Thiosemicarbazide Derivatives Research Articles

Cyanoacetic acid hydrazide: An efficient access for the synthesis of multi‐functional azine and azole derivatives

AbstractHerein, the synthesis of nitrogen‐containing heterocyclic scaffolds from heterocyclization of cyanoacetic acid hydrazide derivatives is described. Thiosemicarbazide derivative1aundergoes base‐mediated cyclization producing pyrazole derivative of type2. The triazolopyridine5was obtained by double cyclization of1aand benzylidene malononitrile. Compound1bcondensed with ethyl chloroformate to furnish pyrazolooxazine8. Compound1bwas added to benzoyl isothiocyanate under thermal condition to form oxadiazine derivative10while, keeping the above reactant under room temperature to form acyclic derivative11. Using CS2as a cyclizing agent for compound1byielded pyrazole derivative13. Treatment of1bwith I2resulted in oxidative cyclization producing pyridazine derivative14. Compound1ccyclized with benzoyl isothiocyanate forming triazolothiazine derivative18. While using cinnamoyl isothiocyanate, the acyclic product22was obtained. Compound1cwas condensed with formaldehyde leading to oxadiazole derivative25.

Synthesis and antioxidant assay of new nicotinonitrile analogues clubbed thiazole, pyrazole and/or pyridine ring systems

AbstractA series of novel nicotinonitrile derivatives were synthesized by hybridization with thiazole, pyrazole, and pyridine ring systems using 4‐aminobenzohydrazide as link‐bridge. The synthetic strategy of nicotinonitrile‐thiazole analogues involves cyclization of the precursor N‐phenyl thiosemicarbazide derivative 4 with chloroacetic acid and phenacyl bromide. The reaction of hydrazide 3 with acetylacetone and/or ethyl acetoacetate was applied as a synthetic route for accessing 2‐((4‐(pyrazole‐1‐carbonyl)phenyl)amino)‐nicotinonitrile derivatives 9–10. The 2‐((4‐(4‐thiazolylidene‐pyrazole‐1‐carbonyl)‐phenyl)amino)nicotinonitriles 14–15 were obtained via a nucleophilic addition of pyrazolone 10 to phenyl isothiocyanate followed by cyclization with chloroacetone, phenacyl chloride, and/or ethyl bromoacetate. The 6‐amino‐4‐aryl‐3,5‐dicyano‐2‐oxo‐1‐(4‐substitutedbenzamido)‐pyridines 19 were synthesized by Knoevenagel condensation N′‐(2‐cyanoacetyl)‐benzohydrazide derivative 16 with substituted benzaldehydes followed by heating with malononitrile. All synthesized products were evaluated for their antioxidant potentialities using of 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) radical cation delcolorization assay. The nicotinonitrile‐thiazole hybrid 6b was found the most promising antioxidant agent with inhibition activity 86.27%.

Synthesis and computer - aided drug design studies of novel thiosemicarbazide derivatives as potent and target - oriented anti - cancer agents

Synthesis and computer - aided drug design studies of novel thiosemicarbazide derivatives as potent and target - oriented anti - cancer agents

Evaluation of New Thiosemcarbazides Derived from Captopril as Angiotensin-Converting Enzyme Inhibitors with Docking Study, and Predicted-ADMET Analysis

A series of new captopril thiosemicarbazide derivatives (2–7) were evaluated in vitro for ACE inhibitor activity, using developed colorimetric assay as a simple, sensitive, and cost-effective method. Compounds (4 and 7), substituted with an electron-withdrawing group, showed good ACE inhibition activity, compared to nonsubstituted derivatives, and compounds substituted with electron-donating groups, with percent inhibition of 76.23±0.44 and 79.22±0.25, and IC50 (0.137 and 0.103 μμ), respectively. The molecular docking study revealed good agreement for compounds (4 and 7) with in vitro findings, respectively, with binding energy (−6.99 and -7.3 Kcal/mol). In silico pre-ADMET analysis, all derivatives are supposed to show appropriate intestinal absorption with low BBB penetration, and a closer carcinogenicity score to zero. The lipophilicity of the synthetic compounds, expressed with Clog p values, showed good correlation with in vitro ACE inhibition activity.

Synthesis, Antimicrobial and Antitumor Evaluations of a New Class of Thiazoles Substituted on the Chromene Scaffold

A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b). The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or Cethoxy- N-hydrazonoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. The newly synthesized compounds were screened for their in vitro antimicrobial and antitumor activities by agar diffusion method and MTT assay, respectively. The results of the antimicrobial activity revealed that some of the new compounds exhibited excellent activity against pathogenic microorganism; Candida albicans compared with Ciprofloxacin and nystatin, as the reference drugs. All of the tested compounds exhibited significant cytotoxic activities comparable to that of the reference drug; Doxorubicin® (on HCT116 (colorectal carcinoma human cell line).

Synthesis and antituberculosis activity of new acylthiosemicarbazides designed by structural modification.

Acylthiosemicarbazides 8a-n were designed by structural modification of lead Compound 7. The syntheses of 8a-n involve a five-step procedure starting from carboxylic acids. Compounds 8a-n were tested against three Mycobacterium tuberculosis strains to measure their inhibitory antituberculosis activities. These activities could be explained according to the presence or absence of the chlorine substituent in the aromatic ring of the amide joined to the thiosemicarbazide core. Thiosemicarbazide derivative 8n is a candidate for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

Utilizing the interfacial reaction of naphthalenyl thiosemicarbazide-modified carbon dots for the ultrasensitive determination of Fe (III) ions

Since thiosemicarbazide contains numerous nitrogen and sulfur atoms in its structural formula that enhance its strong coordinating abilities with metal ions, it is always selected as the mother molecule for the design of metal-ion sensors. In this report, a thiosemicarbazide derivative (4-naphthalenyl-3-thiosemicarbazide (NTSC)) was synthesized via a single step process and covalently conjugated onto the surfaces of carbon dots (CDs). The modified CDs demonstrated excellent monodispersity, good photostability, and tunable luminescence properties. More importantly, the CDs retained a highly specific Fe3+ recognition capacity in contrast to other competing metal ions. Fe3+ can efficiently quench the fluorescence of CDs even at fairly low concentration (30μM) with a detection limit as low as 1.68nM. The fluorescence quenching kinetics are likely to involve static quenching, which is caused by specific interactions between NTSC-CDs and Fe3+ toward the formation of a ground state complex. Due to their excellent optical performance, low toxicity, and good biocompatibility the NTSC-CDs may be applied to the imaging and monitoring of Fe3+ in bacillus subtilis. In effect we successfully fabricated an effective fluorescent nanosensor for both the quantitative detection of Fe3+ in aqueous solutions, and its real-time imaging in vivo.

New series of water-soluble thiosemicarbazones and their copper(II) complexes as potentially promising anticancer compounds

New water soluble thiosemicarbazone ligands, namely 3-(3-{[(aminocarbonothioyl) hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L1Cl), 3-[4-hydroxy-3-({[(methylamino)carbonothioyl]hydrazono}methyl)benzyl]-1-methyl-1H-imidazol-3-ium chloride (H2L2Cl) and 3-(3-{[(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L3Cl) were synthesized through 1:1 condensation reaction of thiosemicarbazide derivatives with 3-(3-formyl-4-hydroxybenzyl)-1-methyl-1H-imidazole-3-ium chloride (SalimiCl) and characterized by elemental analysis and spectroscopic methods (UV–Vis, 1H NMR, FTIR). Single crystals of H2L1Cl and H2L2Cl were prepared for crystallographic analysis, which showed similar X-ray structures for both ligands with chiral P212121 space group. The ligands were used for synthesis of the following copper(II) complexes: [Cu(HL1)Cl]Cl, [Cu(HL2)Cl]Cl·H2O, and [Cu(HL3)Cl]Cl. All complexes were characterized by physico-chemical and spectroscopic methods. The X-ray structure of [Cu(HL1)Cl]Cl was orthorhombic with Pcba space group while [Cu(HL2)Cl]Cl·H2O was triclinic with Pī space group. Both complexes were mononuclear, with tridentate ligands in a thione form. All of the studied compounds showed good solubility and stability in water. The measurement of the molar conductance showed the release of Cl− into solution and substitution of water instead of the coordinated chloride. Among the studied complexes, only [Cu(HL3)Cl]Cl shows a quasi-reversible redox behavior with its reduction and oxidation peak potentials separated by a value of about 0.120V (Epc=−0.310V and Epa=−0.190V) indicating one-step and one-electron transfer for CuII/CuI redox couple. The cytotoxic effect of the compounds was measured using the MTT assay on MCF-7 and K562 cell lines and the results showed that [Cu(HL3)Cl]Cl and H2L3Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the MCF-7 cells showed the apoptosis cell death after treating with the H2L3Cl and [Cu(HL3)Cl]Cl. Also studies of cell cycles confirmed the cell cycle arrest in G2 phase for H2L3Cl and [Cu(HL3)Cl]Cl.

Efficient synthesis and anti-bovine viral diarrhea virus evaluation of 5-(aryldiazo)salicylaldehyde thiosemicarbazone derivatives

An efficient procedure for the synthesis of 5-(aryldiazo)salicylaldehyde thiosemicarbazone derivatives 1-25 was achieved via the condensation of 5-(aryldiazo)salicylaldehyde derivatives I–V with N-(4)-substituted thiosemicarbazide derivatives. Antiviral activity of the synthesized compounds was carried out. From the obtained results, it was noticed that compound 11 has a strong antiviral activity.

Synthesis, in vitro biological evaluation and in silico studies of certain arylnicotinic acids conjugated with aryl (thio)semicarbazides as a novel class of anti-leishmanial agents

Herein we introduce new compounds as conjugates of arylnicotinic acids with aryl (thio)semicarbazide derivatives. Based on a structure-guided approach, they were designed to possess anti-leishmanial activity through anti-folate mechanism, via targeting Leishmania major pteridine reductase 1 (Lm-PTR1). The in vitro anti-promastigote and anti-amastigote activity were promising for many thiosemicarbazide derivatives and superior to the reference miltefosine. The most active compounds 8i and 8j exhibited their anti-amastigote activity with IC50 values of 4.2 and 3.3 μM, respectively, compared to reference miltefosine (IC50 value of 7.3). Their anti-folate mechanism was confirmed via the ability of folic and folinic acids to reverse the anti-leishmanial activity of these compounds, comparably to Lm-PTR1 inhibitor trimethoprim. Interestingly, the in vitro cytotoxicity test of the most active compounds displayed higher selectivity indices than that of miltefosine emphasizing their safety on mammalian cells. Furthermore, the docking experiments on Lm-PTR1 as a putative target rationalized the in vitro anti-leishmanial activity. The in silico predictions exhibited promising pharmacokinetics and drug-likeness profiles of the most active compounds. Generally, this work introduces a fruitful matrix for new anti-leishmanial chemotype which would extend the chemical space for the anti-leishmanial activity.

Biological evaluation of copper(II) complexes on N(4)−substituted thiosemicarbazide derivatives and diimine co-ligands using DNA interaction, antibacterial and in vitro cytotoxicity

A number of alternatives were made to overcome numerous life-threatening infectious diseases by metal-based anticancer compounds. At present, thiosemicarbazones and their metal complexes have received significant consideration as a result of their metal DNA-interaction, structural diversity and availability of bonding modes. In this study, the coordination characteristics of nine diimine copper(II) complexes with sulfur containing ligands, [Cu(L)2] (1–3), [Cu(L)(bpy)]Cl (4–6) and [Cu(L)(phen)]Cl (7–9) (L = H(L1)–H(L3), phen = 1,10-phenanthroline, bpy = 2,2′-bipyridyl, H(L1) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-methylhydrazinecarbothioamide, H(L2) = (Z)-N-ethyl-2-((4-methoxynaphthalen-1-yl)methylene)hydrazinecarbothioamide and H(L3) = (Z)-2-((4-methoxynaphthalen-1-yl)methylene)-N-phenylhydrazinecarbothioamide] have been synthesized from 4-methoxy-1-naphthaldehyde along with N(4)-substituted thiosemicarbazide derivatives. The synthesized ligands and their Cu(II) complexes were characterized through different spectroscopic techniques and square-planar coordination was proposed. Biological evaluation such as DNA-cleavage, antibacterial and in vitro cytotoxicity of thiosemicarbazone ligands and their resultant Cu(II) complexes were analyzed. Interestingly, Cu(II) complex containing heteroaromatic moiety 9 had potential cytotoxic activity with strong DNA-interaction. In the future, these may be helpful to design more effective novel chemotherapeutic drugs.

Studies on Isoniazid Derivatives through a Medicinal Chemistry Approach for the Identification of New Inhibitors of Urease and Inflammatory Markers

A library of thiosemicarbazide derivatives of isoniazid 3–27, was synthesized and evaluated for their anti-inflammatory and urease inhibition activities, by using in vitro bioassays. Among these compounds 9, 10, 12, 21, and 26 were identified as new derivatives. Prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) and infections caused by Helicobacter pylori (ureolytic bacteria), are the two most significant causes of gastric and peptic ulcers. We focused on the identification of the dual inhibitors of inflammation and urease enzyme. Compound 23 was identified as the best dual inhibitor of inflammation (ROS; IC50 = 12.3 µg/mL), and urease enzyme inhibition activity (IC50 = 22.4 µM). Many of these compounds showed comparable activities to the standard anti-inflammatory drug (ibuprofen, IC50 = 11.2 µg/mL) and urease inhibitor (thiourea/acetohydraoxamic acid, IC50 = 21.1/20.3 µM). Compound 12 was found to be the most potent urease inhibitor (IC50 = 12.3 µM) and good inhibitor of inflammation (IC50 = 27.7 µg/mL). Compounds 19, 11, 13, 9, 17, 10, and 16, were also found to be potent inhibitors of urease. Cytotoxicity was also evaluated and all the compounds were found to be non-cytotoxic, except compound 18 and the parent drug isoniazid (IC50 = 29.5 and 28.5 µM, respectively).

Spectroscopic investigation, DFT, fluorescence, molecular docking and biological studies of divalent and trivalent binuclear complexes prepared from benzoyl thiosemicarbazide derivative of 2‐benzylmalonohydrazide

The binuclear Cr (III), Mn (II) and Fe (III) complexes of N,N′‐(2,2′‐(2‐benzylmalonyl)bis (hydrazine‐1‐carbonothioyl))dibenzamide (H4BPCD), which derived from the combination of 2‐benzylmalonohydrazide suspension with benzoyl‐isothiocyanate, have been isolated and investigated by the necessary analytical and spectroscopic techniques. The IR studies show that H4BPCD dispose as a mono‐negative hexadentate ligand (NOS)2 towards Mn (II) ion and tetra‐negative hexadentate (NOS)2 towards both Cr (III) and Fe (III) ions. The values of molar conductance in DMSO suggested the non‐electrolytic nature for all complexes. The magnetic measurements and the electronic transitions data confirmed the hexa‐coordinate geometry of complexes. The DFT geometry optimization of all compounds and IR comparative study of both theoretical and experimental of H4BPCD were carried out. Moreover, the H4BPCD and its Cr (III) complex displayed intra ligand (π → π*) fluorescence emission spectra which corroborate their photoactive nature. The coordinated and crystalline water molecules have been investigated by (TG/DTG) studies. The kinetic and thermodynamic parameters were computed using Horowitz‐ Metzger, Coats‐Redfern and Broido methods. Biological studies of DNA binding, minimum inhibitory concentration, in vitro determination of SOD‐like activity and MTT‐cytotoxicity assay as well as molecular docking studies were tested for the ligand and its complexes.

Synthesis, In Vitro Screening and Docking Studies of New Thiosemicarbazide Derivatives as Antitubercular Agents.

A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81–31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.

Synthesis, antimicrobial activity and molecular docking of di‐ and triorganotin (IV) complexes with thiosemicarbazide derivatives

Six organotin (IV) complexes with two ligands derived from 2,3‐butanedione and thiosemicarbazide have been synthesized and fully characterized by several spectroscopic techniques, including 119Sn NMR and single crystal X‐ray diffraction. Reactions of the ligand diacetyl‐2‐(thiosemicarbazone)‐3‐(3‐hydroxy‐2‐naphthohydrazone), L1H2, with SnR2Cl2 (R = Me, Bu, Ph) lead to the obtaining of complexes 1–3 with general formula [SnR2L1] (R = Me 1, R = Bu 2, R = Ph 3), in which the ligand is doubly deprotonated and behaves as a N2SO donor, whereas from the reactions of diacetyl‐2‐thiosemicarbazone, HATs, with the same organotin precursors any complex could be isolated. By contrast, reaction of HATs with SnR3Cl induces the ligand cyclization to form a 1,2,4‐triazine‐3‐thione that binds to the metal as a monoanionic donor in a mono or bidentate manner to form compounds 4–6 with formula [SnR3L2] (R = Me 4, R = Bu 5, R = Ph 6). The antimicrobial activity of the ligands and the six complexes was tested towards bacteria and fungi, including clinical isolated strains. The results show that the ligands are devoid of activity, except HATs that displays activity against Bacillus subtilis. Conversely, the complexes exhibit good antimicrobial properties against Gram positive and negative bacteria, yeasts and moulds. The best results are obtained for complexes [SnBu3L2] 5 and [SnPh3L2] 6, indicating that their more lipophilic nature could play an important role in the ease of microbial cell penetration. In some cases, these complexes display similar or higher activity than that of ampicillin and miconazole, used as antibacterial and antifungal positive controls, respectively. Docking study with DHPS protein (S. aureus) has shown that out of six drugs, the compound 6 has the best binding affinity (−8.5 Kcal/mol).

Corrosion Inhibition of Copper in Sea Water Using Derivatives of Tetrazoles and Thiosemicarbazide

Corrosion Inhibition of Copper in Sea Water Using Derivatives of Tetrazoles and Thiosemicarbazide

Heterocyclization of Isoniazid: Synthesis and Antimicrobial Activity of Some new Pyrimidine 1, 3-Thiazole, 1, 2, 4-Thiadiazole, and 1, 2, 4-Triazole, Derivatives Derived from Isoniazid

The reaction of isonicotinic hydrazide (1) (isoniazid) with cinnamoyl isothiocyanate (2) afforded cinnamoyl thiosemicarbazide derivative 3. Treatment of 3 with lead acetate in acetic acid, sodium ethoxide, sulphuric acid, chloroacetylchloride and sodium hypochlorite and sodium hydroxide gave the corresponding dihydropyrimidine 4, triazolethiazine 5, 1,3,4-thiadiazole 6, 1,3-thiazole 7 and 1,2,4-thiadiazole 8, respectively. The reactivity of isoniazid 1 towards ammonium thiocyanate, cyclohexanone and acetophenone to give 1,2,4-triazole thione 10, hydrazones 9 and 12 was studied. Treatment of hydrazones 9 and 12 with carbon disulfide and aryl isothiocyanates gave 1,3,4-thiadiazolidine 11 and 1,2,4-triazole thione derivatives 13a, b. The antimicrobial activity of these new compounds has been evaluated against 6 microbial strains. Some of the newly synthesized compounds showed a moderate activity.

Synthesis, biological evaluation, molecular docking and DFT calculations of novel benzenesulfonamide derivatives

The reaction of N-(4-acetylphenyl)benzene sulphonamide derivatives 3a and 3b with N,N dimethyl formamide dimethyl acetal (DMF-DMA) afford acryloyl(phenyl)benzenesulfonamide derivatives 4a and 4b; respectively. The chemical reactivity of enaminonitriles 4a and 4b towards hydrazine hydrate or hydroxylamine was studied for synthesizing of pyrazolyl and isoxazolyl-phenyl benzenesulfonamide derivatives 5a,b and 6a,b; respectively. Also, the treatment of enaminonitriles 4a and 4b with thiosemicarbazide or heterocyclic amines derivatives afford the novel sulfonamide derivatives. Furthermore, the reactivity of acetylsulfonamide derivatives towards nitrogen nucleophiles and dimedone afforded novel benzene sulfonamide compounds. Some of the synthesized chlorinated compounds exhibited excellent in vitro antitumor activity against HepG2 and MCF-7 cell lines. Additionally, further studies were carried out on one of the most effective compounds, 4-chloro-N-(4-(isoxazole-3-yl)phenyl) benzenesulfonamide 6a (ISP), to evaluate its potential interaction against KSHV thymidylate synthase complex. The comprehensive theoretical and experimental mechanical studies of compound 6a (ISP) were compatible with elemental analysis, FTIR, 1H NMR and MS spectral data. The optimized molecular structure and the harmonic vibrational frequencies were examined via Density functional theory (DFT)/B3LYP/6-31G(d) and Hartree-Fock HF/6-31G(d) energies.

Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors.

Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results.

A series of 1,3-imidazoles and triazole-3-thiones based thiophene-2-carboxamides as anticancer agents: Synthesis and anticancer activity

By addition of semicarbazide or phenylhydrazine hydrochloride to thienoylisothiocyanate (1) resulted in building of thiosemicarbazide derivative (2), triazole derivative (4) and thiophene-2-carboxamide (5), respectively. Basic cyclization of compound 2 led to formation of oxadiazine (3). Synthesis of thiadiazine derivative (6) was achieved via reaction of compound 5 and maleic anhydride in triethyl amine. Heating of compound 5 with ethyl chloroacetate or sodium ethoxide produced thiadiazine derivative (7) and triazolethione (8), respectively. Thiosemicarbazide derivative 11 was synthesized by addition of nicotinic hydrazide to compound 1. Refluxing of compound 11 with lead acetate afforded triazole (13). Moreover, acid and base mediated cyclizations of compound 11 gave thiadiazole (12) and 1,2,4-triazolethione (14) throughout thiophene intermediate, respectively. Addition of ethyl 2-aminothiophene-3-carboxylate to compound 1 formed thiourea (15) which was refluxed with ethoxide giving thiophene-3-carboxylic acid (16). Lastly, nucleophilic addition of amino phenol or ethylene diamine to compound 1 yielded oxazine structure (18) and imidazole derivative (19), respectively. The yields of the synthesized compounds were 61-95%. The detailed synthesis and spectroscopic data of the new compounds are reported.