- Accelerating Biphasic Biocatalysis through New Process Windows
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Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high-performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase-transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase-catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high-value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions.
- Huynh, Florence,Tailby, Matthew,Finniear, Aled,Stephens, Kevin,Allemann, Rudolf K.,Wirth, Thomas
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supporting information
p. 16490 - 16495
(2020/07/17)
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- Highly Focused Library-Based Engineering of Candida antarctica Lipase B with (S)-Selectivity Towards sec-Alcohols
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Candida antarctica lipase B (CALB) is one of the most extensively used biocatalysts in both academia and industry and exhibits remarkable (R)-enantioselectivity for various chiral sec-alcohols. Considering the significance of tailor-made stereoselectivity in organic synthesis, a discovery of enantiocomplementary lipase mutants with high (R)- and (S)-selectivity is valuable and highly desired. Herein, we report a highly efficient directed evolution strategy, using only 4 representative amino acids, namely, alanine (A), leucine (L), lysine (K), tryptophan (W) at each mutated site to create an extremely small library of CALB variants requiring notably less screening. The obtained best mutant with three mutations W104V/A281L/A282K displayed highly reversed (S)-selectivity towards a series of sec-alcohol with E values up to 115 (conv. 50%, ee 94%). Compared with the previously reported (S)-selective CALB variant, W104A, a single mutation provided less selectivity, while the synergistic effects of three mutations in the best variant endow better (S)-selectivity and a broader substrate scope than the W104A variant. Structural analysis and molecular dynamics simulation unveiled the source of reversed enantioselectivity. (Figure presented.).
- Cen, Yixin,Li, Danyang,Xu, Jian,Wu, Qiongsi,Wu, Qi,Lin, Xianfu
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supporting information
p. 126 - 134
(2018/12/05)
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- METHOD FOR PRODUCING FLUORINATED HYDROCARBON
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PROBLEM TO BE SOLVED: To provide a method for industrially advantageously producing a fluorinated hydrocarbon. SOLUTION: The method for producing a fluorinated hydrocarbon represented by formula (3) comprises bringing a secondary or tertiary ether compound represented by formula (1) into contact with an acid fluoride represented by formula (2) in the presence of a compound having an N-X bond (X is a halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom) in a halogenated hydrocarbon-based solvent. (R1 and R2 are each independently a C1-C3 alkyl group; R3 is H, a methyl group, or an ethyl group; R4 and R5 are each a methyl group or an ethyl group; and R1 and R2 may be bonded together to form a ring structure.) SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0063; 0067; 0072
(2018/03/09)
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- Enzymatic kinetic resolution of aliphatic sec-alcohols by LipG9, a metagenomic lipase
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Bioprospection for new enantioselective enzymes for application in organic synthesis is a prominent area of investigation in biocatalysis. In this context, here we present the evaluation of an immobilized lipase isolated from a metagenomic library (LipG9) for the enzymatic kinetic resolution (EKR) of aliphatic sec-alcohols, which are still challenging substrates, since low enantioselectivity values are usually observed for these resolutions. LipG9 was successfully employed in EKR of aliphatic alcohols, which were resolved with satisfactory conversions (19-59%) and enantiomeric excesses for alcohols (26-88%) and esters (30-96%) by transesterification reactions, demonstrating that its performance is equal to or better than commercially available enzymes for the same reaction.
- Bandeira, Pamela T.,Alnoch, Robson C.,De Oliveira, Alfredo R.M.,De Souza, Emanuel M.,De O.P., Fábio,Krieger, Nadia,Piovan, Leandro
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- Understanding ketone hydrodeoxygenation for the production of fuels and feedstocks from biomass
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Although we can efficiently convert bioderived furans into linear alkanes, the most energy-intensive step in this approach is the hydrodeoxygenation of the intermediate polyketone. To fully understand this process, we have examined the hydrodeoxygenation of a model compound, 3-pentanone, which allows us to follow this process stepwise using Pd/C, H2 (200 psi), and La(OTf)3 in acetic acid to remove the oxygen atom at temperatures between 25 and 200 C. We have found that ketone reduction to an alcohol is followed by acetoxylation, which provides a more facile route to C-O bond cleavage relative to the parent alcohol. (Chemical Presented).
- King, Amanda E.,Brooks, Ty J.,Tian, Yong-Hui,Batista, Enrique R.,Sutton, Andrew D.
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p. 1223 - 1226
(2015/02/19)
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- Graphite oxide as an efficient solid reagent for esterification reactions
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Esterification of organic acids with alcohols under mild conditions in high yields using graphite oxide, a readily available and inexpensive material, as an effective reagent is described.
- Mirza-Aghayan, Maryam,Rahimifard, Mahshid,Boukherroub, Rabah
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p. 859 - 864
(2014/12/10)
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- Fractional distribution of graphene oxide and its potential as an efficient and reusable solid catalyst for esterification reactions
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Graphene oxide (GrO) prepared by the Hummers method was separated into three different fractions (GrO5000, GrO2000, and GrOres) on the basis of their dispersion stability in the water. Infrared, nuclear magnetic resonance, X-ray photoelectron spectroscopy, and elemental analyses revealed that GrO5000 possesses a high degree of oxygen functionalities including phenolic, carboxylic, and -OSO2H groups, compared with the other fractions. The GrO5000 was found to be a highly efficient and reusable solid catalyst for the esterification of various carboxylic acids with a variety of alcohols to furnish corresponding esters in high to excellent yields. The catalytic activity of the GrO5000 was attributed to the ability of highly polar GrO5000 scaffold to adsorb/attract reactants, where the acid functionalities of GrO5000 facilitated the esterification process efficiently. The chemical and structural features of GrO5000 were discussed to understand the improved catalytic activity compared with GrO2000 and conventional solid acid catalysts.
- Mungse, Harshal P.,Bhakuni, Niharika,Tripathi, Deependra,Sharma, Om P.,Sain, Bir,Khatri, Om P.
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p. 944 - 951
(2015/02/02)
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- Fractional distribution of graphene oxide and its potential as an efficient and reusable solid catalyst for esterification reactions
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Graphene oxide (GrO) prepared by the Hummers method was separated into three different fractions (GrO5000, GrO2000, and GrOres) on the basis of their dispersion stability in the water. Infrared, nuclear magnetic resonance, X-ray photoelectron spectroscopy, and elemental analyses revealed that GrO5000 possesses a high degree of oxygen functionalities including phenolic, carboxylic, and -OSO2H groups, compared with the other fractions. The GrO5000 was found to be a highly efficient and reusable solid catalyst for the esterification of various carboxylic acids with a variety of alcohols to furnish corresponding esters in high to excellent yields. The catalytic activity of the GrO5000 was attributed to the ability of highly polar GrO5000 scaffold to adsorb/attract reactants, where the acid functionalities of GrO5000 facilitated the esterification process efficiently. The chemical and structural features of GrO5000 were discussed to understand the improved catalytic activity compared with GrO2000 and conventional solid acid catalysts.
- Mungse, Harshal P.,Bhakuni, Niharika,Tripathi, Deependra,Sharma, Om P.,Sain, Bir,Khatri, Om P.
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p. 944 - 951
(2015/08/25)
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- Hydroacetoxylation of olefins with acetic acid genetated in situ from vinyl acetate in the presence of ruthenium complexes
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Ruthenium complexes catalyze the decomposition of vinyl acetate releasing the acetic acid and its subsequent addition to linear and cyclic olefins.
- Khusnutdinov,Shchadneva,Khisamova,Dzhemilev
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experimental part
p. 155 - 160
(2011/05/03)
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- Highly efficient and versatile acetylation of alcohols, phenols and amines catalyzed by methylenediphosphonic acid (MDP) under solvent-free conditions
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Methylenediphosphonic Acid (MDP) was found to be a simple, cheap and reusable heterogeneous catalyst for the acetylation of structurally diverse alcohols, phenols and amines with acetic anhydride under solvent-free conditions at room temperature. This method showed preferential selectivity for the acetylation of the amino group in the presence of hydroxyl group. The method is very mild and the yields were in excellent.
- Xie, Minhao,Wang, Hongyong,Wu, Jun,He, Yongjun,Liu, Yaling,Zou, Pei
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experimental part
p. 884 - 886
(2012/04/23)
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- (S)-2-pentyl (R)-3-hydroxyhexanoate, a banana volatile and its olfactory recognition by the common fruit fly, Drosophila melanogaster
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The volatile organic compounds emitted from ripening bananas that elicit an antennal response from the common fruit fly, Drosophila melanogaster, were analyzed by a combination of gas chromatographic-electroantennographic detection, mass spectrometry, and 1H NMR spectroscopy. These analyses revealed that the headspace of ripening bananas contains a number of EAD-active components including the new ester (S)-2-pentyl (R)-3-hydroxyhexanoate, the structural assignment of which was confirmed by chemical synthesis.
- Mowat, Jeffrey,Gries, Regine,Khaskin, Grigori,Gries, Gerhard,Britton, Robert
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scheme or table
p. 772 - 776
(2009/12/25)
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- Enantioselective analysis of secondary alcohols and their esters in purple and yellow passion fruits
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The enantiomeric compositions of the acetates, butanoates, hexanoates, and octanoates of the secondary alcohols 2-pentanol, 2-heptanol, and 2-nonanol were determined in yellow (Passiflora edulis f. flavicarpa) and purple (Passiflora edulis Sims) passion fruits. The compounds were isolated by means of simultaneous distillation-extraction. Enantiodifferentiation was performed via multidimensional gas chromatography using heptakis(2,3-di-O-methyl-6-O-tert- butyldimethylsilyl)-β-cyclodextrin as chiral stationary phase. The series of homologous 2-alkyl esters, which are typical constituents of purple passion fruits, were shown to be present as nearly optically pure (R)-enantiomers. The proportions of the (S)-enantiomers varied in different batches and were dependent on the alcohol moieties of the esters. For minor amounts of esters detected in yellow fruits, the (R)-enantiomers were also dominating. However, the enantiomeric excesses were significantly lower than in the purple variety. Enantioselective analysis of the free alcohols revealed that 2-heptanol exhibited opposite configurations in purple and yellow passion fruits. A similar phenomenon was observed for 2-pentanol, which was present in the yellow fruits as a nearly racemic mixture. Data determined in extracts obtained by other techniques (liquid-liquid extraction, vacuum headspace technique) showed that the isolation procedure had no significant impact on the enantiomeric ratios.
- Strohalm, Hedwig,Dregus, Marta,Wahl, Astrid,Engel, Karl-Heinz
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experimental part
p. 10339 - 10344
(2009/09/25)
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- Structure-function correlation in lipase catalysed esterification reactions of short and medium carbon chain length alcohols and acids
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An attempt has been made to correlate the carbon chain lengths of acids and alcohols to the extent of esterification in the Rhizomucor miehei lipase catalyzed esterification reactions involving acids of carbon chain length C2-C5 and alcohols of carbon chain length C1-C8.
- Divakar, Soundar
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p. 1919 - 1922
(2007/10/03)
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- Bi(III) carboxylates as efficient reagents for preparation of esters under mild conditions. A new method for the protection of carboxylic acids
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Bi(III) carboxylates have been obtained by reaction of triphenylbismuth with various monocarboxylic acids. By a ligand-exchange reaction, these Bi(III) carboxylates react with tertiary or benzylic-type bromides and afford esters. This reaction sequence constitutes a new efficient way for the temporary protection of carboxylic acids under mild conditions.
- Keramane, El-Mehdi,Boyer, Bernard,Roque, Jean-Pierre
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p. 855 - 857
(2007/10/03)
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- FeCl3-adsorbed on montmorillonite K-10: An efficient catalyst for one-pot dealkylation-acetylation of ethers
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Direct conversion of ethers into acetates is achieved by treatment of ethers with acetic anhydride in the presence of FeCl3-adsorbed on montmorillonite K-10.
- Lakouraj, Mansour,Movassagh, B.,Fasihi, J.
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p. 378 - 379
(2007/10/03)
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- Enzymatic resolution of racemic secondary alcohols by lipase B from Candida antarctica
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Chiral intermediates S-(+)-2-pentanol and S-(+)-2-heptanol were prepared by a lipase-catalyzed enzymatic resolution process. Among various lipases evaluated for the stereoselective acylation of racemic alcohols, lipase B from Candida antarctica catalyzed the acylation of the undesired enantiomer of racemic alcohols leaving the desired S-(+)-alcohols unreacted. A reaction yield of 43-45% and an enantiomeric excess (e.e.) of >99% were obtained for S-(+)-2-pentanol or S-(+)-2-heptanol when the reaction was carried out using vinyl acetate or succinic anhydride as acylating agent. In an alternative process, an enantioselective hydrolysis of 2-pentyl acetate was demonstrated using lipase B giving S-(+)-2-pentyl acetate and R-(-)-2-pentanol. A reaction yield of 45% and an e.e. of 98.6% were obtained for S-(+)-2-pentyl acetate.
- Patel, Ramesh N.,Banerjee, Amit,Nanduri, Venkata,Goswami, Animesh,Comezoglu
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p. 1015 - 1019
(2007/10/03)
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- Kinetics and mechanism of nucleophilic displacements with heterocycles as leaving groups. Part 23. Studies at the borderlines between reactions proceeding (i) via free carbocations, (ii) via rate-determining formation of ion-molecule pairs, and (iii) via rate-determining nucleophilic ...
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Evidenece is presented to demonstrate that at the borderline between first order reaction via the formation of free carbocations, both mechanism proceed independently, without merging.Similarly at the borderline between first-order (rate determining formation) and second-order (rate-determining nucleophilic attack) rections of intimate ion-molecule pairs, both reactions again proceed independently.
- Katritzky, Alan R.,Brycki, Bogumil
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p. 1161 - 1169
(2007/10/02)
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- THE REACTION OF LEAD TETRAACETATE WITH HYDROCARBONS
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The free radical reaction of lead tetraacetate with hydrocarbons has been investigated.The products of these reactions are the acetate esters.The hydrogen abstracting species from lead tetraacetate is found to have a primary to secondary to tertiary selectivity of 1:27:123 based upon relative reactivities.
- Mosher, Melvyn W.,Cox, Jeffery L.
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p. 3753 - 3756
(2007/10/02)
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- Nucleophilic Displacement with Heterocycles as Leaving Groups. Part 16. Reactions of Secondary Alkyl Primary Amines with 5,6,8,9-Tetrahydro-7-phenyldibenzoxanthylium Trifluoromethanesulphonate to give Intermediates Solvolysing without Rearrangement
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Representative secondary alkyl primary amines R1R2CHNH2 react with the title pyrylium cation in acetic acid, alcohols, phenols, and NN-dimethylaniline acting as nucleophilic solvents to give O- and C-(secondary alkyl) products.Absence of carbenium ion rearrangements is consistent with reaction via intimate ion-molecule pairs formed rapidly from the corresponding pyridinium cations.
- Katritzky, Alan R.,Lopez-Rodriguez, Maria L.,Keay, James G.,King, Roy W.
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p. 165 - 170
(2007/10/02)
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- Kinetics and Mechanisms of Nucleophilic Displacements whit Heterocycles as Leaving Groups. Part 15. Dependence of Mechanism of Solvolysis of Pyridinium Cations on Solvent Character: Evidence from Rates,p* Values, and Product Analysis
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p* Values are reported for solvolyses of a series of 1-(s-alkyl)pyridinium cations in 2,2,2-trifluoroethanol or 1,1,1,3,3,3-hexafluoropropan-2-ol as solvents in the absence of nucleophiles.The corresponding reactions with pyridine, piperidine, or morpholine as nucleophile in chloroform, acetonitrile, 2,2,2-trifluoroethanol, or 1,1,1,3,3,3-hexafluoropropan-2-ol are kinetically first-order (independent of nucleophile concentration);these allow p* to be calculated. p* Values correlate with solvent ET values except for pentanol and acetic acid, in which cases they are smaller than expected.Product analysis discloses rearrangement products (derived by hydride shifts) only for solvolysis in non-nucleophilic solvents (trifluoroacetic acid and 1,1,1,3,3,3-hexafluoropropan-2-ol) in the absence of added nucleophilic solvents.The results are interpreted in terms of (a) solvent-assisted solvolysis in nucleophilic solvents, (b) SN1 cleavage of the C-N bond in the rate-determining step both for the unimolecular reactions in the presence of external nucleophiles, and for solvolysis in 2,2,2-trifluoroethanol, and (c) rate-determining ion-molecule pair dissociation for solvolysis in trifluoroacetic acid or 1,1,1,3,3,3-hexafluoropropan-2-ol.
- Katritzky, Alan R.,Lopez-Rodriguez, Maria L.,Marquet, Jorge
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p. 349 - 354
(2007/10/02)
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- Kinetics and Mechanisms of Nucleophilic Displacement with Heterocycles as Leaving Groups. 17. Solvolysis of 14-(Primary alkyl)-5,6,8,9-tetrahydro-7-phenyldibenzoacridiniums: Rates, Identification of Products, Activation Parameters, and a General Discussion of Mechanism
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Solvolysis rate are reported for the Me, Et, n-Pr, n-Pent, n-Oct, i-Bu, neo-Pent, PhCH2CH2, and MeOCH2CH2 title compounds in MeOH, EtPH, PentOH, CH3CO2H, and CF3CO2H.Rate variations with alkyl group structure are far less than the corresponding rate variations for the tosylate solvolysis, and afford no evidence for rate-enhancing participation by β-phenyl or β-methoxy groups in the acridinium solvolyses.The n-propyl, n-pentyl, and n-octyl title compounds solvolyze in CH3OD and CH3CO2D to give mixtures of normal and rearranged products, none of which contain deuterium and which are therefore not formed via olefin intermediates.Methanolysis of the isobutyl title compounds occurs via olefin, but the acetolysis also involves an important nonolefinic pathway yielding isobutyl and sec-butyl acetates.Methanolysis products from the neopentyl derivative are heavily deuterated, but acetolysis yields undeuterated neopentyl acetate as well as deuterated tert-pentyl acetate.Product proportions calculated using GC/MS were used to deduce the fractions of reactions by various mechanistic pathways.Individual rates are calculated for solvolysis to the various unrearranged and rearranged products.They indicate that normal substitution in MeOH occurs by a classical SN2 reaction, but that such substitution in AcOH involves ion-pair intermediates.It is concluded that such ion pairs under go Me and H migration after the rate-determining stage, in competition with substitution.Activation parameters provide further evidence for the mechanistic paths proposed which are discussed in relation to literature data available for the corresponding tosylate.
- Katritzky, Alan R.,Dega-Szafran, Zofia,Lopez-Rodriguez, Maria L.,King, Roy W.
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p. 5577 - 5585
(2007/10/02)
-
- Acid-induced 13C Nuclear Magnetic Resonance Chemical Shift Changes of Ether and Ester Carbon Atoms
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13C N.m.r. chemical shifts of ehters dissolved in tetrachloromethane are displaced on addition of trifluoroacetic acid.The displacements result from independent interactions of the acid with the substrate oxygen atoms and alkyl residues.The structure-dependent and stereoselective shift changes are useful for signal assignments, structure determination, conformational analysis, assessment of the distribution of rapidly interconverting conformers of esters, and estimation of the relative basicity of ethers.
- Begtrup, Mikael
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p. 1609 - 1618
(2007/10/02)
-
- Classical Carbonium Ions. Part 13. Rearrangements from Secondary to Primary Alkyl Groups during Reactions involving Carbonium Ions
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The rearrangement of cyclohexylamine to cyclopentylmethyl derivatives, earlier reported in brief, is confirmed.A similar reaction with 4-trans-t-butylcyclohexylamine is shown to give trans-3-t-butylcyclopentylmethyl derivatives, defining the conformational requirements and stereochemical course of the rearrangement.In similar reactions 2-butylamine and 3-pentylamine give, in small yield, derivatives of primary alcohols.Cyclohexyl toluenesulphonate probably gives a very small yield of cyclopentylmethyl acetate.All these reactions involve the formation of products formally derived from carbonium ions much less stable than those initially generated, and yields, though small, are much larger than can be accounted for by classical descriptions.It is proposed that corner-protonated cyclopropanes ('non-classical carbonium ions') are 'intermediates' of very short lifetime in these reactions; the extent to which it is possible to regard species of very short lifetime as intermediates is discussed.
- Cooper, Catherine N.,Jenner, Peter J.,Perry, Nigel B.,Russel-King, Jonquil,Storesund, Hans J.,Whiting, Mark C.
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p. 605 - 612
(2007/10/02)
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- FORMATION DE CETONES ETHYLENIQUES PAR ACTION D'ACIDE ACETYLSULFOACETIQUE SUR DES ALCENES
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Monoalkyl- and 1,2-dialkylethylenes have a similar behaviour under the action of acetylsulfoacetic acid : the reaction does not necessarily stop after the formation of α- or β-enones, the yield of which is highly influenced by reaction time; thus, 1-acetoxy-1,3-dienes are identified in the case of α-enones.A different behaviour is shown by 1,1-dialkyl and trialkylethylenes, which can constitute an interesting source of highly branched enones.With this second group of alkenes, isomerisation of the alkene is sometimes observed prior to acetylation.Lastly, some alkenes undergo acetoxylation at the same time as acetylation.
- Loiseau, Andre-Michel,Luft, Robert,Zunino, Serge
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p. 144 - 152
(2007/10/02)
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- Synthetic applications of α-hydroxydiazenes. III. Uncatalyzed and phenol catalyzed hydroalkylation of alkenes and of azobenzene with alkylazodiphenylmethanols
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Alkylazodiphenylmethanols (C6H5)2C(OH)N=NR, (R = CH(CH3)2, CH2CH3, CH3), when decomposed in the presence of olefinic substrates or in the presence of azobenzene, hydroalkylate those substrates.Addition of R and H across the double bond of an unsymmetric alkene occurs with the regiochemistry expected for a radical mechanism, in which the grooup R adds first.Radical intermediates from decomposition of alkylazodiphenylmethanols have been demonstrated earlier with spin trapping experiments.The fact that addition of phenol can enhance the yield of hydroalkylation product suggests that the process is a radical chain reaction, with chain carrying steps consisting of the reactions: (i) R. + CH2=CHY -> RCH2C.HY (ii) RCH2C.HY + (C6H5)2C(OH)N2R -> RCH2CH2Y + (C6H5)2CO + N2 + R..One deuterioalkylation and some yield-optimizing experiments are also reported.
- Yeung, Dominic W. K.,Warkentin, John
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p. 2386 - 2394
(2007/10/02)
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