Stereochemical applications of mass spectrometry: 1—The utility of electron impact and chemical ionization mass spectrometry in the differentiation of stereoisomeric benzoin oximes and phenylhydrazones

A study of the electron impact and chemical ionization (H₂, CH₄, and iso-C₄H₁₀) mass spectra of stereoisomeric benzoin oximes and phenylhydrazones indicates that while the former can be distinguished only by their chemical ionization mass spectra the latter are readily distinguishable by both their electron impact and chemical ionization mass spectra. The electron impact mass spectra of the isomeric oximes are practically identical; however, the chemical ionization spectra show that the E isomer forms more stable [MH]⁺ and [MH? H₂O]⁺ ions than the Z isomer for which both the [MH]⁺ and [MH? H₂O]⁺ ions are relatively unstable. In electron impact the Z-phenylhydrazone shows a lower [M]⁺˙ ion abundance and more facile loss of H₂O than does the E isomer. This more facile H₂O loss also is observed for the [MH]⁺ ion of the Z isomer under chemical ionization conditions.     

Stereospecific 1,4‐Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes

Reported herein is a stereospecific 1,4‐metallate rearrangement for single‐geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N‐oxides, and amides having a single configuration.     

15N nuclear magnetic resonance spectroscopy. Natural-abundance 15N spectra of aliphatic oximes

¹⁵N chemical shifts of the Z and E isomers of twenty-two ketoximes and fourteen aldoximes have been determined at the natural-abundance level of ¹⁵N, using Fourier transform methods. The influences of π delocalization, methyl substituents and solute concentration on the oxime nitrogen shielding have been determined. The ¹⁵N shifts for oximes of several cycloalkanones have been measured and the influence of ring size on the chemical shifts is discussed.     

Herstellung der 1H-Indazole durch Photolyse von 2-Aminophenylketon-O-(äthoxycarbonyl)oximen und von 3,1,4-Benzoxadiazepin-2 (1H)-onen

1H-Indazoles Obtained by Photolysis of 2-Aminophenylketon-O-(ethoxycarbonyl)oximes and of 3, 1, 4-Benzoxadiazepine-2(1 H)-ones Irradiation of (E)- and (Z)-O-(ethoxycarbonyl)oximes 1 of 2-aminophenyl ketones in solution with UV, and/or visible light gives 1 H-indazole derivatives 2 in high yields (Scheme 1). For this reaction the amino group must be un- or mono substituted. With the N, N-disubstituted (E)- 1d (Scheme 2) no 1 H-indazole formation is observed, because the radicals formed by its photolysis react in an unspecific manner with each other and with the solvent. From the behaviour of (E)- 1d and from the lack of any E/Z-isomerization of 1 we conclude that the photoreaction starts with a splitting of the N, O-bond in two separate radicals, whereas the radical pair produced by the also studied photolysis of 3,1,4-benzoxadiazepine-2(1 H)-one derivatives 3 is fixed in the parent molecule, and therefore tends to recombine. This makes a prolonged irradiation necessary to convert the benzoxadiazepinones 3 into the 1 H-indazoles 2 . The different reaction rates of the (E) and (Z)-isomers of 1 (provided R⁴ = H) are understood by means of different intramolecular H-bridges.     

Stereospecificity of shielding constants of carbon-13 nuclei in 13C NMR spectra of oximes of hetarenecarbaldehydes and alkyl heteryl ketones

It has been discovered that the chemical shifts of carbon atoms in ¹³C NMR spectra of oximes having pyrrolyl, furyl, benzofuryl, thienyl, and pyridyl rings as substituents are changed systematically on going from the E- to the Z-isomer. This makes it possible to use the indicated chemical shifts for establishing the configuration of oximes with heterocyclic substituents and studying the special features of their electronic structure. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1523–1531, October, 2008.     

Die heterolytische Fragmentierung von Benzoin-O-(carbamoyl)oximen

The Heterolytic Fragmentation of Benzoin-O-(carbamoyl)oximes While the known heterolytic fragmentation reactions give only three, thermal decomposition of benzoin-O-(carbamoyl)oximes results in at least four fragments: nitrile or isocyanide, carbonyl compound, CO₂ and amine. This exception is due to the transformation of the nucleofugal group 3 into the unstable carbamic acid and its decomposition (s. Scheme 1). Since only the configuration of benzoin (E)-O-(carbamoyl)oximes is satisfactory for concerted reactions, we conclude that the nitrile producing fragmentation of these (E)-compounds is concerted, whereas in the isocyanide producing fragmentation of the corresponding (Z)-compounds several steps are involved. – In contrast to the benzoin-O-(carbamoyl)oximes the pyrolysis of benzil-(E)-O-(methylcarbamoyl)oxime starts with the elimination of methyl isocyanate and the following fragmentation is that of the oxime.     

The Hartree–Fock ground state of atomic two-electron systems and the Wilson–Silverstone 1s orbital

For the Hartree–Fock ground state of atomic two-electron systems, the variational function of Wilson and Silverstone, ?(r) = (a + kr)^?1 exp(-kr) / (4π)^1/2, can be optimized in two complementary ways. For small values of the atomic number Z, all intergrals have been calculated numerically and optimization can be performed accurately. However, as Z increases, loss of significant figures is increasingly detrimental to the optimization process. For sufficiently large values of Z, the integrals may be replaced by asymptotic expansions in terms of (2a)^?. As a result of optimization, the parameters and expectation values can be given as expansions in terms of (32Z)^?1/2. Both methods yield good results for Z ≈ 25, so that the whole range of Z can be treated accurately. The results have been compared with those derived from other analytical two-parameter functions. It is found that ?(r) is indeed the outstanding two-parameter function, at least for small and intermediate values of Z.     

Grignard-Addition an Pyridin-N-oxid

Addition of phenyl-, alkyl-, alkenyl- and alkinyl-Grignard reagents to pyridine-N-oxide in THF leads to 5-substituted (2Z, 4E)-pentadien-aldoximes 6 having (E) (syn)-configuration of the C, N-double bond. The unsaturated oximes are shown to arise through an electrocyclic ring opening reaction from the primary Grignard adducts 5 . These can be trapped by protonation at low temperature.     

Pronounced stereospecificity of 1H, 13C, 15N and 77Se shielding constants in the selenophenyl oximes as shown by NMR spectroscopy and GIAO calculations

In the ¹H and ¹³C NMR spectra of 1‐(2‐selenophenyl)‐1‐alkanone oximes, the ¹H, the ¹³C‐3 and ¹³C‐5 signals of the selenophene ring are shifted by 0.1–0.4, 2.5–3.0 and 5.5–6.0 ppm, respectively, to higher frequencies, whereas those of the ¹³C‐1, ¹³C‐2 and ¹³C‐4 carbons are shifted by 4–5, ～11 and ～1.7 ppm to lower frequencies on going from the E to Z isomer. The ¹⁵N chemical shift of the oximic nitrogen is larger by 13–16 ppm in the E isomer relative to the Z isomer. An extraordinarily large difference (above 90 ppm) between the ⁷⁷Se resonance positions is revealed in the studied oxime isomers, the ⁷⁷Se peak being shifted to higher frequencies in the Z isomer. The trends in the changes of the measured chemical shifts are well reproduced by the GIAO calculations of the ¹H, ¹³C, ¹⁵N and ⁷⁷Se shielding constants in the energy‐favorable conformation with the syn orientation of the? C?N? O? H group relative to the selenophene ring. Copyright © 2009 John Wiley & Sons, Ltd.     

Configurational assignments of oximes derived from 5-formyl and 5-acyl-1,2,4-triazines

The configuration of (3-substituted)-1,2,4-triazin-5-ylcarbaldoximes and (3-substituted)alkyl-1,2,4-triazin-5-ylketoximes was determined by means of ¹H-nmr, ¹³C-nmr, ¹⁵N-nmr and homonuclear NOE-difference spec-troscopy. Oximes resulting from reaction of 1,2,4-triazines with nitroalkanes were found to be either pure E-isomers or E/Z-mixtures with the amount of E-isomer greatly predominating. Detailed ¹³C-nmr data of the oximes investigated are presented.     

Pentiptycene‐Derived Light‐Driven Molecular Brakes: Substituent Effects of the Brake Component

Five pentiptycene‐derived stilbene systems ( 1 R ; R =H, OM, NO, Pr, and Bu) have been prepared and investigated as light‐driven molecular brakes that have different‐sized brake components ( 1 H < 1 OM < 1 NO < 1 Pr < 1 Bu ). At room temperature (298 K), rotation of the pentiptycene rotor is fast (k_rot=10⁸–10⁹ s^?1) with little interaction with the brake component in the trans form ((E)‐ 1 R ), which corresponds to the brake‐off state. When the brake is turned on by photoisomerization to the cis form ((Z)‐ 1 R ), the pentiptycene rotation can be arrested on the NMR spectroscopic timescale at temperatures that depend on the brake component. In the cases of (Z)‐ 1 NO , (Z)‐ 1 Pr , and (Z)‐ 1 Bu , the rotation is nearly blocked (k_rot=2–6 s^?1) at 298 K. It is also demonstrated that the rotation is slower in [D₆]DMSO than in CD₂Cl₂. A linear relationship between the free energies of the rotational barrier and the steric parameter A values is present only for (Z)‐ 1 H , (Z)‐ 1 OM , and (Z)‐ 1 NO , and it levels off on going from (Z)‐ 1 NO to (Z)‐ 1 Pr and (Z)‐ 1 Bu . DFT calculations provide insights into the substituent effects in the rotational ground and transition states. The molar reversibility of the E–Z photoswitching is up to 46 %, and both the E and Z isomers are stable under the irradiation conditions.     

Stereoselective cycloadditions of (1Z,4R,5R)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to maleimides

A library of 15 1,6,7,9-tetrasubstituted 6,7,9,9a-tetrahydro-5H-pyrazolo[1,2-a]pyrrolo[3,4-c]pyrazole-1,3,5(2H,3aH)-triones was prepared by combinatorial stereoselective cycloadditions of (1Z,4R^∗,5R^∗)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to N-substituted maleimides. Stereochemistry was controlled by the stereodirecting phenyl group at position-3 and by the ortho-substituents at the aromatic ring at position-1′ in azomethine imines. Consequently, two sets of diastereomeric cycloadducts were obtained, one set from the ortho-unsubstituted dipoles and the other set from the ortho-disubstituted dipoles.     

Dimephosphone analogs: II. Dialkyl(diaryl)-(2-methyl-4-oxopent-2-yl)phosphine oxide oximes: Synthesis,structure, and generation of iminoxyl radicals

Dialkyl(diaryl)-(2-methyl-4-oxopent-2-yl)phosphine oxide oximes have been synthesized for the first time. According to the X-ray diffraction data, these compounds in crystal exist as a single E isomer. Their structure in solution and the E/Z isomer ratio were determined by ¹H and ¹³C NMR spectroscopy.     

Study on the preparation of heteroaryl substituted enamines. A simple synthesis of heteroaryl substituted acetaldoximes from enamines

A comparative study of the reactivity of methyl groups towards N, N-dimethylformamide dimethyl acetal and tert-butoxybis(dimethylamino)methane was carried out on methyl substituted six-membered nitrogen containing heterocycles 1 to give enamines 2 , which were easily transformed to oximes by treating with hydroxylamine hydrochloride in methanol. Most of them were isolated as (E, Z)-oximes of heteroarylacetaldehyde ( 11 ), but 5-(1,2,4-triazinyl) substituted derivatives as (E, Z)-oximes of 2,5-dihydro-1,2,4-triazin-(Z)-5-ylideneacetaldehyde ( 11t, 11u , and 12 ). Oximes were finally transformed to the corresponding acetonitriles 16 and 3-(dimethylamino)acrylonitriles 17 .     

Über die Temperaturabhängigkeit der 13C-NMR.-Spektren von Tetracarbonyl (η-(Z)-cycloocten)eisen und (Z)-cycloocten

On the Temperature Dependence of the ¹³C-NMR.-Spectra of Tetracarbonyl (η-( Z )-cyclooctene)iron and of ( Z )-Cyclooctene Reaction of (Z)-cyclooctene (1) with Fe₂(CO)₉ in pentane at 0° yielded tetracarbonyl(η-(Z)-cyclooctene)iron (2) as a yellow oil which can be stored over a longer period only at ?78°. It is shown that the title compounds ( 1 and 2 , respectively) are fluxional. The activation parameters for the conformational C-atom site exchange of (Z)-cyclooctene (1) and tetracarbonyl (η-(Z)-cyclooctene)iron (2) (in CCl₂F₂) have been determined between 113 K and 151 K for 1 and between 151 K and 205 K for 2 , respectively, by a complete line shape analysis of the temperature dependent proton noise-decoupled ¹³C-NMR. signals of the olefinic C-atom. The kinetic data and activation parameters are given in Tables 1 and 2.     

The study of reactions of α-chlorocinnamonitriles with hydroxylamine

The E-isomers of α-chlorocinnamonitriles react with hydroxylamine to give a mixture of isomeric aminoisoxazoles, while the Z-isomers yield 3-aryl-2-chloroacrylamide oximes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1678–1682, July, 2005.     

Synthesis and Properties of 1-(3,4-DI-O-Acetyl-2-Deoxy-2-Hydroxyimino-D-Threo-Pentopyranosyl)Pyrazoles

ABSTRACT

3,4-Di-O-acetyl-2-deoxy-2-nitroso-α-D-xylo-pentopyranosyl chloride (2) reacts with pyrazole to afford 1-[3,4-di-O-acetyl-2-deoxy-2-(Z)-hydroxyimino-α- (3) and β-D-threo-pentopyranosyl]pyrazole (4). The products of condensation were modified at C-2 or C-3 to give pyrazole derivatives with 3-azido-2,3-dideoxy-2-hydroxyimino-pentopyranosyl (5,7,8,9,10), 2-acetoxyimino-2,3-dideoxy-β-D-glycero-pentopyranosyl (12,13), β-D-lyxo- (14), β-D-xylopentopyranosyl (15) structures and 2,3-dihydro-2-pyrazol-1-yl-6H-pyran-3-one oximes (6,11). The conformation of the sugar residue and configuration at the anomeric centre and of the hydroxyimino group were established on the basis of ¹H NMR and polarimetric data.     

Synthesis of <Emphasis Type="Italic">N,N</Emphasis>-disubstituted (<Emphasis Type="Italic">Z</Emphasis>)-<Emphasis Type="Italic">O</Emphasis>-methylnicotinamide oximes

A number of (Z)-N,N-dialkyl- and (Z)-N-acyl-N-alkyl-O-methylnicotinamide oximes was synthesized. Their configuration was confirmed by the NOESY experiment. Evaluation of fungicidal activity of compounds obtained was performed.     

UV-spektroskopische Konfigurationsbestimmung bei stereoisomeren Benzaldehydoximen

Zusammenfassung Die Konfigurationsbestimmung stereoisomerer Aldehydoxime durch Messung der UV-Absorption der undissoziierten und dissoziierten Formen ist auch auf aromatische Aldehydoxime übertragbar. Zwar wird die Regel, daß die Differenz der Frequenzen der Bandenmaxima zwischen Z- und Z^(–)-Form größer ist als zwischen den betreffenden E- und E^(–)-Formen, bei Vorliegen von Substituenten mit +I- und +R-Effekt durchbrochen, doch ist das Verhältnis der molaren Absorptionskoeffizienten von E^(–)- zu Z^(–)-Form stets deutlich größer als eins. Untersucht wurden Oxime brom-, chlor-, cyan-, methoxy-, methyl- und nitrosubstituierter Benzaldehyde.

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UV-spectroscopic differentiation of stereoisomeric benzaldehyde oximes

The configuration assignment of stereoisomeric carbaldehyde oximes by determination of the UV-absorption of the oxime and oximate forms is also applicable to aromatic aldehyde oximes. While the observation, that the band maximum difference between the Z and Z^(–) forms is bigger than between the E and E^(–) forms, is not valid in the presence of +I and +R substituents, the molar absorption coefficient ratio E^(–)/Z^(–) is in any case bigger than one. Bromo, chloro, cyano, methoxy, methyl, and nitro substituted benzaldehyde oximes have been investigated.

     

The fragmentation of ortho-methoxyphenyl-2-propanone oximes and related compounds–further examples of an ortho-effect

An [M ? 31]⁺ ion was a prominent fragment in the mass spectra of three ortho-methoxy-phenyl-2-propanone oximes and is shown to be due to the expulsion of a methoxyl radical from the molecular ion as a result of an ortho-effect. In contrast, an [M ? 31]⁺ ion was absent from the spectra of a structurally related ketone and a hydroxylamine, and was not observed in the spectra of meta- and para-methoxyphenyl-2-propanone oximes.