2-Benzopyran-3-ones stabilised by alkoxy substituents

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1991 2-Benzopyran-3-ones Stabilised by Alkoxy Substituents David P. Bradshaw, David W. Jones * and John Tideswell School of Chemistry, The University, Leeds LS2 WT, UK ~~~ In contrast to the corresponding compounds lacking alkoxy substituents, the 2-benzopyran-3-ones 5, 6, 7 and 9 are stable and easily isolated. In contrast to the 6-methoxy derivative 7, the 7-methoxy isomer 8 cannot be isolated; the stabilising effect of the 6,7-methylenedioxy group in 5 and 9 is therefore due to the alkoxy group at C-6. This is consistent with a donor-acceptor interaction involving the C-6 alkoxy group and the nucleophilic attack by water. 2-Benzopyran-3-one 1 is a reactive intermediate responsible for the yellow colour produced by heating o-formylphenylacetic acid 11 in acetic anhydride.' The pyrone 1 is present in minute concentration in such solutions but has been characterised by trapping, in high yield, with conventional dienophiles ' and simple olefins.2 Photolysis of the bis-lactone 18 at low temperature in a matrix serves to further characterise the pyrone 1; 1 cannot be isolated, probably due to easy hydration back to acid 11.' The l-methyl d,erivative 2 and the l-phenyl derivative 3 also resisted isolation.' It was therefore an agreeable surprise to find that the pyrone 4, used in our podophyllotoxin ~ynthesis,~ was a stable crystalline compound of good shelf life.Herein we report the attempted preparation of a number of new 2-benzopyran-3-ones the properties of which serve to identify the main stabilising effect in 4.Preparation of o-Acylphenylacetic Acids.-The keto-acids 12-14 and 16 all carry an alkoxy group para to the 0x0 group and were readily prepared from the corresponding methyl alkoxyphenylacetates by Friedel-Crafts acylation (R' pyrone carbonyl which decreases reactivity towards 0x0 acid 15 was obtained from 5-methoxy-3-phenylindene by ozonisation followed by oxidative work-up (NaOH/H,O,/ H,O/MeOH). The aldehydo acid 17 was prepared from 6,7- methylenedioxyisochroman-3-one via opening of the lactone ring (NaOH, H20, EtOH), acidification at 0°C and rapid esterification of the unisolated and freshly extracted hydroxy acid. Swern oxidation of the product and ester hydrolysis gave 17.Dehydration of o-Acylphenylacetic Acids.-The foregoing acids were heated in boiling acetic anhydride in an inert atmosphere (2 h) and the product isolated by evaporation of acetic anhydride on a steam-bath under a water-pump vacuum. The residue was triturated with ether and the product purified as detailed in the Experimental section. The stability of 4 was shared by the l-phenyl substituted 6,7- methylenedioxypyrone 5 and the l-phenyl substituted 6,7-dimethoxypyrone 6 showing that oxygen substituents in the l-aryl ring have little influence on stability. This would be expected since the central methoxy in 1,2,3-trimethoxy-COCl/SnCI,/CH2C1,/20 "C) followed by ester hydrolysis. The benzenes does not conjugate efficiently with the aromatic ring,6 and conjugation of the aryl group with the pyrone ring in 4 will be diminished by steric effects.' The stability of the dimethoxy compound 6 rules out any special influence of R2qfR3 the methylendioxy group.? That the C-6, rather than the C-7 alkoxy group, wasA1 1 R1=R2=R3=H 2 R' = Me, R2 = R3 = H 3 R'=Ph,R2=R3=H 4 R' = 3,4, 5-(Me0)3C6H2;R2, R3 = 5 R' = Ph; R2, R3 = OCH20 6 R' = Ph, R2 = R3= OMe 7 R' = Ph, R2 = OMe, R3= H 8 R' = Ph, R2= H, R3 = OMe 9 R' = Me; R2, R3 = OCH20 10 R' = H; R2, R3 = OCHlO responsible for stability was shown by comparing the properties of 7 and 8.The pyrone 7 shared the special stability of 45 and 6 but the 7-methoxypyrone 8 was nonisolable; chromatography of the residue after removal of acetic anhydride gave two OCH20 compounds tentatively assigned as the endo and exo-isomers corresponding to structure 19.These structures show a peri- and regio-selectivity not previously encountered in our work with 2-benzopyran-3-ones. 2-Benzopyran-3-one itself dimerises inefficiently to syn- and anti-dimers of the gross structure 20,3 and its 7-methoxy derivative forms the dimers 21 in good yield.' The structure of the endo-isomer of 19 was supported by the observation of carbonyl absorption at 1765 and 1722 cm-'. The NOESY spectrum showed a nuclear Overhauser effect between HA and the methyl group of the enol ether in 19 thus identifying HAas a broadened singlet at 6 5.37. Double irradiation of HA caused disappearance of a fine splitting in the signal at 3.67 6R2ncHR3 COR'2C02H (ddd, J 9, 4and ca.1 Hz) due to HB, indicating allylic coupling 11 R'=R2=R3=H 12 R' = Ph; R2,R3= OCHpO 13 R' = Ph, R2, R3 = OM* 14 R' = Ph; R2 = OMe; R3= H 15 R' = Ph; R2 = H; R3 = OMe 16 R' = Me; R2, R3 = OCH20 17 R' = H; I?, R3 = OCHp0 between HA and HB and the regio-isomer depicted in 19.18 Similarly, irradiation of the signal at 6 4.98 (HE) led to loss of allylic coupling in the signal due to HD at 6 3.62 (d, J 9 and 1 Hz). Dehydration of 15 in the presence of N-phenylmaleimide t The stability of methylenedioxy groups attached to aromatic rings under strongly acidic conditions is truly remarkable. J. CHEM. SOC. PERKIN TRANS. 1 1991 HC OMe Ph 0 19 R 20 R=H 21 R=OMe 22 R' = Ph, R2= H, R3= OMe 23 R' = Me;R2, R3= OCH20 24 R' = H; R2, R3= OCH20 gave the adduct 22 of the pyrone 8 in 74% yield showing that the pyrone 8 is produced efficiently by acetic anhydride dehydration but fails to survive under the reaction conditions.The stability of l-aryl-6,7-methylenedioxy-2-benzopyran-3-ones encouraged efforts to produce the corresponding 1-methyl derivative. The acid 16 when heated in acetic anhydride produced a deep yellow colour which disappeared upon addition of N-phenylmaleimide with formation of the adduct 23 and a product subsequently identified as 25 and discussed below. After the acid 16 had been heated in acetic anhydride (2 h) attempted isolation of 9 by chromatography at 20 "C failed.Chromatography at -20 OC allowed separation of 9 from 25 and minor by-products and gave 9 as bright yellow crystals (52%) characterised by IR, UV, mass and 400 MHz 'H NMR spectroscopy. Crystalline 9 is unchanged after storage for ca. 1 month at -40 OC. The strong resistance to nucleophilic attack conferred by the methylenedioxy group in 9 is evident on comparing the reaction of 9 and 1,4-diphenyl-2-benzopyran-3-one with boiling methanol. The latter was completely converted into a cis-trans mixture of the pseudo-esters 26 within 1 h. After 11 h the pyrone 9 gave the pseudo-ester 27 (59%) with 23% recovered 9. It is likely that 25 originates from the Diels-Alder adduct 28 of 9 with its tautomer 29. Decarboxylation and p-elimination in 28 would lead to 30 which, in boiling acetic anhydride, could undergo intramolecular Friedel-Crafts acylation and acetyl- ation to give 25.Different structures for this product arising via alternative regioselectivity in either the Diels-Alder or the Friedel-Crafts reaction are 31 and 32 respectively. However only structure 25 would be expected to show the observed NOE between an aromatic methyl and two aromatic protons one of which shows a further NOE with a third aromatic proton (see Experimental section). 'H NMR monitoring of the pyrone 9 when it was heated at 15OOC (15 min) showed its partial conversion (27%) into a product tentatively identified as the tautomer 29. Upon continued heating the 'H NMR signals associated with 29 disappeared and the spectrum indicated a mixture of unidentified products.HH Me 0*)Two28 0 CH2 Me 29 30 0-7 OAc 31 32 Me Me R OH 33 R= E-CH=CHPh 35 36 34 R = 4-MeOC6H4 The stabilising effect of the methylenedioxy group appears insufficient to render isolable the 2-benzopyran-3-one 10 which lacks a substituent at C-1. Although the acid 17 when heated in boiling acetic anhydride in the presence of N-phenylmaleimide gave the adduct 24 in good yield, in the absence of the trap an initial yellow colour tentatively assigned to 10 was rapidly replaced by an insoluble (polymeric?) product. 2-Benzopyran-3-one gives a similar product when generated in a high concentration by thermolysis of 18.3 Simple Huckel calculations for 1 and its 6-and 7-alkoxy derivatives predict LUMO energies of -0.41, -0.46 and -0.42 p units respectively.The more pronounced raising of the LUMO energy of 1by a 6-compared with a 7-alkoxy group is in accord with the importance of the former in stabilising 2- benzopyran-3-ones towards nucleophilic attack. The excep- tional stability of the quinone methide 33 was attributed to 'the J. CHEM. SOC. PERKIN TRANS. 1 1991 extended conjugation of the quinoid nucleus with the cinnamylidene group'. The results reported in the present paper suggest that the stability of 33 as well as 34 is to a greater extent determined by push-pull resonance, e.g. 33 (arrows)." It should be noted that the donor-acceptor interaction in the pyrones described in this work as well as that in 33 and 34 does not tend to restore the aromaticity of the system as it does in citrinin 35 and related compounds.' ' This suggests that 1-donor substituted pyrones 36 should be particularly stable and 36 (X = NMe,) an appealing target for synthesis.Our results also suggest that appropriately placed donor groups could stabilise other o-quinonoid system such as inden-2-ones and 2,3-naph t hoq uinones. Experimental M.p.s were determined with a Kofler hot-stage apparatus and are uncorrected. Unless otherwise stated, IR spectra refer to Nujol mulls, UV spectra to ethanol solutions, and 'H NMR spectra to solutions in deuteriochloroform measured at 90 MHz with a Perkin-Elmer R32 or a JEOL FX 90Q instrument.400 MHz Spectra were obtained on a Bruker WH-400 instrument. J values are given in Hz. Low resolution mass spectra were obtained with a Kratos MS25 instrument and accurate mass measurements were made using a Kratos MS25 instrument and accurate mass measurements were made using a Kratos MS 9150 instrument. Where mass spectral measurements were used to establish molecular formulae the purity of the sample was checked by TLC in more than one solvent system as well as by NMR measurements, and for crystalline material by crystal- lisation to constant m.p. Chromatography on silica refers to short-column chromatography over Kieselgel G(Merck).' Ether refers to diethyl ether and light petroleum to the fraction b.p. 6&80 "C. All reactions were conducted under dry, oxygen- free nitrogen.FriedelLCrifts Acylation of Methyl Alkoxyphenyl-acetates.-The methyl ester (10 mmol) in CH2Cl, (30 ml) was cooled to &5 "C and stannic chloride (16.5 mmol) was added. The acid chloride (13.2 mmol) in CH,Cl, (30 ml) was added over 15 min. The ice-bath was removed and the mixture stirred (24 h). The product was poured into water, isolated in ether in the usual way and purified as indicated. Methyl 2- Benzoyl-4,5-methylenedioxyphenylacetatewas puri- fied by chromatography on silica in ether-benzene (1 :99) (31% yield) (Found: M +, 298.0836. C17H1405 requires M', 298.0841); v,,,/cm-' 1729 and 1652; 6,(90 MHz) 7.85-7.48 (5 H, m), 6.9 (1 H, s), 6.86 (1 H, s), 6.03 (2 H, s), 3.82 (2 H, s) and 3.61 (3 H, s).Methyl 2-henzoyl-4,5-dimethoxyphenylacetatewas purified by chromatography on silica in ethyl acetate-light petroleum (1 :2) (58% yield), m.p. 100-102 "C (from ethyl acetate-light petroleum) (Found: C, 68.9; H, 5.8. C1gH1805 requires C, 68.8; H, 5.8%); v,,,/cm-' 1729 and 1639; 6,(90 MHz) 7.87-7.32 (5 H, m),6.97(1 H,s),6.89(1H,s),3.97(3H,s),3.86(2H,s),3.80(3H, s) and 3.62 (3 H, s). Methyl 2-benzoyl-5-methoxyphenylacetatewas purified by crystallisation from ethyl acetate-light petroleum (1 :2) (71% yield), m.p. 69-70°C (Found: c, 72.0; H, 5.7. Cl7Hl6o4 requires C, 7 1.8; H, 5.7%); v,,,/cm-' 1732 and 1647; 6,(90 MHz) 7.866.87 (8 H, m), 3.96 (2 H, s), 3.88 (3 H, s) and 3.62 (3 H, s). Methyl 2-acetyl-4,5-methylenedioxyphenylacetate was puri- fied by chromatography on silica in ethyl acetate--light petroleum (33 :67) (49% yield), m.p.117-1 17.5 "C (Found: C, 61.1; H, 5.1. C12H12O5 requires C, 61.0; H, 5.1%); v,,,/cm-' 1719 and 1659; 6,(90 MHz) 7.28 (1 H, s), 6.7 (1 H, s), 6.01 (2 H, s), 3.84 (2 H,s), 3.68 (3 H, s) and 2.51 (3 H, s). 171 o-Acylalkoxyphenylacetic Acids.-The ester (2.5 mmol), ethanol (5 ml) and 2h.1 sodium hydroxide solution (5 ml) were boiled under reflux (1 h). The crude acid was isolated in the usual way and purified as indicated. 2-Benzoyl-4,5-methylenedioxyphenylaceticacid was recrystal- lised from MeOH (40% yield), m.p. 182-184 "C (Found: C, 67.6; H, 4.25. C16H1205 requires C, 67.6; H, 4.3%); vmax/cm-' 3198br, 1713 and 1650; 6,[CDC13 and 10% (CD,),SO] (90 MHz) 7.85- 7.45 (5 H, m), 6.90 (1 H, s), 6.85 (1 H, s), 6.05 (2 H, s) and 3.75 (2 H, s).2-Benzoyl-4,5-dimethoxyphenylaceticacid was purified by recrystallisation from ethyl acetate (80% yield), m.p.162-163 "C (Found: C, 68.2; H, 5.35. CI7Hl6O5 requires C, 68.0; H, 5.4%); v,,,/cm-' 3198-2380,1707 and 1652; 6,(90 MHz) 11.26 (1 H, br s), 7.92-7.32 (5 H, m), 6.98 (2 H, s), 3.97 (3 H, s) and 3.80 (5 H, apparent s, OMe and CH,). 2-Benzoyl-5-methoxyphenylacetic acid was purified by recrystallisation from ether (50% yield), m.p. 130-1 3 1 "C (Found: C, 70.8; H, 5.0. C16H1404 requires C, 71.1; H, 5.2%); v,,,/cm-' 321&2380br, 1713 and 1644; 6,(90 MHz) 10.74 (1 H, s), 7.77-6.74 (8 H, m), 3.70 (3 H, s) and 3.69 (2 H, s). 2-Acetyl-4,5-methylenedioxyphenylaceticacid was recrystal- lised from methanol (71% yield), m.p.171-174 "C (Found: C, 59.4; H, 4.5. CllH1005 requires C, 59.5; H, 4.5%); v,,,/cm-' 3350-2450,1707 and 1664; 6H[(CD3)2C0] (90 MHz) 7.41 (1 H, s), 6.87 (1 H, s), 6.09 (2 H, s), 3.87 (2 H, s) and 2.52 (3 H, s). Alkoxy-substituted 2-Benzopyran-3-ones.-The pyrones 5, 6 and 7were prepared by the general procedure involving the o-acylphenylacetic acid (100 mg) and acetic anhydride (4-5 ml), heating under reflux (2 h) and evaporation at 100 "C in a high vacuum. The pyrones were generally obtained in pure form by tri turation with ether. 6,7-Methylenedioxy- 1 -phenyl-2-benzopyran-3-one. (56% yield), m.p. 165-168 "C (Found: c, 72.2; H, 3.7. Cl6Hl0O4 requires C, 72.2; H, 3.8%); v,,,/cm-' 1692; h,,,(CH,CN)/nm 265,320sh and 445 (E 34 057,3230 and 6525); 6H(90 MHz) 7.75- 7.27 (5 H, m), 6.75 (1 H, s), 6.40 (1 H, s), 6.17 (1 H,s) and 5.93 (2 H, s). 6,7-Dimethoxy- 1 -phenyl-2-benzopyran-3-one.(9 1 % yield), m.p. 123-125 "C (Found: C, 72.2; H, 5.0. C17H,404 requires C, 72.3; H, 5.0%); v,,,/cm-' 1691; h,,,(CH,CN)/nm 261 and 322 (E 36 742 and 3768); 6,(90 MHz) 7.88-7.40 (5 H, m), 6.71 (1 H, s), 6.46 (1 H, s), 6.17 (1 H, s), 3.98 (3 H, s) and 3.80 (3 H, s). 6-Methoxy-l-phenyl-2-benzopyran-3-one.(590{ yield), m.p. 94-96 "c(Found: C, 76.2; H, 4.8. Cl6Hl2O3 requires C, 76.2; H, 4.8%); v,,,/cm-' 1695; h,,,(CH,CN)/nm 268 and 320sh (E 26 370 and 4466); 6,(90 MHz) 7.79-7.22 (6 H, m), 6.50 (1 H, dd, J 9 and 2), 6.31 (1 H, d, J2), 6.14 (1 H, s) and 3.90 (3 H, s).2-Benzoyl-4-methoxyphenylacetic Acid.-3-Phenyl-5-meth-oxyindene (409 mg, 1.845 mmol) in dry dichloromethane (24 ml), was cooled to -78 "C and ozonised oxygen bubbled through at 0.1 dm3 min-' and 0.34 kg cmP3 pressure for 5 min. The solvent was evaporated to small volume at 20 "C and the residue stirred vigorously with 2h.1 sodium hydroxide (1 6 ml), hydrogen peroxide (30%; 1.6 ml), methanol (16 ml) and ether (16 ml). After 20 min the mixture was poured into 2h.1 hydrochloric acid (45 ml) and the aqueous phase extracted with ethyl acetate. The organic layer was washed with saturated brine, dried (MgSO,) and evaporated. The crude product crystallised from methanol to give the 0x0 acid 15 as pale yellow needles (301 mg, 60%); m.p.159-161 "C; v,,,/cm-' 1700 and 1650; 6H(CDC13 + 10% [2H6]DMSO) (90 MHz) 7.92-6.82 (9 H, m, ArH and CO,H), 3.77 (3 H, s, OMe), 3.68 (2 H, s); m/z 226 (M -CO,) 209, 181, 165, 105, 77, 51 and 44 (72.2, 15.0, 14.8, 22.1, 39.6, 100,40.1 and 17.3%). The N-Phenylmaleimide Adduct of the Pyrone 8.-The foregoing 0x0 acid (68.0 mg) and N-phenylmaleimide (87 mg) in acetic anhydride (4 ml) were boiled under reflux (2 h). The acetic anhydride was removed under a water pump vacuum while the mixture was heated on a boiling water-bath, and the resulting crude product was chromatographed on silica (35 g). Elution with etherdichloromethane (5 :95) gave the title compound 22 (79 mg, 7473, m.p. 194-195 "C (from ethanol) (Found: C, 73.1; H, 4.6; N, 3.2.C,,H,,NO, requires C, 73.4; H, 4.5; N, 3.3%); v,,,/cm-' 1768 and 1715; 6,(90 MHz) 8.05-6.37 (13 H, m), 4.50 (1 H,d,J9),4.51 (1 H,d, J2),3.82(1 H7dd,J9and2)and3.68(3 H, s, OMe); m/z 381 (M -COz) 234, 189, 165, 119,91, 77 and 44 (39.2, 100.0,21.7, 7.1, 8.7, 5.6, 8.4 and 12.4%). Attempted Preparation of 7-Methoxy-1-phenyl-2-benzopyran-3-one.-The 0x0 acid 15 (99.6 mg) in acetic anhydride (4 ml) was boiled under reflux (2 h). The dark red solution was evaporated to dryness under a water pump vacuum whilst the mixture was heated on a boiling water-bath. During evaporation the intensity of the red colour decreased. The residue was chromatographed on silica in ether-dichloromethane (1 :19) to give the endo-dimer 19 (18.6 mg, lo%), m.p.133-135 "C (from ethanol) (Found: C, 75.9; H, 4.6. C32H2406 requires C, 76.2; H, 4.8%); v,,,/cm-' 1765 and 1722; 6,(400 MHz) 7.52-7.35 (10 H, m), 7.25 (1 H, d, J 8), 6.99 (1 H, d, J 2), 6.90 (1 H, dd, J 8 and 2), 5.37 [1 H, s, with further fine splitting (wffs)], 4.98 (1 H, s, wffs), 4.50 (1 H, d, J4), 3.71 (3 H, s), 3.67 (1 H, dd, J9 and 4, wffs), 3.62 (1 H, d, J 9 wffs) and 3.42 (3 H, s, OMe); m/z 460 (M -COz), 458, 325, 252,224, 105, 83, 69 and 44 (21.3, 45.4, 20.2, 27.3, 35.4, 60.7, 36.5,49.3 and 100%). The eluate obtained immediately before elution of the compound 19 gave a small quantity of a compound tentatively assigned as the exo-isomer 19 (6.3 mg, 470,m.p. 212-215 OC (from ethanol); v,,,/cm-' 1765 and 1722; 6,(400 MHzj 7.65- 7.39 (1 1 H, m,), 6.94 (1 H, dd, J 2 and 8), 6.85 (1 H, d, J 2), 5.73 (1 H, s), 5.37 (1 H, s), 4.46 (1 H, d, J2), 3.74 (3 H, s), 3.72 (1 H, d, J lo), 3.65 (3 H, s) and 3.17 (1 H, dd, J 10 and 2); 3.73 (1 H, dd, J 10 and 1) (partly overlapped by OMe resonance).1-Methyl-6,7-methylenedio~~~~-2-benzupyran-3-one.-2-Acetyl-4,5-methylenedioxyphenylaceticacid (45 mg, 0.202 mmol) and acetic anhydride (3 ml, freshly distilled from quinoline) were boiled under reflux (2 h). The acetic anhydride was removed under a water pump vacuum over a steam bath and the residue triturated with ether (2 x 0.5 ml). The solid product was chromatographed on silica (30 g) in ether-dichloromethane (1:9) at -21 "C. The yellow band gave the crystalline pyrone 9 (22 mg, 52%); v,,,/cm-' 1693; h,,,(CH,CN)/nm 281sh and 406 nm (E 2947 and 4080); 6,(400 MHz) 6.45 (1 H, s), 6.36 (1 H, s), 6.04 (1 H, s), 5.96 (2 H, s) and 2.55 (3 H, s); m/z 204 (M'), 176 (M -CO), 147 (M -CO -HCO), 133 (M -CO -MeCO), 118, 89, 75, 63 and 50 (58.9, 100.0,49.7, 19.8, 11.7,25.9,30.4,21.2 and 19.7%).The least polar fraction from the above chromatography (19 mg) was the polynuclear aromatic compound 25, m.p. 263-265 "C (from ethyl acetate); v,,,/cm-l 1753; 6,(400 MHz) 2.53 (3 H, s), 2.76 (3 H, br s), 6.11 (2 H, s), 6.12. (2 H, s), 7.17 (1 H, s), 7.40 (1 H, s), 7.45 (1 H, s), 8.03 (1 H, s), 8.22 (1 H, br s) and 8.60 (1 H, s); a NOESY spectrum showed the lower field methyl group correlated with the signals at 6 7.45 and 8.22 and that 6 7.45 correlated with no other proton and 6 8.22 correlated with 6 8.02 only.The signals at 7.17 and 7.40 correlated with one another and that at 6 8.60 correlated with no other proton; h,,,(CH,CN)/nm 277 (100, 233) with much weaker peaks at 296,308,323,336,354 and 374 nm; m/z 388 (M+), 346 (M -CH,CO), 317,260,231,200 and 43 (30.5, 100, 14.4, 7.0, 3.9, 17.9 and 63.1%). The N- Phenylmaleimide Adduct of 1-Methyl-6,7-methyl-J. CHEM. SOC. PERKIN TRANS. I 1991 enedioxy-2-benzop~v-an-3-one.-2-Acetyl-4,5-methylenedioxy-phenylacetic acid (100 mg) and acetic anhydride (5 ml) were boiled under reflux (2 h). The acetic anhydride was evapor- ated by heating on a steam-bath under a water pump vacuum. The product was triturated with ether and dried in a high vacuum.The crude product (94 mg), N-phenylmaleimide (94 mg) and benzene (5 ml) were boiled under reflux (30 min). The product was chromatographed on silica in benzene to give the previously described acetate 25 (28 mg) followed by the adduct 23 (30 mg), m.p. 182-1 83 "C (from ether); S(90 MHz) 2.19 (3 H, s), 3.56 (1 H, d, J9), 3.7 (1 H, dd, J9 and 2),4.36 (1 H, d, J2), 6.0 (2 H, AB-system, JAB cu. 1), 6.7 (2 H, m), 6.88 (2 H, apparent s) and 7.35 (3 H, m); m/: 377 (M'), 333 (M -CO,), 214,213, 186, 176, 128, 102,91, 77, 57 and 44 (0.8,8.8,0.6,0.6, 14.8, 1.2,5.1, 1.7, 1.4,2.1,2.5 and 100?/o). The acetate 25 was not produced when 2- acetyl-4,5-methylenedioxyphenylaceticacid (50 mg) was heated with acetic anhydride in the presence of N-phenylmaleimide (50 mgj.Reaction of 1-Methyl-6,7-methylenedio~q~-2-benzopyran-3-one bt%ithMethanol.-The pyrone (44 mg) in dry methanol (4 ml) was boiled under reflux in a base-washed apparatus (1 1 h). The 400 MHz 'H NMR spectrum of the evaporated product indicated unchanged starting material (23"/,), the pseudo-ester 27 (73%) and the related 0x0 ester (4%). The product was chromato- graphed on silica at 20 "C in ether-dichloromethane (1 :9) to give the pseudo-ester 27 (30 mg, 59:/,), m.p. 102-103 "C (from benzene-light petroleum) (Found: C, 60.8; H, 5.2. C,,H120, requires C, 61.0; H, 5.1%); v,,,/cm-' 1736; 6,(90 MHz) 6.85 (1 H, s), 6.62 (1 H, s), 5.99 (2 H, s), 3.61 (1 H, d, J 19.5), 3.78 (1 H, d, J 19.5), 3.34 (3 H, s) and 1.79 (3 H, s); m/z 236 (M+), 205, 192, 177, 162,91,76 and 43 (22.9, 18.5,40.0, 100.0, 15.6,24.0,20.6 and 4 3 .Oo/,).Thermal Stahilitj, qf l-Methyl-6,7-methylenedio-~~~-2-benzo-p~~an-3-one.-The title compozind (10 mg) in dry deuterio- benzene (0.4 ml) was placed in a thermolysis tube which fitted snugly inside an NMR tube. After five freeze-pumpthaw cycles the thermolysis tube was heated in a constant temperature bath and removed at intervals for NMR monitoring at 90 MHz. After 15 min at 150 "C peaks attributed to the tautomer 29 at 6 3.71 (2 H, s), 4.90 (2 H, apparent s), as well as 6.0 (2 H, s), 6.56 (1 H, s) and 6.90 (1 H, s) accounted for 27% of the mixture, the remainder being starting material. After the mixture had been heated for 150 min numerous other peaks appeared in its spectrum; the tube was opened, the solvent evaporated and the residue dissolved in CDC1, and the 400 MHz spectrum obtained.The signal at 6 4.9 due to the exocyclic methylene group now appeared as an AB-system centred at 6 4.93 (JAB 2.5). 2-Formyl-4,5-methylenedioxyphenylaceticAcid.-4,5-Methyl-enedioxyisochroman-3-one' (300 mg), 2~ aqueous sodium hydroxide (5 ml) and ethanol (2 ml) were boiled under reflux (2.5 h). The clear yellow solution was cooled to 20 "C, washed with a little ether, cooled to (r5 "C and acidified to pH 2 when the hydroxy acid was precipitated. The mixture was quickly extracted with ether (2 x ) and treated with diazomethane. Evaporation of the dried (MgS04) ether extract gave the hydroxy ester (230 mg, 71%); 6,(90 MHz) 2.85 (1 H, br s), 3.65 (3 H, s), 3.70 (3 H, s), 4.55 (2 H, s), 5.95 (2 H, s), 6.72 (1 H, s) and 6.89 (1 H, s); v,,,/cm-' 1740, 3 170 and 3280.Without delay the hydroxy ester was oxidised by the Swern procedure. To oxalyl chloride (533 mg) in dichloromethane (9 ml) at -65 "C was added dimethyl sulphoxide (656 mg) in dichloromethane (2.5 ml) slowly with stirring. After the mixture had been stirred for a further 5 min at -65 "C the foregoing hydroxy ester (855 mg) in dichloromethane (5 ml) was added J. CHEM. soc PERKIN TRANS. 1 1991 over 5 min and the mixture stirred for 20 min before triethylamine (1.93 g) was added to it. After being stirred for 5 min at -65 "C the mixture was allowed to reach 20 "C over 20 min, iced water (20 ml) added and the phases separated.The organic layer was washed with water (3 x ), dried (MgSO,) and evaporated. The crude product (852 mg) was chromatographed on silica (100 g) in ethyl acetate-light petroleum (1 :3) to give methyl 2-jormq~l-4,5-methylenedioxyphenylacetate(596 mg, 70%) (Found: M+, 222.0526. CllH1OOs requires M+, 222.0528); v,,,/cm-' 1690 and 1740; 6,(60 MHz) 3.70 (3 H, s), 3.97 (2 H, s), 6.05 (2 H,s), 6.80 (1 H,s), 7.30 (I H, s) and 10.00 (1 H, s); m/z 222 (M+), 190 (M -MeOH), 163,162,149,135,134, 105, 77 and 51 (54.3, 46.8, 84.6, 86.6, 22.8, 100.0,26.3, 26.0, 76.0 and 70.2%)). This ester (1 50 mg), glacial acetic acid (5 ml), water (5ml) and concentrated hydrochloric acid were boiled under reflux (1 h).The cooled product was poured into water (50 ml) and extracted into ethyl acetate (2 x 50 ml). The combined extracts were washed with saturated aqueous sodium hydrogen carbonate (4 x 15 ml) and the combined aqueous extracts acidified with concentrated hydrochloric acid and extracted with ethyl acetate (2 x 50 ml). The organic extract was washed with water, dried (MgS04) and evaporated to give 2-fbrmyl-4,5- methylenedios~phenylaceticacid 17 (124 mg), m.p. 155-158 "C (from benLene) (Found: M', 208.0370. C,,H,O, requires 208.0372); v,,,/cm-' 1600, 1690 and 240G3400; 6,(90 MHz) [(CD,)CO] 4.06 (2 H, s), 6.13 (2 H, s), 6.94 (1 H, s), 7.35 (1 H, s), 10.07 (1 H,s); m/z 208 (M'), 190, 164, 163, 162, 149, 135, 105, 77 and 51 (55.4, 17.3, 72.5, 100, 77.7, 14.5, 64.6, 25.9, 82.7 and 74.3",,,) Dehjvdrurion of 2-Formy1-4,5-methj~lenedioxyphenylucetic Acid in the Presence of N-Phenylma1eimide.-The title acid (50 mg) and N-phenylmaleimide (50 mg) in acetic anhydride (distilled from 17"quinoline; 3 ml) were boiled under reflux (2 h).The acetic anhydride was removed under a water pump vacuum whilst heating on a steam bath and the residue chromatographed on silica in benzene-ther (95: 5) to give the adduct 24(49 mg), m.p. 23G233 "C (from ether); 6,(90 MHz) 3.67 (1 H, dd, J 8.4 and 3.6), 3.96 (1 H,dd, J 8.4 and 4.5), 4.38 (1 H,d, J 3.6), 5.90 (1 H, d, J 4.5). 6.0 (2H, AB system, JAB1, OCH,O), 6.64 (2 H, m), 6.86 (2 H,apparent s) and 7.35 (3 H, m); mjz 363 (M +), 319, 172, 114, 78, 63 and 44 (13.3, 8.8,48.1, 14.0, 100,6.2 and 21.6%).Attempted Preparation of 6,7-Methylenedioxy-2-benzopyran-3-one.-2-Formyl-4,5-methylenedioxyphenylacetic acid (50 mg) was heated in boiling acetic anhydride (distilled from 1% quinoline; 3 ml) for 2 h. After ca. 15 min the solution became cloudy and a precipitate appeared, adhering to the side of the flask. Removal of acetic anhydride by evaporation under a water pump vacuum at 100°C and trituration of the product with ether afforded no crystalline product although the majority of the product was insoluble in ether (polymeric?). TLC on silica [benzene-ther (3 : l)] indicated a complex mixture and very little yellow product. Similar failure resulted from attempted dehydration using dicyclohexylcarbodiimide in boiling benzene (1 h) followed by attempted isolation by chromatography on silica in dichloromethane at -25 "C. References 1 J. M. Holland and D. W. Jones, J. Chem. Sor. C, 1970. 536. 2 D. W. Jones and G. Kneen, J. Chem. Soc., Perkin Trans. 1, 1976, 1647; D. A. Bleasdale and D. W. Jones, J. Cheni. Snc., Chem. Commun., 1985, 1027. 3 D. A. Bleasdale, D. W. Jones, G. Maier and H. P. Reisenauer, J. Chem. SOC.,Chem. Commun., 1983, 1095. 4 D. W. Jones and A. M. Thompson, J. Chem. Soc., C'hem. Conzmun., 1987, 1797; 1988, 1095; 1989, 1370. 5 T. S. Stevens, J. Chem. SOC.,1927, 178. 6 E.g. G. M. Anderson, P. A. Kollman, L. N. Domelsmith and K. N. Houk, J. Am. Chem. Soc., 1979,101,2344. 7 D. W. Jones and R. L. Wife, J. Chem.SOC.,Chem. Commun., 1973,421. 8 D. W. Jones, unpublished observations. 9 L. Jurd, Tetruhedron, 1977,33, 163. 10 For a review of some push-pull systems see R. Gompper and H.-U. Wagner, Angekt,. Chem., Int. Ed. Engl., 1988,27, 1437. 11 For a mechanistic example see M. F. Aldersley, J. M. Benson, F. M. Dean, S. El-Kadri and D. J. Lythgoe, Tetrahedron, 1987,43,5417. 12 B. J. Hunt and W. Rigby, Chem. Znd. (London), 1967. 1868. Puper 0/03 198D Received 17th July 1990 Accepted 23rd August 1990