- Formation of a cyclic tetrahedral intermediate by the addition of water to 2-methyl-4H-3,1-benzoxazine followed by ring opening to 2-aminobenzyl acetate and 2-acetylaminobenzyl alcohol; pH-dependence of rate of reaction and product ratio
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Kinetic studies have shown that addition of water to protonated 2-methyl-4H-3,1-benzoxazine occurs to give a cyclic tetrahedral carbonyl addition intermediate. At pH 7.5, the unprotonated intermediate collapses to give 2-acetylaminobenzyl alcohol. The former reaction is catalysed by buffer base but the latter is uncatalysed. At pH 9-12, reaction of hydroxide ion with protonated 2-methyl-4H-3,1-benzoxazine to give 2-acetylaminobenzyl alcohol becomes important, and at pH >12, the same product is formed by reaction of hydroxide ion with unprotonated 2-methyl-4H-3,1-benzoxazine.
- Dixon, Wendy J.,Hibbert, Frank
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Read Online
- Chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acetylation of nitroarenes using carbon-supported palladium catalytic system in water
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Developing and/or modifying fundamental chemical reactions using chemical industry-favorite heterogeneous recoverable catalytic systems in the water solvent is very important. In this paper, we developed convenient, green, and efficient approaches for the chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acetylation of nitroarenes in the presence of the recoverable heterogeneous carbon-supported palladium (Pd/C) catalytic system in water. The utilize of the simple, effective, and recoverable catalyst and also using of water as an entirely green solvent along with relatively short reaction times and good-to-excellent yields of the desired products are some of the noticeable features of the presented synthetic protocols. Graphic abstract: [Figure not available: see fulltext.].
- Zeynizadeh, Behzad,Mohammad Aminzadeh, Farkhondeh,Mousavi, Hossein
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p. 3289 - 3312
(2021/05/11)
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- Metal-Free C-C/C-N/C-C Bond Formation Cascade for the Synthesis of (Trifluoromethyl)sulfonylated Cyclopenta[ b]indolines
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A bis(triflyl)ethylation [triflyl = (trifluoromethyl)sulfonyl] inserted into a sequential cyclization cascade resulted in the direct formation of gem-bis(triflyl)ated cyclopenta[b]indolines from anilide-derived allenols and alkenols. This catalyst- and irradiation-free sequence facilitated the efficient preparation of functionalized tricyclic indoline cores bearing two contiguous stereocenters. The formed cyclopenta[b]indolines can be easily transformed into a wide variety of triflylated indolines, including the tetracycle ring system found in polyveoline.
- Lázaro-Milla, Carlos,Yanai, Hikaru,Almendros, Pedro
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supporting information
p. 2921 - 2926
(2021/05/05)
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- NOVEL IMIDAZO-PYRAZINE DERIVATIVES
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The invention provides novel imidazo-pyrazine derivatives having the general formula (I), and pharmaceutically acceptable salts thereof, wherein X, m, n, and R1to R3 are as described herein: formula (I). Further provided are pharmace
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Page/Page column 45; 98
(2021/12/31)
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- KMnO4-catalyzed chemoselective deprotection of acetate and controllable deacetylation-oxidation in one pot
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A novel and efficient protocol for chemoselective deacetylation under ambient conditions was developed using catalytic KMnO4. The stoichiometric use of KMnO4 highlighted the dual role of a heterogeneous oxidant enabling direct access to aromatic aldehydes in one-pot sequential deacetylation-oxidation. The reaction employed an alternative solvent system and allowed the clean transformation of benzyl acetate to sensitive aldehyde in a single step while preventing over-oxidation to acids. Use of inexpensive and readily accessible KMnO4 as an environmentally benign reagent and the ease of the reaction operation were particularly attractive, and enabled the controlled oxidation and facile cleavage of acetate in a preceding step. This journal is
- Gurawa, Aakanksha,Kumar, Manoj,Rao, Dodla S.,Kashyap, Sudhir
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supporting information
p. 16702 - 16707
(2020/10/27)
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- Application of Cu(Hdmg)2 as a simple and cost-effective catalyst for the convenient one-pot reductive acetylation of aromatic nitro compounds
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In this article, we have developed a novel and simple one-pot reductive acetylation of aromatic nitro compounds with sodium borohydride (NaBH4) in ethyl acetate (EtOAc) under reflux conditions in the presence of the bis(dimethylglyoximato)copper(II) complex [Cu(Hdmg)2] as an efficient and cost-effective copper-containing catalyst. Notably, using the above-mentioned one-pot reaction, the corresponding acetamide derivatives were obtained in high to excellent yields.
- Zeynizadeh, Behzad,Mousavi, Hossein,Zarrin, Saviz
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p. 928 - 933
(2019/02/19)
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- Divergence in Ynone Reactivity: Atypical Cyclization by 3,4-Difunctionalization versus Rare Bis(cyclization)
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Functionalized ynones can be activated by Tf2C=CH2, which was generated in situ, to form zwitterionic species. These species were trapped in an intramolecular fashion by several nucleophiles to generate two major types of triflones in a divergent manner. Through fine-tuning of the reaction temperature, bis(triflyl)-6-membered- or (triflyl)-5-membered-fused-heterocycles were achieved in reasonable yields in a totally selective manner. In this way, bis(triflyl)flavones, bis(triflyl)thioflavones, bis(triflyl)selenoflavones, (triflyl)benzothienopyrans, (triflyl)benzoselenophenopyrans, (triflyl)vinyl aurones, and (triflyl)pyranoindoles were constructed. Conceivable mechanistic pathways were suggested on the basis of the isolation of several intermediates and the results from control experiments.
- Alcaide, Benito,Almendros, Pedro,Lázaro-Milla, Carlos,Delgado-Martínez, Patricia
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supporting information
p. 8186 - 8194
(2018/06/15)
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- Access to Chiral Seven-Member Cyclic Amines via Rh-Catalyzed Asymmetric Hydrogenation
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A highly efficient asymmetric hydrogenation of azepine/oxazepine-type seven-member cyclic imine hydrochlorides was successfully developed using Rh/bisphosphine-thiourea ligand ZhaoPhos, affording various chiral seven-member cyclic amines with full conversions, high yields, and excellent enantioselectivities (up to 96% yield, >99% ee). Additionally, this asymmetric hydrogenation can proceed well on gram scale with excellent ee value. Moreover, control experimental results displayed that the anion-bonding interaction between the chloride ion of the substrate and thiourea motif of the ZhaoPhos played an important role to obtain excellent enantioselectivity.
- Li, Pan,Huang, Yi,Hu, Xinquan,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 3855 - 3858
(2017/07/26)
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- Synthesis of 1-acyl-3,4-dihydroquinazoline-2(1H)-thiones by cyclization of N-[2-(isothiocyanatomethyl)phenyl] amides generated in situ from N-[2-(azidomethyl)phenyl] amides
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An efficient method for the preparation of 1-acyl-3,4-dihydroquinazoline- 2(1H)-thiones 5 has been developed. The reaction of N-[2-(azidomethyl)phenyl] amides 3, easily prepared by a three-step sequence starting with (2-aminophenyl)methanols, with Ph
- Kobayashi, Kazuhiro,Matsumoto, Naoki
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p. 923 - 930
(2014/08/05)
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- A convenient allenoate-based synthesis of 2-quinolin-2-yl malonates and β-ketoesters
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N-Protected o-aminobenzaldehydes smoothly react with α,γ-dialkylallenoates under Bronsted basic conditions to yield 2,3-disubstituted quinolines. This three-step reaction cascade of Michael addition, aldol condensation, and 1,3-N → C rearrangement uses the complete protecting group as a building block in a highly efficient C,C-bond formation of a new all-carbon quaternary center. Carbamate protected substrates (N-Boc, N-Cbz, N-Alloc) thus give 2-quinolin-2-yl-malonates, while amide protected substrates (N-Ac, N-Bz) afford 2-quinolin-2-yl-β-ketoesters in high yields.
- Selig, Philipp,Raven, William
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p. 5192 - 5195
(2014/12/11)
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- Synthetic studies towards 1,5-benzodiazocines
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Anthranilonitrile reacted with phenylmagnesium bromide to yield a dianion, which when heated (～120 °C) yielded the condensation product 2-(2-aminophenyl)-2,4-diphenyl-1,2-dihydroquinazoline 8. This heterocycle, when treated with palladium acetate, was converted into 6,12-diphenyldibenzo[b,f][1, 5]diazocine 9. Methylmagnesium bromide and anthranilonitrile, under similar conditions directly gave a nitrogen-bridged diazocine, whose structure was determined by X-ray crystallography and also proven to be an analogue of Tro?ger's base. Acid-induced condensation of 2-amino-3-methoxybenzaldehyde gave the trimeric product 45 rather than a dibenzo[b,f][1,5]diazocine.
- Pettersson, Birgitta,Bergman, Jan,Svensson, Per H.
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p. 2647 - 2654
(2013/03/28)
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- Validation of PqsD as an anti-biofilm target in pseudomonas aeruginosa by development of small-molecule inhibitors
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2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are involved in the regulation of virulence factor production and biofilm formation in Pseudomonas aeruginosa. PqsD is a key enzyme in the biosynthesis of these signal molecules. Using a ligand-based approach, we have identified the first class of PqsD inhibitors. Simplification and rigidization led to fragments with high ligand efficiencies. These small molecules repress HHQ and PQS production and biofilm formation in P. aeruginosa. This validates PqsD as a target for the development of anti-infectives.
- Storz, Michael P.,Maurer, Christine K.,Zimmer, Christina,Wagner, Nathalie,Brengel, Christian,De Jong, Johannes C.,Lucas, Simon,Muesken, Mathias,Haeussler, Susanne,Steinbach, Anke,Hartmann, Rolf W.
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p. 16143 - 16146
(2012/11/07)
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- Practical and chemoselective reduction of acyl chloride to alcohol by borohydride in aqueous dichloromethane
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A simple methodology for the reduction of acid chlorides to their corresponding alcohols has been developed. Various carboxylic acids were converted to alcohols in excellent yields using NaBH4-K2CO3 in a mixed solvent system of dichloromethane and water (1:1) in the presence of a phase-transfer catalyst at low temperature. The importance of the work is its simplicity, selectivity, excellent yield, and very short reaction time. This new reduction condition has proved to be an excellent chemoselective method for a range of acid chlorides in the presence of various functional groups.
- Rajan, Ramya,Badgujar, Sachin,Kaur, Kamaljit,Malpani, Yashwardhan,Kanjilal, Pranab R.
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experimental part
p. 2897 - 2907
(2010/11/18)
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- Discovery and development of a new class of potent, selective, orally active oxytocin receptor antagonists
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We report a novel chemical class of potent oxytocin receptor antagonists showing a high degree of selectivity against the closely related vasopressin receptors (Via, V1b, V2). An initial compound, 7, was shown to be active in an animal model of preterm labor when administered by the intravenous but not by the oral route. Stepwise SAR investigations around the different structural elements revealed one position, the arenesulfonyl moiety, to be amenable to structural changes. Consequently, this position was used to introduce a variety of substituents to improve the physicochemical properties. Some of the resulting analogues were found to be superior to 7 both in terms of potency in vitro and aqueous solubility, which translated into significantly improved efficacy in the animal model after intravenous and oral administration. The best compound, 73, potently inhibited oxytocin-induced uterine contractions in nonpregnant rats and reduced spontaneous uterine contractions in late-term pregnant rats.
- Quattropani, Anna,Dorbais, Jér?me,Covini, David,Pittet, Pierre-André,Colovray, Véronique,Thomas, Russell J.,Coxhead, Richard,Halazy, Serge,Scheer, Alexander,Missotten, Marc,Ayala, Guidon,Bradshaw, Charles,De Raemy-Schenk, Anne-Marie,Nichols, Anthony,Cirillo, Rocco,Tos, Enrico Gillio,Giachetti, Claudio,Golzio, Lucia,Marinelli, Paolo,Church, Dennis J.,Barberis, Claude,Chollet, André,Schwarz, Matthias K.
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p. 7882 - 7905
(2007/10/03)
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- Pharmaceutically active sulfanilide derivatives
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The present invention relates to sulfanilide derivatives of formula (I), in which R1 and R2 are optionally substituted aryl and heteroaryl groups and the other variables are as defined in the claims, for use as pharmaceutically active compounds, as well as pharmaceutical formulations containing such sulfanilide derivatives. Said derivatives are useful in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. In particular, the present invention is related to sulfanilide derivatives displaying a substantial modulatory, in particular antagonistic activity, of the oxytocin and/or vasopressin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin and/or vasopressin, including preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. The present invention is furthermore related to novel sulfanilide derivatives as well as to methods of their preparation.
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- New synthesis of benzo[b]furan and indole derivatives from 1,1-dibromo-1-alkenes using a tandem Pd-assisted cyclization-coupling reaction
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We report a new flexible method for the synthesis of 2-functionalized benzo[b]furans and indoles from readily available o-(2,2-dibromovinyl)-phenol, -aniline or -acetanilide using a tandem Pd-assisted cyclization-coupling reaction.
- Thielges, Sabine,Meddah, Emilie,Bisseret, Philippe,Eustache, Jacques
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p. 907 - 910
(2007/10/03)
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- Kinetics and mechanism of the addition of water and ring-opening of 2-methyl- and 2-aryl-4H-3,1-benzoxazines to 2-aminobenzyl esters in the acidic pH range; change in rate-limiting step with buffer concentration and evidence for a tetrahedral carbonyl addition intermediate
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The observed rate coefficients for the reaction of 2-methyl-, 2-phenyl- and 2-(4-nitrophenyl)-4H-3,1-benzoxazines to give the corresponding 2-aminobenzyl esters increase as the pH is lowered and reach a constant plateau value at pH 2-4 depending on the substituent. The plateau region corresponds to complete conversion of the benzoxazine to the protonated benzoxazine (SH+) which is the reactive species. Values of pKSH+ calculated by fitting the appropriate rate expression to the rate-pH profile and the pKSH+ values measured spectrophotometrically before significant reaction to the ester has taken place are in good agreement. For each benzoxazine the observed rate coefficients show a rectilinear dependence on buffer concentration. A mechanism is proposed involving addition of water to the protonated benzoxazine to give a cyclic tetrahedral carbonyl addition intermediate. At low buffer concentrations, buffer catalysed collapse of the intermediate to product is rate-limiting and the reaction is first order in buffer. At high buffer concentrations, collapse of the intermediate to product is rapid and addition of water to the protonated benzoxazine to give the intermediate is rate-limiting.
- Dixon, Wendy J.,Hibbert, Frank,Mills, Judith F.
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p. 1503 - 1509
(2007/10/03)
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- Porphyrin synthesis in surfactant solution: Multicomponent assembly in micelles
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A synthesis of meso-substituted porphyrins in anionic sodium dodecyl sulfate micelles has been developed. Polar, functionalized aromatic aldehydes condense reversibly with pyrrole in the micellar phase. Oxidation of the porphyrinogen then provides functionalized porphyrins in yields of 10-48%. Hydrophobic aldehydes condense irreversibly to give low yields at practical substrate concentrations. Synthesis in D2O solution results in per-β-deuterated porphyrins. A two-phase model is used to rationalize the dependence of porphyrin yield on reactant and surfactant concentration. Micelles are viewed as potential wells which promote porphyrinogen assembly by binding products more tightly than reactants.
- Bonar-Law, Richard P.
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p. 3623 - 3634
(2007/10/03)
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- Rearrangement of N-acyl-3,4-dihydro-1H-2,1-benzoxazines to 2-substituted-4H-3,1-benzoxazines through a retro-Diels-Alder extrusion of formaldehyde
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N-Acyl-3,4-dihydro-1H-2,1-benzoxazines (3) undergo a thermal decomposition involving loss of formaldehyde in a retro-Diels-Alder reaction. The resultant N-acylazaxylylenes? (4) undergo a 6π electrocyclisation to give 2-substituted-4H-3,1-benzoxazines (5) rather than a 4π electrocyclisation to give the N-acyl-1,2-dihydrobenzazetes (6). Compounds 5 have been fully characterised spectroscopically and their data is inconsistent with that reported previously by other workers for what are purported to be the same compounds. 2-Methyl-4H-3,1-benzoxazine (5b) and other 2-alkyl-substituted compounds undergo facile hydrolysis to o-aminobenzyl esters (9) which rearrange to the thermodynamically more stable o-hydroxymethylanilides (10). 2-Phenyl-4H-3,1-benzoxazine (5a) is relatively stable to hydrolysis but undergoes a novel photochemical ring opening (> 254 nm) to give the N-benzoylazaxylylene (12) which can be trapped with alcohols giving o′-alkoxymethylbenzanilides (11). In cyclohexanol at 160°C, the intermediate in the thermal rearrangement of 3a to 5a, N-benzoylazaxylylene (12), was trapped as o′-cyclohexyloxymethylbenzanilide (11b). The rearrangements in mesitylene are unimolecular with activation energies of 35, 37 and 42 kcal mol-1 ? for 3a; 3c and 3d, respectively. The extrusion and electrocyclisation reaction pathways for N-acetyl-3,4-dihydro-2,1- benzoxazine (3b) have been modelled using AM1 molecular orbital theory which predicts both a non-synchronous transition state for the retro-Diels-Alder reaction and the preferred mode of ring closure to be the 6π rather than the 4π electrocyclisation.
- Glover, Stephen A.,Jones, Katherine M.,McNee, Ian R.,Rowbottom, Colleen A.
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p. 1367 - 1376
(2007/10/03)
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- Correlation Analysis of Reactivity in the Oxidation of Substituted Benzyl Alcohols by Pyridinium Hydrobromide Perbromide
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Oxidation of monosubstituted benzyl alcohols by pyridinium hydrobromide perbromide (PHPB) leads to the formation of the corresponding benzaldehydes.The reaction is first order with respect to PHPB.Michaelis-Menten-type kinetics were observed with respect to he alcohol.The oxidation of α,α-dideuteriobenzyl alcohol indicated the presence of a substantial kinetic isotope effect.The rates of oxidation of meta- and para-substituted benzyl alcohols were correlated in terms of Taft's and Swain's dual substituent-parameter equations.The rates of the meta compounds correlated best with Taft's ?1 and ?0R values whereas the para-compounds showed an excellent correlation with Taft's ?1 and ?R + constants.The rates of the otho-substituted alcohols showed very good correlation with Charton's triparametric equation.The rate increased with an increase in the polarity of the solvent.A mechanism involving a rapid reversible formation of an intermediate complex and its subsequent decomposition in the rate-determining step has been proposed.
- Suri, Deepa,Banerji, Kalyan K.,Kothari, Seema
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p. 1734 - 1758
(2007/10/03)
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- Novel reduction of carboxylic acid, ester, amide and nitrile with samarium or ytteribium metal-hydrochloric acid system
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The reduction of organic functionalities with a samarium or ytteribium metal-hydrochloric acid system was investigated. Carboxylic acid, ester, amide and nitrile were rapidly reduced to the corresponding alcohol or primary amine with samarium or ytteribium metal in the presence of hydrochloric acid at room temperature under an argon atmosphere in good yields. Carboxylic acid was similarly reduced to alcohol with a magnesium or yttrium-hydrochloric acid system.
- Kamochi,Kudo
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p. 402 - 404
(2007/10/02)
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- Novel Reduction of Carboxylic Acids, Esters, Amides and Nitriles Using Samarium Diiodide in the Presence of Water
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Aromatic carboxylic acids, esters, amides, nitriles, chlorides, ketones and nitro compounds were rapidly reduced by the samarium diiodide-H2O system to the corresponding products at room temperature in good yields.
- Kamochi, Yasuko,Kudo, Tadahiro
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p. 1495 - 1498
(2007/10/02)
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- Lanthanoids in Organic Synthesis. I. The Novel Reduction of Carboxylic Acids with Samarium Diiodide-Base System
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Aromatic and aliphatic carboxylic acids were rapidly reduced with samarium diiodide by the addition of base in the presence of protic solvent at room temperature to the corresponding alcohols.Sodium benzoate was similarly reduced with samarium diiodide in the presence of H2O in a good yield.In the similar reactions of benzoic acid derivatives bearing carboxyl, formyl, carbamoyl, methoxyl, and chloro groups, these functional groups were also reduced to the corresponding alcohol or amine derivatives.Interestingly, the carboxyl and formyl groups of benzoic acids were partly reduced into the methyl group.
- Kamochi, Yasuko,Kudo, Tadahiro
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p. 3049 - 3054
(2007/10/02)
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- Imidazopyridine compounds and processes for preparation thereof
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The invention relates to an imidazopyridine compound of the formula: STR1 wherein R1 is lower alkynyl, lower alkynyloxy(lower)alkyl or N,N-di(lower)alkylamino(lower)alkynyl, R2 is lower alkyl, R3 is mono (or di or tri)-phenyl(lower)alkyl substituted by one or more substituent(s) selected from cyano, carbamoyl, mono (or di or tri(phenyl(lower)alkylamino, acylamino, carboxy, esterified carboxy, hydroxy, hydroxy(lower)alkyl, acyloxy(lower)alkyl, acyloxy, mono (or di or tri)phenyl(lower)alkoxy, lower alkoxy(lower)alkoxy, tetrahydropyranyloxy, and acylamino(lower)alkyl or mono (or di or tri) phenyl(lower)alkyl substituted by lower alkyl and one additional substituent selected from hydroxy(lower)alkyl, amino, N-lower alkyl-N-acylamino, mono (or di or tri)phenyl(lower)alkylamino, acylamino and lower alkylamino, and R4 is hydrogen or lower alkyl, and a pharmaceutically acceptable salt thereof, useful in the treatment of ulcers.
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