- A comparative LSER study of the reactivity of 2-substituted cyclohex- 1-eneacetic and 2-substituted phenylacetic acids with diazodiphenylmethane in various solvents
-
The rate constants for the reaction of 2-substituted cyclohex-1-eneacetic and 2- substituted phenylacetic acids with diazodiphenylmethane were determined in various aprotic solvents at 30°C. To explain the kinetic results through solvent effects, the second-order rate constants of the examined acids were correlated using the Kamlet-Taft solvatochromic equation. The correlations of the kinetic data were carried out by means of multiple linear regression analysis, and the solvent effects on the reaction rates were analyzed in terms of initial and transition state contributions. The opposite signs of the electrophilic and the nucleophilic parameters are in agreement with the well-known mechanism of the reaction of carboxylic acids with diazodiphenylmethane. The quantitative relationship between the molecular structure and the chemical reactivity is discussed, as well as the effect of the molecular geometry on the reactivity of the examined compounds.
- Nikolic,Uscumlic,Juranic, Ivan O.
-
-
Read Online
- Chemoselective γ-Oxidation of β,γ-Unsaturated Amides with TEMPO
-
A chemoselective and robust protocol for the γ-oxidation of β,γ-unsaturated amides is reported. In this method, electrophilic amide activation, in a rare application to unsaturated amides, enables a regioselective reaction with TEMPO resulting in the title products. Radical cyclisation reactions and oxidation of the synthesised products highlight the synthetic utility of the products obtained.
- Heindl, Sebastian,Lemmerer, Miran,Malzer, Nicolas,Matyasovsky, Ján,Maulide, Nuno,Riomet, Margaux
-
p. 19123 - 19127
(2021/07/26)
-
- EtAlCl2/2,6-Disubstituted Pyridine-Mediated Carboxylation of Alkenes with Carbon Dioxide
-
α-Arylalkenes and trialkyl-substituted alkenes undergo carboxylation with CO2 in the presence of EtAlCl2 and 2,6-dibromopyridine to afford the corresponding α,β- and/or β,γ-unsaturated carboxylic acids. This reaction is suggested to proceed via the electrophilic substitution of EtAlCl2 with the aid of the base, followed by the carbonation of the resulting ate complex. This reaction can be applied to terminal dialkylalkenes by using a mixture of 2,6-di-tert-butylpyridine and 2,6-dibromopyridine.
- Tanaka, Shinya,Watanabe, Kota,Tanaka, Yuuki,Hattori, Tetsutaro
-
supporting information
p. 2576 - 2579
(2016/06/15)
-
- Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: Discovery of deleobuvir (BI 207127)
-
Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design concept that led to the discovery of the phase III clinical candidate deleobuvir (BI 207127). The structure-based strategies employed have general utility in drug design.
- LaPlante, Steven R.,B?s, Michael,Brochu, Christian,Chabot, Catherine,Coulombe, René,Gillard, James R.,Jakalian, Araz,Poirier, Martin,Rancourt, Jean,Stammers, Timothy,Thavonekham, Bounkham,Beaulieu, Pierre L.,Kukolj, George,Tsantrizos, Youla S.
-
supporting information
p. 1845 - 1854
(2014/04/03)
-
- Solvent and structural effects on the activation parameters of the reaction of carboxylic acids with diazodiphenylmethane
-
The kinetics of the reaction of benzoic, 2-methylbenzoic, phenylacetic, cyclohex-1-enecarboxylic, 2-methylcyclohex-1-enecarboxylic, and cyclohex-1-eneacetic acids with diazodiphenylmethane was studied at 30, 33, 37, 40, and 45°C in a set of 12 protic and aprotic solvents. The reactions were found to follow the second-order kinetics. The activation energy as well as the activation parameters, such as the standard entropy, the standard enthalpy, and the standard Gibbs energy of the activation, was calculated from the second-order rate constants. The solvent and structural effects on the activation energy and the standard Gibbs energy of activation, for each examined compound, were analyzed. The results of Kamlet-Taft multiple correlation analysis show that the specific solvent-solute interactions play a dominant role in the governing of the reaction. The signs of the equation coefficients support the proposed reaction mechanism.
- Nikolic,Uscumlic
-
p. 256 - 265
(2013/04/24)
-
- Studies concerning the electrophilic amino-alkene cyclisation for the synthesis of bicyclic amines
-
The bromination of a series of cyclohexenyl substituted secondary amines 1a-i has been investigated using Br2, PHT and NBS. In the case of Br2 and NBS the secondary amines preferentially undergo N-bromination. In contrast, PHT cleanly affords the products of alkene dibromination. In the case of Br2 the N-bromo species then give the products of alkene dibromination, albeit less efficiently. On subsequent treatment with K2CO3 these dibromides form the corresponding hexahydroindoles 2a-h and octahydroquinoline 2i. The presence of an N-substituent bearing a stereogenic centre (1h and 1i) was studied and the products 2h and 2i were isolated with no diastereoselectivity. When NBS was used a novel cyclisation, forming bromo-substituted octahydroindoles 9a,b and d, was observed. In relation to this sequence it was shown that these products were not intermediates in the former Br2/PHT processes and that the reaction only proceeded in the presence of the succinimide by-product of N-bromination.
- Klein, Johannes E. M. N.,Mueller-Bunz, Helge,Evans, Paul
-
supporting information; experimental part
p. 986 - 995
(2009/05/30)
-
- α,β-unsaturated aldehydes as substrates for asymmetric C-C bond forming reactions with thiamin diphosphate (ThDP)-dependent enzymes
-
The enzymes benzaldehyde lyase (BAL) from Pseudomonas fluorescens, benzoylformate decarboxylase (BFD) from Pseudomonas putida and pyruvate decarboxylase (PDC) from Saccharomyces cerevisiae provide different C-C bond forming possibilities of α,β-unsaturated aldehydes with aliphatic and aromatic aldehydes. Structure elucidation and determination of the absolute configuration of the products, which were obtained with high regio- and stereoselectivity were carried out. Selective 1,2-reactivity with yields of 75% and >98% ee, for one single isomer (A) were obtained, by choosing the suitable enzyme in combination with the appropriate substrates. By varying enzymes or substrates the regioisomeric hydroxy ketones C, with up to >99% ee, can be obtained. The application of these new chiral building blocks in the synthesis of natural products or biological active substances is considerably facilitated by applying the different ThDP-dependent enzymes as catalysts.
- Cosp, Anabel,Dresen, Carola,Pohl, Martina,Walter, Lydia,Roehr, Caroline,Mueller, Michael
-
experimental part
p. 759 - 771
(2009/04/10)
-
- Medium-dependent lithiated side products in the reductive lithiation of allylic phenyl thioethers. Diethyl ether versus tetrahydrofuran
-
Diethyl ether is a convenient solvent for the reductive lithiation of allylic phenyl thioethers without the serious complications, which occur when the reaction is carried out in tetrahydrofuran.
- Screttas, Constantinos G.,Heropoulos, Georgios A.,Micha-Screttas, Maria,Steele, Barry R.
-
p. 4357 - 4360
(2007/10/03)
-
- Reaction of N-acetylimidazole with enamines
-
N-Acetylimidazole is a commonly used acylating reagent. When it is allowed to react with several typical enamines, amides are produced rather than the expected acylated enamines.
- Cook, Gilbert,Waddle, Julie L.
-
p. 6923 - 6925
(2007/10/03)
-
- Thallium trinitrate mediated oxidation of 3-alkenols: Ring contraction vs cyclization
-
The reaction of a series of six-membered ring 3-alkenols with thallium trinitrate (TTN) in three different experimental conditions was studied. Either cyclization products or ring contraction products were obtained, depending on the structure of the substrate as well as the nature of the solvent. The reaction of a seven-membered ring 3-alkenol with TTN led to the ring contraction product exclusively.
- Ferraz, Helena M. C.,Longo Jr., Luiz S.,Zukerman-Schpector, Julio
-
p. 3518 - 3521
(2007/10/03)
-
- A new synthesis of β,γ-alkenyl carboxylic acids from α,β-alkenyl carboxylic acid chlorides and α,β-alkenyl aldehydes with one-carbon elongation
-
Reaction of the lithium α-sulfinyl carbanion of chloromethyl phenyl sulfoxide with α,β-alkenyl carboxylic acid chlorides gave γ,δ-alkenyl α-chloro-β-keto sulfoxides in variable yields. The keto sulfoxides were also synthesized from α,β-alkenyl aldehydes in two steps in good overall yields: addition of the lithium α-sulfinyl carbanion of chloromethyl phenyl sulfoxide to α,β-alkenyl aldehydes followed by oxidation of the adducts with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone or Dess-Martin periodinane. These products were treated in sequence with potassium hydride, tert-butyllithium, and 5% aqueous sodium hydroxide, in one flask to give β,γ-alkenyl carboxylic acids with one-carbon elongation in good yields. The procedure offers a new method for synthesizing β,γ-alkenyl carboxylic acids from α,β-alkenyl carboxylic acid chlorides and α,β-alkenyl aldehydes with one-carbon elongation.
- Satoh, Tsuyoshi,Nakamura, Akira,Iriuchijima, Atsuko,Hayashi, Yasumasa,Kubota, Ko-Ichi
-
p. 9689 - 9696
(2007/10/03)
-
- Reactivity of 2-Substituted Cyclohex-1-enylacetic Acids with Diazodiphenylmethane in Various Alcohols
-
The reactivities of 2-substituted cyclohex-1-enylacetic acids with diazodiphenylmethane in eleven alcohols has been investigated.The solvent effect is interpreted in terms of the influence of the relative permittivity on the rate constants.The multiple linear correlation of log k with the Kirkwood function of relative permittivity.Taft ?* value for the alkyl group of the alcohol and the number of γ-hydrogen atoms in the alcohol nγH was highly successful (R=0.9927).The log k values for the various acids were correlated by using the appropriate form of the extended Hammett equation involving inductive, resonance and steric parameters.The reaction of cyclohex-1-enylacetic acid with diazodiphenylmethane in eleven alcohols shows a good linear free energy relationship with the corresponding reaction of phenylacetic acid (R=0.9793).The results obtained for 2-substituted cyclohex-1-enylacetic acids were compared with the results for ortho-substituted phenylacetic acids under the same experimental conditions.
- Uscumlic, Gordana S.,Muskatirovic, Milan D.
-
p. 1799 - 1802
(2007/10/02)
-
- Oxidative Cleavage of Indane-1,2,3-trione-Ene Adducts; a Convenient Synthesis of Allyl and Allenyl Carboxylic Acids
-
The ene adducts formed by the thermal reaction of indane-1,2,3-trione with olefins or terminal alkynes are cleaved in good yield by reaction with periodic acid in dry diethyl ether.Thereby the 2-hydroxyindane-1,2-dione moiety in the adduct is replaced by a CO2H group; hence indane-1,2,3-trione is a masked equivalent of carbon dioxide in the ene reaction.The allyl or allenyl carboxylic acid may be separated from the co-products (phthalic acid and anhydride) by extraction into hexane.
- Gill, G. Bryon,Idris, Muhammad S. Hj.,Kirollos, Kirollos S.
-
p. 2367 - 2370
(2007/10/02)
-
- Preparation of allylic lithium reagents with the allylic system partly incorporated into carbocyclic rings
-
A new method is described for preparation of allylic type organolithiums in which two of the allylic system carbons form part of carbocyclic ring.It involves cleavage of the readily accessible allylic sulfides 1-phenylthiomethylcycloalkanes by the naphthalenelithium in tetrahydrofuran.Carbonation of the reagents has given mixtures of cycloalken-1-yl acetic acids and 2-methylecycloalkane carboxylic acids, the distribution of which is strongly dependent on the ring size; thus the proportion of cycloalkenyl acetic acid, the endocyclic olefinic product, increases sharply on going from C5 to C8 ring derivatives and then considerably less sharply on going from C8 to C10 at which point the carbonation reaction has a high selectivity.It is concluded that the site of attack in the allylic anion by CO2 is determined by the thermochemical stability of the product(s).
- Screttas, Constantinos G.,Smonou, Ioulia C.
-
p. 143 - 152
(2007/10/02)
-
- PYRIDINIUM HALIDE-PROMOTED RING-OPENING REACTION OF CYCLOPROPANECARBOXYLIC ACIDS
-
Cyclopropanecarboxylic acids when heated at 150 deg C with pyridinium chloride (molten salt) or iodide undergo ring fission giving γ-lactones in one step.Saturated bicyclic substrates give cis products, while an α,β-unsaturated compound does not undergo ring opening and produces a mixture of tricyclic γ- and δ-lactones.
- Buttinelli, Paolo,Gargaro, Giuseppe,Loreto, M. Antonietta,Pellacani, Lucio,Tardella, Paolo A.
-
p. 155 - 158
(2007/10/02)
-
- INTRAMOLECULAR DIELS-ALDER CYCLOADDITIONS OF VINYLKETENIMINES. A CONVERGENT ROUTE TO CARBAZOLES AND PYRIDOCARBAZOLE ALKALOIDS
-
The intramolecular Diels-Alder cycloaddition of acetylenic vinylketenimines is the key step of a highly convergent synthesis of carbazoles.A facile synthesis of N-methyl-tetrahydroellipticine has been completed in five isolated steps from N-methyl piperidone.
- Differding, Edmond,Ghosez, Leon
-
p. 1647 - 1650
(2007/10/02)
-
- LONG-ACTING CONTRACEPTIVE AGENTS: LEVONORGESTREL ESTERS OF UNSATURATED ACIDS
-
Esters of levonorgestrel (13β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.
- Wan, A. S. C.,Ngiam, T. L.,Leung, S. L.,Go, M. L.,Francisco, C. G.,et al.
-
p. 339 - 348
(2007/10/02)
-