A facile synthesis of 3‐Substituted 5‐Oxo‐1,2,4‐thiadiazoles from amidoximes

The reaction of amidoximes 1 with 1,1′‐thiocarbonyldiimidazole (TCDI) followed by treatment with silica gel or boron trifluoride diethyl etherate (BF₃·OEt₂) provided 3‐substituted 4,5‐dihydro‐5‐oxo‐1,2,4‐thiadiazoles 2 in moderate yields. The Lewis acids are considered to promote the rearrangement of the thioxocarbamate intermediates 5 to the thiol carbarn ate intermediates 7 , which cyclize to afford 4,5‐dihydro‐5‐oxo‐1,2,4‐thiadiazoles 2 .     

Synthesis of Novel 2‐Amino‐(2‐thioxo‐3‐alkyl‐4‐methyl‐3H‐thiazol‐5‐yl)‐[1,3,4]thiadiazole Derivatives and Their Growth Stimulant Activity

On the base of synthesized 2‐amino and 2‐ethylamino‐(2‐thioxo‐3‐alkyl‐4‐methyl‐3H‐thiazol‐5‐yl)‐[1,3,4]thiadiazoles, their alkyl, acetyl, and alkylacetylamino derivatives are obtained. The alkylation of 2‐ethylamino derivatives can occur at both exo and endo nitrogen atoms of amidine group, and the acetylation takes place exclusively at the exocyclic nitrogen atom. At acetylation of 2‐amino‐[1,3,4]thiadiazoles, only exo substitution is observed. At the further alkylation of these products, a mixture of exo‐ and endo‐substituted forms is obtained. At preliminary screening, the synthesized compounds have shown expressed growth stimulant properties. The activity of the most active derivatives was in the range of 65–100%, compared with that of heteroauxin.     

Synthesis of 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles

Several 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐1,3,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles have been synthesized and the structures of these compounds were established by elemental analysis, MS, IR and ¹H NMR spectral data.     

Soluble poly(ethylene glycol) supported efficient synthesis of 2,5‐disubstituted 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles

An efficient soluble poly(ethylene glycol) (PEG) supported liquid‐phase parallel synthetic method for 2,5‐disubstituted 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles is described. 2‐Aryl‐5‐(4′‐methoxycarbonylphenoxymethyl)‐1,3,4‐oxadiazoles and 2‐aryloxymethyl‐5‐(4′‐methoxycarbonylphenoxyacetamido)‐1,3,4‐thiadiazoles are synthesized in high yield and high purity using this polymer supported strategy. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:664–669, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20253     

The Synthesis of 3‐Amino‐pyrazine‐2‐carbohydrazide and 3‐Amino‐N′‐methylpyrazine‐2‐carbohydrazide Derivatives

In research of new biologically active compounds, the reactions of amino‐pyrazin‐2‐hydrazide and methylhydrazide with isothiocyanates, aromatic aldehydes, ketones, CS₂, and formic acid were made. New thiosemicarbazides, 1,3,4‐thiadiazoles, 1,3,4‐oxadiazoles, and 1,2,4‐triazoles were obtained. New 4‐oxopteridine derivative 26 was also synthesized.     

NMR spectroscopic characterization of new 2,3‐dihydro‐1,3,4‐thiadiazole derivatives

The ¹H and ¹³C NMR resonances of twenty‐seven 2,2‐dimethyl‐5‐(2‐nitrophenyl‐5‐substituted)‐2,3‐dihydro‐1,3,4‐thiadiazoles, and twenty‐seven 3‐acyl‐5‐(2‐amino‐5‐substituted)‐2,2‐dimethyl‐2,3‐dihydro‐1,3,4‐thiadiazoles were assigned completely using the concerted application of one‐dimensional and two‐dimensional experiments (DEPT, HMQC and HMBC). NOESY experiments, X‐ray crystallography and conformational analysis confirm the preferred conformation of these compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

TCT‐DMSO/[bmim]BF4: A novel promoter system for the synthesis of 3,5‐diaryl‐1,2,4‐thiadiazoles at ambient temperature

An efficient and practical procedure for direct synthesis of 3,5‐diaryl‐1,2,4‐thiadiazoles by thioamides with 2,4,6‐trichloro‐1,3,5‐triazine (TCT) and dimethylsulfoxide using 1‐butyl‐3‐methylimidazolium tetrafluoroborate as an eco‐friendly reaction medium under ambient temperature is described. This protocol can be considered as a new procedure for 3,5‐diaryl‐1,2,4‐thiadiazoles synthesis. J. Heterocyclic Chem., (2010).     

Peculiar reaction of N2‐acyl derivatives of 2‐aryl‐5‐hydrazino‐1,3‐oxazole‐4‐carbonitriles with the lawesson reagent

Easily accessible N²‐acyl derivatives of 2‐aryl‐5‐hydrazino‐1,3‐oxazole‐4‐carbonitriles react peculiarly with the Lawesson reagent. In addition to thionation, the reaction involves a recyclization to afford new substituted 2‐(5‐amino‐1,3‐thiazol‐4‐yl)‐1,3,4‐thiadiazoles. Their structure is corroborated spectroscopically and by the X‐ray diffraction method. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:782–785, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20413     

Recent Advances in the Chemistry and Synthetic Uses of Amino‐1,3,4‐thiadiazoles

Amino‐1,3,4‐thiadiazoles, although scarce in nature, constitute a group of nitrogen and sulfur heterocyclic compounds that have shown significant biological activities. Their transformations into other biologically active compounds have been exploited. This review describes the work on the synthesis and reactions of amino‐1,3,4‐thiadiazoles as well as their biological evaluation.     

Synthesis and Antimicrobial Activity of New Derivatives of 1,3,4‐Thiadiazoles and 1,2,4‐Triazoles with 5‐Nitroindazole as Support

The synthesis of new derivatives of 1,3,4‐thiadiazoles and 1,2,4‐triazoles was achieved using the 1,4‐disubstituted thiosemicarbazides as intermediaries.     

Synthesis of 6‐(5‐Methylisoxazol‐3yl)‐3‐alkyl Sulfanyl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazoles

A new series of isoxazole substituted fused triazolo‐thiadiazoles have been synthesized by the cyclocondensation of 5‐methylisoxazole‐3‐craboxylic acid and 4‐amino 1,2‐4‐triazole‐ 3,5‐dithiol using phosphorous oxychloride. The cyclised intermediate 6‐(5‐methylisoxazol‐3‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole‐3‐thiol later on S‐alkylated with different alkyl halides in ethanol to give the title products in good to excellent yields.     

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).     

Reaction with hydrazonoyl halides. Part 32 [1]: Reaction of C‐acyl‐N‐(3‐phenyl‐5‐pyrazolyl)hydrazonoyl chlorides with potassium thiocyanate and synthesis of some new 2,3‐dihydro‐1,3,4‐thiadiazoles and slenadiazoles

C‐acyl‐N‐(3‐phenyl‐5‐pyrazolyl)hydrazonoyl chlorides 1a,b react with potassium thiocyanate and potassium selenocyanate to give 5‐acyl‐2,3‐dihydro‐2‐imino‐3‐(3′‐phenyl)pyrazol‐5′‐yl)‐1,3,4‐thiadiazoles 2a,b and 5‐acetyl‐2,3‐dihydro;‐2‐imino‐3‐(3′‐phenyl)pyrazol‐5′‐yl)‐1,3,4‐selenadiazole 10a,b . Also, 2‐[mercapto‐(methylthio)methylene]indan‐1,3‐dione 16 reacts with hydrazonoyl halides 15 and 22–25 to afford 2,3‐dihydro‐1,3,4‐thiadiazoles 19 and 26–29 , respectively. Structures of the newly synthesized compounds are elucidated on the basis of spectral data, chemical transformations, and alternative synthesis methods. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:468–474, 2001     

An Unexpected Result of the Reaction of Benzothioamide Derivatives with 2‐Aryl‐2‐bromoacetonitriles

Unexpectedly, in the reaction of 2‐bromo‐2‐phenylacetonitrile derivatives with 2 mol‐equiv. of benzothioamide in DMSO, 3,5‐diaryl‐1,2,4‐thiadiazoles were obtained in excellent yields (83–90%) and in short reaction times (5–10 min). It is found that, in DMF, a quite different reaction takes place and 2,5‐diaryl‐1,3‐thiazol‐4‐amines are formed as the main products.     

Microwave Induced Synthesis of 3‐Aryl‐6‐(6‐/8‐substituted 4‐chloroquinoline‐3‐yl) ‐ s ‐triazolo [3,4‐b] −1,3,4‐thiadiazoles

The condensation of 4‐amino‐3‐aryl‐5‐mercapto‐1, 2, 4‐triazoles (1a‐f) with 6‐/8‐substituted 1,4‐dihydro‐4‐oxo‐quinoline‐3‐carboxylic adds (2a‐d) in the presence of phosphorus oxychloride on refluxng or under microwave irradiation gave twenty four novel 3‐aryl‐6‐ (6‐/8‐substituted 4‐chloroquinoline‐3‐yl)‐s‐triazolo[3,4‐b]‐1, 3,4‐thiadiazoles (4a‐x), Considerable increase in the reaction rate has been observed with improved yields under microwave irradiation. The structures of the compounds synthesized were determined by elemental analyses, IR, ¹H NMR and MS spectra. Their spectral properties and the reaction mechanism were also discussed. The preliminary biological test showed that some of compounds bad moderate antibacterial activities.     

Multinuclear magnetic resonance studies of 2‐aryl‐1,3,4‐thiadiazoles

The ¹H, ¹³C and ¹⁵N spectra of aryl‐substituted 1,3,4‐thiadiazoles were recorded. The results obtained were correlated with Hammett coefficients. The experimental results were compared with DFT‐calculated chemical shifts. The results obtained were compared with those for 1,3,4‐oxadiazoles and 1,3,4‐selenadiazoles. Copyright © 2012 John Wiley & Sons, Ltd.     

C5‐Alkyl‐1,3,4‐Oxadiazol‐2‐ones Undergo Dealkylation upon Nitrogen Insertion to Form 2H‐1,2,4‐Triazol‐3‐ones: Synthesis of 1,2,4‐Triazol‐3‐one Hybrids with Triazolothiadiazoles and Triazolothiadiazines

The present study emphasizes on the dealklylation of 3‐aryl‐5‐alkyl‐2‐oxo‐Δ⁴‐1,3,4‐oxadiazoles when reacted with formamide resulting in the formation of 2‐aryl‐2H‐1,2,4‐triazol‐3(4H )‐ones as major product. Subsequent reactions of 2‐aryl‐2H‐1,2,4‐triazol‐3(4H )‐one gave triazolo[3,4‐b ][1,3,4]thiadiazoles and triazolo[3,4‐b ][1,3,4]thiadiazines derivatives incorporated with 1,2,4‐triazol‐3‐one.     

Potassium Carbonate‐Mediated Green and Efficient Synthesis of Imidazo[2,1‐b]‐1,3,4‐thiadiazoles Using PEG as Solvent

Polyethylene glycol (PEG) was found to be an inexpensive nontoxic and effective medium for the synthesis of imidazo[2,1‐b]‐1,3,4‐thiadiazoles in the presence of potassium carbonate as a green base in high yields. In addition, the solvent system can be recovered and reused, making this protocol economically and potentially viable.     

Synthesis of a New Class of Sulfonamido Bis Heterocycles—Pyrrolyl/Pyrazolyl‐1,3,4‐oxadiazoles, 1,3,4‐Thiadiazoles,and 1,2,4‐Triazoles

A new class of sulfonamido bis heterocycles—pyrrolyl/pyrazolyl‐oxadiazoles, thiadiazoles, and triazoles—were prepared from arylaminosulfonylacetic acid hydrazide and E‐aroylethenesulfonylacetic acid adopting simple and versatile synthetic methodologies.     

Reactions with hydrazonoyl halides XXVIII*: Synthesis of some 2‐thiazolylimino‐2,3‐dihydro‐1,3,4‐thiadiazoles

Hydrazonoyl halides have been caused to react with each of methyl 5‐ethoxycarbonyl‐4‐methylthiazole‐2‐aminothiocarbamate, benzyl 5‐ethoxycarbonyl‐4‐methylthiazole‐2‐aminothiocarbamate, and 5‐ethoxycarbonyl‐4‐methylthiazol‐2‐ylphenylthiourea in the presence of triethylamine to give 2‐imino‐(5‐ethoxycarbonyl‐4‐methyl)thiazolyl‐2,3‐dihydro‐1,3,4‐thiadiazoles in good yields. Structures of the new compounds were elucidated on the basis of elemental analyses, spectral data, and alternative methods of synthesis whenever possible. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:213–217, 2000