A Simplified Protocol for Routine Chemoselective Syntheses of
Piperazines Substituted In the 1-Position by an Electron
Withdrawing Group

J 2015

A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group

NĚMEČKOVÁ, Dana and Pavel PAZDERA

Basic information

Original name

A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group

Authors

NĚMEČKOVÁ, Dana (203 Czech Republic, belonging to the institution) and Pavel PAZDERA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Current organic synthesis, Sharjah, Bentham Science Publ Ltd, 2015, 1570-1794

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10401 Organic chemistry

Country of publisher

United Arab Emirates

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Full Text

Impact factor

Impact factor: 2.050

RIV identification code

RIV/00216224:14310/15:00081732

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.2174/1570179411666141001232644

UT WoS

000350751700007

Keywords in English

1-monosubstituted piperazine; ionically-bound substrate; metal catalysis; piperazine; piperazine-1-ium cation; resin supported metal ion; solid phase synthesis

Abstract

V originále

We report a simplified protocol for the routine direct chemoselective preparation of various piperazines substituted in the 1-position by an electron withdrawing group. These syntheses are based on the reaction of piperazine-1-ium cation with different electrophilic reagents such as acyl chlorides, anhydrides, sulfonyl chlorides, carbamoyl chlorides, and nitrourea as well. Piperazine-1-ium cation was chosen because the reactions of piperazine with electrophilic reagents in different solvents at usual temperatures are not chemoselective and provide mixtures comprising 1-substituted, 1,4-disubstituted and unsubstituted piperazine as well. Simultaneously, the mono-protonation of piperazine is the simplest synthetic method for its protection/deprotection in comparison with the currently used mono-benzylation, mono-Boc-protection, etc. Computer modeling of acid-base equilibria for piperazine and model 1-acetylpiperazine was used as the basis for the prediction of reaction conditions suitable for the synthesis. It was found that for in situ generating of starting piperazine-1-ium cation from piperazine the application of acetic acid as reaction medium or the chemisorption of piperazine on weakly acidic cation-exchanger resin were highly acceptable in terms of both reaction times and yields. The using of resin supported piperazine-1-ium cation in reaction with carboxylic anhydrides or nitrourea is an example of the solid phase synthesis with ionically bonded substrate. Furthermore, syntheses in acetic acid medium were effectively catalyzed by Cu+, Cu2+ or Al3+ ions supported on weakly acidic cation-exchanger resin as well. Finally, it was observed that application of the solid support metal catalysis afforded target products in shortened reaction times and in 82-95% yields.

Links

2A-1TP1/090, research and development project

Name: Nové katalyzátory a činidla pro udržitelné zelené syntézy a kombinatoriální syntézy.

Investor: Ministry of Industry and Trade of the CR, New catalysts and reagents for sustainable green syntheses and combinatorial syntheses

Citovat

NĚMEČKOVÁ, Dana and Pavel PAZDERA. A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group. Current organic synthesis. Sharjah: Bentham Science Publ Ltd, 2015, vol. 12, No 2, p. 173-179. ISSN 1570-1794. Available from: https://dx.doi.org/10.2174/1570179411666141001232644.

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   author = {Němečková, Dana and Pazdera, Pavel},
   article_location = {Sharjah},
   article_number = {2},
   doi = {http://dx.doi.org/10.2174/1570179411666141001232644},
   keywords = {1-monosubstituted piperazine; ionically-bound substrate; metal catalysis; piperazine; piperazine-1-ium cation; resin supported metal ion; solid phase synthesis},
   language = {eng},
   issn = {1570-1794},
   journal = {Current organic synthesis},
   title = {A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group},
   url = {https://is.muni.cz/th/ho8ey/clanekCOS.pdf},
   volume = {12},
   year = {2015}
}

TY  - JOUR
ID  - 1217977
AU  - Němečková, Dana - Pazdera, Pavel
PY  - 2015
TI  - A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group
JF  - Current organic synthesis
VL  - 12
IS  - 2
SP  - 173-179
EP  - 173-179
PB  - Bentham Science Publ Ltd
SN  - 15701794
KW  - 1-monosubstituted piperazine
KW  - ionically-bound substrate
KW  - metal catalysis
KW  - piperazine
KW  - piperazine-1-ium cation
KW  - resin supported metal ion
KW  - solid phase synthesis
UR  - https://is.muni.cz/th/ho8ey/clanekCOS.pdf
N2  - We report a simplified protocol for the routine direct chemoselective preparation of various piperazines substituted in the 1-position by an electron withdrawing group. These syntheses are based on the reaction of piperazine-1-ium cation with different electrophilic reagents such as acyl chlorides, anhydrides, sulfonyl chlorides, carbamoyl chlorides, and nitrourea as well. Piperazine-1-ium cation was chosen because the reactions of piperazine with electrophilic reagents in different solvents at usual temperatures are not chemoselective and provide mixtures comprising 1-substituted, 1,4-disubstituted and unsubstituted piperazine as well. Simultaneously, the mono-protonation of piperazine is the simplest synthetic method for its protection/deprotection in comparison with the currently used mono-benzylation, mono-Boc-protection, etc. Computer modeling of acid-base equilibria for piperazine and model 1-acetylpiperazine was used as the basis for the prediction of reaction conditions suitable for the synthesis. It was found that for in situ generating of starting piperazine-1-ium cation from piperazine the application of acetic acid as reaction medium or the chemisorption of piperazine on weakly acidic cation-exchanger resin were highly acceptable in terms of both reaction times and yields. The using of resin supported piperazine-1-ium cation in reaction with carboxylic anhydrides or nitrourea is an example of the solid phase synthesis with ionically bonded substrate. Furthermore, syntheses in acetic acid medium were effectively catalyzed by Cu+, Cu2+ or Al3+ ions supported on weakly acidic cation-exchanger resin as well. Finally, it was observed that application of the solid support metal catalysis afforded target products in shortened reaction times and in 82-95% yields.
ER  -

NĚMEČKOVÁ, Dana and Pavel PAZDERA. A Simplified Protocol for Routine Chemoselective Syntheses of Piperazines Substituted In the 1-Position by an Electron Withdrawing Group. \textit{Current organic synthesis}. Sharjah: Bentham Science Publ Ltd, 2015, vol.~12, No~2, p.~173-179. ISSN~1570-1794. Available from: https://dx.doi.org/10.2174/1570179411666141001232644.

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