Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

N-Methylpyridinium Tosylate Catalysed Green Synthesis,X-Ray Studies and Antimicrobial Activities of Novel (E)-3-Amino-2-(e)-(3, 4-Dihydronaphthalen-1(2H)-Ylidene)Hydrazono)Thiazolidin-4-Ones

Abstract

3,4-Dihydro-2H-naphthalen-1-ones 1,on reaction with thiocarbohydrazide, afforded monothiocarbohydrazones 2, which, on condensation with chloroacetic acid in the presence of an ionic liquid and bromotrimethylsilane furnish (E)-3-amino-2-(E)-(3,4-dihydronaphthalen-1-(2H)-ylidene)hydrazono)thiazolidin-4-ones 3 in quantitative yields. Acetyl derivatives 5 were obtained from 3 with acetic anhydride. Monothiocarbohydrazones 2 on condensation with benzaldehyde yield azomethines 4. The structure of compounds 2–5 has been established by elemental analysis, IR, ¹H NMR, and mass spectral data. The structure of compound 3a has been further confirmed by X-ray crystallographic data. The compounds 2–5 were screened for antimicrobial activity. The thiazolidinones 3a and 3b showed maximum antimicrobial activities.     

Synthesis and Characterization of Some Novel Multisubstituted 6,7-Dihydro-5H-cyclopenta[b]pyridine Derivatives

In this study, we describe systematic preparation of a series of aryl-substituted pyridine derivatives. The 1,5-dicarbonyls (3a–i) were prepared in the solvent-free conditions starting from chalcone derivatives (1a–i). The target compounds, 4-aryl-2-(thiophen-3-yl)-6,7-dihydro-5H-cyclopenta[b]-pyridine derivatives (5a–i), were synthesized by a cyclization reaction of the 1,5-dicarbonyls (3a–i) with ammonium acetate (NH₄OAc) in acetic acid. The characterization of synthesized compounds was proved by elemental analyses, infrared, mass spectrometry, and ¹H and ¹³C NMR spectroscopy.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis,Characterization, and Biological Screening of Some Novel Thiazolidin-4-One and α-Aminophosphonate Derivatives

Abstract

Synthesis of some new functionalized thiazolidin-4-ones and α-amino phosphonate derivatives has been reported. The imines were synthesized from the reaction of various substituted anilines with 1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde in ethanol at reflux condition. The corresponding thiazolidin-4-ones and α-aminophosphonates were prepared by reaction of imines with mercaptoacetic acid and triethyl phosphite, respectively. The structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, and mass spectral data and were evaluated for their antimicrobial activities.

GRAPHICAL ABSTRACT      

Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives

5-HT₃ receptor antagonists, such as Ondansetron, are used for anti-emesis after chemotherapy, radiotherapy and operations. Some Ondansetron analogs possessing piperazine ring as side chains were synthesized in our lab. Thus, one of the two carbonyl groups of starting material 1,3-cyclohexandione (1) was condensed with phenylhydrazine hydrochloride to form monophenylhydrazone (2). 1,2,3,9-Tetrahydro-4H-carbazol-4-one (3) was prepared from 2 via cyclization and rearranged in the presence of ZnCl₂. Through a methylation reaction, compound 3 was converted to 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one (4). 3-Dimethylaminomethyl substituted compound (5) was synthesized from 4 by a Mannich reaction in glacial acetic acid. Nine novel 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives (6a–6i) were synthesized through nucleophilic substitution reaction of 5 with piperazines. The structures of all the target compounds were determined by elemental analysis, IR, MS, ¹H NMR and ¹³C NMR spectra. The results of preliminary pharmacological test show that part of the novel compounds have antiemetic activity comparable to that of the control Ondansetron. __________ Translated from Chinese Journal of Organic Chemistry, 2008, 28(2) (in Chinese)     

Synthesis and biological activity evaluation of new thiazolidinone-diclofenac hybrid molecules

Abstract

A novel series of [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid N`-3-(substituted)-4-thiazolidin-5-ylidenemethyl-hydrazide derivatives has been designed and synthesized. The structures of synthesized compounds were confirmed by their <sup>1</sup>H NMR, <sup>13</sup>C NMR and LCMS spectroscopic data. Target compounds were screened for their in vitro anticancer activity according to US NCI protocols, in vitro trypanocidal activity toward Trypanosoma brucei brucei (Tbb) and evaluated for anti-inflammatory activity on the carrageenan edema model in rats. Biological screening data led to identification of compounds 3.3 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-hydrazide) and 3.7 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-3-(3-trifluoromethylphenyl)thiazolidin-5-ylidenemethyl)-hydrazide) which demonstrated moderate antitumor activity on the non-small-cell lung cancer NCI-H522 and colon cancer HCT-116 cell lines. Several hit compounds (3.2, 3.4) exhibited the promising and significant inhibition growth of the parasites at micromolar concentrations (IC₅₀ values of 4.8 and 7.06?μM, respectively). The synthesized compounds also demonstrated considerable anti-inflammatory effect comparable to the reference non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac sodium or ketorolac tromethamine.     

Synthesis of New Phosphonate Derivatives of Naphtho[2,1-b[Pyran]3,2-e][1,2,4]Triazolo [1,5-c]Pyrimidines

Abstract

The synthesis of new naphthopyranotriazolopyrimidines phosphonates 4a–i in good yields (74%–93%) has been accomplished via Michaelis–Arbusov rearrangement by the reaction of trialkyl phosphite with naphthopyranotriazolopyrimidines chloride 3a–e, which were obtained from α-functionalized iminoethers 1 in two steps. The synthesized compounds 4a–i were completely characterized by IR, ¹H, ¹³C, and ³¹P NMR and HRMS.

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.     

Three component one-pot synthesis of novel pyrimidino thiazolidin-4-ones catalyzed by activated fly ash

Abstract

2-Phenyl-3-(4,6-diarylpyrimidin-2-yl) thiazolidin-4-ones, 12–22, were synthesized with good yields in a short reaction time by the “one-pot” multicomponent reaction of the appropriate 2-amino-4,6-diarylpyrimidines, benzaldehyde, and thioglycolic acid under microwave irradiation in the presence of activated fly ash catalyst. The characterization of these compounds was confirmed by melting point, elemental analysis, MS, FT-IR, and one-dimensional NMR (¹H and ¹³C) spectroscopic data.     

The One Step Synthesis of 2-(2-Bromo-5- methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]- 1,2,4-triazol-6-(5H)-ones and the Evaluation of the Anticonvulsant Activity

A smooth one-step synthesis of 2-(2-bromo-5-methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]-1,2,4-triazol-6-(5H)-ones (4a–n) is described. The newly prepared compounds are characterized by analytical and IR, ¹ H NMR, ¹³ C NMR, and FABMS spectral analysis. A few compounds are screened for anticonvulsant activity. Compounds 4i and 4n exhibit promising anticonvulsant activity and are recommended for further studies.     

Design,synthesis, and biological evaluation of novel substituted imidazo[2,1-a]isoindole derivatives as antibacterial agents

An efficient protocol has been developed for the synthesis of fused imidazo[2,1-a]isoindol-5-ones (2a–d) from 2-iodo benzoic acids and N,N-carbonyldiimidazole (CDI) using one-pot Pd-catalyzed C?C bond coupling. The reaction of imidazo[2,1-a]isoindol-5-one (2a–d) with substituted α-bromo ketones in toluene afforded corresponding imidazo[2,1-a]isoindolium derivatives (3a–i) in good yields. The structures of the title compounds were well established on the basis of infrared (IR), ¹H NMR, carbon-13 nuclear magnetic resonance (¹³C NMR), mass spectral data, and elemental analysis (C, H, and N). In vitro antibacterial results revealed that, the compounds 3b and 3i were found to possess an excellent broad spectrum of inhibiting potency against all the tested bacterial strains with minimum inhibitory concentration values ranging from 3.125 to 25?µg mL^?1.     

Syntheses and Antimicrobial Activity of Some Novel 6‐Substituted Dibenzo[d,f][1,3,2]dioxaphophepin‐6‐oxides,Sulfides, and Selenides

6‐Substituted‐dibenzo[d, f][1,3,2]dioxaposphepin‐6‐oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) were synthesized by reacting 2,2′‐biphenol (1) with phosphorus tribromide in the presence of triethylamine at 0–30°C and subsequent reaction of the monobromide (2) with different Grignard reagents (3) at room temperature. The products (4) were converted to corresponding oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) by oxidation with H₂O₂ at room temperature and refluxing with sulfur and selenium respectively. The chemical structures of all the products were confirmed by analytical, IR, NMR (¹H, ¹³C, and ³¹P), and mass spectral data. Most of these compounds exhibited moderate antimicrobial activity.     

3-(4-取代-哌嗪-1-甲基)-1,2,3,9-四氢咔唑-4-酮衍生物的合成与止吐活性研究

以1,3-环己二酮(1)为起始原料, 一个羰基与盐酸苯肼发生缩合反应生成1,3-环己二酮单苯腙(2), 2在ZnCl₂催化下通过分子内环合、重排反应得到1,2,3,9-四氢咔唑-4-酮(3), 3的甲基化物4在冰醋酸中经Mannich反应获得其3-二甲胺甲基物5, 5与哌嗪类化合物通过亲核取代反应合成了9个未见文献报道的3-(4-取代-哌嗪-1-甲基)-1,2,3,9-四氢咔唑-4-酮衍生物6a～6i. 所有合成的新化合物均经元素分析、红外光谱、质谱和核磁共振光谱证明其结构; 初步药理试验采用顺铂诱导的大鼠干呕模型研究了新化合物的止吐活性, 结果表明部分新化合物活性与昂丹司琼相当.     

Synthesis and antimicrobial activity of novel quinazolinone–thiazolidine–quinoline compounds

A series of 2-(2-chloroquinolin-3-yl)-5-((aryl)benzylidene)-3-(4-oxo-2-phenylquinazolin-3(4H)-yl)thiazolidin-4-ones (V)_1–12 have been synthesized. In order to establish optimization of different parameters of chemical transformation, that is the reaction pathway for each step and reaction conditions in the each step, in the present paper, different solvents and catalysts were used. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR and ¹³C NMR spectral data. All the newly synthesized compounds were screened against various strains of bacteria and fungi.     

Synthesis of Some Prospective Bioactive Azeto[2,1-d][1,5]benzothiazepinones

Ten azeto[2,1-d][1,5]benzothiazepinone derivatives 6a–j were synthesized starting from 4-acetyl-2-phenyl-1,2,3-triazole 1. First, condensation of 1 with various aldehydes 2a–e afforded α,β-unsaturated carbonyl compounds 3a–e, which subsequently underwent cyclization with o-aminothiophenol to yield the corresponding 2,4-disubstituted-1,5-benzothiazepines 4a–e. Treatment of 4a–e with chloroacetyl chloride 5a or phenoxyacetyl chloride 5b by [2+2] cycloaddition reaction gave the title compounds 6a–j. The assignment of the structures of 6a–j was made by ¹H NMR, MS, and elemental analyses.     

Novel synthesis of substituted N-(3-aryl-1,8-naphthyridin-2-yl) and N,N′-bis(3-aryl-1,8-naphthyridin-2-yl)benzene-1,4-diamines and 2-(4-((3-aryl-1,8-naphthyridin-2-yl)amino)phenyl)isoindoline-1,3-diones and their biological evaluation

A straightforward and highly efficient series of new substituted 3-aryl-1,8-naphthyridine derivatives 3a–e, 4a–e, and 6a–e were synthesized. Condensation dissimilar quantities of 2-chloro-3-aryl-1,8-naphthyridine 1a–e with benzene-1,4-diamine 2 and sodium ethoxide refluxing in ethanol solvent yielded the compounds 3a–e and 4a–e. The 2-(4-((3-aryl-1,8-naphthyridin-2-yl)amino)phenyl)isoindoline-1,3-diones 6a–e were obtained by treatment of compounds 3a–e with phthalic anhydride 5 in refluxing N,N-dimethylformamide is described. All synthesized compounds evaluated for their antimicrobial activity. The structures of the compounds have been proven on the established of spectral (IR, ¹H NMR, and ¹³C NMR) data and elemental analyses. The reaction will be characterized by good efficacy, easy workup, simple purification of the products, and availability of catalyst.     

含氮五元杂环酮的拟除虫菊酯的合成、结构和生物活性

以1-对乙氧基-2,2-二氯环丙烷甲酸(1a)和3-(2-氯-3,3,3-三氟-1-丙烯)-2,2-二甲基环丙烷甲酸(1b)为原料, 经酰氯化反应得到酰氯, 再以三乙胺为缚酸剂, 分别与2-烷酮、2-噻唑烷酮、2-噻唑硫酮、1-乙酰基-2-咪唑烷酮、1-甲磺酰 基-2-咪唑烷酮反应, 得到10个新的含氮五元杂环酮的拟除虫菊酯. 化合物结构经¹H NMR, IR, MS和元素分析进行表征. 并用X-ray单晶衍射测定了化合物3-(1-对乙氧基-2,2-二氯环丙烷甲酰)-2-噁唑烷酮(4a-1)的晶体结构. 对合成的化合物进行了初步的生物活性测试, 结果表明, 在试验浓度下部分目标化合物对黄瓜灰霉病菌具有一定得防效作用; 其中, 化合物(4a-1)和3-(3-(2-氯-3,3,3-三氟-1-丙烯)-2,2-二甲基环丙烷甲酰)-2-噻唑烷酮(4b-3)对粘虫也分别有50%及90%的杀虫活性.     

The First Butyltin(IV) Homo- and Heterobimetallic Diethanolaminates

Equimolar reactions of BuSn(OPrⁱ)₃ with diethanolamines, RN(CH₂CH₂ OH) ₂ (abbreviated as RdeaH₂, where R = H or Me), afford dimeric isopropoxo-bridged six-coordinate butyltin(IV) complexes [{Bu(η³-Rdea)Sn(μ-OPrⁱ)}₂] (R = H ( 1 ), Me ( 2 )). Interactions between BuSn(OPrⁱ)₃ and diethanolamines (RdeaH₂) in a 1:2 molar ratio yield monomeric derivatives of the type [BuSn(Rdea)(RdeaH)] (R = H ( 3 ), R = Me ( 4 )). These homometallic complexes on 1:1 reactions with an appropriate metal alkoxide form monomeric heterobimetallic complexes of the type [BuSn (Rdea)₂ {M(OR′)_n}] (R = H, M = Al, R′ = Prⁱ, n = 2 ( 5 ); R = H, M = Ti, R = Prⁱ, n = 3 ( 6 ); R = H, M = Zr, R′ = Prⁱ, n = 3 ( 7 ); R = Me, M = Al, R′ = Prⁱ, n = 2 ( 8 ); R = Me, M = Ti, R′ = Prⁱ, n = 3 ( 9 ); R = Me, M = Ge, R′ = Et, n = 3 ( 10 )). The driving force behind this work was (i) to explore the utility of homometal complexes ( 1 ) –( 4 ) in assembling a metal alkoxide fragment via a condensation reaction and (ii) to gain insights into the structures of new compounds by NMR spectral data. All of these derivatives have been characterized by elemental analysis, spectroscopic (IR, NMR; ¹H, ²⁷Al, and ¹¹⁹Sn) studies, and molecular weight measurements. ¹¹⁹Sn NMR spectral studies indicate that both the homometallic ( 3 ) and ( 4 ) and heterobimetallic ( 5 ) – ( 9 ) complexes exist in a solution in an equilibrium of six- and five-coordinated tin(IV) species.     

Synthesis of Novel bis-Phosphonate Derivatives by Pudovik Reaction

Synthesis of novel bis-(3-methyl-5-nitro-2-oxo-2,3-dihydro-2λ ⁵benzo[1,3,2]oxazaphosphol-2yl)substituted aryl methanes was accomplished by Pudovik reaction. Addition of equimolar quantities of 2-methylamino-4-nitro phenol (1) and ethanol to PCl₃ afforded cyclic condensation product. On reaction with respective aldehydes followed by treatment with phosphorus(III) monochloride of 1, and on subsequent reaction at reflux temperature, this rearranged from P(III) to P(V) state. Their structures were determined by IR, ¹H NMR, ¹³C NMR, ³¹P NMR, and mass spectral data.     

异噁唑基取代的1,2,4-噁二唑啉和吡唑啉类化合物的合成

通过3-乙酰基-5-羟甲基异噁唑衍生的Schiff碱2与由醛肟原位生成的腈氧化物的1,3-偶极环加成反应, “一锅法”制备了5-甲基-5-[5-(叔丁基二甲基硅氧基甲基)-3-异噁唑基]-3-芳基-4-(4-甲氧基苯基)-4,5二氢-1,2,4-噁二唑类化合物4a～4e; 同时由3-乙酰基-5-羟甲基异噁唑衍生的α,β-不饱和酮(5)与取代苯肼的环化反应制备了5-(叔丁基二甲基硅氧基甲基)-3-[(1,5-二芳基)-3-(4,5-二氢吡唑基)]-异噁唑类化合物6a～6i. 所有新化合物的结构经核磁共振谱氢谱和碳谱、质谱、红外光谱以及高分辨质谱等进行了确证.     

2-(2-Hydroxy-4-methoxybenzoyl)benzoic acid derivatives of Group 4 metal alkoxides

Continued exploration of the coordination behavior of derivatives of 2-benzophenone-based ligands with metal alkoxides ([M(OR)₄]) was undertaken from the reaction of 2-(2-hydroxy-4-methoxybenzoyl)benzoic acid (H₂-OBzA) with a series of Group 4 precursors. The products of these reactions were identified as: [(OR)₂Ti(μ-(c,c-OBzA))]₂ (OR?=?OCHMe₂ (OPrⁱ; 1 ?2tol); OCMe₃ (OBu^t; 2 ?THF); OCH₂CMe₃ (ONep; 3)), [[(OPrⁱ)₃Ti(μ-OPrⁱ)Ti(OPrⁱ)₂]₂(μ-(μ_c,μ-OBzA))₂]₂ (4), [(ONep)₃Zr(μ-ONep)₂Zr(ONep)₂]₂(μ-(c,μ-OBzA)₂) (5 ?tol), [(py)(OBu^t)₃Zr]₂(μ-(c,c-OBzA)) (6), [(OBu^t)₂Hf(μ-OBu^t)]₂(μ-(c,η¹-OBzA)) (7) where ‘c’?=?chelating or η²; ‘μ’?=?bridging or η¹,η¹(O,O’); and μ_c?=?bridging chelating or η¹,η¹(O,O’); η^2?:?η¹. The metal centers for each of these compounds adopt a pseudo-octahedral geometry employing the OBzA ligand in numerous binding modes. The different functional oxygens (carboxylate, hydroxyl, and carbonyl) were employed in a variety of coordination modes for 1–7. The complexity of these OBzA-modified compounds is driven by a combination of the coordination behavior of the OBzA moieties, the size of the metal cation, and the pendant chain of the OR ligand. Solution NMR indicates a complex structure exists in solution that was considered to be consistent with the solid-state structure.