Novel asymmetric dihetarylethenes derived from N-isopropylindole and thiophene: synthesis and photochromic properties

Novel asymmetric dihetarylethenes, viz., 3-(1-isopropyl-5-methoxy-2-methyl-1H-indol-3-yl)-4-(3-thienyl)furan-2,5-dione and 1-alkyl/aryl-3-(1-isopropyl-5-methoxy-2-methyl-1H-indol-3-yl)-4-(3-thienyl)-1H-pyrrole-2,5-diones, were obtained. These dihetarylethenes exhibit photochromism in solutions. Replacement of the N-methyl group in the indole fragment by the N-isopropyl group imparts photochromic properties to the resulting furan-2,5-dione derivative. The open forms of (N-isopropylindol-3-yl)pyrrole-2,5-diones are characterized by lower quantum yields of fluorescence, and their cyclic forms are thermally more stable.     

Synthesis and photochromic properties of new nonsymmetric dihetarylethenes ?? indole and thiophene derivatives

New nonsymmetric dihetarylethenes were synthesized: 3-(5-methoxy-1,2-dimethyl-1H-indol-3-yl)-4-(3-thienyl)furan-2,5-dione and photochromic 1-alkyl-(1-aryl)-3-(5-methoxy-1,2-dimethyl-1H-indol-3-yl)-4-(3-thienyl)-1(H)-pyrrole-2,5-diones. The absence of benzoannulation in the indole moiety results in the enhancement of the efficiencies of fluorescence and photocyclization of noncyclic isomers compared to the benzoindole derivatives.     

Synthesis and photochromic properties of novel nonsymmetric dihetarylethenes based on benzindole and thiophene

Novel nonsymmetric dihetarylethenes 3-(5-methoxy-1,2-dimethyl-1H-benzo[g]indol-3-yl)-4-(3-thienyl)-furan-2,5-dione and 1-alkyl- and 1-aryl-3-(5-methoxy-1,2-dimethyl-1H-benzo[g]indol-3-yl-4-(3-thienyl)-1(H)-pyrrole-2,5-diones were synthesized. The substitution of the furandione moiety for pyrroledione gives rise to the radiation and photochemical channels of deactivation of the electron excitation energy of dihetarylethenes. The products of photolysis of pyrrolediones undergo recyclization in both the ground and excited states.     

Synthesis,structures, and photochromic properties of 3-[(<Emphasis Type="Italic">E</Emphasis>)-alk-1-enyl]-4-(1-alkyl-5-methoxy-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indol-3-yl)furan-2,5-diones

New hetarylethenes, viz., 3-[(E)-alk-1-enyl]-4-(1-alkyl-5-methoxy-2-methyl-1H-indol-3-yl)furan-2,5-diones, exhibiting photochromic properties in solution were synthesized. The molecular and crystal structure of 3-(5-methoxy-1,2-dimethyl-1H-indol-3-yl)-4-[(E)-prop-1-enyl]furan-2,5-dione was determined by X-ray diffraction. The initial and photoinduced forms of hetarylethenes are characterized by thermal stability. The open-ring isomers of furandiones exhibit fluorescence with quantum yields of up to 0.1.     

Five-membered dioxoheterocycles: XCIX. Reaction of 1-aryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with indoles. Crystal and molecular structure of substituted 2-(indol-3-yl)pyrrole

1-Aryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones react with indole and 2-methylindole with the formation of methyl 1-aryl-3-aroyl-4-hydroxy-2-(1H-indol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates. Crystal and molecular structure of methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-indol-3-yl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-2-carboxylate was examined.     

Structures and photochromic properties of fulgides based on naphtho[1,2-<Emphasis Type="Italic">b</Emphasis>]furan and benzo[<Emphasis Type="Italic">g</Emphasis>]indole

The novel heterocyclic fulgides, i.e. 3-isopropylidene-4-{1-[5-methoxy-1-(4-methoxy-phenyl)-2-methyl-1H-benzo[g]indol-3-yl]ethylidene}dihydrofuran-2,5-dione and 3-isopropylidene-4-[1-(1-benzyl-5-methoxy-2-methyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione, were prepared and isolated as E-isomers. Photochromism, E-configuration, and high resistance to photocoloration—photobleaching of solutions of these fulgides as well as 3-isopropylidene-4-[1-(5-methoxy-2-methylnaphtho[1,2-b]furan-3-yl)ethylidene]dihydro-furan-2,5-dione and 3-isopropylidene-4-[1-(5-methoxy-2-methyl-1-phenyl-1H-benzo[g]indol-3-yl)ethylidene]dihydrofuran-2,5-dione synthesized previously were shown by X-ray diffraction analysis, ¹H NMR spectroscopy and electronic absorption spectroscopy. The novel fulgides show fluorescence and high thermal stability of photogenerated cyclic form. Repeated photo-coloration—photobleaching is accompanied by reversible photoinduced E—Z isomerization. Benzo[g]indolyl fulgides are characterized by the longer wavelength absorption of both original (E) and photoisomeric cyclic (C) forms as compared to naphthofuran fulgide.     

New photochromic symmetrical and unsymmetrical bis(heteroaryl)maleimides: A spectrokinetic study

The photochromic behavior of two newly synthesized diarylethenes is here presented. The compounds studied are the symmetrical (1-benzyl-3,4-bis(2-methylbenzo[b]thiophen-3-yl)-[1H]-2,5-dihydropyrrol-2,5-dione) and the unsymmetrical (1-benzyl-3-(2-methylbenzo[b]thiophen-3-yl)-4-(2,5-dimethyl-3-thienyl)-[1H]-2,5-dihydropyrrol-2,5-dione). Upon stimulation with UV or violet light, these compounds become red-colored due to photocyclization and cyclorevert to the light yellow open form upon irradiation with visible light. In this work, absorption and fluorescence spectra, molar absorption coefficients of the ethenic and cyclized forms, fluorescence quantum yields and photochemical quantum yields of both the forward and back photoreactions were determined. Temperature, excitation wavelength and solvent effects were explored. The symmetrical compound was found to be a bistable photochrome. In contrast, the unsymmetrical molecule resulted unsuitable as photochrome because of side degradation processes occurring in competition with cyclization.     

Design and synthesis of novel 5,6-bisindolylpyrimidin-4-ones structurally related to ruboxistaurin (LY333531)

2,3-Bis(1-methyl-1H-indol-3-yl) methyl-3-oxopropionate is a key intermediate in the synthesis of a new family of LY333531 analogues. Base-mediated cyclocondensation with thiourea afforded novel 5,6-bis(1-methyl-1H-indol-3-yl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, which was efficiently converted to the pyrimidin-2,4(1H,3H)-dione congener. Synthesis of a six-membered K-252c analogue, 5,6-bis(1-methyl-1H-indol-3-yl)pyrimidin-4(3H)-one, is also described.     

Synthesis of fluoroquinoxalin-2(1<Emphasis Type="Italic">H</Emphasis>)-one derivatives containing substituents in the pyrazine and benzene fragments

6,7-Difluoroquinoxalin-2-one reacted with indoles, 5,5-dimethylcyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, resorcinol, and pyrogallol on heating in acetic acid to give products of hydrogen substitution in the heterocyclic fragment. Heating of 6,7-difluoro-3-(1H-indol-3-yl)quinoxalin-2(1H)-ones with N-methylpiperazine gave the corresponding 7-(4-methylpiperazin-1-yl) derivatives.     

The mechanisms of photochromic transformations of 2-indolylfulgides

Photochromic properties of 2-indolylfulgides, namely, Z-3-[1-(1,3-dimethyl-1H-indol-2-yl)ethylidene]-4-isopropylidenetetrahydrofuran-2,5-dione andE-3-isopropylidene-4-(1-methyl-1H-indol-2-ylmethylidene)tetrahydrofuran-2,5-dione, were studied. The quantum yields of their photochemical isomerizations in toluene and the rate constant of the dark ring-opening in ethanol were determined. The fluorescence spectra of the open and cyclic forms of 2-indolylfulgides were measured. It was assumed that the excited-stateZ-isomer can be transformed into a cyclic isomer without intermediacy of anE-isomer in the ground state. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1026–1029, June, 2000.     

N-Arylation of a hindered indoline as a route to 2-(2-methyl-1-(4-oxo-3,4-dihydrophthalazin-1-yl)-1H-indol-3-yl)acetic acid derivatives

A convenient synthesis of 2-(2-methyl-1-(4-oxo-3,4-dihydrophthalazin-1-yl)-1H-indol-3-yl)acetic acid derivatives is described using a microwave-promoted multi-step S_NAr reaction. The desired products were found to exhibit atropisomerism.     

Aminomethylation of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione

Mannich reactions of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione with formaldehyde and morpholine, piperidine, N-methylpiperazine, and diethylamine gave the corresponding 5-aminomethylsubstituted pyrimidine derivatives. The title compound reacted with excess piperazine to form 3,5-bis-(piperazin-1-yl) derivative, while its reaction with an equimolar amount of piperazine afforded 5,5′-(piperazin-1,4-diylbismethylene)bis[6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione].     

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.     

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.     

Comparison of 2D and 3D cell cultures of colorectal adenocarcinoma as models for drug screening

Russian Chemical Bulletin - The cytostatic effects of 5-fluorouracil, oxaliplatin, and 4-(5-methyl-5H-[1,3]dioxolo[4,5-f]-indol-7-yl)-3-(5-fluoro-1-benzofuran-3-yl)-1 H-pyrrole-2,5-dione...     

Simple procedure for preparation of quinoxalin-2(1H)-one 3-[Oxo(cyclo)alkyl(idene)] derivatives

A simple preparative procedure was developed for 3-(2-oxoalkylidene)-3,4-dihydroquinoxalin-2(1H)-ones, 4,5-dihydroxy-1-[3-oxo-3,4-dihydroquinoxalin-2(1H)-ylidene]-3,5-octadiene-2,7-dione, and 3-(2,3-dihydroxy-4-methyl-5-oxo-1,3-cyclopentadien-1-yl)quinoxalin-2(1H)-one by reaction of methyl ketones first with diethyl oxalate in the presence of sodium, and then with o-phenylenediamine.     

Reaction of methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with ureas: facile entry into the polycyclic meridianin analogues with uracil structural unit

Methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate was prepared simply and efficiently in two steps from 3-indoleacetic acid employing N,N-dimethylformamide dimethylacetal (DMFDMA). Upon treatment of (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with various (thio)ureas in the presence of an acid 2-(1H-indol-3-yl)-3-(3-substituted(thio)ureido)propenoates were obtained in high yields. A base promoted cyclization of these (thio)ureidopropenoate derivatives afforded 5-(indol-3-yl)-3-substituted-pyrimidine-2,4-diones which represent a new family of meridianine analogues.     

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.     

Synthesis and tuberculocidic activity of some 4-arylaminomethylene-3-methyl-1-(pyrimidin-2-yl)pyrazol-5(4H)-ones

4-Arylaminomethylene-3-methyl-1-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)pyrazol-5(4H)-ones were synthesized by a three-component reaction between the 6-methyl-2-(3-methyl-5-oxo-2,5-dihydropyrazol-1-yl)pyrimidin-4(1H)-one, triethoxymethane, and an aromatic amine. These compounds were found to exist as aminomethyleneketones regardless of the electronic effects of substituents in the aromatic fragments. The resulting compounds showed pronounced tuberculocidic activity.     

Oxidation and isomerism of thietane-containing heterocycles

Oxidation of 6-methyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-dione, 5(6)-nitro-1-(thiethan-3-yl)-benzimidazole, 2-methyl-4-nitro-1-(thiethan-3-yl)- and 5-bromo-2-methyl-4-nitro-1-(thiethan-3-yl)imidazoles was examined. Corresponding 1-oxothietan-3-yl- and 1,1-dioxothietan-3-yl derivatives were synthesized for the first time. Some factors affecting the quality of the final products and optimal conditions of the oxidation of thietanyl derivatives of pyrimidine-2,4(1H,3H)-dione, nitrobenzimidazole, and nitroimidazole were found. According to 1H NMR spectroscopy data, the obtained sulfoxides are mixtures of cis/trans isomers, the diastereomers ratio determined by the substituent at position 3 of thietane ring.