Photochromism of Dihydroindolizines. Part III [1]. Synthesis and Photochromic Behavior of Novel Photochromic Dihydroindolizines Incorporating a Cholesteryl Moiety

Ten novel photochromic dihydroindolizines (DHIs) based on 1,5-electrocyclization and bearing a cholesteryl moiety at 7-position of the DHI skeleton were synthesized. 1D, 2D, NOESY ¹H NMR spectra, mass spectrometry, and elemental analysis were used for their characterization. Irradiation of the DHIs in CH₂Cl₂ solution with polychromatic light leads to the formation of red to red-violet colored betaines. Most colored betaine forms are notable in CH₂Cl₂ solution at room temperature because of their slow 1,5-electrocyclization except in one case, where the colored betaine could be observed only after cooling with liquid nitrogen due to the fast electrocyclization back reaction. The kinetics of the reverse 1,5-electrocyclization of the colored betaines into the corresponding DHIs were detected using both UV/VIS and flash photolysis measurements.The presence of three isosbestic points in the fading spectrum of the betaines proved that the thermal back reaction to the DHIs follows a first order mechanism. Tuning of the photophysical properties of DHIs and their colored betaines was achieved by change of substituents in the ester and fluorene regions. A notable increase of the t₃₀-value of some betaines by a factor ranging between 1.01 and 1.57 compared with the betaine form of dicyanopridazine DHI standard (t₃₀=243min) was observed. The high photo-fatigue resistance of these betaines will help to find their applications.     

Photochromism of Dihydroindolizines. Part III [1]. Synthesis and Photochromic Behavior of Novel Photochromic Dihydroindolizines Incorporating a Cholesteryl Moiety

Summary. Ten novel photochromic dihydroindolizines (DHIs) based on 1,5-electrocyclization and bearing a cholesteryl moiety at 7-position of the DHI skeleton were synthesized. 1D, 2D, NOESY ¹H NMR spectra, mass spectrometry, and elemental analysis were used for their characterization. Irradiation of the DHIs in CH₂Cl₂ solution with polychromatic light leads to the formation of red to red-violet colored betaines. Most colored betaine forms are notable in CH₂Cl₂ solution at room temperature because of their slow 1,5-electrocyclization except in one case, where the colored betaine could be observed only after cooling with liquid nitrogen due to the fast electrocyclization back reaction. The kinetics of the reverse 1,5-electrocyclization of the colored betaines into the corresponding DHIs were detected using both UV/VIS and flash photolysis measurements.The presence of three isosbestic points in the fading spectrum of the betaines proved that the thermal back reaction to the DHIs follows a first order mechanism. Tuning of the photophysical properties of DHIs and their colored betaines was achieved by change of substituents in the ester and fluorene regions. A notable increase of the t₃₀-value of some betaines by a factor ranging between 1.01 and 1.57 compared with the betaine form of dicyanopridazine DHI standard (t₃₀=243min) was observed. The high photo-fatigue resistance of these betaines will help to find their applications.Present address: Special Division for Human Life Technology, National Research Institute of Advanced Industrial Science and Technology, 1-8-31, Midorigaoka, Ikeda, Osaka 563-8577, Japan     

Photochromism of dihydroindolizines. Part XV: Synthesis and photophysical properties of dihydroindolizine photoswitches bearing a conjugated aryleneethynylene tripodal linker system

Abstract  

Different photochromic dihydroindolizines (DHIs) bearing conjugated aryleneethynylene tripodal linker systems were synthesized using several Sonogashira coupling reactions. The spirocyclopropene precursors incorporating different acetylenic bridge moieties at the 2-position of the fluorene moiety were synthesized via chemical and photochemical routes. Multiaddressable photochromic properties of the DHI derivatives substituted in the fluorene (region A) and pyridazine (region C) parts were studied. Optimization of the formation of the DHIs was also done by applying different palladium-mediated Sonogashira coupling reactions. Irradiation of the photochromic DHIs with polychromatic light led to colored betaines which undergo thermal 1,5-electrocyclization. The kinetics of the thermal 1,5-electrocyclization were studied by using a multichannel FT–UV–Vis spectrophotometer. A pronounced effect on the kinetic behavior of the 1,5-electrocyclization process of the betaines was observed by changing substitution from non-substituted to dimethyl-substituted pyridazines. Photodegradation experiments and the bleaching and fading cycles revealed high photostability of the betaines under investigation. These properties of betaines of tripodal linker conjugates will help these materials to find applications.     

Photochromism of dihydroindolizines. Part 16: Tuning of the photophysical behavior of photochromic dihydroindolizines in solution and in polymeric thin film

In this work, photochromic materials based on the dihydroindolizine (DHI) system were synthesized in multistep reactions using chemical and photochemical methods. Some of the synthesized photochromic dihydroindolizine derivatives were substituted on the fluorene (region A) and pyridazine (region C) moieties in order to provide the appropriate functionality for optimal tuning of the photochromic properties of the system. Irradiation of the photochromic DHIs with polychromatic light led to ring opened colored betaines, which underwent thermal 1,5-electrocyclization. The red to green colored betaines produced after UV irradiation returned back through 1,5-electrocyclization to the corresponding DHIs with different rate constants depending on the substituents in both fluorene and pyridazine regions. The kinetic measurements of the thermal 1,5-electrocyclization under different temperatures that ranged from −10 to 25 °C showed that the half-lives of the colored betaines fall in the second to hours domain. Interestingly, these materials showed a very good photochromic behavior not only in solution but also in the PMMA matrix. Irradiation of a slide prepared by the deep-coating method led to the formation of the colored betaine and the kinetics of the thermally reversible 1,5-electrocyclization and the AFM image of the film has been recorded. Indeed, the chemical and thermal stability of the investigated betaines in polymer (PMMA) will render such species useful for a plethora of new of applications.     

Synthesis of cns potentially active bicyclic and tricyclic derivatives of pyrazolo[1,5-a][1,3]diazepines

Reaction of 5-ethylamino-3-phenylpyrazole with dicarboxylic acid anhydrides in tetrahydrofuran in the presence of 1,3-dicyclohexylcarbodiimide, afforded bicyclic and tricyclic derivatives of pyrazolo[1,5-a][1,3]-diazepines. The tricyclic derivatives constitute a new class of compounds. Characterisation of these products was effected with ir, pmr, and ¹³C nmr spectral data.     

Reactions of 4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines with α,β‐unsaturated carbonyl compounds

The reaction of 5,7‐diphenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine ( 1 ) with α,β‐unsaturated carbonyl compounds 2a‐f led to the formation of the alkylated heterocycles 3a‐f (Figure 1). However, the reaction of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine ( 5 ) with 2a‐c yielded under the same conditions the triazolo[5,1‐b]quinazolines 6a‐c (Figure 3). In this case, the alkylation is followed by a cyclocondensation. The structure elucidation of the products is based on ir, ms, ¹H and ¹³C nmr measurements and on an X‐ray diffraction study.     

Further Prenylated Bi‐ and Tricyclic Phloroglucinol Derivatives from Hypericum papuanum

From the petroleum‐ether extract of the dried aerial parts of Hypericum papuanum, three new prenylated tricyclic and four new bicyclic acylphloroglucinol derivatives were isolated by bioactivity‐guided fractionation. The structures of the bicyclic compounds enaimeone A, B, and C ( 1 / 1a , 2 / 2a , and 3 / 3a , resp.) were elucidated as rel‐(1R,5R,6S)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐1‐(3‐methylbut‐2‐enyl)‐3‐(2‐methylpropanoyl)‐bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 1 / 1a ), rel‐(1R,5R,6R)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐1‐(3‐methylbut‐2‐enyl)‐3‐(2‐methylpropanoyl)bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 2 / 2a ), rel‐(1R,5R,6R)‐4‐hydroxy‐6‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐3‐(2‐methylbutanoyl)‐1‐(3‐methylbut‐2‐enyl)bicyclo[3.2.1]oct‐3‐ene‐2,8‐dione ( 3 / 3a ). The tricyclic isolates 8‐hydroxy‐3β‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylpropanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 4 ), 8‐hydroxy‐3α‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylpropanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 5 ), and 8‐hydroxy‐3α‐(1‐hydroxy‐1‐methylethyl)‐4,4,7‐trimethyl‐9‐(2‐methylbutanoyl)‐5βH‐tricyclo[5.3.1.0^1,5]undec‐8‐ene‐10,11‐dione ( 6 ), and their corresponding tautomers 4a , 5a , and 6a , were named 1′‐hydroxyialibinones A, B, and D, respectively. Oxidative decomposition of furonewguinone A (=2,3,3a,5‐tetrahydro‐3a‐hydroxy‐2‐(1‐hydroxy‐1‐methylethyl)‐5‐methyl‐5‐(3‐methylbut‐2‐enyl)‐7‐(2‐methylpropanoyl)‐benzofuran‐4,6‐dione; 7 ) led to furonewguinone B (=3,3a,7,7a‐tetrahydro‐3a,6,7a‐trihydroxy‐2‐(1‐hydroxy‐1‐methylethyl)‐7‐methyl‐7‐(3‐methylbut‐2‐enyl)‐5‐(2‐methylpropanoyl)benzofuran‐4(2H)‐one; 8 / 8a ). Structure elucidation was based on extensive 1D and 2D NMR studies, as well as on data derived from mass spectrometry. Furthermore, the cytotoxicity towards KB nasopharyngeal carcinoma cells and the antibacterial activity were determined.     

Synthesis of Novel Tricyclic 1,5‐Benzothiazepine Derivatives Bearing Quinoline Moiety via [2 + 2] Cycloaddition Reaction

A series of new tricyclic 1,5‐benzothiazepine derivatives were synthesized by the reaction of 1,5‐benzothiazepine containing 2‐phenoxy‐quinoline with chloracetyl chloride and phenoxyacetyl chloride. The structures of the target compounds were confirmed by IR, ¹H NMR MS, and elemental analysis.     

Palladium-catalyzed cross-coupling reactions and electrocyclizations—efficient combinations for new cascade reactions

Palladium-catalyzed cross-coupling reactions and electrocyclic transformations as well as cycloadditions can efficiently be combined in one-pot sequences to build up complex molecules from simple precursors. 1,3-Dicyclopropyl-1,2-propadiene (1) could be coupled to various aryl halides, and the 1,3,5-hexatrienes resulting after rearrangement were trapped with different dienophiles. Further exploration of the highly reactive building block bicyclopropylidene (8) demonstrates the combinatorial potential of the two reaction modes in terms of two different three-component reactions, and even a novel four-component reaction was readily developed. Additional increase of complexity was gained by combining an intramolecular Heck reaction with consecutive trapping by 8, which can be carried out with or without 6π-electrocyclization. Finally a Stille-Heck-coupling sequence of substituted 2-bromocycloalkenyl triflates with functionally substituted alkenylstannanes and acrylic esters led to highly substituted 1,3,5-hexatrienes, which smoothly underwent 6π-electrocyclization at elevated temperatures to yield bi- and tricyclic skeletons. With this methodology at hand, a new versatile access to steroid-analogues with a diene moiety in the B ring and a functionality at C-7 was developed.     

Tricyclic heteroaromatic systems. 1,2,3,4-tetrahydropyrazolo[4,3-c][l]benzazepin-1-ones as potential antitumor agents

The synthesis of 1,2,3,4-tetrahydropyrazolo[4,3-c][1]benzazepin-1-ones 1 and that of its 10-methyl derivative 2 is reported. The preparation of the latter from 3-(2-aminobenzyl)3-pyrazolin-5-one and triethyl ortho-formate gave as the main product a derivative of the new tricyclic ring system, pyrazolo[1,5-c][1,3]benzo-diazepine. The structures of the new compounds synthesized were assigned by means of a ¹³C nmr study.     

Umcyclopropanisierung bei der Tetrabromierung eines tricyclischen Ketons zu 3exo, 4endo, 6exo-Tribrom-7-brommethyl-1,5-dimethyl-tricyclo[3.2.1.02,7]octan-8-on

Transcyclopropanation during the Tetrabromination of a Tricyclic Ketone to 3 exo, 4 endo, 6exo-Tribromo-7-bromomethyl-1,5-dimethyl-tricyclo[3.2.1.0^2,7]octan-8-one Bromination of the tricyclic ketone 1 with an excess of bromine at low temperature gives in approximately 30% yield the highly crystalline tricyclic tetrabromide 2 (Scheme 1). The structure of 2 was established by NMR.- and especially X-ray-analysis (Fig.1). Treatment of 1 with 1 mol-equ. of bromine gives an unstable dibromide, to which the structure 3 was assigned on the basis of its NMR.-spectrum and its further bromination to 2 (Scheme 1). In the course of the tetrabromination of 1 the original cyclopropane ring is opened in the first step ( 1 → 3 ) and another cyclopropane ring is formed in the second step ( 3 → 2 ) (cf. Scheme 3).     

Unkatalysierte sigmatrope 1,5-Wanderung von Acylgruppen bei der Thermolyse von 5-Acyl-5-methyl-1,3-cyclohexadienen

Uncatalyzed Sigmatropic 1,5-Shift of Acyl Groups in the Thermolysis of 5-Acyl-5-methyl-1,3-cyclohexadienes Four different 5-acyl-5-methyl-1,3-cyclohexadienes 1a–d (R = COOCH₃, COCH₃, COC₆H₅, CHO) have been shown to yield mixtures of 1,3-disubstituted cyclohexadienes 2–7 and 1,3-disubstituted aromatic product 8 upon thermolysis at 150–300° in solution and at 350–500° in the gas phase in a flow system. Two reaction pathways (A and B in Scheme 2) are considered for the rearrangement of the C-Skeleton. For the ester 1a ¹³C-isotopic substitution shows that products arise to 75–86% through a 1,5-sigmatropic shift of the methoxycarbonyl group ( A in Scheme 2) and to 14–25% through a sequence of reaction steps involving a 1,7-H-shift reaction in an acyclic intermediate ( B in Scheme 2). For the more reactive compounds 1b–d isomerization is assumed to follow the 1,5-sigmatropic pathway exclusively ( A in Scheme 2). A kinetic study yields the following sequence for the migration tendency of acyl groups toward sigmatropic 1,5-shift: COOCH₃ < COCH₃ < COC₆H₅ < CHO.     

A new synthesis of 3(2H)-furanones from acetylenic β-diketones

Thermal cyclization of 1,5-diarylpent-1-yne-3,5-diones led to the formation of 2-benzyliden-5-aryl-3(2H) furanones as well as 2,6-diaryl-4H-pyran-4-ones as minor products. The structure of the furanones was established from their ir, ¹H nmr and mass spectral data. Their reaction with hydrazine hydrate gave pyrazole derivatives.     

Design and Synthesis of Novel 2‐(1,2,4‐triazol‐1‐yl)‐quinoline‐Based Tricyclic 1,5‐benzothiazepine Derivatives

A series of new tricyclic 1,5‐benzothiazepine derivatives containing 2‐(1,2,4‐triazol‐1‐yl)quinoline were synthesized by the reaction of 1,5‐benzothiazepine with benzohydroximinoyl chlorides via 1,3‐dipolar cycloaddition reaction. The structures of the target compounds were confirmed by IR, ¹H NMR, MS, elemental, and X‐ray crystallographic analysis.     

1,5-Electrocyclization of 1-alkyl- 3-[(2Z)-2,4-diaryl-4-oxobut-2-en-1-yl]-1H-benzimidazol-3-ium bromides

Cyclization of 1-alkyl-3-[(2Z)-2,4-diaryl-4-oxobut-2-en-1-yl]-1H-benzimidazol-3-ium bromides occurs in the presence of MeONa at a reduced temperature of 5–10°C via a 1,5-electrocyclization mechanism to give 3a,4-dihydro-3H-pyrrolo[1,2-a]benzimidazoles. These are unstable under the reaction conditions and are readily converted to {1-[2-(alkylamino)phenyl]-4-phenyl-1H-pyrrol-3-yl}(phenyl)methanones.     

Heterocyclic variants of the 1,5-benzodiazepine system. VI. Derivatives of 2-methylthio-4-(p-r-phenyl)-3H-1,5-benzodiazepines

Ethyl 3-[3H-1,5-benzodiazepin-2-yl]carbazates II were prepared in moderate yields from the title compounds and ethyl carbazate. The compounds II were easily transformed into 1H-s-triazolo[4,3-a][1,5]benzodiazepin-1-ones III via a one-step procedure. Reaction of triazolo-1,5-benzodiazepinones III with sodium hydride in methyl iodide gave a mixture of products from which were isolated two compounds IV and V . The structure of all products was confirmed by ir, ¹H nmr and mass spectrometry.     

Synthesis and spectral properties of 2-methylthio-3H-4-(para-substituted-phenyl)-7-[(o-, and p-substituted)-phenylthio]-1,5-benzodiazepines

A series of twelve new 2-methylthio-3H-4-(p-substituted phenyl)-7-[(o-, and p-substituted)phenylthio]-1,5-benzodiazepines, which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3-dimercapto-1-(para-substituted-phenyl)-2-propen-1-one with 3,4-diamino phenyl-R-phenylthio ethers, and subsequently the 1H-1,5-benzodiazepine-2-thiones obtained were treated with sodium hydride and methyl iodide. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and ms.     

Stereochemical aspects of proton chemical shifts. X—The slow exchange 1H NMR spectrum of cis-transoid-cis-perhydroanthracene and of cis-decalin

The slow exchange 360 MHz ¹H NMR spectra of cis-transoid-cis-perhydroanthracene and of cis-decalin have been assigned. Shift increments due to the cis-annelation of a tetramethylene bridge to cyclohexane are presented.     

Thermal transformations of alk-1-enyl-N-phthalimidoaziridines

Thermolysis of alk-1-enyl-N-phthalimidoaziridines leads to products of 1,5-electrocyclization of intermediate azomethine ylides with participation of C=C bonds. If acyl or alkoxycarbonyl substituent is present in the aziridine ring, the C=O bond is also involved. Thermolysis of the title compounds in the presence of N-phenylmaleimide or dimethyl acetylenedicarboxylate under analogous conditions gives products of 1,3-dipolar cycloaddition of azomethine ylides to the double or triple bond of the dipolarophile.     

A short and unequivocal synthesis of 5-aminotetrazolo[1,5-a]-quinazoline as a tricyclic analogue of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035)

The discovery of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035) as an extremely potent inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor led to the preparation of several fused tricyclic quinazoline analogues. The present paper reports a new tricyclic derivative: 5-(3-bromoanilino)-7,8-dimethoxytetrazolo[1,5-a]quinazoline. This compound was synthesized by two different pathways viaa 1,3-dipolar cycloaddition of an azide at carbon 2 of the quinazoline ring.