Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• , were synthesized in satisfactory 26–28% isolated yields. Direct N-alkylation of 1,4,10-trioxa-7,13-diazacyclopentadecane by symmetric DBTAA derivatives bearing bromoalkoxy pendants proceed smoothly at a reasonable level of dilution (1.25 mM). The structures were fully characterized by HR-ESIMS, FTIR

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• this study, the alkylation of 1-adamantyloxy-4,5-diphenylimidazole (8b) with 12b was also attempted under the same conditions. In that case, however, the expected N-alkylation did not occur at room temperature and even after 2 d the starting materials were found unchanged in the reaction mixture. On

• the other hand, the attempted N-alkylation of 8b upon MW irradiation led to the formation of a mixture of starting materials and some unidentified decomposition products. Due to the great importance of both carbocyclic and heterocyclic systems functionalized with the adamantyl group [27], different

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• regioselective manner, without the formation of any byproduct derived from the N-alkylation of the amide group. Structural characterization Table 1 gives the nuclear magnetic resonance spectroscopic data that allowed to confirm the structures of substances 5 and 7, and thus also confirmed the regioselectivity of

• resonance structures due to the adjacent carbonyl, being therefore, less stable (Scheme 5). Reaction paths analysis The paths for the SN2 N-alkylation reaction of both deprotonated species (oxoquinoline and carboxamide N–H units) using bromoethane were obtained. It is worth highlighting that for each of the

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• give 3. Complete conversion of starting material was observed by 1H NMR, however, the isolated yield of 3 was poor possibly due to competing N-alkylation of the Boc group. Isolation of the O-alkyl product 3 was confirmed by 13C NMR. Despite the poor isolated yield of 3 the mass recovery was more than

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• product structure were also found for N-arylation or N-alkylation with tert-butyl fragments in the series of 1,2,3-triazole [15][16], tetrazole [17][18][19][20], and purine [21] derivatives. Meanwhile, knowledge of the accurate chemical structures of N-substituted heterocycles is essential for biomedical

• studies and computer-assisted drug design, e.g., molecular docking techniques. Thus, the development of effective methods for the unambiguous determination of N-alkylation site(s) in the azolo-azine series is important. The data that are required to solve this problem could be provided by 15N NMR

• crystals of adamantylated tetrazolylpyrazole derivatives [37][41]. Discussion Comparison of different NMR approaches for the determination of N-alkylation sites in fused heterocycles. The obtained data permit a comparison of the abilities of different NMR parameters (13C and 15N chemical shifts, JHN and

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• yield of 93%. The dark red pigment 6 is only sparingly soluble in commonly used solvents, and its purification was carried out by multiple washing with methanol. However, its twofold N-alkylation using 2-ethylhexyl bromoacetate in DMF/K2CO3 afforded 7 with a satisfactory yield of 68% and with

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• -deoxy-β-D-galactopyranoside (4) shows that N-alkylation of the amine function is the most advantageous way of modification. An introduction of one ethyl (11), two ethyl (12) or two propyl (13) groups at the amine function improves the antifungal properties of saponins 11–13 in comparison with

• results show how complicated the relationships between structure and biological activity are. Conclusion Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside, as well as its two N-acyl, three 2-ureido and three N-alkyl derivatives are reported. N-Alkylation of the amine function seems to be the most

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• spectroscopy, but the conversion of the starting material was less than 20% after 4 days, and 4 could not be isolated in pure form (Scheme 2). A possible reason for this failure could be the presence of the N–H acidic fragment in 3a, and therefore the tertiary analogue 5 was prepared by N-alkylation of 3a with

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• Anamarija Bris Mateja Dud Davor Margetic Laboratory for Physical-organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia 10.3762/bjoc.13.169 Abstract The mechanochemical N-alkylation of imide derivatives was studied

• synthesis of amines by their reaction with 1,2-diaminoethane. Keywords: ball milling; Gabriel reaction; imides; mechanochemistry; N-alkylation; Introduction The development of environmentally friendly organic reactions is a growing area of interest [1]. The reduction of the impact of chemical reactions on

• time, important progress was made in the development of various solvent-free organic reactions [5], especially by the use of the ball milling technique [6][7][8]. In continuation of our interest in eco-friendly organic syntheses [9][10][11][12][13][14], we studied mechanochemical N-alkylation reactions

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• linked with a central pyrimidine core and another one is linked by a rigid thiophene cycle as a π-conjugated bridge. We have applied a usual synthetic protocol which includes eight successive steps: O-alkylation of 4-methoxyphenol (1), N-alkylation of carbazole (2), formylation or acetylation of a

• ], Ullmann coupling [13][14], Buchwald–Hartwig amination [15] or N-alkylation of carbazole in the presence of alkali metal carbonates under MW irradiation [16]. In our case, the N-arylation was realized under phase transfer conditions using triethylbenzylammonium chloride (TEBA) as a catalyst [17][18

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• synthesis of N-alkylcarboxyspiropyrans (e.g., C4SP) involves N-alkylation of 2,3,3-trimethylindolenine (1) with a bromoalkanoic acid or ester 2, isolation of the resulting indolium salt 3 or treatment with base to generate the exo-methylene enamine 4, then condensation with the appropriate salicylaldehyde 5

• more efficient approach, reacting trimethylindolenine (1) directly with bromoalkanoic acids 2a–g, obviating the requirement for ester hydrolysis (Table 1). N-Alkylation of trimethylindolenine (1) with bromoalkanoic acids/esters is often slow and the solvent choice is crucial in identifying viable

• -bromocarbonyls such as bromoacetic acid are excellent SN2 electrophiles, and N-alkylation of 2,3,3-trimethylindolenine (1) with bromoacetic acid (2a) was successful, if somewhat sluggish, at room temperature. Reaction of the crude indolium salt 3a with 3-methoxy-5-nitrosalicylaldehyde (5) was also conducted at

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• required functionalization of both amino groups present in 2-ABA was achieved by different routes involving selective N-acylation and cesium carbonate-mediated N-alkylation reactions, avoiding protection/deprotection steps. The heterocycles were efficiently synthesized in short reaction times by microwave

• , necessary for the synthesis of dihydroquinazolines 2, were prepared by N-alkylation of the arylamino group present in compounds 4 using alkyl halides. In a previous work [63], we developed a methodology for the selective N-alkylation of anilines with ω-halonitriles in the presence of cesium carbonate and

• favorably with the reported methodologies. The preparation of the required aminoamides involves N-acylation and N-alkylation reactions, which were optimized to achieve selective monofunctionalization thus avoiding additional protection/deprotection steps. A judicious combination of these steps into

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• -protective group (see Scheme 3). The second strategy started with an N-alkylation of the commercially available N-methyl propargylamine with homoallyl bromide providing the tertiary amine 21 in 69% yield which was used without further purification. The subsequent treatment with n-BuLi and trapping with ethyl

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• could be synthesised by incorporation of CO2 from the supercritical solvent into the product. Keywords: continuous flow; heterocycle; N-alkylation; self-optimisation; supercritical CO2; Introduction N-alkylated amines are an important motif present in a range of pharmaceutically and industrially

• catalyst. In this case the only byproduct is water. Another approach to N-alkylation in which water is the only byproduct is the direct substitution of alcohols with amines. It is an attractive method; however, it requires significant activation of the alcohol or amine to proceed efficiently, and often a

• toxic solvents; furthermore post-reaction separation is simplified as the gas/liquid phases separate upon cooling. The use of supercritical methanol (scMeOH) for N-alkylation reactions has been reported before [29][30]. Our own investigations with heterogeneous catalysis in supercritical carbon dioxide

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• chloride to various primary and secondary amines. The authors propose that L1 binding with chloride results in a more electrophilic tritylated DMAP cation, and the binding affinity of the catalyst was found to correlate with the N-alkylation rate. Following the aforementioned studies, the Mancheno group

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• -tetra(prop-2-yn-1-yl)-1,4,8,11-tetraazacyclotetradecane diperchlorate is reported. Keywords: azamacrocycles; biphasic system; cyclam; cyclen; N-alkylation; Findings The tetraazamacrocycles cyclam (1) and cyclen (2) have been the subject of considerable interest over many years [1][2][3][4][5][6][7

• the origins of the differential ‘shaken versus stirred’ outcomes observed in this N-tetraalkylation reaction. To test the generality of the N-alkylation protocol, it was adapted to the preparation of a range of cyclam and cyclen derivatives, 4–12 (Scheme 1 and Table 1). The protocol proved effective

• in achieving N-alkylation with a range of substituted aromatic groups, affording the N-tetraalkyl products in generally good to excellent yields. In some instances the products were found to be partially soluble in the biphasic solvent system, which made isolation slightly less straightforward

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

• products 14b and 14c in a 1:1 ratio. The peaks at 164.3 and 114.4 ppm can therefore be assigned to the ipso carbon and ortho carbon of the p-nitrophenyl substituent in 14c. This observation was particularly interesting as N-alkylation of DBN [36] was not favored and instead underwent substitution. To test

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• this approach was much more variable at larger scales. Further N-alkylation with 3,3-dimethylallyl bromide was conducted using K2CO3. The resulting alkylated compound 4 was easily isolated by chromatography in good yield, however, the reaction was found to be difficult to force to completion

• reduced to the iodinated THQ 14 (see Supporting Information File 1 for crystal structure) using borane·dimethyl sulphide complex. A slight molar excess of the reducing agent causes de-iodination to give 10 in small quantities. N-Alkylation with highly lipophilic alkyl groups such as an isopropyl was next

• . Using 1.25 equivalents appeared to inhibit de-iodination completely, but the cyclisation reaction tended to plateau before full completion. Without the ortho-methyl, preference for isopropylation switched to N-alkylation, providing 50% of 20a and 26% of the O-isopropylimine 20b; a mixture that could be

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• nucleophilic N-alkylation of amides by using pre-functionalized electrophiles such as alkyl halides, alcohols or amines [36][37][38][39][40][41]. An alternative tactic which employs raw C–H bond conversion represents a revolutionary step in the synthesis of N-alkylamides. In 2007, Fu and co-workers [42

• in the presence of Cu(acac)2 and t-BuOOt-Bu enabled the C–H amidation for the synthesis of N-cyclohexyl amides without using a ligand or an additional solvent. More interestingly, the catalytic method was also efficiently applicable for the N-alkylation of sulfoximines for the synthesis of various

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• possessing a bulky aryl group introducing the other bulky N-substituent by means of an N-alkylation [33][34][35][36][37]. Indeed benzimidazolium salts that bear N-alkyl or N-alkenyl substituents can be accessed synthetically by simple routes in comparison with those possessing two N-aromatic substituents. We

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

• systems which are found in streptorubin B and metacycloprodigiosin [148][149][150]. In this context, the cyclooctene 164 was reacted with the intermediate formed in situ from chloramine-T and elemental selenium [151] and yielded the allylic amine derivative 165 (75%). An N-alkylation with propargyl

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• convenient than the use of CsOH·H2O. N-Arylation of MPTTFs and BPTTFs N-Alkylation of MPTTFs and BPTTFs can be easily achieved using SN2 reactions between a deprotonated pyrrole and a suitably activated aliphatic species [19][28]. N-Arylation of MPTTFs and BPTTFs, which allows an annelated TTF to be

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• (bromomethyl)-2-thioxo-1,3-dithiole (6) [21]. In order to determine the optimized experimental procedure to carry out the urea N-alkylation of compound 5, we took advantage from literature of previous works realized on glycoluril for such reaction using a 2,3-bis(halogenomethyl)aryl derivative. Reported

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• . Keywords: antimicrobial activities; D-glucosamine; diosgenin glycosylation; N-alkylation; Introduction Saponins are a group of steroid or triterpenoid glycosides, widely distributed in the plant kingdom [1]. Saponins are characteristic by their foaming properties in aqueous solution, causing them to be

• antimicrobial activity indicate that N-ethyl and N-propyl derivatives exhibit stronger activity against Gram-positive bacteria than the parent diosgenyl 2-deoxy-2-amino-β-D-glucopyranoside hydrochloride. Reagents used for the synthesis of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside (7). N-Alkylation of

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• . Figure 1B). Based on our earlier work [5], we first planned to employ an appropriate bromoalkyl mannoside for N-alkylation of the thymine N3 [28]. In this step, DBU can be employed as non-nucleophilic base [29] leaving the NHBoc group intact. When sodium hydride is employed instead, NHBoc is deprotonated