The isomers of phenalene and their singlet and triplet states: A Hartree–Fock and density functional computational investigation

Each of the isomers of phenalene, 1H-, 2H-, 3aH-, and 9bH-phenalene, as well as the cation, neutral radical, and anion in the phenalenyl system, have been examined at the Hartree–Fock 6-31G(d) and the density functional B3LYP/6-31G(d) levels of theory. The structures and properties of the phenalenes were determined as both singlets and triplets. While the data indicate that both the 9bH- and the 1H-isomer will exist as ground state singlets, the 2H- and 3aH-phenalenes are predicted to exist as ground state triplets; only the synthesis of the 1H-isomer has been reported in the literature. Structurally, 1H- and 2H-phenalene are planar systems, 3aH- and 9bH-phenalene are non-planar systems puckered at the saturated carbon, and the cation, neutral radical, and anion of phenalenyl are planar D_3h systems.     

New Reactions of Amino-Functionalized 3-Vinyl-1H-indoles and Tetrahydropyridin-4-yl Analogues with Dienophiles

Reactions of 3-[2-(morpholin-4-yl)vinyl]-1H-indole ( 1 ), the 1,2-dihydro-9H-carbazole 2 , as well as the 3-(tetrahydropyridin-4-yl)-1H-indoles 3a and 3b with some carbo- and heterodienophiles are described. The scope and limitations of the synthetic utility of these amino- (or homoamino)-functionalized 3-vinyl-1H-indoles are reported and some MO calculations for the qualitative prediction of their reactivities are presented. The reactions gave rise to substitution products, redox products, Diels-Alder adducts, ene adducts, and Michael-type adducts (Schemes 2 and 3).     

Synthesis of some oxadiazole derivatives of d-mannose

The syntheses of 2-methyl-5-[1′,2′,3′,4′,5′-penta-O-benzoyl-D-manno-pentitol-1′-yl]-1,3,4-oxadiazole and 5-methyl-3-[1′,2′,3′,4′,5′-penta-O-benzoyl-D-manno-pentitol-1-′yl]-1,2,4-oxadiazole, as well as their intermediate products, are described. Their ¹H and ¹³C nmr and ms spectra are presented and their preferential conformation in solution are proposed.     

Stereochemical studies-XIV: Cyclic amino alcohols and related compounds-VII

1,3-Tetrahydro-oxazine-2-ones were prepared by the reaction of cis- and trans-2-hydroxymethylcyclohexylamine, as well as cis- and trans-2-aminomethylcyclohexanol with carbamide. Their structure and stereochemical purity were proved by IR and NMR investigations. With the help of the NMR spectra the conformation of these compounds was established. The trans isomers exist in stable chair-chair conformation. Two chair-chair conformations are possible in the case of the cis isomers; one in which the heteroatom and the methylene group of the heteroring are axial and equatorial, respectively and the second in which their positions are reversed. It was proved that the cis isomers are conformationally homogeneous, having the hetero atom in axial position.     

The Synthesis of Novel Iodinated Iminodiacetic Acid Analogues as Hepatobiliary Imaging Agents

The synthesis and characterization of N-[2-[[4-iodo-2,6-bis(1-methylethyl)phenyl]amino]-2-oxoethyl]-N-(carboxymethyl)glycine and N-[2-[(4-iodo-2,6-diethylphenyl)amino]-2-oxoethyl]-N-(carboxymethyl)glycine is presented, as well as a modified and improved synthesis of N-[2-[(2,4-diiodo-6-methylphenyl)amino]-2-oxoethyl]-N-(carboxymethyl)glycine. These compounds are new agents for hepatobiliary imaging.     

Sarcodictyin A and Sarcodictyin B,Novel Diterpenoidic Alcohols Esterified by (E)-N(1)-Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum

The Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)-N(1)-methyl-urocanic acid (= E)-3-(l-methyl-lH-imidazol-4-yl)acrylic acid). They are sarcodictyin A ( = (?)-(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)benzocyclodecen-11-yl (E)-3-(1-methyl-lH-imidazol-4-yl)acrylate; (?)- 1 ) and sarco-dictyin B (the 6-(ethoxycarbonyl analogue; (?)- 2 ). The assignment of the structures is mainly based on 1D- and 2D-NMR data, as well as on chemical transformations of (?)- 1 , such as transesterification with MeONa/MeOH giving methyl (E)-N(1)-methylurocanate ( 3 ) and the free alcohol (+)- 4 and reduction with LiAlH₄ followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)- 4 .     

HYDROGEN BONDING BETWEEN TERTIARY PHOSPHINES AND ALCOHOLS

Abstract

The hydrogen bond between several alcohols, in particular benzyl alcohol and isopropanol, as donors, and a number of tertiary phosphines, as well as a smaller number of tertiary arsines, as acceptors was investigated by means of ir spectroscopy in the temperature range +40° to -20°C. Toluene was used as a solvent. The equilibrium constant K, the hydrogen bond enthalpy -ΔH and the entropy -ΔS were determined. The equilibrium constants as well as the -ΔH values are essentially dependent on the basicity of the phosphines. There is no evidence of any steric influence. In the systems with aliphatic phosphines, the highest equilibrium constants are about 20, the lowest values are near unity. Aromatic phosphines possess a lower affinity of interaction with the alcohols. -ΔH varies for the different systems between 1.2 and 3.5 kcalμmole^?1. Investigating the acceptor power of arsines we found both K and -ΔH one order of magnitude lower than in the case of phosphines.     

The Synthesis of Novel Iodinated Iminodiacetic Acid Analogues as Hepatobiliary Imaging Agents

Summary. The synthesis and characterization of N-[2-[[4-iodo-2,6-bis(1-methylethyl)phenyl]amino]-2-oxoethyl]-N-(carboxymethyl)glycine and N-[2-[(4-iodo-2,6-diethylphenyl)amino]-2-oxoethyl]-N-(carboxymethyl)glycine is presented, as well as a modified and improved synthesis of N-[2-[(2,4-diiodo-6-methylphenyl)amino]-2-oxoethyl]-N-(carboxymethyl)glycine. These compounds are new agents for hepatobiliary imaging.     

Synthesis of Enantiomerically Pure Pheromones of South-Pacific Brown Algae: Hormosirene and Dictyopterene A

Hormosirene ((?)- 1 ; (1R,2R)-1-((1E,3Z)-1,3-hexadienyl)-2-vinylcyclopropane) is the specific sex attractant of several brown algae of the Australian shelf, while dictyopterene A ((+)- 2 ; (1R, 2R)-1-((1E)-1-hexenyl)-2-vinylcyclopropane) is found as a minor constituent of the pheromone bouquets. The asymmetric synthesis of the two hydrocarbons is performed by resolution of the amides (?)- 5 and (+)- 5a obtained from (?)-(R)-2-phenylglycinol and racemic trans-vinylcyclopropanecarboxylic acid (rac- 4 ) on silica gel. Both diastereoisomers are obtained optically pure. They are converted by stereoselective Wittig olefination into the title compounds. Compound (?)- 1 is the active mating pheromone of the reproductive system of the seaweed Xiphophora chondrophylla as established by biological-activity assays.     

Intramolecular diels-alder reactions. 4. Additions to naphthalene

N-Methyl-N-2-propynyl-1-naphthalenecarboxamide, N-methyl-N-2-propynyl-1-naphthaleneacetamide, and N-methyl-N-3-butynyl-1-naphthalenecarboxamide undergo intramolecular Diels-Alder reactions at 190°, 250°, and 270° to give lactams 1,6 , and 9 , respectively. The cyclization temperatures are higher by 80-120° as compared to those of the corresponding anthracene derivatives. Elaboration of lactam 6 gave the trans-4a-aryldecahydroisoquinoline derivative 7a which, as the (-) isomer, was shown to have the same absolute stereochemistry as morphine.     

Preparation and Absolute Configuration of (−)-(E)-α-trans-Bergamotenone

The synthesis, absolute configuration, and olfactive evaluation of (?)-(E)-α-trans-bergamotenone (= (?)-(1′S,6′R,E)-5-(2′,6′-dimethylbicyclo[3.1.1]hept-2′-en-6′-yl)pent-3-en-2-one; (?)- 1 ), as well as its homologue (?)- 19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (?)-α-trans-bergamotene (= (?)-(1 S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1. 1]hept-2-ene; (?)- 2 ), together with those of the structurally related aldehydes (?)- 3a,b and alcohols (?)- 4a,b , have been rigorously assigned.     

The Reaction of Singlet and Triplet Oxygen with 2-Phenylnorbornene

The reaction of singlet oxygen with 2-phenylnorbornene ( 1 ) in aprotic solvents gives 3-formylcyclopentyl phenyl ketone ( 2 ) (10%) and uncharacterized polymer (90%). When methanol is used as solvent, endo-2-phenyl-exo-2-methoxy-exo-3-hydroperoxynorbornane ( 4 ) and endo-2-(anti-1′, 4′-epidioxy-5′,6′-epoxycyclohex-2′-enyl)-exo-2,3-epoxynorbornane ( 6 and 7 ) are obtained in addition to 2 . Triplet oxygen with 1 gave 2 , endo-2-phenyl-exo-2,3-epoxynorbornane ( 8 ), and the trimer 9 or 10 of exo-2,3-epidioxy-endo-2-phenylnorbornane. With protic solvents the amount of epoxide increased at the expense of trimer. The singlet and triplet oxygen reactions are discussed in the light of possible intermediates.     

Synthesis,Structure, and Antimalarial Activity of Some Enantiomerically Pure,cis-fused cyclopenteno-1,2,4-trioxanes

Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes ( 7 , ent- 7 and 8 , ent- 8 ) are prepared (Schemes 1–3). Their identities are established by dye-sensitized photo-oxygenation of ent- 7 and 8 , ent- 8 to the allylichydroperxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanates (Scheme 4), the structures of which are determined by X-ray analysis. The dynamic properties of ent- 7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7 , ent- 7,8 , and ent- 8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O? O σ* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent (Scheme 5).     

Enantioselective Fluorogenic Assay of Acetate Hydrolysis for Detecting Lipase Catalytic Antibodies

An enantioselective fluorogenic assay for the kinetic resolution of chiral alkyl acetates is demonstrated with 7-(3-acetoxybutoxy)-2H-1-benzopyran-2-ones (R)- and (S)- 4 or 7-(3-acetoxy-2-methylpropoxy)-2H-1-benzopyran-2-ones (R)- 4 and (S)- 6 . The alcohols released by hydrolysis of these acetates are oxidized by horse-liver alcohol dehydrogenase to unstable β-(aryloxy)carbonyl compounds, which undergo β-elimination of the strongly fluorescent product umbelliferone (=7-hydroxy-2H-1-benzopyran-2-one; 3 ) (λ_em=460±20 nm, λ_ex=360±20 nm). Enantioselectivities are calculated from the reaction rates for each enantiomeric acetate. For a series of representative lipases, the reactivities and enantioselectivities under preparative conditions are predicted accurately. This highly sensitive enantioselective assay detects as little as 10 μg/ml of hydrolytic enzyme, can be carried out in 96-well microtiter plates, and is compatible with cell-culture media. It is, therefore, suited for screening libraries of antibodies for enantioselective lipase catalytic antibodies.     

Nucleophilic Reactions at Tertiary Carbon. Part 1. The 1,2-dimethyl-1-cyclohexyl cation

Stereoisomeric ion pairs are implicated as intermediates in the solvolysis of cis and trans-1-chloro-1,2-dimethylcyclohexane, cis- 4 and trans- 4 , respectively. This follows from the rates and products of these stereoisomeric tertiary chlorides in 80% ethanol and 50% acetone. The composition of elimination and substitution products from cis- 4 and trans- 4 differs markedly and the differences are accentuated by silver ion. Furthermore, substitution products are formed with predominant inversion of configuration. The equilibrium constant for isomerization of cis- 4 and trans- 4 shows the latter to be more stable by 0.7 kcal/mol. Since the solvolysis rates of the chlorides are equal, the transition state for trans- 4 is also more stable by 0.7 kcal. By inference the intermediates differ by a similar amount of energy which is ascribed to more efficient solvation of the trans ion pair 13 .     

Selektive Synthesen mit Organometallen III. (Z)-Crotylalkoholate mit metalltragenden olefinischen Kohlenstoffatomen

1-Lithiumoxy-2-buten-2-yl-lithium and 1-lithiumoxy-2-buten-3-yl-lithium, both as pure (Z)-stereoisomers, are easily obtained by halogen/metal exchange between s-butyllithium and (E)-2-bromo or (E)-3-bromo 2-buten-1-ol, respectively. The starting materials are readily available through dehydrobromination of threo-2, 3-dibromo 1-butanol. The new organolithium compounds are useful intermediates for the preparation of configurationally homogeneous, specifically substituted and branched alkenols.     

Photochemical reactions. 141st communication. Photochemistry of α,β-unsaturated δ,ϵ-epoxyketones of the ionone series

On n,π*- as well as on π,π*-excitation, the 4,5-epoxy-α-ionones (E)- 1 , (E)- 2 , and (E)- 3 undergo (E)/(Z)-isomerization and subsequent γ-H-abstraction leading to the corresponding 4-hydroxy-β-ionones (E/Z)- 9 , (E/Z)- 13 , and (E/Z)- 17 as primary photoproducts. On photolysis of (E)- 3 , as an additional primary photoproduct, the β,γ-unsaturated σ,?-epoxy ketone 18 was obtained. The other isolated compounds, namely the 2H-pyrans 10A + B and 14A + B as well as the retro γ-ionones 11 and 15A + B , represent known types of products, which are derived from the 4-hydroxy-β-ionones (E/Z)- 9 and (E/Z)- 13 , respectively.     

Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone

Chiral Building Blocks for Syntheses by Kolbe Electrolysis of Enantiomerically Pure β-Hydroxybutyric-Acid Derivatives. (R)- and (S)-Methyl-, and (R)-Trifluoromethyl-γ-butyrolactones, and -δ-valerolactones The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1.4- and 1.5-distance of the functional groups. The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1 – 6 ), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid; see 7 ) are decarboxylatively dimerized or ‘codimerized’ with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate. The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8 ), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9,10 ), of (R)- and (S)-5-hydroxyhexanoic acid (see 11 ) and its trifluoro analogue (see 12, 13 ), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20 ), of (S)-2-hydroxy-4-methylpentanoic acid (‘OH-leucine’, see 21 ), and of (S)-2-hydroxy-6-aminohexanoic acid (‘OH-lysine’, see 22 ). Some of these products are further converted to CH₃- or CF₃-substituted γ- and δ-lactones of (R)- or (S)-configuration ( 14 , 16 – 19 ), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24 ). Possible uses of these new chiral building blocks for the synthesis of natural products and their CF₃ analogues (brefeldin, sulcatol, zearalenone) are discussed. The olfactory properties of (R)- and (S)-δ-caprolactone ( 18 ) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone ( 19 ).     

N-(2-tetrahydrofuranyl)azole nucleoside analogs by reactions of azoles with dihalomethanes in tetrahydrofuran

The reactions of the mono-N-substituted bispyrazolylpyridine 2-(1-methyl-4,5,6,7-tetxahydroindazol-3-yl)-6-(2H-4,5,6,7-tetrahydroindazol-3-yl)pyridine, 3,5-dimethylpyrazole and benzimidazole with sodium hydride and diiodomethane or dibromomethane in tetrahydrofuran produced the unexpected N-tetrahydrofuran-2-yl adducts as well as the expected diazolylmethanes. These side-reactions are thought to involve the 2-halo tetrahydrofuran derivative resulting from a free-radical halogenation by the dihalomethane.     

Synthesis and Neuroprotective Properties of Isosteric Analogs of Nicotine

A method has been developed for the synthesis of isosteric analogs of nicotine involving ethers of S(-)-1-2-pyrrolidinemethanol and S(-)-1-2-pyrrolidineethanol based on the Mitsunobu reaction. The results of testing the synthesized compounds as calcium channel blockers are presented.