1.4- Benzodioxane ring

The benzodioxan ring also serves as the aromatic moiety for one of the ubiquitous analogues of the spirone anxiolytic agents discussed in Chapter 9. In the absence of a specific reference, the requisite intermediate (62-1) could be obtained by reducing the cyano group in nitrile (60-1) with lithium aluminum hydride. Alkylation with the spirone side chain chloride (62-2) would then afford binospirone (62-3). 

O-a-bond, and creating the benzodioxane ring system in 7. Compound numbers relate only to this figure. Contour assignment coloring scheme follows that established in Figure 5.3. 

An imidazole derivative which is also a hypotensive agent by virtue of adrenergic a-2-receptor blockade is imiloxan (75). Its synthe.sis begins by conversion of 2-cyanomethyl-1,4-benzodioxane (72) to its iminosMhylether with anhydrous HC in clhanol (73). Reaction of the latter with aminoacetaldehyde diethylacetal and subsequent acid treatment produces the imidazole ring (74). Alkylation of 74 with ethyl iodide mediated by sodium hydride completes the synthesis [251. 

At the same time, the ring closure of A-(l,3-benzodioxan-7-yl)amino-methylenemalonate (830, R = H) in boiling phosphoryl chloride for 12 hr gave a mixture of l,3-dioxino[4,5-g]quinoline (831) and l,3-dioxino[4,5-/Iquinoline (832, R = H), with an excess of the linear product (831) (72MI5). Starting from the methyl derivative of compound 830 (R = Me), the angular product (832, R = Me) was prepared in 40% yield (72MI4). 

Irradiation of l,3-benzodioxan-4-ones appropriately substituted at position 2 with an aryloxy or thioaryloxy group gives rise to the formation of the same photoproducts as in the PFR of the open ring isomers. Scheme 60 depicts the structures of para-methoxyphenyl ortho- acetoxybenzoate 229 and its cyclic isomer, 2-(para-methoxyphenoxy)-2-methyl-l,3-benzodioxan-4-one 230. Irradiation of 229 or... 

Most partially saturated ring systems, 2,3-dihydro-l,4-dioxin 10 (sometimes named as 1,4-dioxene), 2,3-dihydro-1,4-dithiin 11, 2,3-dihydro-l,4-oxathiin 12, 2,3-dihydro-l,4-benzodioxin or 1,4-benzodioxane 13, 2,3-dihydro-l,4-benzodithiin 14, and 2,3-dihydro-l,4-benzoxathiin 15 are well investigated. Ring numbering for compounds 10-12 is followed as shown, independently of the presence of substituents. 

The potential energy barrier of 1,4-benzodioxan 13 to ring inversion is 1-2 kcal moP lower than that of 1,4-dioxene 10, typically 6.9 and 8.7 kcalmoP (HF/6-31G ) and 7.5 and 8.8kcalmoP (B3LYP/6-31G ), respectively <1998MI173>. 

The majority of the small number of biologically active compounds based on a fused ring system that includes two oxygen atoms consist of 1,4-benzodioxans. All but one... 

Attachment of a base-bearing side chain to the carbocyclic ring of a benzodioxan gives another compound that acts as an a-adrenergic blocker. Mannich reaction of the methyl ketone in (61-2), obtainable by acetylation of the benzodioxan proper (61-1), with phenylpyrrolidine (61-3) and formaldehyde leads directly to proroxan (61-4) [71]. 

The clinical and commercial success of the antidepressant compound fluoxetine (Chapter 2 Prozac) engendered considerable work in other laboratories. A benzo-dioxan based compound that shows similar activity shares only a few stmctural features with the prototype. The benzodioxan nucleus (68-3) is formed by an alkylation reaction between the fluorocatechol (68-1) and the derivative (68-2) from meso, and hence achiral, butanetetrol. The benzyl protecting groups are then removed by hydrogenation over palladium, and the thus-obtained diol is converted to the fiii-toluene-sulfonate (68-4) by reaction with toluenesulfonyl chloride. Treatment of that intermediate with benzylamine leads to fiw-alkylation on the same nitrogen to form a pyrrolidine ring and thus the tricyclic compound (68-5). A second hydrogenolysis step then leads to fluparoxan (68-6) [70]. 

Thermolysis of a benzodioxan leads to a cycloadduct processing the chroman ring system, a key intermediate during synthetic studies on communesin B <20030L3169>. 

It was the purpose of this investigation to synthesize suitable monomers which could conceivably undergo cyclopolymerization or cyclocopolymerization to lead to large ring-containing polymers. A more specific purpose was to synthesize polymers which would contain ring structures in the polymer backbone which may simulate the properties of the crown ethers (2). Thus a variety of monomers, including l,2-bis(ethenyloxy)benzene, l,2-bis(eth-enyloxy)-4-methylbenzene, 1,2-bis(2-ethenyloxyethoxy)benzene and l,t-butyl-3,4-bis(ethenyloxyethoxy)benzene, as well as model compounds 2,3-dimethyl-1,4-benzodioxane and cis- and trans-2,4-dimethyl -1,5-benzodioxepane, were synthesized and studied. This paper deals with cyclopolymerization studies of the four monomers. 

The benzodioxane moiety can be replaced by a variety of other heterobicyclic rings without loss in affinity [60]. A recent example is SDZ 216-525. This compound in which the N-4 of the indolepiperazine is substituted with the saccharinebutyl chain of ipsapirone is a potent and rather selective antagonist at postsynaptic 5-HT1A receptors [61] (Table 12). At the somatodendritic 5-HT1A autoreceptors SDZ 216-525 behaves as a partial agonist [62],... 

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