- Organophotochemical SNAr Reactions of Mildly Electron-Poor Fluoroarenes
-
C–F functionalization of arenes with a range of alcohol and pyrazole nucleophiles has been achieved without the need for metal catalysts or highly electron-poor substrates. Treatment of fluoroarenes with alcohols or pyrazoles and DDQ under irradiation by blue LED light provides the corresponding substituted products. The procedure is complementary to classical SNAr chemistry which generally requires basic reaction conditions and high temperatures, and provides products under non-basic conditions at ≈ 40 °C.
- Burton, Jonathan W.,Genovino, Julien,Lian, Yajing,Monck, Nat,Sheridan, Thomas,Yayla, Hatice G.
-
supporting information
p. 2766 - 2770
(2020/05/18)
-
- Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation
-
Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.
- Mills, L. Reginald,Graham, Joshua M.,Patel, Purvish,Rousseaux, Sophie A. L.
-
supporting information
p. 19257 - 19262
(2019/12/02)
-
- Amplification of Trichloroisocyanuric Acid (TCCA) Reactivity for Chlorination of Arenes and Heteroarenes via Catalytic Organic Dye Activation
-
Heteroarenes and arenes that contain electron-withdrawing groups are chlorinated in good to excellent yields (scalable to gram scale) using trichloroisocyanuric acid (TCCA) and catalytic Brilliant Green (BG). Visible-light activation of BG serves to amplify the electrophilic nature of TCCA, providing a mild alternative approach to acid-promoted chlorination of deactivated (hetero)aromatic substrates. The utility of the TCCA/BG system is demonstrated through comparison to other chlorinating reagents and by the chlorination of pharmaceuticals including caffeine, lidocaine, and phenazone.
- Rogers, David A.,Bensalah, Adam T.,Espinosa, Alvaro Tomas,Hoerr, John L.,Refai, Fares H.,Pitzel, Amy K.,Alvarado, Juan J.,Lamar, Angus A.
-
supporting information
p. 4229 - 4233
(2019/06/17)
-
- Visible-light photocatalytic activation of N-chlorosuccinimide by organic dyes for the chlorination of arenes and heteroarenes
-
A variety of arenes and heteroarenes are chlorinated in moderate to excellent yields using N-chlorosuccinimide (NCS) under visible-light activated conditions. A screening of known organic dye photocatalysts resulted in the identification of methylene green as the most efficient catalyst to use with NCS. According to mechanistic studies described within, the reaction is speculated to proceed via a single electron oxidation of NCS utilizing methylene green under visible-light photoredox pathway. The photo-oxidation of NCS amplifies the electrophilicity of the chlorine atom of the NCS, thus leading to enhanced reactivity as a chlorinating reagent with aromatic substrates.
- Rogers, David A.,Gallegos, Jillian M.,Hopkins, Megan D.,Lignieres, Austin A.,Pitzel, Amy K.,Lamar, Angus A.
-
-
- In situ Generation of Hypervalent Iodine Reagents for the Electrophilic Chlorination of Arenes
-
Efficient metal-free methods for the electrophilic chlorination of arenes using PIFA and simple chlorine sources are reported. The in situ formation of PhI(Cl)OCOCF3 from PIFA and KCl is proposed, which resulted in a chlorinating species for moderately activated arenes. Moreover, the in situ formation of PhICl2 from PIFA and TMSCl resulted in an excellent approach for the chlorination of a great variety of arenes (20 examples) in high yields, even when working on a multigram scale.
- Granados, Albert,Jia, Zhiyu,del Olmo, Marc,Vallribera, Adelina
-
p. 2812 - 2818
(2019/04/08)
-
- From Anilines to Aryl Ethers: A Facile, Efficient, and Versatile Synthetic Method Employing Mild Conditions
-
We have developed a simple and direct method for the synthesis of aryl ethers by reacting alcohols/phenols (ROH) with aryl ammonium salts (ArNMe3+), which are readily prepared from anilines (ArNR′2, R′=H or Me). This reaction proceeds smoothly and rapidly (within a few hours) at room temperature in the presence of a commercially available base, such as KOtBu or KHMDS, and has a broad substrate scope with respect to both ROH and ArNR′2. It is scalable and compatible with a wide range of functional groups.
- Wang, Dong-Yu,Yang, Ze-Kun,Wang, Chao,Zhang, Ao,Uchiyama, Masanobu
-
supporting information
p. 3641 - 3645
(2018/03/13)
-
- Iron(III)-Catalyzed Chlorination of Activated Arenes
-
A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.
- Mostafa, Mohamed A. B.,Bowley, Rosalind M.,Racys, Daugirdas T.,Henry, Martyn C.,Sutherland, Andrew
-
p. 7529 - 7537
(2017/07/26)
-
- Mechanistic study on iodine-catalyzed aromatic bromination of aryl ethers by N-Bromosuccinimide
-
Although iodine-catalyzed reaction has rapid advances in recent years, examples on iodine-catalyzed bromination are rare and the mechanism of these reactions remains unclear. Herein, we reported an I2-catalyzed aromatic bromination of aryl ethers by NBS and presented the details of the mechanistic study including kinetic study and the study of kinetic isotope effects. The study revealed that the reaction was actually catalyzed by IBr formed in the induction period, and the rate-determining step was the HBr-elimination of the Wheland intermediate assisted by IBr.
- Pramanick, Pranab Kumar,Hou, Zhen-Lin,Yao, Bo
-
p. 7105 - 7114
(2017/11/27)
-
- AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES
-
The present invention provides a compound represented by the following formula (I): wherein each symbol is as described in the DESCRIPTION, which has a superior peripheral blood lymphocyte decreasing action, and is useful for the treatment or prophylaxis of autoimmune diseases; prophylaxis or suppression of resistance or acute rejection or chronic rejection of transplantation of organ or tissue; treatment or prophylaxis of graft-versus-host (GvH) disease due to bone marrow transplantation; or treatment or prophylaxis of allergic diseases.
- -
-
Paragraph 0352-0353
(2015/03/16)
-
- Practical and metal-free electrophilic aromatic halogenation by interhalogen compounds generated in situ from N-halosuccinimide and catalytic TMSCL
-
Halomonochloride compounds (ClCl, BrCl, ICl) generated in situ from N-halosuccinimide and catalytic chlorotrimethylsilane (TMSCl, 0.1 equiv) can efficiently halogenate aromatic compounds to give halogenated products in good to excellent yields and selectivities. The reaction can be carried out at room temperature or at lower temperatures, requires only one hour, is practical to apply to a wide range of substrates, and provides a simple access to a variety of haloarene compounds. Georg Thieme Verlag Stuttgart New York.
- Maibunkaew, Tapanee,Thongsornkleeb, Charnsak,Tummatorn, Jumreang,Bunrit, Anon,Ruchirawat, Somsak
-
supporting information
p. 1769 - 1775
(2014/08/05)
-
- A natural-product switch for a dynamic protein interface
-
Small ligands are a powerful way to control the function of protein complexes via dynamic binding interfaces. The classic example is found in gene transcription where small ligands regulate nuclear receptor binding to coactivator proteins via the dynamic activation function 2 (AF2) interface. Current ligands target the ligand-binding pocket side of the AF2. Few ligands are known, which selectively target the coactivator side of the AF2, or which can be selectively switched from one side of the interface to the other. We use NMR spectroscopy and modeling to identify a natural product, which targets the retinoid X receptor (RXR) at both sides of the AF2. We then use chemical synthesis, cellular screening and X-ray co-crystallography to split this dual activity, leading to a potent and molecularly efficient RXR agonist, and a first-of-kind inhibitor selective for the RXR/coactivator interaction. Our findings justify future exploration of natural products at dynamic protein interfaces.
- Scheepstra, Marcel,Nieto, Lidia,Hirsch, Anna K.H.,Fuchs, Sascha,Leysen, Seppe,Lam, Chan Vinh,In Het Panhuis, Leslie,Van Boeckel, Constant A.A.,Wienk, Hans,Boelens, Rolf,Ottmann, Christian,Milroy, Lech-Gustav,Brunsveld, Luc
-
supporting information
p. 6443 - 6448
(2014/06/24)
-
- Phosphoramidate tantalum complexes for room-temperature C-H functionalization: Hydroaminoalkylation catalysis
-
A cooled reaction: Phosphoramidate-ClTaMe3 complexes promote the first example of room-temperature hydroaminoalkylation catalysis. This reaction can be realized under solvent-free conditions and with challenging substrates such as styrenes and dialkyl amines. When using a vinylsilane substrate, for the first time the linear regioisomer is obtained preferentially using a Group5 metal. TBS=tert-butyldimethylsilyl, TMS=trimethylsilyl. Copyright
- Garcia, Pierre,Lau, Ying Yin,Perry, Mitchell R.,Schafer, Laurel L.
-
supporting information
p. 9144 - 9148
(2013/09/12)
-
- 4,5-DIHYDRO-OXAZOL-2-YL AMINE DERIVATIVES
-
The present invention relates to a compounds of formula I wherein R1, R1′, R2, R3, R4, X, Ar, and m are as defined in the specification and claims and pharmaceutically active acid addition salts thereof. Compounds of the invention have Asp2 (β-secretase, BACE 1 or Memapsin-2) inhibitory activity and are useful for the treatment of diseases characterized by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.
- -
-
Page/Page column 24
(2009/09/05)
-
- Metalations utilizing aryllithiums; ortho-functionalization of p-bromoanisole (pBrA)
-
An ortho-metalation protocol has been developed, which permits the survival of a bromine substituent in p-bromoanisole. Eight derivatives of the generated ortho-lithiated intermediate have been prepared. A neglected metalation concept is being explored here; one which proposes that minimizing the pKa difference between the aryl substrate and the conjugate acid of the metalating agent will lead to a regiospecific and selective metalation process.
- Slocum,Reece, Troy L.,Sandlin, Rebecca D.,Reinscheld, Thomas K.,Whitley, Paul E.
-
experimental part
p. 1593 - 1595
(2009/06/18)
-
- Discovery of 5-HT6 receptor ligands based on virtual HTS
-
Based on a pharmacophore alignment on a 5-HT6 ligand applying 4SCan technology, a new lead series was identified and further structurally investigated. Kis down to 8 nM were achieved.
- Tasler, Stefan,Kraus, Jürgen,Wuzik, Andreas,Müller, Oliver,Aschenbrenner, Andrea,Cubero, Elena,Pascual, Rosalia,Quintana-Ruiz, Jordi-Ramon,Dordal, Alberto,Mercè, Ramon,Codony, Xavier
-
p. 6224 - 6229
(2008/03/18)
-
- A simple, efficient and regioselective oxychlorination of aromatic compounds using ammonium chloride and oxone
-
A simple, efficient, mild and regioselective method for oxychlorination of aromatic compounds is reported. The electrophilic substitution of chlorine generated in situ from NH4Cl as a chlorine source and oxone as an oxidant is reported for the first time.
- Narender,Mohan, K.V.V. Krishna,Srinivasu,Kulkarni,Raghavan
-
p. 1335 - 1338
(2007/10/03)
-
- Ethylene-styrene copolymers and phenol-triazole type complexes, catalysts, and processes for polymerizing
-
Metal-ligand complexes that are useful as precursors to catalysts for the polymerization of olefins are provided. Certain of the catalysts are particularly effective at polymerizing ethylene and styrene into copolymers having novel properties, including a low molecular weight and close comparison between vinyl and methyl end groups.
- -
-
-
- Bromodecarbonylation and bromodecarboxylation of electron-rich benzaldehydes and benzoic acids with oxone and sodium bromide
-
Benzaldehydes and benzoic acids bearing ortho- and paraelectron donating substituents having unshared electron-pair have undergone bromodecarbonylation or bromodecarboxylation on treatment with sodium bromide in the presence of Oxone in aqueous methanol.
- Koo, Bon-Suk,Kim, Eun-Hoo,Lee, Kee-Jung
-
p. 2275 - 2286
(2007/10/03)
-
- Selective halogenation of aromatics by dimethyldioxirane and halogen ions
-
The oxidation of halogen anions by dimethyldioxirane (DMD) produced reactive species which led, in acidic media, to the halogenation of activated aromatic rings. The reaction can be efficiently controlled to obtain selective and mixed halogenated species.
- Bovicelli,Mincione,Antonioletti,Bernini,Colombari
-
p. 2955 - 2963
(2007/10/03)
-
- Synthesis of hydroxylated PCB metabolites with the Suzuki-coupling
-
An improved synthesis of hydroxylated polychlorinated biphenyls (PCBs) which are structurally related to the major hydroxy PCB congeners identified in human plasma is described. The coupling of (chlorinated) aryl boronic acids with bromochloro anisoles using the standard conditions of the Suzuki coupling gave the desired hydroxylated PCB metabolites in good to excellent yields. The approach offers the advantage of high selectivity and good yields compared to conventional methods such as the Cadogan reaction and allows the use of less toxic starting materials.
- Lehmler, Hans-Joachim,Robertson, Larry W.
-
p. 1119 - 1127
(2007/10/03)
-
- Reactivity and synthetic utility of 1-(arenesulfonyloxy) benziodoxolones
-
The reactivity and synthetic use of 1-(arenesulfonyloxy)benziodoxolones were studied. In the presence of iodine, 1-(arenesulfonyloxy)benziodoxolones iodinated various aromatics to give iodoarenes in moderate to good yields. In particular, 1-(p-chlorobenzenesulfonyloxy)benziodoxolone showed the best reactivity. Using a halide salt such as lithium bromide or lithium chloride instead of iodine, the corresponding aryl bromides and chlorides were also obtained in good yields. In the absence of aromatics, 1- (arenesulfonyloxy)benziodoxolones gave rise to desulfonyloxyiodination reactions to give the corresponding aryl iodides via electrophilic ipso substitution on the aromatic rings. Furthermore, the l-(p- toluenesulfonyloxy)benziodoxolone/iodine system iodotosyloxylated alkynes in good yields. These reactions proceeded via the formation of arenesulfonyl hypoiodites.
- Muraki, Takahito,Togo, Hideo,Yokoyama, Masataka
-
p. 2883 - 2889
(2007/10/03)
-
- Environment friendly regiospecific bromination of aromatic ethers by N- bromosuccinimide in presence of montmorillonite
-
Reaction of methoxybenzenes and naphthalenes with N-bromosuccinimide in presence of montmorillonite clay (K10) affords excellent yields of regiospecifically brominated products under mild conditions in the absence of solvent.
- Perumal,Vijayabaskar,Gomathi,Selvaraj
-
p. 603 - 604
(2007/10/03)
-
- Substituted terphenyl compounds for the treatment of inflammation
-
A class of terphenyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: STR1 wherein each of R2 and R3 is independently selected from hydrido and halo; or wherein R2 and R3 together form --OCH2 O--; wherein each of R6 through R8 is independently selected from hydrido, lower alkyl, halo, lower alkoxy, lower haloalkyl, and lower dialkylamino; or wherein R6 and R7 together form --OCH2 O; and wherein R12 is selected from lower alkylsulfonyl and aminosulfonyl; or a pharmaceutically-acceptable salt thereof.
- -
-
-
- Mild chlorination of aromatic compounds with tin(IV) chloride and lead tetraacetate
-
SnCl4/Pb(OAc)4 acts as a safe source of Cl2 for the chlorination of aromatic compounds. A variety of aromatic compounds are effectively chlorinated with SnCl4/Pb(OAc)4 under mild conditions. The mixture is a selective chlorinating agent, particularly with polyalkylbenzenes, polycyclic aromatic compounds and anisoles.
- Muathen, Hussni A.
-
p. 8863 - 8866
(2007/10/03)
-
- Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents
-
A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 μM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.
- Li, James J.,Norton, Monica B.,Reinhard, Emily J.,Anderson, Gary D.,Gregory, Susan A.,Isakson, Peter C.,Koboldt, Carol M.,Masferrer, Jaime L.,Perkins, William E.,Seibert, Karen,Zhang, Yan,Zweifel, Ben S.,Reitz, David B.
-
p. 1846 - 1856
(2007/10/03)
-
- Cation Radicals as Intermediates in Aromatic Halogenation with Iodine Monochloride: Solvent and Salt Effects on the Competition between Chlorination and Iodination
-
Three distinct classes of substitutional reactivity can be discerned in the halogenation of a series of methyl-substituted methoxybenzenes (ArH) with iodine monochloride (ICl), namely, exclusive iodination, exclusive chlorination, and mixed iodination/chlorination.Spectral studies establish the prior formation of the charge-transfer complex which suffers electron transfer to afford the reactive triad .+,I.,Cl(-)> according to Scheme 1.Separate reactivity studies show that chlorination and iodination can result from the quenching of the aromatic cation radical by chloride and iodine (atom), respectively.Iodination versus chlorination thus represents the competition between radical-pair and ion-pair collapse from the reactive triad, and it is predictably modulated by solvent polarity and added salt.
- Hubig, S. M.,Jung, W.,Kochi, J. K.
-
p. 6233 - 6244
(2007/10/02)
-
- Antibiotic derivatives of 7-phenyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids
-
1-Substituted-6-fluoro-7-aryl-(8-fluoro)-1,4-dihydroquinol-4-one 3-carboxylic acids having antibacterial activity are prepared by reacting the corresponding alkyl 1-substituted-6-fluoro-7-bromo-(8-fluoro)-1,4-dihydroquinol-4-one-3-carboxylate with an arylmetallic compound and hydrolyzing the ester formed.
- -
-
-
- 107. Substitution electrophile aromatique dans l'anhydride sulfureux liquide. Etude cinetique de la reaction de bromination d'anisoles monosubstitues. Transmission des effets electroniques et caracteristiques de l'etat de transition
-
Reactivity-structure correlations for anisole and eleven of its substituted derivatives established from bromination rate constants in liquid SO2, unlike observations in water, show the reaction to be highly sensitive to substituent effects, (ρ+H2O = -7.1; ρ+SO2 = -10.51).This result is ascribed to the solvation of the methoxy group which decreases the conjugation of para-substituted (ρ+O = -9.70) compared to that of ortho-substituted derivatives (ρ+p = -8.86).The highly solvated transition state lies far from reactants on the reaction coordinate and the positive charge developed in this state is nearly unity.
- Castellonese, Paul,Villa, Pierre
-
p. 1068 - 1077
(2007/10/02)
-
- Formation of Nonaromatic Products in the Chlorination of Simple Substituted Aromatic Ethers
-
The neat chlorination of 4-chloroanisole produces 1,3,4,5,6-pentachloro-4-methoxycyclohexene in 35percent yield.Mono- and dichlorinated anisoles and a variety of simple substituted anisoles were chlorinated to determine the generality of nonaromatic product formation. 3,4-Dichloroanisole, 4-fluoroanisole, 4-bromoanisole, 4-methylanisole, and 4-chlorophenetole form similar products based on their spectral properties.These products are proposed to form by a cis-1,2-chlorine addition followed by rapid cis-1,4 chlorine addition.On the basis of the NMR data, a predominate configuration is proposed.
- Watson, William David
-
p. 5270 - 5276
(2007/10/02)
-
- ETUDE CINETIQUE DE LA REACTION DE BROMINATION DANS LE SO2 LIQUIDE. REACTIVITES DU BENZENE, DES POLYMETHYLBENZENES ET D'ANISOLES SUBSTITUES. DETERMINATION DES REACTIVITES RELATIVES ET CALCUL DES FACTEURS DE VITESSE PARTIELLE
-
Absolute rate constants for the bromination of a series of anisoles and polymethylbenzenes, have been measured in liquid sulfur dioxide at -23 +/- 2 deg C.Rate constants for benzene and toluene were determined by extrapolation as: 9.6E-7 and 4.2E-4 l mol-1 mn-1 respectively.Under these conditions, the bromination of anisole provides 0.56percent ortho- and 98.99percent para-bromoanisole, and the rate relative to benzene is 6.98E8/1.00.These date lead to the partial rate factors for the methoxy group: οOMef = 1.1E7 and pOMef = 4.12E9.The value mOMef = 1.4 is calculated from the rate constant for p-dimethoxy benzene, 10 l mol-1 mn-1.Similarly, in the case of bromination of toluene, a relative rate of 443/1.00, and an isomer distribution of 16percent ortho- and 84percent para, permit the calculation of partial rate for the methyl group:οMef = 212 mMef = 6.4 pMef = 2232 > correlations log k = f(Σ?+), established for the bromination of anisoles and polymethylbenzenes, exhibit large values for their slopes (ρAnisoles+ = -10.51; ρ+polymethylbenzenes = -9.5), and indicate satisfactory additivity of substituent effects.It appears that the + M effect of the methoxy group is less strong in this solvent than it is in water or acetic acid.Despite its low dielectric constant, (D = 17.5 at -20 deg C), liquid sulfur dioxide appearars to be quite a favourable medium for electrophilic aromatic substitution.Thus, for identical experimental conditions, the rate constants for bromination are 1E2 to 1E4 lower than those observed in water, but 1E3 to 1E5 larger than those in acetic acid.
- Castellonese, Paul,Villa, Pierre
-
-