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

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• economical and safe procedure using diethyl 2-acetamidomalonate (4) and propargyl alcohol as starting materials to synthesize 1. The synthesis was completed via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• -pot manner, since more harsh basic conditions are required for carrying out amide hydrolysis of 5. Because the following diazotization of 6 requires strong acidic conditions, the proper choice of acidic hydrolysis and decarboxylation of 5 in H2SO4 thus also further facilitated the one-pot conversion

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• , arenediazonium salts are especially attractive precursors which constitute versatile alternatives to haloarene-based strategies. They are readily available by diazotization of anilines, no toxic metals are required; the bond cleavage generates gaseous N2 which escapes the reaction mixture. Photoredox reactions

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• explored to produce the corresponding functional monomer 4 and thus the β-CD dimer 5. Linker 2 was prepared from methyl 2-aminoterephthalate via a sequence of diazotization–iodination–phosphanylation reactions [4] (Scheme 2a). The new, doubly phosphanylated dimethyl terephthalate linker 3 was prepared from

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• conditions, a production yield of 20 g EDA day−1 was achieved using a microreactor with an internal volume of 100 μL. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. Keywords: diazo compounds; diazotization; ethyl diazoacetate (EDA

• elimination of the sulfone substituent. Additionally, Ley et al. [19] recently prepared a range of α-hydroxy acids in flow starting from the corresponding amino acids, involving diazotization of the amine to the diazonium salt in a biphasic system. Inspired by Ley’s approach, which is significantly more atom

• efficient than the sulfonylhydrazone pathway, we chose to synthesize EDA (1) from glycine ethyl ester (2) using readily available sodium nitrite [20] (Scheme 1). Although the diazotization step itself resembles the first step of Ley’s hydroxy acid synthesis, we specifically aimed to produce and isolate the

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

• František Josefík,
• Markéta Svobodová,
• Valerio Bertolasi and
• Petr Šimůnek

Beilstein J. Org. Chem. 2013, 9, 1463–1471, doi:10.3762/bjoc.9.166

• (diazotization using cold NaNO2/HCl with subsequent precipitation, from the filtered solution of the diazonium chloride, by aqueous sodium tetrafluoroborate). Precipitated diazonium tetrafluoroborates were dried in vacuo in a desiccator and stored in a refrigerator. Compound 6 was prepared from δ-valerolactam

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• developed to solve extraction problems that occur when partition coefficients are low, for example during diazotization of amino acids in flow leading to the corresponding α-hydroxy acids [96]. Three separators were positioned in series to ensure full extraction of the polar product with a variety of

• despite turbulence caused by vigorous evolution of nitrogen gas during the diazotization reaction. Batches of over 20 g were readily prepared by operation of the flow system necessitating separation of over 3 L of solvent. In a single run, the full quantity of α-hydroxyisovaleric acid precursor required

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• began with the acetylation of 4-chloro-3-nitroaniline (9) followed by reduction of the nitro group using iron and hydrochloric acid to generate aniline 10. The azido group was introduced by diazotization/azidation to provide 11. Deacetylation with potassium hydroxide revealed aniline 12, which was then

• azide and acetylene, was prepared from aniline 26. Introduction of the azide was accomplished via diazotization/azidation, followed by standard amide coupling of 27 and 18 to afford final aryl azide photoprobe 28. Table 2 summaries the biological data for the four final candidate photoprobes

A bisazobenzene crosslinker that isomerizes with visible light

• Subhas Samanta,
• Harris I. Qureshi and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2012, 8, 2184–2190, doi:10.3762/bjoc.8.246

• -linked bisazobenzene derivative 2 was prepared by a double diazo-coupling reaction between the donor 1,4-diphenylpiperazine (7) and the acceptor 4-acetamido-3-sulfobenzenediazonium chloride (3), which was synthesized in situ by diazotization of sodium 2-acetamido-5-aminobenzenesulfonate (4) using sodium

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• nitrogen [18] nucleophiles, and the oxidative nucleophilic substitution with Grignard and alkyllithium reagents [19]. Reduction of the nitro group in 1 or 2 to (pentafluorosulfanyl)anilines followed by acylation, SEAr halogenation or diazotization (with follow-up reactions) has also been described [11][20

• and 4, which are available by vicarious nucleophilic substitution (VNS) of commercial nitrobenzenes 1 and 2 with diethyl chloromethylphosphonate [16]. If required, the nitro group can be removed by a reduction/diazotization/reduction sequence before or after the HWE reaction (Scheme 1). The HWE

• conditions were tested, but no system for selective reduction of the nitro group was found. Diazotization was carried out with the aim to prepare 1,2-diarylethane 9d from aniline 8d (Scheme 3). A combination of sodium nitrite and phosphoric acid was used. (With HCl, substitution of the amino function by a

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• aromatic ring and an aryl diazonium cation. The synthesis of azobenzene-dye-coupled DAN 5 began with 4-aminobenzoic acid tert-butyl ester (Scheme 1). Diazotization and coupling with phenol afforded 1 in 60% yield, which was comparable to the reported synthesis [46]. Compound 1 was alkylated with ethyl 4

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• to react with the selenocarboxylates derived from Nα-protected amino acids to form the desired amides. The azides can be readily prepared in excellent yields through diazotization of p-nitroaniline and 7-amino-4-methylcoumarin, followed by treatment with sodium azide, and, more importantly, the

• conjugates. 7-Azido-4-methylcoumarin was readily prepared from 7-AMC by the standard diazotization/sodium azide protocol in a yield of 92%. Under the same reaction conditions described above, the amidation of 7-azido-4-methylcoumarin with various amino selenocarboxylates gave the desired Nα-protected

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• starting from substituted sulfonamides 71. Sulfonamides 71 after diazotization undergo a coupling reaction with malononitrile to generate the hydrazones 72, which on cycloaddition with hydrazine hydrate give the corresponding pyrazoles (Scheme 19). Reaction of ketenes, particularly those with a cyano group