Dioxane Ring Research Articles

Enzyme‐mediated synthesis of new 1,3‐dioxane odorants related to Floropal®

AbstractThe enzyme‐mediated synthesis of enantiomerically enriched 1,3‐dioxane odorants analogous to Floropal® is here described. The complete olfactory evaluation of each sample is also reported. The addition of a single methyl group at C5 of the dioxane ring of Floropal® modifies the elicited odour sensation, still preserving a pleasant character. The substitution of the methyl group at C6 with just an ethyl moiety completely changes the odour profile of the molecule. Even subtler are the odour differences generated by configurational variations. Copyright © 2004 John Wiley & Sons, Ltd.

Structure of two isomers of 2,5-diethoxy-2,5-bis(hydroxymethyl)-[1,4]-dioxane at 100 K

The crystal and molecular structures of the cis- and trans-isomers of 2,5-diethoxy-2,5-bis(hydroxymethyl)-[1,4]-dioxane have been determined by X-ray analysis. The cis- ( I) and trans-isomers ( II) crystallize in the monoclinic (space group P2 1/ c) and orthorhombic ( Pbca) system, respectively. The [1,4]-dioxane ring of the cis-isomer molecule adopts a twist-boat conformation, while the ring of the trans-isomer is a chair. The two ethoxy groups in II are in more crowded axial positions, due to the anomeric effect. The anomeric effect, stronger in the cis-isomer, influences its stability, despite the presence of two bulky hydroxymethyl groups in the equatorial orientation and the low-energy chair conformation of the trans-isomer. Both hydroxyl groups in I and II act as donors in intermolecular two-centre and three-centre O–H⋯O hydrogen bonding, which may be classified as medium strong and weak. Additionally, there are C–H⋯O hydrogen interactions in each crystal; that in the cis-isomer is intramolecular.

Crown ether substituted cobalta bis(dicarbollide) ions as selective extraction agents for removal of Cs+ and Sr2+ from nuclear waste

A series of crown ether derivatives of the cobalta bis(dicarbollide) closo-[(1,2-C2B9H11)2-3,3′-Co]− (1) anion was prepared using two synthetic strategies. The first method employs dioxane ring cleavage of the closo-[{8-(C4H8O2)-1,2-C2B9H10}-3,3′-Co-(1′,2′-C2B9H11)]0 zwitterionic species with sodium oxymethyl crowns, producing a series of anions with spacer bonded crown ether moieties varying in crown ether ring size. Three compounds of this group; closo-[{8-(15-crown-5-CH2O)-(CH2CH2O)2-1,2-C2B9H10}-3,3′-Co-(1′,2′-C2B9H11)]− (2), closo-[{8-(18-crown-6-CH2O)-(CH2CH2O)2-1,2-C2B9H10}-3,3′-Co-(1′,2′-C2B9H11)]− (3) and [{8-(21-crown-7-CH2O)-(CH2CH2O)2-1,2-C2B9H10}-3,3′-Co-(1′,2′-C2B9H11)]− (4) were prepared in high yields. The second approach involved reaction of deprotonated closo-[8,8′-(OH-1,2-C2B9H12)2-3,3′-Co]− with p-toluenesulfonyl esters derived from hydroxymethyl crown ethers. Only compounds bearing one crown ether ring resulted in preparative amount from this reaction, the [(8-{(15-crown-5-CH2O)-1,2-C2B9H10}-3,3′-Co-{8′-(HO)-1′,2′-C2B9H10}]− (5) and [{8-(21-crown-7-CH2O)-1,2-C2B9H10}-3,3′-Co-(8′-HO-1′,2′-C2B9H10)]− (6). All compounds were characterized by high field 1H and 11B NMR methods, HPLC and MS, with electrospray ionization, and the molecular structure of the Cs+ complex of species 5 was determined by single crystal X-ray diffraction analysis. These compounds represent the first examples where oxygen crown ethers were successfully bonded to the cage of anion 1. The scope and limitations of the use of these compounds in the liquid–liquid extraction of Cs+ and Sr2+ from nuclear waste were studied, including comparison of extraction efficiency and selectivity of the covalently bonded species under study with synergistic mixtures of hexabrominated anion 1 with crown ethers. As a rule, crown ethers linked to the cobalta bis(dicarbollide) cage display distribution coefficients for Cs+ and Sr2+ comparable to the crown ethers mixed with the hexabromoderivative of 1, however, they were found to exhibit better selectivity with respect to Na+ cation.

Radical Polymerization of Isomeric Methacrylic Monomers: cis- and trans-(2-Phenyl-1,3-dioxan-5-yl) Methacrylate

Two new monomers, cis-(2-phenyl-1,3-dioxan-5-yl) methacrylate (CPDM) and trans-(2-phenyl-1,3-dioxan-5-yl) methacrylate (TPDM), have been synthesized. The stereochemical configuration in both monomers was unequivocally assigned by correlation 1H−13C NMR experiments. The radical polymerization reactions of both monomers were studied by ultraviolet spectroscopy and electron paramagnetic resonance spectroscopy to determine the polymerization rate parameter kp/kt1/2 and the absolute propagation and termination rate constants (kp and kt) at different temperatures. The values of kp/kt1/2 lie in the range 0.40−0.55 L1/2/(mol1/2 s1/2) for CPDM and 0.29−0.37 L1/2/(mol1/2 s1/2) for TPDM at temperatures between 45 and 70 °C, showing that the polymerization rate of the cis monomer with the substituents in equatorial−axial positions on the dioxane ring is higher than that of its trans counterpart with the phenyl and ester residue in equatorial positions on the dioxane ring. Using EPR measurements of the polymer radical...

Experimental demonstration of anomeric effect and structure: X-ray conformational and configurational analysis of N-2-(1,4-dioxane)- N′-( p-methylbenzenesulfonyl)- O-( p-methylphenoxy) isourea

The conformational, configurational behavior and the structure of N-2-(1,4-dioxane)- N′-( p-methylbenzenesulfonyl)- O-( p-methylphenoxy) isourea ( 1 ) has been studied using X-ray crystallographic analysis. The endo-anomeric effect controls the population of dioxane ring conformers or anomers but not the configuration interconversion of the imine of the imidoyl moiety. X-Ray analysis of 1 demonstrates that the dioxane ring adopts the chair conformation, that the imidoyl amino group prefers axial conformation and that the tosyl and tolyl groups about the CN bond retain the E configuration. Isourea ( 1 ) was synthesized by the thermal decomposition of N′-( p-methylbenzenesulfonyl)- O-( p-methylphenoxy) imidoyl azide in refluxing dioxane.

New organic superconductors consisting of an unprecedented pi-electron donor.

The synthesis and electrochemical properties of a new organic donor, (1,4-dioxan-2,3-diyldithio)dihydrotetrathiafulvalene (DODHT), and the crystal structures and physical properties of its superconducting salts are described. The DODHT molecule has the bulky dioxane ring condensed by cis fusion, and the reduced pi-electron system of DODHT, as compared with conventional tetrachalcogenafulvalene donors, leads to both the weak electron-donating ability and the large on-site Coulomb energy. Nevertheless, DODHT produces the superconducting AsF6 and PF6 salts, which are isostructural and exhibit superconducting transitions at 3.3 and 3.1 K, respectively, under 16.5 kbar.

Synthesis of 12-Hydroxy and 12-Dioxane Derivatives of the closo-1-Carbadodecaborate(1-) Ion. Variations on the Plešek's Cobalt Bis(dicarbollide) Pattern

Synthesis of two new B(12) substituted derivatives of the closo-[1-CB11H12]- anion (1) is reported. The zwitterionic derivative containing dioxane ring {12-[O(CH2CH2)2O]+-1-CB11H11-}0 (2) was obtained in moderate yield using reaction of anion 1 with dioxane as solvent, induced by dimethyl sulfate. The anion [12-(HO)-1-CB11H11]- (3) was obtained in high yield upon treatment of the parent anion with 80% H2SO4 at high temperature. Both compounds containing reactive functionalities were designed to serve as useful synthons for a variety of synthetic purposes. The compounds were characterized by 11B and 1H high-field NMR, IR spectroscopy, mass spectrometry, melting points and TLC. Molecular structure of compound 2 was determined by single crystal X-ray diffraction analysis.

Chemical shift effects in the 13C-NMR spectra of [(C 5H 5)(CO) 2Fe II]-substituted cyclohexanes, dioxanes and tetrahydropyrans

A set of empirically derived 13C-NMR chemical shift additivity constants have been calculated for the Fp-substituent on cyclohexane, tetrahydropyran and dioxane rings. These were tested against a series of alkyl substituted Fp-complexes. These parameters prove to be highly reliable; the calculated and experimental chemical shifts are within ±1 ppm. The parameters vary greatly between ring systems. One explanation for the differences relates to changes in conformation about the bond connecting the Fp-group to the various rings.

Development of Organic Metals Based on the Extended TTF Donors by the [sgrave]-Bond Framework

Investigations of the tetrathiafulvalene (TTF) derivatives extended by the [sgrave]-bond frameworks, such as saturated heterocycles (3–8) and alkyl groups (9), have been undertaken to explore new molecular-based organic metals. TTF donors with the periphery extended by the cis-fused dioxane ring (3) and by linkage of a dichalocogenolane or dioxane ring (4–6 or 7) produce metallic radical-cation salts. While radical-cation salts of the methylated TTF donor (9a) are semiconductive, the ClO4 and PF6 salts of the ethylated one (9b) exhibit metallic conducting behavior for compressed pellets. The crystal structure of the metallic (4)2AsF6 salt is also presented.

Synthesis and Spectroscopic Analysis of a Cyclic Acetal: A Dehydration Performed in Aqueous Solution

The treatment of aldehydes (and ketones) with diols in the presence of acid gives acetals (and ketals) in an equilibrium reaction. Treatment of pentaerythritol with benzaldehyde in aqueous acid gives the monoacetal, 5,5-bis(hydroxymethyl)-2-phenyl-1,3-dioxane. The reaction has a number of interesting features. The isolated product is the monobenzal not the dibenzal, and the reaction, a dehydration, is performed in water. The reaction proceeds to provide the acetal owing to the insolubility of the product in the aqueous reaction medium, thus removing the product from the equilibrium. This experiment is suitable for incorporation into the undergraduate organic laboratory as the synthesis of a product for characterization by melting point, solubility, and proton nuclear magnetic resonance. Only through recognition of the three-dimensional structure of the dioxane ring can students explain the appearance of the 1H NMR spectrum of the product. The hydroxymethyl groups of the product are inequivalent, as are th...

Identification of paraldol-deoxyguanosine adducts in DNA reacted with crotonaldehyde.

Crotonaldehyde (1) is a mutagen and carcinogen, but its reactions with DNA have been only partially characterized. In a previous study, we found that substantial amounts of 2-(2-hydroxypropyl)-4-hydroxy-6-methyl-1,3-dioxane (paraldol, 7), the dimer of 3-hydroxybutanal (8), were released upon enzymatic or neutral thermal hydrolysis of DNA that had been allowed to react with crotonaldehyde. We have now characterized two paraldol-deoxyguanosine adducts in this DNA: N(2)-[2-(2-hydroxypropyl)-6-methyl-1,3-dioxan-4-yl]deoxyguanosine (N(2)-paraldol-dG, 13) and N(2)-[2-(2-hydroxypropyl)-6-methyl-1, 3-dioxan-4-yl]deoxyguanylyl-(5'-3')-thymidine [N(2)-paraldol-dG-(5'-3')-thymidine, 14]. Four diastereomers of N(2)-paraldol-dG (13) were observed. Their overall structures were determined by (1)H NMR, by MS, and by reaction of paraldol with deoxyguanosine and DNA. (1)H NMR data showed that two diastereomers had all equatorial substituents in the dioxane ring, while two others had an axial 6-methyl group. Preparation of paraldol with the (R)- or (S)-configuration at the 6-position of the dioxane ring and the carbinol carbon of the 2-(2-hydroxypropyl) group allowed partial assignment of the absolute configurations of N(2)-paraldol-dG (13). Four diastereomers of N(2)-paraldol-dG-(5'-3')-thymidine (14) were observed. Their overall structure was determined by (1)H NMR, MS, and hydrolysis with snake venom or spleen phosphodiesterase. Reactions of nucleosides and nucleotides with paraldol demonstrated that adducts were formed only from deoxyguanosine and its monophosphates. Experiments with DNA that had been reacted with crotonaldehyde indicated that N(2)-paraldol-dG-containing adducts in DNA are relatively resistant to enzymatic hydrolysis. The results of this study demonstrate that the reaction of crotonaldehyde with DNA is more complex than previously recognized and that stable N(2)-paraldol-dG adducts are among those that should be considered in assessing mechanisms of crotonaldehyde mutagenicity and carcinogenicity.

A Highly Efficient and Shortcut Synthesis of Cyclitol Derivatives via Spiro Sugar Ortho Esters

Preparation of cyclitol derivatives from sugar lactones via spiro sugar ortho esters is described. The key steps are the novel enol ether formation from sugar ortho esters with AlMe 3 and the efficient intramolecular aldol cyclization of alkyl enol ethers with ZnCl 2 in THF/H 2O. Firstly, the spiro sugar ortho esters 3a– c were prepared from the benzyl protected sugar lactones 1a– c and 2,2-dimethylpropanediol ( 2). These ortho esters were efficiently converted into the enol ethers 5a– c by the treatment of AlMe 3 in CH 2Cl 2. The initial step of this reaction was the pyran ring cleavage accompanied by the methyl anion insertion, and the second was the dioxane ring opening caused by the Lewis acidity of AlMe 3. The resulting alkyl enol ethers were treated with DMSO/Ac 2O, and the formed keto compounds were converted into the carbasugars 9a– c by the ZnCl 2-catalyzed aldol cyclization in THF/H 2O. The overall yields of 9a, 9b, and 9c based on the corresponding lactones 1a– c were 64, 64, and 54%, respectively.

Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives.

Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidic conditions afforded a series of dioxane-triazole compounds 14-16. The antifungal activities of the compounds 14-16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.

Molecular Design and Properties of Chemically Cleavable Surfactants

Examination was made of the development and properties of chemically cleavable surfactants. Chemically cleavable surfactants possessing dioxolane, dioxane ring, noncyclic acetal group and carbon-nitrogen double bond were synthesized and found to easily undergo hydrolytic decomposition by acid. Many of these surfactants were noted to have good surface activity and undergo biodegradation in addition to acid-sensitivity. Bis (sodium sulfonated ester) and bis (ammonium bromide) surfactants were synthesized and found to exhibit alkali-sensitivity, surface activity and biodegradability. Ozon-cleavable surfactants bearing carbon-carbon double bonds were also produced and noted to have good surface active properties and biodegradability.

(2S,4S)-4-Hydroxymethyl-1,3-dioxan-2-yl]ferrocene

The structure of the title complex, [Fe(C 5 H 5 )(C 10 H 13 O 3 )], shows the occurrence of two stereogenic centres in the hydroxymethyl-1,3-dioxane fragment. The S configuration found for these chiral C atoms agrees with the synthetic route. The dioxane ring has a nearly perfect chair conformation. O-H...O hydrogen bonds result in the formation of an eight-membered ring built from the arrangement of four complex molecules around a fourfold axis.

Bis(1,3-dioxan-2-yl)arenes: precursors to linked porphyrins.

The crystal structures of two linked-prophyrin precursors have been determined. In the crystalline state, 1,4-bis[2-(1,3-dioxan-2-yl)phenyl]butane, C24H30O4, (I), exists in a stair-like conformation with dioxane rings in chair conformations. The molecule is positioned on an inversion center. In the crystalline state, 1,2-bis(1,3-dioxan-2-yl)benzene, C14H18O4, (II), is arranged in zigzag chains. In each chain, molecules of (II) are tilted 106.2 (1) degree relative to each other. They are also oriented to form a weak C-H...O contact (H...O 2.43 A).

BEDT-TTF derivatives with one and two dioxane rings and their conductive salts

Electron donors 4,5-(1,4-dioxanediyl-2,3-dithio)-4′,5′-ethylenedithiotetrathiafulvalene (DOET) and 4,5;4′,5′-bis (1,4-dioxanediyl-2,3-dithio) tetrathiafulvalene (BDDT) have been synthesized and their molecular and crystal structures have been solved. DOET and BDDT were shown to have bath conformations. Radical cation salts based on these donors have been prepared. The structure of the organic metal (DOET) 2HSO 4 has been determined.

Anti-1,3-diols by Addition of Dialkylzinc Reagents to 4-Acetoxy-1,3-dioxanes.

Dialkylzincs couple with 4-acetoxy-6-alkyl-1,3-dioxanes in the presence of trimethylsilyl triflate (TMSOTf) to form trans-4,6-dialkyl-1,3-dioxanes with excellent diastereoselectivities. These dioxanes could be deprotected to yield anti-1,3-diols. A variety of functional groups are tolerated in the dialkylzinc, although silyl and benzyl ethers led to diminished diastereoselectivities. Substituents at the C5-position of the dioxane ring have little effect on the selectivity, while small C2 (acetal) substituents led to slightly reduced diastereoselectivity. These couplings work best with cyclic acetals, which can be difficult to hydrolyze. The 4-(benzyloxy)butanal (BOB) acetal has been developed as a new cyclic acetal protecting group that is compatible with dialkylzinc coupling reactions. BOB protecting groups are easily removed by catalytic hydrogenation followed by mild acid hydrolysis.

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY OF CARDIAC STEROIDS

High performance liquid chromatography-tandem mass spectrometry (LS/MSn) utilizing an ion trap mass spectrometer has been used for the analyses of representative cardiac steroids. In the case of bufotoxin having a polar residue (suberoylarginine), the positive-electrospray ionization (ESI) was 50 times more sensitive than the atmospheric pressure chemical ionization (APCI) and provided information concerning the molecular weight as well as the structures of both aglycone and suberoylarginine. The corresponding bufogenin showed 2 times better sensitivity in the positive-APCI than ESI. The mass spectrum of digoxin with the positive-APCI showed fragment ions not only derived from aglycone but also formed by losses of sugars. The cleavage of the dioxane ring has been observed on the cardiac glycoside having an unusual sugar linkage. Fast atom bombardment mass spectra of these compounds were examined and compared with the data obtained from LC/MSn.

Structure elucidation of annoheptocins, two new heptahydroxylated C37 acetogenins by high-energy collision-induced dissociation tandem mass spectrometry

Collision-induced dissociation (CID) of lithiated molecules generated by liquid SIMS (LSIMS) from two new natural compounds, annoheptocin A and B, led to their structural elucidation. Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) investigations of their acetonide derivatives displayed obvious differences of reactivity of the lithiated dioxane and dioxolane rings towards CID. The 1,3-dioxane (six-membered) ring could be the target of hydrogen rearrangement processes, leading to the formation of a tetrahydrofuran ring through the loss of a molecule of acetone. Copyright © 1998 John Wiley & Sons, Ltd.