Benzodioxins, synthesis

This intramolecular etherification approach has successfully been applied to the syntheses136 of siccanin137 and clusifoliol,136 and a formal synthesis of morphine.138 Examples of tandem inter- and intramolecular etherification reactions have also been reported which convert catechol and o-aminophenol derivatives into benzodioxins (Equation (24)),139-141 benzodioxepines,142 and morpholines.139,140... 

Cyclizations of o-(a -haloalk oxy)phenols have been widely studied and were used to afford an expedient synthesis of 5-alkyl-2,3-dihydro-l,4-benzodioxins <2004SC2487>. This approach via a nucleophilic substitution was used for the synthesis of 8-substituted-2-hydroxymethyl-l,4-benzodioxane derivatives 164 in an enantiopure form. Use of CsF instead of more basic conditions allowed higher yields and enantiomeric excess (Equation 28) <2001ASC95>. Dry tetrabutylammonium fluoride (TBAF) in THF was required and was basic enough to initiate an intramolecular Sn substitution from the protected phenol 165 to the fluoro-l,4-benzodioxane 166 <1996T6187>. 

Linear annulated dioxins synthesis were reported by analogy with that of the 1,4-benzodioxin series <2002T1533> or in a modification of the Ullmann ether synthesis <2004T8899>. 

Then, nucleophilic aromatic substitution was applied for the synthesis of l,2,4,6,7,9-hexafluoro-l,4-dibenzodioxin from 2,3,4,6-tetrafluorophenol in the presence of sodium /-butylate <1995JFC(73)265>. In a similar way, cyano-1,4-dibenzodioxins and cyano-l,4-dibenzodithiins have been synthesized by fluorine displacement reactions with catechols <2001NJC379, 2001NJC385>. In accordance with a similar mechanism, the synthesis of spiro (l,4-benzodioxin-2,4 -piperidines) 205 and spiro (l,4-benzodioxin-2,3 -pyrrolidines) 206 have been developed from alcohols 207 and 208, respectively, both of them being obtained from 2-fluorophenol 210 with the corresponding epoxide 209 (Scheme 18) <2003SL813>. 

A much improved synthesis of a dioxino[23-e]indolemethanol was described. This procedure now allows the preparation of multigram quantities of the enantiomerically pure compound. Application of this methodology to different 5-hydroxy heterocycles enables access to furo[33- [l,4]benzodioxin, thieno[33-/l[l,4]benzodioxin and l,4-dioxino[23-e]indazole ring systems <99S1181>. 

An enantioselective aryloxylation of aldehydes is based on their prior conversion to an enamine through reaction with a chiral secondary amine catalyst. A subsequent inverse HDA reaction with o-quinones leads to 3-alkyl-2-hydroxy-l,4-benzodioxins with ee ca. 80% (Scheme 47). Manipulation allows the synthesis of (S)-2-alkyl-2,3-dihydro-l,4-benzodioxins <07TL1605>. In like manner, racemic nitidanin, which possesses antimalarial properties, has been synthesised through a regioselective cycloaddition of an o-quinone with a protected 3-arylpropen-l-ol <07TL771>. 

Gara A, Andersson K, Nilsson C, Norstrom A (1981), Chemosphere 10 365-390.. .Synthesis of halogenated diphenyl ethers and dibenzofurans - a discussion of specific isomers available" Gray AP, Cepa SP, Cantrell JS (1975), Tetrahedron Lett. 33 2873-2876.. .Intervention of the Smiles rearrangement in syntheses of dibenzodioxins 1,2,3,6,7,8- and 1,2,3,7,8,9-hexachlorodi-benzodioxin (HCDD) ... 

Dioxin-4-ones, synthesis of 88YGK596, 88YZ805. 2-Methyl-2-oxy- and 2-methyl-2-thio-4H-l,3-benzodioxin-4-ones, synthesis, properties and prodrug potential of 89ACS213. 

Quaglia, W., Pigini, M., Tayebati, S.K., Piergentili, A., Giannella, M., Leonard , A., Taddei, C Melchiorre, C.. 1996. Synthesis, absolute configuration, and biological profile of the enantiomers of trans-[2-(2,6-dimethoxyphenoxy)ethyl][(3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amine (mephendioxan), a potent competitive a -adreno-receptor antagonist. J. Med. Chem. 39, 2253-2258. 

A direct synthesis of 1,4-benzodioxin (174) is feasible by treatment of catechol with E)-2,3-diodo-l-phenylsulfonyl-l-propene in the presence of pyridine or potassium carbonate. Similarly,... 

Benzodioxins.—A synthesis of 5- and 8-hydroxy-l,3-benzodioxin-4-ones from 2,6- and 2,3-dihydroxybenzoic acid, dibromomethane, and benzaldehyde diacetate has been described. AA -Carbonyldi-imidazole reacts with 2-hydroxybenzamide to give the 1,3-benzodioxin in 72% yield (Scheme 9). Amides which lack intramolecular hydrogen-bonding react differently. ... 

Abstract Anhydro sugars have proved to be versatile chiral synthons for the synthesis of chiral heterocycles including pyradazines, oxazines, triazines, chiral morpholines, tetrahydroquinoxalines, benzodioxins, oxazolidinones, episulfides, thiazolines, and cyclic trithiocarbonates. Selected examples are described in this chapter. 

FIGURE 10.28 Synthesis of 2,4,5,7,8-pentamethyl-4//-l,3-benzodioxin-6-ol (PBD). (From Rosenau, T. et al., Cellulose, 9, 283, 2002. Reprinted with permission from Springer.)... 

Spectinomycin 4.50) (decahydro-4a,7,9-trihydroxy-2-methyl-6,8- wmethyl-aminopyrano[2,3-6]benzodioxin-4-one, Trobicin ) inhibits protein synthesis by binding to the 305 ribosomes. It is selective, but weak, and is reserved for treating, intramuscularly, cases of gonorrhoea resistant to penicillin and the tetracyclines B<.tyn et al., 1973). 

Scheme 4.23 Cu-catalyzed domino ring opening/coupling cyclization of o-iodophenols with epoxides Synthesis of 2,3-dihydro-l,4-benzodioxins.

Diene synthesis with 5-vinyl-2,3-dihydro-1,4-dioxins Phenolether ring from acetylene derivs. via 2,3,4a,7-tetrahydro-1,4-benzodioxins... 

Scheme 3.16 Copper-catalyzed synthesis of 1,4-benzodioxins from epoxides.

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