WOLFROM, KOOS,AND BHAT
1058 TABLE I1 MASSSPECTROMETRIC DATA Obsd
CsH& (CnoHt~O6)~+ CiiHioOz CiiH703 (CzlHi407)'+ ( CszHi 7 0 7 ) ' CZOHlzO6 CzoHii07 C22Hla6 CZzHl806 CzzH1707 C23Hzo07 +
(C21H1406)2+ ( C21H1506)2f C21H1506
CsH605 CsH706 ClOHloO6
Calcd
Ferrugone 161.0245 174.0322 174,0669 187.0402 189.0376 196,5475 348.0670 363.0509 377.1049 378.1050 393.0972 408,1195 Durmillone 181.0377 181,5430 363.0879 378.1106 Apiolic Acid 153.0172 181.0123 211,0226 226.0457
161 0239 174.0317 174.0681 187,0395 189.0369 196.5487 348.0634 363.0505 377.1025 378.1103 393.0974 408,1209 I
181.0395 181.5434 363.0869 378.1103 153.0188 181.0137 211.0242 226.0477
Osage Orange Pigments.
VOL. 32
centrated to dryness under reduced pressure. Chromatography on a silicic acid plate (Rr 0.72; 90 benzene, 25 dioxane, 4 acetic acidi5) provided 1.5 mg of apiolic acid, mp 169-172'. The mass spectrum (see Table 11) and infrared spectrum (KBr) were identical with those of authentic apiolic acid: vmgX (KBr) 2930, 2860, 1690, 1630, 1590, 1325, 1070, 1045,965,940 cm-1. Preparation of Authentic Apiolic Acid.-Parsley seed oil (Fritsche Brothers, New York, N. Y.) was distilled through a Podbielniak column at 19 mm to a temperature of 167'. Distillation of the residue at 124-127" (0.3 mm) and recrystallization from pentane provided apiole: mp 29-30.3' (lit." mp 30'); Amax 282 mp (e 904); vmSx (film) 1640, 1610, 1498 (aromatic), 1240, 1060 (CH10), 1045, 952 (OCHZO),990, 910 (vinyl) cm-1; nmr (in CDCl3) 6.33 (aromatic, s, l), 5.95 (OCHzO, s, 2), 3.90 (OCH3, s, 3),3.86 (OCH,, s, 3), ca. 6.0 (vinyl, m, I), ca. 5.2 (vinyl, m, l), ca. 4.9 (vinyl, m, I),ca. 3.4 (allyl, m, I ) , ca. 3.3 ppm (allyl, m, 1); (in benzene) 5.45 (OCHZO,s, 2), 3.75 (OCHa, s, 3),356 (OCH3, s, 3); other resonances were unchanged. Oxidation of this material by alkaline permanganate and crystallization from water gave tt small yield of apiolic acid: mp 175" (lit." mp 175'); nmr (CDC13) ca. 10.5 (1, br), 7.45 (1, s), 6.17 (2,s), 4.18 (3,s), 3.93 ppm (3,9).
Registry No.-I, 7731-08-0; V, 7731-09-1; 111, 773 1-10-4; apiole, 523-80-8. (15) H.J. Petrowitz and G. Pastuska, J . Chromatog., 7, 128 (1962). (16) E.v. Gerichten. Ber. Dtsch. Chem. Ces., 9, 1477 (1876). (17) G. Ciamioian and P. Silber, ibid., 21, 1621 (1888).
XVIII.l Synthesis of Osajaxanthone
M. L. WOLFROM, E. W. KOOS,AND H. B. BHAT Department of Chemistry, The Ohio State University, Columbus, Ohio 4SglO Received October 18,1966 The p-toluenesulfonate ester is established as an effective blocking group for the conversion of phenolic 2,2-dimethylchromanones to chromanols and chromenes. Attempts to prepare osajaxanthone (8) derivatives from 7-hydroxy-5-methoxy-2,2-dimethylchromene( 5 ) failed. The previously synthesized dihydroosajaxanthone monomethyl ether ( 6 ) was converted into osajaxanthone monomethyl ether (8,7 = OMe), dihydroosajaxanthone (7),and osajaxanthone (8),the last named being identical with the natural pigment.
The 2,2-dimethylchromene ring system is of common occurrence in plant pigments, where it is frequently found attached to coumarin, flavone, isoflavone, xanthone, and other heterocyclic ring systems containing the ypyrone nucleus. Two isoflavone pigments, osajin and pomiferin, have been isolated in this laboratory from the fruit of the Osage orange (Maclura pomifera Raf.)3 and have been shown to contain the 2,2TWOxanthone pigdimethylchromene ring ~ y s t e m . ~ ments, macluraxanthone and osajaxanthone (8))isolated from the root bark of this same treel5 have likewise been demonstrated to possess this ring (1) Previous communication in this series: M. C, Wolfrom and H. B. Bhat, Phytochemistry, 4, 765 (1965). (2) W. B. JThalley in "Heterocyclic Compounds," Vol. 7, R. C. Elderfield, Ed., John Wiley and Sons, Inc., New York, N. Y., 1961, p 1; W. D. Ollis and I. 0. Sutherland in "Recent Developments in the Chemistry of Natural Phenolic Compounds," W. D. Ollis, Ed., Pergamon Press Ltd., London, 1961, p 84. (3) E. D. Walter, M. L. Wolfrom, and W. W. Hess, J . Am. Chem. Soe., 60,574 (1938);M. L. Wolfrom, F. L. Benton, A. S. Gregory, W. W. Hess, J. E. Mahan, and P. R. Morgan, ibid., 61, 2832 (1939). (4) M. L. Wolfrom, W. D. Harris, G . F. Johnson, J. E. Mahan, S. M. Moffett, and B. Wildi, ibid., 68, 406 (1946). (5) M. L.Wolfrom, E. E. Dickey, P. McWain, A. Thompson, J. H. Looker, 0. M. Windrath, and F. Komitsky. Jr., J . Ow. Chem., 29, 689 (1964). (6) M. L. Wolfrom, F. Komitsky, Jr., G. Fraenkel, J. H. Looker, E. E. Dickey, P. McWain, A. Thompson, P. Mundell, and 0. M. Windrath, ibid., as, 692 (1964). (7) M. L. Wolfrom, F. Komitsky. Jr., and J. H. Looker, ibid., 80, 144 (1965).
Several approaches to the synthesis of osajaxanthone
(8), the simplest of these Osage orange pigments, have
been under investigation in this laboratory. Dihydroosajaxanthone monomethyl ether (6) was successfully synthesized.' One approach to the synthesis of the natural pigment was to build the xanthone ring onto 7-hydroxy-5-methoxy-2,2-dimethylchromene(5) with a suitably substituted o-hydroxybenzoic acid. To this end 5,7-dihydroxy-2,2-dimethylchromanone' ( 1) was converted into 5-methoxy-7-(p-tolylsulfonyloxy)-2,2dimethylchromanone (2) in one step. Chromanone 2 was converted, in 82% yield, into chromanol 3 by reduction with lithium aluminum hydride and 3 was dehydrated (90% yield) with p-toluenesulfonic acid to form chromene 4. The p-toluenesulfonate group in 4 was then removed to form the desired 5-(methyl ether) ( 5 ) of the 5,7-dihydroxy-2,2-dimethylchromene. Chromene 5 was, however, unsuitable for xanthone formation with the acidic reagents normally employed for this synthesis and only intractable red tars were obtained in the reaction. In view of the reported stability toward nitric acid of the chromene double bond in the closely related, naturally occurring chromene allo-evodionolls such behavior was not anticipated. (8) D. J. McHugh and 9. E. Wright, Australian J . Chem., 1, 166 (1964).
SYNTHESIS OF OSAJAXANTHONE
APRIL1967
During the progress of this work, the notable synthesis of jacareubin was reported by Jefferson and S ~ h e i n m a n n . ~In the work herein recorded, the method established by these investigators was used to introduce the double bond into the chromane ring system. The monoacetate (6,1 = OAc) of the previously synthesized? dihydroosajaxanthone monomethyl ether was brominated with N-bromosuccinimide and the crude product was dehydrobrominated with pyridine followed by deacetylation. Separation of the crude mixture by thick layer chromatography yielded osajaxanthone monomethyl ether (8,7 = OMe), but attempts to demethylate this substance were unavailing. A successful synthesis of osajaxanthone (8) was effected by demethylation, in 15% yield, of previously synthesized7 dihydroosajaxanthone monomethyl ether (6) with aluminum bromide and hydrogen chloride. Dihydroosajaxanthone (7) so obtained was acetylated, brominated, dehydrobrominated, and finally deacetylated as before, to yield osajaxanthone (8) in 33% yield. The synthetic osajaxanthone was identical with the natural pigment in all respects. (See Scheme
1.1 SCHEME I
P
5/
0
OH
O
T
S
+
OMe
woTs 0
2
1
-t
H OH
V 0 n 0 T s
OMe
-F
OMe
aoH 4
3
OMe
5
6
0
0
7
8
Experimental Section 5-Methoxy-2,2-dimethyl-7-(p-tolylsulfonyloxy)chromanone ( 2 ) . -A mixture of 5,7-dihydroxy-2,2-dimethylchromanone'( 1, 10.5 g) , potassium carbonate (50 g), p-toluenesulfonyl chloride (9.5 g, added in two lots a t 30-min intervals), and acetone (150 ml) was refluxed for 5 hr. After cooling, more potassium carbonate (20 g) and methyl iodide (20 ml) were added and refluxing was continued for 16 hr. The mixture was filtered and evaporated to a crystalline residue which was recrystallized 5.90 from dilute methanol: yield 18.0 g 95%); mp 152'; X:I (C=O), 6.25 (aromatic), 7.25, 8.05 (ether), 8.45, 9.10 (ether), 9.80, 10.30, 11.80, and 12.80 w.lo Anal. Calcd for ClgHnoOeS: C, 60.63; H, 5.32. Found: C, 60.42; H, 5.23. 5-Methoxy-aJ2-dimethyl-7-( p-tolylsulfonyloxy)chromanol ( 3 ) . -The chromanone 2 (22.6 g) was suspended in anhydrous ether (500 ml) and heated with powdered lithium aluminum hydride (2.5 g). The mixture was refluxed for 4 hr. After treatment with (9) A. Jefferson and F. Scheinmann, J . Chem. Soc., Org. Sect., 175 (1966). (10) Infrared spectra were measured on a Perkin-Elmer Infracord infrared spectrometer.
1059
dilute acetic acid, the ether layer was washed with water and aqueous sodium hydrogen carbonate solution, dried, and concentrated to a crystalline product: yield 18.5 g (82%), mp 148'; 2.9 (OH), 6.25 (aromatic), 6.9, 7.4, 8.1 (ether), 8.4, 8.5, 9.1 (ether), 9.9, and 11.8 p . Anal. Calcd for CigHnOeS: C, 60.32; H, 5.82; S, 8.46. Found: C, 60.68; H, 5.95; S, 8.56. 5-Methoxy-2,2-dimethyl-7-( p-tolylsulfonyloxy)chromene ( 4 ) A mixture of chromanol 3 (5.0 g), toluene (250 ml), and p toluenesulfonic acid (0.1 g) was distilled slowly for 15 min. The orange solution was cooled, washed with water, dried, and evaporated to dryness under diminished pressure. The residue crystallized from methanol in colorless plates: yield 4.2 g (88'%); mp 98"; : : :X 6.1 (C=C), 6.28 (aromatic), 7.3, 8.1 (ether), 8.5, 8.9, 9.2 (ether), 9.9, 11.7, and 13.6 w . Anal. Calcd for ClgH2006S: C, 63.33; H, 5.56; S, 8.89. Found: C, 63.58; H, 5.66; S, 9.14. 7-Hydroxy-5-methoxy-2,2-dimethylchromene( 5 ) .-A solution of potassium hydroxide (9.0 g) in water (150 ml) and ethanol (150 ml) was prepared. The alkaline solution (225 ml) was added to the chromene 4 (3.0 g) in three 75-ml portions a t l5-min intervals. After refluxing for 1 hr, the solution was cooled, neutralized with acetic acid, and concentrated a t 50' under diminished pressure. The mixture was extracted with ether and the extract was washed successively with aqueous sodium hydrogen carbonate and 3% aqueous sodium hydroxide solution. The sodium hydroxide portion was saturated with carbon dioxide and the crystalline compound that separated was filtered and was recrystallized from ether- etroleum ether (bp 30-60"): yield 1.0 g (60%); mp 104'; 230 mp ( e 17,310), 287 mp ( e 10,290;11 3.05 (OH), 6.12 (C=C), 6.28 (aromatic), 6.90, 8.10 (ether), 8.40, 8.75, 9.05, 9.20 (ether), 9.80, 12.30, and 13.10 p ; nmr spectral2 (CDC18) showed signals for a pair of vinyl doublets a t T 3.3 and 4.43 (J = 10 cps), a six-proton singlet at 8.4 (two CCH, groups, indicating the 2,2-dimethylchromene ring system13), a singlet at 3.6 (OH), a two-proton doublet a t 3.9 (J = 3 cps, aromatic protons), and a three-proton singlet at 6.1 (OCH3). Anal. Calcd for C&403: C, 69.88; H, 6.83. Found: C, 69.79; H, 6.67. When this chromene was employed for xanthone formation with 2-hydroxy-5-methoxybenzoicacid in the presence of phosphorus oxychloride, zinc chloride,14 or polyphosphoric acid,15 only red resins were obtained. Synthesis of Osajaxanthone Monomethyl Ether (8, 7 = OMe) .-A mixture of the monoacetate (790 mg) of the previously synthesized7 dihydroosajaxanthone monomethyl ether (6), N-bromosuccinimide (363 mg)! potassium carbonate (100 mg), and benzoyl peroxide (2 mg) in carbon tetrachloride (100 ml) was refluxed for 8 hr. The cooled mixture was filtered and the filtrate was evaporated to dryness under diminished pressure to obtain a colorless residue. The residue was dissolved in pyridine (50 ml) and heated under a nitrogen atmosphere a t 100" for 1 hr. Evaporation of the pyridine, under diminished pressure, gave a brown syrup which was dissolved in 370 ethanolic sodium hydroxide solution (50 ml) and heated at 85' for 45 min. The solution was acidified with 2 .V hydrochloric acid and the resulting precipitate was collected and purified by thick layer chromatography [silica gel, petroleum ether (bp 65-11Oo)-benzene-ethyl acetate, 4:4: 1 (v/v) developer]. Recrystallization from methanol gave yellow needles: yield 175 mg (22yc);mp 181-182' (lit.? mp 181-182"); with material prepared from the natural pigment, mmp 181-182'; X-ray powder diffraction data 14.26 s, 11.19 m, 9.61 vs (3), 6.97 s, 5.99 s, 5.44 m, 4.90 w, 4.60 w, 4.37 w, 4.17 w, 3.79 m, 3.43 vs ( l ) , 3.30 vs (2), and 3.6 m. The X-ray powder diffraction pattern16 and the infrared spectra were identical with those of a sample prepared from the natural
.-
(11) Ultraviolet spectrum was measured on a Bausch and Lomb Spectronic 505 spectrometer. (12) Nmr spectral data were obtained with a Varian A-60 nmr spectrometer with tetramethylsilane as internal reference. The probe temperature was -30°. (13) B . F. Burrows, W. D . Ollis, and L. M. Jackman, Proc. Chem. Soc., 177 (1960); L. Crombie and J. W. Lown, J . Chem. Soc., 775 (1962). (14) P. K.Grover, G. D . Shah, and R. C. Shah, ibid., 3982 (1955). (15) B . M.Desai, P. R. Desai, and R. D. Desai, J . Indian Chem. Soc., 57, 53 (1960). (16) X-Ray powder diffraction pattern data give interplanar spacings, in angstroms, for Cu Ka! radiation. Relative intensities were estimated visually: 8, strong; m, medium; w,weak; v , very. Three strongest lines are numbered (1, strongest).
1060
VOL.32
HAYSAND LAUGHLIN
pigment. Attempts to demethylate this material by various methods were unsuccessful. Dihydroosajaxanthone (7).-A mixture of the synthetic dihydroosajaxanthone monomethyl ether7 (6, 240 mg), aluminum bromide (500 mg), and anhydrous benzene (20 ml) was saturated with dry hydrogen chloride and refluxed for 2 hr. The mixture was poured into ice and dilute hydrochloric acid and stirred for 1hr. Evaporation of the benzene left a precipitate in the aqueous layer which was collected. Thick layer chromatography [silica gel, petroleum ether (bp 65-110°)-benzene-ethyl acetate, 4:4: 1 (v/v) developer] followed by recrystallization from ethanol gave yellow crystals: yield 35 mg (15%), mp 299-300' dec (lit.? 299-300" dec); mmp 299-300' dec; X-ray powder diffraction datar6 11.79 m, 10.40 s, 9.41 s, 6.81 s, 5.91 s, 5.22 w, 4.55 w, 4.29m, 4.00vs(3), 3.85vs(2), 3 . 2 4 v s ( l ) , and3.00m. X-ray powder diffraction pattern and infrared spectra of the reaction product with the dihydro derivative of the natural pigmenc showed the two to be identical. Osajaxanthone (8).-A mixture of the above synthetic dihydroosajaxanthone (7, 35 mg), sodium acetate (308 mg), and acetic anhydride (4 ml) was refluxed for 2 hr and poured into water. The resulting precipitate was collected and dried. A mixture of the compound (40 mg), N-bromosuccinimide (18.4 mg), potassium carbonate (20 mg), and benzoyl peroxide (1 mg) in carbon tetrachloride ( 2 5 ml) was refluxed for 9 hr. The solu-
tion was cooled and filtered, and the filtrate was evaporated. The residue was dissolved in pyridine and heated under nitrogen at 100" for 1 hr. The pyridine was evaporated under reduced pressure and the syrup that was obtained was dissolved in 1% ethanolic sodium hydroxide solution (30 ml) and heated a t 75' for 1 hr. The solution was acidified with 2 N hydrochloric acid and the resulting precipitate was chrometographed on thick layer plates [silica gel, petroleum ether (bp 65-110°)-benzene-ethyl acetate, 4:4: 1 (v/v) developer]. Recrystallization from methanol yielded yellow needles [yield 10 mg (30%), mp 264' (lit.9 mp 264-265"), with the natural pigment mmp 264'1. The X-ray powder diffraction pattern and the infrared spectra of the compound and the natural pigment5 were identical.
Registry No.-8, 1043-08-9; 2, 7661-00-9; 3, 766101-0; 4,7661-02-1; 5,7661-03-2; 8 (7=OMe), 3257-076; 7, 3257-10-1. Acknowledgments.-This investigation was supported by funds from the State of Ohio administered by the Office of Research, The Ohio State University. We are pleased to acknowledge W. A. Ssarek for the nmr spectrum and T. Radford for helpful discussions. Microanalyses were by W. N. Rond.
Reaction of Tetraalkylphosphonium Salts with Anhydrous Sodium Hydroxide H. R. HAYSAND R. G. LAUGHLIN The Procter & Gamble Company, M i a m i Valley Laboratories, Cincinnati, Ohio 45239 Received July 25, 1966 The reaction of anhydrous sodium hydroxide with tetraalkylphosphonium halides to produce trialkylphosphine oxides and alkanes has been shown to proceed under considerably milder conditions and permit more facile isolation of the phosphine oxides than when aqueous sodium hydroxide is used. Anhydrous dodecyltrimethylphosphonium hydroxide is surprisingly unstable and decomposes rapidly at 25-28'. By contrast, a 0.25 M aqueous solution of this phosphonium hydroxide was refluxed for 40 hr without apparent decomposition. A marked difference in reactivity of the various dodecyltrimethylphosphonium halides with anhydrous sodium hydroxide was observed. Reaction temperatures of 68-80' are required for the chloride, 80-110' for the bromide, and 140-150' for the iodide. An interpretation of these differences based on relative stabilities of ion pairs is suggested. Methyl groups are cleaved faster than dodecyl groups from dodecyltrimethylphosphonium halides by a factor of about 50: 1. This corresponds to a difference in activation energies of about 2.9 kcal between transition states leading to methane and dodecane. This energy difference is attributed largely to the energy difference between the methyl and higher alkyl carbanions.
The reaction of aqueous base with phosphonium salts has long been known to give tertiary phosphine oxides and the hydrocarbons resulting from the most stable carbanion.'J Early workers3 visualized this reaction as proceeding cia a pentacovalent phosphorus intermediate (RIPOH) whose formation was rate determining. Subsequently, it was shown that the reaction of ben~yl-~,6 and phenylphosphonium6J salts in dilute solution is generally second order in hydroxide ion and first order in the phosphonium salt. These facts are best explained by a series of rapidly established equilibria followed by the slow decomposition of the pentacovalent phosphorus anion (R4PO-) to the tertiary
phosphine oxide and the most stable carbanion, which rapidly forms the hydrocarbon.8 Since a polar protic solvent such as water, capable of strong solvation of ions and hydrogen bonding with hydroxide ion, should retard the reaction,6,9110 and because alkyl-substituted phosphonium salts are less reactive to hydroxide ion than benzyl- or phenyl-substituted phosphonium the reaction of anhydrous sodium hydroxide with tetraalkylphosphonium salts was investigated. In addition, t,he use of anhydrous sodium hydroxide was investigated because frequently tertiary phosphine oxides are hygroscopic and very difficult to isolate from aqueous solution.ll Results and Discussion
(1929). (1933).
(1) G. W. Fenton and C. K. Ingold, J . Chem. Soc., 2342 (2) K. D. Berlin and G . B. Butler, Chem. Rev., 60, 243 (1960). (3) L. Hey and C. X. Ingold, J . Chem. soc., 531
(4) M. Zanger, C. A. Vander R e d , and W. E. MoEwen, J . A m . Chem. Soc., 81, 3806 (1959). (5) G . Aksnes and J. Songstad, Acta Chem. Scand., 16, 1426 (1962). (6) H. Hoffmann, Ann., 634, 1 (1960). (7) G. Aksnes and L. J. Brudvik, Acta Chem. Scand., 17, 1616 (1963).
The reactions of dodecyltrimethylphosphonium chloride, bromide, and iodide, methyltridodecylphosphonium bromide, and dodecyltriethylphosphonium chloride with anhydrous sodium hydroxide were generally car(8) W. E. McEwen. K. F. Kumli, A. Blade-Font, M . Zanger, and C. A . Vander Werf, J . A m . Cham. Soc., 86, 2378 (1964). (9) A. J. Parker, Quart. Rev. (London), 16, 163 (1962). (10) M. R. V. Sahyun and D. J. Cram, J . A m . Chem. Soc., 85, 1263 (1963). (11) C. Screttas and A. F. Isbell, J . Ore. Chem., 27, 2573 (1962).
