A Thermodynamic, 13C NMR,and 17O NMR Study of Isomeric 4,7-Dihydro-1,3-dioxepins and 4,5-Dihydro-1,3-dioxepins

The relative thermodynamic stabilities of 4,7-dihydro-1,3-dioxepin (4,6-dioxacycloheptene, 1a) and 4,5-dihydro-1,3-dioxepin (3,5-dioxacycloheptene, 1b), and of a number of their 2-substituted derivatives, have been determined by base-catalyzed chemical equilibration in DMSO solution. Without exception, the 4,5-dihydro isomer is the dominating species at thermodynamic equilibrium. The relative stability of the b form is promoted by the presence of a single alkyl group on C-2, whereas two alkyl groups on C-2 have an opposite effect. In general, the thermodynamic parameters H _m and _Sm , of isomerization vary unexpectedly with the pattern of substitution at C-2. These trends appear to be derived from significant substituent-induced conformational changes in the b isomer, as suggested by ¹³C and ¹⁷O NMR chemical shift data.     

Quantum Chemical Study of the Preferred Conformations,Molecular Geometries,and Relative Thermodynamic Stabilities of 2-Substituted 4-Methylene-1,3-Dioxolanes and 4-Methyl-1,3-Dioxoles

The preferred conformations, molecular geometries, and relative stabilities of carbon–carbon double-bond exo–endo isomeric 2-substituted 4-methylene-1,3-dioxolanes (a) and 4-methyl-1,3-dioxoles (b) have been studied by DFT calculations at the B3LYP/6-31G* level of theory. The main interest of this work was devoted to the contribution of alkoxy substituents on the relative thermodynamic stabilities of these isomeric unsaturated acetals. Comparison of the computational data with previous experimental findings shows both the enthalpies and entropies of the a b isomerization to be accurately predictable by the DFT calculations. Most importantly, the good agreement between experiment and theory proved also to be applicable to the previously observed unexpectedly large effect of 2-alkoxy substitution on the isomer equilibria.     

Cyclohexanone Dimethyl Acetals: A 13C NMR, Thermodynamic, and Ab Initio Study

The spatial structures of a number of mono- and disubstituted 1,1-dimethoxycyclohexanes (cyclohexanone dimethyl acetals) were studied by ¹³C NMR spectroscopy. In the monosubstituted acetals, substituents (Me, Et, i-Pr, and MeO) on C-2 are axially oriented, contrary to their normal, equatorial orientation on C-3 and C-4. Besides the spectroscopic study, the relative thermodynamic stabilities of the cis-trans isomers of a few 2,X-dialkyl (X = 3, 4, 5, or 6) derivatives of the parent cyclohexanone dimethyl acetal were determined by acid-catalyzed chemical equilibration in MeOH solution. In the most stable isomeric form, the 2-substituent is axial and the other equatorial. In the less stable isomer, both substituents are equatorial, excluding the cis-2,6-dimethyl derivative, where the ¹³C NMR shift data point to a predominance of the diaxial form. In general, the enthalpy difference between the isomeric forms is ca. 9 kJ mol^–1, while the entropy term favors the less stable isomer by 4 to 16 J K^–1 mol^–1. In the 2,6-dimethyl derivatives, however, the trans form is favored by only 0.8 kJ mol^–1 in G _m at 298.15 K. The main findings of the experimental work are in good agreement with ab initio calculations.     

Chemical structure and surface activity

Surface tension measurements on aqueous solutions of 2-alkyl-2-methyl-1,3-dioxolanes, 2-alkyl-4-methyl-1,3-dioxolanes, and 2-alkyl-1,3-dioxanes at a temperature of 293.2 K are presented. The surface tension isotherms obtained were used to calculate some adsorption parameters, i. e. the efficiency of surface tension reduction, pC₂₅, surface excess concentration, , and surface area,A, per molecule in the adsorption layer. The Temkin adsorption isotherm equation was used to calculate standard free energy of adsorption, G ⁰ _=0.5 . The increments for a methylene group in the alkyl chain, G ^o [–CH₂–], and for the residual part of the molecule, G ^o [W], were also determined.The results obtained show that: (i) an increase in alkyl chain length at the C-2 carbon atom of the ring by one methylene unit brings about a marked increase in surface activity; (ii) the introduction of a methyl group into the 1,3-dioxolane ring (i. e., at C-2 or C-4 atom) has a weaker effect on surface activity of alkyl-substituted 1,3-dioxolanes, and (iii) the contribution of the 5- and 6-membered 1,3-dioxacyclane rings to a total surface activity of, respectively, 2-alkyl-1,3-dioxolanes and 2-alkyl-1,3-dioxanes is similar.     

2-Cyclopropyliden-1,3-cycloalkandione als Zwischenstufen einer nukleophilen Substitution am Dreiring

Reaction of morpholinobicycloalkyl-dimedone4 C with various CH-acids3 leads to a substitution of theexo-dimedone unit as a consequence of a strong preference of theexo-leaving group in a bicyclic compound of type4 and5, respectively. Dimedone (3 C) as a nucleophile, however, makes theexo substitution unproductive in4 C and allows the displacement of the morpholino moiety leading to12 C. Thus compounds12 C–12 F could be obtained directly from the N,O-acetal1 and the CH-acids3 C–3 F by a twofold substitution, the isolation of the monoalkylated compounds4 not being necessary. Formation of12 C–12 F involves aMichael addition of3 C–3 F to the unstable 2-Cyclopropylidene-1,3-cycloalkanedione intermediates7 C–7 F. Cyclopentanedione3 F as a CH-acid and1 gave the enamine17 F besides12 F. The Hexahydroazepino-N,O-acetal19 in this special case was superior leading exclusively to12 F.

     

17O, 13C, and 1H NMR Studies of p–π Conjugation in 2-Substituted 4-Methylene-1,3-dioxolanes and 4-Methyl-1,3-dioxoles

The ¹⁷O NMR spectra of a number of unsaturated 5-membered cyclic acetals, 2-substituted 4-methylene-1,3-dioxolanes and their endocyclic isomers, 4-methyl-1,3-dioxoles, have been recorded. The ¹⁷O NMR chemical shifts, in comparison with those of similarly 2-substituted 1,3-dioxolanes, were used to explore the variation of the strength of p– conjugation in the unsaturated acetals as a function of the nature of substitution at C2. The ¹⁷O NMR shift data reveal that alkoxy substituents have a significantly more favorable effect on the strength of p– conjugation in 4-methyl-1,3-dioxoles than in 4-methylene-1,3-dioxolanes. This fact appears to be responsible for the previously observed unexpectedly large effect of alkoxy substitution on the relative thermodynamic stabilities of these two classes of isomeric compounds. Additional information of the unexpected charge distribution in 4-methyl-1,3-dioxoles is provided by their ¹H and ¹³C NMR spectra.     

Regio- and stereoselective 1,3-dipolar cycloaddition of arylnitrile oxides to 5-acetoxy-2(5H)-furanone

Summary Arylnitrile oxides undergo regio- and stereo-specific 1,3-dipolar cycloaddition reactions with 5-acetoxy-2(5H)-furanone. In each case a single product3a–3g results from ananti approach to the 5-acetoxy substituent, the oxygen of the 1,3-dipole being attached to C-4 of furan. Under similar conditions 5-benzoyloxy-2(5H)-furanone yields3h–3i. The structures of the adducts were determined by¹H- and¹³C-NMR spectroscopy.

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Regio- und stereoselektive 1,3-dipolare Cycloaddition von Arylnitriloxiden mit 5-Acetoxy-2(5H)-furanon

Zusammenfassung Arylnitriloxide reagieren mit 5-Acetoxy-2(5H)-furanon in einer regio- und stereoselektiven 1,3-dipolaren Cycloaddition. In jedem der untersuchten Fälle ergaben sich die einheitlichen Produkte3a–3g als Folge eineranti-Annäherung an den 5-Acetoxysubstituenten, wobei der Sauerstoff des 1,3-Dipols an das C-4 des Furans addiert. Unter ähnlichen Bedingungen ergab 5-Benzoyloxy-2(5H)-furanon die Produkte3h–3i. Die Strukturen der Addukte wurden mittels¹H-und¹³C-NMR bestimmt.

     

Synthesis of 1,3-bis(acetylacetonyloxy)- and 1,3-bis(benzoylacetonyloxy)benzene and their complexation with lanthanide ions

Claisen condensation of 1,3-bis(methoxycarbonylmethoxy)benzene with acetone and acetophenone afforded new chelating ligands consisting of two β-diketonate fragments, viz., 1,3-bis(acetylacetonyloxy)benzene and 1,3-bis(benzoylacetonyloxy)benzene, which are linked to each other through the resorcinol spacer. In the crystal, 1,3-bis(acetylacetonyloxy)benzene, unlike the starting ester, adopts a planar conformation and exists in the enol form. The acidities of these compounds and their complexation with lanthanide ions in aqueous ethanolic solutions were studied by pH-potentiometry. Depending on the concentration conditions and pH, the La³⁺, Gd³⁺, and Lu³⁺ ions form 1 : 1, 1 : 2, or 1 : 3 complexes with bis(β-diketones). The stability of the complexes increases as the atomic number of the lanthanide increases (La³⁺ < Gd³⁺ ≤ Lu³⁺). The complexation constants and selectivity of complexation substantially increase with increasing degree of deprotonation of the ligands, which indicates that both chelate groups of the ligands are simultaneously involved in coordination. The Ph substituents in bis(β-diketone) have a considerable effect on the composition and stability of complexes with lanthanide ions due to additional noncovalent inner-sphere interactions.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 614–622, March, 2005.     

Synthesis of Benzobis[1,3]oxathiins

Two different synthetic concepts led to the formation of 17, 19 , and 29 , the first structural isomeric benzobis[1,3]oxathiins. Hetero‐Diels? Alder reactions of diethyl mesoxylate 14 and the open valence isomers of the benzobisthietes 12 and 18 yielded the linear benzobis[1,3]oxathiin 17 and its angular isomer 22 , respectively. The isomeric angular system 29 could be obtained by a twofold O,S‐acetalization reaction of the dihydroxydisulfanyl compound 27 and acetone ( 28 ).     

Cycle inversion in 1,3-cyclohexadiene and its 5-alkyl derivatives

Cycle inversion in 1,3-cyclohexadiene and its 5-alkyl derivatives is studied by means of the MMP2 molecular mechanics procedure. The choice of a torsion angle between single bonds as a reaction coordinate is justified. Substituents at the C(5) atom (R=Me, Et,i-Pr,t-Bu) are shown to have little effect on the cycle shape, and the equatorial conformer is preferable to the axial one.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1142–1144, June, 1993.     

Reactions of cyclic 1,3-dicarbonyl compounds with 1,2(1,4)-dihydro-1-methyl-2(4)-methylene-N-heterocycles. A new access to 6,12-methano-dibenz[d,g]-[1,3]oxazocinones

Summary The enamine-type methylene-N-heterocycles1–5 react with cyclic 2-ethoxymethylene-1,3-dicarbonyl compounds6 to give 2-[2-(hetarylidene)ethylidene]-1,3-dicarbonyl compounds7–14. The result of the reactions between 1,2-dihydro-1-methyl-2-methylene-quinoline (1a) and cyclic 1,3-dicarbonyl compounds depends on the nature of the dihydro intermediatesA/B. Dehydrogenation of keton intermediatesA results in 2-(1,2-dimethyl-4(1H)-quinolylidene)-1,3-dicarbonyl compounds17–21. Enol intermediatesB with 6-membered dicarbonyl ring form 6,12-methano-dibenz-[d,g][1,3]oxazocinones22–25.¹H NMR spectra and X-ray structure analysis prove the structure of23.

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Reaktionen cyclischer 1,3-Dicarbonylverbindungen mit 1,2(1,4)-Dihydro-1-methyl-2(4)-methylen-N-heterocyclen. Ein neuer Zugang zu 6,12-Methano- dibenz[d,g][1,3]oxazocinonen

Zusammenfassung Aufgrund ihres Enamincharakters reagieren die Methylen-N-heterocyclen1–5 mit cyclischen 2-Ethoxymethylen-1,3-dicarbonylverbindungen6 zu den 2-[2-(Hetaryliden)ethyliden]-1,3-dicarbonylverbindungen7–14. Das Ergebnis der Reaktionen zwischen 1,2-Dihydro-1-methyl-2-methylen-chinolin (1a) und cyclischen 1,3-Dicarbonylverbindungen hängt von der Natur der zwischenzeitlich entstehenden DihydroverbindungenA/B ab. Die Intermediat-KetoneA gehen durch Dehydrierung während der Reaktion in die 2-(1,2-Dimethyl-4(1H)chinolyliden)-1,3-dicarbonylverbindungen17–21 über. Die Intermediat-EnoleB mit sechsgliedrigem Dicarbonylring bilden in intramolekularer Reaktion die 6,12-Methano-dibenz[d,g][1,3]oxazocinone22–25, deren Struktur am Beispiel der Verbindung23 durch¹H-NMR sowie durch Röntgenkristallstrukturanalyse bewiesen wird.

     

Mass-spectrometric study of 1,3-oxazacyclopentanes

The fragmentation of 1,3-oxazolidines under electron-impact and chemical-ionization (with methane as the gas reagent) conditions and the effect of the substituent in the 2 position of the heteroring on the stability of the molecular ions (M⁺) and on the character of the fragmentation of 1,3-oxazolidines were studied. It is shown that splitting out of an alkyl group from the 2 position is characteristic for electron impact. Processes involving alkylation and protonation with the formation of cluster ions are most characteristic for chemical ionization. In analogy with hydrolysis in the condensed phase, protonated 1,3-oxazolidine molecules split out an aldehyde molecule.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1031–1034, August, 1981.     

Stereoselective Synthesis and Diels-Alder Reactions of (Z)- and (E)-1,2-bis(Phenylthio)-1,3-Butadiene

Bromination of 3-phenylthio-2-sulfolene (2) with N-bromosuccinimide gave 2-bromo-3-phenylthio-2-sulfolene (3) which was converted mainly to 2,3-bis(phenylthio)-2-sulfolene (4) by treatment with sodium phenylthiolate. Thermal desulfonylation of 4 at different temperatures in the presence of a base (DBU) yielded stereoselectively the (Z)- and (E)-1,2-bis(phenylthio)-1,3-butadiene (6). These two geometric isomers could be thermally interconverted. The Diels-Alder reactions of 6 were also investigated. Only the (Z)-diene 6a could undergo the Diels-Alder reaction; the (E)-diene 6b was in situ converted to the Z isomer before undergoing (he Diels-Alder reaction. The reaction of 6a with N-phenylmaleimide gave the cycloaddition product 7 with complete endo selectivity, but under daylight or during chromatography it readily underwent a thioallylic rearrangement to yield 8 with inversion of configuration. The cycloaddition of 6a with methyl acrylate proceeded regiospecifically, but generating a mixture of endo and exo isomers. The endo/exo ratio could be increased by using ZnCl₂ as the catalyst.     

Intramolecular 1,3-dipolar cycloaddition of cyclo-1,3-diene-tethered nitrile oxides

Intramolecular 1,3-dipolar cycloaddition of cyclo-1,3-diene- and -1,3,5-triene-tethered nitrile oxides gave tricyclic isoxazolines as a single stereoisomer in most cases. The relative stereochemistry of tricycle-fused isoxazolines resulting from 1,3-dipolar cycloaddition of cyclo-1,3-diene-tethered nitrile oxides is cis-cis, whereas from cyclohepta-1,3,5-triene-tethered nitrile oxides the cis-trans isomer predominates.     

Epimerization and deuterium exchange studies in selected cis,trans-1-alkyl-2-aryl(alkyl)-3-aroylaziridines

A series of base catalyzed reactions performed on selected cis, trans-1-alkyl-2-aryl(alkyl)-3-aroylaziridines at room temperature reveal the cis isomer to be of greater thermodynamic stability. Furthermore, base catalyzed deuterium exchange studies suggest this to be the case. Solvent effects on the isomeric cis/trans ratios are also presented and discussed.     

NMR studies of 4(3H)-quinazolinones and 4(3H)-quinazolinethiones

Summary Unambiguous¹H and¹³C NMR assignments for 4(3H)-quinazolinones1–6 and their corresponding 4-thiones7–12 have been made. This resulted in the revision of the previous assignments for the two benzenoid carbons (C-5 and C-8) of quinazolinones1,2,4, and5. Thionation of the nucleophilic amides1–6 has been found to cause a distinct change in the¹³C chemical shift of particularly C-4, but also of those of C-4a, C-5, and C-8a. One-bond and several long range heteronuclear coupling constants for the compounds have also been measured.

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Kernresonanzspektroskopie von 4(3H)-Chinazolinonen und 4(3H)-Chinazolinthionen

Zusammenfassung Die¹H- und¹³C-NMR-Spektren der 4(3H)-Chinazolinone1–6 und ihrer entsprechenden 4-Thione7–12 wurden zugeordnet. Dabei zeigte sich, daß eine frühere Zuordnung der beiden benzoiden Kohlenstoffe (C-5 und C-8) der Chinazolinone1,2,4 und5 falsch war. Ersatz des Sauerstoffs durch Schwefel in den nukleophilen Amiden1–6 führt insbesondere für C-4, aber auch für C-4a, C-5 und C-8a zu einer deutlichen Änderung der chemischen Verschiebung. Heteronukleare Kopplungskonstanten über eine und über mehrere Bindungen wurden bestimmt.

     

Synthesis of 4-thia analogues of isoquinoline alkaloids

Summary (±)-4-Thiacarnegin (3) was synthesized by reaction of 6,7-dimethoxy-3-methyl-2H-1,3-benzothiazinium iodide (2) with methyl magnesium iodide, thereby opening a new synthetic route to 4-substituted dihydro-2H-1,3-benzothiazines. Compound3 was also obtained by reduction of 6,7-dimethoxy-3,4-dimethyl-2H-1,3-benzothiazinium iodide (5). In a similar way, reduction of the quaternary salts9 a–c afforded the (±)-4-thia analogues of cryptostilin-I, -II and -III (10 a–c). The isomers of the former compounds (12 a–c) were also synthesized by reduction of the 4H-1,3-benzothiazinium salts11 a–c.

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Synthese von 4-Thiaanalogen von Alkaloiden mit Isochinolingerüst

Zusammenfassung Aus 6,7-Dimethoxy-3-methyl-2H-1,3-benzothiaziniumjodid (2) wurde mit Methylmagnesiumjodid (±)-Thiacarnegin (3) dargestellt. Diese Reaktion bietet ein neues Verfahren für die Synthese von 4-substituierten Dihydro-2H-1,3-benzothiazinen.3 wurde auch durch Reduktion von 6,7-Dimethoxy-3,4-dimethyl-2H-1,3-benzothiaziniumjodid (5) erhalten. Die Reduktion der quartären Ammoniumsalze9 a–c ergab ebenfalls die Cryptostillin I-, II-, III-(±)-4-thiaanalogen Verbindungen (10 a–c). Reduktion der 4H-1,3-Benzothiazinium-Salze11 a–c lieferte die entsprechenden Isomeren12 a–c der obengenannten Verbindungen.

     

Cationic ring‐opening polymerization of novel 1,3‐dehydroadamantanes with various alkyl substituents: Synthesis of thermally stable poly(1,3‐adamantane)s

Cationic ring‐opening polymerizations of 5‐alkyl‐ or 5,7‐dialkyl‐1,3‐dehydroadamantanes, such as 5‐hexyl‐ ( 4 ), 5‐octyl‐ ( 5 ), 5‐butyl‐7‐isobutyl‐ ( 6 ), 5‐ethyl‐7‐hexyl‐ ( 7 ), and 5‐butyl‐7‐hexyl‐1,3‐dehydroadamantane ( 8 ), were carried out with super Brønsted acids, such as trifluoromethanesulfonic acid or trifluoromethanesulfonimide in CH₂Cl₂ or n‐heptane. The ring‐opening polymerizations of inverted carbon–carbon bonds in 4–8 proceeded to afford corresponding poly(1,3‐adamantane)s in good to quantitative yields. Poly( 4–8 )s possessing alkyl substituents were soluble in 1,2‐dichlorobenzene, although a nonsubstituted poly(1,3‐adamantane) was not soluble in any organic solvent. In particular, poly( 8 ) exhibited the highest molecular weight at around 7500 g mol^?1 and showed excellent solubility in common organic solvents, such as THF, CHCl₃, benzene, and hexane. The resulting poly( 4–8 )s containing adamantane‐1,3‐diyl linkages showed good thermal stability, and 10% weight loss temperatures (T₁₀) were observed over 400 °C. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4111–4124     

Synthesis and properties of unique mesoionic 1,3-thiazolium-4-olates

Summary N-bridged 1,3-thiazolium-4-olates were synthesized by reaction of 3-substituted 3-aminothioacrylanilides with bromoacetic acid ethyl ester in refluxing xylene. Their structural aspects were investigated by means of mass, NMR, and absorption spectroscopy. They display an unusual ring-chain tautomeric equilibrium, which is governed by the nature of the solvents and thepH value.

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Synthese und Eigenschaften einzigartiger Mesoionischer 1,3-Thiazolium-4-olate

Zusammenfassung N-verbrückte 1,3-Thiazolium-4-olate wurden durch Reaktion von 3-substitutierten 3-Aminothioacrylaniliden mit Bromessigsäureethylester in siedendem Xylol synthetisiert. Ihre strukturellen Aspekte wurden mit Hilfe von Massen-, NMR- und Absorptionsspektroskopie untersucht. Sie zeigen ein ungewöhnliches Ring-Ketten-Tautomeriegleichgewicht, das durch die Natur des Lösungsmittels und denpH-Wert gesteuert wird.

     

Optisch aktives 1,3-Diferrocenyl-1,3-diphenyl-allen

The title compound 2 was prepared by thermal dehydration of 1,3-diferrocenyl-1,3-diphenyl-propenol (24) with 70% yield.24 was accessible from 1,3-diferrocenyl-propanedione-1,3 (25) in two steps with 10% overall yield: Treatment of25 with phenyllithium gave 1,3-diferrocenyl-3-phenyl-propenone (8) which after repeated reaction with phenyllithium afforded24.Partial optical resolution of2 was achieved by chromatography on triacetyl cellulose in ethanol, whereby both (+)- and (–)-2 were obtained with different enantiomeric purities as could be deduced from the CD-spectra with -values of +0.18 and –1.64, resp., at 480 nm.Attempts to prepare 1,3-diferrocenyl-allene and 1,3-diferrocenyl-1-phenyl-allene failed. In this context several 1,3-diferrocenyl-propenols,-propenones,-propenes,-propanones,-propanes and-butadienes were obtained.

62. Mitt.:M. Benedikt undK. Schlögl, Mh. Chem.109, 805 (1978).