2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.     

Theoretical and experimental NMR studies of the Swern oxidation of methyl 6<Emphasis Type="Italic">α</Emphasis>,7<Emphasis Type="Italic">β</Emphasis>-dihydroxyvouacapan-17<Emphasis Type="Italic">β</Emphasis>-oate

This work describes the synthesis of new derivatives of 6α,7β-dihydroxyvouacapan-17β-oic acid (1) employing the Swern method for the oxidation of C-6 and C-7 of methyl 6α,7β-di-hydroxyvouacapan-17β-oate (2) and the formation of methyl 6,7-dioxovouacapan-17β-oate (3). NMR structural studies associated with theoretical calculations of reaction intermediates and products are also reported. The mixture of methyl 7β-hydroxy-6-oxovouacapan-17β-oate (4; 21%) and methyl 6α-hydroxy-7-oxovouacapan-17β-oate (5; 79%) was the product from the first step of the oxidation of 2. The lower energy of 5, calculated by HF/6-31G* and DFT/BLYP/6-31G* methods, reinforces the thermodynamic control proposed for the reaction. After further Swern oxidation of the mixture of 4 and 5, the isomeric form methyl 6-hydroxy-7-oxovouacap-5-en-17β-oate (6) was obtained. Theoretical calculations indicate a lower energy for the mono-enol 6 than the 1,2-diketo 3 and the other mono-enol methyl 7-hydroxy-6-oxovouacap-7-en-17β-oate (7).     

Synthetische Umwandlung des Abietinsäuregerüstes. Abbau der Carboxylfunktion

Summary Aluminiumoxide-induced rearrangement of the tosylate7 (derived from abietic acid methyl ester byLAH reduction and Tosylation), leads under migration of CH₃-4 to a mixture of exocyclic and endocyclic olefines8 – 11. Photochemical isomerisation of these olefines yields the endocyclic isomer10 as single product.

     

Quantitative HPLC Determination and Stability Studies of Pyridostemin in Extracts and Water Dispersible Granule Formulations of Stemona curtisii

A reversed-phase high-performance liquid chromatographic method has been developed and validated for the determination of pyridostemin, the major pesticidal alkaloid found in Stemona curtisii. This methodology was applied to the investigation of plant extracts and water dispersible granule formulations. Stability indicating procedures have also been carried out. The chromatographic separation was on a C₁₈ column with a mixture of acetonitrile–water–triethylamine (30:70:0.12, v/v/v), using UV detection at 300 nm. Validation procedures showed that the method was specific, accurate and precise. The response was linear over a range of 5–25 μg mL⁻¹ with recoveries in the range of 98.28–102.85%. The RSD for intra- and inter-day precision were <0.72 and <1.29%, respectively. Extraction of plant material with dichloromethane gave a significantly higher pyridostemin content in the crude extracts when compared with extractions in methanol. Partial purification of the crude extracts by silica gel column chromatography was used to concentrate the mixture about fourfold. Degradation behavior of pyridostemin in the partially purified extracts followed first-order kinetics. The main pathways for its decomposition were base hydrolysis and oxidation.     

α-亚胺酮的不对称转移氢化合成(R)-沙丁胺醇

用手性(S,S)-Ru-TsDPEN催化剂不对称转移氢化α-亚胺酮化合物5-[(1,1-二甲基乙基)亚胺基]乙酰基-2-羟基苯甲酸甲酯(2)得光学纯β-氨基芳基乙醇类化合物(R)-5-[2-[(1,1-二甲基乙基)氨基]-1-羟乙基]-2-羟基苯甲酸甲酯(3), 再经一步还原反应即得(R)-(－)-沙丁胺醇. 对反应关键一步α-亚胺酮的不对称转移氢化反应条件进行了研究.     

New chiral spiro[2.5]octanones as products of methylenation of (3<Emphasis Type="Italic">R</Emphasis>, 6<Emphasis Type="Italic">R</Emphasis>)-2-arylidene-6-isopropyl-3-methylcyclohexanones with dimethylsulfoxonium methylide. Synthesis,stereochemistry, and behavior in liquid-crystalline systems

Methylenation of (3R,6R)-2-(4-X-benzylidene)-6-isopropyl-3-methylcyclohexanones (X = F, Cl, Ph) with dimethylsulfoxonium methylide occurs stereoselectively to give 1(S)-(4-X-phenyl)-5(R)-isopropyl-8(R)-methyl-3(R)-spiro[2.5]octanones, whose stereochemistry was established by ¹H NMR spectroscopy. The configuration of the chiral centers in the cyclohexanone fragment and its preferred conformation (methyl is axial and isopropyl is equatorial) in the products do not change with respect to the starting enones. The mutual trans-arrangement of the carbonyl and aryl groups at the newly formed three-membered ring was established; the aryl group also occupies the trans-position with respect to the axial methyl group of the cyclohexanone fragment. Using methylenation of the compound with X = Ph as an example, a mixture of by-products resulting from oxidative hydroxylation at the α-position relative to the carbonyl group was isolated. The resulting chiral spiro[2.5]octanones induce a helical supramolecular ordering in the nematic mesophase of 4-pentyl-4′-cyanobiphenyl and exhibit a twisting power only somewhat (by 20–30%) lower than the starting enones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2331–2341, October, 2005.     

Synthesis and reactions of 2,3-dimethylfuro[3,2-c]pyridines

Summary A number of substituted 2,3-dimethylfuro[3,2-c]pyridines was synthesized. 3-(4,5-Dimethyl-2-furyl)propenoic acid (1) was converted to the acid azide2, which in turn was cyclized to give 2,3-dimethyl-5H-furo[3,2-c]pyridine-4-one (3) by heating at 240°C in Dowtherm. The pyridone3 was chlorinated with phosphorus oxychloride to give4, which was reduced with zinc and acetic acid to 2,3-dimethylfuro[3,2-c]pyridine (5). Treatment of4 with several secondary heterocyclic amines led to compounds6a–6c. Reaction of pyridone3 with phosphorus pentasulfide rendered the thione7, which was methylated to8a. The 4-methoxy derivative8b was obtained from4 with sodium methoxide. 2,3,5-Trimethylfuro[3,2-c]pyridine-4-one (9) was obtained by reaction of3 with methyl iodide.Dedicated to Professor Dr.Fritz Sauter on the occasion of his 65th birthday     

Metal Schiff-Base Complex Catalyzed Oxidation of p-Xylene and Methyl 4-Methylbenzoate to Carboxylic Acids

Oxidation of p-xylene and methyl 4-methylbenzoate were catalyzed by transition metal Schiff-base complexes having the general formula LMCl_1–2 (where M = manganese or ruthenium and L = salen, salicylaldehydeethylenediimine, saloph, salicylaldehyde-o-phenylenediimine and EDTA, ethylenediaminetetraacetate) at 150°C and 500 psig air and gave p-toluic acid (> 85 %) and monomethyl terephthalate (> 70%) as the major oxidation products, respectively.     

Properties of the Macrophomina phaseolina endoglucanase (EGL 1) gene product in bacterial and yeast expression systems

Functional expression of a β-d-1,4 glucanase-encoding gene (egl1) from a filamentous fungus was achieved in both Escherichia coli and Saccharomyces cerevisiae using a modified version of pRS413. Optimal activity of the E. coli-expressed enzyme was found at incubation temperatures of 60°C, whereas the enzyme activity was optimal at 40°C when expressed by S. cerevisiae. Enzyme activity at different pH levels was similar for both bacteria and yeast, being highest at 5.0. Yeast expression resulted in a highly glycosylated protein of approx 60 kDa, compared to bacterial expression, which resulted in a protein of 30 kDa. The hyperglycosylated protein had reduced enzyme activity, indicating that E. coli is a preferred vehicle for production scale-up.     

Optisch aktives 1,3-Diferrocenyl-1,3-diphenyl-allen

The title compound 2 was prepared by thermal dehydration of 1,3-diferrocenyl-1,3-diphenyl-propenol (24) with 70% yield.24 was accessible from 1,3-diferrocenyl-propanedione-1,3 (25) in two steps with 10% overall yield: Treatment of25 with phenyllithium gave 1,3-diferrocenyl-3-phenyl-propenone (8) which after repeated reaction with phenyllithium afforded24.Partial optical resolution of2 was achieved by chromatography on triacetyl cellulose in ethanol, whereby both (+)- and (–)-2 were obtained with different enantiomeric purities as could be deduced from the CD-spectra with -values of +0.18 and –1.64, resp., at 480 nm.Attempts to prepare 1,3-diferrocenyl-allene and 1,3-diferrocenyl-1-phenyl-allene failed. In this context several 1,3-diferrocenyl-propenols,-propenones,-propenes,-propanones,-propanes and-butadienes were obtained.

62. Mitt.:M. Benedikt undK. Schlögl, Mh. Chem.109, 805 (1978).     

Aromatische Spirane, 21. Mitt: Darstellung von Methylphthalaldehydsäuren und ihren Ethylund Methylestern als Synthone für Synthesen von methylierten 2,2′-Spirobiindandionen

Summary The isomeric methyl phthalaldehydic acids11 were obtained from phthalides4 by bromation (NBS) to the 3-bromo derivatives7 and subsequent hydrolysis with water.4 in turn were accessible from dimethyl methyl benzoates1 by dibromination withNBS and subsequent thermical cyclization to the bromo derivatives3 which, on catalytic dehalogenation, afforded the phthalides4. Reaction of11 with methanol or ethanol gave the pseudo-esters13 and14, resp. Short treatment of11 with diazomethane on the other hand yielded the methyl formyl benzoates15b to15e. Prolonged reaction (several hours) gave the oxiranyl compounds17; in addition, the acetonyl derivatives18 were also found, obviously formed by a double methylene insertion into15. All reactions proceeded with good to excellent yields.

     

Stereochemie von Metallocenen, 43. Mitt.: Torsionsisomere Biphenyl-tricarbonylchrom-Komplexe: Darstellung,Konformationsanalyse und Kinetik der Interkonversion

Complexation of methyl 3-nitro-2-(o-tolyl)-benzoate (2, ano-trisubstituted biphenyl) with hexacarbonyl chromium gave the isomeric Cr(CO)₃ complexes3 and4 both existing as two torsional isomersa andb, as seen by nmr. For the main product3 the preferred conformations of the two torsional isomersa andb were deduced by the lanthanide induced shift (LIS) technique. The activation energy for the interconversion process could be determined from kinetic measurements and especially from¹H-nmr coalescence temperature of the methylsignals. The barrier of 91±1.5 kJ/mol (21.7±0.3 kcal/mol) in3 reflects the interaction of theo-H-atom of the benzene ring passing the Cr(CO)₃ moiety of the benchrotrene ring during the interconversion.A partial optical resolution of3 was achieved by asymmetric reduction with a chiral lithium-aluminium hydride yielding (+)-3 with [] _D ²⁰ +30° (benzene) and the levorotatory alcohol (–)-7.

42. Mitt.:K. Schlögl undR. Schölm, Mh. Chem.109, 1227 (1978).     

Complexes of neodymium and dysprosium triiodides with amines. Molecular structures of the {Dy[Me2N(CH2)3NH2]8}I3, NdI3(PriNH2)4, and NdI3(PriNH2)5 complexes

The dissolution of DyI₂ in diamine Me₂N(CH₂)₃NH₂ (DMDA) is accompanied by the disproportionation of the salt, hydrogen evolution, and oxidation of Dy^II to Dy^III. The [Dy(DMDA)₈]I₃ complex (1) was isolated from the solution. The neodymium amide amine complex (PrⁱNH)NdI₂(IPA)₄ was produced by the reaction of NdI₂ with isopropylamine (IPA). The recrystallization of this complex from IPA afforded the NdI₃(IPA)₄ complex (2). The recrystallization of (PrⁱNH)NdI₂(IPA)₄ from a toluene-IPA mixture gave the complex with five amine ligands, NdI₃(IPA)₅ (3). The structures of compounds 1, 2, and 3 were established by X-ray diffraction. Dedicated to Academician G. A. Abakumov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1674–1679, September, 2007.     

Asymmetric addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines

The asymmetric Michael addition of methyl nitroacetate to crotonaldehyde catalyzed by chiral amines was carried out. The maximum chemical yield of diastereomeric products amounted to 95 %. The best asymmetric induction (42 % e.e.) was achieved in the case of catalysis by (S)-prolinol. The diastereomeric mixture was converted to a mixture of stereoisomeric 3-methyl-2-methoxycarbonylpyrrolidines. Absolute configurations of (2S,3S)-and (2R,3S)-isomers formed in excess were determined using GLC by comparison with authentic samples of racemic and optically pure forms of 3-methylproline.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1591–1595, September, 1993.     

Partial Deuterium Labeling of Dimethacrylate Monomers

Summary. Methacrylic acid-d₅ was prepared in a yield of 30% with 98.6% deuterium incorporation using a two step synthesis. A solution of acetone-d₆ and KCN in D₂O was treated with glacial acetic acid to give the cyanohydrin of acetone-d₆. The latter compound was then dehydrated in anhydrous sulfuric acid at 120°C and subsequently hydrolysed in water at 90°C to form methacrylic acid-d₅. Hydrolysis of commercial nonaethyleneglycol dimethacrylate gave a mixture of ethylene glycols. These glycols were combined with methacrylic acid-d₅ in the presence of p-TsOH in benzene to form nonaethyleneglycol dimethacrylate-d₁₀ with ∼21% deuterium incorporation. Deuterated bisGMA was also prepared from methacrylic acid-d₅ and diglycidyl ether of bisphenol-A. Present address: Boron Molecular Pty Ltd, PO Box 756, Noble Park, VIC 3174, Australia     

Topological investigations of the molecular species and molecular interactions that characterize pyrrolidin-2-one + lower alkanol mixtures

Molar excess volumes, V^E, molar excess enthalpies, H^E, and speeds of sound data, u, of pyrrolidin-2-one (i) + ethanol or propan-1-ol or propan-2-ol or butan-1-ol (j) binary mixtures have been determined over entire composition range at 308.15 K. The observed speeds of sound data have been utilized to predict excess isentropic compressibilities, of the investigated binary mixtures. The observed excess thermodynamic properties V^E, H^E and have been analyzed in terms of Graph theory. The analysis of V^E data by the Graph theory suggests that pyrrolidin-2-one exists mainly as a mixture of cyclic and open dimer; ethanol as a mixture of dimer and trimer; butan-1-ol and propan-2-ol as mixture of monomer and dimer and propan-1-ol as a dimer in the pure state, and their mixtures contain 1:1 molecular complex. The IR studies lend additional credence to the nature and extent of interactions for the proposed molecular entities in the mixtures. Also, it has been observed that V^E, H^E and values predicted by the Graph theory compare well to with their corresponding experimental values.     

Syntheses based on anabasine. Preparation and transformations of N-oxides

The oxidation of N-acetyl-and N-benzoylanabasine with the tert-butyl hydroperoxide (TBHP)— MoCl₅ system or MCPBA proceeds selectively at the nitrogen atom of the pyridine ring. The oxidation of N-methylanabasine under similar conditions gives a mixture of stereo-isomeric N-oxides at the piperidine nitrogen atom, their ratio depending on the reagent used. The oxidation of anabasine by TBHP— MoCl₅ or MCPBA is accompanied by dehydrogenation and results in anabaseine N-oxide. The reactions of anabasine and anabaseine pyridine N-oxides with acetic anhydride were investigated. The substituted 1H-3-pyridin-2-ones were prepared. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 322—328, February, 2006.     

Über eine neue Synthese von Desmethylambraoxid

A new synthesis of the title compound starting from abietic acid is described. Regioselective osmylation of the ^{13, 14}-double bond of abietic acid methyl ester (6) and subsequent hydrogenation furnishes dihydrodihydroxyabietic acid methyl ester (12) with anall-trans-connection of the three rings. Periodate cleavage of12 leads to13 which can be transformed into the triester14 byBaeyer-Villiger oxidation. The configuration of the aldehyde group in13 as well of the formyloxy group in14 has been ensured to be equatorial.LAH-reduction of14 leads to the triol16 which after cyclisation and reductive dehydroxylation furnishes the fragrance compound4.

Auszugsweise vorgetragen auf der 5. wissenschaftlichen Tagung der Österreichischen Pharmazeutischen Gesellschaft am 16. April 1985 in Graz.     

LIGAND EXCHANGE AND LIGAND COUPLING VIA THE σ-SULFURANE INTERMEDIATE IN THE REACTION OF ALKYL 2-PYRIDYL SULFOXIDE WITH GRIGNARD REAGENTS: CONVENIENT PREPARATION OF 2,2′-BIPYRIDINES

Abstract

The reaction between methyl 2-pyridyl sulfoxide (1) with Grignard reagents afforded 2,2′-bipyridine (2) in moderate yield. The reaction is considered to involve initial ligand exchange to generate 2-pyridylmagnesium halide which in the subsequent step attacks the original sulfoxide to form the σ-sulfurane that undergoes ligand coupling to afford 2. The reaction of t-butyl 2-pyridyl sulfoxide (3) with C₆H₅MgBr, however, gave only 2-phenylpyridine (4). This may be due to steric hindrance to the initial ligand exchange. Formation of 2 is a convenient process for preparation of 2,2′-bipyridines bearing various substituents.     

7,15-Diazadispiro[5.1.5.3]hexadecan und Derivate, 1. Mitt.: Darstellung der Grundkörper

As starting materials for theoretical and pharmacological studies 7,15-diazadispiro[5.1.5.3]hexadecane (1), its 14-imino-(2) and 14-oxo-derivative (3) were prepared. Reduction of bis-(1-cyanocyclohexyl)-amine (4) withLAH leads to a mixture of1 and2. For the exclusive preparation of1, 4 is treated with conc. H₂SO₄ to yield the corresponding 14,16-dioxohexadecane, which is reduced to1 withLAH. The preparation of3 is effected by acid hydrolysis of acetylated2.