MacMillan, J. published an article in 1959, the title of the article was Griseofulvin. XVII. Synthesis of 7-chloro-4,6-dimethoxy-2′-methylgrisan-3,4′-dione.Product Details of 53724-96-2 And the article contains the following content:
The synthesis is described of grisan and 3-coumaranone spirocyclopentane analogs of some griseofulvin (I) derivatives and of racemates of some I degradation products. (All m.ps. are corrected; absorption spectra determined in EtOH.) Et 6-hydroxy-3-methylcoumarone-2-carboxylate (II), m. 179° (EtOH), ν 1700 cm.-1, λ 313, 282, 241, 210 mμ (log ε 4.30, 4.07, 3.90, 4.24), was prepared in 60% yield by the method of Hantzsch [Ber. 19, 292(1886)]. Treatment of II with Me2SO4 gave 30% 6-methoxy-3-methylcoumarone-2-carboxylic acid (III), m. 184°, and 25% III Et ester (IV), m. 74-5°, ν 1700 cm.-1, λ 312, 285, 243 mμ (log ε 4.44, 4.13, 3.97); esterification of III gave IV. 6-Methoxy-3-methylcoumarone-2-acetic acid (V) chloride and AcCH(MgOEt)CO2Et (VI) gave Et α-acetyl-β-oxo-6-methoxy-3-methylcoumarone-2-γ-butyrate (VII), oil, ν 1714, 1623, and 1587 cm.-1; Cu derivative (VIII), m. 175° (MeOH), ν 1715, 1692, 1671, 1587 cm.-1 VII (7 g.) and 15 mL. concentrated H2SO4 kept 3 days at -5°, diluted with 50 mL. H2O, extracted with Et2O, the Et2O solution extracted with aqueous NaHCO3, and the alk. extract acidified gave 200 mg. V, m. 139-40°; recovery from the Et2O solution gave a pale yellow oil (IX). IX in EtOH passed through a C column, the resulting material triturated for a long time under petr. ether (X) at -50°, and the solid further recrystallized at room temperature gave 2.8 g. Et 6-methoxy-3-methylenecoumaran-2-spiro-1′-(2′-methyl-4′-oxocyclopent-2′-en-3′-carboxylate) (XI), m. 122°, ν 1745, 1707, 1649, 1615, 1595 cm.-1, λ 327, 263, 231, 214 mμ (log ε 3.98, 4.12, 4.35, 4.31); 2,4-dinitrophenylhydrazone, m. 175-6° (C6H6-X). Cyclization of VIII with H2SO4 gave 45% XI. XI (150 mg.) hydrogenated at room temperature and pressure with a catalyst prepared in situ from 7 mg. PdCl2 and 75 mg. C in 10 mL. AcOH (1 mol H absorbed), the recovered gum chromatographed in Et2O on Al2O3, eluted with Et2O, and the product repeatedly triturated with X at 0° gave 105 mg. corresponding 3-Me analog, m. 77-8°, ν 1738, 1698, 1610 cm.-1, λ 320, 302, 281, ∼263,228 mμ (log ε 2.78, 3.45, 3.59, 3.72, 4.25); 2,4-dinitrophenylhydrazone, m. 160° (C6H6-petr. ether). A stream of O3-O passed into 500 mg. XI in 30 mL. CCl4 until the solution became opaque, the filtered solution evaporated, the residual gum mixed with 25 mL. H2O, kept 24 h., and the aqueous phase distilled into saturated dimedon (XII) solution in 10% aqueous alc. gave XII derivative of CH2O, m. 191-2°; an Et2O solution of the residual gum chromatographed on Al2O3, the lowest bright-blue fluorescent band eluted with Et2O and the recovered product boiled with X (110 mg. solid obtained); the solid combined with 100 mg. slightly impure material from the following band fluorescing greenish-blue and recrystallized (petr. ether) gave 200 mg. corresponding 3-oxo compound (XIII), m. 115-17°, ν 1751, 1715, and 1701 cm.-1, λ 321, 275, 232 mμ (log ε 3.98, 4.21, 4.23); mono-2,4-dinitrophenylhydrazone, m. 243° (decomposition) (C6H6-petr. ether). Oxidation of 100 mg. XIII with Fehling’s solution gave 25 mg. 2,4-HO(MeO)C6H3CO2H, m. 154-5°. XIII (70 mg.) and 17.5 mL. 2N HCl and 14 mL. EtOH refluxed 6 h. under N cooled (15 mg. solid separated), EtOH removed in vacuo (15 mg. solid and 30 mg. XIII separated), the combined product purified through the Na salt, and recrystallized (EtOH) gave 23 mg. corresponding acid (XIV), m. 175-7°, ν 1716 and 1697 cm.-1, λ 318, 273, 232, 210 mμ (log ε 4.05, 4.25, 4.30, 4.45). XIV (70 mg.) heated 10 min. at 190-200° in an N atm., the residue sublimed in situ in vacuo, and the sublimate recrystallized (aqueous Me2CO) gave 40 mg. 6-methoxy-3-oxocoumaran-2-spiro-1′-(2′-methylcyclopent-2′-en-4′-one) (XV), m. 193-5°, ν 1713 cm.-1, λ 320, 273, 232, 209 mμ (log ε 3.92, 4.07, 4.16, 4.40); mono-2,4-dinitrophenylhydrazone, m. 238-40° (EtOAc). XV (15 mg.) in 1.5 mL. EtOAc added to a previously catalyst prepared from 10 mg. PdCl2 and 40 mg. C in 1 mL H2O, the mixture shaken with H at room temperature and pressure until absorption ceased (2.4 mol H absorbed in 5 min.), and the product (XVI) (13 mg.) recovered; XVI (13 mg.) chromatographed in C6H6 on Al2O3, a bright-blue fluorescent band eluted with C6H6, the product (2 mg.) recovered, sublimed, and crystallized (petr. ether) gave 0.8 mg. 6-methoxy-3-oxocoumaran-2-spiro-1′-(2′-methylcyclopentane), m. 167-8°, identical with the product from condensation of 6-methoxycoumaran-3-one and CH2Br(CH2)2CHBrMe (cf. preceding abstract). β-Propiolactone (XVII) (8.64 g.) and 19.44 g. 6-methoxy-3-methylcoumarone refluxed 6 h. at 200°, the cooled residue ground with aqueous Na2CO3, the mixture filtered, the Et2O-washed filtrate acidified, the precipitate filtered off, sublimed in vacuo, and the sublimate crystallized (dilute EtOH) gave 4.9 g. 6-methoxy-3-methyl-coumarone-2-β-propionic acid (XVIII), m. 137°, ν 1707 cm.-1, λ 292 and 253 mμ (log ε 3.80, 4.16). 6-Methoxy-3-methylcoumarone-2-acetic acid (440 mg.) and 1 mL. SOCl2 was warmed gently until a clear solution was obtained, volatiles removed in vacuo below 30°, the residual oil in 10 mL. Et2O added at 0° to a 3-fold excess CH2N2 in 15 mL. Et2O, the solution kept 24 h. at 0°, and the Et2O removed in vacuo; the residual crude diazo ketone (m. 118-23°) in 10 mL. dioxane added dropwise with stirring to 2 g. Ag2O in 1 g. Na2S2O3 and 1 g. K2CO3 in 20 mL. H2O at 50-60° (N evolved), after 20 min. the mixture heated 10 min. at 70° and 5 min. at 90°, filtered, the filtrate acidified with dilute HNO3, the oil triturated with H2O, the resulting semisolid sublimed in vacuo, and the sublimate crystallized (dilute EtOH) gave 60 mg. XVIII, m. 137-8°. XVIII treated with PCl5 gave the acid chloride (XIX), green oil; amide, plates (C6H6-petr. ether). XIX in 500 mL. Et2O mixed with a suspension of VI [from 2.7 g. AcCH2CO2Et (XX), 1.2 mL. EtOH, and 0.48 g. Mg in 50 mL. Et2O], the mixture refluxed 24 h., excess dilute AcOH added, the separated Et2O layer washed with aqueous NaHCO3 (from the alk. wash 200 mg. XVIII was isolated on acidification), concentrated, the oil (4.2 g.) chromatographed in C6H6 on Al2O3 and eluted with C6H6 gave, from a narrow fluorescent band, 90 mg. oil, which, on crystallization (petr. ether), afforded 60 mg. XVIII Et ester (XXI), m. 51-2°, ν 1737, 1624, 1594 cm.-1, identical with material obtained by esterifying XVIII, and, from a greenish-red band, 3.1 g. oil, which, heated 4 h. at 100-10°/10-4 mm., yield 2.2 g. crude oxo ester (XXII), giving an intense Fe+++ reaction in EtOH and forming a Cu chelate. Crude XXII (12 g.) in 25 mL. concentrated H2SO4 kept 8 days at 0°, worked up as described above for the lower homolog, and the alk. extract acidified gave a yellow precipitate which decomposed on filtration; the unfiltered mixture extracted with C6H6, the extract passed through silica, and eluted with C6H6 gave 600 mg. XVIII, m. 133-5°; the Et2O solution concentrated, the oil (4.5 g.) chromatographed in Et2O on Al2O3, and eluted with Et2O gave, from a narrow band, 20 mg. XXI, and, from a pale blue band, 4.1 g. oil, which, crystallized (EtOH) and recrystallized (aqueous EtOH), afforded 3.8 g. Et 6-methoxy-2′-methyl-3-methylene-4′-oxogris-2′-ene-3′-carboxylate (XXIII), m. 97-8°, ν 1728, 1668, 1641, 1614 cm.-1, λ 326, 316, 273, 260, 233, 215 mμ (log ε 4.05, 4.09, 4.18, 4.43, 4.37); 2,4-dinitrophenylhydrazone, m. 182° (decomposition). Crude XXII (1.5 g.) mixed with 20 g. polyphosphoric acid (XXIV), kept 4 days at room temperature, and worked up gave 700 mg. XXIII, 30 mg. XXI, and no acidic product. XXIII (1.0 g.) in 30 mL. CCl4 ozonized as above (CH2O isolated with XII), the product chromatographed in Et2O on Al2O3, the yellow gum (510 mg.) treated with EtOH, seeded, and the solid recrystallized (dilute EtOH) gave Et 6-methoxy-2′-methyl-3,4′-dioxogris-2′-ene-3′-carboxylate (XXV), m. 110-11°, ν 1735, 1704, 1686 cm.-1, λ 320, 272, 231, 208 mμ (log ε 3.95, 4.12, 4.17, 4.42), giving an intractable precipitate with Brady reagent. XXV (3 g.) refluxed 4 h. in an N atm. with 300 mL. EtOH and 350 mL. 2N HCl (0.6 mol CO2 evolved), the solution concentrated in vacuo, the aqueous residue extracted with Et2O, the extract washed with aqueous NaHCO3 (recovery gave only a trace of acidic gum), concentrated, the residual oil (1.6 g.) chromatographed in Et2O on Al2O3, and eluted with Et2O gave, from a blue band, 1.5 g. 6-methoxy-2′-methylgris-2′-ene-3,4′-dione, gum, ν 1713 and 1667 cm.-1, λ, 318, 272, 232, 209 mμ (log ε 3.98, 4.13, 4.22, 4.45) [2,4-dinitrophenylhydrazone, m. 230° (EtOAc)], and, from a dark blue band, 20 mg. XXV. 3,2,4,6-Cl(HO)(MeO)2C6HAc (XXVa) (46.0 g.), 66.4 g. CH2BrCO2Et, and 56.0 g. anhydrous K2CO3 in 700 mL. Me2CO refluxed 72 h., filtered, the filtrate evaporated in vacuo, the oil dissolved in 200 mL. EtOH, the solution treated with Et2O, and the precipitate recrystallized (EtOH) gave 56.6 g. 2,6,3,5-Ac(Cl)-(MeO)2C6HOCH2CO2Et (XXVI), m. 72°, ν 1763, 1735, 1684 cm.-1, λ 305, 292, 258, 223 mμ (log ε 3.35, 3.43, 3.70, 4.21); 2,4-dinitrophenylhydrazone m. 136° (EtOAc). With CH2-BrCO2Me in the above experiment, there was obtained the corresponding Me ester (XXVII), m. 103-4° (MeOH), ν 1760 and 1680 cm.-1, λ 305, 293, 268, 233 mμ (log ε 3.35, 3.42, 3.66, 4.20). XXVI (47.4 g.) in 200 mL. EtOH, 300 mL. H2O, and 14 mL. H2SO4 refluxed 4 h., diluted with H2O until cloudy, kept overnight at 5%, the precipitate filtered off, washed with aqueous Na2CO3 (19.7 g. XXVI remained), and the alk. extract acidified gave 19.1 g. acid (XXVIII), m. 144° (C5H6 or H2O), ν 1751 and 1659 cm.-1, λ 301, 292, 258, 224 mμ (log ε 3.42, 3.39, 3.66, 4.19). XXVII (500 mg.) and 20 mL. 3N HCl refluxed 6.5 h., the solid filtered off, dissolved in warm aqueous Na2CO3, the solution treated with C, filtered, and the filtrate acidified at 0° gave 311 mg. XXVIII cyclic form (XXIX) (R = H) (XXX), m. 143-4° (dilute EtOH), ν 1746 cm.-1, λ 275 and 240 mμ (log ε 3.09, 3.95); mixtures of XXVIII and XXX m. 115-40°; a 1:1 mixture (XXXI), m. 119-20°, behaved as a pure compound (see below). XXVII (1.5 g.) and 75 mL. N HCl refluxed 4 h. and worked up gave 1.1 g. XXX, m. 119-20° (C6H6), ν 1749 and 1659 cm.-1, identical with a 1:1 mixture XXVIII and XXX. XXX (29 mg.) in 5 mL. Et2O treated overnight with 1 mol CH2N2 in 5 mL. Et2O and worked up gave 24 mg. XXIX (R = Me) (XXXII), m. 97° (MeOH), ν 1742 cm.-1, λ ∼275 and 235 mμ (log ε 3.07, 3.98). XXVIII treated similarly gave the isomeric open-chain acid (XXXIII), m. 103-4°, mixed m.p. with XXXII 78-85°. XXXIII or XXXII (17.3 g.), 34 g. fused NaOAc, and 100 mL. Ac2O heated under reflux until CO2 evolution ceased (30 min.), the cooled solution diluted with H2O, made alk. with Na2CO3, the product filtered off, passed through a column of Al2O3 in 3 l. C6H6 recovered, and crystallized (EtOH) gave 14 g. 7-chloro-4,6-dimethoxy-3-methylcoumarone (XXXIV), m. 148°, ν 1626, 1611, 1591 cm.-1, λ 320, ∼275, 263, 220, 216 mμ (log ε 2.42, 4.00, 4.19, 4.56, 4.56). XXVI (15.8 g.) refluxed 1 h. with 1 g. Na in 50 mL. EtOH, the cooled solution diluted with 750 mL. H2O, the precipitate (2.7 g.) filtered off, and crystallized (EtOH) gave Et 7-chloro-4,6-dimethoxy-3-methylcoumarone-2-carboxylate (XXXV), m. 172-3°, ν 1712 cm.-1, λ 312, 298, 245, 230 mμ (log ε 4.32, 4.37, 4.34, 4.30); acidification of the filtrate with dilute HCl gave 11.2 g. XXVIII, m. 143°. XXXV (895 mg.) warmed 10 min. at 40° with 6 g. NaOH in 100 mL. 50% aqueous EtOH, diluted with ice and H2O, the solution acidified, and the precipitate (790 mg.) sublimed in vacuo gave the corresponding acid (XXXVI), m. 310° (decomposition), ν, 1671 cm.-1, λ 293 and 238 mμ (log ε 4.26, 4.31); Me ester, m. 196° (MeOH). XXXVI converted to the acid chloride (SOCl2 plus C5H5N) and the latter treated with CH2N2-Et2O gave the diazo ketone (XXXVII), m. 118-20° (Et2O). Attempted Wolff rearrangement of 600 mg. XXXVII as above gave 530 mg. XXXVI, m. 250-60° (decomposition). XXXVI (200 mg.) in 0.5 mL. quinoline heated 5 min. at 190-5° with 100 mg. Cu bronze and worked up gave 150 mg. XXXIV, m. 143°. Anhydrous HCN (200 mL.) added to 142 g. XXXIV in 6 1. Et2O at 0°, a fast stream of dry HCl passed in at 0-5° until absorption ceased (6 h.), the solution kept overnight at 0°, the aldimine-HCl (XXXVIII) filtered off, washed with Et2O, heated with 10 1. H2O at 100%, and the product (XXXIX) (110 g.) filtered off (after 24 h. a second crop XXXVIII separated from the Et2O mother liquor which yielded 27 g. addnl. XXXIX on hydrolysis); XXXIX in C6H6 passed through Al2O3, crystallized (C6H6, EtOH, or Me2CO), sublimed, and the sublimate recrystallized (Me2CO) gave the 2-OHC derivative (XL) m. 183°, μ 1662 cm.-1, λ 341, 312, 253 mμ (log ε 4.24, 4.16, 4.28) [2,4-dinitrophenylhydrazone m. 312°(Me2CO); azlactone m. 235°(EtOAc), giving on alk. hydrolysis 7-chloro-4,6-dimethoxy-2,3-dimethylcoumarone (XLI), m. 290° (MOH), μ and 1596 cm.-1]. XL oxidized with KMn-O4 in aqueous Me2CO gave XXXVI, m. 310° (decomposition). XL (2.26 g.) and 720 mg. XVII refluxed 4 h., cooled, the melt dissolved in 200 mL. Et2O, the solution filtered, the filtrate extracted with aqueous Na2CO3, and the alk. extract acidified gave 720 mg. 7-chloro-4,6-dimethoxy-3-methylcoumarone-2-β-propionic acid (XLII), m. 123-30° (chromatog. followed by recovery from the Ag salt); a sample of XLII was converted by Et2O-CH2N2 to the Me ester (XLIII), m. 102° (MeOH), ν 1739 cm.-1, λ 320, 294, 278, 265, 226, 223 mμ (log ε 2.61, 3.30, 4.05, 4.27, 4.53, 4.52, 4.52). The remaining XLII (500 mg.) methylated as above, the product chromatographed in C6H6 on Al2O3, a pale-blue band eluted with Et2O, the recovered ester (350 mg.) hydrolyzed with N alc. HCl, the compound sublimed in vacuo, and recrystallized (aqueous EtOH) gave XLII, m. 134-5°, ν (Nujol mull) 1722 and 1706 cm.-1, (in CHCl3) 1716 cm.-1 XXXIX (4 g.), 6.7 g. CH2(CO2H)2, 330 mg. piperidine, and 17 mL. C5H5N heated 1 h. at 100° and then 10 min. at 120°, The cooled solution was acidified, the precipitate (6.1 g.) extracted with aqueous Na2CO3 (1.3 g. XXXIV remained), and the alk. extract acidified gave 4.75 g. 7-chloro-4,6-dimethoxy-3-methylcoumarone-2-acrylic acid (XLIV), m. 252° (C6H6), ν 1692 and 1676 cm.-1, λ 329 and 255 mν (log ε 4.44, 4.04); Me ester, m. 179° (MeOH), ν 1709 cm.-1 (a) XLIV (102 mg.) in 50 mL. AcOH added to 0.2 g. Raney Ni in 2 mL. EtOH, hydrogenated at room temperature and pressure until absorption ceased (1 mol H absorbed in 8 h.), the mixture filtered, the filtrate concentrated to 5 mL. in vacuo, 100 mL. H2O added, stored overnight at 5°, the solid (60 mg.) collected, stirred 1 h. with cold dilute HCl, the mixture filtered, the precipitate (35 mg.) purified through the Na salt, and crystallized (petr. ether) gave XLII, identical with XLII as prepared above. (b) Crude XLIV (93 g.) in 3.5 1. 0.1N NaOH hydrogenated at room temperature and pressure in the presence of 50 g. 5% Pd-SrCO3 (absorption ceased after 8 h. when 0.64 mol H was absorbed), 10 g. C added, the filtered solution acidified (38 g. solid obtained and an addnl. 5 g. by repptg. the sticky material from aqueous NaOH), and the product chromatographed in C6H6 on silica gave 39 g. XLII, m. 133-5°, identical with XLII prepared in a. (c) XLIV (56 g., m. 252°) in 2.3 1. 0.1N NaOH hydrogenated as in b (2 mol H absorbed in 1 h.), the acidified solution extracted with Et2O, the extracts concentrated, the combined solids therefrom treated with CH2N2-Et2O, the resulting oil (50.7 g.) chromatographed in C6H6 on Al2O3, and a single bright blue band eluted with C6H6 gave 6.3 g. product (XLV), needles, m. 104-6° (C6H6-petr. ether), and 3.6 g. product (XLVI), prisms, m. 98-100° (MeOH), and, on further elution, 37 g. gum (XLVII). XLV crystallized (MeOH) gave Me 7-chloro-4,6-dimethoxy-3-methylcoumaran-2-β-propionate, prisms, m. 107-8°, ν 1731 cm.-1, hydrolyzed with boiling N NaOH to the corresponding acid, m. 147-8°, ν 1716 cm.-1 XLVI recrystallized (MeOH) gave 2.7 g. XLIII, m. 102°, alk. hydrolysis giving 1.9 g. XLII. XLVII rechromatographed, the single band eluted in 10 equal fractions with C6H6, and fractions 2 and 8 rechromatographed; fraction 2 gave essentially Me 4,6-dimethoxy-3-methylcoumaran-2-β-propionate (XLVIII), uncrystallizable gum, ν 1728 cm.-1, alk. hydrolysis yielding the acid (XLIX), m. 114° (1:1 Et2O-petr. ether); fraction 8 hydrolyzed with NaOH, the product crystallized (1:1 C6H6-petr. ether), the crystals hand-picked, and recrystallized gave 4,6-dimethoxy-3-methylcoumarone-2-β-propionic acid (L), m. 124°. XLIX (2 g.) and 200 mg. S heated 20 min. at 220° and 5 min. at 280°, the product continuously extracted with X, and the resulting crystallized extract hand-picked gave 320 mg. recovered XLIX and 540 mg. L, m. 124°. XLVIII (157 mg.) and 135 mg. ο-chloranil in 5 mL. CHCl3 stored 1.5 h. in the dark, the recovered product chromatographed in C6H6 on Al2O3, the pale blue band eluted with C6H6, and the product (135 mg.) crystallized (1:1 Et2O-petr. ether and then MeOH) gave the coumarone-tetrachloropyrocatechol complex (LI), m. 117°. LI hydrolyzed by alkali and the product crystallized (1:1 Et2OX) gave L, m. 122-4°. XLII (23.5 g.) in 500 mL. dry CHCl3 treated with 20 g. PCl5, the mixture refluxed 0.5 h., volatile products removed at 30° in vacuo, and the residue (LII) kept 4 h. at 12 mm., LII dissolved in 1.5 l. Et2O, 12 g. VI added, the mixture refluxed 24 h., 250 mL. 40% AcOH added, the Et2O layer separated, extracted with Na2CO3 solution (the extract afforded 5.9 g. XLII), and concentrated; the residual oil (25 g.) chromatographed in Et2O on Al2O3 and eluted gave, from a bright-blue band, 800 mg. XLII Et ester (LIII), m. 74-6° (EtOH), and, from an orange-red band, 18 g. orange oil (LIV). LIV heated 2 h. at 110°/10-4 mm. (excess XX removed) gave 14 g. gum (LV), giving a red color with alc. FeCl3 and forming no stable ketonic derivatives LV (12 g.) in 100 mL. Et2O shaken with saturated aqueous Cu(OAc)2 deposited 2.8 g. blue crystals (LVI); the Et2O layer evaporated and the residual gum fractionally crystallized gave 6 g. product (LVII) and 1.8 g. Et α-acetyl-β-oxo-7-chloro-4,6-dimethoxy-3-methylcoumarone-2-γ-carboxylate (LVIII) β-Cu chelate (LIX), m. 98-100° (EtOH), converted to the α-Cu isomer (LX) on continued heating at 120-30°; LVI and LVII combined and crystallized (CHCl3) gave LX, m. 164°. (a) LIX (1.4 g.) and 20 g. XXIV kept 10 days at room temperature, diluted with 50 mL. ice and H2O, extracted with Et2O, the extract washed with aqueous Na2CO3, dried, evaporated, the residual gum (1.18 g.) chromatographed in C6H6 on Al2O3, and the column eluted with C6H6 gave (1) from a narrow blue band, 5 mg. LIII, m. 72-3°, (2) from a greenish-blue band, a gum, which, kept in EtOH, deposited 175 mg. product (LXI), m. 137° and (3) from a blue band, a gum, which, kept in X, deposited 278 mg. product (LXII), m. 129-31°. LXI and LXII combined, recrystallized (EtOH), the crystals (410 mg.) sublimed in vacuo, and the sublimate recrystallized (MeOH) gave Et 7-chloro-4,6-dimethoxy-2′-methyl-3-methylene-4′-oxogris-2′-ene-3′-carboxylate (LXIII), m. 137°, ν 1731, 1680, 1638, 1610 cm.-1, λ282, ∼275, and 253 mμ (log ε 4.30, 4.28, 4.57). (b) LX (500 mg.) and 20 g. XXIV heated 1 h. at 70-80° and worked up as above gave 210 mg. LXIII, m. 137°. (c) LX (1.8 g.) and 30 g. XXIV kept 10 days at room temperature, worked up as above, and the alk. extract acidified gave 600 mg. XLII; some Cu derivative (600 mg.) was regenerated by shaking the acid with aqueous Cu(OAc)2; the remaining gum (320 mg.) chromatographed gave 120 mg. LIII and 5 mg. unidentified compound, m. 181-2° (MeOH). LXIII (248 mg.) in 15 mL. CCl4 ozonized 8 min. at room temperature, CCl4 removed in vacuo, the residue in 20 mL. Et2O and 10 mL. AcOH cooled in ice, treated with 2 mL. H2O and 100 mg. Zn dust, after 12 h. 20 mL. H2O added, the Et2O layer separated, combined with Et2O-washings of the aqueous layer, and worked up gave 5% LXIII, 40% XXVa, 30% Cl-free acidic fraction, and 4% 7-chloro-4,6-dimethoxy-2′-methylgris-2′-ene-3,4′-dione (LXIV), m. 167-8°, ν 1718 and 1683 cm.-1, λ 323, 291, 235, 213 mμ (log ε 3.70, 4.30, 4.19, 4.42). LXIII (137 mg.) in CCl4 ozonized 0.5 h. and worked up gave 10 mg. Cl-free solid, 30 mg. XXVa, 6 mg. LXIII, 1.2 mg. unidentified product, m. 143-9°, and 13 mg. Et 7-chloro-4,6-dimethoxy-3,4′-dioxogris-2′-ene-3′-carboxylate, m. 174° (EtOH), ν 1739, 1705, 1684, 1623, 1593 cm.-1, not hydrolyzed by boiling 1-10N HCl, alk. hydrolysis causing degradation LXIV (10 mg.) in 1 mL. EtOAc added to a previously reduced catalyst prepared from 5 mg. PdCl2 and 20 mg. C in 1 mL. H2O, shaken 6 h. with H at room temperature and pressure (absorption complete in 3 h.), the recovered gum chromatographed in C6H6 on Al2O3, and the recovered gums from each eluate chromatographed on circular paper gave an alc. fraction (not investigated) and the racemate of l,d-7-chloro-4,6-dimethoxy-2′-methylgrisan-3-one, d,d-7-chloro-4,6-dimethoxy-2′-methylgrisan-3,4′-dione, m. 170-5°. The experimental process involved the reaction of Ethyl 6-methoxy-3-methylbenzofuran-2-carboxylate(cas: 53724-96-2).Product Details of 53724-96-2
Ethyl 6-methoxy-3-methylbenzofuran-2-carboxylate(cas:53724-96-2) belongs to benzofuran. Benzofuran is the “parent” of many related compounds with more complex structures. For example, psoralen is a benzofuran derivative that occurs in several plants. Product Details of 53724-96-2
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem