Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• , leading to final lactams 20. This mechanism is partially corroborated by the following multicomponent synthesis where benzamide 21, ortho-functionalized with a terminal alkyne group (Scheme 5), a secondary amine 22 and carbon monoxide (23) react to produce 3-methyleneisoindolinones 24 [80]. A palladium

• conjugate addition of benzamide nitrogen onto the 2-ynamide generates the final cyclization product 24 through allene intermediate 28. Taking into account that the reaction does not take place with internal alkynes, the authors conclude that a terminal alkyne is necessary for the formation of the first

• of any transition metal. Different symmetrically and unsymmetrically substituted aryne precursors 77 and alkyl and aryl isocyanides 42 produced thirteen benzamide derivatives 79, with moderate to good yields. The plausible mechanism for this transformation (Scheme 24) would start with the formation

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• optimal side chain substituents are an o-chlorobenzamide on the 5-position and a non-substituted benzamide on the 2’-position. In absence of any structural information of the inhibitor–target interaction, we were interested in replacing the core tetrahydrofuran scaffold by a pyrrolidine ring in order to

• nucleophile [22][23]. Attempts to substitute the alcohol functionality of 12 via displacement of the derived mesylate with NaN3 failed, similar to previously reported difficulties by Trost et al. [24]. The benzamide substituent was therefore introduced via Mitsunobu reaction with N-Boc-protected ortho

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• compound 37 emerged as the most potent inhibitor of this series. Compounds 37 and 39 furthermore exhibited inhibition of HHQ, PQS and HQNO production in PAO1 strains when treated with 3 × IC50, whereas in PA14 a strong decrease in activity could be observed, especially for 39. Benzamide-benzimidazole (BB

• ) series In 2014, Starkey et al. performed a high-throughput whole-cell screening and identified the benzamide-benzimidazole (BB) motif as a promising scaffold for the inhibition of PqsR [77]. Starting from 41, which was not only able to suppress expression of AQs but also completely blocked pyocyanin

• antagonists displayed activity in a low double-digit µM range, but had only a marginal impact on the production of the virulence factor pyocyanin [83]. Further SPR screenings afforded hits 49–51 with EC50 between 7.5–17.8 µM. When compared to the benzamide class, compound 49 shows no significant increase in

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• -workers [38] demonstrated an elegant approach to highly substituted isoquinolones (e.g., 57a–d, Scheme 8) by employing a SM coupling followed by RCM. To this end, they started with o-vinylbenzoic acid and it was transformed to the benzamide derivatives 50 by employing a four-step synthetic sequence. Later

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• benzaldehydes, aniline and IBX under ball-milling conditions an explosion was observed (Figure 1a; Caution! see experimental section) [30][31] and similar observations were made with Dess–Martin periodinane (DMP). On the other hand, benzamide was found to be unreactive with IBX and no reaction was observed

• IBA (6). Arylamines caused explosion and benzamide was found to be unreactive with IBX. However, the reaction was found to be successful with 2-aminobenzamide under similar conditions (Figure 1). 2-Aminobenzamide having one highly reactive amine part and another unreactive part, can be considered an

• , after extraction of the reaction mixture with DCM, followed by silica gel column chromatography with ethyl acetate/hexane 1:5 as eluent provided product 3a (684 mg, 68%). a) Explosion was observed when an arylamine was mixed with aldehydes in the presence of IBX. b) Benzamide was found to be unreactive

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• procedure provides a wide substrate scope in terms of substituted acetanilides, although the optimised conditions were found to be more forcing than those for the corresponding benzamide substrates. Interestingly, density functional theory (DFT) studies reveal that the major impediment in the mechanism is

• full range of substrates and this presents one of the limitations to date compared with traditional palladium cross-coupling which is diversely applicable. Of interest to us are the readily available benzamide substrates, which are an interesting class of compounds as the amide moiety has been

• exploited as a common directing group [13] and countless pharmaceutical and agrochemical compounds contain these moieties. If the amide is reversed in the benzamide, the resulting compounds are acetanilides, which have been utilised far less as substrates in C–H functionalisation protocols [13], although a

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• . Aliphatic aldehydes gave poor yields, with sterically hindered examples not reacting at all. The author attributed this to the formation of enamines. Under the reported reaction conditions primary aliphatic and aromatic amines all produced imines. The benzamide moiety is somewhat common in biologically

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• steps of diazirine compounds were performed in the dark. N-{2-Oxo-2-[(4-(α-D-mannopyranosyloxy)phenyl)amino]ethyl}-4-(3-trifluoromethyl-3H-diazirin-3-yl)benzamide (3). The glycoamino acid 7 (52.8 mg, 160 µmol) was dissolved in distilled water which contained 50% TFA (5 mL). The solution was then stirred

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• cell lines by interacting non-covalently with the minor groove of the double helical ct-DNA [97]. Barker et al. have designed a series of novel di- and triaryl benzamide MGBs differing in the polar side chain, bonding and substitution patterns and functionalization of benzylic substituents and

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• which contains a free phenol moiety, were also tolerated (69% and 65% yield, respectively), as was the highly deactivated pentafluorophenyl analogue 2j (48%). To briefly explore the effect of chain length on efficiency, the cyclisation of N-(but-3-en-1-yl)benzamide and N-(pent-4-en-1-yl)benzamide was

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• and 8 in 61–75% isolated yields after work-up (Scheme 2, Figure 3). Diastereoselective intramolecular aza-Michael reaction First, the study of the diastereoselective intramolecular aza-Michael reaction of benzamide substrate (S)-6a allowed us to optimize the reaction conditions (Table 1) and latter to

• 6b–d highlighted the diastereoselection of the reaction was highly dependent of the starting benzamide substitution, 44 to 60% de being obtained for 3b–d. Finally, whereas diastereoisomers issued from 6b could be separated by flash chromatography, this was not possible for products 3c and d

• agonist at GABAA (γ-aminobutyric acid type A) benzodiazepine receptors [17]. In order to circumvent any hydrolysis of the ketal group during the preparation of the starting benzamide (see Supporting Information File 1), the synthesis of intermediate 24 was performed according another pathway depicted in

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• . The N-triflylbenzamides 9a–d were stable in basic aqueous solutions whereas the tested bromo-N,N’-bis(triflyl)benzimidamide 12 rapidly hydrolyzed to the corresponding bromo-N-triflylbenzamide 9d. Under conditions simulating ambient PEM fuel cells operation the 4-substituted benzamide derivatives 9a,b

• mixture stirred for 30 min. The precipitate was isolated and dried overnight. The product was purified by recrystallization from toluene. 4-Fluoro-N-((trifluoromethyl)sulfonyl)benzamide (9a) [9]: Synthesized by general procedure. The product was obtained as small clear crystalline flakes (1.88 g, 69%). mp

• (s, 3F), −105.75 (s, 1F); HRMS (TOF) m/z: [M − H]− calcd for C8H4F4NO3S−, 269.9854; found, 269.9888. 4-Trifluoromethyl-N-((trifluoromethyl)sulfonyl)benzamide (9b): Synthesized by general procedure. The product was obtained as white powder (2.83 g, 88%). mp 174–179 °C; 1H NMR (500 MHz, methanol-d4) δ

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• –N bond of benzamide and the formation of N-acylsulfonylguanidine 48 extended by two atoms (Scheme 21b). Biguanides The attachment of an amidine subunit onto the guanidine core, which is typically accomplished by the addition of a carbodiimide molecule, leads to a biguanide framework. In a paper by

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• , 1 h, 25 °C) was performed in order to identify the position(s) of ring metalation of 12. In recovered (about 80%) educt, deuterium incorporation (about 40%; calculated from integrals of the 1H NMR spectrum) was observed exclusively at C-6 of the benzamide moiety (Scheme 6). It is known for decades

• metalation at C-6 of the benzamide moiety was not followed by an equilibration giving the desired 8’-metalated intermediate (which in turn should be trapped by the amide group to give the tetracyclic ketone 6). Probably, the DreM at C-8’ is prevented, since the amide moiety forms a chelate with a lithium ion

• %; calculated from integrals of the 1H NMR spectrum) was exclusively observed at C-6 of the benzamide moiety (Scheme 8). These data show no indication for a DreM at the peri-position C-8’, since neither a 8’-deuterated arylnaphthalene nor a benzo[de]anthracen-7-one was detected. This observation is in

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• . Moderate to good enantioselectivities were afforded with a range of benzamide substrates. Mechanistic investigations were also carried out. Keywords: axial chirality; benzamide; bifunctional organocatalyst; molecular conformation; multipoint recognition; Introduction Bifunctional organocatalysts have

• moderate enantioselectivity (Scheme 2, 2i). In addition, a benzamide with a cyclopropyl group also provided the product in good enantioselectivity (Scheme 2, 2j). Furthermore, when the reaction was carried out using 1k and 1l with 2 equiv of NBA (4a), dibromination proceeded in high yields and moderate

• analysis of the reaction selectivity (the decrease of the enantiomeric purity of 2b was negligible after a day). Furthermore, the reaction of benzamide 5, bearing a protected phenol, was carried out (Scheme 6). It failed to give the corresponding product 6, indicating the significance of multipoint

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• properties [3]. The widely used solvent DMF is an intensely investigated example [4]. Functionalized piperazines [5], especially benzoylated derivatives, are our interest. In the past, mono or bisacylated piperazines with benzamide [6], nicotinamide [7] and isonicotinamide [8][9][10][11] residue were

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• to both of the carbonyl oxygens. During the course of studying the addition of aromatic thiols to α,β-unsaturated benzamides and enones, Chen, Ding, and Wu first reported the conjugate addition of thiophenol (23) to N-methacryloyl benzamide 91 followed by enantioselective protonation using Takemoto’s

• enantioselective Friedel–Crafts addition of pyrroles to imides 84. Kobayashi’s enantioselective addition of malonates to α-substituted N-acryloyloxazolidinones. Chen and Wu’s enantioselective addition of thiophenol to N-methacryloyl benzamide. Tan’s enantioselective addition of secondary phosphine oxides and

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• -methylallyl)benzamide (4a) and cyclohexane (2a) as model compounds (Table 1). As shown in Table 1, we found that the reactions did not happen or gave only a trace amount of the desired product with K2S2O8, AIBN, BPO and TBHP as oxidants (Table 1, entries 1, 3–5). PhI(OAc)2 and DCP could be used as oxidants

• cycloalkanes 2 and N-methyl-N-(2-methylallyl)benzamide (4a). As indicated in Scheme 3, several cycloalkanes were well-tolerated in this radical reaction resulting in the corresponding product. In the case of cyclopentane (2b), a slightly lower chemical yield was obtained (46%, 5ab), while the reactions of

• radical cyclization reaction was proposed (Scheme 6). Initially, DTBP undergoes homolytic cleavage to form the tert-butoxy radical A, which reacts with cyclohexane (2a) affording intermediate B. Then, intermediate B adds to N-methyl-N-(2-methylallyl)benzamide (4a), giving radical intermediate C

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• products 49 or 50 by incorporating phthalimide/saccharin 46. Under the standard conditions, however, the reaction of benzamide with 2-phenylpyridine provided product 51 with low yield (Scheme 14). As a special aromatic system, quinoline N-oxides were well investigated in their reactivity for metal

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• to the para-position of the ether groups of the benzamide rings of oligomers 15a and 15b to produce 20a and 20b [37], respectively (Scheme 9). 1H NMR dilution experiments in chloroform-d revealed that both compounds formed stable homodimers 20a·20a and 20b·20b, with Kdim being 3.0 × 103 and 2.3 × 105

• M−1, respectively. In contrast, even in nonpolar benzene-d6, the Kdim for the dimerization of benzamide was only 40 M−1. The result again shows that the intramolecular hydrogen bonding of the aromatic amide backbones promoted the appended amide subunits to bind in a cooperative manner by

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• hydrazine hydrate and sodium hydroxide. Results and Discussion We initiated our investigation of the direct carbon–carbon coupling of N-(quinolin-8-yl)benzamide (1a) and phenylacetylene (2a). After extensive attempts, 3-benzylidene-2-(quinolin-8-yl)isoindolin-1-one (3a) was formed in 18% yield via the

• -yl)benzamide (1a) as a white solid. Copper-mediated coupling of benzamide 1 and alkynyl substrate 2: The reaction of benzamide 1a with ethynylbenzene (2a) is representative. The dry sealed tube was charged with N-(quinolin-8-yl)benzamide (1a, 99 mg, 0.4 mmol), ethynylbenzene (2a, 82 mg, 0.8 mmol), Cu

• conditions: 1 (0.4 mmol), 2a (0.8 mmol), Cu(OAc)2 (0.4 mmol), K2CO3 (0.8 mmol), DMF (2 mL), 80 °C , 12 h, O2, isolated yield. Copper-mediated reaction of N-(quinolin-8-yl)benzamide with terminal alkynes. Reaction conditions: 1a (0.4 mmol), 2 (0.8 mmol), Cu(OAc)2 (0.4 mmol), K2CO3 (0.8 mmol), DMF (2 mL), 80

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• curcumin analogs. Using this principle, Ahn et al. (2005) [27] left the enone unchanged and prepared various curcumin mimics with asymmetric units bearing alkyl amide, chloro-substituted benzamide, or heteroaromatic amide moieties. These analogs exhibited a stronger anti-angiogenic activity against HUVECs

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• the selective replacement of one of the two hydrogen atoms in the ortho-position of acetanilide; the molar ratio of the C- and O-reagents is close to stoichiometric. The acetoxylation (product 42) and methoxylation (product 43) of N-(2-benzoylphenyl)benzamides 41 at the ortho-position of the benzamide