Reactions of keten acetals. Part 7. Total syntheses of the tetramethyl ethers of the 1-acyl-2,4,5,7-tetrahydroxyanthraquinones rhodolamprometrin and rhodocomatulin

摘要

1852 J.C.S. Perkin IReactions of Keten Acetals. Part 7.l Total Syntheses of the Tetra-methyl Ethers of the I -Acyl-2,4,5,7-tet rahyd rsxyant h raq ui nsnes Fa hodo-lamprometrin and RhodocomatulinBy Jacques Banville and Paul Brassard,* Department of Chemistry, Lava1 University, Quebec, P.Q., CanadaG1 K 7P4Acylketen acetals or (better) their trimethylsilyl enol ethers condense regiospecifically with 2-halogeno-I ,4-naphthoquinones. Reactions of 1,l -dimethoxy-3-trimethylsilyloxyhexa-l,3-diene and -0cta-l.3-diene with 2-chloro-6,8-dimethoxy-1,4-naphthoquinone gave the corresponding 1 -al kyl-2.4.5.7-tetramethoxyanthraquinones.The latter underwent spontaneous photochemical oxidation a t the benzylic position and yielded the titlecompounds. The method has been adapted to provide a simple synthesis of questin.@-UNSATURATED aldehydes, ketones, and esters in thepresence of strong base are known to give cycloadditionproducts, presumably through their enolates.2 It wasexpected that the readily accessible acylketen acetalswould at certain temperatures behave as l-hydroxy-vinylketen acetals, and regiospecifically l y 3 give anthra-quinones having substitution patterns not easily obtainedby other means (e.g. 3-hydroxyl-1-methoxy- and l-alkyl-2,P-dime t hoxyant hraquinones) .The acylketen acetals (4)-(6) were obtained byFriedel-Crafts reactions of acyl chlorides with 1,l-dichloroethylene followed by metho~ydehalogenation.~This method yielded mainly orthoesters, confirming anearlier observation ; however the acylketen acetalscould easily be isolated after heating the crude productsPart 6, J.Banville and P. Brassard, J.C.S. Perkin I , 1976,613.a H. Meerwein, Chem. Ber., 1944, 77, 227; P. G. Sammes andT. W. Wallace, J.C.S. Chem. Comm., 1973,524.at 150 "C under normal pressure for several hours (athigher temperatures, esters are also obtained). Moreoverthe use of slightly less (ca. 1.8 equiv.) than the calculatedamount of methoxide was important in order to avoidsecondary reactions.In a preliminary experiment a large excess of theacetylketen dimethyl acetal (4) was heated with 2-bromo-5-chloro-8-hydroxy-6-methyl-l,4-naphtho-quinone (10) for 30 min at 120 "C; the desired reactionoccurred, but with concomitant transetherificat ion,giving the 1 -hydroxy-6,8-dimet hoxyanthraquinone ( 12)rather than the expected 1,6-dihydroxy-8-methoxy-derivative (14).The yield (39) was inferior to thatJ. Banville, J.-L. Grandmaison, G. Lang, and P. Brassard,Canad. J . Chem., 1974, 52, 80.4 I. Heilbron, E. R. H. Jones, and M. Julia, J . Chem. Sac.,1949,1430; A. N. Nesmeyanov, 0. A. Reutov, and A. S. Gudkova.Izvest. Akad. Nauk S.S.S.R., OtdeI. khim. N a u k , 1961, 260.F. Pochat and E. Levas, Bull. SOG. clzim. France, 1972, 31511976 1853obtained previously 3 with keten dimethyl acetal, butprovided the prospect of preparing the l-alkyl-2,4-dimethoxy-analogues. This possibility was examinedwith 1 ,l-dimethoxyoct-1-en-3-one (6) and the samesubstrate (10) as before, and the 1-butylanthraquinone(13) was isolated in 23 yield.When the reaction wasCQIcoIC H , R CH,R11)R-H I L I R - H(21 H - E t I 5 l R - E t1 3 l R =Bu I 6 ) R -BuMeO, ,OMeCI IMe3Si0bsol; C c bsol; HIICHR(71R :H( 8 ) R : Et19) R - BUMI i( 1 1 1 R - M e+=0112) R':R2:H,R3:RL:Me1131 R': H, R2- Bu,R3-RL:MeI141 R':RZ= R3:H,RL:Me / I151 R': Rz: RL:H,R3-Me0riwapplied to the less reactive (no free per;-hydroxy-group 3, 2-chloro-6,8-dimethoxy-l,4-naphthoquinone(18),6 only 10 of the expected quinone (22) was ob-tained (nevertheless the procedure is extremely simple.)It seemed advisable at this point either to increase theaffinity of the quinone by cleaving the 8-methoxy-groupor to convert the enone into a more reactive form.Therecent preparation of trans-l-methoxy-3-trimethylsilyl-oxybuta-l,3-diene from trans-4-methoxybut-3-en-2-one, chlorotrimethylsilane, triethylamine, and zincchloride seemed to provide the more promising alter-native, even though the effect of the presence of a Lewisacid known to catalyse the polymerisation* of morereactive keten acetals was problematic.Under the prescribed conditions 4,4-dimethoxybut-ti A. Castonguay and P. Brassard, Synth. Comm., 1975,5, 3777 S. Danishefsky and T. Kitahara, J. Amer. Chem. Soc., 1974,* S. M. McElvain, Chem. Rev., 1949, 45, 453.H. 0. House, L. J. Czuba, M. Gall, and H. D. Olmstead, J.(other methods will be communicated shortly).96, 7807.Ovg. Chem., 1969, 34, 2324.3-en-2-one (4) was converted into the trimethylsilyloxy-butadiene (7) in 67 yield; however the use of zincchloride with this type of compound was found to have adeleterious effect, a yield of 8874 being obtained laterwithout it.The higher homologues (8) and (9) couldalso be obtained with only slightly decreased efficiency.Earlier work on the silyl enol ethers derived from alde-hydes and ketones led to the assumption that mixtures ofcis- and trans-isomers of (8) and (9) would be encountered.However the products decomposed during g.1.c. andtheir n.m.r. spectra did not reveal the expected dupli-cation of signals.The usefulness of the new compounds was first testedby treating the diene (7) with the usual substrate, thejuglone (10). At room temperature, the cycloadditionwas complete within a few min, giving a colourlessadduct which was then pyrolysed at 150 "C.Hydroly-sis10 of the silylated compound by refluxing briefly indilute hydrochloric acid gave the desired anthraquinone(14) in 87 yield. When methanolysis of the silyl etherwas attempted before the pyrolytic step, three productswere isolated in similar amounts : the 1,6-dihydroxy-8-methoxyanthraquinone (14) (the normal product) andthe 1,8-dihydroxy-6-met hoxy- and P -h y drox y-6, dime-thoxy-anthraquinones (15) and (12) resulting from initialaddition of methanol to the enol ether with and withoutacidolysis of the acetal. It was also observed that thepresence of fieri-hydroxy-groups on the naplithoquin-ones, which generally have a favourable effect in the caseof unsubstituted keten acetals, is not important whenthese conjugated reagents are used: a (90) yield of theanthraquinone (16) was produced from the juglone ether(11) and the diene (7).A new and simple preparation of questin (17) illus-trates one use of these dienes.In spite of its structuralsimplicity, this compound was not obtained by synthesisuntil 1972.11 A simple reductive dechlorination by sodiumdithionite of the anthraquinone (14) obtained earliergave questin in 70 yield.Rhodolamprometrin and the mono- and di-methylethers of rhodocomatulin are natural products extractedfrom tropical crinoids,l2 and the synthesis of theircompletely O-methylated derivatives could now beenvisaged with the type of diene just described.Asexpected the formation of bulky adducts from the con-jugated keten acetals (8) and (9) and 2-chloro-6,8-dimethoxy-l,4-napthoquinone (18) was more difficult,and required heating at 120 "C for nearly 1 h. Subse-quent pyrolysis produced considerable decomposition andit was eventually found that the aromatisation was bestcarried out by refluxing in methanol for 12 h. The crudeproducts had two constituents : the tetramethoxy-anthraquinone (20) or (22), resulting as before from10 A. E. Pierce, ' Silylation of Organic Compounds,' PierceChemical Co., Rockford, Illinois, 1968, p. 447.11 R. F. Curtis, C. H. Hassall, and D. R. Parry, J.C.S. PerkinI, 1972, 240.12 M. D. Sutherland and J. W. Wells, A u s t d . J . Chern., 1967,20, 515; R.H. Thomson and T. R. Erdman, J.C.S. Perkin I,1972, 12911854 J.C.S. Perkin Iaddition of methanol to the enol ether, and the 2-hydroxyanthraquinone (19) or (21). The mixtures weremethylated directly and gave the tetra-0-methyl ethers(20) and (22) in 81 and 64 yields, respectively.0(181M e o amp;OR2Me0 OMeI191 R': E t , R2=H1201 R'= E t , R2: Mej'1211R':Bu;R2=H122) R1 z 6u,R2=MeO ROMe(231 R : Me(24 1 R : P iThe last step in the syntheses, the oxidation of thehighly hindered benzylic position, was not expected tobe easily accomplished. Indeed a variety of the usualreagents either left the substrates unchanged or causedconsiderable decomposition. It was observed in themeantime that l-butyl-2,4,5,7-tetramethoxyanthraquin-one (22), although not expected to be unstable, seemedto undergo slow deterioration.A sample deliberatelyleft exposed to air and daylight for 2 weeks was partlyconverted into a new compound. The i.r. spectrum ofthis substance showed the characteristic absorption ofa hindered benzylic ketone, and n.m.r. confirmed thetransformation of a butyl into a butyryl group. Thisprocess can be accelerated by bubbling oxygen into aboiling ethanolic solution of the l-alky1-2,4,5,7-tetra-methoxyanthraquinone (20) or (22) while irradiatingwith a 500 W photoflood lamp. After 2-3 h the sub-strate had disappeared and the corresponding compound(23) or (24) was isolated in 34 or 47 yield, respectively.This spontaneous oxidation of a hindered benzylicposition appears to be without precedent in quinonechemistry.EXPERIMENTALM.p.s were taken for samples in capillary tubes with aThomas-Hoover apparatus (calibrated thermometer).1.r.and U.V. spectra were determined with Beckman IR-12and DK-1A spectrophotometers, respectively. N.m.r.spectra were recorded with Varian A-60 and Bruker HX-90spectrometers (tetramethylsilane as internal standard).Woelm silica gel (activity 111), was used throughout fordry column chromatography.l,l-DichZorohex-l-en-3-one (2) .-Anhydrous aluminiumchloride (133.4 g, 1.00 mol) was added in small portionswith stirring to butanoyl chloride (106.6 g, 1.00 mol) in anice-bath, followed at room temperature by 1,l-dichloro-ethylene (dropwise; 2 h). The mixture was stirred for2 h more, poured on ice (1 kg), and extracted with carbontetrachloride (5 x 100 ml).The extracts were steam-distilled and the distillate extracted with the same solvent(5 x 100 ml). After washing with 2 sodium hydrogencarbonate and drying at 0 "C over sodium sulphate (in thepresence of hydroquinone and magnesium oxide), theorganic phase was distilled and gave the enone (2) (83.7 g ,50), b.p. 88-90" a t 20 mmHg; ?2D23 1.484 0; v,, (film)1695 (C:O) and 1575 cm-1 (CIC); 6 (90 MHz; CDCI,)0.93 (3 H, t, J 7.0 Hz, 6-H,), 1.64 (2 H, sextet, J 7.0 Hz,5-H,), 2.53 (2 H, t, J 7.0 Hz, 4-H,), and 6.69 (1 H, s, 2-H)(Found: Cl, 42.85.1,l-Dichloro-oct- 1-en-3-one (3) .-A similar reaction withhexanoyl chloride (134.6, 1.00 mol) gave the enone (3)(94.3 g, 48y0), b.p.106-110" at 10 mmHg; 1.480 0;vmax. (film) 1696 and 1575 c1n-l; 6 (90 MHz; CDCl,) 0.89(3 H, t , J 6.5 Hz, 8-H3), ca. 1.10-1.78 (6 H, m, 5-, 6-,and 7-H,), 2.55 (2 H, t , J 7.5 Hz, 4-H,), and 5.02 (1 H, s,2-H) (Found: C, 49.5; H, 6.35; Cl, 36.35. C,H,,Cl,Orequires C, 49.25; H, 6.2; C1, 36.35). When the dis-tillation is carried out at 0.5 mmHg two products areobtained: the ketone (3), b.p. 60-64", and l,l,l-trichloro-octan-3-one, b.p. 68-72"; n~~~ 1.472 2; vmx. (film) 1728cm-l; 6 (60 MHz; neat) 0.89 (3 H, t , J 5.0 Hz, 8-H,), ca.1.10-1.90 (6 H, m, 5-, 6-, and 7-H,), 2.60 (2 H, t , J 6.0Hz, 4-H,), and 3.92 (2 H, s, 2-13,) this product is unstableand decomposes to the unsaturated ketone (3) within a fewhours.4,4-Diunethoxybut-3-en-2-one (4) .-To a stirred solutionof sodium methoxide from sodium (20.7 g, 0.900 mol) inabsolute methanol (480 ml) , kept at room temperature, wasadded (2 h) 4,4-dichlorobut-3-en-2-one (64.8 g, 0.466 mol).The mixture was stirred for 2 h more at the same temper-ature, filtered, and distilled to give 4,4,4-trimethoxybutan-2-one (56.4 g, 74y0), b.p.82-84" at 12 mmHg; nD251.4228; vm9; (film) 1718 (CO) cm-l; 6 (90 MHz; CCl,)2.12 (3 H, s, 1-H,), 2.77 (2 H, s, 3-H,), and 3.24 9 H, s,4,4,4-(MeO),. Pyrolysis of this orthoester (240.0 g) at140-148 "C (4 h) gave the acylketen acetal(4) (68.0 g, 35y0),b.p. 104-105" at 10 mmHg D ~ ~ 1.492 0 (lit.,6 b.p. 116-117" at 12 mmHg; PZD 1.491 5); vmx. (film) 1680 (CO),1 600br (CC), and 1 280 and 1 235 cm-l (C-OR) ; 6 (60 MHz ;neat) 2.11 (3 H, s, 1-H,), 3.75 and 3.80 2 x 3 H, 2s.4,4-(OMe),, and 4.58 (1 H, s, 3-H), and 4,4,4-trimethoxy-butan-2-one (133.0 g, 55).1,l-Dirnethoxyhex- 1-en-3-one (5) .-A similar reactionwith 1,l-dichlorohex-l-en-3-one (2) (80.0 g, 0.478 mol),sodium (19.8 g, 0.861 niol), and absolute methanol gavea mixture of l,l,l-trirnethoxyhexan-3-one (70.5 g, 73y0),b.p. 53-54' at 0.2 mmHg; T Z D ~ ~ 1.426 5; v,, (film) 1 703(C:O), and 1 125 and 1095 cm-l (C*OR); 8 (90 MHz;CDCl,) 0.83 (3 H, t, J 7.0 Hz, 6-H3), 1.56 (2 H, sextet, J 7.0and 3.29 9 H, s, l,l,l-(OMe), (Found: C, 56.6; H, 9.4.C,H1,04 requires C, 56.8; H, 9.5); and the acylketertmetal (5) (7.3 g , lo), b.p. 74-76" at 0.2 mmHg; DZ31.482 1; vmx.(film) 1672 (CO), 1604 (CIC), and 1241 and1181 cm-1 (C-OR); 6 (90 MHz; CDCl,) 0.90 (3 H, t , J7.0 Hz, 6-H,), 1.59 (2 H, approx. q, 5-H,), 2.44 (2 H, t ,J 7.5 Hz, 4-H,), 3.73 and 3.82 2 x 3 H, 2s, 1'1-(OMe),,and 4.60 (1 H, s, 2-H) (Found: C, 60.9; H, 8.85. C8Hamp;requires C, 60.75; H, 8.9). Pyrolysis of l,l,l-trime-thoxyhexan-3-one (36.0, 0.19 mol) at 150 "C (3 h) gave theunchanged orthoester (18.7 g, b.p. 94-103" at 20mmHg, and the acylketen acetal (5) (12.9 g, 43y0), b.p.74-80" at 0.2 mmHg.l,l-Dirrethoxyoct-l-en-3-one (6) .-An analogous reactionwith 1,l-dichloro-oct-l-en-3-one (3) (36.0 g, 0.184 mol),C,H,CI,O requires C1, 42.45).Hz, 5-H,), 2.53 (2 H, t , J 7.0 Hz, 4-H,), 2.83 (2 H, S, 2-H,)1976 1855sodium (7.6 g, 0.330 mol), and absolute methanol (170 ml)gave a mixture of 1,1,l-trimethoxyoctan-3-one (28.2 g,40y0), b.p.70-71" at 0.05 mmHg; nD20 1.436 7; vmx. (film)1705 (C:O) and 1250 cm-f (C-OR); 6 (90 MHz; CDC1,0.89 (3 H, t , J 7.0 Hz, 8-H,), ca. 1.17-1.72 (6 H, m, 5-, 6-,and 7-H,) 2.56 (2 H, t, J 7.0 Hz, 4-H,), 2.56 (2 H, s, 2-H,),and 3.28 9 H, s, l,l,l-(OMe),; and the acylketen acetal(6) (6.0 g, 18y0), b.p. 86-90' at 0.5 mmHg; nD24 1.460 7;vmax. (film) 1 680 (CIO), 1 600 (C:C), and 1 230 cm-l (COOK);6 (90 MHz; neat) 0.87 (3 H, t, J 6.0 Hz, 8-H,), ca. 1.10-1.70(6 H, m, 5-, 6-, and 7-H,), 2.43 (2 H, t , J 7.0 Hz, 4-H,),3.71 and 3.77 2 x 3 H, 2s, l,l-(OMe)J, and 4.55 (1 H, s,2-H) (Found: C, 64.2; H, 10.0. C,,H,,O, requires C,64.5; H, '3.75).l,l-Di~~zethoxy-S-tri~~zetJ~ylsilylo,t.ybuta- 1,S-diene (7) .-To asolution of 4,4-dimethoxybut-3-en-2-one (4) (85.0 g, 0.653mol), triethylamine (147.0 g, 1.452 mol), and dry benzene(180 ml) was added (15 min) chlorotrimethylsilane (133.0 g,1.224 mol).The mixture was stirred at 38 "C for 3 h, thenat room temperature for 16 h, filtered, distilled to give thediene (7) (116.3 g, 88Oj,), b.p. 84-87' at 10 mmHg; n~~~1.464 0; vm,. (film) 1657 (diene), 1272 and 1251 (CsOR),and 850 cm-1 (SIC str.); 6 (60 MHz; neat) 0.14 (9 H, s,3-OSiMc3), 3.52 and 3.61 2 x 3 H, 2s, l,l-(OMe)2, 3.99(1 euro;3, d, J 1.0 Hz, 4-H), 4.07 (1 H, d, J 1.0 Hz, 4-H), and4.39 (1 euro;3, s, 2-H) (Found: C, 53.6; H, 9.1. C,H,,SiO,requires C, 53.45; H, 8.95).l,l-Dimethoxy-3-trii.net?zylsilyloxyJiexa-1,3-dien~ (8) .- Asimilar reaction with 1, l-dimethoxyhex- l-en-3-one (5)(20.0 g, 0.26 mol), triethylamine (40 ml), benzene (40 ml),and chlorotrimethylsilane (25.6 g, 0.236 mol) yielded thediene (8) (23.0 g, 77), b.p.60-68" at 0.3 mmHg; ?2D241.461 4 ; vmau. (film) 1 650 and 1 620 (C:C), 1 250 and 1 230(CmOR), and 835 cm-l (SiC str.); 6 (90 MHz; CDCl,) 0.15(9 H, s, 3-OSiMe3), 0.93 (3 H, t , J 7.0 Hz, 6-H,), 2.04 (2 H,sextet, 5-H,), 3.56 and 3.65 2 x 3 H, 2s, I,l-(OMe),,3.98 (1 H, s, 2-H), and 4.78 (1 H, t, J 7.0 Hz, 4-H). Thecompouiid appeared to be unstable and an acceptableanalysis was not obtained.1,1-Divtzethoxy-3-t~ii~iethylsilyZoxyocta- 1,S-diene (9) .- Ananalogous reaction of 1, l-dimethoxyoct- l-en-3-one (6)(10.0 g, 0.053 7 mol) with chlorotrimethylsilane (11.0 g,0.101 mol) and triethylamine (16 ml) in benzene (15 ml)gave the diene (9) (11.5 g, 82y0), b.p.70-80" at 0.2 inmHg;nD2* 1.458 2; vmas. (film) 1 655 (CX), 1 250 (C*OR), and 841cm-l (SIC str.) ; 6 (90 MHz; CDCl,) 0.17 (9 H, s, 3-OSiMe3),0.90 (3 H, t, J 7.0 Hz, 8-H,), ca. 1.17-1.44 (4 H, m, 6-,and 7-H,), ca. 1.83-2.17 (2 H, ni, 5-H,), 3.56 and 3.652 x 3 H, 2s, 1,l-(OMe),, 3.99 (1 H, s, 2-H), and 4.78 (1 H,t, J 7.0 Hz, 4-H). The compound becomes discolouredrapidly and a correct analysis was not obtained.4-Chlovo- l-hydroxy-6,8-dimethoxy-3-methylanthraquinone(1 2) .-A mixture of 2-bromo-5-chloro-8-hydroxy-6-methyl-1,4-naphthoquinone (10) (600 mg, 1.99 mmol) and 4,4-dimethoxybut-3-en-2-one (4) (1.301 g, 10.0 mmol) washeated at 120 "C for 30 min, then chromatographed onsilica gel (60 g) (dry column; chloroform), and gave theanthraqriinone (12) (258 mg, 39), m.p.215.0-215.5"(from ethanol-benzene) (lit. ,, m.p. 2 13.0-213. 5"), identicalwith a sample obtained previously (mixed m.p., t.l.c., andi.r. and n.m.r. spectra).thraquinone (13) .-A similar reaction between the napli-thoquinone (10) (400 mg, 1.33 mmol) and 1,l-dimethoxyoct-l-en-3-one (6) (750 mg, 4.03 niniol) (120 "C; 1 h) gave,l-Butyl-8-chloro-5-Izydroxy-2,4-dimethoxy-7-methylan-after chromatography on silica gel (60 g) (dry column;benzene-ethyl acetate, 9 : l), the anthraquinone (13)(120 mg, 23y0), m.p. 162.5-163.0" (from methanol);amp; (EtOH) 229, 255, 264, 285, and 425 nm (log E 4.51,4.29, 4.32, 4.16, and 4.08); vmx.(KBr) 1673 (C:O), 1632(chelated C:O), 1 585 (aryl), and 1 232 and 1 202 cm-lca. 1.37-1.67 (4H, m, 2'- and 3'-H,), 2.43 (3 H, s, 7-CH3),(3 H, s, 4-OCH3), 6.65 (1 H, s, 3-H), 7.04 (1 H, s, 6-H), and12.86 (1 H, s, 5-OH); nz/e 388/390 (M+) (Found: C, 64.55;H, 5.45. C,,H,,C10, requires C, 64.85; H, 5.45).4-Chloro- 1,6-dihydroxy- 8-methoxy-3-methylanthraquinone( 14) .-To a suspension of 2-bromo-5-chloro-8-hydroxy-6-methyl-l,4-naphthoquinone (10) (600 mg, 1.99 mmol) in drybenzene (10 ml) was added l,l-dimethoxy-3-trimethylsilyl-oxybuta-1,3-diene (7) (490 nig, 2.42 mmol). The mixturerapidly became homogeneous; it was refluxed for 1 h, andevaporated, and the residue heated a t 145 "C for 1 11.(a) The crude intermediate, when refluxed for 5 min inmethanol (5 ml) and dilute hydrochloric acid (5 ; 5 ml),gave the anthraquinone (14) (547 mg, 86), m.p.303-304"(from ethanol); A,,,. (EtOH) 222, 251, 273, 286, and 434nm (log E 4.49, 4.09, 4.20, 4.24, and 3.90); vmaX. (KBr) 3 250(free OH), 1668 (C:O), 1625 (chelated C:O), 1598 (aryl),and 1230 and 1 198 cm-l (C-OR); 6 90 MHz; (CD,),SO(C-OR); 6 (90 MHz; CDC1,) 0.95 (3 H, t , J 7.0 Hz, 4'-H3),2.91 (2 H, t , J 8.0 Hz, l'-H,), 3.97 (3 H, S, 2-OCH,), 4.032.32 (3 H, S, 3-CH,), 3.86 (3 H, S, 8-OCH,), 6.69 (1 H, d,J 2.0 Hz, 7-H), 7.00 (1 H, d, J 2.0 Hz, 5-H), 7.14 ( 1 H, S,2-H), and 13.62 (1 H, s, 1-OH); m/e 318/320 (AT+) (Found:C , 60.35; H, 3.35. C6Hl,C10, requires C , 60.3; H, 3.5).(b) When methanol ( 5 ml) was added to the mixture beforepyrolysis, three products were obtained by chromatographyon silica gel (60 g) (dry column; chloroform) (in order ofdecreasing RF value) : 4-chloro- 1,8-dihydroxy-6-methoxy-3-metJzy1anthraquinone (15) (188 mg, 3oy0), m.p.209-210"(from ethanol) ; (EtOH) 226, 252, 269, 288, and 440 nm(log E 4.47, 4.19, 4.24, 4.12, and 4.04); vmaL (KBr) 1674(C:O), 1621 (chelated C:O), 1605 (aryl), and 1260 and1 230 cm-l (C-OR) ; 6 (90 MXz; CDCI,) 2.48 (3 H, s, 3-CH3),3.92 (3 H, s, 6-OCH3), 6.67 (1 H, d, J 2.5 Hz, 7-H), 7.18br(1 H, s, 2-H), 7.33 (1 H, d, J 2.5 Hz, 5-H), and 12.04 and12.69 (2 x 1 H, 2s, 1- and 8-OH); m/e 318/320 ( M f )(Found: C, 60.35; H, 3.25; C1, 10.7. C,,H,,ClO, requiresC, 60.3; H, 3.5; C1, 11.15); 4-chloro-l-hydroxy-6,8-dimethoxy-3-methylanthraquinone (12) (21 6 mg, 33y0),m.p.214.5" ; and 4-chloro-1,6-dihydroxy-8-methoxy-3-methylanthraquinone (14) (160 mg, 25y0), m.p. 299-300".(The two latter compounds were identical to those preparedearlier. )4-Chloro-6-hydroxy- 1,8-dimethoxy- 3-methylanthraquinone(1 6) .-A similar reaction method (a) with 2-bromo-5-chloro-8-methoxy-6-methyl- 1,4-naplithoquinone ( 1 1) (3 16mg, 1.00 mmol) , l,l-dimethoxy-3-trimethylsilyloxybuta-1'3-diene (7) (404 mg, 2.00 mmol) and benzene ( 5 ml) gavethe anthraquinone (16) (300 mg, goyo), m.p. 293" (from 1,2-dichloroethane) (lit. ,13 294-295"), identical with a sampleprepared previously (mixed m.p., t.l.c., and i.r. and n.m.r.spectra).1,6-DiJzydroxy- 8-methoxy-3-methylanthraquinone (Questin)( 17) .-A mixture of 4-chloro- 1,6-dihydroxy-8-methoxy-3-methylanthraquinone (14) (637 mg, 2.00 nimol), sodiumhydroxide ( 1.80 g), sodium dithionite (9.60 g ) , ethanol(50 ml), and water (50 ml) was stirred under nitrogen for12 h at room temperature.Air was then bubbled (3 h)vigorously through the solution, which was then diluted wit1856 J.C.S. Perkin Iwater (300 ml), acidified with dilute hydrochloric acid (lo),saturated with sodium chloride, and extracted with ethylacetate. Evaporation of the extract, crystallisation of theresidue from ethanol, and chromatography on silica gel(40 g) of the mother liquor (dry column; chloroform-ethylacetate-methanol, 69 : 30 : 1) gave questin (17) (401 mg,70), m.p.300-301" (lit., 303,11 301-30313) ; A- (EtOH)224, 248, 285, and 430 nm (log E 4.55, 4.14, 4.35, and 3.95) ;vmx. (KBr) 3 360 (free OH), 1673 (C:O), 1629 (chelatedC O ) , 1 591 (aryl), and 1 266 and 1211 cm-l (C*OR); 68-OCH,), 6.85 (1 H, d, J 2.0 Hz, 7-H), 7. lObr (1 H, s, 2-H),7.21 (1 H, d, J 2.0 Hz, 5-H), and 7.40br (1 H, s, 4-H);vn/e 284 (M+) (Found: C, 67.9; H, 4.4. Cl6Hl,O, requiresC, 67.6: H, 4.25).l-EthyE-2,4,5,7-tetraunethoxyanthraquinone (20) .-A mix-ture of 2-chloro-6,8-dimethoxy- 1,4-naphthoquinone (18) (1 .OOg, 3.98 mmol) and l,l-dimethoxy-3-trimethylsilyloxyhexa-1,3-diene (8) (1.09 g, 4.75 mmol) was heated at 120 "C for 1 h,diluted with absolute methanol (20 ml), and refluxed over-night. Dilute hydrochloric acid (5 ; 10 ml) was added tothe hot suspension, wnich was refluxed briefly, cooled,diluted with water (100 ml), and extracted with ethylacetate (3 x 100 ml) .The extract was evaporated and theresidue was methylated in the usual way by refluxing for18 h in a mixture of dimethyl sulphate (7.6 g), potassiumcarbonate (7.8 g), and acetone (100 ml). The crude productwas chromatographed on silica gel (60 g) (dry column;chloroform-ethyl acetate, 9 : 1), giving the anthraquznone(20) (1.14 g, 81), n1.p. 189.5-190.0" (from methanol);A,,, (EtOH) 224, 265sh, 286, and 410 nm (log c 4.64, 4.32,4.47, and 3.86); vmx. (KBr) 1660 (C:O), 1595 (aryl), and1 240 cm-1 (C-OR); S (90 MHz; CDCl,) 1.21 (3 H, t , J 7.5and 3.99 (4 x 3 H, 4s, 2-, 4, 5-, and V-OCH,), 6.70 (1 H, d,J 2.5 Hz, 6-H), 6.73br (1 H, s, 3-H), and 7.16 (1 H, d, J 2.5Hz, 8-H); mle 356 (M+) (Found: C , 67.45; H, 5.8.C,,H,,06 requires C , 67.4; H, 5.65).similar reaction between 2-chloro- 6,8-dimethoxy- 1,4-naph-thoquinone (2.00 g, 7.94 mmol) and 1,l-dimethoxy-3-trimethylsilyloxyocta-1,3-diene (9) (2.50 g, 9.50 mmol)gave the anthraquinone (22) (1.94 g, 64), m.p.1545-155.0" (from carbon tetrachloride) ; (EtOH) 226, 270,288, and 420 nm (log E 4.50, 4.19, 4.33, and 3.76); vmx.(KRr) 1661 (CZO), 1598 (aryl), and 1249 and I214 cm-l(C-OR); 6 (90 MHz; CDCl,) 0.97 (3 H, approx. t , J ca.6.5 Hz, 4'-H,), ca. 1.33-1.66 (4 13, m, 2'- and 3'-H,), 3.00(2H, approx. t , J c a . 7.0Hz, 1'-H,), 3.90, 3.94, and 3.98 (6H,60 M ~ I Z ; (CD,),SO 2.38 (3 H, S, 3-CH3), 3.92 (3 H, S,Hz, 2'-H,), 3.03 (2 H, 9 J 7.5 Hz, l'-HJ, 3.92, 3.93, 3.94,l-Buty1-2,4,5,7-tetramethoxyanth.p.aquinone (22) .-A3 H, and 3 H, 3.9, 2-, 4-, 5-, and 7-OCH3), 6.68 (1 H, d, J 2.5Hz, 6-H), 6.72br (1 H, s, 3-H), and 7.16 (1 H, d, J 2.5 Hz,8-H); m/e 384 (M+) (Found: C , 68.6; H, 6.4.C2,H,,0,requires C, 68.75; H, 6.3).l-Acety2-2,4,5,7-tet~amethoxyanthraquinone (Tetra-0-methylrhodolampronzetrilz) (23) .-Oxygen was bubbled intoa solution of l-ethyl-2,4,5,7-tetramethoxyanthraquinone(20) (200 mg, 0.56 mmol) in ethanol (20 ml), which wassimultaneously heated under reflux and irradiated with a500 W photoflood lamp (2 h). The residue obtained afterevaporation of the solvent was chromatographed on silicagel (60 g) (dry column; chloroform-ethyl acetate, 9 : 1) andgave the acetylanthraquinone (23) (70 mg, 34y0), m.p.260.5-261.0' (methanol) ; lax, (EtOH) 224, 284, and 415nm (log c 4.54, 4.41, and 3.77); vmx.(KBr) 1 700 (C:O),1 655 (quinone C:O), 1 598 (aryl), and 1 260 and 1 235 cm-l3.91, 3.96, and 4.01 (4 x 3 H, 4s, 2-, 4-, 6-, and 7-OCH3),6.77 (1 H, d, J 2.5 Hz, 6-H), 6.79 (1 H, s, 3-H), and 7.23(1 H, d, J 2.5 Hz, 8-H); vn/e 370 (M+) and 355 (M - CH,)(Found: C, 64.7; H, 5.0. C,oHl,O, requires C, 64.85;H, 4.9).l-ButanoyZ-2,4,5,7-tetramethoxyanth~aquinone ( Tetra-O-methylrhoaocovnatulin) (24) .-A similar reaction (3 h) with1-butyl-2,4,5,7-tetramethoxyanthraquinone (22) (200 mg,0.520 mmol) in ethanol (10 ml) gave the butanoylanthra-quinone (24) (97 mg, 47), m.p. 200-201" (from benzene)(analytical sample, m.p. 210.0-210.5") (1it.,l2 m.p. 203-204and 211-212'); A,,, (EtOH) 224, 284, 342, and 415 nm(log E 4.62, 4.38, 3.63, and 3.79); vmx. (KBr) 1 695 (C:O),1 660 (quinone C:O), 1 595 (aryl), and 1 247 and 1205 cm-l1.86br (2 H, sextet, 3'-H,), 2.75 (2 H, t , J 7.5 Hz, 2'-H,),3.88, 3.93, and 3.99 (6 H, 3 H, and 3 H, 3s, 2 , 4-, 5-, and 7-OCH,), 6.74 (1 H, d, J 2.5 Hz, 6-H), 6.77br (1 H, s, 3-H), and7.20 (1 H, d, J 2.5 Hz, 8-H); m/e 398 (M+) and 355 (M -C,H,) (Found: C , 66.4; H, 5.45. C2,H2,07 requires C,66.3; H, 5.550/,), identical (mixed m.p., t.1.c. in four solventsystems, and i.r. spectra) with an authentic sample.We thank Professor M. D. Sutherland for a sample oftetra-O-methylrhodocomatulin. Financial support fromthe Ministhre de 1'Education du Qukbec and the award ofNational Research Council of Canada scholarships to oneof us (J. B.) are acknowledged.(C-OR) ; 6 (90 MHz; CDC1,) 2.67 (3 H, S , 1-COCHJ, 3.90,(C*OR); 6 (90 MHz; CDC13) 1.03 (3 H, t, J 7.5 132, 4'-H3),6/614 Received, 30th March, 1976113 A. Mahmoodian and C. E. Stickings, Biochem. J., 1964, 92,369