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

• ], ketopiperazinetetrazoles [36], imidazotetrazolodiazepinones [37], tetracyclic tetrazolylpyridoimidazoquinolines [38], bis-heterocyclic 1,5-disubstituted tetrazoleindolizines [39] and (E)-12-tetrazolyl-5H-quinazolino[3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give

• ]quinazolines (Scheme 2D) [40]. There are numbers of Ugi and subsequential Heck (or reductive Heck) reactions that have been developed for the synthesis of poly-heterocyclic compounds [43][44][45][46][47][48][49][50][51]. Reported in this paper is a one-pot Ugi-azide reaction followed by an intramolecular Heck

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• –tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core

• : aromatic nucleophilic substitution; azide–tetrazole equilibrium; 4-azido-2-sulfonylquinazolines; quinazolines; sulfonyl group dance; Introduction The quinazoline core is a privileged structure with a wide range of applications. Quinazoline derivatives exhibit a broad spectrum of biological activities

• [9][10] are commonly employed for quinazoline modification (Scheme 1). Existing literature underscores the reactivity of the C4 position in aromatic nucleophilic substitutions of quinazolines I while achieving regioselective replacement at the C2 position poses challenges [11]. Modification of the C2

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• shown that for the hydroxy derivatives the main pathway of phototransformation is a 6π-electrocyclization of the 1,3,5-hexatriene system and subsequent [1,9]-H sigmatropic shift leading to dihydrobenzo[h]pyrano[2,3-f]quinazolines. At the same time, for methylated analogues the photoreaction proceeds in

• two directions resulting in the formation of a mixture of the corresponding dihydrobenzo[h]pyrano[2,3-f]quinazolines and polyaromatic products. The obtained dihydro derivatives are stable compounds and do not undergo aromatization upon further UV irradiation. The structures of two of the dihydrobenzo

• [h]pyrano[2,3-f]quinazolines were confirmed by X-ray diffraction analysis. Based on the performed studies, a two-stage telescopic method for the synthesis of polyaromatic benzo[h]pyrano[2,3-f]quinazolines including the initial photocyclization of the starting pyrimidines and the final dehydration was

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of natural product-like compound libraries. Keywords: [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines; Introduction An important design concept in current drug discovery includes structural modifications of naturally occurring

• chemistry, and this approach has already provided successful results in the view of reaching biological activity. Thus, angular pyrrolo[1,2-a]quinazolines of type 1 – analogs of naturally occurring vasicinone alkaloids bearing an isomeric linear pyrrolo[2,1-b]quinazoline core [5][6][7][8] – demonstrated

• ring (especially with functional groups) is annulation of the latter moiety to the quinazoline ring. Thus, a series of 1,5-disubstituted pyrroloquinazolines 3 were obtained by a three-component Sonogashira-type coupling of 2-chloro-4-substituted quinazolines 4, propargylic alcohol, and secondary amines

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• ], superbases [6], and as ligands for metal complexation [7]. In organic synthesis, biguanides are precursors to several heterocycles [1] such as 1,3,5-triazines, pyrimidines, boron heterocycles, and benzo[f]quinazolines. The application of biguanides as catalysts has been reported mostly for the

• , the authors observed an intramolecular aromatic electrophilic substitution under high-temperature conditions. This unprecedented reactivity was used in the synthesis of 1,3-diaminobenzoquinazoline derivatives (Scheme 26). After prolonged reflux in octanol, the quinazolines were isolated as free bases

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• -alkyl-4(H)-quinazolines were synthesized. The most potent compound 36 (Figure 15) showed micromolar inhibition in P. aeruginosa and was able to decrease pyocyanin levels down to less than 0.5 µg/mL at 100 µM. Furthermore, AQ signal molecules could also be suppressed. The crystal structure of the PqsR co

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

• involve oxidation or reduction of related heterocycles (quinazolinones, quinazolines or tetrahydroquinazolines) [23][24][25][26][27][28]. Dihydroquinazolines can also be synthesized by heterocyclization of 2-aminobenzylamines (2-ABAs) with different C2 donors [3][16][17][29][30][31][32][33][34][35][36

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• Roma, P.le A. Moro 5, 00185, Rome, Italy Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy 10.3762/bjoc.14.218 Abstract An efficient strategy for the synthesis of 6-unsubstituted indolo[1,2-c]quinazolines is described. The Pd-catalyzed

• reaction of o-(o-aminophenylethynyl) trifluoroacetanilides with Ar–B(OH)2 afforded 2-(o-aminophenyl)-3-arylindoles, that were converted to 12-arylindolo[1,2-c]quinazolines by adding dimethylformamide dimethyl acetal (DMFDMA) to the reaction mixture after extractive work-up. This reaction outcome is

• different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar–I, Ar–Br and ArN2+BF4−, that afforded 12-arylindolo[1,2-c]quinazolin-6(5H)-ones. Moreover, 12-unsubstituted indolo[1,2-c]quinazolines can be obtained both by reacting 2-(o-aminophenyl)indoles with DMFDMA

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• pharmaceutical intermediates [3][4][5][6]. Substituted benzimidazoles occur in veterinary medicines, as anthelmintic agents and are used in a plethora of human therapeutic areas such as psychiatrics, ulcers, hypertension, cancers etc. [7][8][9][10]. Quinazolines and quinazolones are obtained in bioactive

• tetrahydroquinazolines has been demonstrated at room temperature. The reaction involved a one-pot condensation–oxidative dehydrogenation of 2-aminobenzylamine (15) with appropriate aldehydes to dihydroquinazoline 17 and aromatic quinazolines 16 with 1 or 2 equivalents of IBX, respectively (Scheme 4) [35]. The mechanism

• -aminobenzylamines and o-aminobenzyl alcohols 36 and 37, respectively, with appropriate aldehydes to generate substituted quinazolines 38 and 4H-benzo[d][1,3]oxazines 39 in excellent yields [45]. A typical procedure involved the condensation of 36 and 37 in methanol at room temperature to afford the crude

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

• dihydroquinazolines. Some of them involve cyclic precursors such as quinazolinones, quinazolines or tetrahydroquinazolines, which can be reduced or oxidized to yield dihydroquinazolines [17][19][20][21][22][23][24][25]. Heterocyclization of acyclic precursors has also been applied for the synthesis of these

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• anthranilic acid to afford benzoxazines, followed by sequential reaction with ammonia to afford the benzanilide derivatives and finally, benzanilides were cyclized by heating in sodium hydroxide solution and gave quinazolines A2–A6. Methyl 1,2-dihydro-2-oxoquinoline-4-carboxylate (A9) [22][23] was prepared by

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• , resulting from reaction of isocyanide with dialkyl acetylenedicarboxylate, added to the carbonyl group of the acylphosphonate followed by an intramolecular cyclization. A palladium-catalyzed isocyanide-based three-component pathway into phosphorylated quinazolines has been described by Wu et al. [80]. The

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• ], quinolines [9][10][11][12][13] and quinazolines [14][15][16]. Therefore, the search for new methods leading to 2,1-benzisoxazoles is of great interest. For the preparative synthesis of 2,1-benzisoxazoles, in addition to the traditional method based on the reductive heterocyclization of ortho-substituted

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• ]quinazolines were intensively investigated and promising biological activities were observed, such as anticancer, antiviral, antimicrobial, anti-inflammatory and anticonvulsant [3][4][5]. Indeed, some of them are already used as antimicrobial agents and lipid peroxidation inhibitors [6]. Consequently, the

• corresponding quinazolines 4 in high yields (Table 2, entries 2, 3 and 6). In addition changing the position of the fluoro substituent did not affect the yield of the products (Table 2, entries 3–5). To further expand the scope of the protocol, we attempted the synthesis of imine 3g starting from two different

• drawing of 5, [C20H16F2N4O]·2Cl·H2O with 35% probability ellipsoids, showing the atomic numbering scheme. CuI-catalyzed synthesis of benzimidazo[1,2-c]quinazolines 4 by intramolecular N-arylation of bromo-substituted quinazolin-4(3H)-imine derivatives 3. Cu-catalyzed reaction of o-cyanoaniline (1a

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• pyrrole-, furan- and thiophene-fused naphthoquinones [36]. For several years, our group has been interested in developing new synthetic methods for the preparation of heterocycle-fused 1,4-naphthoquinones or heterocycle-tethered 1,4-naphthoquinones. 1,3-Quinazolines are nitrogenated heterocycles that are

• located at 0.641(2) Å out of the plane of the other five atoms C(2), N(1), C(4a), C(10) and C(4). A possible mechanism that could explain the formation of the tetrahydrobenzo[g]quinazolines 13 and 21–25 is shown in Scheme 3. It initially involves the in situ formation of three thermally generated iminium

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• domino cyclization. Based on the previous work for the copper-catalyzed synthesis of 2-amino-1H-indole derivatives and copper-catalyzed N-arylation, we herein report a simple and efficient one-pot method to synthesize indolo[1,2-a]quinazolines by a sequential Ullmann-type C–C and C–N coupling. Compared

• organic chemistry and medicinal chemistry. Experimental General procedure for the synthesis of indolo[1,2-a]quinazolines 4a–4q A dry sealed tube was charged with a magnetic stirrer, substituted N-(2-iodophenyl)acetamide (100 mg for each example, 0.38 mmol), malononitrile or 2-sulfonylacetonitriles (0.46

• tetracyclic compounds containing the indole motif. Synthetic route for indolo[1,2-a]quinazoline derivatives by a sequential Ullmann-type C–C and C–N coupling in one pot. Optimization of the reaction conditions.a Synthesis of indolo[1,2-a]quinazolines 4.a Supporting Information Supporting Information File 382

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis). Results of DFT calculations are presented

• ) pm, respectively. The p-iodophenyl substituent is twisted by −50.7(4)° from the plane of the indazole ring [C4–N2–C1–C53]. Another type of rearrangement occurred on heating the dimerized carbenes 13a–d/14a–d in xylene, as the substituted quinazolines 16a–d were isolated in reasonable yields (Scheme 6

• ). The mechanism can be rationalized by formation of an ylide by 1,7-H-shift from the mesomeric betaine III, followed by ring cleavage of the indazole ring and subsequent ring-closure of the resulting 1,6-dipole to give the quinazolines 16a–d. Single crystals of 16b suitable for an X-ray analysis were

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• Dihydropyridines and piperidines Pyrimidines and quinazolines Pyrazines and piperazines Pyridazines and perhydropyridazines Triazines and polyazacyclic systems Synthetic chemistry can rightfully be considered a prerequisite of our modern society [1]. This discipline supplies many valuable resources to our world

• carmegliptin as its HCl salt. 3. Pyrimidines and quinazolines Whilst pyridine rings and their partially or fully saturated derivatives are very frequent components of pharmaceutical species there are also a considerable number of compounds based on diazine and triazine ring systems. Amongst the diazines

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• strong bases. Han et al. have recently shown the ability of copper salts, in conjunction with oxygen, to catalyze oxidations of 2-substituted tetrahydroquinazoline aminals to quinazolines [35] (Figure 2). In addition, Reddy and co-workers have developed a catalytic system in which 2,3-substituted

• deal of interest in recent years [38][39][40][41][42][43][44]. Han’s copper-catalyzed method for the synthesis of aminals to quinazolines results in high yields [35], but the process is not applicable to mono-oxidation as dihydroquinazolines are not isolated as products in these reactions. We set out

• the oxidation of aminals to quinazolines provided an increased yield of 50% (Table 3, entry 9). The best yields were obtained by using the conditions developed by Reddy and co-workers [36], namely the combined use of catalytic amounts of potassium iodide (20 mol %) and excess TBHP (5 equiv), followed

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• , namely isoquinolines represented by benzophenanthridines [8], oxoaporphines [9], aporphines [10] and benzylisoquinoline [11]; and quinolines represented by quinolones [12] and furoquinolines [10]. Others include carbazoles [13], pyrido-indoles [12] and quinazolines [14]. Arylethanamides and amines have

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• yields. Their synthetic utility was demonstrated by condensation reactions with carbonyl compounds or amines to provide SF5-containing quinolines and quinazolines, respectively. Keywords: benzisoxazoles; pentafluorosulfanyl group; quinazolines; quinolines; sulfurpentafluorides; Introduction Reactions

• has been recently reviewed [28]. In this paper, we report our results on benzisoxazole formation from nitrobenzenes 3 and 4 and further transformations to SF5-containing aminobenzophenones, quinolines and quinazolines. Of these compound types, only some SF5-substituted quinolines are known. Wipf and

• powder in aqueous acetic acid according to the literature procedure (Table 2) [31]. Aminoketones 10 and 11 were investigated as starting substrates in the synthesis of various nitrogen heterocycles by condensation reactions. Several reliable synthetic methods giving quinolones [32][33] or quinazolines

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• derivatives of 1,3-diarylthiobarbituric acids (DTBA) with active methylene compounds, such as malononitrile and ethyl cyanoacetate, in presence of ZnCl2 has been developed. Keywords: benzenoid; ethylcyanoacetate; malononitrile; pyrimidine; 2-thioxoquinazolin-4-ones; Introduction Quinazolines and derivatives

• are of much interest due to their biological activities [1][2]. Additionally, quinazolines are interesting targets for new method development due to their importance in numerous therapeutic areas. Recently, antitumor [3] and anti-HIV activities [4][5] of quinazolines have been described. A large

• number of quinazoline derivatives, which contain the 4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine structural moiety in their heterocyclic rings, possess a wide range of biological activities [6][7][8]. There are a number of synthetic methods available for the preparation of quinazolines [9]. The most

Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones

• Aboul-Fetouh E. Mourad,
• Ashraf A. Aly,
• Hassan H. Farag and
• Eman A. Beshr

Beilstein J. Org. Chem. 2007, 3, No. 11, doi:10.1186/1860-5397-3-11

• -Minia University, 61519-El-Minia, Egypt 10.1186/1860-5397-3-11 Abstract Background Benzimidazoquinazolinones and related quinazolines are classes of heterocycles that are of considerable interest because of the diverse range of their biological properties. Although numerous classes of quinazolines have

• compounds with 2-ethoxymethyleneaminonitriles. [9] A general route to prepare 5,10-dihydro-[1,2,4]-triazolo-[5,1-b]-quinazolines included the reaction of benzophenone and 1-ureidoethylidene-hydrazones with a mixture of triphenylphosphine, carbon tetrachloride, and triethylamine in dichloromethane. [10

• ] Other triazoloquinazolines were obtained from 2'-azidoacetophenone and as well as 2-azidobenzonitrile. [11] Quinazolines were also obtained in moderate yields by an intermolecular reductive N-heterocyclization of 2-nitro-benzaldehydes or 2-nitrophenyl ketones with formamide catalyzed by a combination of