The Microwave-Assisted Dehydrative Cyclization of Thiosemicarbazides Forming Substituted 1,2,4-Triazoles

Different types of 4,5-disubstituted 1,2,4-triazole-3-thiones were prepared by microwave irradiation as well as by a classical method. The beneficial effect of microwave irradiation on the dehydrative cyclization of thiosemicarbazides in different reaction media is described. Our results show that the effect of microwave irradiation on the reaction studied was the shortening of reaction times (from 2–9 h to 2–4 min) and a minor decrease (1–4%) in yields. The structure of the new compounds was established by FTIR, MS, and ¹H NMR spectral data.     

ONE-POT SYNTHESIS OF 1,2,4-TRIAZINES

ABSTRACT

1,2,4-Triazines have been prepared from the one-pot condensation reaction of acid hydrazide (1), ammonium acetate and dicarbonyl compounds (2) on the surface of silica gel in the presence of triethylamine under microwave irradiation.     

Microwave-assisted three component synthesis of novel bis-fused quinazolin-8(4H)-ones linked to aliphatic or aromatic spacer via amide linkages

Abstract

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8-ones) and bis(tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolinones) containing amide linkages were regionselectively prepared via a three-component reaction of bis(aldehydes) with dimedone and 3-amino-1,2,4-triazole (or 2-aminobenzimidazole) under conventional heating as well as under microwave irradiation.     

微波作用下1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑的合成及生物活性

采用微波和相转移催化法通过1-苯基-5-(4-苯基-1,2,4-三唑-5-巯基-3-甲硫基)四唑(2)与2-氯乙酰芳胺(3)反应高效、快速地合成了10种尚未见文献报道的1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑. 其结构经 IR, ¹H NMR, ¹³C NMR 和元素分析表征. 生物活性实验结果表明, 该类化合物在较低浓度下部分化合物对小麦芽有很好的促进作用.     

Regioselective annelation of 3-(prop-2-ynylsulfanyl)-1,2,4-benzotriazine to thiazolo[2,3-c][1,2,4]benzotriazine

Summary Thiosemicarbazide reacted with 1,2-diaminobenzene to give 1,2-dihydro-3-thioxo-1,2,4-benzotriazine (1) in fairly good yield in a solvent free reaction under microwave irradiation.1 was condensed with prop-2ynyl bromide in the presence of sodium methoxide to afford the corresponding 3-(prop-2-ynylsulfanyl)-1,2,4-benzotriazine (5). Transformation of5 to 3-methylidene-2,3-dihydro-9H-thiazolo[2,3-c][1,2,4]benzotriazine (6) was performed in the presence of a palladium salt.

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Regioselektive Anellierung von 3-(prop-2-inylsulfanyl)-1,2,4-benzotriazin zu Thiazolo[2,3-c][1,2,4]benzotriazin

Zusammenfassung Thiosemicarbazid reagierte mit 1,2-Diaminobenzol ohne Lösungsmittel und unter Bestrahlung mit Mikrowellen in guter Ausbeute zu 1,2-Dihydro-3-thioxo-1,2,4-benzotriazin (1), welches in Gegenwart von Natriummethoxid mit Prop-2-inylbromid zum entsprechenden 3-(Prop-2-inylsulfanyl)-1,2,4-benzotriazin (5) kondensiert wurde. Die Umsetzung von5 zu Methyliden-2,3-dihydro-9H-thiazolo[2,3-c] [1,2,4]benzotriazin (6) gelang unter Palladiumkatalyse.

     

微波辅助合成双1,2,4-三嗪化合物及其荧光特性研究

以联苯甲酰、二甲酰肼为原料, 采用微波技术合成了5个双1,2,4-三嗪化合物3, 产率72%～85%, 利用元素分析、MS, IR, ¹H NMR和荧光光谱对其结构进行了表征, 并研究了金属离子对化合物3a的荧光性质的影响. 结果表明, 微波合成具有缩短反应时间、提高产率的优点; Cu^2＋, Ni^2＋等金属离子对化合物3a产生明显的荧光猝灭作用.     

A highly efficient,simple, and ecofriendly microwave-induced synthesis of indolyl chalcones and pyrazolines

Abstract

One-pot synthesis of indolyl chalcones (3a–c) employing indole-3-carboxaldehyde (1) and heteroaryl active methyl compounds (2a–c) under microwave irradiation is described. The indolyl chalcones (3a–c) are transformed into medicinally important pyrazolines (5a–f) using different hydrazines. Application of microwave irradiation leads to many remarkable advantages, such as solvent- and catalyst-free reaction conditions, simple work up procedure, shorter reaction time, in addition to ecofriendly ‘green chemistry’ economical and environmental impacts.     

微波促进下3-(2-苯并呋喃基)-4-氨基-5-巯基-1,2,4-三唑

微波辐射条件下, 首先由2-苯并呋喃甲酰肼依次与二硫化碳和水合肼反应合成3-(2-苯并呋喃基)-4-氨基-5-巯基- 1,2,4-三唑, 进一步在微波辐射条件下由4-氨基-5-巯基-1,2,4-三唑分别与芳甲酸/芳氧基乙酸、α-溴代苯乙酮及芳醛反应以较高产率制得了相应的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑、1,2,4-三唑并[3,4-b]-1,3,4-噻二嗪及4-芳亚甲基亚胺基-5-巯基-1,2,4-三唑. 产物结构经IR, ¹H NMR, MS及元素分析进行了表征.     

Focused microwave irradiation-assisted synthesis of N-cyclohexyl-1,2,4-oxadiazole derivatives with antitumor activity

A facile synthesis of 3,5-disubstituted 1,2,4-oxadiazole derivatives under focused microwave irradiation (FMWI) is reported. Arylamidoximes 1a–i and dicyclohexylcarbodiimide (DCC) were carried out in DMF under FMWI to obtain 1,2,4-oxadiazoles 2a–i in 61–81% yields. All compounds exhibited antiproliferative activities in vitro against three human cancer cell lines HCT-116, PC-3, and SNB-19.     

Efficient Microwave‐Assisted Synthesis of 9,9‐Bis[4‐(2‐hydroxyethoxy)phenyl]fluorene from 9‐Fluorenone and 2‐Phenoxyethanol

9‐Fluorenone (1) smoothly reacts with phenoxyethanol (2) in the presence of Al³⁺‐montmorillonite catalyst and 3‐mercaptopropionic acid as a cocatalyst under microwave irradiation at 160°C for 10 min to give 9,9‐bis[4‐(2‐hydroxyethoxy)phenyl]fluorene (3) in 81% yield, which was much higher than the yield of 33% obtained by conventional heating using an oil bath. A similar acceleration effect of microwave irradiation was observed in other metal‐cation‐exchanged montmorillonite catalysts as well.     

On the 3-Aminophenothiazine Synthesis

Abstract

Investigation of the key step of 3-aminophenothiazine (5) synthesis, that is thiation of N-(4-phenylaminophenyl)-phthalimid (3) was carried out. The best results were achieved using microwave irradiation, when 55% of the pure thiation product 3-phalimidophenothiazine (4) were isolated in 10–20 min reaction time.     

Synthesis,Antiviral, and Antimicrobial Activity of 1,2,4-Triazole Thioglycoside Derivatives

Abstract

The reaction of 5-(2-methylthio)phenyl-1,2,4-triazole-3-thiol with glucosyl, galactosyl, lactosyl bromide, and peracetylated ribose under the conventional and microwave irradiation methods afforded the corresponding S-glycosides. Deacetylation of S-glycosides gave the corresponding deacetylated derivatives. Reaction of 5-(2-methylthio)phenyl-1,2,4-triazole-3-thiol with 4-acetoxybutyl bromide, 2-acetoxyethoxymethyl bromide, 3-chloropropanol, 1,3-dichloroopropan-2-ol, epichlorohydrin, allyl bromide, and propargayl bromide gave the corresponding S-acyclonucleosides, which were deacetylated to give the corresponding deacetylated compounds. All the newly synthesized compounds were characterized by the IR, ¹H, ¹³C NMR, and elemental analyses. Some of these compounds were screened for their antiviral and antimicrobial activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the related elements to view the free supplemental file.     

Synthesis of fused 1,2,4-triazines as potential antimicrobial and antitumor agents

5-Benzylidene-3-(p-chlorophenyl)-2-aminothiocarbonyl-1,2,4-triazine (2) was prepared via condensation of oxazolinone (1) with thiosemicarbazide. Fused 1,2,4-triazine derivatives (3, 4 and 9) were synthesized from the reaction of compound 2 with ω-bromomethyl aryl ketones, ethyl chloroacetate, and acetic anhydride. Treatment of 4 with acetic anhydride and aromatic aldehydes yielded the corresponding acetyl, diacetyl derivatives (6 and 7) and 7-benzylidene-5-(p-chlorophenyl)-4-thioxo-3-arylidene-1,2,4-triazino [2,1-a]-1,2,4-triazine-1,8-diones (8). The electron impact mass spectra of both the above series of compounds have also been recorded and their fragmentation pattern is discussed. All synthesized fused 1,2,4-triazine derivatives were primary in vitro screened for their antimicrobial and antitumor activity.

     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

微波辐射下合成5-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-3-(苯基/p-取代苯基)-2H-1',2',4'-三唑[3,4-b]-1

分别采用微波辐射法和加热回流的常规方法, 将1-氨基-2-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-5-巯基-1,3,4-三唑与α-溴代芳基乙酮3a～3e反应, 合成了一系列未见文献报道的1,2,4-三唑[3,4-b]-1',3',4'-噻二嗪类化合物4a～4e 和5a～5e. 微波辐射法具有反应时间短、产率高、副反应少等优点. 标题化合物经元素分析, IR, ¹H NMR, MS确证结构.     

Anil-Synthese. 20. Mitteilung. Über die Herstellung von Stilbenyl-Derivaten des 1,2,4,-Oxadiazols

Preparation of Stilbenyl Derivatives of 1,2,4-Oxadiazoles Schiffs bases derived from 3- and 5-(p-formylphenyl)-phenyl-1,2,4-oxadiazoles and chloroanilines are reacted with various p-tolyl substituted aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide to yield the corresponding heterocyclic substituted stilbenes (‘Anil synthesis’). The reactivity of 5-[4-(chlorophenylimino-methyl)phenyl]-3-phenyl-1,2,4-oxadiazoles is very low and side reactions will predominate.     

Supramolecular assemblies tailored by dipyridyl-1,2-4-thiadiazoles: influence of the building blocks in the predictability of the final network

ABSTRACT

Coordinatively unsaturated dithiophosphato complex [Cd((MeO)₂PS₂)₂] (1) was reacted with the bifunctional ligands 3,5-di-(4-pyridyl)-1,2,4-thiadiazole (L1) and 3,5-di-(3-pyridyl)-1,2,4-thiadiazole (L2) to give the helicoidal coordination polymer (1·L1)_∞ and the paddle-wheel dimer (1·L2)₂, both characterised by single-crystal X-ray diffraction. A comparison of the structures with the different supramolecular constructs obtained by reacting L1 and L2 with differently P-substituted dithiophosphoric Ni^II complexes allowed to evaluate the role of the metal ion for the predictable assembly of this class of coordination polymers.     

Synthesis and Antimicrobial Properties of New Thiosemicarbazide, 1,2,4-Triazole,and 1,3,4-Thiadiazole Derivatives of Sulfanylacetic Acid

Abstract

1,2,4-triazole and 1,3,4-thiadiazole derivatives are still considered a viable lead structure for the synthesis of more efficient antimicrobial agents having a broad spectrum of activity. This study presents the synthesis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Reaction of 4-phenyl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thione with ethyl bromoacetate yields the corresponding ethyl acetate (1). In the subsequent reaction with 100% hydrazine hydrate, the hydrazide (2) was obtained, which was converted with isothiocyanates to new acyl derivatives of thiosemicarbazide (3a–l). The cyclization of these compounds in alkaline media resulted in the formation of new derivatives of 1,2,4-triazole (4a–i), whereas in acidic media new derivatives of 1,3,4-thiadiazole (5a,b,g) were obtained. All synthesized compounds were screened for their in vitro antimicrobial activities.     

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

A Convenient Synthesis of 2-Amino-1,3- selenazoles Using Ionic Liquid and Microwave Irradiation

Abstract

A simple and environmentally benign synthesis of 2-amino-1,3-selenazoles by microwave irradiation using 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF₄) ionic liquid (IL) is described. Acyl halides, phenacyl halides, and α-bromo-β-keto esters easily undergo condensation with selenourea in ([Bmim]BF₄) by microwave irradiation to afford the desired products of good purity in excellent yields. The ionic liquid can be easily recovered and reused at least 10 times without losing its activity. The duration of the reaction ranges from 4–6 min.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT