- Nucleophilic substitution reactions of unbranched alkyl amines using triazine reagents
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Since amines are present in many organic, biological, and drug molecules, a strategy of synthesizing desired compounds by nucleophilic substitution reactions of these amines is very attractive. By using triazine reagents, we have found that nucleophilic substitution reactions of unbranched alkyl amines via morpholine derivatives are feasible. This method can be performed under milder reaction conditions than those in previously reported methods.
- Kitamura, Masanori,Kitaoka, Yuki,Fujita, Hikaru,Kunishima, Munetaka
-
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- Iron(II) and Copper(I) Control the Total Regioselectivity in the Hydrobromination of Alkenes
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A new method that allows the complete control of the regioselectivity of the hydrobromination reaction of alkenes is described. Herein, we report a radical procedure with TMSBr and oxygen as common reagents, where the formation of the anti-Markovnikov product occurs in the presence of parts per million amounts of the Cu(I) species and the formation of the Markovnikov product occurs in the presence of 30 mol % iron(II) bromide. Density functional theory calculations combined with Fukui's radical susceptibilities support the obtained results.
- Cruz, Daniel A.,Sinka, Victoria,De Armas, Pedro,Steingruber, Hugo Sebastian,Fernández, Israel,Martín, Víctor S.,Miranda, Pedro O.,Padrón, Juan I.
-
supporting information
p. 6105 - 6109
(2021/08/18)
-
- Ni-Catalyzed Formal Cross-Electrophile Coupling of Alcohols with Aryl Halides
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Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. We herein demonstrate a strategy building upon in situ halogenation/reductive coupling of alcohols with aryl halides to forge Csp2-Csp3 bonds. The combination of 2-chloro-3-ethylbenzo[d]oxazol-3-ium salt (CEBO) and TBAB as the mild bromination reagents enables rapid transformation of a wide range of alcohols to their bromide counterparts within one to 5 min in CH3CN and DMF, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions in the presence of a chemical reductant. The present method is suitable for arylation of a myriad of structurally complex alcohols with no need for prepreparation of alkyl halides. More importantly, the mild and kinetically rapid bromination process has shown good selectivity in the bromination/arylation of symmetric diols and less sterically hindered hydroxyl groups in polyols, thus offering promise for selective functionalization of diols and polyols without laborious protecting/deprotecting operations. The practicality of this work is also evident in the arylation of a number of carbohydrates, drug compounds, and naturally occurring alcohols.
- Lin, Quan,Ma, Guobin,Gong, Hegui
-
p. 14102 - 14109
(2021/11/20)
-
- Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes
-
Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water ortert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3
- Chen, Shuming,Gieuw, Matthew H.,Houk, K. N.,Ke, Zhihai,Yeung, Ying-Yeung
-
p. 9426 - 9433
(2020/10/02)
-
- Visible Light-Mediated Conversion of Alcohols to Bromides by a Benzothiadiazole-Containing Organic Photocatalyst
-
The search for metal-free, stable and high effective photocatalysts with sufficient photo-redox potentials remains a key challenge for organic chemists. Here, we present a benzothiadiazole-containing molecular organic photocatalyst with redox potentials of ?1.30 V and +1.64 V vs. SCE. The singlet state lifetime is 13 ns. Direct conversion from aliphatic alcohols to bromides has been conducted with the designed organic photocatalyst under visible light irradiation with high efficiency and selectivity. The catalytic efficiency of the novel benzothiadiazole-based photocatalyst is comparable with the state-of-art metal and non-metal catalysts. Furthermore, advanced photophysical studies including time-resolved photoluminescence and transient absorption spectroscopy offer a powerful support for photo-induced electron transfer from photocatalyst to the reactive substrates. Lastly, no photo-bleaching effect is observed, demonstrating the high stability and recyclable of the designed organic photocatalyst. (Figure presented.).
- Li, Run,Gehrig, Dominik W.,Ramanan, Charusheela,Blom, Paul W. M.,Kohl, Fabien F.,Wagner, Manfred,Landfester, Katharina,Zhang, Kai A. I.
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p. 3852 - 3859
(2019/07/15)
-
- Promotion of Appel-type reactions by N-heterocyclic carbenes
-
N-Heterocyclic carbenes (NHCs) have been extensively used as a versatile class of catalysts and ligands in organocatalytic and organometallic chemistry. However, there are only a small number of synthetic applications where they act as reagents. Here we demonstrate that NHCs can be used as stoichiometric redox reagents for Appel-type halogenation reactions of alcohols. This new reactivity reveals a fresh and interesting aspect and enriches the chemistry of NHCs in an underexplored area. The potential of performing this chemical transformation at the catalytic level using an NHC-oxide derivative is also investigated.
- Hussein, Mohanad A.,Nguyen, Thanh Vinh
-
supporting information
p. 7962 - 7965
(2019/07/12)
-
- Nucleophilic Substitution of Aliphatic Fluorides via Pseudohalide Intermediates
-
A method for aliphatic fluoride functionalization with a variety of nucleophiles has been reported. Carbon–fluoride bond cleavage is thermodynamically driven by the use of silylated pseudohalides TMS-OMs or TMS-NTf2, resulting in the formation of TMS-F and a trapped aliphatic pseudohalide intermediate. The rate of fluoride/pseudohalide exchange and the stability of this intermediate are such that little rearrangement is observed for terminal fluoride positions in linear aliphatic fluorides. The ability to convert organofluoride positions into pseudohalide groups allows facile nucleophilic attack by a wide range of nucleophiles. The late introduction of the nucleophiles also allows for a wide range of functional-group tolerance in the coupling partners. Selective alkyl fluoride mesylation is observed in the presence of other alkyl halides, allowing for orthogonal synthetic strategies.
- Jaiswal, Amit K.,Prasad, Pragati K.,Young, Rowan D.
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p. 6290 - 6294
(2019/04/26)
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- Method for reducing residues of N-ethyl-3-phenylpropylamine in alverine
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The invention relates to a method for reducing residues of N-ethyl-3-phenylpropylamine in alverine, and belongs to an impurity removal method of compounds. The method comprises the following steps: dissolving an intermediate alverine crude product containing impurity N-ethyl-3-phenylpropylamine into a water-insoluble organic solvent, extracting an organic layer by using an aqueous solution with appropriate pH and discarding a water layer; drying and filtering the organic layer, decompressing and evaporating the solvent to dryness. According to the method disclosed by the invention, a clear, simple and reliable solution to the residues of the N-ethyl-3-phenylpropylamine in the intermediate alverine is provided for the first time, so that the subsequently produced crude drug citric acid alverine has higher quality and the residue amount does not exceed 0.15 percent. The method has the advantages of simplicity, feasibility, low cost, few wastes and suitability for industrial popularization.
- -
-
Paragraph 0055; 0056
(2018/11/03)
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- Purifying method of N-ethyl-3-phenylpropylamine
-
The invention relates to a purifying method of N-ethyl-3-phenylpropylamine, and belongs to purifying method of compounds. A N-ethyl-3-phenylpropylamine sample with the lower purity is dissolved in a water insoluble organic solvent, the organic phase is extracted for 1-5 times by a water solution with the appropriate pH value, the aqueous phase is combined, alkali or an alkaline solution is added,the pH value is conditioned, the aqueous phase is extracted by the water insoluble organic solvent, the organic phase is combined, drying and filtration are conducted, and the solvent is dried out through decompression. The purifying method has the advantages that the purifying effect is good, the result is stable and reliable, thus the higher and higher quality requirement of the pharmacy industry for the midbody can be better satisfied, and the yield is high and can be as high as 80% or above. Production and operation are safer and more convenient, and the purifying method is suitable for large-scale production.
- -
-
Paragraph 0094-0096
(2018/12/13)
-
- ANTI-FUNGAL TREATMENT
-
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of fungal infections, e.g., aspergillosis, candidiasis, cryptococcosis, histoplasmosis, and the like. For example, the pharmaceutical composition may include a pharmaceutically acceptable carrier or excipient, and a compound represented by Ar— C(=NR1)NR2— A---X— Y— Het2 and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted aryl or nitrogen- containing heteroaryl. R1 and R2 may independently be H, optionally substituted C1-C6 aikyi, or optionally substituted C3-C6 cyeloalkyi. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cyeloalkyi, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C10 alkyi or optionally substituted C2-C10 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
- -
-
Paragraph 00117
(2018/03/25)
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- Preparation and properties of a novel solution of hydrogen bromide (HBr) in 1,4-dioxane: An alternative reagent to HBr gas without protic solvents
-
A solution of hydrogen bromide (HBr) in 1,4-dioxane was prepared and investigated for its ability to brominate alcohols, and hydrobrominate alkenes. This study revealed that the brominating ability of this HBr/1,4-dioxane solution is equal or superior to that of hydrobromic acid or HBr in acetic acid. The solution of HBr in 1,4-dioxane is robust, exhibiting no decomposition of the solvent, and retaining 97% of its original concentration, when kept at ?25 °C for 30 days. This solution is a liquid alternative to HBr gas without protic solvents.
- Nishio, Yuya,Mifune, Ryota,Sato, Taisuke,Ishikawa, Shin-ich,Matsubara, Hiroshi
-
supporting information
p. 1190 - 1193
(2017/03/02)
-
- Bent-core mesogens with an aromatic unit at the terminal position
-
Bent-core liquid crystals with a naphthalene central unit and an aromatic ring at the terminal position of molecular tails were synthesised with the aim of enhancing nanosegregation. It was found that the length of the spacer between the rigid core and the terminal aromatic moiety had a profound influence on the liquid crystal polymorphism. The homologues with short spacers exhibited nematic and columnar phases, whereas the homologue with long spacers exhibited a tilted lamellar phase with a liquid-like in-plane order, indicating an unusual morphology of the densely packed toroidal objects. The morphology can be changed to twisted ribbons by small additives adsorbed on the membrane surface. This is the first example of twisted ribbons constructed by a lamellar system with no long-range in-plane order.
- Bajzíková, Kvetoslava,Svoboda, Ji?í,Novotná, Vladimíra,Pociecha, Damian,Gorecka, Ewa
-
supporting information
p. 4672 - 4679
(2017/07/10)
-
- Stereospecific Electrophilic Fluorination of Alkylcarbastannatrane Reagents
-
We report the use of isolable primary and secondary alkylcarbastannatrane nucleophiles in site-specific fluorination reactions. These reactions occur without the need for transition metal catalysis or in situ activation of the nucleophile. In the absence of the carbastannatrane backbone, alkyltin nucleophiles exhibit no activity towards fluorination. When enantioenriched alkylcarbastannatranes are employed, fluorination occurs predominately via a stereoinvertive mechanism to generate highly enantioenriched alkyl fluoride compounds. These conditions can also be extended to stereospecific chlorination, bromination, and iodination reactions.
- Ma, Xinghua,Diane, Mohamed,Ralph, Glenn,Chen, Christine,Biscoe, Mark R.
-
supporting information
p. 12663 - 12667
(2017/09/11)
-
- Chromenes involving a two-photon absorbing moiety: Photochromism via intramolecular resonance energy transfer
-
New derivatives involving the photochromic 2H-benzo[h]chromene moieties covalently linked to the 2,7-bis(carbazolyl)fluorene-derived two-photon absorbing moiety were designed to enable the possibility of resonance energy transfer from the fluorene donor to the photochromic acceptor. The longest wavelength absorption of the photochromic acceptors overlaps with the fluorescence band of the two-photon absorbing donor and the distance between the both moieties is about 5-7 ?. Rapid coloration of colorless solutions was observed upon one- and two-photon absorption.
- Bekere, Laura,Lokshin, Vladimir,Sigalov, Mark,Gvishi, Raz,Zhao, Peng,Hagan, David J.,Van Stryland, Eric W.,Khodorkovsky, Vladimir
-
p. 1143 - 1148
(2016/02/19)
-
- Manganese-Catalyzed Borylation of Unactivated Alkyl Chlorides
-
The use of low-cost manganese(II) bromide (MnBr2) and tetramethylethylenediamine (TMEDA) catalyzes the cross coupling of (bis)pinacolatodiboron with a wide range of alkyl halides, demonstrating the first manganese-catalyzed coupling with alkyl electrophiles. This method allows access to primary, secondary, and tertiary boronic esters from the parent chlorides, which were previously inaccessible as coupling partners. The reaction proceeds in high yield with as little as 1000 ppm catalyst loading, while 5 mol % can provide high yields in as little as 30 min. Finally, radical-clock experiments revealed that at 0 °C direct borylation outcompetes alternative radical processes, thereby providing synthetically useful, temperature-controlled reaction outcomes.
- Atack, Thomas C.,Cook, Silas P.
-
supporting information
p. 6139 - 6142
(2016/06/09)
-
- An efficient and selective method for the iodination and bromination of alcohols under mild conditions
-
A straightforward and effective procedure for the conversion of a variety of alcohols into the corresponding alkyl iodides and bromides is described using KX/P2O5 (X = I, Br). The reactions were easily carried out in acetonitrile under mild conditions. Using this method, the selective conversion of benzylic alcohols in the presence of aliphatic alcohols was achieved.
- Khazdooz, Leila,Zarei, Amin,Aghaei, Hamidreza,Azizi, Ghobad,Gheisari, Mohammad Mehdi
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p. 168 - 171
(2015/12/30)
-
- Novel citric acid alverine crystal form and preparation method thereof
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The invention relates to a novel citric acid alverine crystal form, a preparation method thereof and a medicine composition using the crystal form as an active ingredient. The preparation method comprises the steps that phenylpropanol which is cheap and easy to obtain and serves as a start and is subjected to sulfoacid esterification and bromination to obtain 3-phenyl bromo propane; adding ethylamine hydrochloride in batches into excessive feed of the 3-phenyl bromo propane under the condition that organic base triethylamine and phase transfer catalyst exist to generate alverine free base in a 'one pot' mode; an organic layer is purified to be reacted with citric acid to produce crude citric acid alverine; the crude citric acid alverine is recrystallized through N-methyl pyrrolidone-water-DMF mixed solvent to obtain the novel crystal form B. Characteristic diffraction peaks are achieved at the positions of 4.18, 15.21, 20.53 and other positions of the value of 2 theta. The synthetic process route of the crystal form has the advantages that raw materials are easy to obtain, few reaction steps are needed, the condition is mild, operation is simple, and yield is high, and is environmentally friendly and easy to industrialize.
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-
- Light-mediated deoxygenation of alcohols with a dimeric gold catalyst
-
A new protocol for the reductive deoxygenation of primary alcohols was explored. This photo-mediated method combines a novel approach to bromination of alcohols merged with the powerful reducing capability of [Au2(dppm)2]Cl2 [dppm = 1,1-bis(diphenylphosphino)methane] as a photoredox catalyst. The highly efficient methods discussed are marked by the use of UVA light-emitting diodes, which have significantly reduced reaction times and lowered setup cost.
- McCallum, Terry,Slavko, Ekaterina,Morin, Mathieu,Barriault, Louis
-
supporting information
p. 81 - 85
(2015/02/18)
-
- Mechanistic insights into Br?nsted acid-induced nucleophilic substitution of aliphatic imidazole carbamate with halide ions
-
Herein we report interesting reactivity of imidazole carbamate towards nucleophilic substitution with halide ions under Br?nsted acidic conditions. Depending upon reaction conditions, halide ions could readily attack the carboxyl position and trigger decarboxylative alkyl halide formation. Alternatively, halide ions were also found to competitively undergo nucleophilic acyl substitution, which ultimately results in the generation of carbonate dimerization product.
- Saputra, Mirza A.,Forgey, Rashel L.,Henry, Jeffrey L.,Kartika, Rendy
-
p. 1392 - 1396
(2015/03/04)
-
- Bimodal ligands with macrocyclic and acyclic binding moieties, complexes and compositions thereof, and methods of using
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Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacyclcododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders.
- -
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Page/Page column 109; 110; 137 - 139
(2015/09/23)
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- Rasta resin-triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions
-
Heterogeneous polymer-supported triphenylphosphine oxides based on the rasta resin architecture have been synthesized, and applied as reagent precursors in a wide range of halogenation reactions. The rasta resin-triphenylphosphine oxides were reacted with either oxalyl chloride or oxalyl bromide to form the corresponding halophosphonium salts, and these in turn were reacted with alcohols, aldehydes, aziridines and epoxides to form halogenated products in high yields after simple purification. The polymersupported triphenylphosphine oxides formed as a byproduct during these reactions could be recovered and reused numerous times with no appreciable decrease in reactivity.
- Xia, Xuanshu,Toy, Patrick H.
-
supporting information
p. 1397 - 1405
(2014/07/22)
-
- Indium(III)-catalyzed reductive bromination and iodination of carboxylic acids to alkyl bromides and iodides: Scope, mechanism, and one-pot transformation to alkyl halides and amine derivatives
-
Highly effective indium(III)-catalyzed reductive bromination or iodination of a variety of carboxylic acids with 1,1,3,3-tetramethyldisiloxane (TMDS) and a source of bromine or iodine is described. This functional group interconversion has high tolerance for several functional groups, such as halogens, a hydroxy group, a nitro group, an olefin part, and a sulfide moiety. This indium catalytic system is also applicable to the reductive iodination of aldehyded, acyl chlorides, and esters. Furthermore, this reducing system can be applied to the one-pot synthesis of alkyl halides and amine derivatives via the addition of nucleophiles. Insight into the reaction mechanism was gained via the time course of 1H and 13C NMR monitoring experiments and the corresponding stepwise reactions.
- Moriya, Toshimitsu,Yoneda, Shinichiro,Kawana, Keita,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
-
p. 10642 - 10650
(2013/11/19)
-
- Indium(III)-catalyzed one-pot synthesis of alkyl cyanides from carboxylic Acids
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The one-pot preparation of alkyl cyanides from carboxylic acids via alkyl iodides or alkyl bromides, which were in situ generated either by indium(III)-catalyzed reductive iodination or bromination of carboxylic acids, is described. Georg Thieme Verlag Stuttgart New York.
- Moriya, Toshimitsu,Shoji, Kohei,Yoneda, Shinichiro,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
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p. 3233 - 3238
(2013/12/04)
-
- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698,7
(2012/12/12)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener. Georg Thieme Verlag KG Stuttgart · New York.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698
(2013/01/15)
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- Indium-catalyzed reductive bromination of carboxylic acids leading to alkyl bromides
-
The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me3SiBr) with a catalytic amount of indium bromide (InBr3) undertook direct bromination of carboxylic acids, which produced the corresponding alkyl bromides in good to excellent yields. The reducing system was tolerant to several functional groups.
- Moriya, Toshimitsu,Yoneda, Shinichiro,Kawana, Keita,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
-
p. 4842 - 4845,4
(2020/09/16)
-
- Visible-light-mediated conversion of alcohols to halides
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The development of new means of activating molecules and bonds for chemical reactions is a fundamental objective for chemists. In this regard, visible-light photoredox catalysis has emerged as a powerful technique for chemoselective activation of chemical bonds under mild reaction conditions. Here, we report a visible-light-mediated photocatalytic alcohol activation, which we use to convert alcohols to the corresponding bromides and iodides in good yields, with exceptional functional group tolerance. In this fundamentally useful reaction, the design and operation of the process is simple, the reaction is highly efficient, and the formation of stoichiometric waste products is minimized.
- Dai, Chunhui,Narayanam, Jagan M.R.,Stephenson, Corey R.J.
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experimental part
p. 140 - 145
(2012/02/06)
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- Catalytic phosphorus(V)-mediated nucleophilic substitution reactions: Development of a catalytic appel reaction
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Catalytic phosphorus(V)-mediated chlorination and bromination reactions of alcohols have been developed. The new reactions constitute a catalytic version of the classical Appel halogenation reaction. In these new reactions oxalyl chloride is used as a consumable stoichiometric reagent to generate the halophosphonium salts responsible for halogenation from catalytic phosphine oxides. Thus, phosphine oxides have been transformed from stoichiometric waste products into catalysts and a new concept for catalytic phosphorus-based activation and nucleophilic substitution of alcohols has been validated. The present study has focused on a full exploration of the scope and limitations of phosphine oxide catalyzed chlorination reactions as well as the development of the analogous bromination reactions. Further mechanistic studies, including density functional theory calculations on proposed intermediates of the catalytic cycle, are consistent with a catalytic cycle involving halo- and alkoxyphosphonium salts as intermediates.
- Denton, Ross M.,An, Jie,Adeniran, Beatrice,Blake, Alexander J.,Lewis, William,Poulton, Andrew M.
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experimental part
p. 6749 - 6767
(2011/10/02)
-
- In situ phosphine oxide reduction: A catalytic appel reaction
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Several important reactions in organic chemistry thrive on stoichiometric formation of phosphine oxides from phosphines. To avoid the resulting burden of waste and purification, cyclic phosphine oxides were evaluated for new catalytic reactions based on in situ regeneration. First, the ease of silane-mediated reduction of a range of cyclic phosphine oxides was explored. In addition, the compatibility of silanes with electrophilic halogen donors was determined for application in a catalytic Appel reaction based on in situ reduction of dibenzophosphole oxide. Under optimized conditions, alcohols were effectively converted to bromides or chlorides, thereby showing the relevance of new catalyst development and paving the way for broader application of organophosphorus catalysis by in situ reduction protocols. Copyright
- Van Kalkeren, Henri A.,Leenders, Stefan H. A. M.,Hommersom, C. Rianne A.,Rutjes, Floris P. J. T.,Van Delft, Floris L.
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supporting information; experimental part
p. 11290 - 11295
(2011/10/19)
-
- Novel preparation of ion-supported triphenylphosphines and their synthetic utility
-
Novel ion-supported Ph3P compounds, 4-(diphenylphosphino)- benzyltrimethylammonium bromide (A) and N-methyl-N-[4-(diphenylphosphino) -benzyl]pyrrolidinium bromide (B), were prepared. Because of their stability in air, ion-supported Ph3P A and B could be used for the halogenation of alcohols, the esterification of carboxylic acid with the Mitsunobu reaction, the Mizoroki-Heck reaction, and the Sonogashira reaction. The advantages of using these ion-supported Ph3P A and B are the simple isolation of the products by ether extraction due to their poor solubility in ether, and the easy recovery of the co-product, ion-supported Ph3PO, by filtration in high yields (>90%), which could be regenerated and reused for the same reactions, in the halogenation of alcohols and the esterification of carboxylic acid with the Mitsunobu reaction. On the other hand, ionic liquid reaction media containing Pd(OAc)2 or PdCl2 and ion-supported Ph3P A or B as catalysts could be reused for the same Mizoroki-Heck reaction and the Sonogashira reaction maintaining high yields, using iodotoluene with methyl acrylate and phenylacetylene, respectively.
- Imura, Yumi,Shimojuh, Naoya,Kawano, Yuhta,Togo, Hideo
-
scheme or table
p. 3421 - 3426
(2010/06/19)
-
- Nucleophile assisting leaving groups: A strategy for aliphatic 18F-fluorination
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(Chemical Equation Presented) A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. TheseNALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong precomplexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in 18F-fluorination reactions using no-carrier-added [ 18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2-3-fold) in radiofluorination yields over traditional leaving groups.
- Lu, Shuiyu,Lepore, Salvatore D.,Song, Ye Li,Mondal, Deboprosad,Cohn, Pamela C.,Bhunia, Anjan K.,Pike, Victor W.
-
supporting information; experimental part
p. 5290 - 5296
(2009/11/30)
-
- Design of new potent and selective secretory phospholipase A2 inhibitors. Part 5: Synthesis and biological activity of 1-alkyl-4-[4,5-dihydro-1,2,4-[4H]-oxadiazol-5-one-3-ylmethylbenz-4′-yl(oyl)] piperazines
-
Among the different PLA2s identified to date, the group IIA secretory PLA2 (sPLA2 GIIA) is implied in diverse pathological conditions. In this work we describe the synthesis, inhibitory activities, and structure-activity relationships (SAR) of a new class of substituted piperazine derivatives. The in vitro fluorimetric assay using two groups of enzymes, GIB and GIIA, revealed several compounds as highly potent inhibitors (IC50 = 0.1 μM). The in vivo activity assessed by ip or per os administration in a carrageenan-induced edema test in rats showed that two compounds proved to be as potent as indomethacin (10 mg/kg).
- Boukli, Latifa,Touaibia, Mohamed,Meddad-Belhabich, Nadia,Djimde, Atime,Park, Chang-Ha,Kim, Jung-Joo,Yoon, Joo-Hyoung,Lamouri, Aazdine,Heymans, Francoise
-
p. 1242 - 1253
(2008/09/17)
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- Stereoretentive halogenations and azidations with titanium(IV) enabled by chelating leaving groups
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Titaniumdoes it again! With the help of nucleophile-assisting leaving groups (NALGs), alkyl bromides, iodides, and, for the first time, azides are obtained from sulfonates withcomplete retention of configuration. Critical to the design of these new titanium(IV) reactions has been the use of NALGs which are thought to chelate the Lewis acid reagent in the transition state promoting an SNi-type mechanism. (Chemical Equation Presented)
- Lepore, Salvatore D.,Mondal, Deboprosad,Song, Ye Li,Bhunia, Anjan K.
-
supporting information; body text
p. 7511 - 7514
(2009/03/12)
-
- Indium-catalyzed cycloisomerization of ω-alkynyl-β-ketoesters into six- to fifteen-membered rings
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(Chemical Equation Presented) Many different sizes of rings available: Heating ω-alkynyl-β-ketoesters in the presence of In(NTf 2)3 (Tf=trifluoromethanesulfonyl) produces six- to fifteen-membered ring products in good yields. The reaction features low catalyst loading and moderately dilute conditions, and the formation of medium-sized rings is sometimes faster than that for the corresponding six-membered rings. A synthesis of (±)-muscone is also reported.
- Tsuji, Hayato,Yamagata, Ken-Ichi,Itoh, Yoshimitsu,Endo, Kohei,Nakamura, Masaharu,Nakamura, Eiichi
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p. 8060 - 8062
(2008/09/18)
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- 4-Aminophenyldiphenylphosphinite (APDPP), a new heterogeneous and acid scavenger phosphinite - Conversion of alcohols, trimethylsilyl, and tetrahydropyranyl ethers to alkyl halides with halogens or N-halosuccinimides
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A new heterogeneous phosphinite, 4-aminophenyldiphenylphosphinite (APDPP), is prepared and used for the efficient conversion of alcohols, trimethylsilyl ethers, and tetrahydropyranyl ethers to their corresponding bromides, iodides, and chlorides in the presence of molecular halogens or N-halosuccinimides. The amino group in this phosphinite acts as an acid scavenger and removes the produced acid. A simple filtration easily removes the phosphinate by-product.
- Iranpoor, Nasser,Firouzabadi, Habib,Gholinejad, Mohammad
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p. 1006 - 1012
(2007/10/03)
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- Facile conversion of alcohols into their bromides and iodides by N-bromo and N-iodosaccharins/triphenylphosphine under neutral conditions
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N-Bromo and N-iodosaccharins in the presence of triphenylphosphine convert alcohols into the corresponding bromides and iodides in good to excellent yields at room temperature under neutral conditions.
- Firouzabadi, Habib,Iranpoor, Nasser,Ebrahimzadeh, Farzaneh
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p. 1771 - 1775
(2007/10/03)
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- NUCLEOPHILE ASSISTING LEAVING GROUPS
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Sulfonate leaving groups include a cation chelating moiety, e.g. a polyether or crown ether. The chelating moiety stabilizes the sulfonate leaving group by forming a complex with a cation of a cation-nucleophile combination. The stabilized leaving group is more easily displaced under many conditions than are standard arylsulfonate leaving groups such as the toxyl group. The chelating moiety also favors certain cations depending on the identity of the moiety thereby enhancing the reaction rate with nucleophilic salts containing the preferred cation. Use of the inventive leaving groups results in improved yields, decreased reaction times and improved product purity.
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Page/Page column 15-16
(2010/11/08)
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- Novel inhibitor compounds specific of secreted non-pancreatic human a2phospholipase of group II
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The present invention relates to a compound of the following formula (I) and pharmaceutical compositions containing the compound of formula (I): wherein D, Y, A, B, p, q, W and R have the same meanings as defined in the specification.
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Page/Page column 11
(2010/02/11)
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- Arylsulfonate-based nucleophile assisting leaving groups
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The synthesis and unique reactivity of a series of arylsulfonate-based nucleophile assisting leaving groups (NALG) containing oligomeric ether units (including crown ethers) attached to the arylsulfonyl ring in the ortho orientation are described. The reactions of a variety of these ether-containing alkyl sulfonates with metal halides proceeded at substantially greater rates than electronically similar sulfonates. These ether-containing leaving groups also displayed marked selectivity for lithium halides relative to the corresponding sodium and potassium salts in nucleophilic displacement reactions.
- Lepore, Salvatore D.,Bhunia, Anjan K.,Cohn, Pamela
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p. 8117 - 8121
(2007/10/03)
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- A novel stereoselective one-pot conversion of alcohols into alkyl halides mediated by N,N′-diisopropylcarbodiimide
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Alcohols can be converted in high yields to the corresponding alkyl halides in a one-pot procedure via the corresponding O-alkylisourea; very short reaction times are possible when microwave irradiation is used.
- Crosignani, Stefano,Nadal, Brice,Li, Zhengning,Linclau, Bruno
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p. 260 - 261
(2007/10/03)
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- A mild, phosphine-free method for the conversion of alcohols into halides (Cl, Br, I) via the corresponding O-alkyl isoureas
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A novel procedure for the conversion of primary and secondary alcohols into the corresponding alkyl chlorides, bromides and iodides is described. The transformation is high-yielding in the case of chlorides and bromides, tolerates a range of functional groups, and does not rely on the use of phosphines.
- Li, Zhengning,Crosignani, Stefano,Linclau, Bruno
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p. 8143 - 8147
(2007/10/03)
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- 2-Trimethylsilylethyl sulfides in the von Braun cyanogen bromide reaction: Selective preparation of thiocyanates and application to nucleoside chemistry
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Mixed 2-(trimethylsilyl)ethyl sulfides were synthesized and used in the von Braun cyanogen bromide reaction for preparing selectively thiocyanates in high yield. We show here that this cleavage reaction is highly selective in methanol in comparison with the reaction of the corresponding non-silyl sulfide analogues. This reaction was applied to the synthesis of nucleosidic thiocyanates such as the new nucleosides 14 and 18 in the search for mechanism-based inhibitors of ribonucleoside diphosphate reductase and bioactive molecules. The selective cleavage is possible for sulfides bearing hydroxyl functions and aromatic rings. The reactions of cyanogen bromide as cyanating and brominating agent were observed for the first time under the same conditions with the naphthoxyhexyl 2-trimethylsilylethyl sulfide 7, which, treated with cyanogen bromide in dichloromethane, led selectively to the p-bromonaphthoxyhexyl thiocyanate 10 in 89% yield. Another reaction induced by cyanogen bromide was observed in dichloromethane with the 2-(trimethylsilylethyl)thio nucleoside 13, which gives the corresponding symmetrical disulfide 21 in good yield.
- Chambert, Stephane,Thomasson, Francois,Decout, Jean-Luc
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p. 1898 - 1904
(2007/10/03)
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- Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects
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The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.
- Hamilton, Gregory S.,Wu, Yong-Qian,Limburg, David C.,Wilkinson, Douglas E.,Vaal, Mark J.,Li, Jia-He,Thomas, Christine,Huang, Wei,Sauer, Hansjorg,Ross, Douglas T.,Soni, Raj,Chen, Yi,Guo, Hongshi,Howorth, Pamela,Valentine, Heather,Liang, Shi,Spicer, Dawn,Fuller, Mike,Steiner, Joseph P.
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p. 3549 - 3557
(2007/10/03)
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- Cesium effect: High chemoselectivity in direct N-alkylation of amines
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A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently. A cesium base not only promoted alkylation of primary amines but also suppressed overalkylations of the produced secondary amines. Various amines, alkyl bromides, and alkyl sulfonates were examined, and the results demonstrated this methodology was highly chemoselective to favor mono-N-alkylation over dialkylation. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the secondary amines exclusively, offering wide applications in peptidomimetic syntheses.
- Salvatore, Ralph Nicholas,Nagle, Advait S.,Kyung, Woon Jung
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p. 674 - 683
(2007/10/03)
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- An efficient route to alkyl chlorides from alcohols using the complex TCT/DMF
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(formula presented) Efficient conversion of alcohols and β-amino alcohols to the corresponding chlorides (and bromides) can be carried out at room temperature in methylene chloride, using 2,4,6-trichloro[1,3,5]triazine and N,N-dimethyl formamide. This procedure can also be applied to optically active carbinols.
- De Luca, Lidia,Giacomelli, Giampaolo,Porcheddu, Andrea
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p. 553 - 555
(2007/10/03)
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- Efficient synthesis of β-amino bromides
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β-Aminoalcohols were smoothly converted to β-amino bromides using thionyl bromide and DMF, which were easily isolated without any further purification. Participation by the β-amino group in brominations not only enhanced reaction rates but also promoted stereo- and regioselectivities. (C) 2000 Elsevier Science Ltd.
- Nagle, Advait S.,Salvatore, Ralph N.,Chong, Byong-Don,Woon Jung, Kyung
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p. 3011 - 3014
(2007/10/03)
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- SUBSTITUTED CYCLOALKANECARBOXYLIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS
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Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula STR1 wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents STR2 the subscript "e" is 2 or 3; the group R 14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript "k" is 0-2; and the group G represents M, STR3 in which M represents--CO 2 H,--CON(R 11) 2, or--CO 2 R 12 ; and R 13 represents any of the side chains of the 19 noncyclic occurring amino acids. "
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- N-substituted imidazol derivative
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The present invention is to provide novel imidazole derivatives effectual as an antihyperlipemic agent and therapeutic and preventive drugs for arteriosclerosis, and to provide methods for manufacturing the said derivatives. More particularly, the present invention is directed to the compounds represented by the following general formula [I]; STR1 wherein R1 is hydrogen or lower alkyl, n is 0 or 1, X is N-r1 wherein r1 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r2)=NO wherein r2 is hydrogen or lower alkyl, m is 0 or an integer of from 1 to 12, and A is methyl or a group represented by the following general formula; STR2 wherein Y is N-r3 wherein r3 is hydrogen or lower alkyl, N(r4)SO2 wherein r4 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r5)=NO wherein r5 is hydrogen or lower alkyl, R2 is a halogen, a lower alkyl, a lower alkoxy, a cycloalkyl or COOr6 wherein r6 is hydrogen or a lower alkyl, and l is 0, 1, 2 or 3, however, m denotes an integer of from 6 to 9 when A is methyl, or m denotes 0 or an integer of from 1 to 6 when A is a group represented by the following general formula; STR3 and X and Y are each independently CH2 when m is 0, the pharmaceutically-acceptable salts thereof and methods for manufacturing the said compounds and the pharmaceutically-acceptable salts thereof.
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- Unusually Long Lifetimes of the Singlet Derived from 4-Azido-2,3,5,6-tetrafluorobenzamides
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Laser flash photolysis (308 nm, 20 ns, 150 mJ) of 4-azido-2,3,5,6-tetrafluorobenzamides, esters, and thioesters generate singlet nitrenes which can be intercepted with pyridine to produce strongly absorbing ylides.It was possible to resolve the rate of formation of the ylides as a function of pyridine concentration.This has lad to direct measurements of the absolute rate constants of (a) the reaction of the nitrene with pyridine, (b) ring expansion of the nitrene to a ketenimine, and (c) singlet to triplet nitrene intersystem crossing.
- Marcinek, Andrzej,Platz, Matthew S.,Chan, Stephen Y.,Floresca, Rey,Rajagopalan, Krishnan,et al.
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p. 412 - 419
(2007/10/02)
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