http://www.mdpi.com/section/organic_synthesis http://www.mdpi.com/1420-3049/17/2/1548/ Benzo-condensed four-ring heterocycles, such as benzoxetes 1 and benzothietes 3 represent multi-purpose starting compounds for the preparation of various higher heterocyclic ring systems. The thermal or photochemical valence isomerizations between the benzenoid forms 1,3 and the higher reactive o-quinoid structures 2,4 provide the basis for the synthetic applications. On the other hand, this valence isomerization impedes in particular the generation and storage of 1 because the thermal equilibrium 1 2 is completely on the side of 2. Thus, the number of erroneous or questionable benzoxete structures published to date is surprisingly high. On the contrary, the thermal equilibrium 3 4 is on the side of the benzothietes 3, which makes them easily accessible, especially by different flash vacuum pyrolysis techniques. The present article gives a survey of the preparations of 1 and 2, and tries to stimulate their use in synthetic projects. Naphtho-condensed and higher condensed compounds and compounds with an exocyclic C=O or S=O double bond (lactones, thiolactones, sulfoxides and sulfones) are not covered in this article. http://www.mdpi.com/1420-3049/17/2/1548/ Tue, 07 Feb 2012 00:00:00 CET Molecules 2012-02-07 17 2 Review 1548 1570 1420-3049 Benzoxetes and Benzothietes ¾ Heterocyclic Analogues of Benzocyclobutene 2012-02-07 doi: 10.3390/molecules17021548 Herbert Meier http://www.mdpi.com/1420-3049/17/2/1233/ An efficient synthesis of a highly potent and selective IP (PGI2 receptor) agonist that is not structurally analogous to PGI2 is described. This synthesis is accomplished through the following key steps: Nucleophilic ring-opening of 3-(4-chlorophenyl)-oxazolidin-2-one prepared by a one-pot procedure with 4-piperidinol and selective O-alkylation of 1-(2-(4-chlorophenylamino)ethyl)piperidin-4-ol. The obtained compound is a potent and selective IP agonist displaying a long duration of action. http://www.mdpi.com/1420-3049/17/2/1233/ Tue, 31 Jan 2012 00:00:00 CET Molecules 2012-01-31 17 2 Article 1233 1246 1420-3049 Synthesis of Novel IP Agonists via N-Aminoethyl Cyclic Amines Prepared by Decarboxylative Ring-Opening Reactions 2012-01-31 doi: 10.3390/molecules17021233 Yasuhiro Morita Takeshi Ishigaki Kuniaki Kawamura Ryoji Hayashi Masafumi Isogaya Mika Kitsukawa Mitsuko Miyamoto Masashi Uchida Katsuhiko Iseki http://www.mdpi.com/1420-3049/17/1/1002/ Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity. http://www.mdpi.com/1420-3049/17/1/1002/ Thu, 19 Jan 2012 00:00:00 CET Molecules 2012-01-19 17 1 Article 1002 1024 1420-3049 Antifungal Activity of Eugenol Analogues. Influence of Different Substituents and Studies on Mechanism of Action 2012-01-19 doi: 10.3390/molecules17011002 Héctor Carrasco Marcela Raimondi Laura Svetaz Melina Di Liberto María V. Rodriguez Luis Espinoza Alejandro Madrid Susana Zacchino http://www.mdpi.com/1420-3049/17/1/971/ Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl3 gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH2)2·H2O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a–c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity. http://www.mdpi.com/1420-3049/17/1/971/ Wed, 18 Jan 2012 00:00:00 CET Molecules 2012-01-18 17 1 Article 971 988 1420-3049 Synthesis, Reactions and Antimicrobial Activities of 8-Ethoxycoumarin Derivatives 2012-01-18 doi: 10.3390/molecules17010971 Hany M. Mohamed Ashraf H. F. Abd El-Wahab Kamal A. Ahmed Ahmed M. El-Agrody Ahmed H. Bedair Fathy A. Eid Mostafa M. Khafagy http://www.mdpi.com/1420-3049/17/1/897/ 3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N-methyl-benzimidazole with the cyanoanhydride formed by condensation of cyanoacetic acid with acetic anhydride, leads to the formation of 2-(1,3-diacetyl-2,3-dihydro-1H-benzo[d]-imidazol-2-yl)acetonitrile (5), whose structure was confirmed by X-ray crystallographic analysis. 3-Oxoalkanenitriles 3a,b were observed to undergo condensation reactions with dimethylformamide dimethyl acetal (DMFDMA) to afford the corresponding enamino-nitriles, which react with malononitrile to give 2-dialkylaminopyridines through a pathway involving a new, unexpected rearrangement process. Reactions of 3-oxoalkanenitriles with ethyl acetoacetate were found to afford 2-oxopyran-3-carbonitriles, also occurring via this unexpected rearrangement process. Mechanisms to account for both rearrangement reactions are suggested. In addition, reactions of 3-oxoalkanenitriles with acetylacetone in acetic acid in the presence of ammonium acetate result in the formation of pyridine-3-carbonitriles. Finally, upon heating in the presence of zeolite 3-oxoalkanenitriles 3b,c self-trimerized to produce the corresponding aniline derivatives 23b,c. http://www.mdpi.com/1420-3049/17/1/897/ Wed, 18 Jan 2012 00:00:00 CET Molecules 2012-01-18 17 1 Article 897 909 1420-3049 Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines 2012-01-18 doi: 10.3390/molecules17010897 Hamad M. Al-Matar Khaled D. Khalil Mona F. Al-Kanderi Mohamed H. Elnagdi http://www.mdpi.com/1420-3049/17/1/645/ The phenolic Schiff bases I–VI were synthesized by condensation reactions between various diamines, namely o-dianisidine, o-tolidine and ethylenediamine with vanillin or p-hydroxybenzaldehyde and subsequent reactions between these phenolic Schiff bases and epichlorohydrin to produce new diglycidyl ethers Ia–VIa. The structures of these compounds were confirmed by CHN, FT-IR, 1H-NMR, and 13C-NMR spectroscopy. Their thermotropic liquid crystalline behavior was studied using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). All the diglycidyl ethers prepared exhibit nematic mesophases, except for Va and VIa, which did not show any transition mesophases, but simply flow to liquids. http://www.mdpi.com/1420-3049/17/1/645/ Tue, 10 Jan 2012 00:00:00 CET Molecules 2012-01-10 17 1 Article 645 656 1420-3049 Synthesis of New Liquid Crystalline Diglycidyl Ethers 2012-01-10 doi: 10.3390/molecules17010645 Issam Ahmed Mohammed Rashidah Mohamed Hamidi http://www.mdpi.com/1420-3049/17/1/571/ Solvent-free Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes (aryl aldehydes) using solid NaOH (20 mol%) and applying a grinding technique were studied. Quantitative yields (96–98%) of α,α-bis-(substituted-benzylidene)cycloalkanones were obtained. Aliphatic aldehydes also provided α,α-bis-(substituted-alkylidene)cycloalkanones in very good yields with minor amounts of a-(substituted-alkylidene)cycloalkanones. The catalytic performance of solid NaOH was examined. The molar ratio of NaOH was optimized. The catalytic effect of solid NaOH was also evaluated by comparing it with KOH, NaOAc, and NH4OAc and it turns out that 20 mol% of solid NaOH was good enough to catalyze the Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes. Additionally, the regioselectivity of the Claisen-Schmidt reaction of acetone with benzaldehyde was examined. Using the same method, we could synthesize the corresponding bis-benzylidene- and mono-benzylideneacetone separately in 98% and 96% yields, respectively. http://www.mdpi.com/1420-3049/17/1/571/ Mon, 09 Jan 2012 00:00:00 CET Molecules 2012-01-09 17 1 Article 571 583 1420-3049 A Facile Solvent Free Claisen-Schmidt Reaction: Synthesis of α,α′-bis-(Substituted-benzylidene)cycloalkanones and α,α′-bis-(Substituted-alkylidene)cycloalkanones 2012-01-09 doi: 10.3390/molecules17010571 A. F. M. Motiur Rahman Roushown Ali Yurngdong Jahng Adnan A. Kadi http://www.mdpi.com/1420-3049/17/1/556/ The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF3×OEt2. Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC50 values of five synthesized compounds indicated they were as good antioxidants as Trolox™. http://www.mdpi.com/1420-3049/17/1/556/ Fri, 06 Jan 2012 00:00:00 CET Molecules 2012-01-06 17 1 Article 556 570 1420-3049 Synthesis and DPPH Radical Scavenging Activity of Prenylated Phenol Derivatives 2012-01-06 doi: 10.3390/molecules17010556 Mauricio Osorio Jacqueline Aravena Alejandra Vergara Lautaro Taborga Evelyn Baeza Karen Catalán Cesar González Marcela Carvajal Héctor Carrasco Luis Espinoza http://www.mdpi.com/1420-3049/17/1/511/ A series of benzoxazine monomer supramolecules with different substituted groups on their benzene ring was prepared with a Mannich reaction and characterized by FTIR, 1H-NMR and MS. The obtained products were 3,4-dihydro-3-(2’-hydroxyethylene)-6-methyl-2H-benzoxazine (BM1), 3,4-dihydro-3-(2’-hydroxyethylene)-6-ethyl-2H-benz-oxazine (BM2), and 3,4-dihydro-3-(2’-hydroxyethylene)-6-methoxy-2H-benzoxazine (BM3). The efficiency of alkali metal ion extraction from the products was determined with Pedersen’s technique, while the complexation of the Ce(III) ion was confirmed by the Job’s and the mole ratio methods. The evidence of complex formation between benzoxazine monomers and Ce(III) ions was obtained with FTIR and a computational simulation. Single phase ceria (CeO2) as observed with XRD was successfully prepared by calcinating the Ce(III)-benzoxazine monomer complexes at 600 °C for 2 h. In addition, the geometry of the ceria nanoparticles confirmed by TEM is spherical, with an average diameter of 10‑20 nm. http://www.mdpi.com/1420-3049/17/1/511/ Thu, 05 Jan 2012 00:00:00 CET Molecules 2012-01-05 17 1 Article 511 526 1420-3049 The Effect of Alkali and Ce(III) Ions on the Response Properties of Benzoxazine Supramolecules Prepared via Molecular Assembly 2012-01-05 doi: 10.3390/molecules17010511 Attaphon Kaewvilai Sawittree Rujitanapanich Worawat Wattanathana Chatchai Veranitisagul Songwut Suramitr Nattamon Koonsaeng Apirat Laobuthee http://www.mdpi.com/1420-3049/17/1/463/ Quantum mechanics density functional calculations provided gas-phase electron distributions and proton affinities for several mono- and diaza[5]helicenes; computational results, together with experimental data concerning crystal structures and propensity to methylation of the nitrogen atom(s), provide a basis for designing azahelicene complexes with transition metal ions. http://www.mdpi.com/1420-3049/17/1/463/ Thu, 05 Jan 2012 00:00:00 CET Molecules 2012-01-05 17 1 Article 463 479 1420-3049 Quantum Mechanics Calculations, Basicity and Crystal Structure: The Route to Transition Metal Complexes of Azahelicenes 2012-01-05 doi: 10.3390/molecules17010463 Tullio Caronna Franca Castiglione Antonino Famulari Francesca Fontana Luciana Malpezzi Andrea Mele Daniele Mendola Isabella Natali Sora http://www.mdpi.com/1420-3049/17/1/227/ A new series of 6-substituted-4-methyl-3-(4-arylpiperazin-1-yl)cinnolines 8–10 were synthesized as potential antifungal agents via intramolecular cyclization of the respective 1-(2-arylhydrazono)-1-(4-arylpiperazin-1-yl)propan-2-ones 5–7, mediated by polyphosphoric acid (PPA). The amidrazones themselves were synthesized via direct interaction of the appropriate hydrazonoyl chlorides 4a–d with the corresponding N-substituted piperazine in the presence of triethylamine. The structures of the new prepared compounds were confirmed by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor, antibacterial, and antifungal activity of the newly synthesized compounds was evaluated. http://www.mdpi.com/1420-3049/17/1/227/ Wed, 28 Dec 2011 00:00:00 CET Molecules 2011-12-28 17 1 Article 227 239 1420-3049 Synthesis and Biological Activity of Some 3-(4-(Substituted)-piperazin-1-yl)cinnolines 2011-12-28 doi: 10.3390/molecules17010227 Eman D. Awad Mustafa M. El-Abadelah Suzan Matar Malek A. Zihlif Randa G. Naffa Ehab Q. Al-Momani Mohammad S. Mubarak http://www.mdpi.com/1420-3049/17/1/151/ We describe a protocol developed for the preparation of β-enaminoketones derived from 1,3-cyclohexanediones, and their subsequent reduction by sodium in THF-isopropyl alcohol to afford cis- and trans-3-aminocyclohexanols. http://www.mdpi.com/1420-3049/17/1/151/ Tue, 27 Dec 2011 00:00:00 CET Molecules 2011-12-27 17 1 Article 151 162 1420-3049 Synthesis of cis- and trans-3-Aminocyclohexanols by Reduction of β-Enaminoketones 2011-12-27 doi: 10.3390/molecules17010151 Iris Montoya Balbás Blanca Eda Domínguez Mendoza Mario Fernández-Zertuche Mario Ordoñez Irma Linzaga-Elizalde http://www.mdpi.com/1420-3049/17/1/1/ We report the synthesis and characterization of a variety of trans-3,4-substituted cyclopentanones and the corresponding tosylhydrazone derivatives starting with diethyl fumarate. Protection of the keto group followed by selective monohydrolysis of esters was achieved, resulting in cyclopentanones with different substituents at positions 3 and 4. The tosylhydrazone derivative of each cyclopentanone intermediate was prepared in moderate to good yields. These compounds are potential precursors for functionalized methanofullerenes. http://www.mdpi.com/1420-3049/17/1/1/ Thu, 22 Dec 2011 00:00:00 CET Molecules 2011-12-22 17 1 Article 1 14 1420-3049 Facile Preparation of the Tosylhydrazone Derivatives of a Series of Racemic trans-3,4-Substituted Cyclopentanones 2011-12-22 doi: 10.3390/molecules17010001 Kamal H. Bouhadir Bilal Abou Aleiwe Fares A. Fares http://www.mdpi.com/1420-3049/16/12/10387/ The formation of (E)-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-yl)hydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1) and isatin (or isatin derivatives) 2 at room temperature. The (E)-products could be isomerized into corresponding the (Z)-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4–7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H)-thione (11). The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. http://www.mdpi.com/1420-3049/16/12/10387/ Thu, 15 Dec 2011 00:00:00 CET Molecules 2011-12-15 16 12 Article 10387 10408 1420-3049 Synthesis and Antibacterial Activities of Novel 2,5-Diphenylindolo[2,3-e] Pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines 2011-12-15 doi: 10.3390/molecules161210387 Kamal F.M. Atta Omaima O.M. Farahat Somaya M. Ghobashy Mohamed G. Marei http://www.mdpi.com/1420-3049/16/12/10256/ Irradiation of 1-substituted benzotriazole arylhydrazones 3a–c, 4a,b and 5a,b with a 16 W low pressure mercury arc-lamp (254 nm) for 24 h gave phenanthridin-6-yl-2-phenyldiazines 9a–c, phenanthridin-6(5H)-ones 10a–c, 1-anilinobenzimidazoles 11a–c, 2-aryl-1H-benzimidazoles 12a–c, 1-arylamino-1H-benzimidazol-2-carboxylic acid ethyl esters 14a,b, 1-aryl-1H, 9H-benzo [4,5][1,2,3] triazolo[1,2-a]tetrazole-3-carboxylic acid ethyl esters 16a,b, 1-arylamino-2-benzoylbenzimidazoles 18a,b and 2-benzoylbenzoxazole 21. http://www.mdpi.com/1420-3049/16/12/10256/ Thu, 08 Dec 2011 00:00:00 CET Molecules 2011-12-08 16 12 Article 10256 10268 1420-3049 The Photochemistry of Benzotriazole Derivatives. Part 2: Photolysis of 1-Substituted Benzotriazole Arylhydrazones: New Route to Phenanthridin-6-yl-2-phenyldiazines 2011-12-08 doi: 10.3390/molecules161210256 Nader A. Al-Jalal Maher R. Ibrahim Nouria A. Al-Awadi Mohamed H. Elnagdi http://www.mdpi.com/1420-3049/16/12/10187/ 2-(6,8-Dibromo-2-methylquinazolin-4-yloxy)-acetohydrazide (4) was prepared by the reaction of 6,8-dibromo-2-methylbenzo-[d][1,3]oxazin-4-one with formamide to afford quinazolinone 2, followed by alkylation with ethyl chloroacetate to give the ester 3. Treatment of ester 3 with hydrazine hydrate and benzaldehyde afforded 4 and styryl quinazoline 5. The hydrazide was reacted with triethyl orthoformate, acetylacetone and ethyl acetoacetate and benzaldehyde derivatives to afford the corresponding pyrazoles 6, 7, 9 and hydrazone derivatives 10a-c. Cyclization of hydrazones 10a-c with thioglycolic acid afforded the thiazole derivatives 11a-c. Reaction of the hydrazide with isothiocyanate derivatives afforded hydrazinecarbothioamide derivatives 12a-c, which cyclized to triazole-3-thiols and thiadiazoles 13a-c and 14a-c, respectively. Fusion of the hydrazide with phthalimide afforded the annelated compound 1,2,4-triazolo[3,4-a]isoindol-5-one (15). The newly synthesized compounds were characterized by their spectral (IR, 1H-, 13C-NMR) data. Selected compounds were screened for analgesic activity. http://www.mdpi.com/1420-3049/16/12/10187/ Wed, 07 Dec 2011 00:00:00 CET Molecules 2011-12-07 16 12 Article 10187 10201 1420-3049 Synthesis and Analgesic Activity of Some New Pyrazoles and Triazoles Bearing a 6,8-Dibromo-2-methylquinazoline Moiety 2011-12-07 doi: 10.3390/molecules161210187 Hosam A. Saad Nermen A. Osman Ahmed H. Moustafa http://www.mdpi.com/1420-3049/16/12/9886/ Dimethyl lithosermate B (DLB) is a highly potent natural antioxidant and antidiabetic polyphenol with unknown mode of action. To determine its cellular targets, a photochemical and fluorescent dimethyl lithopermate B probe was designed and efficiently synthesized. The dual-labeled chemical probe for biological application was evaluated by UV and fluorescence to determine its electrochemical absorption and emission properties. This probe could be valuable for investigating ligand-protein interactions and subcellular localization. http://www.mdpi.com/1420-3049/16/12/9886/ Mon, 28 Nov 2011 00:00:00 CET Molecules 2011-11-28 16 12 Article 9886 9899 1420-3049 Synthesis of a Dual-Labeled Probe of Dimethyl Lithospermate B with Photochemical and Fluorescent Properties 2011-11-28 doi: 10.3390/molecules16129886 Eunyoung Lim Jeremy Ricci Mankil Jung http://www.mdpi.com/1420-3049/16/11/9620/ Here we describe the efficient synthesis of alkyl 4-arylsubstituted-6-chloro-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylates and 4-arylsubstituted-4,7-dihydro-furo[3,4-b]pyridine-2,5(1H,3H)-diones via microwave-accelerated reaction of alkyl 4-arylsubstituted-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylates with the appropriate reagents. This eco-friendly approach to these valuable dihydropyridine derivatives does not involve the harsh or highly contaminating conditions common in classical heating and offers a reduction or even elimination of solvent use and recovery, simplification of the work-up procedures, facility of scale up, and low energy consumption, in addition to moderate to higher yields. http://www.mdpi.com/1420-3049/16/11/9620/ Mon, 21 Nov 2011 00:00:00 CET Molecules 2011-11-21 16 11 Article 9620 9635 1420-3049 Eco-Friendly Methodology to Prepare N-Heterocycles Related to Dihydropyridines: Microwave-Assisted Synthesis of Alkyl 4-Arylsubstituted-6-chloro-5-formyl-2-methyl-1,4-dihydropyridine-3-carboxylate and 4-Arylsubstituted-4,7-dihydrofuro[3,4-b]pyridine-2,5(1H,3H)-dione 2011-11-21 doi: 10.3390/molecules16119620 Hortensia Rodríguez Osnieski Martin Margarita Suarez Nazario Martín Fernando Albericio http://www.mdpi.com/1420-3049/16/11/9553/ A copper(I)-mediated one-pot synthesis of 2,3-dihydro-1H-indazole heterocycles has been developed. This synthetic route provides the desired indazoles in moderate to good yields (55%–72%) which are substantially better than those achievable with an alternative two-step reaction sequence. The reaction is tolerant of functionality on the aromatic ring. http://www.mdpi.com/1420-3049/16/11/9553/ Wed, 16 Nov 2011 00:00:00 CET Molecules 2011-11-16 16 11 Article 9553 9561 1420-3049 One-Pot Synthesis of Novel 2,3-Dihydro-1H-indazoles 2011-11-16 doi: 10.3390/molecules16119553 Gary W. Breton Antonio J. Lepore http://www.mdpi.com/1420-3049/16/11/9274/ This review aims to highlight microwave-assisted organic synthesis as applied to medicinal chemistry in the last years, showing some reactions performed under microwave irradiation for the synthesis of distinct structurally molecules of biological interest, divided into the following groups: antineoplastics, anti-inflammatory, antimicrobial agents, antivirals, agents for the treatment of neglected diseases and central nervous system-acting prototypes. http://www.mdpi.com/1420-3049/16/11/9274/ Mon, 07 Nov 2011 00:00:00 CET Molecules 2011-11-07 16 11 Review 9274 9297 1420-3049 MAOS and Medicinal Chemistry: Some Important Examples from the Last Years 2011-11-07 doi: 10.3390/molecules16119274 Nailton M. Nascimento-Júnior Arthur E. Kümmerle Eliezer J. Barreiro Carlos A. M. Fraga http://www.mdpi.com/1420-3049/16/11/9041/ A novel synthesis of triazolo[1,2-a]indazole-1,3,8-trione derivatives by reaction of urazole, dimedone and aromatic aldehydes under conventional heating and microwave irradiation and solvent-free conditions using silica nanoparticles prepared from rice husk ash as catalyst is described. The new method features high yields, multicomponent reactions and environmental friendliness. http://www.mdpi.com/1420-3049/16/11/9041/ Wed, 26 Oct 2011 00:00:00 CEST Molecules 2011-10-26 16 11 Article 9041 9048 1420-3049 One-Pot and Efficient Synthesis of Triazolo[1,2-a]indazole-triones via Reaction of Arylaldehydes with Urazole and Dimedone Catalyzed by Silica Nanoparticles Prepared from Rice Husk 2011-10-26 doi: 10.3390/molecules16119041 Hooshang Hamidian Samieh Fozooni Asadollah Hassankhani Sayed Zia Mohammadi http://www.mdpi.com/1420-3049/16/11/8992/ The reactions of 2-, 3- and 4-aminopyridines with 4,5-dichloro-1,2,3-dithiazol-ium chloride (Appel salt) 4 to give N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)pyridin-X-amines 1a (X = 2), 1g (X = 3) and 1k (X = 4) were optimized with respect to base, temperature and reaction time. Based on these conditions a total of thirteen [(dithiazol-ylidene)amino]azines 1a-m were prepared and fully characterized. http://www.mdpi.com/1420-3049/16/11/8992/ Tue, 25 Oct 2011 00:00:00 CEST Molecules 2011-10-25 16 11 Article 8992 9002 1420-3049 Synthesis of [(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)amino]azines 2011-10-25 doi: 10.3390/molecules16118992 Panayiotis A. Koutentis Maria Koyioni Sophia S. Michaelidou http://www.mdpi.com/1420-3049/16/10/8803/ A microwave assisted method for the synthesis of some typical 4-substituted oxazolidinone chiral auxiliaries used in asymmetric synthesis is reported in this work. Under these conditions, treatment of (S)-phenylalaninol, (S)-phenylglycinol, (S)-valinol and (1S, 2R)-norephedrine with ethyl carbonate or carbon disulfide under the appropriate and specific microwave reaction conditions, led to an efficient synthesis of some oxazolidin-2-ones, oxazolidine-2-thiones and thiazolidine-2-thiones. The methodology reported in this paper provides these chiral auxiliaries with improved yields and a remarkable reduction on the reaction times, particularly in the case of thiazolidine-2-thiones, as compared with the conventional methods. All the auxiliaries prepared here show spectroscopic data in full agreement with those previously reported in the literature. http://www.mdpi.com/1420-3049/16/10/8803/ Thu, 20 Oct 2011 00:00:00 CEST Molecules 2011-10-20 16 10 Article 8803 8814 1420-3049 Microwave-Assisted Improved Synthesis of Oxazolidin-2-ones, Oxazolidine-2-thiones and Thiazolidine-2-thione Chiral Auxiliaries 2011-10-20 doi: 10.3390/molecules16108803 Rosmarbel Morales-Nava Mario Fernández-Zertuche Mario Ordóñez http://www.mdpi.com/1420-3049/16/10/8788/ A series of new 8-arylhydrazono-2-(benzylsulfanyl)-7H-purin-6-ones 6 were synthesized, their electronic absorption spectra in different organic solvents of varying polarities were investigated and their acid dissociation constants in both the ground and excited states were determined spectrophotometrically. The tautomeric structures of such products were elucidated by spectral analyses and correlation of their acid dissociation constants with the Hammett equation. The results indicated that the studied compounds 6 exist predominantly in the hydrazone tautomeric form 6A in both the ground and excited states. http://www.mdpi.com/1420-3049/16/10/8788/ Wed, 19 Oct 2011 00:00:00 CEST Molecules 2011-10-19 16 10 Article 8788 8802 1420-3049 Synthesis, Acidity Constants and Tautomeric Structure of the Diazonium Coupling Products of 2-(Benzylsulfanyl)-7H-purin-6-one in Its Ground and Excited States 2011-10-19 doi: 10.3390/molecules16108788 Elham S. Darwish Mosselhi A. Mosselhi Farag M. Altalbawy Hosam A. Saad http://www.mdpi.com/1420-3049/16/10/8745/ An efficient synthesis of functionalized spiropyrrolizidine oxindoles via a three-component tandem cycloaddition has been achieved. This strategy can provide direct and rapid access to spiropyrrolizidine oxindoles in high yields (up to 99%) with excellent diastereoselectivities (up to 99:1 dr). The features of this procedure are the following: mild reaction conditions, high yields, high diastereoselectivities, one-pot procedure and operational simplicity. http://www.mdpi.com/1420-3049/16/10/8745/ Wed, 19 Oct 2011 00:00:00 CEST Molecules 2011-10-19 16 10 Article 8745 8757 1420-3049 Facile Synthesis of Functionalized Spiropyrrolizidine Oxindoles via a Three-Component Tandem Cycloaddition Reaction 2011-10-19 doi: 10.3390/molecules16108745 Yong-Mei Xie Yu-Qin Yao Hong-Bao Sun Ting-Ting Yan Jie Liu Tai-Ran Kang http://www.mdpi.com/1420-3049/16/10/8733/ In this work, an efficient microwave-assisted methodology for the esterification of unprotected α-amino acids is described. Ionic esterified amino acids were synthesized in satisfactory yields in a facile one-pot solventless protocol from unprotected amino acids and alcohols under acid catalysis (MsOH or p-TsOH) to afford the pure products after a simple work-up procedure. This procedure can also be extended to the preparation of long and short chain alkyl and benzyl esters. http://www.mdpi.com/1420-3049/16/10/8733/ Wed, 19 Oct 2011 00:00:00 CEST Molecules 2011-10-19 16 10 Article 8733 8744 1420-3049 Efficient Microwave-Assisted Synthesis of Ionic Esterified Amino Acids 2011-10-19 doi: 10.3390/molecules16108733 Ricardo Cerón-Camacho Jorge Aburto Luisa E. Montiel Eugenio A. Flores Frisia Cuellar Rafael Martínez-Palou http://www.mdpi.com/1420-3049/16/10/8629/ The Schiff base hydrazone ligand HL was prepared by the condensation reaction of 7-chloro-4-quinoline with o-hydroxyacetophenone. The ligand behaves either as monobasic bidentate or dibasic tridentate and contain ONN coordination sites. This was accounted for be the presence in the ligand of a phenolic azomethine and imine groups. It reacts with Cu(II), Ni(II), Co(II), Mn(II), UO2 (VI) and Fe(II) to form either mono- or binuclear complexes. The ligand and its metal complexes were characterized by elemental analyses, IR, NMR, Mass, and UV-Visible spectra. The magnetic moments and electrical conductance of the complexes were also determined. The Co(II), Ni(II) and UO2 (VI) complexes are mononuclear and coordinated to NO sites of two ligand molecules. The Cu(II) complex has a square-planar geometry distorted towards tetrahedral, the Ni(II) complex is octahedral while the UO2 (VI) complex has its favoured heptacoordination. The Co(II), Mn(II) complexes and also other Ni(II) and Fe(III) complexes, which were obtained in the presence of Li(OH) as deprotonating agent, are binuclear and coordinated via the NNNO sites of two ligand molecules. All the binuclear complexes have octahedral geometries and their magnetic moments are quite low compared to the calculated value for two metal ions complexes and thus antiferromagnetic interactions between the two adjacent metal ions. The ligand HL and metal complexes were tested against a strain of Gram +ve bacteria (Staphylococcus aureus), Gram −ve bacteria (Escherichia coli), and fungi (Candida albicans). The tested compounds exhibited high antibacterial activities. http://www.mdpi.com/1420-3049/16/10/8629/ Thu, 13 Oct 2011 00:00:00 CEST Molecules 2011-10-13 16 10 Article 8629 8645 1420-3049 Synthesis, Characterization and Biological Activities of Cu(II), Co(II), Mn(II), Fe(II), and UO2(VI) Complexes with a New Schiff Base Hydrazone: O-Hydroxyacetophenone-7-chloro-4-quinoline Hydrazone 2011-10-13 doi: 10.3390/molecules16108629 Nora H. Al-Shaalan http://www.mdpi.com/1420-3049/16/10/8353/ In this work, two ligands: 4-(trans-2-Methyl-2-butenoic acid)-2,2'-bipyridine) (L1) and 5-(trans-2-methyl-2-butenoic acid)-1,10-phenanthroline (L2), with the corresponding mixed-ligand heteroleptic Ru(II) complex were synthesized and characterized by FT-IR, 1H-, 13C-NMR spectroscopy and elemental analysis. The influence of the mixed functionalized polypyridyl ruthenium(II) complex on the photophysical and electrochemical properties were investigated and compared to individual single-ligand homoleptic complexes. Interestingly, the mixed-ligand complex formulated as [RuL1L2(NCS)2] exhibits broad and intense metal-to-ligand charge transfer (MLCT) absorption with a high molar extinction coefficient (λmax = 514 nm, ε = 69,700 M−1 cm−1), better than those of individual single-ligand complexes, [Ru(L1)2(NCS)2] and [Ru(L2)2(NCS)2], and a strong photoluminescence intensity ratio in the red region at λem = 686 nm. The electrochemical properties of the complex indicated that the redox processes are ligand-based. http://www.mdpi.com/1420-3049/16/10/8353/ Fri, 30 Sep 2011 00:00:00 CEST Molecules 2011-09-30 16 10 Article 8353 8367 1420-3049 Synthesis, Photophysical and Electrochemical Properties of a Mixed Bipyridyl-Phenanthrolyl Ligand Ru(II) Heteroleptic Complex Having trans-2-Methyl-2-butenoic Acid Functionalities 2011-09-30 doi: 10.3390/molecules16108353 Adewale O. Adeloye http://www.mdpi.com/1420-3049/16/9/7736/ A series of 3,5-disubstituted pyrazole-1-carboxamides were obtained by treatment of chalcones with semicarbazide hydrochloride in dioxane containing sodium acetate/acetic acid as a buffer solution. N-acetyl derivatives of pyrazole-1-carboxamides were isolated in good yields either by treatment of the carboxamide derivatives with acetic anhydride or refluxing chalcones with semicarbazide in ethanol containing few drops of acetic acid to give the corresponding hydrazones. Subsequent treatment of hydrazones with acetic anhydride gave the desired N-acetyl pyrazole-1-carboxamides derivatives. When chalcones were refluxed with dioxane containing few drops of acetic acid, 4,5-dihydropyrazole-1-carboxamides were isolated, which were subsequently oxidized using 5% sodium hypochlorite in dioxane to afford pyrazole-1-carboxamides. The structures of isolated compounds were confirmed by elemental analyses and spectral methods. The isolated compounds were tested for their antimicrobial activities. http://www.mdpi.com/1420-3049/16/9/7736/ Fri, 09 Sep 2011 00:00:00 CEST Molecules 2011-09-09 16 9 Article 7736 7745 1420-3049 Synthesis and in Vitro Antimicrobial Activity of Some Pyrazolyl-1-carboxamide Derivatives 2011-09-09 doi: 10.3390/molecules16097736 Essam Mohamed Sharshira Nagwa Mohamed Mahrous Hamada http://www.mdpi.com/1420-3049/16/9/7377/ A practical protocol for the preparation of (5Z)-2-alkylthio-5-arylmethylene-1-methyl-1,5-dihydro-4H-imidazol-4-one derivatives is reported. The new compounds were obtained in good yield and stereoselectivity in two steps, namely a solvent-free Knoevenagel condensation under microwave irradiation, followed by an S-alkylation reaction with various halogenoalkanes. http://www.mdpi.com/1420-3049/16/9/7377/ Tue, 30 Aug 2011 00:00:00 CEST Molecules 2011-08-30 16 9 Article 7377 7390 1420-3049 A Practical Approach to New (5Z) 2-Alkylthio-5-arylmethylene-1-methyl-1,5-dihydro-4H-imidazol-4-one Derivatives 2011-08-30 doi: 10.3390/molecules16097377 Khadidja Bourahla Ludovic Paquin Olivier Lozach Laurent Meijer François Carreaux Jean Pierre Bazureau http://www.mdpi.com/1420-3049/16/9/7256/ Graphite oxide and graphene oxides have been used as solid catalysts for the synthesis of 5,5-dialkyldipyrromethanes and calix[4]pyrroles in organic and aqueous solutions at room temperature. http://www.mdpi.com/1420-3049/16/9/7256/ Thu, 25 Aug 2011 00:00:00 CEST Molecules 2011-08-25 16 9 Article 7256 7266 1420-3049 Use of Graphite Oxide and Graphene Oxide as Catalysts in the Synthesis of Dipyrromethane and Calix[4]pyrrole 2011-08-25 doi: 10.3390/molecules16097256 Shive Murat Singh Chauhan Sweta Mishra http://www.mdpi.com/1420-3049/16/8/7081/ 5-Aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines 1 were used as precursors for the preparation of a new series of 5-aryl-8-phenylpyrazolo[1,5-c]-1,2,4- triazolo[4,3-a]pyrimidines 2. The reactions of 2 with certain electrophilic reagents gave the respective 6-substituted derivatives 3-5 rather than the 7-isomeric products. Formylation of the key compounds 1 with ethyl formate yielded the formyl derivatives 6. Furthermore, boiling of compounds 1 with acetic acid afforded 7-acetylhydrazino-5-aryl-2-phenylpyrazolo[1,5-c]pyrimidines 7. Bromination of 7 yielded the dibromo- derivatives 8, while their iodination and nitration gave the monosubstituted derivatives 9 and 10, respectively. Also, treatment of 1 with boiling acetic anhydride yielded the triacetyl derivatives 11. The structure of synthesized products was confirmed by elemental analyses, IR, 1H NMR and MS spectra. http://www.mdpi.com/1420-3049/16/8/7081/ Thu, 18 Aug 2011 00:00:00 CEST Molecules 2011-08-18 16 8 Article 7081 7096 1420-3049 Synthesis and Electrophilic Substitutions of Novel Pyrazolo[1,5-c]-1,2,4-triazolo[4,3-a]pyrimidines 2011-08-18 doi: 10.3390/molecules16087081 Kamal F.M. Atta http://www.mdpi.com/1420-3049/16/8/7043/ A highly specific and sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA）was developed for the first time for the detection of chrysoidine, a dye banned in soybean milk film. Two haptens with different spacer arms were synthesized to produce antibodies. Both homologous and heterologous immunoassay formats were compared to enhance the icELISA sensitivity. The heterologous icELISA exhibited better performance, with an IC50 (50% inhibitory concentration) of 0.33 ng/mL, a limit of detection (LOD, 10% inhibitory concentration) of 0.04 ng/mL, and a limit of quantitation (LOQ, 20%–80% inhibitory concentration) from 0.09 to 4.9 ng/mL. The developed icELISA was high sensitive and specific, and was applied to determine chrysoidine in fortified soybean milk film samples. The results were in good agreement with that obtained by high-performance liquid chromatography (HPLC) analyses. http://www.mdpi.com/1420-3049/16/8/7043/ Wed, 17 Aug 2011 00:00:00 CEST Molecules 2011-08-17 16 8 Article 7043 7057 1420-3049 Development of a Highly Sensitive and Specific Immunoassay for Determining Chrysoidine, A Banned Dye, in Soybean Milk Film 2011-08-17 doi: 10.3390/molecules16087043 Hongtao Lei Jin Liu Lijun Song Yudong Shen Simon A. Haughey Haoxian Guo Jinyi Yang Zhenlin Xu Yueming Jiang Yuanming Sun http://www.mdpi.com/1420-3049/16/8/7019/ A series of different 1-monosubstituted and 1,1-disubstituted 1,2,3,4-tetrahydro-isoquinolines was synthesized in high yields from different ketoamides. We have developed a convenient method for the synthesis of disubstituted derivatives by interaction of ketoamides with organomagnesium compounds, followed by cyclization in the presence of catalytic amounts of p-toluenesulfonic acid (PTSA). A number of substituents at the C-1 in the isoquinoline skeleton were introduced varying either carboxylic acid or organomagnesium compound. Some of the obtained 1,1-dialkyl-1,2,3,4-tetrahydro-isoquinolines possess contractile activity against guinea pig’s gastric smooth muscle preparations. http://www.mdpi.com/1420-3049/16/8/7019/ Tue, 16 Aug 2011 00:00:00 CEST Molecules 2011-08-16 16 8 Article 7019 7042 1420-3049 Synthesis and Contractile Activity of Substituted 1,2,3,4-Tetrahydroisoquinolines 2011-08-16 doi: 10.3390/molecules16087019 Iliyan Ivanov Stoyanka Nikolova Dimo Aladjov Iliyana Stefanova Plamen Zagorchev http://www.mdpi.com/1420-3049/16/8/6858/ Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). In recent years our research group has been engaged in the stucture-function study of this enzyme and in the development of some three-dimensional pharmacophore models which have led to the identification of a large series of potent HIV-1 integrase strand-transfer inhibitors (INSTIs) bearing an indole core. To gain a better understanding of the structure-activity relationships (SARs), herein we report the design and microwave-assisted synthesis of a novel series of 1-H-benzylindole derivatives. http://www.mdpi.com/1420-3049/16/8/6858/ Thu, 11 Aug 2011 00:00:00 CEST Molecules 2011-08-11 16 8 Article 6858 6870 1420-3049 Microwave Assisted Organic Synthesis (MAOS) of Small Molecules as Potential HIV-1 Integrase Inhibitors 2011-08-11 doi: 10.3390/molecules16086858 Stefania Ferro Sara De Grazia Laura De Luca Rosaria Gitto Caterina Elisa Faliti Zeger Debyzer Alba Chimirri http://www.mdpi.com/1420-3049/16/8/6833/ New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one (4), 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol-2(3H)-one (5), 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N-phenylhydrazinecarbothioamide (7), 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one (8) and 7-[(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methoxy]-2H-chromen-2-one (9) were prepared starting from the natural compound umbelliferone (1). The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR). http://www.mdpi.com/1420-3049/16/8/6833/ Wed, 10 Aug 2011 00:00:00 CEST Molecules 2011-08-10 16 8 Article 6833 6843 1420-3049 The Use of Umbelliferone in the Synthesis of New Heterocyclic Compounds 2011-08-10 doi: 10.3390/molecules16086833 Ahmed A. Al-Amiery Ahmed Y. Musa Abdul Amir H. Kadhum Abu Bakar Mohamad http://www.mdpi.com/1420-3049/16/8/6741/ A conformational search of 5,12-dihydro-5,12-ethanonaphthacene-13-carbaldehyde predicted the presence of twelve conformations. The geometry of the twelve conformations established at the B3LYP/6-31G* level showed only six unique ones. Vibrational frequencies were calculated at the B3LYP/6-31G* level. The calculated vibrational frequencies enabled us to interpret the appearance of two bands corresponding to the C=O stretching mode of 5,12-dihydro-5,12-ethanonaphthacene-13-carbaldehyde. The first band corresponded to the 5,12-dihydro-5,12-ethanonaphthacene-13-carbaldehyde structure where the aldehyde group O atom was above the benzene or naphthalene ring. The other band was due to the O atom of the aldehyde group pointing out of the benzene or naphthalene ring. http://www.mdpi.com/1420-3049/16/8/6741/ Tue, 09 Aug 2011 00:00:00 CEST Molecules 2011-08-09 16 8 Article 6741 6746 1420-3049 Computational and Spectral Investigation of 5,12-Dihydro-5,12-ethanonaphthacene-13-carbaldehyde 2011-08-09 doi: 10.3390/molecules16086741 Usama Karama Adel A. El-Azhary Abdulrahman I. Almansour Abdulla A. Al-Kahtani Turki M. Al-Turki Mohammed H. Jaafar http://www.mdpi.com/1420-3049/16/8/6549/ A novel series of 7,7-diphenyl-1,2-dihydroimidazo[2,1-c][1,2,4]triazin-6(7H)-one 6a–h, were easily prepared via reactions of novel 2-hydrazinyl-4,4-diphenyl-1H-imidazol-5(4H)-one (2) with hydrazonoyl halides 3a–h. In addition, we also examined the reaction of compound 2 with commercially available active methylene compounds to afford new pyrazoles containing an imidazolone moiety, expected to be biologically active. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H-NMR and mass spectral data. The antifungal and antibacterial activities of the newly synthesized compounds were evaluated. http://www.mdpi.com/1420-3049/16/8/6549/ Thu, 04 Aug 2011 00:00:00 CEST Molecules 2011-08-04 16 8 Article 6549 6560 1420-3049 Synthesis and Antimicrobial Activity of Some New Pyrazoles, Fused Pyrazolo[3,4-d]-pyrimidine and 1,2-Dihydroimidazo-[2,1-c][1,2,4]triazin-6-one Derivatives 2011-08-04 doi: 10.3390/molecules16086549 Sobhi Mohamed Gomha Huwaida M.E. Hassaneen http://www.mdpi.com/1420-3049/16/8/6502/ A series of new bis(heterocycles) featuring thieno[2,3-b]thiophene rings was synthesized in a combinatorial manner. Intramolecular cyclization of enaminone derivatives with appropriate N-nucleophiles afforded the target compounds. All compounds were characterized by 1H-, 13C-NMR, GCMS, IR, and UV-Vis spectrometry. These compounds represent a new class of sulfur- and nitrogen-containing heterocycles that should also be of interest as new materials. http://www.mdpi.com/1420-3049/16/8/6502/ Wed, 03 Aug 2011 00:00:00 CEST Molecules 2011-08-03 16 8 Article 6502 6511 1420-3049 1,1’-(3-Methyl-4-phenylthieno[2,3-b]thiophene-2,5-diyl)diethanone as a Building Block in Heterocyclic Synthesis. Novel Synthesis of Some Pyrazole and Pyrimidine Derivatives 2011-08-03 doi: 10.3390/molecules16086502 Yahia Nasser Mabkhot Abdullah Mohammed Al-Majid Assem Barakat Saeed Alshahrani Yamin Siddiqui http://www.mdpi.com/1420-3049/16/8/6470/ A catalytic system consisting of the ruthenium(II) complex [Ru(η3-2-C3H4Me)(CO)(dppf)][SbF6] (dppf = 1,1’-bis(diphenylphosphino)ferrocene) and trifluoroacetic acid has been used to promote the coupling of secondary propargylic alcohols with 6-chloro-4-hydroxychromen-2-one. The reactions afforded unusual 2-methylene-2,3-dihydrofuro[3,2-c]chromen-2-ones in good yields. http://www.mdpi.com/1420-3049/16/8/6470/ Tue, 02 Aug 2011 00:00:00 CEST Molecules 2011-08-02 16 8 Article 6470 6480 1420-3049 Expeditious Entry to Novel 2-Methylene-2,3-dihydrofuro[3,2-c] chromen-2-ones from 6-Chloro-4-hydroxychromen-2-one and Propargylic Alcohols 2011-08-02 doi: 10.3390/molecules16086470 Noel Nebra Alba E. Díaz-Álvarez Josefina Díez Victorio Cadierno http://www.mdpi.com/1420-3049/16/7/6129/ Knoevenagel condensation of 2-(benzothiazol-2-ylthio) acetonitrile (2) with either furan-2-carbaldehyde or thiophene-2-carbaldehydes leads to E-isomers 4a–b exclusively, while the condensation of the compound 2 with benzaldehyde or para-substituted benzaldehydes with an electron-donating group afforded E/Z mixtures 4c–e with preferentially formation of the E-isomer. Condensation of furan-2-carbaldehyde (3a) with either 1-(benzothiazol-2'-ylthio) propan-2-one (5) or 2-(2'-oxo propylthio)-3-phenyl-quinazolin-4(3H)-one (9) leads exclusively to the Z-isomers of 6 and 10, respectively. The structures of the newly synthesized compounds were elucidated by elemental analyses, 1H-NMR and 13C-NMR spectra, COSY, HSQC, HMBC, NOE, MS and X-ray crystallographic investigations. http://www.mdpi.com/1420-3049/16/7/6129/ Wed, 20 Jul 2011 00:00:00 CEST Molecules 2011-07-20 16 7 Article 6129 6147 1420-3049 Synthesis and E/Z Configuration Determination of Novel Derivatives of 3-Aryl-2-(benzothiazol-2'-ylthio) Acrylonitrile, 3-(Benzothiazol-2'-ylthio)-4-(furan-2''-yl)-3-buten-2-one and 2-(1-(Furan-2''-yl)-3'-oxobut-1''-en-2-ylthio)-3-phenylquinazolin-4(3H)-one 2011-07-20 doi: 10.3390/molecules16076129 Fatima Al-Omran Rafat M. Mohareb Adel Abou El-Khair http://www.mdpi.com/1420-3049/16/7/5886/ Friedel-Craft acylation at 100 °C of 2,5,9,9-tetramethyl-6,7,8,9-tetrahydro-5H-benzocycloheptene [ar-himachalene (1)], a sesquiterpenic hydrocarbon obtained by catalytic dehydrogenation of α-, β- and γ-himachalenes, produces a mixture of two compounds: (3,5,5,9-tetramethyl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-ethanone (2, in 69% yield), with a conserved reactant backbone, and 3, with a different skeleton, in 21% yield. The crystal structure of 3 reveals it to be 1-(8-ethyl-8-hydroperoxy-3,5,5-trimethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-ethanone. In this compound O-H…O bonds form dimers. These hydrogen-bonds, in conjunction with weaker C-H…O interactions, form a more extended supramolecular arrangement in the crystal. http://www.mdpi.com/1420-3049/16/7/5886/ Thu, 14 Jul 2011 00:00:00 CEST Molecules 2011-07-14 16 7 Article 5886 5895 1420-3049 Friedel-Craft Acylation of ar-Himachalene: Synthesis of Acyl-ar-Himachalene and a New Acyl-Hydroperoxide 2011-07-14 doi: 10.3390/molecules16075886 Issam Hossini Mohamed Anoir Harrad Mustapha Ait Ali Larbi El Firdoussi Abdallah Karim Pedro Valerga M. Carmen Puerta http://www.mdpi.com/1420-3049/16/7/5682/ A series of S-glycosyl and S-alkyl derivatives of 4-amino-3-mercapto-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (1) were synthesized using different halo compounds such as preacetylated sugar bromide, 4-bromobutylacetate, 2-acetoxyethoxy-methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, allyl bromide, propargyl bromide, phthalic and succinic acids in POCl3. The structures of the synthesized compounds have been deduced from their elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR) data. Some of the synthesized compounds were screened as anticancer agents. Significant anticancer activities were observed in vitro for some members of the series, and compounds 4-Amino-3-(3-hydroxypropylthio)-6-(2-(2-thienyl)vinyl)-1,2,4-triazin-5(4H)-one (12) and 3-(4-Oxo-3-(2-(2-thienyl)vinyl)-4H-[1,3,4]thiadiazolo-[2,3-c][1,2,4]tr-iazin-7-yl)propanoic acid (18) are active cytotoxic agents against different cancer cell lines. http://www.mdpi.com/1420-3049/16/7/5682/ Mon, 04 Jul 2011 00:00:00 CEST Molecules 2011-07-04 16 7 Article 5682 5700 1420-3049 Synthesis and Anticancer Activity of Some New S-Glycosyl and S-Alkyl 1,2,4-Triazinone Derivatives 2011-07-04 doi: 10.3390/molecules16075682 Hosam A. Saad Ahmed H. Moustafa http://www.mdpi.com/1420-3049/16/7/5665/ Treatment of substituted benzyl alcohols with tosyl chloride resulted in the formation of the corresponding chlorides, not the usual tosylates. A series of experiments demonstrated that it was possible to predict whether chlorination or tosylation would occur for substituted benzyl alcohols and pyridine methanols. Treatment of electron withdrawing group-substituted benzyl alcohols with tosyl chloride gave the corresponding chlorides in moderate yields under mild conditions, which provided a simple way to directly prepare chlorides from alcohols. http://www.mdpi.com/1420-3049/16/7/5665/ Fri, 01 Jul 2011 00:00:00 CEST Molecules 2011-07-01 16 7 Article 5665 5673 1420-3049 Treatment of Alcohols with Tosyl Chloride Does Not always Lead to the Formation of Tosylates 2011-07-01 doi: 10.3390/molecules16075665 Rui Ding Yong He Xiao Wang Jingli Xu Yurong Chen Man Feng Chuanmin Qi http://www.mdpi.com/1420-3049/16/7/5591/ An indirect competitive enzyme-linked immunosorbent assay (icELISA) with enhanced specificity for melamine in milk was developed. Three haptens of melamine with different spacer-arms were used to prepare different plate coating antigens. It was found that the icELISA show best sensitivity and specificity to melamine when using the coating antigen prepared by coupling 3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylthio)propanoic acid (Hapten C) with ovalbumin (OVA). The 50% inhibitory concentration (IC50) value was 35.4 ng·mL−1, the limit of detection (LOD) was 8.9 ng·mL−1 and the detectable working range (20–80% inhibitory concentration) was from 14.9 to 108.5 ng·mL−1, respectively. Compared to the ELISA results previously reported, the developed icELISA in the present study showed a much lower cross-reactivity to cyromazine, a fly-killing insecticide widely used in vegetables and stables. Recoveries obtained from milk samples in this study were in agreement with those obtained using the HPLC-MS method, indicating the detection performance of the icELISA could meet the requirement of the residue limit set by the Codex Alimentarius Commission. Therefore, the developed immunoassay can be applied for the analysis of melamine presented in milk. http://www.mdpi.com/1420-3049/16/7/5591/ Thu, 30 Jun 2011 00:00:00 CEST Molecules 2011-06-30 16 7 Article 5591 5603 1420-3049 Development of a Specifically Enhanced Enzyme-Linked Immunosorbent Assay for the Detection of Melamine in Milk 2011-06-30 doi: 10.3390/molecules16075591 Hongtao Lei Rui Su Simon A. Haughey Qiang Wang Zhenlin Xu Jinyi Yang Yudong Shen Hong Wang Yueming Jiang Yuanming Sun http://www.mdpi.com/1420-3049/16/7/5527/ 2-(Alkyl-1-yl)-1H-imidazol-5(4H)-ones 5a–n were synthesized via nucleophilic substitution of the methylsulfanyl group of the corresponding 2-(methylthio)-1H-imidazol-5(4H)-ones 3a–c with suitably substituted secondary amines. The starting 2-thioxo- imidazolidin-4-ones 2a,2b were prepared by condensation of thiohydantoin and benzo[b]-thiophene-3-carbaldehyde or benzofuran-3-carbaldehyde under microwave irracdiation (MW) conditions. 2-Methylthio derivatives 3a–c were prepared by treatment of 2a–b with methyl iodide in the presence of aqueous sodium hydroxide. http://www.mdpi.com/1420-3049/16/7/5527/ Wed, 29 Jun 2011 00:00:00 CEST Molecules 2011-06-29 16 7 Article 5527 5537 1420-3049 Microwave Assisted Synthesis of Novel Functionalized Hydantoin Derivatives and Their Conversion to 5-(Z) Arylidene-4H-imidazoles 2011-06-29 doi: 10.3390/molecules16075527 Sukanta Kamila Haribabu Ankati Edward R. Biehl http://www.mdpi.com/1420-3049/16/7/5496/ 2-Amino-5-(2-aryl-2H-1,2,3-triazol-4-yl)-1,3,4-thiadiazoles 2-4 have been synthesized by the reaction of 2-aryl-2H-1,2,3-triazole-4-carboxylic acids 1 with thiosemicarbazide. Their reaction with phenacyl (p-substituted phenacyl) bromides led to formation of the respective 6-aryl-2-(2-aryl-2H-1,2,3-triazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazoles 5. Reactivity of the latter fused ring towards reaction with different electrophilic reagents afforded the corresponding 5-substituted derivatives 6-8. The structure of the above compounds was confirmed from their spectral characteristics. Some of these compounds were found to possess slight to moderate activity against the microorganisms Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and Escherichia coli. http://www.mdpi.com/1420-3049/16/7/5496/ Tue, 28 Jun 2011 00:00:00 CEST Molecules 2011-06-28 16 7 Article 5496 5506 1420-3049 Synthesis and Antibacterial Activities of Novel Imidazo[2,1-b]-1,3,4-thiadiazoles 2011-06-28 doi: 10.3390/molecules16075496 Kamal F. M. Atta Omaima O.M. Farahat Alaa Z. A. Ahmed Mohamed G. Marei http://www.mdpi.com/1420-3049/16/7/5362/ A novel bis-iodurated polyether compound, based on an unprecedented tetra-THF backbone, has been isolated as a trace by-product of the oxidation of squalene with the catalytic system RuO2(cat.)/NaIO4. The double erythro configuration of the central portion of the molecule furnishes the first indirect support of the previously postulated pathway operating in the oxidative pentacyclization of the isoprenoid substrate. A bidirectional double oxidative bis-cyclization is invoked to explain the formation of this compound. The isolated substance was successfully subjected to a double rearrangement-ring expansion to give a novel bis-THF-bis-THP compound. http://www.mdpi.com/1420-3049/16/7/5362/ Mon, 27 Jun 2011 00:00:00 CEST Molecules 2011-06-27 16 7 Article 5362 5373 1420-3049 Isolation of a Bis-Iodurated Tetra-THF as a Trace Product from the Oxidation of Squalene with RuO4 and Its Double Ring Expansion to a Novel bis-THF-bis-THP Compound 2011-06-27 doi: 10.3390/molecules16075362 Vincenzo Piccialli Sabrina Zaccaria Roberto Centore Angela Tuzi Nicola Borbone Giorgia Oliviero http://www.mdpi.com/1420-3049/16/6/5241/ N-containing heteroaromatics are important substructures found in numerous natural or synthetic alkaloids. The diversity of the structures encountered, as well as their biological and pharmaceutical relevance, have motivated research aimed at the development of new economical, efficient and selective synthetic strategies to access these compounds. Over more than 100 years of research, this hot topic has resulted in numerous so-called “classical synthetic methods” that have really contributed to this important area. However, when the selective synthesis of highly functional heteroaromatics like indoles, quinolones, indoxyls, etc. is considered these methods remain limited. Recently transition metal-catalysed (TM-catalysed) procedures for the synthesis of such compounds and further transformations, have been developed providing increased tolerance toward functional groups and leading generally to higher reaction yields. Many of these methods have proven to be the most powerful and are currently applied in target- or diversity-oriented syntheses. This review article aims at reporting the recent developments devoted to this important area, focusing on the use of heterogeneous catalysed procedures that include either the formation of the heterocyclic ring towards the nuclei or their transformations to highly substituted compounds. http://www.mdpi.com/1420-3049/16/6/5241/ Thu, 23 Jun 2011 00:00:00 CEST Molecules 2011-06-23 16 6 Review 5241 5267 1420-3049 Recent Advances in the Synthesis of N-Containing Heteroaromatics via Heterogeneously Transition Metal Catalysed Cross-Coupling Reactions 2011-06-23 doi: 10.3390/molecules16065241 Laurent Djakovitch Nelly Batail Marie Genelot http://www.mdpi.com/1420-3049/16/6/5228/ Two basic and simple synthetic routes for mono- and bis-maleimide bearing 1,4,7-triazacyclononane-N,N’,N’’-triacetic acid (NOTA) chelators as new bifunctional chelators are described. The syntheses are characterized by their simplicity and short reaction times, as well as practical purification methods and acceptable to very good chemical yields. The usefulness of these two synthetic pathways is demonstrated by the preparation of a set of mono- and bis-maleimide functionalized NOTA derivatives. In conclusion, these two methods can easily be expanded to the syntheses of further tailored maleimide-NOTA chelators for diverse applications. http://www.mdpi.com/1420-3049/16/6/5228/ Wed, 22 Jun 2011 00:00:00 CEST Molecules 2011-06-22 16 6 Article 5228 5240 1420-3049 Maleimido-Functionalized NOTA Derivatives as Bifunctional Chelators for Site-Specific Radiolabeling 2011-06-22 doi: 10.3390/molecules16065228 Christian Förster Maik Schubert Hans-Jürgen Pietzsch Jörg Steinbach