Modified coumarins. 29. Synthesis of structural analogs of natural 6-arylfuro[3,2-g]chromen-7-ones

Abstract

UDC 547.814.5 3-Substituted 6-arylfuro [3,2-g]chromen-7-ones, structural analogs of natural furocoumarins, were synthesized by linear annelation of a furan fragment to a 3-arylcoumarin system.Furocoumarins are structurally varied natural compounds that are mostly derivatives of the linear furocoumarin psoralene [1]. The heightened interest in furocoumarins is due to the important role that they play in the life processes of plants and animals and their high and varied biological activity [2]. In most instances furocoumarins are unsubstituted in the 2-and 3-positions of the pyran-2-one ring. However, compounds containing aryl substituents in these positions have been isolated from natural sources. Examples of such secondary metabolites based on the 3-arylcoumarin core are pachyrrhizin {6-(6-methoxy-1,3-benzodioxol-5-yl)furo[3,2-g]chromen-7-one}, which was isolated from the plants Pachyrrhizus erosus [3][4][5], P. tuberosus [6], Neorautassenia pseudopachyrriza [7], and N. edulis [8][9][10]; neofolin {9-methoxy-6-(6-methoxy-1,3-benzodioxol-5-yl)furo[3,2-g]chromen-7-one}, which was isolated from Neorautanenia ficifolia [11]; and 6-(2,4,5-trimethoxyphenyl)furo[3,2-g]chromen-7-one, which is produced by P. tuberosus [6].We synthesized substituted 6-arylfuro[3,2-g]chromen-7-ones, structural analogs of natural furocoumarins, based on the 3-arylcoumarin core.7-Acetoxycoumarins 1-5 were prepared by a Perkin-Oglialoro reaction [12] of 2,4-dihydroxybenzaldehyde and substituted phenylacetic acids in acetic anhydride in the presence of pyridine. Acidolysis of 1-5 formed 7-hydroxy-3-arylcoumarins 6-10 that were required for further transformations.The reaction of hydroxycoumarins 6-10 with α-haloketones under Williamson conditions produced the corresponding substituted oxoethers 11-24. The alkylating agents in these syntheses were chloroacetone (11-15), 1-chloropinacolone (16-18), phenacylbromide (19 and 20), 4-methylphenacylbromide (21), 4-fluorophenacylchloride (22), and 3-methoxyphenacylbromide (23 and 24). 1, 6: R 1 = R 2 = H; 2, 7: R 1 = H, R 2 = F; 3, 8: R 1 = H, R 2 = Cl; 4, 9: R 1 = H, R 2 = OMe; 5, 10: R 1 = R 2 = OMe 11, 25: R 1 = R 2 = H, R 3 = CH 3 ; 12, 26: R 1 = H, R 2 = F, R 3 = CH 3 ; 13, 27: R 1 = H, R 2 = Cl, R 3 = CH 3 14, 28: R 1 = H, R 2 = OMe, R 3 = CH 3 ; 15, 29: R 1 = R 2 = OMe, R 3 = CH 3 ; 16, 30: R 1 = R 2 = H, R 3 = (CH 3 ) 3 C 17, 31: R 1 = H, R 2 = F, R 3 = (CH 3 ) 3 C; 18, 32: R 1 = H, R 2 = OMe, R 3 = (CH 3 ) 3 C; 19, 33: R 1 = H, R 2 = Cl, R 3 = Ph 20, 34: R 1 = R 2 = OMe, R 3 = Ph, 21, 35: R 1 = R 2 = H, R 3 = 4-Me-Ph; 22, 36: R 1 = H, R 2 = OMe, R 3 = 4-F-Ph 23, 37: R 1 = R 2 = H, R 3 = 3-MeO-Ph; 24, 38: R 1 = H, R 2 = Cl, R 3 = 3-MeO-Ph

Electron‐Donating and Electron‐Withdrawing Subunit Effects on Coumarin‐BODIPY Dyads: Optical and Electrochemical Properties and Molecular Interactions

“…4,4’‐Difluoro‐8‐(4‐iodo)‐phenyl‐1,3,5,7‐tetramethyl‐4‐bora‐3a,4a‐diaza‐s‐indacene, 7‐hydroxy‐3‐(p‐tolyl)coumarin and 7‐hydroxy‐3‐(p‐fluorophenyl)coumarin were synthesized according to procedures giving in the literature [36–38] …”

Synthesis and Evaluation of Two Coumarin‐Type Derivatization Reagents for Fluorescence Detection of Chiral Amines and Chiral Carboxylic Acids

“…2,4‐Dihydroxybenzaldehyde ( 1 , 2.76 g, 20.0 mmol) and p ‐methoxyphenylacetic acid (3.32 g, 20.0 mmol) were refluxed in a mixture of pyridine (30 mL) and acetic anhydride (30 mL) for 9 h. After cooling to room temperature, the precipitate was filtered off and washed with MeOH (30 mL) to give the product as a white solid (1.92 g, 6.2 mmol, 31%): mp 168–170 °C (lit . mp 181–182 °C); 1 H NMR (500 MHz, DMSO‐ d 6 , 25 °C) δ 2.31 (s, 3H, H 3 CCO), 3.80 (s, 3H, OCH 3 ), 7.02 (d, 2H, 3 J = 8.9 Hz, 3´‐H, 5´‐H), 7.16 (dd, 1H, 3 J = 8.5 Hz, 4 J = 2.2 Hz, 6‐H), 7.28 (d, 1H, 4 J = 2.2 Hz, 8‐H), 7.69 (d, 2H, 3 J = 8.9 Hz, 2´‐H, 6´‐H), 7.79 (d, 1H, 3 J = 8.5 Hz, 5‐H), 8.19 (s, 1H, 4‐H); 13 C NMR (125 MHz, DMSO‐ d 6 , 25 °C) δ 21.0, 55.4, 109.7, 113.8, 117.6, 118.8, 125.9, 126.9, 129.3, 129.9, 138.8, 152.5, 153.3, 159.8, 168.9.…”

“…The pH was adjusted to 2 with 2 N HCl. The precipitate was filtered off and recrystallized from MeOH (105 mL) to give the product as yellow needles (973 mg, 3.6 mmol, 73%): mp 228 °C (lit . mp 215–216); 1 H NMR (500 MHz, DMSO‐ d 6 , 25 °C) δ 3.78 (s, 3H, CH 3 ), 6.73 (d, 1H, 4 J = 2.3 Hz, 8‐H), 6.80 (dd, 1H, 3 J = 8.5 Hz, 4 J = 2.6 Hz, 6‐H), 6.98 (d, 2H, 3 J = 8.9 Hz, 3´‐H, 5´‐H), 7.56 (d, 1H, 3 J = 8.5 Hz, 5‐H), 7.64 (d, 2H, 3 J = 8.8 Hz, 2´‐H, 6´‐H), 8.05 (s, 1H, 4‐H), 10.51 (br s, 1H, OH); 13 C NMR (125 MHz, DMSO‐ d 6 , 25 °C) δ 55.3, 101.8, 112.2, 113.5, 113.8, 122.0, 127.5, 129.6, 129.8, 139.9, 154.8, 159.3, 160.3, 161.1.…”

“…The product, (R)-2-(3-(methoxycarbonyl)-2-oxochroman-7yloxy)propanoic acid (7), was obtained as a white solid (310 mg, Synthesis of 3-(4-Methoxyphenyl)-2-oxo-2H-chromen-7-yl Acetate (8) 2,4-Dihydroxybenzaldehyde (1, 2.76 g, 20.0 mmol) and pmethoxyphenylacetic acid (3.32 g, 20.0 mmol) were refluxed in a mixture of pyridine (30 mL) and acetic anhydride (30 mL) for 9 h. After cooling to room temperature, the precipitate was filtered off and washed with MeOH (30 mL) to give the product as a white solid (1.92 g, 6.2 mmol, 31%): mp 168-170°C (lit. 27 (10) 7-Hydroxy-3-(4-methoxyphenyl)-2H-chromen-2-one (9, 537 mg, 2.0 mmol), triphenylphosphine (1.04 g, 4.0 mmol) and methyl (S)-(À)-lactate (312 mg, 3.0 mmol) were dissolved in THF (30 mL) and cooled to 0°C. Di-tert-butyl azodicarboxylate (690 mg, 3.0 mmol) was added portionwise and the solution was stirred for 2 h at room temperature.…”

Synthesis of benzofurans from the cyclodehydration of α-phenoxy ketones mediated by Eaton’s reagent

“…As a typical example, the synthesis of 3-phenylbenzofuran 2a from α-phenoxy acetophenone 1a is illustrated in Scheme 3. It can be accessed by refluxing 1a in ethanol in the presence of a base (Path 1) such as KOH with subsequent acidification 29,30 or in the presence of acid (Path 2), for example, Lewis acids such as TiCl 4 , 31 Bi(OTf) 3 , 32 BCl 3 , 33,34 and Al 2 O 3 35 or Brønsted acids such as triflic acid, 36 methanesulfonic acid (MeSO 3 H), 37–40 and p -toluenesulfonic acid. 41,42 In addition, a few transition-metal catalysts (path 3) such as Ir or Pd have been used to facilitate cyclodehydration reaction.…”