Benzodioxin derivatives

The oxymercuration reaction of various 2-substituted 1,4-benzodioxin derivatives 35 in the presence of a suspension of mercuric acetate in water/THF followed by treatment in situ with sodium chloride and then with sodium borohydride as a reducing agent provided in excellent yields the expected hemiketals 36 (Scheme 2) <1997X2061 >. 

Another route uses alkyloxyphenols (188) which, when treated with various arylsulfenyl chlorides yield the corresponding 2,3-dihydro-1,4-benzodioxin derivatives (189) by intramolecular cyclization <86JPR137>. 

Friedel-Crafts reactions. Phenylsulfenylation is conveniently carried out using N--oenylthiophthalimide. Acylation of benzodioxin derivatives in the presence of AlCl,-A.M.A without solvent is regioselective. This complex behaves similarly to AICI3-DMSO a.-d AIC1,-DMF. 

Quinoxaline derivatives and benzodioxin derivatives [67] possess interesting biological properties [68-85]. From the easily accessible chiral synthons, benzyl 4-0-triflyl-2,3-anhydro-yS-L-ribopyranoside (1) and benzyl 4-0-triflyl-... 

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... 

The X-ray structures of two l,3-benzodioxin-4-one derivatives (28 in Scheme 17) were reported [83T3151 90AX(C)2416] the dioxane ring was present in a half-chair conformation with the alkoxy (phenoxy) substituent in an axial orientation. 

The double )5-scission pathway becomes dominant in bicyclic systems (Equations (7)-(9) and Scheme 13). Thus, cyclopentene ozonide (69) gives cyclopropane (Equation (7)) <68TL329l>. Photolysis of the ozonide derived from 1,4-benzodioxins (70) provides a method for the preparation of labile o-benzoquinones (71) (Scheme 13) <87JOC56l6>. Photolysis can also provide a route to unstable compounds and transient species such as the aziridine-2,3-dione (72) (Equation (8)), identified at 77 K using infrared spectroscopy <80JA6902>. Relatively unstable azacarbapenems (73) have been prepared by photolysis of tricyclic compounds containing a cyclobutene ozonide (Equation (9)). On silica, the 1,2,4-trithiolane (74) underwent photo-equilibration (Equation (10)) with the 1,3-dithetane (75) and sulfur. 

A//abs) were employed as predictors of the antioxidant activity of vitamin E and its analogs <1997HCA1613>. A number of 4//-l,3-benzodioxin-6-ol derivatives 40 were evaluated in this way and a series of 4//-l,3-benzodioxin... 

Dithiin, 1,4-benzodioxin, and its 2-substituted derivatives can be readly deprotonated and trapped with electrophiles although the reaction is more problematic with 1,4-dioxin. Oxanthrene and phenoxathiin are cleaved with lithium <1996CHEC-II(6)447>. A more recent example deals with the metallation at C-3 of the 1,4-benzodioxane 60 bearing a carboxylic acid function at C-2, with lithium diisopropylamide (EDA) and subsequent quench with iodomethane. The corresponding 3-methylated benzodioxane 61 was isolated in 70% yield (Equation 6) <2000EJM663>. 

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>. 

As already mentioned in CHEC-II(1996), 1,4-benzodioxins are often obtained from the corresponding dihydro compounds <1996CHEC-II(6)447>. Thus, elimination reactions of monoiodo and monobromo <2001HC0135> or dibromo benzodioxanes <2000EJM663> allow the formation of various 2-substituted-l,4-benzodioxins in good yields. 6-Methyl-l,4-benzoxathiin was prepared from the saturated derivatives by reaction with SOCI2, then quinoline <2003BML2083>. 

Dihydro-5//-1,4-benzodioxepin (408) and halogenated derivatives (407) and (409) are obtained from 1,4-benzodioxin (406) by dihalogencarbene addition, thermolysis, and reduction (83AG(E)64). 

Benzodioxines. The reaction of benzo-l,4-dioxanes with NBS catalyzed by dibenzoyl peroxide results in 2,3-dibromo derivatives, which undergo denomination to benzo-l,4-dioxines when treated with sodium iodide in acetone (equation I).1... 

Substituted 1,4-benzodioxins yield the 7-aryl compound exclusively under Friedel-Crafts conditions, but the 2,3-dihydro derivatives give a mixture of the 6- and 7- isomers in which the latter predominates (95T2619). The reaction of the tetraoxabicyclo-[4.4.0]decanes with allyltrimethylsilane provides good yields of... 

Few structures of the benzo derivatives of these compounds have been reported, but a typical example of those which have is of 1,3-benzodioxin, in which the dioxin ring adopts an envelope conformation <88Mi 608-0i>. 

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