Phase Transfer Catalysts and Role of Reaction Environment in Nucleophilc Radiofluorinations in Automated Synthesizers

Incorporation of [18F]fluorine into PET radiotracer structure has traditionally been accomplished via nucleophilic pathways. The [18F]fluoride is generated in an aqueous solution via proton irradiation of oxygen-18 enriched water and must to be introduced into water-free organic solutions in order to generate reactive species. Thus nucleophilic 18F-fluorination traditionally included steps for [18F]fluoride concentration on the anion exchange resin, followed by removal of residual water via azeotropic distillation with MeCN, a time-consuming process associated with radioactivity losses and difficult automation. To circumvent this, several adsorption/elution protocols were developed based on the minimization of water content in traditional kryptofix-based [18F]fluoride eluents. The use of pre-dried KOH/kryptofix solutions, tertiary alcohols, and strong organic bases was found to be effective. Advances in transition metal-mediated SNAr approaches for radiolabeling of non-activated aromatic substrates have prompted development of alternative techniques for reactive [18F]fluoride species generation, such as organic solutions of non-basic alkyl ammonium and pyridinium sulfonates, etc. For radiofluorinations of iodonium salts precursors, a “minimalist” approach was introduced, avoiding the majority of pitfalls common to more complex methods. These innovations allowed the development of new time-efficient and convenient work-up procedures that are easily implementable in modern automated synthesizers. They will be the subject of this review.

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18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

Pharmaceuticals ◽

10.3390/ph14090833 ◽

2021 ◽

Vol 14 (9) ◽

pp. 833

Author(s):

Sandip S. Shinde ◽

Kim-Viktoria Bolik ◽

Simone Maschauer ◽

Olaf Prante

Keyword(s):

Phase Transfer ◽

Boronate Esters ◽

Phase Transfer Catalysts ◽

Tert Butanol ◽

Protic Solvents ◽

Positron Emission ◽

Minimalist Approach ◽

Radiochemical Yields ◽

Additional Base ◽

18F Fluoride

The 18F syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [18F]fluoride from H2[18O]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [18F]fluoride is commonly achieved by phase transfer catalysts (PTC) in aqueous solution, which makes azeotropic drying indispensable. The ideal PTC is characterized by a slightly basic nature, its capacity to elute [18F]fluoride with anhydrous solvents, and its efficient complex formation with [18F]fluoride during subsequent labeling. Herein, we developed tri-(tert-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for 18F-fluorination reactions. The favorable elution efficiency of [18F]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high 18F-recoveries of 96–99%. 18F-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing 18F-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to 18F-fluorination reactions and could be used for elution of [18F]fluoride with MeOH, omitting an additional base and azeotropic drying prior to 18F-labeling. We speculate that the tert-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [18F]fluoride during nucleophilic 18F-fluorination.

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Green Application of Phase-Transfer Catalysis in Oxidation: A Comprehensive Review

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x16666190617154733 ◽

2020 ◽

Vol 17 (4) ◽

pp. 405-411

Author(s):

Chuan-Hui Wang ◽

Chen-Fu Liu ◽

Guo-Wu Rao

Keyword(s):

Organic Chemistry ◽

Green Chemistry ◽

Oxidation Reaction ◽

Phase Transfer Catalysis ◽

Phase Transfer ◽

Important Application ◽

Oxidation Reactions ◽

Comprehensive Review ◽

Phase Transfer Catalysts ◽

Onium Salts

Oxidation reactions have emerged as one of the most versatile tools in organic chemistry. Various onium salts such as ammonium, phosphonium, arsonium, bismuthonium, tellurium have been used as phase transfer catalysts in many oxidation reactions. Certainly, considerable catalysts have been widely used in Phase-Transfer Catalysis (PTC). This review focuses on the application of PTC in various oxidation reaction. Furthermore, PTC also conforms to the concept of “Green Chemistry”. • Oxidation has become one of the most widely used tools in organic chemistry and phase transfer catalysts has been widely used in oxidation. • The application of phase transfer catalysts in oxidation reaction will be summarized. • Phase transfer catalysts have important application in various oxidation reaction.

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Organocatalyzed Heterocyclic Transformations In Green Media: A Review

Current Organocatalysis ◽

10.2174/2213337207999200805115813 ◽

2020 ◽

Vol 07 ◽

Author(s):

Neslihan Demirbas ◽

Ahmet Demirbas

Keyword(s):

Hydrogen Bonding ◽

Phase Transfer ◽

Noncovalent Interactions ◽

Binding Capacity ◽

Chemical Transformations ◽

Organic Transformations ◽

Phase Transfer Catalysts ◽

Waste Production ◽

Synthetic Methodologies ◽

Organocatalytic Reactions

Background: Since the discovery of metal-free catalysts or organocatalysts about twenty years ago, a number of small molecules with different structures have been using to accelerate organic transformations. With the development of environmental awareness, in order to obtain highly privileged scaffolds, scientists have directed their studies towards the synthetic methodologies which minimize or preferably eliminate the formation of waste, avoid from toxic solvents and reagents and use renewable starting materials as far as possible. Methods: In this connection, the organocatalytic reactions providing efficiency and selectivity for most of case have become an endless topic in organic chemistry since several advantages from both practical and environmental standpoints. Organocatalysts supplying transformation of reactants into products with the least possible waste production have been serving to the concept of green chemistry. Results and Conclusion: Organocatalysts have been classified on the basis of their binding capacity to the substrate with covalently or noncovalent interactions involving hydrogen bonding and electrostatic interaction. Diverse types of small organic compounds including proline and its derivatives, phase-transfer catalysts, (thio)urease, phosphoric acids, sulfones, N-oxides, guanidines, cinchona derivatives, aminoindanol and amino acids have been utilized as hydrogen bonding organocatalysts in different chemical transformations.

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