bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conversion of aziridine‐2‐carboxylic esters into 2H‐azirine‐2‐carboxylic esters
Authors: Legters Johan , Thijs Lambertus , Zwanenburg Binne 
Published: September 2010

AbstractAziridine‐2‐carboxylic esters 1 were converted into 2H‐azirine‐2‐carboxylic esters 4 in two steps. Treatment of 1 with tert‐butyl hypochlorite in ether gave smooth N‐chlorination. Reaction of N‐chloroaziridines 2 with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) or 1,4‐diazabicyclo[2.2.2]‐octane (DABCO) gave 2H‐azirine‐2‐carboxylic esters 4 in moderate yields, with concomitant formation of aziridines 1. Aziridines 1 could readily be N‐brominated with N‐bromosuccinimide. Treatment of N‐bromoaziridines 3 with base, however, did not lead to azirine formation. N‐Halogenated aziridines 2 and 3 exist as mixtures of invertomers, which slowly interconvert in solution.
Synthesis and spectroscopic characterization of the doubly locked 9E,11Z retinal model systems 7E,13E‐11,19–10,20‐dimethanoretinal and its 13Z isomer
Authors: Groesbeek M. , Robijn G. W. , Lugtenburg J. 
Published: September 2010

Abstract7E,13E‐11,19‐10,20‐dimethanoretinal (1) and its 13Z isomer 2 were prepared from β‐ionone, using the novel synthon 2‐(diethoxyphosphinyl)‐5,5‐dimethoxyhexanenitrile. This synthon was also used to prepare 7E,9E,13E‐10,20‐methanoretinal (3) and its 13Z isomer 4 in high yield, starting from β‐ionone. Spectroscopic analysis (mass, 1H and 13C NMR and UV/Vis) of these compounds is discussed. The introduction of the methano bridges leads to minimal steric and electronic changes. The photostationary state reached from 1 and 2 has the 13Z form 2 as the main constituent. This is one of the very few with a Z form as the main constituent of the photostationary state. 1 and 2 are very sensitive to acid‐catalyzed isomerization of the 13‐C14‐C double bond. The presence of the 11,19‐methano bridge is responsible for this efficient Z‐E isomerization.
Towards a rational design of resolving agents. Part IV. Crystal packing analyses and molecular mechanics calculations for five pairs of diastereomeric salts of ephedrine and a cyclic phosphoric acid
Authors: Leusen Frank J. J. , Slot Hubert J. Bruins , Noordik Jan H. , van der Haest Albertus D. , Wynberg Hans , Bruggink Alle 
Published: September 2010

AbstractDetailed structural studies of five pairs of diastereomeric salts of ephedrine and halogen‐substituted chiral cyclic phosphoric acids indicate a correlation between the efficiency of the resolution process and the lattice energy difference between the salts of a diastereomeric pair. Attempts to model such a correlation quantitatively by lattice energy calculations with Molecular Mechanics (MM) methods have not yet been successful. The MM techniques proved unable to reproduce the crystal structures with sufficient accuracy. However, the results of the analyses qualitatively support the presumed correlation, and show that the five resolutions are directed by different acid‐base interactions in the hydrophobic layers.
Synthesis of 5β‐alkylthebaines, 5β‐alkyl‐10α‐ethylthebaines and 5β,10α, 10β‐triethylthebaine; Diels‐Alder reactions to 5β‐alkyl‐ and 5β‐alkyl‐10α‐ethyl‐6α, 14α‐ethenoisomorphinans (chemistry of opium alkaloids, Part XXXVI
Authors: Woudenberg R. H. , Oosterhoff B. E. , Lie T. S. , Maat L. 
Published: September 2010

Abstract5β‐Ethylthebaine (3), together with 5β‐butylthebaine (4), was obtained from thebaine (1) after reaction with butyllithium and ethyl iodide. With butyllithium and diethyl sulfate, thebaine yielded 5β‐ethylthebaine (3), 5β, 10α‐diethylthebaine (5), and 5β, 10α, 10β‐triethylthebaine (6). The ratio of the compounds (3:4 and 3:5:6) depended on the excess of reagents used. Employing the reversed sequence of addition of reagents, that is, first diethyl sulfate and then butyllithium, we prepared 5β, 10α‐diethylthebaine (5) and 5β‐methyl‐10α‐ethylthebaine (8) from 5β‐ethylthebaine (3) and 5β‐methylthebaine (7), respectively. These alkylation reactions are discussed in terms of Pearson's hard‐soft acid‐base theory.Diels‐Alder reaction of 3, 5 and 8 with ethyl acrylate gave exclusively 7α‐substituted 6α, 14α‐ethenoisomorphinans 9, 10 and 11, respectively. Esters of the cycloadducts 9 and 11 were converted into their tertiary alcohols 12 and 13 with methylmagnesium bromide. The 3‐methoxy group in 12 and 13 was hydrolyzed with a solution of potassium hydroxide in 1,2‐ethanediol to give phenols 14 and 15.
Dual behaviour of sepiolites as single electron acceptors or Lewis acids: Reactivity of two α‐acetoxystyrenes adsorbed on a iron(III)‐exchanged sepiolite
Authors: Baldoví Vicenta , Corma Avelino , García Hermenegildo , Iborra Sara , Miranda Miguel A. , Primo Jaime 
Published: September 2010

AbstractIron(III)‐exchanged sepiolites exhibit dual behaviour as catalysts in the reactions of α‐acetoxystyrenes 1a,b; operating as Lewis acids (to give 2–5) in thermolysis reactions under reduced pressure or as single‐electron acceptors (to give 7) in photolysis under aerobic conditions.
Palladium‐catalyzed allylation of α‐hydroxy acids
Authors: Moorlag Henk , de Vries Johannes G. , Kaptein Bernard , Schoemaker Hans E. , Kamphuis Johan , Kellogg Richard M. 
Published: September 2010

AbstractMandelic and lactic acids are converted to the 1,3‐dioxolan‐4‐ones by treatment with acetone dimethyl acetal. Deprotonation followed by treatment with an allyl acetate and a catalytic amount (1 mol %) of palladium catalyst afforded the allylated dioxolanones, which could be hydrolyzed to the corresponding α‐allyl α‐hydroxy acids. The lithium enolate of the dioxolanone of mandelic acid was also coupled with methallyl, cinnamyl, geranyl and (E)‐1‐methyl‐2‐butenyl acetates. The zinc enolate of the dioxolanone of lactic acid reacted smoothly with allyl acetate in a catalyzed reaction whereas no detectable reaction was observed when the lithium enolate was used. This appears to be the result of complications arising from the enhanced basicity of the lithium compared to zinc enolate.Various attempts were made to achieve enantioselectivity using chiral ligands on the palladium catalyst. The zinc enolates were found to provide better results although the enantioselectivity was only modest, about 30% enantiomeric excess being the best result obtained. Chiraphos proved to be the best optically active ligand of a variety tested.
Preparation of bicyclic boroxazolidones from aziridine‐2‐carboxylic esters
Authors: Legters Johan , Thijs Lambertus , Zwanenburg Binne 
Published: September 2010

AbstractAziridine‐2‐carboxylic esters 1 were converted into bicyclic boroxazolidones 3 in a three‐step sequence. First, the ester groups were hydrolyzed either by sodium hydroxide or with lithium hydroxide in methanol. The salts thus obtained were acidified with acetic acid or through a weakly acidic ion‐exchange resin. Treatment of the zwitterionic aziridine‐2‐carboxylic acids 2 with triethyl‐borane in hexane gave boroxazolidones 3 in high yields. Boroxazolidone 3g, obtained from optically active 1g was reconverted to the starting material by 8‐hydroxyquinoline without any loss of optical activity.
SYNthesis LIBrary, an expert system for chemical‐reaction knowledge‐base management
Authors: Chodosh Daniel F. , Hill John , Shpilsky Lev , Mendelson Wilford L. 
Published: September 2010

AbstractSYNLIB (SYNthesis LIBrary) is an expert system which allows laboratory scientists to rapidly and interactively search databases of chemical reaction information. SYNLIB is fully supported on personal computer and RISC workstation platforms and requires minimal computer expertise on the part of the chemist. By encouraging hands‐on access to information, SYNLIB allows complex chemical synthesis concepts to be presented directly to the practicing laboratory scientist. SYNLIB searching enables the user to query chemical reaction knowledge bases for matches to combinations of structural and non‐structural chemical questions. We discuss the design considerations for expert systems specifically for chemists and present an analysis of the chemical‐reaction information available from the published literature. A search for the formation chemistry of functionalized α,β‐unsaturated ketones is used to illustrate the search strategies available.
Generalization and representation of synthesis pathways in the COSYMA system
Authors: Hamm P. , Jauffret P. , Kaufmann G. 
Published: September 2010

AbstractA new approach of computer‐assisted design of organic synthesis is proposed with the COSYMA system. It is based on the similarity between the target molecule and an intermediate or the final product of a well‐known synthesis pathway. Similarity between two molecules is defined as equality of the structures obtained by applying generalization rules to these two molecules. Similarity criteria are described, and associated generalization rules expressed. A new internal representation of synthesis pathways is also described, which fits COSYMA requirements, and consists of time‐independent structural and temporal parts. The temporal part describes variations of atom connectivity in the different synthesis steps.
Acetalation studies. Part IXΦ. Reaction of sucrose and some related sugars with acetone in the presence of iodine; a novel cleavage‐isopropylidenation methodψ
Authors: Verhart Cor G. J. , Caris Brigitte M. G. , Zwanenburg Binne , Chittenden Gordon J. F. 
Published: September 2010

AbstractAn efficient cleavage‐isopropylidenation reaction of sucrose, catalyzed by iodine, is described. Related D‐fructofuranosyl‐containing oligosaccharides, some common disaccharides and their individual monosaccharide units were treated in a similar manner to yield isopropylidenated monosaccharide derivatives. The reaction conditions are particularly mild and selective. Some mechanistic aspects of the procedure are also discussed.
Iodonium ion‐mediated glycosidations of phenyl selenoglycosides
Authors: Zuurmond H. M. , van der Klein P. A. M. , van der Meer P. H. , van der Marel G. A. , van Boom J. H. 
Published: September 2010

AbstractFully benzylated or benzoylated phenyl selenoglycosides can be activated by the promoters iodonium di‐sym‐collidine perchlorate (IDCP) or N‐iodosuccinimide and catalytic triflic acid (NIS/TfOH cat.). The potential of the iodonium ion‐mediated glycosidations of phenyl selenoglycosides is illustrated in the chemoselective synthesis of 1,2‐cis‐or 1,2‐trans‐linked disaccharides.
Sulfonation of [2.2]paracyclophane; structures and modes of formation of the products
Authors: van Lindert Helen C. A. , Koeberg‐Telder Ankie , Cerfontain Hans 
Published: September 2010

AbstractThe sulfonation of [2.2]paracyclophane (1) with (i) sulfur trioxide in the presence of various amounts of dioxane as moderator in dichloromethane as solvent, and (ii) in sulfuric acid containing 98.5 wt‐% H2SO4 acting both as reagent and solvent was studied. The introduction of the first sulfo group is rapid relative to the second one, which always enters only the non‐sulfo‐containing phenylene ring. The rate of sulfonation of 1 with SO3 greatly exceeds that of the acyclic analogue 1,2‐di(p‐tolyl)ethane (2). With 98.5 wt‐% H2SO4, the main product is the ps‐gem isomer, i.e., the 4,15‐disulfonic acid (83%) in addition to the ps‐ortho isomer, and smaller amounts of the ps‐meta and ps‐para isomers. With SO3 as reagent, the sulfo products are 1–4,15‐disulfonic anhydride, and the ps‐ortho, ps‐meta and ps‐para disulfonic acids. On using 4.0 equiv. of SO3, the main product is the 4,15‐disulfonic anhydride (87%). However, with increasing amounts of added dioxane, the yields of the three disulfonic acids increase at the expense of the 4,15‐disulfonic anhydride. Mechanisms for the formation of the sulfo products under the different reaction conditions are suggested and discussed. The relatively high degree of 4,15‐disulfonic anhydride formed in the sulfonation of 1–4‐sulfonic acid with SO3 in the absence of dioxane is explained in terms of intramolecular sulfonation.X‐ray crystal structures for potassium 1–4‐sulfonate and 1–4,15‐disulfonic anhydride were obtained. The former compound suffers from steric strain due to the forced close proximity of the sulfonate group and the C(2)H(2,1), whereas the additional 4,15‐SO2‐O‐SO2‐ bridge of the latter one leads (i) to a very significant strain with the nearest, i.e., the C(3)C(14) ethylene bridge, and (ii) induces some rotation of the two p‐phenylene moieties around the C(3)C(6) and C(11)C(14) axes in opposite directions, the C(4)C(15) interatomic distance being larger than that of the C(8)C(13).
Reactions of ω‐phenylalkenes with sulfur trioxide; sulfonation and Friedel‐Crafts type of cyclization
Authors: Schonk Ruud M. , Bakker Bert H. , Cerfontain Hans 
Published: September 2010

AbstractReactions of ω‐phenylalkenes1a‐31awith sulfur trioxide were studied in the temperature range −60 to 25°C using dichloromethane as solvent and 1.5 mol equiv. of dioxane as reactivity moderator. ω‐Phenylalkenes1a‐7areact just like simple alkenes: at low temperature, they yield the (thermally unstable) β‐sultones1b‐7band4c‐7c, which at 25°C are converted into the corresponding carbyl sulfates. Reactions of ω‐phenylalkenes8a‐10a, which have a ‐(CH2)3‐ linkage between the Ph and the C = C moieties, with 1.1 equiv. of SO3at −60°C yield very rapidly and quantitatively the 1‐(1‐sulfoalkyl)‐1,2,3,4‐tetrahydronaphthalenes8fand9f (= 10f). Reaction of ω‐phenylalkenes11aand12a, having a ‐(CH2)2‐ linkage between Ph and C = C, with 1.1 mol equiv. of SO3at − 60°C leads to quantitative and stereospecific formation of 1‐methyl‐1,2,3,4‐tetrahydronaphthalene ‐2‐sulfonic acids11hand12h, respectively. The 5‐(chlorophenyl)‐2‐pentenes13a‐16aclearly demonstrate the presence of β‐sultones13b‐16band13c‐16cas the sole initial products leading to the Friedel‐Crafts cyclization products13h‐16h. Reaction of 1,3‐diphenyl‐1‐propenes26aand27awith 1.5 equiv. of SO3at − 60°C quantitatively yields β‐sultones26cand27c, which upon raising the temperature to − 20°C, are slowly converted intotrans‐1‐phenylindane‐2‐sulfonic acid (34).Attempted intermolecular Friedel‐Crafts type of sulfoalkylation of arenes using β‐sultones as reagent failed. Reaction of, for example,trans‐4,5‐octanesultone with anisole instead led only to transfer sulfodeprotonation, to yield(E)‐4‐octene and 4‐methoxybenzenesulfonic acid. Mechanisms for the formation of the various products are suggested.
The influence of substituents on the geometry of the cyclopropane ring. VI The molecular and crystal structures of cyclopropanecarboxylic acid and cyclopropanecarbonyl chloride
Authors: de Boer J. S. A. M. , Stam C. H. 
Published: September 2010

AbstractCrystals of cyclopropanecarboxylic acid, C4H6O2, grown from the liquid are triclinic, space groupP1, a =8.6992(6),b= 8.8017(4),c= 6.6930(3) Å, α = 103.71(1), β = 103.93(1), γ = 66.49(1)° (171 K); Z = 4. The finalRfor 1649 independent observed reflexions [I > 3σ(I)] is 0.037. Crystals of cyclopropanecarbonyl chloride, C4H5OCl, grown from the liquid are monoclinic, space groupP21/m. a= 6.287(2),b= 7.092(2),c= 5.647(3) Å, β = 101.84(3)° (151 K); Z = 2. The finalRfor 446 independent observed reflexions is 0.042.The C=O groups in the molecules of both compounds are in the bisectings‐cisconformation. The distal bonds in the cyclopropyl rings have (average) lengths of 1.463(2) and 1.467(2) Å, the average vicinal bond lengths are 1.514(2) and 1.516(2) Å for the acid and the carbonyl chloride respectively (corrected for libration).
The isomerization of α‐pinene oxide with Brønsted and Lewis acids
Authors: Kaminska J. , Schwegler M. A. , Hoefnagel A. J. , van Bekkum H. 
Published: September 2010

Abstractα‐Pinene oxide (2) is a very reactive substrate which isomerizes rapidly under the influence of acid catalysts. A large number of products can be formed from a single intermediate. Selectivity to the industrially important campholenic aldehyde can be achieved with metal‐halogen compounds, especially zinc chloride and zinc bromide. A possible explanation for this behaviour is offered, stipulating a stabilized carbenium‐ion intermediate. Protonic catalysts are typically highly active but unselective. No evidence was found for the earlier reported selectivity to campholenic aldehyde with zeolite catalysts.
Enzymatic enantioselective ester hydrolysis by carboxylesterase NP
Authors: Smeets J. W. H. , Kieboom A. P. G. 
Published: September 2010

AbstractThe enzymatic hydrolysis of a series of carboxylic esters by carboxylesterase NP has been investigated in order to determine the scope and limitations of this enzyme. 2‐Substituted propionates were hydrolyzed with high enantioselectivity when an aromatic moiety was part of the 2‐substituent. Enantioselective hydrolysis could be accomplished with several 2‐arylpropionates, 2‐(aryloxy)propionates and N‐arylalanine esters. The propionate esters yielded propionic acids as (S) enantiomers, whereas the alanine esters yielded the (R) enantiomers. Without a 2‐aryl substituent, the enzymatic hydrolysis of the propionates occurred at a lower rate without acceptable enantioselectivity. In addition to 2‐substituted propionates, only a few other esters were hydrolyzed with high enantioselectivity by carboxylesterase NP, such as some prochiral disubstituted malonates. 1‐Phenylethyl acetate was the only substrate with chirality in the alcohol part of the ester that was found to be hydrolyzed enantioselectively.Carboxylesterase NP proved to be a powerful enzyme for kinetic resolution of propionate esters with an aromatic ring containing a 2‐substituent.
Intramolecular charge‐transfer fluorescence of 1‐phenyl‐4‐[(4‐cyano‐1‐naphthyl)methylene]piperidine (fluoroprobe) as a sensor for phase transitions in the solid state
Authors: Jenneskens Leonardus W. , Verhey Herman J. , van Ramesdonk Hendrik J. , Verhoeven Jan W. , van Malssen Kees F. , Schenk Henk 
Published: September 2010

AbstractAs evidenced by temperature‐dependent wide‐angle X‐ray diffraction (WAXD), the thermochromism of the continuous and time‐resolved (nanosecond time scale) fluorescence behaviour of 1‐phenyl‐4‐[(4‐cyano‐1‐naphthyl)methylene]piperidine (fluoroprobe) dissolved in octadecyl octadecanoate is shown to be a highly sensitive probe for a phase transition in the solid state occurring in the latter.
Synthesis of specifically stable‐isotope‐labeled l‐proline via L‐glutamic acid
Authors: Cappon J. J. , van der Walle G. A. M. , Verdegem P. J. E. , Raap J. , Lugtenburg J. 
Published: September 2010

Abstract(3,4‐13C2)‐L‐proline and (15N)‐L‐proline were prepared from the correspondingly labeled L‐glumatic acids via a single scheme in high yield and on a gram scale. The synthetic route is based on the ring closure of L‐glutamic acid to L‐5‐oxoproline and the selective reduction of the 5‐amide function, without interference with the 2‐carboxylate function and the asymmetric center. The selective reduction is effected by first converting the amide into the corresponding thioamide and subsequently reducing the thioamide to the amine using tributyltin hydride, in combination with protection and deprotection steps. In earlier work we described the preparation of L‐glutamic acid isotopically labeled at any position or combination of positions starting from simple highly enriched synthons. The synthetic scheme in this publication makes L‐proline, 13C‐ or 15N‐labeled at any position or combination of positions, easily available. The labeled L‐prolines are characterized by 1H‐, 13C‐ and 15N‐NMR and mass spectrometry.
Synthesis and physicochemical properties of decanucleotides containing (3′→ 5′)‐O‐CH2‐O‐linkages at predetermined positions
Authors: Quaedflieg P. J. L. M. , Pikkemaat J. A. , van der Marel G. A. , Kuyl‐Yeheskiely E. , Altona C. , van Boom J. H. 
Published: September 2010

AbstractSynthesis of the modified decadeoxynucleotides 16–20 having the sequence d(G1pC2pG)3pT4x1T5x2T6x3T7pG8pC9pG10) and containing one (x2 = CH2, x1 = x3 = p, i.e., 16), two (x1 = x3 = CH2, x2 = p, i.e., 17, x2 = x3 = CH2, x1 = p, i.e., 18 and x1 = x2 = CH2, x3 = p. i.e., 19) or three (x1 = x2 = x3 = CH2, i.e., 20) ‐O‐CH2‐O‐ linkages could be accomplished using the respective mono‐, di‐ or tri(‐O‐CH2‐O) 3′‐O‐phosphoramidites 6, 10 and 14 as the incoming synthons. Hybridization of 16–20 with their native complementary strand afforded stable duplexes, which were studied by 1D‐ and 2D‐1H‐NMR and UV‐hyperchromicity techniques.
Medicinal chemistry: Past, present and future
Authors: So W. 
Published: September 2010

AbstractDrug discovery in the past and, to a lesser extent, at present has been (is) based on molecular manipulation of natural products. In this way, selective local anesthetics have been developed from cocaineFrom atropine via pethidine, potent morphinomimetics, anti‐tussives, anti‐diarrhea agents and neuroleptics of the butyrophenone type have been developed.New lead compounds can also be discovered by general pharmacological screening of new chemical entities, synthesised with a certain pharmacological property in view, but lacking the expected potency. The discovery of the anti‐ulcer agent omeprazole is an example of this approach. Chemical manipulation of known bioactive compounds may also lead to new drugs. The possibility of rational design of new, highly sophisticated and specific drugs depends largely on progress made in the exact understanding, at the molecular level, of agonist/antagonist‐receptor and protein‐protein interactions.
Synthesis and biological properties of selected nucleoside analogues
Authors: Koomen G. J. 
Published: September 2010

AbstractThis paper reviews the research carried out in our laboratory in the field of nucleoside analogues, divided into two main parts: (1) Analogues with modified sugars, describing synthesis of monomers for polynucleotides, in which the ribose moiety has been replaced by amino acids, N‐vinyl‐2‐pyrolidinone, dihydroxy acyclic systems, tetrahydrofuran and tetrahydropyran rings, butyrolactone, pyrrolidine and cyclopentane/cyclopentane systems. (2) Analogues with modified bases, consisting of carbene adducts of pyrimidine nucleosides, benzodiazepine nucleosides, 5‐fluoro‐6‐vinyluracil, glutarimide nucleosides, transition state and suicide inhibitors of adenylosuccinate lyase and fluorescent pyrido[2,1‐i] purine nucleosides. Cytostatic and antiviral activities of a variety of the compounds obtained are discussed.
Industrial transformations of penicillins and cephalosporins
Authors: Verweij Jan , de Vroom Erik 
Published: September 2010

AbstractA survey is presented of transformations of penicillin G into penicillin and cephalosporin derivatives. Amongst other things the issues discussed are the conversion of penicillin G into 6‐aminopenicillanic acid (6‐APA) and some semi‐synthetic penicillins, ring expansion of the penicillin nucleus giving the cephalosporin nucleus and subsequently 7‐aminodeacetoxycephalosporanic acid (7‐ADCA), and the synthesis of various 3′‐substituted cephalosporin derivatives, including the tert‐butyl ester of 3‐(bromomethyl)‐7‐(phenylacetamido)‐3‐cephem 1‐oxide (3‐BMC®).
Synthesis of 6β‐methyl analogues of mifepristone, new selective antiprogestagens
Authors: van den Heuvel M. J. , Groen M. B. 
Published: September 2010

AbstractA new strategy is described to synthesize 19‐norsteroids with substituents at C‐6, C‐11 and C‐17. The strategy is applied to the synthesis of 11β‐[4‐(dimethylamino)phenyl]‐6β‐methyl‐4′, 5′– ‐dihydrospiro[estra‐4,9‐diene‐17,2′‐(3′H)‐furan]‐3‐one (15, Org 31710) and some related compounds. These compounds have been shown to have potent antiprogestational activity and, compared to previously described 11‐aryl‐19‐norsteroids, much reduced affinity for the glucocorticoid receptor.