Synthesis of Imidazo[2,1‐b][2H‐1,3,4]thiadiazines and 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines

Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.     

Different patterns of supramolecular assembly in constitutionally similar 6‐arylimidazo[2,1‐b][1,3,4]thiadiazoles

Four imidazo[2,1‐b][1,3,4]thiadiazoles containing a simply‐substituted 6‐aryl group have been synthesized by reaction of 2‐amino‐1,3,4‐thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6‐(2‐Chlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₆ClN₃S, (I), 6‐(2‐chlorophenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₁H₈ClN₃S, (II), 6‐(3,4‐dichlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₅Cl₂N₃S, (III), and 6‐(4‐fluoro‐3‐methoxyphenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₂H₁₀FN₃OS, (IV), crystallize with Z′ values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C—H...N hydrogen bonds to form ribbons containing alternating R₂²(8) and R₄⁴(18) rings, and these ribbons are linked into a three‐dimensional array by three independent π‐stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π‐stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R₂²(8) dimers by C—H...N hydrogen bonds. Comparisons are made with a number of related compounds.     

Facile routes to 1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazines and 1,2,4‐triazino[3,4‐b][1,3,4]thiadiazine by heteropolyacides

Cyclization of 4‐amino‐6‐methyl‐3‐propargylmercapto‐1,2,4‐triazine‐5‐one 3 and 4‐amino‐3‐propargyl mercapto‐1,2,4‐triazole derivatives 6 were afforded 1,2,4‐triazino[3,4‐b][1,3,4]thiadiazines 4 and 1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazines 7 in presence of heteropolyacids, H₁₄[NaP₅W₂₉MoO₁₁₀] and H₆P₂W₁₈O₆₀ in high yields. Among used heteropoly acids, the yields were higher with H₁₄‐P₅Mo, caused to their high acid strengths.     

Synthesis and X‐ray characterization of 2,5,6‐trisubstituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives

A series of 2,5,6‐trisubstituted imidazo[2,1‐b][1,3,4]thiadiazoles via Mannich reaction of imidazo[2,1‐b][1,3,4]thiadiazoles with morpholine and formaldehyde were synthesized. Structures of all the newly synthesized compounds are well supported by spectral data such as IR, NMR, Mass, and Elemental analysis. Compound 3a has been confirmed by X‐ray diffraction studies. J. Heterocyclic Chem., (2012).     

Facile one‐pot synthesis of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one using heteropolyacid catalysts

[1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazines 2a , 2b , 2c , 2d , 2e , 2f and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one 4 were synthesized by one‐pot cyclocondensation reaction with α‐chloroacetonitrile and α‐haloketones in the presence of catalytic amounts of heteropolyacids in very high yields and rates. J. Heterocyclic Chem., (2011).     

A facile one‐pot synthesis of thiazo[2′,3′:2,1] imidazo[4,5‐b]pyrane; thiazo[2′,3′:2,1]imidazo [4,5,b]pyridine; imidazo[2,1‐b]thiazole and 2‐(2‐amino‐4‐methylthiazol‐5‐yl)‐1‐bromo‐1,2‐ethanedione‐1‐arylhydrazones

Thiazole 1 , when reacted with chloroacetyl chloride, afforded N‐(5‐acetyl‐4‐methylthiazol‐2‐yl) chloroacetamide 2 . It has been found that compound 2 reacted with α‐cyanocinnamonitrile derivatives 6a–c to afford reaction products 8a–c . Also, compound 2 coupled smoothly with benzenediazonium chloride afforded the phenylhydrazone 14 . Coupling of the sulfonium bromide 17 with diazotized aromatic amines or N‐nitrosoacetanilides afforded the arylhydrazones 20a,b . Treatment of 16 with 2‐cyanoethanethioamide afforded [4‐(2‐amino‐4‐methylthiazol‐5‐yl) thiazol‐2‐yl] acetonitrile 22 . © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:362–369, 2000     

Synthesis of α‐[5‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐2‐imidazolylthio]acetic acids

The paper describes synthesis and antituberculosis activity of α‐[5‐(5‐amino‐1,3,4‐thiadiazol‐2‐yl)‐imidazol‐2‐ylthio]acetic acids ( 5a,b ). The compounds were tested against Mycobacterium tuberculosis strain H37Rv in comparison to rifampicin. Compounds exhibited low activity (MIC ≤ 6.25 μg/ml, % inhibition ≥ 24).     

A Facile Synthesis of Novel Dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines Using HTIB

The synthesis of a series of 21 novel 3‐alkyl/aryl‐7/9‐methyl‐10,10a‐dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines ( 4 ) has been achieved by the cyclocondensation between 4/6‐methyl‐2‐tosyloxy‐1‐indanones ( 2 ) and 3‐alkyl/aryl‐4‐amino‐5‐mercapto‐1,2,4‐s‐triazoles ( 3 ). 4/6‐Methyl‐2‐tosyloxy‐1‐indanones ( 2 ) were readily accessible through hypervalent iodine oxidation of 4/6‐methyl‐1‐indanones using [(hydroxy)tosyloxyiodo]benzene (HTIB, Koser's reagent) in acetonitrile.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Synthesis of 6‐Aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐Aryl‐thiazolo[3,2‐b][1,2,4]triazoles

The cyclization of the derivatives of 3‐aminotriazole, 2‐(5‐substituted 4H‐1,2,4‐triazol‐3‐ylamino)‐1‐arylethanones and 2‐(4H‐1,2,4‐triazol‐3‐ylthio)‐1‐arylethanones to yield 6‐aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐aryl‐thiazolo[3,2‐b][1,2,4]triazoles has been described.     

Transformation of 1,2,3‐Thiadiazolyl Hydrazones as Method for Preparation of 1,2,3‐Triazolo[5,1‐b][1,3,4]thiadiazines

The transformation of 1,2,3‐thiadiazolyl hydrazones of aldehydes and ketones including Dimroth rearrangement giving 1‐alkylidenamino‐5‐mercapto‐1,2,3‐triazoles, alkylation of mercapto group of these heterocyclic compounds by α‐bromoacetophenones and cyclization giving 6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b ][1,3,4]thiadizines have been investigated. It was shown that the reaction for hydrazones of acetophenones and benzoaldehydes is diastereoselective. Triazolothiadiazine spiro derivatives were prepared with transformation of hydrazones of cyclic ketones.     

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.     

Synthesis,Structure and Biological Activities of Novel 2‐(Trifluoromethyl)‐ 6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich Base Derivatives Containing Substitutedpiperazine Moiety

A convenient and practicable method for the synthesis of the novel 2‐(trifluoromethyl)‐6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich base derivatives containing various substitutedpiperazine motif has been developed based on the fused‐heterocycle intermediate. The new structures were identified through melting points, ¹H NMR, ¹³C NMR, ¹⁹F NMR, elemental analysis (or HRMS) and X‐ray single‐crystal diffraction. The pesticidal bioassays showed that some of compounds exhibited good fungicidal activities against Cercospora arachidicola, Physalospora piricola and Rhizoctonia cereali at 50 mg/L; some of them displayed favourable insecticidal activities against oriental armyworm (Mythimna separata Walker) at 200 mg/L, particularly, Vk and Vm with mortality rate of 75% and 80% respectively, could be considered as new insecticidal lead compounds for further structural optimization.     

Synthesis and antibacterial studies of 6‐aryl‐2,2a‐dihydro‐naphtho‐[2′,1′‐5,6]pyrano[4,3‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine and its derivatives

Chemoselective synthesis of novel hetero cyclopenta[b]chrysene derivatives, namely, 6‐Aryl‐2,2a‐dihydro‐naphtho[2′,1′‐5,6]pyrao[4,3‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine ( 4a‐j ) under neutral condition has been described. These molecules exhibited good to excellent anti‐bacterial activities.     

Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(as‐triazino[3,4‐b][1,3,4]thiadiazines)

A synthesis of bis(α‐bromo ketones) 5a‐c and 6b,c was accomplished by the reaction of bis(acetophenones) 3a‐c and 4b,c with N‐bromosuccinimide in the presence of p‐toluenesulfonic acid (p‐TsOH). Treatment of 5a‐c and 6b,c with each of 4‐amino‐3‐mercapto‐1,2,4‐triazoles 9a,b and 4‐amino‐6‐phenyl‐3‐mercapto‐1,2,4‐triazin‐5(4H)‐ones 13 in refluxing ethanol afforded the novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 10a‐d and 11a‐c as well as bis(as‐triazino[3,4‐b][1,3,4]thiadiazines) 14a‐c and 15 , respectively, in good yields. Compounds 11b and 11c underwent NaBH₄ reduction in methanol to give the target 1,ω‐bis{4‐(6,7‐dihydro‐3‐substituted‐5H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)phenoxy}butanes 12a and 12b in 42 and 46% yields, respectively.     

Synthesis of substituted 3‐(5‐amino‐[1,3,4]thiadiazol‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones

An efficient two‐step synthesis of novel 3‐(5‐amino‐[1,3,4]thiadiazol‐2‐yl)‐2H‐pyrano[2,3‐c]pyridine‐2‐ones was developed. In the first step, a new 2H‐pyrano[2,3‐c]pyridine‐3‐carboxamide 5 was prepared by Knoevenagel condensation of pyridoxal hydrochloride with cyanoacetamide. In the second step, the reaction of carboxamide 5 with a series of N⁴‐substituted thiosemicarbazides yielded a library of 35 dis crete compounds 8 {1–35} in high yields. The intermolecular recyclization mechanism leading to these products is discussed.     

An efficient microwave‐assisted synthesis furo[3,4‐b]‐[4,7] phenanthroline and indeno[2,1‐b][4,7]phenanthroline derivatives in water

A series of furo[3,4‐b][4,7]phenanthroline and indeno[2,1‐b][4,7]phenanthroline derivatives were synthesized via a three‐component reaction of aromatic aldehydes, 6‐aminoquinoline and either tetronic acid or 1,3‐indanedione in water, under microwave irradiation without use of any catalyst. This green procedure offers several advantages including operational simplicity, clean reaction, and increased safety for small‐scale high‐speed synthesis.     

Synthesis of benzo[c][1,8]phenanthrolin‐6‐one through cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐benzamide derivatives

In the course of our search for compounds with potential antitumor properties we have undertaken the synthesis of benzo[c][1,8]phenanthroline derivatives. Our project required the preparation of 8,9‐dimethoxy benzo[c][1,8]phenanthrolin‐6‐ones. This was first attempted by the lithiumdiisopropylamide cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide. The reaction led to 40% of the unexpected internal Diels‐Alder adduct 3,4‐dimethoxy‐6H‐pyrido[2,3‐i]6,8a‐ethenoindolo[cd]isoquinoline‐2(1H)‐one, which arose from a benzyne intermediate. In a second and more successful approach, the internal biaryl palladium diacetate‐assisted coupling reaction of properly N‐protected N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide was studied. The optimisation of the protecting group necessary for this procedure led to a 64% yield of the target compound starting from N,N‐(isoquinol‐5‐yl)‐bis‐(2‐bromo‐4,5‐dimethoxybenzamide).     

Synthesis and mutagenic potency of structural isomers of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Synthesis of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), three structural isomers, and two desphenyl PhIP congeners has been carried out. Mutagenic potency was evaluated using S. typhimurium strain TA98 in the Ames test. Mutagenic potency increased in relation to structural features in these heterocyclic amines that allow extended resonance between the phenyl and imidazo[4,5‐b]pyridine N²‐amino substituents. By contrast, PhIP isomers, whose substitution disallows involvement of the phenyl group in their aminoimidazo resonance hybrids, and desphenyl congeners were from 86‐ to 234‐fold less mutagenic than PhIP.     

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

Several new pyrimido[4,5‐e ][1,2,4]triazolo[3,4‐b ][1,3,4]thiadiazine derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g ) were synthesized through the condensation reaction of 5‐bromo‐4,6‐dichloropyrimidine ( 1 ) and 4‐amino‐5‐methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 2 ). The single crystal X‐ray data of one of the derivatives confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction.