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     

Rapid synthesis of 2,5‐disubtituted 1,3,4‐thiadiazoles under microwave irradiation

The one pot, three‐components condensation of aromatic aldehydes, hydrazine and sulfur in ethanol under microwave irradiation provided symmetrically 3,5‐disubstituted 1,3,4‐thiadiazoles in high yields and good purity. This reaction must be conducted under pressure of hydrogen sulfide produced in‐situ. The structure of the compounds was confirmed by ¹H, ¹³C NMR, MS and elemental analysis.     

Dithiocarbamates as an Efficient Intermediate for the Synthesis of Symmetrical Substituted 2,5‐Diamino‐1,3,4‐thiadiazoles in Water

Synthesis of symmetrical substituted 2,5‐diamino‐1,3,4‐thiadiazoles is described. Reaction of easily prepared dithiocarbamates with hydrazine gives the corresponding thiadiazoles in moderate to good yields. This method is new, efficient, and simple especially in the work‐up procedure.     

Asymmetric Morita-Baylis-Hillman reaction catalyzed by isophoronediamine-derived bis(thio)urea organocatalysts

New and improved bis(thio)urea catalysts were synthesized from isophoronediamine (IPDA) and tested in the Morita-Baylis-Hillman reaction. The best results were achieved in the reaction of 2-cyclohexen-1-one with cyclohexanecarbaldehyde, using the catalyst depicted above, in combination with a novel base (N,N,N',N'-tetramethylisophoronediamine, TMIPDA) in toluene. The desired Morita-Baylis-Hillman product was obtained in 75% yield and 96% ee.     

One pot diastereoselective synthesis of new chiral spiro‐1,3,4‐thiadiazoles and 1,4,2‐oxathiazoles from (1R)‐thiocamphor

Herein we report an efficient one pot synthesis of new chiral 4,5‐dihydro‐4‐arylspiro[1,3,4‐thiadiazole]‐5,2′‐camphane‐2‐carboxylic acid ethyl esters 5–7 and 4,5‐dihydro‐3‐arylspiro[1,4,2‐oxathiazole]‐5,2′‐camphane 11–13 , using 1,3‐dipolar cycloaddition of nitrilimines 2–4 and nitrile oxides 8–10 to (1R)‐thiocamphor 1 respectively. The structure of the newly prepared 1,3,4‐thiadiazoles 5–7 (obtained as pure diastereoisomers) were fully established via spectroscopic analysis and X‐ray structural analysis which proved the absolute configuration of the C5 spiranic carbon to be (R). NMR spectral analysis were also very useful to show the new 1,4,2‐oxathiazoles 11–13 are mixtures of two (5R)/(5S) diastereoisomers with the ratio 6:4,7:3 and 6:4 respectively.     

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 pyridazinone‐substituted 1,3,4‐thiadiazoles, ‐1,3,4‐oxadiazoles and ‐1,2,4‐triazoles

Several 1‐(1‐aryl‐1,4‐dihydro‐3‐carboxy‐6‐methylpyridazin‐4‐one)‐4‐aryl thio‐semicarbazides and their corresponding oxadiazole, thiadiazole and triazole derivatives were prepared and characterized by their spectral data. The preliminary biological tests showed that some new compounds exhibit good anti‐fungal activity.     

Organocatalysis mediated by (thio)urea derivatives

Over the last decade the potential for N,N-dialkyl(thio)urea derivatives to serve as active metal-free organocatalysts for a wide range of synthetically useful reactions susceptible to the influence of general acid catalysis has begun to be realised. This article charts the development of these catalysts (with emphasis on the design principles involved), from early "proof-of-concept" materials to contemporary active chiral (bifunctional) promoters of highly selective asymmetric transformations.     

Synthesis of 5‐substituted 2‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles

One‐stage synthesis of 5‐substituted (alkyl, aryl, heteroaryl, arylalkyl, heteroalkyl, alkoxy‐, aryloxy)‐2‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles is described. The compounds were prepared by the reaction of sulfinyl‐bis(2,4‐dihydroxythiobenzoyl) (STB) with hydrazides or carbazates. The structure of new compounds was assigned by ir, nmr and ms data.     

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.     

Green synthesis and crystal structure of 4,7‐diaryl‐2‐oxo(thio)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐5‐one derivatives

A green and convenient approach to the synthesis of novel 4,7‐diaryl‐2‐oxo(thio)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐5‐one derivatives from appropriate aromatic aldehydes and 5‐aryl‐1,3‐cyclohexanedione with urea or thiourea in the presence of dilute HCl as catalyst in water is described. This method provides several advantages such as environmental friendliness, low cost, high yields, and simple workup procedure. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR. The crystal and molecular structure of 4‐(4′‐chlorophenyl)‐7‐(4′‐methoxyphenyl)‐1,2,3,4,5,6,7,8‐octahydroquinazoline‐2,5‐dione 5m have been determined by single crystal X‐ray diffraction analysis. The crystal of compound 5m belongs to monoclinic with space group P‐2₁/c, a = 1.4353 (4) nm, b = 1.4011 (4) nm, c = 0.9248 (3) nm, α = 90.00°, β = 101.242 (6)°, γ = 90.00°, Z = 4, V = 1.8241 (9) nm³, R₁ = 0.0448, and wR₂ = 0.1022. J. Heterocyclic Chem., (2011).     

1,3,4‐Thiadiazole, 1,3,4‐thiadiazine, 1,3,6‐thiadiazepane and quinoxaline derivatives from symmetrical hydrazine‐1,2‐dicarbothioamide as well as N,N″‐ethane‐1,2‐diylbis(thiourea) derivatives

Reactions of N,N′‐disubstituted hydrazine‐1,2‐carbothioamides 8a‐c and substituted N,N″‐ethane‐1,2‐diylbis(thioureas) 9a‐c with 2,3,5,6‐tetrachloro‐1,4‐benzoquinone (chloranil, 10a ) and 2,3,5,6‐tetrabromo‐1,4‐benzoquinone (bromanil, 10b ) to form N,N′‐disubstituted 1,3,4‐thiadiazole‐2,5‐diamines 11a‐c , substituted 3‐amino‐6,7‐dichloro‐2,3‐dihydro‐1H‐4,2,1‐benzothiadiazine‐5,8‐diones 12a‐c , 2,3,7,8‐tetrahalothianthrene‐1,4,6,9‐tetrones 13a,b , substituted 5,6,8‐trihalo‐7‐oxo‐3,7‐dihydroquinoxaline‐2H‐carbothioamides 14a‐c, 15a‐c and 7‐substituted imino‐1,3,6‐thiadiazepane‐2‐thiones 16a‐c are reported.     

Fused polyaza‐heterocycles and 1,3,4‐thiadiazoles via a tricyano synthon

Treatment of 2‐cyano‐3‐phenyl‐2‐pentenedinitrile with some heterocyclic diazonium salts afforded the corresponding heterocyclic hydrazones. Some of the latter hydrazones were converted into fused polyaza‐heterocycles upon boiling in pyridine. Reaction of 2‐cyano‐3‐phenyl‐2‐pentenedinitrile with phenylisothiocyanate gave a tricyano‐thiole derivative which on treatment with hydrazonoyl chlorides and 1‐(benzothiazol‐2‐yl)‐2‐bromoethanone furnished 1,3,4‐thiadiazole and thiazole derivatives, respectively.     

Synthesis and Antimicrobial Activity of Some Novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles and 1,3,4‐thiadiazoles

A series of novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles ( 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h ) and 1,3,4‐thiadiazoles ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i ) were synthesized from thiosemicarbazide ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j ). The structures of these newly synthesized compounds were confirmed on the basis of IR, ¹H‐NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d , 7j , 8a , 9a , 9b , and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.     

Iodobenzene diacetate on alumina: Efficient synthesis of 1,3,4‐oxadiazolyl‐1,8‐naphthyridines in solventless system using microwaves

1‐(5‐Aryl‐[1,3,4]oxadiazol‐2‐ylmethyl)‐3‐(p‐methoxyphenyl)‐1H‐[1,8]naphthyridin‐2‐ones ( 5 ) were synthesized by the oxidative cyclization of [2‐oxo‐3‐(p‐methoxyphenyl)‐2H‐[1,8]naphthyridin‐1‐yl]acetic acid arylidene‐hydrazides ( 4 ) with alumina‐supported iodobenzene diacetate (IBD) in solvent‐free conditions under microwave irradiation. The products are obtained in good yields and in a state of high purity.     

An efficient synthesis of pharmacologically active derivatives of 1,3,4‐oxadiazoles

A simple and environmental friendly microwave irradiation method is devised for the synthesis of derivatives of 1,3,4‐oxadiazoles viz., 6a‐e and 7h‐q in 75–90% yield. Structures of the newly synthesised compounds were confirmed by physical, analytical and spectral (ir, ¹H and ¹³C nmr and ms) data and screened for antiinflammatory, anticonvulsant, antidiuretic and antihaemostatic activities. Some of the compounds have shown potent activities.     

A new convenient way to synthesize 1,3,4‐thiadiazol‐2‐yl urea derivatives under microwave irradiation

A simple and efficient method was developed for the synthesis of 1‐(substituted)‐3‐(5‐(substituted)‐1,3,4‐thiadiazol‐2‐yl) ureas from heterocyclic amino compounds and phenyl‐5‐(pyridine‐3‐yl)‐1,3,4‐thiadiazol‐2‐ylcarbamate( 2 ) or phenyl‐5‐(trifluoro‐methyl)‐1,3,4‐thiadiazol‐2‐ylcarbamate( 5 ) under solvent conditions using microwave irradiation. The products were obtained in satisfactory yield as we expected. The reactions can be realized by conventional heating, but we find that the condition of microwave is better according to the reaction time. New 1‐(substituted)‐3‐(5‐(substituted)‐1,3,4‐thiadiazol‐2‐yl) urea derivatives are reported. The products were characterized by ¹H NMR, ESI‐MS, and Elemental analysis. The crystal structure of compound 6h was determined by X‐ray single crystal diffraction. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:621–629, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20489     

Synthesis and anti‐HIV activity of new chiral 1,2,4‐triazoles and 1,3,4‐thiadiazoles

5‐substituted 4‐(4‐chlorophenyl)‐4H‐1,2,4‐triazol‐3‐thiones 3 and 2‐substituted 5‐(4‐chlorophenylamino)‐1,3,4‐thiadiazoles 4 were prepared from the intermediate thiosemicarbazides 2 under basic and acidic conditions, respectively. The thiosemicarbazides, in turn, were prepared by the reaction of hydrazides 1 with 4‐chlorophenylisothiocyanate in MeOH. Some of the new synthesized compounds were assayed against HIV‐1 and HIV‐2 in MT‐4 cells. All the compounds were inactive except 3f , which showed an EC₅₀ value of 23.9 μg/mL and 9.9 μg/mL against HIV‐1 and HIV‐2 with a therapeutic index of 3 and 7, respectively. It means that compound 3f was cytotoxic to MT‐4 cells at CC₅₀ of 72.7 μg/mL in both strains. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:316–322, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20282