Synthesis and Structure of 2-Isobutyl-6-(2'''',4''''-dichlorophenyl)imidazo[2,1-b]-1,3,4-thiadiazole

1INTRODUCTIONThethiadiazoleandimidazolecompoundsareextensivelystudiedduetotheirspectrumbioacti-vities[1～4].Amongthem,theimidazo[2,1-b]-1,3,4-thiadiazolederivativesarepharmaceuticallyimpor-tantbecauseoftheirimmunostimulant[5],antifugal[6],antimicrobial[7]…     

X-ray Diffraction Analysis of Zn(II) Acetate Complex with 2-Amino-5-ethyl-1,3,4-thiadiazole

Results of a single-crystal X-ray diffraction study of the complex of zinc(II) acetate with 2-amino-5-ethyl-1,3,4-thiadiazole were presented. The coordination polyhedron of the complex has a distorted tetrahedral configuration with nitrogen atoms of the two 2-amino-5-ethyl-1,3,4-thiadiazole molecules and oxygen atoms of the two acetate ions coordinated to the central ion.     

Coordination behaviour of 2-halo-1,3,4-thiadiazoles towards cobalt(ii) and nickel(ii)

Summary A series of cobalt(II) and nickel(II) 2-X-1,3,4-thiadiazole complexes (X=Cl or Br) were investigated by electronic, n.m.r., Raman and i.r. spectroscopy, and by thermogravimetric analyses, magnetic moments and conductivity measurements.The complexes havepseudo-tetrahedral or pseudo-octa-hedral stereochemistries with MN₂X₂ (X=Cl or Br), MN₄X₂ (X=Cl, Br or O) or MN₃O₃ chromophores.The ligands are mono- or bi-dentate without involving the sulphur atom. Surprisingly, the chloro-derivative ligand seems to be more nucleophilic than the bromo-analogue.The computed (CNDO/2) molecular orbital indices for the uncomplexed ligands indicate that the coordination sites are the nitrogen atoms.In connection with our previous work⁽¹⁾ on the coordination ability of heterocyclic ligands with interesting biological^(2,3) and pharmaceutical⁽⁴⁾ properties and containing endocyclic nitrogen and sulphur donor atoms, we have considered the 1,3,4-thiadiazole ring, which is the main framework of a very important class of diuretic drugs, the sulphonamide inhibitors⁽⁵⁾ of the zinc m tallo-enzyme carbonic anhydrase.In this study we have investigated the coordination behaviour of the 2-chloro-1,3,4-thiadiazole(ctz) and the 2-bromo-1,3,4-thiadiazole (btz).     

Tetragonal-pyramidal complex of copper nitrate with 2-Amino-5-ethyl-1,3,4-thiadiazole

A complex compound of Cu(II) nitrate with 2-amino-5-ethyl-1,3,4-thiadiazole was synthesized and its structure was studied by the methods of IR spectroscopy and X-ray crystal analysis. The complex has the composition Cu(NO₃)₂(2-amino-5-ethyl-1,3,4-thiadiazole)₄ with four molecules of the heterocyclic ligand (coordination through nitrogen atoms of thiadiazole rings) and one of nitrate ions (the other is replaced in the second sphere) entering into the coordination sphere of the complex polyhedron. The internal coordination sphere of the complex has the form of a tetragonal pyramid with 2-amino-5-ethyl-1,3,4-thiadiazole ligands in the sites of its base and the oxygen atom of the nitrate ion in a slightly distorted vertex of the pyramid.     

Heterocyclization of 2-(Propargylsulfanyl)-1,3-thiazole Derivatives by the Action of Halogens

Reactions of 2-(propargylsulfanyl)-5-methyl-1,3,4-thiadiazole, N-[5-(propargylsulfanyl)-1,3,4-thiadiazol- 2-yl]benzamide, 2-(propargylsulfanyl)-1,3-benzothiazole, and 2-(propargylsulfanyl)-4,5-dihydro-1,3- thiazole with iodine involved annulation of the unsaturated substituent with formation of fused thiazole ring. 2(5)-(Propargylsulfanyl)-1,3,4-thiadiazole derivatives reacted with bromine to give mixtures of heterocyclization products and bromine adducts to the triple bond. The bromination of 2-(propargylsulfanyl)-4,5-dihydro- 1,3-thiazole afforded only the bromine addition product to the triple bond.     

Syntheses of arylsulfonyl-1,3,4-thiadiazoles

Reaction of sodium arylsulfinate with 2-aryl-5-chloro-1,3,4-thiadiazole gave 2-aryl-5-arylsulfonyl-1,3,4-thiadiazole (3) in good yield. Starting from readily available 2-amino-5-benzylmercapto-1,3,4-thiadiazole compound 7 was obtained in three steps in moderate yield. Reaction of compound 7 with sodium arylsulfinate afforded 2,5-diarylsulfonyl-1,3,4-thiadiazole ( 11 ). Oxidation of compound 10 with hydrogen peroxide in acetic acid gave 2-arylsulfonyl-5-benzylsulfonyI-1,3,4-thiadiazole ( 12 ), in high yield.     

Preparation of halomethyl-1,3,4-thiadiazoles. Conversion to 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole,an important antimicrobial agent

A new route for the synthesis of 2-amino-5-(l-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole ( 1 ) is described. This route was based upon the preparation of 2-amino-5-halomethyl-1,3,4-thiadiazoles by condensation of haloacetic acids with thiosemicarbazide. One of these intermediates, 2-acetamido-5-dichloromethyl-1,3,4-thiadiazole ( 4 ), was hydrolyzed to the corresponding 5-amino-2-carboxaldehyde 6 , which was trapped as its oxime 5 . 5-Acetamido-1,3,4-thiadiazole-2-carbonitrile ( 7 ), formed upon dehydration of 5 , was then converted into 2-amino-5-(2-imidazolyl)-1,3,4-thiadiazole ( 11 ) by a route based on the Pinner amidine synthesis. Methylation and nitration of the imidazole moiety then completed the preparation of 1.     

N-H?S hydrogen bonding in 2-mercapto-5-methyl-1,3,4-thiadiazole. Synthesis and crystal structures of mercapto functionalised 1,3,4-thiadiazoles

The synthesis and crystal structures of three mercapto functionalised 1,3,4-thiadiazoles and the crystal structure of 2-mercapto-5-methyl-1,3,4-thiadiazole are described. In the solid state, 2-mercapto-5-methyl-1,3,4-thiadiazole 1 forms a thioamide tautomer as shown by FTIR and Raman spectroscopy as well as X-ray crystallography and as theoretically predicted. The molecules are connected to form chains via N-H?S hydrogen bonds with N?S=328.3 pm. Bis(2-methyl-1,3,4-thiadiazolyl)-5,5′-disulfide 2, the disulfide of 1, as well as 2-(tert-butyldithio)-5-methyl-1,3,4-thiadiazole 3 and 2,5-bis(tert-butyldithio)-1,3,4-thiadiazole 4 have been synthesised and characterised by vibrational spectroscopy and X-ray diffraction.     

The mass spectrometric fragmentation patterns of some biologically active 1,3,4-thiadiazoles

Mass spectra of some twelve derivatives of 1,3,4-thiadiazole are reported. The fragmentation scheme of the 1,3,4-thiadiazole ring is specific and indicative as to the structure. Derivatives of 5-phenyl-1,3,4-thiadiazoles show rearrangement to isothiocyanates.     

Synthesis and reactivity of acyclic and macrocyclic uracils bridged with five-membered heterocycles

Replacement of terminal atoms of Br in 1,3-bis(bromopentyl)-5(6)-substituted uracils with 2-mercapto-5-methyl-1,3,4-thiadiazole, 2,5-dimercapto-1,3,4-thiadiazole, 2-mercaptoimidazole, and 2-mercaptobenzimidazoles resulted in a series of acyclic compounds and isomeric heterocyclophanes. Structures of macrocyclic regioisomers were unambiguously determined by NMR data. One of the regioisomers exhibits a hypochromic effect with respect to model compounds. The acyclic uracils obtained bridged with five-membered heterocycles are alkylated with methyliodide and methyl tosylate, and oxidated with m-CPBA, H₂O₂, and I₂.     

2-Azido-1,3,4-thiadiazoles, 2-Azido-1,3-thiazoles,and Aryl Azides in the Synthesis of 1,2,3-Triazole-4-carboxylic Acids and Their Derivatives

Diazotization of 2-amino-1,3,4-thiadiazoles gave 1,3,4-thiadiazole-2-diazonium sulfates which were converted to 2-azido-1,3,4-thiadiazoles. The latter reacted with ethyl acetoacetate in the presence of sodium methoxide in methanol to produce 1-(5-R¹-1,3,4-thiadiazol-2-yl)-5-R²-1H-1,2,3-triazole-4-carboxylic acid derivatives. The reactions of 2-azido-5-methyl-1,3,4-thiadiazole and 2-azido-1,3-thiazole with ethyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate led to the formation of 1,2,3-triazole ring under milder conditions (K₂CO₃, DMSO). Various 1,2,3-triazole-4-carboxylic acid derivatives were synthesized.     

Structure determination of 2-amino-5-benzylmercapto-1,3,4-thiadiazole and characterization of its copper complex

The crystal structure of 2-amino-5-benzylmercapto-1,3,4-thiadiazole (Ben-SNTD) has been determined. The thiadiazole ring is planar and aromatic, and the 1,3,4-thiadiazole-2-amino-5-thiol moiety is covalently bound to the benzyl group through the sulphur atom. Spectroscopic evaluation and thermal analysis of the complex formed between Ben-SNTD and CuCl₂ indicate a compound with a CuL₂ type structure.     

FT-Raman spectroscopy of the reaction of polybutadiene with mercapto-thiadiazoles

Mercapto-thiadiazoles having potential anti-wear behaviour are reacted with polymers with existing viscosity index-improving properties in order to produce materials which may find a use as multifunctional lubricant additives. 2,5-Dimercapto-1,3,4-thiadiazole, 2-amino-5-mercapto-1,3,4-thiadiazole and 2-methyl-5-mercapto-1,3,4-thiadiadiazole were reacted with low MW polybutadiene containing vinyl-1,2, cis-1,4 and trans-1,4 (C=C) groups. The reactions were monitored using FT-Raman spectroscopy in order to determine quantitatively the consumption of the individual structural units when reacted with thiadiazoles. 2,5-Dimercapto-1,3,4-thiadiazole reacted readily with the polybutadiene, achieving 80% reaction within a few hours. The thiadiazole reacted selectively with the order of addition being cis>vinyl>trans. 2-Amino-5-mercapto-1,3,4-thiadiazole and 2-methyl-5-mercapto-1,3,4-thiadiazole were found to react more slowly and hence to a lesser extent (40 and 25%, respectively) over a similar time scale.     

Theoretical studies of molecular structure and vibrational spectra of 2-amino-5-phenyl-1,3,4-thiadiazole

The molecular geometry and vibrational frequencies of 2-amino-5-phenyl-1,3,4-thiadiazole (C8H7N3S) in the ground state has been calculated using the Hartree-Fock and density functional method (B3LYP) with 6-31G(d) basis set. The optimized geometric bond lengths and bond angles obtained by using HF and DFT (B3LYP) show the best agreement with the experimental data. Comparison of the observed fundamental vibrational frequencies of 2-amino-5-phenyl-1,3,4-thiadiazole (C8H7N3S) and calculated results by density functional B3LYP and Hartree-Fock methods indicate that B3LYP is superior to the scaled Hartree-Fock approach for molecular vibrational problems.     

Novel fluorescent N,O-chelated fluorine-boron benzamide complexes containing thiadiazoles: Synthesis and fluorescence characteristics

A series of N-(5-phenyl-1,3,4-thiadiazol-2-yl)benzamide derivatives and their corresponding BF₂ complexes were synthesized, and their photophysical properties were determined. The effect of the derivatives with various substituents on the benzamide ring and phenyl-1, 3, 4-thiadiazole ring were examined in different organic solvents and in the solid state. These dyes enjoy a series of excellent photophysical properties including the large Stokes shift, solid-state fluorescence, and aggregation-induced emission effect (AIEE).     

Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9 (3H)-one derivatives. I.

A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives 4a--z were synthesized from 5-substituted 1,3,4-thiadiazol-2-amines 5 by the following consecutive reactions: pyrimidine ring closure with bis(2,4,6-trichlorophenyl) malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4, involving reaction of 5-substituted 2-azido-1,3,4-thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure. The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated.     

A five-coordinate complex of copper chloride with 2-amino-5-ethyl-1,3,4-thiadiazole

A complex of Cu(II) chloride with 2-amino-5-ethyl-1,3,4-thiadiazole (AET) was prepared, and its structure was studied by IR spectroscopy and single crystal X-ray diffraction. The complex has the composition CuCl₂(AET)₄. The coordination sphere of the copper atom includes four molecules of the heterocyclic ligand coordinated via N atoms of thiadiazole rings and one of Cl^? anions; the second Cl^? anion is in the outer sphere.     

Substituent effect on oxidative cyclization of aldehyde thiosemicarbazones with ferric chloride

The reactivity of aldehyde thiosemicarbazones 1 with ferric chloride solutions was examined. When compounds 1 are not substituted on the N-2 nitrogen atom formation of 1,3,4-thiadiazole 3 heterocyclic ring was observed. In contrast 1,2,4-triazoline 4 and/or 1,3,4-thiadiazoline 5 heterocyclic rings were afforded when N-2 nitrogen atom carried a methyl or a phenyl group. The reaction mechanism is also discussed.     

Condensation of thiourea with uracyl derivatives containing ketone and ketoester fragments,alkylation and macrocyclization of the condensation products

By condensation of thiourea with 6-methyluracyl derivatives containing ketone and ketoester fragmenst in the alkyl chains attached to the nitrogen atoms of the pyrimidine ring the products containing 6-methyl- or 3,6-dimethyluracyl fragment and one or two 6-methyl-4-oxo-2-thio-1,2,3,4-tetrahydropyrimidin-5-yl fragments were synthesized. These compounds can be alkylated with alkyl bromides.     

Chemoselective one-pot synthesis of 2-phenylamino-5-alkylthio-1,3,4-thiadiazole derivatives from phenylthiosemicarbazide and CS2

A novel and fairly efficient chemoselective one-pot method has been developed for the synthesis of both 2-phenylamino-5-alkylthio-1,3,4-thiadiazole and bis-(2-phenylamino-5-alkylthio-)1,3,4-thiadiazole derivatives from phenylthiosemicarbazide and CS₂.