New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• mixture at reflux temperature for 30 hours. All final pyrrolo[1,2-a]quinoxalin-4-one compounds have been isolated by simple, non-chromatographic methods. The reaction pathway involves the intermediate N-alkylation of the imidazole ring with one equivalent of alkyl bromoacetate yielding 1

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

• 1,2,3-triazidoguanidinium salt [16][17]. Direct N-alkylation reactions of the triaminoguanidinium ion are not known. Triaminoguanidinium salts are soluble only in water or in hot alcohol/water mixtures, but not in the common organic solvents, which prevents the use of alkylating reagents such as alkyl

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• caused an unusual activation of the alcohol moiety, leading to N-alkylation. In the presence of iPr2NEt, reaction of HATU with benzyl-, n-butyl-, and p-nitrobenzyl alcohol led to the formation of the corresponding 1-alkoxy-1H-7-azabenzotriazoles [39]. The regiochemistry in these reactions was identical

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

• affinity for the target/receptor and improved protease stability, bioavailability and specificity [6][7][8]. Conformational bias can be achieved via N-alkylation, α-alkylation or the introduction of alkene amide bond isosteres, but also via local or global cyclization. A prominent advantage of cyclized

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• Julian Fischer Simon Millan Helmut Ritter Institute of Organic Chemistry and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.9.318 Abstract N-alkylation of N,N'-(hexane-1,6-diyl)bis(4-methylbenzenesulfonamide) with

• [16][17][18]. To our best knowledge, CD mediated N-alkylation of sulfonamides is not yet described. Generally, only a few examples are known in literature about CD assisted alkylation of amines in aqueous solution [19][20][21][22]. Hence, in this work, we wish to present our direct and CD mediated

• -methylbenzenesulfonamide) (3), as precursor for the subsequent N-alkylation and further Prilezhaev epoxidation, was synthesized easily from p-toluenesulfonyl chloride (1) and hexamethylenediamine (2) [23]. The resulting crystalline sulfonamide was first described in 1927 prepared from 1,6-dibromohexane and p

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• limitation of the reaction was established. The N-alkylation of the isatins is usually accompanied by the formation of spiro epoxyoxindoles. Experimental Reagents and apparatus: Melting points were taken on a hot-plate microscope apparatus. IR spectra were obtained on a Bruker Tensor 27 spectrometer (KBr

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• -alkenyl carbamates. Results and Discussion Simple N-alkenyl ureas 1 were prepared by a reported method [2] entailing N-acylation of an acetophenimine with an isocyanate, followed by N-alkylation of the resulting urea. When urea 1a was treated with t-BuLi or s-BuLi in THF at −78 °C for one hour, followed

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• assembly of the 2-nitrobenzenesulfonyl-(Nosyl, further abbreviated with Ns)-protected spermine backbone 8 on a solid phase via Fukuyama Ns strategy [51]. The next step was the Ns protection of the residual primary amine with 6.00 equiv of Ns-chloride and 12.0 equiv 2,4,6-collidine in CH2Cl2 followed by N

• -alkylation with 5-chloropent-1-yne to insert the terminal alkyne moiety. To accomplish that, we used 10.0 equiv of alkyne and 15.0 equiv of K2CO3 in DMF; the reaction led to resin 9 with virtually quantitative yield, as shown in Scheme 1. For the CuAAC with the azides moieties 4, 6 and 7, respectively, we

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• introduced. The synthetic strategy allows broad structural variation of this new drug-like heterobicyclic scaffold. In addition to extensive NMR and MS analyses, the structure of one derivative was confirmed by X-ray crystallography. Keywords: hydantoins; hydrazides; imidazotriazines; N-alkylation; regio

• intramolecular heterocyclization, formally by dehydration, would afford the 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6-diones III. The success of this route, however, depends on two factors: (i) the preferred regioselectivity of the successive N-alkylation steps for the formation of II; and (ii) the

• ) (Scheme 2). According to our retrosynthetic analysis (Scheme 1), and based on an efficient protocol for the regioselective N-alkylation of hydantoins, we applied a four-step procedure for the synthesis of differently substituted 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6-diones 23–29 (Scheme 3). The

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• )-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. Keywords: asymmetric synthesis; (R)-tert-butanesulfinamide; cinacalcet hydrochloride; naphthyl ethyl sulfinamide; regioselective N-alkylation; Introduction Cinacalcet hydrochloride

• at room temperature for 2 h to give the product in 85% yield (Scheme 6). Regioselective N-alkylation of N-tert-butanesulfinamides was difficult to achieve as S-alkylation can also be possible [26]. To our knowledge, limited procedures were reported for the regioselective N-alkylation of N-tert

• reaction progress, i.e., n-BuLi, LDA, Cs2CO3 with dppf/PdCl2, K2CO3 with Cu(I)/L-proline, NaH and TEA. All of them failed to initiate the reaction. Only LiHMDS worked well for the regioselective N-alkylation of sulfinylamide 4a in a better yield (72% isolated pure product) than the earlier reported

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• ring [19]. We have now developed this concept further toward a library synthesis of functionalized azepino-isoindolinone derivatives. Results and Discussion N-Alkylation of phthalimide with 4-penten-1-ol under Mitsunobu conditions, followed by NaBH4 reduction and pivaloate protection of the

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• solutions. Interestingly, the probe is only slightly responsive to Hcy and GSH. Results and Discussion N-Alkylation of trans-1,2-diaminocyclohexane with a pair of 9-carboxamidoquinoline moieties through methylene linkers afforded multifunctionalized ACAQ (Figure 2). Bearing six metal ligating sites, ACAQ

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• desired optically active natural product in 41% overall yield. After analyzing the structure of (−)-julocrotine, we set out to synthesize it in only three steps from commercially available L-Cbz-glutamine, in a sequence of cyclization (a), N-alkylation (b), and the removal of the protecting group followed

• chiral center of 4 can be observed even in the presence of weak bases such as potassium carbonate [17]. Thus, we decided to use a base-free N-alkylation protocol, namely the Mitsunobu reaction of 3 and the readily available 2-phenylethanol [18]. This protocol gave the desired optically active product in

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• Imines and oximes are versatile synthetic intermediates for the preparation of dyes, pharmaceuticals, and agricultural chemicals. Sun et al. have reported a multi-task Au/hydroxyapatite reagent for the heterogeneous catalyzed oxidation of alcohols and amines to imines or oximes [56]. N-alkylation of

• primary amines is an important reaction in organic synthesis. He et al. developed an efficient gold-catalyzed one-pot selective N-alkylation of amines with alcohols [57]. In their study, gold nanoparticles supported on titania act as an efficient heterogeneous catalyst for the reaction to give the N

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• steps involved. All attempts to achieve metathesis on another diene precursor having an endocyclic N-atom (the result of N-alkylation of 77 with 3-iodo-2-(methoxymethyloxy)prop-1-ene) led to either recovery of the starting material or olefin isomerization, even in the presence of a number of ruthenium

Identification and synthesis of impurities formed during sertindole preparation

• I. V. Sunil Kumar,
• G. S. R. Anjaneyulu and
• V. Hima Bindu

Beilstein J. Org. Chem. 2011, 7, 29–33, doi:10.3762/bjoc.7.5

• (23) following the reaction sequence used to synthesize 1 (Scheme 6). During the N-alkylation reaction there is always the probability of dialkylation, hence the dialkylated piperidine 28 was synthesized by prolonged condensation of imidazolidinone 16 with sertindole (1), followed by purification by

Conjugated polymers containing diketopyrrolopyrrole units in the main chain

• Bernd Tieke,
• A. Raman Rabindranath,
• Kai Zhang and
• Yu Zhu

Beilstein J. Org. Chem. 2010, 6, 830–845, doi:10.3762/bjoc.6.92

• , and the chromophore requires to be functionalized with polymerizable groups. The solubility can be increased by N-alkylation [10], arylation [11] or acylation [12] of the lactam units thus preventing hydrogen bond formation between the chromophores. Polymerizable groups can be attached to the aryl

• in Scheme 1. For the preparation of brominated diphenyl-DPPs it is necessary to start from bromobenzonitrile and a succinic acid ester and to prepare first the dibromophenyl-DPP pigment, which is subsequently N-alkylated to yield the soluble dibromo-dialkyl-DPP monomer M-1. While the N-alkylation of

• . Conclusion Diaryldiketopyrrolopyrroles are insoluble red pigments, which on N-alkylation of the lactam groups and bromine substitution of the aryl groups can be converted into readily soluble monomers suitable for Pd-catalyzed polycondensation reactions. Using Suzuki, Stille, Heck and other aryl-aryl

Synthesis of some novel hydrazono acyclic nucleoside analogues

• Mohammad N. Soltani Rad,
• Ali Khalafi-Nezhad and
• Somayeh Behrouz

Beilstein J. Org. Chem. 2010, 6, No. 49, doi:10.3762/bjoc.6.49

• that among published methods for N-alkylation of imidazole derivatives [26][27][28][29][30][31][32][33][34], the method developed by Liu et al. [35] was the most appropriate one for N-alkylation of azoles and their derivatives, since in this method the formation of quaternary imidazolium salts is

• Table 1 indicates, the N-alkylation reactions of nucleobases were achieved regioselectively. In the case of pyrimidine nucleobases, N(1)-alkylated compounds 1h–1l were the major products (43%, 40%, 51%, 47% and 28%); however, N(1),N(3)-dialkylated adduct was also observed in trace amounts (<10

• –1o. Thus, we have modified Scheme 1 by using DMF as the solvent of choice for nucleobases (Scheme 2). Thus, the condensation of purine and pyrimidine nucleobases as well as theophylline and theobromine with 2-bromoacetophenones using K2CO3 in anhydrous DMF under reflux conditions provides the N

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• 17a or bromopropionate 17b suffered from competing N-alkylation but returned acceptable yields of the esters 18a and 18b (Scheme 6). As with 13, we anticipated that the silyl ketene acetal derivatives 19 would be challenging to isolate, so both starting esters 18a and 18b were treated with LDA and

Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors

• Georg Schitter,
• Elisabeth Scheucher,
• Andreas J. Steiner,
• Arnold E. Stütz,
• Martin Thonhofer,
• Chris A. Tarling,
• Stephen G. Withers,
• Jacqueline Wicki,
• Katrin Fantur,
• Eduard Paschke,
• Don J. Mahuran,
• Brigitte A. Rigat,
• Michael Tropak and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2010, 6, No. 21, doi:10.3762/bjoc.6.21

• Kids Hospital, 555 University Avenue, University of Toronto, Ont., Canada M5G 1X81 10.3762/bjoc.6.21 Abstract N-Alkylation at the ring nitrogen of the D-galactosidase inhibitor 1-deoxygalactonojirimycin with a functionalised C6 alkyl chain followed by modification with different aromatic substituents

Synthesis of imidazol- 1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

• Santosh Kumar Singh,
• Narendra Manne,
• Purna Chandra Ray and
• Manojit Pal

Beilstein J. Org. Chem. 2008, 4, No. 42, doi:10.3762/bjoc.4.42

• -acetic acid hydrochloride was achieved via N-alkylation of imidazole using tert-butyl chloroacetate followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized imidazol-1-yl-acetic acid hydrochloride was

• then utilized to prepare zoledronic acid. Keywords: ester; N-alkylation; imidazol-1-yl-acetic acid hydrochloride; zoledronic acid; Introduction Zoledronic acid (Z, Figure 1) [1][2][3][4][5][6][7] is a third-generation bisphosphonate (or diphosphonate) derivative characterized by a side chain that

N-1 regioselective Michael- type addition of 5-substituted uracils to (2-hydroxyethyl) acrylate

• Sławomir Boncel,
• Dominika Osyda and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2007, 3, No. 40, doi:10.1186/1860-5397-3-40

• against numerous DNA-viruses.[5] One of the most convenient methods of uracil ring N-alkylation is the Michael-type addition. Other general ways of alkylation are: nucleophilic substitution of halogenoalkyl substrates by activated uracil rings (in the N-anionic or O-persililated derivatives);[6][7

Reactions of glycidyl derivatives with ambident nucleophiles; part 2: amino acid derivatives

• Gerald Dyker,
• Andreas Thöne and
• Gerald Henkel

Beilstein J. Org. Chem. 2007, 3, No. 28, doi:10.1186/1860-5397-3-28

• model compound (Scheme 2, see Supporting Information File 1 for full experimental data), readily accessible as a mixture of diastereoisomers by N-alkylation of racemic 4 [8] with epibromohydrin (2a) in DMSO. Again, under basic as well as acidic conditions (for instance heating in trifluoroacetic acid