Α-halocarbonyl Compounds Research Articles

Visible Light-Induced Three-Component Alkoxyalkylation of Alkenes with α-Halocarbonyls and Alcohols.

A visible-light-induced three-component alkoxyalkylation of alkenes has been developed under the photocatalysis of fac-Ir(ppy)3. The alkene substrate scope included aryl and aliphatic alkenes as well as electron-rich and electron-deficient alkenes, allowing the facile coupling with a diverse array of α-halocarbonyl compounds. The redox potential-guided orchestration of radical processes with precision allows rapid access to highly functionalized products that are useful building blocks in organic synthesis.

Synthesis and Antimicrobial Evaluation of 2-[2-(9H-Fluoren-9-ylidene)hydrazin-1-yl]-1,3-thiazole Derivatives

Fluorenyl-hydrazonothiazole derivatives 2–7 were synthesized by the Hantzsch reaction from 2-(9H-fluoren-9-ylidene)hydrazine-1-carbothioamide (1) and the corresponding α-halocarbonyl compounds in THF or 1,4-dioxane solvent. A base catalyst is not necessary for synthesising thiazoles, but it can shorten the reaction time. The antimicrobial properties of all synthesized compounds were screened for multidrug-resistant microorganism strains. The minimum inhibitory concentration of the tested compounds against Gram-positive bacteria and fungi was higher than 256 μg/mL, but several compounds had activity against Gram-positive strains.

Green synthesis of novel coumarin derivatives via grinding approach and their antimicrobial evaluation

ABSTRACT Herein, a rapid, clean, less expensive and environmentally friendly route to a novel series of coumarins bearing thiazoles or 1,3,4-thiadiazoles was developed via grinding method under solvent conditions. Thus, 6-bromo-3-(2-bromoacetyl)-2-chromen-2-one was treated with cyanothioacetamide to produce thiazole-2-acetonitrile derivative 2, which was then transformed to iminocoumarins by reacting with hydroxyaldehydes. Hydrolysis of iminocoumarins by conc. HCl furnished coumarins. Furthermore, treatment of compound 2 with phenylisothiocyanate produced thioanilide which interacts with hydrazonoyl chloride and/or α-halocarbonyl compounds afforded 1,3,4-thiadiazole and thiophene derivatives, consequently. All the newly prepared coumarins were screened against six pathogenic microorganisms. The results indicated that compounds 7 and 12 were the most effective against Bacillus pumilis, while compound 4b was highly active against Streptococcus faecalis. Also, compound 5b was highly active against Enterobacter cloacae. Compounds 2 and 7 were higher active compared with reference drug ketoconazole against fungi Saccharomyces cerevisiae.

Access to All-Carbon Quaternary Centers by Photocatalytic Fluoroalkylation of α-Halo Carbonyl Compounds.

Perfluoroalkyl groups have become significantly important in pharmaceutical and agrochemical applications. In this study, we present a visible light-mediated photoredox neutral strategy for the fluoroalkylation of tertiary alkyl chlorides under transition-metal-free conditions. This method allows for the facile synthesis of fluoroalkylated all-carbon quaternary centers, exhibiting excellent functional group compatibility. Mechanistic studies reveal the involvement of two reactive radical intermediates and the in situ formation of metal enolates in a radical-polar crossover manner. The versatility of this methodology is demonstrated through synthetic transformations based on the carbonyl group, showcasing its potential for the rapid assembly of diverse organic molecules bearing fluoroalkyl all-carbon quaternary centers.

Synthesis, cytotoxic evaluation, molecular docking studies and drug-likeness analysis of some novel 2-[(9-ethyl-9H-carbazol-3-yl)imino]thiazoles/thiazolidinones

A novel series of some 2-[(9-ethyl-9H-carbazol-3-yl)imino]thiazoles/thiazolidinones was synthesized and established by spectroscopic tools and elemental analysis. The synthetic strategy depended on cyclization of 1-(9-ethyl-9H-carbazol-3-yl)-3-phenylthiourea (2) with different α-halocarbonyl compounds and some carbon electrophiles under mild reaction conditions. All products were screened for their in vitro cytotoxic activities toward three human cancer cell lines (MCF-7, HepG-2 and HCT-116). Interestingly, the particular carbazolyl derivatives 7, 13, 14 and 16 exhibited promising cytotoxicity results against all the evaluated cell lines. Also, molecular docking studies for the highly bioactive compounds were achieved to investigate the binding mode toward (VEGFR-2-KDR) receptor. Moreover, anticancer results were validated computationally by applying SwissADME server.

New Functionalized Morpholinothiazole Derivatives: Regioselective Synthesis, Computational Studies, Anticancer Activity Evaluation, and Molecular Docking Studies

Abstract: A new series of skeletons 2-(morpholinoimino)-4,5-disubstituted-3- phenylthiazoles (2-15) was synthesized. The methodology involved the reactions of 1- morpholino-3-phenyl-thiourea (1) with a variety of α-halocarbonyl compounds under Hantzsch reaction conditions. The reaction mechanism for some postulated routes was modeled using quantum mechanical calculations in order to investigate the regioselectivity preference of this reaction in terms of thermodynamics. The quantum mechanical computations compiled with experimental IR, 1H- and 13C-NMR spectral analysis supported the favorable product, which has a thiazole ring bearing the morpholinoimino moiety at position C−2. All synthesized products were screened using the sulforhodamine B (SRB) assay for their cytotoxic properties against various cancer cell lines. Fortunately, the target compounds 2, 4, 5, 6, 11, and 12 were discovered to be comparable to doxorubicin in terms of their potency against all evaluated cell lines. Utilizing flow cytometry, apoptosis and cell cycle analyses were determined and supported by molecular docking studies. All tumor cells were significantly early- and late-apoptotic affected by the products 2, 4, 5, 6, 11 and 12, and these products also significantly halted all studied types of cancer cells in both S and G2 phases. The discovered compounds 2 and 12 were then subjected to a molecular docking experiment to examine how they bind with the VEGFR-2-KDR receptor.

Kinetics of Ring Closure Thiazole Cyclization Using 3-Chloroacetylacetone with Thioamides

Background: Thiazoles are an important heterocycle which exhibits various bioactivities. Thiazole ring is found in core structure of various medicinally useful compounds. It shows biological activities like anti-inflammatory, antibacterial, antifungal, antioxidant, cytotoxicity, anticonvulsant, insecticidal, anticancer and antitumor. Thioamides are reported to show bioactivities like antibacterial, antileukemia, antifungal, anti-arthritic, antimalarial and cytotoxic. Hantzsch synthesis is one of the most efficient reactions for thiazole formation which is a cyclization reaction between thioamides and α-halo carbonyl compounds. A very few reports on kinetic investigation of thiazole formation are available. Previously we have studied thiazole formation using 3-chloroacetylacetone and substituted thioureas by pH metric study. The reaction between 3-chloroacetylacetone and Thioamides is not reported yet. The present work deals with kinetics and mechanistic study of ring closure of thiazole using thioamides and 3-chloroacetylacetone. The reaction has been carried out in water-ethanol system at 303K. The kinetic investigations are carried out pH metrically. Nature of reaction is explained on the basis of thermodynamic parameters. Reaction products are isolated and characterized on the basis of spectral data. The effect of temperature on reaction rate is studied at 30°C to 50°C. Thermodynamic parameters are evaluated. Objective/s: To determine the order of reaction. • To determine the rate of reaction. • To evaluate the rate of reaction at various temperatures. • To determine the rate of reaction in different media. • To study the effect of dielectric constant, ionic strength etc. • To observe calculation of energy of activation, enthalpy of activation, entropy of activation and free energy of activation. • To propose reaction mechanism considering various thermodynamic parameters. Method: Measuring the change in pH, the concentration of H+ ion will be determined and accordingly rate of reaction will be calculated. Result: Van’t Hoff’s differential method and the stoichiometric study suggested that one mole of Thioamides reacts with one mole of 3-chloroacetylacetone. The rates of reaction are measured at different concentration of Thioamides at constant concentration of 3-chloroacetylacetone. The plot of log (dc / dt) against log [3-chloroacetylacetone] and log [ Thioamides] is also straight line and slope of the plot is nearly one with respect to both. At five different temperatures second order rate constants are determined. The energy of activation (Ea) is determined by plotting graph of logk versus 1/T and other thermodynamic parameters are calculated. The negative entropy of activation (∆S*) of this reaction specifies rigid nature of the transition state. The entropy of activation (∆S*) is negative value and it specifies that less stable noncyclic reactants convert into stable cyclic product. Free energy of activation (∆G*) is calculated [Table 1], Graph 1. Reacting species are oppositely charged according to salt effect [Graph 2]. In water-isopropyl alcohol system reaction is fast than water-ethanol system [Graph 3]. Conclusion: • Using Van’t Hoff’s differential method the rate of reaction between 3-chloroacetylacetone and Thioamides is found to be one with respect to both components. • The proposed rate law also shows that the order of reaction is two. • Negative entropy (∆S*) shows that from open chain compound cyclic compound is formed. Nucleophilic addition and addition–elimination reaction take place. • Oppositely charge species are present in reaction. • Rate increases with increase in dielectric constant. Isopropyl alcohol-water system shows high-rate constant as compared to Ethanol-water system.

Site-Selectivity of the Reaction of 3-Amino-4-Cyano-5-Phenyl-1H-Pyrrole-2-Carboxylic Acid Amide with α-Halocarbonyl Compounds. Antimicrobial Activity and Docking Study for COVID-19 of the Products

In this context, we are interested to study the site-selectivity of the reaction of 3-amino-4-cyano-5-phenyl-1H-pyrrole-2-carboxylic acid amide 1 with different types of hydrazonoyl halides as well as the α-haloketones. The products of these reactions were confirmed from their spectral data and conformational studies to be pyrrolo[1,2-d][1,2,4]triazine and pyrrolo[1,2-a]pyrazine derivatives. We used docking studies to test the ability of the new synthesized pyrrolo[1,2-d][1,2,4]triazine and pyrrolo[1,2-a]pyrazine derivatives to dock and inhibit the microbes and COVID-19 proteins. The results of both docking studies revealed a strong fit of almost the tested derivatives into the active sites of peroxiredoxin 5 (Pdb: 2WFC; the overexpressed proteins in Candida albicans) and COVID-19 main protease (Pdb: 6LU7; severe acute respiratory syndrome coronavirus 2). Moreover, the antimicrobial activity of the products was investigated against two selected Fungi species and two G+ and two G− bacteria. The results of antimicrobial activity indicated that almost all derivatives showed no activity against fungi species, while all of them have moderate activity against bacteria strains (G+ and G− bacteria).

Novel Bis-Thiazole Derivatives: Synthesis and Potential Cytotoxic Activity Through Apoptosis With Molecular Docking Approaches.

A series of bis-thiazoles 5a–g were synthesized from bis-thiosemicarbazone 3 with hydrazonoyl chlorides 4a–g. Reaction of 3 with two equivalents of α-halocarbonyl compounds 6–8, 10, and 12a–d afforded the corresponding bis-thiazolidines 9, 11, and 13a–d, respectively. Condensation of bis-thiazolidin-4-one 9 with different aromatic aldehydes furnished bis-thiazolidin-4-ones 14a–d. Compounds 5a–g, 9, and 13a,c,d were screened in vitro for their cytotoxic activities in a panel of cancer cell lines. Compounds 5a–c, 5f–g, and 9 exhibited remarkable cytotoxic activities, especially compound 5c with potent IC50 value 0.6 nM (against cervical cancer, Hela cell line) and compound 5f with high IC50 value 6 nM (against ovarian cancer, KF-28 cell line). Compound 5f–induced appreciated apoptotic cell death was measured as 82.76% associated with cell cycle arrest at the G1 phase. The apoptotic pathways activated in KF-28 cells treated with 5a, 5b, and 5f were further investigated. The upregulation of some pro-apoptotic genes, bax and puma, and the downregulation of some anti-apoptotic genes including the Bcl-2 gene were observed, indicating activation of the mitochondrial-dependent apoptosis. Together with the molecular docking studies of compounds 5a and 5b, our data revealed potential Pim-1 kinase inhibition through their high binding affinities indicated by inhibition of phosphorylated C-myc as a downstream target for Pim-1 kinase. Our study introduces a set of bis-thiazoles with potent anti-cancer activities, in vitro.

Quaternary stereocentres via catalytic enantioconvergent nucleophilic substitution reactions of tertiary alkyl halides

The development of efficient methods, particularly catalytic and enantioselective processes, for the construction of all-carbon quaternary stereocentres is an important (and difficult) challenge in organic synthesis, due to the occurrence of this motif in a range of bioactive molecules. One conceptually straightforward and potentially versatile approach is the catalytic enantioconvergent substitution reaction of a readily available racemic tertiary alkyl electrophile by an organometallic nucleophile; however, examples of such processes are rare. In this report, we demonstrate that a nickel-based chiral catalyst achieves enantioconvergent couplings of a variety of tertiary electrophiles (cyclic and acyclic α-halocarbonyl compounds) with alkenylmetal nucleophiles to form quaternary stereocentres with good yield and enantioselectivity under mild conditions in the presence of a range of functional groups. These couplings, which likely proceed via a radical pathway, provide access to an array of useful families of organic compounds, including intermediates in the total synthesis of two natural products, (−)-eburnamonine and madindoline A.

3-Oxobutanamides in Heterocyclic Synthesis: Synthesis, Antimicrobial and Antioxidant Activity of Pyridine, Thiophene, Diazepine and Thiazole Derivatives

In the last few years we and others reported a variety of synthesis of heteroaromatics that have been developed utilizing β–oxoanilides as readily obtainable compounds. In this study, treatment of 3-Oxobutanamides 1 with phenyl isocyanate at room temperature in basic medium and DMF afforded thiocarbamoyl derivative 3 through intermediate 2 upon treatment with dilute HCl. The non-isolable potassium salt 2 was allowed to react with α-halo carbonyl compounds such as ethyl chloroacetate and chloroacetonitrile in dry DMF at room temperature to furnished thiophene 6 and thiazole derivative 9 respectively. Compound 6 was treated with hydrazine hydrate in ethanol to yield thiophene-5-carbohydrazide derivative 7. Also, compound 1 reacted with malononitrile and sulfur element in refluxing absolute ethanol and triethylamine to yield thiophene derivative 11, which reacted with formic acid and α-chloro acetylchloride to give thieno[2,3-d]pyrimidine derivative 12 and chloro acetamide derivative 13. Treatment of compound 13 with ammonium thiocyanate led to thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivative 15 through non-isolable 14. Also, condensation of 1 with malononitrile and ethylene diamine afforded the pyridine derivative 17 and 1,4-diazepine derivative 18. The structures and formulas of all the synthesized compounds were supported by spectral data. Some of the synthesized compounds were evaluated for their antibacterial and antioxidant activity. These compounds showed different degrees of activity.

Dipolar repulsion in α-halocarbonyl compounds revisited.

The concept of dipolar repulsion has been widely used to explain several phenomena in organic chemistry, including the conformational preferences of carbonyl compounds. This model, in which atoms and bonds are viewed as point charges and dipole moment vectors, respectively, is however oversimplified. To provide a causal model rooted in quantitative molecular orbital theory, we have analyzed the rotational isomerism of haloacetaldehydes OHC–CH2X (X = F, Cl, Br, I), using relativistic density functional theory. We have found that the overall trend in the rotational energy profiles is set by the combined effects of Pauli repulsion (introducing a barrier around gauche that separates minima at syn and anti), orbital interactions (which can pull the anti minimum towards anticlinal to maximize hyperconjugation), and electrostatic interactions. Only for X = F, not for X = Cl–I, electrostatic interactions push the preference from syn to anti. Our bonding analyses show how this trend is related to the compact nature of F versus the more diffuse nature of the heavier halogens.

Efficient synthesis and characterization of novel bis(chromenes) and bis(benzo[f]chromenes) linked to thiazole units

New carbothioamides, linked to chromene or benzo[f]chromene units, were taken as key synthons for the present study. These carbothioamides were prepared, in good yields, by the cyclocondensation of the appropriate 2-hydroxybenzaldehydes or 2-hydroxy-1-naphthaldehyde with 2-cyanoethanethioamide. Next, the precursors carbothioamides were reacted with different α-halocarbonyl compounds and bis(α-bromoketones). These reactions afforded the corresponding 4-(substituted)thiazoles and thiazol-4(5H)-ones, in addition to bis(thiazoles), linked to different cores. Additionally, thiazol-4(5H)-ones were condensed with the appropriate bis(aldehydes) to yield the corresponding bis(thiazol-4(5H)-ones), linked to chromene or benzo[f]chromene units via different cores.

Synthesis, Antimicrobial and Anticancer Evaluations of Novel Thiazoles Incorporated Diphenyl Sulfone Moiety

A novel series of thiazoles incorporated phenylsulfonyl group have been designed and synthesized from the treatment of N-(1-(4-(phenylsulfonyl)phenyl)ethylidene)hydrazine carbothioamide with various types of α-halocarbonyl compounds in one-pot reaction strategy under microwaves irradiations. Studying all possible spectral data for the prepared compounds were proved their structure as well as the suggested mechanism of their reactions. The results of antimicrobial activity of some selected derivatives proved their potency in which some derivatives showed activity exceeded the activity of the reference drugs. In addition, selected derivatives were investigated for their anticancer activities against HepG-2 and HCT-116 cell lines to shed some light on the anticancer activity of the newly synthesized thiazole derivatives. One of the tested thiazole derivatives showed good activity in comparison with doxorubicin reference.

Photoenzymatic enantioselective intermolecular radical hydroalkylation.

Enzymes are increasingly explored for use in asymmetric synthesis1-3, but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis4 has spurred the discovery of novel reactivity from known enzymes5. However, so far photoinduced enzymatic catalysis6 has not been used for the cross-coupling of two molecules. For example, the intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in achieving stereochemical control of the remote prochiral radical intermediate7. Here we report a visible-light-induced intermolecular radical hydroalkylation of terminal alkenes that does not occur naturally, catalysed by an 'ene' reductase using readily available α-halo carbonyl compounds as reactants. This method provides an efficient approach to the synthesis of various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99 per cent yield with 99 per cent enantiomeric excess), which otherwise are difficult to access using chemocatalysis. Mechanistic studies suggest that the formation of the complex of the substrates (α-halo carbonyl compounds) and the 'ene' reductase triggers the enantioselective photoinduced radical reaction. Our work further expands the reactivity repertoire of biocatalytic, synthetically useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.

One-Pot Synthesis of Thieno[2,3-b]pyridine and Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine Derivatives

2-Acyl-4,5,6-trialkyl-3-aminothieno[2,3-b]pyridines, 8′-ethyl-7′,9′-dimethyl-1′H-spiro[cyclohexane-1,2′-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin]-4′(3′H)-one, and 7,8,9-trimethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-amine have been synthesized by one-pot three-component condensation of 3-methyl(ethyl)pentane-2,4-diones with cyanothioacetamide and α-halocarbonyl compounds, cyclohexanone, or formamide. The structures of some of the synthesized thieno[2,3-b]pyridine derivatives have been studied by X-ray analysis.

Synthesis of Thiazolyl-N-phenylmorpholine Derivatives and their Biological Activities.

Morpholine and thiazole rings are two heterocycles which are wellknown with a wide spectrum of different biological activities, especially antitumor activity. The aim of the work is to design and synthesize hybrid heterocyclic compounds of morpholine and thiazole moieties via the reaction of morpholino-thiosemicarbazone derivatives with various α-halocarbonyl compounds and screening their antitumor activity against three tumor cell lines namely, TK-10, MCF-7 and UACC-62. An efficient synthesis of a series of N-phenylmorpholine derivatives linked with thiazole moiety was accomplished. The reaction of N-subistituted-2-(N-phenylmorpholine)ethylidene) hydrazine- 1-carbothioamide (thiosemicarbazone derivative) with acetyl and ester-hydrazonoyl chlorides, α-chloroketones, or α-bromoesters afforded the corresponding thiazole derivatives pendent to N-phenylmorpholine moiety in good to excellent yields. Mass, 1H NMR, 13C NMR, and elemental analysis were used to confirm the structure of all the new derivatives. The antitumor activities of synthesized N-phenylmorpholine-thiazole derivatives were investigated against three tumor cells namely, TK-10, MCF-7 and UACC-62. The results of such investigation indicated that some derivatives showed good potential to inhibit the growth of the two cells of the tested tumor cells. One of the tested compounds, N-ethyl thiosemicarbazone derivative 7 revealed potent growth inhibition of all the three tumor cells. We have succeeded to synthesize a series of N-phenylmorpholine derivatives pendant to thiazole moiety as antitumor agents.

Nickel-Catalyzed α-Carbonylalkylarylation of Vinylarenes: Expedient Access to γ,γ-Diarylcarbonyl and Aryltetralone Derivatives.

We report a Ni-catalyzed regioselective α-carbonylalkylarylation of vinylarenes with α-halocarbonyl compounds and arylzinc reagents. The reaction works with primary, secondary, and tertiary α-halocarbonyl molecules, and electronically varied arylzinc reagents. The reaction generates γ,γ-diarylcarbonyl derivatives with α-secondary, tertiary, and quaternary carbon centers. The products can be readily converted to aryltetralones, including a precursor to Zoloft, an antidepressant drug.

Synthesis, Reactions, and Antimicrobial Activity of Novel Heterocyclic Compounds Containing Cyclopenta[d]thieno[2,3-b]pyridine Moiety and Related Fused Heterocycles

We describe a simple method to synthesize novel 4-cyano-1-morpholin-4-yl-6,7-dihydro-5H-cyclopenta[c]pyridine-3-thione by the reaction of 3-amino-1-thioxo-1,5,6,7-tetrahydrocyclopenta[c]thiopyran-4-carbonitrile with morpholine through Dimroth rearrangement. The 1-amino-5-morpholin-4-yl-7,8-dihydro-6H-cyclopenta[d]thieno[2,3-b]pyridine-2-carboxamide, which was synthesized by two methods, was used as a versatile precursor for synthesis of new thienopyrimidines fused to cyclopenta[d]pyridine ring system. Consequently, reaction of the amino-carboxamide with diethylmalonate, triethyl orthoformate, and cycloalkanones afforded the corresponding fused pyrimidine heterocycles. On the other hand, chloroacetylation of the amino-carboxamide using chloroacetyl chloride in dioxane produced the chloroacetyl amino derivative that in turn underwent cyclocondensation upon reaction with acetic anhydride to give the chloromethyl pyrimidinone. The latter compound was subjected to react with various nitrogen nucleophiles by nucleophilic substitution reactions to yield the akyl (aryl)amino methyl pyrimidinones. Subsequently, treatment of the phenyl aminomethyl derivative with formaldehyde under Mannich conditions produced the imidazopyridothienopyrimidine ring system. Similarly, reaction of the phenyl aminomethyl pyrimidonone with chloroacetyl chloride afforded a new heterocyclic system namely, cyclopentapyridothienopyrimidopyrazine. On the other hand, reaction of the amino-carboxamide with carbon disulfide in pyridine led to the formation of oxopyrimidine thione, which was alkylated by the reaction with different α-halo carbonyl compounds. The newly synthesized compounds were fully characterized on the basis of elemental and spectral analyses. Alternatively, some of these compounds revealed promising antibacterial and antifungal activities through the in vitro screening.

Synthesis and Antimicrobial Activity of Novel Piperidinyl Tetrahydrothieno[2,3-c]isoquinolines and Related Heterocycles.

A novel series of 1-amino-2-substituted-5-piperidinyl-6,7,8,9-tertahydrothieno[2,3-c]isoquinolines (4a–e) was synthesized upon treatment of 4-cyano-1-piperidinyl-5,6,7,8-tetrahydroisoquinline-3(2H)-thione (2) with α-halo carbonyl compounds such as chloroacetone, ethyl chloroacetate, 2-bromoacetophenone, chloroacetamide, and chloroacetanilide. Construction the pyrrolyl ring associated with the thienotetrahydroisoquinoline moiety was achieved by treatment of compounds 4a, b with 2,5-dimethoxytertahydrofuran in acetic acid. 1-Pyrrolyl-2-substituted-thieno[2,3-c]isoquinolines 5a and 5b which in turn were used as multipurpose precursors for synthesis of other new heterocycles. Assignments of the chemical structures of the respectively synthesized thienotetrahydroisoquinolines and their derivatives were established on the bases of elemental and spectral techniques (Fourier transform infrared, 1H NMR, 13C NMR, and mass spectroscopy). Furthermore, certain compounds were screened for their antimicrobial activity which revealed promising activities against various pathogenic strains of bacteria and fungi.