficient data are presently available for many compounds that thermodynamic cycles can be constructed to evaluate the reliability of the measure- ments. A protocol for doing so is described. © 2003 American Institute of Physics. ͓DOI: 10.1063/1.1529214͔ Key words: compendium; enthalpies of condensation; evaporation; organic compounds; vaporization enthalpy. Contents inorganic compounds, 1880–2002. ............. 820 1. Introduction................................ 519 8. References to Tables 6 and 7.................. 853 2. Reference Materials for Vaporization Enthalpy Measurements.............................. 520 List of Figures 3. Heat Capacity Adjustments. ................. 520 1. A thermodynamic cycle for adjusting vaporization ϭ 4. Group Additivity Values for C (298.15 K) enthalpies to T 298.15 K.................... 521 pl 2. A hypothetical molecule illustrating the different Estimations................................ 521 hydrocarbon groups in estimating C ........... 523 5. A Thermochemical Cycle: Sublimation, p Vaporization, and Fusion Enthalpies...........
    [Show full text]