1.4- Dioxepin-5-ones

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

There are relatively few entries in the non-fused dioxepin area, and most of these focus on reactions of these systems. For example the triflic acid-initiated polymerisation of 1,3-dioxepane in the presence of acetic acid and hexanedicarboxylic acid has been studied and mechanistic aspects discussed <00JPS(A)1232>. Biodegradable microspheres for the controlled delivery of drugs have been made from copolymers and homopolymer blends of L-lactide and l,5-dioxepan-2-one <00PP1628>. Ring contraction of 5-methylene-l,3-dioxepanes (eg. Ill) on reaction with trimethylsilyl trifluoromethanesulfonate in the presence of base afforded the exo tetrahydropyrans, in good yields <00TL2171>. 

It has been reported that 1 l//-dibenzo[h,< ][ ,4]dioxepin-l 1-one (dep-sidone) (243) undergoes photochemical decarboxylation and yields dibenzo-furan (59%) on irradiation with a high-pressure mercury lamp. The authors do not report whether the irradiation was conducted through silica or borosilicate glass. 

The 6,7-dihydro-5/f -1,4-dioxepin (266) has been prepared (54CR(38)982). and more recently it has been shown that the 2,3-dihydro-5jF/-l,4-dioxepins (263) and (265) can be produced from 1,4-dioxine-halocarbene adducts (264), either by heating under reflux in xylene or by treatment with bases. The allylic chlorine atom in (263) is readily substituted by alkoxide or cyanide ions (77ZC331, 76UKZ968). Saturated rings of type (267) have been prepared by the treatment of cyclic acetals of ethane-1,2-diol with vinyl ethers in the presence of boron trifluoride, and l,4-dioxepan-5-one (268) has been prepared by the reaction of bromoform and silver nitrate with aqueous dioxane (60AG415). 

One general method for the preparation of 6,7-dihydro-l,4-dioxepins of type (362) involves ring expansion thus, treatment of 2-(methoxymethyl)-l,3-dioxane (361) with dodecylbenzenesulfonic acid at 250°C and simultaneous distillation gave (362) with 69% conversion and 84% selectivity... 

Synthesis of 1,2-dioxepane derivatives can be achieved through mainly four methods, three of which have the potential 0-0 bond already in one reactant, namely ozone, oxygen gas, or a hydroperoxide moiety. The fourth method involves the linking of two oxygen atoms to form a 1,2-dioxepine bond. 

The noncatalytic oxidation of 4,7-dihydro-l,3-dioxepin 46a with nitrous oxide in liquid phase at 220 °C produces 1,3-dioxepan-5-one however, the conversion is very slow <2004ASC268>. 

Treatment of 1,3-dioxalanes 20 with thionyl chloride and then 48% hydrobromic acid gave 7-(perfluoroalkyl)-2,3-dihydro-57/-l,4-dioxepin-5-ones, 50-95% yield (Equation 8) <2001TL2305>. 

A serendipitous synthesis of the l,4-dioxepin-5-one derivative 228 has been reported based on acid chloride formation from the acid 227, followed by a ring opening and ring closing sequence on exposure of the acid chloride to 48% HBr solution [01TL2305]. 

The catechol 153 has been used in an efficient 3-step synthesis via 154 of the perfumery component Calone 1951 , 7-methyl-benzo[6][l,4]dioxepin-3-one 156 <05TL39>. The diester/ester intermediates 155 were converted to 156 in high yield in a short (4 min) microwave-assisted hydrolysis/decarboxylation sequence. 

Since 4,7-dihydro-l,3-dioxepin (IA) is both the simplest and one of the more easily prepared 1,3-dioxepin monomers (Table I), copolymerization of equimolar mixtures of IA-MA were first examined under a variety of conditions (Table II). As shown, yields of 1 1 alternating IA-MA copolymer are highly dependent upon polymerization conditions, with highest conversions obtained in 1,2-dichloroethane solvent. Also, incremental or controlled addition of initiator improves yields of copolymer. Using DCE solvent, the copolymers precipitated during polymerization. Copolymerization without added initiator was not observed. 

In the ROMP of cyclooctadiene (Mi) with 4,7-dihydro-2-phenyl-l,3-dioxepin (M2) catalyzed by Ru(=CHR)(Cl)2(PCy3)2, where R = CH=CPh2 or Ph, M2 is about half as reactive as Mi. By using a small proportion of M2, one can produce a polymer of Mi containing occasional M2 units, which may be broken by hydrolysis to yield 1,4-hydroxytelechelic polybutadiene M /M 1.2) (Fraser 1995b). 

FIGURE 10.5 Synthesis of 2,2-bis(trifluoromethyl)-4,5-dihydro-l,3-dioxepine-5-ones 12. 

FIGURE 10.6 Rearrangement of 4,5-dihydro-2/f-l,3-dioxepine-5-ones to enols 13. 

So far, only one example of enantioselective desymmetrization of olefins with (q -arene)Ru(II) half-sandwich complex 78 has been reported [43]. It was found, that isomerization of 2-n-butyl-4,7-dihydro-l,3-dioxepin 79 with a plane of symmetry, leads to the (-1-)-enantiomer of 2-n-butyl-4,5-dihydro-l,3-dioxepin... 

Besides the fully unsaturated 5 f-l,4-dioxepin (45), the unsaturated 1,4-dioxepins, 6,7-dihydro-5Ef-l,4-dioxepin (46), and 2,3-dihydro-5 f-l,4-dioxepin (47), incorporate either the structural feature of an enediol ether or an enol ether. One general method for the preparation of seven-membered rings of type (46) involves ring expansion thus, treatment of 2-(methoxymethyl)-l,3-dioxane with dodecylbenzenesulfonic acid in vacuum gas oil at 250 °C and simultaneous distillation gave (46) with 69% conversion and 84% selectivity. Several 6,6-disubstituted derivatives (49), which have found interest as intermediates for agrochemicals, drugs, and plastics, have analogously been... 

Compounds (141) have been tested for antimicrobial activity. 4-Phenyl-3,4-dihydro-l,5-dioxepin-2-one undergoes ring fission on treatment with LDA to afford catechol monocinnamate <94MI 912-... 

Lichen depsidones (1 lH-dibenzo[f),e]dioxepin-ll-ones) as potential novel pharmacologically active compounds 12MR0178. 

A useful silver carboxylate-promoted macrolactonization process, that avoids high-dilution conditions or slow-addition techniques, allowed the efficient conversion ofbromocarboxyfic acids 166 into 1,4-benzoxazepino-nes or -diones 167, and a single example of a benzo[e] [1,4]dioxepin-5(3fJ)-one 168 (13T8386). 

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