Zur Reaktionsweise von Enaminen mit Cyclopropenonen V. Einsatz von β-Carbonyl-enaminen

Diphenylcyclopropenone ( 10 ) was heated with five different β-carbonyl-enamines, namely 4-pyrrolidino-pent-3 E-en-2-one ( 12 ), 4-dimethylamino-pent-3E-en-2-one ( 13 ), 4-dimethylamino-but-E-en-2-one ( 14 ), 3-dimethylamino-1-phenyl-prop-E-en-1-one ( 15 ) and ethyl 3-pyrrolidino-isocrotonate ( 16 ). The resulting reactions were more sluggish than those of 10 with ordinary enamines. The main reaction (between 10 and 69% yield) was in all cases a ‘C, N-insertion’. The major products were: from 12 : an inseparable mixture of 4-methyl-6-oxo-2,3-diphenyl-hepta-2E, 4E-dienoic acid pyrrolidide ( 17 ) and its 2Z, 4E-stereomer ( 18 ); from 13 : 4-methyl-6-oxo-2, 3-diphenyl-hepta-2E-dienoic acid dimethylamide ( 19 ) and its 2Z, 4E-stereomer ( 20 ); from 14 : 6-oxo-2, 3-diphenyl-hepta-2E, 4E-dienoic acid dimethylamide ( 21 ); from 15 : 6-oxo-2,3,6-triphenyl-hexa-2E, 4E-dienoic acid dimethylamide ( 22 ); and from 16 : 5-ethoxycarbonyl-4-methyl-2, 3-diphenyl-penta-2E, 4E-dienoic acid pyrrolidide ( 23 ) and its 2Z, 4E-stereomer ( 24 ). The constitutions of 17 to 24 were derived mainly from spectral properties. For these products the E-configuration at the 4,5-double bond was assigned on the assumption that the insertion of the side-chain (cyclopropenone carbons) between the enamine carbon and nitrogen atoms occurred with retention of configuration, as had been concluded earlier. This was confirmed in the cases of 21 and 22 by the trans-coupling between H? C(4) and H? C(5) in the ¹H? NMR. spectrum, the educts ( 14 and 15 ) having the E-configuration. The configurational difference between the stereomeric products 17 / 18 , 19 / 20 and 23 / 24 was, therefore attributed to the 2,3-double bond. This was confirmed by aqueous acid treatment in the case of the pair 19 / 20 : The 2E-configuration for 19 followed from its conversion to 4-acetonyl-4-methyl- 2,3-diphenyl-isocrotonolactone ( 25 ) and the 2Z-configuration of 20 by its conversion first to a mixture ol two diastereomers of (presumably) 1-acetyl-4-dimethylaminocarbonyl-2-methyl-3- phenyl-l,4-dihydronaphthalene ( 27a ) and then, under more drastic conditions, to 6-methyl-11H-benzo[a]fluorene ( 26 ).The structures of 25 and of 26 were derived from their spectral properties, and that of the 27a -mixture was made probable by the plausibility of its intermediacy on the way to 26 . A pathway for the conversion of 20 to 27a (scheme 3) and of the latter to 26 (scheme 4)is proposed. In the case of the reaction of 10 with 12 , two stereomeric basic by-products were isolated (combined yield 150/,). Their structures as traw- and cis-4-acetonyl-4,5-diphenyl-3-pyrrolidinocyclopent-2-en-ones ( 30 and 31 ) were deduced from their spectral properties and from those of their hydrochlorides 32 and 33 . The enamino-ketone function was found to be resistant to a number of reagents, among which were excess sodium borohydride, which converted 30 to the secondary alcohol 34 , and excess methyllithium, which converted 31 to the tertiary alcohol 35 . A mechanism (called ‘rearrangement’) is proposed (scheme 5) for the formation of the enaminoketones (such as 30 and 31 ), which proceeds via the same ammonio-enolate intermediate ( 36 ) which plays a role in the formation of the major products, the amides (such as 17 to 24 ). It is suggested (scheme 6) that the 3-membered ring of the ammonio-enolate 40 may open in three ways, one of which leads to the amides and another to the enamino-ketones.     

Highly Diastereoselective,Biogenetically Patterned Synthesis of (+)‐(1S,6R)‐Volvatellin (=(+)‐(4R,5S)‐5‐Hydroxy‐4‐(5‐methyl‐1‐methylenehex‐4‐en‐2‐ynyl)cyclohex‐1‐ene‐1‐carbaldehyde)

The synthesis of volvatellin ( 4a ), previously isolated from a herbivorous marine mollusk, was achieved with high diastereoselectivity from putative dietary oxytoxin‐1 ( 2 ). A biogenetically patterned carbonyl‐ene route was chosen, proceeding from 2 predominantly via the trans cyclization product 3 without the use of enzymes. This challenges the involvement of enzymes in the formation of 4a in nature. The optical purity and absolute configuration (1S,4S,6R), assigned to 3 from high‐field ¹H‐NMR examination of its Mosher (MTPA) esters 6 , was retained on its chemical conversion to (+)‐(1S,6R)‐configured 4a and is consistent with the (4S) configuration previously established for caulerpenyne ( 1 ).     

Stereochemistries of electron impact induced hydrogen abstraction reactions proceeding through 6-membered transition states

The stereochemistries of nine electron-impact induced eliminations proceeding from derivatives of the cis-4-t-butyl system have been determined. The predominant cis elimination observed in every case is consistent with the substantial integrity of the cyclohexyl ring prior to fragmentation, and with a cyclic transition state for hydrogen abstraction. The stereochemistries of electron impact induced eliminations from 11 derivatives of the trans-4-t-butylcyclohexyl system exhibit a dichotomy. The predominatn trans stereochemistry observed in six electron impact induced eliminations, and the nonstereospecific electron impact induced dehydration of trans-4′-t-butylcyclohexyl-ethanol are consistent with nonconcerted elimination from a chair-like cyclohexyl ring. Conversely, the McLafferty rearrangement of trans-4′-t-butyl-cyclohexyl-2-propanone proceeds nonstereospecifically. trans-4-t-Butylcyclohexyl acetaldehyde, 2-methyl-3-(trans-4′-t-butylcyclohexyl)-1-propane and trans-4-t-butylcyclohexyl-S-methyl xanthate exhibit predominant cis McLafferty rearrangement stereochemistry. This result may be due to fragmentation through boat-like conformers in these compounds.     

Die Synthese von 4-Alkylchinuclidinen. Chinuclidinreihe, 11. Mitteilung

The syntheses of 4-methyl-, 4-ethyl-, 4-isopropyl-and 4-t-butylquinuclidine are described. The key step in the synthesis of 4-t-butylquinuclidine involves a modified Koch-Haaf reaction leading from a δ-amino-tert. alcohol to an ester of the homologous acid.     

Synthesis of optically active 2-benzyldihydrobenzopyrans for the hypoglycemic agent englitazone

Two syntheses of some optically active 2-benzyl-2,3-dihydro-4H-benzopyrans and benzopyran-4-ones are presented. An asymmetric synthesis starting from D- and L-phenylalanine was used to provide both enantiomers of 2-benzyl-6-(methoxycarbonyl)-2,3-dihydro-4H-benzopyran-4-one 19. Phenylalanine was diazotized in aqueous sulfuric acid to 2-hydroxy-3-phenylpropionic acid 6 which was converted in four steps to 1-bromo-2-(4-methoxycarbonylphenoxy)-3-phenylpropane 11. (4R,S)-Benzamido-2-benzyl-2,3-dihydro-6-(methoxycarbonyl)-4H-1-benzopyran-4-carboxylic acid 16 was prepared from 11 by amidoalkylation with α-hydroxyhippuric acid in methanesulfonic acid solution followed by spiroalkylation to (4R,S)-2-benzyl-2,3-dihydro-6-(methoxycarbonyl)spiro[4H-benzopyran-4,4′-2′-phenyloxazolidin]-5′-one 15. After the phenyloxazolidin-5-one 15 was hydrolyzed to the spirobenzamido carboxylic acid 16 , oxidative decarboxylation with sodium hypochlorite yielded optically active 2-benzyl-6-(methoxycarbonyl)-2,3-dihydro-4H-benzopyran-4-one 19. The ketone in 19 was reduced by hydrogenation over palladium on carbon to a methylene group and the ester was converted to the aldehyde to give both isomers of the desired intermediate 2-benzyl-6-(formyl)-2,3-dihydro-4H-benzopyran 25. The second synthesis relied on an enzymatic hydrolysis of ethyl 2,3-dihydrobenzopyran-2-carboxylate 27 with the lipase from P. fluorescens to provide the desired 2R-ester. The ester group in (R)- 27 was converted to the triflate (R)- 29. Displacement of the triflate group with phenylmagnesium bromide and cuprous bromide as catalyst gave 2R-benzyl-2,3-dihydro-4H-benzopyran (R)- 30. Formylation of (R)- 30 provided 2R-benzyl-6-(formyl)-2,3-dihydro-4H-benzopyran (R)- 25 identical with that from the first synthesis. These optically active intermediates are used in the preparation of the hypoglycemic agent englitazone.     

Structures and Bonding Situation of Iron Complexes of Group‐13 Half‐Sandwich ECp* (E = B to Tl) Based on DFT Calculations

Quantum chemical calculations at the BP86 level with various basis sets (SVP, TZVPP, and TZ2P+) were carried out for the Fe(CO)₄ of group‐13 half‐sandwich ECp* [Fe(CO)₄‐ECp*] ( Fe4‐E ) (E = B to Tl). The chemical bonding of the Fe(CO)₄‐ECp* bond was analyzed with charge‐ and energy decomposition methods. The calculated equilibrium structures of complexes Fe4‐E show that the ligands ECp* are bonded in an end‐on way to the fragment Fe(CO)₄ in Fe4‐E with E = B to Ga. The compound Fe4‐In has a distorted end‐on ligand InCp*. In contrast, Fe4‐Tl has a side‐on bonded ligand TlCp*. The calculated bond dissociation energies (BDEs) suggest that the bond in the iron group‐13 half‐sandwich complexes Fe4‐E decreases from Fe4‐B to Fe4‐Tl . Natural bond orbital (NBO) analysis of the bonding situation reveals that the Fe(CO)₄←ECp* donation in Fe4‐E comes from the σ lone‐pair orbital of ECp*. Bonding analysis indicates that the ligand ECp* in complexes are strong σ donors and the NOCV pairs of the bonding show small π‐back donation from the Fe(CO)₄ to the ECp* ligands.     

The influence of terminal chlorine on the mesomorphic properties of new thiobenzoates containing two and three benzene rings

New liquid crystalline chloro‐substituted thioesters containing two and three benzene rings have been synthesized. 4‐Chlorophenyl 4‐n‐alkoxythiobenzoates and 4‐chlorophenyl 4‐n‐alkoxybenzoyloxy‐4′‐thiobenzoates are referred to as nO.SCl and nO.OSCl, respectively, where n varies from 4 to 16 for nO.SCl, from 4 to 10 for nO.OSCl and denotes the number of carbon atoms in the alkyl chain. Their mesomorphic properties were investigated by means of polarizing optical microscopy, differential scanning calorimetry, transmittance light intensity and X‐ray diffraction measurements. The nO.SCl homologous series possesses smectic A (SmA) and nematic (N) phases for n?=?4, 5, 6 while higher homologues have only an enantiotropic SmA phase. Those from the nO.OSCl homologous series have enantiotropic N and SmA phases and higher transition temperatures. The range of the N phase decreases, and of the SmA increases, with the elongation of the alkoxy chain in the nO.OSCl homologous series. The effect on mesomorphic behaviour of terminal alkoxy chain lengthening and replacement by chlorine on the other side of the molecule is discussed.     

Imidazolyl derivatives of the thiochroman ring

The synthesis of 2-(1H-imidazol-1-yl)-4H-1-benzothiopyran- 4 -ones 3 from 3-bromo-4H-1-benzothiopyran-4-ones 1 and imidazole is described. The reaction of 1 with secondary amines gives the corresponding 3 -amino-thiochromones 11. Compounds 3 can be oxidized to the sulfones 4 from which the thiochromanols 5 and thiochromene 7 can be easily obtained. 3-Bromo-2,3-dihydro-6-methyl-4H-1-benzothiopyran-4-one 12 and imidazole led by dehydrohalogenation to thiochromone, while the ketal 13 rearranged to benzo[b]thiophene 16.     

Symbiosis between Microorganisms from Kombucha and Kefir: Potential Significance to the Enhancement of Kombucha Function

Gluconacetobacter sp. A4 (G. sp. A4), which had strong ability to produce d-saccharic acid 1, 4 lactone (DSL), was the key functional bacteria isolated from the kombucha preserved. This paper investigated the interaction between G. sp. A4 and ten different strains of lactic acid bacteria (LAB) obtained from kefir. The result suggested that the LAB promoted DSL production of G. sp. A4 to different extents, ranging from 4.86% to 86.70%. Symbiosis between G. sp. A4 and LAB was studied. LAB’s metabolites, xylitol, and acetic acid, were utilized by G. sp. A4, and it promoted the growth of G. sp. A4 and yield of DSL. Therefore, in developing starter cultures for kombucha fermentation process, a mixed flora of LAB and G. sp. A4 would be the optimal combination.     

Simple Synthesis of 4‐Substituted 1(2H)‐Isoquinolinones via Electrophilic Trapping of Lithiated Mono‐ and Dianion Precursors

Synthetic routes have been developed to access 4‐substituted 1(2H)‐isoquinolinones from readily available precursors. This is achieved via electrophilic trapping of di‐ and monolithium anions derived from alkyllithium exchange of 4‐bromo‐1(2H)‐isoquinolinones and corresponding 4‐bromo‐1‐methoxyisoquinolines, respectively. Products derived from the latter are then hydrolyzed to the target 4‐substituted 1(2H)‐isoquinolinones. The methodology has potential application to access 4‐substituted 1(2H)‐isoquinolinones with additional substituents in either ring.     

Spectrophotometric Method for the Determination of Polyphenol Oxidase Activity by Coupling of 4-tert-Butyl-o-Benzoquinone and 4-Amino-N,N-Diethylaniline

ABSTRACT

We describe a spectrophotometric analytical method for the detection of polyphenol oxidase activity in an aqueous solution. The assay is based on the coupling reaction between 4-tert-butyl-o-benzoquinone, generated during the enzyme-catalyzed reaction acting on 4-tert-butylcatechol, and the aromatic amine, 4-amino-N,N-diethylaniline to yield a blue adduct (λ_max 625 nm). This blue adduct exhibited spectral features different from the parent phenol and from the o-quinone. Polyphenol oxidase activities extracted from potatoes, and sunflower seedlings were assayed. The proposed method presents several advantages over the spectrophotometric measurement of 4-tert-butyl-o-benzoquinone. The duration of the linear period was increased, allowing a better determination of its value. The molar extinction coefficient of the blue adduct was higher than that of the 4-tert-butyl-o-benzoquinone; therefore the limitation i8542948 by the comparatively low ? for the 4-tert-butyl-o-benzoquinone is overcome. This is of great importance when considering the inertness of the 4-tert-butyl-o-benzoquinone towards some common coupling agents such as 3-methyl-benzothiazolin-2-one hydrazone.     

Spectroscopic and spectrometric studies of anion recognition with calix[4]pyrroles in different reaction conditions

The binding studies of calix[4]pyrroles (1–6) with fluoro, chloro, bromo, iodo and sulphato anions generated from normal-tetrabutylammoniumfluoride, normal-tetrabutylammoniumchloride, normal-tetrabutylammoniumbromide, normal-tetrabutylammoniumiodide, and normal-tetrabutylammoniumsulphate respectively were investigated by electrospray ionization mass spectrometry (ESI-MS) in dichloromethane–acetonitrile in negative ion mode. The efficacy of a particular calix[4]pyrrole to bind with anions was found maximum at low cone voltage of the instrument, at high cone voltage the binding was suppressed due to removal of anion from the cavity of the macrocycles. The binding strength was found inversely proportional to the size of anion for a particular calix[4]pyrrole. The fragmentation pattern of calix[4]pyrrole was observed at higher cone voltage of ESI-MS and was interpreted. The association constants of calix[4]pyrroles and anions obtained from electronic transition studies were in good agreement with that observed from ¹H NMR titration studies.     

Imidazolyl derivatives of the chroman ring 3

The synthesis of 2-methyl-3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones 4 is described starting from 2-acetoxybenzoyl chlorides and 1,2-dimethylimidazole. Chromones 4 undergo alkaline ring opening to the corresponding 1-(2-hydroxyphenyl)-2-(1-methyl-1H-imidazol-2-yl)ethenols 5 which give ring closure to 2-substituted 3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones or 2,3-dihydro-3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones. The corresponding chromanols and chromenes can be easily obtained from chromones 4 .     

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 .     

Chemistry of O-Benzoquinones and Masked O-Benzoquinones I. Diels-Alder Reactions of O-Benzoquinones with Dimethyl Acetylenedicarboxylate and Phenylacetylene

Diels-Alder reactions of six o-benzoquinones with dimethyl acetylenedicarboxylate has been examined. The yields of adducts vary with the natures of the o-benzoquinones, 3,4-Di-n-propyl-(1c), 3,6-di-n-propyl (1d). 3. 4-diallyl-(1e) and 3, 6-diallyl-o-benzoquinone (1f) are found to give bicyclic a-diketones exclusively without the formation of 1,4-dioxine derivatives, the yields ranging from 20 to 70%. In the case of 4, 5-dimethoxy-o-benzoquinone, dimethyl 4, 5-dimethoxyphthalate is produced in 42% yield, presumably derived from the decomposition of the corresponding initially formed α-diketone. 3, 6-Di-n-propyl-4, 5-dimethoxy-o-benzoquinone deteriorates without addition to dimethyl acetylenedicarboxylate upon heating. The additions of o-benzoquinones 1c , 1d and 1f to phenylacetylene are also studied. The yields of adducts, α-diketones, range from 23% to 82%.     

Photochemical reactivity of α,β-unsaturated δ-lactams: Synthesis of seco-steroids. Photochemical reactions. XIII [1]

The UV. irradiation of 17 β-hydroxy-2-aza-4-androsten-3-one (1) , N-methyl-17 β-hydroxy-2-aza-4-androsten-3-one (3) , 17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (2) and N-methyl-17 β-hydroxy-4-aza-5 β-androst-1-en-3-one (4) , gives rise to 1,10-seco (from 1 and 3 ) and 5, 10-seco (from 2 and 4 ) steroids.     

Die Strukturdynamik von Pentadienylmetall-Verbindungen mit endständiger Alkyl-Gruppe: zugleich «stereoselektive» und «stereodefensive» Synthese eines natürlichen Riechstoffes

Structural Dynamics of Pentadienyl Metal-Compounds Bearing a Terminal Alkyl Substituent: Both ‘Stereoselective’ and ‘Stereodefensive’ Synthesis of a Natural Perfume . The (2Z, 4E)-, (2E, 4Z)- and (2E, 4E)-isomers of 2,4-decadien-1-ol (5) have been obtained with high and predictable stereochemical homogeneity starting from both (Z)- and (E)-1, 4-decadiene. These hydrocarbons were hydroxylated in a reaction sequence consisting of metallation (by means of s-butyllithium or butyllithium/potassium-t-butoxide, giving rise to organometallic intermediates of specific conformation), dimethoxyborylation and oxidation. The different decadienols as well as (2E, 4Z)-2, 4-undecadien-1-ol were converted into the isovalerates, the ester derived from (2E, 4Z)-2, 4-decadien-1-ol being a natural flavor component.     

Synthesis of hexa-, tetra-, and dihydroxanthene derivatives from salicylaldehyde aminals

Salicylaldehyde aminals react with cyclohexanone upon heating to form tetrahydroxanthene derivatives. The structure of one of these derivatives,viz., 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene, was established by X-ray diffraction analysis. The scheme of the reaction was suggested, which involves cycloaddition of intermediateo-methylenequinone (from aminal) and enamine (from cyclohexanone). The reactions of salicylaldehyde aminals with enamines that formed from cyclohexanone can successively afford derivatives of hexahydroxanthene, tetrahydroxanthene, and dihydroxanthene. Procedures were developed for the synthesis of these compounds.N-Substituted 4a-amino-7-nitro-1,2,3,4-tetrahydro-4aH-xanthenes were also prepared by the reactions of dialkylammonium 2-formyl-4-nitrophenoxides with the above-mentioned enamines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 959–965, May, 1999.     

Synthesis and Self‐Aggregation of Enantiopure and Racemic Molecular Tweezers Based on the Bicyclo[3.3.1]nonane Framework

A pair of molecular tweezers (syn‐ 4 ) that consists of quinoline and pyrazine units fused to a bicyclic framework is presented. The tweezers were synthesised both as a racemic mixture (rac‐ 4 ) and an enantiomerically pure form ((R,R,R,R)‐ 4 ) starting from either racemic or enantiomerically pure bicyclo[3.3.1]nonane‐2,6‐dione ( 3 ). Homochiral dimers were observed in the solid state for rac‐ 4 . The self‐association of both rac‐ 4 and (R,R,R,R)‐ 4 was studied in solution. A weak self‐association constant in CDCl₃ was estimated by ¹H NMR spectroscopic dilution titration experiments in both cases, following several proton resonances. For this purpose, a general normalisation model for the accurate determination of association constants from multiple datasets was developed. In contrast to the solid state, no diastereomeric discrimination was observed for rac‐ 4 in solution.     

Convergent Versus Divergent Three-Step Synthesis of the First (4-Aminophenoxy)alkanoic Acid–Based Tripodal Melamines

Starting from N-(4-hydroxyphenyl)acetamide (Paracetamol, convergent approach) or from cyanuric chloride in reaction with 4-aminophenol (divergent approach), two synthetic routes toward novel tripodal N-substituted melamines as s-triazine derivatives of (4-aminophenoxy)acetic acid or of 4-(4-aminophenoxy)butyric acid are comparatively defined. The key steps consist of Williamson etherification of N-masked forms of 4-aminophenol and acidic hydrolysis of the N- and/or O-protected (4-aminophenoxy)alkanoic segments.