The preparative synthetic approach to 4-(triﬂuoromethoxy)piperidine and 4-(triﬂuoromethoxymethyl)piperidine

Aim. To develop a convenient synthetic approach for the preparation of multigram amounts of 4-(triﬂuoromethoxy)-piperidine and 4-(triﬂuoromethoxymethyl)piperidine – promising building blocks for medicinal chemistry.Results and discussion. 4-(Triﬂuoromethoxy)piperidine (8.4 g) and 4-(triﬂuoromethoxymethyl)piperidine (12.9 g) were synthesized in 5 stages starting from 4-hydroxypiperidine (the overall yield 40 %) and 4-(hydroxymethyl)piperidine (the overall yield 13.5 %), respectively.Experimental part. The first stage of the synthetic strategy was acylation of 4-hydroxypiperidine with benzoyl chloride. N-benzoyl-4-hydroxypiperidine obtained was transformed to N-benzoyl-4-(triﬂuoromethoxy)piperidine in two stages using the Hiyama method (the synthesis of the corresponding S-methyl xanthate with the subsequent desulfurization/ﬂuorination using N-bromosuccinimide and Olah’s reagent). Then the N-benzoyl group was reduced to benzyl one, which was removed using 1-chloroethyl chloroformate. The similar approach was applied to the synthesis of 4-(triﬂuoromethoxymethyl)piperidine starting from 4-(hydroxymethyl)piperidine. The structure and composition of the compounds synthesized were confrmed by 1Н, 13C and 19F NMR spectroscopy,mass-spectrometry and elemental analysis.Conclusions. The synthetic approach developed is a convenient method for the multigram preparation of4-(triﬂuoromethoxy)piperidine and 4-(triﬂuoromethoxymethyl)piperidine and can be used for the synthesis of other secondary amines containing the CF3O-group.Key words: ﬂuorination; triﬂuoromethoxy group; xanthate; piperidine; protection group

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α-(Imino)pyridyldifluoroethyl Phosphonates: Novel Promising Building Blocks in Synthesis of Biorelevant Aminophosphonic Acids Derivatives

Organics ◽

10.3390/org2020007 ◽

2021 ◽

Vol 2 (2) ◽

pp. 72-83

Author(s):

Oksana M. Shavrina ◽

Lyudmyla V. Bezgubenko ◽

Andrii V. Bezdudny ◽

Petro P. Onys’ko ◽

Yuliya V. Rassukana

Keyword(s):

Carbon Atom ◽

Building Blocks ◽

Synthetic Approach ◽

Phosphonic Acids ◽

Aminophosphonic Acids ◽

Convenient Synthetic Approach

A convenient synthetic approach to previously unknown NH-iminophosphonates bearing 2-, 3-, and 4-pyridyldifluoromethyl groups at the imine carbon atom was developed. The synthetic potential of these novel building blocks was demonstrated by their conversion into highly functionalized acyclic and heterocyclic aminophosphonates and phosphonic acids combining in their structure biorelevant aminophosphonic fragment, difluoromethyl group, and pyridyl, piperidyl, thiazolidin-4-one, or thiazidinan-4-one heterocyclic moieties in a single molecular platform.

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Electrochemical Synthesis of Allylic Amines from Alkenes and Amines

10.33774/chemrxiv-2021-11hm2 ◽

2021 ◽

Author(s):

Diana Wang ◽

Karina Targos ◽

Zachary Wickens

Keyword(s):

Aliphatic Amine ◽

Reactive Intermediates ◽

Building Blocks ◽

Electrochemical Process ◽

Biologically Active ◽

Secondary Amines ◽

High Yield ◽

Mechanistic Studies ◽

Allylic Amines ◽

Synthetic Strategy

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C–H amination strate-gies remain limited with respect to the viable N-substituents. Herein we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionali-zation of feedstock gaseous alkenes at 1 atmosphere. In the case of 1-butene, remarkable Z-selective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.

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A convenient synthetic approach to obtain meso-Uracil-BODIPY

Synlett ◽

10.1055/a-1545-7086 ◽

2021 ◽

Author(s):

Mariachiara Trapani ◽

Hans Elemans ◽

Maria Angela Castriciano ◽

Angelo Nicosia ◽

Placido Giuseppe Mineo ◽

...

Keyword(s):

Mass Spectrometry ◽

Steady State ◽

Low Cost ◽

Photophysical Properties ◽

Aldehyde Group ◽

Synthetic Approach ◽

Time Resolved Fluorescence ◽

Time Resolved ◽

Uracil Derivatives ◽

Convenient Synthetic Approach

An effective and convenient protocol for the synthesis of 1-Substituted-6-formyl-uracil derivatives has been developed. A three-step sequence has allowed obtaining new 6-Formyl uracil with various substituents at N-1, in large quantity using low-cost precursors. Uracil molecules containing an aldehyde group have been used as useful precursors for the preparation of meso-(1’-Substituted-6’-uracil)-BODIPY derivatives. In this way, regioselectively functionalized BODIPYs directly connected to a nucleobase were prepared in yields from 30 to 45%. MALDI-TOF mass spectrometry, NMR, UV-vis absorption, steady-state and time-resolved fluorescence spectroscopies have been used to characterize the structures and the spectroscopic/photophysical properties of the obtained dyes.

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Functionally Substituted Enamines as Building Blocks in Heterocyclic Synthesis: Reactivity of Glyoxal Diphenylhydrazone toward Electrophilic Reagents

Journal of Chemical Research ◽

10.3184/030823405774909441 ◽

2005 ◽

Vol 2005 (11) ◽

pp. 729-732 ◽

Cited By ~ 5

Author(s):

Huwaida M. E. Hassaneen ◽

Tayseer A. Abdallah ◽

Hamdi M. Hassaneen ◽

Mohamed H. Elnagdi

Keyword(s):

Acetic Acid ◽

Acetic Anhydride ◽

Benzoyl Chloride ◽

Phosphorus Oxychloride ◽

Aromatic Aldehydes ◽

Building Blocks ◽

Secondary Amines ◽

Vilsmeier Reaction ◽

Heterocyclic Synthesis ◽

Electrophilic Reagents

Glyoxalbis(phenylhydrazone) 1a reacts with aromatic aldehydes and secondary amines to yield either propan-1,2-dialdiphenylhydrazones 2 or arylazopyrazoles 7 depending on the nature of utilised aldehyde. The reactivity of 1a with phosphorus oxychloride (POCl3) and dimethylformamide (DMF) (Vilsmeier reaction) afforded the cinnolin-3-carbaldehyde phenylhydrazone 11. Compound 1a afforded also the tribenzoyl derivative 16 on treatment with benzoyl chloride. Only the diacetyl derivative 17 was produced on refluxing 1a in acetic anhydride. The diphenylhydrazone 20 was produced on treatment of 19, prepared via coupling 18 with benzenediazonium chloride followed by phenylhydrazine. This cyclised into pyrazole 21 on reflux in acetic acid.

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Application of Nitrogen Heterocyclic Carbenes in Organocatalysis

Current Catalysis ◽

10.2174/2211544709999201201120617 ◽

2020 ◽

Vol 09 ◽

Author(s):

Minita Ojha ◽

R. K. Bansal

Keyword(s):

Asymmetric Catalysis ◽

Building Blocks ◽

Structural Features ◽

Heterocyclic Carbenes ◽

Stetter Reaction ◽

Metal Pollutants ◽

Synthetic Strategy ◽

Wide Range ◽

Benzoin Condensation ◽

Nitrogen Heterocyclic

Background: During the last two decades, horizon of research in the field of Nitrogen Heterocyclic Carbenes (NHC) has widened remarkably. NHCs have emerged as ubiquitous species having applications in a broad range of fields, including organocatalysis and organometallic chemistry. The NHC-induced non-asymmetric catalysis has turned out to be a really fruitful area of research in recent years. Methods: By manipulating structural features and selecting appropriate substituent groups, it has been possible to control the kinetic and thermodynamic stability of a wide range of NHCs, which can be tolerant to a variety of functional groups and can be used under mild conditions. NHCs are produced by different methods, such as deprotonation of Nalkylhetrocyclic salt, transmetallation, decarboxylation and electrochemical reduction. Results: The NHCs have been used successfully as catalysts for a wide range of reactions making a large number of building blocks and other useful compounds accessible. Some of these reactions are: benzoin condensation, Stetter reaction, Michael reaction, esterification, activation of esters, activation of isocyanides, polymerization, different cycloaddition reactions, isomerization, etc. The present review includes all these examples published during the last 10 years, i.e. from 2010 till date. Conclusion: The NHCs have emerged as versatile and powerful organocatalysts in synthetic organic chemistry. They provide the synthetic strategy which does not burden the environment with metal pollutants and thus fit in the Green Chemistry.

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