Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• subject of extensive study since the mid-twentieth century [1]. Obtained from the base-catalyzed condensation of para-alkylated phenols and formaldehyde, calix[4]arenes have cyclic bowl-like structures which provide various sites for controlled chemical modifications. The versatility of calix[4]arenes has

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• corresponding N-oxide followed by Cope elimination gave olefin 62. Cleavage of olefin 62 with OsO4 and NaIO4 afforded ketone intermediate 10, which was enolized by (iPr)2NLi (LDA) and further reacted with formaldehyde to afford hydroxy ketone 63. Protection of the hydroxy group of 63 as 2-methoxypropyl ether

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• ]arenes with sodium sulfite and formaldehyde according to a general synthetic procedure [15]. While the synthetic procedure for water soluble RSAs is straightforward, purification of the final products is tricky and highly substrate-dependent. RSA 1 was obtained in 92% yield after purification involving

• column anion exchange using DOWEX® 50W resin. Chiral resorcinarenes (R)-2 and (S)-2 were synthesized by the Mannich reaction of C-(3-hydroxypropyl)resorcin[4]arene with (R)- or (S)-2-phenylethylamine and formaldehyde in methanol in 38% yield for (R)-2 and 36% yield for (S)-2 yields according to modified

• Information File 1). Tetrakis((α)–methylbenzylaminomethyl)resorcin[4]arenes ((R)-2 and (S)-2) were obtained according to the literature procedures [16]. To a solution of C-(3-hydroxypropyl)resorcin[4]arene (720 mg, 1 mmol) and excess formaldehyde (40% in water, 1 mL) in methanol (30 mL), (R)-(+)-1

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

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• [10][11] and cucurbiturils [12][13]. CTVs are cyclic trimers, originally formed from veratrole upon condensation with formaldehyde, which adopt a bowl-shaped form as the most stable conformation. Chiral derivatives result when the aromatic residues carry either one, three or two different additional

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• the well-studied cyclodextrins and crown ethers. Calixarenes are products of phenol–aldehyde condensation, as the aromatic components may derived from phenol, resorcinol, or pyrogallol; the aldehyde most often used for phenol is simple formaldehyde (methanal, HCHO), while larger aldehydes (e.g

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• steroids using a carboxylic acid group at the side chain [22][23]. As shown in Scheme 5, the implementation of the Ugi-4CR with a variety of amines and isocyanides – keeping formaldehyde as the oxocomponent – enabled the generation of azasteroid libraries based on androstanic (18) and pregnanic (19

• their subsequent utilization in the Ugi-4CR with monoprotected amino acids (used either as amino or carboxylic acid components) and formaldehyde as fixed oxo component. Amazingly, the Ugi-4CR of steroidal triisocyanide 26 with three equivalents of Boc-tryptophan allowed the formation of twelve covalent

• components, keeping formaldehyde as oxo component to obtain a single stereoisomer. The library was also integrated by the Ugi-4CR products derived from the 6β-ecdystereoidal amine (also used as precursor of isocyanide 28), while all compounds were evaluated as antiproliferative agents against T-leukemia cell

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• formaldehyde allowed the rapid production of eight functionalized macrocycles (Scheme 30). Another method using repetitive Ugi reactions has been described for the macrocyclization of peptides [48]. The approach was based on double Ugi-4CR involving a peptide diacid, a diisocyanide, methylamine and

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• simplest of the formaldehyde-type acetals, methoxymethyl (MOM) [2], is rather stable to acidic hydrolysis. The acetaldehyde acetals, 1-ethoxyethyl (EE) [2][3] and tetrahydropyranyl (THP) [2] are widely used as protecting groups, but they have a disadvantage of generating an additional asymmetric center

• oxocarbenium ion determine, which one of the alkoxy groups is protonated and released as an alcohol. The two proposed competing pathways are illustrated in Scheme 2. Salomaa has shown earlier [12] with formaldehyde acetals that the structural effects on the stability of the oxocarbenium intermediate are

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• ] and one of the level 4 solutions – the formolase pathway (Figure 2b) – was demonstrated already in vitro [17]. This pathway relies on three new-to nature reactions, the most prominent one being the name-giving formolase reaction, which allows the subsequent condensation of three formaldehyde molecules

• diversity of enzymatic scaffolds [36][37][38][39]. One example is formaldehyde lyase (or “formolase”) – the key enzyme of the formolase pathway – that was crafted from a benzaldehyde lyase, which showed initially some side reactivity with formaldehyde [17][24]. Other examples are propionyl-CoA oxidase and

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• -Ring 17, D-35392 Giessen, Germany Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland 10.3762/bjoc.15.43 Abstract Adamantyloxyamine reacts with formaldehyde to give N-(adamantyloxy)formaldimine as a room-temperature-stable compound that exists in

• imidazole N-oxides with 1-bromopentane or 1-bromododecane open access to diversely substituted, non-symmetric 1,3-dialkoxyimidazolium salts. Adamantyloxyamine reacts with glyoxal and formaldehyde in the presence of hydrobromic acid yielding symmetric 1,3-di(adamantyloxy)-1H-imidazolium bromide in good yield

• , after hydrazinolysis with N2H4.H2O in slight excess. The crude product was reacted with formaldehyde in boiling MeOH, and after 1 h, crystalline N-(adamantyloxy)formaldimine (6a) was isolated in 90% yield. The spectroscopic data indicate that this imine exists in solution in monomeric form exclusively

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• reaction failed to occur with aliphatic aldehydes viz. formaldehyde, heptanal, pentanal and hexanal. The structure of all the indole–cyclododeca[b]pyridine-3-carbonitrile hybrid heterocycles 7 was elucidated by NMR spectroscopy. Furthermore, the analysis of 1H NMR spectra revealed that the indole

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• converts to the product in the same yields (55.2, 55.9 and 54.3%, respectively) [71]. Another research reported for sulfonated carbon material is using low-cost resorcinol (130) and formaldehyde (131) solution. In this case, resorcinol (130) was added to a stirring solution of aqueous ammonia solution

• , absolute ethanol, and deionized water. In the next step, formaldehyde (131) solution was added and stirred for 24 h at 30 °C. The resulted solution was placed in a Teflon-sealed autoclave and heated at 100 °C for 24 h. Subsequently, the product was centrifuged, washed, and dried. The carbon nanospheres

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• ][10]. These include aromatic amines as polymers [11][12], cardanol-based phosphates as modifiers for epoxy resins [13], cardanol grafted natural rubber as rubber plasticizers [14], amine-based surfactants [15] and phenol/cardanol-formaldehyde based adhesives [16]. The chemical valorization of

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

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

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• more recent method starts from an aromatic amine and formaldehyde in the presence of ionic liquids and a controlled amount of 1-methyl-3-(2-(sulfoxy)ethyl)-1H-imidazol-3-ium chloride as the catalyst. The reaction affords the corresponding 1,4-dihydroquinzolin-3-ium tetrafluoroborates, which upon

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• (4) in a similar way, from the reaction of 6-tert-butylazulene with formaldehyde [16]. Compound 4 is the first reported “wide-rim” functionalized calix[4]azulene (Figure 1). Recently, we reported the synthesis of tetrakis(5,7-diphenyl)calix[4]azulene (5) (or octaphenylcalix[4]azulene, “OPC4A”, Figure

• Suzuki–Miyaura coupling reaction of bromobenzene with 5,7-di(Bpin)azulene, which in turn was formed via the exhaustive borylation of azulene with excess bis(pinacolato)diboron (B2pin2) [21]. Cyclocondensation of 5,7-diphenylazulene with formaldehyde produced 5 [22] under conditions similar to those used

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

• . Yadav et al. reported a very efficient one pot protocol of β-hydroxy sulfides synthesis from disulfides and styrenes in open air, at room temperature, using inexpensive Rongalite [sodium formaldehyde sulfoxylate (Na(HOCH2SO2)·2H2O)], as a promoter (Scheme 30) [67]. The protocol is compatible with

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• glycols, epoxides, and olefins takes place by the action of hypervalent iodine [38][71][72]. For example, Havare and Plattner reported the oxidative cleavage of α-aryl aldehydes using iodosylbenzene to give chain-shortened carbonyl compounds and formaldehyde [71]. In the field of carbohydrate chemistry

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• formaldehyde (e.g., from the softeners of the plastic tubes) not only during the reaction steps (cleavage, ligation) but also under the HPLC purification conditions which has a high impact on the yield [35]. Secondary structure determination by electronic circular dichroism spectroscopy ECD spectra of GnRH-III

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

• reaction is an important, one-pot, multicomponent, C–C bond forming reaction that is widely used in the syntheses of many biologically active and natural compounds [1][2][3][4][5]. Originally, the Mannich product is formed through a three-component reaction containing a C–H acid, formaldehyde and a

• formaldehyde and 2,2-disubstituted acetaldehydes 28. Formaldehyde, as a non-enolizable compound is more likely to give Mannich base product 30. In contrast, enolizable 2,2-disubstituted aldehydes easily form enamines 31 that undergo cycloaddition with electron-deficient o-QMs giving 2,2-dialkyl-3-dialkylamino

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• formaldehyde to produce the phosphorothioate ON. Despite these promising results, further studies on the use of these prodrugs to control genetic expression have not been carried out. Thus far, most of these results were obtained for thymidine homopolymers [32]. The reason is that the synthesis of ON prodrugs

• shown to improve RNA nuclease resistance and not to hamper duplex dsRNA formation, and they are removed by cellular esterases. Indeed, 2’-O-acyloxymethyl ONs are converted to unmodified RNAs by carboxyesterase-mediated deacylation with the release of formaldehyde to produce the parent RNA (Scheme 10

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

• 58 and formaldehyde (R’= H, 47) were performed under microwave and conventional heating conditions by Quiroga et al. [65] (Scheme 18). Both the reaction conditions resulted in the formation of pyrazolo[3,4-b]pyridine-5-spirocycloalkanediones 76 but an additional compound 3-tert-butyl-1-phenylindeno

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• ) [54] to a Mannich-type reaction with L-proline and formaldehyde (Figure 3). The precursor preCA, in turn, was obtained by an acid-catalysed condensation between resorcinol and butyraldehyde. Of course, the main difference between the syntheses of CAP and CAPS is constituted by the choice of the

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• difficulties, some reactions are very efficient as reported below. 6.1. Moedritzer–Irani reaction The reaction of an amine (primary or secondary amine), formaldehyde (aqueous or solid paraformaldehyde) and phosphorous acid in acidic media produces amino-bis(methylenephosphonic acid, Figure 30A,B). This

• consequence, the stoichiometry must be adapted and 2 equivalents of both formaldehyde and phosphorous acid must be used. The reaction is also applicable to secondary amine and produce mono-aminomethylene phosphonic acid (Figure 30B). The yield of this reaction is variable as illustrated in Figure 30C. The

Novel approach to hydroxy-group-containing porous organic polymers from bisphenol A

• Tao Wang,
• Yan-Chao Zhao,
• Li-Min Zhang,
• Yi Cui,
• Chang-Shan Zhang and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 2131–2137, doi:10.3762/bjoc.13.211

• connecting phenolic molecules with formaldehyde or other aromatic aldehydes to form cross-linking structures through the simple Bakelite-type chemistry to obtain great number of polymers with different functionalities. Phloroglucinol has been utilized as a monomer by Kanatzidis and Katsoulidis [23][24] to