The pKa and pH dependence of the formation of nitroxide radicals from some drug substances with an aliphatic secondary amino group by oxidation with hydrogen peroxide. An Electron Spin Resonance (ESR) Study

The pKa and pH dependence of the formation of nitroxide radicals from the following drugs that contain an aliphatic secondary amino group, by oxidation with hydrogen peroxide, have been studied by ESR spectroscopy: Ephedrine, (1R,2S)-1-phenyl-2-methyl-aminopropanol, timolol, (S)-1-(tert-butyl-amino)-3-[(4-morpholino-1,2,3-thiadiazol-3-yl)ox y]-2- propanol, metoprolol, 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-2-propanol and terodiline, N-tert-butyl-3,3-diphenyl-1-methylpropylamine. Radicals were formed from the non-ionized base only. Therefore, the pKa value of the amine and the pH of the reaction mixture is of crucial importance for the yield of nitroxide radical. At 37 degrees C the pKa values of 1-3 are about 9.2, and of 4 about 9.6, which means that 1.5% of 1-3, and 0.6% of 4, are present in the reactive base form at the physiological pH of 7.4. Horse-radish peroxidase was found both to enhance radical production and to decrease the life-time of the radicals formed in the reaction with hydrogen peroxide.     

New Chiral Metal Cluster Systems for Catalytic Asymmetric Syntheses of Chiral Alcohols

The efficient chiral Ru3(CO)12 systems were prepared in situ from Ru3(CO)12 and various chiral diiminoor diamino-diphosphine tetradentate ligands. The systems have been used for the asymmetric transfer hydrogenation of propiophenone in 2-propanol, leading to 1-phenyl-1-propanol in a 98% yield and 96% e.e. The IR study suggests that the carbonyl hydride anion [HRu3(CO)11]^- most probably exists as a principal species under the reaction conditions. The high chiral efficiency may be due to the synergetic effect produced by the neighboring ruthenium atoms and a special chiral micro-environment involving the polydentate ligand and the Ru3 framework.     

Synthesis of 3-Diaminomethylene-2(3 H )-furanones by Reaction of 2-Amino-4,5-dihydro-3-furancarboxamides with Amines

 The reaction of 2-amino-4,5-dihydro-3-furancarboxamides with morpholine in the presence of acetic acid in pyridine or under the influence of ammonium acetate gave the corresponding 3-diaminomethylene-4,5-dihydro-2(3H )-furanones; 4,5-dihydro-2-morpholino-3-furancarboxamides were not isolated. One of the former reacted with benzylamine to give (E )- and (Z )-3-(amino-(benzylamino)-methylene)-4,5-dihydro-4-phenyl-2(3H )-furanones and 2-benzylamino-4,5-dihydro-4-phenyl-3-furancarboxamide.     

A one-pot reaction of (chlorocarbonyl) phenyl ketene with β-ketoamides and thiochromen-2-one

Readily available (chlorocarbonyl)phenyl ketene and a varied set of β-ketoamides were reacted in a one-step procedure to produce 2-pyrone derivatives. β-Ketoamide derivatives are versatile intermediates for the synthesis of heterocyclic compounds. For instance, 1-morpholino-3-phenyl-1,3-propanedione, 1-phenyl-3-piperidino-1,3-propanedione, 1-phenyl-3-pyrrolidino-1,3-propanedione, 1-piperidino-1,3-butanedione, 1-morpholino-2-phenyl ethanone were used in these reactions to produce 2-pyrone derivatives. In addition, the preparation of 4-hydroxy-3-phenylthiochromeno[4,3-b]pyran-2,5-dione derivatives and 4-hydroxy-7-methyl-3-phenyl pyrano[3,2-c]chromeno-2,5-dione were described. For the synthesis of these compounds 4-hydroxy-2H-thiochromen-2-ones and 4-hydroxy-8-methyl-2H-chromen-2-one were reacted with (chlorocarbonyl)phenyl ketene and the final products were isolated in good yields.     

Synthesis of 3-Diaminomethylene-2(3<Emphasis Type="BoldItalic">H</Emphasis>)-furanones by Reaction of 2-Amino-4,5-dihydro-3-furancarboxamides with Amines

Summary.  The reaction of 2-amino-4,5-dihydro-3-furancarboxamides with morpholine in the presence of acetic acid in pyridine or under the influence of ammonium acetate gave the corresponding 3-diaminomethylene-4,5-dihydro-2(3H )-furanones; 4,5-dihydro-2-morpholino-3-furancarboxamides were not isolated. One of the former reacted with benzylamine to give (E )- and (Z )-3-(amino-(benzylamino)-methylene)-4,5-dihydro-4-phenyl-2(3H )-furanones and 2-benzylamino-4,5-dihydro-4-phenyl-3-furancarboxamide. Received October 4, 2001. Accepted October 10, 2001     

Effect of Chiral Additives in the Preparation of Cellulose-Based Chiral Stationary Phases in HPLC, and Effect on Enantiomer Resolution

Chiral stationary phases (CSPs) for high-performance liquid chromatographic (HPLC) have been prepared by coating silica gel with cellulose tribenzoate or cellulose trisphenylcarbamate. The effect of chiral additives on preparation of the CSPs was studied with (+)-l-mandelic acid, (−)-2-phenyl-1-propanol, (+)-1-phenyl-1,2-ethanediol and (−)-1-(1-naphthyl)ethanol as chiral additives for cellulose tribenzoate and (−)-2-phenyl-1-propanol and (+)-phenylsuccinic acid as chiral additives for cellulose trisphenylcarbamate. The results showed that chiral recognition by these stationary phases was increased in comparison with the original CSPs, especially the resolution (R _S) obtained. The method can be used to improve the efficiency of enantiomer separation by silica gel stationary phases coated with polymers.     

Studies on the chemistry of 2-(2-oxo-3-phenylpropyl)-benzaldehydes: novel total synthesis of 3-phenylnaphthalen-2-ols and 2-hydroxy-3-phenyl-1,4-naphthoquinones

We describe the first studies on the chemistry of 2-(2-oxo-3-phenylpropyl)benzaldehydes, which were converted into 3-benzylisochromen-1-ones via the corresponding 2-(2-oxo-3-phenylpropyl)benzoic acid. The 2-(2-oxo-3-phenylpropyl)benzaldehydes proved to be convenient starting materials for the synthesis of 3-phenyl-2-naphthols. Oxidation of the latter compounds resulted in a novel, efficient synthesis of 3-phenyl-1,2-naphthoquinones, which were efficiently transformed into 2-hydroxy-3-phenyl-1,4-naphthoquinones.     

毛细管电泳测定4个不对称合成化合物的光学纯度

采用毛细管电泳技术,以α-环糊精、β-环糊精和β-环糊精聚合物为手性选择剂,对4种不对称合成物3-(二乙基氨基)-1-苯基-1-丙醇(a)、1-苯基-3-(1-哌啶）-1-丙醇(b)、3-吗啉-1-对甲苯基-1-丙醇(c)和1-（4-氯苯基）-3-吗啉-1-丙醇(d)的消旋体和光学活性异构体进行了手性分离。 结果发现,使用20 kV的分离电压,以浓度为30 g/L的β-环糊精聚合物的80 mmol/L三羟甲基氨基甲烷缓冲溶液（pH=3.2）为背景电解质溶液,4种化合物在40 min内均可得到基线分离。 根据对映异构体峰面积和保留时间的比值确定了4种不对称化合物的光学纯度。 测定的RSD均不大于1.5%。     

Short-range interactions within molecular complexes formed in supersonic beams: structural effects and chiral discrimination

One- and two-color, mass-selected R2PI spectra of the S1<--S0 transitions in the bare chiral chromophore R-(+)-1-phenyl-1-propanol (R) and its complexes with a variety of alcoholic solvent molecules (solv), namely methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, S-(+)-2-butanol, R-(-)-2-butanol, 1-pentanol, S-(+)-2-pentanol, R-(-)-2-pentanol, and 3-pentanol, were recorded after a supersonic molecular beam expansion. Spectral analysis, coupled with theoretical calculations, indicate that several hydrogen-bonded [R.solv] conformers are present in the beam. The R2PI excitation spectra of [R.solv] are characterized by significant shifts of their band origin relative to that of bare R. The extent and direction of these spectral shifts depend on the structure and configuration of solv and are attributed to different short-range interactions in the ground and excited [R.solv] complexes. Measurement of the binding energies of [R.solv] in their neutral and ionic states points to a subtle balance between attractive (electrostatic and dispersive) and repulsive (steric) forces, which control the spectral features of the complexes and allow enantiomeric discrimination of chiral solv molecules.     

Intermediates of Asymmetric Oxidation Processes Catalyzed by Vanadium(V) Complexes

The [VO(acac)₂]/Schiff base [R-2-(N-3,5-di-tert-butylsalicylidene)amino-2-phenyl-1-ethanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3,3-dimethyl-1-butanol, S-2-(N-3,5-di-tert-butylsalicylidene)amino-3-methyl-1-butanol, or R-2-(N-3,5-di-tert-butylsalicylidene)amino-3-phenyl-1-propanol]/H₂O₂ catalytic systems for the asymmetric oxidation of sulfides and the [VO(acac)₂]/(3bR,4aR)-2-(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)ethanol/tert-butyl hydroperoxide/TBHP and VO(OAlkyl)₃/[2,2]paracyclophane-4-carboxylic acid N-(1,1-dimethylethyl)-N-hydroxamide/TBHP catalytic systems for the asymmetric epoxidation of allylic alcohols were studied using ¹³C, ⁵¹V, and ¹⁷O NMR spectroscopy. The key intermediates of these systems (peroxo and alkylperoxo complexes of vanadium(V)) were detected, their structures in solution were studied, and the reactivity was evaluated.     

Vinyl Ethers Containing an Epoxy Group: XXIII. Reactions of Alkynylmagnesium Bromides with Glycidol Ethers: Synthesis and Thermal Transformations of 1-[2-( Vinyloxy)ethoxy]- and 1-(Allyloxy)-5-hexyn-2-ols, -5-phenyl-4-pentyn-2-ols,and -3-bromo-2-propanols

Reaction of 2-[2-(vinyloxy)ethoxy]methyl- and 2-(allyloxymethyl)oxiranes with 2-propynyl- and phenylethynylmagnesium bromides (10–55°C, 0.5–4 h) resulted in new representatives of the series of 1-organyloxy-5-hexyn-2-ols, -5-phenyl-4-pentyn-2-ols, and -3-bromo-2-propanols in 50–99% yields. During distillation the 1-[2(vinyloxy)ethoxy]-5-phenyl-4-pentyn-2-ol and -3-bromo-2-propanol transform respectively into 2-methyl-4-(3-phenyl-2-propynyl)- and 2-methyl-4-(bromomethyl)-1,3,6-trioxocanes via intramolecular cyclization involving the hydroxy and vinyloxy groups.     

Highly efficient chiral metal cluster systems derived from Ru3(CO)12 and chiral diiminodiphosphines for the asymmetric transfer hydrogenation of ketones

The chiral Ru cluster-based catalyst systems generated in situ from Ru3(CO)12 and chiral diiminodiphosphine tetradentate ligands effected asymmetric transfer hydrogenation of propiophenone in 2-propanol, leading to 1-phenyl-1-propanol in 94% yield and with 96% ee.     

Enantioselective addition of diethylzinc to aldehydes catalyzed by monosubstituted [2.2]paracyclophane-based N,O-ligands: remarkable cooperative effects of planar and central chiralities

Diastereomeric monosubstituted [2.2]paracyclophane-based N,O-ligands, which unite the planar and central chiral elements, were optimized for the enantioselective diethylzinc addition to aldehydes. (S)-1-{(S_p)-[2.2]Paracyclophan-4-yl}methyl-2-pyrrolidine-α,α-diphenylmethanol (S_p,S)-3 catalyzed the addition to give (R)-1-phenyl-1-propanol in a high yield and with a good enantioselectivity (91% ee).     

First catalytic enantioselective synthesis of the cocaine abuse therapeutic agent (S)-(+)-1-(4-{2-[bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol

(S)-(+)-1-(4-{2-[Bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol, which is a promising candidate as a cocaine abuse therapeutic agent, is prepared in several steps. The key asymmetric step is the catalytic enantioselective addition of dimethylzinc to either 2-chloro or 2-bromoacetophenone catalyzed by the use of different chiral isoborneolsulfonamide ligands in the presence of titanium tetraisopropoxide. The synthesis of a new isoborneolsulfonamide ligand bearing a trifluromethyl substituent and its use in this addition is also presented.     

(5R,6R)-6-苯基-5-(苯磺酰基乙酰基)二环[2.2.1]-2-庚烯的合成及结构表征

报道了一种制备4-苯基-1-苯磺酰基-3-丁烯-2-酮的新合成方法. 4-苯基-3-丁烯-2-酮与溴化试剂Ph₃P^＋CH₂CH₂- COOHBr 作用, 得到1-溴-4-苯基-3-丁烯-2-酮, 不经分离直接与苯亚磺酸钠发生亲核取代反应, 得到4-苯基-1-苯磺酰基-3-丁烯-2-酮. 将此反应产物作为亲双烯体与环戊二烯在手性钛金属催化剂催化下进行不对称Diels-Alder反应, 得到了＞99% ee 的环加成产物(5R,6R)-6-苯基-5-(苯磺酰基乙酰基)二环[2.2.1]-2-庚烯. 用X衍射法对产物的晶体结构进行了测定, 讨论了反应机理, 通过元素分析, NMR, MS对产物的结构进行了表征.     

The reactions of 4-dicyanomethylene-2-phenyl-4H-1-benzopyran and some benzologs with nucleophiles

4-Dicyanomethylene-2-phenyl-4H-1-benzopyran (1) reacts with primary amines under mild conditions to give 4-imino-3-alkyl-5-alkylimino-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]-pyridine derivatives which, in turn, are hydrolyzed with acid to 4-imino-3-alkyl-2-phenyl-3,4-dihydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. When more vigorous conditions are employed for the reactions of 1 with primary amines, Dimroth rearrangements take place and the products are derivatives of 4-alkyl- (or aryl)amino-5-alkyl- (or aryl)imino-2-phenyl-5H-[1]benzopyrano-[3,4-c]pyridine. The latter compounds are hydrolyzed by acid to the corresponding 5-pyridone derivatives. The reaction of 1 with piperidine gives 2-phenyl-4-piperidyl-5H-[1]benzopyrano-[3,4-c]pyridin-5-one. Sodium methoxide reacts with 1 to give 3-cyano-2-methoxy-4-(2-hydroxyphenyl)-6-phenylpyridine. Two benzologs of 1 have been allowed to react with primary and secondary amines and the products are analogous to those obtained from 1 .     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

2-Polyfluoroalkylchromones. 8. 2-Trifluoromethyl- and 6-nitro-2-trifluoromethylchromones in reactions with amines

The reactions of 6-nitro-2-trifluoromethylchromone with benzylamine, ethanolamine, and aniline afforded 3-benzyl(2-hydroxyethyl,phenyl)amino-4,4,4-trifluoro-1-(2-hydroxy-5-nitrophenyl)but-2-en-1-ones, respectively, whereas the reactions with ethylenediamine and diethylenetriamine gave rise to 5-(2-hydroxy-5-nitrophenyl)-7-trifluoromethyl-2,3-dihydro-1H-1,4-diazepine and 5-(2-hydroxy-5-nitrophenyl)-7-trifluoromethyl-1,4,8-triazabicyclo[5.3.0]dec-4-ene, respectively. Morpholine added at the double bond of 2-trifluoromethyl- and 6-nitro-2-trifluoromethylchromones to form 2-morpholino-2-trifluoromethylchroman-4-one and its 6-nitro-substituted analog, respectively, whereas piperidine reacted only with 2-trifluoromethylchromone to yield 2-piperidino-2-trifluoromethylchroman-4-one.     

The influence of ligand side chain on the enantioselectivity of Lewis acid catalyzed Diels-Alder reactions

The enantioselective Lewis acid-catalyzed Diels-Alder reaction of 3-(2-propenoyl)-1,3-oxazolidin-2-one 8 with cyclopentadiene was examined using a series of chiral mox ligands 2-6, deferring in the side chain at 2-position of the chiral oxazoline and in the nature of the substituent at the chiral center (4-position) of the oxazoline ring, and a combination of N-[(1R)-2-chloro-1-phenylethyl]-2-[(4R)-4-phenyl-4,5-dihydrooxazol-2-yl]butyramide 2-MgI(2)-I(2) was the most efficient catalyst.     

Conversion of 2-amino-3-phenyl-4-quinolone to 1H-2,3-dihydro-2,9-dioxo-10-phenylimidazo[1,2-a]quinoline

1H-2,3-Dihydro-2,9-dioxo-10-phenylimidazo[1,2-a]quinoline has been obtained from 2-amino-3-phenyl-4-quinolone by acylation with chloroacetyl chloride and cyclization of the intermediate 2-di(chloroacetyl)amino-3-phenyl-4-chloroacetoxyquinoline. The reaction of the latter with morpholine was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 388–390, March, 1990.