Simultaneous quantification of N‐butylthiophosphoric triamide and dicyandiamide in urea formulation by liquid chromatography with tandem mass spectrometry

A new liquid chromatography with tandem mass spectrometry method employing a mixed‐mode zwitterionic stationary phase was developed for simultaneous determination of urease inhibitor (N‐butylthiophosphoric triamide) and nitrification inhibitor (dicyandiamide) in urea fertilizer. Molecular modeling based on density functional theory calculations was employed to provide an insight into the interaction mechanism of urea, dicyandiamide, and N‐butylthiophosphoric triamide with zwitterionic stationary phase in chromatographic separation system. The detection of analytes was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The ion transitions monitored were m/z 85→68 for dicyandiamide and m/z 168.2→74 for N‐butylthiophosphoric triamide, respectively. The standard calibration curves of dicyandiamide and N‐butylthiophosphoric triamide were linear over the range of 1.0 ? 15 ppm (coefficient of determination = 0.9984), 0.05 ? 1 ppm (coefficient of determination = 0.9995), with limit of detection of 25 and 5 ppb, respectively. The recoveries of low, middle, and high concentrations were from 96.7 to 105.8% for N‐butylthiophosphoric triamide and 94.4 to 105.8% for dicyandiamide with accuracy (relative error %) of ≤5.8% and ≤5.8%, the precision (coefficients of variation) was ≤2.0% and ≤2.9%, respectively. The validated method was successfully applied on real urea samples to determine N‐butylthiophosphoric triamide and dicyandiamide simultaneously.     

Guignardic Acid,a Novel Type of Secondary Metabolite Produced by the Endophytic Fungus Guignardia sp.: Isolation,Structure Elucidation,and Asymmetric Synthesis

A UV‐guided fractionation of the AcOEt extract of the fermentation broth of Guignardia sp., an endophytic fungus from the leaves of the tropical tree Spondias mombin, resulted in the identification of the new metabolite (−)‐(2S,5Z)‐2‐(1‐methylethyl)‐4‐oxo‐5‐(phenylmethylene)‐1,3‐dioxolane‐2‐carboxylic acid ( 1 ), isolated as NH salt 1a . The metabolite 1 was designated (−)‐(S)‐guignardic acid. This first member of a new class of natural compounds contains a dioxolanone moiety formed by fusion of 2‐oxo‐3‐phenylpropanoic acid (phenylpyruvic acid) and 3‐methyl‐2‐oxobutanoic acid (dimethylpyruvic acid), products of the oxidative deamination of phenylalanine and valine, respectively. The structure of 1a was deduced from spectral data (UV, IR, MS, ¹H‐ and ¹³C‐NMR) and confirmed by asymmetric synthesis.     

Melamium Thiocyanate Melam,a Melamium Salt with Disordered Anion Sites

Melamium salts are a group of ionic carbon nitride type compounds that has been investigated only scarcely. We herein present a novel representative of this group. A melamium thiocyanate melam (1:1) adduct was synthesized from dicyandiamide and ammonium thiocyanate in sealed glass ampoules. The structure of the adduct was determined from single‐crystal X‐ray diffraction. Melamium thiocyanate melam crystallizes in monoclinic space group P2₁/c (no. 14) with lattice parameters of a = 3.6041(11), b = 28.532(7), c = 10.937(4) Å, β = 99.051(14)°, and Z = 4. While the melamium ions form 2D extended hydrogen bridged networks, the thiocyanate ions are disordered and no distinct structural sites could be assigned to the respective atoms. Instead, continuous columns of electron density located in channels in the porous structure were identified as potential space for anion locations. The compound was further characterized by elemental analysis, FTIR spectroscopy and solid‐state MAS‐NMR spectroscopy of the nuclei ¹H, ¹³C and ¹⁵N. Rietveld refinement of powder samples was performed for phase analysis. Furthermore, DSC‐TG was used to investigate the thermal behavior of the compound.     

Synthesis,photopolymerization, and adhesive properties of new bisphosphonic acid monomers for dental application

Four new monomers, 3‐(N‐methylacrylamido)propylidenebisphosphonic acid, 3‐(N‐propyl‐acrylamido)propylidenebisphosphonic acid, 3‐(N‐hexylacrylamido)propylidenebisphosphonic acid, and 3‐(N‐octylacrylamido)propylidenebisphosphonic acid, have been synthesized in good yields and fully characterized by ¹H, ¹³C, ³¹P NMR, and HRMS. The copolymerization of these monomers with N,N′‐diethyl‐1,3‐bis(acrylamido)propane (DEBAAP) has been investigated with differential scanning calorimetry. These mixtures show a higher reactivity than DEBAAP. New self‐etch dental primers, based on these acrylamide monomers, have been formulated. Dentin shear bond strength measurements have shown that primers based on these bisphosphonic acids assure a strong bond between the tooth substance and a dental composite. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5258–5271, 2009     

Synthesis,Antiproliferative Activity and DNA-Binding Properties of Nitrogen and Sulfur Heterocyclic Norcantharidin Acylamide Acid

Three novel norcantharidin acylamide acids (L¹?N‐thiadiazole norcantharidin acylamide acid, C₁₀H₁₁N₃O₄S; L²?N‐thiazole norcantharidin acylamide acid, C₁₁H₁₂N₂O₄S and L³?N‐benzothiazole norcantharidin acylamide acid, C₁₅H₁₄N₂O₄S) were synthesized by the reactions of norcantharidin (NCTD?7‐oxabicyclo[2,2,1]heptane‐2,3‐dicarboxylic acid anhydride, C₈H₈O₄) with 2‐amino‐1,3,4‐thiadiazole (C₂H₃N₃S), 2‐aminothiazole (C₃H₄N₂S) and 2‐aminobenzothiazole (C₇H₆N₂S), respectively. Their structures were characterized by elemental analysis, IR, and NMR. The inhibition rates of L³ was much higher than those of L¹ and L² against human hepatoma cells SMMC7721 cell lines in vitro. The interaction between the compounds and DNA was studied by means of fluorescence quenching studies and viscosity measurements. The emission intensities decreased obviously with increasing concentration of the compounds in the fluorescence quenching experiments. The linear Stern‐Volmer quenching constant K_sq values were 0.62 (L¹), 0.55 (L²) and 1.08 (L³), respectively. The binding abilities followed the trend from high to low were L³, L¹ and L², respectively. The results of viscosity measurements showed that L¹ and L² might bind to DNA via partial intercalation, while L³ bound mainly in intercalation.     

Activity of SiDbCl in the Electrooxidation of Ascorbic Acid,Dopamine, and Uric Acid

Selective electroanalytical responses for ascorbic acid, dopamine and uric acid at a carbon modified electrode based on 3‐n‐propyl‐1‐azonia‐4‐azabicyclo[2.2.2]octane silsesquioxane chloride (SiDbCl) is reported. The overlapped peaks observed at an unmodified electrode are resolved into three well defined voltammetric peaks allowing the simultaneous determination of the three species. Detection limits of 37, 0.3 and 0.1 μmo L⁻¹ of ascorbic acid, dopamine and uric acid, respectively, were calculated from calibration curves based on differential pulse voltammetric experiments performed in Britton ‐ Robinson buffer solution at pH 7.04.     

Reaction of <Emphasis Type="Italic">N,N</Emphasis>′-bis(trimethylsilyl)dicyandiamide with bis(η<Superscript>5</Superscript>-cyclopentadienylvanadium) dichloride

1,3,5-Tris[bis(η⁵-cyclopentadienyl)chlorovanadium]melamin is prepared in high yield by the reaction of N,N′-bis(trimethylsilyl)dicyandiamide with bis(η⁵-cyclopentadienylvanadium) dichloride in tetrahydrofuran. As side products, trimethylchlorosilane and cyclopentadiene formed. Reaction of N,N′-bis(trimethylsilyl) dicyandiamide with benzoyl chloride results in the formation of tris(benzoyl)melamin.     

Ligand‐Modification Effects on the Reactivity,Solubility, and Stability of Organometallic Tantalum Complexes in Water

Tantalum complexes [TaCp*Me{κ⁴‐C,N,O,O‐(OCH₂)(OCHC(CH₂NMe₂)?CH)py}] ( 4 ) and [TaCp*Me{κ⁴‐C,N,O,O‐(OCH₂)(OCHC(CH₂NH₂)?CH)py}] ( 5 ), which contain modified alkoxide pincer ligands, were synthesized from the reactions of [TaCp*Me{κ³‐N,O,O‐(OCH₂)(OCH)py}] (Cp*=η⁵‐C₅Me₅) with HC?CCH₂NMe₂ and HC?CCH₂NH₂, respectively. The reactions of [TaCp*Me{κ⁴‐C,N,O,O‐(OCH₂)(OCHC(Ph)?CH)py}] ( 2 ) and [TaCp*Me{κ⁴‐C,N,O,O‐(OCH₂)(OCHC(SiMe₃)?CH)py}] ( 3 ) with triflic acid (1:2 molar ratio) rendered the corresponding bis‐triflate derivatives [TaCp*(OTf)₂{κ³‐N,O,O‐(OCH₂)(OCHC(Ph)?CH₂)py}] ( 6 ) and [TaCp*(OTf)₂{κ³‐N,O,O‐(OCH₂)(OCHC(SiMe₃)?CH₂)py}] ( 7 ), respectively. Complex 4 reacted with triflic acid in a 1:2 molar ratio to selectively yield the water‐soluble cationic complex [TaCp*(OTf){κ⁴‐C,N,O,O‐(OCH₂)(OCHC(CH₂NHMe₂)?CH)py}]OTf ( 8 ). Compound 8 reacted with water to afford the hydrolyzed complex [TaCp*(OH)(H₂O){κ³‐N,O,O‐(OCH₂)(OCHC(CH₂NHMe₂)?CH₂)py}](OTf)₂ ( 9 ). Protonation of compound 8 with triflic acid gave the new tantalum compound [TaCp*(OTf){κ⁴‐C,N,O,O‐(OCH₂)(HOCHC(CH₂NHMe₂)?CH)py}](OTf)₂ ( 10 ), which afforded the corresponding protonolysis derivative [TaCp*(OTf)₂{κ³‐N,O,O‐(OCH₂)(HOCHC(CH₂NHMe₂)?CH₂)py}](OTf) ( 11 ) in solution. Complex 8 reacted with CNtBu and potassium 2‐isocyanoacetate to give the corresponding iminoacyl derivatives 12 and 13 , respectively. The molecular structures of complexes 5 , 7 , and 10 were established by single‐crystal X‐ray diffraction studies.     

Determination of three Tumor Biomarkers (Homovanillic Acid,Vanillylmandelic Acid,and 5‐Hydroxyindole‐3‐Acetic Acid) Using Flow Injection Analysis with Amperometric Detection

Flow injection analysis with amperometric detection (FIA‐AD) at screen‐printed carbon electrodes (SPCEs) in optimum medium of Britton‐Robinson buffer (0.04 mol ? L^?1, pH 2.0) was used for the determination of three tumor biomarkers (homovanillic acid (HVA), vanillylmandelic acid (VMA), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA)). Dependences of the peak current on the concentration of biomarkers were linear in the whole tested concentration range from 0.05 to 100 μmol ? L^?1, with limits of detection (LODs) of 0.065 μmol ? L^?1 for HVA, 0.053 μmol ? L^?1 for VMA, and 0.033 μmol ? L^?1 for 5‐HIAA (calculated from peak heights), and 0.024 μmol ? L^?1 for HVA, 0.020 μmol ? L^?1 for VMA, and 0.012 μmol ? L^?1 for 5‐HIAA (calculated from peak areas), respectively.     

Simultaneous determination of oleanolic acid,ursolic acid,quercetin and apigenin in Swertia mussotii Franch by capillary zone electrophoresis with running buffer modifier

The method of capillary zone electrophoresis (CZE) with direct UV detection was developed for the determination of oleanolic acid, ursolic acid, quercetin and apigenin. and then for the first time successfully applied to the analysis of four analytes in Swertia mussotii Franch and its preparations. Various factors affecting the CZE procedure were investigated and optimized, and the optimal conditions were: 50 × 10^?3 mol/L borate‐phosphate buffer (pH 9.5) with 5.0 × 10^?3 mol/L β‐cyclodextrin, 15 kV separation voltage, 20 °C column temperature, 250 nm detection wavelength and 5 s electrokinetic injection time (voltage 20 psi). Under the conditions, oleanolic acid, ursolic acid, quercetin and apigenin could be determined within the test ranges with a good correlation coefficient (r² > 0.9991). The limits of detection for conditions, oleanolic acid, ursolic acid, quercetin and apigenin were 0.3415, 0.2003, 0.0062 and 0.2538 µg/mL, respectively, and the intra‐ and inter‐day relative standard deviations were no more than 4.72%. This procedure provided a convenient, sensitive and accurate method for simultaneous determination of oleanolic acid, ursolic acid, quercetin and apigenin in S. mussotii Franch. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis,properties, and sulfonation of novel dendritic multiblock copoly(ether‐sulfone)

Multiblock copoly(ether‐sulfone)s ( PES s) bearing anchor units for the construction of dendritic blocks were synthesized by two‐step reactions: (1) synthesis of PES block with both phenoxide end‐groups; (2) chain extension and end‐capping of the block by use of excess novel hexafunctional agent, hexakis(4‐(4‐fluorophenylsulfonyl)phenyl)benzene. The optimum average block length (n) and amount (x) of the hexafunctional agent used for the synthesis of high‐molecular‐weight PES without crosslinking were n = 26 and x = 2.6 equiv, respectively. The dendritic blocks in the PES were constructed by the aromatic nucleophilic substitution reaction of the activated aromatic fluoride groups on the anchor units using 4‐tritylbenzenethiol. The clean substitution of the fluoride groups in the PES was confirmed by ¹H NMR and ¹⁹F NMR. Three sulfonic acid groups were introduced on the pendant phenyl rings of the trityl groups in the PES by the reaction with chlorosulfonic acid. This is the first example of a dendritic PES bearing clusters of sulfonic acid groups only on the dendritic blocks. Cast films of presulfonated dendritic PES were strong and flexible, however, the membranes of sulfonated dendritic PES were brittle so that the conductivity measurements were not performed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6365–6375, 2008     

Tautomerization of Phenols,Part III,The Anthrone−Anthrol Equilibrium in Aqueous Solution

The equilibrium between 10H‐anthr‐9‐one and 9‐anthrol favors the ketone, which ionizes as a carbon acid in aqueous base. Rates of equilibration were measured over the pH range 1 – 13 in aqueous solution (25°, ionic strength I=0. M ). Five independent thermodynamic and kinetic parameters were determined by analysis of the pH‐rate profile: the equilibrium constant of enolization, pK_E=2.17, the ionization quotient of anthrol, pQ=7.84, and the rate constants of enolization catalyzed by acid, k=2.2⋅10⁻⁴ M ⁻¹ s⁻¹, base, k=51.0 M ⁻¹ s⁻¹, and water, k=1.21⋅10⁻⁵ s⁻¹. Structure‐reactivity relationships strongly support the view that pH‐independent enolization of anthrone in water proceeds by rate‐determining ionization of the C‐acid.     

Mononuclear vs. binuclear carboxylates of copper(II) with 2,2′‐bipyridine: Synthesis,characterization, structural description,and properties

Two new copper(II) carboxylate complexes with 2,2′‐bipyridine and para‐nitrophenyl acetate (complex 1 ) and phenyl acetate (complex 2 ) have been synthesized; isolated in quantitative yield; and characterized using fourier‐transform infrared spectroscopy (FT‐IR), electron paramagnetic resonance, absorption spectroscopy, electrochemistry, and powder and single crystal X‐ray diffraction (XRD) techniques. Being mononuclear, the geometry around copper in complex 1 is a Jahn–Teller distorted octahedral, while complex 2 is binuclear with slightly distorted square pyramidal geometry around both copper ions. Powder XRD indicated several peaks in spectra of both complexes, which coincided with their theoretical spectra. FT‐IR results of the carboxylate stretching frequency were in accordance with the single crystal structure data. Electron paramagnetic resonance spectra of complexes 1 and 2 yielded g_┴ values of 2.06161 and 2.24623 and 1.94959, respectively, indicating a localized electron in b₁ (d _x²_–y²‐orbital). Ultra‐violet (UV)–visible spectroscopy and electrochemistry helped in characterization, as well as in deoxyribonucleic acid (DNA)‐binding ability of the complexes, yielding DNA‐binding constant values = 1.351 × 10⁴ and 1.361 × 10⁴ and 1.820 × 10⁴ and 2.426 × 10⁴ M^?1, respectively, for complexes 1 and 2 . The complexes demonstrate good biological potential.     

Synthesis,Characterisation, and Biodistribution of Radioiodinated C‐Hydroxy‐Carboranes

The synthesis, radiolabelling and biodistribution of iodinated C‐hydroxy‐nido‐carborane ligands is described. Microwave heating by using NaF in aqueous ethanol was used to prepare {sodium [7‐hydroxy‐7,8‐dicarba‐nido‐undecaborate], nido‐carboranol} and {sodium [7‐hydroxy‐7,8‐dicarba‐nido‐undecaborate‐8‐carboxylic acid], nido‐salborin} in 97 and 90 % yield, respectively. Radioiodination of these nido‐carboranes was completed by using both ¹²⁵I and ¹²³I, and the products were obtained in high radiochemical purity (>99 %) and yield (72 to 87 %). The structures of the radiolabelled products were validated through comparison to authentic standards. Biodistribution studies in BALB/c mice showed low accumulation of the labelled compounds in the liver and intestines, which are sites where labelled carboranes typically localise. The labelled cluster bearing hydroxy and carboxylic acid groups on the two carbon vertices demonstrated preferential clearance through the kidneys and low thyroid uptake. This compound had substantially reduced non‐specific binding than the deshydroxy analogue making it an attractive bifunctional ligand for preparing targeted molecular imaging and therapy agents.     

Novel Bisphosphonates Derived from 1H‐Indazole, 1H‐Pyrazolo[3,4‐b]Pyridine,and 1H‐Pyrazolo[3,4‐b]Quinoline

Novel tetraethyl ethylene‐1,1‐bisphosphonate esters derived from 1H‐indazole, 1H‐pyrazolo[3,4‐b]pyridine, and 1H‐pyrazolo[3,4‐b]quinoline were synthesized by a Michael addition reaction of tetraethyl ethylidene‐1,1‐bisphosphonate with the corresponding heterocycle, using conventional heating and microwave‐assisted methods. The microwave‐assisted method provides shorter reaction times and better yields. The hydrolysis of bisphosphonates afforded the corresponding bisphosphonic acids or salt, using concentrated hydrochloric acid or TMSBr/collidine, respectively. All new compounds were fully characterized, and their structures were assigned using ¹H, ³¹P, and ¹³C NMR and IR spectroscopies and mass spectrometry. The molecular structure of compound 6 was confirmed by X‐ray diffraction studies.     

Synthesis, Radiolabelling and in vitro Stability Study of 99mTc(CO)+3 Labeled Dendrimer PAMAM-Folic Acid Conjugate

Dendrimer polyamidoamine generation five‐folic acid conjugate was synthesesed and radiolabelled with fac‐[^99mTc(CO)₃(H₂O)₃]⁺, its in vitro stability was evaluated further. Both of the labeling yield and radiochemical purity of the G5‐FA‐DTPA‐^99mTc(CO)₃ conjugate exceeded 95%. More than 95.7% and 93.1% of the conjugate still keeps its original structure in PBS and new‐born calf serum solution respectively.     

Crystal Structure and Properties of the Carboxylic Acid Derivatives of Schizonpeta mulifida (L.) Briq.

The chemical constituents of the carboxylic acid derivatives from the ear of Schizonepeta were investigated. ¹H and ¹³C NMR chemical shifts of the carboxylic acid derivatives were accurately assigned. Two carboxylic acid derivative constituents were separated by a silica gel column. The structures were elucidated by the physical and chemical properties, IR, ¹H NMR, ¹³C NMR, MALDI‐TDF‐MS and X‐ray single crystal diffractometry. They were identified as 3‐imino‐N‐(α‐imidoethylamino)butyrolactam and neononane tetracid, respectively. The antitumoral activity on liver tumor cells SMMC‐7721 was determined in vitro. The experimental results showed that the former was better than the latter, and with increasing the concentration of the former the inhibitory activity was increased.     

Reactions of Fe2(μ‐odt)(CO)6 (odt = 1, 3‐oxadithiolate) with small bite‐angle diphosphines to afford the monodentate,chelate, and bridge diiron complexes: Selective substitution,structures, protonation,and electrocatalytic proton reduction

Selective substitutions of Fe₂(μ‐odt)(CO)₆ (odt = 1,3‐oxadithiolate, A ) and small bite‐angle diphosphines (Ph₂P)₂X [X = CH₂ (dppm) or N (CH₂CHMe₂) (dppa)] have been well investigated in this study. With Me₃NO·2H₂O in MeCN at room temperature, the reaction of A and dppm produced the monodentate complex [Fe₂(μ‐odt)(CO)₅(κ¹‐dppm)] ( 1 ), whereas the similar reaction with dppa afforded the chelate complex [Fe₂(μ‐odt)(CO)₄(κ²‐dppa)] ( 2 ). Using UV irradiation in toluene emitting at 365 nm, the treatment of A and dppm rarely resulted in the formation of the bridge complex [Fe₂(μ‐odt)(CO)₄(μ‐dppm)] ( 3 ), whereas the similar treatment with dppa formed the chelate complex 2 . Under thermolysis condition, refluxing solution of A with dppm or dppa gave the bridge complex 3 and [Fe₂(μ‐odt)(CO)₄(μ‐dppa)] ( 4 ), respectively, in which the former was formed in toluene (110 °C) but the latter was produced in xylene (138 °C). All the new complexes 1 – 4 obtained above were characterized by element analysis, FT‐IR, NMR (¹H, ³¹P) spectroscopies, and particularly for 1 – 3 by X‐ray crystallography. Furthermore, the in situ protonations of 2 with a weak acid HOAc (acetic acid) and a strong acid TFA (trifluoroacetic acid) are explored by means of FT‐IR and NMR (¹H, ³¹P) spectra. In addition, the electrochemical behaviors of 2 – 4 are studied and compared through cyclic voltammetry (CV) in the absence and presence of a strong acid (TFA) as a proton source, indicating that they all are active for electrocatalytic proton reduction to hydrogen (H₂).     

Studies on Orientation of Cyclization in Thiazolo‐Quinazoline Heterocyclic System Through NMR,DFT, and X‐ray Diffraction

1‐(4‐Methoxyphenyl)‐1,2,5,6‐tetrahydrobenzo[f]quinazoline‐3(4H)‐thione 3 , obtained by the condensation of 2‐tetralone 1 , 4‐methoxy benzaldehyde 2 with thiourea, on reaction with chloroacetic acid and 1,2‐dibromoethane furnishes compounds 12‐(4‐Methoxyphenyl)‐9,12‐dihydro‐5H‐benzo[f]thiazolo[2,3‐b]quinazolin‐10(6H)‐one 4 and 12‐(4‐Methoxyphenyl)‐‐6,9,10,12‐tetrahydro‐5H‐benzo[f]thiazolo[2,3‐b]quinazoline 5 and not their possible isomers 7 and 8 , respectively. The regiochemistry of the cyclized products and their structure is established by elemental analysis, ¹H NMR, ¹³C NMR, IR, and mass spectral data. Density functional theory (DFT) calculations have been carried out for compounds 4 and 5 and their isomers 7 and 8 with Jaguar version 6.5112 using Becke three parameter Lee‐Yang‐Parr density functional method and 6‐31G** basis set. X‐ray diffraction studies indicate that compound 4 crystallizes in the triclinic space group P‐1, with Z = 4 and cell parameters a = 9.5558(8) Å, b = 9.6363(4) Å, c = 20.9728(11) Å, α = 87.652(4)?, β = 77.283(5)?, and γ = 70.437(5)?. ¹H and ¹³C NMR of compounds 4 and 5 and their isomers 7 and 8 , respectively, have been calculated and correlated with experimental results. 2‐Arylidene derivatives of 4 were obtained by two routes, and their structure was established by spectral data. The lowest energy optimized geometry of the compound 4 in gas phase is consistent with that obtained by X‐ray crystallographic studies.     

Synthesis and Antimicrobial Evaluation of Some Novel 5‐Phenyl‐5H‐thiazolo[4,3‐b][1,3,4]thiadiazole Systems

Condensation of 2‐amino‐5‐phenyl‐5H‐thiazolo[4,3‐b] [1,3,4] thiadiazoles ( 1 ) with some carboxylic acid derivatives furnished corresponding compounds 2–4 , respectively. Alkylation of 1 with benzoylchloride and 4‐chlorobenzyl chloride afforded thiazolo[4,3‐b][1,3,4]thiadiazole derivatives 5 and 6 , respectively. Similarly, transformation of 1 with chloroacetyl chloride yielded chloroacetamide derivative 7 . The later compound was subjected to react with potassium thiocyanate or piperazine whereby, the binary thiazolidinone derivative 8 and N ¹ ,N⁴‐disubstituted piperazine 9 were produced, respectively. Also, the reactivity of 1 toward various active methylene reagents was investigated. Accordingly, our attempts to synthesize the tricyclic heterocyclic system 10 , 11′ , 12 ^′ by reaction of 1 with chloroacetonitrile, 4‐oxo‐4‐phenylbutanoic acid and/or diethylmalonate in presence of acetyl chloride was furnished 10 , 11 , and 12 . The newly synthesized compounds were screened as antimicrobial agent.