Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• on a support. This was demonstrated by the synthesis of a mixed triazole-hydrazone ligand 10 by CuAAC reaction of 3 with phenyl azide (Scheme 3) (for application of mixed triazole-imine ligands see [31][32][34]). Reaction of α-halogen-substituted hydrazones 1 with ammonia Addition of α-halohydrazones

• ://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge, CB21EZ, UK; or deposit@ccdc.cam.ac.uk). Proposed approach to the synthesis of I. Synthesis of α-halogen-substituted hydrazones 1 from α-halocarbonyl compounds and acylhydrazines or carbazates. Synthesis of a mixed triazole

Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications

• Desta Gedefaw,
• Marta Tessarolo,
• Margherita Bolognesi,
• Mario Prosa,
• Renee Kroon,
• Wenliu Zhuang,
• Patrik Henriksson,
• Kim Bini,
• Ergang Wang,
• Michele Muccini,
• Mirko Seri and
• Mats R. Andersson

Beilstein J. Org. Chem. 2016, 12, 1629–1637, doi:10.3762/bjoc.12.160

• -difluoro-2H-benzo[d][1,2,3]triazole (Tz) have attracted much attention and effectively employed in BHJ PSCs due to their intrinsic advantages, potentials and versatility [14][15]. Thanks to the desirable properties such as structural rigidity, planarity, extended π-conjugation length and favorable

• , is a moderately weak electron-deficient unit that can be easily synthesized and its properties can be finely modulated by attaching groups on the reactive nitrogen atom of the triazole ring [15][19][20]. Here we report the synthesis and characterization of two novel donor polymers, PTzBDT-1 and

• , 0.23 mmol) and 4,7-bis(5-bromothiophen-2-yl)-2-(2-butyloctyl)-5,6-difluoro-2H-benzo[d][1,2,3]triazole (3, 0.15 g, 0.23 mmol) were dissolved in toluene (10 mL) and degassed with N2 gas for 10 minutes. Pd2(dba)3 (4.2 mg, 2 mol %) and P(o-tolyl)3 (6.3 mg, 9 mol %) were added and purged with nitrogen gas

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• of 26% (28, Scheme 2). It is not yet clear as to why such a low conversion and isolated yield was obtained although the reduced nucleophilicity and higher potential for coordination of the triazole to the copper catalyst might inhibit catalyst turnover and account for this. Alternatively, using 3

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• dichloromethane at room temperature was used (Table 1 and Figure 2). Due to the highly exothermic nature of the triazole formation, a high dilution of the reaction mixture and low catalyst loadings are necessary to prevent a thermal runaway. In order to compare the catalytic activity of complex 2 with

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• : cancer; cN-II inhibitors; nucleotide; phosphonate; triazole; Introduction Nucleotidases are an important family of enzymes involved in the metabolism of nucleotides [1]. In particular, human cytosolic 5’-nucleotidase II (cN-II) catalyses the dephosphorylation of purine 5’-monophosphate derivatives to

• ) [7], we were interested in studying the effect of replacing the nucleobase by a 1,2,3-triazole moiety, linked to various substituents, with the aim to retain or modulate essential elements for enzyme recognition. Indeed, the assembly of the triazole ring with various substituents confers to the final

• between the anomeric proton H1 and the H4 (Figure 2). Consequently, both protons are located on the same face of the furanose ring and to the opposite face of the C4–C5 bond. The formation of the triazole ring was confirmed through the presence of a single signal of the triazolyl proton at δ = 7.94 ppm

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• indicate that the presence of the triazole moiety in the linker slightly perturbs the triplex formation. Conclusion Diverse bifunctional linkers of different length, hydrophobicity and flexibility for insertion of terminal azide or alkyne groups into biomolecules were synthesized and applied for

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• : cycloaddition; copper catalyst; ethynylstibane; organic azide; 1,2,3-triazole; Introduction The 1,3-dipolar azide–alkyne cycloaddition (AAC) has been effective for the synthesis of a wide variety of 1,2,3-triazoles [1]. However, this reaction has some limitations such as the requirement of high temperature and

• ) using 5 mol % of various Cu catalysts under aerobic conditions in THF at 60 °C (Table 1, entries 1–9). The results showed that CuBr was the best catalyst and gave the highest yield of the expected 5-stibano-1,2,3-triazole 3a (Table 1, entry 2). The reaction without the Cu catalyst did not afford 3a

• product (Table 1, entry 7). Heating of 5-stibano-1,2,3-triazole 3a in the presence of Cu(OAc)2 (5 mol %) under aerobic conditions in THF at 60 °C for 3 h afforded 4 in 91% yield. Furthermore, heating of 1 without 2a under the same conditions did not give the phenylacetylene and the starting compound was

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• reaction, Lou and Cheng explored the addition of various nitrogen [54], sulfur [55], and carbon nucleophiles [56][57] to α-branched vinyl ketones (Scheme 29). The nitrogen heterocycles benzotriazole (126a), triazole (126b), and 5-phenyltriazole (126c), all reacted smoothly with vinyl ketone 118. To achieve

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• Republic of China 10.3762/bjoc.12.85 Abstract A series of copper complexes (3–6) stabilized by 1,2,3-triazole-tethered N-heterocyclic carbene ligands have been prepared via simple reaction of imidazolium salts with copper powder in good yields. The structures of bi- and trinuclear copper complexes were

• atmosphere at room temperature. Keywords: copper; CuAAC reaction; : N-heterocylic carbene; 1,2,3-triazole; Introduction N-Heterocyclic carbene (NHC) have interesting electronic and structural properties. This resulted in their use as versatile ligands in organometallic chemistry and homogeneous catalysis

• , the easy synthesis and versatile coordination ability of 1,2,3-triazoles have led to an explosion of interest in coordination chemistry [21] and homogeneous catalysis [22][23][24][25][26]. Although a number of metal complexes containing 1,4-disubstituted-1,2,3-triazole ligands were well studied

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• emerge but when they do, they represent plenty of scope for creative chemical design. At the time, I observed that the triazole linkages were used to bring together two modules, be they a fluorescent tag “clicked” onto a protein or redox-active group “clicked” together with a polymer. But I also thought

• there must be some latent functionality deriving from the intrinsic structure of the triazole that remained unexplored. It was clear later that Stefan Hecht and Steve Craig had similar thoughts. Invoking Hoffmann’s dictum [9], I originally wondered if the triazoles were the same as pyridines for the

• indicated that triazoles are sterically small. In the iron complex, we saw the ferrous ion’s preference for triazole change to a water molecule when oxidized up to the harder ferric ion. This process did not occur with the terpyridine control complex. Thus, we reasoned water could easily slip past the

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• chiral NHC-catalysts used for asymmetric homobenzoin condensation. A rigid bicyclic triazole precatalyst 15 in an efficient enantioselective benzoin reaction. Inoue’s report of cross-benzoin reactions. Cross-benzoin reactions catalysed by thiazolium salt 17. Catalyst-controlled divergence in cross

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• is the Cu(0)-catalysed azide–alkyne cycloaddition (CuAAC) that can be further enhanced by simultaneous US/MW irradiation [18]. The formation of triazole-substituted CDs has been investigated by US irradiation and products can be synthesized in 2–4 hours (Scheme 2) [19]. Scondo et al. have reported a

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• ); the second route starts from the same tosylated intermediate 18, substituted by an azide function, precursor of a triazole ring used to link the aldoxime moiety (pathway ii, Scheme 4). Following this second approach, Kubik et al. published new α-, β- and γ-CD derivatives functionalized with hydroxamic

• macromolecule. Efficiency of compounds 23a–i against chemical warfare agents: Amongst the derivatives 23a–i with the pyridine aldoxime linked to the CD by a triazole ring, compound 23a is the most interesting scavenger. To access more potent compounds, Kubik et al. later introduced two α-nucleophiles on A and D

• to the rigidity of the triazole-based spacer. Introduction of hydroxamic acids via a Huisgen reaction on α-, β- and γ-CD also leads to scavengers sharing the same level of efficiency than a glucose unit bearing the same functionnal group. These surprising results proved that for these derivatives

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• 0.32 (CH2Cl2/MeOH/NH4OH 6% 10:1:0.1); [α]D24 +4.88 (c 1.92, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 4H, H-triazole), 4.54 (s, 8H, OCH2-triazole), 4.44 (t, J = 6.6 Hz, 8H, 3’-H), 4.32 (dd, J = 11.7, 5.3 Hz, 4H, 3-H), 4.05 (t, J = 4.7 Hz, 4H, 4-H), 3.98–3.95 (m, 4H, 5-H), 3.42 (s, 8H, CCH2O), 2.71 (dd

• , J = 12.0, 5.3 Hz, 4H, 2-Ha), 2.59 (dd, J = 11.7, 2.9 Hz, 4H, 6-Ha), 2.47–2.41 (m, 8H, 2-Hb + 6-Hb), 2.36 (t, J = 6.6 Hz, 8H, 1’-H), 2.11–2.03 (m, 8H, 2’-H), 1.49 (s, 12H, Me), 1.35 (s, 12H, Me) ppm; 13C NMR (50 MHz, CDCl3) δ 145.1 (s, 4C, C-triazole), 123.3 (d, 4C, C-triazole), 109,0 (s, 4C, acetal

• ), 77.3 (d, 4C, C-4), 72.2 (d, 4C, C-3), 68.9 (t, 4C, CCH2O), 68.0 (d, 4C, C-5), 64.8 (t, 4C, OCH2-triazole), 56.1 (t, 4C, C-6), 54.8 (t, 4C, C-2), 53.4 (t, 4C, C-1’), 47.7 (t, 4C, C-3’), 45.2 (s, CCH2O ), 28.3 (q, 4C, Me), 27.3 (t, 4C, C-2’), 26.3 (q, 4C, Me) ppm; MS (ESI) m/z (%): 1335.83 (100) [M + Na

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• different azides, followed by the sequential Swern oxidation and Ohira–Bestmann homologation provided the ethynyltriazole intermediate 9, finally another CuAAC resulted in the formation of unsymmetrical 4,4'-bi(1,2,3-triazole)s 10 (Scheme 4). The synthesis of 5,5'-bitriazoles Originally, in the research of

• the CuAAC reaction, the 5,5'-bitriazoles were usually considered as an undesired side product or impurity in the Huisgen cycloaddition. In general, they are the oxidative coupling product of the triazole-copper species. The 5,5'-bitriazoles were usually formed as the major product by the facilitation

• highest activity. In 2010, Nandurdikar et al. linked the two (or four) molecules of NO donor prodrugs together through the triazole spacers [22], which has potential application as NO-releasing materials. They first prepared the benzylidene-protected 2,2-di(azidomethyl)propane-1,3-diol containing the

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• ” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• have always been my favorite. When I performed my postdoctoral research in Denmark, I used fluorine-containing precursors to build catenanes [8], and many years later, I utilized fluorine as a hydrogen bonding acceptor to develop aromatic amide and triazole foldamers [9][10]. Postdoctoral research at

• -triazole foldamers. In 2008, several groups independently described that the intermolecular C–H····Cl− hydrogen bonding could induce benzene-linked 1,2,3-triazole oligomers to form folded or helical conformations [61][62][63]. Currently, this family of foldamers have found wide applications in anion

• binding and design of photo-active molecular devices [64][65][66]. We were interested in developing inherently folded structural patterns for aromatic oligotriazole backbones. In 2009, Yuanyuan Zhu established that 1,5-diphenyl-1,2,3-triazole formed an intramolecular six-membered C–H····OMe hydrogen bonds

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• Since the discovery in 2002 that copper(I) could catalyze the Huisgen alkyne–azide [3 + 2] cycloaddition with high selectivity for the 1,4-triazole [1][2], the so-called copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) has become a privileged reaction which is widely employed in all areas of the

• coworkers addressed several of these points; they proposed an optimized catalytic system composed of CuSO4, an accelerating and water-soluble tris-triazole THPTA (tris[(1-hydroxypropyl-1H-1,2,3-triazol-4-yl)methyl]amine) ligand with a ligand/copper ratio equal to at least 5 to effectively trap the reactive

• experiment the solution was irradiated for 1 h at 365 nm with a TLC lamp placed at ≈1 cm from the tube, and then left under ambient laboratory light. In these conditions, the reaction proceeded to full conversion in ≈2 h, 80–90% of the triazole being formed after 1 h. The triazole 9 was then isolated in 91

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and

• IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro. Keywords: antimicrobial; chalcone; cholesterol; cytotoxicity; glycoside; triazole; Introduction Cholest-5-en-3β-ol (cholesterol, 1

• , hydroxyalkyl-1,2,3-triazoles were reported as valuable pharmacophores [36]. The products were isolated in good yields and the H-5 signal of triazole (1H NMR) could be observed as a singlet at δ ≈ 7.5 ppm. Compound 11a was further converted into the corresponding bromo derivative 12 in good yield under the same

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• , 97:3 v/v) to give 2 (1.2 g, 70%) as a white foam. 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 4H, H5 of triazole), 7.18 (d, J = 8.6 Hz, 8H, H2&H6 of Ph), 6.89 (d, J = 8.6 Hz, 8H, H3&H5 of Ph), 5.38 (s, 8H, N-CH2-Ph), 4.32 (s, 8H, AcS-CH2-), 4.13 (s, 8H, CH2-pentaerythritol), 2.31 (s, 12H, -SAc); 13C NMR (125

• ) under N2. The mixture was stirred for 30 min and the progress was monitored by TLC. Solvents were removed by evaporation and the product was purified by silica gel chromatography (DCM/MeOH, 95:5 v/v) to give 3 (120 mg, 19%) as a thick oil. 1H NMR (500 MHz, CDCl3) δ 7.40 (s, 4H, H5 of triazole), 7.18 (d

• , J = 8.6 Hz, 8H, H2&H6 of Ph), 6.88 (d, J = 8.6 Hz, 8H, H3&H5 of Ph), 5.42 (s, 8H, N-CH2-Ph), 4.30 (s, 8H, S-CH2-triazole), 3.97 (s, 8H, CH2-pentaerythritol), 3.79 (t, J = 5.5 Hz, 8H, CH2OH), 2.73 (br t, 8H, S-CH2CH2) ppm; 13C NMR (100 MHz, CDCl3) δ 158.9, 144.2, 129.6, 127.2, 121.9, 115.2, 66.4

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• –tetrathiafulvalenes [14], porphyrin–cyanines [15], porphyrin–carotenes [16], porphyrin–arene diimide [17] and porphyrin–fluorocene or rhodamine [18] have also been synthesized in which the porphyrin unit acts as an electron acceptor. Recently, the 1,2,3-triazole scaffold has been successfully employed to connect

• ] including anti-oxidative [35], antihypertensive [36], anti-inflammatory [37] and antiplatelet agents [38]. They have also been used as fluorophores and exhibited good fluorescence properties when attached to a triazole ring [39][40]. Owing to the biological significance of porphyrins, 1,2,3-triazoles and

• -diethynylxanthen-9-one. In addition, a new series of various β-triazole-linked porphyrin–xanthone conjugates and xanthone-bridged triazoloporphyrin dyads were synthesized through click chemistry in moderate to good yields. The preliminary photophysical evaluation of these π-conjugated molecules revealed a

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• Zachary L. Palchak Paula T. Nguyen Catharine H. Larsen Department of Chemistry, University of California, Riverside, CA 92521, USA 10.3762/bjoc.11.154 Abstract Propargylamines are popular substrates for triazole formation, but tetrasubstituted variants have required multistep syntheses involving

• stoichiometric amounts of metal. A recent cyclohexanone–amine–silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection–triazole formation reported herein offers rapid access to alpha-tetrasubstituted

• ; copper catalysis; multicomponent reactions; tetrasubstituted carbon; triazole; Introduction 1,2,3-Triazoles demonstrate wide spread application in biological systems and drug development [1][2][3][4][5][6][7][8][9][10][11][12]. Copper-catalyzed azide–alkyne cycloadditions (CuAAC) regioselectively

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• ] have reported the synthesis of a glycotriazolophane 309 (carbohydrate–triazole–cyclophane hybrid) from a sugar amino acid via a copper-catalyzed azide-alkyne cycloaddition sequence. An aminosugar acid was identified as a useful building block to generate cyclophanes. Thus, the treatment of 304 with

• 308 in the presence of CuSO4 and sodium ascorbate in acetonitrile/water to deliver the desired cyclophane derivative 309 (56%, Scheme 53). Similarly, a novel BINOL-based cyclophane 310 has been synthesized via click chemistry by incorporating two triazole moieties in the macrocycle [187]. Li and co

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ). More recently, the Jamison group also reported upon a short flow synthesis of the antiepileptic agent rufinamide (95) [87]. The 1,2,3-triazole ring was prepared via a dipolar cycloaddition between an in situ generated benzylic azide and propiolamide (also prepared in situ), which by maintaining a low

• ]. Importantly in this study, a flow reactor consisting of copper tubing maintained at 110 °C (6.2 minutes residence time) was employed as this would release small amounts of copper salts catalysing the regioselective triazole formation. A cautionary note regarding the potential of generating copper azide within

• focused upon a dipolar cycloaddition between azide 100 and (E)-methyl 3-methoxyacrylate (101) to yield triazole 102 that was converted into rufinamide (95) (Scheme 18). The benefits of using this alternative dipolarophile 100 are that it is not only considerably cheaper and less toxic than 98, but it also

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• . Keywords: 3-azido-1-propyne oligomer; CuAAC polymerization; hydrodynamic radius; methyl iodide; pulse-field-gradient spin-echo NMR; quarternization; Introduction The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) efficiently yields 1,4-disubstituted-1,2,3-triazole from rather stable azides and

• chemistry [8][9][10][11][12] to materials science [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], as well as polymer synthesis [30][31][32][33][34][35][36]. Most of these studies deal with the 1,2,3-triazole moiety just as a linker. However, since 1,2,3-triazole possesses a large

• dipole moment and aromaticity, 1,2,3-triazole itself may be a functional group. Polymers composed of dense 1,2,3-triazole moieties on the backbone are thus promising as functional materials. Recently, we have investigated the CuAAC polymerization of 3-azido-1-propyne (AP) using 3-bromo-1-propyne as a