Synthesis, properties, and redox behavior of mono-, bis-, and tris[1,1,4,4,-tetracyano-2-(1-azulenyl)-3-butadienyl] chromophores binding with benzene and thiophene cores

Mono-, bis-, tris-, and tetrakis(1-azulenylethynyl)benzene and mono- and bis(1-azulenylethynyl)thiophene derivatives 5-10 have been prepared by Pd-catalyzed alkynylation of ethynyl arenes with 1-iodoazulene derivative or the 1-ethynylazulene derivative with tetraiodobenzene and iodothiophenes under Sonogashira-Hagihara conditions. Compounds 5-10 reacted with tetracyanoethylene in a [2+2] cycloaddition reaction to afford the corresponding 1,1,4,4,-tetracyano-2-(5-isopropyl-3-methoxycarbonyl-1-azulenyl)-3-butadienyl chromophores 12-16 in excellent yields, except for the reaction of the tetrakis(1-azulenylethynyl)benzene derivative. 1,1,4,4,-Tetracyano-2,3-bis(1-azulenyl)butadiene (17) was also prepared by the similar reaction of bis(1-azulenyl)acetylene (11) with tetracyanoethylene (TCNE). The redox behavior of novel azulene derivatives 12-17 was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed multistep electrochemical reduction properties. Moreover, a significant color change was observed by visible spectroscopy under electrochemical reduction conditions.     

Synthesis of Some New Pyrazolopyridines,Pyrazolothienopyridines, Pyrazolopyridothienopyrimidines and Pyrazolopyridothienotriazines

Pyrazolo[3,4-b]pyridine derivative 3a was prepared and reacted with methyl iodide to give 4 or 5 depending on reaction conditions. Oxidation of 3a with iodine produced the corresponding disulphide derivative 6 , whereas oxidation with KMnO 4 gave the corresponding oxo derivative 7 . Oxidation of 4 afforded the corresponding sulphone derivative 8 , which on boiling in NaOH solution gave 7 . The reaction of compound 3a with chloroacetonitrile, ethyl chloroacetate, phenacyl bromide, and chloroacetanilide afforded 9a , b , 11 , and 12 respectively. Cyclication of the products 9a , b , 11 , and 12 yielded 10a , b , 13 , and 14 respectively. The reaction of compound 14 with ethyl orthoformate, nitrous acid, acetic anhydride, benzaldehyde, urea, CS 2 , and phenyl isothiocyanate afforded compounds 15-21 respectively.     

Syntheses of (+)-cytisine, (-)-kuraramine, (-)-isokuraramine, and (-)-jussiaeiine A

Total syntheses of (+)-cytisine, (-)-kuraramine, (-)-isokuraramine, and (-)-jussiaeiine A were achieved via a samarium diiodide-promoted reductive deamination reaction, followed by simultaneous recyclization of a proline derivative to give the corresponding delta-lactam derivative, as a key step.     

Absolute stereochemistries and total synthesis of (+)-arisugacins A and B, potent, orally bioactive and selective inhibitors of acetylcholinesterase

In the current studies, we used the Kakisawa-Kashman modification of the Mosher NMR method to determine the complete absolute stereochemistry of arisugacins. We also report the convergent total synthesis of (+)-arisugacins A and B by a sequence including (i) ruthenium complex-catalyzed asymmetric reduction of the cyclohexenone derivative; (ii) stereoselective construction of the arisugacin skeleton by a Knoevenagel-type reaction of an α,β-unsaturated aldehyde derivative with production of a 4-hydroxy-2-pyrone derivative as a key reaction; and (iii) stereoselective dihydroxylation to give the diol derivative, followed by deoxygenation. Accordingly, we defined the absolute structures of arisugacins A and B as 4a-(R),6a-(R),12a-(R), and 12b-(S). Finally, we characterized the bioactivities of the synthetic intermediates to understand the structure-activity relationships of the arisugacins.     

Synthesis of naphthalenes through three-component coupling of alkynes, Fischer carbene complexes, and benzaldehyde hydrazones via isoindole intermediates

The synthesis of naphthalene derivatives through three-component coupling of 2-alkynylbenzaldehyde hydrazones with carbene complexes and electron-deficient alkynes has been examined. The reaction involves formation of an isoindole derivative, followed by intramolecular Diels-Alder reaction, followed by nitrene extrusion. The reaction was highly regioselective using unsymmetrical alkynes.     

Oxazolidine Formation,or Loss of Acid,from Attempted Fluorination of Amide Side‐Chain in 2‐Nitroimidazoles

Reaction of Etanidazole (a 2‐nitroimidazole derivative with an amide side‐chain containing a hydroxyethyl group) with triflic anhydride gives, depending on conditions, a trifluoromethyl(sulfonyl)oxazolidine via a cyclization reaction, or a fluorine‐free formate derivative; reaction with tosyl chloride gives only a chloroethyl derivative. An attempt to replace a Br‐atom in a related propyl‐containing amide side‐chain by a F‐atom forms instead a propylene derivative via loss of HBr. The studies stem from interest in use of 2‐nitroimidazoles with fluorine‐containing amide side‐chains as hypoxia markers.     

Surface modification of GC and HOPG with diazonium, amine, azide, and olefin derivatives

Surface modification of glassy carbon (GC) and highly oriented pyrolytic graphite (HOPG) was carried out with diazonium, amine, azide, and olefin derivatives bearing ferrocene as an electroactive moiety. Features of the modified surfaces were evaluated by surface concentrations of immobilized molecule, blocking effect of the modified surface against redox reaction, and surface observation using cyclic voltammetry and electrochemical scanning tunneling microscope (EC-STM). The measurement of surface concentrations of immobilized molecule revealed the following three aspects: (i) Diazonium and olefin derivatives could modify substrates with the dense-monolayer concentration. (ii) The surface concentration of immobilized amine derivative did not reach to the dense-monolayer concentration reflecting their low reactivity. (iii) The surface modification with the dense-monolayer concentration was also possible with azide derivative, but the modified surface contained some oligomers produced by the photoreaction of azides. Besides, the blocking effect against redox reaction was observed for GC modified with diazonium derivative and for HOPG modified with diazonium and azide derivatives, suggesting fabrication of a densely modified surface. Finally, the surface observation for HOPG modified with diazonium derivative by EC-STM showed a typical monolayer structure, in which the ferrocene moieties were packed densely at random. On the basis of those results, it was demonstrated that surface modification of carbon substrates with diazonium could afford a dense monolayer similar to the self-assembled monolayer (SAM) formation.     

6,7-二乙酰氧基黄芩素的一步合成、选择性水解及甲醚化

以中药黄芩中的主要活性成分黄芩苷为原料,在醋酸钾、吡啶催化回流条件下,用醋酐为乙酰化试剂,以67.6%的收率一步实现了6,7-二乙酰氧基黄芩素的合成,6,7-二乙酰氧基黄芩素经K2CO3/丙酮-水条件下的水解反应或Me2SO4/K2CO3/丙酮中的甲醚化反应以良好收率及高选择性得到6-乙酰氧基黄芩素或7-甲氧基-6-乙酰氧基黄芩素.     

5,6-Dihydro-4h-imidazole[4,5,1-i,j]quinoline derivatives

2-Alkyl(dialkyl)amino derivatives of I and their respective cyclic ammonium salts were obtained by reaction of the 2-chloro derivative of 5,6-dihydro-4H-imidazole [4,5,1-i,j ]quinoline (I) and its methiodide with amines. The eycloammonium salt was converted into 2-amino(alkylimino)-l,2-dihydro derivatives of 5. Methoxy- and methyl-substituted I readily formed 2-amino derivatives by reaction with sodium amide. Comparison of the UV spectra of the 2-amino derivative of I and its fixed tautomeric form indicates that the 2-amino derivative of I exists primarily in the amino form in dioxane and CC14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1410–1413, October, 1970.     

General one-pot, three-step methodology leading to an extended class of N-heterocyclic cations: spontaneous nucleophilic addition, cyclization, and hydride loss

A new class of phenanthridinium derivative has been isolated from the reaction of 2-bromoethyl-phenanthridinium bromide with a range of primary amines in excellent yields. The reaction pathway is unprecedented and proceeds via three cascade steps: nucleophilic attack of a primary amine on the iminium moiety of a heteroaromatic ring system and cyclization to form a five-membered ring, followed by hydride loss to yield a rearomatized dihydro-1H-imidazo[1,2-f]phenanthridinium derivative. A range of NMR phase transfer experiments were carried out to elucidate the mechanistic pathway, and the methodology has been further developed by means of a biphasic system using N-bromosuccinimide as a co-oxidizing agent. The method has also been extended to other N-heterocyclic cation derivatives such as quinolinium and quinazolinium.     

Cyclization of pyrazolones: novel synthesis of pyrano,pyrido, pyrimido and spiropyrazole derivatives

Depending on the reaction conditions, two alternative cyclizations are possible for [3?+?3] cyclocondensation of pyrazolone derivative 1a and ethyl cyanoacetate of type pyrano [2,3-c] pyrazol-6(1H)-one 2 and pyrano [2,3-c] pyrazol-4(1H)-one 3. Keeping of enaminic system 3 and benzylidene malononitrile in the presence of catalytic amount of trimethylamine resulted in pyridine cyclization affording pyrazolopyranopyridine derivative 4, not 5. The pyrazolone derivative 6a was obtained as a result of the acid-mediated addition reaction between compound 1a, urea and/or ammonium thiocyanate. In addition, the bispyrazolone of type 6b was obtained from the condensation reaction of urea and pyrazolone derivative. The spiro compound 7 was obtained from the double-addition reaction of pyrazolone to cinnamoyl isothiocyanate. A one-pot three-component condensation of a 3-hydroxybenzaldehyde, pyrazolone 1a, urea and/or thiourea under Biginelli conditions resulted in tetrahydropyrazolo pyrimidine derivatives 8a and 8b, respectively. The acid-mediated reaction of benzaldehyde and pyrazolone derivative 1a in the presence of Ac₂O yielded styrylpyrazole derivative 9. The polyfunctionalized product 9 reacted with hydrazine to furnish pyrazolotriazoloe of type 10. Treatment of styrylpyrazole derivative 9 with aniline furnished the aniline derivative 11 and none of the expected polyheterocyclic derivative 12 was obtained. Compound 9 undergoes pyridine cyclization to produce 13 under the effect of urea. N-phenyl pyrazolone converted into pyrano-dipyrazolone derivative 14. Pyran of type 14 underwent a ring transformation upon treatment with urea and/or thiourea to give the same dipyrazolo pyrimidine derivative 15. The newly synthesized compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, ESI/LC-MS and elemental analysis.     

Synthesis and Reactions of 3‐Methylthiazolo[3,2‐a]Benzimidazole‐2‐Carboxylic Acid Hydrazide: Synthesis of Some New Pyrazole, 1,3‐Thiazoline, 1,2,4‐Triazole and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐Thiadiazine Derivatives Pendant to Thiazolo[3,2‐a]Benzimidazole Moiety

The reaction of 3‐methylthiazolo[3,2‐a]benzimidazole‐2‐carboxylic acid ethyl ester (1) with hydrazine hydrate gives the hydrazide 2 which reacts with CS₂/KOH to afford the potassium salt 3. Treatment of 3 with l‐aryl‐2‐bromoethanones 4a,b afforded the 1,3‐thiazoline derivatives 6a,b, respectively, while the reaction of 3 with hydrazine hydrate afforded 1,2,4‐triazole‐3‐thione derivative 9. The reaction of 9 with l‐aryl‐2‐bromoethanones 4a,b and with hydrazonyl chlorides 11a,b gave the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives 10a,b and 12a,b, respectively. Treatment of hydrazide 2 with phenyl isothiocyanate in refluxing benzene gave the thiosemicarbazide derivative 16. The latter reaction gave 1,3,4‐oxadiazole derivative 17 when benzene was replaced by DMF. Cyclization of the thiosemicarbazide derivative 16 with NaOH resulted in the formation of the 1,2,4‐triazole‐3‐thione derivative 18.     

Highly Stereoselective Cationic Cyclization Assisted by a Sulfenyl Group. Scope, Limitation, and Mechanism

When 8-acetoxy-2-methyl-9-(phenylthio)-2-nonene (1a) was treated with an acid, followed by a base, alkylative cyclization proceeded to give a mixture of 1,2-disubstituted cyclohexanes: 2a, 3a, and 4a. The stereochemistry of the reaction was only slightly affected by the leaving group and the reaction conditions, such as the temperature, solvent, and acid. However, the bulkiness of the sulfenyl group had a great effect on the stereochemical course of the reaction. High trans selectivity was attained when 1c (a derivative of 1a with a bulkier sulfenyl group) was used as a substrate. On the other hand, the length and rigidity of the carbon chain of the substrate also had a major effect on the stereochemistry of the reaction; a high cis selectivity was observed when 10a (a one-carbon-fewer analog of 1a) or 15a (a derivative with one more double bond in the carbon chain than in 1a) was used as the substrate. The reaction proceeded via a 6,5- or 5,5-fused-ring intermediate. The sulfenyl-group-assisted reaction could be a useful method for the stereoselective cyclization of acetates of alpha-sulfenylated secondary alcohols.     

Synthesis,DFT Study,and Antitumor Activity of Some New Heterocyclic Compounds Incorporating Isoxazole Moiety

Thiazolidin‐4‐one derivative 3 was synthesized by the transformation of chloroacetamide derivative 2 with NH₄SCN.The condensation of 3 with p‐anisaldehyde afforded the corresponding arylidene derivative 4 . Also, the alkylation of chloroacetamide derivative 2 with different heterocyclic compounds was investigated. Annulation of 5‐amino‐3‐methylisoxazole ( 1 ) with α‐halocarbonyl compounds 12 and 14 furnished pyrrolo[3,2‐d]isoxazole and isoxazolo[5,4‐b]azepin‐6‐one derivatives 13 and 15 , respectively, while reaction of 1 with 1‐chloro‐4‐(chloromethyl)benzene gave the monoalkylated product 17 . The newly synthesized compounds were screened for their antitumor activity, and the geometry optimizations are in a good agreement with the experimentally observed data.     

Synthesis,mechanism of formation and spatial arrangement of (2S,3S,6R)-2,6-diphenyl-3,4-dimethyl-6-ol

Alkylation of alkaloid D-pseudoephedrine with bromoacetophenone results in a morpholine derivative. Structural and energy characteristics of the molecules of the starting, intermediate, and final reaction products were calculated by ab initio method in the HF/6-31G(d,p) approximation. The spatial structure of the final reaction product was determined by X-ray diffraction analysis.     

Studies on the chemistry of O,N- and S,N-containing heterocycles. 4 . Investigations on the nucleophilic substitution of activated 1,5-benzothiazepines

The reaction of the activated 1,5-benzothiazepine 1a with various amines is studied. In contrast to the phenylsubstituted derivative 1b no ring contraction but nucleophilic substitution is observed. Two novel ring systems 8 and 9 are obtained by nitrosation of 3g and by reaction of 1a with anthranilic acid, respectively.     

Gas-chromatographic determination of trace amounts of tetrodotoxin in water,drugs, and blood plasma

A method has been developed for the determination of tetrodotoxin in water, blood plasma, and drugs at a level of 0.05—1.0 µg/mL. The method is based on the hydrolytic decomposition of tetrodotoxin by a sodium hydroxide solution, extraction of 2-amino-6-hydroxymethyl-8-hydroxyquinazoline using liquid–liquid extraction, preparation of its derivative by reaction with N,O-bis(trimethylsilyl)trifluroacetamide, and the determination of the derivative by gas–liquid chromatography with a mass-spectrometric detector.     

Studies on pyran,its analogs,and related compounds

The bromination of 6,7-dibenzyloxy-4-methylcoumarin has given 6,7-dibenzyloxy-3-bromo-4-methylcoumarin and this has been converted by the Perkin reaction into 5, 6-dibenzyloxy-3-methylbenzofuran and its 2-carboxy derivative. 5, 6-Dihydroxy-3-methylbenzofuran-2-carboxylic acid has been synthesized by the catalytic debenzylation of the latter compound.     

Michael Addition Reaction without Catalyst：The Synthesis of 2—Amino—5,6,7,8—tetrahydro—5—oxo—4—aryl—7,7—dimethyl—4H—benzo—[b]—pyran Derivatives

A serices of tetrahydrobenzo-[b]-pyran derivative was synthesized by the reaction of arylmethylene malononitrile or arylmethylene cyanoacetate with dimedone in ethylene gylcol at 80℃ without catalyst. The structures of the two products were characterized by X-ray diffraction.     

Thermolysis,photolysis, and oxidation of an overcrowded 1,3,2-dithiastannetane derivative

Reactions of a sterically crowded 1,3,2-dithiastannetane derivative bearing 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl (=Tbt) and 2,4,6-triisopropylphenyl (=Tip) groups on the tin atom are described. Both thermolysis and photolysis of the 1,3,2-dithiastannetane [Tbt(Tip)SnS₂CPh₂] resulted in the formation of products derived from the corresponding stannanethione [Tbt(Tip)Sn=S], while the oxidation reaction by m -chloroperbenzoic acid gave a novel tincontaining heterocyclic system, an 1,2,4,5-oxadithiastannolane derivative.