Synthesis,characterization, and antimicrobial activity of new benzofuran derivatives

Russian Journal of General Chemistry - A novel series of (5-substituted-1-benzofuran-2-yl)(2,4-substituted phenyl)methanones (4a–4i) have been prepared by the Knoevenagel condensation of...     

Stereospecific synthesis of oxazolo[3,4-b]tetrahydroisoquinolin-3-ones,analogs of podophyllotoxin,via benzotriazole methodology

A stereospecific synthesis of 2-azapodophyllotoxin analogues based on benzotriazole methodology is reported. Intramolecular Friedel–Crafts reactions of benzotriazole Mannich adducts 2/3b–l afforded 5-substituted oxazolo[3,4-b]tetrahydroisoquinolines 5b–l as pure stereoisomers.     

Furan derivatives—LXXVII : Synthesis and study of sulphides and sulphones of 5-nitrofuran series

Two series of 5-nitro-2-furfurylarylsulphides 4a–4f and 5-nitro-2-furfurylarylsulphones 5a–5g were prepared by the reaction of 5-nitrofurfurylbromide¹ with 4-substituted thiophenols 2a–2f and with 4-substituted benzenesulphinic acids 3a–3g, respectively. In these compounds the transmission of polar effects of the substituents by the -S- and SO₂ groups, respectively, was found to take place. pK Values of compounds studied has been determined spectroscopically.     

Efficient and Convenient Protocol for the Synthesis of Novel 1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines

The novel triazolothiadiazine analogs 5a–p were obtained via a multistep synthetic sequence beginning with 5-substituted 4-amino-1,2,4-triazole-3-thiols 1. Compound 1, in reaction with various aromatic aldehydes 2 in acetic acid, afforded Schiff bases 3a–p. Cyclization of 3a–p with ethyl chloroacetate 4 in the presence of sodium hydride at room temperature gave triazolothiadiazines 5a–p in good yields.     

Recyclization of 5-carbethoxy-4-methyl-2-mercapto(amino,hydroxy) pyrimidines to give 5-acetyl-2-mercapto(amino,hydroxy)-4-hydroxypyrimidines

Conditions for the selective preparation of 5-carbethoxy-4-methyl-2-substituted pyrimidines or 5-acetyl-4-hydroxy-2-substituted pyrimidines by condensation of ethoxymethyleneacetoacetic ester with 1,3-binucleophiles are proposed. It is shown that under the influence of sodium ethoxide 5-carbethoxy-4-methyl-2-substituted pyrimidines undergo rearrangement to 5-acetyl-4-hydroxy-2-substituted pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1558–1559, November, 1982.     

Synthesis and Antimicrobial Evaluation of Novel N-Substituted β-Hydroxy Benzimidazole Sulfone Fluoroquinolones by Selective Oxidation Using Ticl4-H2O2

Abstract

The synthesis of N-substituted β-hydroxy benzimidazole sulfones containing 8-methoxy fluoroquinolone has been described and they were evaluated for antimicrobial activities. The compounds of N-substituted β-hydroxy benzimidazole sulfides (4a–e) and N-substituted β-hydroxy benzimidazole sulfones (5a–e) at C-7 of fluoroquinoline exhibited superior activity in vitro. 8-Methoxy fluoroquinolone carboxylic acid (1), reaction with piperizine in acetonitrile in presence of triethylamine under reflux gives 7-piperazinyl-8-methoxyfluoroquinolone (2). The latter is reacted with epichlorohydrine in presence of NaOH in acetone yielded N-substituted epoxide (3), which on treatment with 5-substituted-2-mercaptobenzimidazoles gives N-substituted β-hydroxy benzimidazole sulfides (4). Further, 4 on treatment with TiCl₄-H₂O₂ and in DCM yielded the corresponding N-substituted β-hydroxy benzimidazole sulfone (5).     

Photochemistry of imidazolides. I. The photo-Fries-type rearrangement of N-substituted imidazoles.

A number of N-substituted imidazoles 1a–1i have been found to photo-isomerize to give the corresponding 2-substituted- and 4(or 5)-substituted imidazoles ( 2a–2i and 3a–3i ). The role of a dissociative path in these reactions has been demonstrated.     

Selenium heterocycles. XXIX. Reaction of substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate,ethyl azidoformate and phenyl azide

Reaction of 5-substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate, phenyl azide and ethyl azidoformate afforded 2-substituted ω-carbethoxy-1,4-thiaselenafulvenes (II) , 5-substituted 2-phenylimino-1,3-thiaselenoles (IV) and 5-substituted 2-carbethoxyimino-1,3-thiaselenoles (V) , respectively. The structure of these compounds were confirmed by spectroscopic methods and chemical analysis.     

Choline chloride–ZnCl2: Recyclable and efficient deep eutectic solvent for the [2+3] cycloaddition reaction of organic nitriles with sodium azide

Herein we report first time choline chloride–zinc chloride based deep eutectic solvent is a green and efficient reaction medium for the [2+3] cycloaddition reaction of organic nitriles with sodium azide to afford the corresponding 5-substituted 1H-tetrazoles. The present method provides an environment-friendly route, short reaction times with excellent yields, safe process, and simple workup which make this method an attractive and useful contribution to the existing conventional processes for the synthesis of 5-substituted 1H-tetrazoles.     

Synthesis of 5-fluoro-2-methyl-3-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)-4(3H)-quinazolinone and related compounds with potential antiviral and anticancer activity

The synthesis of ten new substituted 1,3,4-thiadiazolyl-4(3H)-quinazolinones 8–11, 13, 17 , and 20–23 is reported. Compounds 8–11 were prepared by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7. Compound 13 was obtained by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) with DL-α-amino-?-caprolactam (12) . Compound 17 was synthesized by condensation of 6-bromo-2-methyl-3,1-benzoxazin-4-one (16) and 2-amino-5-t-butyl-1,3,4-thiadiazole (5) . Compounds 20–23 were obtained by condensation of 5-chloro-6,8-dibromo-2-methyl-3,1-benzoxazin-4-one (19) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7, respectively. The substituted 3,1-benzoxazin-4-ones 3, 16, and 19 were obtained in good yield by refluxing the appropriate anthranilic acid, 1,15 , and 18 with acetic anhydride (2) .     

An Efficient Approach to the Synthesis of Ethyl α-Cyanoalkyl β-Substituted Acrylates by the HWE Olefination of Ethyl 2-(Diethoxyphosphoryl) Cyanoalkanoates

Ethyl α-cyanoalkyl β-substituted acrylates 5a–i were prepared in good yields on a synthetic scale by Horner–Wadsworth–Emmons olefination of the corresponding ethyl 2-(diethoxy-phosphoryl) cyanoalkanoates 3a–c using different aldehydes and anhydrous potassium carbonate in dry THF at reflux.     

Comparison between non-peripherally and peripherally tetra-substituted zinc (II) phthalocyanines as photosensitizers: Synthesis,spectroscopic, photochemical and photobiological properties

A series of zinc phthalocyanines tetra-α-substituted with 4-(butoxycarbonyl) phenoxy groups (1a) or 4-carboxylphenoxy groups (2a) or 4-(2-carboxyl-ethyl)phenoxy groups (3a), and the corresponding tetra-β-substituted (1–3b) analogues, have been synthesized and characterized. The effects of the position of substituents at the phthalocyanine skeleton on their spectroscopic, photochemical and photobiological properties have been revealed. When compared with the tetra-β-substituted phthalocyanines, the corresponding tetra-α-substituted analogues exhibit a less aggregating trend in the cellular growth medium, a slightly higher singlet oxygen quantum yield and higher photo-stability in DMF, and a comparable cellular uptake. As a result, the tetra-α-substituted zinc phthalocyanines exhibit a higher photocytotoxicity toward MGC803 human gastric carcinoma cells than the tetra-β-substituted counterparts. Among all these compounds, phthalocyanine 2a shows the highest photodynamic activity, which may mainly be due to its non-aggregated nature in cellular culture medium and high cellular uptake.     

Benzofuran derivatives. Part 4 , synthesis of benzofurans and 2,3,4,5-tetrahydro-1-benzoxepin-3,5-diones

By treatment of ethyl 4- or 5-substituted 2-acetylphenoxyacetates 1 with potassium hydroxide in dry dioxane, benzofurans 2–7 and 2,3,4,5-tetrahydro-1-benzoxepin-3,5-diones 8 were obtained. The relative yields of benzofurans 2–7 and 2,3,4,5-tetrahydro-1-benzoxepin-3,5-diones 8 varied with the types of 4- or 5-substituents. The electron-donating 4-methoxyl group favored the formation of benzoxepins. On the other hand, electron-withdrawing substituents such as the 4-nitro group favored the formation of benzofurans. When esters 1 were treated with sodium amide, 2,3-dihydrobenzofurans 2 were obtained exclusively regardless of 4- or 5-substituents.     

Alkyl- and arylthiation of uracil and indole

5-Alkyl- or arylthio-2,4-pyrimidinediones, 1–8 , were prepared from uracil and alkane- or arenesulfenyl chlorides. Indole reacted similarly to give the 2,3-di- and 3-substituted derivatives, 15–19 .     

A Divergent Polyene Cyclization for the Total Synthesis of Greenwayodendrines,Greenwaylactams, Polysin and Polyveoline

We present a concise asymmetric total synthesis (5–8 steps) of nine sesquiterpenoid alkaloids featuring four different tetra-/pentacyclic scaffolds. To this end, a novel, bioinspired indole N-terminated cationic tricyclization has been developed, enabling the divergent synthesis of greenwayodendrines and polysin. Subtle variation of the C2-substituted indole cyclization precursor allowed switching between indole N- and C-termination. For the latter, a subsequent Witkop oxidation enabled conversion of the cyclopentene-fused indole into the eight-membered benzolactam to directly furnish the family of greenwaylactams. In addition, a diastereomeric C-termination product has been elaborated to provide access to polyveoline.     

Synthesis,Crystal Structure,and Spectral Characterization of Flumatinib Mesylate

Flumatinib mesylate, a 3-substituted picolinamide derivative structurally similar to imatinib mesylate, was prepared. The compound was characterized by infrared, ultraviolet, NMR, and electrospray ionization–mass spectra together with x-ray crystal structure analysis.     

Chemistry of 2-substituted benzimidazoles. 1. 5-Amino-2-methyl(aryl, arylalkyl, pyridyl)benzimidazoles

A series of 2-substituted benzimidazoles was synthesized. These products were consecutively converted into 5-nitro- and 5-amino-2-substituted benzimidazoles.Russian People's Friendship University, 117198 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 493–500, April, 200.     

Synthesis and Anticancer Evaluation of 2-{4-[5-(5-Substituted arylpyrimidin-2-yl)-1H-pyrazol-3-yl]-phenyl}thiazolo[4,5-b]pyridine Derivatives

Russian Journal of General Chemistry - In the present study a new series of 2-{4-[5-(5-substituted arylpyrimidin-2-yl)-1H-pyrazol-3-yl] phenyl}thiazolo[4,5-b]pyridine derivatives (11a–11j)...     

Tetrazoles: LIII. Microwave-activated acylation of 5-substituted tetrazoles

The acylation of 5-aryl(hetaryl)tetrazoles with acetic and benzoic anhydrides under microwave irradiation gave the corresponding 2-substituted 5-methyl-and 5-phenyl-1,3,4-oxadiazoles in high yields. The use of microwave activation reduces the reaction temperature by 30–40°C and shortens the reaction time by a factor of 5 to 7.     

1,3,4-THIADIAZOLES. REGIOSELECTIVE O-DEMETHYLATION ON DEHYDRATIVE CYCLIZATION OF 1-(3,4,5-TRIMETHOXYBENZOYL)4-SUBSTITUTED THIOSEMICARBAZIDES WITH SULPHURIC ACID

Cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-substituted thiosemicarbazides 2a–g with sulphuric acid at ambient temperature afforded the selectively demethylated products 2-(4-hydroxy-3,5-dimethoxyphenyl)-5-substituted amino-1,3,4-thiadiazoles 4a–g. Meanwhile, dehydrative cyclization of 1-(3,4,5-trimethoxybenzoyl)-4-(benzyl or t-butyl)thiosemi- carbazides 2h, i with sulphuric acid yielded 2-(4-hydroxy-3,5-dimetho xyphenyl)-5-amino-1,3,4-thiadiazole 5. On the other hand, dehydration of 2h, i by heating with phosphorus oxychloride yielded 2-(3,4,5-trimethoxyphenyl)-5-amino-1,3,4-thiadiazole 6.