Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• deuterium incorporation in the benzylic position of 16 and 3h through acid-catalyzed imine–enamine tautomerization is dependent on the strength of the acid used (Figure 1). The rate of deuterium incorporation in 2-benzylpyridine (16, pKa ≈ 5.2) is much faster when using TFA-d1 than with AcOH-d4 [34][35

• ]. With the less basic 2-benzyl-5-chloropyridine (3h, pKa ≈ 3.0) the difference is even more pronounced: Almost no deuterium incorporation could be detected using AcOH-d4 while the reaction ran smoothly using the stronger acid TFA-d1. From this we conclude that when the pyridine nitrogen becomes less

• basic and protonation by the acid thus becomes more difficult, using more equivalents of the acid or a stronger acid is needed to reach full conversion. When we compare the different pKa values of substituted pyridines we see that 2-benzylpyridine (16, pKa ≈ 5.2) is one of the most basic pyridines [34

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• of steroids, to determining hydrocarbon pKa values using electrochemistry. The lesson learned, and one I tried to put into practice in my independent career (see below), is that it is very much possible to run a research group focused in quite different areas of chemistry. With an NSF-NATO

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• databank (3C6G), while the α-MGS structure was extracted from the International Union of Crystallography (KP2293) database, see Figure 1. According to the ChemAxon method [25][26][27], the calculated pKa of three hydroxy groups are 7.4 (O6), 7.8 (O3), and 8.2 (O5). For that reason, the α-mangostin was

Convenient preparation of high molecular weight poly(dimethylsiloxane) using thermally latent NHC-catalysis: a structure-activity correlation

• Stefan Naumann,
• Johannes Klein,
• Dongren Wang and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2015, 11, 2261–2266, doi:10.3762/bjoc.11.246

• , emphasizing that nucleophilicity is crucial for successful polymerization. Furthermore, it is interesting to note that the six- and seven-membered NHCs do not show any reactivity here, in spite of being very strong bases. While for a compound like 6-iPr a pKa-value of 28.2 (aqueous solution, 25 °C) was found

• , the five-membered imidazolium derivative 5-Mes was determined to have a pKa-value of only 20.8 (which compares to 15–19 for typical alcohols; in turn, silanols are even more acidic than the corresponding alcohols) [28][29][30][31][32]. At the same time, 5Me-Me-CO2 successfully catalyzed PDMS-formation

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• , the addition of amino additives such as pyridine, morpholine, Et3N or DBU was shown to be detrimental to the G-HII-catalyzed dimerization of styrene (Table 2). Moderate to poor yields in stilbene 7’ were obtained and the value of the yields was correlated with the pKa of the couple ammonium/amine. An

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• [26][27]. Superoxide O2−• is a highly reactive molecule [26][28] and it acts as a strong Brönsted base removing a proton from substrates to an extent equivalent to that of the conjugate base with a pKa value of approximately 23 in water [29][30]. A number of weakly acidic organic compounds are

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• ][28]. Thus, the indole NH group (pKa about 21 in DMSO) should be able to serve as a stoichiometric proton source that, after β,β'-coupling, would convert one of the Sm(III) enolates to the ketone. Attack of the remaining Sm(III) enolate would lead to Dieckmann-type ring closure, followed by

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• initio methods [50]. The pKa values for N-methylindole, N-methylpyrrole and N-(dimethylamino)pyrrole as CH acids in THF were experimentally determined by Fraser et al [51]. The latter are more related to our goals and were found to be in good agreement with those computed within the DFT framework

• weak CH acidic compounds while the pKa values in THF solution (Figure 5) covered a 28.8–45.0 span. These data allow the assignment of potential deprotonation sites in the investigated substrates. Also the correlation between gas-phase ΔGacid and the pKa(THF) values can be tracked. In all cases, the CH

• contrast, the regioselectivity observed in case of substrate 2a cannot be explained by the pKa values as the only reason. Otherwise, deprotonation would have been also observed at the 2 position of the indole ring. Whereas the azole nitrogen in 2a cannot coordinate a metal through its electron lone pair

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• -phenylamino-1-deoxy-D-manno-heptulose 10 were obtained as pure α-anomers in 77% and 24% yield, respectively (Scheme 3). The low yield of compound 10 may be explained by the low pKa value (4.62) of aniline compared to a pKa of 8.15 for propargylamine, the latter being clearly more efficient as a nucleophile

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• times) was found to depend on the nucleophilic strength of the intermediate enolates, and ultimately on pKa values (reactivity scale: diethyl malonate pKa 13.5 > acetoacetate pKa 11.0 > acetylacetone pKa 8.9). As an example, diethyl malonate reacted with allyl methyl carbonate much faster than

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• compounds in the 1930s and 1940s [22][23]. It is a strong acid (pKa ≈ 0.5), quite volatile (bp. 72 °C) and miscible with water, fluorocarbons and most organic solvents [22]. In the late 1940s and throughout the 1950s, trifluoroacetic acid and trifluoroacetic anhydride were the subjects of a number of

• acids were recrystallized from suitable solvents such as acetone, lower alcohols and H2O. Acylation reactions in MeSO3H are more vigorous and exothermic than in CF3CO2H since MeSO3H (pKa ≈ −2) is a stronger acid than CF3CO2H (pKa ≈ 0.5). Their densities are the same (1.48 g/mL at 25 °C), but the melting

• acyl chlorides. The acylating activity of the medium was then fortified by the addition of trifluoromethanesulfonic acid (CF3SO3H), one of the strongest of all acids known (pKa ≈ −5.5), comparable to, or exceeding perchloric and fluorosulfonic acid (although the ordering of acidities is highly

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

• , the tumor cells express pro-angiogenic factors including growth factors such as the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and enzymes such as cyclooxygenase 2 (COX-2) and protein kinase A (PKA) as well as signaling molecules such as integrins. The evoked cascade

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• ] showed one hydrogen bond, located between N6 of TA and N3 of cytidine (Figure S2B, Supporting Information File 1). If TA is protonated on N1 to form TAH+, it could form a wobble-pair with C [47][83] (Figure 3A), which would be expected to decrease the mobility of the spin label. The apparent pKa of the

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• rather low yields (Table 3, entry 5). The longer electrolysis caused the formation of complicated products. This result is quite different from the case of 1b and 1d (Table 2, entry 1 and Table 3, entry 1). Such different anodic behavior may be attributable to different pKa values of the α-proton of the

A facile synthesis of functionalized 7,8-diaza[5]helicenes through an oxidative ring-closure of 1,1’-binaphthalene-2,2’-diamines (BINAMs)

• Youhei Takeda,
• Masato Okazaki,
• Yoshiaki Maruoka and
• Satoshi Minakata

Beilstein J. Org. Chem. 2015, 11, 9–15, doi:10.3762/bjoc.11.2

• organic bases like DABCO (pKa 8.93 in DMSO [32]) and DBU (pKa 23.9 in MeCN [33]) gave a lower yield (32%) and no product, respectively (Table 1, entries 14 and 15). As results, the use of the moderately weak organic base 2,6-lutidine (pKa 6.72 in water [34]) successfully afforded 2a in high yield (Table 1

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• 2 d reaction time. The decreasing yield was rationalized by the increasing consumption of propargyl glycidyl ether by hydrolysis with increasing OH− concentration. On the other hand, due to the low pKa ≈ 12 of polyglucanes, deprotonation still takes place at very low concentrations of OH− [42][43

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

• Monica Ferro,
• Franca Castiglione,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• two gels loaded with IP – CDNSEDTA 1:4 and CDNSEDTA 1:8 – were 6.9 and 6.5, respectively. Taking into account the literature pKa values [33] of EDTA for the ionization of the four COOH groups ( pKa1 = 0.0, pKa2 = 1.5, pKa3 = 2.0, pKa4 = 2.7), the contribution of the two NH+ groups (pKa5 = 6.1, pKa6

• = 10.4) and the pKa value of IP in its acid form (4.91), it is reasonable assuming that the majority of the COOH groups present in our systems are, in the pH interval of our preparations, present in the COO− form and that one NH+ group is significantly contributing. As a consequence, an overall negative

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• . The olefin-substituted compound 3p (Table 1, entry 16) underwent a smooth reaction to afford nortricyclene 5m (Scheme 2). The cyclooctane-fused adducts 3o/4o (Table 1, entry 15) afforded exclusively the elimination product 6c in excellent yield. As the pKa of the conjugate acid of the superoxide ion

Second generation silver(I)-mediated imidazole base pairs

• Susanne Hensel,
• Nicole Megger,
• Kristina Schweizer and
• Jens Müller

Beilstein J. Org. Chem. 2014, 10, 2139–2144, doi:10.3762/bjoc.10.221

• attempt to increase the stability of the imidazole–Ag(I)–imidazole base pairs, additional shielding of the central silver(I) ions could be accomplished by introducing methyl groups on the imidazole moieties. A comparison of the pKa values [36] of 1-methylimidazole (pKa = 7.21), 1,2-dimethylimidazole (pKa

• = 8.22) and 1,4-dimethylimidazole (pKa = 7.75) indicates that this modification is also expected to slightly increase the basicity of the ligand, thereby also contributing to the formation of a more stable metal complex. Results and Discussion Synthesis and characterization of the nucleosides Scheme 2

• the two hydroxy functions with the dimethoxytrityl and the 2-cyanoethyl-N,N-diisopropylphosphoramidite moieties, finally resulting in the formation of 4a/4b suitable for automated solid-phase oligonucleotide synthesis. The pKa values of the free nucleosides 2a/2b were determined by pD-dependent 1H NMR

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• the lack of product formation for 2-hydroxy-6-trifluoromethylnaphthylene photo-dehydrofluorination reported by Seiler and Wirz [51]. For the 1,5-HNA acetate, the less reactive (higher pKa) of the leaving OAc group of 27 vs DEP, fluorescence decay and reversible ESIPT processes are major factors

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• identified as 2,3-butanedione and is produced from the side-chain of RF by the action of singlet oxygen. Its formation is greatly affected by the pH of the medium as the highest content of this compound was found at pH 6.5, followed by 4.5 and 8.5 [59]. RF is highly sensitive to pH and has pKa values of 1.7

• reaching a maximum at pH 10. This is probably due to the higher reactivity of the flavin triplet in this region [24] (Figure 3). The slight decline above pH 10 is due to the anion formation (pKa 10.2). In acidic region, the slight increase (about 2 folds) in the rate of degradation of RF at pH 3 is due to

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• stoichiometry (preQ1:TFA) based on 1H NMR spectra and consideration of pKa values. However, it is noteworthy that a crystal structure of the preQ1·TFA salt that was crystallized from saturated aqueous solution showed the co-existence of mono- (N(C'7)) and dications (N(C'7), N3) in the crystal [11]. The

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• nucleoside-derived allenes 97 (the uridine example shown), and a number of amines 100 (four equivalents, Scheme 41). The polyfunctional products 101 were obtained with excellent (Z)-stereoselectivity. The authors noticed a pronounced relationship between pKa of the amine and the isolated yield of the product

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• (Figure 3). This O,C-digeranyl geminal bisphosphonate was expected to preserve a V-like structure very similar to that of DGBP. However, the presence of an oxygen substituent on the geminal carbon should lower the pKa of bisphosphonate 6 relative to that of compound 5, which might enhance its similarity