[130-15-4]  · C10H6O2  · 1,4-Naphthoquinone  · (MW 158.16)

(dienophile used to synthesize various aromatic rings via Diels-Alder or cycloaddition-type reactions;1 undergoes amination,2 allylation,3 cyclooligomerization,4 and Thiele-Winter acetoxylation to give the 1,2,4-triacetoxynaphthalene5)

Physical Data: mp 126 °C, begins to sublime below 100 °C; d 1.422 g cm-3.

Solubility: sparingly sol cold water; slightly sol pet ether; freely sol hot alcohol, ether, benzene, chloroform, carbon disulfide, acetic acid; sol alkali hydroxide solutions, giving a reddish brown solution.

Form Supplied in: yellow triclinic needles from alcohol or pet ether.

Handling, Storage, and Precautions: toxic and irritant.

Synthesis of Aromatic Systems.

1,4-Naphthoquinone is used to synthesize various products that contain an aromatic ring. These syntheses are most commonly executed via Diels-Alder and cycloaddition-type reactions.

Diels-Alder Reactions.

A method for preparing naphthacenequinones employs a very convenient, three-step, one-pot sequence consisting of an initial Diels-Alder cycloaddition of an isobenzofuran with an appropriate dienophile such as 1,4-naphthoquinone (eq 1).6

The Diels-Alder reactivity of in situ-generated N-benzoylindole-2,3-quinodimethane has been expanded considerably to include reactions with carbon dienophiles (e.g. 1,4-naphthoquinone) which furnish a variety of [b] annulated indoles as well as functionalized and annulated carbazoles.7 In another variation of this reaction, 2- and 3-vinylindoles react with 1,4-naphthoquinone to afford new six-ring annulated carbazoles (eqs 2 and 3).8

1,4-Naphthoquinone is the reagent of choice in a new approach to the synthesis of 2H-isoindole-4,7-diones (eq 4).9

A simple synthesis of spirodiones via p6s + p2s photocyclization of the Diels-Alder adducts obtained by reaction of spiro[4.2]heptadiene and spiro[4.4]nonadiene with 1,4-naphthoquinone in homogeneous and miscellar media is illustrated in eq 5.10

Stereoselective syntheses of quinone-annulated 2,3-bis(methylene)-7-oxabicyclo[2.2.1]heptanes involves 1,4-naphthoquinone as a dienophile. The products are promising building blocks for the synthesis of antineoplastic antibiotics.11 Treatment of furan-annulated 3-sulfones with 1,4-naphthoquinone at 150 °C for 4 h gave 1,4-epoxy-2,3-bis(methylene)-1,4,4a,9a-tetrahydroanthraquinone in 58% yield (eq 6).11

Biologically Significant Products.

Several Diels-Alder reactions involving 1,4-naphthoquinone have importance for the preparation of biologically active compounds. For example, the trifluoromethyl group is an increasingly popular aromatic substituent in compounds synthesized for biological applications. However, only a handful of methods are available for its introduction into aromatic compounds. Its use was consequently limited, but a new method using 1,4-naphthoquinone was found to be effective for this purpose. Triethyl(trifluoromethyl)silane and tri-n-butyl(trifluoromethyl)silane were found to react with the quinone by addition to one of the carbonyl atoms, giving dienones containing geminal trifluoromethyl substituents.12

Another application involves the reaction of 1,4-naphthoquinone and pyrroline, giving one major new product (eq 7) which was isolated in moderate yield (25%).13 This new product has significance in the synthesis of ansamyocin and mitomycin antibiotics.

Aromatic polyketide antibiotics generally fall into two structural classes, linear and nonlinear polyketides. Although enormous effort has been devoted to the synthesis of the linear polyketides, the nonlinear aromatic polyketides have received relatively little attention.14 With a vinylquinone acetal as the diene and 1,4-naphthoquinone as the dienophile, the nonlinear benzathracenedione can be synthesized in 24% yield (eq 8).14

Additional Cycloadditions.

Allylic cyanides cycloadd to 1,4-naphthoquinone at room temperature. Treatment of the crude mixture with Potassium Fluoride in refluxing methanol gives compound (1) in 61% yield (eq 9).15

A general and simple route to the synthesis of triptycene derivatives involves cycloaddition of 1,4-naphthoquinone with anthracene and subsequent treatment of the resulting adduct with Lithium Aluminum Hydride followed by p-Toluenesulfonyl Chloride in pyridine (eq 10).16

A reaction of 1,4-naphthoquinone with the diene 3-vinylpyrrole gives an indole in 21% yield (eq 11).17

Amination of Naphthoquinones.

A new method for the synthesis of aminonaphthoquinones uses 1,4-naphthoquinone and Azidotrimethylsilane (eq 12).2

Allylation of Substituted p-Quinones.

1,4-Naphthoquinone reacts with allylindium sesquiiodide to give allylquinols in excellent yield.3 This reaction has been extended to prenylation and nerylation of napthoquinone as well (Table 1; Scheme 1).

Cyclooligomerization of Quinones.

When treated with acid, 1,4-naphthoquinone gives a dimer, 5,8-dihydroxydinaphtho[1,2-b:2,1-d]furan (2), 15,18-dihydroxydinaphtho[2,1-d:2,1-d]naphtho[1,2-b:4,3-b] difuran (3) and a tetramer, tetranaphthyleno[5,6-bcd:11,12-bcd:17,18-bcd]tetrafuran (4).4

Thiele-Winter Acetoxylation.

1,4-Naphthoquinone can undergo the Thiele-Winter reaction.19 From a synthetic point of view the most important feature is the introduction of an oxygen onto an aromatic nucleus. Burton and Praill showed that perchloric acid is probably the most effective catalyst for effecting the transformation (eq 13).19

Related Reagents.

1,4-Benzoquinone; 1,3-Diphenylisobenzofuran.

1. Butz, L. W.; Rytina, A. W. OR 1949, 5, 136.
2. Husu, B.; Stanislav, K.; Kadunc, Z.; Tisler, M. M 1988, 119, 215.
3. Araki, S.; Katsumura, N.; Butsugan, Y. JOM 1991, 415, 7.
4. Hogberg, H. ACS 1972, 26, 309.
5. McOmie, J. F. W.; Blatchly, J. M. OR 1972, 19, 199.
6. Dodge, J.; Bain, J.; Chamberlin, R. JOC 1990, 55, 4190.
7. Haber, M.; Pindur, U. T 1991, 47, 1925.
8. Pindur, U.; Pfeuffer, L.; Eitel, M.; Rogge, M.; Haber, M. M 1991, 122, 291.
9. Schubert-Zsilavecz, M.; Likussar, W.; Gusterhuber, D.; Michelitsch, A. M 1991, 122, 383.
10. Singh, V.; Raju, B. N. S.; Deola, P. T. SC 1987, 17, 1103.
11. Suzuki, T.; Kubomura, K.; Takayama, H. CPB 1991, 39, 2164.
12. Stahly, P.; Bell, D. JOC 1989, 54, 2873.
13. Michael, J. P.; Cirillo, P. F.; Denner, L.; Hosken, G. D.; Howard, A. S.; Tinkler, O. S. T 1990, 46, 7923.
14. Parker, K. A.; Ruder, S. M. JACS 1989, 111, 5948.
15. Differding, E.; Vandevelde, O.; Roekens, B.; Trieu Van, T.; Ghosez, L. TL 1987, 28, 397.
16. Patney, H. K. S 1991, 694.
17. Murase, M.; Yoshida, S.; Hosaka, T.; Tobinaga, S. CPB 1991, 39, 489.
18. Thiele, J.; Winter, E. LA 1900, 311, 341.
19. Burton, H.; Praill, P. F. G. JCS 1952, 755.

Erica Caldwell, Laurent Deloux & Morris Srebnik

The University of Toledo, OH, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.