Catechols 1,4-benzodioxanes

Azaloxan (12) is an antidepressant agent. Its synthesis can be accomplished starting with the reaction of catechol (7) and 3,4-dibromobutyronitrile (obtained by addition of bromine to the olefin) to give l,4-benzodioxan-2-ylacetonitrile (8). A series of functional group transformations ensues [hydrolysis to the acid (9), reduction to the alcohol (10) and conversion to a tosylate (11)] culminating in an SN-2 displacement reaction on tosylate 11 with l-(4-piperidinyl)-2-imidazolidi-none to give azaloxan (12) [3]. 

This type of reactivity has been exploited for the preparation of 1,4-benzodioxanes from catechols and propargylic carbonates. Using 2,2 -bis(diphenylphosphino)-l,T-binapthyl (BINAP), this process has been rendered asymmetric with ee s up to 97% (Equation (68)).254,255... 

Benzodioxanes (6, 516). The earlier synthesis of benzodioxanes by oxidative coupling of catechol derivatives with methoxypropenylphenols has been extended to the first synthesis of the complex benzodioxane silybin (3) shown in equation (I).2 The starting materials are (2R,3R)-dihydroqucrcctin (I) and coniferyl alcohol (2). In this case, the reaction is not regioselective, 3 and the isomeric 4 being obtained in nearly equal amounts. 

The monobenzo-fused derivatives of 1,4-dioxin, 1,4-oxathiin and 1,4-dithiin, (345), (346) and (347), can all be prepared by base-catalyzed reaction between the appropriate 1,2-disubstituted benzene and an a-haloketal via an intermediate 2-alkoxy-2,3-dihydro derivative (348). The pyrolysis of the acetoxy derivative (349) at 450°C gives (345 80%) (67ZC152). 2-Hydroxy-2-phenyl-l,4-benzodioxane, from catechol and phenacyl bromide, is dehydrated to (345) by thionyl chloride in pyridine. 

Racemic 2,3-butanediol was converted to the racemic ditosy-late, which was then treated with catechol under the influence of NaOH in dimethylformamide (DMF) to yield the desired compounds, cis- and trans-2,3-dimethyl-l,4-benzodioxane [3] and [4]. The solid trans isomer [4] was obtained by repeated recrystallization from methanol. Column chromatography of the mother liquid using AloOj as adsorbent and petroleum ether and diethyl ether in a 1 1 ratio as eluent, gave pure liquid cis isomer [3]. By comparison with the PMR spectra (8) of pure trans- and cis-2,3-dimethyldi-oxane, the solid isomer was identified as trans, and the liquid isomer as cis. The compounds were further characterized by IR, NMR, CMR and elemental analyses. The CMR spectral data for 2 and 4 are summarized in Table I. 

Dimeth.y1-l,4-benzodioxane [3] [41. Into a stirred solution of 62 g (1.1 mole) K0H, 55 g (0.5 mole) catechol and 1.5 1 DMF in a flask, equipped with mechanical stirrer, pressure-equalizing addition funnel and condenser with drying tube, was added a solution of 2,3-butanediol ditosylate in 500 ml DMF. After stirring at room temperature for 24 hours and refluxing 24 hours, it was mixed with twice the volume of water and extracted with twice the volume of diethyl ether. The extract was dried over anhydrous MgS04 and condensed in a rotary evaporator. Fract. dist. (vac) gave 24 g mixture of cis- [3] and trans-2,3-dimethyl-1,4-benzodioxane [4]. Yield 29.23%. b.p. 96-100°C/6 mm. Anal. Calcd. for C-.H. O, C, 73.12 H, 7.36. Found C, 73.27 H, 7.40. u c c... 

Substitution reactions of attylic systems. An access to allylic thiols is based on substitution by MeCOSK with (dbaljPdj-dppb as catalyst. 2-Alkylidene-3-alkyl-l,4-benzodioxanes are readily formed in a reaction between catechols and propargylic carbonates. ... 

Cleavage of 1,4-benzodioxane. Treatment of 1,4-benzodioxane (1) with -butyllithium in ether at 0° results in formation of the monovinyl ether of catechol (2). ... 

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