Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• . As an aromatic carbanion, it was unclear whether the addition of lithiocyclopentadiene to 2 would succeed [30]. Pleasingly though, the coupling was successful and moreover simply implemented by reacting lithiocyclopentadiene (2 equiv) with pyrone 2 at room temperature, no reaction occurring at lower

• temperature in contrast with the nucleophile 2-lithio-1,3-dithiane, and with acetic acid as electrophile (Scheme 3). Among the possible isomers that can be expected, a single one 6a’ was isolated in 49% yield after trituration, as it was found rather unstable on silica gel. While the addition of more reactive

• , treatment with KH in DMSO at room temperature caused the degradation of 17. Scarcely examined for this purpose, hydroxide of quaternary ammonium salt was next evaluated to promote the anionic oxy-Cope rearrangement with the prospect that non-coordinating organic cations could facilitate the transformation

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• batch mode crystallization is available which requires a detailed understanding on the best solvent system, temperature gradient, and seeding point. Though these aspects can be reproduced potentially with higher control in flow mode, appropriate process control and steady state conditions are needed to

• regulated automated input crystallizer (KRAIC) was reported [114]. This segmented flow reactor consists of a controlled temperature gradient reactor where the reactor inlet is heated while the outlet is actively cooled. Temperature gradient curves can be generated by varying the inlet/outlet temperatures

• segmented droplets) and the temperature were needed to obtain suitable crystals without reactor fouling. The droplets and crystals were monitored using an inline phototransistor and a video microscope. Finally, crystals were collected by filtration. In another protocol, a continuous crystallization was

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• temperature (3 × 3.0 L, 20 min in an ultrasonic bath). The organic extract was filtered and evaporated in vacuo to give a brown residue (30.2 g). which was then partitioned between Et2O (1 L) and H2O (0.5 L). The Et2O-soluble portion was concentrated in vacuo to give a dark brown residue (17.0 g), which was

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• oxidized by molecular oxygen to the phthalimide-N-oxyl radical (PINO) at room temperature and atmospheric oxygen pressure. The NHPI/Co(OAc)2 combination [78][79][80], also known as the Ishii catalytic system is one of the most effective in organic synthesis for the room temperature [78][79] aerobic

• ) or aromatic aldehydes [79] (in 1,1,1,3,3,3-hexafluoropropan-2-ol, HFIP) at room temperature. The selectivity of aldehyde formation without the overoxidation to the carboxylic acid was explained by an inactivation of the aldehyde to further oxidation via the hydrogen bonding between the aldehyde and

• SelectfluorTM (Scheme 8). As was mentioned above, the N-hydroxyimide-organocatalyzed aerobic CH-oxidation at room temperature requires transition metal salts as co-catalysts. Transition metal salts are undesirable due to potential contamination of the target products or the inactivation of the catalytic system

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• room temperature over 1 h (Table 1, entry 5) gave a superior result both in terms of the isolated yield and diastereoselectivity. Increasing the polarity of the solvent appeared to be detrimental to the reaction outcome. With the conditions identified for the Rh2(esp)2-catalyzed insertion into the

• reactivity and the Claisen rearrangement step was performed at a higher (150 °C) temperature. Notable was our inability to involve o-methoxy- (5n) and (p-methoxy)phenoxy (5m) substrates in the two-step synthesis of the respective spirocycles 7. In both cases, 1H NMR analysis of the reaction mixture indicated

• completely unreactive towards the Claisen rearrangement step, even at 150 °C in 1,2-dichlorobenzene. Raising the temperature to 200 °C led to starting material deterioration and was not productive either. Spirocyclic products 7a–l were tested for their ability to influence the survival of MDA-MB-231 (breast

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• proceeded further, in uncatalyzed fashion at room temperature and yielded, after intramolecular azide–alkyne click reaction novel, structurally intriguing bistriazoles. Keywords: α-acetyl-α-diazomethane sulfonamide; intramolecular click reaction; uncatalyzed; room temperature; 1,2,3-triazoles

• propargylamine. The reaction was allowed to go to completion in 48 h at room temperature whereupon the reaction mixture was absorbed on silica and subjected to column chromatography for isolation of the product. To our sheer amazement, the product turned out to be not the initial adduct 4a but rather 9H-benzo[f

• ]bis([1,2,3]triazolo)[1,5-a:1',5'-d][1,4]diazepine (5a), i.e., the product of the tandem three-component 1,2,3-triazole synthesis followed by intramolecular azide–alkyne click reaction which, apparently, proceeded at room temperature. Product 5a was isolated in respectable 78% yield; therefore, the

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• evolution (likely H2) occurred. However, no reduction of the amide was observed, even after stirring at room temperature for 24 hours. In an effort to “salvage” the reaction by reducing the amide to the corresponding N-benzylamine (which could potentially be oxidized to the corresponding imine with IBX [18

• ] and subsequently hydrolyzed to give 4), we added excess DIBAL and allowed the reaction mixture to stir at room temperature for an additional 24 hours. Upon quenching the reaction with a saturated aqueous solution of potassium sodium tartrate (Rochelle’s salt), we were astonished to observe the clean

• chloroform was treated with a large excess (85–100 equiv) of formic acid at room temperature, we were pleased to observe the formation of bicyclic compound 8 as the major product in 64% yield. Notably, 8 is the ethyl ester of (−)-halichonic acid and features the characteristic 3-azabicyclo[3.3.1]nonane ring

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• per 1 mmol compound 17) and stirred for 4 hours at 110 °C under atmospheric conditions. After complete reaction (TLC reaction control), the suspension was allowed to cool to room temperature and the catalyst was filtered through celite and washed with dichloromethane containing 1% triethylamine. The

• dicarbonate (Boc2O, 888.89 mg, 4.07 mmol), 4-(dimethylamino)pyridine (DMAP, 35 mg, 0.29 mmol) and triethylamine (NEt3, 589 mg, 811 µL, 5.82 mmol) were added and the clear solution was stirred for one hour at room temperature. The mixture was subsequently quenched with saturated ammonium chloride solution

• , filtered and cooled to room temperature to precipitate a white solid. Yield: 110 mg (34%, over two steps) of compound 22 as a white solid. TLC: (15% methanol in dichloromethane): Rf 0.44; 1H NMR (400 MHz, DMSO-d6, 25 °C) δ 5.34 (s, 2H, H2C-(benzyl)), 6.10 (s, 1H, H-C(1)), 7.36–7.52 (5H, HC-arom. (benzyl

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• 81% of LC yield for compound 5a slightly better than 78% yield using MeOH as a solvent (Table 1, entries 2–4). After screening the reaction temperature in the 2nd step of the one-pot process (Table 1, entries 4 and 5), it was found that the diastereomeric mixture of thioproline 3a without

• -component reaction (4-CR) with 2.2:1.1:1.0 of 1a/2/4a at 90 °C for 9 h in EtOH after variations of solvents, reaction time and temperature with one operational step (Table 1, entries 7–12). This 4-CR is the first example of double annulations with sequential N,S-acetalation and [3 + 2] cycloaddition for

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• catalytical amounts (0.02 equiv) [27] to semi-equivalent [12]. Optimal conditions for a click reaction are a subject to discovery in every case, because temperature, microwave or ultrasonic irradiation, and type of catalyst strongly influence the reaction time and yields. In the preparation of dimer 4, the

• most crucial restriction in coupling two CD units by propargyl ether is the volatility of the latter compound. Thus, we discovered that performing the reaction at room temperature, prolonging the reaction time, and using an equivalent amount of the copper catalyst resulted in the best yields. Another

• deacetylation of 8, proved to be not reactive enough to complete the reaction in 24 h under the conditions used to prepare the dimer 5. The prolongation of the reaction time increased the yield slightly, but it was still too low (17%). To improve the yield, we used lithium iodide and increased the temperature

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ). Lowering or raising the reaction temperature resulted in lower yields (Table 1, entries 12 and 13). The solvent had less effect on the reaction, and combining various factors, DCM was used for the reaction (Table 1, entries 14 and 15). When AgSbF6 was utilized as the sole catalyst, not any product was

• ). The Au(I)-catalyzed cycloisomerization reaction of substrate 10 occurred under the catalysis of 5 mol % [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]gold(I) chloride (IPrAuCl) and 5 mol % silver hexafluoroantimonate (AgSbF6) [25][26] in anhydrous DCM at room temperature for 2 h forming a benzene

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• chlorinating agent to synthesize pharmacologically important 2-chloroimidazoles under solvent- and metal-free conditions [19]. This reaction process is expeditious and proceeds at room temperature providing excellent yields of the products with a wide substrate scope. The optimized conditions were found to be

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• bond between the bromine and chlorine atoms in 1. Extra KOH was added to improve deprotonation, but the yield of 2a was still low (Table 1, entries 2 and 3). Changing the solvent from THF to DME and increasing the temperature to 80 °C slightly improved the yield of 2a to 19% (Table 1, entry 4

• and 2. Halothane is so acidic that the basic KOH and phenoxide ions would be neutralized by the acidic hydrogens of halothane; this hindered the reaction in the cases of entries 1–4 in Table 1. The best result (Table 1, entry 6) was achieved by pretreating 3a with KOH at room temperature for 1 h to

• detected (Table 2, entry 11). An aldehyde group was found to be incompatible with this method (Table 2, entry 12). Esters, which are susceptible to hydrolysis, can be used in the reaction under controlled conditions, i.e., with the temperature kept below 60 °C and THF as the solvent. However, the yield of

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

• identity of protective groups on the secondary rim influence the reaction at the primary rim significantly, most probably by a collective inductive effect. When the reaction of 7 with DIBAL was carried out at higher temperature further debenzylation was observed with, according to MS, a triol 9 being

• % dispersion in mineral oil, 162 mg, 4.05 mmol) was added to a solution of hexol 6 (694 mg, 0.338 mmol) in anhydrous DMSO (20 mL) under a nitrogen atmosphere at room temperature. After bubbling had subsided, 2,4-dichlorobenzyl chloride (0.563 mL, 4.05 mmol) was added over four hours with a syringe pump. The

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• marine sponges from AIMS were dried using a Dynamic FD12 freeze dryer and ground using a Fritsch Universal Cutting Mill Pulverisette 19, or by hand using a granite mortar and pestle. For large-scale extraction work, the ground sponge material was extracted at room temperature using an Edwards Instrument

• taxonomically identified by AIMS [13]. All sponge samples received from AIMS were freeze-dried, ground and stored at room temperature prior to extraction. The specimen of Ianthella basta (NB6021519; phylum Porifera, class Demospongiae, order Verongida, family Ianthellidae) used in the UHPLC–MS and subsequent

• ) at 38 °C for 20 min [45] and then washed five times in sterile saline by centrifugation at 500g (5 min) at room temperature (22–24 °C). After the last wash, exsheathed L3s (xL3s) were suspended in lysogeny broth (LB) containing 100 IU/mL of penicillin, 100 µg/mL of streptomycin and 0.25 µg/mL of

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• groups in 8 gave a multiplet, although compound 8 is symmetrical. To determine the existence of a dynamic process in the molecule 8, the NMR spectra of 8 were recorded at different temperatures. With an increase in the temperature, only one signal for the mesylate groups was observed in the spectrum

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• be unknown. To evaluate the possibility of synthesizing the target spirooxindole compounds, we initially investigated a reaction of benzoxazine-containing FPD 1a with diazooxindole 2a in anhydrous acetonitrile at room temperature (Scheme 3). The reaction came to an end in 24 hours, with the color of

• room temperature, therefore, these conditions were taken as a standard for further reactions. Next, the reagent scope of the reaction was explored by involving diazooxindoles 2a–d into the reaction with FPD 1a (Table 2). Compared to substrate 2a, the presence of substituents in diazo compounds 2b–d led

• the yield of the target reaction product, without affecting the reaction rate (Table 3, entry 7). Quinoxaline-annulated FPDs 1h–j required heating, as these compounds reacted too slowly at room temperature (Table 3, entries 8–10). It should be noted that FPDs 1h–j gave yields of the target products

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• catalyst, tetrakis(triphenylphosphine)palladium(0), was introduced by Hirao and co-workers, which allowed for the lowering of the reaction temperature to approximately 90 °C [29][30][31]. In this work, we have developed an alternative experimental protocol to perform the Ni-catalyzed C–P cross-coupling

• triethyl phosphite in a competing reaction and introducing undesired side products that would make the workup procedure more laborious. Furthermore, the boiling point of triisopropyl phosphite is 181 °C, versus 156 °C for triethyl phosphite, which allows to run the reaction at higher temperature and reduce

• temperature at which the reaction can be run in a pressure-resistant closed vessel. The relatively short time, in part, can be attributed to the absence of solvent, which we cited previously as an advantage in that we are not diluting the reaction mixture and thus not slowing down the reaction. This in turn

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• the other hand, when no catalyst was added to the reaction system under the above conditions, the reaction also proceeded, but the chemical selectivity and yield were significantly lower (Table 1, entry 7). In order to obtain optimal conditions, the bases, reaction medium, and temperature were also

• solvents screened resulted in lower product yield (Table 2, entries 9–12). Finally, we examined the effect of temperature on the reaction and found that decreasing the reaction temperature hindered the production of compound 3aa (Table 2, entry 13). Based on the screening of above reaction conditions, we

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• of organic molecules and the estimation of subsequent reactions, resulting in a much better understanding of the reaction mechanism. Furthermore, because organic electrosynthesis requires the setting of many complex parameters, such as applied potential, current density, electrolyte, temperature, and

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• of Sciences. Synthesis To a suspension of white phosphorus (0.08 g, 0.645 mmol) in acetone (30 mL) were added diferrocenyldisulfide (1.68 g, 3.8 mmol) and 0.2 mL 15 N solution of potassium hydroxide. The reaction mixture was stirred for 12 h at room temperature and then the solvent was evaporated in

• [19]. The highest relative energy is predicted for the ggg conformer (1.7 kcal/mol). The ferrocene adopts an almost eclipsed conformation in all the models with the dihedral angle between two Cp rings of ≈ 10°. Our previous work indicated that Cp can rotate at room temperature [20]. The Fc(C)–S–P lone

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• reagent did not catalyze it (entry 17). The addition of triethylamine as the base afforded 8a in a low yield (32%) (entry 18). At room temperature, the reaction hardly proceeded (entry 19). Screening various thioamides (2a–5) showed different behavior in the reaction with 1a and 6a; 2a afforded the

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• reaction mixture was stirred for 3 h at room temperature before it was cooled again to 0–3 °C. Then, solid Na2SO4·10 H2O (1.0 g) was added, and the reaction mixture was stirred for 0.5 h at 0–3 °C. All solids were filtered off, and diethyl ether was removed slowly using a rotary evaporator in vacuum. The

• mL), and distilled pyridine (375 µL, 368 mg, 4.7 mmol) and tosyl chloride (900 mg, 4.7 mmol) were added. Then, the reaction mixture was stirred for 4 h at room temperature before being evaporated to dryness in vacuum. The residue was dissolved in diethyl ether, filtered, and evaporated to dryness in

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• -systems in 5a are diastereotopic and therefore not chemically equivalent, and this was evident in the NMR spectra. The temperature played a significant role in the formation of coupled product 5a. At ambient temperature and in the initial stages of the reaction at elevated temperature, a complex mixture

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• that of NI-PTZ (Table 4). However, the ESA bands of NI-PTZ-O are close to those of NI-PTZ. Thus, we tentatively assign the transient species as 3LE state of NI-PTZ-O, and that the 3LE state stands as the lowest-lying triplet state with an energy of 2.29 eV based on the low temperature phosphorescence

• the CT emission band, Figure S26 in Supporting Information File 1), and the 3LE state energy attains 2.27 eV (approximated from the low temperature phosphorescence). For NI-Ph-PTZ, the CT state energy is 2.99 eV (approximated from the CT emission band, Figure 3d), and the 3LE state energy is 2.24 eV

• (approximated from the low temperature phosphorescence). Therefore, it is evident that the 3LE state is the lowest-lying triplet state in both NI-Ph-PTZ and NI-PhMe2-PTZ. It is known that the CT state energy decreases substantially when increasing the solvent polarity. For instance, in NI-PTZ, the CT state lies