The synthesis of imidazo[4,5-c] - and v-triazolo[4,5-c] pyridazines

The parent imidazo[4,5-c]pyridazine (IV) has been prepared for the first time by three different routes. 1-Methylimidazo[4,5-c]pyridazine (XX) and 3-methylimidazo[4,5-c]pyridazine (XXVII) have been prepared by unequivocal syntheses. The constitution of the methylation product of imidazo[4,5-c]pyridazine-2-thiol (VIII) has been shown to be 2-methylthioimidazo[4,5-c]-pyridazine (IX) by the unequivocal syntheses of 1-methylimidazo[4,5-c]pyridazine-2-thiol (XXIII) and 3-methylimidazo[4,5-c]pyridazine-2-thiol (XXXIII). Likewise, the structure of the methylation product (XIII) was shown to be S-methylation by the unequivocal syntheses of 1-methyl-2-methylthio-6-chloroimidazo[4,5-c]pyridazine (XXIV) and 3-methyl-2-methylthio-6-chloroimidazo[4,5-c]pyridazine (XXXI), respectively. Several 7-substituted amino-v-triazolo-[4,5-c]pyridazines (XXXVIII) have been prepared from 7-chloro-v-triazolo[4,5-c]pyridazine (XXXVII).     

Brominated and iodinated thiofluoresceins

Conditions were found for the synthesis of mono-, di-, tri-, and tetrabromo- and -iodo-substituted thiofluoresceins. Iodination and bromination of thiofluorescein with molecular iodine and bromine in 1 N aqueous sodium hydroxide gave mixtures of the corresponding 2,4,5,7-tetra- and 2,4,5-trihalo derivatives in 71/14 (Y = I) and 73/13% yield (Y = Br), respectively. In the reactions of thiofluorescein with bromine in acetic acid and with iodine in methanol at a substrate-to-halogen ratio of 1 : 2, 4,5-dibromo- and 4,5-diiodothiofluoresceins were isolated in 56 and 67% yield. Analogous reactions with equimolar amounts of the reactants produced 59% of 4-bromothiofluorescein and 51% of 4-iodothiofluorescein.     

The synthesis of lmidazo[4,5-d] pyridazines. VI. v-Triazolo[4,5-d] pyridazines,pyrazino[ 2,3-d ] pyridazines and 7H-Imidazo [4,5-d] tetrazolo[ 1,5-b] pyridazine

Several pyridazines have been prepared as intermediates in the synthesis of monosubstituted imidazo[4,5-d]pyridazines, monosubstituted v-triazoIo[4,5-d]pyridazines and monosubstituted pyrazino [2,3d] pyridazines. The new ring system, 7H-imidazo[4,5-d]tetrazolo[l,5-b] pyridazine (XIV) has been prepared unsubstituted. Furthermore, unsubstituted imidazo[4,5-d]pyridazine (XI) has been prepared. Calculations for XI and XIV were made by approximate SCF LCAO-MO with CNSO II theory.     

Synthesis of imidazo[4,5-b]- and [4,5-c]pyridines

2-Arylimidazo[4,5-b]- and [4,5-c]pyridines have been prepared by treatment of the appropriate 2,3- or 3,4-diaminopyridine with an aromatic carboxylic acid in the presence of polyphosphoric acid. Other derivatives have been prepared by similar cyclisation of diaminopyridines using triethyl orthoformate, urea, thiophosgene and thiourea and the properties of some N-oxides have been investigated. A number of the arylimidazopyridines have been screened for mutagenicity.     

Reductive coupling of α,β-enones I: Reduction of methyl-vinyl ketone and mesityl oxide.

Reductive coupling of methyl-vinyl ketone with TiCl₄-Mg gives pinacol $\text{1}$ (25%). According to the reducing agents, mesityl oxide yields 2,4,5,7-tetramethyl-octa-2,4,6-triene $\text{3}$ (with 4TiCl₃-LialH₄), triene $\text{3}$ or 2,4,5,7-tetramethyl-octa-2,6-dien-4,5-diol $\text{5}$ (with TiCl₄-Mg), pinacol $\text{5}$ (with VCl₃-Mg), and 2-acetyl-1,3,3,4,4-pentamethyl-cyclopentane $\text{7}$ (with CrCl₃-Mg or FeCl₃-Mg or ZrCl₄ or ZrCl₄-Mg) as major products.     

α-Thioureidoalkylation of urea heteroanalogs

α-Thioureidoalkylation of urea heteroanalogs such as thiosemicarbazide, amino-guanidine, sulfamide, and sulfonamides with 4,5-dihydroxyimidazolidine-2-thiones has been studied. Previously unknown 4,5-bis[thiosemicarbazido(guanidinoamino)]imidazolidine-2-thiones, 5,7-dialkylperhydroimidazo[4,5- e][1,2,4]triazine-3,6-dithiones, 4,6-diethyl-5(3H)-thioxotetrahydro-1 H-imidazo[4,5- c][1,2,5]thiadiazole 2,2-dioxide, and 1,3-dialkyl-4-[guanidinoimino(arylsulfonylimino)]imidazolidine-2-thiones have been synthesized.     

Mass spectra of some steroidal diols

The mass spectral fragmentations of a number of steroidal 3,5- and 4,5-diols and some derivatives have been examined using high resolution mass spectrometry and deuterium labelling. Although the 3,5- and 4,5-diols have very similar mass spectra those of the derived ketols are quite characteristic. A pathway for the formation of the important m/e 332 ion in the mass spectrum of cholestan-4β,5α-diol has been postulated.     

The synthesis of several imidazo[4,5-d]isothiazoles. Derivatives of a new ring system

Several derivatives of the new imidazo[4,5-d]isothiazole ring system have been synthesized from the appropriately substituted isothiazolediamines. The reaction of 3-methyl-4,5-diaminoisothiazole ( 4a ) with diethoxy-methyl acetate gave a low yield of 3-methylimidazo[4,5-d]isothiazole ( 5a ). However, the analogous reaction of 4,5-diaminoisothiazole ( 4b ) with diethoxymethyl acetate failed to yield the parent imidazo[4,5-d]isothiazole ring system. The diamines 4a and 4b were readily cyclized with thiocarbonyldiimidazole to give the unstable thiones 6a and 6b , which were alkylated in situ to afford good yields of the corresponding 5-methylthioimidazo[4,5-d]isothiazoles 7a and 7b , respectively. Neither of these compounds could be reduced to the corresponding 5-unsubstituted derivatives via treatment with Raney nickel. To the best of our knowledge, this is the first report of the imidazo[4,5-d]isothiazole ring system.     

Synthesis of some pyrimido[4′,5′:4,5]thieno[2,3-b]quinolines and related heterocycles

Several thieno[2,3-b]quinolines 6a-i have been synthesized. These compounds were used as key intermediates in the synthesis of oxazino[4′,5′:4,5]thieno[2,3-b]quinoline 8 , pyrimido[4′,5′:4,5]-thieno[2,3-b]quinolines 9–12 , triazino[4′,5′:4,5]thieno[2,3-b] quinolines 14 and imidazo[4′,5′:4,5]-thieno[2,3-b]quinolines 17 .     

2,3,9,10-Tetrachlorobenzo[1,2-b: 4,5-b']bis[1,4]benzodioxin,a homologue of TCDD

Catechol and 4,5-dichlorocatechol have been condensed with 1,5-dichloro-2,4-dinitrobenzene to provide benzo[1,2-b: 4,5-b ]bis[1,4]benzodioxin and its 2,3,9,10-tetrachloro derivative, respectively. The latter compound is a novel homologue of the extremely toxic 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD).     

α-Thioureidoalkylation of 4-alkyl- and 4-phenylthiosemicarbazides

Previously unknown 1,3-dialkyl-4,5-bis[4-alkyl(phenyl)thiosemicarbazido]imidazolidine-2-thiones and 4,5,7-trialkylperhydroimidazo[4,5-e]-1,2,4-triazine-3,6-dithiones have been synthesized by the α-thio-ureidoalkylation of 4-alkyl(phenyl)thiosemicarbazides using 1,3-dialkyl-4,5-dihydroxyimidazolidine-2-thiones.     

几种芴衍生物(有机材料增感剂)的13C核磁共振研究

利用FX-60Q脉冲付里叶变换核磁共振波谱仪(磁场强度为14093高斯,观察频率为15.04MH_z)测定了四种劳衍生物的非去偶谱、偏共振谱和质子完全去偶谱。借助于偏共振技术、质子噪声(宽带)去偶、取代基化学位移加合规则以及模式化合物比较,确定了各峰的化学位移和一键、二键及三键偶合常数。实验结果表明,用化学位移和偶合常数的值除帮助识别各峰的归属外,还能推断未知化合物的碳键状态及取代基电负性的大小,对鉴别化合物结构可提供有用的线索。     

Condensed Thienopyrimidines. 19. Study of the Heterocyclization of 2-Hydrazino-6,6-dimethyl-5,6-dihydro-8H-pyranothieno[2,3-d]pyrimidin-4-one

Novel condensed pyrano[4',3':4,5]thieno[3,2-e]triazolo[3,4-b]pyrimidine derivatives have been synthesized from 2-amino-3-carbethoxy-5,5-dimethyl-4,5-dihydro-7H-thieno[2,3-c]pyran.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene. 4. Synthesis of 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines

Thirteen 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines 11 have been synthesized in three steps from 4-amino-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene ( 6 ), which was obtained from the reduction of either 4-azido 4 or 4-hydroxyimino 5 derivatives. All the compounds have been evaluated as potential antidepressive agents.     

Synthesis and total 1H-NMR assignment of naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]-thieno[2,3-c] [1,10]phenanthroline

Naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]thieno[2,3-c][1,10]phenanthroline, two novel polycyclic heterocyclic ring systems, have been synthesized in four steps from known starting materials. The total ¹H nmr spectral assignments were made using a COSY experiment to identify the spin systems.     

New strategies and building blocks for functionalised 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene derivatives,including pyrrolo-annelated derivatives and pi-extended systems with intramolecular charge-transfer

A range of new functionalised 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene (TTFAQ) derivatives have been synthesised from the key di(halomethyl) building blocks, 10-[4,5-bis(bromomethyl)-1,3-dithiol-2-ylidene]-anthracene-9(10H)-one 10, 10-[4,5-bis(chloromethyl)-1,3-dithiol-2-ylidene]anthracene-9(10H)-one 11 and 9-[4,5-bis(chloromethyl)-1,3-dithiol-2-ylidene]-10-[4,5-bis(hexylsulfanyl)- 1,3-dithiol-2-ylidene]-9,10-dihydroanthracene 18. A Diels-Alder strategy comprising trapping of the transient exocyclic diene 19, which is derived from 18, with 1,4-naphthoquinone leads to the aromatised TTFAQ anthraquinone system 21. Horner-Wadsworth-Emmons olefination of 21 with the anion generated from reagent 22 gave the fused bis(TTFAQ) structure 23. Pyrrolo-annelated derivatives 30-34 have been obtained in a sequence of reactions from compound 10. Mono-formylation of the pyrrole ring of 32 and 33 under Vilsmeier conditions gave 35 and 36 which upon reaction with 2,4,5,7-tetranitrofluorene gave the donor-pi-acceptor diads 38 and 39. Cyclic voltammetry (CV) in solution for all the TTFAQ derivatives shows the typical quasi-reversible two-electron oxidation wave of the TTFAQ core at potentials which vary slightly depending on the substituents. For example, the value of Eox is raised by the electron withdrawing anthraquinone and tetranitrofluorene units of 21 and 38, respectively. The CV of the conjugated TTFAQ dimer 23 showed two, two-electron oxidation waves corresponding to the sequential formation of 23(2+) and 23(4+) (delta Eox = 130 mV) providing evidence for a significant intramolecular electronic interaction, i.e. the dication 23(2+) acts as a conjugated donor-pi-acceptor diad, thereby raising the oxidation potential of its partner TTFAQ unit. Spectroelectrochemical studies on 23 support this explanation. A strong intramolecular charge transfer band at lambda max 538 nm is seen in the UV-Vis spectra of the TTFAQ-pi-tetranitrofluorene diads 38 and 39. The X-ray crystal structures are reported for compounds 30, 33 and 34. The pyrrolo-TTFAQ moiety adopts a saddle-shape with the central ring of the dihydroanthracene moiety folded along the C(9) ... C(10) vector in each case. Significant intermolecular interactions are observed in the structures.     

4,5‐Dihydro‐1,2,3‐oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations

4,5‐Dihydro‐1,2,3‐oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N‐nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5‐dihydro‐1,2,3‐oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by ¹H, ¹³C, and ¹⁵N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N‐nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5‐dihydro‐1,2,3‐oxadiazole.     

Synthesis of 1,4-benzodiazepino[4,5-d][1,4]benzoxazepines

The novel 1,4-benzodiazepino[4,5-d][1,4]benzoxazepine ring system has been constructed via preformed benzoxazepine intermediates. Several derivatives have been prepared as potential anxiolytic agents.     

Thermal and photochemical reaction of isoxazolone with indole-2,3-dione derivatives

The reaction of indole-2,3-dione derivatives with five membered heterocycle, viz isoxazolone under ther mal as well as photochemical conditions is described. While under refluxing ethanol these conditions afforded 2,3-dihydro-3-(5′-oxo-3′-phenylisoxazolidyl)indol-2-one 3 and a spiro product 2′,3′-dihydro-3,7-diphenylspiro[diisoxazolo[4,5-e:4,5-b]pyran-8,3′-indol]-2′-one 4 , the uv light induced irradiation mainly produced 4,5-dioxo-3-phenylisoxazolo[5,4-b][1]benzazepine 5 and 3-phenylisoxazolo[5,4-b]quinoline-4-carboxylic acid 6 . The products have been characterised on the basis of spectral data and elemental analyses.     

Palladium-Catalyzed C-H Bond Functionalization of Benzo[1,2-b : 4,5-b′]dithiophene-4,8-dione: A One Step Access to 2-Arylbenzo[1,2-b : 4,5-b′]dithiophene-4,8-diones

The reactivity of benzo[1,2-b : 4,5-b′]dithiophene-4,8-dione in Pd-catalyzed C−H arylation was investigated. Using aryl bromides as aryl source in the presence of carbonate bases in 1,4-dioxane, the mono-C2-arylated benzo[1,2-b : 4,5-b′]dithiophene-4,8-diones were regioselectively obtained. This procedure allowed to introduce both electron-rich and electron-poor aryl substituents on the benzo[1,2-b : 4,5-b′]dithiophene-4,8-dione unit. These conditions were also effective for the coupling with 1-bromonaphthalene, 9-bromophenanthrene as well as aryl bromides bearing synthetically useful nitrile, chloro and methoxy substituents. The photophysical properties of representative arylated compounds have been performed by joint experimental and theoretical studies.