The chemistry of the lsquo;insoluble redrsquo; woods. Part XII. Some reactions of isoflavylium salts

摘要

1976 1389The Chemistry of the ' Insoluble Red 'Woods. Part X1I.l Some Reactionsof lsoflavylium SaltsBy Mohga M. E. Badran and W. Basil Whalley," The School of Pharmacy, The University of London, LondonVarious methoxyisoflavylium perchlorates have been condensed with NN-dimethylaniline to yield 2-substitutedflav-3-enes' which were oxidised to the corresponding, highly coloured, 2-(p-dimethylaminophenyl) isoflavyliumWClN 1AXsalts.FLAVYLIUM salts (functioning as electrophiles) rapidlycondense with NN-dimethylaniline to furnish 293 4-sub-stituted flavylium derivatives, of type (1). We nowreport the results of an analogous investigation with iso-flavylium salts which are readily available from our earlierre~earch.~The present work was prompted by our continuinginterest in the ' insoluble red ' woods, which furnish,inter alia, the complex anhydrobenzopyranol basessantalinl and santarubin,l to which we have assignedthe structural type (2).More recently, unequivocalevidence for these structures has been provided byMerlini et aLs These pigments exhibit a novel andunique combination of two C,, flavanoid equivalents, andone possible biogenetic mode for achieving the first phaseof biosynthesis would be as illustrated in (3), a processwhich would also simply and elegantly explain the co-occurrence of the isomeric santalin and santarubin.To test the general validity of this hypothesis we haveinvestigated the behaviour of isoflavylium salts asPart XI, D. W. Mathieson, B. J. Millard, J. W.Powell, andR. Wizinger and H. Luthiger, Helv. Chim. Acta, 1953,36, S26.M. Blackburn, G. B. Sankey, A. Robertson, and W. B.W. B. Whalley, J.C.S. Perkin I, 1973, 184.Whalley, J . Chem. SOC., 1957, 1573.potential electrophiles. Thus, when a solution of 7-methoxyisoflavylium perchlorate (4) and NN-dimethyl-aniline in methanol was warmed on a steam-bath amixture of the benzopyranol methyl ether (5; R = OMe)and a product formulated as 2-(fi-amp;methylaminophenyl)-7-methoxyisoflav-3-ene (6) was rapidly formed. Thecondensation proceeded even more readily, and in almostquantitative yield, in the absence of a solvent. Then.m.r. spectrumof (6) has signals at 7 7.15 (6 H, s, NMe,),6.36 (3 H, s, OMe), and 2.60-3.80 (14 H, m, aromatic),and was not very informative concerning the structure.The U.V.spectrum A,, 209,257, and 335 nm (log e 4.54,4.67, and 4.27) was similar to that of 7-methoxy-2-methylisoflav-3-ene (5; R = Me) A,, 210, 245, and323 nm (log E 4.32, 4.24, and 4.43) and to that of themethyl ether of 7-methoxy-3-phenylbenzopyranol (5 ;R = OMe) A,, 210, 247, and 323 nni (log e 4.39, 4.20,and 4.45) ; this correspondence clearly supported struc-ture (6) as opposed to the alternative (7). This con-clusion is in accord with general theoretical principles.* C . A. Anirudhan, W. B. Whalley, and M. M. E. Badran, J.A. Arnone, L. Camarda, L. Merlini, and G. Nasini, J.C.S.Chem. SOC., 1966, 629.Perkin I, 1975, 1861390 J.C.S. Perkin IHydrogenation of the isoflavene (6) readily gave theisoflavan (euro;9, the n.m.r.spectrum of which exhibitedsignals at T 7.12 (6 H, s, NMe,), 6.92 (2 H, m, CH,),6.55 (I H, m, benzylic proton at C-3), 6.12 (3 H, s, OMe),4.62 (1 H, d, 0-CH), and 2.75-3.38 (12 H, m, aromatic).Comparison of these data with those for the correspond-ing 7-methoxyisoflavan , (9) confirms the structure (6).The isoflav-3-ene (6) formed a monopicrate, a methiodide,and a methosulphate.Oxidation of the isoflav-3-ene (6) occurred most readilyin ethereal solution with hydrogen chloride to form thecolourless 3-phenylbenzopyran-2-01 as a gum, character-ised as the intensely coloured picrate (10; R = C,H,N,-0,), the perchlorate (10; R = ClO,) and tetrachloro-ferrate (10; R = FeCl,). The cation may also bewritten as (ll).The isoflav-3-ene (6) is very resistant to the action ofd';CH( 6 )N Me,( 7 )alkali. Oxidation with potassium permanganate fur-nished (i) 4-dimethylaminobenzil (12; R = Me), (ii) 4-methylaminobenzil (12 ; R = H), (iii) 4-(N-methyl-formamido)benzil (12; R = CHO), and (iv) 2-hydroxy-4-methoxybenzoic acid.( 8 ) 191(10)(11) (121Similar series of derivatives were prepared by theaction of NN-dimethylaniline upon 2',7-dimethoxy-,3',4',7-trimethoxy-, and 4',5,7-trimethoxy-isoflavyliumperchlorates.The ease of condensation of NN-dimethylaniline with4', 5,7-t rime t hoxyisoflavylium perchlorat e is convincingcollateral evidence for the occurrence of substitution atC-2; we have established previously3 that a C-5 sub-stituent in the flavylium system essentially inhibits sub-stitution at C-4.These results provide a priori evidence for the generalvalidity of the concept that the illustrated mechanism(3) is a feasible step in the biosynthetic derivation ofsantalin and its congeners from an isoflavanoid residueand an equivalent open chain C,, unit.EXPERIMENTALLight petroleum refers to the fraction of b.p.60-80".Derivatives of 7-Metlaoxyiso~avylium Perchlorate.-A mix-ture of 7-methoxyisoflavylium perchlorate (0.3 g) and NN-dimethylaniline (0.3 ml) was warmed on a steam-bath for1-2 min; methanol (5 ml) was then added. Purificationof the crystalline precipitate from methanol gave 2-(p-dimethylamino~henyl)-7-methoxyisoflav-3-ene (6) (0.28 g) inneedles, m.p.151" Found: C, 80.5; H, 6.5; N, 4.0; OMe,9.2. C,,H,,NO(OMe) requires C, 80.6; H, 6.5; N, 3.9;OMe, 8.7 I. Prepared quantitatively in alcoholic solution,the picrate formed golden-yellow plates, m.p. 184" (decomp.)Found: C, 61.8; H, 4.5; N, 9.2; OMe, 5.5. C,,H,,N,O,-(OMe) requires C, 61.4; H, 4.5; N, 9.5; OMe, 5.3y0.Hydrogenation of this isoflav-3-ene (60 mg) dissolved inethanol (60 ml) containing 5 palladium-carbon (25 mg)proceeded rapidly to yield 2-(p-dimethy2um,zinophenyl)-7-rnethoxyisojhww (8) (40 mg), which separated from ethanolinneedles, m.p. 125" (Found: C, 79.9; H, 7.0; N, 3.9; OMe,7.1. C,,H,,Tbsol;;O, requires C, 80.2; H, 7.0; N, 3.9; OMe,8.6). The picrate formed yellow needles, m.p. 167"(decomp.) (from ethanol) (Found: C, 61.2; H, 4.9; N, 9.1.C,OH,,N,O, requires C, 61.2; H, 4.8; N, 9.5).Methyl1976 1391ation of the isoflavene (6) (25 mg) in boiling acetone (10 ml)containing an excess of methyl iodide during 4 h, gave thequaternary methiodide (25 mg), which formed plates, m.p.130" (deconip.) (from light petroleum-acetone-ethyl acetate)(Found: C, 59.6; H, 5.6; I, 24.2; N, 2.1. C,,H,,INO,requires C, 60.1; H, 5.2; I. 25.3; N, 2.8). Preparedsimilarly, the methosulphate formed needles, m.p. 163" (de-conip.) (from light petroleum) (Found: C, 63.9; H, 6.0;N, 2.6; S, 6.1. C,,H29N0,S requires C, 64.6; H, 6.0; N,3.0; S, 6.7).2- (p-Dimethylaminophenyl) -7-methoxy-3+henyl- l-benzo-pyra.~z-2-ol.-A solution of the isoflavene (6) (0.2 g) in ethylacetate (20 ml) was saturated at 0 "C with hydrogen chloride.The solution became intense blue-brown in colour; 24 hlater the mixture was diluted with methanol (20 ml) andthe solvent removed in vacuo.The residue was dissolvedin methanol (20 ml) containing sodium acetate and thecolourless solution was diluted with water (50 ml). Theproduct was extracted with chloroform t o yield 2-(p-dimethylaminophenyl)-7-methoxy-3-phenyl- l-benzopyran-2-01 as a gum. Prepared from a solution of this pyranol inmethanol by addition of 60 perchloric acid, 2-(p-dimethyl-aminopli enyl) -7-methoxyisoflavylium perchlorate formed in-tensely blue needles, m.p. 262" (decomp.) (Found: C, 62.6;H, 4.8; C1, 7.9; N, 2.8. C,4H,,ClN06 requires C, 63.3; H,4.9 ; C1, 7.8 ; N, 3.1 yo). The picrate separated from ethanolin olive-green plates, m.p.221" (decomp.) (Found: C, 61.2;H, 4.1; N, 9.3. Camp;,,N4Og requires C, 61.6; H, 4.1; N,9.6). The tetrachloroferrate separated from methanol indark blue rosettes, m.p. 177" (decomp.) (Found: C, 51.5;H, 3.9; Fe, 9.5; N, 2.0. C,,H,,Cl,FeNO, requires C , 52.0;H, 4.0; Fe, 10.1; N, 2.5).Oxidative DegradatioN of the Isoflav-3-ene (6) .-Potassiumpermanganate (1 g) in water (27 ml) was added during 5 ht o a solution of the isoflav-3-ene (0.2 g) in acetone (25 ml)(with stirring). The products from three oxidations wereisolated in the normal manner and combined to yield (i) 4-dimethylaminobenzil (30 mg), m.p. 114" (Found: C, 75.4;H, 6.1; N, 5.8. Cak. for C16H15N02: c, 75.8; H, 6.0; N,5.5y0), identical with an authentic specimen ; (ii) 4-methyl-aminobend (25 mg) in yellow prisms, m.p.85" (from lightpetroleum) (Found: C, 75.1; H, 5.5; N, 6.0. C,,Hl,NO,requires C, 75.3; H, 5.4; N, 5.9), vmx. 1 630 (CEO), 1 670( G O ) , and 3 370 cm-l (NH), 7 1.93-3.53 (9 H, m, ArH),5.33br (1 H, s, NH), and 7.10 (3 H, s, NMe); (iii) 4-(N-methylformamido) bend (10 mg), which separated from lightpetroleum in yellow needles, m.p. 118" (Found: C, 71.5;H, 4.8; K, 5.6. Cl,Hlamp;O, requires C, 71.9; H, 4.9; N,5.2y0), "; 0.28 (1 H, s, CHO), 1.80-2.73 (9 H, m, ArH), and6.63 (3 H, s, NMe) ; (iv) 2-hydroxy-4-methoxybenzoic acid(20 nig), identical with an authentic specimen.Derivatives of 4', 7-Dimethoxyiso~avyliunz Perchlorate.-Prepared from this perchlorate (0.1 g) and dimethylaniline(0.1 ml) , 2-(p-divnethylaminophenyl)-4', 7-dimethoxyisoflav-3-ene formed needles (80 mg), m.p.128" (from methanol)Found: C, 77.2; H, 6.3; N, 3.4; OMe, 16.5. C,,HlgNO-(OMe), requires C, 77.5; H, 6.5; N, 3.6; OMe, 16.070.The picrate separated from ethanol in golden-brown needles,m.p. 161" (decomp.) (Found: C, 60.9; H, 4.6; N, 8.6.C31H,,N40,0 requires C, 60.4; H, 4.6; N, 9.1).2- (p-Dimethylaminophenyl) -7-niethoxy-3- (4-methoxy-pheny1)- 1-benzopyran-2-01 formed a colourless gum, theperchlorate of which separated from methanol in intenselygreen plates, n1.p. 233" (decomp.) (Found: C, 61.8; H,5.0; C1, 7.4; N, 2.5. C,,H,,ClNO, requires C, 61.8; H,5.0; C1, 7.3; N, 2.9). The picrate formed olive-greenplates, m.p.205" (decomp.) (from ethanol) (Found: C, 60.5;H, 4.3; N, 8.7. C3,H,,N,0,,requiresC, 60.6; H, 4.3; N,Hydrogenation of 2-(p-dimethylaminophenyl)-4',7-cli-methoxyisoflav-3-ene gave the isoflavan in needles, m.p.177" (fromethanol) Found: C, 76.7; H, 7.1; N, 3.5; OMe,16.8. C,,H,,NO(OMe), requires C, 77.1; H, 7.0; N, 3.6;OMe, 15.9. The picrate formed yellow needles, m.p.155' (decomp.) (from aqueous ethanol) (Found: C, 60.9;H, 5.1; N, 8.2. C,,H30N401, requires C, 60.2; H, 4.9; N,Derivatives of 2', 7-Dimethoxy isoflavylium Perchlorate .-Prepared in the usual manner, 2-(p-dimethylaminophenyl) -2',7-dimethoxyiso$av-3-ene formed needles, m.p. 131" (frommethanol) Found: C, 77.7; H, 6.6; N, 3.6; OMe, 16.1.C,3H,gNO(OMe), requires C, 77.5; H, 6.5; N, 3.6; OMe,16.0y0.The picrate separated from aqueous ethanol ingolden-yellow needles, m.p. 147" (decomp.) (Found : C,60.5; H, 4.6; N, 8.9. C3,H,,N40,, requires C, 60.4; H,4.6; N, 9.1).Although the corresponding benzopyranol was a gum,2-(p-dimethylamino~henyl)-2,7'-dimethoxyisoflavylium per-chlorate formed intensely blue needles, m.p. 278" (decomp.)(from methanol) (Found: C, 61.2; H, 5.0; N, 2.2. C,,H,,-CINO, requires C, 61.8; H, 5.0; N, 2.9). The picrateformed dark blue prisms, m.p. 244" (decomp.) (from ethanol)(Found: C, 61.5; H, 4.5; N, 9.4. C,,H,,N4010 requires C,60.6; H, 4.3; N, 9.1).Derivatives of 3',4', 7-Trinzethoxyisoflavyliunz Peych1orate.-Prepared in the usual manner, 2-(p-dimethylaminophenyl)-3',4', 7-trimethoxyisoflav-3-ene formed needles, m.p.80" (frommethanol) Found: C, 64.6; H, 6.25; N, 3.4; OMe, 22.6.C,,H,,NO(OMe), requires C, 74.8; H, 6.5; N, 3.4; OMe,22.3. The picrate separated from aqueous ethanol ingolden-yellow needles, m.p. 180" (decomp.) (Found : C,59.6; H, 4.8; N, 8.4. C,,H,,N40,, requires C, 59.4; H,4.7; N, 8.7).Oxidation of this isoflav-3-ene with hydrogen chlorideduring 24 h, in ethyl acetate, gave the unstable 2-(p-di-rnethylawinophenyl)-3',4', 7-trimethoxyisoflavylium chloride incherry-red needles, m.p. 149" (decomp.) (Found: C, 64.8;H, 5.8. C,,H,,C1N04 requires C , 64.1; H, 5.8). Theperchlorate formed intensely dark blue plates, m.p. 138" (de-camp.) (from methanol) (Found: C, 59.7; H, 5.1; C1, 6.9;N, 2.3. C2,H2amp;lN08 requires C, 50.6; H, 5.1; C1, 6.9;N, 2.7).The picrate separated from alcohol in dark blueprisms, m-p. 190" (decomp.) (Found: C, 59.7; H, 4.3; S,8.7. C32H,,N4011 requires C , 59.6; H, 4.4; N, 8.7).Derivatives of 4', 5,7-Trimethoxyisoflavylium Perchlorate.-The condensation product from NN-dimethylaniline andthis perchlorate was a gum, which was oxidised to 2-(p-dimethylaminophenyl) -5,7-dimethoxy-3- (4methoxyphenyl) -benzobpyran-2-01 (non-crystalline) . The perchlorate sep-arated from methanol as intensely green-blue leaflets, m.p.144" (decomp.) (Found: C, 59.7; H, 5.1; N, 2.3. C,,H,,-ClNO, requires C, 60.5; H, 5.1 ; N, 2.7). The correspond-ing picrate formed dark violet prisms, m.p. 180" (decomp.)(from ethanol) (Found: C, 59.4; H, 4.6; N, 8.6. C39H2,-N401, requires C, 59.6; H, 4.4; N, 8.7).Derivatives of 2',4',7-Trimethoxyisoflavylium Perchlorate.-2-(p-Dimethylaminophenyl) -2', 4', 7-trimethoxy isoflav-3-eneseparated from methanol in needles, m.p. 131" (Found: C,74.9; H, 6.6; N, 3.1. C,,H2,NO4 requires C, 74.8; H,9.1 Yo).9.1).H. Staudinger, Ber., 1913, 4, 3535J.C.S. Perkin I6.5; N, 3.4). The picrate formed green rosettes, m.p. The analyses were performed by Mr. G. Crouch and his168" (decornp.) (from aqueous ethanol) (Found: C, 69.5; associates. One of us (M. M. E. B.) is indebted to theH, 4.7; N, 8.5. C,,H,,,N,O,, requires C , 59.4; euro;3, 4.7; N, U.A.R. Government for financial assistance.8.7). 5/2271 Received, 19th November, 1975