Synthesis and Antimicrobial Activity of Some Novel Hydrazide,Pyrazole, Triazine,Isoxazole, and Pyrimidine Derivatives

In continuation of our efforts to find a new class of antimicrobial agents, a series of pyrazole, 1,2,4‐triazine, isoxazole, pyrimidine, and other related products containing a hydrazide moiety were prepared via the reaction of 2‐cyano‐N‐((2‐methoxynaphthalen‐1‐yl)methylene) acetohydrazide ( 1 ) with appropriate chemical reagents. These compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration against most of test organisms was performed. Among the tested compounds 4 , 5 , 6 , and 16 displayed excellent antimicrobial activity. All the synthesized products were confirmed by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data.     

新型吡啶衍生物的合成

以2-甲基吡啶为原料,经氧化、硝化、还原反应合成了重要中间体4-氨基-2-甲基吡啶(3); 3分别经1,4-加成反应、Heck反应及取代反应合成了11个吡啶类化合物(4~14),其中5, 6和8~14为新化合物,其结构经¹H NMR, ¹³C NMR, MS和HR-MS进行表征。     

Novel and Efficient Synthesis of Pyrimidine Derivatives

A new series of 1-alkyl-2-oxo-1,2-dihydro-pyrimidine-5-carboxalic acid amides is described. The reaction of N-((E)-3-(dimethylamino)-2-formylacryloyl) formamidine, an intermediate obtained by Vilsmeier–Haack formylation of acetonitrile with various mono-substituted ureas, provides such compounds in good yields.     

Synthesis of Some New Pyridine and Pyrimidine Derivatives Containing Benzothiazole Moiety

A variety of pyridine and pyrimidine rings incorporating benzothiazole moiety were synthesized by reaction of 1‐(2‐benzothiazolyl)‐1‐cyano‐3‐chloroacetone ( 1 ) with 2‐pyridone, 2‐thioxopyridine, thiouracil, and 2‐thioxopyrimidine derivatives to give compounds 7,9‐dimethylfuro[2,3‐b:4,5‐b′]dipyridin‐4‐ol 5 , 4, 6‐diphenylthieno[2,3‐b]pyridin‐2‐yl 9 , 2‐(benzo[d]thiazol‐2‐yl)‐2‐(7‐substituted‐5‐oxo‐5H‐thiazolo[3,2‐a]pyrimidin‐3‐yl)acetonitriles 12a and 12b , pyrimido[2,1‐b][1,3]thiazepine‐3‐carboxamide 15 , and benzo[4,5]thiazolo[3,2‐b]pyridazine‐3‐one 20 , respectively.     

Reactions of Benzoyl Isothiocyanate with Active Methylene Reagents: A Novel Synthesis of Thiophene,Thiazoline and Thieno[2,3-d]Pyrimidine Derivatives

Various derivatives of thiophene, thiazoline and thienopyrimidine have been synthesized via the reaction of active methylene reagents (la-j) with benzoyl isothiocyanate in the presence of potassium hydroxide, followed by the subsequent treatment of the potassium salt intermediates 2a-j with phenacyl bromide or ethyl chloroacetate. The stability of the formed adducts 3 and 12 or their selective cyclization depends on both the nature of the active methylene reagent and the α-halocarbonyl compounds.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

新型含吲唑环嘧啶衍生物的合成

以6-硝基-1H-吲唑为原料,经氮原子甲基化、催化氢化还原、亲核取代以及烷基化反应制得关键中间体N(2′-氯嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺(5);5与芳香胺进行亲核取代反应合成了一系列新型取代氨基嘧啶衍生物——N-(2′-取代氨基嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺,其结构经1H NMR和MS表征.     

Synthesis and Reaction of Novel Spiro Pyrimidine Derivatives

2‐Mercapto‐6‐[(pyridin‐4‐ylmethylene)‐amino]‐3H‐pyrimidin‐4‐one 1 was synthesized from Schiff base reaction of 6‐amino‐2‐thiouracil with isonicotinaldehyde. The reaction of 1 with hydrazonyl chloride 2a , 2b , 2c , 2d afforded the novel pyrimidin‐4‐one 3a , 3b , 3c , 3d . Compounds 3a , 3b , 3c , 3d reacted with methyl iodide to give 4a , 4b , 4c , 4d . Subsequently, reaction of 4a , 4b , 4c , 4d with triethylamine as a catalyst in dry chloroform yielded tetraaza‐spiro[4.5]deca‐2, 8‐dien‐7‐one 5a , 5b , 5c , 5d . In addition, reaction of 1 with acrylonitrile gave pyrimidin‐propionitrile 6 . The cyclization of 6 by reacting with sodium ethoxide to give pyrimido [2, 1‐b] [1,3] thiazin‐6‐one 7 . The refluxing of 1 with bromine in acetic acid yielded 2‐bromo‐pyrimidin‐4‐one 8 . The latter compound 8 reacted with sodium azide gave tetrazolo‐pyrimidine 10 . The chemical structures of the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral analysis.     

Synthesis of Novel Chromene,Pyridine, Pyrazole,Pyrimidine, and Imidazole Derivatives via One‐pot Multicomponent Reaction

New series of chromenes 2 – 4 , pyridines 5 – 8 , and pyranopyrazoles 9a,b were synthesized via one‐pot multicomponent reaction of 4‐tosyloxybenzaldehyde ( 1 ) and malononitrile with phenols, amines or hydrazines, and ethyl acetoacetate, respectively. Compound 9a was reacted with acetic anhydride, formic acid, or formamide to afford N ‐acetyl derivative 10 and pyrazolopyranopyrimidines 11 – 13 , respectively. Imidazole derivatives 14 and 15a – d were obtained by multicomponent reaction between compound 1 with ammonium acetate and benzil or aromatic amines in (1:2:1) or (1:1:1:1) ratio, respectively. The structures of new compounds were elucidated by elemental and spectral analyses.     

A Convenient Synthesis and Pharmacological Activity of Novel Annelated Pyrimidine Derivatives

Simple and convenient synthesis for a series of 2,3‐diglycosylpyrimidine 4 , pyrazolo[3,4‐d]pyrimidine 8 , ditetrazolo[1,5‐a;1′,5′‐c]pyrimidine 9 , 2,9a,10‐triazaanthracene 12 , thieno[2,3‐d]pyrimidine 14 , 1,3,5,7‐tetraazafluorene‐8‐one 15 , 1,3,5‐triazafluorene‐8‐one 16 , 1,3‐diazafluorene 21a,b derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6‐[5‐(4‐bromophenyl)ox‐azol‐4‐yl]‐4‐oxo‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile ( 2 ) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.     

新型含嘧啶的苯氧乙酸酯类衍生物的合成

以对羟基苯甲醛和一氯乙酸为起始原料,经羟醛缩合、关环及酯化等反应合成了6个含有嘧啶杂环的新型苯氧乙酸酯类衍生物,其结构经¹H NMR, ¹³C NMR, IR和HR-ESI-MS表征。     

芳酰基吡咯里嗪衍生物的设计与合成

COX和5-LOX双重抑制剂通过同时阻断炎症介质前列腺素和白三烯的形成, 产生协同的抗炎作用, 可以提高疗效, 同时避免COX抑制剂引发的副作用. 以芳基吡咯里嗪为先导物, 设计合成了2类15个5或6位芳酰基取代的7-芳基-2,3-二氢-1H-吡咯里嗪衍生物进行抗炎活性研究; 也可以其为模板进行结构修饰与优化, 设计合成更好的COX/5-LOX双重抑制剂. 同时分析了同分异构体III和IV的波谱学性质, 并确证了化合物的结构.     

新型噻吩并嘧啶酮类衍生物的合成及其抑菌活性

以1,2,4-三氮唑为起始原料,经取代、Gewald反应、Wittig反应和成环反应合成了7个新型的含氟噻吩并嘧啶酮类衍生物——2-二烷氨基-3-对氟苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮(6a~6g),其结构经1H NMR,MS和元素分析表征。抑菌活性测试结果表明:6对棉花枯萎菌、水稻纹枯菌、黄瓜灰霉菌、小麦赤霉菌、苹果轮纹及棉花炭疽具有较好的抑制作用,其中2-二异丁氨基-3-对氟苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮(6f)的抑菌活性最好,在用药量为5×10-5g·L-1时,对棉花枯萎菌的抑制率为85%。     

Design,Synthesis of Novel Thiourea and Pyrimidine Derivatives as Potential Antitumor Agents

1,3‐Bis‐(arylidene)thiourea derivatives ( 11a‐c ) were prepared by reacting thiourea ( 9 ) with bezaldehyde, p‐chlorobenzaldehyde or p‐anisaldehyde ( 10a‐c ) respectively. Further reaction of ( 11b ) with acetyl acetone, ethyl acetoacetate, malononitrile and acetic anhydride gave tetrahydropyrimidine‐2‐thiones ( 12‐14 ) and 1,3‐diacetyl thiourea ( 15 ). Compound ( 11b ) reacted with chloroacetyl chloride to give the corresponding pyrimidin‐4‐one derivative ( 16 ). Reaction of ( 12‐14 ) with acetic acid in aqueous sodium nitrite yielded the corresponding oxime derivatives ( 17‐19 ). The triazole ( 20 ) was achieved via refluxing of ( 19 ) in dimethylformamide. Reaction of ( 16 ) with mercaptoacetyl chloride gave the sulfanyl‐acetic acid ( 21 ) which afforded the dihydrazinyl ( 22 ) up on treatment with hydrazine hydrate. Newly synthesized compounds ware characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR and mass spectra). The investigated compounds were screened for their cytotoxicity, i.e. compounds 19 , 20 and 22 exhibited highly potential antitumor activity.     

2‐Cyanoacetamide in the Synthesis of Heterocyclic Compounds: Synthesis of New Polysubstituted Pyrazole,Pyridine and Pyrimidine Derivatives

Phenylmethylenecyanoacetamide ( 1 ) was successfully transferred into polysubstituted pyrazole, pyridine and pyrimidine derivatives in a one‐pot reaction step. Hydrazine hydrate ( 2a,b ), cyanoacetamide ( 6a ), cyanothioacetamide ( 6b ), cyanoacetic acid hydrazide ( 6c ), thiosemicarbazide ( 10 ), urea ( 14a ), thiourea ( 14b ) and 2‐phenylenediamine ( 24 ) were selected as amine nucleophile reagents.     

Cycloaddition of Porphyrins to Isatin: Synthesis of Novel Spiro Porphyrin Derivatives

Isatin undergoes regioselective 1,3‐dipolar cycloaddition reactions with porphyrin azomethine ylides derived from Ni(II) β‐formyl‐meso‐tetraphenylporphyrins in the presence of N‐methylglycine to afford novel spiro porphyrin derivatives.     

Synthesis and Optical Properties of Novel Carbazole Derivatives Containing Pyridine Ring

A series of novel monodisperse, well‐defined molecules with a pyridine core and carbazole arms were synthesized by simple procedures with Iodo‐reaction and Ullmann reaction. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR, and elementary analysis. Moreover, the fluorescence spectra showed that these compounds exhibited strong fluorescence with the maximum wavelengths ranging from 373 to 385 nm.     

The Utility of p-N-Succinimidobenzoyl Isothiocyanate in Synthesis of Benzoxazole,Quinazoline, Pyrimidine, 1,2,4-Triazoline, 1,3-Thiazolidine,and Thiourea Derivatives

Reactions of p-N-succinimidobenzoyl isothiocyanate (1) with different nucleophilic reagents afforded adducts. Simultaneous or subsequent cyclization of these adducts gave access to a variety of different heterocycles, including benzoxazole, quinazoline, pyrimidine, 1,2,4-triazoline, 1,3-thiazolidine and others. The structures of the new products were confirmed by their micro-analytical and spectral data.

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