Synthesis of 2,5-Disubstituted 3,6-Diamino-1,4-benzoquinones
Louis S. Hegedus, Roy R. Odle, Peter M. Winton, and Paul R. Weider
J. Org. Chem., 47, 2607-2613 (1982)
Abstract
A general synthetic approach to a wide variety of 2,5-disubstituted 3,6-diamino-l,4-benzoquinones was developed. Bromanil was diaminated with ammonia, and adjacent NH2 and OH groups were protected as benzoxazoles by treatment with a carboxylic acid chloride followed by a polyphosphate ester cyclization-dehydration. The resulting 2,5-dibromobenzobis(oxazoles) were monolithiated by halogen-metal exchange with n-butyllithium and then reacted with a variety of electrophiles. The remaining bromide was replaced in a similar fashion. Alternatively the second bromide was replaced by reaction with H allylnickel halide complexes. The benzoxazole protecting group could be hydrolyzed with zinc(II) chloride/HCl-aqueous ethanol under an inert atmostphere. Air oxidation of the resulting hydroquinone under neutral conditions gave the desired 2,5-disubstituted 3,6-diamino-1,4-benzoquinone in good to excellent overall yield. This method was used to synthesize precursors to the basic ring system of the mitomycin antineoplastic antibiotics. Acid hydrolysis of the benzoxazole protecting group under oxidizing conditions resulted in the production of 2,5-disubstituted 3,6-dihydroxy-1,4-benzoquinone. Methylation followed by reaction with ammonia gave the desired diaminoquinone.
Experimental
Preparation of 2,5-Diamino-3,6-dibromohydroquinone (1)
2,5-Diamino-3,6-dibromoquinone (2 g, 6.76 mmol) was mixed with Na2S2O4 (2.8 g, 16.1 mmol) in 60 mL of H2O and warmed under nitrogen until the red color of the starting material had disappeared. The mixture was fiitered, and the off-white crystals were washed with H2O and ethanol and air dried to give 1.81 g (90%) of the desired product. This material could be used without further purification.
J. Org. Chem., 50(22), 4282-8 (1985)
Here is another paper, although its probably less relevant due to the reagents used.
Reactions of some 5,6-dihalo-2-cyclohexene-1,4-diones (1,4-benzoquinone dihalides) in boron trifluoride diethyl etherate.
Norris, R. K.; Sternhell, S., Aust. J. Chem., 26(2), 333-43 (1973)
Abstract
Treatment of five 1,4-benzoquinone dihalides in BF3.Et2O gives isomeric dihalohydroquinones. With the exception of the conversion of 5,6-dichloro-2-cyclohexene-1,4-dione into 2,3-dichlorohydroquinone, which is a true keto-enol isomerization, these products arise through elimination of hydrogen halides followed by readdn.
https://www.thevespiary.org/rhodium/Rhodium/chemistry/p2p.enolate.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/p2p.enolate.html)