Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• first delipidated with n-hexane. Phytic acid was extracted with 1 M HCl for 1 h. After extraction, the pH value was adjusted to 4.5 with 8.0 M NaOH, which is the isoelectric point of rice bran protein. Solids were removed via filtration and centrifugation followed by supernatant collection. The phytate

• yield and purity exhibited a trade-off relationship [1], and the yield increased with increasing supernatant pH. Because the phytic acid purity was prioritized in this work, the pH value was increased by the addition of 1.5 M Na2CO3 up to pH 7 to form a phytate precipitate. Finally, the collected

• for 1 h. The delipidated rice bran was filtered through a non-woven filter and dried in air overnight. A 1.0 M HCl solution (300 mL) was poured into the rice bran, and the produced mixture was stirred with a magnetic stirrer for 1 h. After stirring, the pH of the extract was adjusted to 4.5 with 8.0 M

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• of strain TMPU-A0679 grown on ISP medium No. 2 (yeast extract 0.4%, malt extract 1.0%, glucose 0.4%, and agar 1.5%; adjusted to pH 7.3) was used to inoculate a 500 mL Erlenmeyer flask containing 100 mL of the seed medium (potato starch 2.4%, yeast extract 0.5%, glucose 0.1%, peptone 0.3%, Ehrlich

• meat extract 0.3%, and CaCO3 0.4%; adjusted to pH 7.0). The flask was incubated on a rotary shaker at 180 rpm at 27 °C for 4 days. One milliliter of the seed culture was transferred into sixty 500 mL Erlenmeyer flasks containing 100 mL of ISP2 medium No. 2. Fermentation was conducted on a rotary shaker

• concentrated under reduced pressure to remove the solvent. The resulting aqueous solution (400 mL) was extracted twice with EtOAc (400 mL × 2, pH 3). The combined EtOAc layer was dried over Na2SO4 and concentrated under reduced pressure to yield crude material (922 mg). This material was then dissolved in a

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• in water of 8.5 ± 0.3 mg/mL, leading to a solution with a pH of 6.24 ± 0.01. However, the kinetic solubility appears low; when preparing a solution of 5 mg/mL, the container must be shaken for several minutes. Previously, we reported the solubility of 1 in buffer at pH 7.4 to be 0.4 mg/mL, which is

• pH 7.4 at 25 °C, as indicated by the constant peak area (no significant change in AUC) and the absence of new peaks after 4 weeks of storage. In analogy to the buffered solutions, we could not detect additional species besides 1 after 4 weeks in water, when stored at 25 °C. This indicates that

• aqueous solutions of 1·HCl may be prepared and stored well in advance of any application or investigation. Subsequently, the apparent pKa values (concentration-based) for 1 were determined to be 8.4 ± 0.1 and 10.7 ± 0.1 for the protonated amine and phenol, respectively, and the calculated pH-dependent

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• displays a λmax at 605 nm at neutral to slightly alkaline conditions with additional absorptions at 354 nm and 315 nm. As the pH of the solution increases from neutral values to 12.3, there is a transition to a new λmax at 756 nm with additional absorptions at 461 nm and 326 nm. Isosbestic points at 648 nm

• and 508 nm suggest only two species are in solution. Plotting absorbance versus pH reveals a pKa value of 11.3 ± 0.05 (Supporting Information File 1, Figure S25). Additional increases in pH lead to a decrease in the absorbance at 755 nm and a growing absorbance at 461 nm indicating a second

• deprotonation. Examining the absorbance at 755 nm versus pH yields a second pKa value at 13.0 ± 0.11 (Supporting Information File 1, Figure S26). As shown in Figure 1B, the corresponding disulfonate of 6,6’-dibromoindigo, 9, shows similar UV–vis spectra to compound 10. Specifically, 9 shows a λmax at 606 nm and

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• ratio of Cl:Br shifting from 1:2 at 10 M CH2Cl2 to 29:1 at 0.1 M CH2Cl2. This finding indicates that non-indium coordinated solvent acts as the active nucleophile. The potential formation of chlorobromomethane in this reaction was not explored. When R = Ph (compound 248), the formation of only alkenyl

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• oxidation was quantified by Griess assay, which serves as a generally accepted tool to estimate the NO release. The amounts of NO2− generated from nitro-NNO-azoxy compounds at pH 7.4 and 37 °C (physiological conditions) for 1 h were estimated spectrophotometrically via Griess reaction. According to the

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• alcohols with aromatic substituents 1d (R1 = Ph, R2 = Me) and 1e (R1 = R2 = Ph) were found to be less productive: the reaction required a 2-fold longer time (30 min) and resulted in lower yields of salts 2d,e likely due to side polymerization (Table 2, entries 3 and 4). At the same time, the yields of

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• (Scheme 8) [92]. Finally, an investigation of the influence of pH on the absorption and fluorescence spectra in aqueous solution was carried out under various pH values for compounds 3n (Figure 8) and 4n (Figure S252 in Supporting Information File 1), as changes in pH are known to significantly affect

• absorption and emission processes [93][94]. Compound 3n is reported to have an ampholyte character existing in two equilibria in aqueous solutions (Scheme 9) [95][96]. Visually, the solutions lacked coloration under acidic pH compared to the neutral conditions. This observation was further analyzed

• quantitatively using UV–vis absorption spectroscopy. At acidic pH, only broad absorption bands at 370 nm and 325 nm were detected for compounds 3n and 4n, respectively. These results can be attributed to a phototautomerism effect in both the ground and excited states [97]. Additionally, fluorescence spectra

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• phosphate buffer (pH 7.1) was chosen to test the materials’ stability in an aqueous environment. 1H NMR measurements showed that neither material released BU into organic solvents in the absence of anions. This was unexpected for SG-BnBU, since BnBU is readily soluble in chloroform and dichloromethane and

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• ) EYPC/Chol 6:4, and g) DPPC. Right column: Absorbance changes at 365 nm over ten consecutive photoisomerization cycles for the same lipid compositions: b) EYPC, d) EYPC/Chol 8:2, f) EYPC/Chol 6:4, and h) DPPC. All experiments were performed at 25 °C using LUVs suspended in HEPES buffer (10 mM, pH 7.2

• mol % at 25 °C. The fluorescent emission of sulforhodamine B was measured before and after 1 minute irradiation with 370 nm light (pink strips) or 467 nm light (purple strips), and after 5 minutes post-irradiation. The LUVs are suspended in a buffer solution containing HEPES buffer (10 mM, pH 7.2) and

• different lipid compositions suspended in a solution of HEPES buffer (10 mM, pH 7.2). Rotaxane 1 (10 mol % with respect to the total lipid concentration) dissolved in DMSO was added to the LUVs. The data represent the average of independent experiments conducted in triplicate. Evaluation of effect of axle 3

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• dibenzocarbazole derivative 1m underwent nitration to afford 2m in 55% yield. Likewise, 2-Ph-, 2-OMe-, and 2-Cl-substituted carbazoles were efficiently converted under the standard conditions, affording the corresponding C1 nitration products 2n–p in good yield, whereby C–H activation selectively occurred at the

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• bulky stoppers at both ends to prevent dethreading (Figure 1) [1][8]. Functionalization of the axle with recognition sites allows the macrocycle to shuttle between positions in response to external stimuli, including light, redox, temperature, pH, and reactions with chemicals such as carbodiimides [9

• . Although no shuttling or energy transfer process was observed, both rotaxanes presented good photoisomerization behavior. Remarkably, the use of cucurbit[6]uril macrocycles enhanced the photoisomerization. Later, Liu and co-workers designed a symmetric [3]rotaxane where the pH-responsive shuttling motion

• , which had a DB24C8 macrocycle on one end and a TPE unit as the stopper on the other end (Figure 8) [60]. The shuttling between the BAA (off) and MTA (on) recognition sites, induced by changes in pH, enabled the photochromism of the rotaxane to be switched on and off. Specifically, the dithienylethene

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• KGaA (Darmstadt, Germany). For gastrointestinal permeability studies, ʟ-α-phosphatidylcholine and cholesterol were purchased from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). Phosphate buffered saline (0.01 M, pH 6.5 and 7.4) was prepared from pre-mixed PBS powder also sold by Sigma-Aldrich (Merck

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• (E)-9b, the highest concentration achieved in DMSO was 0.5 mM, while for (E)-9a it was 1 mM (DMSO solubility results of the compounds can be found in Supporting Information File 1). 5 μL of the stock solutions was pipetted into a 96-well plate containing 495 μL PBS (pH 6.5) in each well to achieve

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• conditions, resulting in the formation of the corresponding oxazoles (33b–j) in 43–80% yields. Xanthenes bearing Me, t-Bu, MeO, Ph, Cl, CF3 and naphthyl groups were applicable as well, generating the desired 33k–r in moderate yields. According to the results of control experiments and previous studies [220

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• acid (ALA), and benzylic acid (BA). These acids were oxidized and gave formaldehyde, acetaldehyde, acetone, benzaldehyde, acetophenone, and benzophenone, respectively. By increasing pH and concentration, the rate of the reactions increased, but decreased upon increasing the amount of Cl− ions (Scheme

• reported by Strizhov et al. [125]. The liable equilibrium transformation requires precisely pH-controlled conditions. In neutral medium, the furanone is in the form of its cis tautomer, while upon a slight increase in the pH, its cyclic original tautomer undergoes a ring opening with the formation of

• protonated forms (Scheme 40). HFO can be hydrolyzed to succinic acid, however, it is a slow process in aqueous solution. In NaOH solution at pH 9–10, a complete conversion of HFO to succinic acid is rapidly achieved (Scheme 41) [126]. Substitution and condensation reactions of HFO (crude from furfural

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• the presence of Fe(dpm)3/Ph(iPrO)SiH2 proceeded smoothly to furnish the tetracyclic product 39 in 56% yield with 2.5:1 ratio. Finally, removal of the acetonide and the Bn protecting group completed the total synthesis of (+)-aplysiasecosterol A (6). Total synthesis of (+)-cyrneine A, (−)-cyrneine B

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• anticipated that if we run the work-up procedure under more basic conditions, one would be able to obtain solely double cyclization products. Indeed, alternation of the work-up protocol by employing an aged solution of K2CO3/MeOH (stood at rt overnight, pH 11) to quench the DMDO oxidation reaction of

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• titration with calf thymus DNA (0–290 μM base pairs) in 100 mM KCl, 20 mM Tris-HCl, pH 8.0. Synthesis of 12-modified indolo[1,2-c]quinazoline derivatives. Synthesis of indolo[1,2-c]quinazoline-12-carboxamides 7a–c. Mannich aminomethylation of indolo[1,2-c]quinazolines 1 and 8. Synthesis of 5-(3-aminopropyl

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• on intermediate allyl cation (Scheme 1C). The obtained tetrahydrofuran and pyrrolidine derivatives with highly substituted vinyl side-chains are regarded as privileged structures in medical chemistry [23][24]. Moreover, the resulting styryl functionality (Ph-C=C-) is often found in drug molecules as

• NMR spectra. Interestingly, the internal alkyne 7c (R = Ph, Si = TIPS) was completely unreactive under both standard arylation conditions (70 °C in EtOAc) and higher reaction temperatures (110 °C in BuOAc). In these cases, the starting material was recovered with no signs of degradation. This

• standard column chromatography techniques (30–50% DCM). Iodanes, containing electron-rich aryl groups (p-Tol, m-MeO-C6H4, Ph) or halogens (Br, F) gave the highest tetrahydrofuran 8 yields (70–83%). In contrast, electron-withdrawing group-containing iodanes, especially those holding nucleophilic heteroatoms

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , tryptophan residues), as well as the overall structure of the protein. The peak intensity and shape can vary depending on pH, ionic strength, and protein conformation. However, under our conditions, the HSA oxidation was consistent, well‐defined, and served as a clear baseline reference. Subsequent to

• carbon, scan rate: 0.1 V/s, pH 6.7. Chemical structure of alkylating fragment of 1–3 and the associated chemical pathway of its covalent attachment to HSA. Synthesis of glycidyl esters of phosphorus acids 1–3. IC50 values (μM ± SD) for glycidyl esters of phosphorus acids 1–3 in human skin fibroblasts

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• total charge of 2.2 F/mol was delivered. The reaction mixture was poured into a beaker with 10 mL of distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. 10 mL of ethyl acetate were then added, and the two phases were separated. The aqueous phase was then extracted with

• experiments were conducted until a total charge of 4.15 F/mol was delivered. The reaction mixture was then poured into a beaker with distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. Ethyl acetate was added, and the two phases were separated. The aqueous phase was then

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• photoswitches (Figure 6) [5]. N-Methylation of indole 2b increases the lifetime due to a preference for the inversion with respect to the rotation mechanism. Interestingly, the isomerisation of the non-methylated 2a is also strongly influenced by protic solvents, by the pH of the solution, and by the

• concentration of the photoswitch in solution: when MeOH or water are present, the lifetimes drop significantly, and particularly at pH 4, as consequence of more favourable intermolecular proton transfer. Calculations show that water molecules bridging between two Z-isomers favour the formation of hydrazone and

• stabilises one of the two isomers via the formation of a hydrogen bond (Scheme 30) [95]. This peculiarity makes this photoswitch class extremely susceptible to solvent polarity [96][97][98], pH [98][99][100][101], and metal coordination [102][103][104]. With such variability, predicting which is the most

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• release systems based on host–guest selective recognition, self-assembly, and nano-valves by the use of of calixarenes and pillararenes from five perspectives: pH, light, enzyme, hypoxia, and multi-stimuli combination responses. Furthermore, the article projects the future clinical application prospects

• in pH, light, and enzyme activity, the binding affinity between the guest and host molecules can be altered, thereby achieving controlled drug release and targeted delivery. (2) Drugs are loaded into self-assembled host–guest systems [29][30][31][32]. The chemical structure or properties of the host

• or guest molecules are altered upon exposure to specific stimuli, such as light, pH changes, or enzymes. This modification induces the disassembly of the host–guest complex, thereby releasing the encapsulated drugs. Fundamentally, this mechanism relies on controlling the assembly and disassembly

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• nitrogen source followed by thin-layer chromatography and reversed-phase (RP)-HPLC to isolate and purify the compound from a complex mixture of indole alkaloids [11], (ii) prepared by aerobic incubation of indole-3-pyruvic acid at pH 7.4, 37 °C for 24 h followed by isolation and purification using RP-HPLC

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• synthesis of imines and enamines [36][37]. In our reducing system H3PO2 could act as an effective reductant due to its high solubility in neat conditions (Table 1, line 1) (in form of morpholinium hypophosphite). Nonetheless reductive potential of hypophosphite is pH-dependent (−1.65 V at pH 14 vs −0.5 V at

• pH 0) [19], and usage of an additional amount of base leads to stronger reductive properties. Moreover, the role of the cation could be critical for the thermal stability against disproportionation or aerobic oxidation of hypophosphite [38]; salts with larger cations are also more soluble in organic

• system is more efficient than the earlier described usage of the pure NaH2PO2: higher solubility of the potassium, rubidium and cesium salts compared to the sodium and lithium and a proper pH of the reaction medium. Acidic catalysis strongly accelerates the rate of hemiaminal and iminium ion formation