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].     

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.     

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.     

Stereochemistry of heterocycles

Methods were developed for the synthesis of 2-ethoxy-1,4-butanediol and 2-ethoxy-1,4-pentanediol. The latter was a mixture of diastereomers. These diols were used to synthesize 5-ethoxy-1,3-dioxepan and 2,2,4-trimethyl-6-ethoxy-1,3-dioxepan. Gas-liquid chromatography was used to demonstrate that 2,2,4-trimethyl-6-ethoxy-1,3-dioxepan is a mixture of cis and trans isomers; the ratio of these isomers is similar to the ratio of diastereomers in the starting 2-ethoxy-1,4-pentanediol. The configurations of the indicated isomers were evaluated by conformational analysis.See [1] for communication XIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 3–6, January, 1972.     

Stereochemistry of heterocycles

Some 2,5-dialkyl-2-methyl-1,3-dioxanes and 5-alkyl-2-methyl-2-phenyl-1,3-dioxanes have been synthesized. All the compounds studied consist of epimeric mixtures of geometric isomers the equilibrium in the course of the formation of which is shifted in the direction of the isomers with the diequatorial position of the largest substituents. The predominant conformation of the molecules of both isomers is the chair conformation. The cis isomers of the substances investigated consist of mixtures of conformers.For Communication XIX, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1240–1245, September, 1973.     

Esters of 2,5-multisubstituted-1,3-dioxane-2-carboxylic acid: their conformational analysis and selective hydrolysis

The carbomethoxy group at the C2 position of the 2,5-multisubstituted 1,3-dioxanes prefers the axial conformation rather than the equatorial one due to an anomeric effect. The trans isomers of the 5-monosubstituted compounds are more selectively hydrolyzed than the cis isomers. Based on the calculated results, hydrolysis to the trans isomers is attributed to the larger carbonyl charges of the trans than those of the cis isomers. The anomeric and homoanomeric effects will explain the axial preference of the carbomethoxy group and selective hydrolysis to the trans isomers. Furthermore, the calculated stability between the cis and trans isomers is in good agreement with the experimental results in the equilibrium state.     

Stereochemistry of heterocycles

A number of 4-methyl-5-alkyl-5--methoxyethyl- and 2,2,4-trimethyl-5--methoxyethyl-1,3-dioxanes were synthesized. Precision rectification was used to isolate the individual stereoisomers, the configurations and preferred conformations of which were confirmed by IR and PMR spectroscopy. The reduction of the alkyl--methoxyethylacetoacetic esters, which gives the starting compounds for the synthesis of 1,3-dioxanes of 2-alkyl2--methoxyethylbutane-1, 3-diols, proceeds stereospecifically.See [1] for communication XVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1475–1479, November, 1972.     

Stereochemistry of heterocycles

The conformations of stereoisomeric 2,5-dialkyl-1,3-dioxanes were studied by means of dipole moments (DM), and it was shown that the low-boiling isomers have a chair conformation or a somewhat distorted symmetrical boat conformation, while the high-boiling isomers have a chair conformation with diequatorial orientation of the substituents. The DM measurements lead to values for the ketals which are closest to those calculated for the chair conformation.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 593–596, May, 1971.The authors sincerely thank Academician D. A. Arbuzov for his unflagging interest and involvement in this investigation.     

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 of the complexes of copper(ii) with two identical α-amino acid ligands,relative stability of the cis and trans isomers

Conclusions The energy closeness of the cis and trans isomers of the (Ala)₂Cu complexes, and consequently the possibility of the presence of the cis isomers in the equilibrium mixture, was shown. The differences in the energies of the cis and trans isomers increase in the complexes with the N-mono- and N,N-dimethyl-substituted alanine. The coexistence of both isomers is thereby possible for the monosubstituted compounds, but the disubstituted cis isomers are virtually unrealized. According to the conformational calculations, the formation of the optically active compounds containing ligands of one configurational series is more preferred among the complexes considered.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2484–2487, November, 1987.     

Crystallinity and thermal properties of polyamides containing cis- and trans-1,3-cyclohexane rings

The cyclohexane ring-containing polyamide 1,3-CBMA-6 was synthesized from 1,3-cyclohexane-bismethylamine (1,3-CBMA) and adipic acid (6), and effects of cis/trans isomers of the ring on crystallinity and thermal properties were studied. Polymers with high cis and high trans contents, respectively, were made by polymerizing the 1,3-CBMA-6 salts of 98% cis and 93% trans derived from the salt of 75/25 (cis/trans) by fractional crystallization. A polymer with 97% cis content was highly crystalline, with a melting temperature of 253°C, while one with 93% trans contents was amorphous. In contrast to this, little difference was found in the glass transition temperature of 97 and 84°C. These results indicate that the isomers affect the conformation of the molecular chains, which determines the crystallinity and melting temperature, but they do not much affect the mobility of the chains as manifested by the glass transition.     

拓扑异构体的研究(Ⅰ)C型与S型拓扑异构体的波谱性质及结构鉴定

利用 ¹H和 ¹³C NMR, IR, UV, SEM对合成的4种C型和S型拓扑异构体进行了结构表征和分析, 发现对于不同拓扑结构的C型和S型分子可以通过 ¹H NMR来鉴别, 而对于相同拓扑结构的S型cis(SC)和trans(ST)分子, C型 cis(CC)和trans(CT)分子则要结合 ¹³C NMR来鉴别. 四种拓扑异构体的IR, UV, 波谱性质以及SEM图象没有显著的差异.     

Synthesis and three-dimensional structure of the benzoates and p-nitrobenzoates of the geometrical isomers of substituted 4-hydroxypiperidines

The corresponding stereoisomeric p-nitrobenzoates were obtained by reaction of the geometrical isomers of 1,3-dimethyl-, 1,2,5-trimethyl-, and 1-tert-butyl-3-methyl-4-hydroxypiperidines with p-nitrobenzoyl chloride. The stereoisomers of the corresponding benzoates were also synthesized from the geometrical isomers of 1,3-dimethyl-4-hydroxypiperidines. The primary conformations of the investigated compounds in solution were established by means of their PMR spectra.     

1,3‐dipolar cycloaddition reactions of 2‐substituted azomethine N‐oxides with N‐benzyl maleimides leading to the synthesis of stereoisomers

The azomethine N‐oxides ( 1 ) on reacting with N‐benzylmaleimide ( 2 ) provide a mixture of stereoisomers 2,3‐diphenyl‐5‐benzyl‐4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6–dione derivatives ( 3 ) in good yields. These isomers have been assigned cis and trans configurations ( 3‐A and 3‐B ) with respect to proton C₃‐H on the azomethinic carbon on the basis of their PMR and H‐NMR COSY data. The ratio between cis and trans isomers has been found to be dependent on substituents present at ortho position of C‐phenyl aldehydic moiety. The salient feature of these 1,3‐dipolar cycloaddition reactions lies in that the benzylic protons on N‐benzyl moiety suffer gem coupling, indicating magnetic nonequivalence. J. Heterocyclic Chem.,, (2012).     

Hybrid density functional theory study of fragment ions generated during mass spectrometry of 1,3-dioxane derivatives

It was recently reported that the cis,cis and trans,trans diastereoisomers of four 2(r)-R-2,4(R),6(S)-trimethyl-1,3-dioxane derivatives show distinct electron ionization mass spectra. As a possible explanation for this finding, the authors suggested that the ions generated during the mass spectrometry of these compounds could follow different fragmentation patterns that initiate from different ion conformations. In this report, hybrid density functional theory methods have been used to investigate the conformational preference of three ions involved in the mass spectrometry of some 1,3-dioxane derivatives. We found that there is indeed more than one stable ion conformation for each of the investigated ions. Energy profiles along the torsional coordinates connecting the conformers are presented, and factors influencing the relative stability of ion conformations are discussed.     

An investigation of intramolecular hydrogen bonds and the spatial conformations of the stereoisomeric α-oxoalcohols of the cyclohexane,piperidine, and decahydroquinoline series

The influence of the conformation of the geometric isomers of 1-acetyl-4-tert-butylcyclohexan-1-ol and of 4-acetyl-1, 2-dimethyldecahydroquinoline on the nature of the intramolecular hydrogen bonds has been studied by IR spectroscopy, and on the basis of the results obtained the configurations and conformations of the geometric isomers of the 4-acyl-1,2,5-trimethylpiperidin-4-ols have been established.Conformational stability of the stereoisomers of ketols of the piperidine series has been found.It has been shown that the geometric isomers of each of the compounds studied with axially orientated acyl groups exist in solutions in the form of an equilibrium mixture of two rotameric forms. The enthalpy of an intramolecular hydrogen bond in these compounds is 0.5–0.7kcal/ mole.     

Chiral high-performance liquid chromatographic separations of vinca alkaloid analogues on alpha 1-acid glycoprotein and human serum albumin columns.

Separations of the stereoisomers of a series of tetracyclic and pentacyclic vinca alkaloid analogues having two or three chiral centres were performed on Chiral-AGP and Chiral-HSA high-performance liquid chromatographic columns. Phosphate buffers with pH 5-7 containing 5-35% acetonitrile or 2-propanol were used as mobile phases. The results were in accordance with previous binding data obtained with native AGP and on an HSA-Sepharose column. Whereas on Chiral-AGP the retention of the trans isomers having 1(R),12b(S)-indolo[2,3-a]quinolizidine or the corresponding 3(S),16(R)-eburnane absolute configurations was exceedingly high, on Chiral-HSA the trans isomers, independently of their absolute configurations, were more retained. Eburnane-type compounds could also be separated according to the configuration of the chiral centre at position 14. A comparison of the chromatographic properties of the vinca alkaloids on the Chiral-AGP and Chiral-HSA columns demonstrates that these compounds are bound with higher affinity to the AGP phase. The AGP column resolves a very broad range of vinca alkaloids compared with the HSA column. Higher stereoselectivity and a much better chromatographic performance were also obtained on the Chiral-AGP column.     

Stereochemically general approach to adjacent bis(tetrahydrofuran) cores of annonaceous acetogenins

A series of six 2,5-disubstituted adjacent bis(tetrahydrofuran) stereoisomers with trans/erythro/cis, trans/threo/trans, or cis/threo/cis relative stereochemistry have been synthesized from known dihydroxycyclooctenes via ring opening/cross metathesis and Pd(0)-mediated asymmetric double cycloetherification. The stereochemistry of four of these isomers has been found in the biologically active annonaceous acetogenin natural products. [reaction: see text].     

Six-membered heterocycles

2-Methyl-5-hexyl- and 2-isopropyl-5-hexyl-1, 3-dioxanes have been synthesized for the first time by the condensation of 2-hexyl-1, 3-propane-diol with acetaldehyde and isobutyraldehyde, and they have been separated into their stereoisomers by fractionation in efficient columns. It has been shown by a study of their PMR spectra that the low-boiling isomers have the cis- and the high-boiling isomers the trans-configuration. A study of the PMR spectra has enabled us to show not only the configuration but also the predominant conformations of the isomers; the cis-isomer exists predominantly in the unsymmetrical boat conformation with a diequatorial location of the substituents and the trans-isomer in the chair conformation, also with a diequatorial arrangement of the substituents.