Aminyloxide (nitroxide)—XXIV: Empirische ermittlung der spindichteverteilung in aminyloxiden

¹⁷O-Labelled aminyloxides 1–8 (dialkyl-, alkylaryl-, diaryl-, acylaminyloxides and amidinyloxides) have been prepared by various methods. The ESR spectra of 1a and 4 have been measured in various solvents, showing a very good correlation between a^N respectively a^O and the E_T-values of solvents. From the solvent-dependence of the coupling constants of 1a Q-values have been evaluated for the simplified equation aⁱ = Q_iiⁱ × pⁱ (Q_NN^N = 33.1 G; Q_oo^o = 35.3 G). These values were used to calculate the spin density ?^N and ?^o of the aminyloxides 1–8. The Q-values are shown to be reasonable by summation of the spin density of all positions for the radicals 4–7. which gives one with only small deviations. In most of these radicals in which the unpaired electron is delocalized into the conjugated π-system ?^N is reduced significantly, as compared to dialkyl-ammyloxides, whereas ?⁰ is only lowered to a small extent.     

The synthesis of αβ-unsaturated ketones from β-silylenones and β-silylynones

Conjugate addition, followed by alkylation, bromination and desilyl-bromination make the β-silylketone (4) an a³d³-synthon (5) and the β-silylynone (6) a 2a³d³-synthon (7).     

Reversible pyranyl complex formation and the mechanism of rearrangement to (η-6-oxocycloheptadienyl)Mn(CO)3 complexes in the reaction of β-cyclomanganated 1,5-diarylpenta-1,4-dien-3-ones and alkynes; the crystal structure of [2,4-diphenyl-6-(2-phenylethenyl)pyranyl-η]tricarbonylmanganese

[1-Phenyl-2-[(E)-3-phenylprop-2-en-1-oyl-κO]ethenyl-κC¹]tetracarbonylmanganese (1a) reacts with PhCCH in CCl₄ at room temperature to form [2,4-diphenyl-6-(2-phenylethenyl)pyranyl-η⁵]tricarbonylmanganese (2a), whose X-ray crystal structure is reported to complement that of its isomer [6-oxo-2,4,7-triphenylcyclohepta-1,4-dienyl-1,2,3,4,5-η]tricarbonylmanganese (3a), previously obtained from the reaction under reflux; but for 1a and PhCCPh the pyranyl complex cannot be isolated before rearrangement to the 3a analogue occurs. More forcing reaction conditions for 1a with Me₃SiCCH and for [1-(2-trifluoromethylphenyl)-2-[(E)-3-(2-trifluoromethylphenyl)prop-2-en-1-oyl-κO]ethenyl-κC¹]tetracarbonylmanganese (1b) with Me₃SiCCH and PhCCH give new analogues of 3a where previously only 2a analogues had been isolated.The reaction in CCl₄ under reflux of PhCCH and the β-deuterio analogue of 1a, [1-phenyl-2-[(E)-3-phenylprop-2-en-1-oyl-3d-κO]ethenyl-κC¹]tetracarbonylmanganese, gave deuteriated 3a with exo-D at the α-carbon, C7. This is inconsistent with the Mn-mediated Ph migration mechanism originally proposed to accommodate the endo position of Ph in 3a, and instead it implicates a cyclopropyl carbonyl-addition intermediate or a cyclopropyl acyl-substitution transition state in the key rearrangement step for 2a → 3a.     

Reaktionen von tricarbonyl-chrom-η6λ3-phosphorin-komplexen zu tricarbonyl-chrom-η6λ5-phosphorin-ylid-komplexen

The tricarbonylchromium η⁶π⁶ complexes of 2,4,6-triphenyl- and 2,4,6-tri-t-butyl-λ³-phosphorins 3a and 3b add nucleophiles regio- and stereo-specifically to the phosphorus atom in the exo-position giving the λ⁴-phosphorin anions which now add electrophiles in the endo position, giving η⁵π⁶-λ⁵-phosphorin ylide complexes 5a and 5b, respectively. The ¹H, ¹³C and ³¹P NMR spectra of 3a and 3b and especially 5a and 5b are discussed with respect to the stereoisomeric complexes 5a having two different exocylic substituents at the phosphorus atom, synthesized from e.g. 1-ethyl-1-methyl-2,4,6-triphenyl-λ⁵-phosphorin and Cr(CO)₆. The tricarbonylchromium-1,1,-dialkyl or alkyl-aryl-2,4,6-tri-t-butyl-λ⁵-phosphorin 5b can only be synthezised from tricarbonylchromium-2,4,6-tri-t-butyl-λ³-phosphorin by addition of nucleophiles and electrophiles since the corresponding λ⁵-phosphorin derivatives are not available. By removal of the tricarbonylchromium residue from the λ⁵-phosphorin-ylide complexes 5b, however, also 2,4,6-tri-t-butyl-λ⁵-phosphorins can be prepared.     

Solvent-dependent reactivities of acyclic nitrones with β-diketones: catalyst-free syntheses of endiones and enones

Reactions of the nitrones ^?O⁺N(Me)C(H)Ar 1 (Ar=phenyl 1a, 4-methylphenyl 1b, 2,4,6-trimethylphenyl 1c, and anthracen-9-yl 1d) with the cyclic β-diketones 1,3-indandione 2 or barbituric acid 3 in CH₂Cl₂, afford the corresponding endiones 2′a–2′d or 3′a–3′d. In contrast, dimedone 4 reacts with 1a or 1b to give the endione 4′a or 4′b and the bis-adduct 4″a or 4″b. Nevertheless, reaction of 4 with 1c or 1d in CH₂Cl₂ furnishes only the endione adducts 4′c or 4′d. However, the reaction of 4 with 1a or 1b in methanol gives only 4″a or 4″b, respectively. Among acyclic β-diketones only malonic acid 7 reacts with 1a–1c. Reaction of 7 with 1a in CH₂Cl₂ forms cinnamic acid 7″a, whereas in the case of 1b, the endione 7′b and (E)-3-p-tolylacrylic acid 7″b are obtained. The nitrone 1c reacts with 7 in CH₂Cl₂ to afford the endione 7′c or with acetone yielding (E)-4-mesitylbut-3-en-2-one 8. X-ray analyses are reported for 4′c, 5, and 7″b. In addition, the calculated acidity of the hydrogen at the α-C atom is shown to correlate with the reactivity of the β-diketones with nitrones.     

A radical version of the bromine cyclization of alkenols

The scope of an alkoxyl radical version of the classical bromine cyclization was explored. Oxygen-centered radicals were generated in photochemically initiated radical chain reactions from N-alkenoxy-4-(p-chlorophenyl)thiazole-2(3H)-thiones 5a–c, N-alkenoxy-4-methylthiazole-2(3H)-thiones 13, 14, 21, rac-23, and N-alkenoxypyridine-2(1H)-thiones 6d–f, 16, rac-25. Thus, 2-(2-bromopropyl)-substituted tetrahydrofurans 4a–c, which are minor compounds (< 10 %) in NBS-mediated bromine cyclizations of corresponding alkenols 1a–c, were prepared in 87–90 % yield and with good to excellent diastereoselectivities. Further, photochemical conversions of O-alkyl thiohydroxamates 14, 16 and 21 in benzene and BrCCl₃ afforded β-oxy-functionalized bromomethyl substituted tetrahydrofurans 29, 34, and 36. The results of this study indicate, that efficient 5-exo-trig cyclizations of β-oxy-substituted 4-penten-1-oxyl radical require an electronwithdrawing substituent at the β-heteroatom substituent. In the third part of the study a synthetically useful new access to oxabicyclo〚4.3.0〛nonanes rac-38 and rac-40 is reported which takes profit from highly diastereoselective 5-exo-trig-ring closures and, in case of the formation of rac-40, stereoselective bromine atom transfer.     

Vinyl polymerization. 432. Initiation mechanism of uncatalyzed polymerization in the presence of copper(II) ion

The initiation mechanisms of the uncatalyzed polymerization of methyl acrylate and methyl methacrylate by the system of starch, α-amylase or water-soluble nylon 3/copper(II) ion/H₂O were investigated by spin trapping techniques. Using 2,4-dimethyl-3-nitrosobenzene sulfonate d₈ and 5,5-dimethyl-1-pyrroline-N-oxide as the water-soluble spin trapping agents, the simultaneous generation of both monomer and hydroxyl radicals has been observed, and the propriety of the initiation mechanism proposed previously was confirmed. Thus, the initiation of polymerization in the presence of copper(II) ion was concluded to take place through a hydrogen atom transfer from the complexed water to the β-carbon of the complexed monomer.     

Aminyloxide—XVIII : ESR-spektroskopische untersuchung der tautomerie beim “hydrolyseprodukt des porphyrexids”

The hydrolysis of porphyrexine 2a yields 3a not 1a, as was shown by means of the ¹⁵N-labelled compound 2c. Analysis of the ESR spectra of radicals 4 derived from 3 shows that in dimethylsulfoxide these radicals exist in the tautomeric form B whereas in dioxan they exist in form A. The stabilization of form B in dimethylsulfoxide is shown to be due to a specific effect of the solvent.     

New cyclometalated palladium(II) complexes with iminophosphines: Crystal structures of [Pd(C^N)(o-Ph2PC6H4–CH=NR)][PF6] (C^N=azobenzene,R=Et; C^N=2-phenylpyridine,R=Me)

The synthesis of new cyclometalated compounds of palladium(II) with the mixed-donor bidentate ligands o-Ph₂PC₆H₄–CH=NR is described. Two series of complexes [Pd(C^N)(o-Ph₂PC₆H₄–CH=NR)][PF₆] have been prepared using either azobenzene or 2-phenylpyridine as cyclometalated ligands [C^N=azobenzene (azb); R=Me (1a), Et (2a), ⁿPr (3a), ⁱPr (4a), ^tBu (5a), Ph (6a), NH–Me (7a); C^N=2-phenylpyridine (phpy); R=Me (1b), Et (2b), ⁿPr (3b), ⁱPr (4b), ^tBu (5b), Ph (6b), NH–Me (7b)]. The new complexes were characterized by partial elemental analyses and spectroscopic methods (IR, FAB, ¹H and ³¹P NMR). The molecular structures of compounds 2a (monoclinic, P 2₁/n) and 1b (monoclinic, C 2/c) have been determined by a single-crystal diffraction study. In both cases this technique revealed the relative trans configuration between the phosphorus atom and the nitrogen atom of the ortho-metalated ligand.     

SPIN TRAPPING OF THE SUPEROXIDE RADICAL BY 4-(N-METHYLPYRIDINIUM) t-BUTYL NITRONE

The synthesis of 4-(N-methylpyridinium) t-butyl nitrone (4-MePyBN) and its use as a spin trap for superoxide radicals produced in aqueous solutions is reported (a^N= 13.78 G, a^H_ß= 1.65 G, and g = 2.0091). The half-life of the spin adduct as a function of pH (83 s at pH 5.5, 78 s at pH 7.0, and 65 s at pH 8.0) the effects of iron salts, diethylenetriaminepentacetic acid (DETAPAC), and superoxide dismutase were examined, and comparisons made between 4-MePyBN and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin trapping agents for the superoxide radical.     

Vinylphosphite-Vinylphosphonate Rearrangement in Acyclic and Cyclic Systems

Abstract

Acyclic vinylphosphites (1) with π-acceptors at the β-carbon atom of vinyloxylic system and some cyclic vinylphosphites, 4-methylen-1,3,2-dioxaphosphorines (2) with electron withdrawing groups at C⁵ in the heterocycle, and 4-methylen-1,3,2-oxazaphosphorines (3), may undergo earlier unknown vinylphosphite-vinylphosphonate rearrangement. This rearrangement seems formally like a migration of the phosphorus-containing fragment to a-carbon of vinyloxylic system and results in the formation of acyclic vinylphos-phonates (4) in the case of (I), 2-oxo-3-methylen-1,2-oxa-phospholenes (5) and 2-oxo-5-methylen-1,2-azaphospholenes (6) in the cases (2) and (3) respectively. Isomerization is favoured by electrondonating groups at the phosphorus (111) atom. It is likely that the rearrangement of (1) and (2) proceeds through the stage of formation of cyclic oxeten-cation and disubstituted phosphite-anion as intermediates, which then combine to vinylphosphonates.     

Synthesis,antimicrobial and cytotoxic activity of novel azetidine-2-one derivatives of 1H-benzimidazole

A series of 1-methyl-N-[(substituted-phenylmethylidene)-1H-benzimidazol-2-amines (4a–4g) were prepared via the formation of 1-methyl-1H-benzimidazol-2-amine (3), which was prepared by the cycloaddition of o-phenylenediamine (1) with cyanogen bromide in the presence of aqueous base followed by N-methylation with methyl iodide in the presence of anhydrous potassium carbonate in dry acetonitrile. Moreover, the four-membered β-lactam ring was introduced by the cycloaddition of 4a–4g and chloroacetyl chloride in the presence of triethylamine catalyst to give 3-chloro-1-(1-methyl-1H-benzimidazol-2-yl)-(4′-substituted)-phenylazetidin-2-one 5a–5g. A total of 14 compounds were synthesized and characterized by IR, ¹H NMR, ¹³C NMR and Mass spectral technique, in addition they were evaluated for anti-bacterial and cytotoxic properties. Among the chemicals tested 4a, 4b, 5a, 5b, 5g exhibited good antibacterial activity and 5f, 5g shown good cytotoxic activity in vitro.     

Synthesis of 4-aryl-substituted β-lactam enantiomers by enzyme-catalyzed kinetic resolution

Enantiopure 4-phenyl- and 4-(p-tolyl)-2-azetidinones 3a, 3b, 4a and 4b (with e.e.s of ≥96%) were prepared through lipase-catalyzed asymmetric butyrylation of the primary OH group of N-hydroxymethylated β-lactams (±)-5 and (±)-6 at the (R)-stereogenic centre or by lipase-catalyzed asymmetric debutyrylation of O-butyryloxymethyl-2-azetidinones (±)-7 and (±)-8 at the (R)-stereogenic centre. The ring-opening of lactams 5a, 5b, 6b and 8a with HCl/EtOH afforded the corresponding β-amino ester enantiomers 9a, 9b, 10a and 10b with e.e.s of ≥92%.     

Regioselectivity in the 1,3-dipolar cycloaddition of adamantylidenefulvene and its modification by inclusion in cyclodextrins' solutions

The 1,3-dipolar cycloaddition of adamantylidenefulvene (1) with 2 equiv of nitrile oxides 2a-d gave 1/1 cycloadducts, 3a-d and 4a-d, as the major products, and four other 1/2 minor cycloadducts 5-8a,b. The ratios of 1/1 cycloadducts 3a-d to 4a-d in THF solution were about 1/1 in the four different nitrile oxides 2a-d studied and microwave was found to accelerate the reactions and enhance their yields. It is noteworthy that the regioselectivity of 3a/4a was enhanced to 71/29 in β-cyclodextrin (β-CD) aqueous solution compared to that of 40/60 in the absence of β-CD. The regioselectivity of 3b/4b was further enhanced to 99/1 when 4-tert-butylphenyl hydroximinoyl chloride (9b) was complexed with β-CD and then proceeded to react with 1; this is in sharp contrast with that of 33/67 in the absence of β-CD. The binding constant of 1·β-CD in acetone-d₆/D₂O (1/1) was determined to be 188±9 M⁻¹ by ¹H NMR titration experiments. The binding mode of 1·β-CD was further determined by ROESY experiment. Furthermore, molecular dynamic simulations were carried out to provide information of the complexation modes of 1·β-CD, 3a·β-CD, 4a·β-CD, 9a·β-CD, and 9b·β-CD. It was found that both steric and electrostatic effects play important roles in determining the regio- and stereochemistry of 1,3-dipolar cycloaddition of 1. Finally, β-CD is shown to serve as a chiral shift reagent to differentiate the enantiomers of 4a in ¹H NMR.     

Trichloro- and methyldichlorogermyl monochelates and dibromo- and dichlorogermyl bischelates derived from N,N-disubstituted amides of 2-hydroxycarboxylic acids

The reactions of GeCl₄, GeBr₄, and MeGeCl₃ with O-trimethylsilyl derivatives of N,N-disubstituted amides of 2-hydroxycarboxylic acids afforded pentacoordinate and hexacoordinate neutral (O,O)-mono- and (O,O)-bischelates. The reactions of glycolic acid derivatives with GeX₄ produced bischelates X₂Ge[OCH₂C(O)NR²R³]₂ 7a,c,d (X = Cl, R² = R³ = Me (a), (CH₂)₅ (c), (CH₂CH₂)₂O (d)) and 8a (X = Br). By contrast, the reactions of lactic and mandelic acid derivatives with GeCl₄ and MeGeCl₃ gave monochelates Cl₃Ge[OCH(R¹)C(O)NR²R³] (S)-9a–c (R¹ = Me) and Cl₂MeGe[OCH(R¹)C(O)NR²R³] 10a (R¹ = H), (S)-11a,b (R¹ = Me), and (S)-12a (R¹ = Ph) (R²R³ = (CH₂)₄ (b)), respectively. According to the X-ray diffraction data, the Ge atom in bischelates 7c,d and 8a has a coordination number 6, and its coordination polyhedron can be described as a slightly distorted octahedron. In monochelates (S)-9a-c, 10a, (S)-11a,b, and (S)-12a, the Ge atom has a coordination number 5, and its coordination polyhedron can be described as a trigonal bipyramid with two halogen atoms or one halogen atom and one ethereal oxygen atom in equatorial positions and the halogen atom and the amide oxygen atom in the axial positions. The bonds in the axial positions are somewhat longer than the corresponding bonds in tetracoordinate Ge compounds.     

Carbene—23: Phosphene: [2+2]-und [4 + 2]-cycloaddition von (diphenylmethylen) phenylphosphan-oxid mit α,β-ungesättigten ketonen

The photolysis of 1 produces the carbene 2, which is transformed into the short lived phosphene 4 by phenyl migration. With the α, β-unsaturated ketones 6a–d in a [2+2] cycloaddition 4 yields the 1,2λ⁵-oxaphos-phetanes 7a–d The heterocycles partially undergo a photofragmentation, which produces the olefines 9a–d and the heterocumulene 8. If 4 is generated from 1 under thermal conditions in the presence of 6a–c, formation of four membered rings and fragmentation is observed too; in addition 4 undergoes a [4+2] cycloaddition with the hetero-1, 3-dienes 6a–c, leading to 15a-c. This behaviour corresponds to that of the carbonylanalogue diphenyl-ketene with 6a (formation of CO₂ and 9a via the β-lactone 16 such as of 17).     

DNA damage induced via independent generation of the radical resulting from formal hydrogen atom abstraction from the C1′-position of a nucleotide

Background: Deoxyribonucleotide radicals resulting from formal C1′-hydrogen atom abstraction are important reactive intermediates in a variety of DNA-damage processes. The reactivity of these radicals can be affected by the agents that generate them and the environment in which they are produced. As an initial step in determining the factors that control the reactivity of these important radical species, we developed a mild method for their generation at a defined site within a biopolymer.Results: Irradiation of oligonucleotides containing a photolabile nucleotide produced C1'-DNA radicals. In the absence of potential reactants other than O₂, approximately 90% of the damage events involve formation of alkaline-labile lesions, with the remainder resulting in direct strand breaks. The ratio of alkaline-labile lesions to direct strand breaks (∼ 9:1) is independent of whether the radical is generated in single-stranded DNA or double-stranded DNA. Strand damage is almost completely quenched under anaerobic conditions in the presence of low thiol concentrations. Competition studies with 02 indicate that the trapping rate of C1′-DNA radicals by β-mercaptoethanol is ∼ 1.1 x 10⁷ M⁻¹s⁻¹Conclusions: The mild generation of the C1'-DNA radical in the absence of exogenous oxidants makes it possible to examine their intrinsic reactivity. In the absence of other reactants, the formation of direct strand breaks from C1′-radicals is, at most, a minor pathway. Competition studies between β-mercaptoethanol and 02 indicate that significantly higher thiol concentrations than those in vivo or some means of increasing the effective thiol concentration near DNA are needed for these reagents to prevent the formation of DNA lesions arising from the C1'-radical under aerobic conditions.     

Photochemistry of β,γ-enones-VIII: On the remarkable photostability of some β,γ.β',γ'-dienones and the 1,3-acyl shift photoreactivity of two β,γ.γ',δ'-dienones

The direct irradiation of the β,γ.β',γ'-dienones 1–5 and the β,γ.γ',δ'-dienones (E)-6a, (E)-7a and 8a at λ 300 nm has been studied. The β,γ.β,γ'-dienones 1–5 are remarkable photostable for λ ? 300 nm, even upon prolonged irradiation, in contrast to simple β,γ-enones which upon irradiation exhibit α-cleavage, γ-hydrogen abstraction, (E)-(Z) isomerization and oxetane formation. The observed photostability of the β,γ.β',γ'-dienones is rationalized in terms of a rapid radiationless decay of the excited singlet state, enhanced by CT-interaction between the carbonyl ¹(n-π*) state and the homoconjugated 1,4-diene moiety, which precludes fluorescence, photochemical reactions and intersystem crossing (ISC).The β,γ.γ',δ'-dienones (E)-(6a), (E)-7a and 8a exhibit only a 1,3-acyl shift (1,3-AS) without (E)-(Z) isomerization of the alkenyl moiety, to yield (E)-6b, (E)-7b and 8b. It is concluded that the 1,3-AS proceeds from the ¹(n-π*) state with a rate which is very large relative to the rate of ISC to the ³(n-π*) state, thus precluding any internal triplet energy transfer (1TET) from the ³(n-π*) to the ³(π-π*) state which would manifest itself by (E)-(Z) isomerization.     

Stereospecific conversion of cyclic phosphorothioates into chlorophosphates

The reaction of the individual diastereoisomeric cyclic phosphorothioates 2a, 2b in the trans-2,4,7-trioxa-3-phosphabicyclo (4.4.0) decane and 4a, 4b in the trans-2,4,7-trioxa-3-phosphabicyclo (4.3.0) nonane series with sulphuryl chloride affords the corresponding sulphenyl chlorides 5a, 5b, 6a, 6b with retention of the configuration of the phosphorus atom. The reaction of the latter with phosphorus trichloride leads stereospecifically to the chlorophosphates 7a, 7b, 8a and 8b with full retention of configuration at phosphorus.     

Synthesis and structure of new copper(II) coordination compounds with 8-quinoline aldehyde semicarbazones and thiosemicarbazones

Copper(II) salts were reacted with various quinoline aldehyde chalcogensemicarbazones to yield compounds formulated as Cu(HL)X₂ · nH₂O (I: HL = quinoline aldehyde thiosemicarbazone (HL¹), X = ClO₄, n = 2; II: HL = quinoline aldehyde 4-C₂H₅-thiosemicarbazone (HL^1a), X = NO₃, n = 0; III: HL = quinoline aldehyde semicarbazone (HL²), X = ClO₄, n = 3 and IV: HL = quinoline aldehyde 4-Ph-semicarbazone (HL^2a), X = NO₃, n = 1). Regardless of the reagent ratio, the products were compounds having the metal: ligand ratio of 1: 1, where the organic ligand was coordinated tridentate in a molecular form. Single-crystal X-ray diffraction showed that, depending on the chalcogen atom in the organic ligand (S or O), the substituent in the 4th position (at the terminal nitrogen atom), and the specifics of the acido ligand, complexes I–IV had appreciably differing molecular structure organizations. The structures of I and III are formed by a 1D charged coordination polymer, ClO ₄ ^? anions, and water molecules and may be described by the formula [Cu(HL)(H₂O)(ClO₄)] _n (ClO₄) _n · nH₂O. Copper(II) coordination polyhedra in I and II are (4 + 2) and (4 + 1 + 1) tetragonal bipyramids, respectively. In II and IV, the structures are monomeric and can be described as [Cu(HL^1a)(NO₃)₂] with the metal coordination polyhedron shaped as a (4 + 1) tetragonal pyramid in II and as [Cu(HL^2a)(H₂O)(NO₃)](NO₃) with the metal coordination polyhedron shaped as a (3 + 2) trigonal bipyramid in IV. The structure of II is built of molecular complexes, each comprising, apart from ligand HL^1a, two monodentate coordinated NO ₃ ^? groups. The oxygen atom of one anion together with the NNS donor atom set of ligand HL^1a form the base, and the oxygen atom of the other anion is in the apex of the coordination polyhedron. In IV, the structure is ionic and built of NO ₃ ^? anions and [Cu(HL^2a)(H₂O)(NO₃)]⁺ complex cations, where a cationic coordination polyhedron has a trigonal-bipyramidal configuration with organic ligand HL^2a positioned along the long edge. The bipyramidal base is made up by the oxygen atoms of the coordinated water molecule and monodentate nitrato group and the nitrogen atom N2 of the azomethyne group.