Photocyclization Reaction Research Articles

Synthesis of Highly Fluorescent Thiazole Fused Benzo[a] Carbazoles by Sunlight Driven Photocyclization of Indolylthiazoles

AbstractHerein we report for the first time a sunlight‐driven, irreversible photocyclization reaction of indole‐linked trisubstituted thiazoles, for the synthesis of highly fluorescent thiazole‐fused benzo[a]carbazoles using a mixture of solvents (CH3CN: DMSO; 3 : 1). Ring opening of indole moiety was observed in the case of thiazole derivatives having 2‐methyl indole substituents. Under similar reaction conditions, photocyclization of trisubstituted thiazoles having cyclic 1,3‐dicarbonyls in place of indole moiety also worked. This reaction provides products having two medicinally important moieties thiazole and benzocarbazoles. We have studied the photophysical properties of all the products and found that most of the synthesized products have very good fluorescence quantum yields.

Visible Light-Induced 6π-Heterocyclization/Dehydroaromatization for Synthesis of Indoloquinolinone Skeletons.

In this work, we report a protocol for the synthesis of an indoloquinolinone skeleton using visible light-induced energy transfer. This method avoids the premodification of substrates and exhibits high yields. For gram-scale reactions, only 0.01 mol % (100 ppm) of photosensitizer is required for rapid conversion. Mechanistic studies revealed that this reaction differs from conventional 6π photocyclization reactions; undergoing a process involving 6π cyclization due to energy transfer and dehydrogenation due to product self-catalysis has been experienced.

Expanding the Color Range of Photoresponsive Multicolor Luminescent System Through Host-Guest Interaction.

Photoresponsive multicolor luminescent systems offer interesting functions, which have led to applications in anticounterfeiting and biological imaging. However, expanding the color range of these materials remains a challenging task. Herein, a carbazole-modified dithienylethene derivative (DTE-CZ) that exhibits modulated fluorescence color changes through the photocyclization reaction and photolysis reaction is synthesized. DTE-CZ emits orange fluorescence, and it can release a fluorophore which emits blue fluorescence by the photolysis reaction, resulting in the color change. Upon complexation of DTE-CZ with cucurbit[10]uril (CB[10]), the fluorescence wavelength will have a blue shift and the photolysis reaction will be inhibited. Benefiting from the influence of CB[10] and the photolysis reaction of free guests, the color range of the photoresponsive system which is composed of free guests and host-guest complexes is further extended. White light emission along with a color shift from yellow-green to blue was achieved by adjusting the ratio of free guests to host-guest complexes. Finally, the photoresponsive multicolor systems are utilized to construct a photostimulated PVA film and an information encryption system. This work provides an alternative strategy for the preparing of photoresponsive multicolor luminescent system and modulation of its color range.

Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Continuous Flow Synthesis of Benzotriazin-4(3H)-ones via Visible Light Mediated Nitrogen-Centered Norrish Reaction.

We report a new protocol for the synthesis of substituted benzotriazin-4(3H)-ones which are underrepresented heterocyclic scaffolds with important pharmacological properties. Our method exploits acyclic aryl triazine precursors that undergo a photocyclization reaction upon exposure to violet light (420 nm). Continuous flow reactor technology is exploited to afford excellent yields in only 10 min residence time with no additives or photocatalysts needed. The underlying reaction mechanism appears to be based on an unprecedented variation of the classical Norrish type II reaction with concomitant fragmentation and formation of N-N bonds. Scalability, process robustness, and green credentials of this intriguing transformation are highlighted.

Polycyclic Heteroaromatic π‐Linkers Provide Dithienylethene Switches with Favorable Thermal and Photochemical Properties for Solar‐Energy Storage

AbstractDithienylethene photoswitches with an aromatic π‐linker as the bridge between the two thiophene units are attractive starting materials for developing molecular solar thermal energy (MOST) storage systems, partly because the aromaticity of their ring‐open forms is a favorable feature with regard to the energy‐storage densities of their ring‐closed forms produced by photoinduced electrocyclization (photocyclization) reactions. At the same time, this typically leads to small barriers for their thermal cycloreversion reactions, which are not desirable in this context. Here, we use computational methods to show that this problem can be circumvented with polycyclic heteroaromatic π‐linkers. Specifically, through the tuning of the aromatic character of the individual rings of such a π‐linker (like indole or isoindole), it is shown to be possible to strike a delicate balance between the seemingly contrasting requirements of simultaneously achieving both a high energy‐storage density and a large cycloreversion barrier. Furthermore, this design is also found to provide for a quick and efficient photocyclization reaction, owing to the onset of excited‐state antiaromaticity in the π‐linker upon light absorption of the ring‐open form. Altogether, dithienylethenes with polycyclic heteroaromatic π‐linkers appear to have both thermal and photochemical properties suitable for further development into future MOST systems.

Dihydrophenanthrene Open-Shell Singlet Diradicals and Their Roles in the Mallory Photocyclization Reaction.

A computational study (ωB97X-D/6-31G(d)) of the Mallory photocyclization reaction has revealed that the well-established dihydrophenanthrene (DHP) intermediates can adopt either closed-shell (CS) or open-shell-diradical (OS) singlet ground states. A detailed study of the properties of DHPs allowed their classifications as OS, borderline-OS, borderline-CS, or CS intermediates. The triplet electronic state and higher energy CS* isomer of all the OS singlet diradicals were computationally located, and the expected relationship between the diradical index, yo, and the triplet energy and the OS-CS* energy gaps was established. The importance of aromaticity in stabilizing the OS singlet diradicals was confirmed by using the Harmonic Oscillator Model of Aromaticity (HOMA). The thermal decompositions of DHPs by cycloreversions to regenerate the Mallory starting materials were also studied. The cycloreversion mechanism was described as a homolytic cleavage characterized by an anchimeric assistance continuum promoted by bis-β-homolytic cleavage.

Extraction of the intrinsic rate constant for a photocyclization reaction in capillary microreactors using a simplified reactor model

Extraction of the intrinsic rate constants for a photocyclization reaction from a simplified reactor model.

New insights into the photocyclization reaction of a popular diarylethene switch: a nonadiabatic molecular dynamics study.

Diarylethene (DAE) molecular switches have continued to attract the attention of researchers for over 20 years. Their remarkable photophysical properties endow them with countless applications in photonics and molecular technologies. However, despite extensive experimental and theoretical research, the mechanism of DAE photoswitching is not yet fully rationalized. In this work, we investigate the ring closure dynamics of a popular DAE switch, 1,2-bis(3-methyl-5-phenyl-2 thienyl)perfluorocyclopentene (PT), using nonadiabatic molecular dynamics (NAMD) simulations. Employing the fewest switches surface hopping protocol, along with the semi-empirical multireference ODM2/MRCI-SD method, we investigate possible reaction pathways for this photoprocess, as well as their timescales and resulting photoproducts. Furthermore, using a dynamic configuration-space sampling procedure, we elucidate the role of triplet states in the photocyclization of PT, supporting available experimental data for the closely related DMPT molecule, which indicate an ultrafast intersystem crossing (ISC) transition competing with the singlet-driven photoswitching reaction. Our findings not only corroborate experimental studies on DAE switches, but also provide new mechanistic insights into the potential use in the rational design of DAE switches tailored for specific technological applications.

Direct photochemical intramolecular [4 + 2] cycloadditions of dehydrosecodine-type substrates for the synthesis of the iboga-type scaffold and divergent [2 + 2] cycloadditions employing micro-flow system.

Photocyclisation reactions offer a convenient and versatile method for constructing complex polycyclic scaffolds, particularly in the synthesis of natural products. While the [2 + 2] photocycloaddition reaction is well-established and extensively reported, the [4 + 2] counterpart via direct photochemical means remains challenging and relatively unexplored. In this work, we devised the rapid assembly of the iboga-type scaffold through photochemical intramolecular Diels-Alder reaction using a common biomimetic dehydrosecodine-type intermediate having vinyl indole and dihydropyridine (DHP) sub-units. Exploiting a micro-flow system, the medicinally important iboga-type scaffold was obtained up to 77% yield under mild, neutral conditions at room temperature. This study demonstrated the site-selective activation of the DHP moiety by direct UV-LED irradiation, eliminating the need for external photocatalysts or photosensitisers and showing good tolerance to a wide range of stabilised dehydrosecodine-type substrates. By adjusting the spatial arrangement of the DHP ring and the vinyl indole group, this versatile photochemical approach efficiently facilitates both [4 + 2] and [2 + 2] cyclisations, assembling architecturally complex multicyclic scaffolds. Precise photoactivation of the DHP subunit, generating short-lived biradical species, enabled the new way of harnessing the hidden but innately pre-encoded reactivity of the polyunsaturated dehydrosecodine-type intermediate. These photo-mediated [4 + 2] cyclisation and divergent [2 + 2] cycloadditions are distinct from biosynthetic processes, which are mainly mediated through concerted thermal cycloadditions.

Theoretical Study of the Photocyclization Reaction-Induced Dual Aggregation-Induced Emission Phenomenon.

Photochromic molecules with aggregation-induced emission (AIE) effects are of great value and prospective in various practical applications. To explore its inherent mechanism, the open isomer ap-BBTE and the closed isomer c-BBTE were chosen to perform the theoretical calculation using the quantum mechanics/molecular mechanics model combined with thermal vibration correlation function formalism. The calculations show that the photocyclization (PC) reaction from ap-BBTE to c-BBTE facilitates an improvement in the AIE effect. It is found that the fluorescence quantum yield (ΦF) enhancement of ap-BBTE is attributed to the restriction of the low-frequency rotational motion of the benzothiophene moiety and the high-frequency stretching vibrations of the C-C bond between the benzothiophene and benzylbis(thiadiazole) vinyl groups after aggregation. For c-BBTE, the increase in ΦF upon aggregation is mainly due to the suppression of the high-frequency stretching vibration of the C-C bond between the benzothiophene and the benzobis(thiadiazole) vinyl groups. In addition, the AIE effect was also enhanced from ap-BBTE to c-BBTE, which is consistent with the experimental phenomenon. The corresponding emission spectrum red-shifted from ap-BBTE to c-BBTE in both dilute solution and the crystalline state due to the improved intramolecular conjugation of c-BBTE. Moreover, the PC reaction from ap-BBTE to c-BBTE easily occurs in an excited state with a low energy barrier transition state by forming a C-C bond between benzothiophene groups effectively in dilute solution. Our calculations provide theoretical guidance for the further rational design of efficient AIE luminogens.

Internal Heavy-Atom Effect on Visible-Light-Induced Cyclization Reaction in Diarylethene-Perylenebisimide Dyads.

All-visible-light switchable diarylethene-perylenebisimide (DAE-PBI) dyads having bromine heavy atoms in the molecule were designed and synthesized. Very recently, we found a unique visible-light-induced cyclization reaction in a DAE-PBI dyad. The dyad exhibited reversible cyclization and cycloreversion reactions upon alternate irradiation with green (500-550 nm) and red (>600 nm) light. From the experimental results, it was suggested that the triplet state of DAE unit was generated via multiplicity conversion based on intramolecular energy transfer from the singlet excited state of PBI unit and that the cyclization reaction of DAE unit proceeded from the triplet state. In addition, it was revealed that the reactivity remarkably increased in a solvent containing heavy atoms such as carbon tetrachloride and iodoethane (i.e., external heavy-atom effect). Based on such results, in this study, we attempted to design and synthesize novel DAE-PBI dyads introducing bromine heavy atoms at different positions in the molecule. The synthesized dyads exhibited higher quantum yields of photocyclization reaction under visible-light irradiation even in a heavy-atom-free solvent compared to the previous dyad having no heavy atoms. The magnitude of enhancement well correlated to the contribution ratio of atomic orbital of bromine to the molecular orbital in LUMOs. These results indicated that the internal heavy atom effectively contributed to the visible-light-induced cyclization reaction in DAE-PBI dyads. Such an internal heavy-atom effect will pave the way for new molecular design to develop all-visible-light-activatable molecular switches.

Synthesis and Properties of Boron-Containing Heteromerous Bistricyclic Aromatic Enes: Structural Effects on Thermodynamic Stability and Photoreactivity.

Overcrowded bistricyclic aromatic enes (BAEs) have several conformations such as twisted and anti-folded conformers, and their stereochemistry and chromism have been studied in earnest. In this study, boron-containing heteromerous BAEs having various tricyclic structures were synthesized and their photophysical properties investigated. Single-crystal X-ray analysis revealed that the introduction of a rigid fluorene unit resulted in a twisted conformer, whereas the introduction of flexible units such as thioxanthene and 9,9-dimethyl-9,10-dihydroanthracene units resulted in an anti-folded conformer. The absorption spectra of the heteromerous BAEs were dependent on the introduced tricyclic structures, suggesting the immense impact of the tricyclic structures on the electronic structures of BAEs. DFT calculations revealed the large effect of the flexibility of the tricyclic structures on the thermodynamic stability of the conformers. In addition, the boron-containing heteromerous BAEs underwent photocyclization reactions, indicating their potential application as precursors of polyaromatic hydrocarbons and helical aromatic materials.

A comparative study on optical properties of pyrene-fused [4]helicenes and vinyl precursors

Polycyclic aromatic hydrocarbon-fused [n]helicene derivatives (PAH-fused [n]helicenes) have been widely investigated due to their excellent photoelectric and chiroptical properties. Herein, a series of pyrene-fused helicenes were synthesized by a photocyclization reaction and characterized by 1H/13C NMR spectroscopy and single crystal X-ray diffraction. All compounds and their vinyl precursors were studied as emitting materials. The experimental results reveal that these compounds possess reasonable emission efficiency (ΦFL = 97% for 3a) and tunable optical properties, and a wide emission band from bluish violet for 3c (401 nm) to green-yellow for 4c (530 nm) was observed. The detailed investigation indicated that an efficient, structure-controlled strategy was established to develop pyrene-based [n]helicene materials.

Photoinduced Reactions of Styrylpyridine Derivatives for the In Situ Formation of Selective Ligands for Apyrimidinic DNA

AbstractThe photocyclization reaction of sterically demanding styrylpyridine derivatives was investigated and shown to depend on the type of substituent. With this method, a 2,2‐diphenyl‐1,3‐benzodioxolo‐annelated benzo[c]quinolizinium was synthesized, and its association with regular and abasic site‐containing DNA (AP‐DNA) was investigated by absorption, fluorescence, circular and linear dichroism spectroscopy. Specifically, this ligand binds preferentially to AP‐DNA relative to regular duplex DNA, and the AP‐DNA/ligand complex is formed in situ upon irradiation of the styrylpyridine substrate in the presence of the DNA.

Spectrofluorometric investigations on the solvent effects on the photocyclization reaction of diclofenac

The solvent effects on the photochemical conversion rate of the photosensitizing drug diclofenac (DCF) were investigated using steady-state fluorescence spectroscopy. The spectral information obtained for the photochemical reaction of DCF in a set of neat solvents demonstrates that the photoconversion reaction rate of DCF is not only medium polarity dependent but also hydrogen-bonding dependent. The solvent effects were qualitatively and quantitatively assessed employing various solvatochromic models, including multi-parameter linear regression analysis (MLRA). Interestingly, the MLRA results (R = 0.99) revealed that the photoconversion rate increases with increasing solvent polarizability (π*) and H-bond donor capability (α), whereas the rate decreases with increasing hydrogen-bond acceptor capability (β). However, predominant effect of the solvent acidity compared to basicity and polarizability was observed. A hypothesis rationalizing the effects of H-bonding and medium polarity on DCF photoconversion reaction is presented and discussed.

Navigating Visible‐Light‐Triggered (aza and thia) Paternò‐Büchi Reactions for the Synthesis of Heterocycles

AbstractHarnessing visible light to trigger (aza and thia) Paternò‐Büchi reaction injects new vitality into [2+2] photocyclization reaction and enable impressive reactivity modes. The popular (aza and thia) Paternò‐Büchi reaction is one of the most efficient ways to synthesize strained four‐membered heterocycles. Recently, visible‐light‐triggered (aza and thia) Paternò‐Büchi reactions have received considerable attentions as this strategy has overcome some long‐standing challenges, and remarkable achievements have been made within this field. Strained four‐membered heterocyclics with favorable properties provide a perfect combination of stable skeletons for pharmaceutical chemistry and reaction intermediates for further transformation. In this review, we highlight the most recent advances in visible‐light‐triggered (aza and thia) Paternò‐Büchi reaction with an emphasis on reaction mechanism and applications. Organization of the review follows a subdivision according to reaction type and substrate classes.

Naphthalimide-based probe as an in situ indicator of photochemical reaction for self-reporting imidazole ring formation

Fluorescent probes were promising ultrasensitive candidates in the sensing area. Herein, a fluorescent indicator bearing an active photochemical reactive site based on naphthalimide was designed and synthesized. Under UV irradiation, the photocyclization reaction to form imidazole occurred through the intramolecular addition reaction between α-amine and imine. This photochemical reaction was dynamically monitored in real time by significant fluorescence and UV spectrum changes. The reaction mechanism was further verified by NMR, MS, IR and free radical quenching reaction. The photocyclization reactions of analogous substrates based on this mechanism were also monitored by self-reporting spectrum changes.

Photochromic Single-Component Organic Fulgide Ferroelectric with Photo-Triggered Polarization Response.

Organic photochromic compounds have been widely investigated for optical memory storage and switches. Very recently, we pioneeringly discovered optical control of ferroelectric polarization switching in organic photochromic salicylaldehyde Schiff base and diarylethene derivatives, differently from the traditional ferroelectrics. However, the study of such intriguing photo-triggered ferroelectrics is still in its infancy and relatively scarce. In this manuscript, we synthesized a pair of new organic single-component fulgide isomers, (E and Z)-3-(1-(4-(tert-butyl)phenyl)ethylidene)-4-(propan-2-ylidene)dihydrofuran-2,5-dione (1E and 1Z). They undergo prominent photochromism from yellow to red. Interestingly, only polar 1E has been proven to be ferroelectric, while the centrosymmetric 1Z does not meet the basic requirement for ferroelectricity. Besides, experimental evidence shows that the Z-form can be converted to the E-form by light irradiation. More importantly, the ferroelectric domains of 1E can be manipulated by light in the absence of an electric field, benefiting from the remarkable photoisomerization. 1E also adopts good fatigue resistance to the photocyclization reaction. As far as we know, this is the first example of organic fulgide ferroelectric reported with photo-triggered ferroelectric polarization response. This work has developed a new system for studying photo-triggered ferroelectrics and would also provide an expected perspective on developing ferroelectrics for optical applications in trap future.

Phototunable Cell Killing by Photochromic Diarylethene of Thiazoyl and Thienyl Derivatives.

We report a unique phototunable cell killing technique using diarylethene molecules as photo-isomerizing-molecular switches. These molecules were delivered to DNA in the cell nucleus due to closed-form generated by UV light, and then blue light triggered cell killing. A UV light irradiation switches the open form, having no DNA intercalation activity, to the closed form to induce intercalation in DNA. This isomer, thus prepared ready for the action, exerts photocytotoxicity upon the subsequent blue light irradiation. Molecular biological analysis clarifies that photocytotoxicity is due to DNA double-strand breaks. Since cell death is observed only when irradiated with light where both the open- and closed-ring isomers have absorption, the possible mechanism of cell death is assumed to be due to the repeated photocyclization and photocycloreversion reactions of the diarylethene molecules, which induce irreparable damage to DNA. This unique photo-controllable action in a cell system can provide the basis of a novel scheme of phototherapy.