- Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non-Activated Aliphatic C?H Bonds via Metallocarbene Intermediates
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Combining an electrophilic iron complex [Fe(Fpda)(THF)]2 (3) [Fpda=N,N′-bis(pentafluorophenyl)-o-phenylenediamide] with the pre-activation of α-alkyl-substituted α-diazoesters reagents by LiAl(ORF)4 [ORF=(OC(CF3)3] provides unprecedented access to selective iron-catalyzed intramolecular functionalization of strong alkyl C(sp3)?H bonds. Reactions occur at 25 °C via α-alkyl-metallocarbene intermediates, and with activity/selectivity levels similar to those of rhodium carboxylate catalysts. Mechanistic investigations reveal a crucial role of the lithium cation in the rate-determining formation of the electrophilic iron-carbene intermediate, which then proceeds by concerted insertion into the C?H bond.
- Hernán-Gómez, Alberto,Rodríguez, Mònica,Parella, Teodor,Costas, Miquel
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supporting information
p. 13904 - 13911
(2019/08/30)
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- Exploring the effect of chirality on the therapeutic potential of N-alkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease
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In the frame of a research program aimed to explore the relationship between chirality of iminosugars and their therapeutic potential, herein we report the synthesis of N-akyl L-deoxyiminosugars and the evaluation of the anti-inflammatory properties of selected candidates for the treatment of Pseudomonas aeruginosa infections in Cystic Fibrosis (CF)lung disease. Target glycomimetics were prepared by the shortest and most convenient approach reported to date, relying on the use of the well-known PS-TPP/I2 reagent system to prepare reactive alkoxyalkyl iodides, acting as key intermediates. Iminosugars ent-1-3 demonstrated to efficiently reduce the inflammatory response induced by P. aeruginosa in CuFi cells, either alone or in synergistic combination with their D-enantiomers, by selectively inhibiting NLGase. Surprisingly, the evaluation in murine models of lung disease showed that the amount of ent-1 required to reduce the recruitment of neutrophils was 40-fold lower than that of the corresponding D-enantiomer. The remarkably low dosage of the L-iminosugar, combined with its inability to act as inhibitor for most glycosidases, is expected to limit the onset of undesired effects, which are typically associated with the administration of its D-counterpart. Biological results herein obtained place ent-1 and congeners among the earliest examples of L-iminosugars acting as anti-inflammatory agents for therapeutic applications in Cystic Fibrosis.
- De Fenza, Maria,D'Alonzo, Daniele,Esposito, Anna,Munari, Silvia,Loberto, Nicoletta,Santangelo, Alessandra,Lampronti, Ilaria,Tamanini, Anna,Rossi, Alice,Ranucci, Serena,De Fino, Ida,Bragonzi, Alessandra,Aureli, Massimo,Bassi, Rosaria,Tironi, Matteo,Lippi, Giuseppe,Gambari, Roberto,Cabrini, Giulio,Palumbo, Giovanni,Dechecchi, Maria Cristina,Guaragna, Annalisa
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- Aliphatic C-H Bond Iodination by a N-Iodoamide and Isolation of an Elusive N-Amidyl Radical
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Contrary to C-H chlorination and bromination, the direct iodination of alkanes represents a great challenge. We reveal a new N-iodoamide that is capable of a direct and efficient C-H bond iodination of various cyclic and acyclic alkanes providing iodoalkanes in good yields. This is the first use of N-iodoamide for C-H bond iodination. The method also works well for benzylic C-H bonds, thereby constituting the missing version of the Wohl-Ziegler iodination reaction. Mechanistic details were elucidated by DFT computations, and the N-centered radical derived from the used N-iodoamide, which is the key intermediate in this process, was matrix-isolated in a solid argon matrix and characterized by UV-vis as well as IR spectroscopy.
- Artaryan, Alexander,Mardyukov, Artur,Kulbitski, Kseniya,Avigdori, Idan,Nisnevich, Gennady A.,Schreiner, Peter R.,Gandelman, Mark
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p. 7093 - 7100
(2017/07/26)
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- PROCESS FOR THE PREPARATION OF N-IODOAMIDES
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The present invention provides new stable crystalline N-iodoamides - 1-iodo- 3,5,5-trimethylhydantoin (1-ITMH) and 3-iodo-4,4-dimethyl-2-oxazolidinone (IDMO). The present invention further provides a process for the preparation of organic iodides using N-iodoamides of this invention and recovery of the amide co-products from waste water.
- -
-
Paragraph 00291-00292
(2015/05/26)
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- Synthesis of σ receptor ligands with unsymmetrical spiro connection of the piperidine moiety
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The symmetrically connected spiro[[2]benzopyran-1,4′-piperidines] 1 are highly potent and selective σ1 receptor ligands. Changing the position of the spirocyclic nitrogen atom led to the unsymmetrically connected spiro[[2]benzopyran-1,3′-piperidines] 2 with a reduced distance between the aromatic system and the basic nitrogen atom. The synthesis of 2 was performed by halogen-metal exchange at the aryl bromide 3 followed by addition to the piperidone 5 and intramolecular transacetalization. The yield of 2a was considerably improved by transmetallation of the aryllithium intermediate 4a with CeCl3 (4c). The cis and trans diastereomers cis-2 and trans-2 were separated and characterized by nuclear Overhauser effect. After removal of the benzyl group, the secondary amine 2b was alkylated with various alkyl and arylalkyl halides. The σ1 and σ2 receptor affinity of the spirocyclic piperidines 2 were determined with receptor binding studies. Compared with the spirocyclic piperidines 1, the unsymmetrically connected piperidines 2 show remarkably reduced σ1 receptor affinities, whereas the selectivity over σ2 and NMDA receptors was retained. A stereoselective interaction of the σ1 receptor protein with the cis- or trans-configured spirocyclic compounds 2 was not observed. It was shown that alkyl residues at the N-atom can replace the lipophilic N-arylalkyl groups and interact with the primary hydrophobic binding site of the σ1 receptor protein.
- Jasper, Annemarie,Schepmann, Dirk,Lehmkuhl, Kirstin,Vela, Jose Miguel,Buschmann, Helmut,Holenz, Joerg,Wuensch, Bernhard
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experimental part
p. 4306 - 4314
(2009/12/24)
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- Simple synthesis of fresh alkyl iodides using alcohols and hydriodic acid
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A simple synthesis of fresh alkyl iodides using alcohols and hydriodic acid (HI) is reported. The alkyl iodides were obtained in quick and easy work-up with good to excellent yields (66-94%) and very high purities (97-99%). Freshly prepared iodomethane and 1-iodobutane were applied to synthesize biologically relevant 3,7-dimethyladenine and 9-butyladenine, which were characterized thoroughly using 1D and 2D NMR, individually.
- Klein, Suzane M.,Zhang, Cungen,Jiang, Yu Lin
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p. 2638 - 2641
(2008/09/19)
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- Reactivity of anionic nucleophiles in ionic liquids and molecular solvents
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The nucleophilic reactivity of a representative series of anions has been measured in [hmim][ClO4] 3i, [hm2im][ClO4] 3′i, and [hmim][PF6] 3l ILs in the reaction with n-alkyl methanesulfonates and compared with that found in common molecular solvents (MeOH, DMSO, PhCl). The reactivity is found to depend on both the imidazolium cation-anion interaction and the specific solvation by water present in the IL, the water playing the main effect, in particular with hydrophilic anions. Removal of the largest quantity of water remarkably increases the ion pair reactivity in the IL up to rate constant value k comparable with those obtained in DMSO and in low polarity media (PhCl).
- Betti, Cecilia,Landini, Dario,Maia, Angelamaria
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p. 1689 - 1695
(2008/09/18)
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- Methods for producing acetic acid
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A method produces acetic acid by continuously reacting methanol with carbon monoxide in the presence of a rhodium catalyst, an iodide salt, methyl iodide, methyl acetate, and water; and thereby producing acetic acid at a production rate of 11 mol/L·hr or more while keeping the acetaldehyde content of a reaction mixture to 500 ppm or less, in which the reaction is carried out at a carbon monoxide partial pressure in a gaseous phase of a reactor of 1.05 MPa or more and/or at a methyl acetate content of the reaction mixture of 2 percent by weight or more to thereby keep the production rate of acetaldehyde to 1/1500 or less that of acetic acid. This method can reduce production of by-products without reducing the reaction rate of acetic acid even at a low water content and a low hydrogen partial pressure in a reaction system.
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Page/Page column 9-10
(2008/06/13)
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- Spiro[benzopyran] or spiro[benzofuran] derivatives which inhibit the sigma receptor
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The present invention relates to compounds (I) having pharmacological activity towards the sigma (σ) receptor, and more particularly to spiro[benzopyran] or spiro[benzofuran] derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis. wherein m is selected from 1 or 2, p is selected from 1 or 2, and m + p is either 2 or 3; n is selected from 0 or 1; R1, R2 are as defined in the application.
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Page/Page column 28-29
(2008/06/13)
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- Iodination of alcohols using triphenylphosphine/iodine under solvent-free conditions using microwave irradiation
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A straightforward and effective procedure for the conversion of benzylic, allylic and aliphatic alcohols to the corresponding iodides using Ph3P/I2 under solvent-free conditions using microwave irradiation is reported.
- Hajipour, Abdol Reza,Falahati, Ali Reza,Ruoho, Arnold E.
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p. 4191 - 4196
(2007/10/03)
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- Anion nucleophilicity in ionic liquids: A comparison with traditional molecular solvents of different polarity
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The nucleophilic reactivity of a homogeneous series of anions (halides, pseudohalides and organic anions) in the ionic liquids [hexmim] [ClO 4] and [hexmim] [PF6] has been measured in their reaction with n-alkyl methanesulfonates, and compared with that found in traditional molecular solvents of different polarity, that is, chlorobenzene, DMSO, and MeOH.
- Landini, Dario,Maia, Angelamaria
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p. 3961 - 3963
(2007/10/03)
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- Direct bromination and iodination of non-activated alkanes by hypohalite reagents
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The direct functionalisation of alkanes through bromination and iodination has been successfully achieved. The combination of stoichiometric mixtures of elemental halogen and sodium alkoxides leads to the formation of alkyl hypobromites and hypoiodites as reagents. The halogenation occurs without external photostimulation under thermal reaction conditions. Georg Thieme Verlag Stuttgart.
- Montoro, Raul,Wirth, Thomas
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p. 1473 - 1478
(2007/10/03)
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- Direct Iodination of Alkanes
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(Matrix presented) A cheap and efficient iodination of hydrocarbons can be achieved by generating tert-butyl hypoiodite from iodine and sodium tert-butoxide. The alkane is reactant and solvent, and this metal-free process provides a clean solution for their direct iodination.
- Montoro, Raul,Wirth, Thomas
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p. 4729 - 4731
(2007/10/03)
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- Activation of alkanes upon reaction with PhI(OAc)2-I2
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You can also choose from alkanes! Either mono- or bifunctional iodo derivatives can be prepared from alkanes (see scheme) in an efficient and selective manner by using PhI(OAc)2, I2, and an alcohol.
- Barluenga, Jose,Gonzalez-Bobes, Francisco,Gonzalez, Jose M.
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p. 2556 - 2558
(2007/10/03)
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- New halogenation reagent system for one-pot conversion of alcohols into iodides and azides
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In Situ generation of hydrogen iodide from methanesulphonic acid/sodium iodide in different solvents was found to be an attractive reagent system for the chemoselective conversion of various alcohols to their corresponding iodides. Moreover, treatment of benzylic and allylic alcohols with this reagent system, followed by substitution with azide ion, produced the corresponding azides in one pot in good yields.
- Kamal, Ahmed,Ramesh,Laxman
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p. 827 - 833
(2007/10/03)
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- Primary and secondary 5-(alkyloxy)thianthrenium perchlorates. Characterization with 1H NMR spectroscopy, reactions with iodide and bromide ion, and thermal decomposition in solution
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A series of 5-(alkyloxy)thianthrenium perchlorates has been made in which the alkyl group is primary (1a-1p) and secondary (2a-2g). Preparations were carded out by reaction of the corresponding alkanol with thianthrene cation radical perchlorate in CH2Cl2 solution followed by precipitation of the perchlorate salt with dry ether. 1H NMR spectroscopy reveals that the presence of a stereogenic center in the alkyl group causes inequivalence in the ordinarily paired protons (e.g., H-4, H-6) of the thianthrenium ring. Reaction of iodide and bromide ion with primary alkyl-group compounds (e.g., methyl, ethyl, propyl, butyl) gave the alkyl halide in very good yield and by a second-order kinetic displacement. The second product was thianthrene 5- oxide (ThO). Rate constants for some of these reactions are reported. Reaction of secondary alkyl group compounds (e.g., 2-propyl, 2-pentyl, 2- hexyl, and 3-hexyl) with iodide ion gave good yields of alkyl iodide but also increasing evidence for a side reaction at the sulfonium sulfur, leading to I2, thianthrene, and secondary alkanol. Decomposition of some compounds at 100°C in solution (acetonitrile or 1,2-dichloroethane) was studied and gave alkene(s) and ThO.
- Zhao, Wenyi,Shine, Henry J.
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p. 695 - 702
(2007/10/03)
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- Reactions of nucleophilic substitution involving solid organic halogen compounds under shear deformation at high pressure
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Under conditions of shear deformation and high pressures (SD + HP), reactions of nucleophilic substitution were studied: 1) the replacement of aliphatic halogen atom with alkaline metal halides (halo-substituted aliphatic carboxylic acids, 1-bromoadamantane); 2) the replacement of halogen atom in aromatic nucleus (halobenzoic acids, dihalobenzenes) with halogen of salt; 3) the replacement of aliphatic halogen with hydroxyl (hydrolysis in a solid phase); 4) the replacement of halogen with amino group under deformation of the samples of ammonium α-halocarboxylates to give the corresponding amino acids.It was found that the exchange of the halogen atoms bonded with aliphatic carbon is most intensive in the mixtures of alkaline metal iodides with bromo-substituted acetic acid and propionic acids: the exchange reaction in these mixtures is observed even during grinding in the mortar. Unlike the liquid phase, under conditions of SD + HP exchange of the halogen atom of the aromatic nucleus with alkaline metal halides, proceeds successfully, and the reactivity of halides increases in the series Na K Rb Cs.Under SD + HP, 1-Br-adamantane reacts with water to form 1-adamantanol.A high reactivity of the water adsorbed by the reagents is observed. - Key words: shear deformation, high pressure, halogen derivatives of carboxylic acids, dihalobenzenes, alkaline metal halides, ammonium salts of halogen derivatives of carboxylic acids, amino acids, halo-substituted adamantanes, adamantanol, nucleophilic substitution reaction, hydrolysis, ball mill.
- Zharov, A. A.,Chistotina, N. P.,Gaziev, R. G.,Yakovleva, I. I.
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p. 1050 - 1055
(2007/10/02)
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- Electroorganic chemistry; 145: Coupling reaction of an olefin with a radical NO.3 generated by anodic oxidation of NO-3
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When NO-3 is electrochemically oxidized in the presence of a variety of terminal and 1,2-disubstituted olefins 1 in a mixed solvent system (MeCN:H2O:Et2O = 10:2:1), a radical NO.3 is generated from NO-3 and nitrate esters 3 are formed by a new coupling reaction of the olefin with the radical. The products 3 can be further transformed into the corresponding alcohols 4 and alkyl iodides 5. Under the same reaction conditions, 1,1-di- and 1,1,2-trisubstituted olefins 6 do not give nitrate esters but afford oxazoline derivatives 7. (1S,5S)-(-)-β-Pinene (13) is diastereoselectively transformed into (1S,2R,5S)-(-)-myrtanol (14) by this technique.
- Shono,Chuankamnerdkarn,Maekawa,Ishifune,Kashimura
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p. 895 - 897
(2007/10/02)
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- Diiodosilane. 2. A Multipurpose Reagent for Hydrolysis and Reductive Iodination of Ketals, Acetals, Ketones, and Aldehydes
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The reaction patterns of diiodosilane (SiH2I2, DIS) with ketals, acetals, ketones, and aldehydes were explored.The reagent may be used for mild cleavage of ketals and acetals either hydrolytically to give the parent carbonyl functionality or reductively to produce the corresponding alkyl iodide.At low temperatures (-42 deg C) and short reaction times (few minutes), catalytic amounts (5-10 molpercent) of DIS provide clean deprotection of various ketals and acetals to yield ketones and aldehydes, with no apparent reduction of the latter.At temperatures above 0 deg C, DIS effectively reduces ketals and acetals to iodoalkanes.This reduction is quite general both with respect to ketals and acetals and unprotected ketones and aldehydes.Reaction rates, however, are strikingly dependent on the substrate, with the following tendencies: (a) aromatic functionalities are generally reduced much faster than their aliphatic analogues; (b) ketals and acetals are rapidly reduced to the corresponding iodoalkanes, while free aldehydes, and particularly ketones, are essentially inert under the reaction conditions (but can be significantly activated by catalytic amounts of iodine); (c) dimethyl ketals form the parent ketones preferentially, while all other ketals, including diethyl ketals and dioxolanes, are reduced to iodoalkanes.
- Keinan, E.,Perez, D.,Sahai, M.,Shvily, R.
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p. 2927 - 2938
(2007/10/02)
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- Vinylic Organoboranes. 9. A General Stereospecific Synthesis of (Z)- and (E)-Disubstituted Alkenes via Organoboranes
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A general and stereospecific synthesis of (Z)-disubstituted alkenes using mono- and dihaloboranes is presented.The hydridation of dialkylhaloboranes in the presence of 1-alkynes provides the corresponding dialkylvinylboranes (1), representing the first general synthesis of such derivatives.Treatment with iodine in the presence of sodium methoxide induces the migration of one of the alkyl groups from boron to the adjacent carbon, followed by a rapid deiodoboronation to afford (Z)-disubstituted alkenes (2) in high yields.Similarly, the hydroboration of 1-alkynes with alkyl bromoboranes (R1BHBr*SMe2, 4) followed by iodination in the presence of sodium methoxide in methanol affords (Z)-disubstituted alkenes (2) in good yields.Both procedures constitute a general one-pot synthesis of (Z)- disubstituted alkenes from an alkene and 1-alkyne.A simple synthesis of Muscalure (7), the sex pheromone of the housefly (Musca domestica), is achieved in good yields.An alternative general stereospecific synthesis of (Z)- and (E)-disubstituted alkenes based on alkenylboronic esters is also described.
- Brown, Herbert C.,Basavaiah, Deevi,Kulkarni, Surendra U.,Bhat, Narayan G.,Prasad, J. V. N. Vara
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p. 239 - 246
(2007/10/02)
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- ORGANOBORANES FOR SYNTHESIS.9. RAPID REACTION OF ORGANOBORANES WITH IODINE UNDER THE INFLUENCE OF BASE. A CONVENIENT PROCEDURE FOR THE CONVERSION OF ALKENES INTO IODIDES VIA HYDROBORATION
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The reaction of organoborane with iodine is strongly accelerated by sodium hydroxide.Organoboranes derived from terminal alkenes react with the utilization of approximately two of the three alkyl groups attached to boron, providing a maximum of 67percent yield of alkyl iodide.Thus, hydroboration-iodination of 1-decene gives a 60percent yield of n-decyl iodide.Secondary alkyl groups, derived from internal alkenes, react more sluggishly and only one of the three alkyl groups attached to boron is converted to the iodide.Thus, the procedure applied to 2-butene provides a 30percent yield of 2-butyl iodide.The use of disiamylborane bis-(3-methyl-2-butylborane, Sia2BH as hydroborating agent increases the yield of iodides from terminal alkenes since the primary alkyl groups react in preference to the secondary siamyl groups.Consequently, hydroboration of 1-decene with Sia2BH, followed by iodination gives a 95percent yield of n-decyl iodide.The use of methanolic sodium methoxide in place of sodium hydroxide provides alkyl iodides in considerably higher yields.The combination of hydroboration with iodination in the presence of a base provides a convenient method for the anti-Markovnikov hydroiodination of alkenes.The base-induced iodination of organoboranes proceeds with the inversion of configuration at the reaction center, as shown by the formation of endo-2-iodonorbornane from tri-exo-norbornylborane.
- Brown, Herbert C.,Rathke, Michael W.,Rogic, Milorad M.,de Lue, Norman R.
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p. 2751 - 2762
(2007/10/02)
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- Radical Cations from Alkyl Iodides in Aqueous Solution
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Radical cations RI(1+) and (RIIR)(1+) are generated upon OH radical-induced oxidation of alkyl iodides in acidic (pHOH-adduct.Although alkyl iodide radical cations have been reported to exist in a solid, low-temperature matrix, they have so far not been detected in the liquid, particularly the aqueous phase.Both radical cations establish an equilibrium: .For R=Me the stability constant of the 2?-1?* three-electron-bonded species has been estimated to K>/=5E4 mol-1dm3. (RIIR)(1+) exhibits a strong optical absorption band in the visible; λmax is red-shifted with increasing electron-releasing power of R and ranges from 4115 nm (R=Me) to 470 nm (R=s-C4H9).The molecular radical cation absorbs in a comparatively much narrower range from 310-320 nm.It is suggested that it exists as (RIOH2)(1+), i.e. as an associate with one water molecule.The alkyl iodide radical cations are strong oxidants. (MeIIMe)(1+), for example, oxidizes I(1-) and Me2S with rate constant values of 7.7E9 mol-1dm3s-1 and 3.6E9 mol-1dm3s-1, respectively.
- Mohan, Hari,Asmus, Klaus-Dieter
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p. 1795 - 1800
(2007/10/02)
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- The efficiency of diphenylalkylsulfonium salts as alkylating agents
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A series of the title reagents have been used for the alkylation of a number of nucleophiles including iodide, cyanide, thiocyanate and fluoride ions as well as ethyl acetoacetate, phenylacetonitrile and a variety of nitrogen heterocyclic compounds.The results compared favorably with literature methods.
- Badet, Bernard,Julia, Marc,Lefebvre, Christian
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p. 431 - 434
(2007/10/02)
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- Antibiotics and derivatives thereof having β-lactamase inhibitory activity and production thereof
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A novel antibiotic substance of the formula STR1 wherein R1 is CH3 and R2 is --CH2 --CH2 -- or R1 is H and R2 is --CH=CH--; and R3 represents hydrogen, lower alkyl or triphenylmethyl, and including the salts of the compound of formula (I) wherein R3 is hydrogen, said antibiotic substance having strong antibiotic activity and β-lactamase inhibiting effect, and a method for producing the same by aerobic cultivation of Streptomyces A271.
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- A Mild and Convenient Procedure for Conversion of Alkenes into Alkyl Iodides via Reaction of Iodine Monochloride with Organoboranes
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Alkenes are rapidly converted to alkyl iodides under mild conditions via a hydroboration-iodination sequence which utilizes iodine monochloride as the iodination agent.The iodination proceeds with inversion of configuration.A series of functionally substituted iodides was synthesized via the new products.
- Kabalka, George W.,Gooch, Eugene E.
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p. 3578 - 3580
(2007/10/02)
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- Derivatives of 6,7 or 8 cycloalkyl 4-oxo quinoline 3 carboxylic acid
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wherein Ph denotes a 1,2-phenylene radical which carries cycloaliphatic radical, Rx denotes a free or etherified hydroxyl group or a free or substituted amino group, Ro denotes an alkyl radical, a free hydroxyl group or a hydroxyl group etherified by lower alkyl or, above all, a hydrogen atom and R1 denotes an aliphatic or cycloaliphatic hydrocarbon radical which is optionally substituted by hydroxyl, an araliphatic radical or a hydrogen atom, and their salts, which possess valuable analgesic, anti-inflammatory, anti-microbial and histamine liberation inhibiting properties.
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