Benzoquinone derivatives. Part I. Reactions of primary aliphatic amines with embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) and di-o-methylembelin

摘要

1975 327Benzoquinone Derivatives. Part 1. Reactions of Primary AliphaticAmines with Embelin (2,5- Dihydroxy-3-undecyl-l.4- benzoquinone) andD i - 0- met hylem be1 inBy Balawant S. Joshi and Venkatesh N. Kamat, Ciba-Geigy Research Centre, Goregaon, Bombay 400063,The reaction of embelin with some primary aliphatic amines has been reinvestigated. Embelin reacts with methyl-amine to give the 5-methylamino-derivative ( 2 ) or the quinone bismethylimine (9). depending on he conditions.2-Hydroxy-5-methylamino-3-undecyl-l.4-benzoquinone 1 -methylimine (1 1) is obtained by the reaction ofdi-O-methylernbelin with methylamine. The products of condensation of several primary aliphatic amines withembelin and its di-O-methyl derivative have been characterized.IndiaEMBELIN (l), the major chemical constituent of Embeliavibes Burn.and Embelia tsjeriam Cottam is reputed topossess anthelminthic activ3y.l We were interested inthe preparation of some aliphatic amino-derivatives ofembelin in order to investigate their pharmacologicalprofiles. Primary aliphatic amines are known to reactwith 1,4-benzoquinones to give nuclear aminated quin-ones. 2-4When embelin was heated in acetic acid with methyl-amine (2 mol. equiv.), a compound was obtained whichon the basis of spectroscopic data could be formulated as(2) or (3). Its n.m.r. spectrum showed an olefinic protonsignal at 6 5-2 and a doublet at 2.85 (3H, J 5 Hz, NHMe).En order to choose between the two structures, the mono-methylamino derivative was O-acetylated ; the productshowed the ring olefinic proton signal at 6 5.4.Di-acetylembelin (4), obtained by heating embelin withacetic anhydride: showed a deshielded olefinic proton( 6 5-8- 6-55), the shift being due to the para-magnetic anisotropic effect of the 5-a~etoxy-group.~-*If the methylamino-derivative had structure (3), theO-acetyl derivative would be expected to show a similardownfield shift of the olefinic proton signal by about 0.7p.p.m. The product is therefore assigned structure (2)and its acetyl derivative structure (5). The less hindered5-hydroxy-group of embelin appears to be replaced firstby methylamine. Alkaline hydrolysis of (2) gave embe-lin. Compound (2) was also the major product whenembelin was heated with 6 mol. equiv.of methylamine inacetic acid or with 2 mol. equiv. of methylamine at 230"without solvent. Methylation of embelin (1) with alimited amount of diazomethane afforded 5-O-methyl-embelin; use of an excess of reagent gave the di-0-methyl derivative (6). The monomethyl ether formed anacetyl derivative, which showed an olefinic proton signalat 8 5.9. Treatment of 5-0-methylembelin with 2 mol.equiv. of methylamine in ethanol gave compound (2).Similar treatment of embelin gave a mixture from whichonly about 15 of (2) could be isolated. Nucleophilicdisplacement of halogeno, alkoxy-, or alkyl substituentsfrom benzoquinones by alkylamines has been re-ported.2*9-11 However, some alkoxy-hydroxytoluquin-The Merck Index, Merck amp; Co. Inc., Rahway.New Jersey,1968, p. 406.2 D. W. Cameron and P. M. Scott, J . Chem. SOC., 1964, 5669.A. Hikosaka, Bull. Chem. SOC. Jafian, 1970, 48. 3928.W. K. Anslow and H. Raistrick. Biochem. J., 1938, 32, 803.R. Kaul, A. C. Ray, and S. Dutt, J. Indian Chem. SOC., 1929,6, 677.ones do not undergo replacement of the hydroxy-sub-stituent when treated with methylarnine.ll The form-ation of (2) from embelin therefore could be rationalized0 0R2HN ' ' CHiCH,,MeRO0 0( 1 ) R = H R' R 2( 4 ) R = AC ( 2 ) H Me( 5 ) Ac Me ( 6 ) R = Me(10) Me Me0I I(14) H E t(15) H CH2-CH2-0MeNHMe (16) H Pr"(17) H Bun(18) H CH2iOHHO(19) H CH2Ph(201 H CHiCHZPh( 3 )in terms of a 1,Zaddition of methylamine, followed byelimination of water (Scheme 1).Acetylation of embelin with acetic anhydride andpyridine afforded an unexpected product (7), identifiedon the basis of its U.V.(Am, 243 nm), i.r. Y,, 1780 cm-l(acetate) and n.m.r. spectra a 8.63 (2H, d, d, J 6 and 1.5Hz, pyridine a-protons), 7.25 (2H, d, d, J 6 and 1.5 Hz,p-protons), 26br (2H, ArCH,), 2.3 (6H, s, 2- and 4-OAc),and 1-98 (6H, s, 1- and 6-OAc), 1.3 (18H, s), and 0.9 (3H,m). Its mass spectrum showed the niolecular ion atm/e 541 and successive loss of four acetate units. Itsformation may be explained by attack of the acyl-pyridinium cation on the unsubstituted position of thequinone ring in embelin, to give (8) as an intermediate.When embelin was heated with 6 mol. equiv. or anexcess of 33 methylamine in ethanol, the bismethyl-imine (9) was obtained, identified on the basis of elemen-tal analysis and spectroscopic data. Its i.r.spectrumJ. A. Ballantine and C. T. Pillinger, Tetrahedron, 1967, 23,1961.R. E. MooreandP. J. Scheuer, J. Org. Chem., 1966,31,3272.8 H. Ogawa and S. Natori, Chem. and Pharm. Bull. Japan,9 J. Hoffmann, Ber., 1901, 34, 1668.1968, 16, 1709.l o 0. Boters, Ber., 1902, 35, 1602.l1 W. K. Anslow and H. Raistrick, J. Chem. SOC., 1939, 1446328 J.C.S. Perkin Iamine.12 Rao and Venkateswarlu claim to haveisolated compound (9), m.p. 167-168" (cf. our value of248"), by heating embelin with 2 mol. equiv. of methyl-amine without s01vent.l~ No proof was given for thisformulation except elemental analysis. Under the con-ditions described by Rao and Venkateswarlu we isolatedmainly compound (2), m.p.164", and, as a minor product,(9), m.p. 246-248". The m.p.s of the compounds ob-tained by Heffter and by Rao appear to indicatestructure (2) , and the compound isolated by Kaul et al.,although its m.p. is lower, structure (9). The form-ation of (2) or (9) from embelin therefore appears to besolvent-dependent .The bis-methylimine (9) is probably formed by two 1,Z-additions of methylamine to the quinone carbonyl groups ;its n.m.r. spectrum indicates that it exists predominantlyin the tautomeric form illustrated rather than as the 2,5-bismethylamino-l,4-quinone.did not show any carbonyl bands and its n.m.r. spectrumexhibited signals at 6 9.17 (2H, OH, exchanged by D,O),NHMeOH NMe( 1 ) - NHIMc HO 4s- Ho(-):0 0Ji0a ( 2 ) bR=CH2 loMeSCHEME 15-05 (lH, s, olefinic), and 3.15 (6H, s, =NMe).Compound(9) was also obtained by treating the monomethylamino-derivative (2) with an excess of methylamine in ethanol,or (in 15 yield) by heating embelin with an excessof methylamine at 200" without solvent.Kaul et al. obtained ' dimethylaminoembelin,' m.p.216", by heating embelin with an excess of dimethylaminey42*C H 23 9 Me YAcO HO ' ' CHiCH2I9Me$OHNRR0 H$oI Ibsol;N'Ac(81in methanol.6 Heffter and Feuerstein reported the form-ation of ' methylaminoembelin,' m.p. 1666", by con-densing embelin (then named embelic acid) with methyl-12 A. Heffter and W. Feuerstein, Arch. Pharm., 1900, 288, 16.13 T.V. P. Rao and V. Venkateswarlu, Tetrahedron, 1964, 20,969.N R ~ 0I I 0 NMeR' R2 (12)( 1 1 ) H Me(131 Ac Me(28) H Et( 2 9 ) H CHICH2-OMe(30) H Prn(31) H Bun( 3 2 ) H CH2iOH(331 H CH2Ph(34) H CHiCH,PhMethylation of compound (2) with diazomethane gavethe methyl ether (10). Treatment of di-O-methyl-embelin with an excess of methylamine in ethanol at 26or 80" afforded a bismethylamino-derivative, m.p. 152",isomeric with (9). Its i.r. v,, 3320 (NH), 3280(OH), and 1640 and 1620 cm-1 (C:O) and n.m.r.spectra 6 6.7br (lH, NH, exchanged by D,O), 5.22 (lH,s, olefinic), 3.21 (3H, s, =NMe), and 2-88 (3H, d, J 5 Hz,-NHMe; becomes a singlet on addition of D,O)suggested the structure (11) or (12). The singlet at 6 3.21and the doublet at 2.88 clearly show that the methylgroups are attached to a tertiary and a secondary nitro-gen atom, respectively. In the spectrum of compound(9) the six-proton singlet at 6 3.15 is ascribed to the twomethylimino-groups.Similar doublet N-methyl peaksin the spectra of methylamino-derivatives have beenobserved for some alkylaminobenz~quinones.~~A number of methoxy-benzoquinones and -tolu-quinones have been condensed with methylamine to14 K. Yoshihira, S. Sakaki, H. Ogawa. and S. Natori, Chem.and Pharm. Bull. Japan, 1968,16,23831975 329afford bismethylaminobenzoquinones by displacementof the methoxy- and methyl groups.ll It is difficult tochoose between the structures (11) and (12) from thepresent evidence; however the formulation (11) is pre-ferred for the following reasons: (a) one of the probablemodes of the formation of the compound is as shown in(611, amp;-additionNH2Me0MeHN (JyI INH2M.e 201, amp;addition / bsol; 1, amp;additionOHMeHN QR;:0 I..MeHN0J 0MeHN amp;:reOH-MeOH0MeHN' +OH ' R0( 2 )H201, amp;-addition .OH-MeOHNMe NMeMeHN $e = MeHNamp;I1 O h0( b l (a) (11)SCHEME 2 R = CH,,,,MeScheme 2; (b) addition of the second methylamino-group at the less hindered carbonyl group would beexpected; (c) the compound gives no colouration withion (111) chloride.* U.V., i.r., n.m.r., and mass spectral data of all products areavailable as Supplementary Publication No.SUP 21223 (4 pp.).For details of Supplementary Publications see Notice to AuthorsNo.7 in J.C.S. Perkin I, 1974, Index issue.Compound (11) was also obtained by reaction of (10)with methylamine in ethanol. In order to identify theintermediates formed in this reaction, di-O-methyl-embelin (6) was treated with methylamine at low tem-perature. The mixture obtained contained predomin-antly (ll), and also compounds (2) and (10). Hydrolysisof compound (1 1) with 5N-sulphuric acid gave 2-hydroxy-5-methylamino-3-undecyl-l,4-benzoquinone (2). Acetyl-ation of (11) gave a monoacetyl derivative (13), whosen.m.r. spectrum showed an olefinic proton signal at6 5.5.The generality of the reactions described above hasbeen shown by reactions of embelin (1) and di-O-methyl-embelin (6) with various aliphatic amines.Thus thecondensation of embelin with ethyl-, p-methoxyethyl-,propyl-, butyl-, 4-hydroxybutyl-, benzyl-, and phen-ethyl-amine in acetic acid afforded compounds (14)-(20), respectively (Tables 1 and 4). When the reactionof embelin was carried out with an excess of any of theabove-mentioned amines in ethanol, bisalkylimines (21)-(27), respectively, were obtained (Tables 2 and 5). Raoand Venkateswarlu report the production of the di-imine (26), m.p. 156-157", from the reaction of embelinwith benzylamine (2 mol. equiv.) in acetic acid.13 How-ever, the m.p. they report appears to correspond to theamino-quinone (19). Di-O-methylembelin (6) reactedwith these amines to afford compounds (28)-(34) ,respectively (Tables 3 and 6):The mass spectra of the alkylamino-quinones can beinterpreted in a similar way to those of long-chainalkylated hydroxy-benzoq~inones.~~EXPERIMENTALU.V. and i.r.spectra were determined with BeckmanDK-2A and Perkin-Elmer Infracord spectrophotometers.N.ni.r. spectra were taken with a Varian A-60 spectrophoto-meter (tetramethylsilane as internal reference). Massspectra were taken with an Atlas CH-7 spectrometer by useof the direct inlet system.Isolation of ErnbeZin (1).-The dried berries of Embeliatsjeriam Cottam (5 kg) were extracted with hot hexane(4 x 15 1). Evaporation, and crystallization of the residuefrom methanol gave embelin as orange plates (83 g), m.p.146", affording a red-brown colouration with alcoholic iron-(111) chloride; amp;= (EtOH) 290 nm (log E 4.32); v,,,(Nujol) 3300 (OH), and 1640 and 1620 cm-1 (chelatedcarbonyls); 6 (CD,),SO 5.8 (lH, s, 6-H), 2.4br (2H, t,ArCH,), 1.3 (18H, s, CH,), and 0.9 (3H, m, Me); m/e 294(M+, 40), 155 (30), 154 (loo), 153 (20), and 142 (15).5-O-~et~yZembeZin.-Embelin ( 5 g) was dissolved in ether( 150 ml) and ethereal diazomethane from nitrosomethylurea(6 g) was added.Removal of solvent and crystallizationfrom hexane afforded Z-hydroxy-5-~~ethoxy-3-undecyZ- 1,4-benzoquinone as yellow needles (2.0 g), m.p. 95-96', givinga violet colouration with iron(rr1) chloride; vmx. 3380 (OH),1640, and 1600 cm-l; 6 (CDCl,) 7-45 (lH, s, OH, exch. byD,O), 5.0 (lH, s, 6-H), and 3.9 (3H, s, OMe) (Found: C, 70.4;H, 9.4. C,,H,,O, requires C, 70.1; H, 9.2), M+, 308.The O-acetate formed lemon-yellow plates, n1.p.78" (Found :C, 68.5; H, 8.8. C2oH3oO5 requires C, 68.5; H, 8-6?/,).l5 H. Ogawa, S. Sakaki, K. Yoshihira, and S. Natori. Tetm-hedron Letters, 1968, 1387330 J.S.C. Perkin I2,5-Di-O-msthylembeZin (6) .-Enibelin (3 g) dissolved inether (I00 ml) was treated with an excess of diazomethane inether and left overnight. Removal of solvent and crystal-lization from aqueous methanol afforded the diether (6)(2.5 g), m.p. 58"; (EtOH) 288 nm (log E 4.13); v-(Nujol) 1670 and 1640 cm-1 (quinone) ; 6 (CDC1,) 5.75 (lH, s,6-H), 4.1 (3H, s, OMe), 3.85 (3H, s, OMe), 2-45br (2H, t,ASH,), 1.3 (18H, s), and 0.9 (3H, m); rn/e 322 (M+, loo),307 (5), 279 (lo), 275 (7), 183 (40), 182 (QO), 169 (60), and167 (60).Di-O-metyZembelin (4) .-Embelin (500 mg) was refluxedwith acetic anhydride (10 ml) for 1 h, and poured on crushedice.The precipitate was collected and crystallized fromaqueous methanol to afford the diacetate (4) (400 mg) as paleyellow needles, m.p. 59" (lit.,6 54'); amp;= (EtOH) 263 nm(log E 4.1); v,, (Nujol) 1800 and 1780 (acetate), and 1680afford pinkish red needles (2) (2.2 g), giving a dark violetcolouration with alcoholic iron(II1) chloride.(b) Embelin (2.94 g) and methylamine (3 ml; 33ethanolic solution) were heated under reflux at 230" for 30min. The mixture was ,poured into dilute hydrochloric acidand the precipitate collected. Crystallization from aceticacid gave (2) (1.4 9). T.1.c. of the mother liquor showedspots corresponding to compounds (9) and (11).(c) 5-O-Methylembelin (120 mg) in ethanol (15 ml) wasrefluxed with methylamine (80 mg) for 1 h.The precipitatewas collected and crystallized from acetic acid to give (2)2-A cetoxy-5-methylamino-3-undecyl- 1,4-benzoquinone (5).-A solution of compound (2) (300 mg) in pyridine (3 ml) andacetic anhydride (1.5 ml) was left overnight, then poured oncrushed ice. The precipitate crystallized from aqueous(80 mg) *TABLE 1Spectral data for 5-alkylamino-2-hydroxy-3-undecyl-1,4-benzoquinonesA-.(EtOH)/nm (log E) urn=. (Nujol)/cm-l 6 (p.p.m.) (CDCI,) m/e313, 600 (4.23, 3.1) 3300 (NH), 1668 (c--O) 5.2 (1H. s), 2.85 (3H, d, J 5 Hz. 307 (Mf, 100). 167 (86),NHMe; s on addition of D,O)64br (lH, NH, exch.D,O), 6.4(lH, s). 3.2 (2H, d, J 6 Hz,NHCH,), 3.42 (3H, s, OMe)7.25 (5H, s, Ph), 6.5br (lH,exch. D,O), 5.4 (lH, s), 3.35(2H, m, ArCH,), 3.0 (2H, q,NHCH,)166 (80), 164 (26), 138 (25)361 (M+, 80), 306 (60), 211(40), 210 (loo), 198 (15),166 (60)397 (Mf, 70), 306 (loo), 267(30), 256 (60), 166 (go),162 (20)315, 500 (4.27, 3.16)315, 600 (4.24, 3-16)3300, 16403360, 3300, 1660TABLE 2Spectral data for 2,5-dihydroxy-3-undecyl-1,4-benzoquinone bisalkyliminesA,,.(EtOH)/nm (log E) u-.(Nujol)/cm-l 6 (p.p.m.) (CDCI,) m/e216, 340infl., 360(4-46, 4-45, 4.48)216, 360 (4.47, 4.5)3180, 1590, 15103180, 1600, 16209-17br (2H, exch. D,O), 6.05(lH, s), 3-15 (6H, s, =NMe)84br (2H, exch. D,O), 5.2 (lH,s), 3-66 (8H, S, W* 2 Hz,=NCH,CH,*OMe), 3.4 (6H, s,OMe)9-17br (2H, exch.D,O), 7.25(lOH, S, Ph), 4-8 (lH, s), 3-65(4H, t, CH,Ph), 3.0 (4H, t,=NCH,)320 (M+, 30), 193 (la), 180(45). 179 (loo), 151 (16)408 (Mf, loo), 363 (30), 361(30), 349 (25), 331 (20), 268(30), 267 (98)500 (M+, 56), 409 (60). 407 (loo), 369 (80)256, 366 (3.89, 4-46) 3180, 1680, 1640and 1630 cm-l (quinone); 6 (CDCl,) 6.55 (lH, s, 6-H), 2.4(2H, m), 2.32 (6H, s, AcO), 1.3 (18H, s), and 0.9 (3H, m)(Found: C, 66.3; H, 8.3. Calc. for C,,H,O,: C, 66.6;H, 8.0).1,2,4,5-Tetra-acetoxy-3-pyvidyL6-undecylbenzene (7) .-Asolution of embelin (500 mg) in pyridine (5 ml) and aceticanhydride (10 ml) was kept overnight at 25", then dilutedwith crushed ice, and extracted with methylene chloride.The organic layer was washed with 5 hydrochloric acid,aqueous 5 sodium hydrogen carbonate, and water, thenevaporated. Crystallization of the residue from aqueousmethanol gave prisms (300 mg), m.p.115"; Lax. (EtOH)243 nm (log E 4.2); vmaX (Nujol) 1780 (acetate) and 1600cm-l; for n.m.r. data see Discussion section; m/e 541(Mf, l), 499 (5), 457 (16), 415 (25), 373 (loo), 274 (25),259 (20), and 233 (100) (Found: C, 66.2; H, 7.5; N, 2.7.C,,,H,,NO, requires C, 66-5; H, 7.2; N, 2.6).2-Hydroxy-5-methylamino-3-undecyZ- 1,4-benzoquinone (2).-(u) A mixture of embelin (2.94 g), methylamine (3 ml; 33ethanolic solution), and glacial acetic acid (40 ml) was heateda t 100" for 3 h. The crystalline residue which separated oncooling was collected and recrystallized from acetic acid tomethanol to give brownish needles (200 mg), m.p.78"; A,,(EtOH), 214, 289, and 490 nm (log E 4.3, 4.0, and 3.4) ; v,,(Nujol) 3260 (NH), 1760 (acetate), and 1660 and 1658 cm-1(quinone); 6 (CDCl,) 5-9br (lH, NH, exch. by D,O), 5.4 (lH,s, 6-H), 2.9br (3H, NHMe; becomes singlet on addition ofD,O), 2-38 (3H, s, AcO), 2.4 (2H, m) 1.3 (18H, s), and 0.9(3H, m) (Found: C, 69.2; H, 8.9; N, 4.0. C,,H,,NO, re-quires C, 68.7; H, 8.9; N, 4.0); Mf, 349.2-Methoxy-5-methylamino-3-undecyE 1,4-benzoquinone (1 0).-To a solution of compound (2) (300 mg) in methanol (10ml) and ether (40 ml), an excess of ethereal diazomethanewas added and the mixture was left overnight. Removal ofsolvent and crystallization from aqueous methanol affordedmaroonplates (18) (170 mg), m.p. 90"; Lx (EtOH) 312 and500 nm (log E 4-1 and 3-2) ; vmZ (Nujol) 3300 (NH) and 1650and 1640 cm-1 (quinone) ; 6 (CDC1,) 6.0br (lH, NH, exch.byD,O), 5.27 (lH, s, 6-H), 4.15 (3H, s, OMe), 2.85 (3H, d, 1 5Hz, NHMe; becomes singlet on addition of D,O), 2.4 (2H,m), 1.3 (18H, s), and 0.9 (3H, m) (Found: C, 71.0; H, 9.9;N, 4.6. Camp;amp;,NO3 requires C, 71.0; H, 9.7; N, 4.3).2,5-Dihydroxy-3-undecyL1,4-benzoqzcinone 1,4-Bismethyl-imine (9).-(a) A mixture of embelin (2.94 g), methylamin1975 331TABLE 3for 5-alkylamino-2-hydroxy-3-undecyl- 1,4-benzoquinone 1-alkyliminesCom-pound(11)(29)Spectral data215, 343 (4.42, 4.42)(34) 345 (4.47)Method ofof prep. 7abbaabbabaanYield75153765546651865107075()vmaI.(Nujol)/cm-l 6 (p.p.m.) (CDCI,) nz / e1590 s), 3.21 (3H, s, =NMe), 2-88 (loo), 151 (30)3320, 3280, 1640, 1620, 6.7br ( l H , exch.D20), 5.22 ( l H , 320 (M+, loo), 180 (30), 179(3H, d, J 6 Hz, NHMe; s onaddition of D20)6.8br (2H, exch. D20), 5.3 (lH,s), 3-65br (4H, s, NH-CH,.=N-CH2), 3.41 (3H, s, OMe),3.37 (3H, s, OMe), 3.1-3-6exch. D20), 5.3 (lH, s), 3-75(2H, t, J 7 Hz, =N*CH2), 3.3(2H, t , J 6 Hz, d on additionof D20, NHCH,), 2-95 (4H,m, CH2Ph)3320, 3250, 1650, 1625, 408 (M+, 40), 376 (loo), 363(46), 331 (60), 268 ( 5 ) , 267(15), 235 (15)1570(4H9 m, CH2)3300, 3230, 1640, 1610, 7.25 (lOH, s, Ph), 6-7br (lH, 500 (M+, 40), PO8 (loo), 3591600, 1550 (lo), 305 (15)TABLE 45-AlkyIamino-2-hydroxy-3-undecyl- 1,4-benzoquinones 7Found () Required (yo)A AI .I r Mp.("C) Formula C H N C H I?164 C18H29N03 70.5 9.8 4.4 70.3 9.5 4.671.1 9.9 4.6 71.0 9.7 4.49.7 4.7 68.3 9.5 4.0 68.74.7 71.6 9.9 4.2105 C21H3SN03 72.6 10-1 4.3 72.2 10.1 4-0120 C19H31N03105 C20H33N04 100 C20H33N03 71.5 10-284 C21H35N04 69.1 9.5 3.8 69.0 9.6 3.875.5 9.0 3.9 75.2 8.7 3.775.5 8.9 3.5160 C24H23N03 138 C25H35N03 75.3 9.0 3.4Embelin was refluxed with the appropriate amine (2 mol. equiv.) for 3 h; a, in glacial acetic acid; b, in ethanol.TABLE 52,5-Dihydroxy-3-undecyl- 1,4-benzoquinone 1,4-bisalkyliminesFound (76)Method of Yield r A Compound prepn.? (yo) M.p. "(C) Formula C H NRequired (7;)C H Na 56 248 C,,H3,N20, 71.3 10.3 8.8 71.2 10.1 8.7b 15a 40 235 C2,H,,N202 72.6 10.7 8.3 72.4 10.4 8.0a 20 200 C2,H4amp;N2O4 67.7 10.1 6.8 67-6 9.9 6.9a 66 215 C23H40N,02 73.7 11.1 7.7 73.4 10.7 7.4b 30b 40a 50 138 C2,H,,N,04 68.6 10.3 6.7 68.8 10.2 6-4a 85 230 C31H40N20, 78.8 8.8 6.3 78.8 8.5 5.9( 9)(21)(22)(23)t 24)(25)(26)(27)n 75 210 C25H44N202 74.5 11.3 7.1 74.2 11.0 6.9U 75 185 C3,H,,N,02 79.1 9-2 5.6 79.2 8.9 5.6a Embelin was refluxed with the appropriate amine (6 mol.equiv.) for 3 h in ethanol. b Embelin was heated at 200" with t h eappropriate amine (6 mol. equiv.) for 3 h.TABLE 65-Alkylamino-2-hydroxy-3-undecyl- 1 ,4-benzoquinone l-alkylimines 7Found (yo) Required ()* Yield r 7 ,- Compound () M.p.("C) Formula C H N C H71.6 10.3 8-7 71-2 10.110.6 8.3 72.4 10.467.7 10.1 6.8 67.6 9.973.4 10.7 73.4 10.9 7-67.3 74.2 11.0 74-4 11.268.8 10.2 68.8 10.3 6.76.1 78.8 8.58.965 152 C19H32N20248 52 C23H40N20425 72 C23H40N20250 82 C25H44N20245 83 C25H44N20440 107 C21H,N,0, 72.6(11)(28)(29)(30)(31)(32)(33)(34)81 lo C31H40N202 78.5 8.750 75 C33H44N,02 79.3 9.2 5.8 79.2t Di-U-methylembelin was refluxed with the appropriate amine (6 mol. equiv.) for 3 h in ethanol."8-78.06.97-46.96.45-95.332(10 ml; 33 ethanolic solution), and ethanol (90 ml) washeated a t 100" for 3 11. The precipitate obtained on coolingwas collected and crystallized from ethyl acetate to afforddark blue needles (9) (1.8 g).The violet alcoholic solutionbecame brown on addition of iron(II1) chloride.(b) A mixture of compound (2) (90 mg), methylamine(1 ml; 33 ethanolic solution), and ethanol (3 ml) washeated a t 100" for 1 h, then cooled. The solid was collectedand crystallized from ethyl acetate to afford dark blueneedles (27 mg), identical with compound (9) obtained in (a)(mixed m.p., t.l.c., and i.r. spectra).2-Hydroxy-5-methylamino-3-undecyl- $,4-benzoquinone 1 -Methylimine (1 1) .-(u) A solution of di-O-methylembelin (6)(1-2 g) in ethanol (20 ml) and methylamine (4 ml; 33ethanolic solution) was kept a t 25" for 20 min. The crystal-line precipitate which separated was collected and crystallizedfrom niethylene chloride-methanol to afford violet plates(11) (0.8 g ) .The purple colour of a solution of (11) inethanol faded to a pale colour on addition of iron(m)chloride.(b) A mixture of compound (6) (800 mg), ethanolic 33:4methylamine (2.5 ml), and ethanol (20 ml) was heated underreflux for 3 h. Crystallization of the product whichseparated on cooling gave (1 1) (500 mg) .(c) A. mixture of compound (6) (320 nig), ethanolic 3376methylamine (100 mg), and ethanol (5 ml) was kept a t 10"for 30 min and a t 25" for 1 h. The crystalline precipitatewas collected (170 mg) and recrystallized from methylenechloride-methanol to afford violet plates (1 1) (1 50 mg) .J.C.S. Perkin IThe mother liquor was evaporated to dryness and the residuechromatographed on silica gel. Elution with benzene gavecompounds (2) (50 mg), m.p. 162-164O, and (10) (35 mg),m.p. 89-90', identified by mixed m.p., t.l.c., and i.r. spec-tral comparison.2-Acetoxy-5-.~zetJ~ylamino-3-undecyl- 1 ,Cbenzoquinone 1 -Methylimine (1 3) .-Compound (1 1) (300 mg) was refluxedwith acetic anhydride (6 ml) for 2 h. The mixture wasfiltered and the filtrate poured on crushed ice; the solidproduct crystallized from aqueous methanol to give brick-red needles (100 nig), m.p. 68"; A,. (EtOH) 216, 285, and350 nm (log E 4-41, 3.73, and 3-6) ; v, 3280 (NH) and 1670cm-l (acetate); 6 (CDCI,) 5.9br (lH, NH), 5-5 (lH, s, 6-H),3.1 (3H, s, =NMe), 2.9 (3H, d, J 5 Hz, NHMe), 2-4 (2H, m),1.9 (3H, s, AcO), 1-3 (18H, s), and 0.9 (3H, m); m/e 362(Mi, go), 320 (loo), 207 (20), 179 (go), and 151 (50)(Found: C, 69.3; H, 10.0; N, 7.8. C21H34K203 requiresC, 69.6; H, 9.5; N, 7.7).Acidic Hydrolysis of Compound (1 1) .-Compound (1 1) (30mg) was heated with 5~-sulphuric acid (15 ml) a t 140" for1.5 h. The mixture was diluted with crushed ice and thecollected precipitate was washed with water and crystallizedfrom methanol to afford pinkish needles of compound (2)(10 mg), m.p. 162-164".We thank Professor T. R. Govindachari for his interest inthis work, Dr. S. Selvavinayakam and his associates foranalytical and spectral data, and Dr. P. C. Parthasarathyfor discussions.4/1678 Received, 9th August, 1974