Photochemistry of 3-alkoxychromones: photocyclisation of 2-aryl-6-chloro-3-{(thiophen-2-yl)methoxy}chromones

ARTICLE

Photochemistry of 3-alkoxychromones: photocyclisation of 2-aryl-6-chloro-3-{(thiophen-2-yl)methoxy}chromones

Ramesh C. KambojI, ^*; Urmila Berar^I; Surinder Berar^I; Zeba N. Siddiqui^II; Satish C. Gupta^I

^IDepartment of Chemistry, Kurukshetra University, Kurukshetra-136 119, India

^IIDepartment of Chemistry, Aligarh Muslim University, Aligarh, India

ABSTRACT

1,4-Biradicals generated upon photo-irradiation of 2-aryl-3-{(thiophen-2-yl)methoxy}chromones produced angular tetracyclic products bearing the thienyl group. The dehydrogenation and ring contraction products were also observed depending upon the electron density on the 2-aryl ring.

Keywords: alkoxychromone, type-II reaction, 1,4-biradical, ring contraction, angular tetracyclic

RESUMO

1,4-Biradicais gerados da fotoirradiação de cromonos 2-aril-3-[(tiofen-2-il)metóxi] produziram compostos tetraciclicos angulares contendo grupos tienil. A dehidrogenação e contração do anel dos produtos foram também observadas dependendo da densidade elétrica no anel 2-aril.

Introduction

Conjugated enones bearing the alkoxy and/or alkyl group at C-3, on photoirradiation with UV light undergo γ-hydrogen abstractions.^1-4 The products obtained, depend upon the nature of the substituents present in the substrates, for example, 2-alkyl-3-arylcyclohex-2-enones⁵ and 3-alkoxy-2-phenyl-4-oxo-4H-1-benzopyran,^6-8 afforded the photocyclised angular products whereas 3-methoxy-2-methylchromones⁹ have been found to furnish the novel dimeric oxetanol. In 3-alkoxy-2-arylchromones, the synthetic applications of these γ-hydrogen abstractions include the formation of vinyl ethers,¹⁰ spiropyrans,¹¹ pyranopyrones,¹² pyranoalcohols,¹³ angular tetracyclics¹⁴ etc. In these phototransformations, the primary reaction is the n-Π^* excitation of the C=O group that subsequently abstracts hydrogen from the 3-alkoxy group leading to the formation of the 1,4-biradical.^5-8 The nature of the 3-alkoxy group has been found to have a profound effect on the fate of 1,4-biradical^10,13 to form the mesomeric biradicals. To examine the effect of (thiophen-2-yl)methoxy group at 3-position of the chromones with different 2-aryl groups and also to study the possibility of photo-transposition¹⁵ reactions of the thiophene when tied to the chromones, in this work we report the synthesis and the photolytic behavior of the chromones 2(a-g).

Results and Discussion

The 2-aryl-3-{(thiophen-2-yl)methoxy}chromones 2(a-g) were obtained by reacting 3-hydroxybenzopyrans^16-171(a-g) with 2-(chloromethyl)thiophene¹⁸ using anhydrous K₂CO₃/n-Bu₄N⁺ I^- in anhydrous acetone as the solvent as shown in Scheme 1.

The structures of the benzopyrans 2(a-g) were derived from their spectral data (IR, ¹H, ¹³C NMR, Experimental section).

The photoirradiation of the methanolic solution of 2(a-d) with pyrex filtered UV light from a 125W Hg vapour lamp under the nitrogen atmosphere (Scheme 2) produced the photoproducts 3(a-d) and 4a, 4c. In spite of our best efforts, the compound 4a could not be isolated in the pure form and its structure was derived from the NMR data of the reaction mixture enriched in 4a by the repeated crystallization of 3a.

The other chromones 2e and 2f under the similar photolytic conditions produced the photoproducts 3e, 4e and 3f, 3f', 4f, 4f' respectively in 10-35% yields (Scheme 3).

The photoirradiation of 2g, a regio-isomer of 2e, in the methanolic solution (0.001mol L^-1) with pyrex filtered UV light for 40 min gave 3g (50%, Scheme 4). No secondary photoproducts corresponding to 4f and 4f' were furnished.³¹

The structures of all the photoproducts were confirmed by the comparison of their spectral parameters (IR, ¹H, ¹³C NMR) with those of the starting substrates 2(a-g) and also from their elemental analysis. The photoproducts 3(a-d) showed the IR absorption between 1630-1650 cm^-1 for the pyrone C=O group. In their ¹H NMR spectra, the proton H-5 was found almost in the aromatic region of spectrum between δ 6.58-6.80 whereas in 4a and 4c it had the upfield resonance at δ ca. 5.00.

Regarding the stereochemistry of photoproducts 3f, 3f', 3e and 3g, the conformation of ring C is a half-chair. The protons H-11b and H-3a are in the cis-disposition (cis C/D ring junction) which has been derived from the observation that the J_3a,11b = 8.1-10.5 Hz which is in accordance with J/Φ relationships^19,20(karplus rule) and the earlier studies.²¹ In compounds 3f, 3e and 3g, the coupling constant J_3a,4ca. 8.4 Hz for H-3a and H-4 protons places them in a cis-orientation, which finds support from the literature studies¹⁶ thus positioning the 4-thienyl group in Ψ-equatorial position on the half-chair conformation of the ring C (Figure 1). Further, in the photoproduct 3f' (stereoisomer of 3f), the orientation of H-3a and H-4 is trans (J_3a,4 = 2.1 Hz) with thienyl group in Ψ-axial conformation. This has made the stereocentre at C-4 to have a R configuration in the compounds 3e, 3f and 3g and a S configuration in the compound 3f'. The absolute configuration at C-11b and C-3a is R and S respectively in 3f, 3e, 3g and 3f'. The MM2 energy minimized structures of the compounds 3f and 3f' are shown in Figure 1 and their J/Φ data has been given in Table 1 which also confirms the above findings about the stereochemistry of the photoproducts.

In the secondary photoproducts 4f and 4f' obtained from the photolysis of 2f, the cyclopropyl protons²² H-1a and H-9b are cis (J = 9.0 Hz) placed to each other and the H-1 is trans to both H-1a (J_1,1a = 4.2/3.3 Hz) and H-9b (J_1,9b = 3.6/3.9 Hz); the -CHO group is exo to the pyran ring C. In 4f, the H-2 has been observed as doublet (J_2,1a = 2.4 Hz), inferring that the plane containing H-1a and H-2 possesses Φ_2,1aca. 50º (Figure 2) whereas its isomeric compound 4f' has been found to possess different stereochemistry at C-2 with Φ_2,1aca. 75º (J 1.2 Hz). The thienyl group at C-2 is below the plane in 4f and above the plane in 4f' (Figure 2). The difference in chemical shift of H-1 (0.4 ppm) in 4f and 4f' is because of the proximity to the pyran oxygen (ring C). The distance between H-1 and one of the sp³ orbital of pyran oxygen is 2.25 Aº in 4f whereas in 4f' it is 2.35Aº leading to extra deshielding in the former. A similar explanation can be given to explain the observed downfield shift in δ value of H-1 (ca. 0.65 ppm) as compared to that reported in literature²³ for cyclopropane carboxaldehyde (δ 2.60) fused to the cyclohexane ring.

The carbon skeleton of photoproducts 3b, 4c, 3c, 3d, 3e, 4e and 3g was further confirmed from their fully proton decoupled ¹³C NMR spectra (Experimental section).

Regarding the effect of substituent at 2-position of the chromones 2(a-g) on the product formation/distribution, it has been observed that in the case of furyl chromones 2f and 2g only the cyclised products are obtained. From the others substrates 2a-2e (phenyl, thiophene), the photodehydrogenated cyclised products along with the cyclised products are also formed. For such difference, the assignable reason could be the different degree of aromaticity of the C-2 ring moiety. The aromatic character increases from furan via thiophene to benzene. So, the gain in energy by dehydrogenation is higher in 3a-3d leading to the predominant formation of these aromatized photoproducts. The dehydrogenation re-establishes aromaticity. Since the aromatic character is less expressed in the case of thiophene, the dehydrogenation is less dominant here (4e). Obviously, the low aromatic character of furan is insufficient to favour formation of dehydrogenation products and hence only the cyclised products are furnished.

A possible mechanism involving the 1,4-biradical intermediate (Scheme 5) formed by the γ-hydrogen abstraction from -OCH₂- by the photo-excited C=O akin to some earlier reports^6-8 may be envisioned for these phototransformations. The 1,4-biradical expectedly undergoes bond formation between the -CH- and the carbon atom of aryl ring at C-2 followed by product formation 3f, 3f', 3e, 3g and 4a, 4c through 1,5- and 1,7-H-shifts respectively. The dehydrogenated products 3a-3d and 4e are formed directly by the expulsion of H₂ during the cyclisation and not by the dehydrogenation of their respective dihydroderivatives^6,8 as confirmed by the photolysis of pure isolated dihydrocompounds when no aromatization could be detected; only polymeric products were formed. In the chromone 2f, when the 2-aryl group is the furyl moiety, in addition to the dihydro products 3f and 3f', the other photoproducts 4f and 4f' were also realized from the further photoisomerisation of 3f and 3f' where the dihydrofuran ring D undergoes ring contraction mechanism^24-27 to provide the cyclopropylaldehyde moiety. That the fused cyclopropylaldehyde 4f and 4f' are furnished from 3f and 3f' was confirmed by the observation that these on further irradiation under identical conditions provided 4f and 4f' along with some other minor products which escaped isolation. In this ring contraction mechanism, the biradical intermediate 6 is stabilized by the double bond of the pyrone moiety making the C-O bond amenable to cleavage. A similar ring contraction mechanism could not be observed in photolysis of 2g which only yielded 3g (Scheme 6).

Also, 3g on further photoirradiation did not furnish any ring-contracted product similar to 4f. This is probably due to the lack of stabilization of possible biradical³¹9 (Scheme 6), which is not in conjugation with the double bond of the pyrone ring.

In all these chromones 2(a-g), the often occurring phototransposition^15,28-30 reactions of alkyl/aryl thiophenes were not observed though they bear alkyl thiophene or both aryl and alkyl thiophene groups (2e).

Conclusions

Hydrogen abstraction from the 3-alkoxy group by the excited C=O is the preferred reaction pathway for the formation of photoproducts. The (thiophen-2-yl)methoxy radical generated undergoes cyclisation only similar to the allyl and benzyl radicals. No photo-transposition reactions of the thiophene ring were observed in these compounds.

Experimental

General

Melting points were determined in open capillaries and are thus uncorrected. ¹H NMR and ¹³C NMR spectra were recorded on a 300 MHz (for ¹³C frequency = 75 MHz) Bruker spectrophotometer using TMS as the internal standard. IR spectra were recorded on a Buck Scientific 500 spectrophotometer using KBr pellets. Mass spectra recorded are either EI or FAB⁺. Elemental analysis was carried out on a Perkin Elmer 2400 instrument. TLC plates were coated with silica gel G (suspended in CHCl₃-MeOH) and iodine vapours were used as the visualizing agent. The columns for purification were packed with silica gel 100-200 mesh in petroleum ether-benzene (9:2) and left overnight before use. The elution was carried out with increasing proportion of benzene in the petroleum ether-benzene mixture. The compounds 3f, 3f' and 4f, 4f' were separated by using silica gel of 200-400 mesh (ACROS Organics) for column chromatography. All photochemical reactions were conducted under a nitrogen (99.9%) atmosphere. Any trace of oxygen and moisture from the procured nitrogen was removed by passing through the alkaline pyragallol solution and concentrated sulfuric acid respectively.

Synthesis of benzopyrans 2(a-g)

6-Chloro-2-phenyl-3-{(thiophen-2-yl)methoxy}-4-oxo-4H -1-benzopyran, 2a: The 3-hydroxychromone, 1a (2.72 g, 0.01 mol), 2-(chloromethyl)thiophene (1.32 g, 0.01 mol), anhydrous K₂CO₃ (1.0 g) and tetra-n-butylammonium iodide (100 mg) were refluxed in anhydrous acetone (50 mL) for 3 h. Filtration, evaporation of the solvent and crystallization of the residue from methanol gave 2a (2.40 g, 65%), light brown solid; mp 86-89 ºC; IR ν_max/cm^-1: 1645 (C=O); ¹H NMR (CDCl₃) δ 8.26 (1H, d, J_m = 2.4 Hz, H-5), 8.00 (2H, m, H-2', H-6'), 7.63 (1H, dd, J_m = 2.4 Hz, J_o = 8.7 Hz, H-7), 7.49 (4H, m, H-8, H-3', H-4', H-5'), 7.22 (1H, dd, J_5'',3'' = 1.2 Hz, J_5'',4'' = 5.1 Hz, H-5"), 6.95 (1H, dd, J_3'',4'' = 3.6 Hz, H-3"), 6.87 (1H, dd, J_4'',3'' = 3.6 Hz, J_4'',5" = 5.1 Hz, H-4"), 5.38 (2H, s, -OCH₂-); ¹³C NMR (CDCl₃) δ 174.0 (C-4), 156.9 (C-8a), 153.6 (C-2), 139.1 (C-2"), 138.4 (C-3), 133.7 (C-7), 130.8 (C-5), 130.6 (C-1'), 128.9 (C-3' C-5'), 128.5 (C-4'), 128.4 (C-6), 128.3 (C-2', C-6'), 126.9 (C-4a), 126.5 (C-4"), 126.1 (C-3"), 125.1 (C-5"), 119.8 (C-8), 67.6 (-OCH₂-); Anal. Calc. for C₂₀H₁₃ClO₃S: C, 65.13; H, 3.55. Found: C, 65.02; H, 3.57.

The other ethers 2b-2g were synthesized by using the above described procedure starting from the compounds 1b-1g (0.01 mol each) respectively.

6-Chloro-2-(4'-methylphenyl)-3-{(thiophen-2-yl)methoxy}-4-oxo-4 H-1-benzo-pyran,2b: Yield 2.30 g (60%), light brown solid; mp 128-131 ºC; IR ν_max/cm^-1: 1641 (C=O); ¹H NMR (CDCl₃) δ 8.24 (1H, d, J_m = 2.4 Hz, H-5), 7.92 (2H, d, J_o = 8.4 Hz, H-2', H-6'), 7.60 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-7), 7.47 (1H, d, J_o = 9.0 Hz, H-8), 7.35 (2H, d, J_o = 8.4 Hz, H-3', H-5'), 7.22 (1H, dd, J_5'',4'' = 4.8 Hz, H-5"), 6.97 (1H, dd, J_3'',4'' = 3.0 Hz, H-3"), 6.87 (1H, m, H-4"), 5.36 (2H, s, -OCH₂-), 2.44 (3H, s, -CH₃); ¹³C NMR (CDCl₃) δ 173.9 (C-4), 153.6 (C-8a), 141.4 (C-2), 138.6 (C-2"), 135.4 (C-4'), 133.8 (C-3), 133.6 (C-7), 130.7 (C-5), 129.4 (C-6), 129.1 (C-3', C-5'), 128.8 (C-4"), 128.4 (C-5"), 127.7 (C-1'), 126.9 (C-3"), 126.5 (C-2', C-6'), 125.1 (C-4a), 119.7 (C-8), 67.5 (-OCH₂-), 21.6 (4'-CH₃); Anal. Calc. for C₂₁H₁₅ClO₃S: C, 65.88; H, 3.95. Found: C, 65.73; H, 3.90.

6-Chloro-2-(4'-methoxyphenyl)-3-{(thiophen-2-yl)methoxy}-4-oxo-4 H-1-benzopyran,2c: Yield 2.57 g (65%), light brown solid; mp 118-120 ºC; IR ν_max/cm^-1: 1639 (C=O); ¹H NMR (CDCl₃) δ 8.24 (1H, d, J_m = 2.7 Hz, H-5), 8.02 (2H, d, J_o = 9.0 Hz, H-2', H-6'), 7.60 (1H, dd, J_m = 2.7 Hz, J_o = 9.0 Hz, H-7), 7.46 (1H, d, J_o = 9.0 Hz, H-8), 7.35 (2H, d, J_o = 8.4 Hz, H-3', H-5'), 7.22 (1H, dd, J_5'',4'' = 5.1 Hz, H-5"), 6.97 (3H, m, H-3", H-3', H-5'), 6.88 (1H, dd, J_4",3" = 3.6 Hz, J_4",5" = 5.1 Hz, H-4"), 5.36 (2H, s, -OCH₂-), 3.89 (3H, s, -OCH₃); Anal. Calc. for C₂₁H₁₅ClO₄S: C, 63.24; H, 3.79. Found: C, 63.13; H, 3.74.

6-Chloro-3-{(thiophen-2-yl)methoxy}-2-(3',4',5'-trimethoxyphenyl)-4-oxo-4 H-1-benzopyran, 2d: Yield 2.60 g (57%), pale yellow solid; mp 129-131 ºC; IR ν_max/cm^-1: 1643 (C=O); ¹H NMR (CDCl₃) δ 8.17 (1H, d, J_m = 2.4 Hz, H-5), 7.55 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-7), 7.42 (1H, d, J_o = 9.0 Hz, H-8), 7.15 (1H, dd, J_5'',4'' = 5.1 Hz, H-5"), 6.90 (1H, d, J_3",4" = 3.3 Hz, H-3"), 6.81 (1H, dd, J_4",3" = 3.3 Hz, J_4",5" = 5.1 Hz, H-4"), 5.27 (2H, s, -CH₂-), 3.86 (3H, s, C_4'-OCH₃), 3.77 (6H, s, C_3' & C_5'-OCH₃); ¹³C NMR (CDCl₃) δ 173.8 (C-4), 156.4 (C-8a), 153.5 (C-2), 152.9 (C-3', C-5'), 140.6 (C-4'), 139.3 (C-2"), 138.6 (C-3), 133.7 (C-7), 130.8 (C-5), 128.3 (C-6), 127.0 (C-4"), 126.6 (C-5"), 125.5 (C-1'), 125.2 (C-3"), 125.0 (C-4a), 119.7 (C-8), 106.7 (C-2', C-6'), 68.0 (-OCH₂-), 61.0 (4'-OCH₃), 56.3 (3', 5-OCH₃); Anal. Calc. for C₂₃H₁₉ClO₆S: C, 60.20; H, 4.17. Found: C, 60.12; H, 4.18.

6-Chloro-2-(2'-thienyl)-3-{(thiophen-2-yl)methoxy}-4-oxo-4 H-1-benzopyran, 2e: Yield 2.98 g (80%), pale yellow solid; mp 122-124 ºC; IR ν_max/cm^-1: 1639 (C=O); ¹H NMR (CDCl₃) δ 8.24 (1H, d, J_m = 2.4 Hz, H-5), 7.96 (1H, dd, J_3',5' = 0.9 Hz, J_3',4' = 3.6 Hz, H-3'), 7.65 (1H, dd, J_5',3' = 0.9 Hz, J_5',4' = 4.8 Hz, H-5'), 7.63 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-7), 7.47 (1H, d, J_o = 9.0 Hz, H-8), 7.29 (1H, dd, J_3",5" = 0.9 Hz, H-3"), 7.20 (1H, dd, J_4',3' = 3.9 Hz, J_4',5' = 4.8 Hz, H-4'), 7.17 (1H, d, H-5"), 6.95 (1H, dd, J_4",3" = 3.3 Hz, J_4",5" = 5.1 Hz, H-4"), 5.64 (2H, s, -OCH₂-); ¹³C NMR (CDCl₃) δ 174.1 (C-4), 153.0 (C-8a), 149.8 (C-2), 138.0 (C-4a), 133.5 (C-7), 132.5 (C-2'), 131.8 (C-2"), 130.1 (C-6), 129.9 (C-5'), 129.1 (C-4"), 127.9 (C-4'), 127.4 (C-3"), 126.6 (C-5"), 125.6 (C-3), 125.1 (C-5), 124.5 (C-3'), 119.5 (C-8), 67.0 (-OCH₂-); Anal. Calc. for C₁₈H₁₁ClO₃S₂ : C, 57.67; H, 2.96. Found: C, 57.48; H, 2.92.

6-Chloro-2-(2'-furyl)-3-{(thiophen-2-yl)methoxy}-4-oxo-4 H-1-benzopyran, 2f: Yield 2.15 g (60%), pale yellow solid; mp 114-115 ºC; IR ν_max/cm^-1: 1640 (C=O); ¹H NMR (CDCl₃) δ 8.22 (1H, d, J_m = 2.4 Hz, H-5), 7.67 (1H, m, H-5'), 7.61 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-7), 7.50 (1H, d, J_o = 9.0 Hz, H-8), 7.36 (1H, dd, J_3',5' = 1.8 Hz, J_3',4' = 3.3 Hz, H-3'), 7.28 (1H, dd, J_5'',3'' = 1.8 Hz, J_5'',4'' = 5.1 Hz, H-5''), 7.11 (1H, dd, J_3",5" = 1.8 Hz, J_3'',4'' = 3.0 Hz, H-3"), 6.93 (1H, dd, J_4",3" = 3.0 Hz, J_4",5" = 5.1 Hz, H-4"), 6.60 (1H, dd, J_4',5' = 1.8 Hz, J_4',3' = 3.3 Hz, H-4'), 5.57 (2H, s, -OCH₂-); ¹³C NMR (CDCl₃) δ 172.2 (C-4), 154.2 (C-8a), 151.5 (C-2), 145.3 (C-5'), 144.2 (C-2'), 138.4 (C-4a), 137.1 (C-2"), 132.9 (C-7), 130.5 (C-6), 127.8 (C-4"), 127.0 (C-3"), 126.3 (C-5''), 125.2 (C-5), 124.9 (C-3), 119.7 (C-8), 110.1 (C-4'), 109.2 (C-3'), 67.2 (-OCH₂-); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.11; H, 3.11.

6-Chloro-2-(3'-furyl)-3-{(thiophen-2-yl)methoxy}-4-oxo-4 H-1-benzopyran, 2g: Yield 2.43 g (68%), light brown solid; mp 126-128 ºC; IR ν_max/cm^-1: 1646 (C=O); ¹H NMR (CDCl₃) δ 8.27 (1H, t, J_2',4' = 0.6 Hz, H-2'), 8.24 (1H, d, J_m = 2.4 Hz, H-5), 7.61 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-7), 7.52 (1H, t, J_5',2' = 1.5 Hz, J_5',4' = 1.8 Hz, H-5'), 7.45 (1H, d, J_o = 9.0 Hz, H-8), 7.29 (1H, dd, J_5'',3'' = 1.2 Hz, J_5'',4'' = 5.1 Hz, H-5"), 7.12 (1H, d, J_3",4" = 3.3 Hz, H-3"), 6.96 (2H, m, H-4", H-4'), 5.58 (2H, s, -OCH₂-); ¹³C NMR (CDCl₃) δ 172.8 (C-4), 153.2 (C-8a), 152.0 (C-2), 145.7 (C-5'), 143.4 (C-2'), 138.5 (C-4a), 138.0 (C-2"), 133.4 (C-7), 130.7 (C-6), 128.6 (C-4"), 127.0 (C-3"), 126.8 (C-5"), 125.2 (C-3), 125.1 (C-5), 119.5 (C-8), 117.7 (C-3'), 108.7 (C-4'), 67.2 (-OCH₂-); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.21; H, 3.05.

Photolysis of benzopyrans 2a-2g

General procedure: A deoxygenated solution of chromone 2a (200 mg) in magnesium dried methanol (150 mL) was refluxed for 5 min. The solution was degassed with nitrogen for 1 h and then irradiated in a pyrex vessel under nitrogen atmosphere for 40 min with a 125W Hg vapour lamp. The removal of the solvent under reduced pressure left a red gummy mass that was chromatographed over a column of silica gel to yield 3a and 4a.

Other compounds 2b-2g (200 mg each) were also photolysed by following the same procedure to yield the respective products. In all these cases the yield of the photoproducts ranges between 20-50%. The rest of the material was a mixture of unidentifiable polymeric products and starting chromone.

Compound 3a: Yield 52 mg (26%), off-white solid; mp 180-182 ºC; R_f 0.68 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1640 (C=O); ¹H NMR (CDCl₃) δ 8.26 (1H, d, J_m = 2.1 Hz, H-8), 7.97 (1H, m, H-1), 7.64 (1H, dd, J_m = 2.1 Hz, J_o = 9.0 Hz, H-10), 7.57 (2H, m, H-2, H-3), 7.52 (1H, d, J_o = 9.0 Hz, H-11), 7.42 (1H, m, H-4), 7.23 (1H, d, J_5',4' = 5.1 Hz, H-5'), 6.90 (2H, m, H-4', H-3'), 6.65 (1H, s, H-5); m/z 366 (M⁺, 100%); Anal. Calc. for C₂₀H₁₁ClO₃S: C, 65.49; H, 3.02. Found: C, 65.31; H, 2.99.

Compound4a: Yield 20% (calculated from ¹H NMR spectrum of mixture); R_f 0.68 (5% ethyl acetate in benzene); ¹H NMR (CDCl₃) δ 8.24 (1H, d, J_m = 2.4 Hz, H-8), 7.60 (1H, dd, J_m = 2.4 Hz, J_o = 8.7 Hz, H-10), 7.44 (1H, d, J_o = 8.7 Hz, H-11), 7.18 (1H, d, J_5',4' = 3.3 Hz, H-5'), 7.06 (1H, d, J_4',3' = 3.6 Hz, H-4'), 6.90 (1H, d, J_3',4' = 3.6 Hz, H-3'), 6.80 (1H, br s, H-1), 5.88 (1H, m, H-3), 5.39 (1H, d, J = 9.9 Hz, H-4), 5.00 (1H, d, J_5,4a = 11.1 Hz, H-5), 3.46 (1H, m, H-4a), 3.03 (2H, m, H-2).

Compound3b: Yield 60mg (30%), off-white solid; mp 207-209 ºC; R_f 0.67 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1635 (C=O); ¹H NMR (CDCl₃) δ 8.23 (1H, d, J_m = 2.4 Hz, H-8), 7.82 (1H, d, J_o = 7.8 Hz, H-1), 7.58 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-10), 7.49 (1H, d, J_o = 9.0 Hz, H-11), 7.36 (2H, m, H-3', H-5'), 7.08 (1H, dd, H-2), 6.88 (2H, m, H-4', H-4), 6.58 (1H, s, H-5), 2.45 (3H, s, -CH₃); ¹³C NMR (CDCl₃) δ 173.0 (C-7), 153.5 (C-11a), 151.0 (C-13), 149.8 (C-2'), 135.3 (C-3), 134.0 (C-6a), 133.0 (C-10), 130.0 (C-8), 127.9 (C-4), 127.3 (C-2), 126.9 (C-4"), 126.6 (C-11), 125.9 (C-9), 125.7 (C-3'), 125.2 (C-5'), 124.0 (C-4a), 122.3 (C-12b), 119.6 (C-11), 74.7 (C-5), 22.0 (3-CH₃); m/z 380 (M⁺, 100%); Anal. Calc. for C₂₁H₁₃ClO₃S: C, 66.23; H, 3.44. Found: C, 66.25; H, 3.36.

Compound3c: Yield 44 mg (22%), light brown solid; mp 140-142 ºC; R_f 0.54 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1637 (C=O); ¹H NMR (CDCl₃) δ 8.25 (1H, d, J_m = 2.4 Hz, H-8), 7.89 (1H, d, J_o = 8.4 Hz, H-1), 7.58 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-10), 7.49 (1H, d, J_o = 9.0 Hz, H-11), 7.37 (1H, s, H-5'), 7.09 (1H, dd, J_2,4 = 2.1 Hz, J_2,1 = 8.4 Hz, H-2), 6.90 (2H, m, H-3', H-4'), 6.79 (1H, d, J_4,2 = 2.4 Hz, H-4), 6.58 (1H, s, H-5), 3.97 (3H, s, -OCH₃); ¹³C NMR (CDCl₃) δ 170.3 (C-7), 162.6 (C-3), 154.0 (C-11a), 152.0 (C-12a), 148.7 (C-2'), 135.8 (C-6a), 133.1 (C-10), 130.6 (C-8), 128.3 (C-9), 128.0 (C-7a), 127.3 (C-1), 126.9 (C-4"), 126.6 (C-3"), 125.4 (C-5"), 125.0 (C-4a), 124.3 (C-12b), 119.5 (C-11), 114.8 (C-2), 111.7 (C-4), 74.8 (C-5), 55.7 (3-OCH₃); m/z 396 (M⁺, 100%); Anal. Calc. for C₂₁H₁₃ClO₄S: C, 63.56; H, 3.30. Found: C, 63.21; H, 3.34.

Compound4c: Yield 59 mg (30%), white solid; mp 163-166 ºC; R_f 0.58 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1648 (C=O); ¹H NMR (CDCl₃) δ 8.22 (1H, d, J_m = 2.7 Hz, H-8), 7.56 (1H, dd, J_m = 2.7 Hz, J_o = 8.7 Hz, H-10), 7.39 (2H, m, H-11, H-5'), 7.14 (1H, d, H-3'), 7.02 (1H, m, H-4'), 6.86 (1H, br s, H-1), 5.20 (2H, m, H-4, H-5), 3.67 (3H, s, -OCH₃), 3.38 (1H, m, H-4a), 2.38 (1H, m, H-2a), 1.98 (1H, m, H-2b); ¹³C NMR (CDCl₃) δ 170.6 (C-7), 152.9 (C-11a), 144.6 (C-3), 139.4 (C-6a), 138.4 (C-2'), 133.9 (C-10), 133.0 (C-12b), 130.5 (C-8), 128.8 (C-12a), 127.9 (C-9), 127.1 (C-7a), 126.8 (C-4'), 125.5 (C-3'), 124.7 (C-5'), 123.9 (C-1), 120.2 (C-4), 119.4 (C-11), 79.0 (C-5), 40.9 (4-OCH₃), 40.8 (C-4a), 39.9 (C-2); m/z 398 (M⁺, 100%); Anal. Calc. for C₂₁H₁₅ClO₄S: C, 63.24; H, 3.79. Found: C, 63.19; H, 3.78.

Compound3d: Yield 40 mg (20%), light brown solid; mp 200-203 ºC; R_f 0.47 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1636 (C=O);¹H NMR (CDCl₃) δ 8.15 (1H, d, J_m = 2.1 Hz, H-8), 7.50 (1H, dd, J_m = 2.1 Hz, J_o = 9.0 Hz, H-10), 7.43 (1H, d, J_o = 9.0 Hz, H-11), 7.11 (2H, m, H-1, H-5'), 6.78 (3H, m, H-3', H-4', H-5), 3.95 (3H, s, C₄-OCH₃), 3.88 (3H, s, C₃-OCH₃), 3.77 (3H, s, C₂-OCH₃); ¹³C NMR (CDCl₃) δ 172.8 (C-7), 154.6 (C-11a), 152.9 (C-12a), 149.4 (C-2'), 145.0 (C-4), 142.8 (C-2), 136.2 (C-3), 134.4 (C-6a), 133.2 (C-10), 130.6 (C-8), 126.8 (C-9), 126.6 (C-4'), 126.4 (C-5'), 125.4 (C-3'), 125.3 (C-7a), 121.0 (C-12b), 119.5 (C-4a), 119.5 (C-11), 101.1 (C-1), 69.7 (C-50), 61.1 (4-OCH₃), 61.1 (3-OCH₃), 56.4 (2-OCH₃); m/z 456 (M⁺, 100%); Anal. Calc. for C₂₃H₁₇ClO₆S: C, 60.46; H, 3.75. Found: C, 66.31; H, 3.74.

Compound3e: Yield 42 mg (21%), off-white solid; mp 179-182 ºC; R_f 0.48 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1655 (C=O); ¹H NMR (CDCl₃) δ 8.16 (1H, d, J_m = 2.4 Hz, H-7), 7.52 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-9), 7.34 (1H, d, J_o = 9.0 Hz, H-10), 7.28 (1H, m, H-5'), 7.07 (1H, d, J_3',4' = 3.3 Hz, H-3'), 6.94 (1H, dd, J_4',3' = 3.3 Hz, J_4',5' = 4.8 Hz, H-4'), 6.33 (1H, d, J_2,3 = 6.3 Hz, H-2), 5.30 (1H, dd, J_3,3a = 3.0 Hz, J_3,2 = 6.3 Hz, H-3), 5.08 (1H, d, J_4,3a = 9.6 Hz, H-4), 4.98 (1H, d, J_11b,3a = 8.1 Hz, H-11b), 3.60 (1H, m, J_3a,3 = 3.0 Hz, J_3a,4 = 9.6 Hz, H-3a); ¹³C NMR (CDCl₃) δ 170.4 (C-6), 153.5 (C-10a), 148.6 (C-11a), 139.6 (C-2'), 138.6 (C-6a), 134.7 (C-9), 130.6 (C-8), 128.3 (C-2), 127.4 (C-4'), 126.8 (C-3'), 126.4 (C-4), 125.5 (C-7), 124.7 (C-5a), 121.6 (C-5'), 119.6 (C-10), 72.5 (C-4), 51.5 (C-3a), 46.2 (C-11b); m/z 374 (M⁺, 100%), 320 (M⁺-54, 39%); Anal. Calc. for C₁₈H₁₁ClO₃S₂ : C, 57.67; H, 2.96. Found: C, 57.45; H, 2.94.

Compound4e: Yield 40 mg (20%), light brown solid; mp 122-125 ºC; R_f 0.34 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1642 (C=O); ¹H NMR (CDCl₃) δ 8.16 (1H, d, J_m = 2.4 Hz, H-7), 7.56 (1H, d, J_2,3 = 5.1 Hz, H-2), 7.50 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-9), 7.39 (1H, d, J_o = 9.0 Hz, H-10), 7.28 (1H, m, H-5'), 7.22 (1H, dd, J_3',5' = 1.2 Hz, J_3',4' = 5.1 Hz, H-3'), 6.91 (1H, d, J_3,2 = 5.1 Hz, H-3), 6.86 (1H, dd, J_4',5' = 3.6 Hz, J_4',3' = 5.1 Hz, H-4'), 6.74 (1H, s, H-4); ¹³C NMR (CDCl₃) δ 172.2 (C-6), 153.0 (C-10a), 147.9 (C-11a), 145.1 (C-3a), 139.4 (C-2'), 139.0 (C-6a), 134.9 (C-11b), 133.2 (C-9), 130.8 (C-8), 129.5 (C-2), 127.2 (C-4), 126.9 (C-3'), 126.8 (C-3), 125.7 (C-7), 125.5 (C-5a), 122.6 (C-5'), 119.4 (C-10), 74.0 (C-4); m/z 372 (M⁺, 100%); Anal. Calc. for C₁₈H₁₁ClO₃S₂ : C, 57.98; H, 2.43. Found: C, 58.00; H, 2.40.

Compound3f: Yield 49 mg (25%), pale yellow solid; mp 188-191 ºC; R_f 0.60 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1652 (C=O); ¹H NMR (CDCl₃) δ 8.24 (1H, d, J_m = 2.7 Hz, H-7), 7.63 (1H, dd, J_m = 2.7 Hz, J_o = 9.0 Hz, H-9), 7.50 (1H, d, J_o = 9.0 Hz, H-10), 7.38 (1H, d, J_5',4' = 5.1 Hz, H-5'), 7.17 (1H, d, J_3',4' = 3.0 Hz, H-3'), 7.04 (1H, dd, J_4',3' = 3.0 Hz, J_4',5' = 5.1 Hz, H-4'), 6.59 (1H, br s, H-2), 5.28 (1H, d, J_4,3a = 8.4 Hz, H-4 ), 5.02 (1H, t, J_3,2 = 2.7 Hz, J_3,3a = 2.7 Hz, H-3), 4.70 (1H, d, J_11b,3a = 10.5 Hz, H-11b), 3.43 (1H, d{t}, J_3a,3 = 2.1 Hz, J_3a,4 = 8.4 Hz, J_3a,11b = 10.5 Hz, H-3a). m/z 358 (M⁺, 100%); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.10; H, 3.05.

Compound3f': Yield 34 mg (17%), pale yellow solid; mp 165-170 ºC; R_f 0.56 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1652 (C=O); ¹H NMR (CDCl₃) δ 8.23 (1H, d, J_m = 2.4 Hz, H-7), 7.61 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-9), 7.48 (1H, d, J_o = 9.0 Hz, H-10), 7.36 (1H, dd, J_5',4' = 5.1 Hz, H-5'), 7.17 (1H, d, J_3',4' = 3.0 Hz, H-3'), 7.04 (1H, dd, J_4',3' = 3.0 Hz, J_4',5' = 5.1 Hz, H-4'), 6.39 (1H, br s, H-2), 5.66 (1H, d, J_11b,3a = 8.1 Hz, H-11b), 5.43 (1H, d, J_4,3a = 2.1 Hz, H-4 ), 5.10 (1H, t, J_3,3a = 2.1 Hz, J_3,2 = 2.1 Hz, H-3), 4.11 (1H, d{t}, J_3a,3 = 2.1 Hz, J_3a,4 = 2.1 Hz, J_3a,11b = 8.1 Hz, H-3a). m/z 358 (M⁺, 100%); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.02; H, 3.02.

Compound4f: Yield 40 mg (20%), brown solid; mp 190-193 ºC; R_f 0.41 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1707 (-CHO), 1660 (C=O); ¹H NMR (CDCl₃) δ 9.79 (1H, d, J_CHO,1 = 2.4 Hz, -CHO), 8.23 (1H, d, J_m = 2.7 Hz, H-5), 7.59 (1H, dd, J_m = 2.7 Hz, J_o = 9.0 Hz, H-7), 7.43 (1H, d, J_o = 9.0 Hz, H-8), 7.39 (1H, dd, J_5',3' = 2.1 Hz, J_5',4' = 5.1 Hz, H-5'), 7.22 (1H, dd, J_3',5' = 2.1 Hz, J_3',4' = 3.6 Hz, H-3'), 7.04 (1H, dd, J_4',3' = 3.6 Hz, J_4',5' = 5.1 Hz, H-4'), 5.27 (1H, d, J_2,1a = 2.4 Hz, H-2 ), 3.27 (1H, d{dd}, J_1,CHO = 2.4 Hz, J_1,9b = 3.6 Hz, J_1,1a = 4.2 Hz, H-1), 2.89 (1H, dd, J_9b,1 = 3.6 Hz, J_9b,1a = 9.0 Hz, H-9b), 2.82 (1H, d{dd}, J_1a,2 = 2.4 Hz, J_1a,1 = 4.2 Hz, J_1a,9b = 9.0 Hz, H-1a); m/z 358 (M⁺, 44%), 329 (M⁺-29, 100%); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.30; H, 3.00.

Compound4f': Yield 22mg (11%), light brown solid; mp 168-170 ºC; R_f 0.35 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1705 (-CHO), 1657 (C=O); ¹H NMR (CDCl₃) δ 9.40 (1H, d, J_CHO,1 = 5.7 Hz, -CHO), 8.23 (1H, d, J_m = 2.7 Hz, H-5), 7.59 (1H, dd, J_m = 2.7 Hz, J_o = 9.0 Hz, H-7), 7.43 (1H, d, J_o = 9.0 Hz, H-8), 7.39 (1H, dd, J_5',3' = 2.1 Hz, J_5',4' = 5.1 Hz, H-5'), 7.22 (1H, dd, J_3',5' = 2.1 Hz, J_3',4' = 3.6 Hz, H-3'), 7.04 (1H, dd, J_4',3' = 3.6 Hz, J_4',5' = 5.1 Hz, H-4'), 5.46 (1H, d, J_2,1a = 1.2 Hz, H-2), 2.87 (1H, d{dd}, J_1,1a = 3.3 Hz, J_1,9b = 3.9 Hz, J_1,CHO = 5.7 Hz, H-1), 2.75 (1H, dd, J_9b,1 = 3.9 Hz, J_9b,1a = 9.0 Hz, H-9b), 2.53 (1H, d{dd}, J_1a,2 = 1.2 Hz, J_1a,1 = 3.3 Hz, J_1a,9b = 9.0 Hz, H-1a); m/z 358 (M⁺, 38%), 329 (M⁺-29, 100%); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.08; H, 3.10.

Compound 3g: Yield 100 mg (50%), off-white solid; mp 142-144 ºC; R_f 0.62 (5% ethyl acetate in benzene); IR ν_max/cm^-1: 1645.0 (C=O); ¹H NMR (CDCl₃) δ 8.23 (1H, d, J_m = 2.4 Hz, H-7), 7.59 (1H, dd, J_m = 2.4 Hz, J_o = 9.0 Hz, H-9), 7.42 (1H, d, J_o = 9.0 Hz, H-10), 7.33 (1H, d, J_5',4' = 5.1 Hz, H-5'), 7.20 (1H, d, J_3',4' = 3.0 Hz, H-3'), 7.02 (1H, m, H-4'), 6.52 (1H, d, J_2,1 = 2.4 Hz, H-2), 5.41 (1H, t, J_1,2 = 2.4 Hz, J_1,11b = 2.4 Hz, H-1), 5.30 (1H, d, J_4,3a = 6.6 Hz, H-4), 5.20 (1H, dd, J_3a,4 = 6.6 Hz, J_3a,11b = 9.6 Hz, H-3a), 4.27 (1H, dd, J_11b,3a = 9.6 Hz, H-11b); ¹³C NMR (CDCl₃) δ 170.4 (C-6), 153.6 (C-10a), 151.5 (C-11a), 147.7 (C-2), 138.9 (C-6a), 137.4 (C-2'), 133.5 (C-9), 130.6 (C-8), 126.9 (C-4'), 126.9 (C-3'), 125.5 (C-7), 124.8 (C-5a), 124.3 (C-5'), 119.5 (C-10), 100.8 (C-1), 81.2 (C-4), 73.1 (C-3a), 41.4 (C-11b); m/z 358 (M⁺, 100%); Anal. Calc. for C₁₈H₁₁ClO₄S: C, 60.26; H, 3.09. Found: C, 60.35; H, 3.06.

Acknowledgment

Financial support from the Council of Scientific and Industrial Research (CSIR), New Delhi for carrying out this work is highly acknowledged.

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Received: March 29, 2009

Web Release Date: November 19, 2009

Publication Dates

• Publication in this collection
  16 Mar 2010
• Date of issue
  2010

History

• Received
  29 Mar 2009
• Accepted
  19 Nov 2009