Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• Chemistry, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany 10.3762/bjoc.12.146 Abstract A practical method was elaborated for the synthesis of (aminomethylene)bisphosphine oxides comprising the catalyst- and solvent-free microwave-assisted three-component condensation of primary amines

• oxide, and we aimed at the preparation of new derivatives. Results and Discussion Synthesis of alkylamino- and (phenylaminomethylene)bisphosphine oxides In the first series of experiments, the condensation of primary amines, such as butyl-, cyclohexyl- and benzylamine or aniline with triethyl

• primary amines with triethyl orthoformate and diethyl phosphite. Spectral characterization of N-ethyl- (4) and N-formyl- (5) (aminomethylene)bisphosphonates and imine-type intermediates 6a and 6b. Synthesis of (dialkylaminomethylene)bisphosphonates 8a–g. Condensation of aniline, triethyl orthoformate and

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• (10b), propylacrylamide (10c), and pentylacrylamide (10d, Table 1). Based on the classification reported by Grubbs [20], these substrates are type II when used in the presence of catalyst 3. Propyl- and pentylacrylamide (10c and 10d) were synthesized from acrylic acid and the respective primary amines

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• another report [39], the major products formed from triplet nitrenes are primary amines 4 through hydrogen-atom abstraction [58], secondary amines, 1,2-arylhydrazides and azo compounds 5, which are obtained by recombination of radicals [59]. Moreover, it was shown that yields of primary amines increased

• ethanol. As can be seen in Table 3, the photolysis of 1c,d in a 1,4-dioxane/water mixture under these conditions lead to decreased yields of 2c,d and to the formation of azepine 3c and primary amines 4c,d with significant yields. An explanation for the decreased yields observed for isoxazoles 2c,d may be

• the photo-induced breaking of the C–Br bond that completely changed the way of the reaction. However, this possibility does not explain the formation of primary amines 4c,d. It should be noted that the photolysis of double ortho-substituted azides (Table 3, entries 2, 4, R2 ≠ H) did not lead to the

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• separated by column chromatography. After debenzylation, the resultant primary amines were connected with amido aldehydes 6 substituted with different moieties R and R' by reductive amination with R being either a hydroxy group or a hydrogen and R' representing an alkyl, allyl, ester or a protected amino

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

• was reacted with different azides catalyzed by the Cu(II)–TBTA complex and sodium ascorbate in a bi-phasic system of CH2Cl2/H2O as the solvent, giving the desired bistriazoles 59 in good yield; (3) Deprotection of the N-Boc group with TFA, and the obtained primary amines was transformed to the

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• , several pathways are involved in the amine-induced catalyst decomposition depending on the nature of the amine and of the ruthenium complex. Non-bulky primary amines can attack directly benzylidene species and are responsible for the fast degradation of the catalyst. In the case of a phosphine-containing

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• 1,2-diazine or imine co-reactants to yield functionalized hydrazones or benzylanilines. SCPC with tertiary amines enabled electron-deficient alkenes to be alkylated and furoquinolinones to be accessed. Primary amines on their own led to self-reactions involving C–N coupling and, with terminal diamines

• product 11a was formed by attack of this species anti to the menthyloxy substituent of 6. The electrophilic intermediate radical thus formed readily ring closed on to the electron rich aromatic ring furnishing 11a and 11b after oxidative rearomatization. When primary amines 12 were irradiated on their own

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• convenient one-pot process for the synthesis of miscellaneous cyclic imides in high yields starting from readily available primary amines and cyclic anhydrides. A plausible radical mechanism involving DMSO has been proposed. The application of this facile one-pot imide forming process has been demonstrated

• method to construct the imide functionality is to react the corresponding primary amines with cyclic anhydrides to form amic acids, which are then cyclized using acetic anhydride and sodium acetate in a separate step [26]. Hexamethyldisilazane–zinc chloride has also become one of the most widely used

• a convenient one-pot process for the preparation of structurally diverse cyclic imides starting from readily available primary amines and cyclic anhydrides using APS–DMSO as an efficient and novel dehydrating reagent and its application to a drug synthesis. The scope of the developed protocol was

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• -2025, USA 10.3762/bjoc.11.86 Abstract The success of siRNA-based therapeutics highly depends on a safe and efficient delivery of siRNA into the cytosol. In this study, we post-modified the primary amines on dendritic polyglycerolamine (dPG-NH2) with different ratios of two relevant amino acids, namely

• broader distribution of the final nanoparticles. The size of dPG-13Arg and dPG-13His complexes was slightly smaller than the other dPG-based vectors. The surface charge of the final nanoparticles was comparable to the corresponding complexes of siRNA and dPG-NH2 50% with terminal primary amines and about

• cytotoxicity of the nanoplexes. Replacing the primary amines on dPG-NH2 with histidine groups would possibly decrease the density of positive charge on dPG and increase cell viability. The best cytotoxicity profile was observed for dPG-8Arg30His with no considerable cytotoxicity (cell viability ≥ 90%) up to N

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• literature [19]. The transformation started from the mesylation of the hydroxy groups on the hPG. In the next step, the mesylated polyglycerol was converted to poly(glycerol azide). In the last step, azide functionalities (N3) were reduced to primary amines (-NH2) via Staudinger reduction to obtain the

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• [19] are used as precursors for chiral β-amino alcohols. As precursors for α-chiral primary amines, fenchone [20] and camphor [21][22] are typically employed. Furthermore, optically pure dehydroabietylamine is readily available and applicable without further modification [23][24][25]. Among the

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• , 3u, and 3v in good yields (76–88% yields), respectively. Finally, primary amines were examined. The reaction with excess benzylamine (5.0 equiv) in the presence of Zn(OTf)2 as the catalyst afforded the desired product 3w in 98% yield. However, when n-BuNH2 was used as the substrate, the yield was

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• to primary amines. Secondary amines cannot be detected reliably and aromatic and tertiary amines do not yield positive test results either [24]. One report on the non-quantitative application of the Kaiser test on ethylene diamine functionalized nanodiamond has been reported recently [25]. For

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• was emitted by NBD/DDY/catalase, which is probably due to very low fluorescence quantum yields reported for NBD derivatives of primary amines in water [39]. Furthermore, NBD (9) is not suitable for standard SDS-PAGE (12% gels) as the dye smears and therefore potentially covers fluorescent signals of

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• been found to catalyze a variety of carbon–carbon bond-forming reactions [25][26][27][28][29][30]. Small peptides derived from acyclic amino acids, primary-secondary diamines, Cinchona-based primary amines, and thioureas with a primary amine functionality etc., have found many successful applications

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

• subsequent 3-CR with diketene 98 and a wide variety of primary amines to afford the triazole linker. The scope of the Ugi reaction was investigated with several aliphatic and aromatic aldehydes and amines and gave the Ugi-products in good yields (34-61%). Moreover, the scope of sequential cycloaddition was

•  48). In a combined approach, Gunawan et al. also described such an Ugi-azide reaction to develop γ/δ/ε-lactam tetrazoles [126][127]. Depending on the keto-ester or acid used, an Ugi reaction with different primary amines, isocyanides and TMSN3 followed by subsequent cyclization gave either γ-, δ- or

• reported [147]. A wide variety of aldehydes, primary amines and carboxylic acids were tolerated resulting in a library of 80 different linear dipeptides. Cleavage from the carbonate resin with KOt-Bu afforded compound 176 which was converted to the methyl ester 177 using NaOMe (Scheme 54). Subsequent TFA

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

• expansion of its scope to include difficult substrates such as aliphatic primary amines and ammonia, the development of highly enantioselective A3-coupling reactions with broad substrate specificity, and the incorporation of the A3-coupling reaction into tandem processes are all challenges that are expected

• as a powerful tool for the synthesis of medium-sized libraries of bioactive compounds. Thus, straightforward syntheses of 1,3-disubstituted-1,2-dihydroisoquinolines have been achieved by three-component reactions between alkynylbenzaldehydes 25 (γ-carbonylalkyne), primary amines 26 (mainly anilines

• -protons and thus allowing for an easy α-deprotonation with weak bases (Scheme 32) [86][87]. Recently, Orru’s group successfully translated the stepwise Schöllkopf–Van Leusen synthesis of dihydroimidazoles 65 in a MCR involving isocyanides 61, aldehydes 62 and primary amines 63 [88]. Initial results

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• ][37][38]. Although the scope of the reaction was demonstrated to be quite broad, some limitations were noticed, especially in reactions involving aryl halides. For instance, primary amines and enolizable aldehydes were unusable in this process. As a part of our ongoing efforts to improve reliability

• room temperature. To the best of our knowledge, this constitutes the first manganese-mediated multicomponent reaction involving aryl halides as the source for nucleophilic species. Results and Discussion We previously reported that primary amines are not active in a Mannich-like multicomponent reaction

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

• readily converted to their 9-epi-amino derivatives and are well established in HB catalysis [31]. The PV-amide catalysts are efficiently accessible through addition of the lithium alkoxides (1,2,4,5, Scheme 1) or primary amines to N,N'-diarylphosphordiamido chloridates in THF or pyridine (6–7f, Scheme 1

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• , followed by two kinds of library diversification involving 1) Michael addition of a set of primary amines and the subsequent nucleophilic ring closure to give the difluoroquinolone system, 2) intermolecular nucleophilic aromatic substitution with various amines and hydrolysis of ester moieties to afford a

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• stable towards piperidine exposure and the activated species should selectively react with primary amines without prior decomposition. Indeed, all glyco-building blocks described here, fulfil these criteria and can be applied for sequential coupling under PyBop or HATU activation and Fmoc deprotection

Direct electrophilic N-trifluoromethylthiolation of amines with trifluoromethanesulfenamide

• Sébastien Alazet,
• Kevin Ollivier and
• Thierry Billard

Beilstein J. Org. Chem. 2013, 9, 2354–2357, doi:10.3762/bjoc.9.270

• ago, we have described an easy access to trifluoromethanesulfenamides [36], starting from DAST, Ruppert reagent, and primary amines [37]. However, even though this strategy gave good results with primary amines, secondary amines do not react under these conditions, thus limiting the access to a large

• volatility, some compounds (3h and 3i) have not been isolated. Imines can be also trifluoromethylthiolated in good yields (3m). Even if our first developed method is compatible with primary amines [37], they can also react under these new conditions, as illustrated with the aniline (3n). Amino alcohols and

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA) as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused

• ninhydrin to form Schiff bases. To overcome the above problems we have designed an operationally simple one-pot reaction for the synthesis of pyrrole-fused isocoumarins (5 or 8) from the ninhydrin adducts of acetylacetone/ethyl acetoacetate (6 or 7) [43] and primary amines 2 under solvent-free conditions

• aromatic primary amines under the optimized conditions (Table 1, entry 14). As becomes evident from Table 2, all the primary amines reacted well with adducts 6 and 7 affording the desired products 5 and 8 in good yields. The results show that solvent-free conditions and the SSA catalyst are crucial

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

• condensation of primary amines with o-diacylbenzene 19 (Scheme 2) [13]. After initial formation of 20, isomerization to 21 and 22 can occur through a sequential dehydration–hydration process. Dimerization of 21 and 22 generates 23, the substrate for a formal retro-Aldol reaction. Loss of formaldehyde gives 24

• , which is spontaneously oxidized to the intensive blue-violet pigment 25. This reaction sequence is characterized by its high sensitivity and has found application as a marker in analytical chemistry (e.g. staining of primary amines) [14][15]. The following review section highlights synthetic and

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• reaction of commercially or synthetically available 4,6-dichloropyrimidines with an excess of primary amines in boiling 2-propanol. As it is was shown by us earlier, the starting compounds 1 underwent smooth and high-yielding N-nitrosation reactions by using sodium nitrite in acetic acid at room