Chemistry of azidoquinones and related compounds

View Article Online / Journal Homepage / Table of Contents for this issue Published on 01 January 1973. Downloaded by University of California - Irvine on 08/07/2015 23:49:59. Chemistry of Azidoquinones and Related Compounds By H. W. Moore DEPARTMENT O F CHEMISTRY, UNIVERSITY OF CALIFORNIA, IRVINE, C A L I F O R N I A , 92664, U . S . A . 1 Introduction Azidoquinones constitute a remarkably versatile class of synthetically useful reagents. They are easily prepared and can function as penultimate precursors to a large variety of other compounds, among which are azidohydroquinones,ly2 aminoq~inones,1-~ y-cyanoalkylidene-A5~~-butenolides,4 2-cyanocyclopent-4- ene-l,3-diones,6 azepine-2,5-diones,6 diacyl cyanides,’ 3-cyano-2-aza-l,4- quinones, 4-acetoxy- 1,2-quinone-2-(N-a~etyl)imines,~ trans,trans- 1,4-diacetoxy- cis,cis- 1,4-dicyanobuta- 1,3-diene~,~ 2-alkenyl-2,3-dihydroindole-4,7-dione~,’~ benzo[ flindole-4,9-diones,” and cyanoketens. l2 Many of these compounds are themselves members of new or relatively unexplored classes of compound and should find synthetic utility in their own right. It is the purpose of this review to discuss the synthesis and chemistry of azidoquinones as well as certain of those compounds to which they are structurally and chemically related. 2 Synthesis of Azidoquinones The literature contains over seventy examples of variously substituted mono-, di-, and poly-azido-l,4-benzo-, -1 ,4-naphtho-, and -1,2-naphtho-quinones. Almost without exception these compounds are prepared by the reaction of halogeno- or acetoxy-substituted quinones (1) with inorganic azide in aqueous alcohol, being generally obtained as highly coloured crystalline solids which are safely manipu- lated under normal laboratory conditions. One exception is tetra-azido-l,4- b e n z ~ q u i n o n e , ~ a * beautiful ~ ~ J ~ deep-purple solid which is extremely shock and thermally sensitive and should be handled with great caution. The fact that L. F. Fieser and J. L. Hartwell, J. Amer. Chem. SOC., 1935, 57, 1482. H. W. Moore and H. R. Shelden, J . Org. Chem., 1968,33,4019. E. Winkelmann, Tetrahedron, 1969, 25, 2427. H. W. Moore, H. R. Shelden, D. W. Deters, and R. J. Wikholm, J. Amer. Chem. Soc., 1970, W. Weyler, jun., D. S. Pearce, and H. W. Moore, J . Amer. Chem. SOC., 1973, 95, 2603. H. W. Moore, H. R. Shelden, and W. Weyler, jun., Tetrahedron Letters, 1969, 1243. 7 J. A. Van Allen, W. J. Priest, A. S. Marshall, and G. A. Reynolds, J . Org. Chem., 1968,33, * D. S. Pearce and H. W. Moore, unpublished results. D. S. Pearce, M. S. Lee, and H. W. Moore, J . Org. Chem., in the press. P. Germeraad and H. W. Moore, J . Org. Chem., in the press. l1 P. Germeraad and H. W. Moore, J . Org. Chem., in the press. l* H. W. Moore and W. Weyler, jun., J. Amer. Chem. SOC.. 1970, 92, 4132. la A. Korezynsky and St. Namylslowski, Bldl. SOC. chim. France, 1924, 35, 1186. lP K. Fries and P. Ochwat, Ber., 1923, 56, 1291.


Synthesis of Azidoquinones
The literature contains over seventy examples of variously substituted mono-, di-, and poly-azido-l,4-benzo-, -1 ,4-naphtho-, and -1,2-naphtho-quinones. Almost without exception these compounds are prepared by the reaction of halogeno-or acetoxy-substituted quinones (1) with inorganic azide in aqueous alcohol, being generally obtained as highly coloured crystalline solids which are safely manipulated under normal laboratory conditions. One exception is tetra-azido-l,4b e n z~q u i n o n e ,~*~~J~ a beautiful deep-purple solid which is extremely shock and thermally sensitive and should be handled with great caution. The fact that

Chemistry of Azidoquinones and Related Compound3
quinones bearing halogenoJ6 as well as acetoxy-le groups are readily available translates to a versatile synthesis of azidoquinones (2). Yields are usually high, particularly when the leaving group is a halide ion.

Reactions of Azidoquinones
A. Reduction.-Azidoquinones are reduced under a variety of conditions to the corresponding primary aminoquinones (Na2S201, H2/Pd-C, HJPt,O, H2/Pt-C).1s2J7-1B The scope of this reaction has not been extensively explored. However, it does appear to provide potentially one of the best methods of introducing an amino-substituent on to the quinoid nucleus. The yields are high and the conditions mild.

Chemistry of Azidoquinones and Related Compounds
An additional use of this reaction has recently a~peared.'~ The naturally occurring aminoquinone rhodoquinone-9 (1 3)a1 was obtained from the azidoquinone (14) via sodium dithionite reduction to the azidohydroquinone (15) and subsequent thermal decomposition.

Moore
The thermal chemistry of certain of these 1,4-diacetoxyazidobenzenes has been studied.s The monoazides, (26a, b, and d) smoothly rearrange with nitrogen loss in refluxing chlorobenzene to the respective N-acyl-1 ,2-quinoneimines (28)-(30) whereas (26e) gives the carbazole (31) when decomposed under the same conditions. The formation of the N-acyl-l,2-quinoneimines is unusual since it involves an acyl migration to an azide nitrogen, a rarely observed process.3o Other known

Moore
A particularly interesting example of this pyrolytic cleavage was observed when 1,4-diacetoxy-2,3-diaidonaphthalene (26h) was thermally decomposed. The presumed intermediate quinodimethane collapsed to the truns-and cis-benzocyclobutenes (35) and (36). In addition, the unexpected isoquinoline (37) was isolated as the major product. The formation of 1,4-diacetoxy-3-cyanoisoquinoline (37) from (26h) is most intriguing and must result from a very deepseated rearrangement. An attractive possibility for such a mechanism is based upon the fascinating gas-phase equilibrium of phenylnitrenes and cx-pyridyl-~a r b e n e s .~~ In the case at hand, the nitrene (38) could rearrange to the azidocarbene (39), which upon nitrogen loss would give (37).

Chemistry of Azidoquinones and Related Compounds
C. Reactions of Azidoquinones with Nucleophi1es.-The reactions of azidoquinones with nucleophilic species have not received detailed study. This should be a worthwhile area for investigation since both quinone nuclei and azide groups are susceptible to nucleophilic attack. The former would give azidohydroquinones and their transformation products, e.g. substituted aminoquinones, and the latter could result in diazo-transfer reaction^.^^ Examples related to each have been observed. 2-Azido-5-t-butyl-l,4-benzoquinone (40) and 2-azido-l,4-naph- (46 1 Moore thoquinone (41) readily react with thiol nucleophiles. For example, the former reacts with ethyl mercaptoacetate to give the heterocyclic quinone (42) and the latter reacts with thiophenol to give the aminoquinone (43).37 More interestingly, the enolate anion of diethyl malonate reacts with (40) giving a 70% yield of the indolequinone derivative (44), presumably arising via the azidohydroquinone (45) and aminoquinone (46) intermediate^.^? Mosby and S i l~a~~-~O have investigated the reactions of certain 2,3-diazido-1,4-quinones with phosphines and phosphites. When two molar equivalents of triphenylphosphine were added to a solution of 2,3-diazido-l,4-naphthoquinone (47), 2,3-triphenylphosphoranylidenearnino-1,6naphthoquinone (48) and the interesting and unanticipated triazoline (49) were isolated. The ratio of these products was markedly dependent upon the solvent employed; in benzene the ratio (48) Table 1 428 OH (64) '    The conversion of (69) into (62i) required no external source of acid. Simply refluxing a solution of the azidoquinone (69) in chloroform for a few minutes induced its rearrangement to the butenolide in 65% isolated yield. Here, an intramolecular acid-catalysed process can be envisaged, as shown. This rearrangement is not simply a thermal process since, as is discussed below, azidoquinones thermally ring-contract to 2-cyanocyclopent-4-ene-l,3-diones.

Moore
Earlier, it was pointed out that thymoquinone (20) rearranges to the butenolide (21) when treated with hydrazoic acid in trichloroacetic acid at 64 0C.z7028 One of the key steps in this reaction has been shown to be an example of the acidcatalysed rearrangement of an azidoquinone, namely, the rearrangement of pivotal biological importance, can be viewed as derivatives of the partially reduced cyclopentene-1,3-dione ring system. Of importance here is the fact that this basic ring system can be conveniently prepared in good yield from the readily available 2-azido-l,4-benzo-and -ly4-naphtho-quinones. The general structures (63) and (79) illustrate the synthetic scope of this transformation. Table 2 For R1-R8, see Table 2.
Substituents for compound (79) The mechanism of this reaction has been studied in some detail? Based upon product analysis, activation parameters, and the absence of kinetic solvent effects and substituent effects, the mechanism shown in Scheme 1 has been presented.

R '
The synthetic limitations of this reaction thus far reported are for those azidoquinones in which the substituent adjacent to the azide group is a proton, a vinyl group, or a substituted amino-function. Those which are unsubstituted give a complex mixture of products upon pyrolytic decomposition, whereas those which are vinyl substituted are thermally converted into indolequinones,ll i.e.,

66
The synthesis of indolequinones as outlined above constitutes one of the best routes to this class of compound. An illustration of the synthetic utility of this reaction is the construction1' of 6,7-benzo-2,3-dihydro-5,8-dioxo-1H-pyrolo-

-azido-3-alkyl(aryl)-l,4-quinones ring-contract to 2-cyano-3-alkyl(aryl)cyclopent-4-ene-l ,3-dionesss and 2-azido-3-vinyl-l,4-quinones ring-close to the corresponding indolequinones.ll
The photolytic ring-contraction has particular advantages for the synthesis of 4-azido-2-cyanocyclopent-4-ene-l,3-diones (96) from the corresponding 2,sdiazido-l,6benzoquinones (97). As discussed below, these diazidoquinones also thermally ring-contract to the azidocyclopentene-l,3-diones. However, such products readily cleave under the reaction conditions giving two molecules of the correspondingly substituted cyanoketen. No such cleavage is observed when the photolytic ring-contraction is carried out in benzene with 3600 A light.  One novel feature of this transformation is the photolytic cycloaddition of the organic azide to the carbon-carbon double bond of the diene. Such a reaction is certainly well known in the thermal chemistry of organic a~i d e s ,~~ but appears to be without precedent under photolytic conditions. Cycloadditions of this type may be limited to those azides which can accept light of relatively low energy (> 3600 A) such as the highly coloured azidoquinones. Light of higher energy may result in nitrene formation, thus leading to other products. Cleavage of 2,5-and 2,6-Diazido-l,4quinones.-It has been shown that the thermal ring-contraction of monoazidoquinones to 2-cyanocyclopent-66 G. L'Abbe, Chem. Rev., 1969,69,345.

Chemistry of Azidoquinones and Related Compounds
The generation of cyanoketens by the classical dehydrohalogenation of the corresponding acid chlorides may be difficult. This is csrtainly true for t-butylcyanoketen (104a) since reaction of a benzene solution of 2-cyano-3,3-dimethylbutyrylchloride (108) with a catalytic amount of triethylamine gives a good yield of 1,3-di-t-butyIallene ( The same product was immediately formed when a solution of the keten was similarly treated. The reaction was shown to Moore involve a triethylamine-catalysed dimerization of t-butylcyanoketen to the p-lactone (1 10) which then reacted further with the amine, as indicated, to give the allene (109). On the other hand, when t-butylcyanoketen is generated by pyrolysis of 2,5-diazido-3,6-di-t-butyl-l,4-benzoquinone (103a) it is stable for days in benzene even at the reflux temperature. Even though t-butylcyanoketen is reluctant to self-condense in benzene, it quite readily undergoes cycloaddition to other substrates. Addition to alkenes,12 a1 kynes,6O allenes,6l and carbodi-irnidesl2 have been reported, and selected examples are outlined in Scheme 3.

Chemistry of Azidoquinones and Related Compounh
H. Thermal Rearrangement of 2,3-Diazido-l,4quinones.-2,3-Diazido-l,4quinones (1 11) undergo a fascinating rearrangement to 2-aza-3-cyano-l,4quinones (1 12) when decomposed in refluxing chlorobenzene.* This reaction constitutes the first unambiguous synthesis of the new heterocyclic azabenzoquinone ring system. All other reported examples are hydroxy-derivatives which have several tautomeric possibilities, the azaquinone form being only one, and no evidence has been presented which would allow one to determine which isomer or isomers In the azanaphthoquinone series one example has recently been described; 2-aza-3-phenyl-lY4-naphthoquinone has been prepared by two different r~u t e s . * *~~~~~*
The following sections summarize the limited results in these areas.

M e o W M e
-MeOH NaN3 [ ] 0 (142) In the past thirty-five years alone well over one hundred and fifty richly substituted primary amino-1 ,dbenzo-and -1 ,dnaphtho-quinones have been reported in the literature. The plethora of such readily available starting materiaIs along with the rich chemistry of the amino-group and the quinone nucleus should make a study of their oxidative rearrangements most worthwhile.
Certainly a large number of other cyclic and acyclic vinyl azides meeting the structural requirements outlined above should be investigated. Some such work has already been done and is outlined be lo^.^^-^*