bluuebunny/crossref_metadata_2025 huggingface dataset:
An Expeditious Library Synthesis of N‐Monoalkylated Aminopiperidines and ‐pyrrolidines
Authors: Ayesa Susana , Argyropoulos Dimitris , Maltseva Tatiana , Sund Christian , Samuelsson Bertil
Published: June 2004

N‐Monosubstituted aminopiperidines and ‐pyrrolidines are important building blocks for the synthesis of small‐molecule compound libraries. We have developed a practical solid‐phase route to N‐monosubstituted aminopiperidines and ‐pyrrolidines utilizing a selective reductive alkylation of primary or secondary amines attached to a Merrifield or Wang resin. Purification is achieved by simple filtration after each reaction step. The synthetic route developed can be readily applied to an extensive pool of commercially available aromatic and aliphatic aldehydes for conversion into the corresponding N‐monoalkylated diamino templates. Solid‐phase NMR spectroscopy was used to monitor the reactions. The new pulse sequences described in this report have further extended the usefulness of this nondestructive analytical methodology. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Tuning Second‐Order Optical Nonlinearities in Push‐Pull Benzimidazoles
Authors: Carella Antonio , Centore Roberto , Fort Alain , Peluso Andrea , Sirigu Augusto , Tuzi Angela
Published: June 2004

The synthesis and full characterization of new chromophores with second order optical nonlinearities containing the 2‐phenyl‐(5,6)‐nitrobenzimidazole group is reported. Starting from 2‐{4‐[(4‐N,N‐dihydroxyethylamino)phenylazo]phenyl}‐5(6)‐nitrobenzimidazole, a combined theoretical and experimental approach, including theoretical computations of second order nonlinear optical activity (MNDO/AM1), X‐ray structural analysis and synthetic strategies, has led to a significant optimization (more than 50%) of the NLO activity of related chromophores. The results indicate that 6‐nitro‐substituted compounds are more active than 5‐nitro‐substituted ones and that a further increase of NLO activity can be achieved by insertion of a carbon−carbon double bond between the benzimidazole and 2‐phenyl rings. Calculations also suggest that an additional improvement of the nonlinearity should be expected upon functionalization of the N1 atom of the 6‐nitrobenzimidazole with electron‐withdrawing groups. Experimental nonlinearities (EFISH technique, μβ/10−48esu, λ = 1.907 μm, DMF solution) between 940 and 1550 were measured. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Terpenoid Lactones with the p‐Menthane System
Authors: Dams Iwona , Białońska Agata , Ciunik Zbigniew , Wawrzeńczyk Czesław
Published: June 2004

Starting from (R)‐(+)‐ and (S)‐(−)‐pulegone enantiomeric pairs of hydroxy lactones and keto lactones were obtained by Claisen rearrangement of cis‐pulegols and lactonization of epoxy esters. The hydroxy lactones were reduced with LiAlH4 in order to assign the configuration of the chiral centers. The structures of the synthesized compounds were established on the basis of spectroscopic and crystallographic data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
New, Sesquiterpenoid‐Type Bicyclic Compounds from the Buds of Betulapubescens − Ring‐Contracted Products of β‐Caryophyllene?
Authors: Klika Karel D. , Demirci Betül , Salminen Juha‐Pekka , Ovcharenko Vladimir V. , Vuorela Satu , Can Başer K. Hüsnü , Pihlaja Kalevi
Published: June 2004

The essential oils obtained from the buds of Betula pubescens ssp. pubescens and B. pubescens ssp. czerepanovii were analyzed both by GC and GC/MS and, of the 31 compounds identified, 14‐acetoxy‐β‐caryophyllene was determined to be the main component in both oils in addition to 25 other previously known compounds. Three of the compounds were isolated from the oils and further characterized by NMR spectroscopy and mass spectrometry, including a new bicyclic aldehyde (4,8,8‐trimethyl‐2‐methylenebicyclo[5.2.0]nonane‐4‐carbaldehyde, birkenal), a new tricyclic lactone (1,4,4,8‐tetramethyl‐10‐oxatricyclo[6.2.1.02,5]undecan‐9‐one, hushinone), and the recently described 6‐hydroxycaryophyllene. The isolation of birkenal also enabled identification of its corresponding alcohol {(4,8,8‐trimethyl‐2‐methylenebicyclo[5.2.0]non‐4‐yl)methanol, birkenol} and the acetate of this alcohol {(4,8,8‐trimethyl‐2‐methylenebicyclo[5.2.0]non‐4‐yl)methyl acetate, birkenyl acetate}, both of which are also novel compounds and are present in the two essential oils. These new compounds, bearing evident sesquiterpenoid traits, potentially arise biosynthetically as ring‐contracted products of β‐caryophyllene or a derivative thereof. The fifth novel compound present in the oils was determined to be the acetate of 6‐hydroxycaryophyllene. The preferred conformations of the seven‐ or nine‐membered rings in these structures were also determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Syntheses of 7‐(2‐Hydroxy‐1‐phenylethyl)‐ and 7‐(2‐Hydroxy‐2‐phenylethyl)guanine, DNA Adducts Derived from Styrene 7,8‐Oxide
Authors: Novák Jan , Linhart Igor , Dvorˇáková Hana
Published: June 2004

7‐(2‐Hydroxy‐1‐phenylethyl)‐ and 7‐(2‐hydroxy‐2‐phenylethyl)guanines are important DNA adducts which can be used as markers of exposure to styrene. Two synthetic routes leading to these compounds are presented using allyl‐protected bromohydrins as synthetic equivalents of styrene oxide to alkylate 2‐amino‐6‐chloropurine or 7‐methyl‐10‐oxo‐9,10‐dihydropyrimido[1,2‐a]purine as precursors to guanine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
New Perfluoroalkyl‐Substituted Bisoxazolines as Chiral Ligands in Asymmetric CuII‐Catalyzed Reactions
Authors: Simonelli Barbara , Orlandi Simonetta , Benaglia Maurizio , Pozzi Gianluca
Published: June 2004

Two new enantiomerically pure perfluoroalkyl‐substituted bisoxazolines (F‐Box) have been prepared by a reaction sequence that involves formation of the properly functionalized Box followed by introduction of one or two n‐C8F17 residues. These ligands were employed for the first time in the Mukaiyama aldol addition of silylketene thioacetals to methylpyruvate promoted by Cu(OTf)2 (up to 85% ee) and in the ene reaction between α‐methylstyrene and ethylglyoxalate in the presence of Cu(OTf)2 (up to 74% ee). We compared the reactivities of the new ligands with those of two other chiral fluorous bisoxazolines that we have reported previously. In both cases, the F‐Box that has the lower fluorine content performed better, in terms of chemical yield and enantioselectivity, than the more‐fluorinated one. The recovery and recycling of the ligands is realized either by phase separation of the reaction solvents or by filtration through a short plug of fluorous silica gel. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Organic Bases as Additives to Improve the Radiochemical Yields of [11C]Ketones Prepared by the Suzuki Coupling Reaction
Authors: Rahman Obaidur , Llop Jordi , Långström Bengt
Published: June 2004

The Suzuki cross‐coupling reaction was employed in the syntheses of eight new [11C‐carbonyl]ketones. The reactions between the corresponding boronic acids and the corresponding triflates were performed in the presence of [11C]carbon monoxide and a palladium(0) complex as the catalyst. Lithium bromide was added to facilitate the reactions, and different bases were tested to improve the radiochemical yields. All the ketones were synthesised, with the achievement of isolated radiochemical yields (decay‐corrected) of between 14 and 74%. Important improvements in the radiochemical yield were achieved by use of tetrabutylammonium fluoride in the synthesis of ketones incorporating alkyl groups, while potassium tert‐butoxide was the best base among those tested for improving the radiochemical yields in the syntheses of biaryl ketones. The optimal amount of base was determined in all cases. Only for compounds 3e and 3h were better radiochemical yields obtained when no base was used. No radiochemical impurities were detected after isolation of the compounds. The specific radioactivity for compound 3a was determined, and a value of 200 GBq/μmol was obtained. Compound 3b was labelled simultaneously with [11C] and (13C)carbon monoxide and the position of the labelled atom was determined and confirmed by 13C NMR spectrometry. Tetrabutylammonium fluoride and potassium tert‐butoxide are reported as useful bases for Suzuki carbonylation with [11C]/(13C)carbon monoxide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Dialkylation of Various Butane‐2,3‐diacetals Using Allylsilane and 1,8‐Bis(trimethylsilyl)‐2,6‐octadiene
Authors: Mariet Natacha , Pellissier Hélène , Ibrahim‐Ouali Malika , Santelli Maurice
Published: June 2004

We report in this paper a greatly improved procedure for the formation of a range of 1‐acetyl‐1‐methyl‐2,5‐divinylcyclopentanes from 1,8‐bis(trimethylsilyl)octa‐2,6‐diene (BISTRO) and 1,2‐diacetals prepared directly from biacetyl. These 1‐acetyl‐1‐methyl‐2,5‐divinylcyclopentanes are building blocks for the synthesis of 2‐ and 3‐methoxy‐12‐oxo‐17β‐vinylestranes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of an Optically Active Decahydro‐6‐isoquinolone Scaffold with a Quaternary Stereocenter
Authors: Christoffers Jens , Scharl Heiko , Frey Wolfgang , Baro Angelika
Published: June 2004

A straightforward synthesis of optically active decahydro‐6‐isoquinolone derivative 3, containing a quaternary stereocenter, is reported. The starting (R)‐configured enantiopure enone 2, which is readily accessible through a copper‐catalyzed, L‐valine amide mediated Michael reaction and a subsequent Robinson annulation, was hydrogenated with Pd/C in iPrOH to give the decahydroisoquinolone 4. Treatment of 4 with ethyleneglycol in the presence of PPTS yielded the dioxolane‐protected derivative 7. A sequence of ester reduction with LiAlH4 and subsequent Ley oxidation of the resulting primary alcohol 10 accomplished the synthesis. Enantiomerically pure aldehyde 3, with three groups for further functionalization, was thus obtained in 63% overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
4H‐Imidazoles and Imidazoles from Anionic and Dipolar Electrocyclization Reactions of 2,4‐Diazapenta‐1,3‐dienes
Authors: Habersaat Nils , Fröhlich Roland , Würthwein Ernst‐Ulrich
Published: June 2004

1‐Amino‐2,4‐diazapenta‐1,3‐dienes 5 are synthesized by the activation of N‐acylamidines 2 with trifluoromethanesulfonic anhydride and subsequent condensation with amino compounds 4. When the amino compounds 4 possess electron‐withdrawing substituents (e.g. alkoxycarbonyl groups, fluorenyl derivatives) this condensation leads instead to 4H‐imidazoles 6 and imidazoles 7. These reactions are considered to be 1,5‐dipolar electrocyclization reactions of 1,5‐dipoles that are tautomers of the 2,4‐diazapenta‐1,3‐dienes 5. Deprotonation of 5b,f by the use of strong organic bases yields the corresponding imidazoles 7b,c after amine elimination during the anionic 1,5‐electrocyclization reaction. Results of quantum chemical model calculations (RHF, MP2, SCS‐MP2, G3, DFT) performed on the parent 2,4‐diazapentadienyl anion 9a, its lithium compound 9a‐Li, the corresponding 1,5‐dipole 12 and their substituted derivatives are in accordance with the suggested reaction mechanism. X‐ray data are given for the 2,4‐diazapenta‐1,3‐dienes 5a·F3CSO3H, 5c, 5d·F3CSO3H, 5e,f and the spirocyclic 4H‐imidazole derivatives 6b−d. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Thienodolin
Authors: Engqvist Robert , Javaid Atif , Bergman Jan
Published: June 2004

We report a total synthesis of the alkaloid thienodolin (1a), as well as its 5‐chloro isomer 1b and its unsubstituted analogue 1c, in three steps from the corresponding oxindoles 8a−c. The preparation was achieved through an initial Vilsmeier−Haack−Arnold reaction (chloro‐formylation) followed by protection at the indole nitrogen, creation of the fused thiophene ring by nucleophilic substitution at the 2‐position and an intramolecular cyclization using mercaptoacetamide. This gave 1a, 1b and 1c in total yields of 42%, 35% and 37%, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Interchangeable PEG‐Supported Synthesis of Peptide‐Oligonucleotide Chimeras
Authors: Adamo Ilaria , Ballico Maurizio , Campaner Pietro , Drioli Sara , Bonora Gian Maria
Published: June 2004

A procedure has been developed for the preparation of peptide‐PEG‐oligonucleotide conjugates: the two sequences were synthesized at the extremities of the same commercial high‐molecular‐weight polyethylene glycol (PEG) starting both from the peptide as well as from the oligonucleotide component. The commercial PEG was modified at its terminal hydroxyl functions with two orthogonal protecting groups (DMT and Fmoc). The selective removal of those groups allowed the synthesis of the chimeras following two different, interchangeable strategies. Comparison of the final conjugates suggested that their production was equally effective. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Facile Cleavage of Si−C Bonds during the Sol‐Gel Hydrolysis of Aminomethyltrialkoxysilanes − A New Method for the Methylation of Primary Amines
Authors: Adima Augustin , Bied Catherine , Moreau Joël J. E , Wong Chi Man Michel
Published: June 2004

The reaction of chloromethyltriethoxysilane with (1R,2R)‐bis(methylamino)cyclohexane (1) afforded the corresponding bis‐silylated compound 2. The sol‐gel hydrolysis of 2 did not give the expected bridged silsesquioxane owing to quantitative Si−C‐bond cleavage. Instead, silica and (1R,2R)‐bis(dimethylamino)cyclohexane (3) were obtained. This reaction was exploited to propose a new route for the methylation of amines. Such methylation reaction of amines could be extended to other amines and provides a new method for the selective monomethylation of primary amines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Metabolites of the Ah Receptor Ligand 6‐Formylindolo[3,2‐b]carbazole
Authors: Wahlström Niklas , Romero Ivan , Bergman Jan
Published: June 2004

Synthesis of the five mono‐ and di‐hydroxylated metabolites of the aryl hydrocarbon receptor high affinity ligand 6‐formylindolo[3,2‐b]carbazole is described. The structures of the metabolites were unequivocally established as 2‐hydroxy‐, 8‐hydroxy‐, 2,10‐dihydroxy‐, 4,8‐dihydroxy‐ and 2,8‐dihydroxyindolo[3,2‐b]carbazole‐6‐carboxaldehyde. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A Mechanistic Rationale for the Mode Selectivity in the Intramolecular Cyclization of Ethylene‐Tethered Iminoketenimines: [2+2] versus [4+2] Stepwise Cycloadditions
Authors: Alajarín Mateo , Sánchez‐Andrada Pilar , Vidal Angel , Tovar Fulgencio
Published: June 2004

A stepwise mechanism, via a zwitterionic intermediate, has been established by ab initio and DFT calculations for the intramolecular cyclization of N‐(3‐azabut‐3‐enyl)ketenimine into its corresponding [2+2] cycloadduct. The control of the mode selectivity ([2+2] versus [4+2] cycloaddition) in the intramolecular cyclization of C‐vinyl‐N‐(iminoethylene)ketenimines, which favors the [4+2] cycloadducts, also has been rationalized by comparing the energies calculated for both reaction pathways; the results have been confirmed by a quantitative kinetic analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Incorporation of Diarylbutylamine Pharmacophore into Indeno‐ or Naphtho[1,2‐b]pyran Ring Systems
Authors: Maertens Faye , Toppet Suzanne , Compernolle Frans , Hoornaert Georges J.
Published: June 2004

Various conformationally constrained forms of the diarylbutylamine pharmacophore were accessed by incorporating it into heterocyclic ring systems, i.e., indeno[1,2‐b]furan, indeno[1,2‐b]pyran, naphtho[1,2‐b]furan, and benzo[h]chromene. These compounds were formed by epoxidation of 2‐alkenyl‐substituted 1‐indanols or 1‐naphthalenols. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
First Total Synthesis of Naturally Occurring (−)‐Nitidon and Its Enantiomer
Authors: Bellina Fabio , Carpita Adriano , Mannocci Luca , Rossi Renzo
Published: June 2004

The first total synthesis of naturally occurring (−)‐nitidon and its enantiomer is reported. The best of the routes investigated for preparation of these enantiomerically pure compounds involves a modification of the Cadiot−Chodkiewicz reaction and the Sharpless asymmetric epoxidation of an (E)‐2‐ene‐4,6‐diyn‐1‐ol as key steps and proceeds in five steps and 18% overall yield. Both enantiomers of nitidon and some related 6‐(1,3‐diyn‐1‐yl)‐2H‐pyran‐2‐ones have been found to exhibit significant cytotoxic activity against human cancer cell lines in vitro. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Phenylacetylene Dendrimers Having Sterically Congested Diazo Units and Characterization of Their Photoproducts
Authors: Itoh Tetsuji , Maemura Toshiyuki , Ohtsuka Yusuke , Ikari Yoshiyuki , Wildt Holger , Hirai Katsuyuki , Tomioka Hideo
Published: June 2004

The compound (4‐tert‐butyl‐2,6‐dimethylphenyl)(2,4,6‐tribromophenyl)diazomethane (1a), a precursor for persistent triplet carbene, was found to be stable enough to survive Sonogashira coupling reaction conditions to give (4‐tert‐butyl‐2,6‐dimethylphenyl)(2,6‐dibromo‐4‐ethynylphenyl)diazomethane (2a). The diazomethane 2a was used as a starting compound for synthesis of phenylacetylene dendritic molecules having peripheral diazo groups by the convergent method. Thus, tridendrons with peripheral groups bearing 3 (3a), 6 (6a), and 12 (8a) diazo units were prepared, in which diazo groups were introduced so as to generate polycarbenes in a ferromagnetic fashion. In order to characterize the spin states of carbenes generated by the photolysis of these dendrimers, the magnetic susceptibility of the photoproducts was measured. Although the data for the photoproduct of the tris(diazo) compound were fitted with S = 2.5, those for the photoproducts of hexakis and dodecakis(diazo) compounds were fitted with S = 1.62, a value that is much smaller than the theoretically predicted value and even smaller than that of triscarbene. The results are interpreted in terms of the disjoint‐nondisjoint concept. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004
X‐ray Crystal Structure Study of Sterically Congested Diphenyldiazomethanes
Authors: Iikubo Takashi , Itoh Tetsuji , Hirai Katsuyuki , Takahashi Yasutake , Kawano Masaki , Ohashi Yuji , Tomioka Hideo
Published: June 2004

X‐ray crystallographic structures were determined for five diphenyldiazomethanes (DDMs) with various ortho substituents, namely, bis(2,4,6‐trichlorophenyl)diazomethane, bis(2,4,6‐tribromophenyl)diazomethane, bis(4‐tert‐butyl‐2,6‐dibromophenyl)diazomethane, (4‐tert‐butyl‐2,6‐dimethylphenyl)(2,4,6‐tribromophenyl)diazomethane, and [4‐tert‐butyl‐2,6‐bis(trifluoromethyl)phenyl](4‐tert‐butyl‐2,6‐dibromophenyl)diazomethane, and for bis(4‐bromophenyl)diazomethane, a DDM with no ortho substituents. The correlation between the structural parameters, the ESR zero‐field splitting (ZFS) parameters and the lifetimes of the triplet diphenylcarbenes (DPCs) generated from these diazo compounds was examined. It is noted that as ortho substituents are introduced onto the phenyl rings of the DDMs, the interplanar angle between the two phenyl rings increases, while the angle of the diazo carbon changes very little. DDM 6‐N2, from which the longest‐lived triplet carbene is generated, is shown to have the largest interplanar angle of the DDMs examined. The bond distances between the aromatic carbons and the ortho substituents as well as the van der Waals radii of the substituents were also examined. These studies do not provide a quantitative correlation between the structural parameters of the precursor DDMs and the ZFS parameters and lifetimes of their photoproducts, triplet DPCs, but show how steric shielding of the ortho substituents affects the structures and stabilities of triplet DPCs. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Formation of the B Ring in Steroids and Hopanoids from Squalene
Authors: Hess B. Andes
Published: June 2004

See original Eur. J. Org. Chem. 2004, 2239 2242 (DOI: 10.1002/ejoc.200300684).
Cover Picture: Fluorescence Assay and Screening of Epoxide Opening by Nucleophiles (Eur. J. Org. Chem. 12/2004)
Authors: Badalassi Fabrizio , Klein Gérard , Crotti Paolo , Reymond Jean‐Louis
Published: June 2004

The cover picture shows blue‐fluorescent enzyme assays. The intense blue fluorescence of umbelliferone is readily detected under UV illumination (356 nm) when this fluorescent product is released from non‐fluorescent ether precursors. This fluorescent signal is the key to a number of high‐throughput enzyme assays, usually in a 96‐well microtiter‐plate format as shown. Fluorescence enzyme assays involving epoxide opening reactions with nucleophiles are discussed in the article by J.‐L. Reymond et al. on page 2557 ff.
A staggered conservative scheme for every Froude number in rapidly varied shallow water flows
Authors: Stelling G. S. , Duinmeijer S. P. A.
Published: June 2004

This paper proposes a numerical technique that in essence is based upon the classical staggered grids and implicit numerical integration schemes, but that can be applied to problems that include rapidly varied flows as well. Rapidly varied flows occur, for instance, in hydraulic jumps and bores. Inundation of dry land implies sudden flow transitions due to obstacles such as road banks. Near such transitions the grid resolution is often low compared to the gradients of the bathymetry. In combination with the local invalidity of the hydrostatic pressure assumption, conservation properties become crucial. The scheme described here, combines the efficiency of staggered grids with conservation properties so as to ensure accurate results for rapidly varied flows, as well as in expansions as in contractions. In flow expansions, a numerical approximation is applied that is consistent with the momentum principle. In flow contractions, a numerical approximation is applied that is consistent with the Bernoulli equation. Both approximations are consistent with the shallow water equations, so under sufficiently smooth conditions they converge to the same solution. The resulting method is very efficient for the simulation of large‐scale inundations. Copyright © 2003 John Wiley & Sons, Ltd.
Computation of strongly swirling confined flows with cubic eddy‐viscosity turbulence models
Authors: Yang Xiaodong , Ma Huiyang
Published: June 2004

An investigation on the predictive performance of four cubic eddy‐viscosity turbulence models for two strongly swirling confined flows is presented. Comparisons of the prediction with the experiments show clearly the superiority of cubic models over the linear k–εmodel. The linear k–εmodel does not contain any mechanism to describe the stabilizing effects of swirling motion and as a consequence it performs poorly. Cubic models return a lower level of Reynolds stresses and the combined forced‐free vortex profiles of tangential velocity close to the measurements in response to the interaction between swirl‐induced curvature and stresses. However, a fully developed rotating pipe flow is too simple to contain enough flow physics, so the calibration of cubic terms is still a topic of investigation. It is shown that explicit algebraic stress models require fewer calibrations and contain more flow physics. Copyright © 2003 John Wiley & Sons, Ltd.
Verification testing in computational fluid dynamics: an example using Reynolds‐averaged Navier–Stokes methods for two‐dimensional flow in the near wake of a circular cylinder
Authors: Richmond‐Bryant Jennifer
Published: June 2004

Verification testing was performed for various Reynolds‐averaged Navier–Stokes methods for uniform flow past a circular cylinder at Re= 5232. The standard and renormalized group (RNG) versions of the k–ε method were examined, along with the Boussinesq, Speziale and Launder constitutive relationships. Wind tunnel experiments for flow past a circular cylinder were also performed to obtain a comparative data set. Preliminary studies demonstrate poor convergence for the Speziale relationship.

Verification testing with the standard and RNG k–ε models suggests that the simulations exhibit global monotonic convergence for the Boussinesq models. However, the global order of accuracy of the methods was much lower than the expected order of accuracy of 2. For this reason, pointwise convergence ratios and orders of accuracy were computed to show that not all sampling locations had converged (standard k–ε model: 19% failed to converge; RNG k–ε model: 14% failed to converge). When the non‐convergent points were removed from consideration, the average orders of accuracy are closer to the expected value (standard k–ε model: 1.41; RNG k–ε model: 1.27). Poor iterative and global grid convergence was found for the RNG k–ε/Launder model. The standard and RNG k–ε models with the Boussinesq relationship were compared with experimental data and yielded results significantly different from the experiments. Copyright © 2003 John Wiley & Sons, Ltd.
A discontinuous Galerkin method/HLLC solver for the Euler equations
Authors: Remaki Malika , Habashi Wagdi G.
Published: June 2004

This paper proposes a fully three‐dimensional non‐linear Euler methodology for solving aerodynamic and acoustic problems in the presence of strong shocks and rarefactions. It uses a discontinuous Galerkin method (DGM) within the element, and a Riemann solver (HLLC) at the boundaries to propagate rarefactions while preserving the entropy condition and capturing shocks with no spurious oscillations. This approach is thought to marry the best aspects of finite element and finite volume methods, achieving conservation while not requiring the solution of a large matrix. Examples in which shock and rarefaction waves are well captured are presented and the propagation of acoustic pulses is well demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.
Efficient solution of the steady‐state Navier–Stokes equations using a multigrid preconditioned Newton–Krylov method
Authors: Syamsudhuha  , Silvester David J.
Published: June 2004

An inexact Newton's method is used to solve the steady‐state incompressible Navier–Stokes equations. The equations are discretized using a mixed finite element approximation. A new efficient preconditioning methodology introduced by Kay et al. (SIAM J. Sci. Comput., 2002; 24: 237–256) is applied and its effectiveness in the context of a Newton linearization is investigated. The original strategy was introduced as a preconditioning methodology for discrete Oseen equations that arise from Picard linearization. Our new variant of the preconditioning strategy is constructed from building blocks consisting of two component multigrid cycles; a multigrid V‐cycle for a scalar convection–diffusion operator; and a multigrid V‐cycle for a pressure Poisson operator. We present numerical experiments showing that the convergence rate of the preconditioned GMRES is independent of the grid size and relatively insensitive to the Reynolds number. Copyright © 2003 John Wiley & Sons, Ltd.
Who becomes a chair?
Authors: Carroll James B. , Wolverton Mimi
Published: June 2004

This chapter describes characteristics of department chairs and identifies various tasks and challenges that they face during their time in office.
Socializing new chairs
Authors: Thomas Jerry R. , Schuh John H.
Published: June 2004

This chapter, which focuses on the socialization process for new chairs, offers suggestions and recommendations for practice.
The professional development of department chairs
Authors: Hecht Irene W. D.
Published: June 2004

This chapter identifies a number of resources that department chairs can use in their professional development.
The interim chair: Special challenges and opportunities
Authors: Rud Jr. Anthony G.
Published: June 2004

A substantial number of individuals serve as interim chairs each academic year. This chapter addresses their unique needs and provides suggestions on serving in this difficult role.
Measuring the performance of the chair
Authors: Mitchell Judy Nichols
Published: June 2004

A fact of administrative life is that chairs are evaluated on a periodic basis. This chapter addresses issues related to the performance evaluation of department chairs.
The department chair's balancing acts
Authors: Gmelch Walter H.
Published: June 2004

This chapter examines the various roles, challenges, and responsibilities that department chairs must balance in the course of their work.
The end of the reign: Department chair no more
Authors: Smith Earl
Published: June 2004

This chapter examines aspects of the life of the chair after the person returns to full‐time service as a faculty member.
Postradiotherapy surveillance practice for head and neck squamous cell carcinoma—too much for too little?
Authors: Schwartz David L. , Barker Jerry , Chansky Kari , Yueh Bevan , Raminfar Leila , Drago Pamela , Cha Christine , Austin‐Seymour Mary , Laramore George E. , Hillel Allen D. , Weymuller Ernest A. , Wallner Kent E.
Published: June 2004

Introduction.

Limited information is available regarding surveillance patterns after head and neck cancer radiotherapy. We cataloged follow‐up for a specified patient cohort treated at three neighboring university, community, and Veterans Administration institutions.

Methods.

One hundred fifteen patients were treated with curative intent between 1994–1998 with definitive or postoperative radiotherapy for newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. One hundred patients had continuous follow‐up at their treating institution and were included for analysis. Median follow‐up until disease recurrence or censorship was 28.5 months.

Results.

Median follow‐up frequency was 5.7 visits/year and was highly variable. Although visit frequency correlated with disease stage and the presence of high‐risk disease features, this association was lost when patients with early recurrences were removed from analysis. Procedure and test utilization closely mirrored visit frequency, resulting in a wide range of estimated yearly charges ($0–15,668/year; median, $1,772/year). Actuarial 3‐year overall survival for the study group was 71%. Eighty‐six percent (19 of 22) of potentially salvageable locoregional failures were discovered secondary to symptomatic complaint rather than by test results. Disease failure, whether detected by symptom or testing, predicted for poor survival (22% at 24 months after recurrence).

Conclusions.

Postradiotherapy surveillance for head and neck cancer is inconsistently pursued. A proven correlation between intensive follow‐up and improved patient survival is lacking. Surveillance directed by patient symptoms should be investigated as an alternative approach. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Rim versus sagittal mandibulectomy for the treatment of squamous cell carcinoma: Two types of mandibular preservation
Authors: Guerra Mario Fernando Muñoz , Campo Francisco J. Rodríguez , Gías Luis Naval , Pérez Jesús Sastre
Published: June 2004

Background.

The role of conservative mandibulectomy for patients with bone invasion from squamous cell carcinoma remains poorly defined. However, marginal mandibular resection is biomechanically secure in its design while maintaining the mandibular continuity. This procedure has proven to be a successful method of treating squamous cell carcinoma with limited mandibular involvement.

Purpose.

The purpose of this study was to analyze our results after the use of a marginal technique for the treatment of oral and oropharyngeal cancer and to compare two types of mandibular conservative procedures: rim resection versus sagittal inner mandibulectomy.

Methods.

A retrospective review of a cohort of 50 patients (global group) who underwent mandibular conservative resection for previously untreated squamous cell carcinoma was performed. Two subgroups were considered: rim group (n= 37) and sagittal group (n= 13). Clinical evaluation and preoperative radiologic studies were the means used to evaluate bony invasion and to decide on the extent of mandibulectomy. The treatment outcome after these two types of mandibular resection was calculated and compared using analysis by the Pearson χ2test, logistic regression model for multivariate analysis, and the Kaplan‐Meier method to determine survival.

Results.

In the sagittal group, specimens from 2 patients (11.7%) demonstrated tumor invasion on decalcified histologic examination, whereas the rim group showed 11 cases (29.7%) with bone invasion. Local recurrence was observed in the follow‐up of 10 patients. No statistical relationship was found between the presence of histologic bone invasion and the risk of local recurrence. The size of bone resection >4 cm (p= .002) and tumor invasion of surgical margins (p= .039) were found to be associated with increased local recurrence rates. In multivariate analysis, lymph node affectation significantly correlated with histologic mandibular involvement (p= .02). In the global group, the 5‐year observed survival rate was 56.97%. Overall survival and rate of recurrence were comparable in both groups. In the global group, tumor infiltration beyond the surgical margin was statistically related with poor survival (p= .01).

Conclusions.

Analysis of this series disclosed that marginal mandibulectomy is effective in the control of squamous cell carcinomas that are close to or involving the mandible. In carefully selected patients, sagittal bone resection seems to be as appropriate as rim resection in the local control of these tumors. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Eating ability in head and neck cancer patients after treatment with chemoradiation: A 12‐month follow‐up study accounting for dropout
Authors: Rademaker Alfred W. , Vonesh Edward F. , Logemann Jeri A. , Pauloski Barbara Roa , Liu Dachao , Lazarus Cathy L. , Newman Lisa A. , May Annette Hamner , MacCracken Ellen , Gaziano Joy , Stachowiak Linda
Published: June 2004

Background.

Head and neck cancer patients treated with chemoradiation have difficulty eating a normal diet. This study was designed to characterize eating ability over 12 months after chemoradiation treatment. Analyses take patient dropout into account.

Methods:

Two hundred fifty‐five patients with head and neck cancer treated with chemoradiation were followed for 12 months. Eating ability was analyzed using generalized linear model methods that accounted for non‐ignorable dropout.

Results.

Eating ability was compromised immediately after treatment and improved over 12 months to near pretreatment levels. Ability to eat at most 50% of the diet orally did not return to baseline levels (p < .05). However, the percent of patients eating a normal diet did return to baseline levels. Accounting for dropout modified the results, but the pattern of significance was similar.

Conclusions.

Treatment of head and neck cancer with chemoradiation has a significant effect on eating ability, which improves after 12 months after treatment. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: Part 1, pathogenesis and prophylaxis of mucositis
Authors: Scully Crispian , Epstein Joel , Sonis Stephen
Published: June 2004

Background.

Oral mucositis is a common sequel of radiotherapy, chemotherapy, and radiochemotherapy in patients with cancer or patients requiring hemopoietic stem cell transplants. Mucositis has a direct and significant impact on the duration of disease remission and cure rates, because it is a cancer treatment–limiting toxicity. Mucositis also affects survival because of the risk of infection and has a significant impact on the quality of life and cost of care.

Methods.

This article reviews publications on the etiopathogenesis and prevention of oral mucositis accessible from a MEDLINE search using as key words, mucositis, radiotherapy, chemotherapy, hemopoietic stem cell transplant, and oral.

Conclusions.

Of the current available products, ice chips and benzydamine have the strongest scientific evidence of support for prophylaxis of mucositis. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Benign metastasizing pleomorphic adenoma of the parotid gland: A clinicopathologic puzzle
Authors: Marioni Gino , Marino Filippo , Stramare Roberto , Marchese‐Ragona Rosario , Staffieri Alberto
Published: June 2004

Background.

Pleomorphic adenoma constitutes the most common benign parotid gland tumor. Local recurrence after surgical treatment (lateral or total parotidectomy) has been described in 1% to 5% of cases. Malignant degeneration has been reported in 2% to 9% of cases of pleomorphic adenoma of salivary gland origin. Metastasizing pleomorphic adenomas without histologic evidence of malignancy have rarely been reported. Metastatic lesions have been discovered in bone, lymph nodes, the lung, oral cavity, pharynx, skin, liver, retroperitoneum, kidney, calvarium, and central nervous system. To the best of our knowledge, we hereby report the first case of pleomorphic adenoma of the parotid gland metastasizing to the ipsilateral maxilla.

Methods.

We simultaneously examined apoptosis‐related protein expression and markers of cell‐proliferation activity in our case of benign pleomorphic adenoma metastasis and compared outcome with a control group of primary parotid pleomorphic adenomas.

Results.

Analysis of p53, Bcl‐2, MIB1, CD 105, p27, and p21 expression did not reveal significant differences between metastasizing pleomorphic adenoma of the salivary gland and the control group of primary parotid pleomorphic adenomas.

Conclusions.

Clinical rather than pathologic evidence seems to justify inclusion of metastasizing salivary pleomorphic adenoma in the group of low‐grade malignant salivary tumors. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Vertical ramus osteotomy combined with a parasymphyseal mandibulotomy for improved access to the parapharyngeal space
Authors: Smith Graham I. , Brennan Peter A. , Webb Andrew A. , Ilankovan Vellupilai
Published: June 2004

Background.

A number of procedures have been described that facilitate access to the parapharyngeal space. Their use may be limited because of restricted access or postoperative morbidity.

Methods.

We describe the use of two mandibular osteotomies to greatly enhance the exposure of the parapharyngeal space, with possible access up to the skull base.

Results.

We have performed this procedure in three cases with minimal postoperative morbidity and no neurologic deficit or occlusal disturbances.

Conclusions.

We have found that the osteotomies described provide far better exposure to this area than a single mandibular osteotomy alone. Furthermore, it avoids a facial scar.
Sinonasal paraganglioma: Endoscopic resection with a 4‐year follow‐up
Authors: Mouadeb Debbie A. , Chandra Rakesh K. , Kennedy David W. , Feldman Michael
Published: June 2004

Background.

Paragangliomas are uncommon neuroendocrine tumors. In the head and neck, they are most commonly seen at the carotid body, the temporal bone, or along the vagus nerve. Sinonasal paragangliomas are extremely rare. Most cases reported describe management by open surgical resection, with sublabial and/or transfacial approaches.

Methods.

We present a case of a large sinonasal paraganglioma successfully managed by endoscopic resection.

Results.

The patient has no evidence of recurrence after 4 years of follow‐up.

Conclusions.

This case demonstrates that sinonasal paragangliomas might be amenable to endoscopic resection. However, the most important priority to consider when selecting a surgical technique is whether adequate excision with clear margins can be obtained. Furthermore, because of the aggressive nature of these tumors, regardless of the surgical approach, long‐term follow‐up is recommended. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Early glottic carcinoma: Treatment according patient's preference?
Authors: Stoeckli Sandro J. , Schnieper Isabel , Huguenin Pia , Schmid Stephan
Published: June 2004

Background.

To analyze the results in early (stage I and II) glottic carcinoma of a single institution with a patient‐oriented concept.

Methods.

After diagnostic workup and multidisciplinary counseling, either radiotherapy or CO2 laser surgery was chosen with respect to the patient's preference.

Results.

Sixty‐five patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5‐year overall survival, disease‐specific survival, and initial local control rate after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs 93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR, 89% vs 67%). Larynx preservation was significantly higher after surgery in T1 tumors (96% vs 82%) and in T2 tumors (89% vs 77%).

Conclusions.

Selection of the treatment modality according to patient's preference results in a comparable control of disease for T1 tumors. The initial local control for T2 tumors is significantly better after surgery. In both stages laser surgery warrants a better larynx preservation rate. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Patient's response using freetext in the University of Washington Quality of Life Scale
Authors: Millsopp Lynne , Humphris Gerry , Lowe Derek , Rogers Simon Neave
Published: June 2004

Background.

The University of Washington Quality of Life Scale is the only validated head‐and‐neck–specific questionnaire that invites patients to write comments in the form of freetext. Freetext allows the questionnaire to record issues raised by the patient.

Method.

Two hundred seventy‐eight consecutive patients treated between 1995 and 1999 by primary surgery for oral and oropharyngeal squamous cell carcinoma completed the UWQOL. Freetext from these patients was independently assessed by the authors.

Results.

Comments were made by 61% of patients at some time. Completion was independent of clinicodemographic characteristics. Comments were predominantly head and neck (39%) and medical (35%). In 55% of cases, the overall tone was negative. Around a quarter of issues was not part of a validated health‐related quality‐of‐life questionnaire.

Conclusions.

Freetext gives the multidisciplinary team a better insight into the concerns of the patient and can be used to promote a holistic approach. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Impact of comorbidity on the outcome of laryngeal squamous cancer
Authors: Paleri Vinidh , Wight Richard G. , Davies Gareth R.
Published: June 2004

Background.

Comorbidity has been shown to be a determinant in treatment selection and survival in various cancers. We have previously shown that the Adult Comorbidity Evaluation—27 index is applicable in a United Kingdom setting, and the process of comorbidity grading by retrospective notes evaluation is an accurate and reliable process.

Methods.

The impact of comorbidity and other factors on survival was examined retrospectively in a cohort of 180 patients with laryngeal squamous cell cancer.

Results.

This study shows for the first time that the higher comorbidity burden seen in supraglottic cancers in contrast to glottic tumors might account for the poorer prognosis. This study also externally validates the composite comorbidity–TNM staging system described by Piccirillo and shows the composite system to be a better predictor of outcome than TNM staging system alone.

Conclusions.

Moderate and severe comorbidity have a greater and statistically significant impact on survival than the TNM staging system. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Carcinoma of the skin with perineural invasion
Authors: Garcia‐Serra Allie , Hinerman Russell W. , Mendenhall William M. , Amdur Robert J. , Morris Christopher G. , Williams Lorna Sohn , Mancuso Anthony A.
Published: June 2004

Purpose.

To evaluate the outcome and patterns of relapse in patients treated for skin carcinoma of the head and neck with either microscopic or clinical perineural invasion.

Methods and Materials.

Radiotherapy alone or combined with surgery was used to treat 135 patients with microscopic or clinical evidence of perineural invasion of skin carcinoma. All patients had at least 2 years of follow‐up.

Results.

The 5‐year local control rates without salvage therapy were 87% with microscopic perineural invasion and 55% with clinical perineural invasion. Overall, 88% of the local failures occurred in patients with positive margins. Almost half of the recurrences in patients with microscopic perineural invasion were limited to the first‐echelon regional nodes. However, only 1 of 11 patients with basal cell carcinoma with microscopic perineural invasion had a nodal failure. Ninety percent of recurrences in patients with clinical perineural invasion occurred at the primary site. Cranial nerve deficits rarely improved after successful treatment of the primary disease. Radiographic abnormalities remained stable 30% of the time when patients had clinical evidence of progressive disease.

Conclusions.

Radiotherapy in patients with skin cancer with clinical perineural invasion should include treatment of the first‐echelon regional lymphatics. The risk of regional node involvement is also relatively high for patients with squamous cell carcinoma with microscopic perineural invasion. In patients with clinical perineural invasion, the poor local control rates with conventional radiotherapy suggest a need for dose escalation with or without concomitant chemotherapy. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Depressive symptoms during and after radiotherapy for head and neck cancer
Authors: Sehlen Susanne , Lenk Marcus , Herschbach Peter , Aydemir Uelker , Dellian Marc , Schymura Beatrice , Hollenhorst Helmuth , Dühmke Eckhart
Published: June 2004

Background.

Patients with head and neck cancer are extraordinarily susceptible to depressive traits. Thus, a general screening of these patients at their first admission to the ital is desirable.

Methods.

From 1997–2001, 133 patients with head and neck tumors filled in the Self‐Rating‐Depression‐Scale (SDS) at the beginning and end of radiotherapy (ti1/ti2), 6 weeks, and 6 months after radiotherapy (ti3/ti4).

Results.

The SDS index increased significantly from 46.44 (ti1) to 48.91(ti2) (p = .025) and then remained stable. The subdomain “somatic‐eating‐related symptoms” at ti1 was significantly lower than ti2 (p < .001). In contrast to inpatients, outpatients and those with conventional instead of hyperfractionated‐accelerated radiotherapy were less impaired by eating‐related symptoms. Patients with higher education showed a lower SDS index and cognitive scale. Marital status, tumor stage, histologic grading, and substance abuse had no influence.

Conclusions.

Patients with a higher risk of depression should receive long‐term monitoring during and after the end of radiotherapy, and prompt intervention strategies should be applied. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000–000, 2003
Photoaddition Reactions of Benzoxazole‐2(3H)‐thiones to Cycloalkenes and Heteroaromatics
Authors: Nishio Takehiko , Shiwa Kiyoko , Sakamoto Masami
Published: June 2004

Photoaddition reactions of benzoxazole‐2‐thiones 1 with cycloalkenes 2 and heteroaromatics 3 were examined. Irradiation of N‐acylbenzoxazole‐2‐thiones 1a and 1b, and 3‐(methoxycarbonyl)‐ and 3‐(phenoxycarbonyl)benzoxazole‐2(3H)‐thiones (1f and 1h, resp.) in the presence of cycloalkenes 2a–2c, cyclohexa‐1,4‐diene (2d), and indene (2e) yielded 2‐substituted benzoxazoles 4–13, 18 and 19, and iminothietanes 14–17, by intramolecular trapping of the acyl or MeOCO and PhOCO groups by thiolate anion of the zwitterionic intermediate I and by the phenolate anion of the zwitterionic intermediate II, respectively, derived from the spirocyclic amino‐thietanes AT formed by [2+2] cycloaddition of the CS bond of 1 and CC bond of 2. Irradiation of 1 in the presence of heteroaromatics 3 gave the 2‐substituted benzoxazoles 20–33 exclusively.