1,5-dioxocins

No 170 NMR spectra were reported for 1,5-dioxocins synthesized in the past decade. 

As for the previous class of 1,5-diheterocins, considerable advances have been made in the chemistry of the 1,5-dioxocins since the publication of CHEC-I in which the few known 1,5-dioxocin derivatives were reported. 

A number of cyclization and condensation reactions have been used to effect 1,5-dioxocin ring closure. Bourgeanic acid, an aliphatic depside isolated from a lichen (Ramalina sp.), cyclizes upon treatment with cold benzenesulfonyl chloride, affording lactone (113) in quantitative yield (Equation (36)) <90JOC5938>. 

No designed ring transformation approaches to the 1,5-dioxocin ring system appear to have been reported. However, purpactin A (111 R = H, R = Ac) is apparently formed nonenzymatically from a related fungal natural product, purpactin B (123), via hydrolysis of the spirodione of the latter followed by spontaneous lactonization (Scheme 35) <91JAN144,92JOCi27l>. 

Besides l,4-dihydro-l,4-diazocines (see Section 1.4.) there are other 1,4-diheterocines that are isoelectronic with the cyclooctatetraene dianion. These systems have primarily found interest as potential 107t-aromatic systems. No extensive delocalization is expected theoretically and calculations predict nonaromatic systems for both 1,4-dioxocin (1) and 1,4-dithiocin (see Section l.ll.).3-4-7... 

In contrast to the 1,4-dithiocin system, 1,4-dioxocin (1) is well-known and has been characterized as an olefinic compound by its spectra as well as its chemical behavior.5-6 The reason why 1,4-dioxocin in contrast to 1.4-dihydro-1.4-diazocine (see Section 1.4.) and 4//-l,4-oxazocinc (sec Section 1.12.), does not qualify as a 107r-aromatic species, is the less pronounced tendency of oxygen atoms for 7t-electron delocalization. An X-ray analysis of the 6-substituted 1,4-dioxocin 2 confirms the presumed nonplanar conformation of the 1,4-dioxocin structural element.9 The eight-membered ring exhibits a twisted boat-chair confirmation. 

Other substituted systems, however, might be planar due to conjugation effects with acceptor substituents, as has been found in an X-ray structural analysis of 1,4-dioxocin-6-carboxylic acid chloride the eight-membered ring is practically planar with a coplanar arrangement of the substituent.9... 

Depending upon the substitution pattern, a thermal valence isomerization of 1,4-dioxocins 4 to the tricyclic jyn-benzene dioxides (xyn-3,8-dioxatricyclo[5.1,0.02-4]oct-5-enes) 3 can be detected. On the other hand, the valence isomerization of sin-benzene dioxides (anti-benzene dioxides do not undergo such rearrangements) provides a general approach to 1,4-dioxocins 4. 

The 6-substituted 1,4-dioxocins can be used to prepare other 6-substituted derivatives by simple functional group transformations.4,8,9 Especially interesting is the synthesis of the 4/7-4-oxo-2,3-dihydropyran-2-yl-substituted derivative 16 from l,4-dioxocin-6-carbaldehyde (15) by a cyclocondcnsation with Danishefsky s diene.9 Dehydrogenation of 16 yields 2 which can be isomerized to the corresponding isomeric. sr/i-benzene dioxide 3 (X = 4/f-4-oxopyran-2-yl), which is identical with and proved the structure of the naturally occurring antibiotic LL-Z 1220.10... 

FIGURE 6.17 Oxidation of a-tocopherol (1) conventionally leads to its spiro dimer (9) via ortho-quinone methide 3 (path A). The zwitterionic o-QM precursor 3a is stabilized by NMMO in complex 17, which upon rapid heating produces small amounts of new dioxocine dimer 18 (path B). Acid treatment of 18 causes quantitative conversion into spiro dimer 9, via o-QM 3 (path C). 

Karhunen, P Rummakko, P. Sipila, J. Brunow, G. Kilpelainen, I. Dibenzo- dioxocins a novel type of linkage in softwood lignins. Tetrahedron Lett. 1995, 36, 169-170. 

Dioxocines 218 are in turn paratropic and exist in equilibrium with their 2o — 2ti valence isomers sjn-benzene dioxides 217 (Scheme 80).259 Their chemistry and behavior in magnetic fields have been evaluated.260 261... 

Isomerization of the bromobenzene dioxide (241) occurred in refluxing CCU and led to a 1 2 equilibrium mixture of (241) and the bromodioxocin (240). The unsubstituted dioxide (238) in benzene at 60 °C gives a mixture containing 95% of dioxocin (239), with Ea for the reaction 115 kJ mol-1. In both cases, the equilibrium can also be reached from the dioxocin side. 

Curiously, a benzene dioxide (242) has also been found in a fungal antibiotic (74JOC435). Isomerization in warm acetic anhydride gave a 9 1 equilibrium mixture of the pyronyl dioxocin (243). 

Benzodioxocin (m.p. 5 °C) (245), prepared from the dihydro compound (244) via either the mono- or di-bromide, shows no aromatic character <67AG(E)697). The H NMR spectrum contains signals in the alkenic region at 8 5.35 and 6.95 p.p.m. for the dioxocin protons. 1,6-Benzodioxocin gives a Diels-Alder adduct (247) and on irradiation undergoes cyclization to the cyclobutene (246). 

Dioxatricyclo[3.3.0.02-4]octenes 1 underwent [2 + 2] cycloreversion on flash-vacuum thermolysis at 550 CC and 0.003 Torr to give 1,4-dioxocins 2 in addition to other products.191... 

SINDOl calculations, which successfully reproduced both the geometry and the aromaticity of the cyclooctatetraene dianion, predict a high degree of bond localization and nonplanarity for 1,4-dioxocin and its derivatives (84JOC4475). 

The parent 1,4-dioxocin (15) is colorless, with its major absorption band well into the ultraviolet [238 nm (3.86)] and a weak shoulder at 285 nm (2.50), a spectrum similar to that of 1,3,6-cyclooctatriene (72AG(E)935). 

Dioxocine (32 X = 0) behaves chemically as an alkene rather than as an aromatic compound. Thus, it is readily hydrogenated to 1,4-dioxocane and polymerizes readily upon standing (72AG(E)935>. 

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