Picrylamino-substituted heterocycles. VI. Pyrimidines

The condensation of various aminopyrimidines with picryl chloride and picryl fluoride has been investigated as part of our continuing effort in the field of picrylamino-substituted heterocycles. Most of the aminopyrimidines that can tautomerize reacted with picryl fluoride to form picryl derivatives of their imino forms, but they gave picrylamino derivatives when they condensed with picryl chloride.     

Picrylamino-substituted heterocycles. V. pyridines

The condensation of various aminopyridines with picryl chloride and picryl fluoride has been investigated as part of our continuing effort in the field of picrylamino-substituted heterocycles. In addition to the expected picrylamino derivatives we obtained the 1-picryl derivatives of the imino forms of some of the amines.     

Magnetische Kernresonanz-Untersuchungen über die struktur der Komplexe aus Nitroaromaten mit azid-ionen 9. Mitteilung über nucleophile aromatische Subsitutionsreaktionen [1]

1. NMR. spectra of solutions of tetraethylammonium azide and 2,4,6-trinitro;benzene derivatives (methyl picrate, picryl chloride and picryl azide, respectively) demonstrate that the reactants probably form σ complexes.     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.     

Reaction of 1,3,4-thiadiazol-2,5-dithiol with <Emphasis Type="Italic">N</Emphasis>-acryloyl-substituted derivatives of several alkaloids

Potentially bioactive 2,5-bis derivatives of 1,3,4-thiadiazole with alkaloid moieties were synthesized by reaction of 1,3,4-thiadiazol-2,5-dithiol with N-acryloyl-substituted derivatives of the alkaloids anabasine, cytisine, and D-pseudoephedrine.     

具有生物活性的1,3,4-噻二唑并[3,2-a]-1,3,5-三嗪衍生物的合成方法

由1，3，4-噻二唑和1，3，5-三嗪稠合而成的1，3，4-噻二唑并[3，2．a]-1，3，5-三嗪衍生物具有广泛的生物活性，是一类重要的药用物质。本文对其在近二十年的合成方法进行了综述，重点介绍通过1，3，4-噻二唑衍生物为母体的合成方法。参考文献45篇。     

Synthesis of some polyureas based on diamino derivatives of bis-1, 3, 4-oxadiazole

Ortho-, meta, and para-nitrobenzoyl derivatives of the dihydrazides of succinic, glutaric, adipic, and azelaic acids are prepared, from which are obtained nitro and amlno derivatives of bis-1,3,4- diazole. Various conditions for synthesizing these compounds are investigated. A series of polyureas is obtained by reacting diamino derivatives of bis-1,3,4-oxadiaole with diisocyanates, and some of their properties are investigated.     

3,6-二取代苯基-二-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物的合成

以2,5-二巯基-1,3,4-噻二唑为原料, 与水合肼缩合, 生成2,5-二肼基-1,3,4-噻二唑. 2,5-二肼基-1,3,4-噻二唑与苯甲酰氯反应生成2,5-二酰肼基-1,3,4-噻二唑, 以POCl₃为环合剂环合酰肼基-1,3,4-噻二唑, 合成3,6-二取代苯基- 二-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物, 合成的新化合物的结构通过元素分析、红外光谱、核磁共振氢谱和质谱予以证实, 并提出了环化反应机理.     

Reactions of Aroylhydrazones,IV: Synthesis of Nitrogen Heterocycles from Opianic Acid Hydrazones

Opianic acid reacts with various hydrazines to yield either hydrazone ( 3, 6 ) or phthalazinone ( 4 ) derivatives depending upon the electronic properties of the substituent attached to the hydrazine molecule. Oxidative cyclization of opianic acid aroylhydrazones with iodine and yellow mercuric oxide gave the 1,3,4-oxadiazole derivatives 21 . The aroylhydrazones were also condensatively cyclized by heating with acetic anhydride to give the 1,3,4-oxadiazoline derivatives 24 . Structures assigned to the prepared compounds were corroborated by studying their chemical as well as their spectral characteristics.     

1,3,4-噻二唑衍生物合成及其生物活性研究进展

1,3,4-噻二唑是含有N、S杂原子的五元杂环化合物,具有多种生物活性。目前,1,3,4-噻二唑及其衍生物广泛用于生物、医药等领域,尤其在抗菌、抗肿瘤、抗癌等方面的研究已取得重大突破。由于1,3,4-噻二唑结构的特殊性以及优越的生物活性,对其进行研究有重要意义。本文主要概述了近年来1,3,4-噻二唑衍生物的几种合成方法以及其在抗菌、抗肿瘤、抗癌方面的研究进展。     

Synthesis and transformations of 2-amino-1,3,4-thiadiazines

Depending on the reaction conditions, 2-amino-1,3,4-thiadiazine and 2-hydrazinothiazole derivatives were obtained by cyclization of thiosemicarbazide with ethyl bromopyruvate in concentrated hydrochloric acid. The rearrangements of 5-carbonyl-substituted 2-amino-1,3,4-thiadiazines to thiazole derivatives in an acidic medium were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 554–558, April, 1991.     

Synthesis of arylethylene derivatives of 2, 5-diphenyl-1, 3, 4-oxadiazole

The synthesis of arylethylene derivatives of 2,5-diphenyl-1,3,4-oxadiazole by the Wittig reaction from 2-(p-bromomethylphenyl)-5-phenyl-1,3,4-oxadiazole and aromatic aldehydes is described. The compounds obtained fluoresce strongly on irradiation with UV light.     

Synthesis and Anti‐cancer Activity of 1,3,4‐Thiadiazole and 1,3‐Thiazole Derivatives Having 1,3,4‐Oxadiazole Moiety

Reaction of 1,3,4‐oxadiazolyl‐phenylthiourea 3 with hydrazonoyl halides gave the corresponding 1,3,4‐oxadiazolylimino‐1,3,4‐thiadiazoles. Also, treatment of 3 with ethyl chloroacetate and α‐haloketones afforded the corresponding thiazolidinone and thiazole derivatives, respectively. The structures of the synthesized products were confirmed by spectral data. Ten compounds were evaluated for their anti‐cancer activity against the colon carcinoma cell line (HCT‐116). The results revealed that 1,3,4‐thiadiazole derivatives 13d and 19c (IC₅₀ = 0.73 and 0.86 µg/mL, respectively) have promising antitumor activity against colon carcinoma (HCT‐116), and most of the tested compounds showed moderate anti‐cancer activity.     

含嘧啶环的1,3,4-噁二唑Mannich碱的合成及生物活性

以芳香酸为原料, 通过酯化、 肼解及环化反应制得中间体5-芳基取代-1,3,4-噁二唑-2-硫酮(C1~C3), 然后中间体与甲醛和取代氨基嘧啶(D1~D5)发生Mannich反应得到一系列新型含有嘧啶环的1,3,4-噁二唑类衍生物(E1~E15). 所得目标化合物的结构经元素分析、 IR及 ¹H NMR确认. 初步的生物活性测定结果表明, 大部分目标化合物对植物病原菌有很好的抑制作用, 其中化合物E3和E8的抑菌效果优于对照药三唑酮.     

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.     

Solid-Phase Synthesis of 2-Arylamino-5-(4-hydroxyphenyl)-1,3,4-thiadiazole Derivatives Based on Resin-Bound Acylhydrazines

A highly efficient, solid-phase synthesis of 2-arylamino-5-(4-hydroxy-phenyl)-1,3,4-thiadiazole derivatives under mild conditions has been developed. The 1,3,4-thiadiazole derivatives were synthesized from resin-bound acylhydrazines in several steps, which gave 78–88% overall yields and excellent purities of the products.     

Derivatives of 4-amino-4H-1,2,4-triazole-3-thiols linked to the pyrrole cycle and some products of their S-alkylation

This study offers an access to 21 new heterocyclic compounds representing pyrrole derivatives of 4-amino-4H-1,2,4-triazole-3-thiols or 1,3,4-oxadiazole-2-thiols. The principal synthetic approach is based on the cyclization of substituted potassium 2-(pyrrolecarbonyl)hydrazine-1-carbodithionate with hydrazine hydrate to 5-(substituted pyrrolyl)-4-amino-4H-1,2,4-triazole-3-thiols, followed by S-alkylation with methyl iodide or benzyl chloride. Among the resulted thirteen S-alkyl derivatives, five 1,3,4-oxadiazole derivatives have been isolated as secondary products and their formation is explained as being the result of S-alkylation of intermediate 1,3,4-oxa-diazole-2-thiols, generated in the alkaline medium. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 383–391, March, 2007.     

2,5-二取代-1,3,4-噻二唑衍生物的合成与表征

苯并噁唑啉酮和1,3,4-噻二唑衍生物具有多种生物活性,制备含有苯并噁唑啉酮结构的1,3,4-噻二唑衍生物非常有意义。本文以邻氨基苯酚和尿素为初始原料,经多步合成反应,制备了10个新的2-(芳甲酰氨基)-5-(2-苯并噁唑啉酮-3-甲基)-1,3,4-噻二唑化合物(7a～7j),并利用IR、1H NMR和元素分析对其结构进行了表征。     

Synthesis,Antimicrobial, and Antioxidant Activities of Some Fused Heterocyclic [1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazole Derivatives

In the present work, we synthesized a series of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives ( 6a , 6b , 6c , 6d , 6e , 6f and 7a , 7b , 7c , 7d , 7e , 7f ) by using simple starting materials, namely, β‐amino acids and different aromatic acid hydrazides. The newly synthesized compounds were characterized by mass, IR, ¹H, and¹³C‐NMR spectral data analysis. The newly synthesized compounds were tested for their antimicrobial activities and antioxidant properties. Compound 6c was a potent microbial agent particularly against Staphylococcus aureus (MIC 3.12 µg/mL) and Candida albicans (MIC 6.25 µg/mL) when compared with the reference drugs ciprofloxacin and fluconazole, respectively. The antioxidant activity of the synthesized compounds was also evaluated by 1,1‐diphenyl‐2‐picryl hydrazyl, nitric oxide, and hydrogen peroxide radical scavenging methods. Compounds 6c , 6f , 7c , and 7f showed good radical scavenging activity due to the presence of electron‐donating group on phenyl ring.     

肼类衍生物在五元唑类杂环合成中的应用进展

简要概述了肼类衍生物的结构及反应活性,总结了近十年来肼类衍生物分别在合成五元唑类杂环如吡唑、噻唑、1,3,4-噁二唑、1,3,4-噻二唑以及三唑类化合物,及其相关的稠杂环如吡唑并某环、s-三唑[3,4-b][1,3,4]-噻二唑、s-三唑[3,4-b][1,3,4]-噻二嗪,以及含有1,2,4-三唑的稠杂环化合物等合成中的应用进展.