The electronic structure and optical activity of conjugated dienes: 1,3-Butadiene and α- and β-phellandrene

The optical activity of conjugated dienes is investigated by means of ab initio SCF–CI calculations. The computed electronic spectrum of trans-1,3-butadiene is shown to be in good agreement with the results of more rigorous calculations of the valence transitions and in satisfactory agreement with experiment. The optical rotatory strengths of the lower electronic transitions of twisted 1,3-butadiene as a function of dihedral angle are presented and simulated CD spectra are produced. The N → V₁ (π₂ → π₃*) transition is predicted to have a positive rotational strength for all dihedral angles that correspond to a right-handed twist of the chromophore, in accord with the empirically deduced “diene rule” although for a twist angle of 60°, the rotatory strength is calculated to be almost zero. The role of the orientation of allylic bonds is investigated in the model system 1-butene in which the rotational strength of the π → π* transition as a function of rotation about the 2,3 bond is determined. The effect of allylic bond disposition in dienes on the optical activity of the long-wavelength π₂ → π₃* transition is simulated by use of the exciton coupling model of Harada and Nakanishi in which two 1-butene molecules with suitable geometries are coupled via interactions of the electric dipole transition moments of their π → π* transitions. The model systems 1,3-butadiene and 1-butene are used to rationalize the apparently anomalous optical activity of (?)-α-phellandrene and (?)-β-phellandrene, both of which should have a diene chromophore with a right-handed twist in their most stable conformers and so should be dextrorotatory. The experimental CD spectrum of α-phellandrene is determined at several temperatures down to ?180°C. The observed variation of the apparent rotational strength of the N → V₁ transition is in good agreement with that predicted by use of the exciton coupling model.     

The high resolution mass spectra of α,β-unsaturated and α-chloromercuri-α,β-unsaturated steroidal ketones

The high resolution mass spectra (500 eV) of some α,β-unsaturated steroidal ketones have been studied and compared with the spectra of the corresponding α-chloromercuri ketones. In the latter, the carbon-mercury bond frequently remains intact at the expense of the fission of two carbon-carbon bonds. The abundance of mercury-containing ions allows the use of the mercury atom fingerprint in confirming ring B fragmentation of the steroid nucleus at C(6)–C(7) and C(9)–C(10) for 5α-androst-1-ene-3,17-dione, 1,4-androstadiene-3,17-dione and their 2-chloromercuri derivatives; and at C(7)–C(8) and C(9)–C(10) for 1,4,6-androstatriene-3,17-dione, 1,4,6-androstarien-17 β-ol-3-one and their 2-chloromercuri derivatives. 2-Chloromercuri-1,4,6-androstatriene-3,17-dione and 2-chloromercuri-1,4,6-androstatrien-17 β-ol-3-one also give an abundant ion as the result of ring C fragmentation at C(8)–C(14) and C(11)–C(12), the chloromercuri group being replaced by a hydrogen atom. This ring C cleavage gives the only recognizable distinctive fragmentation ion for 1,4,6-pregnatriene-3,20-dione and 2-chloromercuri-1,4,6-pregnatriene-3,20-dione. For most of the mercurated steroids, the low resolution mass spectra (70 eV) are reported. In these spectra, the fragmentation patterns are similar to those obtained using the higher ionization energy employed for the high resolution spectra.     

Mass spectra of 17ξ-hydroxy-5ξ-androstane C(3) ketone and C(3ξ) alcohol isomers

Positive ion electron impact mass spectral data for the four isomeric 17ξ-hydroxy-17ξ-methyl-5ξ-androstane C(3) ketones and the eight isomeric C(3ξ) alcohols are reported. In contrast to earlier reports, no general correlation was observed between the [M? H₂O]⁺˙/[M]⁺˙ ratio and the configuration at C(17). The ratios of the intensity of several fragment ions to that of the molecular ion do differentiate between the 5α- and 5β-isomers in both C(3) ketones and alcohols, the extent of fragmentation being greater for 5β-steroids. All of these fragments probably involve elimination of a water molecule at some stage in their formation. Elimination of water is also enhanced for 3α- v. 3β-hydroxysteroids, particularly in a 5β-isomer.     

Fragmentation of oxime and silyl oxime ether odd‐electron positive ions by the McLafferty rearrangement: new insights on structural factors that promote α,β fragmentation

The McLafferty rearrangement is an extensively studied fragmentation reaction for the odd‐electron positive ions from a diverse range of functional groups and molecules. Here, we present experimental and theoretical results of 12 model compounds that were synthesized and investigated by GC‐TOF MS and density functional theory calculations. These compounds consisted of three main groups: carbonyls, oximes and silyl oxime ethers. In all electron ionization mass spectra, the fragment ions that could be attributed to the occurrence of a McLafferty rearrangement were observed. For t‐butyldimethylsilyl oxime ethers with oxygen in a β‐position, the McLafferty rearrangement was accompanied by loss of the t‐butyl radical. The various mass spectra showed that the McLafferty rearrangement is relatively enhanced compared with other primary fragmentation reactions by the following factors: oxime versus carbonyl, oxygen versus methylene at the β‐position and ketone versus aldehyde. Calculations predict that the stepwise mechanism is favored over the concerted mechanism for all but one compound. For carbonyl compounds, C–C bond breaking was the rate‐determining step. However, for both the oximes and t‐butyldimethylsilyl oxime ethers with oxygen at the β‐position, the hydrogen transfer step was rate limiting, whereas with a CH₂ group at the β‐position, the C–C bond breaking was again rate determining. n‐Propoxy‐acetaldehyde, bearing an oxygen atom at the β‐position, is the only case that was predicted to proceed through a concerted mechanism. The synthesized oximes exist as both the (E)‐ and (Z)‐isomers, and these were separable by GC. In the mass spectra of the two isomers, fragment ions that were generated by the McLafferty rearrangement were observed. Finally, fragment ions corresponding to the McLafferty reverse charge rearrangement were observed for all compounds at varying relative ion intensities compared with the conventional McLafferty rearrangement. Copyright © 2012 John Wiley & Sons, Ltd.     

Mass spectrometry of some 10β-Fluoro-1,4-estradien-3-oxo steroids

The mass spectrometric behavior of some 10β-fluoro-1,4-estradiene-3-oxo steroids under two different ionization conditions (electron inpact and fast atom bombardment) was studied with the aid of mass-analyzed ion kinetic energy spectroscopy. The influence of fluorine in the fragmentation pattern was investigated by comparison with the behavior of 10-methyl analogs. In particular, the presence of fluorine at position 10 seems to reflect the weakening of C(9)? C(10) bond. Further, when an acyloxy moiety is present at position 17, the primary ring cleavages typical of steroids become disfavored and fragment ions related to the acyloxy substituents are detected.     

Einfluss funktioneller Gruppen auf die Massenspektren von 17β-Hydroxysteroiden

The different influence of functional groups on fragmentation reactions is demonstrated by the example of 17β-hydroxy-5α-androstanes. In 17β-hydroxy-5α-androstane the tendency of steroids to be cleaved by rupture of the C-13/C-17 bond under production of a charged centre at C-13 is only enhanced by the hydroxyl group. This influence of the hydroxyl group only predominates as long as substituents are absent which need less energy for ionization than is necessary to ionize the C-13/C-17 bond. Even the presence of a double bond may change the fragmentation pattern completely. If, however, an additional alkyl group is located at C-17, ionization occurs with high probability by elimination of an electron from the OH group connected to C-17. Therefore, other main degradation reactions occur than in molecular ions, having the charge located at C-13. In such compounds even the dominant influence of a conjugated system on the fragmentation reactions is considerably reduced. By etherfication of the hydroxyl group this effect is still very much increased. In the course of this investigation some not yet known degradation reactions, rather typical for the presence of certain groups in the steroid skeleton, were found. These are discussed briefly.     

Reaction of diethyl 3-methyl-1,2-butadienylphosphonate with 1,10-diaza-18-crown-6

Reaction of two-fold excess of diethyl 3-methyl-1,2-butadienylphosphonate with 1,10-diaza-18-crown-6 leads to the formation of an adduct whose molecule includes two 1-phosphoryl-3-methyl-2-butene fragments bound together by a crown bridge with the anti location of organophosphorus groups relative to the macrocycle plane. The 1,2-multiple bond of the phosphonate is involved in the reaction. Extraction properties of the diphosphorylated crown ether toward alkali metal picrates were studied.     

Alternating copolymerization of dienes with α-olefins

Alternating copolymerization of butadiene with several α-olefins and of isoprene with propylene were investigated by using a mixture of VO(Acac)₂, Et₃Al, and Et₂AlCl as catalyst. The alternating copolymerization ability of the olefins decreases in the order, propylene > 1-butene > 4-methyl-1-pentene > 3-methyl-1-butene. The study on the sequence of the copolymer of isoprene with propylene by ozonolysis reveals that the polymer chain is reasonably expressed by the sequence \documentclass{article}\pagestyle{empty}\begin{document}$ \rlap{--} [{\rm CH}_{\rm 2} \hbox{--} {\rm CH} \hbox{=\hskip-1pt=} {\rm C(CH}_{\rm 3}) \hbox{--} {\rm CH}_{\rm 2} \hbox{--} {\rm CH(CH}_{\rm 3}) \hbox{--} {\rm CH}_{\rm 2} \rlap{--}]_n $\end{document}. NMR and infrared spectra indicate that the chain is terminated with propylene unit, forming a structure of ?C(CH₃)? CH₂? C(CH₃)?CH₂ involving a vinylene group.     

Lower photoreactivity of 3-methyl-3-(4′-biphenylyl)-t-butene

Direct and sensitized photolyses of 3-methyl-3-(4′-biphenylyl)-1-butene gave 1,1-dimethyl-2-(4′-biphenylyl)cyclopropane as primary product and 2-methyl-4-(4′-biphenylyl)-1-butene as secondary product with quantum yields of 7.6×10^?3 and 5.6×10^?3, respectively. On direct photolysis, the triplet reactant rearranged with a quantum yield of 4.4×10^?3 and is more reactive than the singlet. The exceptionally low photoreactivity shows that the excitation energy is largely localized on the biphenylyl portion but can be delivered to the reaction center slowly.     

Ring-opening polymerization of α,β-disubstituted oxiranes by α-methoxyphenylmethylium hexachloroantimonate

α-Methoxyphenylmethylium hexachloroantimonate was used as a novel initiator for the polymerization of α,β-disubstituted oxiranes such as cyclohexene oxide (CHO) and 2-butene oxide (trans and cis) (2-BO) at ?78°C with dichloromethane or dichloromethane-toluene mixtures as solvents. The CHO polymerization mixture became turbid and the polymer precipitated in dichloromethane. The CHO polymerization proceed quantitatively in dichloromethane–toluene mixtures. The molecular weight distribution of polyCHO obtained was bimodal regardless of the solvent used. The polymerization of trans-2-BO was heterogeneous in both dichloromethane and dichloromethane–toluene mixture. The polymerization mixtures of cis-2-BO were transparent but reached a limit yield which was less than the polymer yield of trans-2-BO. Furthermore, the microstructure of the poly2-BOs were analyzed by Vandenberg's method and the results confirmed Vandenberg's finding that inversion of configuration occurs in the propagation step.     

Effect of a trifluoromethyl group on the polymerizability of α-olefins by transition metal catalysts

Several α-olefins containing the trifluoromethyl group were prepared and characterized. 4,4,4-Trifluoro-1-butene, 3-trifluoromethyl-1-butene, 5,5,5-trifluoro-1-pentene, and 4-trifluoromethyl-1-pentene were homopolymerized with VCl₃–Al(i-Bu)₃ catalyst. The trifluorobutenes gave low-melting polymers with low fluorine contents. Polymers obtained from the trifluoropentenes were soluble having moderately high intrinsic viscosities. Copolymerizations of these monomers with their nonfluorinated homologs by the same catalyst system indicated low reactivities of the fluoromonomers. Nuclear magnetic resonance spectra of the fluorinated and nonfluorinated monomers and their respective spectroscopic studies with the catalyst (C₅H₅)₂TiCl₂–Al(CH₃)₃ indicated an electron deficiency of the vinyl group of the fluorobutenes. This was related to the inductive effect of the trifluoromethyl group. The inductive effect of this group was absent in the fluoropentenes and the nonfluorinated monomers. The electron-deficient vinyl group of the fluorobutenes apparently did not allow these monomers to coordinate with the active sites of the catalyst. Polymerization studies of the nonfluorinated monomers, 1-butene, 3-methyl-1-butene, 1-pentane, and 4-methyl-1-pentene, with the catalyst VCl₃–Al(Bu)₃, were performed in the presence of compounds containing the trifluoromethyl group. Results indicated that this group did not retard the rate of polymerization of these monomers. Evidence is presented to show that a catalytic amount of benzotrifluoride enhanced the rate of polymerization of α-olefins, particularly that of sterically hindered monomers such as 3-methyl-1-butene.     

Chemical Reactivity of Oxo‐ and Aza‐γ‐lactam Rings

Different mechanisms for the alkaline hydrolysis of oxo and aza‐γ‐lactam rings have been studied by ab initio calculations at the MP2/6‐31+G*//MP2/6‐31+G* and B3LYP/6‐31+G*//B3LYP/6‐31+G* levels. The tetrahedral intermediate can undergo two different reactions, the cleavage of the C₂−N₂ bond (the classical mechanism) and the cleavage of the C₂−X₆ bond (X=O, N). Both compounds present similar energy barriers for the classical fragmentation, and show considerably lower barriers for the alternative mechanism. Because of this reactivity, the compounds studied are expected to be β‐lactamase inhibitors.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Conformational energies and rotational barriers in 3-methyl-1-butene and 1-butene: An ab initio and molecular mechanics study

The calculated result obtained with MM2(87) for the rotation of the isopropyl group in 3-methyl-1-butene is not in agreement with experimental data. In order to reparametrize the C_sp2-C_sp3-C_sp-C_sp3 torsional angle, 3-methyl-1-butene and 1-butene have been studied by molecular mechanics (MM2(87)) and ab initio (MP2/6-31G* and MP3/6-31G*) calculations. The reparametrization of the torsional angle gives calculated results from MM2(87) in agreement with experimental data and ab initio calculations for both 3-methyl-1-butene and 1-butene. The calculated barriers for the rotation of alkyl groups in alkylbenzenes are improved with these new parameters.     

Studies in organic mass spectrometry-XIII: Investigation of electron-induced isomerisation of αβ- and βγ-unsaturated esters

The mass spectral fragmentation of methyl esters of α,β- and β,γ-unsaturated carboxylic acids has been studied. Deuterium labelling, metastable ion analysis and high resolution mass spectrometry have been utilised to elucidate the mechanism of a number of fragmentations and to check possible double bond migration prior to fragmentation. Some breakdown modes were found to occur through double bond migration. Additional support was provided by application of the ‘Metastable Ion Characteristics’ method. Partial isomerisation of molecular ions must therefore be accepted.     

ZUM MECHANISMUS MASSENSPEKTROMETRISCHER FRAGMENTIERUNGSREAKTIONEN BEI A/B-CIS- VERKNüPFTEN 3α-HYDROXYSTEROIDEN MIT UND OHNE 11-KETOGRUPPE

Mass spectra of steroids containing a carbonyl group in position 11 and a 3α-hydroxy group in a cis connected A/B ring system are characterised by very strong [M – 72]⁺· key ions and may therefore be clearly differentiated from the spectra of their isomers. The mechanism of this fragmentation reaction was investigated by deuterium labelling and the DADI technique. The 3α-hydroxy group is eliminated together with the 9α-H atom. Next a hydrogen atom is transferred from the A ring to the B/C/D ring system. This causes the cleavage of the C-3? C-4 bond and expulsion of C atoms 1 to 4 as butadiene. In 3α-hydroxy-5α-androstanes possessing no 11-keto group an analogous [M – 18]⁺. fragment is fromed, followed by the elimination of ethylene originating mostly from C-1 and C-2.     

Palladium-catalyzed conjugate addition type reaction of 5-iodopyrimidines with α,β-unsaturated ketones

The reaction of various 5-iodopyrimidines with α,β-unsaturated ketones in the presence of palladium diacetate-triphenylphosphine complex in triethylamine are investigated. In the reaction of 2,4-dialkoxy(or alkylthio)-6-methyl-5-iodopyrimidine the addition of pyrimidine to the carbon? carbon double bond of α,β-unsaturated ketones occurs. In the case of other pyrimidines, according to the decrease of steric hindrance at the 5-position on the pyrimidine ring, the ratio of conjugate addition product was decreased and the usual olefinic substituted product was increased.     

Energy selective excision of CN- following electron attachment to hexafluoroacetone azine ((CF3)2C=N-N=C(CF3)2)

Low energy electron attachment (DEA) to hexafluoroacetone azine (HFAA) leads to a remarkable energy selective excision of CN(-) within a pronounced resonance located at 1.35 eV. The underlying dissociative electron attachment (DEA) reaction involves multiple bond cleavages and rearrangement within the neutral products. A series of further fragment ions (F(-), CF(3)(-), (CF(3))(2)C(-) and (CF(3))(2)CN(-)) are observed from resonant features above 2 eV and only (CF(3))(2)CN(-) is additionally formed within a narrow resonance below 1 eV. In contrast to CN(-) all the remaining fragment ions can be formed by simple bond cleavages with (CF(3))(2)CN(-) being the result of a symmetric decomposition of the target molecule by cleavage of the (N-N) bond with the excess charge localised on either of the identical fragments. Our ab initio calculations predict an adiabatic electron affinity of HFAA close to 2 eV with the geometry of the relaxed anion considerably distorted with respect to that of the neutral molecule.     

Polymer-Attached Thiazolium Salts-Catalyzed Addition of Aldehydes to α, β-Unsaturated Carbonyl Compounds

A homogeneous catalyst, 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride, for addition of aldehydes to activated double bond, was attached to 20% cross-linked polystyrene-divinylbenzene copolymer. The attached catalysts could be easily removed from the reaction mixture. Polymer-attached thiazolium salts in the presence of triethylamine are active catalysts for addition of aromatic and aliphatic aldehydes to α,β-unsaturated ketones to yield γ-diketones.     

Mechanistic Insight into the Facilitation of β‐Lactam Fragmentation through Metal Assistance

The mechanism of OsH₆(PiPr₃)₂‐mediated fragmentation of a 4‐(2 pyridyl)‐2‐azetidinone has been investigated by DFT calculations. The addition of the C4?H bond of the substrate to OsH₂(PiPr₃)₂ allows the active participation of an osmium lone pair in the B‐type β‐lactam fragmentation process. This new mechanism makes the N1?C4/C2?C3 fragmentation of the lactamic core thermally accessible through a stepwise process.