A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• . To demonstrate the practicability of the reaction, a scale-up reaction of ethyl acetoacetate (1a, 28 mmol, 3.64 g) and thiourea (2a,14 mmol, 1.05 g) was carried out under the optimized conditions to give 3a in 50% yield (Scheme 3). In order to better understand the iodide-mediated reaction mechanism

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• . Additional experiments were conducted in order to clarify the reaction mechanism. Under standard conditions, only pyridin-2-ylmethyl diphenylphosphinate (3aa) was produced, and the Pudovik adduct (hydroxy(pyridin-2-yl)methyl)diphenylphosphine oxide (4aa) was not detected (Scheme 4a). The control experiment

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• propose a reaction mechanism (Table 2). First, we carried out the electrolysis of 1 in MeCN–MeOH to confirm whether the reaction intermediate is a radical or cationic species (Table 2, entry 1). As a result, methyl cumyl ether, a methoxy adduct to the benzyl position of 1, was obtained as the main product

• Et4NClO4 (0.1 M). Scan rate: 100 mV/s. Proposed reaction mechanism of electro-conversion of cumene (1) into acetophenone (3). Electro-conversion of 1. Control electrolysis experiments of 1a. Supporting Information Supporting Information File 244: Characterization data and 1H NMR spectra of isolated

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was

• enamine derivatives. As compared to glacial acetic acid [42], ethanol has showed to be the best solvent for the synthesis of these pyrrolidine-2,3-diones and a dramatic increase in the yield of the desired products was also observed. In addition, understanding of the reaction mechanism at the molecular

• )ethylene-1,5-diphenylpyrrolidine-2,3-dione in the present work. To the best of our knowledge, it is the first time the reaction mechanism between 3-pyrrolin-2-one derivative and methylamine was explained in detail via computational studies. Results and Discussion A model reaction of benzaldehyde (1a

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• example, there are two pseudo-tetrasaccharide structures 11a and 11b, which would be hard to separate by preparative-scale purification techniques. Reaction mechanism There are two possible pathways for chain elongation in electrochemical polyglycosylation (Figure 7). In path a, monosaccharide 1a is

• hexasaccharide 6a (5%, 3.1 μmol, 8.2 mg). We ran the process up to the third cycle and isolated octasaccharide 8a (3%, 2.3 μmol, 7.6 mg), which was never isolated after the first cycle and the second cycle. These results also supported the proposed reaction mechanism path a in Figure 7. Conclusion In conclusion

• , we have developed a practical method to synthesize longer-chain oligosaccharides within a short period of time through electrochemical polyglycosylation. A rational reaction mechanism was proposed based on oxidation potentials of the oligosaccharides, and further modification of the protocol was

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• (Table 4, entry 2). Scheme 2 depicts a plausible reaction mechanism. We assume that the current reaction follows a similar mechanism as described in Abushanab’s report [12]. In addition, the current reaction indicated the generation of an EGB (electrogenerated base) [26][27][28][29]. The electrochemical

• cyclopropanetricarboxylates. Previous reports (reactions 1–3) and this work (reaction 4). Plausible reaction mechanism. EGB = electrogenerated base. Reaction optimization. Effect of electricity around 1 F/mol and type of electrochemical cell. Scope and limitations. Scale-up experiments. Supporting Information Supporting

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• coclaurine [28]. The absence of the product 1 in vitro is reasonable because the biosynthesis of 1 requires an additional methyltransferase from S. cattleya for the methoxy group formation. Substrate scope and reaction mechanism After identification of CYP158C1 as the isoflavone dimerization enzyme, we next

• , Supporting Information File 1). Other plant polyketides, such as anthraquinones 19 and 20 and phenylpropanoids 21–24, failed to be dimerized. The reaction mechanism of P450-mediated phenol dimerization is believed to involve oxidative radical–radical coupling, though other mechanisms, such as radical

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• ]. The addition of water may be also important to achieve high diastereoselectivity in the present reaction. On the basis of the results of the control experiments, a plausible reaction mechanism is depicted in Scheme 6. Initially, sec-alcohol 1 is oxidized by an anodically generated Br+ species to

• utility of this transformation. Further investigations of the reaction mechanism are currently underway in our laboratory. Strategies for the synthesis of vic-1,2-diols. Substrate scope. Reaction conditions: 1 (1.0 mmol), Et4NBr (0.1 equiv), imidazole (0.05 equiv), MeCN (5 mL), H2O (125 μL), 50 mA cc, 4 F

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• 72% yield with good selectivity (89%). Both 1f and 1g could be used in this reactions, and the corresponding alcohols 3f and 3g were obtained as major products. Mechanistic studies To gain further insight into the reaction mechanism of the chemoselectivity of a Pd/C cathode system, some additional

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• cyanoformamides [75]. However, all of these works are primarily focused on the substitution reaction of N-substituted carbonylimidazoles. In our previous work, we conveniently prepared formamides by reducing N-substituted carbonylimidazoles with NaBH4 [62] (Scheme 1). The reaction mechanism shows that the H− ion

• had a large steric hindrance like 7b, but also had a strong conjugation system, took much longer time (6 h) to complete the reaction. As shown by the reaction mechanism, the methyl group was converted from the carbonylimidazole moiety by full reduction and therefore no competing overalkylation

• carboxylic acids or isocyanates. The acetamide group was well tolerated in our reduction, implying our method showed interesting reduction selectivity. The synthesis of formamides and monomethylamines. The possible reaction mechanism. RDS = rate determining step. Optimization of the reaction conditions.a

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• relative configuration. For explaining the formation of the two kinds of the compounds, a plausible reaction mechanism was proposed on the basis of the previous works [30][31][32][33][34][35] and the present experimental results (Scheme 2). As described in the previous work, TBAF can act as an effective

• hours afforded the expected product 4d in 45% yield. This result clearly showed that the initially formed functionalized cyclopentene 3b could be smoothly transferred to the carboxamide-bridged dicyclopentene 4d, which also strongly supported the above proposed reaction mechanism. Conclusion In summary

• stereochemistry of the reactions was clearly elucidated and a rational reaction mechanism was proposed. The reactions have the advantages of using readily available reagents, mild reaction conditions, good yields, and high diastereoselectivity, and have potential synthetic applications in organic and medicinal

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• inherent chemistry in these reactions and also points to some understanding of the possible thermodynamic and kinetic control in the enzyme. Results Reaction mechanism To better understand the HP and IE reaction pathways, we performed quantum mechanics (QM) calculations using density functional theory (DFT

• -house code which modifies parameters for cations from existing parameters for neutral molecules. For each intermediate in the reaction mechanism (path HP and IE) we created 100 conformers which were subsequently clustered (a cluster width of 1.0 Å was used). For each unique conformer we performed QM

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• subsequent transformation to 2-cyanonaphthalene-1-ol (3a). Presumed reaction mechanism of electroreductive coupling of 1 with 2a and subsequent transformation to products 3 and 4. Electroreductive coupling of 1a with 2c and subsequent treatment with 1 M HCl. Electroreductive coupling of 1a–h with 2a and

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• result of this reaction, then the less likely occurrence of intermediates 7 and/or 8 could account for this result. However, since from α-ketoaldehydes, this reaction is achieved in the presence of sodium hydroxide, a far more complex reaction mechanism is likely; although to the best of our knowledge

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• resulted in much lower product yields. The detailed reaction mechanism was clarified based on the cathodic reduction of 1 in the presence of deuterated acetonitrile, CD3CN. Keywords: bis(phenylthio)difluoromethane; cathodic reduction; deuteration; o-phthalonitrile mediator; (phenylthio)difluoromethylation

• both radical and anionic intermediates. In order to further clarify the reaction mechanism, the indirect cathodic reduction of compound 1 was performed in the presence of α-methylstyrene in MeCN containing cumene (iPrC6H5) and isopropyl alcohol (iPrOH). The former works as a hydrogen radical source

• the formation of adduct 4 to some extent (from 0% to 14% yield) as shown in Table 3. Therefore, iPrOH seems to promote the radcal addition rather than reduction although the reason has not been clarified yet. Reaction mechanism Although the cathodic reduction of perfluoroalkyl halides usually involves

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• standard conditions did not proceed (Scheme 1, reaction 2). The reaction mechanism for this coupling reaction is presently unclear. We propose that the reaction mechanism may be similar to that of the C(sp)–Se bond formation of terminal alkynes with diaryl diselenides reported by Stieler and Schneider [31

• ]. Based on this report and the above control experiments, a plausible selenation reaction mechanism is shown in Figure 3. The first step of the reaction involves the generation of intermediate A by the oxidative addition of the Cu(I) catalyst to the diselenide 2. The terminal alkyne coordinates with

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• developed the practical synthetic values of the well-known Levy reaction by using inactivated indole derivatives. The outcome of diastereoselectivity of the reaction was clearly elucidated by determination of the several single crystal structures and the analysis of the reaction mechanism. The experimental

• . Synthesis of 3,3'-(arylmethylene)bis(2-methyl-1H-indole). Reaction conditions: 2-methylindole (1.0 mmol), aromatic aldehyde (0.5 mmol), CuSO4 (0.1 mmol), toluene (6.0 mL), 110 °C, 3 h. Isolated yields are shown. Proposed reaction mechanism for the multicomponent reaction. Optimization of reaction

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• attributed to their probable reaction mechanism where the nitrogen atom not only promotes the enolate derivative formation as already described in literature [33][34] but it may also generate a positively charged intermediate at the transition state [35], enhancing the nucleophilic substitution. Obviously

• isocyanide purity (Figure 2), even though, in some cases, a small amount of sulphonyl derivatives or solvent residues can be spotted. These little impurities are due to the isocyanide instability and difficulty in being held. In light of what was said above, it makes sense to hypothesise a possible reaction

• mechanism (Scheme 4). The single equivalent of triethylamine should be able to activate the tautomerism of the formamide through an acid–base reaction [33][42][43][44][45]. The triethylammonium salt produced can be restored as triethylamine through the action of Na2CO3. This proton transfer allows the

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• complex forms with 2OG or with 2OG and fumitremorgin B (PDB IDs: 4Y5T, 4Y5S, 6OXH, 6OXJ, 7DE0, 7ETL, and 7ETK) [68][69][70][71]. Based on these structural and functional analyses, the reaction mechanism of FtmOx1, and especially the role of the active site tyrosine residues in the catalysis, are heatedly

• analysis, the group proposed that Tyr224 is involved in the catalytic mechanism of the FtmOx1-catalyzed endoperoxide formation reaction as an intermediary of hydrogen atom transfer (HAT), similar to Tyr385 in the COX reaction. In this COX-like reaction mechanism (Scheme 5), the Fe(IV)=O species oxidizes

• showed similar reaction kinetics and verruculogen productivity to those of wild type FtmOx1. Interestingly, the Y68F variant generated an unidentified product, which was recently determined to be 26-hydroxyverruculogen [75]. Based on these observations, they proposed an alternative reaction mechanism. In

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• -phenacylidenoxindoles by trialkylphosphine has been previously reported in the literature [65]. For explaining the formation of the two kinds of spiro[cyclohexane-1,3'-indolines] 3 and 5, a plausible reaction mechanism has been proposed (Scheme 1) on the basis of previously reported works and the obtained results from

• , 624.1666; found, 624.1660. Single crystal structure of compound 3l. Single crystal structure of compound 3s. Single crystal structure of compound 3f’. Single crystal structure of compound 5a. Single crystal struture of compound 8a. Proposed reaction mechanism for the compounds 3 and 5. Proposed mechanism

• compound 8a (Figure 5) was determined by X-ray diffraction analysis. From Figure 5, it can be seen that the two oxindole moieties exist on the trans-configuration. Therefore, this reaction showed very high diastereoselectivity. To explain the formation of the dispiro compounds 8, a plausible reaction

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• operation of the gas–liquid oxidation even with air in the flow reactor definitely paved the way for a green and fast oxidation process. Based on the mechanisms reported in the literature [11][31], we hypothesized the plausible reaction mechanism in our flow system as shown in Scheme 2. Firstly, the peracid

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• obtained in moderate to high yields. According to the experimental results and our previous work [27][28], a possible reaction mechanism is given in Scheme 4. At first, NHPI combines with triethyl phosphite to form intermediate 4, which is the loss of ethanol to generate intermediate 5. Then, single

• . A plausible reaction mechanism. Optimization of the reaction conditions.a Supporting Information Supporting Information File 48: Synthetic schemes for products, characterization data, and copies of 1H, 13C, and 19F NMR spectra. Funding We gratefully acknowledge funding from Jiangsu Provincial

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• corresponding products 6n and 6o with 79 and 82% yields, respectively. Nitro and fluoro-substituted aromatic aldehydes efficiently reacted with the chloro and fluoro-substituted anthranilamides and delivered the corresponding products 6q and 6r with good yields. To understand the reaction mechanism, we have

• reaction. So, based on literature reports [53][54][55], we have proposed a reaction mechanism in Figure 5b. Initially, DDQ abstracts a hydride ion from substrate 1a to generate the intermediate A. Then intermediate A undergoes an electrophilic intramolecular cyclization to form the cationic intermediate B

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• compound, 10-imino-2-methylpyrido[1,2-a]pyrrolo[3,4-d]pyrimidine-1,3(2H,10H)-dione (3a), in 97% yield. The chemical structure of product 3a was confirmed by 1H and 13C NMR spectroscopy (Figures S1 and S2 in Supporting Information File 1) and was obtained via the following reaction mechanism: nucleophilic

• novel luminogens for AIEE and are currently investigating the underlying mechanism and future biological applications. Presumed reaction mechanism to produce 3a. Fluorescence spectral profiles of (a) 4a (10−5 M, Exmax = 413 nm) and (b) 4e (10−5 M, Exmax = 415 nm) in H2O/EtOH mixture with different water

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• (Supporting Information File 1). The correlation between two syn-Hs of C4-OH/C2-H and another two syn-Hs of C4-OH/α C5-H were well visualized in the NOESY spectra. In order to explain the formation of dispirocyclopentanebisoxindole after studying some related literatures [23][24][25][29] a plausible reaction

• mechanism is shown in Scheme 4. At first, tosylhydrazine as hydride source [29] promotes reduction of 3-phenacylideneoxindole towards 3-phenacylindolinone A. Then, under basic conditions, the carbanion of 3-phenacylindolinone, which acts as Michael donor, is formed. After this the carbanion undergoes