Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• suggested to be a general base-catalyzed formation of dianionic phosphorane (Scheme 5). The second-order term, which was important especially in guanidine and amidine buffer, was assumed to refer to binding of BH+ to the anionic phosphodiester linkage more or less concerted with the general base-catalyzed

• on buffer concentration was observed. It should be, however, noted that kinetic measurements in the most interesting guanidine and amidine buffers failed, evidently owing to partial decomposition of the buffer constituents during the prolonged incubation at 90 °C. Both cleavage and isomerization were

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• in a ruthenium-catalyzed C–H activation reaction [36]. Most other reported transformations pass via the imidoyl chloride intermediates (equivalent to 10) to the amidine derivatives, which have been used in rearrangement reaction studies [9][37][38][39]. By these means also N,N’-bis(triflyl

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• –N bond of benzamide and the formation of N-acylsulfonylguanidine 48 extended by two atoms (Scheme 21b). Biguanides The attachment of an amidine subunit onto the guanidine core, which is typically accomplished by the addition of a carbodiimide molecule, leads to a biguanide framework. In a paper by

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• combination of the Ugi reaction with other transformations proved to be powerful strategies for the efficient synthesis of novel heterocycles. In 1998, the Groebke–Blackburn–Bienaymé (GBB) reaction, an Ugi-3CR variant was discovered by three groups independently [36][37][38]. The GBB reaction of an amidine

• -ethynylbenzaldehydes 2 and tert-butylisocyanide (3). Indeed, the acetylene group in the aldehyde component had no obvious steric effect on the efficiency of the GBB reaction affording the GBB product in good to excellent yields in most cases. On the other hand, the substituent ortho to the amino group in the amidine

• moderate to good yields, and their structures were unambiguously confirmed by 1H NMR, 13C NMR, and HRMS analysis. Various functionalities related to the amidine and aldehyde components, including electron-donating methoxy and methyl groups or electron-withdrawing halides, were well tolerated. Generally

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• times ranging from 0.5 to 20 h, was not effective in forming the imidazolone of interest. The only product observed was the acylated amidine generated through a nucleophilic addition of the amidine to the ester carbonyl. For the latter compound the best result was obtained for the reaction in ethanol

• reaction mechanism involves a nucleophilic attack on the ester carbonyl, which leads to the formation of an amide intermediate. This means that the amidine does not attack the (more reactive) ketone carbonyl as expected, which would lead to an intermediate imine. Since the more reactive center of the

• , thiophene-2-glyoxylic acid, and N-(2-amino-4-nitrophenyl)acetamide, in accordance with the mechanism proposed in this work. To rationalize why the cyclization reaction between the amidines 8g,h and the α-ketoester did not occur, the HOMO coefficient and charge densities for the nitrogens of the amidine were

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• amidine protection of the exocyclic C6-NH2 group. At the same time, the applied excess of the reagent allowed to transiently form the corresponding nucleoside 2’,3’-O-acetal [32], leaving the primary 5’-OH group available for selective tritylation with 4,4’-dimethoxytrityl chloride to give compound 6

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• Madhuri Vangala Ganesh P Shinde Department of Chemistry, Indian Institute of Science Education and Research, Pune 411 008, India 10.3762/bjoc.12.197 Abstract The amidine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) display nucleophilic behaviour

• nucleophiles towards halo derivatives of main group elements where the DBU and DBN bicyclic rings remained unaffected [10][11]. Later in 1994, Lammers et al. observed the nucleophilicity of amidine bases with 4-halo-3,5-dimethyl-1-nitro-1H-pyrazole and their subsequent ring opening leading to the lactam

• carbohydrate–protein interactions [25], ligation and surfactant properties [26][27]. Although p-nitrophenyl carbonates were extensively utilized in these reactions, the nucleophilicity of amidine bases towards these carbonates was not encountered so far. In continuation of our interest in carbohydrates [28][29

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• . In addition, the resulting ligand families should provide nitrogen and phosphorus donors with varying donor strength (amidine vs imine, phosphine vs heteroatom-bound phosphorus) and different bite angles (five- vs six-membered chelate rings). Results and Discussion Ligand synthesis We based the

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• were found suitable for conversion of substrates into products when water was used as a nucleophile for amide preparations [13][14]. In the direction of amidine synthesis using isocyanide MCRs, a few catalysts such as p-toluenesulfinic acid [15], metal triflates [16], bromodimethylsulfonium bromide [17

• development of a mild, inexpensive and efficient catalytic protocol for the amidine synthesis is highly needed. Iodine is expected to act as a Lewis acid or Brønsted acid in methanol [20]. Apart from oxidation, catalytic iodine provides mild and efficient ways for the formation of C–C and C–N bonds [20]. As a

• part of our ongoing interest towards the synthesis of new molecular libraries [21][22][23][24], we were interested in developing a one-pot MCR strategy for the synthesis of amidines. Results and Discussion To check the feasibility of the iodine-catalyzed amidine synthesis through the modified Ugi

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

• be responsible for forming the amidine, guanidine or tertiary amine-functionalized ILs, after reaction with CO2 to form zwitterionic adducts in a 1:1 manner. Coordination effects between various lithium salts and neutral ligands, and the CO2 capacity of the obtained chelated ILs were investigated

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• tricyclic intermediate 121. Cleavage of the TBS ethers and hydrogenolysis of the benzyl ester in presence of amidine 122 yielded trinem 23a as its amidinium salt 123. Trinem 123 exhibited antibacterial activity against a variety of strains, with MIC’s of 1.0 μg/mL against Staphylococcus aureus 853E and 0.1

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• . An attractive feature of these new morpholino oligonucleotide analogues is the absence of additional chiral centers. Unlike commercially available PMO and PPMO, which are mixtures of diastereomers, oligomers constructed with the use of phosphoromonoamidate [7], oxalyl diamide [8], amidine [9] and

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• produced by a sequence including an initial condensation reaction of the 2-amino-4H-pyrans 9a and 9b with dimethylformamide dimethylacetal (DMFDMA) to yield the amidine-substituted derivatives 32a and 32b. Stirring solutions of these substances in refluxing AcOH/NH4OAc gave the respective pyranopyrimidines

• reacts with DMFDMA to form amidine 38, which undergoes cyclization in refluxing AcOH/NH4OAc to form the 1-amino-pyrrolo[3,4-f]quinazoline 39. We also found that 37a reacts with hydroxylamine hydrochloride in ethanolic sodium acetate solution to form isoindolone derivative 40 (Scheme 11 and Figure 13

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• . Compounds 4 and 5 could not be detected (Scheme 2). When the process was run as a true MCR (mixing the amine, the aldehyde and two equivalents of isocyanide 2a), the adduct 3a was produced in trace amounts and the main product was the α-amino-amidine 4, in good agreement with previous reports [5][6][7][8

Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

• Shinichiro Fuse,
• Nobutake Tanabe,
• Akio Tannna,
• Yohei Konishi and
• Takashi Takahashi

Beilstein J. Org. Chem. 2013, 9, 2336–2343, doi:10.3762/bjoc.9.268

• ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers. Keywords: amidine formation; diimine; flow chemistry; polymerization; Introduction The design of a ligand is a key step in the development of new catalysts because the

• 10 min. After an aqueous workup, the desired product 3b was obtained in a moderate yield (44%) with the concomitant generation of naphthylamine (5) and amide 8. Reportedly, 3a can form an HCl adduct, and the adduct decomposes to the corresponding amidine and imidochloride [25]. It is conceivable that

• Table 1. We speculated that the slightly lower yield of 3c compared to 3b came from the instability of 3c during purification process. The compound 3c was less stable than 3b. Rojas et al. reported that the regioselectivity in the nucleophilic addition of an amidine to an imidochloride depends on the

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

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• introduced by our group, both employing an N-halosuccinimide as the halogen source in combination with either the amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or sodium hydride (NaH). In these reports, the obtained α-halodiazoacetates and α-halodiazophosphonates were successfully applied in

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• radicals (C-radicals) could be trapped by molecular oxygen to form new C–O bonds. For instance, the Cu-catalyzed aerobic reaction of N-alkylamidines afforded aminidyl radicals (N-radicals) by single-electron oxidation and deprotonation of the amidine moiety, which was followed by 1,5-H-radical shift to

• generate the corresponding C-radicals (Scheme 1a) [7]. The successive trapping of the resulting C-radicals with molecular O2 forms peroxy radicals (the C–O bond formation). Reduction of peroxy radicals generates alkoxides, cyclization of which with the amidine moiety finally affords dihydrooxazoles

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• unselective. It appears that the first oxidation occurs exclusively at the aminal site to form deoxyvasicine (2). The presence of the amidine moiety apparently activates the molecule for oxidation at the benzylic position; we have observed that samples of aminal 7 can remain stable in the freezer for years

• , whereas 2 begins to convert to 4 within a day when exposed to atmospheric oxygen. Considering this, we reasoned that addition of a weak acid to protonate the relatively basic amidine moiety of 2 might deactivate the benzylic position toward oxidation while not interfering with the initial aminal oxidation

• was gratifying but somewhat unexpected since Decker reported that samples of the compound completely oxidized to quinazolinone 23 when exposed to air for 24 h [3]. This demonstrates the need for acetic acid to protonate the amidine, preventing further oxidation. While product 16 was obtained in good

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• reactions are described as an excellent synthetic tool for the synthesis of sterically highly hindered endothiopeptides. S-Methylation and subsequent amidine formation can be carried out in an inter- as well as in an intramolecular fashion. The intramolecular approach allows the synthesis of the bottromycin

• by Schipper [20] and Kaneda [21], based on detailed NMR studies. According to them, the bottromycins are cyclic tetrapeptides, connected to a tripeptidic side chain through an amidine structure. The different bottromycins differ only in the substitution pattern of the proline (Figure 1). The three

• -dimensional structure was reported recently by Gouda et al. [22]. This structure is quite unusual, not only because of the amidine moiety but also because most amino acids are found in β-methylated form (tert-leucine can be seen as β-methylvaline). Although a series of synthetic studies towards linear

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• 11e–f had to be constructed through condensation of a protected β-ketoaldehyde with the corresponding amidine. Compound 11e was synthesized from isonicotinonitrile through three steps described previously. Isonicotinonitrile was converted to isonicotinamidine hydrochloride 13 upon reaction in MeOH in

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially

• results in the diaminobutadiene II, which tautomerizes to the stable amidine III. The pyrazoline IV is then formed by an intramolecular SNVin reaction. Finally, HCl elimination affords the pyrazoles 27, 28. The stimulus to investigate such compounds originated from the known pharmacological activities of

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

• derivative 2,4-diaminoindeno[1,2-d]pyrimidin-5-one; this pyrimidine derivative, which was synthesized by heating a ketene dithioacetal, 2-[bis(methylsulfanyl)methylidene]indan-1,3-dione, under reflux with amine and amidine derivatives in pyridine solution, showed blue-green fluorescence in the solid state [6

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• , followed by Pd/Cu-catalyzed decarbonylative alkynylation with terminal alkynes 2, and finally by cyclocondensation of the ynone intermediates with substituted amidine hydrochlorides 4, pyrimidylazulenes 5 were obtained in moderate to good yields in a one-pot fashion (Scheme 5) (for experimental details

• , see Supporting Information File 1). The diversity-oriented nature of this four-component approach to pyrimidylazulenes 5 is underlined by flexible variation of the azulenyl, the alkynyl, and the amidinyl substrates. In particular, the amidine component 4 leads to the formation of aryl (compounds 5a

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

• established which gave the desired product in 90% overall yield (Scheme 33). Alternatively, glycine can be reacted with methyl pentanimidate 169 to form the corresponding amidine 171 in high yield. Cyclisation, followed by a Vilsmeier-type reaction then furnishes the key chloroimidazolyl building block 172 in