Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• synthesis of N-substituted 1,2,3-triazoles via the reactions of organoazides and the in situ prepared N,N-dimethylenaminones by 150 °C microwave irradiation and subsequent heating in toluene at 100 °C, providing an effective protocol of enaminone-based 1,2,3-triazole synthesis. Interestingly, our continuous

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• and alkoxylcarbonyloxy groups generally require long heating times at elevated reaction temperatures (>140 °C) or microwave irradiation (Scheme 2a). In contrast, N-sulfonyloxyanilines are known to readily undergo the [3,3]-rearrangement during the preparation of the starting material below −20 °C due

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• catalyst loading required as well as recoverability and reusability without any significant loss of activity in terms of reaction time, selectivity and yield. For reactions that are sluggish and mostly require heating, microwave irradiation is reported to significantly improve reaction rates, selectivities

• electron rich ones such as p-methylthiophenol, giving the corresponding products in very high yields. Unlike in the microwave irradiation protocol, the reaction of aliphatic thiols with epoxides proceeded smoothly to give excellent yields. In another contribution, Su et al. carried out thiolysis of

• oxidation to β-hydroxy sulfoxides under microwave irradiation. Gallium triflate-catalyzed ring opening of epoxides and one-pot oxidation. Thiolysis of epoxides and one-pot oxidation to β-hydroxy sulfoxides using Ga(OTf)3 as a catalyst. Ring opening of epoxide using ionic liquids under solvent-free

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• reaction conditions were chosen to match the already developed microwave-assisted synthesis of the 5-aminopyrazoles. A solution of the β-ketonitrile in methanol was treated with hydrazine and heated to 150 °C under microwave irradiation for 5 min. The β-ketoester and acetic acid were then simply added to

• the pot and the reaction heated at the same temperature, 150 °C, under microwave irradiation for a further 2 h. The target pyrazolo[1,5-a]pyrimidinone was subsequently isolated in an overall yield of 52%. Once more, a significant improvement was observed using microwave conditions in comparison with

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• A facile Pd-catalyzed C(sp2)–N coupling to provide a range of 2- or 4-[(subst.)phenyl]amino-13α-estrone derivatives has been achieved under microwave irradiation. The reactions were mediated with the use of Pd(OAc)2 as a catalyst and KOt-Bu as a base in the presence of X-Phos as a ligand. The

• (dba)3 as catalysts, X-Phos as a ligand, Cs2CO3 as a base in toluene or DMF solvent under thermal heating or microwave irradiation [18]. We recently described halogenations [19] and Sonogashira couplings on ring A of 13α-estrone and its 3-methyl ether [20]. The 13-epimer of natural estrone is a non

• -estrone 3-methyl ethers are also effective inhibitors [19]. Recently, we carried out the Pd-catalyzed C–C coupling of 2- and 4-iodo-13α-estrones as well as their 3-methyl ethers with p-substituted phenylacetylenes as terminal alkyne partners under microwave irradiation [20]. The regioisomerism markedly

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• as catalysts. These latest strategies provide efficient syntheses under mild conditions without using harsh chemicals. Furthermore, the application of microwave irradiation or sonication is also preferred to conventional heating methods to accelerate the reactions. Synthesis of aminoalkylphenols The

• were also formed in around 90% yields under microwave irradiation (Scheme 7). Miscellaneous reactions It is also known that o-QMs could cross-link two biologically important molecules such as peptides, proteins or nucleic bases. (see section Biological properties) Achieving the reaction under

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• . This transformation is perhaps similar to acetal hydrolysis in neat water under microwave irradiation [41]. Because of this efficient process, compound 11 was isolated in one synthetic operation in 80% yield from amine 9. In the last step, precursor 11 reacted with either amine (R,R)-12 or (S,S)-12, to

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -ketoesters and phenols (the Pechmann condensation) [17]. Recent studies for the metal-catalyzed reactions for the synthesis of the coumarin skeleton are as follows: the Yb(OTf)3-catalyzed microwave irradiation of phenols and propynoic acids [18], the Pd(OAc)2-catalyzed oxidative cyclocarbonylation of 2

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• ] syntheses of heterocyclic compounds. The rDA products can be gained, due to a thermal [4 + 2]-cycloreversion, by distillation under reduced pressure [29], boiling in solvent [30][31], and applying microwave irradiation [32][33][34][35] or flash vacuum pyrolysis [35][36]. rDA reactions under mild conditions

• of our results, tricyclic 15b was also prepared alternately: the mixture of 3-aminobicyclo[2.2.2]oct-5-ene-carboxylic acid, triethylorthoformate, aniline and acetic acid was subjected to microwave irradiation at 120 W at 80 °C for 20 min. After completion of the reaction, as monitored by TLC, 20

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• ). Interestingly, high yields of the corresponding pyrazolo[3,4-b]pyridines 34 were obtained when reactions were carried under solvent-free microwave irradiation. The synthesized pyrazolo[3,4-b]pyridines have shown potential cytotoxic activity against cervical HeLa and prostate DU 205 cancer cell lines. A similar

• reaction of 5-aminopyrazole 16, isatin 54 and 3-oxo-3-phenylpropanenitriles 15 in acetic acid under microwave irradiation at 80 °C in just 20 minutes (Scheme 14). Hao et al. [62] described the unexpected synthesis of naphthoic acid substituted pyrazolo[3,4-b]pyridine derivatives 70 via a three-component

• domino reaction of 5-aminopyrazoles 16, cyclic 1,3-diones 58 and arylglyoxals 98 under microwave irradiation. Triethylamine (20 mol %) as base and DMSO as solvent at 120 °C provided best results with high yields of pyrazolo[3,4-e]indolizines (a derivative of pyrazolo[3,4-b]pyridines) 102 (Scheme 30

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• cyclic structure as in Scheme 10, the formation of tetraoxaadamantanes requires the addition of water from the concave inside. Thus, the bisdioxine 32 did not form a tetraoxaadamantane 33 under the usual reaction conditions, but this was finally achieved in 35% yield by microwave irradiation at 170 °C

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• -protected glycine was condensed with proline methyl ester under microwave irradiation. Subsequent hydrolysis of the ester gave N-protected Gly-Pro-OH (6). Condensation of dipeptide 6 with 1 was achieved using the corresponding acid chloride. Deprotection of the amino group was achieved by treatment with

• ), and the mixture was stirred at room temperature. After the reaction mixture was stirred for 5 min, to the microwave vial was added L-proline methyl ester hydrochloride (4.8 mmol) and the mixture was heated by microwave irradiation for 20 min at 120 °C. The resulting mixture was quenched with water and

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• 36 underwent a ring-closure metathesis reaction in the presence of catalyst 37 under microwave irradiation to give lactam 38. Deprotection of the amine followed by acidic opening of the ring gave the (E)-monofluoroalkene 39 in good yield. The reaction was also performed on the racemic starting

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• –C6H4, 4-I–C6H4, 4-CH3–C6H4, 4-OCH3–C6H4, thien-2-yl, 4-Ph–C6H4, CH3) and 5-aminotetrazole, by using conventional heating in an oil bath or microwave irradiation, was performed in IL. Here, only the 5-trifluoromethyl-substituted tetrazolo[1,5-a]pyrimidines 6a–g were obtained in all cases. Some important

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• of Fmoc-V-OH with H-IA-resin and for the deprotection of Fmoc-IA-resin that were performed during 90 min at room temperature, the coupling steps were performed at 70 °C for 7 min under microwave irradiation. The deprotection steps were carried out with piperidine/DMF 1:4 for 3 min at 70 °C. After the

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• application, glycosyl donor precursors were reacted with phthalic anhydride to afford the corresponding esters. The activation with thionyl chloride was used for tethering the donors to the glycosyl acceptor counterpart and the regioselectivity was controlled using tin-mediated coupling under microwave

• irradiation. The tethered compound 10 was then glycosylated in the presence of NIS/TfOH to afford compound 11 (Scheme 4). The tether was removed with NaOMe and the product was globally acetylated to afford 12 as an α-(1→3)-linked isomer. The regioselectivity in this case was driven by the phthaloyl tether

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• nanoparticles. Both microwave irradiation and conventional heating exhibited high conversion and selectivity to the main product of the reaction in extremely short reaction times. Moreover, reusability studies showed high stability and activity of the nanohybrids TiO2-Fe2O3-PS4 and Fe2O3-PS4-MNP, establishing

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• in the solid-state before having been exposed to microwave irradiation for 1.5–4.5 minutes. In their paper, the authors state: "Aryl isothiocyanate (1 mmol) and aromatic primary amine (1 mmol) were mixed thoroughly in an agate mortar" [33]. Considering the established reactivity pattern of electron

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• Mizoroki–Heck coupling reactions under microwave irradiation (MW) were carried out with a colloidal Pd nanocatalyst stabilized with poly(N-vinylpyrrolidone) (PVP). Many stilbenes and novel heterostilbenes were achieved in good to excellent yields starting from aryl bromides and different olefins. The

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• , robust conditions. Reported protocols have employed chloroform [3], acetonitrile [19], acetone [20], nitromethane [21], 1,2-dichlorobenzene [22], toluene [23], reaction in the absence of solvent [24] or use of microwave irradiation [25]. We found that refluxing acetonitrile was relatively effective, if

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• temperature to 80 °C or increasing to 160 °C by microwave irradiation were not effective for improving the reaction (Table 2, entries 16 and 17). Consequently, we found that the reaction shown in entry 4 afforded the optimal result (see Table S1 in Supporting Information File 1 for further manipulation of the

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• microwave irradiation at 110 ºC for 4 minutes. Due to the easier preparation and the inexpensive reagents required for its synthesis [65], PPE was chosen as cyclodehydrating agent for the preparation of compounds 1. Results and optimized experimental conditions of the MW-assisted ring-closure reaction are

• 5a with PPE/CHCl3 under microwave irradiation led to 1,4-dihydroquinazoline 2a, accompanied by a low percentage of a collateral product. This compound was identified as 2-methyl-1-propylquinazolin-4(1H)-one (6a) (Scheme 3, (a), R1 = Pr, R2 = Me), arising from spontaneous benzylic oxidation of 2a. An

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• arenes can be markedly facilitated using 1-imidoalkylphosphonium salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine. Microwave irradiation also considerably

• does not exert an impact on the reaction rate. As expected, microwave irradiation effectively facilitates the splitting of the highly polar Cα–P+ bond. In order to reduce the Cα–P+ bond strength, and to facilitate the generation of the corresponding 1-imidocarbenium cation, 1-imidoalkylphosphonium

• (5e) and 1-phthalimido-1-phenylmethyltris[p-(trifluoromethyl)phenyl]phosphonium tetrafluoroborate (5h) already react with anisole at 90 °C (Table 3, entries 5 and 10) and even at 60 °C when using microwave irradiation (Table 3, entry 7); the reaction of 5e with 1,3-dimethoxybenzene started at 80 °C

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• with HPA either at rt or at reflux temperature in acetonitrile or toluene. Attempts to trigger the reaction with these substrates by excluding solvent altogether [34] or applying microwave irradiation (up to 2 h at 200 °C in MeCN) were also unsuccessful. Any appreciable conversion led to predominant

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• -glucose in the presence of HCl to provide the methyl glycoside (pathway a, Scheme 6). The reaction proceeds chemoselective at the anomeric position. More recent examples typically use Lewis acids [29][30][31][32][33][34] or microwave irradiation [35][36] to accelerate the reaction. However, shortcomings