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

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

• performed in an undivided cell with NH4I as the mediator and cheap graphite plate as the working electrode. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diones proved to be compatible with the protocol. Since external oxidants and

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• ball mill (Figure 1c) enhances the depolymerization of acid-impregnated chitin more selectively towards glycosidic bond cleavage (i.e., backbone rupture) over amide bond breakage (i.e., deacetylation) [38][45]. Notably, the result is different for the reaction in solution, where scission of both bonds

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ]. In this work, we aimed to set compatible conditions to access formamides, envisioning the possibility of generating the isocyanide in a one-pot, two-step reaction. However, to the best of our knowledge, despite the notable improvement in the mechanochemical synthesis of the amide moiety [44][48][49

• HCO2H derivatives and CH3CO2H and two activating agents for promoting amide coupling. Results and Discussion We started our investigation by reacting p-methoxyaniline (1.0 mmol) with ammonium formate (3.0 mmol) (Table 1, entry 1) in a zirconia jar in the presence of one milling ball of the same material

• was successfully converted into the corresponding formamide 19 as was the poorly nucleophilic diphenylamine (Scheme 2, amide 20). Lastly, we aimed to apply the procedure to the acylation of a series of amines. To our delight, we successfully extended the methodology to the mechanosynthesis of amides

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• the original convergent synthesis plan. Instead of the classical amide coupling, bromo derivative Int1 should allow the formation of the benzothiazine ring as the final step. As an α-halocarbonyl compound, we tried to prepare Int1 through the coupling of bromopyruvic acid and ester, respectively, with

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• indicated by a strong NOESY correlation between the amide NH and the neighbouring methyl group. The structure of TDD These findings not only challenge the originally assigned structure of (E)-4 [9] and confirm the structural revision of (Z)-4 [1], but also question the suggested structural revision that

• material that was obtained as a viscous oil, failed. The X-ray crystallographic analysis of (rac)-4 showed an interesting dimer interaction of its enantiomers through hydrogen bridges between the amide (NH-CO) groups (Figure 2, for crystallographic parameters cf. Supporting Information File 1, Table S1

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

• addition, 1H NMR and FTIR spectra for the crude compound did not show characteristic peaks derived from carboxylic acid and amide. In order to clarify the role of the anode material, we carried out electrochemical measurements (Figure 1). Cyclic voltammetry was performed using BDD as a working electrode. A

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• in organic synthesis and sometimes appear in biologically active compounds, pharmaceuticals, agrochemicals and functional molecules, amidomethylation induced by N-acyliminium ions is a helpful and valuable protocol for direct introduction of an amide function into organic molecules. Generation of N

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

• produced a bridged cyclic 2-oxabicyclo[2.2.1]hept-5-ene D. The further hydration of intermediate D gave intermediate E, which was in turn transferred to cyclopentenyl intermediate F by the ring opening of the bridge ring. In the cyclopentenyl intermediate F, the hydroxy group and the amide group clearly

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

• . Moreover, since no detectable transformations took place when quenching the reaction at −78 °C (at least after three hours when using phenylglyoxal and phenylalanine amide), the reactions were always allowed to warm to room temperature by removal of the dry ice bath. In all our trials, the two isomers 3

• and Table 2, we undertook optimization trials focusing on the condensation between phenylglyoxal (1{1}) and the hydrochloride salts of either alanine amide (2{1}) or phenylalanine amide (2{2}). In the course of this, many reaction parameters were taken into account (i.e., base addition speed (s

• alanine amide (2{1})) was secured. As listed in Table 2, some of the results of the reaction optimization studies using compounds 1{1} and 2{2} followed the trends reported in Table 1. But for entries 16 and 17 in Table 2, a slow addition of the base, at −78 °C, was always used and we also checked that an

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -phenylphosphinamide (92a) and chloromethyl N,N’-dimethyl-N,N’-diphenylphosphondiamide (92b) via an intramolecular Friedel–Crafts alkylation. Although they tried several different amide derivatives, only phosphinamide 92a and phosphonic diamide 92b gave the corresponding 1-methyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2

• by two step hydrolysis gave the same product 223 in 28% yield. Phosphorus tribromide first reacted with more nucleophilic amide nitrogen atom to form dibromophosphanamine derivative 224 by loss of HBr. The more nucleophilic dibromophosphanamine derivative 224 further underwent a nucleophilic addition

• from P-(chloromethyl)amide precursors 92a and 92b through intramolecular Friedel–Crafts alkylation. Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodiamides. Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• solid state by X-ray crystallography (dimer 2), and implicit solvent QM geometry optimizations. N-(Methylamino)peptoids were found to preferentially adopt trans amide bonds with the side chain N–H bonds oriented approximately perpendicular to the amide plane. This orientation is conducive to local

• -substituted glycines [1][2]. They retain the same backbone as peptides except that the side chains are located on the nitrogen atoms of the amide bonds and thus represent an important class of peptide biomimetics [3][4][5], generally with improved cell permeability [6] and proteolytic resistance [7][8

• -supported combinatorial approaches [11][12][13]. The most relevant comparison of peptoids with peptides is in fact with polyprolines due to the presence of backbone tertiary amide linkages, much more prone to cis/trans equilibria than secondary amides. Indeed, in proteins, cis-amide bonds are most often

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• -2-ene-1-carboxylic acid 2f–i. The amide 2f and nitrile 2g [34] were found to be less active dipolarophiles towards the azomethine ylide 1 than hydrocarbons 2a–e. As a result, the corresponding cycloadducts 3f and 3g were obtained in moderate yields (58% and 55%, respectively) as single diastereomers

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• in the fixed-bed material that interact with the oscillating electromagnetic field. Recently, Rebrov and co-workers disclosed the direct amide formation of a carboxylic acid and anilline using high energy ball milling to prepare the sulfated TiO2 (50 wt %)/NiFe2O4 (50 wt %) catalyst that serves as

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

• (40 mol %) in the presence of P(OEt)3 (6 equiv, triethyl phosphite) under air at 100 °C (Table 1). The yield of the corresponding amide 3a was 78% (Table 1, entry 1). The reaction was completely inhibited in the absence of the copper catalyst or P(OEt)3, and no product was detected (Table 1, entries 2

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• showed an amide doublet resonance at 7.09 ppm. On the other hand, the 13C NMR spectra showed all characteristic signals for all of the synthesized compounds, with multiple aliphatic peaks for the cholyl and aliphatic amine moieties. The fingerprint signals for the cholyl moiety (C–OH) were evident in all

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• compounds 8, 20 and 21 albeit in low yields. Due to the extremely low isolated yield of compounds 20 and 21, we looked for an alternative more efficient procedure. In 2008 Sun et al. [32] described a method of karrikin alkylation in position 7 via direct metalation with lithium bis(trimethylsilyl)amide

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• amide functionality [13][14][15][16][17][18][24][25]. At the same time, norbornadiene derivatives are available from metalated substrates. Hence, norbornadiene is deprotonated with the Schlosser base and subsequently trapped by an appropriate electrophile [26][27]. In addition, halogenated norbornadiene

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• under the assumption of a shared biosynthetic origin. Compound 6 shows an optical rotation of = −10.6, which is consistent with the published value of pseudomonin A ( = −9.5) [12]. This natural product is structurally closely related to 6, featuring a terminal amide instead of a carboxylic acid

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• of their derivatives [12][13][14][15][16][17][18][19][20][21][22]. For example (Scheme 1), a one-pot Tf2O-mediated assembly of amides, amines, and ketones provided 3,4-dihydroquinazolines in good yields via successive triflic anhydride-mediated amide dehydration, ketimine addition, and Pictet

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• optimal reaction conditions, we proceeded to evaluate the generality of this nitroso aldol reaction with respect to the amide component of malonamate (Scheme 2). Pleasingly, our strategy was found to be operational with malonamates bearing electronically different substituents such as halo, nitro, acetyl

• absolute configuration of C7 is S. Proposed transition state for the nitroso aldol reaction. Catalytic asymmetric nitroso aldol reaction. Variation of the amide moiety of malonamates. General conditions: 1 (0.20 mmol), 2a (0.24 mmol), 3a (0.04 mmol), toluene (3.0 mL). Yields refer to isolated yields after

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• acid derivative through a user-friendly amide coupling in the presence of EDC·HCl and catalytic amounts of DMAP in CH2Cl2. Under these conditions, the corresponding diphosphine intermediates A (para), B (meta), and C (ortho) were isolated in moderate yields. Finally, gold(I) catalysts could be obtained

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• , epimerization is prevented through deprotonation of amide NH bonds, as argued by Seebach for Li enolates [53][54]. Nevertheless, isoleucine was prone to epimerize under the reaction conditions due to its vicinity to proline and therewith lack of the “protecting” NH group. Since no full conversion was observed

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• , we introduced the N-methylpyrrole (Py) units into the peptides obtained via solution-phase amide bond formation to produce 2a–h, 3a,b, 4a,b, 5a,b, 6a–c, 7, 8a,b, 11a,b, 12a–c, 13, 14, and 15a–c. We conjugated two Py units successively to the peptide ffpy and kept the Boc protecting group of the

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• lithium hydroxide monohydrate [29] to give the desired indole-2-acetic acid (14) in 95% yield. The peptide coupling reaction [30] of indole-2-acetic acid (14) and 2-iodoaniline afforded 15 in 23% yield (Scheme 3). Subsequent protection of both the indole and the amide nitrogen with tert-butyloxycarbonyl

• groups in one step produced 16 in 86% yield. However, attempts to perform the ring-closure reaction of the Boc-protected amide 16 by an intramolecular Heck reaction failed and led to degradation of the starting material. Most likely, the electron-withdrawing tert-butyloxycarbonyl protecting group

• two steps by following known protocols [36]. Fischer indole reaction of this precursor with 1-benzyl-1-phenylhydrazine in acetic acid gave 1a in 55% yield (Scheme 6). The protecting group on the hydrazine moiety is necessary in this case, otherwise amide bond formation would occur after the initial

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• 171.5 and 172.0; 168.6 and 171.0), thus establishing two succinic acid moieties (C22–C25; C33–C36, Figure 2). Connection of these substructures via the amide bonds with an alternate alignment of cadaverine and succinic acid was verified by HMBC correlations from the amide protons to the adjacent

• in 1. Among the five amide bonds, amide protons were present at N21 and N32, thereby leaving N15, N26, and N37 as the hydroxylation sites. This assignment was supported by the 13C NMR chemical shifts. Within each cadaverine moiety, the 13C chemical shifts for the methylenes adjacent to the N

• -hydroxyamide group (C16: δC 46.7; C27: δC 47.2) were obviously larger than the methylenes adjacent to the amide group (C20: δC 38.52; C31: δC 38.52), consistent with the reported data for avaroferrin [22], bisucaberins [18], and nocardamines [23]. However, this trend is inversed in the hydroxamic acid terminus