Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• side reactions was carried out with benzyl 3-amino-4,4,4-trifluorobutanoate (1a) and benzoic acid (3a) as model substrates. The initial reaction of amine 1a and acid 3a in acetonitrile in the presence of diazotization reagent tert-butyl nitrite with CuI (10 mol %) as catalysts for 2.5 h at room

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• , Bunkyo-ku, Tokyo 113-8657, Japan 10.3762/bjoc.20.1 Abstract Recently, we identified the biosynthetic gene cluster of avenalumic acid (ava cluster) and revealed its entire biosynthetic pathway, resulting in the discovery of a diazotization-dependent deamination pathway. Genome database analysis revealed

• biosynthesis by heterologous expression of the cma cluster and in vitro enzyme assays using recombinant Cma proteins. The ATP-dependent diazotase CmaA6 catalyzed the diazotization of both 3-aminocoumaric acid and 3-aminoavenalumic acid using nitrous acid in vitro. In addition, the high efficiency of the CmaA6

• reaction enabled us to perform a kinetic analysis of AvaA7, which confirmed that AvaA7 catalyzes the denitrification of 3-diazoavenalumic acid in avenalumic acid biosynthesis. This study deepened our understanding of the highly reducing type II polyketide synthase system as well as the diazotization

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• (5). This compound was synthesized smoothly within three steps in 16.6% overall yield. The synthetic route commenced from the preparation of N-protected amine 3, followed by the deprotection of benzylamine 3 to furnish 4 and ended with the diazotization of 4 using tert-butyl nitrite. As a result, the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• later to make the synthesis more modular, and the resolution is straightforward late in the synthesis. Additionally, the presence of the nitro group in CPA 2 was chosen for two reasons: 1) the possibility to further functionalize at this position through reduction, diazotization, and metal-catalyzed

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• synthetically and successful syntheses of different manifold isomers. 3,6-Dihydro-4H-pyrazolo[3,4-d][1,2,3]triazin-4-ones 2, as one example of the diverse compound class, can be gained via diazotization of 3-amino-1H-pyrazole-4-carboxamides 1a or 3-amino-1H-pyrazole-4-carbonitriles 1b and subsequent cyclization

• ]triazines 5 and intermediates 9, 12, and 13 and their calculated IC50 values after treatment of HeLa cells with different concentrations of the respective compounds. Synthesis of 3,6-dihydro-4H-pyrazolo[3,4-d][1,2,3]triazin-4-ones 2a,b by diazotization of 3-amino-1H-pyrazole-4-carboxamides 1a or 3-amino-1H

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• of purine [73][74][75][76] or alkylation of inosine or guanosine derivatives (Ib→II, Scheme 1) [30][36]. In the next step, azide can be introduced either by a second SNAr reaction on the C2-halo derivative or by diazotization/azidation at C2. Then, the Cu(I)-catalyzed azide–alkyne cycloaddition

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• (Scheme 7 and Scheme 9). The methodology involves the in situ formation of the aryldiazonium salt by diazotization with tert-butyl nitrite followed by the formation of a trivalent radical chalcogenide. Oxidation to the chalcogenide cation by SET with the cation-radical NiTPP (path a, Scheme 9) or SET with

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• this respect, we elaborated our own procedure for the preparation of aryl-substituted methyl 3-chlorothiophene-2-carboxylates 2, which consists of diazotization of the corresponding 3-aminothiophene-2-carboxylates 1 in acetonitrile solution with an aqueous sodium nitrite (1.1 equiv) solution in the

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• generated separately, using sulfuric acid and sodium nitrite, prior to being added to the monoaminocalix[4]arene 10 at 0 °C. After diazotization (15 min), an aqueous solution of sodium azide was added dropwise. After two hours at 0 °C the reaction was extracted with ethyl acetate, and the monoazidocalix[4

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• antagonists via replacement of a thioether or amide bond by an azo bridge. Synthesis of the differently substituted quinoxaline azobenzene derivatives 5a and 5b via Baeyer [62]–Mills [63] reaction [64][65]. Synthesis of the methoxy-substituted quinoxaline derivative 12a via diazotization [66][67][68][69

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• -hydroxypyroglutamate was employed in the important approach to (2R,4R)-monatin [117]. Carbapenems can be generated from the intermediary enantiomeric 3-hydroxy- or 4 hydroxy-L-glutamic acids in cell-free environments [118]. Diazotization of (2R,3R)-2 provided 2-deoxy-L-1,4-ribonolactone which was later transformed

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• sheet. The carboxyl groups contained in GO and RGO constitute important targets for structural expansion, as COOH moieties can be transformed into, e.g., amide- or ester-type linkages. On the other hand, the functionalization of sp2 carbons is most commonly performed utilizing a diazotization approach

• structures of the modified graphene-family nanoplatforms constitute major inaccuracies. A comment on the functionalization of sp2 carbon: diazotization The diazotization reaction is a widely applied protocol for the functionalization of sp2 carbon in the graphene sheet [9][46][47][48]. This phenomenon is

• desirable due to the commercial accessibility of the reactants (aromatic amines). The diazotization reaction is also a versatile approach, as a wide range of arylamines (bearing various substituents) can be subjected to the process [9]. This reaction’s mechanism is not fully understood, but several

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• instead of pyrophoric Raney nickel. Finally, a diazotization procedure with subsequent azide substitution [37][38] gave calix[4]arene azide derivatives 4 and 8. For the latter reaction a mixture of DMF/glacial acetic acid 3:1 was found to be the optimal solvent. The structures of macrocycles 4 and 8 were

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• . The amino group can be easily transformed into numerous functional groups including halides or cyano groups, which is known as the Sandmeyer reaction. This transformation contained two steps: Diazotization of aromatic amines led to aryldiazonium salt, followed by conversion of diazonium group into

• salt. Later, the same group developed a one-pot Sandmeyer trifluoromethylation combining the diazotization and the Sandmeyer reaction (Scheme 26) [46]. This reaction proceeded smoothly using tert-butyl nitrite as the diazotization reagent, TMSCF3 as the trifluoromethylation reagent in the presence of

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• view to its subsequent elaboration, e.g., via diazotization. However, a variety of reduction conditions resulted either in no observable reaction (Table 2, entries 1 and 2), or else in defluorination at the benzyl position (Table 2, entry 3). The latter proceess is precedented [41]. Since none of the

• bypassing any diazotization process. Hydrogenation of 41 with 10% Pd/C in the presence of acetic anhydride allowed the isolation of acetanilide 43 in moderate yields (Table 2, entries 4−6). It was found that the acetic anhydride solvent needed to be freshly distilled in every case in order for the reaction

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• according to the procedures previously described in literature [14][23]. In order to obtain phosphoramidite 11 we have developed a synthesis (Scheme 2) based on L-threonine as a starting material. L-Threonine was converted to bromo-derivative 6 by a diazotization reaction using sodium nitrite followed by

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• II azo dye was used as a model reaction for the study. At found optimal azo coupling reaction temperature and pH an investigation of the optimum flow rates of the reactants for the diazotization and azo coupling reactions in Little Things Factory-MS microreactors was performed. A conversion of 98

• reaction conversions ranging between 66–91% were attained. Keywords: azo coupling; diazotization; microreactor; scale up; Introduction Going green, a familiar catch phrase in the chemical industry, in addition to environment protection laws have influenced and also triggered the development of cleaner

• -naphthol. The method boasts of shorter reaction times [4] with high yields (Scheme 2). Mirjalili et al. also used silica supported boron trifluoride and was able to carry out diazotization at room temperature [5] after they discovered that the diazonium salts obtained were stable at room temperature even

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• , nitro(pentafluorosulfanyl)benzenes are widely-available primary industrial products and starting materials to other SF5-benzenes which were prepared by reduction followed by condensation or diazotization chemistry [8][14][15][16], SEAr [17], SNAr [18][19][20][21][22][23][24], or metal-catalyzed cross

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• electron-enriched arenes [7][8][9], diazotization/halogenations of anilines [10], and ortho-lithiation/halogenations sequence [11] among others are widely used as traditional strategies for creating C–X bonds. However, one or more problems such as poor site-selectivity, reliance on toxic halogen sources

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• . Starting from aniline derivative 1b, a one pot diazotization–borylation sequence using different acids afforded the corresponding borylated product 2b in good yields (Table 3). Suzuki–Miyaura cross-coupling reactions of boronates 2a and 2b with aryl iodides using a simple system without any optimization

• B2pin2. Importantly, the yields of SF5-phenyl iodides 10a and 10b using our two-step diazotization–iodination method significantly exceed those obtained by classical Sandmeyer reaction (ca. 80% yield over two steps compared to 63% for 10a and 50% for 10b by one-pot Sandmeyer procedure requiring 10 fold

• tetrafluoroborates 3a and boronates 2b. One pot diazotization-borylation of 1ba. Hydrodediazoniation of 3a and 3b with THFa. Supporting Information Synthesis and characterization of all products, copies of 1H, 13C, and 19F NMR spectra of newly synthesized products, and X-ray crystallographic files of the compounds

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• enzyme affinity. Results and Discussion Azobenzenes can be synthesized by a variety of known chemical transformations [8]. Among them the most widely used is the diazotization of aniline, followed by trapping of the diazonium salt with an electron-rich aromatic compound (such as anilines and phenols

• have the biggest impact on the electronic properties of the sulfonamide group due to communication through the conjugated π-system of the aromatic units and the diazene unit. Commencing with the diazotization of sulfanilamide and subsequent reaction with phenol, N,N-diethylaniline or N-phenylmorpholine

• -pot reaction over three steps in 25%. By diazotization of 1d and trapping the salt with TMS-azide, we obtained azido azobenzene 1e in 63% yield through a [3 + 2] and retro-[3 + 2] cycloaddition (Scheme 1b) according to the procedure of Barral et al [10]. For the Mills reaction, different nitroso

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• was achieved by palladium-catalyzed reduction [10] followed by diazotization of the amine and subsequent substitution with azide [30]. 4-Bromobenzaldehyde (7) was readily converted to ethynyl-F-BODIPY 11 according to the literature procedures [11][31]. Azido-F-BODIPY 9 and ethynyl-F-BODIPY 11 were