摘要:
1758 J. Chem. SOC. (C), 1970 183- and 383-Bis(methoxyphenyI)naphtho[~,l -b]pyrans By W. D. Cotterill, R. Livingstone," and M. V. Walshaw, Department of Pure and Applied Chemistry, The Polytechnic, H uddersfield Reactions between 5,6-benzocournarin and o-, M-, and p-methoxyphenylmagnesium bromides yield, inter aha, 1,3- and 3,3-bis(methoxyphenyI) naphthoC2.1 -b] pyrans. 5,6-BENZOCOUMARIN (I) was treated with either 2- or 3-methoxyphenylmagnesium bromide, and the resulting Grignard complex was decomposed with ammonium chloride solution to give, following separation by chromatography, the corresponding 3-(2-hydroxy-l- napht hyl) - 1,l -bis (methoxypheny1)prop-%en- 1-01 (I Ia or b) , and 2,3-dihydro-l,3-bis(methoxyphenyl)-1 H-naph- th0[2,1-b]pyran-3-01 (IIIa or b) .%JJ In neither Grig- nard reaction was any 3-(2-hydroxy-l-naphthyl)-l,3- bis(methoxypheny1)propan-l-one formed.3- (2- Hydroxy-l-naphth yl) -1, l-bis- (2-methoxyphenyl) prop-2- en-1-01 (IIa) on treatment with acetic anhydride in pyridine gave a monoacetate, 3- (2-acetoxy-l-naphthy1)- 1,l-bis-( 2-methoxyphenyl)prop-2-en-l-o1 (IId) . Com- pound (IIb) under similar conditions failed to give a monoacetate. The reaction between 5,6-benzocoumarin and 4- methoxyphenylmagnesium bromide gave no diol (IIc) , but a mixture of 3,3-bis-(4-methoxyphenyl)-3H-naphtho- [2,1-b]pyran (IVc), and 2,3-dihydro-1,3-bis-(kmethoxy- phenyl) -1H-napht ho [2, l-b] pyran-3-01 (I IIc) .2bj a 7 f Al- l G. Kauffmann, Bar., 1883, 16, 685. (a) A. Lowenbien, Ber., 1924, 57, 1571; (b) R. Livingstone, D. Miller, and S.Morris, J . Clzenz. SOC., 1960, 5148; (c) C. S. Barnes, J. L. Occolowitz, and M. I. Strong, Tetrahedvon, 1963, 19, 839; (d) J . Cottam and R. Livingstone, J. Chem. Soc., 1964, 5228; ( e ) D. Abson, K. D. Bartle, J. Bryant, R. Livingstone, and R. B. Watson, ibid., 1965, 2978; (f) J. Cottam, R. Living- stone, M. V. Walshaw, K. D. Bartle, and D. TIT. Jones, ibid., 1965, 5261; (g) J. Cottam and R. Livingstone, ibid., 1965, 6646.Org. 1759 coho1 (IIIc) was not obtained pure, because on recrystal- lisation partial dehydration occurred yielding 1,3- bis- (4-methoxyphenyl)-lH-naphth0[2, l-b] pyran (Vc) . R' (1) (11) a; R1 = 2-MeO*C6H4, R2 = OH b; R1 = 3-MeOC6H,, R2 = OH c; R1 = 4-Me0.C6H,, R2 = OH d; R1 = 2-MeOC6H,, R2 = OAc e ; R1 = Ph, R2 = OH f; R1 = Ph, R2 = OAC Complete dehydration to the naphthopyran (Vc) was achieved on heating a mixture of the crude alcohol and potassium hydrogen sulphate.When 3-(2-hydroxy-l- naphthy1)-1,l-bis(methoxypheny1)prop-2-en-1-01 (IIa or a ; R1 = R3 = 2-MeO-C6H,, R2 = OH b; R1 = R3 = 3-MeO*CGH4, R2 = OH c ; R1 = R3 = 4-MeO-C6H4, R2 = OH d ; R1 = R2 = 2-MeO-C6H4, R3 = OH e ; R1 = R2 = 3-MeOC6H4, R3 = OH f; R1 = R2 = 4-MeOC6H4, R3 = OH g; R1 = R2 = 2-Me0.C6H4, R3R4 = 0 h; R1 = R2 = 3-MeOC6H4, R3R4 = 0 i; R1 = R2 = 4-MeOC6H4, R3R4 = 0 j; R1 = R3 = 2-Me0C6H4 k; R1 = R3 = 3-MeOC6H4 m; R1 = R3 = 2-MeOC6H4, R4 = OH n; R1 = R3 = 3-MeOCGH4, R4 = OH 0; R1 = R3 = 4-Me0.C6H,, R4 = OH p; R1 = 2-MeO*C6H4, R3R4 = 0 q; R1 = 3-MeOCGH4, R3R4 = 0 r ; R1 = 4-MeOC,H4, R3R4 = 0 s; R1 = R2 = 2-MeOC6H4 t ; R1 = R2 = 4-MeO*C,H4 ~1 R2 (HX) 1; R1 = R3 = 4-MeO'C6H4 q!$$ H i 0 H, (111) U ; R1 = R3 = Ph, R2 = OH b) was boiled with acetic acid, the diol was dehydrated and cyclised to give the corresponding 3,3-bis(methoxy- phenyl)-3H-naphtho[2,1-b]pyran (IVa or b).Similarly, alcohols (IIIa and b) were dehydrated to give 1,3-bis- (2-methoxypheny1)- and 1,3-bis-(3-methoxyphenyl)-lH- naphtho[2,l-b]pyran (Va and b) respectively. Partial dehydration and cyclisation occurred when the mixture of products from the Grignard reaction was set aside for several weeks, or steam-distilled to remove the di- methoxybiphenyl, a by-product of the Grignard reaction. "R M. Imoto, J . Chem. SOC. Japan, 1937, 58, 932; (Chem. Abs., 1938, 32, 534.) The 3,3-bis (methoxyphenyl) -3H-napht ho [2, l-b] pyrans (IVa and c) were also prepared by dehydration of the 2,3-dihydro-3,3-bis (methoxyphenyl) -1H-naphtho [2,l-b]- pyran-1-01s (IIId and f) afforded by the reduction of the corresponding dihydronaphthopyranones (IIIg and i) with lithium aluminium hydride. The 2,3-dihydro- 3,3-bis (met hoxypheny1)napht ho [2, l-b] pyran-l-ones (I IIg and i) were obtained following the ring closure, under acidic conditions, of the chalcones (VIa and c) produced by condensing l-acetyl-%naphthol with the appropriate dimethoxybenzophenone in benzene in the presence of sodium t-b~toxide.~ Since the condensations gave a mixture of chalcone and the required ketone, subsequent treatment of the mixture with acid afforded just the ketone. The dihydronaphthopyran-1-01s (IIId and f) were difficult to purify owing to the ease with which they were dehydrated to form naphthopyrans.This was particularly so in the case of 1,2-dihydr0-3,3-bis-(4- methoxyphenyl)-1H-naphtho[2,l-b]pyran-l-ol (IIIf) which could only be characterised as the acetate. Chalcone (VIb) was obtained from l-acetyl-%naphthol and 3,3'-dimethoxybenzophenone but it could not be cyclised to 2,3-dihydro-3,3-bis- (3-methoxypheny1)naph- tho[2,1-b]pyran-l-one (IIIh). Alcohol (IIIe) was, there- fore, not obtained and so no unambiguous synthesis of naphthopyran (IVb) was achieved, but its n.m.r. spectrum was similar to those of naphthopyrans (IVa and c). The 1,3-bis(methoxyphenyl)-lH-naphtho[2,1-b]pyrans (Va, b, and c) on catalytic hydrogenation gave the 2,3- dihydro-l,3-bis (methoxyphenyl) -1H-naphtho [2, l-b] - HA a; R1 = R2 = 2-MeOC,H, b; R1 = R2 = 3-MeOC;Hi c; R1 = R2 = 4-MeOC,H4 d ; R1 = 2-MeOC6H4 e ; R1 = 3-MeOC6H4 a ; R = 2-MeOC6H4 b; R = 3-MeOC6H4 f; R1 = 4-MeO*C6H, C ; R = 4-MeO*C,&4 R1, R2, RS, and R4 = H unless otherwise stated.pyrans (IIIj, k, and 1); these were also obtained by reduction of the 1,3-bis(methoxyphenyl)-3H-naphtho- [2,l-b]pyrans (VIIa, b, and c), prepared by the de- hydration of the 2,3-dihydro-1 ,3-bis (met hoxypheny1)- lH-naphth0[2,l-b]pyran-l-ols (IIIm, n, and 0) on boiling with acetic acid. In the case of 2,3-dihydro-l,3-bis-(2- methoxypheny1)- and 2,3-dihydro-l,3-bis-(4-methoxy- phenyl)-lH-naphtho[2,l-b]pyran-l-o1 a mixture of the respective 1 H- and 3H-naphthopyrans was obtained 4 G. A. Holmberg, A d a .Chem. Scand., 1951, 6, 421; L. H. Klemm, R. Mann, and C. D. Lind, J . Org. Chem., 1958, 23, 349; L. H. Klemm, E. P. Antoniades, and C. D. Lind, ibid., 1962, 27, 519. 5 S. Wawzonek, R. C. Nagler, and L. J. Carlson, J . Anzer. Chem. SOC., 1954, 76, 1080.1760 J. Chem. SOC. (C), 1970 after boiling with acetic acid for 1 11. 2,3-Dihydro-l,3- bis- (3-met hoxypheny 1) - 1 H-naphtho [Z, l - b J pyran-1-01 appeared to give only the 3H-isomer. On boiling with acetic acid for 48 h, the dihydro-1H-naphthopyran-1-01s (IIIm, n, and 0) were converted completely into the corresponding 1,3-bis(methoxyphenyl)-lH-naphtho- [2,1-b]pyrans (Va, b, and c). 1,3-Bis-(Z-methoxy- phenyl) -3H-naphtho [2, l-b] pyr an (VI I a) on similar treatment gave 1,3-bis- (2-me thoxyphenyl) -1H-naphtho- [Z,l-b]pyran (Va).The alcohols (IIIm, n, and 0) were prepared by treating the appropriate 2,3-dihydro-3- (methoxyphenyl)naphtho[2,l-b]pyran-l-one (IIIp, q, or r) with the required methoxyphenylmagnesium bromide. Ketones (IIIp, q, and r) were obtained when the 1-(2- hydroxy-l-naphthyl)-3- (methoxyphenyl)prop-2-en-l- ones (VId, e, and f), prepared by the condensation of l-acetyl-2-naphthol with the requisite methoxybenz- aldehyde in aqueous ethanolic potassium hydroxide solution, were cyclised under acidic conditions. Cyclis- ation of chalcone (VIe) did not take place readily. The chalcones (VId, e, and f) proved difficult to purify and could not be characterised satisfactorily. However, the chalcones (VId and f), on treatment with acetic an- hydride in pyridine, were converted into the acetates (VIIIa and b); these were also obtained as the main products when the ketones (IIIp and r) were boiled With acetic anhydride and potassium acetate.With a longer period of boiling, ketone (IIIr) gave a second product (IXa) whose structure wa,s supported by spectroscopic evidence. (VIII) a; R = 2-MeOC,H4 R b ; R = 4-Me0.C6H4 A similar compound, believed to be (IXb), was isolated as the only product when ZJ3-dihydro-3-(3- methoxyphenyl)naphtho[2,1-b]pyran-l-one (IIIq) was boiled with acetic anhydride and potassium acetate. Compounds (IXa and b) showed carbonyl absorption in the i.r. region at 1735 cm-l, indicating the presence of either an ester or a 8-lactone. Since there is no peak in the n.m.r. spectrum of compound (IXb) corresponding to the methyl protons of an acetyl group, compound (IXb) must be a &lactone.Similar reactions have been reported for related flavan-4-ones.6 TABLE 1 X.m.r. data Aromatic protons 1'95-3.29 1 * 9 6-3.3 5 1.95-3.34 2-15-3.32 2.08-3.27 2'13-3.33 2-25-3.30 2.12-3.25 2.13-3'23 7 -- HB HA 3.45 3.77 3.82 3.93 4.15 4.22 4-69 4.37 4.76 4-09 3.78 4.30 4.00 4.35 4.07 v JAB OAle (Hz) 6.5 1 10.2 6-30 10.2 6.29 10.2 6-02 and 6.23 5.2 6.17 and 6.31 5-2 6.24 and 6.34 5.2 6.15 and 6.72 4.3 6.21 and 6.29 4.2 6.18 and 6.22 4.3 Although the n.m.r. spectra of the alcohols (IIIm, n, and 0) did not allow the stereochemistry at C-1 to be elucidated, the coupling constant Jax suggests that HA and Hx are tram-diaxial and the aryl group at C-3 is therefore equatorial in the preferred conformation.The movement of the hydroxy-proton resonance to lower field in alcohol (IIIm) is probably due to intramolecular hydrogen bonding between the hydroxy- and 2-met hoxy- groups (Table 2). TABLE 2 7 I - pound protons OH OMe HA.B and u J (Hz) Com- Aromatic (IIIm) 1-71-3.29 4.87 6.00 and 6.47 HA 7.43 AB 13.1 HB 6.97 BX 2.1 Hx 4-74 AX 11.5 (IIIn) 1.97-3.27 7.46 6.20 and 6-23 HA 7-24 AB 13-3 HB 7.54 BX 5.2 H x 4.88 AX 8.8 (1110) 2-03-3.23 7.48 6.2 HA 7.32 AB 13.4 HB 7.50 BX 4.5 Hx 4.96 AX 9.5 Reduction of the 3,3-bis(methoxyphenyl)-3H-naphtho- [2,1-b]pyrans (IVa and c) with hydrogen-platinum gave the corresponding 2,3-dihydro-3,3-bis(methoxyphenyl)- 1H-naphtho[Z,l-blpyrans (111s and t). The reaction between 6,6-benzocoumarin and phenyl- magnesium bromide under carefully controlled conditions followed by separation of the products by chromato- graphy gave, besides 3,3-diphenyl-3H-napht ho [Z, 1 -b] - pyran (IVd) and 2,3-dihydro-l,3-diphenyl-lH-naphtho- [2, l-blpyran-3-01 (IIIu) reported previously, 3-(2- hydroxy-l-naphthy1)-1 ,l-diphenylprop-2-en-1-01 %f (IIe). Alcohol (IIe) gave a monoacetate (IIf), and was dehydrated and cyclised on treatment with acetic acid to give 3,3-diphenyl-3H-naphtho[2,1-b]pyran (IVd). The reaction between coumarin and 2-methoxyphenyl- magnesium bromide was also repeated and, in addition to 2,2-bis- (2-met hoxyphenyl) -4H-chromen 2e obtained previously, 3-(2-hydroxyphenyl)-l ,l-bis-(2-methoxy- phenyl)prop-2-en-l-o1 (Xa) and 2,4-bis-(2-methoxy- phenyl)-4H-chromen (XI) were isolated.Compound C.Kuroda, J . Chew. SOL, 1930, 762; T. A. Geissman and R. 0. Clinton, J . Amer. Chew. SOL, 1946, 68, 697.Org. 1761 (Xa) gave a monoacetate (Xb) and on treatment with acetic acid afforded 2,2-bis-(2-methoxyphenyl)-4H- chromen.2e EXPERIMENTAL M.p.s were determined on a Kofler hot-stage apparatus. N.m.r. spectra were determined with a Varian A60A spectrometer for 10% solutions in deuteriochloroform with tetramethylsilane as internal standard. 1.r. spectra were measured with a Hilger-Watts Infrascan spectrometer, H900, for carbon tetrachloride solutions. The acetates were prepared in the cold by use of acetic anhydride and p yridine . The Reaction between 5,6-Benzocoumarin and Various iWethoxyphenylmagnesium Bromides.-5 , 6-Benzocoumarin (0.1 mol) in benzene (300 ml) was added during 1 h to a stirred Grignard solution prepared from the bromo- (methoxy)benzene (0-22 mol), magnesium (0.22 g atom), and ether (100 ml).The solution was boiled for 1 h and set aside overnight. The benzene-ether layer was decomposed with 22% ammonium chloride solution, separated, and dried (Na2S04). After removal of the solvent the products were isolated as follows. (i) 5,6-Benzocoumavi~ and 2-methoxyphenylmagnesium bromide.-Trituration of the residual gum with benzene left a solid. Recrystallisation from ethyl acetate gave 3-(2- hyduoxy- 1-naphthy2)- 1 , 1-bis- (2-methoxyfihenyZ)prop-2-en- 1-ol (IIa) (12.2 g, 29.7%), m.p. 148-149". vmx. 3430 and 3500 cm-1 (Found: C, 78.5; H, 5.8. C,,H,,O, requires C, 78.6; H, 5.9y0), [monoacetate (IId), m.p.138-139", from ethyl acetate-light petroleum (b.p. 60-80"), vmX 1760 and 3550 cm-l (Found: C, 76.5; H, 5-6. C2,H2,05 requires C, 76.6; H, 6*8y0)]. Concentration of the benzene solution yielded a solid , which on recrystallisation from chloroform- ethanol gave 2,3-dihydro-l , 3-bis-(2-rnethoxyfihenyZ)-lH- naphtho[2,l-b]fiyran-3-oZ (IIIa) (5.1 g, 12.3%) , as needles, m.p. 172", v,, 3450 cm-l (Found: C, 78.4; H, 5.8. C27H2404 requires C, 78.6; H, 5*9y0). (ii) 6 , 6-Benzocoumarin and 3-methoxyphenyl magnesium bromide. The residual gum was chromatographed on alumina in benzene solution to give a gum on removal of the solvent. Recrystallisation from benzene-light petroleum (b.p. 80-100') gave 2,3-dihydro-1,3-bis-(3- methoxyphenyZ)- lH-naPhtho[ 2,l-b]pyran-3-ol (IIIb) (8.85 g, 21~4%)~ m.p. 172', v- 3520 cm-l (Found: C, 78.15; H, 6.0.C27H2404 requires C, 78.6; H, 5.9%). Further elution of the alumina with acetone and subsequent removal of the solvent yielded a gum, which on recrystallis- ation from benzene-light petroleum (b.p. 80-100°) gave 3- (2-hydroxy- 1-naphthyZ)- 1,l-bis- (3-methoxy$henyZ)pro$-2-en- 1-oZ (IIb) (13.89 g, 33*6y0), m.p. 114", vmxa 3530 and 3600 cm-l (Found: C, 78-6; H, 5.9. C27H2404 requires C, 78.6; H, 5-9y0). (iii) EiJ6-Benzocoumarin and 4-~ethoxy$henylmagnesium bromide. The residual gum was chromatographed on alumina in benzene-light petroleum (b.p. 80-100°) solution. Removal of the solvent and recrystallisation from ethyl acetate gave 3 , 3-bis-(4-methoxyfihenyZ) -3H-naphtho[2,l-b]- pyran (IVc) (19.1 g, 4 8 ~ 5 % ) ~ m.p.175-176' (Found: C, 81.8; H, 5-7. C27H2203 requires C, 82.2; H, 506%). Further elution of the alumina with chloroform yielded a brown gum, which was fused with anhydrous potassium hydrogen sulphate. The product obtained following the addition of water and isolation with ether was chromato- graphed on alumina in benzene solution. Removal of the solvent yielded a gum, which on recrystallisation from chloroform-ethyl acetate gave 1,3-bis-(4-methoxyPhenyZ)- lH-naphth0[2,l-b]$Jyuan (Vc) (5.0 g, 12.7y0), as plates, m.p. 196" (Found: C, 81.8; H, 5.8. C,,H,,O, requires C, 82.2; H, 5.6%). (iv) 5,6-Benzocoumarin and phenylwagnesium bromide. The mixture of products was chromatographed on alumina in benzene-light petroleum (b.p. 80-looo) solution.Removal of the solvent and recrystallisation from ethyl acetate-methanol gave 3,3-diphenyl-3H-naphtho[2,l-b]- pyran (IVd) (7.5 g, 22.6y0), m.p. and mixed m.p. 161- 162".2b Further elution with chloroform, removal of the solvent , and recrystallisation from benzene-light petroleum (b.p. 80-100') gave 2,3-dihydro- 1 , 3-diphenyl- lH-naphtho- [2,1-b]pyran-3-01 (IIIu) (4.9 g, 13.9y0), m.p. and mixed m.p. 157-159°.2b Final elution with acetone, removal of the solvent, and recrystallisation from benzene-light petroleum (b.p. SO-100') gave 3-(2-hydroxy- 1-naphthyl) - 1'1-diphenyl- $rop-2-en-l-oZ (IIe) (3.6 g, 9.5%), m.p. 145-146', vm, 3530 and 3600 cm-l [monoacetate (IIf), m.p. 164-165" (from methanol), v,, 1750 and 3490 cm-l (Found: C, 82.0; H, 5.7. Compound (IIe) (0-53 g) and acetic acid (30 ml) were boiled for 0.5 h, and poured into water.Isolation with ether and crystallisation from ethyl acetate-methanol gave 3,3-diphenyl-3H-naphtho[2 , 1-blpyran (IVd) (0.36 g, 7 l*6y0), m.p. and mixed m.p. 161-162". (v) Coumarin and 2-methoxy~henylmagnesizam bromide. Trituration of the residual gum with ether gave a solid, which on crystallisation from ethyl acetate-methanol yielded 3-( 2-hydroxyphenyZ)-l , l-bis(methoxy~henyZ)Prop-2- en-1-oZ (Xa) (5.5 g, 32-1y0), m.p. 143-144", v,, 3430 and 3550 cm-l (Found: C, 76.4; H, 6.1. C2,H,,04 requires C, 76-2; H, 601%)~ [monoacetate (Xb), m.p. 121-122' (from methanol), vmx. 1760 and 3550 cm-l (Found: C, 74.3; H, 6-1. C2,H2,05 requires C, 74.2; H, 6-0%]. Removal of solvent from the filtrate and ether washings yielded a gum which was chromatographed on aluminain benzene-light petroleum (b,p.80-100°) solution to give a gum. Further elution with chloroform also gave a gum. Final elution with acetone and removal of solvent gave a gum, which was boiled with acetic acid (20 ml) for 0.5 h, to yield a solid on cooling. Recrystallisation from benzene-light petroleum (b.p. 60-80') gave 2,4-bis-(2-methoxyphenyZ)-4H-ch~omen (XI) (3.4 g, 20.6%), m.p. 141-142", vmX. 1670 cm-l (Found: C, 80.4; H, 5.6. C2,H,,0, requires C, 80.2; H, 5.9%). A solid, m.p. 212", was also isolated in small amount from the acetic acid solution. 3-(2-Hydroxyphenyl)- 1 , 1-bis- (2-metlmxyphenyl)prop-2- en-1-01 (1.15 g), acetic acid (10 ml), and ethyl acetate (10 ml) were boiled for 0.5 h.Removal of the solvent and crystallisation from ethyl acetate-methanol gave 2,2-bis-(2- methoxypheny1)-2H-~hroman (0.87 g, 79*6%), m.p. 162- 163" (lit.,2e 163"). 3,3-Bis-(2-methoxy$JhenyZ)-3H-naphtho[2,l-b]pyran (IVa). -(i) 3-( 2-Hydroxy- 1-naphthy1)-1, 1-bis-( 2-methoxypheny1)- prop-2-en-1-01 (7.1 g), ethyl acetate (50 ml), and acetic acid C27H2203 requires C , 82-2; H, 5.6y0)].1762 J. Chem. SOC. (C), 1970 (30 ml) were boiled for 0.5 h. Concentration of the solution and recrystallisation from ethyl acetate-methanol gave 3,3-bis-(2-methoxyfihenyZ)-3H-naphtho[2,l-b]pyran (IVa) (6-6 g , 97%), m.p. 153' (Found: C, 82.25; H, 5.5. C,,H,,03 requires C, 82.2; H, 5.6%). (ii) 2,3-Dihydro-3,3-bis-(2-methoxyphenyl)-lH-naphtho- [2,l-b]pyran-l-o1 (0.45 g), and anhydrous potassium hydrogen sulphate (0.5 g) were heated at 175' for 0.25 h.Addition of water, isolation with ether, and recrystallisation as in (i) gave the naphthopyran (IVa) (0.33 g, 76-6y0), m.p. and mixed m.p. 151-153'. (iii) 2,3-Dihydro-3,3-bis-(2-methoxyphenyl)-lH-naphtho- C2,l-bIpyran-l-yl acetate (0.4 g) was heated at 200' for 0.5 h to give, on recrystallisation, the naphthopyran (IVa) (0.20 g, 57.6%) , m.p. and mixed m.p. 151-153'. 3,3-Bis-( 3-methoxyphenyl)-3H-naphtho[2,l-b]~yran (Ivb). -3- (2-Hydroxy-l-naphthyl)-l, 1-bis-(3-methoxypheny1)- prop-2-en-1-01 (2.42 g), ethyl acetate (10 ml), and acetic acid (15 ml) were boiled for 2 h. Addition of water and isolation with ether gave a gum, which was chromato- graphed on alumina in benzene solution. Removal of the solvent and recrystallisation from ethyl acetate-light petroleum (b.p. 80-1 00') gave 3,3-bis- (3-methoxy phenyl) - 3H-naphtho[2,1-b]pyran (1.9 g, 82.170), m.p. 101' (Found: C, 82.3; H, 5.6. 3,3-Bis- (4-methoxypheny 2) -3H-nuphtho [2,1 -b]pyran (IVc) . - (i) 2,3-Dihydro- 3,S-bis- (4-methoxyphenyl) - 1 H-naphtho- [2,l-b]-pyran-l-o1 (2.29 g) and acetic acid (50 ml) were boiled for 0.75 h. Addition of water, filtration, and recrystallisation from ethanol-ethyl acetate gave 3,3-bis-(4-methoxyphenyZ)- SH-naphtho[Z, 1-blpyran (IVc) (0.81 g, 37-0%), m.p. and mixed m.p. 175-176O. (ii) 2,3-Dihydro-3,3-bis-(4-methoxyphenyl) -lH-naphtho- [2,l-b]pyran-l-y1 acetate (0.76 g) was heated at 150' for 0-5 h, and the residue was chromatographed on alumina in benzene solution. Removal of the solvent and crystallis- ation from ethanol-ethyl acetate gave the naphthopyran (IVc) (0.51 g, 77.4%), m.p.and mixed m.p. 175-176". 1,3-Bis (wzethoxyphenyl) - lH-rcu~hth0[2,l-b]pyrans .- The 2,3-dihydro- 1,3-bis- (methoxyphenyl) - lH-naphtho[2,l-b]- pyran-3-01 (0.8 g) and acetic acid (10 ml) were boiled for 1 h. The solution was cooled, to yield a solid, which was recrystallised from a suitable solvent to give the 1,3-bis- (methoxyphenyl) - lH-na$htho[2,l-b]pyran. (i) 1,3-Bis-(2-methoxy~FenyZ)-lH-na~htho[2, 1-blfly~an (Va) . This compound, prepared from 2,3-dihydro- 1,3-bis- (2-methoxypheny1)-1H-naphtho[2,1-b]pyran-3-o1 (91.2y0), had m.p. 183" (from ethyl acetate-methanol) (Found: C, 82.4; 33, 5.8. C2,H,203 requires C, 82-2; H, 5.6%). It was also prepared by boiling 1, 3-bis-( 2-methoxypheny1)- 3H-naphtho[2,l-b]pyran (0.39 g) in acetic acid (50 ml) for 48 h (72%) (m.p.and mixed m.p. 183") and isolated by removal of the solvent and chromatography on alumina in benzene solution. (ii) 1,3-Bis-(3-methoxy~henyZ)-lH-na~htho[2,l-b]~yran (Vb) . This compound , prepared from 2,S-dihydro- 1,3-bis- (3-methoxyphenyl) - 1H-naphtho [2 , 1-b] pyran- 3-01 (7 7.9 % ) , had m.p. 97' [from light petroleum (b.p. 100-120")] (Found: C, 82.3; H, 5.9. C2,H2203 requires C, 82-2; H, 5.6%). 2,3-Dihydro-3,3-bis (methoxyphenyl) naphtho [2 , 1-blpyran- 1 - ones.-The dimethoxybenzophenone (50 g) and l-acetyl- 2-naphthol (10.2 g) in benzene (400 ml) were added to sodium t-butoxide [from sodium (5.3 g) and t-butyl alcohol (50 ml)] ; the solution was boiled and stirred for 20 h, and C27H2203 requires C, 82.2; H, 5.6y0).then poured into a stirred mixture of hydrobromic acid (100 ml) and acetic acid (150 ml). The mixture was boiled for 1 h, and set aside overnight. Removal of the solvent from the organic layer gave a gum which was boiled for 3 h with methanol saturated with hydrogen chloride. After removal of the solvent the residue was chromatographed on alumina in benzene solution. Removal of the solvent and recrystallisation from ethyl acetate gave the 2,3-dihydro- 3,3-bis(methoxyphenyl)naphtho[2, 1-blpyran-1-one. (i) 2,3-Dihydro-3,3-bis-(2-methoxyphenyl)naPhtho[2,l-b]- pyran-1-one (IIIg) . This compound, prepared from 2,2'- dimethoxybenzophenone (38-3%), had m.p. 207-208", vmx. 1670 cm-l (Found: C, 78.7; H, 5.7.C2,H2,0, requires C, 79.0; H, 5.4%). (ii) 2,3-Dihyd~o-3,3-bis-(4-methoxyphenyZ)naphtho[2,l-b]- $yyan-l-one (1111). This compound, prepared from 4,4'- dimethoxybenzophenone (32.9y0), had m.p. 135-136", vmX. 1670 cm-l (Found: C, 78.6; H, 5.4. C27H2204 requires C, 79.0; H, 5.4%). (iii) 1- (2-Hydroxy- l-naphthyZ)-3,3-bis- (3-~zetho=cyphenyl)- prop-2-en-1-one (VIb) . This compound, prepared from 3,3'-dimethoxybenzophenone ( 15.7y0), had m.p. 126-127" (from ethanol), vmk 1635, 1670, and 3590 cm-l (Found: C, 79-0; H, 5.6. C2,H220, requires C, 79.0; H, 5.4%). Chromatography in benzene solution yielded unchanged 3,3'-dimethoxybenzophenone. Elution with chloroform gave (VIb). 2,3-Dihydro-3, 3-bis(uvcethoxyphenyl)- 1H-naphtho [2,l-b]- pyran- 1-oh.-Powdered 2,3-dihydro-3,3-bis (methoxy- phenyl)naphtho[2,l-b]pyran-l-one (4 g) was added to an excess of lithium aluminium hydride in dry ether (250 ml) and boiled for 0.5 h.Addition of dilute sulphuric acid, isolation with ether, and recrystallisation from a suitable solvent gave the alcohol. 2,3-Dihydro-3, 3-bis-( 2-methoxyphenyl) - 1H-nuphtho- [2,l-b]pyran-l-ol (IIId) . This compound, prepared from 2,3-dihydro-3,3-bis-( 2-methoxyphenyl)naphtho[2, l-blpyran- 1-one (96.7y0), had m.p. 176-178' [from light petroleum (b.p. 100-120°)], vmX. 3590 cm-l (Found: C , 78.7; H, 6.0. CZ7H2,O4 requires C, 78-6; H, 5.9y0) [acetate, m.p. 194- 196" (from methanol), v,, 1730 cm-l]. 2,3-Dihydro-3 , 3-bis- (4-methoxyphenyl) - 1H-naphtho- [2,1-b]pyran-l-oZ (IIIf). This compound, prepared from 2,3-dihydro-3,3-bis-(4-methoxyphenyl)naphtho[2, l-blpyran- 1-one (4.18y0), had m.p.78-80° [from light petroleum (b.p. 40")], vmx. 3590 cm-l [acetate, m.p. 83-85' (from methanol), vmax. 1730 cm-l (Found: C, 76.7; H, 5.8. C,,H,,O, requires C, 78.65; 13, 5-7%)]. 1- (2-Hydroxy- 1-naphthy Z) -3- (methoxyphenyl)P,rop-2-en- 1 - one.-Sodium hydroxide (6.0 g) in water (12 ml) was added to a solution of 1-acetyl-2-naphthol (9.3 g) and the appro- priate methoxybenzaldehyde (6-8 g) in absolute ethanol (90 ml), and the mixture was set aside for 6 days. Crystals of the 1- (2-hydroxy- 1-naphthyl) - 3- (methoxyphenyl)+rop-2- en-1-one separated, which were filtered off, washed with water, then ethanol, and dried. The residue obtained following the addition of water to the filtrate and isolation with ether was boiled with acetic acid (30-50 ml) for 0.5 h.This solution was poured into water, extracted with ether, and purified as indicated to give the 2,3-dihydro-3- (methoxyphenyl) naphtho [2,1-b]pyran- 1-one. 1- (2-Hydroxy- 1-pzaphthyl) -3- (2-methoxyphenyZ)prop-2- en-1-one (VId) (59.2%) had m.p. 178-180', [acetate (VIIIa), m.p. 120-122' (from methanol), vmX. 1645, 1670, and 1765 cm-1 (Found: C, 76.4; H, 5.3. C,,H,,O, requires C, (i) (ii) (i)Org. 1763 76.3; H, 5.2%)]. 2,3-Dihydro-3-( 2-~nethoxyphenyZ)nu~htho- [2,l-b]pyran-l-one (IIIp), obtained by chromatography on alumina in benzene solution and recrystallisation from ethyl acetate (25.6y0), had m.p. 150-152", vmx. 1675 cm-l (Found: C, 79.1, H, 5-2. C,,H,,O, requires C, 78.9; H, 1-( 2-hydvoxy- l-tnphthyZ)-3-( 3-methoxyflhenyl) - prop-2-en-1-one (VIe) (31.6%), had m.p.178". 2,3-Di- hydro-3- (3-~.nethoxy~henyZ)nuflhtho[2,l-b]~yrun- 1-one (IIIq) (47-2y0), plates, had m.p. 122-123" (from acetic acid), vmX. 1675 cm-l (Found: c, 78.3; H, 5.35. C2,H1,0, requires C, 784; H, 5.3y0). (iii) 1- (2-Hydroxy- 1-naphthyl) -3- (4-methoxyphenyZ)pro~- 2-en-1-one (VIf) (51.3y0), had m.p. 190-192" [acetate (VIIIb), m.p. 114115" (from methanol), vmX. 1645, 1670, and 1765 cm-l (Found: C, 75.85; H, 5.3. C22H1804 requires C, 76.3; H, 5.2%)]. 2,3-Dihydro-3-(4-1aethoxy- ~henyZ)na~htho[2,l-b]pyran-l-one (IIIr), obtained by chromatography on alumina in benzene solution, and re- crystallisation from ethyl acetate (33*5%), had m.p. 146- 147", v,,, 1675 cm-l (Found: C, 79.0; H, 593.C2,H1,0, requires C, 78.9; H, 5.3%). 2,3-Dihydro-3- (2-methoxypheny2) nuphtho[2,1 -b]pyrun- 1- one (IIIp) .-1-( 2-Hydroxy- l-naphthyl)-3-( 2-methoxy- phenyl)prop-2-en-l-one (2.7 g ) and acetic acid (20 ml) were boiled for 0.5 h and poured into water. The product obtained on isolation with ether was chromatographed on alumina in benzene solution. Removal of the solvent and recrystallisation from ethyl acetate gave 2,3-dihydro-3-(2- methoxyphenyl)naphtho[2,l-b]pyran-l-one (1.53 g , 56*7%), as needles, m.p. and mixed m.p. 150-152". 2,3-Dihydro-3- (3-methoxy~henyZ)naphtho [2, 1 -b]pyran- 1- one (IIIq) .-1- (2-Hydroxy- 1-naphthyl) -3- (3-methoxy- pheny1)prop-2-en-1-one (4.25 g), methanol (50 ml), and 46% hydrobromic acid (3 ml) were boiled for 0.5 h, concentrated, and cooled to give a crystalline solid.Recrystallisation from ethyl acetate gave 2,3-dihydro-3-(3-methoxyphenyl)- naphtho[2,l-b]pyran-I-one (2.01 g , 50.1 %), m.p. and mixed m.p. 122-123". 2,3-Dihydro-3- (4-~nethoxyfihenyZ)nuPhtho [2,l-b]pyrun-l- one (IIIr) .-This, prepared like the 2-methoxyphenyl derivative (59.5y0), gave needles, n1.p. and mixed m.p. 146-147' (from methanol-ethyl acetate). Reaction between 2,3-Dihydro-3-(methoxyphenyZ)naphtho- [Z,l-b]pyran-l-ones and Acetic Anhydride-Potassium Acetate.-The 1-ketone (0.5-1.25 g), acetic anhydride (10 ml), and freshly fused potassium acetate (0.5-1.0 g) were boiled for 2 hr. Water was added and the products were isolated with ether and chromatographed on alumina in benz- ene solution and then chloroform to give the 1-(2-acetoxy-l- naphthyZ)-3-(methoxy~henyZ)~~o~-2-en-l-one and the 4-[2- (methoxyphenyZ)vinyl]-5,6-benzocoumarin, respectively, which were recrystallised from suitable solvents.1- (2-A cetoxy- 1-nufihthyl) -3- (2-methoxyphenyZ)prop-2- en-1-one (VIIIa) (65%) had m.p. and mixed m.p. 121-122" (from methanol). (ii) 4- [2-( 3-Methoxypheny Z) vinyg -5,6-benzocoumarin (IXb) (42%) had m.p. 160-162" (from ethanol), v,,, 1625 and 1735 cm-l, 7 1.94-3.09 (aromatic and olefinic HB and Hc), 3.49 (Ha), and 6.13 (OMe) (Found: C, 78.8; H, 4.8. C22HI6O3 requires C, 80.4; H, 4.9%). (iii) 1-(2-A cetoxy-l-naphthyl)-3-(4-methoxy~henyZ)~ropoib-2 en-1-one (VIIIb) (23%) had m.p. and mixed m.p. 114-115" (from methanol) had 4-[2-(4-methoxyj5henyZ)vinyl] 5,6-benzo- coumurin (IXa) (35%) had m.p.165-167" [from ethyl 5'3%). (ii) Crude (i) acetate-light petroleum (b.p. SO-lOO")], vmx. 1625 and 1735 cm-l (Found: C, 80.2; H, 4.7. C22H,,0, requires C, 80.4; H, 4.9%). 2,3-Dihydro- l13-bis (methoxypheny2) - 1H-naphtho [ 2,l-b] - pyruiz- 1-ols .-The 2,3-dihydro-3- (methoxyphenyl) naphtho- [a, l-blpyran- l-one (10.17 g) in benzene (50-200 ml) was added during 0.5 h to a stirred Grignard solution from the methoxybromobenzene (7 g), magnesium (1.06 g), and ether (30-50 ml); the mixture was then boiled for 1 h. After decomposition with ammonium chloride solution and isolation with ether the following dihydronupkthopyrut- 1- 01s were obtained. 2,3-Dihydvo- 1,S-bis- (2-nzethoxyPheny2) - 1H-naphtho- [2,l-b]pyran-l-ol (IIIm). The non-volatile fraction after steam-distillation was triturated with benzene to give the dihydronaphthopyrun-1-ol (31*8%), m.p.243-245", vmax. 3540 cm-l (Found: C, 78.1; H, 5.7. C2,H2104 requires C, 78.6; H, 5.8%). The benzene solution failed to give a solid on attempted crystallisation. The gum and acetic acid (30 ml) were boiled for 1 h and poured into water. Follow- ing isolation with ether, the product was chromatographed on alumina in benzene solution. Removal of the solvent and recrystallisation from ethyl acetate gave 1,3-bis-(2- methoxyphenyZ)-3H-na~htho[2,l-b]~yran (VIIa) (37.3%), m.p. 157" (Found: C, 82-1; H, 5.6. C,,H2203 requires C, 2,S-Dihydro- 1 , 3-bis- (3-methoxyfihenyl) - 1 H-naphtha]- [2,1-b]pyran-l-o2 (IIIn). The gum was chromatographed on alumina in benzene solution.Removal of the solvent gave a gum which was not identified. Further elution with chloroform, removal of the solvent, and recrystallisation from light petroleum (b.p. 100-120") gave the dilzydro- naphthopyran-1-oE (35.7%) , m.p. 141-142", vmX. 3600 cm-1 (Found: C, 78.5; H, 5.9. C2,H2,0, requires C, 78.6; H, 5.9%). 2,3-Dihydro- lJ3-bis- (4-methoxyPhenyE) - 1H-naphtho- [2,1-b]pyvan-l-oZ (1110). Recrystallisation from chloro- form-light petroleum (b.p. SO-lOOO) gave the dihydro- naphthopyran-1-ol (31*5y0), m.p. 213-214", vmx. 3600 cm-1 (Found: C, 78.8; H, 5.65. C27H2404 requires C, 78.6; H, 5*9y0). 1,3 Bis-(methoxyphenyZ)-3-Hnuphtho [2,1-b]pyruns.- (a) The 2,3-dihydro-lJ3-bis(rnethoxyphenyl)-lH-naphtho[2, l-bj- pyran-1-01 (2 g) and acetic acid (30 ml) were boiled for 0.5 h and poured into water.Isolation with ether gave a gum which was chromatographed on alumina in benzene solution. Removal of the solvent gave either the 1,3-bis(methoxy- phenyZ)-3H-nu~lztho[2,l-b]pyran, or a mixture of this with the 1H-isomer, from which the required 3H-naphthopyran was separated. (i) 1,3-Bis- (2-methoxyphenyl) -3H-naphtho [2,l-b]pyran (VIIa) . This compound, prepared from 2,3-dihydro-1,3- bis- (2-methoxypheny1)- 1H-naphtho [2,l-b] pyran- 1-01 (87.8%), had m.p. and mixed m.p. 157" (from ethyl acetate) (Found: C, 82.1; H, 5.6. C2,H,20, requires C, 82.2; H, 5.6). Concentration of the mother liquors and re- crystallisation from ethyl acetate-methanol gave 1,3-bis- (2-methoxyphenyl)-lH-naphth0[2,l-b]pyran (5.3%) , m.p. and mixed m.p. 182-183", i.r.spectrum identical with that of an authentic sample. (ii) 1,3-Bis- (3-methoxyphenyl) -3H-naphtho [2,l-b]Pyrun (VIIb) . This compound was prepared from 2,3-dihydro- 1.3-bis-( 3-methoxyphenyl)-lH-naphtho [2,1-b]pyran- 1-01 ; crystals, obtained after cooling the acetic acid solution, were purified by chromatography (89.4%), m.p. 146-147" [from (i) 82-2; H, 5.6%). (ii) (iii)1764 J. Chem. SOC. (C), 1970 light petroleum (b.p. 100-120')] (Found: C, 82.0; H, 5-75. C27H2203 requires C, 82.2 ; H, 5.6y0). (iii) 1 ,3-Bis- (4-rnethoxyphenyZ) -3H-naphtho[2, l-blfiyran (VIIc). This compound was prepared from 2,3-dihydro- 1,3-bis- (4-methoxyphenyl- lH-naphthol[2, l-b Jpyran- 1-01 (25.17y0), m.p. and mixed m.p. 195-196'. Concentration of the mother liquors and recrystallisation from ethyl acetate-methanol gave 1,3-bis-(4-methoxyfihenyZ)-3H- nuphth42, 1-blpyran (15-8%), m.p.166-167' (Found : C, 81.8; H, 5.4. C2,H2,03 requires C, 82.2; H, 5.6%). (b) The l-alcohol (1.0 g) and acetic acid (50 ml) were boiled for different periods of time. After removal of the solvent the residue was chromatographed on alumina in benzene solution. Removal of the solvent gave a mixture of 1,3-bis(methoxyphenyl)-lH- and 1,5-bis(methoxyphenyl) - 3H-naphtho[2, l-blpyrans, the composition of which was determined from the n.m.r. spectrum (Table 3). TABLE 3 Period of Wt. of boiling residue 1 -Alcohol (h) (g) (ii) 3-Me thox y 1 0.9 1 (ii) 2-Methoxy 1 0.94 48 0.88 48 0.8 1 (iii) 4-Methoxy 1 0.96 48 0.85 1H-Isomer 3H-Isomer 32 68 100 0 5 95 100 0 50 50 100 0 (%I (%) 2,3-Dihydro-l,3-bis(nzethox~~henyZ)-lH-naphtho[2,1-b]- pymns .-Either the 1,S-bis (methoxyphenyl) - 1H-naphtho- [ 2 , l -b] p yran or 1,3-bis (methoxyphenyl) - 3H-naphtho [ 2 , l -b] - pyran (0.5 g), platinum(1v) oxide (0.02-0.04 g), ethyl acetate (90 ml), and acetic acid (80 ml) were shaken in hydrogen until absorption (1 molar equiv.) was complete.Filtration, evaporation, and recrystallisation gave the 2,3-dihydronaphthopyran. [2, l-blpyran (IIIj). This compound was prepared from 1, 3-bis- (2-methoxyphenyl)-lH-naphtho[2, l-blpyran (41 '6%) (i) 2,3-Dihydro-1,3-bis-(2-~nethozyphenyl)-lH-naphiho- or from 1,3-bis-( 2-methosyphenyl)-3H-naphtho[2, l-blpyran (18-3%), and had m.p. 138", from either ethyl acetate-light petroleum (b.p. 60-8O0) or methanol-ethyl acetate (Found : C, 81-55; H, 6.2. (ii) 2,3-Di~ydro-1,3-bis-(3-nzeihoxyphenyZ)-lH-~ap~z~ho- [2, l-blpyran (IIIk). This compound was prepared fron 1,3-bis-( 3-methoxypheny1)- lH-naphtho[2,1 -b] pyran (707;) or from 1,3-bis- (3-methoxyphenyl) -3H-naphtho [2, l-b] pyran (41.1y0), and had m.p. 120-121', from either ethyl acetate- light petroleum (b.p. 60-80") or methanol-ethyl acetate (Found: C, 81.4; H, 6-2. Cz,H2403 requires C, 81.1; H, 6.1%). 2,3-Dihydr.o- l13-bis-(4-unethoxyplzelz_yl) - 1 H-nnplztho- [2,1-b]pyrar. (1111). This compound was prepared from lI3-bis-(4-methoxypheny1) - 1H-naphtho [2,1-b]pyran (344%) or from 1,3-bis-(4-methoxyphenyl)-3H-naphth0[2, l-blpyran (38.0%), and had m.p. 173-174", needles, from either light petroleum (b.p. 100-120") or ethanol-ethyl acetate (Found: C, 814; H, 6-3. Cz&2403 requires C, 81.8; H, 6.1%). 2,3-Dilaydro-3,3-bis(nzethoxypheizyZ)-lH-naphi~~o[2, 1-b]- pyrans .- 3,3-Bis (methoxyphenyl) -3H-naphtho[ 2, l-b] pyran (0-5 g), platinum(1v) oxide (0.02 g), ethyl acetate (50-150 ml) and acetic acid (50 ml) were shaken in hydrogen until absorption (1 molar equiv.) was complete. Filtration, evaporation, and recrystallisation gave the dzlzydro- naphthopyran. (i) 2,3-Dil~ydro-3,3-bis-(2-methoxypheny2)-1H-naphtho- [2, l-blpyran (111s). This compound, prepared from 3,3- bis-( 2-methoxyphenyl)-3H-naphtho[Z, l-blpyran (83~6%)~ had m.p. 176-177' (from ethyl acetate-methanol) (Found: C, 81.3; H, 6.0. C27H& requires C, 81.8; H, 6.1%). 2,3-Dihyd~0-3,3-bis- (4-methoxyphenyl) - 1 H-nuphtho- [2,1-b]pyran (IIIt). This compound, prepared from 3,3- bis-( 4-methoxyphenyl)-3H-naphtho[2, l-blpyran (62-4y0), had m.p. 179' (from ethyl acetate) (Found: C, 81.8; H, 6.0. C&&403 requires C, 81.8; H, 6.1%). [0/069 Receiv~d, Jaizuary 15th, 19701 C27H2403 requires C, 81-8; H, 6.1%). (iii) (ii)
ISSN:0022-4952
DOI:10.1039/J39700001758
出版商:RSC
年代:1970
数据来源: RSC