Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• primary amine catalysts (see Table S1 in Supporting Information File 1) in toluene at room temperature (30–32 °C). When the test reaction was conducted in the presence of 15 mol % of 9-amino-9-deoxy-epicinchonidine (I) as catalyst [30] for 12 h and treated with Ac2O followed by DABCO, the reaction gave

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• , entry 14). Tests using other solvents under these optimized conditions were also carried out (details not given in Table 1, which showed that CH2Cl2 (95% NMR yield), toluene (95% NMR yield), acetonitrile (90% NMR yield), and THF (85% NMR yield) are also very well-tolerated. Having identified high

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• promising (Table 1, entries 5–8). Testing the bis-CF3-substitued B1 first allowed for 75:25 er, but with moderate yield only when carrying out the reaction in toluene in the presence of 3 equiv of K2CO3 (Table 1, entry 5). Lower amounts of base (Table 1, entry 6) or other solvents, as exemplified for CH2Cl2

• (Table 1, entry 7, similar non-selective results were obtained when using THF), were found to be less-suited however. Testing the 3,4,5-trifluorobenzene-decorated catalyst B2 with K2CO3 in toluene next (Table 1, entry 8) allowed for a slightly higher selectivity but still gave only a relatively low yield

• the use of 3 equiv Cs2CO3 in toluene (0.05 M) at room temperature as the best-suited conditions (Table 1, entry 13), allowing for the synthesis of 5a in moderate yield (61%) and enantioselectivity (81:19 er). With optimized conditions for the synthesis of enantioenriched (−)-5a at hand, we next

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• -benzylidenecyclohex-3-en-1-one (2a) and 4-methoxybenzylamine (3a) as starting materials to investigate the feasibility and efficiency of the reaction (Table 1). Initially, the reaction was conducted in the presence of 2.0 equiv of 3a in toluene at 60 °C without any addition of catalysts or additives. To our delight

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• , solvent screening showed that toluene was the most appropriate solvent, while the reaction led to a much lower yield when DMF, MeOH, MeCN, or DCM were used as solvents (Table 1, entries 13–17). On the basis of the above experimental results, the optimized conditions for the thiocyanation of the model

• substrate were concluded to be: 2.0 equivalents of PhICl2 and NH4SCN in toluene at 0 °C, under N2 atmosphere (Table 1, entry 17). With the optimized reaction conditions in hand, the substrate scope of this thiocyanation approach was next investigated (Scheme 2). The results showed that the newly established

• -mediated thiocyanation of pyrazoles. Reaction conditions: under N2 atmosphere, a mixture of PhICl2 (2.00 mmol) and NH4SCN (2.00 mmol) in toluene (5 mL) was stirred at 0 °C for 0.5 h, then 1a (1.00 mmol) was added and stirring continued at 0 °C for 8 h. Isolated yields are given. PhICl2/KSeCN-mediated

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• ). The reaction in toluene, methylene dichloride or acetonitrile at room temperature afforded an unexpected tricyclic compound 4a in 12–18% yields (Table 1, entries 4–6). 1H NMR spectra clearly indicated that two molecules of dimethyl but-2-ynedioates took part in the reaction. The yields of the product

• 4a slightly increased to 29–45% yields when the reaction was carried out at elevated temperature in toluene, methylene dichloride or acetonitrile (Table 1, entries 7–10). When the reaction was carried out in refluxing acetonitrile, the tricyclic compound 4a can be obtained in 47% yield (Table 1

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• anticipated that 1 would similarly undergo Cope rearrangement. However, when we heated 1 up to 200 °C for 5 h, we did not observe any Cope rearrangement products and we were able to recover >90% of 1. DFT calculations [mPW1PW91/6–31+G(d/p)/SMD(toluene)] on the Cope rearrangement of 2 revealed a free energy

• activation energy may allow for oxy-Cope rearrangement at 28 °C. DFT calculations (in toluene) of 5-hydroxyalbireticulene for both the pseudo-axial and pseudo-equatorial conformations of the C5 hydroxy moiety suggest that there is not a significant difference in the free energy barriers for the oxy-Cope

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• second step of this reaction, regio- and stereochemically controlled intramolecular cyclization leads to the formation of versatile nitrogen-containing tricyclic systems. However, these useful organic transformations are usually carried out in highly toxic organic solvents such as benzene, toluene

• yields and the desired stereoselectivity [59][60][61]. The viscous nature of the aminofuranes usually requires the use of toxic solvents such as toluene, and in some studies, solvents such as DMSO, which are difficult to remove from the reaction medium [62][63][64]. Although solvent effects are of little

• reaction medium increases, the size of these lamellar units decreases, increasing the ability to dissolve Diels–Alder components and intermediates. It should be noted that the hydrophobicity of triglycerides is much higher than that of aromatic solvents such as benzene and toluene. For comparison with

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• @(12,2)-SWNT complexes. Chemical structures of Cu-tethered tetragonal nanobrackets 1a and 1b. Synthesis of nanobracket 4. Reaction conditions: i) XPhos Pd G2, XPhos, B2(OH)4, KOAc, EtOH, 80 °C, 2 h; ii) Br-Ar-Br, K2CO3, tetrahydrofuran (THF)/toluene, 80 °C, 16 h; iii) trifluoroacetic acid (TFA), pyrrole

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• results were not fully satisfactory. Considering the poor solubility of fullerene derivatives, toluene, carbon disulfide (CS2), and ortho-dichlorobenzene (o-DCB) were tested as solvent. Surprisingly, the conversion from ketone to thioketone did not occur as anticipated. In another attempt, where the

• due to the lower Tdeg of t-Bu-FIDS. A t-Bu-FIDS film was prepared by vacuum deposition at 0.1 Å/s, as shown in Figure 1d and Figure S4 (Supporting Information File 1). The film was uniform and smooth, with a thickness of approximately 20 nm. The film was rinsed with toluene, and the collected toluene

• -Bu-FIDS (black) and of toluene used to rinse the evaporated film of t-Bu-FIDS (red). Single-crystal structure of t-Bu-FIDS. (a) The π–π distance between two molecules. (b) Crystal packing. Cyclic voltammograms of fullerene derivatives in o-DCB solution containing Bu4N+(CF3SO2)2N− (0.1 M) as

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• carbonyl compounds 1, 2, 3, and 4, dianion 7, phosphorane 8 and synthesis of 1,3-bis(silyloxy)-1,3-butadiene 6a via 5. Conditions: i, Me3SiCl, toluene, NEt3, 24 h; ii, 1) LDA, THF, −78 °C, 1 h; 2) Me3SiCl, −78 to 20 °C, 12 h. Structures of chromones with different substituents located at carbon C-3 and

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• solution of Dip2Si(SiMe3) as a silylene precursor and C60 in toluene was irradiated by a 125-W low-pressure mercury lamp in a quartz tube for 2 h (Scheme 1). During reaction, the color of the solution turned to dark brown. After the photolysis, the bis-silylene adduct 3 was isolated in 36% yield

• calculated respectively for C60, 2, and 3. Experimental Materials and general method: All chemicals were reagent grade, purchased from commercial suppliers. o-Dichlorobenzene (ODCB) was distilled from P2O5 under vacuum before use. Toluene was distilled from benzophenone sodium ketyl under dry N2 prior to use

• period of 200 ms, and a scan rate of 50 mV/s. Synthesis of 3. A degassed solution of Dip2Si(SiMe3) (30 mg) and C60 (4.6 mg) in toluene (20 mL) in a quartz tube was irradiated by a 125-W low-pressure mercury lamp for 2 h [15]. After the photolysis, 2 (22% yield) and 3 (36% yield) were isolated by flash

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ). Once the catalyst was chosen, we investigated the influence of the solvent. For this purpose, we evaluated dichloroethane (DCE), dichloromethane (DCM), toluene, and tetrahydrofuran (THF) as solvents for the transformation (Table 1, entries 16–19), but acetonitrile remained the best solvent. Finally, we

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• the several alcohols and primary amines in the presence of t-BuOK (0.75 equiv) in toluene at 80 °C for 24–48 h and selectively produced the N-alkylated products with good yields (Scheme 3). More interestingly, the first non-noble-metal catalyzed the most challenging N-methylation of amines with

• )phosphine ligand (PN3P) (Mn3) and studied N-methylation reactions in the presence of t-BuOK (20 mol %) at 120 °C for 24 h in toluene [36]. This catalytic system tolerated various functional groups, including nitro, ester, amide, and ketones and gave moderate to good yields (42–98%) of the mono-N-methylated

• alcohols [39]. Various ligands were screened for the N-alkylation of m-toluidine with benzyl alcohol using Mn(CO)5Br (5 mol %) and t-BuOK (1 equiv) in toluene at 140 °C (Scheme 9). Among these, L1 and L2 showed better activity for the N-alkylation reactions. Different substituted anilines and alcohols

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• switching the dienophile from DMAD to acrylonitrile. Once again, compounds 3 and 23 were unreactive, even after 184 hours of reaction time with a 13,500-fold excess of acrylonitrile. The reaction between 3 and a large excess of DMAD (116 equivalents) in boiling toluene (111 °C) was also studied by 1H NMR

• solvent was removed by rotary evaporation at reduced pressure to give a light-yellow solid. TLC (hexane/EtOAc 3:1) indicated no reaction. Additional DMAD was added to the unreacted mixture in the round bottom flask (2.31 g, 16.3 mmol) along with 2 mL toluene. After attaching a reflux condenser, the

• mixture was heated to reflux for 51 hours. The mixture was cooled to room temperature and toluene was removed by rotary evaporation at reduced pressure to give a sticky, dark brown solid. The solid was pre-purified by silica gel CombiFlash chromatography (hexane/EtOAc 9:1) to obtain a yellow oil as crude

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• functionalisation on the aromatic ring when used in the dark [20]. A classic example is the bromination of toluene with molecular bromine. When the system is exposed to light (right side of Figure 1), a radical mechanism is initiated by Br• coming from Br2 homolysis. Propagation involves the reversible abstraction

• developed method was finally successfully scaled up to 10 g scale, giving 3a in excellent isolated yield (87%), with only small amounts of polybrominated byproducts as contaminants (<2%). The pure product was obtained through (unoptimised) crystallisation from toluene, giving 3a in 80% overall yield, and

• (bromomethyl)benzene (3a): For the 10-gram scale procedure, see Figure S1 (Supporting Information File 1), white-yellowish solid, yield: 87%. Recrystallisation from hot toluene gave the pure product as white solid. 1H NMR (400 MHz, 298 K, CDCl3) δ 7.37 (s, 4H), 4.48 (s, 4H) ppm. 1,4-Dibromo-2,5-dimethylbenzene

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• and oscillatory strength for the first fifteen singlet electronic excited states. To assess the influence of solvents, the geometries were optimized and photoswitching properties were determined in different polarity solvents (dielectric constant) including cyclohexane (2.0165), toluene (2.3741

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• ). Reagents and conditions: a) 2-bromo-2-phenylacetyl chloride, TEA, THF, rt, 1 h, b) ethyl acrylate, toluene, 110 °C, 24 h, c) NaOH, H2O, MeOH, 70 °C, 2 h, d) H–ʟ-Tyr–OMe, HOBt, EDCI, TEA, DCM, DMF, rt, 12 h, e) LiOH⋅H2O, H2O, 1,4-dioxane, rt, 2 h. Supporting Information Supporting Information File 4

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• extended numbers of diaryliodonium(III) carboxylates. Various electron-rich arenes were screened as auxiliary aryl groups in the reaction with PhI(OAc)2 (1a) (Scheme 3). However, common partners such as toluene (2a), mesitylene (2b), and anisole (2c) failed to react with PhI(OAc)2 (1a). Therefore, 1,3

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• /PPh3 as catalyst system in the presence of a base (Et3N) in toluene at 110 °C for 5 hours under 10 bar of CO [54]. Guo et al. developed the synthesis from substrates of the same chemical nature but using Pd(OAc)2/BuPAd2 as the catalyst system. In their approach, DABCO was also added to the reaction

• reaction was run in toluene at 100 °C for 24 h under 20 bar of CO [56] (Scheme 25). The other example, however, accomplished the synthesis through Rh-catalysis from substrates without halogens in their structure. This synthesis was published by Huang et al. who obtained good results by using [(Cp*RhCl2)2

• the other hand, Chandrasekhar and Sankararaman reported the same process starting from secondary amines instead of tertiary amines [61]. In this case, the catalyst system was Pd(OCOCF3)2 (10 mol %) and the oxidant Cu(OAc)2 (2 equiv) and oxygen. The reaction was carried out in toluene at 80 °C for 24 h

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• -tetrazole component remaining unreacted. To our delight, the use of toluene/water (9:1) as a biphasic solvent system provided quantitative product formation with 90% isolated yield (Table 1, entry 15). Upon trying to reduce the reaction time and performing the reactions at higher temperature, the product

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• -coupling was carried out using Pd(PPh3)4 as catalyst with K3PO4 as base in toluene as solvent which gave a mixture of different products. Further investigation revealed the presence of the two-fold Sonogashira–Hagihara product, starting material 2, and the desired product 3. Hence, starting material 2 and

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• , DMF/H2O, 60 °C, 18 h. (b) Pd(OAc)2, PPh3, CuI, phenylacetylene, Et3N, 50 °C, 5 h. (c) CuI, neocuproine, 4-MeOC6H4SH, NaOt-Bu, toluene, 110 °C, 13 h. (d) CuI, ʟ-proline, DMF, 80 °C, 14 h. (e) CuI, imidazole, Cs2CO3, DMF, 120 °C, 15 h. (f) 3-Methoxy-2-(trimethylsilyl)phenyl triflate, CsF, MeCN, rt, 18 h

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• solvents including dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), toluene, acetic acid (AcOH) and water (Table 1, entries 9–13) were carried out. However, polar solvents such as AcOH and H2O were proved to be unsuitable for this reaction. For catalysts, we found that Cu(OAc)2 gave the best results

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ) could be prevented when switching to BCl3 (10 mol %). Interestingly, toluene (94), which is generated as a byproduct of the Grob fragmentation, must react more sluggishly with the generated cationic intermediates compared to chloride, as no alkylations of toluene were reported. In 2017, the Snyder group