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Crosslinked copoly(styrene- p -nitrophenylacrylate)s ( 1a, 1b and 1c , containing 2, 4 and 10% divinylbenzene, respectively) reacted readily with secondary amines (piperidine, morpholine, piperazine, N -phenylpiperazine), the course of substitution being influenced by the crosslinking of 1 , solvent polarity (dimethylformamide, methanol, toluene) and the structure of the amine. Steric interactions influenced the transformation of 1a with various primary amines (n-butylamine, i-propylamine and cyclohexylamine) giving the corresponding amides; tertbutylamine and aniline do not transform 1a under similar reaction conditions (dimethylformamide, ( T = 50°C). The swelling ability of the resins depended on the crosslinking of the starting copoly(styrene— p -nitrophenylacrylate) (bd1), the structure of the amide and solvent polarity (water, methanol, dimethylformamide, toluene, chloroform, cyclohexane).

Crosslinked chloromethylated polystyrene (1) and crosslinked copoly(styrene-p-nitro-phenylacrylate) (3) readily reacted with 1,1-dimethylhydrazine, but the course of the reaction was strongly dependent on the structure of the backbone. Monofunctionalization was observed with chloromethylated polystyrene (1) giving the 1,1,1-dimethylhydrazinium chloride derivative (2), while high degree of additional crosslinking took place with crosslinked copoly(styrene-p-nitrophenylacrylate) (3), and additional crosslinking was also observed in functionalization with N-aminopiperidine and N-aminomorpholine. The additional crosslinking suggested a higher backbone mobility in acrylate beads (3) compared to chloromethylated polystyrene (1). The type of transformation and the degree of additional crosslinking also depended on the starting crosslinking of copoly(styrene-p-nitrophenylacrylate) (3; 3a, 2% DVB; 3b, 4% DVB; 3c, 10% DVB). Replacement of p-nitrophenol groups in copoly(styrene-p-nitrophenylacrylate) (3) with hydrazino units resulted in enhanced swelling abilities of the hydrazine derivatives (4, 5, 6) in methanol, dimethylformamide, and chloroform, while formation of the hydrazinium chloride derivative (2) from chloromethylated polystyrene (1) caused enhancement of swelling in methanol but diminished it in toluene. The degree of crosslinking of copoly(styrene-p-nitrophenylacrylate) (3) also influenced the swelling abilities of 3 and its hydrazino derivatives, being higher with 2% cross-linked resins and lower with 4% and 10% crosslinked resins. © 1996 John Wiley & Sons, Inc.

Dibenzofuran, diphenylether and biphenyl were used as a target molecules in an investigation of the effect of N-F type of reagent structure and reaction conditions on the fluorination process. The yields of fluorinated products formed and the regioselectivity depend on the reagent used, and in the reactions with dibenzofuran three products were formed. The ratios of 2-fluorodibenzofuran ( 4 ) and 3-fluorodibenzofuran ( 5 ) formed were: 1.3 for 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (NFTh, 1b), 1.4 for 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA, 1a), and 1.8 for N-fluoro-2,6-dichloropyridinium tetrafluoroborate (FPD-B, 1c). Ortho regioselectivity predominated for all reagents in the fluorination of biphenyl (ortho : para ratio varied from 4.8 to 1.2), while para attack prevailed for diphenylether (ortho : para = 0.9 – 0.7); however substitution of a phenyl ring by a methyl group enhanced the amount of 2-fluoroanisole. Second order rate constants for the fluorination of aromatic molecules with F-TEDA in acetonitrile at 65°C were established: anisole 4.8×10 −3 Lmol −1 s −1 , diphenylether 6.0×10 −4 Lmol −1 s −1 , dibenzofuran 2.5×10 −4 Lmol −1 s −1 and biphenyl 1.0×10 −4 Lmol −1 s −1 .

The transformations of various reagents of the N-F type in water, acetonitrile, alcohols and aqueous solutions of alkali hydroxides were investigated. First-order kinetics for 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA) and 1-hydroxy-4-fluoro-l,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (NFTh) transformations were established: F-TEDA is less stable in water at 60 °C than NFTh, while N -fluorobis(phenylsulphonyl)amine (NFS) is very stable. The addition of acetonitrile to an aqueous solution of F-TEDA enhanced the transformation ( k = 1.3 × 10 −5 s −1 ), while a reaction which was three-times faster was observed in water/ methanol solution ( k = 3.5 × 10 −5 s −1 at 60 °C). The energy of activation for the transformation of F-TEDA in water was found to be 21.1 kcal mol −1 , 20.6 kcal mol −1 in water/methanol solution and 13.8 kcal mol −1 in a water/acetonitrile mixture.

Direct regioselective conversion of a variety of cyclic and acyclic ketones to α-fluoroketones was achieved in high to excellent yield using 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) [AccufluorTM - NFTh] in acetonitrile solution.

Reactions of phenyl-substituted alkenes with SelectfluorTM fluorinating reagent F-TEDA-BF4 in the presence of various alcohols resulted in the formation of vicinal fluoroalkoxy adducts with Markovnikov type of regioselectivity. The stereochemistry of the fluoro-methoxylation addition reaction was found to be slightly syn predominant in the case of (Z)-stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers were formed in the case of (E)-1-phenyl-1-propene and acenaphthylene. In the phenyl-substituted benzocyclene series the stereochemistry of fluoro-alkoxylation was found to be dependent on ring size and on the structure of the alcohol. The resulting vicinal fluoroalkoxy adducts were transformed by heating in aqueous HBr to 2-fluoro-1-phenylbenzocyclenes. Correlation of the logarithms of relative rates of fluoro-methoxylation reactions in a series of ten α-phenyl and α,α-diphenyl acyclic and cyclic alkenes with the ionization potentials of these alkenes resulted in a linear r...

1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) ( Accufluor ™ NFTh) is confirmed as a highly effective reagent for introducing a fluorine atom into organic molecules across a phenyl-substituted carbon-carbon double bond. Quantitative and Markovnikov-type regioselective formation of vicinal fluoro-hydroxy, fluoro-methoxy or fluoro-acetoxy adducts was achieved when phenyl-substituted alkenes were treated with a MeCN solution of NFTh In the presence of water, methanol or acetic acid. The stereochemical course of fluoro-methoxylation reactions in the case of cyclic phenyl-substituted alkenes depends strongly on the structure of the alkene.

Hydroxy-substituted organic molecules were used as target molecules in investigations of the role of the reagent structure on the reactivity of three types of N–F class fluorinating reagents: 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) F-TEDA (1a), N-fluorobis(phenylsulfonyl)amine NSF (1b), and N-fluoropyridinium heptafluorodiborate–pyridine (1/1) NFP (1c). Methanol is stable, but hydroquinone is very quickly transformed in acetonitrile to quinone with F-TEDA at room temperature; on the other hand, NSF is less reactive, while oxidation with NFP is achieved only at an elevated temperature; a structure variation of the hydroquinone derivatives did not influence oxidation. Fluorination was achieved with monohydroxy-substituted aromatic compounds; a similar trend concerning the reactivity of N–F reagent (1) was also observed in reactions with 1- and 2-naphthol, while 9-phenanthrol gave 10,10-difluoro-9-(10H)-phenanthrenone with F-TEDA in acetonitrile and 9,10-phenanthrenequ...

Koper is a historical mediaeval city dating from Venetian times and also a major port on the Adriatic Sea in southern Slovenia in the region known as Istria. It can be described as a national nerve centre due to its port and logistic role, which in turn also makes it one of the eight functional regional centres in Slovenia. As a regional nucleus, it influences economic, social and spatial development and is in turn perceived as a cultural centre and a focal point for the region. It is the smallest of the case studies by far, having an urban population of only 24,000 people (more in the municipality as a whole), although it presents some unique aspects not found in the other case studies.

Three types of bromine complexes with various polymers bearing basic units (pyridine, piperidine and piperazine) were investigated and the role of polymer matrices on reactivity was tested by three types of organic reactions: electrophilic addition, aromatic substitution and radical substitution. Pyridine complex (1a) was most reactive in all three types of reactions, while immobilisation of bromine to polymers bearing more basic units resulted in much less reactive complexes; in the reaction with 1,1-diphenylethylene reactivity was diminished to 29% of that with (1a), when piperidine complex (1b) was used, while only 11% of that of (1a) was achieved with piperazine complex (1c) in methanol. An even greater reduction in reactivity was found in the reaction with anisole where (1b) was 9% and (1c) only 1% as reactive as (1a). Exclusive side chain bromination was observed in the reactions of bromine complexes (1a). (1b) and (1c) in carbon tetrachloride in the presence of dibenzoyl peroxide at 77°C w...

Vicinal alkoxy fluorides are efficiently formed by room temperature reaction of phenyl substituted alkenes with commercially available 1-chloromethyl-4-fluoro-1,4-diazobicyclo[2.2.2]octane bis tetrafluoroborate (Selectfluor™ F-Teda BF4) in CH3CN in the presence of various alcohols. The reaction follows Markovnikov-type regioselectivity, while stereoselectivity in the case of phenyl substituted benzocyclenes strongly depends on the ring size and the structure of the alcohol.

Selective direct introduction of an iodine atom into alkyl-substituted benzene derivatives was effectively achieved by reaction of target molecules with elemental iodine in the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane his(tetrafluoroborate) (Selectfluor F-TEDA-BF 4 ). The number of iodine atoms introduced could be modulated by the molar ratio between substrate, iodine and F-TEDA-BF 4 .

Trifluoromethyl derivatives of aromatic molecules were prepared from aromatic halides, converted to dithiocarboxylic acids through formation of Grignard reagents, followed by fluorination with xenon difluoride at room temperature.

Irradiation of a cyclohexane solution of hexafluorobenzene in the presence of benzophenone resulted in both, substitution and addition products. Similar photoreaction has been observed by irradiation of hexafluorobenzene in some alcohols in the presence of benzophenone. The reaction of pentafluorobenzene with methanol or cyclohexane resulted in the substitution of a 2-or 4-fluoro atom, while the reaction of pentafluoroanisole resulted in the formation of o-, m- and p-isomers. Irradiation of a cyclohexane solution or of an alcohol solution of octafluoronaphthalene yielded 1- and 2-substituted products. On the other hand, the photosubstitution of fluorine atom in pentafluoropyridine took place exclusively at the position four, thus forming 4-cyclohexyl or 4-(1-hydroxyalkyl) substituted products.

The reactions of alcohols with cesium fluoroxysulfate (CsSO4F) in MeCN suspension were studied, and the role of the structure of the alcohol and the reaction conditions on the course of reaction was determined. Secondary benzyl alcohols bearing a nonactivating aromatic ring were selectively oxidized to the corresponding ketones, while the CsSO4F-mediated reaction of phenyl-1-naphthylmethanol resulted in the formation of 1-fluoronaphthalene and benzaldehyde. Cyclic and noncyclic secondary alcohols were readily converted to ketones, as well as 1-hydroxybenzocyclanes to benzocyclanones-1, without any further fluorination or oxidation under the reaction conditions. On the other hand, reactions of primary alcohols with CsSO4F resulted in the formation of acid fluorides derived from further fluorination of aldehydes. Another type of transformation was observed in the case of alcohols bearing a benzyl functional group attached geminal to a hydroxy group, where decarbonylation of reactive intermediates resulting ...

Hydroxyalkyl groups in various aromatic molecules are replaced with a fluorine atom by CsSO4F at room temperature thus regioselectively forming aryl fluorides in high to excellent yields.

Benzyl alkohol and its analogues with a non-activated benzene ring are transformed to fluoromethoxy derivatives by reaction with XeF 2 . The same reaction with diphenyl methanol gives di diphenylmethylether, while 2-phenyl-2-propanol transforms to 2,4-diphenyl-4-methyl-1-pentene.

Aryl–alkyl substituted tertiary alcohols are efficiently converted directly to vicinal fluorohydrins in high yield by reaction with 1-chloromethyl-4-fluoro-1,4-diazobicyclo[2.2.2]octane bis(tetrafluoroborate)(SelectfluorTM F-Teda BF4) in acetonitrile solution.

1-Alkoxy-2-fluoro-1-phenyl benzocycloalkanes are efficiently formed by reactions of 1-phenylbenzocycloalkenes with caesium fluoroxysulpham (CFS) in alcohols (MeOH, EtOH, i-PrOH) at room to moderately elevated temperature. The stereochemistry of the reaction depends on the ring size of the substrate and on the structure of the alcohol, and is syn predominant in the case of fluorination of five-, anti predominant in six-, and slightly to nearly exclusively syn predominant in seven-membered ring benzocycloalkene analogues. The relative rates measured for methoxy-fluorinations of a set of seven phenyl-substituted alkenes with CFS in methanol show a trend to increasing reactivity with decreasing ionisation potential of the named alkenes yielding a linear correlation relationship with a very high correlation factor r=0.945 and slope −1.76, thus indicating that π-bond disruption in the substrate alkene is the rate determinig step of the reaction of the alkenes studied with CFS under the reported reaction parameters.

Three types of bromine complexes with various polymers bearing basic units (pyridine, piperidine and piperazine) were investigated and the role of polymer matrices on reactivity was tested by three types of organic reactions: electrophilic addition, aromatic substitution and radical substitution. Pyridine complex (1a) was most reactive in all three types of reactions, while immobilisation of bromine to polymers bearing more basic units resulted in much less reactive complexes; in the reaction with 1,1-diphenylethylene reactivity was diminished to 29% of that with (1a), when piperidine complex (1b) was used, while only 11% of that of (1a) was achieved with piperazine complex (1c) in methanol. An even greater reduction in reactivity was found in the reaction with anisole where (1b) was 9% and (1c) only 1% as reactive as (1a). Exclusive side chain bromination was observed in the reactions of bromine complexes (1a). (1b) and (1c) in carbon tetrachloride in the presence of dibenzoyl peroxide at 77°C w...

Reactions of phenyl-substituted alkenes with SelectfluorTM fluorinating reagent F-TEDA-BF4 in the presence of various alcohols resulted in the formation of vicinal fluoroalkoxy adducts with Markovnikov type of regioselectivity. The stereochemistry of the fluoro-methoxylation addition reaction was found to be slightly syn predominant in the case of (Z)-stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers were formed in the case of (E)-1-phenyl-1-propene and acenaphthylene. In the phenyl-substituted benzocyclene series the stereochemistry of fluoro-alkoxylation was found to be dependent on ring size and on the structure of the alcohol. The resulting vicinal fluoroalkoxy adducts were transformed by heating in aqueous HBr to 2-fluoro-1-phenylbenzocyclenes. Correlation of the logarithms of relative rates of fluoro-methoxylation reactions in a series of ten α-phenyl and α,α-diphenyl acyclic and cyclic alkenes with the ionization potentials of these alkenes resulted in a linear r...

1 Introduction 2 Reactions Keywords: xenon difluoride; organic molecule functionalization by xenon fluorides; xenon fluoride with alkane reactions; xenon fluoride reactions with alkenes; xenon fluoride reactions with alkanes; xenon fluoride and aromatic molecule reaction; aromatic aldehydes; trifluoromethylene benzene

A new N-F fluorinating reagent 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (AccufluorTM NFTh) was effectively used for selective fluorination of polycyclic aromatics. Naphthalene was site-selectively fluorinated to 1-fluoronaphthalene, phenanthrene to 9-fluorophenanthrene, and pyrene to 1-fluoropyrene. In a series of substituted naphthalenes the regioselectivity and effectiveness of fluorination depended on the position and the nature of the substituents.

Dibenzofuran, diphenylether and biphenyl were used as a target molecules in an investigation of the effect of N-F type of reagent structure and reaction conditions on the fluorination process. The yields of fluorinated products formed and the regioselectivity depend on the reagent used, and in the reactions with dibenzofuran three products were formed. The ratios of 2-fluorodibenzofuran ( 4 ) and 3-fluorodibenzofuran ( 5 ) formed were: 1.3 for 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (NFTh, 1b), 1.4 for 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA, 1a), and 1.8 for N-fluoro-2,6-dichloropyridinium tetrafluoroborate (FPD-B, 1c). Ortho regioselectivity predominated for all reagents in the fluorination of biphenyl (ortho : para ratio varied from 4.8 to 1.2), while para attack prevailed for diphenylether (ortho : para = 0.9 – 0.7); however substitution of a phenyl ring by a methyl group enhanced the amount of 2-fluoroanisole. Second order rate constants for the fluorination of aromatic molecules with F-TEDA in acetonitrile at 65°C were established: anisole 4.8×10 −3 Lmol −1 s −1 , diphenylether 6.0×10 −4 Lmol −1 s −1 , dibenzofuran 2.5×10 −4 Lmol −1 s −1 and biphenyl 1.0×10 −4 Lmol −1 s −1 .

Monosubstituted phenyl ethers were regioselectively iodinated with a mixture of iodine and F-TEDA in acetonitrile at room temperature at the para position, while 1-methoxy-4-substituted benzene derivatives were converted to 2-iodo products in high yield. © 1997 Elsevier Science Ltd.

4-Fluorocyclohexa-2,5-dienone derivatives were obtained in high yield by reaction of para substituted phenols with 1-fluoro-4-chloromethyl-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoro-borate) (1a, SelectfluorTM F-TEDA-BF4) or its 4-hydroxy analogue (1b, AccufluorTM NFTh) in acetonitrile. Estrogen steroids were readily converted to 10β-fluoro-1,4-estradiene-3-one derivatives in high yields.

Reactions of aryl alkyl ketones with 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (AccufluorTM NFTh) in methanol result in selective and almost quantitative formation of the corresponding α-fluoroketones, while in acetonitrile exclusive fluorofunctionalisation of the activated aromatic ring take place.

Reactions of aryl alkyl ketones with methanol solution of elemental iodine and 1-fluoro-4-chloromethyl-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor™ F-TEDA-BF4) result in the formation of corresponding α-iodo ketones, while switch over of the regioselectivity can be directed by using acetonitrile as the solvent and selective iodination of the aromatic site of target molecules is thus achieved.

Benzene derivatives bearing at least one bulky alkyl group (i-Pr or t-Bu) were selectively and effectively iodinated using elemental iodine activated by 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor, F-TEDA-BF 4 ). Iodine atoms were progressively introduced at the most electron-rich and sterically less hindered position on the benzene ring. Not more than three iodine atoms could be progressively bonded to a target molecule bearing a i-Pr or t-Bu group.

It is difficult to imagine organic chemistry without organo-halogen compounds and the molecular halogens needed for their preparation. The halogens have very different reactivity, with iodine usually requiring some form of activation, while others are reactive and hazardous chemicals. To avoid their use, various modified reagents have been discovered (N-bromo- and N-chlorosuccinimide, Selectfluor..), but halogens are used to prepare these reagents and when they are used the atom economy is poor. A better approach, which is based on biomimetric research on oxidative halogenation in nature, consists of generating the halogenating reagent in situ under acidic conditions from a halide salt. The result of such a reaction has been halogenation with 100 % halogen atom economy. Suitable oxidants for the oxidation of halides are hydrogen peroxide and oxygen.

Functionalization of mono- and di-substituted benzene derivative with CsSO 4 F has been modulated by substituents on the benzene ring. α-Hydroxyalkylbenzenes, with a deactivated ring, were oxidized to phenones, while fluorodealkylation was achieved in high yield when electron-donating groups were present in a para position. Electron-withdrawing substituents favoured chain fluorofunctionalization in alkylbenzenes, while ring fluorination was found exclusively in acylamino-derivatized alkylbenzenes; fluoro-addition products were formed in the case of ρ-alkoxy-substituted alkylbenzene derivatives.

The reactions of alcohols with cesium fluoroxysulfate (CsSO4F) in MeCN suspension were studied, and the role of the structure of the alcohol and the reaction conditions on the course of reaction was determined. Secondary benzyl alcohols bearing a nonactivating aromatic ring were selectively oxidized to the corresponding ketones, while the CsSO4F-mediated reaction of phenyl-1-naphthylmethanol resulted in the formation of 1-fluoronaphthalene and benzaldehyde. Cyclic and noncyclic secondary alcohols were readily converted to ketones, as well as 1-hydroxybenzocyclanes to benzocyclanones-1, without any further fluorination or oxidation under the reaction conditions. On the other hand, reactions of primary alcohols with CsSO4F resulted in the formation of acid fluorides derived from further fluorination of aldehydes. Another type of transformation was observed in the case of alcohols bearing a benzyl functional group attached geminal to a hydroxy group, where decarbonylation of reactive intermediates resulting ...

CsSO4F reacted at room temperature, or at 35°C in acetonitrile with various heteroatom-containing organic molecules, and three types of transformations have been observed. Fluoro substitution process took place with triphenylmethane, triphenylsilane, triphenylchlorosilane, 4-tert-butylphenol, benzaldehyde, and octanal, thus forming fluorotriphenylmethane, fluorotriphenylsilane, 2-fluoro-4-tert-butylphenol, benzoyl fluoride, or octanoyl fluoride in high yields. Substitution reaction was accompanied by fluoroaddition process in the case of 2-fluoro-4-tert-butylphenol, where 2,2-difluoro-4-tert-butylcyclohexadienon-4,6 was isolated. CsSO4F easily oxidised secondary alcohols to ketones, and 1,2-dihydroxy-4-tert-butylbenzene to quinone derivate. Oxygenation process was observed in the case of triphenylphosphine, and dibenzotiophene, while ethyl iodide was transformed to ethyliodo(III) difluoride. Solvent plays an important role in these reactions, being successfully performed in CH3CN, and completely inhibited in CH2Cl2, while different shapes of the effect on fluorination of various organic molecules were observed by altering solvent nature by successive mixing of CH3CN with CH2Cl2.