The 4H-chromene fragment is a key structural feature of many biologically active compounds. Among them, promising drugs with anticancer and antibacterial effects were found.1 At the same time, 2-aryl-4H-chromenes (flav-2-enes) are rarely encountered in the structure of natural compounds, which may be explained by their high chemical activity due to which they themselves can potentially be synthetic precursors to many other natural flavonoids and their derivatives.2 Flavonoids A–E can be given as examples of 2-aryl-4H-chromenes of plant origin (Fig. 1).3

Figure 1
figure 1

Natural 2-aryl-4H-chromenes.

Full size image

Currently, the principal methods for the preparation of 2-substituted and 2,4-disubstituted 4H-chromenes are the addition of nucleophiles to benzopyrylium salts, reduction of flavones, cyclization reactions with the participation of α,β-enones, isomerization of 2H-chromenes, and [4+2] cycloaddition involving o-quinone methides.4

As enol esters, flav-2-enes easily enter into addition reactions with electrophilic reagents, are sensitive to oxidants, including atmospheric oxygen, readily hydrolyze to form 2-hydroxydihydrochalcones, and can also undergo disproportionation to chromanes and benzopyrylium salts and isomerize to 2H-chromenes.5 However, the study of the chemical properties and biological activity of flav-2-enes is constrained by their low content in natural sources, low availability of biological material, laborious methods of isolation and purification, as well as a relatively small number of methods for their synthesis. In this regard, the development of novel methods for the preparation of 2-aryl-4H-chromenes is of practical interest.

We have previously developed an efficient approach to the synthesis of 2-acyl-2,3-dihydrobenzofurans and 2-acyl-1,2-dihydronaphtho[2,1-b]furans based on the precursors of o-quinone methides6 and pyridinium ylides as synthetic equivalents of acylcarbenes.7 Using the proposed method, a series of 2-aroyl-2,3-dihydrobenzofurans, both new and previously described in the literature but synthesized by other methods, were obtained (Scheme 1). Diacetates of salicylic alcohols and products of o-aminomethylation and quaternization of phenols 1a–e were used as precursors of benzene o-quinone methides. The reactions were carried out under an inert atmosphere to prevent possible oxidation to benzofurans by heating under reflux in MeCN or in DMF in the case of the less active precursor of o-quinone methide, the phenol Mannich base (X = OH, Y = NMe2). DBU or DIPEA were used as bases to generate pyridinium ylides from N-phenacylpyridinium salts 2a–d. In the case of 2,3-disubstituted dihydrobenzofurans 3f–h, the reaction proceeds diastereoselectively and leads to the transisomers, as evidenced by 1H NMR spectroscopy data. The methine protons of the dihydrofuran ring appear as doublets in the ranges of 4.87–5.00 (3-CH) and 5.77–5.84 (2-CH) ppm with 3J = 6.4–6.7 Hz, which is typical for trans-isomers.

scheme 1

Scheme 1

Upon the action of zinc on 2-aroyl-2,3-dihydrobenzofurans 3а–h in AcOH, it turned out that 3-phenylsubstituted derivatives 3f–h, as well as compound 3d, rearranged into 2-aryl-4Н-chromenes 4a–d in 62–76% yields; however, in the case of substrates 3a–c,e unsubstituted at the C-3 position, the main products were 3-(2-hydroxyaryl)propan-1-ones 5a–d (Scheme 2).

scheme 2

Scheme 2

The reactions were carried out by heating under reflux in AcOH with vigorous stirring for 2–5 h using excess zinc dust. Increasing the stirring speed and the amount of Zn up to 5 equiv shortens the reaction time and increases the product yield. The use of stoichiometric amounts of metal does not lead to complete conversion of dihydrobenzofurans 3a–h even during prolonged heating under reflux of the reaction mixture, which is apparently due to the accompanying reaction of Zn and AcOH with the formation of Zn(OAc)2 and Н2. The tendency of 2-aryl-4Hchromenes to oxidize makes it necessary to use an inert atmosphere to achieve acceptable yields. The obtained 3-(2-hydroxyaryl)propan-1-ones 5a–d may also be of some interest due to the wide spectrum of biological activity of dihydrochalcones, of which they are representatives.8

The successful synthesis of 2-phenyl-4H-chromenes 4e,f from the corresponding 3-unsubstituted 2-benzoyl-2,3-dihydrobenzofurans 3b,c was carried out by replacing the Zn–AcOH reducing system with a combination of Sm with TMSCl in 1,4-dioxane, which made it possible to avoid the formation of 2-hydroxydihydrochalcones 5b,c (Scheme 2). Chromenes 4e,f were obtained in 72 and 61% yields by heating with an excess of finely dispersed Sm and TMSCl in 1,4-dioxane under reflux. It should be noted that although metallic Sm is less active in reduction processes than the widely used SmI2, its use offers a number of advantages. It is much less sensitive to atmospheric oxygen, stable during storage, convenient to use, and is a cheaper reducing agent, and the Sm activity can be easily modified by adding halogen-containing reagents (I2, TMSCl, RHal, HCl, etc.). These factors are responsible for the increasing popularity of the use of metallic Sm in organic synthesis.9

In the 1H NMR spectra of 2,4-diaryl-substituted 4H-chromenes 4a–с, the pyran ring protons appear as doublets at 4.83–4.85 (4-CH) and 5.48–5.56 (3-CH) ppm with 3J = 4.0–4.1 Hz, and the carbon atoms bound to them in the 13C NMR spectra are found in the ranges 41.2–41.3 (C-4) and 99.3–100.8 (C-3) ppm. In the 1H NMR spectra of chromenes 4d–f unsubstituted at position 4, protons at positions 4 and 3 appear, respectively, as a doublet (at 3.51–3.61 ppm) and a triplet (at 5.48–5.56 ppm) with 3J = 3.9 Hz, whereas the carbon atoms bound to them in the 13C NMR spectra resonate in the ranges of 24.2–25.6 (C-4) and 96.4– 97.0 (C-3) ppm.

In the 1H NMR spectra of dihydrochalcones 5a–d, the protons of the methylene groups appear as multiplets at 2.95–3.05 and 3.37–3.46 ppm. The carbonyl carbon atom in the 13C NMR spectra corresponds to the signal at 200.5–202.1 ppm.

The mechanism of the rearrangement of 2-aroyl-2,3-dihydrobenzofurans 3 by the action of Zn in AcOH, apparently, involves a double one-electron reduction of the carbonyl group via ketyl radical I with the formation of organozinc intermediate II. Opening of the dihydrofuran ring in it gives phenolate III, the protonation of which followed by ketalization of 2-hydroxydihydrochalcone IV and dehydration of chromanol V leads to chromene 4 (Scheme 3).

scheme 3

Scheme 3

No dihydrochalcones formed upon the reduction with metallic Sm, which can be explained by a change in the reaction mechanism which apparently involves carbenoidtype intermediates, as was previously described for the reductive rearrangement of annulated dihydrofurans.10

To conclude, we proposed two reduction systems (Zn in AcOH and Sm + TMSCl in 1,4-dioxane) for the transformation of 2-aroyl-2,3-dihydrobenzofurans into 2-aryl-4H-chromenes.

Experimental

IR spectra were registered on a Shimadzu IRAffinity-1 spectrometer equipped with a Specac Diamond ATR GS 10800-B attachment. A JEOL JNM-ECX400 spectrometer was used to record 1H and 13C NMR spectra (400 and 100 MHz, respectively) as well as perform DEPT-135 experiments. NMR spectra were recorded in CDCl3 using residual solvent signals as internal standard (7.26 ppm for 1Н nuclei, 77.2 ppm for 13С nuclei). Elemental analysis was performed on a Euro Vector EA-3000 CHNS-analyzer. Melting points were determined by the capillary method on an SRS OptiMelt MPA100 apparatus. Monitoring of the reaction progress and assessment of the purity of synthesized compounds were done by TLC on Merck Silica gel 60 F254 plates, visualization with UV light or by iodine stain. Merck Silica gel 60, 0.04–0.063 mm fraction was used for column chromatography.

Synthesis of 2-aroyl-2,3-dihydrobenzofurans 3a,e–h (General method). DBU (0.9 ml, 0.91 g, 6 mmol) was added to a mixture of 2-acetoxy-5-chlorobenzyl acetate (0.73 g, 3 mmol) or 2-[acetoxy(phenyl)methyl]phenyl acetate (0.85 g, 3 mmol), pyridinium salt (3 mmol) in MeCN (20 ml), and the resulting solution was heated under reflux under an argon atmosphere for 8 h. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent CCl4–CHCl3, 1:1) followed by recrystallization from EtOH.

Synthesis of 2-aroyl-2,3-dihydrobenzofurans 3b,c (General method). DBU (0.45 ml, 0.46 g, 3 mmol) was added to a mixture of 1-(5-tert-butyl-2-hydroxyphenyl)-N,N,N-trimethylmethane ammonium iodide (1.05 g, 3 mmol) or 1-(2-hydroxy-4,5-dimethylphenyl)-N,N,N-trimethylmethane ammonium iodide (0.96 g, 3 mmol), 2-oxo-2-phenylethylpyridinium bromide (0.83 g, 3 mmol) in MeCN (20 ml), and the resulting solution was heated under reflux under an argon atmosphere for 12 h. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent CHCl3) followed by recrystallization from EtOH.

5-Chloro-2,3-dihydrobenzofuran-2-yl)(phenyl)methanone (3a). Yield 405 mg (52%), colorless crystals, mp 140–141°C. IR spectrum, ν, cm–1: 3063, 1697 (C=O), 1595, 1476, 1447, 1379, 1298, 1279, 1240, 1227, 1173, 1115, 1003, 993, 918, 885, 825, 694, 677. 1H NMR spectrum, δ, ppm (J, Hz): 3.51 (1H, dd, J = 16.0, J = 10.3, 3-CH2); 3.58 (1H, dd, J = 16.0, J = 7.3, 3-CH2); 5.96 (1H, dd, J = 10.3, J = 7.3, 2-CH); 6.77 (1H, d, J = 8.5, H-7); 7.08 (1H, dd, J = 8.5, J = 2.3, H-6); 7.13 (1H, d, J = 2.3, H-4); 7.48–7.52 (2H, m, H-3',5'); 7.62 (1H, t, J = 7.6, H-4'); 8.02 (2H, d, J = 7.8, H-2',6'). 13C NMR spectrum, δ, ppm: 32.4 (CH2); 83.1 (2-CH); 110.8 (CH); 125.1 (CH); 126.0; 127.3; 128.3 (CH); 128.9 (2CH Ph); 129.2 (2CH Ph); 134.0 (CH); 134.3; 157.8 (C-7a); 195.0 (C=O). Found, %: C 69.72; H 4.34. C15H11СlO2. Calculated, %: C 69.64; H 4.29.

[5-( tert -Butyl)-2,3-dihydrobenzofuran-2-yl](phenyl)-methanone (3b). Yield 455 mg (54%), colorless crystals, mp 102–104°C. IR spectrum, ν, cm–1: 2951, 2907, 1692 (C=O), 1595, 1582, 1493, 1449, 1364, 1312, 1233, 1179, 1167, 1123, 1057, 1018, 993, 918, 905, 880, 818, 770, 700, 669. 1H NMR spectrum, δ, ppm (J, Hz): 1.29 (9H, s, C(CH3)3); 3.54 (1H, dd, J = 15.6, J = 10.3, 3-CH2); 3.60 (1H, dd, J = 15.6, J = 7.6, 3-CH2); 5.92 (1H, dd, J = 10.3, J = 7.6, 2-CH); 6.80 (1H, d, J = 8.5, H-7); 7.16 (1H, dd, J = 8.5, J = 2.3, H-6); 7.22 (1H, br. s, H-4); 7.48–7.52 (2H, m, H-3',5'); 7.61 (1H, tt, J = 7.6, J = 1.4, H-4'); 8.03–8.06 (2H, m, H-2',6'). 13C NMR spectrum, δ, ppm: 31.8 (C(CH3)3); 32.9 (CH2); 34.4 (C(CH3)3); 82.9 (2-CH); 109.0 (CH); 121.9 (CH); 124.8; 125.2 (CH); 128.8 (2CH Ph); 129.2 (2CH Ph); 133.7 (CH); 134.7; 144.3; 156.9 (C-7a); 195.8 (C=O). Found, %: C 81.32; H 7.13. C19H20O2. Calculated, %: C 81.40; H 7.19.

(5,6-Dimethyl-2,3-dihydrobenzofuran-2-yl)(phenyl)-methanone (3c). Yield 430 mg (57%), colorless crystals, mp 97–99°C. IR spectrum, ν, cm–1: 2899, 2845, 1674 (C=O), 1597, 1539, 1493, 1447, 1339, 1317, 1256, 1219, 1157, 1126, 1090, 1061, 914, 860, 806, 773, 692, 658. 1H NMR spectrum, δ, ppm (J, Hz): 2.18 (3H, s, CH3); 2.21 (3H, s, CH3); 3.49–3.51 (2H, m, 3-CH2); 5.89 (1H, dd, J = 9.4, J = 8.0, 2-CH); 6.70 (1H, s, H-7); 6.94 (1H, s, H-4); 7.47–7.52 (2H, m, H-3',5'); 7.60 (1H, tt, J = 7.4, J = 1.4, H-4'); 8.01–8.04 (2H, m, H-2',6'). 13C NMR spectrum, δ, ppm: 19.4 (CH3); 20.2 (CH3); 32.8 (CH2); 82.9 (2-CH); 111.0 (CH); 122.2; 125.8 (CH); 128.8 (2CH Ph); 129.1; 129.2 (2CH Ph); 133.7 (CH); 134.6; 136.7; 157.5 (C-7a); 196.0 (C=O). Found, %: C 80.85; H 6.33. C17H16O2. Calculated, %: C 80.93; H 6.39.

[7-(Adamantan-1-yl)-5-( tert -butyl)-2,3-dihydrobenzofuran-2-yl](phenyl)methanone (3d). A mixture of 6-(adamantan-1-yl)-4-(tert-butyl)-2-[(dimethylamino)methyl]-phenol (1.02 g, 3 mmol), 1-(2-oxo-2-phenylethyl)pyridinium bromide (0.83 g, 3 mmol), and Hünig's base (DIPEA) (0.6 ml, 0.45 g, 3.5 mmol) in DMF (10 ml) was heated under reflux under an argon atmosphere for 12 h. The solution was cooled to room temperature and poured into H2O (50 ml). The product was extracted with EtOAc (2×25 ml), the extract was washed with H2O, saturated aqueous NaCl and dried over anhydrous Na2SO4. The solvent was distilled off under reduced pressure, the residue was purified by column chromatography on silica gel (eluent CHCl3) followed by recrystallization from EtOH. Yield 475 mg (60%), colorless crystals, mp 152–154°C. IR spectrum, ν, cm–1: 2965, 2903, 2847, 1694 (C=O), 1599, 1479, 1450, 1362, 1300, 1221, 1177, 1099, 1015, 978, 924, 872, 826, 748, 692. 1H NMR spectrum, δ, ppm (J, Hz): 1.30 (9H, s, C(CH3)3); 1.73 (6H, br. s, 3CH2 Ad); 1.97–2.01 (9H, m, 3CH Ad, 3CH2 Ad); 3.47 (1H, dd, J = 15.6, J = 10.6, 3-CH2); 3.67 (1H, dd, J = 15.6, J = 6.6, 3-CH2); 5.87 (1H, dd, J = 10.6, J = 6.6, 2-CH); 7.06 (1H, d, J = 1.8, H-4(6)); 7.10 (1H, d, J = 1.8, H-6(4)); 7.49 (2H, dd, J = 7.8, J = 7.3, H-3',5'); 7.59 (1H, t, J = 7.3, H-4'); 8.11 (2H, d, J = 7.8, H-2',6'). 13C NMR spectrum, δ, ppm: 29.0 (3CH Ad); 31.8 (3-CH2); 31.9 (C(CH3)3); 34.6 (C(CH3)3); 36.2 (C Ad); 37.1 (3CH2 Ad); 40.5 (3CH2 Ad); 83.0 (2-CH); 119.3 (CH); 121.8 (CH); 125.3; 128.6 (2CH Ph); 129.5 (2CH Ph); 132.7; 133.5 (CH); 135.0; 144.0; 154.5 (C-7a); 196.7 (C=O). Found, %: C 83.94; H 8.32. C29H34O2. Calculated, %: C 84.02; H 8.27.

(5-Chloro-2,3-dihydrobenzofuran-2-yl)(4-methoxyphenyl) methanone (3e). Yield 632 mg (73%), colorless crystals, mp 123–124°C. IR spectrum, ν, cm–1: 2943, 1670 (C=O), 1605, 1574, 1512, 1481, 1447, 1423, 1323, 1273, 1250, 1169, 1115, 1065, 1022, 988, 907, 853, 810, 679. 1H NMR spectrum, δ, ppm (J, Hz): 3.48 (1H, dd, J = 16.0, J = 10.3, 3-CH2); 3.59 (1H, dd, J = 16.0, J = 7.3, 3-CH2); 3.88 (3H, s, CH3O); 5.91 (1H, dd, J = 10.3, J = 7.3, 2-CH); 6.77 (1H, d, J = 8.5, H-7); 6.97 (2H, d, J = 8.9, H-3',5'); 7.08 (1H, dd, J = 8.5, J = 2.3, H-6); 7.14 (1H, br. s, H-4); 8.01 (2H, d, J = 8.9, H-2',6'). 13C NMR spectrum, δ, ppm: 32.4 (CH2); 55.7 (CH3O); 83.0 (2-CH); 110.7 (CH); 114.1 (2CH Ph); 125.1 (CH); 125.9; 127.3; 127.5; 128.2 (CH); 131.6 (2CH Ph); 157.8 (C-7a); 164.2 (COCH3); 193.4 (C=O). Found, %: C 66.47; H 4.48. C16H13СlO3. Calculated, %: C 66.56; H 4.54.

((2 R *,3 R *)-3-Phenyl-2,3-dihydrobenzofuran-2-yl)-( p -tolyl)methanone (3f). Yield 575 mg (61%), colorless crystals, mp 100–101°C. IR spectrum, ν, cm–1: 3028, 2951, 1694 (C=O), 1601, 1477, 1462, 1408, 1234, 1207, 1184, 1099, 1053, 1011, 984, 968, 953, 891, 814, 756, 702. 1H NMR spectrum, δ, ppm (J, Hz): 2.42 (3H, s, CH3); 4.98 (1H, d, J = 6.4, 3-CH); 5.80 (1H, d, J = 6.4, 2-CH); 6.89 (1H, td, J = 7.6, J = 0.9, H Ar); 6.97–7.01 (2H, m, H Ar); 7.19–7.36 (8H, m, H Ar); 7.86 (2H, d, J = 8.3, H Ar). 13C NMR spectrum, δ, ppm: 21.9 (CH3); 51.0 (3-CH); 90.6 (2-CH); 110.1 (CH); 121.7 (CH); 125.4 (CH); 127.5 (CH); 128.3 (2CH); 129.0 (CH); 129.1 (2CH); 129.4; 129.5 (4CH); 132.0; 142.5; 144.9; 159.2 (C-7a); 194.4 (C=O). Found, %: C 83.95; H 5.86. C22H18O2. Calculated, %: C 84.05; H 5.77.

(4-Methoxyphenyl)((2 R *,3 R *)-3-phenyl-2,3-dihydrobenzofuran-2-yl)methanone (3g). Yield 665 mg (67%), colorless crystals, mp 151–152°C. IR spectrum, ν, cm–1: 1684 (C=O), 1597, 1574, 1477, 1462, 1423, 1256, 1231, 1213, 1180, 1049, 1015, 961, 837, 810, 756, 698. 1H NMR spectrum, δ, ppm (J, Hz): 3.87 (3H, s, CH3O); 5.00 (1H, d, J = 6.6, 3-CH); 5.77 (1H, d, J = 6.6, 2-CH); 6.87–6.93 (3H, m, H Ar); 6.97 (1H, d, J = 8.0, H Ar); 7.00 (1H, d, J = 7.6, H Ar); 7.18–7.30 (4H, m, H Ar); 7.31–7.36 (2H, m, H Ar); 7.94 (2H, d, J = 8.9, H Ar). 13C NMR spectrum, δ, ppm: 51.0 (3-CH); 55.6 (CH3O); 90.6 (2-CH); 110.0 (CH); 114.0 (2CH); 121.6 (CH); 125.4 (CH); 127.5 (CH); 127.6; 128.3 (2CH); 128.9 (CH); 129.1 (2CH); 129.5; 131.8 (2CH); 142.5; 159.2 (C-7a); 164.1 (COCH3); 193.2 (C=O). Found, %: C 79.92; H 5.43. C22H18O3. Calculated, %: C 79.98; H 5.49.

((2 R *,3 R *)-3-Phenyl-2,3-dihydrobenzofuran-2-yl)-(3,4,5-trimethoxyphenyl)methanone (3h). Yield 773 mg (66%), colorless crystals, mp 122–124°C. IR spectrum, ν, cm–1: 1688 (C=O), 1584, 1506, 1481, 1456, 1418, 1323, 1248, 1161, 1125, 1036, 989, 860, 822, 762, 698, 625. 1H NMR spectrum, δ, ppm (J, Hz): 3.72 (6H, s, 2CH3O); 3.91 (3H, s, CH3O); 4.87 (1H, d, J = 6.7, 3-CH); 5.84 (1H, d, J = 6.7, 2-CH); 6.88 (1H, t, J = 7.5, H Ar); 6.97 (1H, d, J = 7.6, H Ar); 7.00 (1H, d, J = 8.0, H Ar); 7.12 (2H, s, H-2',6'); 7.19–7.36 (6H, m, H Ar). 13C NMR spectrum, δ, ppm: 52.0 (3-CH); 56.1 (2CH3O); 61.1 (CH3O); 90.7 (2-CH); 106.6 (2CH); 110.1 (CH); 121.7 (CH); 125.4 (CH); 127.7 (CH); 128.3 (2CH Ph); 129.1 (CH); 129.2 (СН, 2CH Ph); 129.2; 129.3; 142.4; 143.1; 153.2 (2COCH3); 159.2 (C-7a); 193.7 (C=O). Found, %: C 73.78; H 5.60. C24H22O5. Calculated, %: C 73.83; H 5.68.

Synthesis of 2-aryl-4 H -chromenes 4a–d and 2-hydroxydihydrochalcones 5a–d (General method). A mixture of 2-aroyl-2,3-dihydrobenzofuran 3a–c,e (1 mmol) and zinc dust (0.33 g, 5 mmol) in AcOH (10 ml) was heated under reflux with vigorous stirring for 2 h (for products 4a–d) or 5 h (for products 5a–d) under an argon atmosphere (TLC control, eluent CHCl3–CCl4, 1:1). After completion of the reaction, the mixture was cooled, poured into H2O (50 ml), and the product was extracted with EtOAc (2×20 ml). The organic phase was washed with H2O, aqueous NaHCO3, saturated aqueous NaCl and dried over anhydrous Na2SO4. The solvent was distilled off under reduced pressure, the residue was purified by column chromatography on silica gel (eluent CHCl3–CCl4, 1:1), followed by recrystallization from a suitable solvent.

Synthesis of 2-aryl-4 H -chromenes 4e,f (General method). TMSCl (0.5 ml, 0.43 g, 4 mmol) was added to a mixture of 2-aroyl-2,3-dihydrobenzofuran 3b,c (1 mmol) and finely dispersed samarium (0.6 g, 4 mmol) in 1,4- dioxane (15 ml). The reaction mixture was heated under reflux with vigorous stirring under an argon atmosphere for 4 h (TLC control, eluent CHCl3–CCl4, 1:1), cooled, and poured into H2O (50 ml). The product was extracted with EtOAc (2×20 ml). The organic phase was washed with H2O, saturated aqueous NaCl and dried over anhydrous Na2SO4. The solvent was distilled off under reduced pressure, the residue was purified by column chromatography on silica gel (eluent CCl4) followed by recrystallization from MeOH.

4-Phenyl-2-( p -tolyl)-4 H -chromene (4a). Yield 227 mg (76%), colorless crystals, mp 137–138°С (EtOH) (mp 137°С11). IR spectrum, ν, cm–1: 3028, 1667 (C=C pyran), 1585, 1512, 1489, 1454, 1323, 1277, 1234, 1115, 1061, 1037, 999, 822, 795, 756, 698. 1H NMR spectrum, δ, ppm (J, Hz): 2.39 (3Н, s, СН3); 4.85 (1H, d, J = 4.1, 4-CH); 5.56 (1H, d, J = 4.1, 3-CH); 6.94–6.99 (2H, m, H Ar); 7.14 (1H, d, J = 7.8, H Ar); 7.17–7.25 (4H, m, H Ar); 7.30–7.35 (4H, m, H Ar); 7.64 (2H, d, J = 8.2, H Ar). 13C NMR spectrum, δ, ppm: 21.4 (СН3); 41.2 (4-СН); 100.2 (3-СН); 116.8 (СН); 123.4; 123.5 (СН); 124.8 (2СН); 126.8 (СН); 127.8 (СН); 128.5 (2СН); 128.8 (2СН); 129.1 (2СН); 129.8 (СН); 131.5; 138.5; 146.9; 147.9; 151.1. Found, %: C 88.47; H 6.03. C22H18O. Calculated, %: C 88.56; H 6.08.

2-(4-Methoxyphenyl)-4-phenyl-4 H -chromene (4b). Yield 225 mg (72%), colorless crystals, mp 116–118°С (EtOH) (mp 118–119°С12). IR spectrum, ν, cm–1: 1665 (C=C pyran), 1609, 1582, 1512, 1485, 1454, 1290, 1252, 1231, 1175, 1111, 1028, 997, 831, 785, 760, 750, 692. 1H NMR spectrum, δ, ppm (J, Hz): 3.84 (3Н, s, СН3О); 4.83 (1H, d, J = 4.0, 4-CH); 5.48 (1H, d, J = 4.0, 3-CH); 6.92 (2H, d, J = 8.9, H Ar); 6.95–6.99 (2H, m, H Ar); 7.12 (1H, d, J = 7.8, H Ar); 7.16–7.25 (2H, m, H Ar); 7.29–7.34 (4H, m, H Ar); 7.67 (2H, d, J = 8.9, H Ar). 13C NMR spectrum, δ, ppm: 41.2 (4-CH); 55.4 (CH3O); 99.3 (3-CH); 113.8 (2CH); 116.8 (CH); 123.5 (2CH); 126.2 (2CH); 126.7 (CH); 127.0; 127.7 (CH); 128.5 (2CH); 128.8 (2CH); 129.8 (CH); 147.0; 147.7; 151.1; 160.0 (COCH3). Found, %: C 84.12; H 5.71. C22H18O2. Calculated, %: C 84.05; H 5.77.

4-Phenyl-2-(3,4,5-trimethoxyphenyl)-4 H -chromene (4c). Yield 258 mg (69%), colorless crystals, mp 167–168°С (EtOH). IR spectrum, ν, cm–1: 2938, 1663 (C=C pyran), 1582, 1506, 1485, 1455, 1414, 1341, 1225, 1126, 993, 932, 841, 792, 756, 696. 1H NMR spectrum, δ, ppm (J, Hz): 3.87 (3Н, s, СН3О); 3.90 (6H, s, 2СН3О); 4.84 (1H, d, J = 4.1, 4-CH); 5.51 (1H, d, J = 4.1, 3-CH); 6.94 (2H, s, H-2',6'); 6.96 (2H, d, J = 3.9, H Ar); 7.12 (1H, d, J = 8.0, H Ar); 7.16–7.25 (2H, m, H Ar); 7.29–7.35 (4H, m, H Ar). 13C NMR spectrum, δ, ppm: 41.3 (4-СН); 56.3 (2CH3O); 61.0 (CH3O); 100.8 (3-СН); 102.3 (2CH); 116.7 (CH); 123.3; 123.7 (CH); 126.9 (CH); 127.8 (CH); 128.5 (2CH Ph); 128.8 (2CH Ph); 129.8 (CH); 130.0; 138.7; 146.7; 147.7; 150.9; 153.2 (2COCH3). Found, %: C 76.90; H 5.96. C24H22O4. Calculated, %: C 76.99; H 5.92.

8-(Adamantan-1-yl)-6-( tert -butyl)-2-phenyl-4 H -chromene (4d). Yield 247 mg (62%), colorless crystals, mp 147–149°С (i-PrOH). IR spectrum, ν, cm–1: 2959, 2905, 2851, 1674 (C=C pyran), 1597, 1497, 1470, 1450, 1362, 1342, 1323, 1285, 1196, 1126, 1045, 999, 872, 756, 737, 687. 1H NMR spectrum, δ, ppm (J, Hz): 1.33 (9H, s, C(CH3)3); 1.80–1.88 (6H, m, 3СН2 Ad); 2.13 (3H, br. s, 3СН Ad); 2.23 (6H, br. s, 3СН2 Ad); 3.61 (2H, d, J = 3.9, 4-CH); 5.56 (1H, t, J = 3.9, 3-CH); 6.95 (1H, d, J = 2.3, H-5(7)); 7.19 (1H, d, J = 2.3, H-7(5)); 7.31–7.43 (3H, m, H Ph); 7.79–7.82 (2H, m, H Ph). 13C NMR spectrum, δ, ppm: 25.6 (CH2); 29.2 (3CH Ad); 31.6 (C(CH3)3); 34.5 (C(CH3)3); 37.2 (3CH2 Ad); 37.4 (C Ad); 40.9 (3CH2 Ad); 97.0 (3-CH); 118.9 (C); 122.3 (CH); 123.7 (CH); 124.9 (2CH); 128.1 (CH); 128.3 (2CH); 135.1; 137.1; 145.2; 148.7; 149.3. Found, %: C 87.25; H 8.59. C29H34O. Calculated, %: C 87.39; H 8.60.

6-( tert -Butyl)-2-phenyl-4 H -chromene (4e). Yield 190 mg (72%), colorless crystals, mp 71–72°С. IR spectrum, ν, cm–1: 2955, 2924, 1670 (C=C pyran), 1503, 1449, 1364, 1267, 1236, 1182, 1130, 1043, 1001, 880, 826, 754, 689. 1H NMR spectrum, δ, ppm (J, Hz): 1.31 (9H, s, C(CH3)3); 3.58 (2H, d, J = 3.9, 4-CH); 5.50 (1H, t, J = 3.9, 3-CH); 6.96 (1H, d, J = 8.5, H-8); 7.08 (1H, d, J = 2.3, H-5); 7.19 (1H, dd, J = 8.5, J = 2.3, H-7); 7.31–7.39 (3H, m, H Ph); 7.66–7.68 (2H, m, H Ph). 13C NMR spectrum, δ, ppm: 24.9 (CH2); 31.6 (C(CH3)3); 34.3 (C(CH3)3); 96.4 (3-CH); 116.2 (CH); 118.9; 124.6 (CH, 2CH Ph); 125.7 (CH); 128.26 (CH); 128.34 (2CH Ph); 134.8; 146.2; 149.2; 149.8. Found, %: C 86.40; H 7.58. C19H20O. Calculated, %: C 86.32; H 7.63.

6,7-Dimethyl-2-phenyl-4 H -chromene (4f). Yield 145 mg (61%), colorless crystals, mp 81–83°С. IR spectrum, ν, cm–1: 2922, 2855, 1667 (C=C pyran), 1624, 1580, 1503, 1447, 1317, 1306, 1261, 1202, 1179, 1099, 1001, 868, 754, 689, 625. 1H NMR spectrum, δ, ppm (J, Hz): 2.20 (3H, s, СН3); 2.23 (3H, s, СН3); 3.51 (2H, d, J = 3.9, 4-CH); 5.48 (1H, t, J = 3.9, 3-CH); 6.83 (2H, s, Н-5,8); 7.29–7.40 (3H, m, H Ph); 7.66–7.68 (2H, m, H Ph). 13C NMR spectrum, δ, ppm: 19.0 (CH3); 19.6 (CH3); 24.2 (CH2); 96.4 (3-CH); 116.6; 117.5 (CH); 124.6 (2CH Ph); 128.2 (CH); 128.3 (2CH Ph); 129.7 (CH); 131.4; 134.9; 135.8; 149.1; 149.9. Found, %: C 86.48; H 6.86. C17H16O. Calculated, %: C 86.40; H 6.82.

3-(5-Chloro-2-hydroxyphenyl)-1-phenylpropan-1-one (5a). Yield 155 mg (59%), slowly crystallizing light-yellow oil, mp 48–50°С. IR spectrum, ν, cm–1: 3322 (ОН), 2832, 1663 (C=O), 1597, 1501, 1450, 1420, 1292, 1269, 1169, 1115, 994, 814, 663. 1H NMR spectrum, δ, ppm (J, Hz): 2.97–3.00 (2H, m, СН2); 3.43–3.46 (2H, m, СН2); 6.85 (1H, d, J = 8.5, H-3); 7.05 (1H, dd, J = 8.5, J = 2.3, H-4); 7.09 (1H, d, J = 2.3, Н-6); 7.43–7.47 (2H, m, Н-3',5'); 7.56–7.60 (1H, m, Н-4'); 7.95–7.98 (2H, m, Н-2',6'); 8.19 (1H, s, ОН). 13C NMR spectrum, δ, ppm: 23.3 (СН2); 40.3 (СН2); 119.1 (СН); 125.2; 127.9 (СН); 128.5 (2СН); 128.8 (2СН); 129.6; 130.2 (СН); 134.1 (СН); 135.9; 153.4 (С–ОН); 202.1 (С=О). Found, %: C 69.17; H 5.08. C15H13ClO2. Calculated, %: C 69.10; H 5.03.

3-[5-( tert -Butyl)-2-hydroxyphenyl]-1-phenylpropan-1-one (5b). Yield 115 mg (41%), light-yellow oil. IR spectrum, ν, cm–1: 3354 (OH), 2959, 1663 (С=О), 1597, 1580, 1504, 1449, 1364, 1271, 1236, 1206, 1182, 1155, 1125, 1098, 976, 826, 741, 687. 1H NMR spectrum, δ, ppm (J, Hz): 1.28 (9H, s, C(CH3)3); 3.02–3.05 (2H, m, СН2); 3.43–3.46 (2H, m, СН2); 6.84 (1H, d, J = 8.2, H-3); 7.11–7.14 (2H, m, H-4,6); 7.42–7.47 (2H, m, H-3',5'); 7.54–7.59 (1H, m, H-4'); 7.97–8.00 (2H, m, H-2',6'). The position of the signal of the proton of the OH group cannot be reliably identified due to its strong broadening. 13C NMR spectrum, δ, ppm: 23.9 (CH2); 31.7 (C(CH3)3); 34.1 (C(CH3)3); 40.6 (CH2); 116.9 (CH); 125.0 (CH); 127.0; 127.4 (CH); 128.4 (2CH); 128.7 (2CH); 133.8 (CH); 136.3; 143.5; 152.2 (C–OH); 202.1 (C=O). Found, %: C 80.75; H 7.80. C19H22O2. Calculated, %: C 80.82; H 7.85.

3-(2-Hydroxy-4,5-dimethylphenyl)-1-phenylpropan-1-one (5c). Yield 160 mg (63%), light-yellow oil. IR spectrum, ν, cm–1: 3454 (OH), 1670 (C=O), 1597, 1580, 1518, 1450, 1412, 1368, 1290, 1204, 1179, 1084, 999, 972, 905, 847, 739, 685, 642, 592. 1H NMR spectrum, δ, ppm (J, Hz): 2.16 (3H, s, СН3); 2.17 (3H, s, СН3); 2.96–2.99 (2H, m, СН2); 3.39–3.42 (2H, m, СН2); 6.72 (1H, s, H-3); 6.87 (1H, s, H-6); 7.42–7.46 (2H, m, H-3',5'); 7.54–7.58 (1H, m, H-4'); 7.95–7.98 (2H, m, H-2',6'). The position of the signal of the proton of the OH group cannot be reliably identified due to its strong broadening. 13C NMR spectrum, δ, ppm: 18.8 (CH3); 19.4 (CH3); 23.1 (CH2); 40.7 (CH2); 118.7 (CH); 124.9; 128.4 (2CH); 128.5; 128.7 (2CH); 131.6 (CH); 133.7 (CH); 136.2; 136.4; 152.3 (C–OH); 202.0 (C=O). Found, %: C 80.21; H 7.09. C17H18O2. Calculated, %: C 80.28; H 7.13.

3-(5-Chloro-2-hydroxyphenyl)-1-(4-methoxyphenyl)-propan-1-one (5d). Yield 227 mg (78%), slowly crystallizing light-yellow oil, mp 65–67°С. IR spectrum, ν, cm–1: 3307 (ОН), 3193, 1663 (С=О), 1593, 1512, 1427, 1327, 1300, 1261, 1177, 1119, 1028, 829. 1H NMR spectrum, δ, ppm (J, Hz): 2.95–2.98 (2H, m, СН2); 3.37–3.40 (2H, m, СН2); 3.85 (3H, s, СН3О); 6.84 (1H, d, J = 8.5, Н-3); 6.90 (2H, d, J = 8.9, Н-3',5'); 7.04 (1H, dd, J = 8.5, J = 2.5, Н-4); 7.07 (1H, d, J = 2.5, Н-6); 7.93 (2H, d, J = 8.9, Н-2',6'); 8.54 (1Н, s, ОН). 13C NMR spectrum, δ, ppm: 23.4 (СН2); 40.0 (СН2); 55.7 (СН3О); 114.0 (2СН); 119.1 (СН); 125.1; 127.9 (СН); 128.9; 129.9; 130.2 (СН); 130.9 (2СН); 153.5 (COH); 164.3 (COCH3); 200.5 (С=О). Found, %: C 66.03; H 5.26. C16H15ClO3. Calculated, %: C 66.10; H 5.20.

Supplementary information file containing 1Н and 13С NMR spectra of all synthesized compounds is available at the journal website http://springerlink.bibliotecabuap.elogim.com/journal/10593.