SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• with potential for further modification by cross-coupling. The full scope of the transformation can be found in Supporting Information File 1, Schemes S2 and S3 [45]. Concerning scope limitations, the azido-alkynylation of vinyl-pyridine 1b was unsuccessful and thiazole 1c only afforded 18% of the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• lead structure with ample space for structural variations. By formally replacing one pyridine moiety of 1,8-naphthyridine 4 by a five-membered thiazole unit, we have identified thiazolo[4,5-b]pyridine 5 as a strong inhibitor of acyl-ACP thioesterase, which has further been confirmed via an X-ray co

• 6). This result indicated that borohydride reagents were able to activate the thiazole moiety in [1,3]thiazolo[4,5-b]pyridines, leaving the pyridine unit unchanged. While sodium cyanoborohydride afforded a comparable result, albeit with lower conversion, the use of silane reagents at elevated

• temperature [23] led to the cleavage of the thiazole ring, furnishing disulfides 18b and 18c exclusively (Table 1, entries 7–10). Interestingly, the reaction of 5 with ammonia borane at elevated temperature in toluene [20] furnished three reaction products with a low yield since 2,3-dihydro[1,3]thiazolo[4,5-b

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• 1,2,3-triazole ring, either an additional pyrimidinedione, 4-nitroimidazole, isoxazole, 1,3,4-triazole, 2-oxochromone or thiazole ring, has been developed. The process was facilitated by a strong base and includes the cycloaddition reaction of 3,3-diaminoacrylonitriles (2-cyanoacetamidines) to

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

• 2017, the Co-catalyzed CDC for the C5-alkylation of oxazole/thiazole substrates with ethers afforded functionalized ethers in moderate to good yields (Scheme 29a) [91]. In 2016, Du et al. demonstrated that the construction of C(sp2)–C(sp3) bonds also proceeded smoothly with coumarins and cyclic or open

• tetrahydropyrans. CDC of thiazole with cyclic ethers. Cu(I)-catalyzed oxidative alkenylation of simple ethers. Cross-dehydrogenation coupling of isochroman C(sp3)–H bonds with anisole C(sp2)–H bonds. Pd(OAc)2/Cu(OTf)2-catalyzed arylation of α-C(sp3)–H bonds of ethers. Cu-catalyzed C(sp3)–H/C(sp2)–H activation

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• esters are also suitable substrates for the reaction. In this case hydrolysis and thiazole ring expansion were accompanied with the change of the thiazolotriazine junction type from thiazolo[3,2-b][1,2,4]triazine to thiazino[2,3-c][1,2,4]triazine. Keywords: N,S-heterocycles; ring expansion; skeletal

• closer location in structures 5 (Figure 3). In the downfield region of the 13C NMR spectra registered without proton decoupling for isomeric acids 4a and 5a, the carbon atom doublets of the carboxyl groups, carbonyl groups of thiazole (for 4a) or thiazine (for 5a) cycles, as well as multiplets of

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• and 3 is the lack of two proton signals associated with the thiazoline moiety. Instead, the proton spectrum of 3 features a signal at δH 8.55 (H-13). The HMBC correlations linking H-13 to 163.3 ppm (C-12) and 146.3 ppm (C-14) indicate the presence of a thiazole rather than a thiazoline moiety. This

• carbon atoms C-13 and C-14 of the thiazole moiety, the loss of one degree of unsaturation and a loss of 2 Da in mass, it can be deduced that compound 5 possesses an alcohol function. Compound 6 (0.4 mg) was obtained as a brown oil. It possesses a molecular ion at m/z 291.1165 [M + H]+, which suggests a

• metabolites that were recovered in this study share a phenolic moiety with a thiazole or thiazoline substituent. This motif is present in many siderophores, e.g., in pyochelin [26], yersiniabactin [28], agrochelin [29], micacocidin [30], the Massilia-derived massiliachelin [18], as well as in piscibactin [31

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts. Keywords: Eschenmoser coupling reaction; Hantzsch thiazole

• with a α-haloketone or α-haloester II. The initially formed α-thioiminium salt III can undergo either a base-catalyzed elimination to give nitrile X and thiol IX [10][11][12] or cyclization to give a thiazole XIII or thiazolone XI depending on the substituent at the carbonyl group Y. Both side

• Y: alkyl, aryl). This reaction pathway represents the well-known Hantzsch thiazole synthesis [13][14][15][16][17][18][19][20][21]. If the imidothioate IV is further deprotonated [10][11][12] at nitrogen using a strong base (e.g., NaOH/H2O or EtONa/DMF are strong enough), then another intramolecular

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• ,t and 4x,y). Lastly, we explored a few heterocycles that resemble imidazo[1,2-a]pyridine to vindicate the generality of this method. Gratifyingly, 6-phenylimidazo[2,1-b]thiazole, 2-phenylbenzo[d]imidazo[2,1-b]thiazole, and 2-phenylimidazo[1,2-a]pyrimidine participated well under the standard

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• alkenyl heteroarenes [61]. The aza-enolates were trapped with various Michael acceptors such as unsaturated ketones, esters, and amides (Scheme 25) [62]. The authors noted a strong substrate dependence of this process. The trapping reaction worked best with benzoxazole-derived substrate, while thiazole

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzamidine hydrochloride G. The reaction of D with amines may require an excessive amount of D due to competition between aminophenol and the byproduct aniline. A similar mechanism is considered for the construction of benzimidazole and thiazole rings. On the other hand, the released bismuth moiety, Ph3Bi=S

• , and achieved the syntheses of 2-aryl- and 2-alkylbenzazoles, such as oxazoles, imidazoles, and thiazole, in satisfactory yields. The protocol was successfully applied to the synthesis of tafamidis, a clinically used drug for transthyretin amyloid inhibition. The reaction is simple, can be performed in

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• pharmaceutical activities such as antimicrobial [2][3], antiviral [4], antitumor [5][6], anti-inflammatory [7][8] and so on. Moreover, as a type of important intermediates, thiazole is of prime importance in organic synthesis [9][10] which is used extensively in the preparation of flavors [11], polymers [12

• ], dyes [13], etc. These important features of thiazoles have driven intense interests in their facile synthesis [14][15][16][17]. Among various synthetic routes to the thiazole unit, the Hantzsch condensation of α-halo ketones (dielectrophiles) with various thioureas (dinucleophiles) should be the most

• and would lead to a large quantity of waste. Considering the importance of thiazoles in synthetic and medicinal chemistry, the development of greener and more atom economic processes for the thiazole synthesis has become increasingly necessary with growing awareness of environmental constraints

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• photophysical changes, have some common structural characteristics. For instance, heterocyclic units containing a nitrogen atom such as pyridine and thiazole, are one of the key structural features either in small molecules or polymers. Thus, the introduction of nitrogen with lone pairs of electrons in

• reaction. In order to clarify the coordination reaction of nitrogen atoms, Bazan’s group designed a conjugated polymer containing pyridine and thiazole groups and small molecule 15 (Figure 8) and compared the 1H NMR spectra and 19F NMR spectra after the addition of 1 equivalent B(C6F5)3 at various

• small molecule 15 containing pyridine and thiazole groups reported by Bazan et al. and pyridine groups-containing diketopyrrolopyrroles (DPP) 16–18 investigated by Huang et al. (a) 1H NMR spectra in the aromatic region and (b) 19F NMR spectra of compound 15 (top) and the mixture with 1 equivalent B(C6F5

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -capping. The resulting compounds were treated with chloroacetic anhydride and then with thiazole. After anion exchange the chiral thiazolium salts (R)-35a/b, which differ in the chain length of the axle, were obtained in 9%/42% overall yield (see Figure 8a). For comparison, a rotaxane containing a BINOL

• -based axle and an achiral macrocycle was also synthesized. This design was chosen to investigate the difference between a covalently and a mechanically linked chiral unit with regard to the chiral induction in asymmetric catalysis. By acylative end-capping, followed by introduction of the thiazole unit

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• combining thiazole, selenazole, pyrazole, indazole, and indole moieties with both carboxyl functional groups and cycloaminyl units [27][28][29][30][31]. In recent decades, various methods of constructing 1,2-oxazole ring systems have been developed [1][2][3][4][5][6][7][32]. The two primary pathways to 1,2

• the range of 14.4–14.7 Hz, while the 3JHN values were in the range of 1–3 Hz [42][43]. The coupling constants 13C,15N of a series of 15N-labeled pyrazoles gave 1JCN values of 8–11 Hz, while 2JCN were less than 2 Hz [44]. The 15N-labeled 1,2-thiazole moiety was readily determined by measuring the

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• , was reported as recently as 2018 [55]. More interestingly, conventional heating in acetic acid of an enaminone bearing a phenacylsulfanyl substituent adjacent to nitrogen on the C=C bond produced ethyl pyrrolo[2,1-b]thiazole-5-carboxylates in moderate yield, while the corresponding microwave-assisted

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• modified natural nucleobase that did not quench the fluorescence upon hybridization [148]. Köhler and Seitz introduced thiazole orange (TO, Figure 10), an intercalator dye originally designed for DNA [149], as a forced intercalation (FIT) probe in PNA. Because of rotation around the methine bond connecting

• thiazole and quinoline, TO fluorescence is almost completely quenched in ssPNA, but increases significantly upon hybridization to the complementary DNA [150]. The intercalation of TO in PNA–DNA duplex restricts rotation around the methine bond enforcing planarity of the two TO’s aromatic system, which

• base pairs in dsRNA [153][154]. Replacement of thiazole in TO with another quinoline gives bis-quinoline (BisQ, Figure 10), a red-shifted PNA nucleobase analogous to TO [155]. Although binding of BisQ with all four natural DNA nucleobases has not been explored in detail, BisQ-modified FIT PNAs showed

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• group stretching relying on buried g-CN structure in hydrogel network. The vTA photografting can be revealed via distinctive signals such as the emergent peak at 3081 cm−1, corresponding to C–H aromatic stretchings arising from the thiazole ring, the neck at 1687 cm−1 signifies the C=N vibration band

• , and at last the intensified peak at 1419 cm−1 indicates a C–N stretching of the thiazole ring. Proceeding the examination by UV–vis spectroscopy, overlaid absorption spectra of the samples revealed the photophysical differences as expected, since HG does not consist of photoactive g-CN particles in

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• ) or leads to a complex and inseparable mixture of products (when starting from 2a,b). The addition of a base (e.g., triethylamine, N-methylmorpholine, ammonia) which was originally found to be beneficial [33] for the rearrangement of the kinetically formed thiazole to the desired product now caused a

• desired Eschenmoser coupling reaction (route b). Therefore, the nucleophilicity of the conjugated base of the nitrogen (benzenecarbimidothioate or thioimidate) is exerted towards the oxindole carbonyl to give the thiazole. Moreover, if both benzene rings contain electron-withdrawing groups, enhancing

• either the leaving ability of the oxindole nitrogen (R1: Cl, NO2) or the acidity of the >C=NH2+ group (R2: Cl, CF3) increasing the proportion of the nucleophile >C=NH, then the formation of the thiazole (route a) is further accelerated (Scheme 2). Although the addition of a base generates the required C3

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• , Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium 10.3762/bjoc.16.243 Abstract N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• a lower affinity [38]. Along the same line, the influence of the length and substituents of the side chains at the G4-DNA ligands have been assessed for quinolinium [43], indoloquinoline [44][45], phenanthroline [46], phenothiazine [47], and thiazole orange [48] derivatives. In these studies, the

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• ; potassium persulfate; thiazole; vinyl azide; Introduction Vinyl azide is one of the most versatile and potent building blocks explored in the synthesis of several heterocycles [1][2][3][4][5]. It can undergo photolysis or thermolysis to afford highly strained three-membered 2H-azirine, which can act as the

• -azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [8][45][46][47][48][49][50] (Scheme 1). Thiazole is a common structural motif that is found in a wide variety of naturally

• existing alkaloids and a number of pharmaceutically active compounds [51][52][53]. 2-Aminothiazole has a thiourea-like character with a tendency to modulate promiscuously multiple biological targets. Thiazole derivatives also exhibit a broad spectrum of biological activities including antiviral, antiprion

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• Thiazolopyrimidines, whose molecules includes both thiazole and pyrimidine rings, have a structural analogy with the antipsychotic drugs ritanserin and setoperone (Figure 1) [1][2][3]. To date, a wide spectrum of biological activity of thiazolopyrimidines has been determined: anticancer [4][5], antimicrobial [6][7

• the latter [22][23][24][25][26][27][28]. Herein, we report the synthesis of a new series of phosphonylated thiazolopyrimidines. In our studies, chloroethynylphosphonate was used as the phosphonylating agent, which allowed the formation of a thiazole ring with simultaneous phosphonylation of the latter

• the 1H NMR spectra, the proton of the thiazole ring of both isomers is represented by a doublet signal in the low field region at δH 7.91 (3JHP = 3.2 Hz) and 8.41 ppm (3JHP = 7.5 Hz), whereas the corresponding proton of the uracil ring resonated as a singlet at δH 6.61 and 6.71 ppm, respectively. Note