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Imidazoles fluorination

Fluorination of thiophene-2,5-dicarboxylic acitl with a sulfur tetrafluoritie-hydrogen fluoride mixture provides 2,5-bis(trifluoromethyl)thiophene in a 69% yield no fluorine addition to the thiophene ring occurs [229J. Also, imidazole mono- and dicarboxylic acids yield only the respective trifluo-romethyliinidazoles [230],... [Pg.250]

Fluorination of organometallics, e.g., Me3Sn-imidazoles, has been used to improve selectivity with the aromatic—metal bond being broken preferentially (86BSF930). [Pg.3]

Kirk and Cohen (1969, 1971, 1973 Kirk et al., 1973) successfully applied the photo-fluoro-de-diazoniation method for the introduction of fluorine into imidazole and its derivatives with various substituents (e.g., histidine) 2- and 4-fluoroimi-dazole had not previously been synthesized by other methods. 2-Fluoroimidazole, in contrast to the 4-isomer, is easily hydrolyzed in water (Kirk et al., 1973). [Pg.281]

Phosphazene polymers can act as biomaterials in several different ways [401, 402,407]. What is important in the consideration of skeletal properties is that the -P=N- backbone can be considered as an extremely stable substrate when fluorinated alcohols [399,457] or phenoxy [172] substituents are used in the substitution process of the chlorine atoms of (NPCl2)n> but it becomes highly hydrolytically unstable when simple amino acid [464] or imidazole [405-407] derivatives are attached to the phosphorus. In this case, an extraordinary demolition reaction of the polymer chain takes place under mild hydrolytic conditions transforming skeletal nitrogen and phosphorus into ammonium salts and phosphates, respectively [405-407,464]. This opens wide perspectives in biomedical sciences for the utilization of these materials, for instance, as drug delivery systems [213,401,405,406,464] and bioerodible substrates [403,404]. [Pg.185]

Examples providing fluorine chemical shift data for trifluoromethyl imidazoles and a benzimidazole bearing a trifluoromethyl group are given in Scheme 5.53. [Pg.182]

Fluorine has been used to modulate the basicity of amines which may lead to an improvement in brain exposure. Recently, the discovery of a series of a4(32 nicotinic acetylcholine receptor (nAChR) potentiators as possible treatment for Parkinson s disease and schizophrenia was were disclosed [40]. Optimization of isoxazole 40 included the bioisosteric replacement of the central amide by an imidazole ring. Introduction of a fluorine at the 6-position of the phenyl ring provided compound 41. This compound had excellent potency but was determined to be a substrate for P-gp (efflux ratio >10). In an attempt to reduce amine basicity and decrease the efflux propensity, the 4-fluoropiperidine 42 was identified which retained potency and had significantly reduced P-gp efflux liability (efflux ratio 1). CNS penetration of 42 was observed in rodents following intraperitoneal (IP) treatment at 5mg/kg and showed a brain concentration of 6.5 gM. [Pg.441]

Oxidative Fluorination of Nitrones to a-Fluorosubstituted Nitroxyl Radicals Formation of nitroxyl radicals by the radical cation route was observed in reactions of various nitrones with xenon difluoride in dry methylene chloride (520, 523). In this reaction, more than 40 nitrones, including 4H -imidazole N,N -dioxides (219), 4H -imidazole TV-oxides (223) and (224), 2H -imidazole N -oxides (225), 2H -imidazole TV,TV-dioxides (226), 3,3,5,5-tetramethylpyrroline N -oxide (TMPO), derivatives of 3-imidazoline-3-oxides (231) and (232), have been examined. ESR spectra of nitroxyl radicals containing one or two fluorine atoms at a-C have been registered (Scheme 2.108) (523). In the case of... [Pg.219]

Deng, W., Molinero, V. and Goddard, W. A., III. 2004. Fluorinated imidazoles as proton carriers for water-free fuel cell membranes. Journal of the American Chemical Society 126 15644-15645. [Pg.189]

Eluorine-18 was also used as a tool for the study of the base promoted HF elimination from 4-fluoro-4-(4 -nitrophenyl)butan-2-one [62] (Scheme 3). The F KIEs values were respectively 1.0037,1.0047 and 1.0013 with formate, acetate or imidazole used as the base. The size of the fluorine KIEs corresponds to 5 -15 % of the estimated maximum for complete C-F bond breakage and is consistent with a postulated ElcB-E2 Hke or ElcBjp mechanism. [Pg.211]

Yet a further variation of this theme consists in the replacement of the bridging methylene group by sulfur to give a thiadiazepine as the central ring. The starting thiophene ether (26-3) is obtained by the nucleophilic aromatic displacement of fluorine in nitrobenzene (26-1) by the anion from imidazole-2-thiol (26-2). The nitro... [Pg.511]

Fluorination of perchloro bis(imine) 4 with sodium fluoride in tetramethylene sulfone at 120 JC takes place with ring formation to give the perfluoro imidazole derivatives 5-7.13... [Pg.550]

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... [Pg.706]

The most important applications of the in situ photochemical fluorodediazoniation start from heterocyclic amines for which the diazonium tetrafluoroborates are impossible to isolate. In this way, fluorinated imidazoles,123-253,254-257 261 benzimidazoles,262 pyrazoles,254-256,262 indazoles,158 thiazoles,259 and triazoles259-262 have been prepared (Table 4). Some of these are the precursors of biologically active compounds such as fluoro-substituted histidines or histamines,123,253-257,258 or 5-fluoro-l/ -D-ribofuranosylimidazole-4-carboxamide.261... [Pg.722]

The utility of TOSMIC in MCR reactions has also received recent interest in the pharmaceutical arena as an approach to the preparation of imidazoles 91. Originally reported by van Leusen in 1977 [76], and involving cycloaddition of tosyl-methyl isocyanides to carbon-nitrogen double bonds, recent elegant work by Sisko et al. has heightened its profile with the description of a one-pot synthesis of imidazole 92, a potent inhibitor of p38 MAP kinase, implicated with the release of the pro-inflammatory cytokine TNF-a (Scheme 11.19) [77]. In this particular example a fluorinated analogue of TOSMIC 90, is employed. [Pg.330]

The fluorines of a CF2H group at the 2-position of an imidazole or benzimidazole are more highly shielded than those at the 2-position of indole (Scheme 4.76). Included are compounds with the CF2H group bound to nitrogen. [Pg.183]

SAR studies have shown that a weakly basic imidazole or 1,2,4-triazole rings substituted only at the N-l position are essential for activity. The substituent must be lipophilic in character and usually contains one or more five or six membered ring systems, some of which may be attached by an ether, secondary amine or thioether group to the carbon chain. The more potent compounds have two or three aromatic substituents, which are singly or multiply chlorinated or fluorinated at positions 2, 4 and 6. These nonpolar structures give the compounds a high degree of lipophilicity, and hence membrane solubility. [Pg.134]

Furin and co-workers prepared several fluorinated diazetines by the reaction of perfluoro compound 131 with isopropyl amine, /-butyl amine, 2-amino-6-bromobenzothiazole, and 2-amino-1-methyl imidazole in THF in the presence of triethylamine (Equation 32) <2000RJ0109>. The same group also reported the formation of several diazetidines 132 and 133 by the reaction of perfluoro compound 131 with 2-nitro-, 4-nitro-, or pentafluoro-aniline in the presence of triethylamine (Scheme 15, Section 2.13.7.2) <2000JFC(104)263>. [Pg.673]

Heterocyclic systems, mainly pyrazoles296, imidazoles and thiophenes297, have all been reacted, though in every case the conversions were kept very low in order to minimize side reactions. Chambers and coworkers circumvented this problem by reacting benzene and imidazole tin derivatives with fluorine and obtaining much better yields and conversions (equation 176)298. [Pg.679]

The fluorination of the inner surface of intravenous tubing, using atmospheric pressure plasma glow (APG), has been evaluated to enhance biocompatibility and suppress plasticiser migration (273). The effect of plasma treatment on the migration of DOA, and an EVA-carbon monoxide terpolymer as partial or complete replacement, into isooctane solution has given positive results (231). A closed system microwave plasma reactor was used to react imidazole molecules to PVC surfaces with the claim that the resulting PVC was useful as an implant for biomedical applications, on the basis of spectroscopic studies (368). [Pg.34]

With certain 4,4-bis(trifluoromethyl)-3-aza-l-oxabutadienes this transformation can be achieved on heating with metals (91CZ253), especially zinc (89CHE1418) or with zinc/ultrasound (91CZ253). The fluorine atom at C—5 can be readily replaced by various nucleophiles (88S194). Via this route, 4-trifluoromethyl-l,3-oxazoles, -1,3-thiazoles, and -imidazoles can be introduced into many compounds of biological interest (Scheme 85). [Pg.42]


See other pages where Imidazoles fluorination is mentioned: [Pg.136]    [Pg.136]    [Pg.1030]    [Pg.282]    [Pg.212]    [Pg.173]    [Pg.155]    [Pg.412]    [Pg.564]    [Pg.82]    [Pg.216]    [Pg.355]    [Pg.306]    [Pg.33]    [Pg.1030]    [Pg.526]    [Pg.142]    [Pg.142]    [Pg.265]    [Pg.72]    [Pg.7]    [Pg.21]    [Pg.395]    [Pg.1056]    [Pg.329]    [Pg.146]    [Pg.499]    [Pg.354]    [Pg.188]   
See also in sourсe #XX -- [ Pg.57 , Pg.355 ]




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Fluorinated imidazoles

Ring-fluorinated imidazoles

Ring-fluorinated imidazoles synthesis

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