N-fluoropyridinium Salts Research Articles

Alpha,alpha-gem-Difluorination of alpha-(alkylthio)acetophenone derivatives with N-fluoropyridinium salts.

The alpha,alpha-gem-difluorination of 2',4'-difluoro-alpha-(methylthio)acetophenone (1a) with N-fluoropyridinium salts gave 2',4',alpha,alpha-tetrafluoro-alpha-(methylthio)acetophenone (3a). This reaction was accelerated by the addition of zinc chloride, zinc bromide or anhydrous iron(III) chloride, and higher yields than the reaction without additives were obtained. The gem-difluorination reaction using FP-T300 in the presence of zinc bromide was applicable to other alpha-(alkylthio)acetophenone derivatives (1).

Synthesis, Properties, and Reactivity of N,N‘-Difluorobipyridinium and Related Salts and Their Applications as Reactive and Easy-To-Handle Electrophilic Fluorinating Agents with High Effective Fluorine Content1

N,N‘-Difluoro-2,2‘-, -2,4‘-, -3,3‘-, -4,4‘-bipyridinium and substituted N,N‘-difluoro-2,2‘-bipyridinium bis(triflates), bis(tetrafluoroborates), bis(hexafluorophosphates), and bis(hexafluoroantimonates) 1−9 were synthesized in high yields by the direct fluorination of a mixture of a bipyridyl and a Lewis acid, a Brønsted acid, or the alkali metal salt of an acid. The higher homologues, trimer 10 and polymer 11, were also synthesized. Unsubstituted or electron-donating group-substituted N,N‘-difluorobipyridinium salts are stable nonhygroscopic crystals, while the electron-withdrawing group-substituted N,N‘-diflurobipyridinium salts 3, 5, and 6 are moisture-sensitive crystals. Hydrolysis of 1b in boiling water gave 3,3‘-dihydroxy-2,2‘-bipyridyl. The reactivity determination indicated that the fluorinating capability decreased in the order 2,2‘- ≫ 2,4‘ > 3,3‘- ≈ 4,4‘-isomer ≫ N-fluoropyridinium salt and that the two N−F moieties in a molecule were effective for fluorination. This fluorination occurred in a step-by-step manner, and the reactivity difference between the first and second fluorinations was very small. N,N‘-Difluoro-2,2‘-bipyridinium bis(tetrafluoroborate) (1b) is thus shown to be a highly reactive and easy-to-handle electrophilic fluorinating agent with the high effective fluorine content (103.3 g/kg) for preparing many fluoro organic compounds.

N-Fluoropyridinium salt and process for preparing same

N-Fluoropyridinium salt and process for preparing same

The First Synthesis of 1-Fluoro- and 1,3-Difluoroazulenes

Abstract 1-Fluoro- and 1,3-difluoroazulenes were synthesized by the reaction of azulene with N-fluoropyridinium salts in acetonitrile. Methyl azulene-1-carboxylates were also fluorinated to give the corresponding 3-fluoro derivatives. On the basis of the UV-visible absorption spectra, the fluorine atom acts as an electron-donating group to the azulene π-system due to the +Iπ effect.

Derivatives of N-Fluoropyridinium Salt

Derivatives of N-Fluoropyridinium Salt

Reaction of N-fluoropyridinium salts with wittig reagents: A novel and convenient approach to symmetric trans-olefins

N-fluoropyridinium salts were found to react with Wittig reagents containing electron-withdrawing groups to give olefins in 47–83% yield. The mechanism of this conversion is believed to involve single-electron transfer from Wittig reagent to N-fluoropyridinium cation.

A novel synthesis of 2-substituted pyrido[1,2-a]-1,3,5-triazin-4-ones by the reaction of N-fluoropyridinium salts with cyanate ion and carbonitriles: Evidence in support of a carbene intermediate

A carbene 5″ derived from N-fluoropyridinium cation is the suggested intermediate in the novel synthesis of pyridotriazines 3.

Synthesis of A-ring fluorinated derivatives of (17 alpha,20E/Z)-[125I]iodovinylestradiols: effect on receptor binding and receptor-mediated target tissue uptake.

We have prepared a series of 2- and 4-fluoro derivatives of the isomeric (17 alpha,20E)- and (17 alpha, 20Z)iodovinylestradiols (IVE2) and also the analogs substituted with either a 7 alpha-methyl (7 alpha-Me-IVE2) or 11 beta-methoxy group (11 beta-OMe-IVE2) and evaluated their in vitro and in vivo properties. Electrophilic substitution of the estrone derivatives with N-fluoropyridinium salt gave the 2- and 4-fluoro analogs which were subsequently converted to the 17 alpha-ethynyl derivatives. The tributylstannyl intermediates were obtained from the corresponding 17 alpha-ethynyl analogs using azobisisobutyronitrile or triethylborane as catalyst. All 12 products were also prepared as their no-carrier-added [125I]iodovinyl analogs via destannylation of the tributylstannyl precursors. Binding affinity for the estrogen receptor (ER) was in general higher for the 4-F derivatives as compared to the 2-F derivatives, while the 20Z isomers of the same compounds showed somewhat higher ER binding affinity as compared to the 20E isomers. The combination of an A-ring fluoro and 7 alpha- or 11 beta-substituent decreased ER binding affinity. Substitution of a fluoro atom at C-4 on either the 17 alpha-ethynylestradiol or isomeric 17 alpha-IVE2 enhanced the affinity of the parent molecule for the ER. A-ring fluorination of all other analogues tested had no effect or depressed ER binding affinity. Varying incubation conditions showed substantial differences in ER binding kinetics between the 20E and 20Z isomers. Tissue distribution in immature female rats showed that the highest uterus uptake and uterus to blood/nontarget ratios in the IVE2 series were obtained with the 4-F-(17 alpha,20Z)IVE2 isomer. The combination of A-ring fluoro and 7 alpha- or 11 beta-substitution decreased uterus uptake but had little or no effect on uterus to blood/nontarget ratios. The highest uterus to blood ratios were observed for the 4-F-(17 alpha,20E)11 beta-OMe-IVE2 (75 at 6 h and 125 at 12 h pi) reflecting rapid blood clearance and in vivo stability, as confirmed by the low levels of thyroid radioactivity. The lack of correlation between ER binding affinities and uterus uptake, and/or uptake ratios, suggests that other factors, including nonspecific binding and metabolic processes, also are involved in the tissue localization process. Our data suggest that 4-F substitution onto (17 alpha,20Z)IVE2 and (17 alpha,20E)11 beta-OMe-IVE2 enhances the potential of these compounds to function as SPECT imaging agents of ER-rich tissues.

フッ素化試薬の最近の進歩

This paper reviews the recent development of the fluorinating agents. The agents are classified into two categories -nulceophilic and electrophilic fluorinating agents- and summarized. The agents included are new ammonium, phosphonium, and phosphazenium fluoride salts, hypofluorites, N-fluorosulfonamides, N-fluoropyridinium salts, N-fluoroamides, N-fluoroquinuclidinium salts and some others. The fluorinations with the agents are also described.

Controlled selective fluorination with N-fluoropyridinium salt system

Controlled selective fluorination should be of great importance in preparing desired fluoroorganic molecules. We have developed N- fluoropyridinium salts as power and structure-variable fluorinating agents. In these studies, we found that counteranion part of the N-fluoropyridinium salts functions considerably in selective fluorination. This talk will discuss about the synthesis of a series of counteranion-bound N-fluoropyridinium salts and controlled selective fluorination with them. ▪

Three general courses for the reaction of N-fluoropyridinium salts with nucleophiles containing lone electron pair.

The N-fluoropyridinium salts (NFS) were found to be efficient fluorinating reagents for carbanions, Grignard reagents, electron rich aromatics, etc. (X-philic attack, path 1 ). The NFS when treated with Et 3N or pyridine give 2-substituted pyridines (obviously via formation of intermediate P +, path 3 ). Recently we have found that N-fluoropyridinium tetrafluoroborate ( FPT ) reacts with carbanions with the formation of 2- and 4-substituted pyridines via cine-(tele)-AE a-substitution ( path 2 ). Here we report that path 1 is realized in the reactions of FPT with sulfides, while triaryl(alkyl)-phosphines and -arsines react according to the path 2. ▪

Mo calculation study of the fluorinating reaction of N-fluoropyridinium salts

N-fluoropyridinium salts (I) react with carbon nucleophiles by F transfer 1). In order to investigate the mechanism of the reaction and substituent effect on the pyridine rings, the heat of formation and charge distributions of various N- fluoropyridinium cations and corresponding pyridine derivatives are calculated by semiempirical and ab initio MO methods. The calculation results show that the cation has small negative charge on N and ▪ positive charges on ortho C's, and well interpret the by-products of this reaction 1). The fluorinating power is related to the NF bond disassosiation energies and they depend on the F charges (not N charges). The possible reaction mechamism and intermediate will be discussed.

Synthesis of N-fluorodinitromethylpyridinium salts as first examples of hitherto unknown class of compounds

Pyridinium salts bearing strong electron-withdrawing groups at positively charged cyclic nitrogen are of great interest because of their incredible synthetic possibilities. Thus the chemistry of N-fluoropyridinium salts is being intensively developed now. Even more interesting in a theoretical aspect are N-fluorodinitromethylpyridinium salts, for fluorodinitromethyl group is close to fluorine atom in its −I effect but in contrast to the latter does not possess +M effect. The synthesis of first representatives of previously unknown class of compounds, N-fluorodinitromethylpyridinium salts (I), was carried out by fluorination of pyridine dinitromethylide with cesium fluoroxysulfate (CEFOX). This reaction is the first example of successful fluorination of ylide structures with CEFOX ▪ As expected, salts of this type are of exceptional activity towards nucleophiles. Thus, reactions of I even with low reactive carbanions proceed practically instantly with introduction of C-nucleophiles at position 4. At present we study the chemical transformations of I as the most interesting examples of extremely activated pyridinium salts.

N-F 19-fluorine nuclear magnetic resonance of N-fluoropyridinium salts

N-F 19 F chemical shifts of N-fluoropyridinium salts are independent of the nature of counteranions clearly supported their completely ionic structure. The 19F chemical shifts of β and γ-substituted N- fluoropyridinium salts are both correlated to pKa values of the corresponding pyridines, but in different ways. However, the shifts of α- substituted N-fluoro salts except for those with alkyl substituents were abnormal upfield shifts due to nonbonded electronic interactions, regardless of the pKa's. The relationship between variable fluorinating power and 19F chemical shifts of N-fluoropyridinium salts was also discussed.

Syntheses and Properties of N-Fluoropyridinium Salts

Abstract Various stable N-fluoropyridinium salts with a non- or weakly nucleophilic counter anion such as TfO−, FSO3−, BF4−, SbF6−, ClO4−, CH3SO3− etc., or with an electron-donating or -withdrawing substituent(s) on the pyridine ring were synthesized and their properties investigated. N-Fluoropyridinium-2-sulfonates, N-fluoroquinolinium triflate, and highly hindered N-fluoro-2,6-di-t-butylpyridinium salts were also synthesized. They were synthesized by counter anion displacement reactions of unstable pyridine-F2 compounds, fluorination of salts of pyridines with protonic acids or silyl esters with F2, and/ or fluorination of Lewis acid complexes of pyridines. The scope of each method was examined in detail. Each of the N-fluoropyridinium salts was assigned as the first stable 1 : 1 salt structure of the pyridine nucleus and halogen atom on the basis of the spectral and elemental analyses. The stability depended on the nucleophilicity or basicity of the counter anions and electronic nature or position of the ring substituents. These results and NMR analyses clearly showed the unstable pyridine-F2 compounds to have N-fluoropyridinium fluoride salt structure. Some N-fluoropyridinium triflates were hydrolyzed and the products were examined, suggesting a unique hydrolysis mechanism.

Reactions of N-Fluoropyridinium Salts with Phosphorus- and Arsenic-containing Nucleophiles

The direction of reaction of N -fluoropyridinium tetrafiuoroborate with phosphorus- and arsenic-containing nucleophiies PR 3 and AsR 3 ( cine -AE a substitution or X-philic attack) has been found to depend on the nature of R.

Power- and structure-variable fluorinating agents. The N-fluoropyridinium salt system

N-Fluoropyridinium salts provide a new system of fluorinating agents by which a wide range of nucleophilic substrates differing in reactivity can be fluorinated due to the varying degree of fluorinating power and also fluorinated very selectively through structural alteration. The scope of selective fluorination should be broadened considerably on the basis of the present results. The N-fluoropyridinium salt system should thus make possible the preparation of many useful organofluoro compounds

ChemInform Abstract: Preparation of 2‐Fluoropyridines (IV) via Base‐Induced Decomposition of N‐Fluoropyridinium Salts (III).

ChemInformVolume 20, Issue 43 Heterocyclic Compounds ChemInform Abstract: Preparation of 2-Fluoropyridines (IV) via Base-Induced Decomposition of N-Fluoropyridinium Salts (III). T. UMEMOTO, T. UMEMOTO Sagami Chem. Res. Cent., Sagamihara, Kanagawa 229, JapanSearch for more papers by this authorG. TOMIZAWA, G. TOMIZAWA Sagami Chem. Res. Cent., Sagamihara, Kanagawa 229, JapanSearch for more papers by this author T. UMEMOTO, T. UMEMOTO Sagami Chem. Res. Cent., Sagamihara, Kanagawa 229, JapanSearch for more papers by this authorG. TOMIZAWA, G. TOMIZAWA Sagami Chem. Res. Cent., Sagamihara, Kanagawa 229, JapanSearch for more papers by this author First published: October 24, 1989 https://doi.org/10.1002/chin.198943171AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue43October 24, 1989 RelatedInformation

Preparation of 2-fluoropyridines via base-induced decomposition of N-fluoropyridinium salts

Preparation of 2-fluoropyridines via base-induced decomposition of N-fluoropyridinium salts

Base-initiated reactions of N-fluoropyridinium salts; a novel cyclic carbene proposed as a reactive species

A new type of base-initiated reactions of pyridinium salts was found and a novel cyclic carbene was proposed as the reactive species.