Photocyclization Products Research Articles

Controllable Versatility in a Single Molecular System from Photoisomerization to Photocyclization

AbstractCyanostilbene is a typical photoresponsive group with multiple photochemical reactions. However, it is still challenging to achieve multiple photochemical reactions and versatility in the same molecular system at one wavelength excitation. The cyanostilbene‐based molecule synthesized in this work can undergo photoisomerization and photocyclization in sequence under continuous illumination at 365 nm in solution. This process is demonstrated by nuclear magnetic resonance, high‐resolution mass spectroscopies, and single crystal X‐ray diffraction. The fluorescence intensity of the solution gradually increases by more than ten times with the extension of the illumination time due to the formation of a photocyclization product with a high fluorescence quantum yield. Based on this interesting phenomenon, the multifunctional applications of this system are presented. This provides a design idea for multifunctional molecules via photochemical reactions.

Synthesis, Photochemistry, Computational Study and Potential Application of New Styryl-Thiophene and Naphtho-Thiophene Benzylamines.

In this research, the synthesis, photochemistry, and computational study of new cis- and trans-isomers of amino-thienostilbenes is performed to test the efficiency of their production and acid resistance, and to investigate their electronic structure, photoreactivity, photophysical characteristics, and potential biological activity. The electronic structure and conformations of synthesized thienostilbene amines and their photocyclization products are examined computationally, along with molecular modeling of amines possessing two thiophene rings that showed inhibitory potential toward cholinesterases. New amino-styryl thiophenes, with favorable photophysical properties and proven acid resistance, represent model compounds for their water-soluble ammonium salts as potential styryl optical dyes. The comparison with organic dyes possessing a trans-aminostilbene subunit as the scaffold shows that the newly synthesized trans-aminostilbenes have very similar absorbance wavelengths. Furthermore, their functionalized cis-isomers and photocyclization products are good candidates for cholinesterase inhibitors because of the structural similarity of the molecular skeleton to some already proven bioactive derivatives.

Construction of 3,12-Diazatetracyclododecane-dienes through Unexpected Visible-Light-Induced Radical Cascade Cyclization.

A novel visible-light-induced cascade radical cyclization reaction of 3-cyano-4-aryl-1,4-dihydropyridines for the construction of 3,12-diazatetracyclododecane-diene derivatives is reported for the first time. In the presence of 410 nm blue LED lamp as the light source and ethanol as the solvent, the reactions proceed smoothly to afford photocyclization products in good yields. The process is carried out through the breaking of original C═C double bonds and the formation of three new single bonds in one pot and proved to be able to tolerate different substituents.

Methoxy-substituted naphthothiophenes – Single molecules' vs. condensed phase properties and prospects for organic electronics applications

A series of tricyclic naphthothiophenes – photocyclization products (8-methoxynaphtho[1,2-b]thiophene; 6,7-dimethoxynaphtho[1,2-b]thiophene; 8-methoxynaphtho[2,1-b]thiophene) have been studied. HOMO and LUMO levels, as well as a gap between them was accessed by cyclic voltammetry and optical spectroscopy. Double potential step chronoamperometry showed that the former naphthothiophene exhibits slower current decay than the other substances. Charge carrier mobility measured by the CELIV technique was estimated to be of the order of 10−4 cm2V−1s−1 for 0.2 µm films and approaches 10−1 cm2V−1s−1. for the 5 µm film of 8-methoxynaphtho[1,2-b]thiophene. It is believed the high mobility is associated with the ordering of the high conductivity axis of the microcrystals in the layers.

Thienyl-phenyl Ethylenes with Crown Ether Fragments and Their Photocyclization Products: UV-Vis, NMR, Redox Response for Complexation. A 18-Crown-6 Ether Restricted with a Tricyclic Aromatic Moiety

Thienyl-phenyl Ethylenes with Crown Ether Fragments and Their Photocyclization Products: UV-Vis, NMR, Redox Response for Complexation. A 18-Crown-6 Ether Restricted with a Tricyclic Aromatic Moiety

Substituent Effects on Selective Syntheses of Fused‐Ring Heterocycles Based on Carbazole and Naphthalene by Photocyclization: Synthesis, Crystal Structures, and Properties

AbstractTwo new different types of fused‐ring heterocycles based on the carbazole and naphthalene, that is, 10‐bromine‐7‐hexyl‐7‐monoaza[6]helicene (7) and 14‐hexyl‐11‐(thiophen‐2‐yl)‐14H‐phenanthro[4, 3‐b]carbazole (10) were successfully synthesized through the introduction of bromine and thiophene subtituents into 9‐Hexyl‐9‐carbazole‐3‐carbaldehyde. Their structures were fully characterized by 1H NMR, 13C NMR, mass spectroscopy and single‐crystal X‐ray diffraction pattern. Single‐crystal structures revealed that compound 10 possessed less distortion and deformation, and better planarity than compound 7. Compounds 7 and 10 had good solubility and thermal stability (Td = 236.82 °C for 7, Td = 214.96 °C for 10). These compounds had absorption maximum peaks at 319 nm for 7, 337 nm for 10, and emitted blue light with the peaks at 435 nm for 7, 447 nm for 10 in dichloromethane. The fluorescence quantum yields of compounds 7, 10 in different solvents were measured in the range of 8% ‐ 18%, 35% ‐ 74%, respectively. These results showed that introducing the functional substituent group of thiophene to the carbazole could not only transform photocyclization products from helicenes into other types of fused‐ring heterocyclic compounds but also increase the fluorescence quantum yields of compound 10 by more than three and half times. The simple synthetic method would pave the way for obtaining fused‐ring heterocycles with diverse types and various properties.

Regiospecific Photocyclization of Mono- and Bis-Styryl-Substituted N-Heterocycles: A Synthesis of DNA-Binding Benzo[c]quinolizinium Derivatives.

Regiospecific C-N photocyclization of mono- and bis-styryl-substituted N-heterocycles was investigated. We demonstrated that the C-N regiospecificity of the photoinduced electrocyclization is a general feature of ortho-styryl-substituted N-heterocycles comprising one and two nitrogen atoms. This phototransformation provides a straightforward synthesis of the pharmaceutically important benzo[c]quinolizinium cation and its aza-analogues. Noticeably, bis-styryl derivatives undergo only one-fold cyclization with the second styryl fragment remaining uninvolved in the cyclization process. Photocyclization products of monostyryl derivativatives intercalate into calf thymus DNA (ct DNA), whereas photocyclization products of bis-styryl derivativatives possess a mixed binding mechanism with ct DNA. The results can be used for development of novel DNA-targeting chemotherapeutics based on benzo[c]quinolizinium derivatives.

Reactions of intramolecular C-N photocyclization and photoaddition to the double bond of methoxy- and methoxycarbonyl-substituted styrylbenzoquinolines

Photochemical reactions of C-N photocyclization and ethanol photoaddition, which are side reactions relative to photoisomerization, have been studied for 3-(3-methoxystyryl)benzo[f]quinoline (3MSBQ) and 3-(4-methoxycarbonylstyryl)benzo[f]quinoline (4MCSBQ). The overall quantum yield of the side reactions is almost two orders of magnitude below that of photoisomerization. The presence of several photoproducts has been revealed by principal component analysis. By electrospray mass spectrometry and absorption and emission electron spectroscopy, it has been found that the photoproducts are 12b-azoniabenzo[c]chrysene derivatives formed via the intramolecular C-N photocyclization and adducts with ethanol, of which the former dominate for 3MSBQ and the latter are prevalent for 4MCSBQ. The relative stability of the primary photocyclization products for a series of styrylbenzoquinolines calculated by the DFT (B3LYP/6-31G*) method correlates qualitatively with experimental data on the formation of the final oxidized condensed products.

Co-Crystals and Salts Obtained from Dinitrogen Bases and 1,2,3,4-Cyclobutane Tetracarboxylic Acid and the Use of the Latter As a Template for Solid-State Photocyclization Reactions

The synthesis, isolation, and characterization of a series of co-crystals and adducts of 1,2,3,4-cyclobutane tetracarboxylic acid (H4CBTC) with the dinitrogen bases 1,2-bis(4-pyridyl)ethane (BPA) and 1,2-bis(4-pyridyl)ethylene (BPE), respectively, are reported. The thermal stability and interconversion process between the dihydrated salt [BPAH2][H2CBTC]·2H2O and its dehydration product and the use of this latter to obtain the neutral co-crystal [BPA]2·[H4CBTC] have been investigated. The products obtained with 1,2-bis(4-pyridyl)ethylene (BPE), namely, the salt [BPEH][H3CBTC] and the co-crystal [BPE]2·[H4CBTC] are prearranged in space so as to be able to react photochemically yielding rctt-tetrakis(4-pyridyl)cyclobutane (TPCB). Recrystallization from ethanol of the photocyclization products yields the channeled structure of the solvated co-crystal [TPCB]·[H4CBTC]·EtOH.

Photoinduced CC‐coupling Reactions of Rigid Diastereomeric Benzophenone‐Methionine Dyads

The reactions of ketone/methionine systems are widely used as efficient and selective sources of biorelevant radical species. In this study, we address intramolecular variants of this couple with respect to its photosynthetic utility and as a mechanistic model of underlying elementary reaction steps of biological importance, especially with respect to the study of photoinitiated electron transport in complex peptides. The outcomes of this study are two-fold: (1) steady-state irradiation of sterically constrained benzophenone/methionine dyads afforded stable photocyclization products with high yield and product selectivity. (2) Mechanistic insights into the triplet-triggered product formation were obtained from an analysis of the flash photolysis results and the molecular structure of the stable product formed upon irradiation. Time-resolved experiments identified (net) hydrogen-atom transfer from the methionine as the mechanism of the triplet quenching and the resulting biradicals as the major precursor of the isolated stable product. Both the analyses of triplet quenching and stable-product formation in the diastereomeric pairs point to effects of chiral center configuration, i.e., significant stereoselectivity is observed for all elementary steps. The underlying stereochemical restraints were quantitatively addressed by means of molecular dynamics simulations.

Does one-photon photocyclization of trans-diarylethylenes involve adiabatic trans-to-cis photoisomerization? potential energy surface calculations for 1-styrylnaphthalene

Potential energy surface (PES) for 1-styrylnaphthalene was calculated by PM3 method for the S0 state and PM3-CI(2x2) method with configuration interaction for the S1 state. Scanning PES along both isomerization and cyclization reaction coordinates enabled to reveal the minimum energy path (MEP) with low barriers on the S1 PES from E-isomer to dihydrocyclophotoproduct (DHP). This is consistent with formation of the photocyclization product in one-photon process during irradiation of E-isomer. Additionally, the MEP was found to bypass the coordinate region of Z-isomer, i.e. one-photon E-isomer-to-DHP photocyclization does not demand participation of the excited Z-isomer. Therefore, adiabatic trans-to-cis isomerization is likely not an intermediate stage on the E-isomer photocyclization pathway, and experimentally observed one-photon formation of the DHP from the E-isomer is likely not an evidence for adiabatic trans-to-cis photoisomerization, as it is usually assumed. According to the results obtained, two photochemical reactions of E-isomer, photoisomerization to Z-isomer and photocyclization to DHP, are not consecutive but parallel reactions with branching at perpendicular conformer on the S1 PES. © 2012 Wiley Periodicals, Inc.

Synthesis of Paullone and Kenpaullone Derivatives by Photocyclization of 2‐(2‐Chloro‐1H‐indol‐3‐yl)‐N‐arylacetamides

AbstractAn efficient synthesis of paullone and kenpaullone derivatives in moderate to high yields has been achieved through photocyclizations of (2‐chloro‐1H‐indole‐3‐yl)‐N‐arylacetamides in acetone at room temperature. Paullone and kenpaullone have been obtained easily and in high yields by deprotection of the photocyclization products.

Crystal Structures of Thiobarbiturate with N-Phenylalkyl Group and Its Photocyclization Product

The photo-irradiation of thiobarbiturates (1) with an N-phenylalkyl group gives bicyclic fused pyrimidine derivatives (2) through a Norrish type II reaction. The crystal structures of dihydro-1,5,5-trimethyl-3-(3-phenylpropyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione (1a) and the photocyclization product (2b) of dihydro-1,5,5-trimethyl-3-(3-phenylbutyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione (1b) were elucidated by X-ray crystallographic analysis. The photocyclization product (2b) was determined to be 1,6,7,8-tetrahydro-1,3,3-trimethyl-9-phenyl-2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione.

Quantum-chemical study of the photoisomerization and photocyclization reactions of styrylquinolines: Potential energy surfaces

The cross sections of potential energy surfaces (PES) for the S0 and S1 states were calculated by the semiempirical PM3 and PM3-CI (8 × 8) methods, respectively, along the reaction coordinate of the isomerization and cyclization of 2- and 4-styrylquinolines (SQ). The PES of the S0 state exhibits three minima separated by the transition-state barriers of isomerization and cyclization corresponding to three isomeric SQ forms, the E- and Z-isomers and the dihydrogenated cyclic product. On the PES of the S1 state, the “perpendicular minimum” at dihedral angle values of ∼ 90° corresponds to the transition state of the isomerization reaction and the pericyclic minimum with a distance of 1.7–2.0 A between the atoms involved in cyclization corresponds to the transition state of the cyclization reaction. With simultaneous scanning of the PES of the S1 state along the isomerization and cyclization reaction coordinates, the minimal-energy path was found for 4SQ, which makes it possible to explain the formation of the photocyclization product in the single-photon process upon irradiation of the E-isomer. It was found that the PM3 method overestimates the stability of the structures in which the aromatic ring is oriented perpendicular to the plane of the molecule, resulting in virtual minima on the PES of the S1 states.

Comparative semiempirical and DFT study of styrylnaphthalenes and styrylquinolines and their photocyclization products

AbstractSemiempirical molecular orbital (PM3, PM6, and RM1) and density functional theory (DFT) (B3LYP/6‐31G*) studies are carried out for 1‐ and 2‐styrylnaphthalenes and their aza‐derivatives—2‐ and 4‐styrylquinolines. Relative stabilities of three isomeric forms: E‐ and Z‐isomers and the closed‐ring dihydrocyclophotoproduct (derivative of dihydrophenanthrene) are calculated. Compared to PM3, PM6 and especially RM1 understate heats of formation; in some cases, PM6 and RM1 even place Z‐isomer in energy below E‐isomer. PM3 rather close to DFT predicts heats of isomerization reaction, whereas PM6 and especially RM1 underestimate these values. Semiempirical methods in comparison with DFT markedly underestimate heats of cyclization reaction; however, reproduce trends in relative stabilities of different isomers in dependence on the structure of styrylnaphthalenes and styrylquinolines. Qualitative correlation is found between calculated relative stabilities of the closed‐ring forms (heats of cyclization reaction) and experimental data: cyclized products with low heats of cyclization are observed in steady‐state photolysis and those with high heats of cyclization are not. In the latter case, the closed‐ring compounds, if formed in the excited state, due to thermal instability decompose rapidly with ring opening in the ground state that prevents their observation. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Quantum-chemical study of aza derivatives of styrylnaphthalenes and their photocyclization products

Quantum-chemical calculation of 1- and 2-styrylnaphthalenes and their aza derivatives 2- and 4-styrylquinolines were carried out by the DFT B3LYP/6-31G* method. The relative stability of the products of their photoisomerization, (E)- and (Z)-isomers and of the photocyclization products, the corresponding derivatives of dihydrophenanthrene (DHP), was calculated. It has been shown that, by the DHP stability, the diarylethylenes in question are divided into two groups in qualitative agreement with experimental data on their photochemical activity in the photocyclization reaction.

Chiral photochemistry within natural and functionalized cyclodextrins: Chiral induction in photocyclization products from carbonyl compounds

Chiral induction in products resulting from hydrogen abstraction upon excitation of carbonyl compounds included in four cyclodextrin related host systems has been examined. The chiral induction obtained in photoproducts is moderate. Results suggest that there is potential to improve the asymmetric interaction between the reactant molecules and the supramolecular host cyclodextrins. However, no models that would help us to predict the outcome of chiral induction in a photochemical reaction have resulted from this investigation. Given the use of cyclodextrins as chiral stationary phases in HPLC and GC separations we are optimistic that there is considerable potential for cyclodextrins as chiral hosts in photoreactions.

Photolysis of the herbicide sulcotrione: formation of a major photoproduct and its toxicity evaluation

Sulcotrione is a selective herbicide marketed for use in maize since 1993, but its environmental fate is not yet fully elucidated. A major metabolite resulting from cleavage between the two ring moieties, leading to 2-chloro-4-mesylbenzoic acid (CMBA), has been identified; it presents a rather low toxicity. In photochemical studies this compound has also been claimed to be formed in high proportions. The present authors recently found that, under irradiation, sulcotrione mainly yields a cyclization product (CP). Thus, Sulcotrione photochemistry is still a matter of debate. The aim of the present work was to give an unequivocal answer to this issue. The potential toxicity of CP, CMBA and sulcotrione towards three organisms considered as representative of aquatic ecosystems was also evaluated. The main transformation product of sulcotrione is the cyclization product (CP), and CMBA is formed in smaller amounts. For the toxicological approach, the tested organisms were a bacterium, Vibrio fischeri (Bejerinck) Lehmann & Neumann, an alga, Pseudokirchneriella subcapitata (Korshikov) Hindak, and a protozoan, Tetrahymena pyriformis (Ehrenberg) Lwoff. Sulcotrione is more harmful towards the alga, but CP is more toxic to the bacterium and the protozoan. It must be noted that the measured toxicities are nonetheless rather low. On irradiation, sulcotrione mainly gives the photocyclization product, which presents a higher toxicity than sulcotrione and CMBA. This cyclization product should thus be considered in sulcotrione environmental risk assessment.

Optimizing high-performance liquid chromatography method with fluorescence detection for quantification of tamoxifen and two metabolites in human plasma: Application to a clinical study

We set an improved high-performance liquid chromatography method with fluorescence detection HPLC-FLU assay with more sensitivity and precision for the quantification of tamoxifen and two metabolites: 4-hydroxytamoxifen and N-desmethyltamoxifen. The compounds and internal standard, mexiletine, were separated with an Agilent Extend C 18 column set at 65 °C and a mobile phase of methanol–1% triethylamine aqueous solution (pH 11; 82:18, v/v). The detection system utilized offline ultraviolet irradiation to convert the analytes to their respective photocyclisation products, followed by fluorescence detection ( λ ex = 260 nm and λ em = 375 nm). The limits of quantification for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in plasma were improved to 0.5, 0.5 and 0.1 ng/ml, respectively. And the retention times for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen were minimized to 11, 10 and 3.9 min, respectively. A single stage liquid–liquid extraction method for determination of these triphenylethylene drugs in plasma was developed, with high extraction efficiency and rapid sample treatment for target compounds. The method has been validated for use in a clinical bioavailability research of tamoxifen.

Synthesis of Heteroaryl Imines: Theoretical and Experimental Approach to the Determination of the Configuration of CN Double Bond

The reaction between an iminophosphorane with furan-2-carbaldehyde, thiophene-2-carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde at 60 degrees C gives the corresponding trans imines in 53-84% yields, while the same reaction at 100 degrees C gives a mixture of the corresponding trans and cis imines. Whether the iminophosphorane reacted with 5-nitrofuran-2-carbaldehyde or 5-nitrothiophene-2-carbaldehyde only the trans imines were obtained in 85-89% yields. The irradiation of the imines obtained from thiophene-2-carbaldehyde and thiophene-3-carbaldehyde gave the corresponding photocyclization products. Cis/trans stereochemistry of the imines can be assigned simulating the UV-vis spectra. In the case of the imine from furan-2-carbaldehyde the computed spectra are characterized by an intense absorption at 361 and 357 nm respectively for the trans-1 and trans-2 structures. No other absorptions of comparable intensity have been predicted: the agreement with the experimental spectrum can be considered good. Furthermore, the experimental weak peaks at 280 and 270 nm can be associated to the computed transitions at 278 and 260 nm for the trans-1 isomer. Several minima of the energy surface can be assigned to the cis isomer, and they all present a very similar energy. The structures of the cis-1 and cis-2 isomers present quite coincident computed electronic spectra. In both cases, the computed spectrum shows two principal features. For the cis-1 structure, the first characteristic absorption is located at 414 nm and the second one at 284 nm. For the cis-2 structure, the first feature is located at 412 nm and the second one at 286 nm. The second transition is computed somewhat more intense. The experimental spectrum could be the consequence of similar populations of the planar cis structure (cis-3) and nonplanar cis structures (cis-1, cis-2, and their enantiomers).