Structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone as chiral component of liquid-crystalline systems

The spatial structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone prepared by photochemical isomerization of the E-isomer was studied by analyzing the magnitudes and temperature dependence of the proton spin-spin coupling constants obtained by ¹H NMR spectroscopy and the results of molecular modeling using semiempirical quantum chemical AM1 and PM3 methods and the density functional theory (DFT). Comparison of the results obtained for the Z-and E-isomers shows that in both cases the conformational equilibrium for both isomers is characterized by significant preference of the chair conformer having an equatorial methyl group, namely, − ΔH (chair a ⇌ chair e) = 1.98–2.12 and 1.36–1.54 kcal mole⁻¹ for the Z-and E-isomers, respectively. Distinctions in the non-planarity of the enone fragment and cyclohexanone ring in the Z-and E-isomers under study following from the results of mathematical modeling were confirmed by the experimental values of the geminal spin-spin coupling constants of protons of the methylene groups in α,α ′-positions with respect to the enone group. Quantum chemical calculations of the Z-isomer revealed the existence of intramolecular hydrogen bond between the carbonyl oxygen and the nearest aromatic proton in ortho-position of the benzene ring. Possible reasons for different helical twisting power of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone and the E-and Z-arylidene derivatives of 1R, 4R-isomenthone in the mesophase are discussed based on the results of molecular structure studies for these compounds. In the text below the unsaturated ketones under study will be called “arylidene cyclohexanone derivatives” for convenience of comparing the characteristics of methylcyclohexanone and isomenthone derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 962–972, June, 2006.     

Conformations of Z- and E-isomers of some chiral (1R,4R)-2-arylidene-p-menthan-3-ones

The ¹Í NMR method in combination with molecular simulation was used to study conformations of Z- and E-isomers of (1R,4R)-cis-2-(4-methoxyphenyl)benzylidene-p-menthan-3-one. In solutions the Z-isomer, unlike the conformationally uniform Å-isomer, is an equilibrium mixture of chair conformers with the substantial predomination of one form with the axially oriented methyl and equatorial isopropyl groups (75—78%). The enone group is more nonplanar in the Z-isomer than in the Å-isomer. For the isopropyl fragment, the equiprobable existence of trans- and two gauche-rotamers for the Z-isomer and a substantial predomination of gauche-forms in the case of the E-isomer were established.     

NMR spectroscopic study of the (Z)/(E)-isomerism of 1-aryl-3-arylamino-2-propen-1-ones in solution and in the crystalline state

Summary ¹H,¹³C, and CP/MAS¹³C NMR spectra of sixp-substituted 1-aryl-3-arylamino-2-propen-1-ones in solution and in the solid state are reported and discussed. In the proteon-accepting solvent dimethylsulfoxide, electronegative substituents shift the isomeric equilibrium to the (E)-isomer. Bulky substituents promote crystallization of the (Z)-form.

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NMR-Spektroskopische Untersuchung der (Z)/(E)-Isomerie von 1-Aryl-3-arylamino-2-propen-1-onen in Lösung und im Kristallzustand (Kurze Mitt.)

Zusammenfassung ¹H-,¹³C- und CP/MAS-¹³C-NMR Spektren von sechsp-substituierten 1-Aryl-3-arylamino-2-propen-1-onen in gelöstem und festem Zustand werden berichtet und diskutiert. In protonenakzeptierendem Dimethylsulfoxid verschieben elektronegative Substituenten das Gleichgewicht zum (E)-Isomer. Große Substituenten begünstigen die Kristallisation in der (Z)-Form.

     

Diastereoselective bromination of(R)-N-cinnamoyl-4-phenyloxazolidin-2-one in the presence of Lewis acids

The stereochemistry of addition of Br₂ toE-andZ-(R)-N-cinnamoyl-4-phenyloxazolidin-2-ones was studied. It was established that both theE-andZ-isomers give only two out of four possible diastereoisomers in the presence of Lewis acids (BPr₃ or AlBr₃). The absolute configurations of the diastereoisomers [(2S', 3R') and (2R', 3S') of the side chain] were established by X-ray structural analysis. The stereochemistry observed is a consequence of the stepwise bromination and the absence of bridging bromine atoms along the reaction coordinate. In the case of theZ-isomer, the diastereoselectivity of the reaction was high, whereas it is low in the case of theE-isomer. It was suggested that at the first stage of addition of Br₂ at the C=C bond, the attack of the Br⁺ cation occurs at the α position, and the second stage of transfer of Br⁻ occurs with the participation of boron or aluminum complexes in the intermediate state of the bromination reaction. This hypothesis as well as the results of calculations of the initial conformations of the substrates provide an explanation of the regularities observed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1022–1028, May, 1997.     

NMR-spektroskopische Untersuchungen zurE/Z-Isomerie von substituierten Dithiocarbazinsäurederivaten

Summary NMR-spectroscopic investigations of substituted dithiocarbacinic acid derivatives show the existence of configurational isomers relative to the C=N double bond, but no tautomerism. We applied chemical shift differences in the¹H-,¹³C- and¹⁵N-NMR-spectra, N - H and C - H coupling constants and NOE difference measurements in the solvents CDCl₃,DMSO-d ₆ and partly CD₃OD in order to discriminate between the isomers and to determine the configurational composition. Compounds4 and5 exist asE-isomers in all solvents, compounds1, 2 and3 as a mixture ofE/Z-isomers. InDMSO-d ₆ theE-form is the preferred isomer.

     

Synthesis and Photoisomerization of 3-Cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one

The condensation of 4-nitrobenzaldehyde with 3-cyano-4,6,6-trimethyl-5,6-dihydropyran-2-one leads to the formation of a crotonization product and a compound of the Michael adduct type. The main product of the photochemical conversion of (E)-3-cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one is the Z-isomer. Investigation of the photoisomerization of 3-cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one by the semiempirical AM1 method showed that in the ground state the E-isomer was thermodynamically more stable than the E-isomer. E-Z-photoisomerization is effected most probably through the lowest excited singlet state S₁.     

E—Z-Izomerization of 2-methylenethiazolidin-4-ones

The equilibrium concentrations of E- and Z-isomers of thiazolidin-4-ones containing exocyclic double bonds in positions 2 and 5 of the cycle were determined in DMSO-d₆. The influence of the nature of the substituents on the equilibrium position was found. Electron-releasing substituents stabilize the E,Z-configuration and electron-withdrawing substituents stabilize the Z,Z-configuration. The association constants of E- and Z-2-ethoxycarbonylmethylenethiazolidin-4-ones with the sodium cation were determined by ¹H NMR spectroscopy.     

13C and19F NMR study of α,β-difluorostyryl derivatives of transition metal carbonylates. A method of signal assignment based on the carbon—fluorine spin-spin coupling constants

The¹³C and¹⁹F NMR spectra ofZ- andE-isomers of β-X-substituted α,β-difluorostyrenes (X=F, Cl, CpFe(CO)₂, Re(CO)₅, Re₂(CO)₉Na) were studied. Direct and long-range (across 1–5 bonds) spin-spin coupling constants and the (¹³C−¹²C) isotope shifts in the¹⁹F NMR spectra were determined. The study of the¹³C satellites in the¹⁹F NMR spectra of substituted difluorostyrenes permitted assignment of the¹³C NMR signals of the vinylic carbon atoms. Similarly, the signals in¹⁹F NMR spectra were assigned based on coupling constants of fluorine withipso-carbon. These assignments were found to be in good agreement with the data available from the literature (X=F, Cl). The developed approach was applied to the elucidation of the structure ofZ−PhCF=CClFe(CO)₂Cp. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya. No. 8, pp. 1575–1579, August, 1998.     

4-(1-Alkylbenzimidazol-2-ylazo)-2-pyrazolin-5-ones: specific features of prototropic tautomerism

Quantum chemical calculations, ¹H and ¹³C NMR, and X-ray studies showed that, in contrast to 4-arylazo-2-pyrazolin-5-ones, 4-(1-alkylbenzimidazol-2-ylazo)-2-pyrazoline-5-ones mainly exist in the condensed phase as unusual ketoazine tautomers of high polarity, while the ketohydrazone tautomer stabilized by intramolecular hydrogen bond apparently predominates in the gas phase. According to calculations, various types of tautomerism are possible for 4-(benzimidazol-2-ylazo)-2-pyrazolin-5-ones, including mono- and bimolecular 1,3-, 1,5-, and 1,7-prototropic migrations proceeding by the single- and double-proton transfer mechanism with low activation energies (ΔE ^≠ ≈ 2–14 kcal mol⁻¹). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1467–1478, July, 2008.     

Singlet-Oxygen Ene Reactions of (E)-4-Propyl[1,1,-2H3]oct-4-ene. Short Communication

Rose bengal-sensitized photooxygenation of 4-propyl-4-octene ( 1 ) in MeOH/Me₂CHOH 1:1 (v/v) and MeOH/H₂O 95:5 followed by reduction gave (E)-4-propyl-5-octen-4-ol ( 4 ), its (Z)-isomer 5 , (E)-5-propyl-5-octen-4-ol ( 6 ), and its (Z)-isomer 7 . Analogously, (E)-4-propyl[1,1,1-²H₃]oct-4-ene ( 2 ) gave (E)-4-propyl[1,1,1-²H₃]oct-5-en-4-ol ( 14 ), its (Z)-isomer 15 , (E)-5-[3′,3′,3′-²H₃]propyl-5-octen-4-ol ( 16 ), its (Z)-isomer 17 , and the corresponding [8,8,8-²H₃]-isomers 18 and 19 (see Scheme 1). The proportions of 4–7 were carefully determined by GC between 10% and 85% conversion of 1 and were constant within this range. The labeled substrate 2 was photooxygenated in two high-conversion experiments, and after reduction, the ratios 16/18 and 17/19 were determined by NMR. Isotope effects in 2 were neglected and the proportions of corresponding products from 1 and 2 assumed to be similar (% 4 ≈? % 14 ; % 5 ≈? % 15 ; % 6 ≈? % ( 16 + 18 ): % 7 ≈? % ( 17 + 19 )). Combination of these proportions with the ratios 16/18 and 17/19 led to an estimate of the proportions of hydroperoxides formed from 2 . Accordingly, singlet oxygen ene additions at the disubstituted side of 2 are preferred (ca. 90%). The previously studied trisubstituted olefins 20–25 exhibited the same preference, but had both CH₃ and higher alkyl substituents on the double bond. In these substrates, CH₃ groups syn to the lone alkyl or CH₃ group appear to be more reactive than CH₂ groups at that site beyond a statistical bias.     

Reduction of (<Emphasis Type="Italic">E</Emphasis>)-3-aryl-2-(thiazol-2-yl)acrylonitriles with lithium aluminum hydride

Reduction of (E)-3-aryl-2-(4-arylthiazol-2-yl)acrylonitriles with lithium aluminum hydride in dry ether afforded (Z)-1-amino-3-aryl-2-(thiazol-2-yl)prop-1-ene derivatives in 15 to 40% yields. The structure of (Z)-1-amino-3-(2-chlorophenyl)-2-[4-(4-methylphenyl)thiazol-2-yl]prop-1-ene was confirmed by X-ray diffraction analysis. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1301–1303, May, 2005.     

The (E)/(Z)-ratio in the reaction of 5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines with bromine

Summary 3-Aryl-, 3-benzyl-, and 3H-5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines3a–h react with bromine in acetic acid solution to give mixtures of the respective 5-aroylmethylene (E) and (Z) diastereomeric derivatives5 and6. They contain more than 85% of the (E)-diastereomers along with some pure isomers. The intermediacy of the 5-bromo derivatives4 is proven and a plausible route of the reaction is presented. Structures of compounds3–6 are evidenced by analytical and spectral data.

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Das Verhältnis von (E)- und (Z)-Isomeren bei der Reaktion von 5-(2-Aryl-2-oxomethyl)-2-thioxo-4-oxo-1,3-thiazolidinen mit Brom

Zusammenfassung 3-Aryl-, 3-Benzyl- und 3H-5-(2-Aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidine3a–h reagieren mit Brom in essigsaurer Lösung zu Gemischen der entsprechenden diastereomeren 5-Arylmethylen-Derivate ((E) und (Z))5 und6. Sie enthalten mehr als 85% des (E)-Diastereomeren. Die intermediäre Natur der 5-Brom-Derivate4 wird bewiesen; ein Reaktionsweg wird vorgeschlagen. Die Strukturen der Verbindungen3–6 werden durch analytische und spektroskopische Daten abgesichert.

     

Synthesis and spectral properties of cyclopropyl-substituted phosphaalkenes

Cyclopropanecarboxylic acid chlorides5a-d react with tris(trimethylsilyl)phosphane6 in benzene at –2 °C to form cyclopropylcarbonyl-bis(trimethylsilyl)phosphanes7. These products undergo silylic rearrangement at 25 °C to yield phosphaalkenes8. Compounds 8a,b,d are formed as mixtures ofZ- andE-isomers where the latter predominate. In the case of8c, theZ-isomer is formed exclusively.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 684–689, April, 1994.The authors are grateful to the Fonds der Chemischen Industrie (Germany) for financial support of this work. A. B. Kostitsyn is also grateful to the Deutscher Akademischer Austauschdienst for a grant to carry out this study. For a preliminary communicationcf. Ref. 1.     

New synthesis of ( E )-3,7-dimethyl-2,7-octadienylpropionate and ( E )-3,7-dimethyl-2-octen-1,8-diol, pheromone components of San Jose scaleinsect Quadraspidiotus pernicious and african monarch butterfly Danaus chrysippus

6-Methyl-6-hepten-2-one (3) on reaction with ethyl α-dimethylphosphonate/NaH gives a mixture of (E)-and (Z)-conjugated esters. The major (E)-isomer, (E)-ethyl-3,7-dimethyl-2,7-octadienoate (4), on reduction with LiAlH₄ at room temperature furnishes (E)-3,7-dimethyl-2,7-octadien-l-ol (5) which on propionylation affords (E)-3,7-dimethyl-2,7-octadienyl propionate (1). Carbinol (5) is converted into its silyl ether (E)-2,6-dimethyl-8-t-butyldimethylsilyloxy-l,6-octadiene (6) witht-Bu(Me)₂SiCl in CH₂Cl₂, which on hydroboronation-oxidation with 9-BBN/NaOH-H₂O₂ followed by disilylalion with (n-Bu)₄N⁺ F⁻ at room temperature, gives (E)-3,7-dimethyl-2-octen-l,8-diol (2).     

Crown ether styryl dyes

A novel styryl dye containing benzodithia-18-crown-6 andN-(4-sulfobutyl)benzothiazolium fragments was synthesized. The complex formation of thecis-isomers of several photochromic styryl dyes containing dithia-15(18)-crown-5(6) fragments with Hg²⁺ and Mg²⁺ ions was studied. The stability constants of the complexes with Mg²⁺ and the relative stability constants of the complexes with Hg²⁺ (with respect to benzo-1,10-dithia-18-crown-6 ether) were measured. The fact that the stability constant increases 11-fold on going from thetrans- to the correspondingcis-isomer was attributed to the formation of an anion-“capped” complex. For Part 22, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2213–2220, December, 1997.     

On the chemistry of pyrrole pigments,XCVII: Synthesis,stereochemistry, and solvatochromic effects of a 1-(dipyrrinon-9-yl)-3-(dipyrrinon-9-ylidene)-1-propene

Summary By condensing a dipyrrinon-9-yl-acrolein with a dipyrrinone unsubstituted in position 9, an unsymmetricb-vinylogous verdinoid pigment was prepared. The configuration of this molecule was elucidated by means of 2D¹H NMR experiments to be (4Z,10E,12Z,17Z) in solutions of chloroform and dimethylsulfoxide, and its conformation was derived to be 5syn,9syn,11anti,16syn. The pronounced solvatochromic effect of this molecule with a cyclic helical geometry could be explained by solvent induced conformational changes.

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Zur Chemie von Pyrrolpigmenten, 97. Mitt.: Synthese, Stereochemie und Solvatochromer Effekt eines 1-(Dipyrrinon-9-yl)-3-(dipyrrinon-9-yliden)-1-propens

Zusammenfassung Durch Kondensation eines Dipyrrinon-9-yl-acroleins mit einem in Position 9 unsubstituierten Dipyrrinon wurde ein unsymmetrischesb-vinyloges verdinoides Pigment dargestellt. Die Konfiguration dieses Moleküls wurde mit Hilfe von 2D-¹H-NMR-Experimenten in Lösungen von und Dimethylsulfoxid als (4Z,10E,12Z,17Z) abgeleitet; seine Konformation konnte zu 5syn,9syn,11anti,16syn festgelegt werden. Die ausgeprägte Solvatochromie dieses Moleküls mit cyclisch helikaler Geometrie konnte auf solvensinduzierte konformative Veränderungen zurückgeführt werden.

     

H NMR Dynamic study of thermal Z/E isomerization of 5-substituted 2-alkylidene-4-oxothiazolidine derivatives: Barriers to rotation about CC bond

The rotational barriers between the configurational isomers of two structurally related push–pull 4-oxothiazolidines, differing in the number of exocyclic CC bonds, have been determined by dynamic ¹H NMR spectroscopy. The equilibrium mixture of (5-ethoxycarbonylmethyl-4-oxothiazolidin-2-ylidene)-1-phenylethanone (1a) in CDCl₃ at room temperature to 333 K consists of the E- and Z-isomers which are separated by an energy barrier ΔG^# 98.5 kJ/mol (at 298 K). The variable-temperature ¹H NMR data for the isomerization of ethyl (5-ethoxycarbonylmethylidene-4-oxothiazolidin-2-ylidene)ethanoate (2b) in DMSO-d₆, possessing the two exocyclic CC bonds at the C(2)- and C(5)-positions, indicate that the rotational barrier ΔG^# separating the (2E,5Z)-2b and (2Z,5Z)-2b isomers is 100.2 kJ/mol (at 298 K). In a polar solvent-dependent equilibrium the major (2Z,5Z)-form (>90%) is stabilized by the intermolecular resonance-assisted hydrogen bonding and strong 1,5-type S · · · O interactions within the SCCCO entity. The ¹³C NMR Δδ_C(2)C(2′) values, ranging from 58 to 69 ppm in 1a–d and 49-58 ppm in 2a–d, correlate with the degree of the push-pull character of the exocyclic C(2)C(2′) bond, which increases with the electron withdrawing ability of the substituents at the vinylic C(2′) position in the following order: COPh COEt > CONHPh > CONHCH₂CH₂Ph. The decrease of the Δδ_C(2)C(2′) values in 2a–d has been discussed for the first time in terms of an estimation of the electron donor capacity of the S fragment on the polarization of the CC bonds.     

Studies on chiral thiophosphoric acids and their derivatives: 4. The stereospecific synthesis of optically active O-ethyl O-phenyl O-(1-methyl-2-ethoxycarbonyl) vinyl phosphorothionate

The stereoisomers (3 and 4) of O-ethyl O-phenyl O-(1-methyl-2-ethoxycarbonyl) vinyl phosphorothionate have been synthesized by the reaction of optically active O-ethyl O-phenyl phosphorothiochloride 2 with ethyl acetoacetate under different conditions. 3 (100% Z-isomer, determined by ¹H NMR) was synthesized by the reaction of 2 with ethyl sodio-acetoacetate in the mixed solvent of 1:3 toluene-dioxane at 50°C. 4 (>95% E-isomer) was obtained by the reaction of 2 with ethyl acetoacetate in presence of t-BuOK in DMSO at 15°C. 100% E-isomer 4 was separated from crude 4(>95% E-isomer) by column chromatography on silica gel (petroleum ether-ether 6:1). By this reaction either Z- or E-isomers were formed with inversion of the configuration at phosphorus atom. Thus, six stereoisomers of 3 and 4 which were prepared from 2 (RS, S, R) by the above method namely (RS)-Z, (R)-Z, (S)-Z and (RS)-E, (R)-E, (S)-E.     

New polyhydroxysteroids and steroid glycosides from the far east starfishCeramaster patagonicus

Two new polyhydroxysteroids and five new glycosides were isolated from the starfishCeramaster patagonicus and their structures were elucidated: 5α-cholestane-3β,6α,15β,16β,26-pentol, (22E)-5α-cholest-22-ene-3β,6α,8,15α,24-pentol, (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β,4β, 6α,8,15β,16β,28-heptol (ceramasteroside C₁), (22E)-28-O-[O-(2,4-di-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β, 6α,8,15β,16β,28-hexol (ceramasteroside C₂), (22E)-28-O-[O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β,6α,8,15β,16β 28-hexol (eramasteroside C₃), (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-methyl-5α-cholest-22-ene-3β,4β,6α,8, 15β, 26-hexol (ceramasteroside C₄), and (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-xylopyranosyl]-5α-cholest-22-ene-3β,6α,8,15β,24-pentol (ceramasteroside C₅)). Three known polyhydroxysteroids (24-methylene-5α-cholestane-3β,6α,8,15β,16β,26-hexol, 5α-cholestane-3β,6α,8,15β,16β,26-hexol, and 5α-cholestane-3β,6β,15α,16β,26-pentol) were also isolated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 190–195, January, 1997.     

A Note on Stereochemical Observations of the Deprotonation of Ethyl 2-Alkenoates

Deprotonation of ethyl (E)-2-alkenoates 1 , 3 and 4 yields after protonation the double bond migrated (3 Z)-isomers 5 , 7 and 9 as major products. In contrast, deprotonation and reprotonation of ethyl (Z)-2-pentenoate ( 2 ) gives the (3 E)-isomer 6 exclusively. These findings are explained by reaction paths starting from different ester conformations.