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Org. Synth. 2003, 80, 227

DOI: 10.15227/orgsyn.080.0227

PREPARATION OF 9,10-DIMETHOXYPHENANTHRENE AND 3,6-DIACETYL-9,10-DIMETHOXYPHENANTHRENE

[(Phenanthrene, 9,10-dimethoxy- and Ethanone, 1,1'-(9,10-dimethoxy-3,6-phenanthrenediyl)bis-)]

Submitted by Kamil Paruch, Libor Vyklicky, and Thomas J. Katz¹.

Checked by Mitsuru Kitamura and Koichi Narasaka.

1. Procedure

Caution: Dimethyl sulfate is highly toxic and a potential carcinogen. It should be handled with appropriate safeguards in a well-ventilated fume hood.

A. 9,10-Dimethoxyphenanthrene. A mixture of 26 g (0.125 mol) of 9,10-phenanthrenequinone (Note 1), 13 g (0.04 mol) of tetrabutylammonium bromide (Bu₄NBr), 65 g (0.37 mol) of sodium dithionite (Na₂S₂O₄), 250 mL of tetrahydrofuran (THF), and 250 mL of water is shaken for 5 min in a 2-L separatory funnel. Dimethyl sulfate (62 mL, 0.65 mol) is added, followed by an aqueous solution of sodium hydroxide (64 g, 1.6 mol, in 125 mL of water) and 200 g of ice. The mixture is shaken for 5 min and, after another 200 g of ice has been added, shaken for another 10 min. Ethyl acetate (EtOAc, 100 mL) is added and the mixture is shaken. The aqueous phase is separated and extracted with EtOAc (2 × 100 mL). The combined organic extracts are washed with water (3 × 100 mL), 15% aqueous ammonia (2 × 100 mL), water (3 × 100 mL), and finally brine (100 mL). The solution is dried over sodium sulfate (Na₂SO₄) and filtered. The solvents are removed under vacuum (initially using a water aspirator, then at 0.5 torr). The residue, a thick brown oil. is dissolved in 80 mL of a ca. 2:1 mixture of dichloromethane (CH₂Cl₂) and hexane and poured onto a plug of neutral alumina, from which it is eluted with a 170-mL portion of the solvent mixture. After the solvent has been removed, the residue is dried under vacuum (ca. 0.5 torr) to give 23.7 g (80%) of 9,10-dimethoxyphenanthrene as a yellow oil (Note 2).

B. 3,6-Diacetyl-9,10-dimethoxyphenanthrene. A 1-L, three-necked, round-bottomed flask, fitted with an addition funnel, mechanical stirrer, and hydrogen chloride trap, is charged with 23.7 g of 9,10-dimethoxyphenanthrene and 120 mL of CH₂Cl₂ (Note 3). The solution is cooled in an ice-bath, and acetyl chloride (120 mL, (Note 4)) is added slowly. The cooling bath is removed, and over the course of 5 min, 44 g (0.33 mol) of aluminum chloride (Note 5) is added in portions to the stirred solution. The mixture is stirred for 15 min at ambient temperature and then carefully poured onto 1 L of crushed ice. The organic phase is separated, and the aqueous phase is extracted three times with 120-mL portions of CH₂Cl₂. The combined organic phases are washed with 120 mL of water, then with 120 mL of saturated aqueous sodium bicarbonate (NaHCO₃). The solution is dried over Na₂SO₄ and filtered. The solvent is removed, and the residual solid is suspended in 120 mL of methanol (MeOH), filtered, washed with an additional 120 mL of MeOH, and then dried (80°C/ca. 0.5 torr) to afford 24.8 g (77% yield based on dimethoxyphenanthrene, 62% yield based on phenanthrenequinone) of 3,6-diacetyl-9,10-dimethoxyphenanthrene as a slightly pale yellow solid (Note 6).

2. Notes

1. 9,10-Phenanthrenequinone (95%), purchased from Acros, was used as received. The checkers purchased it from Tokyo Chemical Industry.

2. In two runs, the checkers obtained 27.0 and 25.7 g (91% and 90% yields). IR (neat film between NaCl plates) cm⁻¹: 2936, 1602, 1327, 1070. ¹H NMR (CDCl₃, 500 MHz in accord with the literature²) δ: 4.10 (s, 6H), 7.59-7.65 (m, 4H), 8.24 (dd, J = 8.0, J = 1.5, 2H ), 8.64 (dd, J = 7.0, J = 1.5, 2H); ¹³C NMR (CDCl₃, 75 MHz) δ: 60.9, 122.1, 122.6, 125.8, 126.8, 128.6, 129.1, 143.9. HRMS (FAB) m/z calcd for C₁₆H₁₄O₂: [M]⁺ 238.0994; found 238.1003.

3. Dichloromethane was distilled from CaH₂.

4. Acetyl chloride (98%), purchased from Aldrich Chemical Company, Inc., was used as received. The checkers purchased it from Tokyo Chemical Industry.

5. Aluminum chloride (98%), purchased from Aldrich Chemical Company, Inc., was used as received. The checkers purchased it from Wako Pure Chemical Industry.

6. In two runs, the checkers obtained 26.6 and 28.8 g (82% and 83% yields). Samples can be purified further by crystallization from MeOH, but no significant amounts of impurities are detected when the material is analyzed before crystallization by means of ¹H NMR and ¹³C NMR spectroscopy and HPLC (reverse phase, 5 μm LiChrospher^(r) 100 from Hewlett-Packard, acetonitrile-H₂O gradients varying from 80:20 to 100:0). The pure product is a white solid, mp 160-161°C. IR (CCl₄) cm⁻¹: 2939, 1687, 1611, 1318, 1059. ¹H NMR (CDCl₃, 400 MHz) δ: 2.82 (s, 6 H), 4.13 (s, 6 H), 8.20 (dd, J = 8.5, 1.3, 2 H), 8.32 (d, J = 8.5, 2 H), 9.31 (d, J = 1.3, 2 H); ¹³C NMR (CDCl₃, 75 MHz) δ: 27.0, 61.1, 122.8, 123.6, 126.3, 128.5, 132.6, 134.7, 145.5, 198.0. UV-vis (CH₃CN, c = 1.81 × 10⁻⁴ M): λ_max (log ε) 266 (4.05), 325 nm (4.06). Anal. Calcd for C₂₀H₁₈O₄: C, 74.52; H, 5.63. Found: C, 74.52; H; 5.66.

Handling and Disposal of Hazardous Chemicals

The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.

These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.

3. Discussion

Almost no 9,10-dialkoxyphenanthrenes are known, and the quantities of those few made by other methods are either small or unstated.²^,³ The best alternative procedure gave 9,10-dimethoxyphenanthrene when 9,10-phenanthrenequinone was combined first with sodium in diglyme and then with dimethyl sulfate, but the yield after two chromatographic purifications was 51%.^2b The only other reported alkylations of phenanthrene-9,10-diol are by 1-chloro-2-diethylaminoethane in 10% yield,^3f and by 1,2-di(bromomethyl)benzene in 22% yield.^3g Unlike the procedure recorded here, none of these employ two-phase alkylations catalyzed by phase transfer agents.⁴

3,6-Diacetyl-9,10-dimethoxyphenanthrene has not been prepared by any other method. However, two related compounds, 9,10-di-TBDMSO- and 9,10-diphenyl-methylenedioxyphenanthrene, have been prepared by brominating phenanthrene-9,10-dione, converting the diones to the ethers, coupling the dibromides with tributyl(1-ethoxyethenyl)stannane by the Stille method, and hydrolyzing the enol ethers.⁵ The procedure described here circumvents three disadvantages of the tin reagents used in the Stille procedure: expense, toxicity, and the need for chromatography to remove side products, mainly Bu₃SnBr. 3,6-Diacetyl-9,10-dialkoxyphenanthrene, like the 9,10-di-TBDMSO- and 9,10-diphenylmethylenedioxy-derivatives, combines with 1,4-benzoquinone to give a [7]helicenebisquinone.⁶

There are no reported alternatives to the current procedure for the acylation of a phenanthrene using the Friedel-Crafts reaction.⁷^,⁸ Indeed, alternative methods to cleanly prepare 3,6-disubstituted derivatives of phenanthrene by means of electrophilic substitution are not known,⁹^,¹⁰^,¹¹ nor is there a precedent for the electrophilic substitution of any 9,10-dialkoxyphenanthrene.

References and Notes

Department of Chemistry, Columbia University, New York, NY 10027.
(a) Eichner, M.; Merz, A. Tetrahedron Lett. 1981, 22, 1315; (b) Rio, G.; Berthelot, J. Bull. Soc. Chim. France 1972, 822.
(a) Dannenberg, H.; Keller, H.-H. Chem. Ber. 1967, 100, 23; (b) Adams, C.; Kamkar, N. M.; Utley, J. H. P. J. Chem. Soc., Perkin Trans. 2 1979, 1767; (c) Sucharda-Sobczyk, A.; Syper, L. Rocz. Chem. 1975, 49, 749; (d) Santamaria, J.; Ouchabane, R. Tetrahedron 1986, 42, 5559; (e) Goldschmidt, S.; Schmidt, W. Chem. Ber. 1922, 55, 3197; (f) Fourneau, E.; Matti, J. Bull. Soc. Chim. France 1942, 633; (g) Kurebayashi, H.; Mine, T.; Harada, K.; Usui, S.; Okajima, T.; Fukazawa, Y. Tetrahedron 1998, 54, 13495.
Dehmlow, E. V.; Dehmlow, S. S. "Phase Transfer Catalysis"; VCH: New York, 1993.
Fox, J. M.; Goldberg, N. R.; Katz, T. J. J. Org. Chem. 1998, 63, 7456.
Paruch, K.; Vyklicky, L.; Katz, T. J. Org. Synth. 2003, 80, 233.
Monoacylations: (a) Mosettig, E.; van de Kamp, J. J. Am. Chem. Soc. 1930, 52, 3704; (b) Gore, P. H. J. Org. Chem. 1957, 22, 135; (c) Blin, P.; Bunel, C.; Maréchal, E. J. Chem. Res. (S) 1978, 206; (d) Fernández, F.; Gómez, G.; López, C.; Santos, A. J. Prakt. Chem. 1989, 331, 15.
The only diacylations are by phthalic anhydride with aluminum chloride in "tetrachloroethane" and by benzoyl chloride with AlCl₃ in the absence of additional solvent. The diketones were isolated in 15% and unspecified yields, respectively, and their structures were not determined. Clar, E.; Kelly, W. J. Am. Chem. Soc. 1954, 76, 3502.
Upon sulfonation, phenanthrene-3-sulfonic acid gives mainly (but not exclusively) the 3,6-disulfonic acid (Fieser, L. F. J. Am. Chem. Soc. 1929, 51, 2471), but the starting phenanthrene-3-sulfonic acid can be obtained from phenanthrene in only ca. 25% yield, and then isolated only from a mixture including a comparable amount of the 2-sulfonic acid (Fieser, L. F. Org. Synth., Coll. Vol. II 1943, 482).
Cerfontain, H.; Koeberg-Telder, A.; Laali, K.; Lambrechts, H. J. A. J. Org. Chem. 1982, 47, 4069.
Schmidt, J.; Schairer, O. Chem. Ber. 1923, 56, 1331.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

9,10-Phenanthrenedione (9); (84-11-7)

9,10-Dimethoxyphenanthrene:
Phenanthrene, 9,10-dimethoxy- (8, 9); (13935-65-4)

Tetrabutylammonium bromide:
1-Butanaminium, N,N,N-tributyl-, bromide (9); (1643-19-2)

Sodium dithionite:
Dithionous acid, disodium salt (8Cl, 9Cl); (7775-14-6)

Dimethyl sulfate:
Sulfuric acid, dimethyl ester (8, 9); (77-78-1)

Acetyl chloride (8, 9); (75-36-5)

Aluminum chloride:
Aluminum chloride (AlCl₃) (9); (7446-70-0)

3,6-Diacetyl-9,10-dimethoxyphenanthrene:
Ethanone, 1,1'-(9,10-dimethoxy-3,6-phenanthrenediyl)bis- (9); (310899-08-2)

Notes

References/EndNotes

Article Compounds

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