Quinoline derivatives are valuable scaffolds in medicinal and synthetic organic chemistry. In this work, a series of 3-formyl-2-allyloxyquinolines were synthesized from 2-chloro-3-formylquinolines prepared via the Meth-Cohn protocol, followed by acetal protection and alkoxide substitution. The Baylis-Hillman reaction of these quinolinic aldehydes with methyl acrylate in the presence of DABCO afforded the corresponding β-hydroxy acrylate adducts in good yields. To prevent undesired transformations of the hydroxyl functionality, these adducts were protected as tert-butyldimethylsilyl ethers. However, reduction of the silylated Baylis-Hillman adducts with LiAlH4 did not furnish the anticipated allylic alcohols. Instead, the reaction proceeded through a competing reduction-elimination pathway, leading to mixtures of unsaturated esters and primary alcohols. The product distribution was influenced by the substitution pattern of the quinoline framework.
ChujoIMasudaYFujinoK, et al.Synthetic study on novel immunosuppressant KF20444. Bioorg Med Chem2001; 9: 3273–3286.
2.
LarsenRDCorleyEGKingAO, et al.Practical route to a new class of LTD4 receptor antagonists. J Org Chem1996; 61: 3398–3405.
3.
ChenY-LFangK-CSheuJ-Y, et al.Synthesis and antibacterial evaluation of certain quinolone derivatives. J Med Chem2001; 44: 2374–2377.
4.
RomaGBraccioMDGrossiG, et al.1, 8-Naphthyridines IV. 9-Substituted N, N-dialkyl-5-(alkylamino or cycloalkylamino)[1, 2, 4] triazolo [4, 3-a][1, 8] naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities. Eur J Med Chem2000; 35: 1021–1035.
5.
DubéDBlouinMBrideauC. Quinolines as potent 5-lipoxygenase inhibitors: Synthesis and biological profile of L-746,530. Bioorg Med Chem Lett1998; 8: 1255–1260.
6.
MaguireMPSheetsKRMcVetyK, et al.A new series of PDGF receptor tyrosine kinase inhibitors: 3-Substituted quinoline derivatives. J Med Chem1994; 37: 2129–2137.
7.
BillkerOLindoVPanicoM, et al.Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature1998; 392: 289–292.
8.
SchwanWRDunekCGebhardtM, et al.Screening a mushroom extract library for activity against Acinetobacter baumannii and Burkholderia cepacia and the identification of a compound with anti-Burkholderia activity. Ann Clin Microbiol Antimicrob2010; 9: 4.
9.
MarkeesDGDeweyVCKidderGW. Antiprotozoal 4-aryloxy-2-aminoquinolines and related compounds. J Med Chem1970; 13: 324–326.
10.
AlhaiderAAAbdelkaderMALienEJ. Design, synthesis and pharmacological activities of 2-substituted 4-phenylquinolines as potential antidepressant drugs. J Med Chem1985; 28: 1394–1398.
11.
HinoKNagaiYUnoH. Synthesis and pharmacological activities of 3-phenyl-2-(1-piperazinyl)quinolines and related compounds. Chem Pharm Bull1987; 35: 2819–2824.
12.
CampbellSFHardstoneJDPalmerMJ. 2,4-Diamino-6,7-dimethoxyquinoline derivatives as α1-adrenoreceptor antagonists and antihypertensive agents. J Med Chem1988; 31: 1031–1035.
13.
SnyderHRFreierHEKovacicP, et al.Synthesis of 4-hydroxyquinolines. VIII. Some halogen containing 4-aminoquinoline derivatives. J Am Chem Soc1947; 69: 371–374.
14.
ElderfieldRCKreysaFJDunnJH, et al.A Study of the Synthesis of Plasmochin by the Reductive Amination Method with Raney Nickel. J Am Chem Soc1948; 70: 40–44.
15.
PalmerKJHollidaySMBrogdenRN. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs1993; 45: 430–475.
16.
BurckhalterJHTendickFHJonesEM, et al.Aminoalkylphenols as antimalarials. II.1 (Heterocyclic-amino)-α-amino-o-cresols. The synthesis of Camoquin. J Am Chem Soc1948; 70: 1363–1373.
17.
BurckhalterJHDeWaldHATendickFH. An alternate synthesis of Camoquin. J Am Chem Soc1950; 72: 1024–1025.
18.
ZuoRGarrisonATBasakA, et al.In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candidaalbicans and Cryptococcus neoformans. Int J Antimicrob Agents2016; 48: 208–211.
19.
NwakaSHudsonA. Innovative lead discovery strategies for tropical diseases. Nat Rev Drug Discov2006; 5: 941–955.
20.
El ShehryMFGhorabMMAbbasSY, et al.Quinoline derivatives bearing pyrazole moiety: Synthesis and biological evaluation as possible antibacterial and antifungal agents. Eur J Med Chem2018; 143: 1463–1473.
21.
SavegnagoLVieiraAISeusN, et al.Synthesis and antioxidant properties of novel quinoline–chalcogenium compound. Tetrahedron Lett2013; 54: 40–44.
22.
PierreFO’BrienSEHaddachM, et al.Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties. Bioorg Med Chem Lett2011; 21: 1687–1691.
23.
JoshiPVSayedAARaviKumarA, et al.4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity. Eur J Med Chem2017; 136: 246–258.
24.
BorsoiAFAliceLMSperottoN, et al. Antitubercular activity of novel 2-(quinoline-4-yloxy)acetamides with improved drug-like properties. ACS Med Chem Lett2022; 13: 1337–1344.
ChoCSOhBHKimJS, et al.Synthesis of quinolines via ruthenium-catalysed amine exchange reaction between anilines and trialkylamines. J Chem Soc Chem Commun2000: 1885–1886.
27.
JiangBSiY-G. Zn(II)-Mediated alkynylation−cyclization of o-trifluoroacetyl anilines: One-pot synthesis of 4-trifluoromethyl-substituted quinoline derivatives. J Org Chem2002; 67: 9449–9451.
28.
SkraupZH. Eine synthese des chinolins. Ber Dtsch Chem Ges1880; 13: 2086–2087.
29.
FriedländerP. Ueber o-amidobenzaldehyd. Ber Dtsch Chem Ges1882; 15: 2572–2575.
30.
ManskeRHFKulkaM. The Skraup synthesis of quinolines. Org React1953; 7: 59.
31.
LindermanRJKirollosKS. Regioselective synthesis of trifluoromethyl substituted quinolines from trifluoroacetyl acetylenes. Tetrahedron Lett1990; 31: 2689–2692.
32.
TheoclitouM-ERobinsonLA. Novel facile synthesis of 2,2,4 substituted 1,2-dihydroquinolines via a modified Skraup reaction. Tetrahedron Lett2002; 43: 3907–3910.
33.
CombesA. Sur une nouvelle méthode de synthèse des quinoléines. Bull Soc Chim Fr1888; 49: 89.
34.
DoebnerOvon MillerW. Ueber eine dem Chinolin homologe Base. Ber Dtsch Chem Ges1881; 14: 2812–2817.
35.
ChoCSOhBHShimSC. Ruthenium-catalyzed synthesis of 2-ethyl-3-methylquinolines from anilines and triallylamine. Tetrahedron Lett1999; 40: 1499–1500.
36.
DeSKGibbsRA. A mild and efficient one-step synthesis of quinolines. Tetrahedron Lett2005; 46: 1647–1649.
TaguchiKSakaguchiSIshiiY. Synthesis of quinolines from amino alcohol and ketones catalyzed by [IrCl(cod)]2 or IrCl3 under solvent-free conditions. Tetrahedron Lett2005; 46: 4539–4542.
39.
LiY-FWuZ-GShiJ, et al.FeCl3-promoted formation of C–C bonds: synthesis of substituted quinolines from imines and electron-deficient alkynes. Tetrahedron2014; 70: 8971–8975.
40.
ZhuMFuWXunC, et al.An efficient synthesis of substituted quinolines via indium(III) chloride catalyzed reaction of imines with alkynes. Bull Korean Chem Soc2012; 33: 43–47.
41.
Meth-CohnONarineBTarnowskiB. A versatile new synthesis of quinolines and related fused pyridines, Part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes. J Chem Soc Perkin Trans1981; 1: 1520–1530.
42.
AggarwalVKMereuA. Superior amine catalysts for the Baylis–Hillman reaction: the use of DBU and its implications. Chem Commun1999: 2311–2312.
43.
RezguiFEl GaiedMM. DMAP-catalyzed hydroxymethylation of 2-cyclohexenones in aqueous medium through Baylis-Hillman reaction. Tetrahedron Lett1998; 39: 5965–5966.
44.
GoleaLChebakiRLaabassiM, et al.Synthesis, characterization of some substituted quinolines derivatives: DFT, computational, in silico ADME, molecular docking and biological activities. Chem Data Collect2023; 43: 100977.
45.
SrihariEKumarGSKumarCNSSP, et al.Synthesis and antimalarial activity of Baylis-Hillman adducts from substituted 2-chloroquinoline-3-carboxaldehydes. Heterocycl Commun2011; 17: 111–119.
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