Acid-catalyzed Addition Research Articles

Headspace Compounds from Centaurea cyanus L. Honey: The Occurrence of 3,4-Dihydro-3-Oxoedulan

Within the framework of our bioorganic studies and in an effort to identify headspace volatile organic constituents (HS-VOCs) restricted to specific honey types, we performed the chemical screening of cornflower Centaurea cyanus L. honey from Poland. The main components of specific honey volatiles belong, in general, to three principal groups of organic compounds: terpenes, norisoprenoids, and benzene derivatives [1]. Other compounds, like some alcohols, branched aldehydes, and furan/pyran derivatives, can be related to the honey processing and/or storage conditions [2]. No information is presently available on those HS-VOCs that are useful for chemical authentification of the floral origin of C. cyanus L. honey. Therefore, the aim of the present study was to identify them using headspace solid-phase microextraction (HS-SPME) and gas chromatography with mass spectrometric detection as well as with flame ionization detection (GC-MS and GC-FID). HS-SPME is a solvent-free isolation technique and has been proven effective for the isolation of honey VOCs [3–5]. This paper reports the identification, for the first time, of norisoprenoids as characteristic components of cornflower honey headspace, particularly the occurrence of the bicyclic oxoedulan skeleton. Preliminary experiments were carried out in order to compare the obtained chromatograms in terms of number of extracted compounds and peak areas, and the most suitable HS-SPME fiber was selected to be DVB/CAR/PDMS. A total of 32 organic compounds was identified from the samples and are listed in Table 1 according to the elution order on a HP-5MS column. The group of C 13 - and C 9 -norisoprenoids, a class of carotenoid-derived compounds with 3,5,5-trimethylcyclohex-2-enic structures, was the most abundant among isolated HS-VOCs of cornflower honey. The dominant C 13 compound was 3,4-dihydro-3-oxoedulan (2,3,5,6,8,8a-hexahydro-2,5,5,8a-tetramethyl-7H-1-benzopyran-7-one, also known as 2,5,5,8a-tetramethyl2,3,5,6,8,8a-hexahydro-7H-chromen-7-one; 18.60–44.97%) with mass spectrum (EI, 70 eV), m/z (I rel , %): 208 (M + , 7), 193 (100), 166 (7), 151 (15), 149 (6), 124 (30), 123 (10), 122 (8), 109 (65), 107 (32), 105 (10), 93 (10), 91 (18), 81 (11), 79 (16), 57 (10), and 55 (10) that correspond to the spectra of the same C 13 -norisoprenoid found in oak wood [6]. The compound 3,4-dihydro-3-oxoedulan and the saturated analog tetrahydro-3-oxoedulan are also components of Burley tobacco [7], and the former also occurs in passion fruit [8]. However, this is the first report on 3,4-dihydro-3-oxoedulan with high abundance in honey headspace that can be useful for characterization of C. cyanus L. honey. The formation of the oxoedulan by intramolecular acid-catalyzed conjugate addition may well take place in acidic medium (e.g., hive conditions). Such reactions have already been utilized in the synthesis of the oxoedulans [9]. Polyhydroxylated C 13 -norisoprenoids (e.g., 3-hydroxy-retro--ionol) are natural precursors of edulans [10]. The oxoedulan structure contains epoxide with the oxo group in position 3, so it is more volatile in comparison with its hydroxylated precursors, which can exhibit hydrogen donor and acceptor properties in the formation of hydrogen bonds in the honey-water solution. Therefore, 3,4-dihydro-3-oxoedulan was abundant in the headspace, while hydroxylated or polyhydroxylated C 13 -norisoprenoids were not expected to be found due to their limited headspace participation. However, several lower molecular oxygenated C 9 -norisoprenoids were found: 4-oxoisophorone (3,5,5-trimethylcyclohex-2ene-1,4-dione; 4.35–11.23%), isophorone (3,5,5-trimethyl-cyclohex-2-en-1-one; 1.12–5.48%), and 2-hydroxyisophorone (2-hydroxy-3,5,5-trimethyl-2-hydroxycyclohex-2-en-1-one; 0.00–2.30%). Previous studies showed that the types and amounts of norisoprenoids are related to the honey botanical origin and have been proposed as chemical markers of the honey floral source [1].

Thermodynamics based stability analysis and its use for nonlinear stabilization of the CSTR

We show how the availability function as defined from the entropy function concavity can be used for the stability analysis and derivation of control strategies for non-isothermal Continuous Stirred Tank Reactors (CSTRs). We first propose an overview of the required thermodynamic concepts. Then, we show how the availability function restricted to the thermal domain can be used as a Lyapunov function. The derivation of the control law and the way the strict entropy concavity is insured are discussed. Numerical simulations illustrate the application of the theory to the open loop stability analysis and the closed loop control of liquid-phase non-isothermal CSTRs. The proposed approach is compared with the classical proportional control strategy. Two chemical reactions are studied: the acid-catalyzed hydration of 2-3-epoxy-1-propanol to glycerol subject to steady state multiplicity and the production of cyclopentenol from cyclopentadiene by acid-catalyzed electrophilic addition of water in dilute solution exhibiting a non-minimum phase behavior.

Acid-Catalyzed Nucleophilic Additions to Carbonyl Groups: Is the Accepted Mechanism the Rule or an Exception?

The transesterification reaction, and in particular the methanolysis of ethyl acetate with sulfuric acid as catalyst, is used as a model reaction to study the acid-catalyzed nucleophilic addition to a carbonyl group. Continuum solvation methods (SMD and IEF-PCM) and the MPWB1K functional are used. The reaction mechanism is studied in methanol and in acetonitrile as solvents. Our results indicate that the acid-catalyzed addition mechanism is stepwise, and the transition state (TS) is a contact ion-pair. The counteranion of the acid catalyst remains in the reaction site playing an important role in the TS of this reaction. Changes in the reaction kinetics and the ionic/nonionic nature of the TS with the ionizing ability of the solvent and the strength of the acid catalyst are explored. Additional calculations at the CBS-Q3 level of theory reinforce the conclusions of this paper. The results obtained allow the generalization of important ideas regarding the mechanism of the nucleophilic addition to carbonyl groups.

Asymmetric Brønsted Acid-catalyzed Intramolecular aza-Michael Reaction – Enantioselective Synthesis of Dihydroquinolinones

The enantioselective synthesis of 2-aryl-substituted 2,3-dihydroquinolin-4-ones, a class of heterocyclic compounds with interesting biological activities, has been achieved through a Brønsted acidcatalyzed enantioselective intramolecular Michael addition. The products are available in moderate to high yields and with good enantioselectivities.

Stereoselective Synthesis of 2,6-Cis-Substituted Tetrahydropyrans: Brønsted Acid-Catalyzed Intramolecular Oxa-Conjugate Cyclization of α,β-Unsaturated Ester Surrogates

Intramolecular oxa-conjugate cyclization (IOCC) of α,β-unsaturated carbonyl compounds, triggered by deprotonation with a base, represents a straightforward method for the synthesis of tetrahydropyrans. However, it has been known that stereochemical outcome of IOCC depends on the local structure of substrates and sometimes requires harsh reaction conditions and/or prolonged reaction times for selective formation of 2,6-cis-substituted tetrahydropyrans. These shortcomings limit the feasibility of IOCC in the context of complex natural product synthesis. In this paper, we describe Brønsted acid-catalyzed IOCC of α,β-unsaturated ester surrogates (e.g., α,β-unsaturated thioesters, oxazolidinone imides, and pyrrole amides) under mild reaction conditions, which affords a series of synthetically versatile 2,6-cis-substituted tetrahydropyran derivatives with good to excellent stereoselectivity (dr from 7:1 to >20:1). These α,β-unsaturated carbonyl compounds were found to be more reactive than the corresponding oxoesters that are generally unreactive toward Brønsted acid-catalyzed intramolecular oxa-conjugate additions. The product tetrahydropyrans could be transformed into various derivatives in an efficient manner, highlighting the usefulness of our methodology.

Chemoselective reactions of trimethylsilylpropynal with aminopyrimidines and amino acid esters

Highly efficient chemoselective 1,2-addition of 2-aminopyrimidines and D,L-amino acid esters to substituted propynals was performed. Acid-catalyzed addition of 2-aminopyrimidine and 2-amino-4-methylpyrimidine to trimethylsilyl- and phenylpropynals gave previously unknown acetylenic aminals. Reactions of α-amino acid methyl esters (alanine and lysine) with trimethylsilylpropynal led to the formation of new aza enynes in high yield. Regardless of the reactant ratio, trimethylsilylpropynal reacted with lysine at both amino groups with formation of bis-aza enyne.

ChemInform Abstract: Lewis Acid-Catalyzed Addition Reaction of Disulfides to 3-Carene.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Conformationally Restricted Spin Labelled Nucleotides: A Model Study of the Synthesis and Properties of the 2′,3′-O-Spiro Ketal of Uridine and 4-Oxo-2,2,6,6-tetramethyl-1-piperidyloxy.

The synthesis of 2′,3′-O-(1-oxy-2,2,6,6-tetramethyl-4-piperidylidene)uridine 13 is described in a model study directed at the corresponding spin labelled spiro ketal derivative of ATP (adenosine triphosphate)1 and of other nucleotides. The synthesis proceeds via acid-catalysed addition of 5′-O-benzoyluridine to 1-acetoxy-4-methoxy-2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine 9. The spiro ketal 11 from this reaction exists as two slowly interconverting conformers at room temperature. Prolonged alkaline hydrolysis and concomitant aerial oxidation gives the required product 13.

ChemInform Abstract: Composition of Mixtures of Hydrocarbons After Birch-Reduction of Substituted Benzenes and Acid-Catalyzed Addition of Alcohols to Alkylsubstituted Cyclohexenes and Cyclohexa-1,4-dienes.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Acid-Catalyzed Addition of N-Aryl Imines to Dihydrofuran. Postulated Dependence of the Reaction Mechanism on the Relative Face of Approach of Reactants.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Unusual Reactivity of Bent Acenes: Reactions of (6)(1,4) Naphthalenophane and (6)(1,4)Anthracenophane with Electrophiles.

The unusual reactivity of [6](1,4)naphthalenophane (2) and [6](1,4)anthracenophane (3), the smallest-bridged acenophanes hitherto known, in electrophilic reactions has been disclosed. These reactions include (i) acid-catalyzed telomerization, (ii) peracid oxidation, and (iii) addition with dienophiles. Semi-empirical molecular orbital calculations (MNDO and MNDO/PM3) were performed in order to compare the geometries, energies, and bonding characters of 2 and 3 with those of [6]paracyclophane (1)

ChemInform Abstract: A New Procedure for the Preparation of Bilirubin IIIα from Bilirubin IXα.

Abstract A procedure for the preparation of bilirubin IIIα with an overall 15% yield from the natural, unsymmetric bilirubin IXα is described which does not require hplc separation at any stage. The process involves: 1) quantitative, acid-catalyzed addition of ethanethiol to the exo vinyl group of bilirubin IXα to give the bilirubin IXα thioether adduct 1; 2) acid-catalyzed constitutional isomerization (scrambling) of 1 to a statistical mixture containing ca. 25% of the bilirubin IIIα bis-thioether adduct 2; 3) 3-chloroperoxybenzoic acid (or, less efficiently, periodate) oxidation of 2 (in that statistical mixture) to the corresponding, more polar, bis-sulfoxide 4, followed by its simple chromatographic separation from the reaction mixture; and 4) thermal elimination in the bis-sulfoxide 4 to bilirubin IIIα.

On the reactivity of isoindolo[2,1-a]quinazoline-5-ones

Base- and acid-catalyzed nucleophilic addition of 11 H -isoindolo[2,1- a ]quinazoline-5-one to aromatic aldehydes and maleimides was investigated. The aldol adducts and condensation products were obtained stereoselectively. Main diastereomers of the Michael adducts were isolated in 74–89% yield, and converted by N -methylation to new stable α-substituted isoindole derivatives, for which 6-methylisoindolo[2,1- a ]]quinazoline-5-one stands as the unsubstituted reference. The stability of the latter was monitored in moist aerated CDCl 3 solution, and one of the oxidative hydrolysis product was characterized by X-ray diffraction analysis as the corresponding N -arylphthalimide. The reactivity of the unsubstituted 6-methylisoindolo[2,1- a ]]quinazoline-5-one was also investigated with acetylenic Michael acceptors. Fully conjugated isoindole derivatives possessing an original pull–push–pull structure were obtained. The conformations and molecular orbitals of the dibenzoylacetylene adduct were studied at the DFT level of theory. Its static quadratic hyperpolarizabilty β 0 was also calculated at the ZINDO level.

ChemInform Abstract: Reactivity of 2-Methylene-1,3-dicarbonyl Compounds. Stereoselective and Asymmetric Diels-Alder Reactions.

The Diels-Alder reaction of 1,1-dicarbonylethenes 1 with dienes was investigated. The adduct of the reaction of 1, whose two carbonyl groups were different, with cyclopentadiene showed moderate stereoselectivity and this was explained by FMO theory. However, in the Lewis acid-catalyzed addition, the reaction proceeded with high stereoselectivity to give the exo adduct 3x. This might be due to steric hindrance because the benzene ring cannot orient in the plane of the conjugated system in the metal-chelated enedione 6. Applying this principle to (1'R,2'S,5'R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate (1d), we achieved a diastereomeric Diels-Alder reaction to afford 3x-R, whose structure was confirmed by the X-ray crystal analysis.

Kinetics and mechanism for the acid-catalyzed addition of propionic acid to tetradecenes and hexadecenes

We developed a kinetic model for the reversible direct addition of propionic acid to linear tetradecences and linear hexadecenes on Amberlyst 15 at 93°C. The model addresses concurrent double bond isomerization of the olefins and assumes carbenium ion formations to be rate limiting for all conversions; it is detailed enough to include terms for multiple isomers of esters and olefins. The reaction was first order in olefin and in ester but was one-half order in propionic acid. Gas chromatography was the analytical method employed to follow the reactions, and this study represents a novel use of this analytical method to elucidate carbenium ion behavior. The model includes five rate-determining steps and five fast steps. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 354–371, 2010

Acid-catalyzed intramolecular oxa-Michael addition reactions under solvent-free and microwave irradiation conditions

The acid-catalyzed intramolecular oxa-Michael addition of (E)-1-aryl-4-hydroxy-4-methyl- -pent-1-en-3-ones under solvent-free and microwave irradiation conditions has been investigated. The results showed that Bronsted acids are more efficient than Lewis acids in this reaction. Up to 90% conversion and 81% yield were obtained using trifluoromethanesulfonic acid (triflic acid) as the catalyst, with short reaction times and an environmentally benign procedure.

New class of reactive novolac: synthesis of bisphenol A-based novolac with methylol groups

We successfully prepared a new class of a reactive novolac (3) having a methylol moiety as a functional group derived from its precursor synthesized by the acid-catalyzed addition–condensation of a bisphenol A derivative and formaldehyde. Curing reaction between 3 and the low-molecular-weight phenolic resin (4) afforded the curing product, which showed enhanced thermal stability compared with 4 or the conventional phenolic resin. Consequently, 3 can be applied as a curing agent to modify the thermal property of 4.

Glycosylation of aromatic amines II: Kinetics and mechanisms of the hydrolytic reaction between kynurenine and glucose

The kinetics of the weakly basic aromatic amine, kynurenine, with glucose were studied as model reactants aimed at mechanistic understanding of pharmaceutically relevant amine-aldehyde reactions. The reaction kinetics of the forward and reverse processes (glycosylamine formation and hydrolysis) were studied under first-order conditions in aqueous solutions at 40°C in the pH range 1–6.5 in the presence of various buffers. The α-and β-glycosylamines were reversibly formed via an acyclic imine that was not present in detectable quantities. Rate-limiting formation of the imine was complex and involved the addition of the amine and aldehyde to form the carbinolamine followed by the acid-catalyzed dehydration to the imine. The pH-rate profile was characterized by three kinetically distinguishable processes. At lower pH values, the profile was consistent with specific acid-catalyzed rate-determining addition of amine and aldehyde. In the pH range of 4–6 a downward bend was attributable to the change in rate determining step from addition to dehydration. In the pH region of 2–3 the rate law was described by specific acid catalysis and solvolysis of the zwitterionic form of kynurenine. Nonlinear buffer effects and Brönsted plots were shown to be consistent with this interpretation of the pH-rate profile. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4616–4628, 2009

Gas-Phase Facial Diastereoselectivity of Equatorial and Axial 4-Chloro-adamant-2-yl Cations

The acid-catalyzed addition of CH3(18)OH to 2-methylene-adamantanes bearing a chlorine atom in the 4-equatorial (1e) or 4-axial (1a) position has been investigated in the gas phase, at 760 Torr, in the 40-120 degrees C temperature range. Two different experimental approaches were employed: (1) by adding neutral CH3(18)OH to the 2-methyl-4-Cl-adamant-2-yl cation, generated by protonation of the corresponding 2-methylene-4-Cl-adamantane (the extracomplex reaction) and (2) by reaction of 2-methylene-4-Cl-adamantane with CH3(18)OH2+, generated by methylation of H2(18)O (the intracomplex reaction). The crucial role of the nature of the noncovalent intermediates involved along the reaction coordinates emerges from the difference between the results obtained in the extracomplex and intracomplex reactions for both substrates investigated. The kinetic and stereochemical results indicate that the 4-Cl substituent plays a different role depending on its equatorial or axial orientation. Examination of the experimental results in the light of MP2/6-31G* theoretical calculations provides important information about the intrinsic factors governing the facial diastereoselectivity of trigonal carbocations. The effects due to differential face solvation phenomena emerge from the comparison of the present gas-phase results with those obtained from strictly related studies in solution.

Acid-Catalyzed Cascade Ring-Opening and Addition Reactions of Arylvinylcyclopropenes with α,β-Unsaturated Substrates, Scope and Limitations

Catalyzed by Al(III) catalyst, arylvinylcyclopropenes react with alpha,beta-unsaturated substrates smoothly to produce the Diels-Alder adducts in moderate to good yields through a cascade ring-opening reaction/Diels-Alder cycloaddition. On the other hand, strong Brønsted acid TfOH can promote the cascade intramolecular Friedel-Crafts/1,4-addition reaction to produce indene derivatives in moderate to good yields under mild conditions. The acidity of the catalysts plays a key role in these reactions.