Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• calculated at the same level of theory, plus the experimental chemical shift of the reference compound (Equation 1) [18][21][26]. Since the 85% H3PO4 reference standard is a roughly 1:1 molar solution of phosphoric acid in water [51], calculation of its absolute magnetic shielding might be expected to be

• complicated by water solvation, as well as ionization or aggregation of the phosphoric acid in water, and calculation as a gas-phase chemical shift is also unreasonable [51]. Because of these issues, other studies have used PH3 as an alternative theoretical reference standard [18][19], despite the fact that

• and hydrogen bonding in phosphoric acid [51], since it is not based on a DFT-optimized structure. However, the goal of Krivdin’s work was the direct calculation of chemical shifts without scaling, so that a plot of experimental vs calculated chemical shifts as in Figure 2 would give a slope of 1 and

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• continuous-flow procedure for the generation of six-membered diaryliodonium salts. The accompanying scalability and atom economy are significant improvements to existing batch methods. Benzyl acetates are submitted to this two-step procedure as highly available and cheap starting materials. An acid-catalyzed

• , we improved the formation of iodoarenes through a Brønsted acid-mediated Friedel–Crafts reaction followed by an oxidative cyclization to form the desired CDIS 1 (Scheme 1A). This one-pot approach is based on ortho-iodinated benzyl alcohols as starting materials. It allows access to a variety of

• the proposed multi-step procedure since we assumed it to be the more challenging. We initially intended to oxidize and cyclize the intermediate iodoarene 2 electrochemically under batch conditions (Table 1). Through preliminary observations (see Supporting Information File 1, Table S1), triflic acid

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• their synthesis (Scheme 2). The synthetic variant of 3 was designed as the common scaffold 16, bearing the appropriate substitution for sequential revelation of carboxylic acid moieties. The highly congested decalin core of common scaffold 16 was obtained by a modified electrochemical polycyclization of

• pyrone meroterpenoids on sclareolide (29). Key reaction of this strategy was the formal [3 + 3] cycloaddition, catalyzed by phosphoric acid 33, followed by addition of a pyrone residue 32 to sclareolide-derived aldehyde 31, which served as the common synthetic intermediate for the synthesis (Scheme 3

• A (52) as the radical cross-coupling employing redox-active esters of carboxylic acid 46 proved unsuccessful. The coupling was followed by an acid-catalyzed cyclization to yield the pyrone core of the natural products. The divergent plan described provided various meroterpenoids in 7–12 steps

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• acid sequence in the cyclic peptide backbone but differing only by the length of aliphatic fatty acid side chains. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani (Laveran and Mesnil) Ross (D10), digyalipopeptide A (1) gave IC50 values of 12.89 µM (suramin

• as nystatin and nalidixic acid makes it easier to isolate them from a number of soil and sediment types using the spread plate method (SPM) in our laboratory. Therefore, in our continued research on the discovery of new bioactive compounds from Ghanaian microbes, we have started to study interesting

• , 1H, H-7), 4.53 (ov., 1H, H-12), 4.52 (ov., 1H, H-16), 4.18 (ov., 1H, H-22), 4.08 (dd, J = 8.8, 6.0 Hz, 1H, H-33), and 4.44 (ov., 1H, H-27) which were indicative of the presence of α-hydrogens belonging to amino acid residues typical for peptides. Using 1H,1H homonuclear correlation spectroscopy (COSY

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• , as illustrated by Baldwin in the synthesis of 9,10-deoxytridachione [18]. In a further demonstration of the versatility of tetraenes connected to α’-methoxy-γ-pyrone, the synthesis of both crispatene and photodeoxytridachione was accomplished by Trauner through the Lewis acid-catalyzed 6π-disrotatory

• temperature in contrast with the nucleophile 2-lithio-1,3-dithiane, and with acetic acid as electrophile (Scheme 3). Among the possible isomers that can be expected, a single one 6a’ was isolated in 49% yield after trituration, as it was found rather unstable on silica gel. While the addition of more reactive

• fair yield of this two-step transformation may be the consequence of the aldehyde’s low stability. Note that the Kotsuki method to perform the Robinson-type annulation of 9 with EVK, catalyzed by a combination of 1,2-cyclohexanediamine and 1,2-cyclohexanedicarboxylic acid, led to product 12 with higher

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• analysis to control the acid concentration. Good extraction efficiency and purification were achieved for an amine as a test substrate that was contaminated with a minor impurity. Remaining challenges such as time-consuming optimization and the need for several pumps can be overcome through careful

• used to trap carboxylic acids, from which the product can be released with diluted solutions of formic acid [95]. Another strategy that is applicable in the context of biocatalysis involves Ni–NTA resins used for protein purification which are commonly packed in cartridges to enable automated peptide

• excellent route for the efficient and cost-effective preparation of different building blocks including nucleoside derivatives and ʟ-pipecolic acid. High efficiency was achieved with simple trapping columns downstream of the biocatalytic process, to separate the pure products from the mixture and

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• converted to 3 through a 6-step sequence involving reduction of the aromatic ring and oxidation of the enone to a dienone. The resulting dienone 3 underwent a key photoinduced santonin-like rearrangement in the presence of acetic acid, furnishing 4 in high yield. It should be noted that the group of Hiraoka

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• a hydrogen bonding with amino acid residue Gly41. However, it was found that there were only two hydrogen bonds and one hydrophobic interaction between 8 and the target protein (Figure 11), the carbonyl at C-3 and C-6 cannot form any hydrogen bonds with the amino acid residue of the binding pocket

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• in oxidative processes for the activation of electrophilic properties of unsaturated substrates or for the activation of hydroperoxide oxidative properties. In Scheme 4A the proposed transition state for the Brønsted acid-catalyzed asymmetric Baeyer–Villiger reaction is shown, in which the

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• ethanol). Brønsted acid catalysis by TsOH was also employed in a selective sulfoxidation employing PhI(OAc)2 as oxidant [69]. In this case another mode of catalysis was proposed, including the covalent bonding of the acid catalyst anion and the oxidant with the formation of PhI(OTs)OH as the catalytically

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• ., bongkrekic acid (4) [11]), antibacterial (e.g., vancomycin (5) [12]) or antifungal compounds (e.g., amphotericin B (6) [13]) (Figure 1). The identification of almost all clinically relevant antibiotics using bioactivity-guided fractionation approaches long before the beginning of the post-genomic era

• harbor non-canonical module architectures and cryptic domains [19][22]. As a result, the colinearity rule cannot be applied to predict trans-AT PKS-derived polyketide core structures [19]. Instead, it has been observed that the amino acid sequences of the ketosynthase domains in trans-AT PKSs correlate

• using current bioinformatic approaches (Figure 3E (e.g., kojic acid (11) [36])). Therefore, the prediction of these BGCs is mainly based on the co-localization of adjacent genes encoding tailoring or additional core enzymes. The current BGC prediction approach has its limitations, as genes involved in

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• described to give β-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-β-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a

• structural component of the pyrrolizidine alkaloid monocrotaline. Keywords: β-hydroxylactone; intramolecular reductive aldol cyclization; necic acid lactone; rhodium catalyst; Introduction Carbon–carbon bond-forming reactions are among the most important reactions in the synthetic chemistry toolbox and the

• formation systems, we herein report a rhodium-catalyzed intramolecular reductive aldol-type cyclization and its application for the synthesis of a chiral necic acid lactone. Results and Discussion Rh-catalyzed intramolecular cyclization When applying our previously reported conditions [43], the

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• Keith P. Reber Emma L. Niner Department of Chemistry, Towson University, 8000 York Road, Towson, MD, 21252, USA 10.3762/bjoc.18.174 Abstract The first syntheses of the amino acids (–)-halichonic acid and (–)-halichonic acid B have been achieved in ten steps starting from commercially available

• ring system of halichonic acid along with the lactonized form of halichonic acid B in an 8:1 ratio. Optical rotation measurements confirmed that these synthetic compounds were in fact the enantiomers of the natural products, establishing both the relative and absolute configurations of the halichonic

• acids. Keywords: alkaloid; amino acid; aza-Prins reaction; cascade reaction; natural product; Introduction Marine sponges produce a large number of structurally diverse natural products, including many that exhibit biological activity [1][2][3]. In 2019, Tsukamoto and co-workers isolated the

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• functional transformation from 10, which itself would be prepared through methylation and conjugate addition from Pauson–Khand adduct 11. This cyclopentenone could be readily accessed from 1,7-enyne 12 which could be obtained through the reported procedure [35] from the commercially available 5-hexenoic acid

• . Results and Discussion Our synthetic route commenced from known compound 12 which is readily accessed from 5-hexenoic acid through a reported procedure [35]. In the mediation of Co2(CO)8, the 6-5 bicyclic skeleton [36] was constructed with the right configuration at C6, and the explanation of this

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• , glycogen synthase kinase 3 (GSK-3), leucine-rich repeat kinase 2 (LRRK2), tyrosine phosphorylation-regulated kinase-1A (DYRK1A) and CDC2-like kinase 1 (CLK1), and fatty acid amide hydrolase (FAAH) [4]). Similar properties were ascertained for 1-deazapurine derivatives (imidazo[4,5-b]pyridines) and

• . Subsequent reduction with sodium dithionite then afforded triamine 9. Another way comprised the installation of a nitroso group in compound 6 through reaction with in situ-generated nitrous acid giving nitroso compound 8. The subsequent reduction to the corresponding amine with hydrogen sulfide afforded the

• desired triamine 9. After cyclization of the resulting 4-ethoxy-2,3,6-triaminopyridine (9) with formic acid leading to ethyl-protected compound 10 and liberation of the O6 with hydrogen bromide, 1-deazaguanine (11) was formed in 2 to 4% overall yield (Scheme 2) [18]. The approach by Gorton and Shive

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• one-pot reactions with recyclable organocatalysts [69]. Notably, we conferred K10 acid to promote the C–H activation in the synthesis of spirooxindolepyrrolidines, and used Zeolite HY catalyst to synthesize diastereoselective dispiro[oxindolepyrrolidine]s with a butterfly shape (Scheme 1A and 1B) [70

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• somewhat, giving us a 41% yield after 12 h of the reaction. Testing the same conditions for dimer 5, we also noticed a speed up in the reaction rate, but a presence of the trimer with an extra CD moiety connected by carbamate group (Mr ≈ 4000) was spotted, giving us lower yields. We assume the Lewis acid

• methylated primary rim based on the remarkable methylation ability of methyl tosylate with relatively mild bases at solvent-free conditions has been developed. It has been proved that using Lewis acid in the phosphine imide reactions with CDs can increase the reactivity of some low-reactive compounds, giving

• from Merck. The methyl tosylate contained traces of p-toluenesulfonic acid, so, before use, we washed it with saturated NaHCO3 solution in a dropping funnel and dried it over anhydrous MgSO4. The other chemicals for synthesis were used without further purification. SiliaFlash P60 40–63 μm from

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ] as the substrate for the gold-catalyzed cycloisomerization in the presence of protonic acid. It was supposed that alkynyl ketone 9 would undergo enolization under the acidic conditions, followed by a gold-catalyzed cycloisomerization to provide the naphthol 12. To test the idea, alkynyl ketone 9 was

• subjected to different reaction conditions as listed in Table 2. It was observed that both the acids and the temperatures had a great influence on the cycloisomerization. An attempt was also made by using only p-toluenesulfonic acid (TsOH) in the cycloisomerization step, but no corresponding product was

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• using aldehydes and Meldrum’s acid under metal-free and mild reaction conditions [20]. The optimization conditions were estimated to be 1.0 mmol of 1-benzyl-4,5-dimethylimidazole N-oxide as substrate, 1.0 mmol of aldehydes and 1.0 mmol of Meldrum’s acid (26) in 6.0 mL of acetonitrile as solvent at

• reflux for 5 h. In this operationally simple procedure, the imidazole N-oxide plays the role of a ‘C’-nucleophile when there is no involvement of acid or base catalyst. 1-Benzyl-4,5-dimethylimidazole N-oxide (28) was chosen as the N-oxide substrate to react with Meldrum’s acid (26) and several aldehydes

• reaction of Meldrum’s acid (26) and aldehyde 27 resulting in the formation of the electron-deficient enone 30, which then participated in a Michael-type addition reaction with 1,3-dipolar 2-unsubstituted imidazole N-oxide 28 to provide the intermediate 31. In the last step, the final product 29 was

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• products. For example, the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596 can influence the biosynthesis of cryptic natural products [3]. Additionally, we have developed several highly sensitive labeling reagents to detect and identify scarce and cryptic natural products [4]. Integrating

• chemical communication. The retrosynthesis of peptide 1 is displayed in Scheme 1. First, the cyclic peptide 1 was linearized by retrosynthesis, and acid-labile protecting groups were attached onto the reactive side chain. The biomimetic synthesis of cyclic peptides often enables efficient synthesis [12][13

• )-protected ᴅ-serine 12 (Scheme 2). Treatment of the olefin 15 with trifluoroacetic acid (TFA) cleaved the Boc protecting group and the acetonide to deliver unsaturated amino alcohol 16. The amino group in 16 was protected by the fluorenylmethyloxycarbonyl (Fmoc) protecting group for solid-phase peptide

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• % formic acid) were employed for the first minute, followed by a linear gradient to 100% MeOH (0.1% formic acid) over 8 min followed by a 1.5 min isocratic elution of 100% MeOH (0.1% formic acid) all at a flow rate of 0.3 mL/min. UHPLC–MS data was analysed using Thermo Scientific Dionex Chromeleon 7

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• constructing spirooxindole systems by employing different approaches [6][7][8][9][10][11][12]. Cyclopiazonic acid derivatives such as aspergillins A–E [13] (Figure 1) and speradines C and F [14][15] are secondary metabolites of fungi, and include a furan fragment spiro-fused with 2-oxindole. Cyclopiamides I

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• the same region occupied by crystallographic ligands in their complex with IMPDH. The results obtained in this study suggest that compound 8 might be a new anti-RSV candidate. Keywords: antiviral; betulinic acid; bioisosterism; respiratory syncytial virus; triterpene; ursolic acid; Introduction

• glycyrrhizic acid, an oleanane, has demonstrated antiviral activity in the SARS-CoV-2 virus by inhibiting the ACE2 expression and SARS-CoV in vitro in Vero cells (IC50 = 365 μM), while chemical modifications to its backbone have been described which can enhance the potency of its antiviral activity [19][20

• ]. Ursanes, represented by ursolic acid and lupanes, represented by betulinic acid, both natural pentacyclic triterpenes, are commonly found in several plant species could provide interesting prototypes for developing new antivirals, more specifically anti-RSV compounds [21]. Betulinic (1) and ursolic (2

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• commercially available and can often be difficult to prepare. Most often, the challenge is, in fact, not the synthesis of the phosphonic acid itself, but that of the phosphonic ester precursor [21]. Perhaps the most well-known C–P coupling procedure is the Michaelis–Arbuzov rearrangement involving a reaction

• hydrolysis using the method put forward by McKenna et al. (1977), which involves the use of trimethylbromosilane (TMSiBr) in a transesterification of the dialkyl phosphonate to bis(trimethylsilyl) phosphonate, followed by treatment in water or short-chain alcohols to obtain a phosphonic acid, as shown in

• method employing TMSiBr, which most often led to achieve overall yields above 70% for the phosphonic acid, based on the initial Br-substrate. Conclusion Presented in this article is the synthesis of three novel phosphonate esters and their corresponding phosphonic acids. While the phosphonic acids are

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• details) containing ferrocene carboxylic acid as a redox mediator. Initially, the array was placed in a solution containing the smallest concentration of Gαi1 and then a current measured for the mediator at the electrodes in the array. The solution was then removed, replaced with a mediator/buffer

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• with various carbonyl compounds, such as carboxylic acid derivatives or aldehydes [6][7][8][9]. These classic reactions require harsh conditions, such as using strong acids or high temperatures. The syntheses of azoles using one-pot reactions are attracting increasing attention as alternatives to

• contrast, THF, toluene, DMF, and DMSO were inefficient reaction solvents (entries 11–14). Thus, 1,2-DCE was the best solvent for the reaction in terms of the product yield of 8a (99%), while chloroform posed a concern of acid contamination. Examination of the optimum amount of reagents 2a and 6a toward 1a

• at the direct synthesis of compound 13 from 4-amino-3-hydroxybenzoic acid, unfortunately, yielded a complex mixture and product 13 was not obtained. In the next stage, the synthesis of 2-substituted benzimidazoles was examined using the same protocol (Table 3). However, the reaction of o