A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• found that the product was produced in slightly lower yields of 42% and 55%, respectively. Using the optimized conditions (Table 1, entry 3), we prepared both benzyl (2b, 79%) and cyclohexyl (2c, 83%) substituted 1,2,4-thiadiazoles as representatives for a substitution pattern with various alkyl

• carbodiimide and thiourea units under in situ conditions. The product structure was confirmed by single crystal X-ray analysis in the solid state. The substitution pattern (aryl, benzyl, sec-alkyl) may be varied easily to achieve potentially biologically active compounds with interesting properties. The free

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• anaesthesia. Keywords: active pharmaceutical ingredient; binding constant; cyclodextrin; derivatization; gas chromatography; sevoflurane; substitution pattern; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-1,4-linked glucose units. Those CDs consisting of 6, 7, and 8 glucose units are called α

• (Figure 1) showed a rather broad molecular weight distribution typical for CD derivatives with statistical substitution pattern. On the other hand, nearly uniform CD derivatives were synthesized by regioselective deprotonation of all 2-OH positions with NaH in DMF solution according to Tian and D’Souza

• MS of 3b1 (Figure 1) showed a significantly lower polydispersity than 2b1. Also the 1H NMR spectrum of 3b1 was much better resolved than the one of the statistical derivative 2b1 due to its homogenous substitution pattern and uniform lengths of the oligoethylene oxide groups (Figure 2). All β-CD

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

• Joscha Vollmeyer,
• Friederike Eberhagen,
• Sigurd Höger and
• Stefan-S. Jester

Beilstein J. Org. Chem. 2014, 10, 2774–2782, doi:10.3762/bjoc.10.294

• the role of intraannular substituents on the 2D supramolecular surface patterns of macrocyclic compounds. Therefore, in addition to the concentration-driven conformational polymorphism that is yet attributed to a distinct extraannular substitution pattern as discussed above, we evaluate the role of

Synthesis and properties of novel star-shaped oligofluorene conjugated systems with BODIPY cores

• Clara Orofino-Pena,
• Diego Cortizo-Lacalle,
• Joseph Cameron,
• Muhammad T. Sajjad,
• Pavlos P. Manousiadis,
• Neil J. Findlay,
• Alexander L. Kanibolotsky,
• Dimali Amarasinghe,
• Peter J. Skabara,
• Tell Tuttle,
• Graham A. Turnbull and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2704–2714, doi:10.3762/bjoc.10.285

• under ambient conditions and UV-illumination is presented in Figure 2. The effect of the substitution pattern of the BODIPY core with fluorene arms (either at the α- or β-positions) on the optical properties of the materials can be observed with the naked eye. The compounds of the Y-Bn (n = 1–4) series

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• imidazo[1,2-b]pyrazole core is definitely an attractive synthetic target, in view of its noteworthy pharmacological potential, which is strongly affected by the ring substitution pattern and the level of ring saturation. Among others, anti-inflammatory [37][38], antiviral [28][39] and antidiabetic [40

• simple, green access to highly substituted 1H-imidazo[1,2-b]pyrazoles with easily variable substitution pattern and does not require complex purification techniques. The conventional GBB-3CR. Plausible products 6A–H. Synthesis of 6 via the sequential one-pot method. Solvent and catalyst screen of the GBB

Visible light photoredox-catalyzed deoxygenation of alcohols

• Daniel Rackl,
• Viktor Kais,
• Peter Kreitmeier and
• Oliver Reiser

Beilstein J. Org. Chem. 2014, 10, 2157–2165, doi:10.3762/bjoc.10.223

• substitution pattern of benzoates we intended to shift the electrochemical reduction potentials of the substances into a region that could be accessed by common visible light photocatalysts. The substituents should be as inert as possible in order not to interfere with the photochemical reaction itself

Aryl substitution of pentacenes

• Andreas R. Waterloo,
• Anna-Chiara Sale,
• Dan Lehnherr,
• Frank Hampel and
• Rik R. Tykwinski

Beilstein J. Org. Chem. 2014, 10, 1692–1705, doi:10.3762/bjoc.10.178

• , unfortunately, no clear trend observed for the oxidation potentials based on the substitution pattern of the aryl moieties, although both oxidations appear somewhat easier for pentacene 3f as a result of the two electron-donating methoxy groups attached to the pendent phenyl ring. Aryl-substituted pentacenes 3a

• –k each show one reversible reduction event in a rather narrow range of −1.59 to −1.68 V. Similar to that observed for the oxidation potentials, there is no obvious trend that can be identified in the reduction potentials based on substitution pattern, aside from the observation that the silyl

• change the electronic properties of the pentacene skeleton itself. Aryl-substitution pattern does however, have a considerable effect on solid-state arrangement of the molecules, and X-ray crystallographic analysis afforded insight on the packing arrangements of the synthesized pentacenes. In spite of

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• molecules were incorporated into the final product, whereas two additional equivalents were consumed capturing hydrochloric acid. In this way, the 1H-pyrazole 27 with an exceptional substitution pattern was obtained in 64% yield. The same reaction was applied to 5-arylmethylidene-thiazolidin-4-one 25 which

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• started our investigation with the preparation of azide-substituted cationic titanocenes. To this end, the titanocene carboxylates 1–3 shown in Figure 1 were employed as substrates because their substitution pattern should allow a first simple assessment of structure–activity relationships. The compounds

• through 1,3-dipolar cycloaddition markedly changes the activity of our titanocenes as a function of the substitution pattern. The most active complexes are highlighted in Figure 3. Gratifyingly, 18, together with a ketone-substituted titanocene, displays the highest activity against the BJAB cell line of

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• . While polyzwitterions based on N-functionalized chitosan [14][15] or 6-desoxy-6-aminocelluloses [16] are composed like synthetic polybetaines, a few cellulose-based zwitterions are described where the isoelectric point and the properties in solution could be tuned by varying the substitution pattern [17

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• -substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful starting point for the discovery of novel bioactive molecules. Keywords: diol synthesis; nucleoside; PreQ0

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• , attempts to move away from 2b to less electron-rich dienes such as 2c, 2d and 2e (Table 1, entries 2–4), failed to produce any of the desired endoperoxide products and mainly oxidative cleavage adducts were observed. Given the lack of reactivity of this alkene substitution pattern, we turned our attention

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• depends on the choice of potential reaction partners, but also on its substitution pattern and the reaction conditions. As examples, when N1 is substituted with a methyl group, the carbene can be trapped by elemental sulfur, isocyanates, and isothiocyanates which form indazolethione 4, indazolium-3

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• ]. Depending on the substitution pattern for the central 2,2’-bipyridines, three conceptually different types of allosteric receptors can be obtained: 4,4’- or 6,6’-substitution, both leading to positive allosteric receptors, meaning that they adopt an open anti-conformation in the free state where the two

• on-state in the absence of the effector and changes its conformation to the open off-state upon binding of it. In this article we present the synthesis of three new cyclodextrin-functionalised 2,2’-bipyridines 1–3 differing in the bipyridine’s substitution pattern (Scheme 2) and their metal complexes

• well defined [Zn(1)2] complexes which, together with the NMR data, proof that zinc(II) ions are suitable to act as an effector for 1. Changing the substitution pattern to 6,6’ like in ligand 2, however, makes it impossible to form a 1:2 complex due to the steric crowding around the metal binding site

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• to prepare the spirooxindoles with this novel substitution pattern. Thus, the acid additives were examined and the optimization results are listed in Table 2. To our delight, the addition of 4-nitrobenzoic acid reversed the regioselectivity of this reaction, and the ratio of 5a/4a was increased from

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• -selective fashion, as the cis-isomers are generally thermodynamically favored even with large R-groups on the exo-nitrogen substituents [39][40][41]. The situation is less clear for N(ring)-aryl-cyclodiphosphazanes, in which, dependent on the substitution pattern either cis or trans-isomers are favored [42

• yields but a lower enantioselectivity. Chlorine and fluorine in meta-position also lead to diminished yields and lower enantioselectivities (Table 3). Concerning the substitution pattern a clear trend that correlates the increasing electron-withdrawing properties of substituents on the phenyl ring with

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• natural product. To unambiguously prove the substitution pattern at the aromatic ring system, the phenolic OH-group was selectively methylated using diazomethane. The resulting methyl ether was irradiated in a 1D NOE experiment, which resulted in the expected strong increase of the proton bound to C-6

• of existing coumarin structures in literature, the 5-hydroxy-7-nitro substitution pattern combined with the unusual long-chain, fully saturated alkyl substituent at C-4 are unique to the myxcoumarins 7 and 9. With the production of myxothiazol A (5) and aurachin A (6), the investigated strain

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• describes the cyclization of differently substituted derivatives under identical conditions. Notably, the yield of macrolactones is significantly affected by the substitution pattern and increases from 27% for the unsubstituted lactone 34 (Scheme 7) to 53% for the 9-methyl-substituted derivative 36 (Scheme

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• , although giving lower yields. A broad substitution pattern on the (hetero)aryl ring was compatible with the reaction, and the “imino” C–H was selectively trifluoromethylated (Table 18). When carrying out the reaction in the presence of TEMPO, the desired reaction was almost completely shut down, while a

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• rosiglitazone (1.40) with its structure only differing in the substitution pattern of the parent pyridine ring. Its synthesis begins with the hydroxymethylation of 2-methyl-5-ethylpyridine (1.11), a commodity chemical obtained from the condensation of acetaldehyde with ammonium acetate (Scheme 12) [43]. At

• from the bacterial cell. Due to the elaborate substitution pattern of the parent quinolone ring systems these compounds are usually prepared via a linear consecutive sequence. In the case of moxifloxacin, an intramolecular base catalysed nucleophilic aromatic substitution is used to prepare the

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• potential allylic radicals like 11-R1 and 11-R2, 11-R3 is up to 8 kcal/mol more stable. Within the subset of allylic radicals that differ only by their alkyl substitution pattern (11-R1, 11-R2, 12-R1 and 12-R2) the energetic differences are less pronounced. Equally, the reasons for the small variations in

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• substitution pattern of the D-ring bares most of the functionalities, i.e., a secondary and a tertiary alcohol, the former of which is commonly glycosylated with 2,6-dideoxy sugars (Figure 1) [3]. These carbohydrates are of highest importance for the biological activity of anthracyclines and bind to the minor

• ]. Opening of the silyl ether moiety was accomplished by treatment with TBAF in quantitative yield and gained access to the natural substitution pattern of the carbohydrate backbone. It was not possible to open the silyl ether moiety of 26 by the utilization of Cs2CO3 in methanol starting from 13 as

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• process competition scenario. The noticed scope endorses an active involvement for a highly reactive gold–vinylidene intermediate as responsible for the selectivity of the eventual cyclization step, in agreement with the tentative mechanistic rationale depicted in Scheme 4A. Though the substitution

• pattern is not the one commonly associated with conventional electrophilic aromatic substitution reactions, other mechanism should not be disregarded on the basis of the structure of the final product. So, the alternative mechanistic description summarized in Scheme 4B cannot be firmly rejected, at the

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• (1,3-dihydro-2H-isoindole-1,3-dione, 4) substitution pattern. The isoindole structure has attracted scientists for decades and can be found in several natural and pharmaceutical compounds [2][3]. A number of structures were explored over the years and promising drug conjugates such as 5–11 could be

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• were observed. Benzo[ghi]perylenes are typical byproducts observed in the photocyclization of [5]helicene-like molecules. Reactions to obtain selectively helicenes or benzo[ghi]perylenes, regardless of the substitution pattern, are still a challenging task. A functionalizable [6]helicene (2r) was