New N,S-Derivatives of Nitrodienes from Thioallyl-and Thiodibromopropyl Nitrodienes

Compound 3 and 5a, b were obtained from the reaction of 1,3,4,4-tetrachloro-1-thioallyl-2-nitro-1,3-butadiene (1) with thiomorpholine (2) and piperazine derivatives 4a, b in dichloromethane. The reaction of compound 1 and bromine gave compound 6. Compounds 8 and 10 were obtained from the reaction of 6 with 1-(diphenylmethyl)piperazine (7) and piperidine (9) in dichloromethane. The derivative 13 was synthesized from the reaction of 4-bromo-1,1,3,4-tetrachloro-2-nitro-1,3-butadiene (11) and allylmercaptane (12). Compounds 15 and 16a, b were obtained from the reaction of 1-allyl-4-bromo-1,3,4-trichloro-2-nitro-1,3-butadiene (13) with morpholine (14) and the piperazine derivatives 16a, b, in dichloromethane, respectively.     

Synthetic Access to New Pyridone Derivatives through the Alkylation Reactions of Hydroxypyridines with Epoxides

General methods for the preparation of a variety of pyridone and oxypyridine derivatives are described. 2‐,3‐,4‐Hydroxy pyridine and 2‐pyridinemethanol were alkylated with ethylene‐, propylene‐, and stryrene‐oxide and epichlorohydrin in the presence of different Lewis acids as a catalyst. The best yield of 3a was achieved in the presence of CdI₂/BF₃ · OEt₂. The corresponding pyridone derivatives (3a–d, 7a–d) were obtained from the reaction of 2‐and 4‐hydroxypyridine with oxiranes in good yields, whereas oxypyridine derivatives (5a–d, 9a,b) were obtained from reactions of 3‐hydroxypyridine and 2‐pyridinemethanol with oxiranes. Chlorohydrines (3d, 5d, 7d) were easily converted to corresponding epoxy derivatives (10, 11, 12) in basic medium; then amino alcohols (13–17) were obtained from the reaction of these epoxy derivatives with amines.     

Synthesis,characterization, and investigations of antimicrobial activity of 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4(5H)-dione

Chalcone-like compounds 3a–l, 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one, were synthesized from the addition of different benzaldehyde derivatives (2a–l) to 1,2,3,4-tetrahydro-1-napthalone (1) in basic medium. Mn(OAc)₃-mediated addition of dimedone (4) to chalcone-like compounds gave the spirobenzofuran derivatives (5a-l), 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4 (5H)-dione, in good yields. The structures of synthesized compounds 5a–l were elucidated on basis of spectral data (NMR, IR) and elemental analysis. In addition, their antibacterial activities were screened against some human pathogenic microorganisms.     

Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

Novel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K_i values in the range of 18.90?±?2.37 ?58.25?±?13.62?nM for hCA II and 5.72?±?0.98 ?37.67?±?5.54?nM for hCA I. Also, the K_i parameters of these compounds for AChE were obtained in the range of 25.47?±?11.11???255.74?±?82.20?nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K_i value of 70.55?±?12.30?nM against hCA II, and 67.17?±?9.1?nM against hCA I, and tacrine inhibited AChE showed K_i value of 263.67?±?91.95.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Heteroaromatization with Sulfonamido Phenyl Ethanone,Part I: Synthesis of Novel Pyrrolo[2,3-D]Pyrimidine and Pyrrolo[3,2-E][1,2,4]Triazolo[1,5-C]Pyrimidine Derivatives Containing Dimethylsulfonamide Moiety

4-(5-Amino-4-cyano-1-p-tolyl-1H-pyrrol-3-yl)-N,N-dimethyl-benzenesulfonamide (4) was prepared and converted to several pyrrolo[2,3-d]pyrimidin-5-yl)-N,N-dimethyl-benzenesulfonamide derivatives (5,7,9, and 13). Cyclocondensation of 13 with different electrophilic carbon reagents afforded several 4-(N,N-dimethylaminosulfonylphenyl)]pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]-pyrimidine derivatives (14–17,19, and 20); IR, ¹HNMR, and mass spectra of the newly synthesized compounds were recorded. Most of the obtained compounds were screened against Gram-positive and Gram-negative bacteria and fungi, for which some of these derivatives gave promising results.     

Studies on Pyrazine Derivatives,XLIV: Synthesis and Tuberculostatic Activity of 4-Substituted 3,4,5,6-Tetrahydro-2H-[1,2′]-Bis-Pyrazine Derivatives

2-chloro-3-cyanopyrazine was a substrate in the syntheses of some potentially tuberculostatic pyrazine derivatives. This compound, upon action of secondary amines, pyrazine derivatives 1-phenyl-, 1-piperonyl-, 1-(4-fluorophenyl)-, 1-(2-pyridil)-, and 1-benzylpiperazine, gave the corresponding nitriles ( 1a–e ). Compounds 1c , d , e were changed into the amidoximes ( 2c , d , e ) by hydroxylamine action. Derivatives 1a–e were transformed into the corresponding thioamides ( 3a–e ) when treated with ammonium polysulphide. Two of these, thioamides, 3a and 3b , in the cyclization reactions with ethylenediamine gave the imidazolines ( 4a , b ) with phenacyl bromide—the thiazole derivatives ( 5a , b ). The compounds obtained were tested in vitro for their tuberculostatic activity. The tuberculostatic activity of compound 5b was the highest: MIC 3.1–7.8 μ g/mL.     

Synthesis and Antimicrobial Properties of New Thiosemicarbazide, 1,2,4-Triazole,and 1,3,4-Thiadiazole Derivatives of Sulfanylacetic Acid

Abstract

1,2,4-triazole and 1,3,4-thiadiazole derivatives are still considered a viable lead structure for the synthesis of more efficient antimicrobial agents having a broad spectrum of activity. This study presents the synthesis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Reaction of 4-phenyl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thione with ethyl bromoacetate yields the corresponding ethyl acetate (1). In the subsequent reaction with 100% hydrazine hydrate, the hydrazide (2) was obtained, which was converted with isothiocyanates to new acyl derivatives of thiosemicarbazide (3a–l). The cyclization of these compounds in alkaline media resulted in the formation of new derivatives of 1,2,4-triazole (4a–i), whereas in acidic media new derivatives of 1,3,4-thiadiazole (5a,b,g) were obtained. All synthesized compounds were screened for their in vitro antimicrobial activities.     

Antimicrobial and antiquorum-sensing activity of Ricinus communis extracts and ricinine derivatives

Ricinine (1), a known major alkaloid in Ricinus communis plant, was used as a starting compound for the synthesis of six ricinine derivatives; two new and four known compounds. The new derivatives; 3-amino-5-methyl-1H-pyrazolo[4,3-c]pyridin-4(5H)-one (2), and 3-amino-5-methyl-1-(phenylsulfonyl)-1H-pyrazolo[4,3-c]pyridin-4(5H)-one (3), as well as the previously prepared derivatives (4–7) were subjected for antimicrobial and antiquorum-sensing evaluation in comparison to different R. communis extracts. Acetyl ricininic acid derivative (5) showed the highest antimicrobial activity among all tested derivatives against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeuroginosa and Candida albicans. However, compound 7 (4-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide) showed the highest antiquorum-sensing activity among all tested compounds and extracts. These findings proved the usefulness of ricinine as a good scaffold for the synthesis of new antimicrobial and antiquorum-sensing derivatives in spite of its poor contribution to the antimicrobial activity of the plant extracts.     

Synthesis of fused 1,2,4-triazines as potential antimicrobial and antitumor agents

5-Benzylidene-3-(p-chlorophenyl)-2-aminothiocarbonyl-1,2,4-triazine (2) was prepared via condensation of oxazolinone (1) with thiosemicarbazide. Fused 1,2,4-triazine derivatives (3, 4 and 9) were synthesized from the reaction of compound 2 with ω-bromomethyl aryl ketones, ethyl chloroacetate, and acetic anhydride. Treatment of 4 with acetic anhydride and aromatic aldehydes yielded the corresponding acetyl, diacetyl derivatives (6 and 7) and 7-benzylidene-5-(p-chlorophenyl)-4-thioxo-3-arylidene-1,2,4-triazino [2,1-a]-1,2,4-triazine-1,8-diones (8). The electron impact mass spectra of both the above series of compounds have also been recorded and their fragmentation pattern is discussed. All synthesized fused 1,2,4-triazine derivatives were primary in vitro screened for their antimicrobial and antitumor activity.

     

Synthesis of a series of triple-bridged cyclotriphosphazene hexa-alkoxy derivatives and investigation of their structural and mesomorphic properties

Triple diamino-bridged cyclotriphosphazene (1) was reacted in a 1:8 stoichiometry with the sodium derivatives of long-chain diols [1-octanol, 1-decanol, 1-dodecanol, 1-hexadecanol] tetrahydrofuran (THF) at room temperature to form hexa-substituted cyclotriphosphazene derivatives (2, 3, 4 and 5, respectively), whose mesomorphic behaviours were investigated for their possible applications as liquid crystals. The cylindrical-type cyclotriphosphazene derivatives (2–5) were characterised by mass and elemental analyses and by Fourier transform infrared spectroscopy (FT-IR), ¹H and ³¹P {¹H} NMR spectroscopies. The thermal and mesomorphic properties were investigated by differential scanning calorimetry and by polarising optical microscopy, respectively. It was found that liquid crystal materials could be obtained from compounds 3 and 4 with alkoxy chains rather than using aromatic ring(s) as mesogens as published previously.     

New N-aryloxy-phthalimide derivatives. Synthesis,physico-chemical properties,and QSPR studies

Starting from N-hydroxyphthalimide 1 and the reactive fluoro- or chloro-nitroaryl derivatives 2, 3 and 4a-e (2-chloro-3,5-dinitropyridine; 3, NBD-chloride; 4a, 1-fluoro-2,4-dinitrobenzene; 4b, picryl chloride; 4c, 4-chloro-3,5-dinitrobenzotrifluoride; 4d, 2-chloro-3,5- dinitrobenzotrifluoride; 4e, 4-chloro-3,5-dinitrobenzoic acid) the corresponding N-(2-nitroaryloxy)-phthalimide derivatives 5a-e, or 6 and 7 were obtained and characterized by IR, UV-Vis ¹H-NMR and ¹³C-NMR spectroscopy. The TLC behavior and the hydrophobicity of these derivatives have been experimentally evaluated by R_M0 parameters (using RP-TLC). The experimental R_M0 parameters were compared with the calculated partition coefficient, log P. A QSPR study was also performed to establish possible correlations between the structure and physical properties (λ_max and R_M0) of compounds 5a-e, 6, and 7.      

Studies on 1-Deoxynojirimycin-Containing Glycans: Synthesis of Novel Disaccharides Related to Lactose,Lactosamine, and Chitobiose

Abstract

Suitably protected 1-deoxynojirimycin (l, 5-dideoxy-l, 5-imino-D-glucitol; DNJ) and its 2-acetamido derivative, i.e., 2, 3, 6-tri-O-benzyl-.N-benzyloxycarbonyl-l, 5-dideoxy-1, 5-imino-D-glucitol (6) and 2-acetamido-3, 6-di-O-benzyl-N-benzyloxycarbonyl-1, 2, 5-trideoxy-l, 5-imino-D-glucitol (14) were each coupled with methyl 2, 3, 4, 6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (15) in the presence of dimethyl(methylthio)-sulfonium triflate (DMTST) as a promoter, to give 16 and 18, which were converted to the novel disaccharides (20, 21) related to lactose and lactosamine. Coupling of 14with methyl 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-l-thio-β-D-glucopyranoside (22) gave achitobiose analog (25). O-(β-D-Galactopyranosyl)-(l→3)-DNJ derivatives (38, 39) and O-(β-D-glucopyranosyl)-(l→3)-DNJ (45) were also synthesized. Conformational analysis of a variety of DNJ derivatives, based on the ¹H NMR data, is also discussed.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Synthesis of New Spirodifuranose Derivatives by Reduction of Stable Spiro-Endoperoxides

Synthesis of three new stable spirodifuranose derivatives (3, 5, and 7), which cannot be obtained easily using ordinary synthetic methods, has been achieved by reduction of 3-O-acetyl and 3-O-methyl derivatives of (4R)-1,2-O-alkylidene-5-eno-4,7-epidioxy-5,6,8-trideoxy-α-D-threo-1,4-furano-4,7-diulo-octoses (1, 4, and 6).     

Synthesis,Characterization, and Spectroscopic Properties of Hexa(4-Bromo-2-Formyl-Phenoxy)Cyclotriphosphazene and Hexa(4-Chloro-2-Formyl-Phenoxy)Cyclotriphosphazene and Fully Substituted Cyclotriphosphazene Derivatives Bearing a Schiff Base at Room Temperature

Abstract

Hexa(4-bromo-2-formyl-phenoxy)cyclotriphosphazene (2) and hexa(4-chloro-2- formyl-phenoxy)cyclotriphosphazene (3) were obtained from the reactions of hexachloro- cyclotriphosphazene (1) with 5-bromosalicylaldehyde and 5-chlorosalicylaldehyde in the presence of (C₂H₅)₃N and K₂CO₃ at room temperature, respectively. The new two organocyclotriphosphazenes bearing formyl groups were reacted with 4-cyano aniline, 2-phenyl aniline, 4-aceto aniline, 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, 2-(4-morpholino)ethyl amine, 4-carboxy aniline, 4-carbomoyl aniline, 2-mercapto aniline, and 5-amino isoquonoline to prepare cyclotriphosphazene derivatives containing a Schiff base at room temperature. However, fully phenoxy-substituted cyclotriphosphazenes containing a Schiff base were isolated from the reactions of the compound 2 and 3 with 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, and 2-(4-morpholino)ethyl amine. The structures of the synthesized compounds were characterized by elemental analysis, IR, and NMR (¹H, ¹³C, ³¹P) spectroscopy. According to the results of the analysis, all synthesized compounds were found to be fully substituted organocyclotriphosphazenes, such as hexa[4-bromo-2-(5-chloro-2-hydroxy-pheyliminomethyl)phenoxy]cyclotriphosphaze (2a). All cyclotriphosphazene derivatives synthesized gave fluorescence emission peaks in range between 300 nm and 410 nm.     

A CONVENIENT SYNTHESIS OF 1,3-DISUBSTITUTED-4-(1′,3′-DITHIOLANE/DITHIANE-2′-YLIDENE)-2-PYRAZOLIN-5-ONES

1, 3 - Disubstituted- 4 - (1′, 3′- dithiolane /dithiane - 2′- ylidene) - 2 -pyrazolin-5-one derivatives like (1a–c), (2a–c), (3a–c) have been obtained by condensation of 2-pyrazolin-5-ones (1), (2) and (3) with carbon disulfide in presence of triethylamine followed by the reaction with 1,2-dibromoethane (4a), 1,3-dibromopropane (4b) and 1,3-dibromobutane (4c) respectively.     

Bisabocurcumin, a new skeleton curcuminoid from the rhizomes of Curcuma longa L.

A new skeleton bisabolane-type sesquiterpene curcuminoid,bisabocurcumin(1),along with 5 known compounds,curcumin(2), demethoxycurcumin(3),bidemethoxycurcumin(4),(1E,4E)-1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-1,4-dien-3-one(5),and (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxy phenyl-)-penta-1,4-dien-3-one(6)were isolated from the rhizomes of Curcuma longa L.Their structures were determined on the basis of spectroscopic analysis.Bisabocurcumin(1) is firstly obtained from nature with a new skeleton combined by a bisabolane-type sesquiterpene and a 1,7-diphenylheptanoid through a C-C bond.     

Synthesis,characterization, antioxidant properties and DFT calculation of some new pyrimidine derivatives

Abstract

In this study, 5-benzoyl-4-(4-(methylthio)phenyl)-6-phenyl-1,2,3,4-tetrahydro-2-thioxo (1), oxo (2) and imino (3) pyrimidine derivatives were prepared via Multicomponent Cyclocondensation Reactions (MCRs). The compounds thiazolo[3,2-a]pyrimidin-3(5H)-one (4) and thiazin-4(6H)-one (5) were obtained via the reaction of compound 1 with bromoacetic acid and 3-bromopropionic acid, respectively. Structures were determined by using FT-IR, ¹H/¹³C NMR and elemental analyses. Also the compounds 4 and 5 were analyzed by X-ray single crystal analysis. All compounds were investigated as corrosion inhibitors using density functional theory (DFT) at the level of B3LYP/6-31G (d, p). According to the calculations, the compound 3 appears to be a good inhibitor for corrosion. On the other hand, total antioxidant properties were measured in vitro by DPPH^?, ABTS^?+ test, hemolysis of phenylhydrazine erythrocytes and metal chelating effect. The results were compared with standard antioxidants such as trolox and α-tocopherol. These data revealed that compounds 1, 2 and 5 are more active with respect to 3 and 4 in scavenging the radicals.