Conformation of 5,5-disubstituted 2,2-dimethyl-1,3-dioxanes

It was established by PMR spectral data that in solutions of derivatives of 5-acetoxymethyl-, 5-methyl-, and 5-hydroxymethyl-2,2-dimethyl-1,3-dioxanes with nitrogen-containing substituents (2,4-disubstituted 1,3,5-triazin-6-ylamino, benzamido, and nitro groups) with an N-C₍₅₎ bond the 1,3-dioxane ring exists in the chair conformation with primarily an axial orientation of the nitrogen-containing substituent. Depending on the nature of the substituents attached to the C₍₅₎ atom, the 1,3-dioxane ring may exist either in the stable chair conformation or may undergo rapid inversion of the chair-chair type at 20 °C.The author sincerely thanks A. I. Kol'tsov for his assistance in recording and interpreting the PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 468–473, April, 1985.     

Rotamere 2-Phenyl-1,3-dioxane

By means of dipole moment measurements, NMR-spectroscopical methods and force field calculations of o-, m- and p-substituted 2-phenyl-1,3-dioxanes a systematic study concerning the rotameric behaviour of the phenyl group was performed.In o-substituted 2-phenyl-1,3-dioxanes the preferred conformation of the phenyl ligand was found to be displaced about 60 degs. from thecisoid-bisectional conformer. Introduction of an additional substituent in the second o-position gives rise to a change in the rotameric state, the preferred conformation now being bisectional. In contrast, the barriers resisting rotation about the C_ar–C-2-bond in 2-phenyl-1,3-dioxane and its m- and p-substituted derivates turn out to be much lower. Thus at room temperature an ensemble of approximately bisectional rotamers exists.The conformations and rotational barriers determined are discussed in terms of non bonded and dipole-dipole interactions.

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6. Mitt.:H. Lehner, Mh. Chem.107, 565 (1976).     

Steerochemistry of heterocycles.

The stereochemical peculiarities of substituted 1,3-dioxanes and 1,3-dithianes are discussed. The high probability of the existence of flexible conformations in these series, the considerable energy preference of the 5-C-axial position in the chair conformation of 1,3-dioxanes and 1,3-dithianes, and the definite preference of the 2-C-axial position in the chair conformation of 1,3-dithianes as compared with the axial conformations of the cyclohexane type are noted. The PMR spectra of stereoisomeric 2,5-dimethyl-5-isopropyl-1,3-dioxanes, 2-methy-l5-isopropyl-1,3-dithianes, and 2,2,5-trimethyl-1,3-dithiane are described, and their configurations and preferred conformations are proved. The results of a study of the epimerization of stereoisomers of substituted 1,3-dioxanes and 1,3-dithianes are examined, and the conformational energies of individual substituents in the 5-position of these cyclic systems are calculated on the basis of this examination.See [48] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 582–592, May, 1971.     

Stereochemie der heterocyclen—XXXI : Die konfiguration und bevorzugte konformation substituierter 4-methyl-1,3-dioxane

The configuration and conformation of some stereoisomers of 4,5-, 4,5,5- and 2,2,4,5-substituted 1,3-dioxanes are examined. The stereospecifity of the reduction of alkylacetoacetic esters to 2-alkylbutandiols-1,3 and to 4,5-, 2,2,4,5-substituted 1,3-dioxanes is studied. ¹H-NMR-Data of cis- and trans-configurated 4,5- and 2,2,4,5-substituted 1,3-dioxanes are reported.     

Synthesis and nonchair conformations of 2,2-disubstituted 4,4-dimethyl-1, 3-dioxanes

The fundamental possibility of the synthesis of 2-substituted 1,3-dioxanes by reaction of 1,3-dioxanium perchlorates with organometallic compounds is demonstrated. A method for the synthesis of acyl derivatives of heterocycles was developed on the basis of these compounds. The existence of 2,2,4,4-substituted 1,3-dioxanes in the twist conformation was shown by ¹H NMR spectroscopy; the twist conformation is explained by the effect of nonbonded 1,3-syn-axial interactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1172–1179, September, 1978.     

Conformational analysis—XXI : H NMR Conformational Study of Alkyl-Substituted 2-Oxo-1,3,2-Dioxathianes

2-Oxo-1,3,2-dioxathiane and all methyl- and several alkyl-substituted 2-oxo-1,3,2-dioxathianes were prepared for a ¹H NMR conformational study. The conformational energy of the axial SO group in CCl₄, - ΔG^θ_SO = 14.8±0.3kJ mol^?1, was determined by chemical equilibration of the epimeric cis-4,6-dimethyl derivatives and it was found to decrease with the increasing solvent polarity. The conformational equilibria of alkyl-substituted derivatives were solved and the proportions of the conformers estimated using ¹H NMR chemical shifts, vicinal coupling constants and in three cases also dipole moments. The configurational interactions in the C₄C₅C₆ moiety are close to the corresponding values of 1,3-dioxanes.     

Zum rotameren Verhalten des Phenyl- und Phenyltricarbonylchrom-liganden in 2-substituierten 1,3-Dioxanen: Ein Vergleich

Dipole moment measurements, NMR-spectroscopical methods and dipole-dipole interaction calculations applied to 2-benchrotrenyl-1,3-dioxanes and a comparison with o-substituted 2-phenyl derivatives furnish evidence, that in both cases the rotameric state is mainly determined by the steric demand of the substituent being attached to phenyl: the declination angle () of the Cr(CO)₃-group from the bisectional cisoid relation (with respect to H on C-2) is identical with that for the ortho substituent and amounts to about 60 degs. The influence of the Cr(CO)₃-fragment on the conformational behaviour of the benzene moiety in geminal 2,2-disubstituted derivatives is consistent with these results: the assumption of an axial and gonal conformation for the phenyl ring, which had recently been established for 2-alkyl-2-phenyl-1,3-dioxanes, is no longer valid for the 2-alkyl-2-phenyltricarbonylchromium compounds.

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40. Mitt. über Stereochemie von Metallocenen; 39. Mitt. siehe Lit.

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Herrn Prof. Dr.H. Nowotny mit besten Wünschen zum Geburtstag gewidmet.     

17O NMR spectra of equatorial and axial hydroxycyclohexanes and 5-hydroxy-1,3-dioxanes and their methyl ethers

¹⁷O chemical shifts of axial hydroxyl groups in cyclohexanols are upfield of those of corresponding equatorial groups, but in 5-hydroxy-1,3-dioxanes the opposite is observed: the axial OH resonates downfield of the equatorial OH. The situation is the same in the corresponding methyl ethers and is, thus, not a result of intramolecular hydrogen bonding in the axial 5-hydroxy-1,3-dioxane, but appears to parallel the effect on ¹³C and ¹⁹F shifts observed in corresponding equatorial and axial 5-methyl- and 5-fluoro-1,3-dioxanes, which has been attributed to an upfield shifting effect of the antiperiplanar γ-located heteroatoms. Surprisingly, the reciprocal effect is not seen in the ring ¹⁷O shifts of the 5-hydroxy-1,3-dioxanes. A δ compression shift is seen in the ¹⁷O spectrum of trans-3,3,5-trimethylcyclohexanol (syn-axial OH and CH₃), analogous to the effect earlier reported in ¹³C spectra. Conversion of four of the alcohols to methyl ethers produces a large upfield effect on the ¹⁷O shift, larger in the cyclohexanols than in the 1,3-dioxane-5-ols. Similar upfield shifts have been recorded in the literature; their extent depends on whether the alcohols are primary, secondary or tertiary.     

Application of Empirical and Quantum-chemical Computational Methods in the Determination of the Free Conformational Energy of Substituents in 1,3-Dioxanes

The advantages and disadvantages of empirical and quantum-chemical methods for the determination of the free conformational energy of methyl and phenyl substituents at the C₍₄₎ and C₍₅₎ atoms of the ring in the molecules of 1,3-dioxanes are analyzed.     

Rh2(OAc)4-catalyzed reaction of 1,3-dioxanes with methyl diazoacetate

The reactions of methyl diazoacetate with 1,3-dioxanes in the presence of Rh₂(OAc)₄ afford 1,4-dioxepanes in up to 46% yields. The insertion of methoxycarbonylcarbene into the C—O bond occurs only in the case of 2-phenyl-1,3-dioxanes.     

Boat conformation in 2,5-substituted 1,3-dioxanes

The calculation of the energy equilibrium according to Pitzer between the chair and boat conformations in 2,5-substituted 1,3-dioxanes is presented, as well as the energies of the electrostatic dipole interactions. It is shown that the unsymmetrical boat conformation is stabilized in 2,5-dialkyl- and in 2,2-dimethyl-5-alkyl-5--alkoxyalkyl-1,3-dioxanes because of the presence of hetero atoms in the ring, because of the introduction of substituents in the 2 and 5 positions, and because of the interaction between the hybridized, unshared electron pairs of the oxygen atom at the apex of the boat with the hydrogen atom of the CH₂ group.     

Stereostructure of 2-ethynyl-substituted 2,4,4-trimethyl-1,3-dioxanes

It has been shown by PMR spectrometry and x-ray structure analysis that the six-membered 1,3-dioxane ring of 2-ethynyl-substituted 2,4,4-trimethyl-1,3-dioxanes, either in solution or in the solid state, exists in a nearly ideal chair conformation with an axial position of the ethynyl substituent. Kuban State Technological University, Krasnodar 350072, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 163–169, February, 1998.     

Zur konformativen Anordnung dipolarer Substituenten in 5-Stellung von 1,3-Dioxanen

Summary The conformation of a series of 5-nitro-1,3-dioxanes, 1,3-dioxane-5-hydroxylamines and the corresponding nitrones, obtained from the latter, has been studied by NMR spectroscopy. In the case of the nitrones, a preferred conformation of the -N(O)CHR ³ substituent to the C⁵, N single bond was found, and it was concluded therefrom on the identical conformational behaviour of the nitro analogoues. A structurally similar spiro compound confirms the suggestions given. In the case of the spiro compound, the intramolecular N-inversion process could be studied by dynamic NMR spectroscopy; the free energy of activation is given.

     

Stereochemistry of heterocycles

2-Methyl-and 2,5-dialkyl-5-phenoxy-1,3-dioxanes were synthesized and separated into their geometrical isomers by precision rectification. The configuration and conformations of these isomers were determined by PMR spectroscopy. It is shown that the low-boiling trans isomers exist primarily in the chair conformation with an equatorial phenoxy group, whereas the high-boiling cis isomers exist primarily in the chair conformation with an axial phenoxy group.     

Research on furan acetal compounds

The configuration and preferred conformations of a number of stereoisomeric 2-(α-furyl) 1,3-dioxanes were established by PMR spectroscopy. It is shown that cis orientation of the NO₂ groups with respect to the furyl ring is primarily realized for 2-(α'-nitro-α-furyl)-5-ethyl-5-nitro-1,3-dioxanes.     

O-17 NMR spectra of ring compounds. Correlation of 17O and 13C methyl substitution parameters

The ¹⁷O NMR spectra of 22 1,3-dioxanes, four exanes, four 4-heterooxanes, four tetrahydrofurans and four 1,3-dioxolanes have been recorded and methyl substitution parameters determined for the 1,3-dioxanes. The parameters, including γ_a, correlate linearly with corresponding ₁₃C parameters for methyloxanes.     

NMR experiments on acetals—57 : Conformational study of 5-alkylidene-1,3-dioxanes

From an extensive ¹H-NMR comparative study (homo-INDOR-, and nmdr-assisted) of a series of 2-, 4- and 2,4-substituted 5-alkylidene-1,3-dioxanes it is concluded that the basic conformation is a flattened chair (Fig. 5c,f). This is substantiated by the low barrier to ring reversal in 5-methylidene- and 5-propylidene-1,3-dioxane of ?G^≠ ～ 5·5 kcal/mole (T_c resp. ?158° and ?161°).     

Spectres RMN et analyse conformationnelle de germa-4 dioxannes-1,3

Methods for the calculation of the torsional angle of the C? C linkage

1 Voir Réf. 1.

are applied to some 4-germa-1,3-dioxanes. It is thereby shown that 4,4-diethyl-2trichloromethyl-4-germa-1,3-dioxane in CCl ₄ and C ₆ D ₆ adopts the chair conformation, with the equatorial C? Cl ₃ group distorted by the presence of the germanium: the torsional angle of the Ge-CH ₂ -CH ₂ -O-fragment is 45°. The most stable 6-alkyl derivatives ( cis isomers) have the same conformation; the less stable trans - tert -butyl isomer prefers a skew-boat form compatible with a torsional angle of about 60°.     

Alkoxy compounds

Twenty-six previously unreported 5-alkoxymethyl-2,5-dialkyl-1,3-dioxanes have been synthesized by the condensation of 2-alkoxymethyl-2-alkylpropane-1,3-diols with aldehydes. It has been shown by an analysis of the PMR spectra of these dioxanes that the 1,3-dioxanes considered are mixtures of two stereoisomers. In some cases these mixtures have been resolved into the individual isomers by vacuum fractionation in efficient columns. The configurations and conformations of the stereoisomeric 5-alkoxymethyl-2,5-dialkyl-1,3-dioxanes have been established by the NMR method; it has been shown that the lower-boiling isomers have the trans configuration and predominantly the chair conformation and the higherboiling isomers the cis configuration and predominantly an unsymmetrical boat conformation.For part XX, see [7].     

Electron impact mass spectra of 5,5-bis(carboethoxy)-1,3-dioxanes

Electron impact-induced fragmentations of 2-substituted 5,5-bis(carboethoxy)-l,3-dioxanes were studied by exact mass measurements and metastable ion analysis. The substituent R on C(2) of the heterocyclic ring has little influence on the principal cleavage reactions. Elimination of CH₂O/CO and C₂H₄O/C₂H₄/C₂H₅OH are common fragmentations for ions containing the 1,3-dioxane moiety or the OC₂H₅ group, respectively. The abundant ions at m/z 173 and 127 serve as structural probes for the class of compounds studied. Primary fragmentations implying the ester function are of little importance.