Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate,thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reacted with ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.

     

Preparation and some spectroscopic properties ofN-heterocyclic derivatives of a novel 1-pyrroline C18 fatty ester

A C₁₈ 1-pyrroline fatty ester, methyl 8-(5-hexyl-2-pyrrolin-1-yl)octanoate (1), was prepared from methyliso-ricinoleate. The C=N bond of the pyrroline ring was oxidized bym-chloroperoxy-benzoic acid to yield a mixture of oxaziridine isomers 2a,2b, which decomposed during gas chromatographic analysis to a 2,5-disubstituted pyrrole derivative, methyl 8-(5-hexyl-1H-pyrrole-2-)octanoate (3). Compound 3 was also obtained by reaction of 2a,2b with dilute HCl in methanol. Reaction of compound 1 with iodo-methane formed anN-methyl iminium iodide intermediate 4, which on reduction with sodium borohydride furnished a mixture ofcis/trans-N-methyl-2,5-disubstituted pyrrolidine derivatives, methyl 8-(cis/trans-5-hexyl-N-methyl-pyrrolidine-2-)octanoates 5a,5b. Reduction of compound 1 with NaBH₄ gave a mixture ofcis/trans-isomers of 2,5-disubstituted pyrrolidine derivatives, methyl 8-(5-hexyl-pyrrolidine-2-)octanoates 6a,6b. Acetylation of compounds 6a,6b with acetic anhydride furnished the correspondingN-acetyl pyrrolidines 7a,7b. When compound 1 was treated with perchloric acid, the corresponding iminium perchlorate derivative, methyl 8-(5-hexyl-1-pyrrolinium perchlorate-2-)octanoate 8 was obtained. The structures of the various derivatives were characterized by a combination of chromatographic, mass spectral and spectroscopic techniques.     

Fluorination Studies on Glycyrrhetic Acid Derivatives

Attempts to introduce a fluorine atom directly at the C-3 position of the triterpenoidal glycyrrhetic acid 1 by reacting the tosylate 2 with KF, or methyl glycyrrhetate 5 with Et₂NCF₂CHCIF, failed. The ring A olefin 3 and the rearrangement product 4 were obtained. The homoannular diene 7 was treated with NOF, but only nitroso-fluorine compounds 8, 9 were isolated. Nitrosyl fluoride was also reacted with olefin 3 . A difluoro compound 10 and the expected 2-keto-3α-fluoro compound 11 were obtained. The above two olefins were also reacted with bromine fluoride. Although the diene 7 gave only fluorine-free compounds 13, 14 , the expected fluoro-bromine compound 16 was obtained from 3 . When the 2β-fluoro-3α-bromo compound was treated with Bu₃SnH, the bromine atom was replaced by hydrogen and the 2β-fluoro compound 17 was formed.     

Synthesis of novel heterocyclic polyimides containing trimellitimide acid moieties

4‐Nitrobezoyl chloride (2) was reacted with isoeugenol in chloroform in the presence of triethyl amine and ester (4) was obtained in high yield. Ester (4) was reacted with SnCl₂·2H₂O to give amine‐ester (5), and subsequently was reacted with trimellitic anhydride (6) and novel isoeugenol ester‐imide derivative (7), as a new monomer was obtained in quantitative yield. Compound (7) was characterized by high‐field ¹H–NMR, IR, and elemental analysis and then was used for the preparation of model compound (9) and polymerization reactions. 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione (PhTD) (8) was allowed to react with compound (7). The reaction is very fast and gives only one double adduct (9) via Diels–Alder and ene pathways in excellent yield. The polymerization reactions of novel monomer (7) with bistriazolinediones [bis(p‐3,5‐dioxo‐1,2,4‐triazolin‐4‐ylphenyl)methane (10) and 1,6‐bis(3,5‐dioxo‐1,2,4‐triazolin‐4‐yl)hexane (11)] were carried out in N,N‐dimethylacetamide (DMAc) at room temperature. The reactions are exothermic, fast, and gave novel heterocyclic polyimides (12) and (13) via repetitive Diels–Alder‐ene polyaddition reactions. Some structural characterization and physical properties of these novel heterocyclic polyimides are reported. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1716–1725, 2001     

Efficient synthesis of N-substituted-N'-arylcarbonylthioureas under solvent-free conditions

A convenient method for the synthesis of N-substituted-N'-arylcarbonylthioureas under solvent-free conditions has been developed. Ammonium thiocyanate and acid chlorides were mixed, and stirred at room temperature without a solvent, to give the corresponding isothiocyanates, which reacted smoothly with arylamines to produce the aryl(alkyl)carbonylthioureas in good yields. Unusually large values of ⁵ J _FH=12.2–15.1 Hz are observed for 1-(2-fluorobenzoyl)-thiourea derivatives, which provide information about the Ar-C-N-H torsions in these compounds.     

α-tocopherol oxidation mediated by superoxide anion (O 2 − ). II. Identification of the stable α-tocopherol oxidation products

The present paper describes the identification of two stable end products of α-tocopherol oxidation that were previously detected among the products of the reaction of α-tocopherol with superoxide anion (O ₂ ⁻ ) under aprotic conditions. One compound, previously designated compound A, was identified astrans-7-hydroxy-trans-8,8a-epoxy-α-tocopherone, and the other, designated compound B, was identified ascis-7-hydroxy-cis-8,8a-epoxy-α-tocopherone. It was also observed that under protic conditions (10% water in acetonitrile) the reaction of α-tocopherol with O ₂ ⁻ did not produce compounds A and B, but rather α-tocopheryl quinone, α-tocopherol dimer, α-tocopherol dihydroxy dimer, and the previously designated compound C. Compound C was identified in the present study as α-tocopheryl-quinone-2,3-epoxide.     

Investigation on the Hydrogen Abstraction from Methyl Glucoside by Active Oxygen Species under Oxygen Delignification Conditions. Part 2: Study on the C-2 Position

Abstract

It was investigated whether active oxygen species (AOS) generated in situ by reacting a phenolic compound, 2,4,6-trimethylphenol, with O₂ abstract the C-2 hydrogen from a carbohydrate model compound, methyl β-d-glucopyranoside (MGPβ), under conditions simulating oxygen delignification (0.5 mol/l NaOH, 0.36 mmol/l FeCl₃, 1.1 MPa O₂, 95°C). MGPβ was degraded less than methyl β-d-mannopyranoside (MMPβ) when they were reacted together with AOS. It was suggested that the configurational difference at their C-2 positions results in their different reactivity toward AOS. When MGPβ and methyl β-d-(2-²H)glucopyranoside (MGPβ-2D) were reacted together with AOS, MGPβ was degraded slightly but more than MGPβ-2D, which clearly indicates that the C-2 hydrogen of MGPβ is abstracted by AOS. MGPβ and MGPβ-2D were also subjected together to alkaline H₂O₂ treatment (0.5 mol/l NaOH, 0.36 mmol/l FeCl₃, 58.8 mmol/l H₂O₂, 95°C) in which oxyl anion radical (O^-?) is likely the only AOS to degrade these compounds. At least some AOS other than O^-? abstract the C-2 hydrogen from MGPβ in the aforementioned oxygen-alkali treatments.     

AMAT的硝化反应及其MNCIO的合成

2－乙酰基－7－甲胺基Zhou酮（AMAT）（1）与硝酸反应，得到2－乙酰基－7－基胺基－4－硝基恶酮（2）。谷物化合物2在碱性条件下水解，得到3－乙酰基－5－硝基Zhou酚酮（3）。化合物3与盐酸羟胺反应，得到3－甲基－5－硝基－8H－环庚并[d]异恶唑－8－酮（MNCIO）（4）。它们的结构均经红外光谱、核磁共振谱得到证实。其中化合物2是未见文献报道的新化合物。     

Biotransformation of three aromadendrane‐type sesquiterpenoids by Aspergillus wentii

BACKGROUND: The biotransformation of sesquiterpenoids, which are a large class of naturally occurring compounds, using microorganisms as a biocatalyst to produce useful novel organic compounds was investigated. The biotransformation of sesquiterpenoids, (+)‐aromadendrene ( 1 ), (−)‐alloaromadendrene ( 2 ) and (+)‐ledene ( 3 ) has been investigated using Aspergillus wentii as a biocatalyst. Results: Compound 1 was converted to (−)‐(10S,11S)‐10,13,14‐trihydroxyaromadendrane ( 4 ). Compound 2 was converted to (+)‐(1S,11S)‐1,13‐dihydroxyaromadendrene ( 5 ) and (−)‐5,11‐epoxycadin‐1(10)‐en‐14‐ol ( 6 ). Compound 3 was converted to compound 6 , (+)‐(10R,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 7 ) and (+)‐(10S,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 8 ). The structure of the metabolic products has been elucidated on the basis of their spectral data. CONCLUSION: Compound 1 gave only one product that was hydroxylated at C‐10, C‐13 and C‐14. By contrast, compounds 2 and 3 gave a number of products, one of which was common. The differences in oxidation of 1–3 are due to the configuration of the C‐1 position. Compounds 4–8 were new compounds. Copyright © 2008 Society of Chemical Industry     

Synthesis and Antimicrobial Evaluation of Some Novel Bis-α,β-Unsaturated Ketones,Nicotinonitrile, 1,2-Dihydropyridine-3-carbonitrile,Fused Thieno[2,3-b]pyridine and Pyrazolo[3,4-b]pyridine Derivatives

The title compounds were prepared by reaction of 1,1′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)diethanone (1) with different aromatic aldehydes 2a–c, namely Furfural (2a), 4-chlorobenzaldehyde (2b) and 4-methoxybenzaldhyde (2c) to yield the corresponding α,β-unsaturated ketones 3a–c. Compound 3 was reacted with malononitrile, 2-cyanoacetamide or 2-cyanothioacetamide yielded the corresponding bis[2-amino-6-(aryl)nicotinonitrile] 4a–c, bis[6-(2-aryl)-2-oxo-1,2-dihydropyridine-3-carbonitrile] 5a–c or bis[6-(2-aryl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile] 6a,b, respectively. The reaction of compound 6a with each of 2-chloro-N-(4-bromophenyl) acetamide (7a), chloroacetamide (7b) in ethanolic sodium ethoxide solution at room temperature to give the corresponding 4,4′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis-6-(2-furyl)thieno[2,3-b]pyridine-2-carboxamide] derivatives 9a,b. While compound 6a reacted with hydrazine hydrate yielded the 4,4′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis[6-(2-furyl)-1H-pyrazolo[3,4-b]pyridin-3-amine] 11. The structures of the products were elucidated based on their spectral properties, elemental analyses and, wherever possible, by alternate synthesis. Antimicrobial evaluation of the products was carried out.     

Synthesis and Antimicrobial Activity Evaluation of Imidazole-Fused Imidazo[2,1-b][1,3,4]thiadiazole Analogues

Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20 a – g , 21 a – g , and 22 a – g ) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram-positive and -negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline ( 21 a ) showed the highest activity against C. albicans (MIC₅₀=0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.     

6-(3-甲基-4-对甲苯磺酰基-2-丁烯基)-2,3,4,5-四甲氧基甲苯的合成

对甲酚(Ⅰ)在铁粉催化下与溴反应得到2,3,6 三溴 4 甲基苯酚(Ⅱ)(收率78%);Ⅱ在碘化亚铜催化下与甲醇钠反应后再与硫酸二甲酯反应得到2,3,4,5 四甲氧基甲苯(Ⅲ)(收率92 5%);Ⅲ与溴反应得到6 溴 2,3,4,5 四甲氧基甲苯(Ⅳ)(收率85%);Ⅳ与镁反应得到格氏试剂后,在碘化亚铜催化下与(E) 4 氯 2 甲基 1 对甲苯磺酰基 2 丁烯(Ⅴ)偶联反应合成了辅酶Q10中间体6 (3 甲基 4 对甲苯磺酰基 2 丁烯基) 2,3,4,5 四甲氧基甲苯(Ⅵ)(收率81%)。四步反应总收率49 6%,产物经1HNMR确证其双键为E 异构体。     

Organoselenium Chemistry. Preparation of Allyl and Homoallyl Amines by Aminomethylation of Phenylseleno-Substituted Allyl Tin Reagents

Metalation of methallyl phenyl selenide, allyl phenyl selenide, and methallyl phenyl sulfide followed by tri-n-butylstannylation gave exclusively the γ-stannylated sulfide or selenide (e.g., 1-phenylseleno-2-methyl-3-tri-n-butylstannyl-1-propene ( 5 )). Compound 5 reacts with a series of immonium electrophiles to give products of aminomethylation α- to selenium. Electrophiles have included N-(bromomethyl)phthalimide/ZnBr₂, Eschenmoser salt (dimethylmethyleneammonium iodide), and Mannich reagents generated in situ from diethylamine, piperidine, isopropyl sarcosinate and benzylmethylamine. The selenide from the last of these amines (N, 3-dimethyl-N-benzyl-2-phenylseleno-3-butenamine, 10 ) has been subjected to further transformations as follows: (1) treatment of 10 with trimethylstannyllithium results in replacement of phenylseleno by stannyl; this allyltin ( 11 ) can then again be aminomethylated giving compound 12 or 13 ; (2) oxidation of 10 gives amino alcohol 14 by [2, 3] sigmatropic rearrangement of the allyl selenoxide; (3) photolysis of 10 results in 1,3-rearrangement of the phenylseleno group; oxidative rearrangement of this allyl selenide gives amino alcohol 16 . The phthalimidomethylation product ( 6 ) is converted to a precursor for the side chain of the cytokinin zeatin by oxidation and [2, 3] sigmatropic rearrangement.     

Nitriles in heterocyclic synthesis. Part III: New sulpha drugs related to cyanopyridine derivatives

4-Hydroxyacetophenone (1) was reacted with cinnamonitrile derivatives (2–6) to give 3-cyano-4-(substituted phenyl)-6-(p-hydroxyphenyl)-pyridines (7–11). Interaction of compounds 7–9 with 4-substituted heterocyclo-benzenesulphonyl diazoniura chloride gave the corresponding 3-cyano-4-(sub-stituted phenyl)-6-(3′-azobenzene sulphonamido-4′-hydroxyphenyl) pyridines (12–29). The corresponding iron (III) copper (II) and mercury (II) chelates were also prepared in a 1:2 metal-to-ligand ratio. All the synthesized compounds were characterized on the basis of microanalysis, IR and ¹H-NMR spectrometry.     

Synthesis and properties of 4-hydroxy-2,3,5,6-tetrabromobenzyl phosphonates and effects of their flame retardance on impact polystyrene

p-Cresol was converted into 2,3,5,6-tetrabromocresol by AlCl₃ catalyst bromination, and then further brominated to 4-hydroxy-2,3,5,6-tetrabromobenzyl bromide (HTBBB) in benzene by light. HTBBB reacted easily with trialkyl phosphite to produce 4-hydroxy-2,3,5,6-tetrabromobenzyl phosphonates (HTBBPs) in solvents. Although the reaction of HTBBB with triaryl phosphite was slower than that with trialkyl phosphite, it does produce corresponding phosphonate with ease. Except for DMF, DMAc, chloroform, and tetrahydrofuran, HTBBP was difficult to dissolve in ordinary organic solvents. Of all the synthesized HTBBP, dimethyl hydroxy-2,3,5,6-tetrabromobenzyl phosphonate showed the poorest solubility. With the addition of these new compounds containing bromine and phosphorus atoms to HIPS as flame retardants, the results of oxygen index measurement showed that the flame resistance of these compounds was greater than the additive effect of the two corresponding individual brominated compound and phosphorus-containing compound. It means that these new compounds seem to act synergistically as flame retardants in HIPS. Simultaneous addition of bominated compound and phosphorus-containing compound to HIPS ends up with a similar effect as mentioned above, but the new compounds can prevent the exclusion of phosphorus-containing compound from polymer matrix.     

Mechanochemistry of Syringylglycerol-β-Guaiacyl Ether and Its Similarity to the Conventional Bleaching of Mechanical Pulps

Syringylalcohol (1), α-methyl syringylalcohol (2), 3, 4, 5-trime-thoxyphenyl methylcarbinol (3) were dispersed onto filter paper pulp or linter pulp, and treated, respectively, with a ceramic ball mill (CBM) or a vibration ball mill (VBM-1 or -2) under air for 1h. Mechanical treatment of VBM-2, having the more rigid surface of linter pulp, furnished the p-carbonylphenols (5), (6), and 3, 5-dimethoxy-p-benzoquinone (7). Mechanical treatments of syringylgl-ycerol-β-guaiacyl ether (4) with CBM, VBM, and a laboratory refiner provided α-(2-methoxyphenoxy)-β-hydroxypropiosyringone (8) in the highest yield and a less yield of p-quinone derivative (7) and others as shown in TABLE 2 and FIGURE 3. When treated the resultant mixture with alkaline H₂0₂, the chromophore (III) can be decomposed, but remarkable amounts of the leucochromophre (IV) are produced as shown in FIGURE 4.     

Review of the hydrolysis of iron(III) and the crystallization of amorphous iron(III) hydroxide hydrate

Hydrolysis of ferric solutions leads initially to mono- and dinuclear species which interact to produce further species of higher nuclearity. These polynuclear species age eventually to either crystalline compounds or to an amorphous precipitate (amorphous iron(III) hydroxide hydrate). Amorphous iron(III) hydroxide hydrate is thermodynamically unstable and gradually transforms to α-FeO(OH) and α-Fe₂O₃. These crystalline products form by competing mechanisms and the proportion of each in the final product depends on the relative rates of formation. The master variable governing the rates at which these compounds form is pH. Other important factors are temperature and the presence of additives. Most additives retard the transformation and by suppressing formation of α-FeO(OH) lead to an increase in the amount of α-Fe₂O₃ in the product; some additives also directly promote formation of the latter compound. Metal ions can oftxen replace a proportion of Fe in the α-FeO(OH) and α-Fe₂O₃ lattices. At high enough concentrations they can induce formation of additional phases. Additives may also modify the morphology of the crystalline products.     

[AgPb2I3(OH)2]: An unprecedented quaternary heterometallic semiconducting framework synthesized under ionothermal condition

We reported herein an unprecedented quaternary heterometallic framework, namely, [AgPb₂I₃(OH)₂] (1), which was successfully produced under ionothermal condition. In the title compound, [Pb₄(OH)₄] cubane and [Ag₂I₆] building blocks are jointed together to give a (6,6)-connected pcu topology. Compound 1 shows not only remarkable luminescent emissions, but also semiconducting properties tuned by the corresponding metal halide components.     

阿达帕林的合成工艺研究

以1-金刚烷醇、4～溴苯酚为原料,在浓硫酸催化下制得2-（1-金刚烷基）-4-溴苯酚,产物再用硫酸二甲酯甲基化得到2-（1-金刚烷基）-4-溴苯甲醚,2-（1-金刚烷基）～4-溴苯甲醚的格氏化产物再与6-溴-2-萘甲酸甲酯反应,制得6～[3-（1-金刚烷基）-4-甲氧基苯基]-2-萘甲酸甲酯,该产品在氢氧化钠作用下皂化...     

Microwave Discharge of O2 and CO2 as a Synthetic Tool for Oxidations of Unsaturated Compounds Adsorbed on Solid Supports

Cis and trans stilbene, styrene, 1-decene and 6-dodecene adsorbed on silica gel were reacted with oxygen atoms produced by microwave discharge of O₂ and CO₂. At 0°C these compounds gave mainly epoxides and carbonyl compounds as in neat liquid reactions. Below — 60°C ozonolysis products were formed; cis and trans stilbene and styrene gave benzaldehyde while 1-decene and 6-dodecene resulted mainly in ozonides.