Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• closure to furnish the 1,2,4-triazolium 97 (Scheme 18) [65]. In the last example of this section, only one nitrogen atom of the hydrazone takes part in the cycloaddition reaction. In 2018, Zhang et al. realized the electrochemical (3 + 2)-cycloaddition of trimethylsilyl azide (102) with aldehyde-derived N

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• from triazenylpyrazoles. Initial experiments with TFA and trimethylsilyl azide at 0–25 °C in DCM failed for 4-substituted pyrazoles; the formation of the target products was only observed when 5-methylpyrazoles such as 15b were used. Therefore, a modified procedure was applied, heating the triazenes to

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• be a challenging substrate for MCRs and this was also the case for the synthesis of oxo-tetrazoles via a Passerini tetrazole reaction [19]. In a model reaction, we investigated benzyl isocyanide (1 equiv), paraformaldehyde (2 equiv) and trimethylsilyl azide (1 equiv) as easily available substrates

• . Trimethylsilyl azide is considered as a safe replacement of metal azides. We started the solvent optimization with MeOH and H2O as solvent system at room temperature, however, it did not yield any product even after 3 days (Table 1, entry 1). The use of DMF to improve the solubility of the paraformaldehyde solid

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• the reported procedures [41], the Ugi-azide reaction of 2-bromobenzaldehyde (1a, 1 mmol), allylamine hydrochloride (2, 1 mmol), trimethylsilyl azide (3, 1 mmol) and tert-butyl isocyanide (4a, 1 mmol) in MeOH at 40 °C for 24 h afforded 1,5-DS-1H-T 5a in 92% yield after chromatography purification. Our

• mmol), trimethylsilyl azide (3, 1 mmol), and tert-butyl isocyanide (4a, 1 mmol) was stirred in MeOH at 40 °C for 24 h, and after the reaction was completed, the solvent was evaporated under vacuum to give crude Ugi adduct 5a which was used for the intramolecular Heck reaction without further

• reactions in hands, we next evaluated the substrate scope by synthesizing 11 derivatives (Scheme 4) using nine benzaldehydes 1, two isonitriles or ethyl isocyanoacetate 4, allylamine hydrochloride (2), and trimethylsilyl azide (3) for the initial Ugi-azide reaction. Among them, products 6a and 6b from the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reactivity than electron-withdrawing groups, and the thiolation occurred mainly at the para position to the hydroxy group in phenols. In 2016, the azidoarylthiation of various alkenes 9 by trimethylsilyl azide (10) and N-(organothio)succinimide 1 to the corresponding products containing ortho-sited azide and

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• the dual catalytic ATRA-RLT cycle. III: Our lab and Xu reported photochemical diazidation of alkenes carried out using iron and trimethylsilyl azide. IV: The proposed mechanism for photoinduced LMCT between iron and azide ligands as well as RLT on azidoalkyl radical intermediates. Pioneering and

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• examining of other potential arenes capable of undergoing electrophilic aromatic substitution would expand the applicability of the reaction. Carboazidation In 2018, Yang investigated the three-component carboazidation of styrene derivatives 115 with alkanes 101/139b and trimethylsilyl azide for the

• carboazidation product was observed. In the same year, the Xu laboratory demonstrated Togni’s reagent could be employed for the synthesis of γ-azido fluoroalkanes [128]. In 2019, Chu and co-workers demonstrated the three-component carboazidation of alkenes with chloroalkanes and trimethylsilyl azide could be

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• selective activity towards certain tumor cell lines. Keywords: antiproliferative activity; Schmidt reaction; steroids; tetrazoles; trimethylsilyl azide; Introduction Bile acids are naturally occurring steroidal surfactants that play various biological roles. Besides the well-known role as lipid

• hydrazoic acid and the formation of lactam, which often prevails, especially when hydrazoic acid is generated in situ by the action of Brønsted acid on sodium azide [25]. The use of trimethylsilyl azide (TMSN3) instead of hydrazoic acid for many transformations has gained attention since TMSN3 is less

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• -nitro-1,3-enynes 34 with amines, and trimethylsilyl azide (TMSN3, Scheme 16) [61]. The reaction could be carried out efficiently in the presence of 2.0 equiv of Cu(OAc)2·H2O. Interestingly, the addition of 10 mol % MnCl2 could promote the reaction more smoothly. A wide range of substituted aromatic

• products 52 were obtained efficiently through the cascade reactions of enynals 51, primary amines, aliphatic isocyanides, and trimethylsilyl azide. The following reaction involves Ag-catalyzed intramolecular 5-endo-dig cyclization and base (DMAP)-promoted oxidative isomerization. The presence of DMAP is

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• diphenyl phosphoryl azide (DPPA), trimethylsilyl azide (TMSA) and tetrabutylammonium azide (TBAA) are suitable for the reaction. Continuous flow C-3 mesyl shikimate azidation using either DPPA or TMSA. The use of either DPPA or TMSA as the azidating agent for mesyl shikimate 4 was investigated in a

• 4 in the presence of various azidating agents. Sodium azide (NaN3), diphenylphosphoryl azide (DPPA), trimethylsilyl azide (TMSA) and tetrabutylammonium azide (TBAA) were the various azidating agents investigated in this system. Two syringe pumps were used to pump reagents from two 10 mL SGE Luer

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• aldehydes were reacted in parallel with trimethylsilyl azide and tritylamine under microwave irradiation – followed by removal of the trityl group and acylation to afford the N-acylaminomethyltetrazoles 1a–s and 2a–l. The functionalized tetrazoles were obtained in moderate to excellent yields over three

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of polystyrene resin 3 as the amine component. After resin removal with piperidine in DMF, a combinatorial strategy of replacing the carboxylic acid component with trimethylsilyl azide (TMSN3) (azido-Ugi reaction) or cyanic acid, followed by Fmoc removal (TFA), allowed the formation of the tetrazole

• bis(1,5-disubstituted tetrazoles). Methyl isocyanoacetate 13a was used as an essential component in the first hydrazino-Ugi-azide reaction allowing consecutive Ugi reactions to take place. In the first step, 13a, hydrazides, aldehyde or ketone, trimethylsilyl azide (TMSN3) and ZnCl2 (10 mol %) in

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• pentaacetyl glucose (1) with trimethylsilyl azide in the presence of SnCl4 directly into azide 8 (Scheme 5) as was previously described for the classical batch preparation [39]. At a resident time of 7 minutes an 80% yield of azide 8 could be achieved. Conclusion In conclusion, we have demonstrated that low

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• was applied for the presented approach. Therefore, 5a and 5b had to be converted first to the unsaturated esters 6a and 6b (Scheme 2) [20][21]. These compounds were reacted with trimethylsilyl azide (TMSN3) under Pd0 catalysis. With this protocol, the azide was introduced under double inversion of the

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• ], glycoconjugates [30][31][32], N-glycosyl heterocycles [33][34], N-glycosyl triazole [35][36], etc. Glycosyl azides can be accessed from the corresponding glycosyl halides [37][38][39][40] by nucleophilic displacement with NaN3 or using trimethylsilyl azide in the presence of a phase transfer catalyst [41][42][43

• ][44][45]. More commonly, glycosyl azides are synthesized from per-O-acetylated sugars using trimethylsilyl azide in the presence of a variety of Lewis acids such as SnCl4 [46], TiCl4 [47][48], BF3·OEt2 [49], TMSOTf [50][51], etc. However, at higher concentration Lewis acids can potentially lead to

• slow anomerization [52]. In 2011, Chen’s group reported that 5 mol % FeCl3 can catalyze the reaction of trimethylsilyl azide with per-O-acetylated β-monosaccharides to afford glycosyl azides in 3–7 h, whereas per-O-acetylated β-di- and trisaccharides required 22–28 h for complete conversion [53

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• tetrazoles are intermolecular cycloaddition reactions and isocyanide-based multicomponent reactions (IMCRs). Indeed, the Ugi-multicomponent reaction using TMSN3 (trimethylsilyl azide) as acid component, originally reported by Ugi in 1961 [10], is one of the best and most general methods for the synthesis of

• and 6 with hydrazine monohydrate, following a known procedure (Scheme 2) [31]. To access the acylhydrazino-tetrazoles, the hydrazides 2a–c were subjected to a multicomponent reaction comprising an aldehyde or ketone 7a–h, trimethylsilyl azide (TMSN3, 8), methyl isocyanoacetate (9) and ZnCl2 (10 mol

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• obtained allylic epoxides were regio- and stereoselectively opened with trimethylsilyl azide under palladium catalysis. Finally, a suitable deprotection protocol, starting with acidic acetate cleavage and ozonolysis was established. Peracetylation of the products simplifies purification and subsequent

• (CHCO2Me)) generated allylic epoxides 4a–c, which in turn permitted the application of reliable palladium chemistry for the epoxide opening [27][28][29]. Thus, compounds 4a–c were regio- and stereoselectively opened with trimethylsilyl azide and Pd(PPh3)4 as a catalyst [30], furnishing syn-azido alcohols

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• substrate afforded nucleosides 30 bearing a N-acyl α-amino acid amide moiety at the uracil C-5 carbon atom (Scheme 14) [79]. The variant of the reaction with trimethylsilyl azide (TMS-N3) in place of the carboxylic acid gave the tetrazole-substituted nucleosides 31 [79]. Products 30 and 31 were obtained as

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• supposed to be the main species after azido iodination, was regenerated by first ion exchange to the iodide form 2. Next, oxidation to the bisacetoxy iodate(I)-complex 7 was achieved by treatment with diacetoxyiodo benzene. Finally, pumping of a solution of trimethylsilyl azide (TMSN3) in dichloromethane

Recent advances in the development of alkyne metathesis catalysts

• Xian Wu and
• Matthias Tamm

Beilstein J. Org. Chem. 2011, 7, 82–93, doi:10.3762/bjoc.7.12

• starts from N-heterocyclic carbenes 1 which react with trimethylsilyl azide to afford 2-trimethylsilyliminoimidazolines 2. After treatment with methanol, the corresponding imidazolin-2-imines 3 can be conveniently isolated [60]. Deprotonation by alkyl lithium reagents leads to imidazolin-2-iminato

Controlling hazardous chemicals in microreactors: Synthesis with iodine azide

• Johan C. Brandt and
• Thomas Wirth

Beilstein J. Org. Chem. 2009, 5, No. 30, doi:10.3762/bjoc.5.30

• [24][25]. Highest yields were obtained with commercially available tetrabutylammonium azide (Aldrich), although great care has to be taken as this compound is very hygroscopic. Calculations indicate that the synthesis of iodine azide from trimethylsilyl azide and iodine monochloride is slightly

• ratio of about 1:3 of trimethylsilyl azide and trimethylsilyl chloride upon reaction with iodine monochloride. This mixture was not efficient in the reaction with aldehydes, only an unidentifiable mixture of products was obtained. The reactivity of carbamoyl azides is analogous to isocyanates, compound