Studies on Enethiol-Thione Equilibrium of Some 1,5-Disubstituted 2,4-Dithiobiurets

Eaethiol contents of 1, 5-diphenyl 2, 4-dithiobiuret (DP); 1, 5-di-p-tolyl 2, 4-dithiobiuret (DPT); 1-phenyl 5-p-tolyl 2, 4-dithiobiuret (PPT); 1-phenyl 5-o-tolyl 2, 4-dithiobivret (POT); and 1-methyl 5-p-tolyl 2, 4-dithiobiuret (MPT) have been studied by alkali titration method in methanol and by spectrophotometric method in different solvents of varying polarities, ranging from pyridine (Z, 64.0) to methanol (Z, 83.6). Free energy of tautomerisation has been calculated. The effect of substituents on the phenyl group on enethiol contents have been studied. It has been observed that temperature has no effect on enethiol-thione equilibrium.     

Biomimetic synthesis of 4-acetylbenzoxazolin-2(3H)-one isolated from Zea mays

4-Acetylbenzoxazolin-2(3H)-one has been prepared biomimetically during attempts to synthesize the hemiacetalic hydroxamic acid 5-acetyl-2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one by the immediate degradation of this unstable compound generated as an intermediate. Thus, 4-acetylbenzoxazolin-2(3H)-one recently isolated from Zea mays kernels, and similar to other benzoxazolin-2(3H)-ones known from plant sources, is assumed to have originated from the degradation of natural 5-acetyl-2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one which in turn could have been enzymatically released by a β-glucosidase from the corresponding 2-β-D-glucoside.     

The vilsmeier reaction in the synthesis of 3-substituted [1]benzopyrano[4,3-b]pyridin-5-ones. An unusual pyridine ring closure

Starting from 4-chlorocoumarin-3-carbaldehyde (1) and Wittig phosphoranes 2a-d the title compounds 6a-c have been synthesized via a four-step sequence. The intermediate 4-alkylamino-3-vinylcoumarins 5a-k have been prepared by the reaction of 4-chloro-3-vinylcoumarins 3a-d with primary amines 4a-h . The coumarin derivatives 5 (except 5k ) underwent an unusual pyridine ring closure under Vilsmeier conditions to form the benzopyrano[4,3-b]pyridines 6 . When the aminoaldehydes 7 were treated with the Wittig reagent 2b the fused N-alkyl-2 (1H) -pyridinones 8 have been obtained as expected.     

Purine nucleosides XXVIII. The synthesis of 7-(2′-deoxy-α- and β-d-ribofuranosyl)purines from 2′-deoxyribofuranosylimidazoles. Preparation of the 2′-deoxy derivative of the nucleoside from pseudovitamin B12 factor G

The synthesis of 1-(2′-deoxyribofuranosyl)imidazoles have been achieved for the first time via the fusion method of glycosidation. 4-Amino-5-carboxamido-1-(2′-deoxy-α-D-ribofuranosyl)-imidazole ( 8 ) and 4-amino-5-carboxamido-1-(2′-deoxy-β-D-ribofuranosyl)imidazole ( 10 ) have been obtained and their structures established by spectroscopic methods. The first examples of 7-(2′-deoxyglycosyl)purines [7-(2′-deoxy-α-D-ribofuranosyl)hypoxanthine ( 6 ) and 7-(2′-deoxy-β-D-ribofuranosyl)hypoxanthine ( 11 )] have been obtained from the requisite 2′-deoxyribofuranosylimidazoles. The preparation of 6 has furnished the 2′-deoxy derivative (α-configuration) of the nucleoside from pseudovitamin B₁₂ Factor G, which constitutes the first 2′-deoxy derivative of any nucleoside isolated from the various naturally occurring pseudovitamin B₁₂ factors.     

Synthesis of cis and trans Whisky and Cognac lactones by the regiocontrolled alkylation of 2-(trimethylsiloxy)furan

The racemic cis- and trans-5-butyltetrahydro-4-methylfuran-2-ones ( = whisky lactones) and their higher homologues tetrahydro-4-methyl-5-pentylfuran-2-ones ( = cognac lactones) have been prepared in 2–3 steps from 2-(trimethylsiloxy)furan. Regioselective alkylation of the latter afforded the 5-butyl- and 5-pentylfuran-2(5H)-ones which served as precursors for the stereocontrolled construction of either diastereoisomer of the beverage lactones. The structure and tautomerization of the diazomethane adducts of these 5-alkylfuran-2(5H)-ones are also described.     

Synthesis and Absolute Configuration of Naturally Occurring Dactyloxene-B and -C

Natural (+)-dactyloxene-B (12) and -C (13) have been synthesized starting from (+)-trans-2, 5, 6-trimethyl-l-cyclohexene-l-carbaldehyde (1) which is shown to have the (5S, 6R)-configuration by chemical correlation with (+)-(2R, 3S, 6S)-2, 3, 6-trimethylcyclohexanone. The absolute configurations are therefore (2R, 5R, 9S, 10R) for (+)-dactyloxene-B and (2R, 5S, 9S, 10R) for (+)-dactyloxene-C.     

Pyridazines. XV. Synthesis of 6-aryl-5-amino-3(2H)-pyridazinones as potential platelet aggregation inhibitors

Several 3(2H)-pyridazinones with amino groups at the 5-position of the pyridazine nucleus have been prepared. The 6-aryl-5-halo-3(2H)-pyridazinones obtained from mucochloric and mucobromic acid lead to the corresponding 5-alkylamino-3(2H)-pyridazinones, which were tested as platelet aggregation inhibitors.     

Synthesis of 2-substituted benzimidazole-5-carbamates as potential antifilarial agents

A number of 2,5-disubstituted benzimidazoles have been prepared from 2-benzyl-5-nitrobenzimidazole ( 5 ) and 2-p-fluorobenzyl-5-nitrobenzimidazole ( 6 ), and evaluated as potential antifilarial agents. None of the compounds prepared in this study have demonstrated any significant antifilarial activity.     

Synthesis of novel pyrrolidin-2-ones: γ-aminobutyric acid cyclic analogues

Some new N-substituted pyrrolidin-2-ones, cyclic analogues of baclofen and of 3-(5-methoxybenzo-[b]furan-2-yl)-γ-aminobutyric acid, have been prepared and characterized, starting from 4-(4-chlorophenyl)-pyrrolidin-2-one and 4-(5-methoxybenzo[b]furan-2-yl)pyrrolidin-2-one.     

Synthesis, crystal structures and spectroscopic properties of two novel oxamido-bridged trinuclear complexes [Cu2M] (M = Cu, Zn)

Based on the complex ligand CuL (H₂L = 2,3-dioxo-5,6:14,15-dibenzo-7,13-diphenyl-1,4,8,12-tetraazacyclo-pentadeca-7,13-diene), two novel oxamido-bridged trinuclear complexes have been prepared. They are of the formula Cu(CuL)₂(ClO₄)₂ · 4C₂H₅OH (1) and [(CuL)₂Zn(C₂H₅OH)₂](ClO₄)₂ · 2C₂H₅OH (2). The crystal structures of the two complexes have been determined by X-ray crystallography. In complex (1), the central Cu is in a complete square-planar environment, bonding to four oxygen atoms of the oxamido macrocyclic ligand, while in complex (2), the Zn center is six-coordinate in an octahedral geometry, the four oxygen donors from macrocyclic ligand form the basal plane and the axial positions are occupied by other oxygen atoms from C₂H₅OH molecules. The spectroscopic properties have been investigated and the EPR spectra have been simulated by WINEPR and SimFonia programs.     

Synthesis and Fungicidal Activity of 1,3,4-Oxadiazole Substituted Acylthioureas

A series of N′-(5-aryl-1,3,4-oxadiazole-2-yl) actylthioureas have been synthesized from p-chlorophenoxyacetic acid, and then substituted 2-amino-5-aryl-1,3,4-oxadiazoles reacting with acylthiocyanoester, which are derived from the second step, are used. Their structures are confirmed by Infrared, ¹H nuclear magnetic resonance, and elementary analysis. From biological testing, it is found that some of these compounds have good fungicidal activity. Translated from Chemical Research and Application, 2005, 17(2) (in Chinese)     

Methylthiofurane: Herstellung und Reaktionen

Preparation and Reactions of Methylthiofurans By lithiation of 3,4-dimethoxyfuran, 2-methylfuran and furan, followed by reaction with dimethyldisulfide, the methylthiofurans 2, 8 , and 10 have been prepared. Reaction of 8 with maleic anhydride has yielded 6-methyl-3-(methylthio)phthalic anhydride ( 9 ), a yellow substance with a strong greenish fluorescence, obviously formed by elimination of H₂O from an unstable cycloadduct. An analgous reaction of 2 resulted in an unexpected mixture from which the following yellow compounds were isolated: 3-hydroxy-4,5-dimethoxy-6-(methylthio)phthalic anhydride ( 3 ), 4-hydroxy-5-methoxy-3,6-bis(methylthio)phthalic anhydride ( 4 ), and bis(S-methyl) (2Z,4E,6Z)-2,3,6,7-tetramethoxy-4,5-bis(methylthio)-2,4,6-octatrienethioate ( 5 ). Compound 5 is also formed on standing of 2 at RT. Mild acid hydrolysis of 2 results in ring-opening accompanied by an intramolecular oxido-reduction to yield S-methyl(3Z)-3-methoxy-4-(methylthio)-2-oxo-3-butenethioate ( 6a ). The structures of compounds 5 and 6a have been determined by X-ray analysis.     

Neue Phellandren-Derivate aus dem Wurzelöl von Angelica archangelicaL

New Phellandrene Derivatives from the Root Oil of Angelica archangelica L . 2-Nitro-1,5-p-menthadiene ( 5 ), trans- and cis-6-nitro-1(7), 2-p-menthadiene ( 6 and 7 ), trans-1(7), 5-p-menthadien-2-yl acetate ( 9 ) and a formal phellandrene derivative, 7-isopropyl-5-methyl-5-bicyclo [2.2.2]octen-2-one ( 16 ), have been identified in the root oil of Angelica archangelica L . Starting from (?)-(R)-α-phellandrene ( 1 ) (R)- 5 , (4R, 6S)- 6 /(4R, 6R)- 7 , (2S, 4R)- 9 and (1R, 4R, 7R)- 16 as well as (2S, 4R)- 11 , (2R, 4R)- 12 and (2R, 4R)- 10 have been prepared.     

New 2‐methylisothiazolones

New N,N'‐bis(alkoxycarbonyl)‐L‐cystine bis(methylamides) 4a, 4b and N,N'‐bis(benzyloxycarbonyl)‐L‐cystine bis(methylamide) 4c have been synthesized by mixed anhydride method from the essential amino acid L‐cystine 1 in good yield. These cystine bis(methylamides) 4a,b,c have been cyclized with sulfuryl chloride. New 2‐methyl‐4‐amino‐3‐isothiazolone and 5‐chloro‐2‐methyl‐4‐amino‐3‐isothiazolone hydrobromide salts 7, 8 have been obtained by deacylation of 2‐methyl‐4‐(benzyloxycarbonyl)amino‐3‐isothiazolone 5c and 5‐chloro‐2‐methyl‐4‐(benzyloxycarbonyl)amino‐3‐isothiazolone 6c with hydrogen bromide in acetic acid. The microbicidal effect of the new 2‐methy]‐3‐isothiazolones 5a,b,c; 6a,b,c; 7 and 8 compounds obtained by the above method has been investigated.     

pH-metric studies on formation constants of the complexes of substituted pyrazoles with some lanthanide metal ions and the influence of ionic strengths on complex equilibria in a 70% dioxane-water mixture

The pK a values of N-heterocyclic compounds (substituted pyrazoles) in a 70% (v/v) dioxane-water mixture have been determined using pH-metric measurements. The stability constants of the complexes of Dy(III), Nd(III), Sm(III), and Tb(III) with 3-(2-hydroxyphenyl)-5-methylpyrazole, l-phenyl-3-(2-hydimyphenyl)-5-methylpyrazole 3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole, and l-phenyl-3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole have been determined by the pH-metric method at ( 300 ± 0.1) K. The effect of ionic strengths on the complexes of Sm³⁺ and Pr³⁺ ions with pyrazole has been investigated in the internal from 0.02 to 0.1 mol dm⁻³ (sodium perchlorate) in the pH range 2–3.     

Synthesis of 2,5-diisoxazolyltetrahydrofurans

The synthesis of 2,5-bis(3-bromo-5-isoxazolyl)tetrahydrofuran ( 2 ) and 2,5-bis(3-methoxy-5-isoxazolyl)tetrahydrofuran ( 3 ) have been accomplished in three and four steps respectively. Cis- and trans-isomers have been separated and fully characterized. Differently from synthetic schemes so far utilized for the preparation of the 2,5-diheteroaryltetrahydrofuran analogs, our approach involves the direct synthesis of a key intermediate containing both isoxazole rings and diol function for the final cyclization. Starting from succinic aldehyde, the new 1,7-octadiyne-3,6-diol ( 4 ) was prepared and was submitted to a double cycloaddition with bromonitrile oxide to yield the key intermediate 1,4-bis(3-bromo-5-isoxazolyl)-1,4-butanediol. The methoxy analogs 3 were obtained by methanolysis of the bromo derivatives 2 .     

A flexible asymmetric approach to methyl 5-alkyltetramates and its application in the synthesis of cytotoxic marine natural product belamide A

By using a methyl tetramate derivative (R)‐ or (S)‐ 9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)‐ or (S)‐5‐alkyltetramates ( 2 ) is disclosed. Among the synthesized methyl 5‐alkyltetramates 2 , methyl 5‐methyltetramate ( 2 a ) is found in cytotoxic mirabimide E ( 4 ) and dysideapyrrolidone ( 5 ), and methyl 5‐benzyltetramate ( 2 g ) is a substructure in the potent antineoplastic dolastatin 15 ( 3 ). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A ( 7 ) has been achieved in seven steps from (S)‐ 9 , with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)‐belamide A ( 7 ) been confirmed, but also the solvent used for recording the ¹³C NMR spectrum, the ¹³C NMR spectrum data correlation, and optical rotation data of natural belamide A ( 7 ) have been revised.     

A chemical study of burley tobacco flavour (Nicotiana tabacum L.) VI. Identification and synthesis of four irregular terpenoids related to solanone, including a 'prenylsolanone'.

Four novel constituents of Burley tobacco condensate have been identified as (E)-5-isopropyl-7-(2-methyl-tetrahydrofur-2-yl)-hept-6-en-2-one ( G ), (E)-5-isopropyl-7-(2-methyl-tetrahydrofur-2-yl)-hept-6-en-2-ol ( H ), (E)-4-methyl-7-isopropyl-10-oxo-undec-5-en-4-olide ( I ), and (E, E)-6,12-dimethyl-9-isopropyltrideca-5,10,12-trien-2-one ( J ) or ‘prenylsolanone’. Compounds G , H , and I were synthesized from norsolanadione ( 1 ), compound J from solanone ( A ). These substances belong to a growing family of tobacco metabolites structurally related to solanone ( A ). Their possible formation from cembrene-type precursors is briefly outlined.     

A Theoretical Study on the Tautomerism of C-Carboxylic and Methoxycarbonyl Substituted Azoles

DFT calculations (B3LYP/6-31+G^**) have been carried out on 106 tautomers and conformers of NH-azoles bearing CO₂H and CO₂CH₃ groups. The following azoles systems have been studied: 2-substituted pyrroles, 2-substituted indoles, 2-substituted imidazoles, 2-substituted benzimidazoles, 4(5)-substituted imidazoles, 3(5)-substituted pyrazoles, 3-substituted indazoles (1H and 2H), 3,4(5)-substituted-1,2,3(5)-triazoles, 2,3(5)-substituted-1,2(3),4-triazoles, 4(5)-1,2,3,4(5)-tetrazoles. In the case of pyrazole, 3,5-disubstituted derivatives have also been computed, including four dimers.Dedicated to our friend Professor Vladimir I. Minkin on his 70th anniversary.     

Insertion of ethyl diazoacetate into the platinum–carbon bond of Pt(diphosphine)(halide)(aryl) complexes. X-ray structure of the Pt{(2<Emphasis Type="BoldItalic">S</Emphasis>,4<Emphasis Type="BoldItalic">S</Emphasis>)-bdpp)}I(Ph) complex

Pt(diphosphine)X(aryl) complexes [diphosphine = 1,3-bis(diphenylphosphino)propane (dppp), 2,4-bis(diphenylphos phino)pentane (bdpp); aryl = phenyl, 2-thiophenyl; X = Cl, I] have been reacted with ethyl diazoacetate in chloroform. It has been revealed by in␣situ n.m.r. studies that the starting compounds insert the carbene, formed from ethyl diazoacetate, into the Pt–aryl group resulting in Pt(diphosphine)X{CH(aryl)COOC₂H₅}. Depending on the reaction conditions (reaction time, ratio of the reactants) and the ligands various side-reactions have been observed: (i) the formation of Pt(diphosphine)X₂ in chloroform, (ii) the insertion of the :CHCOOC₂H₅ fragment into the Pt–halide bond of the dihalogeno complexes Pt(diphosphine)X₂ resulting in the exclusive formation of Pt(diphosphine)X(CHXCOOC₂H₅). Diastereoselective insertion reactions have been observed in the presence of (S,S)-bdpp as diphosphine. The Pt{(S,S)-bdpp)}I(Ph) complex has been characterized by X-ray crystallography.