Heterocycles dioxanes

Andre and co-workers have utilised kneading and neat grinding in the investigation of solvate and salt formation involving the small heterocycles dioxane, morpholine or piperazine and the API 4-aminosahcylic add. In particular, the use of mechanochemical approaches has led to the simple formation of solvate and salt forms that were otherwise obtained using more complex solution-based routes. 

Thio-2-oxoselenazolidine can be obtained in 89% yield by treating the 2,4-dione with P4SJ0 in boiling dioxane (81). This structure is found in heterocyclic indigo-type dyes (Scheme 78). 

Similar dehydrofluorination occurs with polyfluorinated heterocycles. 2,2-Bis(trifluoromethyl)-3,4-difluorooxetane gives 3-fluoro-4,4-bis(trifluoromethyl)-2-oxete [19] (equation 17), and heptafluoro-p-dioxane yields hexafluoro-p dioxene [20] (equation 18)... 

Hydroxypyridine (86, R = H) and its derivatives also belong to the class of heterocyclic enols. In benzene and dioxane, 3-hydroxy-pyridine occurs as the neutral molecule (and not as a betaine).Its reaction with diazomethane, in heterogeneous media, gives a mixture of 3-methoxypyridine (86, R = Me) (10%) and l-methyl-3-hydroxy-pyridinium betaine (87) (30%If tert-butanol is used as a... 

It forms a complex with dioxane contg 2 moles of TNMe to one of dioxane, mp 44—4.5°, bp at 8mm, 61—2° (Ref 19a, p 33). It reacts with aromatic dlazonium salts to give compds of the type ArN NC(N02)3. The compds are relatively unstable and their expl props have not been examined (Ref 12). It reacts with N-hydroxymethyl compds to form adducts of the type RNHCH2C(N02)3. The same compds are formed from TNMe, formaldehyde, and the amine or from trinitroethanol and the amine (Ref 31). It forms complexes with N-contg heterocyclics whose expl props have not been examined (Ref 42). It forms complexes with benzene and methylbenzenes. The formation constants for these complexes vary from 8.46 for the benzene complex to 279.4 for the hexa methylbenzene complex (Ref 49)... 

Rhenium(VI) complexes, 4,194 alkoxides, 4,196 amides, 4,194 amines, 4,199 carboxylates, 4,199 dimethylformamide, 4,199 dioxane, 4,198 halides, 4,195,199 2-hydroxypyridine, 4,199 imides, 4,194 magnetic behavior, 1,271 mixed sulfur-nitrogen compounds, 4,196 N heterocycles, 4,199 nitrides, 4,194 oxide halides, 4, 195 oxoanions,4,196 pyridine, 4,199 sulfates, 4,198 sulfur compounds, 4,196 tellurates, 4,198... 

Heterocyclic N-oxides such as pyridine, quinoline, or isoquinoline N-oxides can be converted into a mixture of 2- and some 4-cyanopyridines, 2- or 4-cyanoquino-lines, or 1-cyanoisoquinolines, in 40-70% yield, in a Reissert-Henze reaction, by activation of the N-oxide function by O-acylation [1] or O-alkylation [2, 3] followed by treatment with aqueous alkali metal cyanide in H2O or dioxane. 

One synthetic approach involves cyclization of a substituted six-membered heterocycle which becomes the central ring of the product (6 6 6). For example, the reaction of 2,6-diaminopyridine with 2,2-dimethyl-l,3-dioxane-4,6-dione and trimethoxymethane gives the bis-adduct 118 which is a precursor to the angular tricyclic product 119 (Scheme 14) <2005AXCol>. 

In terms of economical synthetic approaches to indoles, the synthesis of this heterocycle from anilines and trialkylammonium chlorides was effected in an aqueous medium (H20-dioxane) at 180°C in the presence of a catalytic amount of ruthenium(III) chloride hydrate and triphenylphosphine together with tin(II)chloride <00TL1811>. Muchowski devised a novel synthetic route to indole-4-carboxaldehydes and 4-acetylindoles 86 via hydrolytic cleavage of W-alkyl-5-aminoisoquinolinium salts 85 to homophthaldehyde derivatives upon heating in a two phase alkyl acetate-water system containing an excess of a 2 1 sodium bisulfite-sodium sulfite mixture <00JHC1293>. 

Heterocyclic compounds are frequently used as hydrogen donors in the reduction of C-C double and triple bonds catalyzed by complexes of transition metals. Cyclic ethers such as [l,4]dioxane (39) and 2,3-dihydrofuran are known to donate a pair of hydrogen atoms to this type of compound. 2,3-Dihydro-[l,4]di-oxine (41), the product of dioxane (39), is not able to donate another pair of hydrogen atoms [46, 60, 73, 74]. These heterocyclic compounds are in general also very good solvents for both the catalyst and the substrates. 

Luhmer, M., Stein, M. L. and Reisse, J. Relative polarity of 1,3-dioxane and 1,4-dioxane studied by the reaction field theory and via computer simulations, Heterocycles, 37 (1994), 1041-1051... 

The reactions of 5-acyl-2,2-dimethyl-4,6-dioxo-l, 3-dioxanes (1373) with urea, thiourea, sulfamide, hydroxylamine, or 1-substituted hydrazines gave monocyclic six- and five-membered heterocycles (1374-1378) in good yields [79JAP(K) 106466],... 

Some of these heterocycles provide us with valuable laboratory solvents, e.g. the ethers tetrahydrofuran and dioxane (1,4-dioxane). Others are useful as organic bases, e.g. piperidine, pyrrolidine, and... 

Another type of heterocycle containing two heteroatoms susceptible of being cleaved reductively are 1,3-dioxanes or 1,3-oxathianes 422. They were treated with lithium and a catalytic amount of DTBB (4.5%) in THF at room temperature (Y = O) or at —78 °C (Y = S) to yield, after hydrolysis with water, functionalized homobenzylic alcohols 425 (Scheme 119) . The participation of intermediates 423 and 424 has been postulated in order to explain the obtained results. 

When treated with lithium in boiling ether, the heterocycle is cleaved, and subsequent carbonation results in the benzocoumarin 251 (Scheme 67). However, if the solvent is dioxane, the intermediate 250 is able to abstract a proton from the solvent and hydrolysis then results in 2-biphenylol. ... 

The diastereoselectivities in the nucleophilic addition reactions of l,3-dioxane-5-ones 37 and l,3-dithiane-5-ones 38 were studied by employing two newly available theoretical tools, the exterior frontier orbital electron (EFOE) density of the 7tc=o -orbitals and the 7t-plane-divided accessible space (PDAS) as quantitative measures of the 7t-facial steric effects <1999CRV1243, 1999CC621, 1999CL1161, 2000H(52)1435, 2001HAC358>. The two parameters predict correctly the experimentally observed stereochemical reversal of 37 and 38 (R = Ph see Table 1) in particular, the PDAS values for both substrates clearly show the opposite steric environment about the carbonyl carbon atom of these heterocyclic ketones and prove sizeable ground-state conformational differences to be responsible for the observed reversed facial stereoselection. 

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

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