Diversity-oriented synthesis of quinolines via Friedländer annulation reaction under mild catalytic conditions. Journal of combinatorial chemistry 12, 100–10 (2010) (original) (raw)
Journal of combinatorial chemistry 12, 100–10 (2010)
An efficient and practical method has been manifested for the diversity-oriented synthesis of quinolines via Friedländer annulation reaction for the generation of a wide range of structurally interesting and pharmacologically significant compounds by using ceric ammonium nitrate as a catalyst (10 mol %) at ambient temperature in 45 min. A variety of functional groups are introduced at various positions of the quinoline moiety, and further the diversity of the core skeleton was expanded at R 1 and R 2 positions by the synthesis of various hybrids. Initial screening of the compounds for cytotoxicity against a series of cancer cell lines showed promising results. Figure 1. Some biologically active quinolines.
RSC Advances, 2013
General procedure for synthesis of 2-mercaptoquinoline-3carbaldehyde (1a-c) 2 1.3 General experimental procedure and analytical data for synthesis of thiopyrano[2,3-b]quinoline-3-carbaldehyde (3a-c) 3 1.4 General experimental procedure for synthesis of pyrazolo[4'',3'':5',6']pyrano[4',3':5,6] thiochromeno[2,3-b] quinolines (5a-r) 4 1.5 Analytical data for compounds 4-7 1.6 Single crystal X-Ray data of 5a 8-9 1.7 2D NMR experiments: NOE and Cosy for 5a 10-11 1.8 1 H NMR, 13 C NMR and Mass Spectral Data 12-32 1.1 General methods All solvents and reagents were used as supplied from commercial sources. The recorded melting points are uncorrected. IR spectra were recorded in KBr on Shimadzu FT-IR 8401 spectrometer and are reported in wave numbers (cm-1). A single crystal-X-ray diffraction data were collected on X'calibur CCD area-detector diffractometer equipped with graphite monochromated MoKα radiation ((λ=0.71073 Å). 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance 400 spectrometer operating at 400 MHz for 1 H NMR and 100 MHz for 13 C NMR as solutions in CDCl 3 , unless otherwise indicated. Chemical shifts are reported as parts per million (ppm, d) and referenced to the residual protic solvent. Coupling
A series of 2- naphthyridin-2-yl-4-Arylquinoline-3-carbonitriles (3a-i) has been synthesized by multicomponent reaction via one-pot conden sation of various aryl aldehydes, 3,5-dimethyl-2-[1,8]naphthyridin-2-yl-phenylamine and malononitrile in the presence of p-dimethylaminopyridine (DMAP, 10 mol %) as a catalyst in Ethanol with good yields. Keywords: 3,5-Dimethyl-2-[1,8]naphthyridin-2-yl-phenylamine and 2-Amino-5,7-dimethyl-8-[1,8]naphthy ridin-2-yl-4-Aryl-quinoline-3carbonitriles, Malononitrile and DMAP. INTRODUCTION Naphthyridines are an important class of pharma ceutically active compounds as they have excellent biological activities, antibacterial, 1,2 antimycobacterial, 3 antitumor, 4 antiinflam matory, 5 antiplatelet, 6 gastric antisecretary, 7 antiallergic, 8 local anaesthetic 9 and benzodia zepine receptor activity. 10 Nalidixic acid, for example, possesses strong antibacterial activity and used mainly for the treatment of urinary tract infections with gram negative pathogens 11 . In addition, Gemifloxacin is antimicrobial and antibacterial 12 . For these reasons their synthesis has always attracted the attention of synthetic organic chemists. Among the variety of strategies for the construction of 1,8naphthyridine moiety, one of the most important methods is Friedlander condensation of 2aminonicotinaldehyde with carbonyl compounds containing α-methylene group in the presence of an acid 13 or base 14 catalyst. As a step in this direction and in the continuation of our work on 1,8-Naphthyridines 20-25 , synthesis of the compounds depicted in the title were W WO OR RL LD D J JO OU UR RN NA AL L O OF F P PH HA AR RM MA AC CY Y A AN ND D P PH HA AR RM MA AC CE EU UT TI IC CA AL L S SC CI IE EN NC CE ES S V Vo ol lu um me e 2 2, , I Is ss su ue e 5 5, , 3 39 99 98 8--4 40 00 04 4. . R Re es se ea ar rc ch h A Ar rt ti ic cl le e I
2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in 40-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed by condensation with triethyl orthoformate, isopropylaldehyde, o-nitro-and p-nitrobenzaldehyde, respectively. The two 2-subtituted dihydroquinazolinones obtained either by using isopropylaldehyde, o-nitro-or p-nitrobenzaldehyde, were separated and purified before their NMR spectra in CDCl 3 solutions were recorded. The detection of the low energy conformation of O=C-N-phenethyl segment in solution allowed the correlation of the NMR data with the configuration of newly stereogenic carbon C-2; thus, one diastereomer was labeled SS while the other was RS. Configurations determined by the NMR method were corroborated by X-ray diffraction analysis. X-ray structures of each diastereomeric series showed characteristic conformational types: a propeller-like for the SS and a hairpin for the RS series. Interatomic distances of the hairpin conformation suggest the existence of intramolecular face-to-face interactions between two aromatic rings.
Chem. Heterocyclic Compds. 2009, 45, 308-316
were obtained for the first time from 8-aminoquinolines using the Povarov reaction. Various oxidizing agents were shown to effect the elimination of the substituent at C(4) with subsequent aromatization of the tetrahydroquinoline fragment.
Inorganica Chimica Acta, 2011
a b s t r a c t Treatment of 7,8-benzo[h]quinoline (bhq-H, 1) and 10-methyl benzo[h]quinoline (bhq-Me, 3) with [Rh(C 2 H 4 ) 2 (THF) 2 ] [BF 4 ] resulted in double C-H activation of aliphatic and aromatic C-H bonds, yielding the Rh(III) complexes 4 and 5, respectively. The structures of 4 and 5 were revealed by X-ray diffraction. The reaction of 1 with two other slightly different rhodium precursors, [Rh(olefin) n (THF) 2 ][BF 4 ] (COE (n = 2), COD (n = 1)), led to completely different products, a dinuclear complex 7 and a trinuclear complex 6, respectively, which were characterized by X-ray diffraction. Complex 6 exhibits a rare linear Rh-Rh-Rh structure. Utilizing excess of 1 with [Rh(COD)(THF) 2 ][BF 4 ] led to the formation of a new product 8 with no C-H bond activation taking place. Additional C-H activation products of 1, cationic and neutral, in the presence of P i Pr 3 (9a, 9b and 10) are also presented. respectively, using a Bruker AMX-400 NMR spectrometer and at 500, 125 and 202 MHz, respectively, for 1 H, 13 C and 31 P, using a Bruker Avance-500 NMR spectrometer and at 250, 101 and 235, respectively, for 1 H, 31 P and 19 F NMR using a Bruker DPX 250 spectrometer. All spectra were recorded at 23°C unless stated otherwise. NMR measurements were performed in CD 2 Cl 2 , C 6 D 6 , CD 3 CN and acetone-D 6 . 1 H, 13 C { 1 H} NMR chemical shifts are reported in ppm down-field from tetramethylsilane. 1 H NMR chemical shifts are referenced to the residual hydrogen signal of the deuterated solvent (7.15 ppm for benzene, 5.32 ppm for dichloromethane, 1.94 ppm for acetonitrile and 2.04 ppm for acetone). In 13 C{ 1 H} NMR measurements the signals of deuterated benzene 1 H NMR (acetone-d 6 ): 9.53 (d, 3 J H,H = 5.4 Hz, 1H, Ar), 8.66 (d, 3 J H,H = 8.3 Hz, 1H, Ar), 8.01 (d, 3 J H,H = 8.8 Hz, 1H, Ar), 7.93 (d, 3 J H,H = 5.9 Hz, 1H, Ar), 7.90 (m, 2H, Ar), 7.85 (d, 3 J H,H = 7.3 Hz, 1H, Ar), 7.62 (d, 3 J H,H = 7.6 Hz, 1H, Ar), 4.19 (dd, 2 J Rh,H = 10.1 Hz, 2 3 J Rh,C = 2.0 Hz, Ar), 115.04 (s, Ar), 110.11 (d, 2 J Rh,C = 2.40 Hz, Ar), 105.56 (br s, Ar), 97.80 (dd, 3 J Rh,C = 6.9 Hz, 3 J Rh,C = 102.4 Hz, @CH of COD), 90.76 (d, 3 J Rh,C = 3.4 Hz, @CH of COD), 79.30 (dd, 3 J Rh,C = 13.0 Hz, 3 J Rh,C = 84.1 Hz, @CH of COD), 77.34 (dd, 3 J Rh,C = 13.6 Hz, 3 J Rh,C = 183.7 Hz, @CH of COD), 32.05 (s, -CH 2 of COD), 31.18 (s, -CH 2 of COD), 29.49 (s, -CH 2 of COD), 29.0 (d, 3 (CD 2 Cl 2 ): 9.46 (d, 3 J H,H = 3.8 Hz, 1H, Ar), 8.48 (d, 3 J H,H = 7.6 Hz, 1H, Ar), 7.84 (m, 2H, Ar), 7.77 (d, 3 J H,H = 8.9 Hz, 1H, Ar), 7.52 (d, 3 J H,H = 6.4 Hz, 1H, Ar), 7.33 (m, 3 J H,H = 7.6 Hz, 2H, Ar), 2.08 (m, 3 J H,H = 3.8 Hz, 6H, PCH(CH 3 ) 2 ), 1.03 (dist. dd, 3 J H,H = 6.4 Hz, 3 J P,H = 14.0 Hz, 18H, PCH(CH 3 ) 2 ), 0.71 (dist. dd, 3 J H,H = 6.4 Hz, 3 J P,H = 14.0 Hz, 18H, PCH(CH 3 ) 2 ), À12.51 (br s, 1H, Rh-H). 13 C{ 1 H} NMR (CD 2 Cl 2 ): 151.54 (s, Ar), 150.95 (s, Ar), 149.04 (br d, 2