CONFORMATION OF EIGHT-MEMBERED DIOXATHIASILOCIN HETEROCYCLES IN SOLUTION

Abstract

The dibenzo[d,g][1,3,6,2]dioxathiasilocin derivatives 3a-f were prepared by the reaction of the thiobisphenols 1a-b with the corresponding dichlorosilanes 2a-e using triethylamine as an acid acceptor. The free energy of activation for ring inversion of the 2,4,8,10-tetra-tert-butyl-substituted 3a was determined by variable temperature ¹H NMR to be 13.9 kcal/mol. The ¹H NMR spectral data of 3a requires that the ring conformer possess a σ plane of symmetry passing through the silicon and bridging sulfur atoms. In the variable temperature ¹H NMR spectra of the 2,4,8,10-tetramethyl-substituted 3b no evidence was observed for the slowing of ring inversion at-55^oC, suggesting that the energy of activation for ring inversion is less than 10.9 kcal/mol. The ¹H NMR spectral data of 3e-f indicates the presence of equilibrating conformational isomers. The results of this study supports the suggestion that steric factors are a major contributor to the barrier of ring inversion for the dibenzo-[d, g][1,3,6,2]dioxathiasilocin ring system.     

SYNTHESIS AND CONFORMATIONAL STUDIES OF A NUMBER OF SATURATED BICYCLIC SIX-MEMBERED RING PHOSPHITES

Abstract

An ¹H NMR study of the conformation of the dioxaphosphorinane ring of a number of diastereoisomeric bicyclic saturated six-membered ring phosphites (3ab-10ab) has been performed. The dioxaphosphorinane ring of these phosphites is transannelated with a tetrahydrofuran, cyclopen-tane, tetrahydropyran or cyclohexane ring. The substituent on the phosphorus atom is a methoxy or phenoxy group. It is shown that the cis isomers 3a-10a prefer a chair conformation of the dioxaphosphorinane ring, independent of the substituent on the phosphorus atom and of the nature of the transannelated ring. In contrast, for the trans isomers 3b-10b a twist rather than a chair conformation of the dioxaphosphorinane ring is preferred. The fraction of the twist conformer in the trans isomers is mainly determined by the substituent on phosphorus. The size and composition of the transannelated ring are relatively unimportant in this respect. For both cis and trans isomers the preferred geometry is solvent-independent. The measured ^3JPOCH couplings of the cis isomers 3a-10a are used to formulate an expression for the dependence of such couplings upon dihedral angles in bicyclic phosphites.     

Ab Initio Study of Ring Flipping of the Overcrowded Peri-Substituted Naphthalenes

Ab inintio molecular orbital and density functional theory method were used to investigate the structural and dynamic behavior of 1,8-di-tert-butyl naphthalene (1), 1,8-bis(trimethylsilyl)naphthalene (2), 1,8-bis(trimethylgermyl)naphthalene (3), and 1,8-bis(trimethylstannyl)naphthalene (4). HF/3-21G//HF/3-21G results revealed that the ring flipping barrier height of compound 1–4 is 92.59, 32.13, 26.76, and 15.46 kJ mol^?1 respectively. The obtained results show that the transition state structure for ring flipping of the bulky-groups is in a planar form with naphthalene ring. Contrary to compound 1, the ring flipping of compounds 2–4 occurred easily at room temperature. Also, MP2/3-21G//HF/3-21G energy calculation, show that the enantiomerization energy of compounds 1–4 are 97.99, 33.24, 26.80, and 15.38 kJ·mol^?1 respectively. The required energy for ring inversion of compounds 1–4 are 85.09, 27.26, 21.54, and 10.21 kJ mol^?1 respectively, as calculated by B3LYP/3-21G//HF/3-21G method. It can be concluded that the lower energy barrier of the ring flipping of compounds 2–4 is related to the increasing of the bond lengths of Si—C, Ge—C, and Sn—C, in contrast to C—C bond.     

Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS

The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB₂, has been studied. A total of 22 metabolites were identified and structurally characterized. The metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z 344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z 344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3) dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360, M13), resulting from a combination of monohydroxylations on both the naphthalene and indole rings (m/z 360, M16), or a combination of monohydroxylations on the naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation (m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6) N-dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7) N-dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and M5); 8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326, M22); 9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).     

The molecular and crystal structures of two diastereomeric 3,4-dihydropyrromethenones

The molecular and crystal structures of the two racemic diastereomeric 3,4-dihydropyrromethenone derivatives1 and2 of configurations (Z) and (E) were determined at 93 K (1, 2) and at room temperature (1). From an analysis of the crystallographically observed temperature coefficients a pseudorotation flexibility of the pyrrolidinone ring in the crystal is deduced. In both compounds a nearly orthogonal arrangement between the two heterocyclic ring systems is observed, which is ascribed to the steric bulk of the substituents in positions 1 and 3 of the pyrrolidinone ring.Herrn Prof.Josef Schurz zum 60. Geburtstag gewidmet.     

Substitutions- und Additionsreaktionen an Spiro-oxiranen

Nucleophilic substitution at the spiro carbon atom as well as the CH₂-group takes place with spiro-oxiranes1,6 and7, whose spiro carbon atom bear electron withdrawing substituents. In some cases by elimination of formaldehyde a transformation to the corresponding reductone systeme (5,11,16) is observed. In other cases, e.g. with tertiary amines, betaines (2,9,12) are formed, which by elimination of the base rearrange to dioxolenes (3,10). Addition of polar reagents like aryl isocyanate or chloral leads to ring expansion of the threemembered ring to form the five ring systems17,18,20,22 or24.

Herrn emer. o. Univ. Prof. Dr.Erich Ziegler, Institut für Organische Chemie, Karl-Franzens-Universität Graz, mit besten Wünschen zur Vollendung des 70. Lebensjahres gewidmet.     

Synthesis and Conformational Analysis of 1, 2-Anhydro-3, 4-di-O-benzyl-6-deoxy-α-D-glucopyranose

Abstract

The title 1, 2-anhydro sugar (10) was synthesized from methyl 4, 6-O-benzylidene-α-D-glucopyranoside or from 1, 2-O-ethylidene-α-D-glucopyranose. The key intermediate for the synthesis was 2-O-acetyl-3, 4-di-O-benzyl-6-deoxy-β-D-glucopyranosyl fluoride (8)which was transformed into the target compound by ring closure with potassium tert-butoxide. Calculations by the modified Karplus equation from vicinal coupling constants of 10 suggested that the conformation of 10 was almost an ideal ⁴ H ₅ for the pyranose ring. Conformational analysis for the 1, 2-O-(R)-ethylidene intermediates 17 and 20 revealed that their pyranose ring basically adopted a B₂,₅ conformation.     

Synthesis and Application of 3,3-Spirocyclopropane Derivatives Obtained from 1,2:5,6-Di-O-Isopropylidene-α-D-Glucofuranose

Abstract

3,3-Spirocyclopropane derivatives (5 and 7) were prepared by three different methods of cyclopropanation starting from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2). Subsequent radical induced cyclopropane ring opening reaction stereo-specifically provided the 3-C-allyl derivative (9). However, activation of the cyclopropyl ring through the aldehyde (10) followed by hydrogenation gave a quaternary chiral derivative (11) which was elaborated to the versatile intermediate (1) by using Bamford-Stevens reaction.

     

Crystal and Molecular Structures of (E)-(2-Phenylethenyl)cyclooctatetraene and (E)-(2-(4-Nitrophenyl)ethenyl)cyclooctatetraene. Conformations of Substituted Cyclooctatetraenes

The single crystal x-ray structures of (E)-(2-arylethenyl)cyclooctatetraenes 1 and 2 have been determined. The nitro group in 2 does not influence the geometry of the COT ring relative to that of 1. The influence of various substituents on several structural parameters of the COT ring are analyzed in terms of steric/electrostatic and electronegativity effects of the substituent.     

New dopants for induced ferroelectric SC* phases containing 1,3-dioxolan-2-one as a chiral heterocycle

Abstract

The synthesis, phase behaviour and spontaneous polarization of a new class of chiral dopants for induced ferroelectric phases of general structure 6 and 9, possessing a 1,3-dioxolan-2-one ring, are described. One of the new compounds exhibits a S_A phase. When the chiral ring system is positioned terminally to the mesogen (6) the cis disubstituted compounds show higher induced spontaneous polarization than those with an analogous trans configuration.     

Thallium(III) Nitrate Mediated Ring Contraction of 2‐Aryl‐1,2,3,4‐tetrahydro‐4‐quinolones: Stereoselective Synthesis of trans Methyl 2‐Aryl‐2,3‐dihydroindol‐3‐carboxylates

The ring contraction of N‐acetyl‐2‐aryl‐1,2,3,4‐tetrahydro‐4‐quinolones 1a–d with thallium(III) nitrate in trimethyl orthoformate afforded stereoselectively trans methyl N‐acetyl‐2‐aryl‐2,3‐dihydroindol‐3‐carboxylates 5a–d by oxidative rearrangement of aryl ring A.     

Synthese neuartig substituierter Pyridazin-6(1H)-one

Summary Arylhydrazono acetamides1 react with chloroacetic acid chloride to give N-chloroacetyl derivatives2. Subsequent reaction with pyridines followed by ring closure yield 1-(4-amino-6-oxo-pyridazin-5-yl)-pyridinium chlorides3. Analogously, 1-(6-oxo-pyridazin-5-yl)-pyridinium chloride (5) and 6-oxo-5-pyridinio-pyridazin-4-olate (4) are formed from phenylhydrazono derivatives and pyridine. Treatment of3 and4 with hydrazinium hydrate gives 4,5-diamino-6-oxo-pyridazin-3-carbohydrazides6 and 5-amino-4-hydroxy-pyridazin-6(1H)-one (8). An analogous ring cleavage of3e and5 gives rise to 4,5-diamino- and 5-amino-pyridazin-6(1H)-ones7. On treatment of the pyridinium salts3 with caustic soda in water, nucleophilic addition of the amino group to the pyridinium ring takes place and stable dehydrated products9 are isolated.

Herrn Professor Dr. Fritz Sauter zum 65. Geburtstag gewidmet     

Substituted Quinolinones,Part 11: Efficient Synthesis of Different 3‐(4‐Arylidene and Hetarylidene‐5‐oxopyrazolin‐3‐yl) quinolin‐2‐ones

Several 3‐(4‐arylidene and hetarylidene‐5‐oxopyrazolin‐3‐yl)quinolin‐2‐ones 6–26 were synthesized in an efficient methodology utilizing both pyrazolinylquinolinone 2 and its chromenylmethylene derivative 10. Compound 2 was derivatized by Knoevenagel condensation with different carbonyl compounds. Nucleophilic ring opening–ring closure (RORC) of the compound 10 furnished the desired 4‐methylenepyarzolinone bearing novel five‐, six‐, and seven‐membered heterocycles, in good yields.     

Formal Total Synthesis of Ipomeamarone via the [2+3] Dihydrofuran Annulation

A formal synthesis of (2R-cis)-4-methyl-1-(2,3,4,5-tetrahydro-5-methyl-[2,3′-bifuran]-2-pentanone, or ipomeamarone (1) [494-23-5] was accomplished from 3-furaldehyde 5 and ethyl-2-bromocrotonate 4. The key step involved the formation of the dihydrofuran ring in 2 via a vinyloxirane rearrangement of 3 in the [2+3] dihydrofuran annulation. Mechanistic duality of reactions of those tetrahydrofurans possessing acidic hydrogens adjacent to the ring is addressed.     

Catalytic Hydrogenation of Chiral 2-(2-Furyl)-3,4-dimethyl-5-phenyloxazolidine

Reduction of chiral 2-(2-furyl)-3,4-dimethyl-5-phenyloxazo-lidines-1,3 by H₂/Raney nickel proceeds simultaneously as hydrogenation of the furan ring and opening of the oxazolidine ring on C2-O bond. Diastere-oselectivity in the first reaction was established as ca 40% and 80% depending on the configuration of the oxazolidine 1 and 2.     

Catalytic Oxidative Domino Degradation of Alkyl Phenols Towards 2- and 3-Substituted Muconolactones

The catalytic oxidative domino degradation of phenols was investigated. Hydrogen peroxide (30% aq.) was used as an oxidant and 2,2′-dinitro-4,4′-ditrifluoromethyldiphenyl diselenide 4e as a catalyst. The products were muconic acid 5, and muconolactones muconolactones—5-carboxymethylfuran-2(5H)-ones 7 and 9. Phenols with alkyl groups at 2 or 4 positions of the benzene ring were converted regioselectively to corresponding muconolactones substituted at alkenylene ring carbon atoms. The reaction mechanism is proposed.     

Synthesis of Piperidine Derivatives by Reduction of Pyridinium Salts

Piperidine derivatives 1a–e and 2a–f have been prepared by the reduction of 3‐and 4‐substituted pyridinium salts with NaBH₄ in moderate to excellent yields. The reactions regioselectively give 1,2,5,6‐tetrahydropyridines, and the yields depend greatly upon the nature of substituents on the phenyl ring and on the nitrogen atom, the nature and the position of the substituents on the pyridyl ring, and the chain length between the aryloxy and the pyridyl groups.     

Reduction of 2-amino-1-(4-nitrophenyl)-1 H-pyrido[3,2-b]indole-3-carbonitrile by sodium borohydride and sodium cyanoborohydride

The reduction of pyridoindole derivative 1 by sodium borohydride in methanol gives 4,5-dihydropyridoindole 2. On treatment of 5H-pyrido[3,2-b]indolium chloride 3 with sodium cyanoborohydride in methanol in the presence of hydrogen chloride, reduction of the pyridine ring is accompanied by reduction of the CN group, resulting in the formation of tetrahydropyridoindole 4. Compound 4 reacts with DMF dimethyl acetal to yield amidine 6, and refluxing of 4 with acetic anhydride results in tetrahydropyridine ring cleavage yielding indolylacrylonitrile 9. The hydrochloride and chloride of compounds 4 and 6 were obtained     

Synthesis and structural investigation of new isothiochromen-4-one 2,2-dioxide derivatives

This article presents a combined experimental and computational study of novel isothiochromene 2,2-dioxide derivatives, which were synthesized by the electrophilic substitution reactions. The compounds have been studied by NMR, IR spectroscopy and single-crystal X-ray analysis. According to X-ray diffraction data, the six-membered ring of 6 adopts a distorted half-chair conformation, but in case of compounds 7 and 8, we have a twist-boat conformation of the six-membered ring with deviation of the S1 and C8 atoms from the mean plane of the remaining atoms of the ring, respectively. Results of quantum-chemical calculations of possible isomers and tautomers of the isolated oxime 8 and azo compounds 10 at the B3LYP/aug-cc-pVDZ level indicate that the oxime-oxo tautomer (8a) is more stable than the nitroso-hydroxy tautomer (8b) in agreement with the crystal data and that the keto tautomer (II) is more stable than the hydroxyl tautomer (I) and zwitterion tautomer (III), because of a strong intramolecular hydrogen bond N–H···O.

     

不同氟取代基对苝酰亚胺电子迁移率的影响

利用空间电荷限制电流(SCLC)法测试了二种氟代苝酰亚胺的电子迁移率, 一种是N,N'-二(五氟代苯基)-3,4,9,10-苝四羧基二酰亚胺(1), 另一种是N,N'-二(1,1-二氢十五氟代辛基)-3,4,9,10-苝四羧基二酰亚胺(2). 结果发现, 化合物2的电子迁移率要比1高1～2个数量级. UV-Vis, XRD, SEM和AFM等表征手段证明, 这一现象可以用不同的氟取代基导致不同的聚集态结构来解释: 对于化合物1而言, 苯环平面与苝环平面之间存在大的夹角, 破坏了苝酰亚胺分子的平面性, 再加上刚性的氟代苯环大的空间位阻作用, 化合物1分子无法依靠相邻苝环之间的重叠排列而结晶, 只能无序堆积形成非晶膜; 与之相反, 在化合物2分子中苝环上的端基是柔性的锯齿状氟代烷基链, 空间位阻小, 化合物2分子能通过相邻苝环之间相互接近而形成的π-π偶合作用而结晶, 因此有利于电子在苝酰亚胺分子间的跳跃传输.