Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• heating was to prevent the removal of the base-labile protecting group in 3 by the excess strong base by allowing the excess base to be consumed selectively via β-elimination of the tosylate in 1. The product of premature removal of the base-labile protecting group – an alkoxide – would complicate the

• mixture was cooled to −78 °C, and then the monomer solution was added and the reaction mixture was warmed to room temperature slowly before heating to 60 °C. The careful manipulation of the temperature allowed the excess base to be selectively consumed via β-elimination of the tosylate of the monomer

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• ). As expected, substituents at the ortho-position of the anilines affected the N-arylation reactions due to the steric hindrance exerted by these groups. In fact, reactions with 2-methoxy-substituted N-methylaniline 9c were slower, but we obtained high conversions within 20 min under microwave heating

• we used 2-fluoroaniline (14b), we obtained derivatives 15c and 15d in 60 and 56% yields, respectively, after heating for 40 min (Scheme 4). Then, the derivatives 15a–d were efficiently N-methylated with iodomethane in the presence of sodium hydride, to afford the corresponding methylated 4

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• –Volhard–Zelinsky-type ring-opening reaction of 1a (Table 1). In this reaction, the corresponding acid bromide is formed in situ by heating with Br2 and a substoichiometric amount of PBr3; the acid bromide is then converted into 2,5-dibromopentanoic acid (2a) via hydrolysis during the workup under open-air

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• appeared to be stable towards heating and underwent intramolecular cyclocondensation performed in diphenyl ether at 230 °C giving target products 7 in good to high yields (see Table 1). Since it was not possible to predict a priori which of the nitrogen atoms of 7 would participate in PIFA-promoted

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• , US causes cavitation within the sample, the collapse of which is accompanied by very high local heating. Alternative approaches rely on inducing strong shear forces by strong mixers or dispersers. An interesting method in this regard is the use of DAC, which is also considered to be a speed-mix

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• selective acetylation [43], followed by oxidation. Enones 4 and 8 were prepared by dehydrogenation of corresponding ketones with SeO2 in refluxing acetic acid [44]. Microwave-assisted heating of the reaction mixture in a closed vessel (150 °C) helped in decreasing the reaction time for dehydrogenation

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• derivative 28, which has a lower tendency for ring expansion. At room temperature, this substrate stopped at the hydrated intermediate 29, which could be isolated and remained intact when heated to 80 °C alone in 1,4-dioxane. Inclusion of the gold catalyst while heating, however, initiated the rearrangement

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• which a polymer becomes soluble upon heating, and the LCST is the temperature at which polymers become insoluble upon heating. Any LCST or UCST behaviour can be identified from a polymer/solvent phase diagram, if it has both one-phase and two-phase regions [34][36]. Most commonly, the physical change in

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• , underwent cyclization in the presence of silica gel to give ethyl 6-(hetero)aryl-2,3-dihydro-1H-pyrrolizine-5-carboxylates within minutes upon microwave heating in xylene at 150 °C. Instead of functioning as a nucleophile, the enaminone acted as an electrophile at its carbonyl group during the cyclization

• cyclization to the expected pyrrolizinone 13a or tautomer 13a' did not take place (Table 1, entry 1). More vigorous conditions were therefore investigated. Heating 15a in acetic acid (150 W) for 10 minutes at 140 °C produced a new product in 72% yield (Table 1, entry 2). However, the isolated product was not

• 20 and 21). More interestingly, microwave heating at 150 °C for no more than 10 minutes of a solution of 15a in xylene with montmorillonite K10, an acidic layered aluminosilicate clay often used as a catalyst in microwave-assisted organic synthesis [41][42][43][44], also afforded the pyrrolizine 19a

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• salts or the substitution of thermal heating for LED irradiation resulted in a low yield of the cross-coupling products 22 and 23, indicating the necessity of the copper salt and LED irradiation. Mild conditions, such as Pd-free and high reaction yields at room temperature, make this method a very

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• to optimize the reaction conditions. Considering no additional reagents were needed in the reaction, only the solvents were screened initially. In fact, the reaction was performed just by heating the mixture of substrates 1a and 2a (1a/2a = 2:1) in solvents at the indicated temperature. Among the

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• =C (1570–1605 cm−1) and C=O stretching (1640–1710 cm−1) region of the infrared spectra of P1 recorded during heating. These regions are specific to the perylene moieties in the polymers and, therefore, allow a direct observation of the π–π interactions in the polymer. Both the C=C and C=O vibrations

• are sensitive to the electron density in the perylene systems, which changes depending on the strength of π–π interactions [28][29][30]. During heating, the C=C stretching vibrations located at 1578 and 1594 cm−1 show opposite behavior regarding their wavenumber position: While the band at 1578 cm−1

• noticeable broadening during heating, which is most significant for the C=O vibration at 1656 cm−1. This indicates a broader distribution of species contributing to the IR spectrum, which is consistent with increased mobility of the perylene moieties which allows for more possible geometries. Furthermore, it

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• horizontally in a muffle furnace. The applied heating program was as follows: firstly, the temperature raised to 893 K in 5 h and kept at this temperature for 5 h. Next, the temperature was lowered to 758 K in the span of 6 h and the temperature was kept at this temperature for 2 h. Finally, the oven was

• cooled to 393 K in 5 h, and it was left for natural cooling afterwards. After the heating process, the ampoule was cracked in dry toluene and the crystalline BP was separated. In order to remove surface impurities, the BP crystals were transferred into absolute ethanol and sonicated for 30 minutes. The

• copolymer (Ps-b-PCL). a) DSC thermogram of photoinduced synthesis of nanocomposite networks (heating rate: 10 °C/min). b) FTIR spectra of Alk-5, Az-3 monomers and the corresponding cross-linked polymer. (a, b) TEM images of cross-linked polymer at two different magnifications, c) HAADF-STEM image and d) the

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• column chromatography. Low-pressure liquid chromatography was performed over Merck LiChroprep Lobar-A Si gel 60 (240 × 10 mm) with an FMI QSY-0 pump (ISCO). Merck precoated silica gel F254 plates and RP-18 F254s plates were used for TLC. Spots were detected on TLC under UV light or by heating after

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• light source, while heating the reaction vessel to 35 °C, mimicking the temperature generated by the light source. This control experiment confirmed the need for a light source, as only trace amounts of reaction product were formed after 24 h without irradiation (Table 1, entry 10). Despite the

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• , Fukutomi, and Nakayama [19] reported the synthesis of what they described as ‘true polyazulene’ through a cationic polymerization reaction. Their protocol involved heating the trifluoroacetic acid (TFA) solution of azulene (1) followed by treatment with triethylamine to obtain a brown polymeric product

• the azulene units in 1,3-polyazulene 5. The robustness of the 1,3-polyazulene backbone was evidenced by TG analysis where it retained over 60% of its mass even after heating to 1000 °C. The absorption spectrum recorded in chloroform revealed a considerable red shift in the absorption band of 1,3

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• critical solution temperature. In the case of a polymer with a UCST, the polymer is in a phase-separated, collapsed state below this temperature. Heating increases the solubility until only one phase is present above the UCST. Schematically, the chains are in stretched conformation and soluble in all

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• ) and Yang (2016) [82][83]. Both reactions used aerial oxygen as the oxidizing agent for sulfur (Scheme 15). Shibahara utilized 20 mol % copper(I) thiophene-2-carboxylate (CuTC) as the catalyst, where heating N-methylindole (1) with elemental sulfur in DMSO as solvent at 90 °C under aerial oxygen led to

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -4j < unsubstituted 4a < 3,5-diCl 4t < 2,6-diCl 4r < pentachloro 4v, in good agreement with the decreasing order of the pKa values of the pyridines. For example, in order to fluorinate phenol, triMe 5-4j needed heating at 100 °C in a haloalkane solvent for 24 h, whereas pentachloro 5-4v required only

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• disclosed here are an improvement compared to the state of the art. For example, addition product 1c has been obtained in 93% conversion before using 10 mol % TPP, 3 equiv c and heating the reaction mixture for 8 h under refluxing conditions [14]. However, with base catalysis (KOt-Bu) even better results

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• )amine (TTTA) as ligand, and THF as solvent at 50 °C. The obtained sulfonamide-tethered 5-iodo-1,2,3-triazoles 103 were then cyclized upon heating in the presence of Cs2CO3 to give triazole-fused sultams 104. A good to excellent yield of sultam derivatives 104 containing aryl and alkyl substituents on

• sterically hindered 1-(2-bromophenyl)-1,2,3-triazole derivatives 130. The target compounds, triazolo[1,5-a]indolones 131, were then obtained from 130 in high yield using catalytic amounts of Pd(OAc)2 and PCy3, carbon monoxide, and potassium carbonate and with heating in toluene at 120 °C. The structure of

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• methanol and gentle heating was necessary to optimize the formation of 75 from 74. As is usual in these Mukaiyama-like reaction conditions, the developed hydromethylation tolerated an array of functional groups and the late-stage functionalization of complex natural products (75e–g). Deuterated and other

• substituted hydrazones obviated their generation in situ, and as ethanol was identified as a better solvent in the initial coupling step, no solvent exchange was necessary in the fragmentation step of the hydrazide intermediate. The addition of triethylamine and heating the reaction to 80 °C for 1 hour were

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• source. Compound 14 could only be purified by recrystallization; all attempts to purify 14 by column chromatography led to complex mixtures of which the only identifiable product was 15. Even recrystallization can be problematic. Heating 14 leads to an elimination reaction that re-forms the initial

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• ) and aryl substituents (1q,r) afforded the corresponding compounds 3 in 51–82% yield (Table 2, entries 14–19). Heating of isoquinolinium salt 1t with the TTMSS/AIBN system, disappointingly, led to intensive tarring without the formation of the cyclization product in even trace amounts. Salts with

• XRD-analysis (Figure 3). It was found that both salt 17a and base 18a can be isomerized into isomer 19 under heating in the presence of AlCl3 via migration of the 3-Ph-group into the position 2 (Scheme 6). Compounds 18a, 19 can be quantitatively N-alkylated by MeI at room temperature and by BnBr at 40

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• , 51%), p-TsOH (entry 12, 5%), and InCl3 (entry 13, traces), in acetonitrile at room temperature. Among these, the presence of I2 led to the highest yield of 51% (Table 1, entry 11). This trend was consistent: Upon heating to 40 °C, reactions with FeCl3 (Table 1, entry 14) or p-TsOH (entry 15) yielded