Efficient Protocol for Novel Hybrid Pyrimidines Synthesis: Antiproliferative Activity, DFT Analyses, and Molecular Docking Studies.

An efficient, microwave/ultrasound-irradiated synthesis of novel chromenopyrimidines has been established. 2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (1) underwent cyclization reactions with various assorted reagents under sustainable conditions to afford a family of fused pyrimidine derivatives. The proposed structures of the designed fused pyrimidines were confirmed by several spectral techniques. Moreover, the targeted pyrimidines were estimated for their in vitro cytotoxic activities toward three carcinoma cell lines: breast (MCF7), hepatocyte (HepG2), and lung (A549) cancer cell lines, as well as one noncancerous cell line (MCF-10A). Structure-activity relationship (SAR) analyses revealed that derivatives 3 and 7 exhibited the highest potency in inhibiting the growth of cancer cells tested in vitro. Particularly, 3-amino-4-imino-5-(thiophen-2-yl)-3,4,5,7,8,9-hexahydro-6H-chromeno[2,3-d]pyrimidin-6-one (3) displayed a robust impact with IC50 values ranging from 2.02 to 1.61 µM. Interestingly, compound 3 was observed to have low cytotoxicity toward noncancerous cell (MCF-10A) compared to the standard drug (Doxorubicin). Further, quantum chemical computations of the designed molecules utilizing density functional theory (DFT) were conducted and shown to be compatible with the observed antiproliferative properties. Thorough docking investigations revealed that the assembled compounds possess exceptionally low binding energies toward our three selected proteins: 4b3z-Lung, HepG2-2JW2, and 6ENV-MCV-7. Based on these intriguing results, compound 3 could be further evaluated for preclinical screening, potentially paving the way for its utilization as a promising cancer treatment.

High-Pressure Metal-Free Catalyzed One-Pot Two-Component Synthetic Approach for New 5-Arylazopyrazolo[3,4-b]Pyridine Derivatives.

An appropriate and efficient Q-tube-assisted ammonium acetate-mediated protocol for the assembly of the hitherto unreported 5-arylazopyrazolo[3,4-b]pyridines was demonstrated. This methodology comprises the cyclocondensation reaction of 5-amino-2-phenyl-4H-pyrazol-3-one with an assortment of arylhydrazonals in an NH4OAc/AcOH buffer solution operating a Q-tube reactor. This versatile protocol exhibited several outstanding merits: easy work-up, mild conditions, scalability, broad substrate scope, safety (the Q-tube kit is simply for pressing and sealing), and a high atom economy. Consequently, performing such reactions under elevated pressures and utilizing the Q-tube reactor seemed preferable for achieving the required products in comparison to the conventional conditions. Diverse spectroscopic methods and X-ray single-crystal techniques were applied to confirm the proposed structure of the targeted compounds.

Green Protocol for the Novel Synthesis of Thiochromeno[4,3-b]pyridine and Chromeno[4,3-b]pyridine Derivatives Utilizing a High-Pressure System.

A suitable and effective Q-tube-assisted strategy for the synthesis of novel, unrivalled thiochromeno[4,3-b]pyridine and chromeno[4,3-b]pyridine derivatives has been sophisticated, which includes ammonium acetate-mediated cyclocondensation reactions between 3-oxo-2-arylhydrazonopropanals and heterobenzocyclic ketones such as thiochroman-4-one and chroman-4-one, respectively. The high-pressure Q-tube reactor was shown to be superior to conventional heating. Furthermore, this Q-tube reactor-assisted protocol is safe owing to facile pressing and sealing, a broad substrate scope, and simple work-up and purification processes, as well as being scalable and having a high atom economy. The proposed mechanistic route includes two sequential dehydrative stages. In this investigation, X-ray crystallographic analysis was performed to authenticate the targeted products.

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole Derivatives.

An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido[1,2-b][1,2,4]triazine and pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under high-pressure conditions. In addition, trifluoroacetic acid was used to induce this transformation. In this research, conducting the targeted reactions under high pressure using the Q-tube reactor was found to be superb in comparison to that under the traditional refluxing conditions. X-ray single-crystal analysis was utilized in this study to authenticate the structure of the synthesized products.

High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents.

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a-e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j exhibited promising cytotoxicity's against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

Palladium-Catalyzed Q-Tube-Assisted Protocol for Synthesizing Diaza-dibenzo[a,e]azulene and Diaza-benzo[a]fluorene Derivatives via O2 Acid-Promoted Cross-Dehydrogenative Coupling.

An appropriate and efficient Q-tube-assisted palladium-catalyzed strategy for the synthesis of novel, unparalleled diaza-dibenzo[a,e]azulene and diaza-benzo[a]fluorene derivatives has been sophisticated, which includes oxygen and AcOH-induced oxidative C(sp3)-C(sp2) cross-dehydrogenative coupling reactions of 1-amino-2-imino-4-arylpyridine-3-carbonitriles with benzocyclic ketones such as benzosuberone, tetralone, thiochromone, and chromone, respectively. This Q-tube gas purging kit assisted-protocol features safe due to easy pressing and sealing, a wide substrate scope, easy workup and purifying phases, and the use of O2 as a benign oxidant, in addition to being scalable and having a high atom economy. The suggested mechanistic pathway includes a formal dehydrative step followed by palladium AcOH-induced CH(sp3)-CH(sp2) oxidative cross-coupling. In this study, X-ray crystallographic analysis has been used to authenticate the targeted products.

Author Correction: The first Q-Tube based high-pressure synthesis of anti-cancer active thiazolo[4,5-c]pyridazines via the [4 + 2] cyclocondensation of 3-oxo-2-arylhydrazonopropanals with 4-thiazolidinones.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The first Q-Tube based high-pressure synthesis of anti-cancer active thiazolo[4,5-c]pyridazines via the [4 + 2] cyclocondensation of 3-oxo-2-arylhydrazonopropanals with 4-thiazolidinones.

A novel and efficient protocol for the synthesis of thiazolo[4,5-c]pyridazine derivatives was developed. The approach utilizes a high pressure Q-Tube reactor to promote cyclocondensation reactions between 3-oxo-2-arylhydrazonopropanals and 4-thiazolidinones. The process has a significantly high atom economy and a broad substrate scope, as well as being applicable to gram scale syntheses. The in vitro cytotoxic activities of the synthesized thiazolo[4,5-c]pyridazine derivatives were examined utilizing a MTT colorimetric assay with doxorubicin as a reference anti-cancer drug and three human cancer cell lines including HCT-116 (colon), MCF-7 (breast) and A549 (lung). The results show that thiazolopyridazines 7c, h, k and p have high cytotoxic activity against the MCF-7 cell line with respective IC50 values of 14.34, 10.39, 15.43 and 13.60 µM. Moreover, the thiazolopyridazine derivative 7s also show promising cytotoxic activity against the HCT-116 cell line with IC50 = 6.90 µM . Observations made in this effort serve as a basis for further investigations into the design and preparation of new anti-cancer drugs.

A facile, practical and metal-free microwave-assisted protocol for mono- and bis-[1,2,4]triazolo[1,5-a]pyridines synthesis utilizing 1-amino-2-imino-pyridine derivatives as versatile precursors.

A facile and effective assembly of several substituted functionalized mono- and bis-[1,2,4]triazolo[1,5-a]pyridines from conveniently attainable 1-amino-2-imino-pyridines has been established. Using microwave irradiation speeds up the reaction efficiently, proceeding with a higher rate and yields than with conventional heating. In the presented protocol, a broad variety of carboxylic acids could be employed effectively to synthesize the respective derivatives via direct metal-free C-N bond construction. Interestingly, other substrates such as aldehydes (or their arylidene malononitriles), phenyl isothiocyanate, glyoxalic acid, and acrylonitriles could also provide the corresponding 1,2,4-triazolo[1,5-a]pyridines successfully. This versatile and convergent approach performs well with both deactivating and activating substrates in an environmentally benign manner compared with other already reported protocols. Other notable merits of the current strategy involve no need for column chromatography, no tedious work-up, and a direct pathway for the fast design of triazolopyridine frameworks. The identity of the newly synthesized compounds was established using several spectroscopic techniques, and X-ray single-crystal tools were employed to authenticate the suggested structures of some representative samples.

Synthetic Strategy for Pyrazolo[1,5-a]pyridine and Pyrido[1,2-b]indazole Derivatives through AcOH and O2-Promoted Cross-dehydrogenative Coupling Reactions between 1,3-Dicarbonyl Compounds and N-Amino-2-iminopyridines.

An efficient method has been developed for the synthesis of uniquely substituted pyrazolo[1,5-a]pyridine and pyrido[1,2-b]indazole derivatives, which involves acetic acid and molecular oxygen promoted cross-dehydrogenative coupling reactions of respective ß-ketoesters and ß-diketones (like ethyl acetoacetate, ethyl benzoylacetate, methyl propionylacetate, acetylacetone, dimedone, 1,3-cyclohexanedione, and 1,3-cyclopentanedione) with N-amino-2-iminopyridines. The proposed tentative mechanism involves formal acetic acid-promoted oxidative C(sp3)-C(sp2) dehydrogenative coupling followed by dehydrative cyclization under a catalyst-free condition within high atom economy processes.

Scalable Sonochemical Synthetic Strategy for Pyrazolo[1,5-a]pyridine Derivatives: First Catalyst-Free Concerted [3 + 2] Cycloaddition of Alkyne and Alkene Derivatives to 2-Imino-1H-pyridin-1-amines.

A highly efficient and convenient one-pot sonochemical synthetic strategy has been sophisticated for synthesizing a novel class of polysubstituted pyrazolo[1,5-a]pyridines via [3 + 2] cycloaddition of dialkyl acetylenedicarboxylates, ethyl propiolate, and alkenes to 2-imino-1H-pyridin-1-amines under catalyst-free conditions. A series of uniquely substituted pyrazolo[1,5-a]pyridines has been synthesized with a very good to excellent yield, and the mechanistic pathway that involves a [3 + 2] annulation process was also proposed. In this study, several spectroscopic tools of analyses were employed for structure elucidation, and the X-ray single-crystal technique was utilized to confirm the proposed mechanism and the regioselectivity.

Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(sp2)-C(sp3) Coupling Reactions between 1-Amino-2-imino-pyridines and 1-Aryl-5-pyrazolones.

A novel, metal catalyst-free, and efficient method has been developed for the synthesis of (pyrazol-4-ylidene)pyridine derivatives. The process involves dehydrogenative coupling of 1-amino-2-imino-pyridines with 1-aryl-5-pyrazolone derivatives utilizing O2 as the sole oxidant. The new method benefits from a high atom economy, efficiency, and substrate scope, as well as the simplicity of reaction and product purification procedures.

Sustainable and scalable synthesis of polysubstituted bis-1,2,4-triazoles, bis-2-iminothiazolines and bis-thiobarbiturates using bis-N,N-disubstituted thioureas as versatile substrate.

An expedient and tandem regioselective one-pot protocol for the sono-synthesis of bis-[1,2,4]-triazol-3-yl amines and bis-2-iminothiazolines from corresponding bis-1,3-disubstituted thioureas has been developed. The products' regioselectivity correlate well with the pK as of the parent amines, in which the amine possessing higher pK a goes to the ring nitrogen, whereas the other nitrogen remains flanked as an exocyclic nitrogen of the bis-triazole or bis-thiazole moieties. Further, the sonochemical preparation of both bis-5-(2-nitrobenzylidene) thiobarbiturates and bis-2-thioxoimidazolidine-4,5-diones from bis-1,3-disubstituted thioureas has also been achieved. The obtained bis-5-(2-nitrobenzylidene)thiobarbiturates easily underwent reductive cyclization to afford the corresponding bis-5-benzo[c]isoxazol-3-ylidenethiobarbiturates. The scope and limitations of these strategies have been studied. Moreover, the suggested methodologies have advantages such as broad functional group tolerance, mild conditions, operational simplicity and applicability on a gram scale. Furthermore, the protocols scored well in a number of green metrics, subsequently showing these approaches to be environmentally benign and sustainable processes.

A sustainable strategy for the synthesis of bis-2-iminothiazolidin-4-ones utilizing novel series of asymmetrically substituted bis-thioureas as viable precursors.

A novel series of asymmetrically substituted bis-thioureas has been synthesized in an effective pattern via the reaction of diamines with isothiocyanates utilizing the ultrasonic irradiation as a sustainable energy source. This reaction performs well at mild conditions to give the products in quantitative yields for a broad scope of substrates. The bis-thiourea derivatives are used for the design of unprecedented series of bis-2-iminothiazolidin-4-ones promoted by the ultrasonic irradiation. The reaction affords the formation of regioselective products, which depends on the pK as of the diamines. The diamine linked to the thiourea possessing lower pK a is involved in the imino part, and the diamine having higher pK a is a part of the other heterocyclic nitrogen. Moreover, this new strategy has excellent environmental parameters, demonstrating that this protocol is a green and sustainable process.

l-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moiety via sustainable sonochemical approach.

The efficient, highly convenient synthesis of polysubstituted pyridine derivatives was established via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidene malononitriles and arylidene ethyl cyanoacetates in the presence of l-proline as an efficient organocatalyst for this type of ultrasonic-mediated Michael addition. The mechanistic pathway and factors affecting this reaction were also established. The main characteristics of this procedure are high yields, use of a cost-effective catalyst, and easy work-up and purification.

Synthesis of a new class of Pyridazin-3-one and 2-amino-5-arylazopyridine derivatives and their utility in the synthesis of fused azines.

A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives 3 were formed as the sole isolable products in excellent yield. The 6-acetyl-3-oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding enaminone derivative 4, which reacts with a variety of aminoazoles to afford the corresponding azolo[1,5-a]pyrimidine derivatives 5-7. Also, in order to explore the viability and generality of a recently uncovered reaction between 3-oxo-2-arylhydrazonopropanals and active methylene compounds, a variety of 2-amino-6-aryl-5-arylazo-3-aroylpyridines 16-19 were prepared by reacting 3-oxo-2-arylhydrazonopropanals with miscellaneous active methylene compounds like 3-oxo-3-phenylpropionitrile, hetaroylacetonitriles and cyanoacetamides. These 2-aminopyridine derivatives undergo smooth reactions with cyanoacetic acid that led to the formation in high yield of a new class of 1,8-naphthyridine derivatives 24. The structures of all new substances prepared in this investigation were determined by the different analytical spectroscopic methods, in addition to the X-ray crystallographic analysis.

Approaches towards the synthesis of a novel class of 2-amino-5-arylazonicotinate, pyridazinone and pyrido[2,3-d]pyrimidine derivatives as potent antimicrobial agents.

BACKGROUND: Despite significant progresses in antimicrobial therapy, infectious diseases caused by bacteria and fungi remain a major worldwide health problem because of the rapid development of resistance to existing antimicrobial drugs. Therefore, there is a constant need for new antimicrobial agents. There are a large number of heterocyclic derivatives containing nitrogen atoms that possess a broad spectrum of biological activities including pyridine and pyridazine, which are two of the most important heterocycles in medicinal chemistry. RESULTS: The reaction of 3-oxo-2-arylhydrazonopropanals 2 with ethyl cyanoacetate and malononitrile 3a,b has led to the formation of 2-amino-5-arylazo-6-aryl substituted nicotinates 8a-k as sole isolable products when the aryl group in the arylazo moiety was substituted with an electron-withdrawing group like Cl, Br, NO2. The pyridazinones 10 were formed from the same reaction when the arylazo moiety was phenyl or phenyl substituted with an electron-donating group. The 2-aminoazonicotinates 8 were condensed with DMF-DMA to afford the amidines 13a,b, which then were cyclized to afford the targeted pyrido[2,3-d]pyrimidine derivatives 15a,b, respectively. The structures of all new substances prepared in this investigation were determined by using X-ray crystallographic analysis and spectroscopic methods. Most of the synthesized compounds were tested and evaluated as antimicrobial agents and the results indicated that many of the obtained compounds exhibited high antimicrobial activity comparable to ampicillin, which was used as the reference compound. CONCLUSION: A general rule for the synthesis of 2-amino-5-arylazo-6-aryl substituted nicotinic acid and pyridazinone was established using 3-oxo-2-arylhydrazonopropanal as a precursor. Moreover, a novel route to pyrido[2,3-d]pyrimidine was achieved. Most of the synthesized compounds were found to exhibit strong inhibitory effects on the growth of Gram-positive bacteria especially Bacillus subtilis. Compounds 1a, 8a-h, 10a-c, 15b and 16 showed a broad spectrum of antimicrobial activity against B. subtilis.

Organocatalysis in heterocyclic synthesis: DABCO as a mild and efficient catalytic system for the synthesis of a novel class of quinazoline, thiazolo [3,2-a]quinazoline and thiazolo[2,3-b] quinazoline derivatives.

BACKGROUND: There are only limited publications devoted to the synthesis of especially thiazolo[3,2-a]quinazoline which involved reaction of 2-mercaptopropargyl quinazolin-4-one with various aryl iodides catalyzed by Pd-Cu or by condensation of 2-mercapto-4-oxoquinazoline with chloroacetic acid, inspite of this procedure was also reported in the literature to afford the thiazolo [2,3-b] quinazoline. So the multistep synthesis of the thiazolo[3,2-a]- quinazoline suffered from some flaws and in this study we have synthesized a novel class of thiazoloquinazolines by a simple and convenient method involving catalysis by 1,4-diazabicyclo[2.2.2]octane (DABCO). RESULTS: A new and convenient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through the reaction between methyl-2-(2-thio-cyanatoacetamido)benzoate (4) and a variety of arylidene malononitriles 8a-i in the presence of DABCO as a mild and efficient catalytic system via a Michael type addition reaction and a mechanism for formation of the products observed is proposed. Moreover 4 was converted to ethyl-2-[(4-oxo-3,4-dihydroquinazolin-2-yl)thio]acetate (10) upon reflux in ethanol containing DABCO as catalyst. The latter was reacted with aromatic aldehydes and dimethylformamide dimethylacetal (DMF-DMA) to afford a mixture of two regioselectively products with identical percentage yield, these two products were identified as thiazolo[3,2-a]quinazoline 9,13 and thiazolo[2,3-b]quinazoline 11,12 derivatives respectively. The structure of the compounds prepared in this study was elucidated by different spectroscopic tools of analyses also the X-ray single crystal technique was employed in this study for structure elucidation, Z/E potential isomerism configuration determination and to determine the regioselectivity of the reactions. CONCLUSION: A simple and efficient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through DABCO catalyzed Michael type addition reaction. In addition many fused quinazoline and quinazoline derivatives were synthesized which appeared as valuable precursors in synthetic and medicinal chemistry.

4-Thiazolidinones in heterocyclic synthesis: synthesis of novel enaminones, azolopyrimidines and 2-arylimino-5-arylidene-4-thiazolidinones.

The 4-thiazolidinones 3a-d were used as a key intermediates for the synthesis of 2-arylimino-5-arylidene-4-thiazolidinones derivatives 7a­p via nucleophilic addition reactions with the arylidene malononitrile. Moreover the 4-thiazolidinones 3a and 3c condensed with the DMF-DMA to form the corresponding enamines 8 and 9 depending on the reaction conditions. Otherwise the 4-thiazolidinone 3b reacts regioselectively with DMF-DMA to afford the enaminones 10 and 11, respectively. The latter reacts with many heterocyclic amines affording polyfunctionally substituted fused pyrimidine derivatives 13-18. The enamine 8b was also reacted with the 3-amino-1,2,4-triazole to afford the acyclic product 19, which could not be further cyclized to the corresponding tricyclic system 20. Moreover the 4-thiazolidinone 3c reacted with the benzenediazonium chloride to afford the arylhydrazones 12. The X-ray single crystal technique was employed in this study for structure elucidation and Z/E potential isomerism configuration determination. The X-ray crystallographic analyses of eight products could be obtained, thus establishing with certainty the structures proposed in this work.

2-Aminothiophenes as building blocks in heterocyclic synthesis: synthesis and antimicrobial evaluation of a new class of pyrido[1,2-a]thieno[3,2-e]pyrimidine, quinoline and pyridin-2-one derivatives.

Multisubstituted 2-aminothiophenes 1a-c can be readily cyanoacylated via reaction with cyanoacetic acid in presence of acetic anhydride under a microwave irradiation to form the corresponding cyanoacetamides 2a-c, which condensed with DMF-DMA to form the corresponding enamines 4 that reacted with hydrazine hydrate to yield the aminopyrazoles 5. Moreover the cyanoacetamides 2a-c reacted with a variety of arylidenmalononitrile to afford a novel pyrido[1,2-a]thieno[3,2-e]pyrimidine derivatives 12a-o. In addition the enamines 4a,b reacted with malononitrile to afford the pyrido[1,2-a]thieno[3,2-e]pyrimidine derivatives 19a,b. The cyanoacetamides 2a,b reacted also with salicylaldehyde to afford the quinoline derivatives 24a,b. Moreover the cyanoacetamides 2a,b reacted with the enaminones 25a-c to form the corresponding Pyridin-2-one derivatives 29a-c. Reactions of 2a,c with bezenediazonium chloride afford the arylhydrazones 30a,b that reacted with chloroacetonitrile to form the acyclic product 31 which could not be further cyclized to the corresponding 4-aminopyrazole. The X-ray crystallographic analyses of seven products could be obtained thus establishing with certainty the proposed structures in this work. Most of the synthesized compounds in this investigation were tested and evaluated as antimicrobial agents.