1.3- Dioxan 2-phenyl-, preparation

Prins reaction. 4-Phenyl-/n-dioxane was prepared first by H. J. Prins in 1919 by reaction of styrene and formaldehyde in the presence of sulfuric acid, but the correct structure was inferred only in 1930. A modern procedure calls for stirring a mixture of formalin, coned, sulfuric acid, and styrene under gentle reflux for 7 hrs. The mixture is cooled, and the product collected by extraction with benzene. 

Oxidation of phenyl hexyl sulphide with sodium metaperiodate gave also only a trace amount of the corresponding sulphoxide72. On the other hand, Hall and coworkers73 prepared benzylpenicillin and phenoxymethyl penicillin sulphoxides from the corresponding benzyl esters by oxidation with sodium metaperiodate in dioxane solution with a phosphate buffer. A general procedure for the synthesis of penicillin sulphoxides was reported later by Essery and coworkers74 which consists in the direct oxidation of penicillins or their salts with sodium metaperiodate in aqueous solution at pH 6.5-7.0. 1-Butadienyl phenyl sulphoxide 4475 and a-phosphoryl sulphoxides 4576 were also prepared by the same procedure. 

Phenylthio acetals are much more easily prepared from the corresponding 4-acetoxy-l,3-dioxanes [45] (Eq. 29). The dioxane 125 gave the phenyl sulfides 185 in essentially quantitative yield on treatment with BF3 OEt2 and thiophenol at -78 °C. This method has been used to prepare compound 185 on a 40 g scale. 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

The method outlined here competes well with the method developed earlier by Danheiser, et al.618 Its superiority is based on the fact that phenyl ester enolates give almost the same results as the S-phenyl thiolester enolates. However, handling the malodorous benzenethiol for the preparation of the active acid derivative and during workup of the p-lactone can be avoided. In addition, phenol is much cheaper than benzenethiol. The method is well suited for the preparation of p-lactones from symmetrical and unsymmetrical ketones. In addition to 3,3-dimethyM-oxaspiro[3.5]nonan-2-one, ( )-3-ethyl-1-oxaspiro[3.5]nonan-2-one and (3R, 4R )- and (3R, 4S )-4-isopropyl-4-methyl-3-octyl-2-oxetanone were prepared by this procedure in high yields (Notes 11 and 12). In the case of unsymmetrical ketones the less sterically crowded diasteroisomer is formed preferentially. With aldehydes as the carbonyl component the yields are unsatisfactory, because of the competitive formation of 1,3-dioxan-4-ones.6... 

Spoly(vinylbenzylchloride). -Cross-linked using divinylbenzene. Chloromethylated, cross-linked polystyrene resins were obtained coiranercielly from Bio-Rad Laboratories. Percent chloromethylation js based on the available phenyl groups in the polymer that is minus the percent cross-linking. =D=dioxane E ethanol. Percent of available chloromethyl croups reacted with donor. —Percent reaction x percent chloromethylation. Polymer prepared by free-radical polymerization of 60.00 para-neta chloromethylated sytrene (Dow Chemical). Reaction heated at 50-55°C. 

DePuy, as early as 1966 [14], reported that cw-1-methyl-2-phenylcyclopropanol gave exclusively deuterated 4-phenyl-2-butenone in 0.1 M NaOD/D20/dioxane. However, homoenolates derived from simple cyclopropanols by base-induced proton abstraction fail to react with electrophiles such as aldehydes and ketones, which would afford directly 1,4-D systems. Lack of a reasonably general preparative method was another factor which impeded the studies of homoenolate chemistry. For this reason, in the past twenty years more elaborated cyclopropanols, which might be suitable precursors of "homoenolates", have been prepared and studied. 

Aiyl-l,2,5-thiadiazoles or 3-aryl-4-halogeno-l,2,5-thiadiazoles can be readily prepared from l-aryl-2-haloethanone or 1-aryl-2,2-dihalogenoethanone oximes and tetrasul-fur tetranitride ". For instance, interaction of dichloroacetophenone oxime 280 with S4N4/dioxane at reflux afforded 3-phenyl-4-chloro-l,2,5-thiadiazole 281 in 98% yield (equation 121). 

A similar spiro-fused starting material was prepared to study the thermolysis of a 1,3-dioxane analog. As found for the dithia compound (cf. Section 8.11.6.3.1), a carbene-derived dimer was formed as the major detectible product (20%) <2002TL1927>. Other products, such as tricycle 185, have been identified in subsequent studies <2004CJC1769>. However, phenyl substitution at G-4 provided completely different thermolysis products, probably via formation of an open-chain bis-radical. Thus, 3-phenyl-7-butyrolactone and, after CO2 extrusion, phenylcyclo-propane are the major reaction products (Scheme 58) <2002CJC1187>. 

Preparation of l-p-nitrophenyl-4-p-nitrobenzoxy-2,6,7-trioxabicyclo-[2.2.2]octane by the reaction of 2-phenyl-5,5-bis(p-nitrobenzoxymethyl)-l,3-dioxane with p-nitrophenylhydrazine and acetic acid [202]. 

Condensation (dioxan + cone. HC1) of p-benzyloxy benzoin with various phenols or naphthols gives 3-(p-benzyloxyphenyl)-2-phenyl-benzofurans, starting material for the preparation of diarylbenzofurans and of 1,2-diphenylnaphtho[2,1 -6]furans with antifertility activity.83... 

Compound 98 was condensed with o-aminothiophenol, 2-aminoethanol, or cystamine in refluxing diphenyl ether through an intermolecular cyclization with the elimination of two molecules of water to give the polyfused derivatives 101-103, respectively. Also, the reactions of 98 with dimethylthiomethylenemalononitrile in boiling dimethylforma-mide (DMF) were studied. The dimethylthiomethylenemalononitrile was prepared via the reaction of malononitrile with CS2 with 2 equiv of methyl iodide in a one-pot reaction using liquid-liquid phase-transfer catalysis (PTC) technique (NaOH/dioxane/tetrabutylammonium bromide (TBAB)). The product of this reaction was identified as 8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-77/-pyrano[3,2-/][l,2,4]-triazolo[3,4-A][l,3,4]thia-diazepine 104 (Scheme 10). 

The precursor semicarbazones 256 and 260 were also prepared from the reaction of 1,2-diaza-l,3-butadienes 254 and 258 and activated methinic compounds such as diethylphenylmalonate, trimethylmetanetricarboxylate, 2,2-dimethyl-5-phenyll,3-dioxane-4,6-dione, 255, and dimethyl nitromalonate 259 in the presence of catalytic amount of MeONa or NaH in THF (Scheme 34) <2003JOC1947>. 

Freifelder obtained an 82% yield of benzylhydrazine by hydrogenating a freshly prepared hydrazone over Pd-C in ethanol at 0.3 MPa H2 in less than 30 min.83 However, when the hydrazone was allowed to stand for several days to a week, the yield dropped to 45-48%. In the hydrogenation of phenylacetone hydrazone, Biel et al. observed that the formation of large amounts of jV,iV -bis(l -phenyl-2-propylidene)hydrazine took place when hydrogenation proceeded slowly and incompletely with such catalysts as Pd-C, rhodium, ruthenium, and platinum oxide, and with solvents such as alcohol, water, ethyl acetate, tetrahydrofuran, and dioxane. The A(A%disubstituted hydrazine was obtained when the hydrogenation proceeded slowly to completion, as over platinum oxide in aqueous acetic acid. With Raney Ni in ethanol, the azine and l-pheny-2-propylamine were formed almost exclusively. 1-Phenyl-2-propylhy-drazine was obtained in acceptable yields of 55-70% by use of platinum oxide or supported platinum in alcoholic acetic acid at a pressure of 13.8 MPa H2. The products obtained over platinum oxide in various conditions are summarized in eq. 8.40.78... 

The absorption maxima in toluene and ethanol, the thermal fade rate constants in toluene and dioxane, and the kinetic parameters AH and AS for a series of F-phenyl- and T-carbethoxymethyl-6-nitro BIPS having also methoxy, bromo, or nitro substituents in the 8-position have been recorded. The effects of the substituents on the Xmax and the rate constants are discussed. The preparation of 1-carbethoxy-methylFischer s base is given in detail.112... 

In a subsequent investigation by the author, 2-[5-(4-fluoro-phenyl)-4-pyridin-4-yl-lH-imidazol-2-yl]-5-methyl-[l,3]dioxane, (I), was prepared (2). 

Another important use of SeOj is in the oxidation of CH3 groups to CHO, but not to COOH group. But such CH3 group must be activated by a carbonyl or other group. Thus phenyl glyoxal has been prepared in about 72% yield by refluxing a solution of acetophenone in the medium of dioxane for about 4 hours. 

Segi and co-workers reported a more efficient procedure that furnished both phenyl- and alkyl-telluraldehydes (92). The new tellurating reagent (94) reacts directly with aldehydes in refluxing dioxane, and in the presence of a diene, the expected adducts 93 (R = Ph, n-Pr, and f-Bu) are formed in 44-62% yield (89JA8749). Telluroketones were prepared similarly and trapped with cyclopentadiene. 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

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