Electron and hydrogen self-exchange of free radicals of sterically hindered tertiary aliphatic amines investigated by photo-CIDNP

• Martin Goez,
• Isabell Frisch and
• Ingo Sartorius

Beilstein J. Org. Chem. 2013, 9, 437–446, doi:10.3762/bjoc.9.46

• . With Equation 2, the free energy of the relayed deprotonation can be estimated from the reduction potential Φred (DH•+) of the radical cation (see, Table 1, but taken relative to NHE instead of SCE), the pKa of the protonated amine (8.9 [43]), and the calculated heats of formation ∆Hf of D• (+208 kJ

• more excellently described by a single exponential, with the same implications for the mechanism as in the case of DABCO. The free energy for the deprotonation of the radical cation by the amine itself can again be calculated with Equation 2. The pKa value of is only known in aqueous diglyme, where it

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• similar extinction coefficients and quantum yields as compound 1a, according to the literature [20][21]. However, their pKa values are significantly different from those of 1a, as shown in Table 3. The pKa values are calculated from the absorbance at 360 nm at different pH values illustrated in Figure 3

• , by using the Henderson–Hasselbalch equation. The halogenation of 1a at the 6-position decreases the pKa value, which makes compounds 1b and 1c good substitutes for 1a in fluorescent labeling and other investigations in biological systems. Screening for the synthetase/tRNA pair for 1b and 1c is under

• . The fluorescent group wouldn’t cause significant perturbations on proteins due to its small size, thus, it greatly extends the scope of fluorescence imaging techniques. Compound 1a has a pKa of 7.8 and only its conjugate base is fluorescent. This limits its usage in the fluorescence imaging in vivo

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• hydroxide ions in basic media; therefore, when calculating the NaOH concentration required for preparation of the solutions it is necessary to take this fact into account. Since we did not find values for the pKa of DIMEB in the literature, we used the pKa value of β-CD, viz. 12.20 [29][30]. Chemical

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• on the basis of in vitro cruzain activity (Table 1). Nor could the trends be explained as an effect of lysosomotropism, since enhanced potency was observed only for the 4-pyridyl analogues and not for 2- or 3-pyridyl analogues, which have similar pKa values. Instead, we considered that additional

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• -deficient pyridine ring. The pKa value of 7-azaindole is ~4.9, and it undergoes self-association through hydrogen-bonding to form a dimer in solution and phototautomerizes by an excited-state double-proton-transfer (ESDPT) process [1][48]. In the presence of copper or palladium catalysts azaindole undergoes

Self-assembled organic–inorganic magnetic hybrid adsorbent ferrite based on cyclodextrin nanoparticles

• Ângelo M. L. Denadai,
• Frederico B. De Sousa,
• Joel J. Passos,
• Fernando C. Guatimosim,
• Kirla D. Barbosa,
• Ana E. Burgos,
• Fernando Castro de Oliveira,
• Jeann C. da Silva,
• Bernardo R. A. Neves,
• Nelcy D. S. Mohallem and
• Rubén D. Sinisterra

Beilstein J. Org. Chem. 2012, 8, 1867–1876, doi:10.3762/bjoc.8.215

• -Ni/Zn/βCD presented smaller particles and a more homogeneous particle size distribution. Higher porosity for this MHM compared to Fe-Ni/Zn was observed by Brunauer–Emmett–Teller isotherms and positron-annihilation-lifetime spectroscopy. Based on the pKa values, potentiometric titrations demonstrated

• ferrite surfaces. It can also be observed that the potentiometric curve for Fe-Ni/Zn/βCD exhibits at least four transitions, two in addition to the pure Fe-Ni/Zn. The pKa values of the ferrites were calculated by using the Henderson–Hasselbalch Equation 1, at the point where [A−] = [HA] [36]: Transitions

• at pKa 6.5 and 13.5 were attributed to the ionization of ferrite groups in the MHM system, since Fe-Ni/Zn also presented close transition values (pKa 6.5 and 12.6). Thus, transitions at pKa 5.5 and 9.4 in the Fe-Ni/Zn/βCD were attributed to the ionization of βCD primary and secondary hydroxy groups

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• the physicochemical properties of imidazo[5,1-c][1,2,4]triazine-3,6-dione derivatives we determined water-solubility, log P, and pKa values for compound 25 as a representative of this new class of heterocyclic compounds. Water solubility at physiological pH of 7.4 was found to be 47 µg/mL, which is a

• suitable range for perorally active drugs. A pKa value of 10.0, and a logP value of 3 was determined. Thus, the molecule will be uncharged under physiological conditions and the logP value is in a range which allows us to predict oral bioavailability [29]. Conclusion In conclusion, we have designed and

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• ) (Figure 2). All of these screened catalysts are bifunctional compounds possessing hydrogen-bonding donor and acceptor moieties. Catalysts based on thiourea and squaramide differ from each other in their possible hydrogen-bond angles, rigidity of conformation, and pKa values [20]. Although the two

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• Cation affinity values are important guidelines for the reactivity of Lewis and Brønstedt bases [1][2][3]. While proton affinity numbers (either as gas phase proton affinities or as solution phase pKa values) have been used for a long time in quantitative approaches to describe base-induced or base

Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

• Fátima M. P. de Rezende,
• Marilua A. Moreira,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2012, 8, 1227–1232, doi:10.3762/bjoc.8.137

• steric effect, but it suppresses adventitious metabolism, influences the pKa of functional groups, and alters solution conformation [12]. In this context, conformational screening and theoretical evaluation of 2-fluorobicyclo[2.2.1]heptan-7-ols (2-fluoronorbornan-7-ols, compounds 5–8 in Figure 1

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• nucleophiles [45][46][47][48][49][50][51][52][53][54][55]. In this realm, we [53][55] and others [54] have focused efforts on catalyzing benzylic substitutions with less-stabilized (DMSO pKa ~ 20–30) nucleophiles through decarboxylative coupling. In the present context, we hypothesized that a broad diversity

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• ] designed a Brønsted base whose pKa changes with light. The study focuses on the azobenzene 22, which possesses, in an aromatic ring, a spirocyclic lactone fused to a conformationally restricted piperidine (Figure 19). In the structure of the trans isomer 22, the pair of unshared electrons of nitrogen is

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• the molecules via hydrogen bonds. The idea was to synthesize europium(III) complexes containing the new ligands. Since the pyrrole amine is a very weak acid (pKa = 23.0) [17] it can only be deprotonated by hard bases, such as n-butyllithium or sodium hydride [18]. Therefore we chose to work in water

The importance of the rotor in hydrazone-based molecular switches

• Xin Su,
• Timo Lessing and
• Ivan Aprahamian

Beilstein J. Org. Chem. 2012, 8, 872–876, doi:10.3762/bjoc.8.98

• equilibrium constant of the protonation step, KI is the equilibrium constant for the rotation process, and KS is the overall equilibrium constant for the switching reaction. The pKa of PPH-1 is actually log10KP, so KS also equals . From the above equations, it becomes clear that KS can be used as an index to

• evaluate the feasibility of the switching process in hydrazone-based switches; the larger the KS value, the easier the switching process. In the case of PPH-1 versus PPH-5, since the acetyl group is a stronger electron-withdrawing group than the ester group, the basicity (pKa) of the pyridyl group in PPH-1

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• speculate that the relative difficulty in the reaction is due to the reduced availability of the lone pair of the morpholine nitrogen compared to the piperidine nitrogen (pKa 8.36 versus 11.22) [31], retarding the rate of nucleophilic attack. Another possibility is that the oxygens in the pendant chains can

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• that the combination of a pentafluorophenyl triazolium carbene 5 and a Brønsted acid with low pKa value may provide new opportunities for the design of reaction pathways in which the carbene and the acid play different roles. The idea to use a very weak base in NHC catalysis has also been described by

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• system LAKE [23] for chemical equilibrium analysis and with MS-Excel [24]. Data of all titrations (78 titration points in total) were included in the calculation. The formation constants for the vanadium oxo-anions of the VO43−/H+-subsystem [21], the pKa value of Zn-benzylcyclene 1 [14] as well as the

• pKa values of the buffers [25] were adopted from literature. The influence of the ionic medium was taken into account in the calculation by means of the Davies equation [26]. The most important ternary species in the equilibrium model that fit the recorded data are presented in Table 1. According to

• these data, the association constant for the protonated monovanadate HVO42− with 1 is about 103.8 M−1, while the association constant for V2O74− is Ka = 106.2 M−1. The pKa value for the coordinated divanadate is 8.4 and therewith, 1.9 pKa units lower than for the uncoordinated V2O74− ion. The binding of

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• , although structurally different, indene and indole show similar pKa values of 20.1 and 21.0 in dimethylsulfoxide solution, respectively [23][24]. During the course of our studies on indene-based ligands of general type 1 with biological effects on the central nervous system, we found that different

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• the reactivity of the 2-lithio-oxazoles resulting from the ready deprotonation, with n-BuLi at low temperature, of the most acidic C2-proton (pKa = 20–22 was suggested), which is complicated by the coexistence of a ring-open isonitrile tautomer. In particular, the treatment by trimethylstannylchloride

• preferred which is more in accordance with previous observations and a specific directed nitrogen-chelating effect (Scheme 20). Thus, C2-selectivity may arise from a prior interaction of the palladium catalyst with nitrogen. The coordination of oxazole to arylpalladium(II) complex may lower the pKa of

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• pyridine ring can most probably be attributed to the higher acidity of the aldoxime proton in pyridinium aldoximes, for example. For reference, the pKa of the aldoxime proton in 3-formylpyridine oxime amounts to 10.36 and that of the corresponding proton in the 1-methiodide of 3-formylpyridine oxime to

• 9.22. Correspondingly, the pKa of the aldoxime proton in 4-formylpyridine oxime (9.99) also decreases by more than one order of magnitude to 8.57 upon methylation of the ring nitrogen [46]. Thus, oximes on pyridinium rings are deprotonated more easily, which renders them more nucleophilic. The

• . While the latter effect is presumably due to the lower acidity of ketoximes with respect to aldoximes by ca. one order of magnitude [32], the higher activity of 1b with respect to 1c is more likely to be a structural effect, since on the basis of the pKa values of 1-methiodides of 3-formylpyridine oxime

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• for DME, followed by loss of the α-carbonyl hydrogen as H+ to give a mono-ketonate complex B. The proton may combine with chloride counterion to give HCl, which is only weakly dissociated in acetonitrile (the pKa of HCl in MeCN has recently been measured as 10.6) [99]. Complex B would then be attacked

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• phosphate and sulfate for neutral receptors in DMSO-d6/0.5% water and have been shown to perturb the pKa of bound guests (Table 1) [38][39]. X-ray crystal structures of a variety of complexes with anions revealed the adoption of the syn–syn conformation in the solid state upon anion complexation. With the

The role of silver additives in gold-mediated C–H functionalisation

• Scott R. Patrick,
• Ine I. F. Boogaerts,
• Sylvain Gaillard,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2011, 7, 892–896, doi:10.3762/bjoc.7.102

• profile of 1 appears linked to bond acidity, and was found to functionalise selectively the most electron-deficient C–H bond in a substrate. Unfortunately, the reactivity of 1 was limited to bonds with a pKa value below 30.4 [12]. Current gold research has shown that silver salts can not only improve

• reaction times and yields [13][14], but also allow the C–H functionalisation of previously unreactive substrates. Larrosa has recently disclosed a mild methodology for the Au(I)-mediated C–H functionalisation of 1,3,5-trifluorobenzene (2, pKa DMSO 31.5 [15]) using a mixture of reagents and additives

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• [35]. In this regard, the surface area, the material of construction and the reactor use history have to be considered. In addition, the stainless steel components of the flow reactor are prone to corrosion if harsh conditions, such as concentrated acids are used [36]. Hydrazoic acid itself (pKa 4.7

• through stainless steel coils at 220 °C provide testimony to the fact that even mild acids (the pKa of AcOH is 4.75) can act as corrosive reagents on stainless steel in an elevated temperature regime. Aqueous HCl is a much stronger acid and lacks the oxidizing properties that stainless steel requires to

Anion–π interactions influence pK_a values

• Christopher J. Cadman and
• Anna K. Croft

Beilstein J. Org. Chem. 2011, 7, 320–328, doi:10.3762/bjoc.7.42

• aromatic substitution. The pKa' values for these 1,8-disubstituted arene naphthols have been measured in acetonitrile/water (R = NO2, 8.42; R = Cl, 8.52; R = H, 8.56; R = Me 8.68; and R = OMe, 8.71) and indicate a correlation with the electronic nature of the arene substituent, as determined through LFER

• analysis. Contributions to the relative pKa' values have been interpreted, using M06-2X DFT calculations, as consisting of two components: A small contribution from initial OH–π bonding in the starting materials and a larger contribution from anion–π interactions in the products. Such effects have

• implications for a range of other systems. Keywords: anion–π; DFT; intramolecular interaction; LFER; pKa; Introduction There are numerous examples in nature of interactions involving aromatic systems and these interactions underpin many modern supramolecular binding agents, with clear applications in