Ring cleaving selenenylation and sulfenylation of cyclopropane derivatives promoted by TiCl4

A synthesis of 2-selenenyl and sulfenyl 4-oxoesters based on Lewis acid promoted activation of methyl 2-trimethylsiloxy cyclopropanecarboxylates is reported. A mechanistic scheme for this new C-Se and C-S forming reaction is disclosed.     

A comparison of conformational energies calculated by molecular mechanics (MM2(85), Sybyl 5.1, Sybyl 5.21, and ChemX) and semiempirical (AM1 and PM3) methods

Conformational energies of different conformers have been calculated for a series of molecules using various molecular mechanics and semiempirical methods. The quality of the force fields has also been tested by calculating barriers to rotation about carbon-carbon bonds. The molecular mechanics force fields used are MM2(85), Sybyl 5.1, Sybyl 5.21, and ChemX, ver. Jan 89. The semiempirical methods used are AM1 and PM3. Molecules with different functional groups, for which good experimental data exist, have been selected. The semiempirical methods generally calculate barriers to rotation which are lower than the experimentally determined. The conformational energies for hydrocarbons are reasonably well reproduced by all tested methods although MM2(85) gives the quantitatively best agreement with experiments. For compounds containing oxygen, nitrogen and halogens MM2(85) gives results which are in best agreement with the experimentally determined values.     

From protein domains to drug candidates-natural products as guiding principles in the design and synthesis of compound libraries

In the continuing effort to find small molecules that alter protein function and ultimately might lead to new drugs, combinatorial chemistry has emerged as a very powerful tool. Contrary to original expectations that large libraries would result in the discovery of many hit and lead structures, it has been recognized that the biological relevance, design, and diversity of the library are more important. As the universe of conceivable compounds is almost infinite, the question arises: where is a biologically validated starting point from which to build a combinatorial library? Nature itself might provide an answer: natural products have been evolved to bind to proteins. Recent results in structural biology and bioinformatics indicate that the number of distinct protein families and folds is fairly limited. Often the same structural domain is used by many proteins in a more or less modified form created by divergent evolution. Recent progress in solid-phase organic synthesis has enabled the synthesis of combinatorial libraries based on the structure of complex natural products. It can be envisioned that natural-product-based combinatorial synthesis may permit hit or lead compounds to be found with enhanced probability and quality.     

Photochemistry and mobility of stilbenoid dendrimers in their neat phases

Selectively deuterated, dodecyloxy substituted stilbenoid dendrimers of the first and second generation were synthesized by a convergent synthesis, using the Wittig-Horner reaction. The photochemistry and the fluorescence in the different crystalline and liquid crystalline phases were investigated. Molecules deuterated at the alpha-position of the alkoxy chains were used to study the photoreactions in the neat phases by 1H NMR. Reactions of the double bonds are exclusively observed in the liquid crystal phases. No photoreactions occur in the crystalline state. The mobility of the dendrimers was studied by means of 2H solid-state NMR spectroscopy. The onset of the photochemistry for dendrimer 1 [all-(E)-1,3,5-tris[2-(3,4,5-tridodecyloxyphenyl)ethenyl]benzene] corresponds to the increasing mobility at the Cr/LC transition. The first generation dendrimers still show large angle motion, whereas dendrimers of the second generation 2 [all-(E)-1,3,5-tris(2-[3,5-bis[2-(3,4,5-tridodecyloxyphenyl)ethenyl]phenyl]ethenyl)benzene] are restricted to librational motions. Photochemical conversion and fluorescence quenching for first and second generation dendrimers 1 and 2 increase with increasing molecular motion and reach a maximum in the isotropic phase.     

Synthesis,purification, and structural characterization of the dimethyldiselenoarsinate anion

A novel arsenic-selenium solution species was synthesized by reacting equimolar sodium selenite and sodium dimethylarsinate with 10 mol equiv of glutathione (pH 7.5) in aqueous solution. The solution species showed a single (77)Se NMR resonance at 112.8 ppm. Size-exclusion chromatography (SEC) using an inductively coupled plasma atomic emission spectrometer (ICP-AES) as the simultaneous arsenic-, selenium-, sulfur-, and carbon-specific detector revealed an arsenic-selenium moiety with an As:Se molar ratio of 1:2. Electrospray ionization mass spectrometry (ESI-MS) of the chromatographically purified compound showed a molecular mass peak at m/z 263 in the negative ion mode. Fragmentation of the parent ion (ESI-MS-MS) produced (CH(3))(2)As(-) and Se(2)(-) fragments. Arsenic and selenium extended X-ray absorption fine structure spectroscopy (EXAFS) of the purified species revealed two As-C interactions at 1.943 A and two As-Se interactions at 2.279 A. On the basis of these results this novel solution species is identified as the dimethyldiselenoarsinate anion.     

Nucleophilic alkylations of 3-nitropyridines

3-Nitropyridine and 4-substituted-3-nitropyridines were reacted with chloroform, methyl chloroacetate and ethyl 2-chloropropionate under vicarious nucleophilic substitution (VNS) conditions. Substitution was obtained in the ortho or para position to the nitro group with acceptable to good yields and regioselectivity. With potassium 5-nitropyridine-2-sulfonate the substitution took place in the 4-position. Further substitution of the sulfonate group proved to be possible.     

2-Stannyl-1, 3-dithiane Herstellung,Sn/Li-Transmetallierung und Verwendung für Cyclisierungen

2-Stannyl-1,3-dithianes. Preparation, Sn/Li-Transmetallation, and Use for Cyclizations In order to test the possibility of generating nucleophilic 2-lithio-1, 3-dithiane centers in the presence of electrophilic groups in the same molecule, the stannylated dithianes 1 - 3 were prepared or generated. Solutions of the lithio derivatives 2a and 2b could either be obtained by metallation of 1 with lithiumdiisopropylamide (LDA) or by transmetallation of 3 with alkyllithium reagents. Alkylations of 2 led to the alkyl-stannyl-dithianes 4 - 7 . Additions of the trimethylstannylated lithiodithiane 2a to aldehydes and ketones at low temperature led - after hydrolysis - to the adduct alcohols 8 ; warming up to room temperature before hydrolysis furnished keten thioacetals 9 only with acetone (→ 9b ) and cyclohexanone (→ 9c ) as carbonyl component, while still the simple adducts 8a and 8d were isolated with benzaldehyde and cyclohexenone, respectively. Methyl benzoate and benzoic acid anhydride reacted with 2a to produce the tin-free derivatives 12 and 14 , respectively. It is shown that the Sn/Li-exchange at the 2-position of dithianes 4 - 7 , 15 and 16 takes place within minutes at ?78°, whereas H/Li-metallation does not occur at all at this temperature. In situ preparation of the cyclization products 17 - 19 from halo-epoxides is described. The overall yields of Sn/Li-exchange ( 3 → 2 ), epoxyalkylation ( 2 → 15 and 16 , repectively), Sn/Li-exchange in 15 and 16 , cyclization (→ 17 – 19 ) are twice as high (up to 80%) with the tributylin than with the trimethyltin derivatives. The intramolecular 1, 3 nucleophilic reaction 20a → 17 is complete within 5 min at ?78°. The total yields of cyclization products by the tin route ( 3b → 16 → 20b → 18 + 19 ) and by direct metallation (1, 3-dithiane → 21b → 20b → 18 + 19 ) are 63 and 30%, respectively.     

Development and single-laboratory validation of a reversed-phase liquid chromatography-electrospray-tandem mass spectrometry method for identification and determination of acrylamide in foods

A rapid and accurate method using reversed-phase liquid chromatography-tandem mass spectrometry interfaced with electrospray was developed for determination of acrylamide in cooked food samples. A simplified sample treatment procedure using an extraction step with acidified water without cleanup was developed. A C18 column with an aqueous formic acid-methanol mixture as the mobile phase was used under isocratic conditions. The method was validated in-house for robustness, limits of detection (LOD) and quantitation (LOQ), linearity, recovery, and accuracy both on standard and baked-product and potato flour matrixes. Good results in the low ppb level were obtained for LOD (< 15 microg/kg) and LOQ (< 25 microg/kg) of acrylamide in samples. Excellent linearity (r2 = 0.999-1.000) was established over 2 orders of magnitude by performing statistical tests. The absence of both constant and proportional systematic errors demonstrated good method accuracy. Excellent results were obtained for intraday repeatability (RSD < 1.5%) and between-day precision (RSD < 5%). Extraction recoveries from food products were calculated in the 97 +/- 3-99 +/- 2% (n = 6) range with a labeled internal standard (13C3-acrylamide). The applicability of the method to determination of acrylamide in cooked food products was demonstrated.     

Nonlinear optical properties, synthesis, structures and spectroscopic studies of N-(4-nitrobenzylidene)-o-fluoroamine and N-(3-nitrobenzylidene)-p-fluoroamine

N-(4-nitrobenzylidene)-o-fluoroamine (1) and N-(3-nitrobenzylidene)-p-fluoroamine (2) have been synthesized. The crystal structures of both compounds have been defined by X-ray diffraction analysis, and characterized by FT-IR and UV-visible instrumental methods. The recorded spectrum by UV-visible spectroscopy for the investigated compounds show good transparency in the visible region, and have solvatochromic behavior in the UV region, implying nonzero microscopic first hyperpolarizability. We also report ab initio quantum chemical calculations of the electric dipole moments (mu) and the first hyperpolarizabilities (beta) of the studied compounds. Our results suggest that the investigated ligands might have microscopic nonlinear optical (NLO) behavior with nonzero values.