Investigation of the reactions of fluorine containing 3-hydrazino-5H-1, 2, 4-triazino[5, 6-b]indoles with ethyl acetoacetate. Synthesis of some novel tetracyclic ring systems

Novel tetracyclic ring systems viz. 3-methyl-1-oxo-12H-1, 2, 4-triazepino[3′,4′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 4a ) and 3-methyl-5-oxo-12H-1, 2, 4-triazepino[4′,3′:2, 3][1, 2, 4]triazino[5, 6-b]indole ( 5a ), having angular and linear structures respectively, were synthesized by the cyclization of 3-oxobutanoic acid [5H-1, 2, 4-triazino-[5, 6-b]indole-3-yl]hydrazone ( 3a ). However, cyclization of 3b (R = CH_a, R¹ = R² = H) afforded the angular product 4b exclusively. Moreover, cyclization of 3c (R = R³ = H, R¹ = F) yielded 7-fluoro-1-0xo-10H-1, 3-imidazo[2′,3′:3, 4][1, 2, 4]triazino[5, 6-b]indole ( 6c ) and 7-fluoro-3-oxo-10H-1, 3-imidazo[3′,2′:2, 3][1, 2, 4]triazino-[5, 6-b]indole ( 7c ) instead of the expected triazepinone derivatives. Compound 3d (R = R¹ = H, R² = CF₃) also gave an imidazole derivative but only one angular product was obtained. In all these reactions, formation of the angular product involving cyclization at N-4 is favoured. Characterization of these products have been done by elemental analyses, ir, pmr, ¹⁹F nmr and mass spectral studies.     

Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.     

Fluoroazoles. III. Synthesis and 1H and 1–9F nmr spectra of 3-, 4-, and 5-fluoro-1-methylpyrazole

The three monofluoro derivatives of N-methylpyrazole have been synthesized. 3-Fluoro-1-methylpyrazole and 4-fIuoro-1-methylpyrazole were prepared from the appropriate amines by diazotization and photochemical irradiation of the diazonium salts in tetrafluoroboric acid. 5-Fluoro-1-methylpyrazole was obtained from 1-acetyl-3-fluoropyrazole and methyl fluorosulfonate, and also by direct methylation of 3(5) fluoropyrazole with dimethyl sulfate. The ^1–9F chemical shifts of these N-methylated fluoroazoles cover a great range (ca. 50 ppm) and show a good correlation with the chemical shifts of H₃, H₄, and H₅ protons of 1-methylpyrazole. An unexpected long-range coupling ⁵J (F-CH₃) is observed in 3-fluoro-1-methylpyrazole.     

Ringschlüsse an Chinonylmethanfarbstoffen und analogen Merocyaninen. 6. Mitteilung. Über die Reaktivität des Cyclohexylrestes in 2-Chlor-3-[(1-cyclohexyl-6-fluor-3-methyl-1H-chinoxalin-2-yliden)methyl]-1,4-naphthochinon

Ring Closure in Quinonylmethane Dyes On the Reactivity of the Cyciohexyl Moiety in 2-Chloro-3-[(1-cyclohexyl-6-fluoro-3-methyl-1H-quinoxalin-2-ylidene)niethyl]-1,4-naphthoquinonc The reactive title compound ( 1a , X = F , R ¹ = C⁶H¹¹, R ²=Cl) was obtained from the reaction of 1-cyclohexyl-6-fluoro-2,3-dimethylquinoxalinium perchlorate with 2,3-dichloro-1,4-naphthoquinone. Upon treatment with pyridine and acetic acid in acetone and separation of the desired naphthophenazinone 2a , an unexpected azepinoquinoxaline 4a was isolated. The structure of 4a was determined by its mass and 360-MHz-¹H-NMR. spectra in connection with decoupling experiments.     

Copper(II) complexes containing chiral substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine ligands: Synthesis, X-ray structural studies and asymmetric catalysis

New chiral N,N-bidentate ligands derived from substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridines have been prepared and characterised by means of ¹H, ¹³C NMR spectroscopy and optical rotation. Their Cu(II) complexes were characterized by means of elemental analysis, ¹H NMR spectroscopy and MS. By means of X-ray diffraction, molecular geometry of the complex of 2-(1-methyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine with copper(II) chloride was determined. The complex exhibits heterochiral dimeric arrangement of two square pyramids with one terminal and one bridge-forming chlorine atoms and two nitrogen atoms in the bases of the pyramids. The tops of these pyramids are formed by the remaining chlorine atoms. The complexes prepared catalyse the Henry reaction with the overall yields of 41-97% and with the maximum enantioselective excess of 19%.     

Synthesis of 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates, a new triazafulvalene system

(2E,3Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]succinate 5 obtained by [2+2] cycloaddition of (5Z)-5-[(dimethylamino)methylene]-3-methylimidazolidine-2,4-dione (1) and dimethyl acetylenedicarboxylate (2) followed by substitution of the dimethylamino group with aromatic or heteroaromatic amines, afforded by heating in ethanol in the presence of potassium hydroxide, potassium salts 6. Acidification of 6 with hydrochloric acid afforded mixtures of (E)- and (Z)-isomers of methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates. On the other hand, alkylation of compounds 6 with methyl iodide or benzyl bromide produced the corresponding methyl (E)-4-(2-methoxy- or 2-benzyloxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates 9, derivatives of a new triazafulvalene system.     

Reaction of 3-oxo-N-phenylbutanethioamide with 5-amino-1H-1,2,4-triazoles

Reactions of 3-oxo-N-phenylbutanethioamide with 3-substituted 5-amino-1H-1,2,4-triazoles in acetic acid led to the formation of 5-methyl-7,8-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thiones, 7-methyl-5,8-dihydrol[1,2,4]triazolo[1,5-a]pyrimidine-5-thiones and 7-methyl-5-phenylamino[1,2,4]triazolo[1,5-a]pyrimidines. The structure of the products was proved by the ¹H and ¹³C NMR spectra, X-ray diffraction data, and chemical transformations.     

Synthesis,antimicrobial and cytotoxic activity of novel azetidine-2-one derivatives of 1H-benzimidazole

A series of 1-methyl-N-[(substituted-phenylmethylidene)-1H-benzimidazol-2-amines (4a–4g) were prepared via the formation of 1-methyl-1H-benzimidazol-2-amine (3), which was prepared by the cycloaddition of o-phenylenediamine (1) with cyanogen bromide in the presence of aqueous base followed by N-methylation with methyl iodide in the presence of anhydrous potassium carbonate in dry acetonitrile. Moreover, the four-membered β-lactam ring was introduced by the cycloaddition of 4a–4g and chloroacetyl chloride in the presence of triethylamine catalyst to give 3-chloro-1-(1-methyl-1H-benzimidazol-2-yl)-(4′-substituted)-phenylazetidin-2-one 5a–5g. A total of 14 compounds were synthesized and characterized by IR, ¹H NMR, ¹³C NMR and Mass spectral technique, in addition they were evaluated for anti-bacterial and cytotoxic properties. Among the chemicals tested 4a, 4b, 5a, 5b, 5g exhibited good antibacterial activity and 5f, 5g shown good cytotoxic activity in vitro.     

Synthesis of new thietanylpyrimidine and thietanylimidazole derivatives

New thietanyl-substituted derivatives of pyrimidine-2,4(1H,3H)-dione and imidazole were synthesized. The alkylation of 6-methylpyrimidine-2,4(1H,3H)-diones with 2-chloromethylthiirane in water involved the N¹ atom of the pyrimidine ring and afforded 6-methyl-1-(thietan-3-yl)-pyrimidine-2,4(1H,3H)-diones. Under analogous conditions 6-aminopyrimidine-2,4(1H,3H)-dione gave rise to 6-(thietan-3-ylamino)pyrimidine-2,4(1H,3H)-dione. Unsymmetrically substituted 2-methyl-4(5)-nitro- and 5(4)-bromo-2-methyl-4(5)-nitro-1H-imidazoles reacted with 2-chloromethylthiirane to produce mixtures of isomeric 2-methyl-4(5)-nitro-1-(thietan-3-yl)-1H-imidazoles and 5(4)-bromo-2-methyl-4(5)-nitro-1-(thietan-3-yl)-1H-imidazoles.     

取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

为了寻求新的含吡唑双杂环先导化合物. 用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物. 化合物结构用IR, ¹H NMR, MS和元素分析进行了表征. 并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构. 晶体为单斜晶系, P2₁/n (#14)空间群, a＝1.52175(3) nm, b＝0.52970(1) nm, c＝1.58185(3) nm, β＝104.893(4), V＝1.2323(4) nm³, Z＝4, D_c＝1.45 g/cm³, F(000)＝560.00, R₁＝0.064, wR₂＝0.193. 初步生物活性实验结果表明, 在25 mg/L浓度下, 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c), 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%. 在500 mg/L浓度下, 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d), 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cinc-ticeps)的抑制活性达到53.37%.     

New chiral ligands and iron(III) complexes based on 2,6-bis(1-benzyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-on-2-yl)pyridines

New ligands and their complexes with iron(III) chloride have been suggested and prepared: (R,S)-, (R,R)- and (S,S)-2,6-bis(1-benzyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-on-2-yl) pyridines. Both the ligands and their complexes were characterised by ¹H and ¹³C NMR spectroscopy, optical rotation and X-ray diffraction.     

Stereoselective cycloadditions of (1Z,4R,5R)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to maleimides

A library of 15 1,6,7,9-tetrasubstituted 6,7,9,9a-tetrahydro-5H-pyrazolo[1,2-a]pyrrolo[3,4-c]pyrazole-1,3,5(2H,3aH)-triones was prepared by combinatorial stereoselective cycloadditions of (1Z,4R^∗,5R^∗)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to N-substituted maleimides. Stereochemistry was controlled by the stereodirecting phenyl group at position-3 and by the ortho-substituents at the aromatic ring at position-1′ in azomethine imines. Consequently, two sets of diastereomeric cycloadducts were obtained, one set from the ortho-unsubstituted dipoles and the other set from the ortho-disubstituted dipoles.     

Synthesis and reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole

The palladium-catalyzed cross-coupling reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole with aryl iodides provided high yields of the corresponding 5-aryl-4-fluoro-1H-pyrazoles. Furthermore, these cross-coupling reactions proceeded smoothly under an atmosphere of carbon monoxide (CO) to afford the corresponding 5-acyl-4-fluoro-1H-pyrazoles as CO-insertion products.     

Lewis acid-catalyzed asymmetric radical additions of trialkylboranes to (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl-2H-azirine-3-carboxylate

The asymmetric addition of alkyl radicals to (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl-2H-azirine-3-carboxylate (1) yielding the corresponding 2-alkylaziridine-2-carboxylates has been investigated. High diastereoselectivities and good yields were obtained in the addition of primary alkyl radicals to azirine 1, while secondary radicals gave a lower dr. The influence of Lewis acids was also investigated; 10 mol% of CuCl were found to increase the dr.     

Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

Synthesis of 3-(aminooxoethyl)-6-methyl-1-(thiethan-3-yl)-pyrimidine-2,4-(1H,3H)-diones

A new approach to prepare 2-chloroacetamides has been developed, based on the reaction of chloroacetyl chloride with excess of secondary amines. Alkylation of 6-methyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-dione with the synthesized 2-chloroacetamides in the presence of potassium carbonate has afforded N ³-acetamido-substituted 6-methyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-diones.     

Synthesis,pharmacokinetics, and biological activity of a series of new pyridonecarboxylic acid antibacterial agents bearing a 5-fluoro-2-pyridyl group or a 3-fluoro-4-pyridyl group at N-1

The 1-(5-fluoro-2-pyridyl) or 1-(3-fluoro-4-pyridyl) group was introduced in the syntheses of new pyridonecarboxylic acid antibacterial agents. 1-(5-Fluoro-2-pyridyl)-6-fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxoquinolone-3-carboxylic acid 7b (DW-116) showed a moderate in vitro antibacterial activity but it was found to have very excellent pharmacokinetic profiles so that 7b (DW-116) showed dramatic increased in vivo efficacy.     

Syntheses, characterization, X-ray crystal structures and emission properties of five oxovanadium(V) complexes with pyridyl/pyrimidyl-pyrazole derived ditopic ligands

Four oxovanadium(V) complexes of heterocycle based ditopic ligands PyPzOAP (N-[amino(pyridin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PyPzOAPz (N-[amino(pyrazin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PymPzOAP (N-[amino(pyridin-2-yl)methylidene]-1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-1H-pyrazole-3-carbohydrazonic acid) and PyPzCAP (5-methyl-1-(pyridin-2-yl)-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) and a binuclear (di-μ-oxo) oxovanadium(V) complex of the ligand PymPzCAP (1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) have been investigated. The ligands act as uninegative NNO tridentates donors for the VO₂⁺ ion exhibiting their monotopicity. The ligands show varying emission properties due to the presence of fluophoric groups like 1-(2-pyridyl)pyrazole or 1-(2-pyrimidyl)pyrazole. The vanadium(V) complexes show fluorescence quenching with respect to the used ligands to a varying extent. The complexes were characterized by UV-Vis, IR, cyclic voltammetry and X-ray crystallography.     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

Synthesis of 5-fluoro-2-methyl-3-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)-4(3H)-quinazolinone and related compounds with potential antiviral and anticancer activity

The synthesis of ten new substituted 1,3,4-thiadiazolyl-4(3H)-quinazolinones 8–11, 13, 17 , and 20–23 is reported. Compounds 8–11 were prepared by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7. Compound 13 was obtained by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) with DL-α-amino-?-caprolactam (12) . Compound 17 was synthesized by condensation of 6-bromo-2-methyl-3,1-benzoxazin-4-one (16) and 2-amino-5-t-butyl-1,3,4-thiadiazole (5) . Compounds 20–23 were obtained by condensation of 5-chloro-6,8-dibromo-2-methyl-3,1-benzoxazin-4-one (19) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7, respectively. The substituted 3,1-benzoxazin-4-ones 3, 16, and 19 were obtained in good yield by refluxing the appropriate anthranilic acid, 1,15 , and 18 with acetic anhydride (2) .