Cyclocondensation Reaction Research Articles

Transition-metal-free approach to quinolines via direct oxidative cyclocondensation reaction of N,N-dimethyl enaminones with o-aminobenzyl alcohols.

A transition-metal-free method for the construction of 3-substituted or 3,4-disubstituted quinolines from readily available N,N-dimethyl enaminones and o-aminobenzyl alcohols is reported. The direct oxidative cyclocondensation reaction tolerates broad functional groups, allowing the efficient synthesis of various quinolines in moderate to excellent yields. The reaction involves a C (sp3)-O bond cleavage and a C=N bind and a C=C bond formation during the oxidative cyclization process, and the mechanism was proposed.

Spectrophotometric studies on some new hydroxyl-azo dyes derived from 6-ethyl-4-hydroxyquinoline-2(1H)-one

PurposeThis paper aims to synthesize 6-ethyl-4-hydroxyquinolin-2(1H)-one as a new enol-type coupling component in the preparation of some 3-arylazo-4-hydroxyquinolin-2(1H)-one dyes and evaluate the solvent effects on their absorption in ultraviolet-visible spectra.Design/methodology/approach6-Ethyl-4-hydroxyquinolin-2(1H)-one was synthesized by thermal cyclocondensation reaction of N, N′-bis(4-ethylphenyl) malonamide at 130–140°C in polyphosphoric acid. This compound was then applied in the azo-coupling reaction with some aniline-based diazonium salts, so as to prepare seven new mono-heterocyclic azo dyes. The structures of the compounds were confirmed using mass spectroscopic technique. Fourier transform infra red (FT-IR) and 1H proton nuclear magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13 C NMR) studies on the structure of the azo compounds revealed that they exist as two E- and Z-isomers of hydrazone tautomer both in solid and solution state. The effects of acid and base on the visible absorption spectra of the dyes were also evaluated and discussed.FindingsUltra violet-visible UV-vis absorption spectra of the dyes didn’t show significant variation by changing of solvents because of intramolecular H-bonding between proposed hydrazone forms and 2- and 4-keto functions in their structures. The spectra of the dyes were not sensitive to the addition of acid but were very sensitive to base.Originality/valueThe synthesized 3-arylazo-4-hydroxyquinolin-2(1H)-one dyes are new members in the 4-hydroxyquinolin-2(1H)-one azo dyes family, where very few details regarding the synthesis of such dyes are reported before in the literature. They are unique in terms of synthesis and spectral properties.

Hantzsch-Like Synthesis, DNA Photocleavage, DNA/BSA Binding, and Molecular Docking Studies of Bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) Analogs Linked to Naphthalene Core.

The cyclocondensation reaction of aldehydes with dimedone and bis(6-aminopyrimidin-4-one) in acetic acid led to the formation of the corresponding bis(pyrimido[4,5-b]quinoline-4,6-diones) which are known as bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) analogs in a single step. Also, bis(pyrimido[4,5-b]quinoline-4,6-diones) which are linked to naphthyl core via phenoxymethyl linkage is prepared. The interactions of the synthesized compounds with DNA and bovine serum albumin (BSA) were studied. Gel electrophoresis assay was used to show the capability of the compounds to photocleave the supercoiled pBR322 plasmid DNA in UV-A (365 nm). Besides, the most photocleavable compound, bis(tetrahydropyrimido[4,5-b]quinoline-4,6-dione) linked to pyridin-3-yl at position-5 exhibits good binding affinities toward CT-DNA and BSA as supported by UV/VIS spectral studies. In addition to the experimental findings, a molecular docking simulation was performed to collect detailed binding data for this compound to both biomolecules.

Synthesis, Characterization and Molecular Docking of New Naphthalene-Based Chalcone and Pyrazoline Compounds

Most chemotherapeutic drugs are unable to distinguish between healthy and cancerous cells, resulting in the risk of side effects and drug resistance. There is a continuous effort to find new agents to help bring this disease under control. Compounds with bioactive natural product scaffolds have been of great interest due to their low toxicity and high efficacy. In this study, new naphthalene-based chalcone 1 and pyrazoline 1A compounds were synthesized via a Claisen-Schmidt condensation and cyclo-condensation reaction, respectively. These compounds were characterized using the Fourier Transform Infrared (FT-IR), 1H, and 13C Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular docking activities were performed to study the interactions between these new compounds with breast cancer protein, 3ERT as estrogen receptor-α (ERα). Chalcone 1 and pyrazoline 1A compounds obey Lipinski's rule whereby pyrazoline 1A showed the lowest binding energy of -9.47 kcal/mol, inhibition constant of 113.93 mM and log P of 2.30. Interaction of pyrazoline 1A with 3ERT protein exhibited the hydrogen bonding with GLY521 amino acid, while the hydrophobic interactions were observed with LEU346, LEU384, LEU391, LEU525, LEU387, MET343, ALA350, and MET421 amino acids. Pyrazoline 1A is expected to show promising activities as an anticancer agent.

Molecular Docking Study, Synthesis and Characterization of New Hybrid Anthracene-Thiophene Compounds with Chalcone and Pyridine Scaffolds

Breast cancer is a major health problem with an increasing number of cases over the years. Few classes of anticancer agents have been developed, but they established toxic effects on normal cells. In this study, a new hybrid anthracene-thiophene chalcone 1 has been synthesized via a Claisen-Schmidt condensation of substituted anthracene aldehyde and a thiophene ketone. The cyclo-condensation reaction of chalcone 1 formed a new anthracene-thiophene pyridine 2. The synthesized compounds were structurally characterized by Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular docking activities using AutoDock 4.2 software were performed to study the intermolecular interactions between these compounds with breast cancer protein, 3ERT as the estrogen receptor-α. Chalcone 1 showed free binding energy of -9.81 kcal/mol, while pyridine 2 exhibited better free binding energy of -10.45 kcal/mol against 3ERT protein. The interactions in pyridine 2 include one hydrogen bonding with MET343 amino acid and several hydrophobic interactions such as π-σ interaction with LEU384, π-anion interaction with ASP351, π-alkyl interactions with ALA350, LEU346, LEU391, LEU525, and MET388 and also a π-sulfur interaction with MET343. Chalcone 1 has only noncovalent interactions such as π-σ interaction with THR347 and π-alkyl interactions with ALA350, LEU346, LEU349, LEU387, LEU391, LEU525, and MET388. The molecular docking study of these compounds indicated that chalcone 1 and pyridine 2 showed a promising anticancer effect.

Mortar–Pestle Grinding Technique as an Efficient and Green Method Accelerates the Tandem Knoevenagel–Michael Cyclocondensation Reaction in the Presence of Ethylenediamine Immobilized on the Magnetite Nanoparticles

In this research, we successfully designed and synthesized a new core-shell-structured inorganic-organic hybrid magnetic nanocatalyst via the ethylene diamine immobilized to the core-shell Fe3O4 nanomagnetic particles (Fe3O4@SiO2@(CH2)3/EDA). A variety of analyses such as fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), elemental mapping (WDS), thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD) and Brunauer-Emmet-Teller (BET) were used to characterize the as-synthesized nanocatalysts. The activity of this as-synthesized nanocatalysts can be successfully used in the grinding synthesis of various aldehydes, malononitrile and dimedone under solvent- and metal-free conditions at room temperature to give 2-amino-4H-benzo[b]pyran derivatives within high purity and excellent yields. Easy fabrication of Fe3O4@SiO2@(CH2)3/EDA, waste reduction, effective for large scale synthesis, simple work-up procedure, adherence to the basics of green chemistry, high catalytic efficiency in very small amounts (0.05 g), environmentally friendly and based on natural ingredients are the great advantages of the current method. In particular, due to the super magnetic behavior of the catalyst, it can be easily recovered with the use of an external magnet from the reaction mixture, and it can be reused over 7 successive times with no decrease in the yields and activity.

Chickpea Leaf Exudates: A Highly Efficient Natural Brønsted Acidic Medium for the Synthesis of Pyran-annulated Heterocycles

Abstract:We reported Chickpea leaf exudates (CLEs) as a Brønsted acid, naturally available biodegradable, eco-friendly, and reusable reaction medium for highly efficient and facile one-pot synthesis of pyran-annulated heterocyclic systems, like 7-aryl-benzopyrano[4,3-b]benzopyran-6,8- diones,tetrahydrobenzo[b]pyran, and dihydropyrano[c]chromenes scaffolds. The analogous products were obtained via tandem Knoevengel-Michael addition and cyclo condensation reaction in ethanol at room temperature with 90-96% yields in a short reaction time. Moreover, the reaction media containing Bronsted acids can be easily recovered and reused up to five times, slightly decreasing product yields.

Synthesis and evaluation of a new series of spiro aryl dioxolane compounds: A new scaffold as potential poly(ADP‐ribose)polymerase‐1 (PARP‐1) inhibitors

AbstractA new series of spiro aryl dioxolane derivatives were synthesized and evaluated to find a new scaffold as potential poly(ADP‐ribose)polymerases‐1 (PARP‐1) inhibitors. This key starting compound, 2,6‐bis(methoxybenzylidene)cyclohexanone, was functionalized with different nucleophilic reagents via cyclocondensation reactions to obtain new benzylidene scaffolds containing diverse aryl groups such as spiroindazoleorquinazoline [1,3]dioxolane compounds. Furthermore, the Michael addition reaction of bis‐benzylidene with some active methylene compounds afforded spirochromene‐ or naphthalene‐[1,3]dioxolane compounds. All the synthesized compounds revealed promising inhibition with IC50 values in the nanomolar range (0.997–2.698 nM), not significantly different from that of Olaparib (IC50 = 0.861 nM). Compounds 5b and 15 (IC50 = 1.009 and 0.997 nM) showed the highest potency among all the prepared compounds and accordingly their ability to inhibit the growth of BRCA1 mutated breast cancer cell line MDA‐MB‐436 was tested, where compound 5b (IC50 = 0.67 μM) showed a potency ten folds higher than that of Olaparib but compound 15 (IC50 = 7.47 μM) exerted lower activity but still comparable to that of Olaparib (IC50 = 6.84 μM). Both resulted in the arrest of cell cycle at S phase and caused cell apoptosis. In silico studies including absorption, distribution, metabolism, excretion (ADME) properties, drug‐likeness, and molecular docking were carried out to support the above‐mentioned findings. This work presents compounds 5b and 15 as promising scaffolds as PARP‐1 inhibitors.

Methylene Blue as a Photo-Redox Catalyst: The Development Synthesis of Tetrahydrobenzo[b]pyran Scaffolds via a Single-Electron Transfer/Energy Transfer.

In a green tandem reaction using aldehyde derivatives, malononitrile, and dimedone, a radical tandem Knoevenagel–Michael cyclocondensation reaction of tetrahydrobenzo[b]pyran scaffolds was developed. Using visible light as a sustainable energy source, methylene blue (MB+)-derived photo-excited state functions were employed in an aqueous solution as single-electron transfer (SET) and energy transfer catalysts. The range of yields is quite uniform (81–98%, average 92.18%), and the range of reaction time is very fast (2–7 min, average 3.7 min), and the point mentioned in the discussion is that the procedure tolerates a range of donating and withdrawing groups, while still giving very excellent yields. The reaction is fairly insensitive to the nature of the substituents. Research conducted in this project aims to develop a non-metallic cationic dye that is both inexpensive and widely available for more widespread use. In addition to energy efficiency and environmental friendliness, methylene blue also offers an excellent atom economy, time-saving features, and ease of use. As a result, a wide range of long-term chemical and environmental properties can be obtained. The turnover number and turnover frequency of tetrahydrobenzo[b]pyran scaffolds have been computed. Surprisingly, gram-scale cyclization is a possibility, implying that the technology may be applied in industries.

Efficient Synthesis of 6,7-Dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile Compounds and Their Applicability As Inhibitor Films for Steel Alloy Corrosion: Collective Computational and Practical Approaches.

An effective method for designing new heterocyclic compounds of 6,7-dihydro-5H-cyclopenta[b]pyridine-3-carbonitrile derivatives (CAPDs) was presented through cyclocondensation reaction between 2,5-diarylidenecyclopentanone derivatives and propanedinitrile, and the cyclocondensation reaction succeeded using a sodium alkoxide solution (sodium ethoxide or sodium methoxide) as the reagent and the catalyst. The synthesized CAPD derivatives were employed as novel inhibitors for carbon steel (CS) corrosion in a molar H2SO4 medium. The corrosion protection proficiency was investigated by electrochemical measurements (open circuit potential vs time (EOCP vs t), potentiodynamic polarization plots (PDP), and electrochemical impedance spectroscopy (EIS)) and surface morphology (scanning electron microscopy (SEM)) examinations. The results show that the CAPD derivatives exhibit mixed type inhibitors and a superior inhibition efficiency of 97.7% in the presence of 1.0 mM CAPD-1. The adsorption of CAPD derivatives on the CS interface follows the Langmuir isotherm model, including physisorption and chemisorption. Scanning electron microscopy (SEM) exploration confirmed the adsorption of the CAPD derivatives on the CS substrate. Monte Carlo (MC) simulations and DFT calculations revealed that the efficacy of the CAPD molecules correlates well with their structures, and this protection was attributed to their adsorption on the CS surface.

Microwave-assisted Multi-component Reaction for the Green Synthesis of Novel 4-(5-hydroxybenzo[a]phenazin-6-yl)-5-phenyl-1, 3-dihydro-2H-imidazol-2-one Using H3PW12O40@nano-TiO2 as Recyclable Catalyst

ABSTRACT In this context, we have demonstrated a highly efficient and green process for the preparation of various potentially biologically active functionalized 4-(5-hydroxybenzo[a]phenazin-6-yl)-5-phenyl-1,3-dihydro-2H-imidazol-2-one derivatives via a one-pot, the four-component cyclo-condensation reaction in the presence of catalytic amounts of phosphotungstic acid supported on TiO2 as a nontoxic, highly reactive, and eco-friendly solid acid catalyst under MWI in solvent-free conditions. The crystallinity and the crystallite size nano-TiO2 were fabricated and characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), scanning electron microscopy (FESEM), Thermogravimetric Analysis (TGA), Fourier transform infrared (FT-IR), Brunauer-Emmett-Teller (BET), and atomic force microscopy (AFM). We believe that this work can provide new insights into the fabrication of high-performance photocatalysts and facilitate their practical application in environmental issues.

Synthesis and biological evaluation of 3, 4 -dihydropyrimidines thiones derivatives

3, 4-dihydropyrimidin-2(1H)-thiones, derivatives were synthesized by one pot solvent free green modified Biginelli cyclocondensation reaction catalyzed by triphenylphosphine as Lewis base. The structures of the synthesized compounds have been elucidated by IR, 1H NMR and elemental analysis. Synthesized compounds were screened for their antimicrobial screened against the E.coli and staphylococcus aureus, Salmonella typhi, Bacillus subtilis, Escherichia coli and antifungal activity against Aspergillus niger, Penecillium crysogenum, Aspergillus flavus, and Candida albicans.

Design, synthesis, AChE/BChE inhibitory activity, and molecular docking of spiro[chromeno[4,3-b]thieno[3,2-e]pyridine]-7-amine tacrine hybrids

A new series of 12 examples of spiro[chromeno[4,3-b]thieno[3,2-e]pyridine]-7-amines tacrine hybrids (3) were designed and synthesized as cholinesterase inhibitors. These new compounds were synthesized at 20-33% yields by a one-pot two-step cyclocondensation reaction of 2-aminothiophene-3-carbonitriles (1) with spiro[chroman-2,10-cycloalkan]-4-ones (2) using AlCl3 as the catalyst without solvent and under conventional thermal heating. Subsequently, these new tacrine hybrids were subjected to AChE and BChE inhibitory activity evaluation and molecular docking studies. In vitro cholinesterase assays and in silico docking indicated that all new tacrine analogs 3 were not AChE inhibitors. However, the molecules without a carbocyclic moiety geminated to the thiophene ring, i.e., spiro scaffolds that originated from cyclopentanone (3aa), cyclohexanone (3ba), and cycloheptanone (3ca) showed the highest inhibitory potency against the BChE enzyme, thereby proving to be promising candidates for evaluation in Alzheimer's disease synthetic models.

Synthesis and Tyrosinase Inhibitory Activity of (E)-5-Benzyl-7- (3-Bromobenzylidene)-3-(3-Bromophenyl)-2-Phenyl-3,3a, 4,5,6,7-Hexahydro-2H-Pyrazolo[4,3-c]Pyridine

The tyrosinase enzyme plays an essential role in the pigmentation of human skin, fruits, and vegetables. It has been tied with several human skin diseases and post-harvest problems. Hence, the tyrosinase enzyme becomes an excellent therapeutic target to overcome these issues. This study aimed to screen tyrosinase inhibitors by synthesizing halogen-substituted pyrazolopyridine derivatives. The pyrazolopyridine compound was obtained through two stages of synthesis. First, the intermediate compound, a derivative of 3,5-bis(arylidene)-4-piperidone, was synthesized through the Cleisen-Schmidt condensation reaction of 4-piperidone and benzaldehyde derivatives. Furthermore, the intermediate compound was reacted with phenylhydrazine through a cyclocondensation reaction to produce the titled compound with an 11% yield. The chemical structure of the target compound was identified through the interpretation of UV, FTIR, NMR, and HRMS spectra. Then an in vitro assay was conducted on the tyrosinase enzyme of the fungus Agaricus bisporus by detecting the presence of dopachrome at a wavelength of 492 nm. As a result, the in vitro assay showed that the titled compound had a weak inhibitory activity, and the IC50 value was > 500 µM. Thus, the synthesized compound is considered inactive.

Planar and Helical Dinaphthophenazines.

In this study, we report the synthesis of a series of planar and helical dinaphthophenazines by cyclocondensation reactions between the newly developed 9,10-bis((triisopropylsilyl)ethynyl)anthracene-1,2-dione and different diamines. Their optoelectronic and electrochemical properties are studied by ultraviolet–visible (UV–vis) spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and density functional theory calculations.

Design, Synthesis, and Biological Evaluation of Novel Trifluoromethoxy Substituted Pyrazolines as Potential Tubulin Assembling Inhibitors

Breast cancer is a major health problem with an increasing number of cases over the years. Few classes of anticancer agents have been developed but they established toxic effects on normal cells. Despite the availability of many effective drugs to treat different types of cancers, chemotherapeutic drugs are unable to distinguish between healthy and cancerous cells, resulting in the risk of side effects and drugs resistance. There is a continuous effort to find new agents to help bring this disease under control. In this study, novel fluorinated pyrazolines derivatives (2a-c) were designed and synthesized via cyclo-condensation reaction of commercially available trifluoromethoxy phenylhydrazine with a series of chalcone derivatives (1a-c). These pyrazoline compounds, 2a-c exhibited inhibitory activity against MCF-7 cell lines with the IC50 values of 7.62 ± 0.69, 29.61 ±1.60 and 14.38 ± 0.69 μM, respectively. These values are comparable to the positive control, Doxorubicin (IC50 of 17.44 ± 5.32 μM). Pyrazoline 2a exhibited the best free binding energy of-10.8 kcal/mol compared to pyrazoline 2b and 2c which showed the free binding energy of-8.6 and-9.5 kcal/mol, respectively. Molecular docking results of pyrazoline 2a exhibited good interaction between OCF3 moiety with EGFR active site, forming three π bonds which enhanced the anticancer activity. Therefore, pyrazoline 2a would provide promising access to future studies as a potential antitumor agent. Keywords: Fluorinated compounds, trifluoromethoxy, pyrazoline derivatives, molecular modelling, anticancer activity

Design, Synthesis, and Anti-mycobacterial Evaluation of New 3,5-Disubstituted-pyrazole-1-carbothioamides

Two series of new 3,5-disubstituted-pyrazole-1-carbothioamides (4a-f and 5a-e) were designed and synthesized through condensation reaction between chalcones and thiosemicarbazides under alkaline condition via cyclocondensation reaction. The structures have been elucidated by Fourier-transform infrared (FTIR), High-resolution mass spectrometry (HRMS), one- and two-dimensional nuclear magnetic resonance (NMR) analyses. These compounds were assayed for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Ra using the Tetrazolium microplate assay (TEMA) method. As a result, six compounds (i.e., 4a, 4d, 4f, 5a, 5c, and 5d) showed a weak activity with minimum inhibition concentration (MIC) between 650–530 μM, and other compounds showed no inhibition against MTB. In addition, all tested compounds also did not show any cidal effects for minimum bactericidal concentration (MBC), even at the highest test concentration.

Conjugates of Lupane Triterpenoids with Arylpyrimidines: Synthesis and Anti-inflammatory Activity

Semisynthetic triterpenoid betulonic acid is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of hybrid compounds, containing betulonic acid carboxamide and arylpyrimidine fragments. A total of 15 conjugates were prepared using the cyclocondensation reaction of new terpenoid alkynyl ketones with amidinium salts. The main synthetic approach to betulonic acid amide-derived alkynylketones was based on the cross-coupling reaction of N-(4-ethynylphenyl)- or N-(2-(4-ethynylphenyl)-1-(methoxycarbonyl)ethyl)- substituted betulonic acid carboxamide with aroylchlorides. Cyclocondensation of alkynones with amidine or guanidine hydrochlorides by reflux in MeCN in the presence of K2CO3 led to the formation of terpenoid pyrimidine hybrids in 52-89% isolated yield. Anti-inflammatory properties of new type of triterpenoid-pyrimidine conjugates were studied using the histamine- and concanavalin A- induced mouse paw edema models. In a model of acute inflammation betulonic acid amide-arylpyrimidines containing a 4-fluorophenyl substituent at the C-6 position of pyrimidine ring exhibited significant and selective anti-inflammatory activity. Compounds containing the 4-bromophenyl- substituent in the pyrimidine ring revealed selective anti-inflammatory activity in the model of immunogenic inflammation (concanavalin-A model). It should be noted that the methoxycarbonyl substituted ethane link between pharmacophore ligands (betulonic acid carboxamide and arylpyrimidine) has a significant effect on anti-inflammatory activity in both in vivo models of inflammation. It was shown by molecular docking that the new derivatives are incorporated into the binding site of the protein Keap1 Kelch-domain by their pyrimidine substituent with the formation of more non-covalent bonds.

Synthesis and Antimicrobial Screening of 3-Fluoromethyl Pyrazole Derivatives

A new series of 1-(5-(4-alkoxy-3-(methylsulfonyl)phenyl)thiophen-2-yl)-5-substituted-3-(trifluoromethyl)-1H-pyrazole have been synthesized by a cyclocondensation reaction of 1,1,1-trifluoropentane-2,4-dione (1a) with (5-(4-methoxy-3-(methylsulfonyl)phenyl)thiophen-2-yl)hydrazine (2). The structure of 1-(5-(4-alkoxy-3-(methylsulfonyl)phenyl)thiophen-2-yl)-5-substituted-3-(trifluoromethyl)-1H-pyrazole derivatives was characterized by spectroscopic analysis. The synthesized 3-(trifluoromethyl)-1H-pyrazole derivatives were screened for in vitro antibacterial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388) Bacillus subtilis (NCIM 2063) and Staphylococcus albus (NCIM 2178) and in vitro antifungal activity against Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). The compounds 4-(5-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)-2-(methylsulfonyl)phenol (4) and 1-methyl-4-(4-(5-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)-2-(methylsulfonyl)phenoxy)pyrrolidin-2-one (6e) showed moderate to good antibacterial and antifungal activity.

Synthesis of new thiazine and thiazole derivatives via cyclization reactions; investigating their electronic properties and determination of antioxidant properties

Abstract(4‐[2,4‐dimethoxyphenyl]‐6‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)(phenyl) methanone (1) have been prepared by Biginelli three‐component cyclocondensation reaction of catalyzed with p‐toluene sulfonic acid in ethanol. Pyrimido[2,1‐b]thiazine (2) and thiazolo[3,2‐a]pyrimidine (3) derivatives were obtained by a simple one‐pot condensation reaction of starting compound 1 and 3‐bromopropionic acid, bromoacetic acid and, respectively. By performing the reactions of compound 3 with heteroaromatic and aromatic aldehydes, arylidine‐bicyclic thiazolo pyrimidine compounds (4–9) were synthesized. Theoretical calculations and molecular electrostatic potential maps of all synthesized compounds were performed using the Gaussian software package Density Functional Theory (DFT/6‐31G: B3LYP). In addition, studies were carried out to determine the antioxidant properties of all the compounds obtained by the DPPH method, and compound 1 was found to be the most effective compound. The structures of the newly synthesized compounds were analyzed using spectroscopic methods such as IR, 1H, and 13C.