New developments in the synthesis of lower fluorinated pyridines via diazotization-fluorination of aminopyridines in anhydrous hydrogen fluoride

Boudakian, Max M.

doi:10.1016/s0022-1139(00)82666-4

Cited by 24 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…48Ϫ50°C/12 Torr (ref. [19] 169.5°C); n D 20 ϭ 1.5137 (ref. [19] 3-Chloro-2,6-difluoropyridine (3): Analogously as described for the preparation of product 1 using 1,1,2-trichloro-1,2,2-trifluoroethane (6.0 mL, 9.4 g, 50 mmol); colorless liquid; m.p.…”

Section: -Bromo-26-difluoropyridine (2)mentioning

confidence: 99%

The Structural Proliferation of 2,6‐Difluoropyridine through Organometallic Intermediates

Schlosser

Rausis

2004

Eur J Org Chem

View full text Add to dashboard Cite

Contrary to a literature claim, 2,6‐difluoropyridine‐3‐carboxaldehyde can be readily prepared by consecutive treatment of 2,6‐difluoropyridine with lithium diisopropylamide and N,N‐dimethylformamide. Regioselective displacements of fluorine from the aldehyde by nucleophiles were carried out. To demonstrate the versatility of the organometallic approach, some two dozens of further 2,6‐difluoropyridine derivatives were prepared applying a combination of modern organometallic methods such as site selective hydrogen/metal and halogen/metal permutations and deprotonation‐triggered heavy halogen migrations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

show abstract

Section: -Bromo-26-difluoropyridine (2)mentioning

confidence: 99%

The Structural Proliferation of 2,6‐Difluoropyridine through Organometallic Intermediates

Schlosser

Rausis

2004

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…Fluoropyridine can be synthesized in higher yield by diazotion/fluorination of aminopyridine (8) and by fluoride exchange with chloropyridine (9). However, these methods require an appropriate precursor whereas electrochemical fluorination uses pyridine itself, this may be an important consideration in fluorinationof pyridine derivatives: the lower yield of the direct electrochemical method may be higher than the overall yield of a procedure that requires synthesis of an intermediate.…”

Section: Methodsmentioning

confidence: 99%

Selective Electrochemical Synthesis of 4-Fluoropyridine Using Et3n-3hf

Fang¹,

Tao²,

Kan³

et al. 2004

Heterocyclic Communications

View full text Add to dashboard Cite

Pyridine was electrochemically fluorinated at platinum anode at constant voltage in acetonitrile solutions containing Et 3 N'3HF, as supporting electrolytes and fluorine sources. The present electrolyte solution system was mild and suitable for the fluorination of pyridine. Thus, 4-fluoropyridine has been synthesized. InteroductionIt is well recognized that incorporation of fluorine atoms into the organic molecules used for medicines can significantly alter their biological function. Fluoro organic compounds have special chemical and physical properties. Especially, partially fluorinated compounds are useful in the fields of materia! science and medicinal chemistryTo date, many methods of fluoroorganics preparation of fluoroorganics have been developed 12 ', the construction of ring-fluorinated heterocyclic systems has been less explored. Recently, selective electrochemical fluorination has been shown to be a highly efficient new tool for synthesizing various fluoroorganic compounds. The reaction can be carried out under mild conditions using relatively simple equipment and also avoiding hazardous or toxic reagents, which are necessary in chemical fluorination. However, only limited examples of selective anodic fluorination of heterocycles have been reported to date <3 " 5) , and in all cases, low yields and poor selectivities appeare to be the major problems in electrochemical synthesis.Because pyridine is very resistant to oxidation, it his been used as a solvent for electrochemical reactions. Huba (6) made 2-fluoropyridine as a by-product of electrolysis in pyridine/anhydrous hydrogen fluoride (AHF) mixtures (70/30 w/w) but that system requires special AHF-resistant equipment and is unsuitable for synthesis with pyridine derivatives and fluoride sources other than AHF Later, James R. Ballinger <7) reported that in his cell, the applied potential was 2.5 V and a supporting electrolyte solution was 0.5 Μ Me4NF-2HF in MeCN, 2-fluoropyridine has been synthesized in 22% yield by electrochemical fluorination of pyridine. His system requires special equipment and rigorous materials. In this paper ,We disclose a practical and efficient selective anodic fluorination of pyridine obtained 4-fluoropyridine by using a conventional Et 3 N'3HF as both supporting electrolyte and the fluorine source. The result of anodic fluorination of pyridine is summarized in Scheme 1. F fS Et 3 N · 3HF MeCN Scheme 1 Experiment Acetonitrile (HPLC grade) is dried further by distillation from phosphorus pentoxide and from calcium hydride. Pyridine is distilled from KOH pellets. 2-Fluoropyridine and 3-Fluoropyridine are obtained from Acros Chemical Co. Et 3 N 3HF is obtained from Aldrich Chemical Co. The electrolysis cell is a 50-ml glass beaker cooled by an enclosed ice-water jacket. Into the cell are placed a 4.3cm : platinum sheet anode and a 1.44 cm 2 platinum sheet cathode, a magnetic stirring bar, a tube for bubbling NaOH-dried and MeCN-saturated nitrogen through the cell solution.The potential is controlled by a potentiostat with a digi...

show abstract

“…All common reagents were purchased from Aldrich Chemical Co. (Milwaukee, WI) or Lancaster Synthesis Inc. (Windham, NH) and were used without further purification. The following compounds, 4-fluoropyridine ( 32 ), , 4-(1-indolyl)pyridine ( 33 ), and 4-chloro-1-methylpyridinium iodide ( 37 ), were synthesized as described previously. The synthesis of compound 41 will be described separately .…”

Section: Methodsmentioning

confidence: 99%

Studies on the Monoamine Oxidase-B-Catalyzed Biotransformation of 4-Azaaryl-1-methyl-1,2,3,6-tetrahydropyridine Derivatives

Mabic

et al. 1999

J. Med. Chem.

View full text Add to dashboard Cite

The substrate properties of a series of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluate the contribution of electronic, polar, and steric parameters to the MAO-B-catalyzed oxidation of this type of cyclic tertiary allylamine to the corresponding dihydropyridinium metabolite. No significant correlation could be found with the calculated energy of the C-H bond undergoing cleavage. A general trend, however, was observed between the magnitude of the log P value with the magnitude of kcat/Km. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate properties, however, were observed when benzoazaarenes replaced the corresponding five-membered azaarenes. These results are consistent with our previously published molecular model of the active site of MAO-B.

show abstract

New developments in the synthesis of lower fluorinated pyridines via diazotization-fluorination of aminopyridines in anhydrous hydrogen fluoride

Cited by 24 publications

References 21 publications

The Structural Proliferation of 2,6‐Difluoropyridine through Organometallic Intermediates

The Structural Proliferation of 2,6‐Difluoropyridine through Organometallic Intermediates

Selective Electrochemical Synthesis of 4-Fluoropyridine Using Et3n-3hf

Studies on the Monoamine Oxidase-B-Catalyzed Biotransformation of 4-Azaaryl-1-methyl-1,2,3,6-tetrahydropyridine Derivatives

Contact Info

Product

Resources

About