Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• substituent, each with a different means of cyclisation. A versatile and stable quinolin-2-one intermediate was identified, which could be reduced to the corresponding THQ with borane reagents, or to the DHQ with diisobutylaluminium hydride via a novel elimination that is more favourable at higher

• also use Lewis acids [7]. The resultant quinolin-2-one is then reduced using strong hydride reducing agents such as LiAlH4 [8]. Similar THQs have also been prepared by a reductive Beckmann rearrangement of an oxime using diisobutylaluminium hydride (DIBAL) [9]. In contrast to this variety, the

• considered (Scheme 6). The quinolin-2-one 13 was predicted to be a more amenable alkylation partner than the THQ 14 due to the likely lower pKa of the amide proton. To assess this, 13 was reacted with NaH and 2-iodopropane in DMF at 80 °C overnight. However, 13 displayed a marked lack of reactivity towards

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• towards the control of polymer functionalization and living or switchable polymerizations. Keywords: acid; activation by acid; metathesis; polymer; quinolin; ruthenium; triggerable; Introduction The modulation of the activity of enzymes by chemical triggers, e.g., by allosteric binding is ubiquitous in

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• these more challenging substrates. Interestingly, phenyl(quinolin-2-yl)methanone (6a) and phenyl(quinolin-4-yl)methanone (6b) were formed in moderate yields indicating that larger aromatic systems are compatible with the reaction conditions. In the case of 2-(4-chlorobenzyl)pyrimidine (5c) the standard

• oxidation of the methyl group was seen [25]. Applications An example of an important pharmaceutical which is industrially prepared from an azinyl benzoazinyl ketone, namely (2,8-bis(trifluoromethyl)quinolin-4-yl)(pyridin-2-yl)methanone (10), is the antimalarial Mefloquine (13) [36]. This drug is listed on

• . This compound is structurally interesting as it is activated by both a pyridin-2-yl and a quinolin-4-yl moiety (Scheme 2, bottom). The synthesis of substrate 12 was accomplished by a cross-coupling reaction of pyridine alcohol 11 with commercial 4-chloro-2,8-bis(trifluoromethyl)quinoline (7b) according

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• synthesis of a lactam via chelating-group-assisted copper catalysis. As outlined in Scheme 8, the N-quinolin-8-yl substituted amides 27 could be smoothly transformed into lactams 28 and/or 28' via C–H amidation by using Cu(OAc)2 as catalyst and Ag2CO3 as a base. In a specific case, the C(sp2)–H bond could

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

• copper-catalyzed arene C–H methoxylation using the generally applicable quinolin-8-yl [40] as DG, Stahl et al. [41] discovered that using a CuCl/LiCl/O2/AcOH catalytic system resulted in the formation of C-5 chlorinated quinoline, demonstrating the pivotal role of the DG in inducing the reaction pathway

• functionalized 8-methylquinolinyl substrates reported by Sanford et al. [43], Daugulis and co-worker [44] established in 2013 a copper-catalyzed arene C–H o-fluorination of N-(quinolin-8-yl)benzamides 14. The mono- and/or difluorination took place in the presence of CuI, N-methylmorpholine N-oxide (NMO) and

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• hydrazine hydrate and sodium hydroxide. Results and Discussion We initiated our investigation of the direct carbon–carbon coupling of N-(quinolin-8-yl)benzamide (1a) and phenylacetylene (2a). After extensive attempts, 3-benzylidene-2-(quinolin-8-yl)isoindolin-1-one (3a) was formed in 18% yield via the

• -substituted benzamides occurred predominantly at less sterically congested sites (3j, 3k). A ortho-substituted and a tetrahydronaphthalene derivative worked well, respectively, and provided moderate yields (3l, 3m). We also tested a variety of terminal alkynes as coupling partners with N-(quinolin-8-yl

• quinolin-8-amine was easily removed and recycled by treatment of 3a with hydrazine hydrate and NaOH in EtOH at 120 °C under microwave irradiation (Scheme 4). Both electron-rich and electron-deficient 4-benzylphthalazin-1(2H)-one derivatives were obtained in good yields (4b, 4k). The halo-substituted phenyl

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• involving unactivated alkyl groups of C-reagents are considered below. The amide moiety was most commonly employed as the directing group. The alkoxylation of alkyl groups of N-(quinolin-8-yl)amides 84 [81], picolinamides 85 [62], and N-(2-pyridin-2-yl)propan-2-yl)amides 86 [63], the trifluoroacetoxylation

• -pyridylsulfoximines 88. Using the N-(quinolin-8-yl)amide directing group Pd(OAc)2 catalyzed the double sp3 C–H alkoxylation of 96 for the synthesis of symmetric acetals 97 and unsymmetric acetals [84] (Scheme 20). The method demonstrates good functional group tolerance and the applicability in the synthesis of

• products containing α-hydrogen next to an amide moiety. Copper-catalyzed acyloxylation of methyl groups of N-(quinolin-8-yl)amides 99 was achieved [85] (Scheme 21, product 100); the reaction requires higher temperatures (170 °C) then Pd(OAc)2 catalyzed alkoxylation of analogous substrates in the presence

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• does not occur in aqueous acetonitrile although diethyl phosphate is released. Other substitution patterns on the naphthyl or quinolin-5-yl core, such as the 2,6-naphthyl 10 or 8-benzyloxyquinolin-5-yl 24 platforms, also do not rearrange by aryl migration upon photolysis and, therefore, do not proceed

• to completion. The 2,6-naphthyl ketone platform instead remains intact whereas the quinolin-5-yl ketone fragments to a much more complex, highly absorbing reaction mixture that competes for the incident light. Keywords: caged phosphates; hydroxynaphthylacetyl; organophosphorus; photo-Favorskii

• -hydroxynaphthalen-1-yl)-2-oxoethyl (1,4-HNA, 14a) and its methoxy ether (1,4-MNA, 14b), and 8-(benzyloxy)quinolin-5-yl)-2-oxoethyl (5,8-BQA, 24), each modeled after the p-hydroxyphenacyl (pHP, 4) chromophore were synthesized as illustrated in Scheme 1 and Scheme 2. Synthesis of the extended 2,6-HNA phosphate ester

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ]quinolin-11(5H)-ones via [4 + 2] imino-Diels–Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the

• been studied. In continuation of our efforts on the development of novel synthetic methodologies [27][28][29][30][31][32][33][34][35][36], we report herein a systematic study of steric and electronic effects of aryl substituents leading to substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones

• fashion or otherwise) with N-(2-substituted phenyl)-1-oxo-1H-isoindolium ions. Conclusion 6,6a-Dihydroisoindolo[2,1-a]quinolin-11(5H)-one derivatives were synthesized from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions in fair to good yields. As expected

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

• three new alkaloids, namely 1-hydroxy-10-methoxy-7H-dibenzo[de,g]quinolin-7-one (zanthoxoaporphine A, 2), 1-hydroxy-7H-dibenzo[de,g]quinolin-7-one (zanthoxoaporphine B, 3) and 1,8-dihydroxy-9-methoxy-7H-dibenzo[de,g]quinolin-7-one (zanthoxaporphine C, 4), and a known lignan identified as sesamin (1

• carbon atoms C-5 (δ 145.7), C-3a (δ 130.2) and C-3 (δ 139.5); and between H-11 and carbon atoms C-11a (δ 139.3) and C-10 (δ 125.6); while H-8 was correlated with C-9 (δ 130.8) and C-7a (δ 124.5). From the above-mentioned data the structure of 3 was confirmed as 1-hydroxy-7H-dibenzo[de,g]quinolin-7-one

• -dihydroxy-9-methoxy-7H-dibenzo[de,g]quinolin-7-one, which was named zanthoxoaporphine C. Due to the substantial amount of compounds 1 and 2, their effect against third-instar Anopheles gambiae larvae was evaluated (Table 3). Compound 2 exhibited moderate larvicidal activity after 24 hours with a LC50 at

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• , 413.2587; found, 413.2583. 9,9'-[(2-Methylphenyl)methylene]bis(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol) (15): 8-Hydroxyjulolidine (14, 500 mg, 2.6 mmol) and o-tolualdehyde (12, 154 µL, 1.3 mmol) were dissolved in propionic acid (15 mL) and catalytic p-TsOH acid was added. The reaction was

• [17.7.1.1{5,9}.0{2,17}.0{4,15}.0{23,27}.0{13,28}]octacosa-1(27),2(17),4,9(28),13,15,18-heptaen-9-ium (HR101, 10): 9,9'-[(2-Methylphenyl)methylene]bis(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol) (15, 91 mg, 0.19 mmol) and chloranil (69 mg, 0.28 mmol) in MeOH/CHCl3 (1:1, 10 mL) were stirred at 23

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• Wentao Gao Guihai Lin Yang Li Xiyue Tao Rui Liu Lianjie Sun Institute of Superfine Chemicals, Bohai University, Jinzhou 121000, China 10.3762/bjoc.8.213 Abstract An efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives 4a–l

• thereof. However, to the best of our knowledge, there are very few reports in which a medium-sized seven-membered benzoxepin ring is fused to a quinoline unit. In this context, Bera et al. [20] described a one-pot method for the synthesis of 6,7-dihydrobenzo[2,3]oxepino[4,5-b]quinolin-12-ols. However, the

• 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-ones 4a–l. The advantages of the current protocol include the ready availability of starting materials, ease of experimental operation, and satisfactory yields, which contribute to the usefulness of this method. These compounds belong to a new class of

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• reported to afford several different tricyclic products. Thus, in an early report [18], the reaction of the three components in ethanol under conventional heating afforded mainly the corresponding pyrazolo[3,4-b]quinolin-5-ones. This finding was later supported by other authors [19]. Recently, the results

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• . 3-(6-bromo-2-(4-chlorophenyl)quinolin-3-yl)propan-1-ol (19) Following the general procedure B, the oxidation of 17,17' afforded compound 19 as a white solid (60%). 1H NMR (400 MHz, CDCl3) δ 7.92–7.87 (m, 3H), 7.67 (dd, J = 2.2, 8.9 Hz, 1H), 7.44–7.37 (m, 4H), 3.51 (t, J = 6.2 Hz, 2H), 2.85–2.77 (m

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• intermediate via an intramolecular cycloaddition [165]. A subsequent intermolecular hydroamination of the intermediate, followed by a cyclization, leads to the observed products. Our group also investigated the construction of highly functionalized pyrrolo[1,2-a]quinolin-1(2H)-ones 340 via a AuBr3/AgSbF6

Synthesis of 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles

• Yang Li and
• Wentao Gao

Beilstein J. Org. Chem. 2010, 6, 966–972, doi:10.3762/bjoc.6.108

• Yang Li Wentao Gao Institute of Superfine Chemicals, Bohai University, Jinzhou 121000, China 10.3762/bjoc.6.108 Abstract A simple and efficient synthesis of novel 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles, utilizing sodium ethoxide as a catalyst via a Friedländer condensation

• quinolyl-substituted heterocycles [32][33][34], we report herein the synthesis of novel 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles. Results and Discussion In order to construct the desired quinolyl-substituted carbazoles, we devised a route that made use of a Friedländer condensation

• 9-ethyl-3-(quinolin-2-yl)-9H-carbazoles and 9-ethyl-3,6-bis(quinolin-2-yl)-9H-carbazoles might be synthesized. Indeed, this was found to be the case as shown in Scheme 1. The Friedländer condensation reaction of 3-acetyl-9-ethyl-9H-carbazole (1) with 1 molar equivalent of β-aminoaldehydes or β

Gold film- catalysed benzannulation by Microwave- Assisted, Continuous Flow Organic Synthesis (MACOS)

• Gjergji Shore,
• Michael Tsimerman and
• Michael G. Organ

Beilstein J. Org. Chem. 2009, 5, No. 35, doi:10.3762/bjoc.5.35

• C22H15NO: 309.1154; found 309.1143. [6-(3-Fluorophenyl)quinolin-8-yl](phenyl)methanone (4g). Following the general MACOS benzannulation protocol, 2-(2-phenylethynyl)-nicotinaldehyde (1f) and 1-ethynyl-3-fluorobenzene were reacted and 750 μL of the crude reaction mixture were collected. Purification by

• ). Anal. Calcd. for C22H14FNO: C, 80.72; N, 4.28; H, 4.31; found C, 80.77; N, 4.56; H, 4.09. HRMS calcd. for C22H14FNO: 327.1059; found 327.1046. Phenyl-[6-(trimethylsilyl)quinolin-8-yl]methanone (4h). Following the general MACOS benzannulation protocol, 2-(2-phenylethynyl)-nicotinaldehyde (1f) and TMS

• , 4.62; H, 6.07. HRMS calcd. for C19H19NOSi: 305.1236; found 305.1232. [6-(4-Bromophenyl)quinolin-8-yl]-phenylmethanone (4i). Following the general MACOS benzannulation protocol, 2-(2-phenylethynyl)-nicotinaldehyde (1f) and 1-bromo-4-ethynylbenzene were reacted and 700 μL of the crude reaction mixture

Quinoline based receptor in fluorometric discrimination of carboxylic acids

• Kumaresh Ghosh,
• Suman Adhikari,
• Asoke P. Chattopadhyay and
• Purnendu Roy Chowdhury

Beilstein J. Org. Chem. 2008, 4, No. 52, doi:10.3762/bjoc.4.52

• spectrophotometer and a PerkinElmer LS-50B spectrofluorimeter, respectively. FTIR spectra were obtained from a PerkinElmer L120-000A model. 2-(Quinolin-8-yloxy)ethanol (3) To a mixture of 8-hydroxyquinoline (1 g, 6.80 mmol) and potassium carbonate (0.95 g, 6.80 mmol) in dry CH3CN, 2-chloroethanol (1.11 g, 13.7 mmol

• = 8.00 Hz), 7.47–7.40 (3H, m), 7.11 (1H, d, J = 8.00 Hz), 5.54 (1H, br s, OH), 4.28 (2H, t, J = 4.00 Hz), 4.08 (2H, t, J = 4.00 Hz). ESI (positive ionisation) mass: 212.1 (M + Na)+, 190.1 (M + H)+. FTIR (ν cm−1, KBr) 3400, 3157, 2922, 1577, 1380, 1116. N-({6-[2-(Quinolin-8-yloxy)ethoxy]methyl}pyridin-2

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline- 2,4(1H,3H)-dione compounds

• Oldřich Paleta,
• Karel Pomeisl,
• Stanislav Kafka,
• Antonín Klásek and
• Vladislav Kubelka

Beilstein J. Org. Chem. 2005, 1, No. 17, doi:10.1186/1860-5397-1-17

• observed reaction to be due to the increased electron-withdrawing character of the acyl moiety. According to Scheme 2, the reaction of 3-(halogenoacyloxy)quinoline-2,4(1H,3H)-diones 4-6 with triethyl phosphite gave two kinds of products: the product of the Perkow reaction (8) and 1-alkyl-4-ethoxy-quinolin