Diazaquinone

Pyridazine-3,6-diones (diazaquinones) are prepared from cyclic hydrazides by oxidation with lead tetraacetate or other oxidizing agents, such as r-butyl hypochlorite, chlorine or nickel peroxide. 

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

Cycloadditions of diazaquinones with unsaturated compounds yield diazacyc-lobutanes, from which N-substituted 3-hydroxypyridazin-6(l/f)-ones are formed after addition of water, t-butanol or acetic acid (Scheme 56). The same types of compound are also obtained from enamines. 

Similarly to PTAD, diazaquinone 662 reacts with 625 at elevated temperature to give even lower yields of the corresponding bicyclic compound 671 (Equation 99) <1999JHC627>. 

Six-membered ring ADC compounds can be generated by oxidation of the corresponding cyclic hydrazides. Pyridazine-3,6-dione (12) and phthalazine-1,4-dione (13, R = H), often called diazaquinones,4 are stable in solution only at low temperature, but can be generated, and intercepted at higher temperatures.39-43 Fusion of an extra benzene ring increases stability44 and the tetracyclic compound 14 is relatively stable.45 Substituted phthala-zine-l,4-diones have been widely studied because of their involvement in... 

Novel steroidal pyridazines are readily prepared from ADC compounds and steroidal A2,4-dienes,163 A14,1 -dienes,164 and A16,20-dienes.165 ADC compounds are also commonly used in the protection of the steroid 5,7-diene system (see Section V,A). These Diels-Alder adducts of steroidal dienes and azo dienophiles should not be confused with the so-called azasteroids, which are also prepared from ADC compounds. Cyclic ADC compounds such as the pyrazole-3,5-diones (7), and the diazaquinones 12 and 13 readily add to dienes to give bicyclic pyridazine derivatives,166168 and these reactions have been adapted to the synthesis of 5,10-diazasteroids (106).42 Similarly, the 13,14-diaza- (107) and 13,14,16-triazasteroid (108) ring systems have been prepared.169... 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

The only diazaquinones derived from p-benzoquinone are pyridazinedi-one 68 and a limited number of its derivatives. Since both the synthesis and the reactivity of these compounds are similar to corresponding higher analogs such as phthalazinediones, they will be treated together in Section V. 

Three different types of condensed diazaquinones, as exemplified by benzo analogs 81-83 can be formally anticipated. All reported attempts to prepare 81 have failed to date (76MI1, 760PP45) and the author is not aware of any reported synthesis of compounds similar to 82. On the other hand, 83 and other diazaquinones derived from 68 are important both from a theoretical point of view and as intermediates in organic synthesis, and this subject has been partially reviewed (78H1771). In keeping with the consistency of this review, the author has decided to cover the most important achievements in the field as well as all relevant publications that have appeared after the aforementioned review was published. However, additional pertinent information and literature references are cited in the previously mentioned review. 

Although some diazaquinones can be isolated, these species are generally formed in situ by reactions that utilize Clement s procedure (lead tetraacetate in acetonitrile) or Kealy s procedure (/-butyl hypochlorite in acetone). Kealy s procedure is preferred when pure solutions of diazaquinones free of inorganic salts and unreacted starting hydrazides are re-... 

The same behavior toward butadiene derivatives is documented for several bicyclic and polycyclic diazaquinones. Phthalazinedione 83a when treated with a wide variety of dienes afforded adducts 95 (60JOCI724 62JA966, 62JOC1115 70BCJ3926 75MI3 76H135). The unusual amino acid derivative 96 was prepared in a similar fashion (Scheme 23) (91CZ292). 

The potent dienophilic character of the diazaquinones has been demonstrated, in that phthalazinedione 83a reacted with some dienes known to be resistant toward Diels-Alder addition (Scheme 29). Diene 123, deactivated both by a bulky substituent and by the 1-methoxycarbonyl substituent, provides 124 below room temperature (73JA8380). Phthalazinedione 83a reacts even with cyclooctadiene (Scheme 29), providing compound 125 at 0°C (66JOC3862). 

Diazaquinones 68, 83a, and 90 have been shown to provide adducts with various isoprenoids, as exemplified by the /3-myrcene adduct 140 (87H193). The side-chain double bonds of these adducts can be functionalized by epoxidation with 3-chloroperoxybenzoic acid or via bromination with IV-bromosuccinimide to provide the corresponding derivatives 141 and 142, respectively (Scheme 34). 

The use of Diels-Alder adducts of diazaquinones for protecting of steroidal 14,16-dienes, e.g., 143, has been reported (68CC1434). Both isomers were isolated, but compound 145 prevailed (Scheme 35). 

The concept of using diazaquinones for diene system protection was accomplished in the case of some vitamin D derivatives, as shown in Scheme 37 (86JOC4819). Acetyl vitamin D2152 was protected with phtha-lazinedione 83a, providing a mixture of both possible stereoisomeric adducts from which 153 was isolated. Then usual ozonolysis procedure afforded aldehyde 154, which after the Wittig coupling and hydrogenation provided 155. The most difficult part of the sequence proved to be the deprotection of this compound, but this transformation was accomplished... 

Diazaquinones are very sensitive to the nucleophilic addition of water thereby leading to the formation of dimeric compounds. Thus, pyrida-zinediones 68 provide 163, the corresponding maleic anhydride 164, and nitrogen (62JA966). Phthalazinedione 83a gave 165 likely in the same manner (Scheme 41). 

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