Benzo -1,3-dioxane

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]. 

A simple diagnostic method has been proposed to distinguish regioisomers of natural benzo-dioxane lignoids (Fig. 16) with different aryl (Ar) and alkyl (R) substituents (07 8 -l to 07 8 -13), based on small, but systematic differences in 13C chemical shifts of C-7 and C-8 of the coumarin moiety, provided that both isomers are available (86). 

Amino-6,7-dimethoxy-2-quina2olinyl)-4-(1,4-benzo-dioxan-2-ylcarbonyljpiperazine monomethanesulfonate,... 

Habermann, J., Ley, S.V., Scicinski, J.S., Scott, J.S., Smits, R., and Thomas, A.W., Clean synthesis of a-bromo ketones and their utilization in the synthesis of 2-alkoxy-2,3-dihydro-2-aryl-l,4-benzo-dioxanes, 2-amino-4-aryl-l,3-thiazoles and piperidino-2-amino-l,3-thiazoles using polymer-supported reagents, J. Chem. Soc., Perkin Trans. 1, 2425, 1999. 

S >Olmethaxytrltyl>2 -d oxythylmldlne-3 -phosphate (3). A sohjllon ot 1 mmol ot 1 (T thymine, DMT-4,4 -dimethoxyti1tyl) in dioxane (8 mL), pyridine (1 mL) and a slight excess ot 2-chloro-5,6-benzo-1,3-dioxaphosphorfn-2-one 2 (1 mi. ot a 1.2S M solution in dioxane) was stirred at 20 C After 5 mki TLC Indicated complete conversion oM Into 3 with zero mobility. Water was added and after work up 3 was isolated in 88% yield. 

Another photocyclization to a benzo[c]phenanthridine was reported (127). Oppenauer oxidation of ( )-ophiocarpine (92) with potassium fm-butoxide and benzophenone in dioxane effected C-6—N bond cleavage to afford the hydroxyisoquinoline 219 via berberinephenolbetaine (121) (Scheme 39). Although photolysis of 219 gave only the oxepine 221, that of its methyl ether 220 furnished directly norchelerythrine (222) through electrocyclization followed by spontaneous elimination of methanol. 

Reagent-grade dioxane (2 1.) is heated to reflux with the sodium ketyl of benzophenone prepared from 10 g. of benzo-phenone and 1 g. of sodium until a deep blue solution results. If the color is not developed, another portion of benzophenone and sodium is added and the heating continued until the color persists. The peroxide-free dioxane is distilled from the flask and is used immediately. 

Benzo[ ]perimidinone carbaldehyde and carboxylic acid derivatives have also been prepared by alkyl oxidation. Thus, treatment of the 2-methyl derivative 588 with selenium dioxide at reflux in dioxane gave the aldehyde 589, which then gave carboxylic acid 590 on reaction with sodium chlorite <2001JME2004>. 

In this chapter, the structures and chemistries of 1,3-dioxins, 1,3-oxathiins, and 1,3-dithiins are described, including both their fully saturated forms (1, 7, and 13) as well as their benzo analogs (6, 11, 12, and 17). The formally fully unsaturated monocyclic structures (4, 9, 10, and 16) contain only one endocyclic double bond with further unsaturation being accomodated by exocyclic double bonds (2, 3, 5, 8, 14, and 15), for example, by the introduction of a carbonyl group. Well known and intensively studied are the Meldrum s acid derivatives 18 and 19. In addition, 1,3-dioxane, 1,3-oxathiane, and 1,3-dithiane moieties can be part of spiro structures as well as hi- and tricyclic analogs. And finally, both the structures and chemistries of the corresponding sulfoxides and sulfones are also reported. 

Routes to benzo-fused derivatives of 1,4-dioxanes, 1,4-oxathianes and 1,4-dithianes make use of anions or dianions of the appropriate 1,2-disubstituted benzene. An alternative approach to the synthesis of 1,4-benzodioxanes involves Diels-Alder addition reactions of alkenes across the quinone function of 1,2-benzoquinones, e.g. (352) — (353). 

Furan is resinified by sulfuric acid but it can be sulfonated with the complex of sulfur trioxide with pyridine or dioxane. Depending on conditions the 2-sulfonic or the 2,5-disulfonic acid may be obtained. Furan-2-carboxylic acid can be sulfonated with oleum. Benzo[6]furan is polymerized by sulfuric acid. The 2-sulfonic acid has been obtained by oxidation of the sulfinic acid available in turn by treatment of the lithio derivative with sulfur dioxide. Benzo[6]furan with the sulfur trioxide-pyridine complex allegedly affords the 3-sulfonic acid. 

The transannular formation of sulfonium ion intermediates is not limited to six-membered rings. A similar contraction of a benzo[6]thiepin derivative occurred when (288) was refluxed in dry dioxane, giving a quantitative yield of (289) (74CC626). 

Benzyl L-glutamate-NCA was polymerized in dioxane at rt using (benzo-15-crown-5)-4-amine as initiator. The ratio of the NCA to the initiator was 50. The polymer with C-terminal crown ether was characterized by FTIR. 

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... 

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