HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• conditions and the employment of relatively complex starting materials [19]. A more efficient way of obtaining this nucleus is through the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between amidines (aminoazoles), aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis [20

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

• -triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N1 position . Keywords: Cornforth rearrangement; cycloaddition reactions; 3,3-diaminoacrylonitriles; heterocyclic azides; 1,2,3-triazole; Introduction Heteroaryl amidines are widely used in the

• properties of the triazoles thus obtained [9][10][11][12]. It should be noted that the synthesis of amidines containing other heterocycles in addition to 1,2,3-triazole in the molecule has not been described in the literature. In this regard, it is of interest to develop an effective method for the synthesis

• of hybrids of 1,2,3-triazole with other heterocycles and to identify biologically active compounds among the synthesized compounds. It is known that the cycloaddition reaction of azidopyrimidinediones with enamines [13] represents an effective method for the synthesis of pyrimidinyl amidines [14

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• ], amidines [11], isothioureas [12][13], whereas thioureas [14][15], ureas [16], phosphoric acids [17][18], and squaramides [19][20] fall into the second category. The Friedel–Crafts reaction, discovered by Charles Friedel and James Crafts in 1877 allows the aromatic C–H bond functionalization through the

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• , carboxylic acids, tetrazoles, aldehydes, amidines, and amides [7][8][9][10][11]. This has been suitably transformed into structurally diverse and complex molecules. In 1927, Pongratz reported a method towards cyanation reactions [12]. From then, onwards, cyanation gained prime focus and achieved much

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• amidines with alkynes catalyzed by either rhodium or ruthenium [55][56][57], or a metal-catalyzed aminative cyclization of 2-alkynylbenzonitriles with secondary amines [58]. Despite the advantages associated with the aforementioned protocols such as the functional group tolerance and huge substrate scope

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

• desired product 97. 6.2.3 Thiopyrano-, pyrano[4,3-d]pyrimidines: Jiang and co-workers [86] proposed a three-component reaction involving aldehydes 5, tetrahydrothiopyran-4-ones 100 and amidines 75 under microwave irradiation using t-BuOH as solvent and t-BuOK as a base. This reaction provided easy access

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -bond adduct. The first light-promoted three-component reaction has been realized by a halogen-bond adduct, forming perfluoroalkylated pyrimidines 26 (Scheme 8). A variety of perfluorinated chains were assembled with methylene compounds and guanidines or amidines, giving the corresponding

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• amidines at the C2 position of DBO in moderate to good overall yields. In vitro antibacterial testing of the compounds was performed against ten bacterial strains containing different β-lactamase enzymes. The compounds were tested alone and in combination with the existing antibiotic, meropenem. All

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• a variety of pyrimidine derivatives, 6, using amidines including guanidine [34]. First of all, various bases were employed for the reaction of the model substrate 2a. During initial testing, guanidine hydrochloride at 25 °C for 4 h in acetonitrile (Table 5, entries 1–7) as well as sodium carbonate

• notable features of this method, which is worthy of attention. Furthermore, the high electrophilicity of ynones 2 obtained was nicely demonstrated through two representative reactions, namely 1) Michael additions of β-keto carbonyl compounds and 2) amidines and guanidine for the construction of aromatic

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

• thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• -triazine-2,4-diamines in 44–72% yields that employed the reaction of isothiocyanates with sodium hydrogen cyanamide and amidines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and heating at 75 °C for 3 h. Recently, Ma et al. [33] described a one-pot two step procedure for

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• , the presence of an N-atom in the amidine structure leads to opportunities as ligands and organocatalysts [6][7][8]. N-Sulfonylamidines and N-sulfonylimidates are members of a specific class of these amidines. One initial methodology developed for the formation of sulfonylamidines was based on the

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• . Results and Discussion Synthesis of fluorinated pyrimidines To synthesize 2-alkyl- and 2-aryl-substituted 5-fluoro-4-aminopyrimidines, the reaction of 8 with various amidines was investigated. Different formamidinium and guanidinium salts were tested (Table 1) to evaluate the effect of the counter ion

• producing alkyl-substituted pyrimidine derivatives was investigated (Scheme 2). Starting from formamidine hydrochloride, compound 10a was synthesized in 85% yield. A variety of amidines with different steric hindrance such as methyl, cyclopropyl and tert-butyl substitution was used, and all substituents

• obtained in excellent yields of 93% and 97%, respectively, and represent potential substrates for subsequent cross-coupling reactions, which would provide structurally more complex products. Amidines with heterocyclic substituents were also evaluated. While the pyridine-substituted derivative 10o furnished

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• amidines and amides was observed [4]. Moreover, the formazan-type products, the formation of which was observed in reactions of chloroethynylphosphonates with arylhydrazines, were not detected [16]. The structures of [1,2,4]triazolo[4,3-a]pyridines 3–8 were confirmed by IR, 1Н, 13C and 31P NMR spectroscopy

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

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

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• conditions that are incompatible with nitro or cyano groups. In this context, and as part of our ongoing research on heterocyclic amidines (vide infra) and amidine N-oxides we report herein the first method for the synthesis of 2-alkyl/aryl-N-aryl-3,4-DHQs 1 bearing electron-withdrawing groups in the aryl

• -arylations of unprotected primary diamines have not been systematically investigated yet. Regarding the last step of the sequence leading to compounds 1, our group has worked extensively on ring-closure reactions leading to nitrogen-containing heterocycles such as 5–8-membered cyclic amidines [81][82][83], N

• have also been reported [91]. These transient intermediates have been characterized spectroscopically and, in some cases, were isolated from the reaction medium [94][95][96][97]. In relation to our research, nitrilium ions are also known to mediate the synthesis of acyclic amidines by reaction with

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• ambient temperature and pressure [19][20][21][22]. Furthermore, cyclic amidines and guanidines, such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), exhibited an excellent efficiency of CO2 capture and release [23][24][25][26][27][28][29][30][31][32][33]. In

• a low magnetic field, because the electrons on bicarbonate and guanidinium carbons were delocalized on oxygen and nitrogen atoms by their resonance effect, respectively. Previously, some researchers have reported similar assignments for zwitterion adducts of amidines and guanidines [29][30][31]. The

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• Namitharan has very recently demonstrated that a one-pot palladium-catalyzed Heck coupling allows for transferring the aryl group of (diacetoxyiodo)arenes released after a metal-free methylenation reaction (Scheme 45) [110]. The latter that is performed by reacting PhI(OAc)2 with DMSO, applies to amidines 97

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• values (66% for 33b) are obtained. In another tandem procedure, a metal-free C(sp3)–H olefination of amidines 34 with DMSO and PIDA derivatives 20b was developed by Namitharan and co-workers [49]. A Pd(II)-catalysed Heck reaction of the formed exocyclic double bond with the emerging iodoarene yields

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

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

• the presence of EDCl, DMAP and HOBt in N,N-dimethylformamide at room temperature for the synthesis of the corresponding amide derivatives 218 (Scheme 58). Song et al. [134] explored the synthesis of pyrazolo[3,4-d]pyrimidine derivatives 221 through the intermediacy of amidines 219 obtained by reaction

• of 5-amino-4-cyanopyrazole 208 with N,N-dimethylformamide dimethyl acetal (DMFDMA) in acetonitrile at reflux temperature. Amidines 219 were condensed with appropriate 2-amino-5-subsitituted-1,3,4-thiadiazoles 220 under microwave irradiation in acetic acid for the generation of the desired pyrazolo

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

• effort has been devoted to the development of efficient, general and expeditious methods for their synthesis [1][2]. Cyclic amidines are compounds of interest due to their multiple pharmacological properties, some of which derive from their interaction with a specific receptor [3][4]. Six-membered

• heterocylic amidines (1,4,5,6-tetrahydropyrimidines) display biological activity as anthelmintics used in medical practice (pyrantel, morantel and oxantel) [5][6], nicotinic agonists [7], antidepressants [8] and selective inhibitors of M1 acetylcholine receptors [9][10], among others. Their benzannulated

• heterocycles. Many methods use 2-aminobenzylamine (2-ABA) that reacts with amidines, carboxylic acids, orthoformates, or aldehydes in oxidative conditions to yield N-unsubstituted dihydroquinazolines [11][16][26][27][28][29][30][31][32][33][34][35]. A different approach is based on the heterocyclization of

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• hand, we then set out to explore the reaction scope for the library generation of structurally diverse imidazo[1,2-a]pyridine-fused isoquinolines and the results are collected in Table 2. Initially, several GBB adducts 4 were synthesized through GBB reaction of amidines 1, substituted 2

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• ] and aromatic amidines resulted in glyoxalate-substituted pyrido[1,2-a]pyrimidinone, thiazolo[3,2-a]pyrimidinone and pyrimido[1,2-a]benzimidazole. Pyrazinones and quinoxalinones were obtained through the reaction of these glyoxalates with ethylenediamine and 1,2-phenylenediamine derivatives. On the

• other hand, the reaction of glyoxalates with amidines did not lead to the formation of imidazolones, but rather N-acylated products were obtained. All the products were isolated in good yields. DFT-B3LYP calculations provided HOMO/LUMO coefficients, charge densities, and the stability energies of the

• functionalized heterocycles can also lead to the formation of polyazaheterocycles. Our research group has reported the synthesis of ethyl 5-carbonylpyrimidine-4-carboxylates from unsymmetrical enaminodiketones and amidines and their application in the preparation of pyrimido[4,5-d]pyridazin-8(7H)-ones [8]. One

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

• with a large substrate scope. Keywords: carbonates; DBN; DBU; lactams; p-nitrophenyl; Introduction Among various organic bases, amidines such as DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) having an imino group attached to the α-carbon of the amine are

• synthetically useful and strong neutral bases. Besides, DBU and DBN catalyze various organic reactions such as dehydrohalogenations [1], carbonylations [2], amidations [3] and Baylis–Hillman reactions [4]. These bicyclic amidines have been thought to be non-nucleophilic bases, but meanwhile numerous examples

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• synthesis. Keywords: cyclic amidines; medium size heterocycles; microwaves; PPE; PPSE; Introduction The synthesis of new nitrogen heterocycles has a great interest in medicinal chemistry since they are part of many drugs and represent structures with a wide therapeutic potential [1][2]. 2

• -Iminoazacycloalkanes are cyclic amidines where the formally sp2 nitrogen is exocyclic. These compounds have been described as selective inhibitors of the inducible form of human nitric oxide synthase (iNOS), which catalyzes the reaction to form nitric oxide via the oxidation of L-arginine to L-citrulline [3][4][5][6

• of conventional heating [17]. In previous work, we reported the microwave-assisted synthesis of 5 to 8 membered cyclic amidines by cyclodehydration of N-aryl-N´-acyl-1,n-alkanediamines (n = 2–5) promoted by polyphosphoric acid (PPA) esters PPE and PPSE (Scheme 1, reaction 1) [41][42][43]. In this