The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• atom from the other substrates (in our case, from 5-AT) to yield 2-aminopyrimidines 4a,b. In addition, the counter synthesis of pyrimidines 4a,b was realized by the reaction of esters 1a,b with guanidine carbonate under similar conditions (Scheme 2). Earlier, pyrimidine 4a that exhibited antiviral

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

• modulation of its amino groups at 3 and 8 positions of the phenanthridine ring [52][53]. Systematic changing of the ethidium bromide exocyclic amines into guanidine, pyrrole, urea, and various substituted ureas revealed importance of electron-donor properties of substituents at the 3- and 8-position of the

• the excited state between the 6-phenyl ring and the phenanthridinium chromophore, which controls the non-radiative relaxation [56]. Substituted phenanthridine derivatives In particular guanidine- and urea-substituted derivatives attracted a lot of attention due to the different interactions with

• affinity, thus the affinity of guanidine derivative 2 (Figure 2) towards AT-rich DNA sequences was significantly stronger compared to ethidium and comparable to that of the known DNA minor groove binder furamidine. The above mentioned guanidine-induced switch of the DNA- and RNA-binding mode [57] inspired

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• inside a cavity of the cation, being fixed there by three N–H···Cl hydrogen bonds; this suggests that the cation can also serve as a receptor for other anions of appropriate size and shape. The triaminoguanidinium salt 7a was easily deprotonated to afford the corresponding neutral tris(ureido)guanidine 8

• -triaminoguanidine 9 was obtained, no matter whether a 1:1 or a 3:1 stoichiometry of the reactants was applied (Scheme 4). Notably, not the expected guanidine hydrochloride but the neutral guanidine 9 was obtained. Obviously, the basicity of guanidine 9 is much lower than, for example, the parent compound, 1,2,3

• -triaminoguanidine. Attempts to convert 9 into the corresponding triaminoguanidinium salt with strong acids failed. Structural and NMR data of guanidinium salts 7 and guanidine derivative 8 The solid-state structures of guanidinium salt 7a and the neutral guanidine derivative 8 display a common structural motif: the

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• in the respective carbamates (onium salts) [39]. As previously reported, strong amidine and guanidine bases such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) can form the base-CO2 zwitterionic adduct in a 1:1 manner under strictly anhydrous conditions (Scheme 1c) [40][41]. Herein, we present such a

• -functionalization of the organic base enhanced the complexation ability. For example, ΔHf decreased from −56.49 kal mol−1 (OctIm) to −91.17 kcal mol−1 (PEG150MeIm) for imidazole (Table 1, entry 2 vs 3), from −47.79 kcal mol−1 (OctTMG) to −106.56 kcal mol−1 (PEG150MeTMG) for guanidine (Table 1, entry 6 vs 7), and

• signals of the four methyl groups in guanidine of PEG150MeTMG shifted from 2.63–2.72 ppm to 2.96 ppm after reacting with equimolar amounts of LiNTf2 (Figure 2b). The corresponding anion CF3SO3−, the twelve protons moving only from 2.63–2.72 ppm to 2.71–2.75 ppm, indicate that there is only little

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

• ]-guanidine as cost-affordable 15N sources. Such derivatives are required to explore the binding process of the preQ1 base to RNA targets using advanced NMR spectroscopic methods. PreQ1 base specifically binds to bacterial mRNA domains and thereby regulates genes that are required for queuosine biosynthesis

• for 15N incorporation. For [15N1,15N3,H215N(C2)]-7-(aminomethyl)-7-deazaguanine (1), we started with the reaction of methyl cyanoacetate (4) and [15N3]-guanidine hydrochloride (5) under basic conditions to give the corresponding [15N1,15N3,H215N(C2)]-2,6-diaminopyrimidin-4-one (6) in high purity after

• was accessible by first synthesizing ethyl [15N]-2-cyanoacetate (11) from 2-bromoacetic acid (9) and potassium cyanide [15N]-KCN, followed by esterification (Scheme 3). All further steps were conducted in direct analogy as described for target 1, namely reaction with guanidine hydrochloride to furnish

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• converted to ester (aprotic ones) by initiation of the ring-opening polymerization of glycidol. The immobilization of polypeptides turned the zeta potentials into plus (–36.8 mV → +14.2 to +44.1 mV) due to the protonation to the basic groups in the peptides; imidazole, amine, and guanidine. These zeta

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• isoquinolinium-2-ylamide 43 undergoes a [3 + 2]-cycloaddition reaction with carbodiimide 54. Further intramolecular rearrangement yields the desired 1-(isoquinolin-1-yl)guanidine 55. Moreover, isoquinolinium-2-ylamides 43 can participate as 1,3-dipoles in [3 + 2]-cycloaddition reactions with in situ generated

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

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• enantioselectivities [38]. Notably, the reaction between an achiral fluorocarbon nucleophile with MBH carbonates, to afford compounds with chiral quaternary carbon centres bearing a fluorine atom, remains a formidable task. Since 2009, we developed a highly enantioselective and diastereoselective guanidine-catalyzed

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• enantioselectivity of the β-(N-acylamino)aryl thioether (up to 92% ee), with only 1 mol % of chiral guanidine OC-46 as a catalyst. Based on density functional theory (DFT) calculations, a plausible mechanism indicated that the hydrogen-bonding interaction between the chiral guanidine and the carbonyl group in meso-N

Isolation and X-ray characterization of palladium–N complexes in the guanylation of aromatic amines. Mechanistic implications

• Abdessamad Grirrane,
• Hermenegildo Garcia and
• Eleuterio Álvarez

Beilstein J. Org. Chem. 2013, 9, 1455–1462, doi:10.3762/bjoc.9.165

• complexes with iodoaniline and guanidine, respectively, (see Scheme 1) that give some clue about the reaction mechanism of the catalytic process. Results and Discussion In order to provide further support to the mechanistic proposal for the C–N insertion promoted by palladium(II) suggested by us [20], in

• were fully characterized by analytical and spectroscopic data (see Supporting Information File 1, experimental section). Structure of guanidine 5a was confirmed by single-crystal X-ray analysis, Figure 4 shows the corresponding ORTEP for compound 5a as well as some views of the crystal packing (see

• also Supporting Information File 1, Table S4 and Figure S20 and for full details of crystallographic data see Supporting Information File 2). Beside X-ray crystal analysis of guanidine 5a, guanidines 5a–c were also characterized by 1H, 13C and 19F NMR spectroscopy and combustion analysis (see Figures

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

• Piyush K. Agarwal,
• Meena D. Dathi,
• Mohammad Saifuddin and
• Bijoy Kundu

Beilstein J. Org. Chem. 2012, 8, 1901–1908, doi:10.3762/bjoc.8.220

• dimethyl acetal to form (E)-3-(dimethylamino)-1-(1-methyl-1H-indol-3-yl)-2-nitroprop-2-en-1-one (6a) [63][64][65][66], which was then converted to 4-(1-methyl-1H-indol-3-yl)-5-nitropyrimidin-2-amine (7a) in the presence of guanidine hydrochloride. Finally, the desired substrate 4-(1-methyl-1H-indol-3-yl

• potassium tert-butoxide in DMSO. Reaction of 15 with N,N-dimethylformamide dimethyl acetal provided 16, which was cyclized in the presence of guanidine hydrochloride and N,N-dimethylguanidine sulfate to give the nitro products 17a,b and 17c. Finally, the desired substrates 18 were obtained by reducing 17

Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• Philipp Viehmann Stefan Hecht Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany 10.3762/bjoc.8.209 Abstract A novel design as well as a straight-forward synthesis for a photoswitchable guanidine catalyst is reported. Intense studies of the

• photochromic properties demonstrated the reversible switchability of its photosensitive azobenzene moiety. Its activity in the ring-opening polymerization (ROP) of rac-lactide was investigated as well. The obtained results are discussed, and an additional guanidine was synthesized and utilized in the ROP of

• [17], TBD is a difficult target for the incorporation of photoresponsive switches. Recent work indicates that the activation mechanism for acyclic guanidines, such as guanidine 1 (Scheme 1), is strongly dependent on the formation of hydrogen bridges to monomer and initiator [18]. Note that with

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• guanidine-thiourea organocatalysts would perform as well as or even better than amine-thioureas and imidazole-thioureas. Generally, guanidines are well-known basic catalysts in organic synthesis, but only scattered examples of chiral guanidines as organocatalysts are known [49]. Indeed, only one guanidine

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

• guanidine motif have only a moderate influence on the affinity to the acetyl cation. Michael-acceptor affinities (MAA) A large number of reactions induced or catalyzed by Lewis bases involve initial or rate-limiting reaction with neutral electrophiles such as alkyl halides (substitution) or Michael

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• esterification to give the methyl ester 14 in excellent yield. Reaction of 14 with di(tert-butoxycarbonyl)guanidine under Mitsunobu conditions [27] proceeded smoothly to give 15 in 86% yield. Hydrolysis of the methyl ester followed by acidic work up to enable extraction of the resulting carboxylic acid gave 12

Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

• Kenichirou Yokota,
• Masayori Hagimori,
• Naoko Mizuyama,
• Yasuhisa Nishimura,
• Hiroshi Fujito,
• Yasuhiro Shigemitsu and
• Yoshinori Tominaga

Beilstein J. Org. Chem. 2012, 8, 266–274, doi:10.3762/bjoc.8.28

• -dioxides (3a–g), 2-amino-4-methylsulfanylbenzo[4,5]thieno[3,2-d]pyrimidine (6), and 2-amino-4-methylsulfanyl-7-methoxybenzo[4,5]furo[3,2-d]pyrimidine (7), were synthesized in good yields from heterocyclic ketene dithioacetals (1a–c) and guanidine carbonate (2a) or (S)-methylisothiourea sulfate (2b) in

• , we prepared new pyrimidine derivatives, which have solid-state blue fluorescence, by means of a one-pot synthesis, involving the reaction of ketene dithioacetals, amines, and guanidine carbonate in pyridine [5]. We have also reported the one-pot synthesis of a new, fluorescent, fused pyrimidine

• reaction of 1a with guanidine carbonate (2a) in pyridine under reflux gave the expected product, 2-amino-4-(methylsulfanyl)benzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxide (3a) in 89% yield (Scheme 1). Based on our findings that diaminopyrimidine derivatives show blue fluorescence in the solid state [5], we

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• glutathione and protein synthesis as well as cytochrome P450. Characteristic features of cylindrospermopsins include a guanidine moiety and a hydroxymethyluracil attached to the tricyclic carbon skeleton. According to feeding assays, the polyketide chain assembly starts with the activation of guanidinoacetate

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• of various fused heterocyclic compounds. In recent years, we have reported one-pot cyclizations of DTBA with hydrazine [23][24], hydroxylamine [25], guanidine [26], etc. In addition, one-pot cyclizations of DTBA-derived arylidenes have also been reported. Recently, we reported the synthesis of fused

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• tetrafluoroborate 42 is obtained as colorless crystals. An initial series of experiments to optimize the reaction conditions for efficient trifluoromethyl group transfer to indanone carboxylate were found to be the use of DBU as base and dichloromethane as solvent at room temperature. Guanidine bases, such as TMG

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties. Keywords: carbopeptoids; glycoclusters

• , thioureas can be easily transformed into carbodiimides and thus serve as key intermediate in the synthesis of other pseudoamide functionalities (urea, guanidine, etc.) [70][71][72][76][77][78][79]. Thirdly, thiourea bridges provide efficient anchoring points for bidentate hydrogen-bonding recognition, which

• –(C=S) bond (Figure 18). β-(1→6)-Linked thioureido-di- and trisaccharides were used to obtain the corresponding ureido- and guanidine-linked oligomers. These compounds were evaluated as phosphate binders in water [76]. Association constants (Kas) for the binding of dimethyl and, especially, phenyl

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• activity was investigated in benzyl ester cleavage, nitroarene reduction and a Diels–Alder reaction. The modified flavins photocatalyze the reactions, but the introduced substrate binding site does not enhance their performance. Keywords: flavin; guanidine; Kemp’s acid; photocatalysis; template

• carboxyl group with Boc-protected guanidine was achieved using standard peptide coupling conditions. Boc-deprotection with hydrogen chloride in diethyl ether yielded the guanidinium chloride salts 1 and 2 (Scheme 2). The guanidinium salts are soluble in water and methanol, but also in chloroform and

• acid) and mono Boc-protected guanidine were prepared by known methods [21][50][51][52]. All other chemicals were purchased from commercial suppliers, checked by 1H NMR spectrometry and then used as received. Solvents were distilled before use. Flash column chromatography was carried out on silica gel

A facile synthesis and fungicidal activities of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin- 4(3H)-ones

• Yang-Gen Hu,
• Ai-Hua Zheng,
• Xu-Zhi Ruan and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2008, 4, No. 49, doi:10.3762/bjoc.4.49

• carbodiimides 4, which were allowed to react with secondary amines to provide guanidine intermediates 5. Even in refluxing toluene, compounds 5 did not cyclize. However, in the presence of a catalytic amount of sodium ethoxide, compounds 5 were converted easily to 2-(dialkylamino)-5,6-dimethylthieno[2,3-d

• ]. The solitary formation of 8 can be rationalized in terms of a base catalyzed cyclization of the guanidine intermediate 7 to give 8 across the arylamino group rather than the alkylamino one. This may probably be due to the preferential generation of –N−Ar from more acidic –NHAr. The results are also