- Decarboxylative Bromination of Sterically Hindered Carboxylic Acids with Hypervalent Iodine(III) Reagents
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Sterically hindered three-dimensional (3D) alkyl halides are promising precursors for various reactions; however, they are difficult to synthesize via conventional reactions. We present an efficient and practical method for decarboxylative bromination of sterically hindered 3D aliphatic carboxylic acids using commercially available (diacetoxyiodo)benzene and potassium bromide, one of the most stable and cheapest bromine sources in nature. The present method features a metal-free/Br2-free system, mild reaction conditions, one-pot operation under air at room temperature, wide functional group compatibility, and gram-scale synthetic capability. This highly efficient reaction cleanly converts a broad range of carboxylic acids, the most inexpensive and readily available sources of highly strained/naturally occurring/drug-related scaffolds, into the corresponding alkyl bromides in good to high yields.
- Kanazawa, Junichiro,Koyamada, Kenta,Miyamoto, Kazunori,Uchiyama, Masanobu,Watanabe, Ayumi
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supporting information
p. 1328 - 1334
(2020/08/14)
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- MANUFACTURING METHOD OF BROMINATED CYCLOPROPANES
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PROBLEM TO BE SOLVED: To provide a manufacturing method capable of simply providing bromoalkyl cyclopropanes in an industrial scale. SOLUTION: There is provided a manufacturing method of bromoalkyl cyclopropanes represented by the formula (3) or the formula (4) by reacting corresponding alcohols and HBr dissolved in an aprotic solvent such as 1,4-dioxanes and substituting a hydroxyl group by Br. (3) (4), where R1 is H, a C1 to 10 substituted/unsubstituted linear/branched alkyl group, a C3 to 10 substituted/unsubstituted cyclic alkyl group, R2 is a substituted/unsubstituted phenyl group and n is an integer of 1 to 10. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0033
(2017/04/28)
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- METHOD FOR PRODUCING (BROMOMETHYL)CYCLOPROPANE AND (BROMOMETHYL)CYCLOBUTANE
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The present invention relates to a method for obtaining high purity (bromomethyl)cyclopropane and (bromomethyl)cyclobutane, starting respectively with cyclopropylmethanol and cyclobutylmethanol, under synthesis conditions that enable high productivity and high yield.
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Paragraph 0062; 0063
(2016/12/22)
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- A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
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α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
- Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
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p. 420 - 430
(2015/12/31)
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- Production of ethylcycloalkanes bromomethylbiphenyl
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PROBLEM TO BE SOLVED: To provide a production method by which bromomethyl cycloalkanes can be easily obtained in an industrial scale.SOLUTION: A method for producing bromomethyl cycloalkanes comprises brominating cycloalkyl methanols by use of hydrogen bromide, wherein the reaction is carried out in the presence of an ionic liquid.
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Paragraph 0036
(2018/10/16)
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- Rearrangement, nucleophilic substitution, and halogen switch reactions of alkyl halides over NaY zeolite: Formation of the bicyclobutonium cation inside the zeolite cavity
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Rearrangement and nucleophilic substitution of cyclopropylcarbinyl bromide over NaY and NaY impregnated with NaCl was observed at room temperature. The first-order kinetics are consistent with ionization to the bicyclobutonium cation, followed by internal return of the bromide anion or nucleophilic attack by impregnated NaCl to form cyclopropylcarbinyl, cyclobutyl, and allylcarbinyl chlorides. The product distribution analysis revealed that neither a purely kinetic distribution, similar to what is found in solution, nor the thermodynamic ratio, which favors the allylcarbinyl halide, was observed. Calculations showed that bicyclobutonium and cyclopropylcarbinyl carbocations are minimal over the zeolite structure, and stabilized by hydrogen bonding with the framework structure. A new process of nucleophilic substitution is reported, namely halogen switch, involving alkyl chlorides and bromides of different structures. The reaction occurs inside the zeolite pores, due to the confinement effects and is an additional proof of carbocation formation on zeolites. The results support the idea that zeolites act as solid solvents, permitting ionization and solvation of ionic species.
- Franco, Marcelo,Rosenbach Jr., Nilton,Ferreira, Glaucio B.,Guerra, Antonio C. O.,Kover, W. Bruce,Turci, Cassia C.,Mota, Claudio J. A.
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p. 1592 - 1600
(2008/09/18)
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- Triazole derivatives
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The present invention relates to triazole and imidazole derivatives of formula I and to their pharmaceutically acceptable acid addition salts. These compounds are NMDA receptor subtype blockers and are useful for the treatment of diseases related to the NMDA receptor.
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- Process for the production of halogen methyl cyclopropanes and highly pure halogen methyl cyclopropanes
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The invention relates to a process for the preparation of halogenomethylcyclopropanes.
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- Method for producing bromomethylcyclopropane
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A method for producing bromomethylcyclopropane is provided, comprising reacting an organic sulfonyl halide with cyclopropylmethanol in the presence of a tertiary amine in a non-protic solvent, to generate cyclopropylmethyl organic sulfonate, and reacting the resulting cyclopropylmethyl organic sulfonate with an alkali metal bromide and/or a quaternary ammonium bromide in a non-protic polar solvent.
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- Esterification of carboxylic acid salts
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Mono- or polycarboxylic acid esters are prepared by reacting a salt of such carboxylic acid with an organic halocompound, e.g., a (cyclo)alkyl, (cyclo)alkenyl, aryl or aralkyl halide, in an aqueous reaction medium, in the presence of a catalytically effective amount of a phase transfer catalyst, for example an onium salt.
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- Indole derivatives as 5-HT1-like agonists
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Compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 is a substituted alkylene; C3 -C7 cycloalkyl optionally substituted with HO; C3 -C6 alkenyl optionally substituted with aryl; C5 -C7 cycloalkenyl; or C3 -C6 alkynyl; R2 is H; halo; F3 C; NC; R8 R9 NOC; a substituted alkylene; R8 R9 NO2 S; R10 S(O)m ; R12 CON(R11); R10 SO2 N(R11); R8 R9 NOCN(R11); R10 O2 CN(R11); R13 (CH2)n CH=CH; or R7 O are selective 5-HT1 -like receptor agonists useful in the treatment of migraine, cluster headache, chronic paroxysmal hemicrania and headache associated with vascular disorders.
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- Penta and tetrasubstituted piperidines and compositions and method of treating psychosis
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The invention is related to compounds, being useful in treating psychosis, of the formula: STR1 wherein: R1 is hydrogen, lower-alkyl or phenyl-lower-alkyl; R2 and R4 are the same or different lower-alkyl; R3 is hydrogen or lower-alkyl; m is two or three; n is an integer from zero to three; and R5 is hydrogen, lower-alkyl, C3 -C7 -monocyclic cycloalkyl, allyl, or propargyl; or a pharmaceutically acceptable acid-addition salt thereof.
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- A Convenient Large-Scale Synthesis of Cyclobutyl Halides
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An improved method for the preparation of multigram quantities of cyclobutyl halides is described.The Grignard reactivity of these halides is also discussed.
- Dupont, Andrea C.,Audia, Vicki H.,Waid, Philip P.,Carter, J. Paul
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p. 1011 - 1021
(2007/10/02)
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- Bicyclo-octane and bicyclo-nonane derivatives, processes for their preparation and their use as herbicides
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Bicyclo-octane and bicyclo-nonane derivatives are described having herbicidal and plant growth regulating properties. The derivatives are based on the general formula
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- Rate constants for abstraction of bromine from bromotrichloromethane by butyl, cyclopropylmethyl, and phenyl radicals in solution
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The radical chain decomposition of cyclopropylmethyl(1-hydroxy-1-methylethyl)diazene ((CH3)2C(OH)N=NCH2- 1) at 253-341 K in hexafluorobenzene or in dichloromethane solution containing bromotrichloromethane affords cyclopropylmethyl bromide, 4-bromo-1-butene, 1-bromo-5,5,5-trichloro-2-pentene, and 3,5-dibromo-1,1,1-trichloropentane from the cyclopropylmethyl portion of 1.Other major products are nitrogen, acetone, and chloroform.The rate constant for formation of cyclopropylmethyl bromide by attack of cyclopropylmethyl free radicals from 1 at bromine of BrCCl3 (kBrcpm) was calculated from the product composition using the known rate constant for rearrangement of cyclopropylmethyl radicals to 3-buten-1-yl radicals.At 25 deg C, kBrcpm = 6.5 x 1E8 M-1s-1 and the temperature dependence is given by log (kBrcpm/M-1s-1) = (10.6 +/- 0.3) - (2.4 +/- 0.4)/θ, where θ = 2.3RT kcal/mol-1.Non-chain decomposition of (CH3)2C(OH)N=N-R (2, R = Bu, and 3, R = Ph) in the presence of excess 1,1,3,3-tetramethylisoindolin-2-yloxyl (4) and bromotrichloromethane afforded BuBr and PhBr, respectively, in yields determined by the relative concentrations of 4 and BrCCl3.Rate constants for coupling (kc) of Bu. and Ph. with 4 were assumed to be proportional to rate constants for diffusion controlled reactions, kd, which were estimated from measured viscosities.Values of kBrBu and kBrPh, calculated from kc and product yields for reactions at 80 deg C, are 0.26 x 1E9 and 1.55 x 1E9 M-1s-1, respectively.The relative radical reactivities toward BrCCl3 at 80 deg C are Ph, 6; cpm, 5; Bu, 1.
- Mathew, Lukose,Warkentin, John
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- Absolute Rate Constants for Bromine Abstraction from N-Bromoimides and Br2 by Alkyl Radicals
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Imidyl radicals react with cyclopropanes solely via hydrogen abstraction.In the case of methylcyclopropane, the major product (cyclopropylcarbinyl bromide) is derived from abstraction of hydrogen from the methyl group.The resultant cyclopropylcarbinyl radical is partioned between two pathways: (1) abstraction of Br from N-bromoimide and (2) rearrangement to the allylcarbinyl radical (eventually yielding 4-bromo-1-butene).Since the absolute rate of the rearrangement is known, an absolute rate constant for the abstraction of Br from N-bromoimides by alkyl radicals can be derived (CH2Cl2 solvent, 15 deg C), k ca. (1.3-1.6)1xE10 M-1s-1.Reactions carried out in the presence of Br2 provide a third pathway for scavenging of the cyclopropylcarbinyl radical, providing kBr2=2.2x1E10 M-1s-1.Thus, trapping of primary R. by either N-bromoimides or Br2 occurs at rates that are diffusion-controlled.
- Tanko, James M.,Skell, Philip S.,Seshadri, Sri
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p. 3221 - 3225
(2007/10/02)
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- HOMOLYTIC DISPLACEMENT AT CARBON CENTRES. XII. REGIOSPECIFIC FORMATION OF N-ALLYL AND N-CYCLOPROPYLCARBINYL SULPHONAMIDES AND OF ALLYL AND CYCLOPROPYL HALIDES IN THE REACTION OF N-HALOGENO COMPOUNDS WITH ORGANOCOBALOXIMES
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Several but-3-enyl and allylcobaloximes react regiospecifically with N-chloro-N-methyl sulphonamides to give N-cyclopropylcarbinyl- or rearranged N-allyl-N-methyl sulphonamides, by a process which is believed to take place by the attack of an N-centred radical at the terminal unsaturated carbon of the organic ligand, with displacement of cobaloxime(II).In contrast, N-bromoacetamide and several other N-halogenoimides react regiospecifically to the cyclopropylcarbinyl halide or the rearranged allyl halide by a process in which a halogen-containing free radical species attacks the terminal unsaturated carbon of the organocobaloxime.
- Johnson, Michael D.,Lampman, Gary M.,Koops, Roger W.,Gupta, B. Das
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p. 281 - 288
(2007/10/02)
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- 2-N-Cycloalkylmethyl 3-oxo 5,6-diaryl-as-triazines
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The present invention concerns new 2-N-cycloalkylmethyl 3-oxo 5,6-diaryl as-triazines, their method of production, pharmaceutical compositions thereof, and their use as medicaments, for treating pain. The derivatives of 2-N-cycloalkylmethyl 3-oxo 5,6-diaryl as-triazine according to the invention have the general formula I STR1 in which Ar represents a phenyl, furyl, thienyl, or pyridyl group, which group may possibly be substituted by a lower C1 to C4 alkoxy radical, in particular by the methoxy radical, and n is a whole number having a value of 1 to 4.
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- Regioselective Route to Sterically Hindered Cyclopropylcarbinyl Halides
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Reaction of cyclopropylcarbinyl alcohols 1 with hexachloroacetone and triphenylphosphine resulted in 80 - 90 percent yields of the corresponding cyclopropylcarbinyl chlorides 4 regioselectively, with no trace of the homoallylic chloride 2 or the chlorocyclobutane derivative 6a.Similar reaction of 1 with bromine and triphenylphosphine, in dimethylformamide, gave 65 - 80 percent yields of the cyclopropylcarbinyl bromide 5 with trace amounts of the homoallylic bromide 3 but no detectable bromocyclobutane derivative 6b.These reactions are amenable to the preparation of very sterically hindered cyclopropylcarbonyl halides, heretofore inaccessible, regioselectively and in a facile manner.
- Hrubiec, Robert T.,Smith, Michael B.
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p. 431 - 435
(2007/10/02)
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- Reactivity of an α-Acyl-α-cyclopropyl-carbenium Ion: a Highly Stereoselective Cyclopropylmethyl-Cyclopropylmethyl Rearrangement
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The complete stereoselectivity in a cyclopropylmethyl-cyclopropylmethyl rearrangement which has been investigated is rationalized in terms of a highly preferred conformation of the transient α-acyl-α-cyclopropyl-carbenium ion.
- Pardo, Claude,Charpentier-Morize, Micheline
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p. 1037 - 1039
(2007/10/02)
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- Reactions of cyclopropylcarbinol in dilute hydrochloric acid
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The treatment of cyclopropylcarbinol (1-OH) with dilute HCl has been used as a method for the preparation of cyclobutanol (2-OH).While 2-OH is the major product in this reaction, a careful investigation showed the presence of a total of 13 products, namely the alcohols 1-OH, 2-OH, and allylcarbinol (3-OH), cyclopropylcarbinyl, cyclobutyl and allylcarbinyl chlorides (1-Cl, 2-Cl and 3-Cl, respectively), dicyclopropylcarbinyl, cyclobutyl cyclopropylcarbinyl, allycarbinyl cyclopropylcarbinyl, dicyclobutyl and allylcarbinyl cyclobutyl ethers (1-O-1, 2-O-1, 3-O-1, 2-O-2, and 3-O-2, respectively), as well as butyraldehyde and isobutyraldehyde.The alcohols, chlorides, and ethers likely arose from reactions of the bicyclobutonium ion with available nucleophiles in the reaction mixture.The minor amounts of the two aldehydes may be due to a ring opening isomerization of 2-methylcyclopropanol, the latter in turn resulted from a net 1,3-hydride shift in the cyclopropylcarbinyl cation, probably via an edge-protonated cyclopropane-type of species.Treatment of cyclopropylcarbinol (1-OH-α-14C) with dilute HCl gave samples of 1-OH-x-14C, 2-OH-x-14C, and 3-OH-x-14C the degradation of which showed that all three methylene groups in these alcohols have become equivalent, indicating a complete equilibration between isotope-position labeled bicyclobutonium ions.
- Lee, Choi Chuck,Cessna, Allan J.
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p. 1075 - 1079
(2007/10/02)
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- N-dealkylation of N-alkyl-14-hydroxymorphinans and derivatives thereof
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There is provided a novel, high yield, method of dealkylating N-alkylated 14-hydroxymorphinans and derivatives thereof including, inter alia, oxymorphone and oycodone. There are thus provided, inter alia, more efficient routes for the formation of naloxone, naltrexone, and nalbuphine. In the principal step of the process, the dealkylation using certain oxycarbonyl halides (or haloformates) is carried out on the N-alkyl-14-acyloxy-morphinan which it is desired to dealkylate.
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- Alkyltin cyclopropylcarbinylsulfonate
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Pesticidal and anti-inflammatory cyclopropyl compounds, cyclopropyl intermediates for the preparation of pesticidal compounds, especially chrysanthemic acid-like intermediates, and a process for preparing same.
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