WO2009088281A2 - Processus de synthèse d'ionophores et molécules obtenues à partir de ceux-ci - Google Patents

Processus de synthèse d'ionophores et molécules obtenues à partir de ceux-ci Download PDF

Info

Publication number
WO2009088281A2
WO2009088281A2 PCT/MY2009/000011 MY2009000011W WO2009088281A2 WO 2009088281 A2 WO2009088281 A2 WO 2009088281A2 MY 2009000011 W MY2009000011 W MY 2009000011W WO 2009088281 A2 WO2009088281 A2 WO 2009088281A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
diol
lipophilic
ionophore
metal cation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/MY2009/000011
Other languages
English (en)
Other versions
WO2009088281A3 (fr
Inventor
Mohd Rais Ahmad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mimos Bhd
Original Assignee
Mimos Bhd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mimos Bhd filed Critical Mimos Bhd
Publication of WO2009088281A2 publication Critical patent/WO2009088281A2/fr
Publication of WO2009088281A3 publication Critical patent/WO2009088281A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/333—Ion-selective electrodes or membranes
    • G01N27/3335—Ion-selective electrodes or membranes the membrane containing at least one organic component
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D323/00—Heterocyclic compounds containing more than two oxygen atoms as the only ring hetero atoms

Definitions

  • lipophilic neutral ion carrier molecules specifically, lipophilic metal ion ionophores. It may be used as a component in the cocktail preparation for forming a hydrophobic polymer membrane for selectively lOdetecting metal cations and which may be useful in ion-sensitive field effect transistor (ISFET) of ion-selective electrode (ISE) sensing devices. Process for forming these ionophores and certain intermediate compounds is also disclosed.
  • ISFET ion-sensitive field effect transistor
  • ISE ion-selective electrode
  • An ionophore is typically a neutral lipophilic molecule found embedded in biological membrane systems for transporting ions across the membrane,
  • ionophores are known to be ion-specific; hence, for example, monensin is known as a Na + carrier, ionomycin for Ca 2+ , valinomycin for K + , and FCCP for H + to name but a few.
  • Such ionic transportation features has been duplicated in non-biological systems and implemented as biosensor membrane.
  • a polymeric membrane is doped with a specific ionophore to give the membrane chemical sensing ability to selectively bind desired ions and produce electrochemical
  • Crown ethers is known in the art as heterocycles that strongly solvate cations by coordinating the cation within its crown ring with its oxygen atoms.
  • the size of the crown ring determines the size of the cation it can solvate.
  • U.S. Patent No. 7,208,121 granted 24 th April 2007 lOdiscloses 5 ionophore molecules including 2 crown ethers, i.e. (i) BME-44 which has bis or two 15-crown-5 rings each suitable to solvate K + , and (ii) 6,6- dibenzyl-14-crown-4 which is suitable to solvate Li + .
  • U.S. Patent No. 5,290,950 discloses a wide range of tetrasubstituted cyclohexa ⁇ es having ionophoric groups which may be a crown, podand or cryptand capable of
  • pentaerythritol is a known compound having a general formula as follows:
  • Pentaerythritol is a white, crystalline odorless solid. It is a polyol and can be procured in large quantity from Aldrich Chemical Co. (a member of Sigma- Aldrich Group) at economical cost.
  • pentaerythrito! is known to be used in constituting the hydrophobic layer of synthetic lipid membranes such as disclosed in U.S. Patent No. 5,798,030 (Raguse) wherein tetra-alkylated pentaerythritol derivative is used. It is also known to be used as a cross-linking agent in the polymerization of membrane layers such as that disclosed in U.S. Patent No. 5,852,126 (Barnard). None of the prior art documents disclosed pentaerythritol in the synthesis of ionophores.
  • n O 1 1, 2.
  • the n number of oxygen atoms, along with 2n number of methylene (CH 2 ) units, of each of the cyclic polyether substituent is varied to derive an ionophore having specific affinity to any one of lithium (Li + ), sodium (Na + ) and potassium (K + ) cations.
  • a process for synthesising a lipophilic metal cation ionophore comprising the steps of: (i) converting pentaerythritol into a protected diol with two tosylate leaving groups having a general Formula I as follows:
  • the derivation of the lipophilic protected diol of Formula I from pentaerythritol in step (i) above includes the steps:
  • the aforesaid organometallic conversion of the lipophilic protected dioi of Formula I into a corresponding lipophilic diol of Formula Ha involves a Grignard reaction, including using hexadecylmagnesiumbromide [CH 3 (CH 2 )IsMgBr] as the Grignard reagent.
  • a Il is a 1,3-dioxane, and which may be extracted from the reaction mixture and deprotected to provide the corresponding diol of Formula Ha.
  • the diol silyl ether of Formula II! in step (iii) is obtained from direct silylation of a dioxane compound.
  • the diol silyl ether of Formula III is prepared from 2,2-bis(hydroxymethyl) propionic acid by protecting the two hydroxyl groups followed by reduction of the carboxylic 5group and silylation of the alcohol product.
  • the reaction preferably takes place in THF and in an inert atmosphere with sodium hydride (NaH).
  • the number n of oxygen atoms and the number 2 ⁇ of methylene units, in the resultant silylated cyclic polyether of Formula IV are predetermined in the synthesis by affinity to specific cation, including any one of lithium, sodium and lOpotassium, desired of the subsequent-lipophilic carrier of Formula V.
  • the lipophilic diol of Formula Na and the silyi cyclic polyether of Formula IV are each dissolved in THF and are added to each other in a proportion of 1:2.
  • the lipophilic metal 15cation ionophore is crystalized from resultant residue in methanol of the reaction mixture.
  • this stage involves converting pentaerythritol, as a starting material, into a protected diol with two tosylate leaving group having a general 5Formula I, and converting it via an organometallic reaction into a lipophilic protected diol having a Formula II.
  • the protected diol of Formula I needs to be prepared first using standard preparative procedure with pentaerythritol as the starting material.
  • lOPentaerythritol and common reagents used in our trials may be purchased from Fluka/Sigma-Aldrich and, in our trials, we were able to use them without further purification.
  • Two hydroxyl groups are protected first followed by conversion of the two remaining hydroxyl groups to tosylate leaving groups. These standard conversion steps give protected diol I in high yields.
  • Grignard reagent preferably Grignard reagent is used.
  • Hexadecylmagnesium-bromide is prepared from hexadecyl- bromide using literature procedure.
  • the alkyl bromide may be purchased from Sigma-Aldrich and is first freshly distilled under reduced pressure.
  • reaction vessel we use a 500 ml, one-necked, round-bottomed flask which is equipped with septum, magnetic stirring bar, addition funnel and argon line. The flask is flame-dried and cooled to room temperature in a desicator. An argon atmosphere is introduced and copper iodide (CuI) (1.89 g,
  • reaction mixture is then transferred to a 1 -litre separatory funnel to have its layers separated.
  • the aqueous layer is extracted four times with 50-ml lOof methylene chloride.
  • the organic layer and extracts were then combined and dried with magnesium sulfate.
  • the drying agent is separated by titration followed by distillation of the solvent to give about 0.03 mol of yellowish oil. This material is to be used in the next step without further purification.
  • the protected diol of Formula Il is deprotected using a standard procedure to give the
  • 20[0026]Diol silyl ether of Formula III can be prepared from direct silylation of commercially available dioxane compound.
  • This diol silyl ether can be prepared from commercially available 2,2-bis(hydroxymethyl)pr ⁇ pionic acid using well- known procedure, i.e. protection of the two hydroxyl groups followed by reduction of the carboxylic group and silyiation of the alcohol product.
  • the ice-water bath is then removed and the reaction mixture stirred for additional 2 hours at room temperature.
  • the reaction mixture is stirred for additional 12 hr at room temperature before the flask is immersed in ice-water bath. After the mixture is cooled to 0 0 C, ice-water is added slowly to IOdestroy unreacted NaH.
  • the ionophore molecules synthesized from the above process can be 20characterized using spectroscopic methods and other conventional analytical means to show that the particular molecule has been successfully synthesized.
  • Bis-crown ether of Formula V is found to have good binding characteristics on metal cations.
  • Depends on the number of oxygen atoms (n 0, 1 or 2) of the crown ether group, it can be designed to recognize and specifically binds 25lithium, sodium and potassium.
  • the ionophores can be used to prepare cocktails of hydrophobic polymeric membrane.
  • the prepared cocktails can be applied on ISE or ISFET surfaces such that the sensitivity and selectivity of the hydrophobic membrane 30can be characterized from the respective response and selectivity plots.
  • Our present invention can thus be applied to fabricate chemical sensor platform for the analysis of cations such as soil macronutrients, in vivo biochemical analysis of plant nutrient uptake and determination of the extent of contamination of ground water and river caused by fertilizers, natural causes or accidental spills, for example.
  • economically viableroutes are thus provided for the syntheses of highly lipophilic metal cations io ⁇ ophores in large quantities or volume production using commercially available starting materials and chemical reagents that can be procured cheaply from various sources and at bulk quantities.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Electrochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)

Abstract

L'invention concerne un nouvel ionophore lipophile à cations métalliques comprenant deux substituants polyéther cycliques de formule moléculaire suivantes, dans lesquelles n = 0, 1, 2, qui au même titre que les 2n unités de méthylène (CH2) de chaque substituant de polyéther cyclique se modifient pour dériver un ionophore présentant une affinité spécifique avec un cation lithium (Li+), sodium (Na+) et potassium (K+). Indépendamment des composés intermédiaires, l'invention concerne un processus de synthèse de l'ionophore à partir de pentaérythritol, comprenant une première conversion en diol présentant deux groupes partants de tosylate, puis une conversion,avant la déprotection du diol, en un diol protégé lipophile au moyen d'une réaction de Grignard. Un éther de silyle de diol est synthétisé en un polyéther cyclique à l'aide d'un groupe partant de tosylate qui est ensuite mis en réaction avec le diol déprotégé, ce qui permet d'obtenir l'ionophore liphophile à cations métalliques souhaité.
PCT/MY2009/000011 2008-01-08 2009-01-07 Processus de synthèse d'ionophores et molécules obtenues à partir de ceux-ci Ceased WO2009088281A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MYPI20080030 2008-01-08
MYPI20080030A MY157983A (en) 2008-01-08 2008-01-08 A process for synthesizing ionophores and molecules obtained therefrom

Publications (2)

Publication Number Publication Date
WO2009088281A2 true WO2009088281A2 (fr) 2009-07-16
WO2009088281A3 WO2009088281A3 (fr) 2009-10-15

Family

ID=40853642

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/MY2009/000011 Ceased WO2009088281A2 (fr) 2008-01-08 2009-01-07 Processus de synthèse d'ionophores et molécules obtenues à partir de ceux-ci

Country Status (2)

Country Link
MY (1) MY157983A (fr)
WO (1) WO2009088281A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3897971A4 (fr) * 2018-12-17 2022-10-19 6th Wave Innovations Corp. Extraction de lithium avec des éthers couronnes

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5136033A (en) * 1987-08-24 1992-08-04 Allied-Signal Inc. Ion selective fluorogenic reagents
DE3827438A1 (de) * 1988-08-12 1990-03-01 Bayer Ag Beschichtete traeger mit ultraduenner, mehrlagiger beschichtung, verfahren zu ihrer herstellung und polyurethane als zwischenprodukte fuer die beschichteten traeger
US5958782A (en) * 1993-10-21 1999-09-28 Minnesota Mining And Manufacturing Company Cation-sensing composite structure and compounds for use therein
KR100264357B1 (ko) * 1998-09-28 2000-08-16 이종훈 세슘이온을 선택적으로 추출할 수 있는 칼릭[4]아렌 크라운유도체의 합성

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3897971A4 (fr) * 2018-12-17 2022-10-19 6th Wave Innovations Corp. Extraction de lithium avec des éthers couronnes

Also Published As

Publication number Publication date
MY157983A (en) 2016-08-30
WO2009088281A3 (fr) 2009-10-15

Similar Documents

Publication Publication Date Title
Guram et al. Insertion chemistry of Cp2Zr (. eta. 2-C, N-CH2 {6-Me-pyrid-2-yl})+: facile zirconium-mediated functionalization of methyl carbon-hydrogen bonds of 2, 6-lutidine
Nakata et al. Stereoselective synthesis of six-and seven-membered ether rings based on the ring expansion
CN115417882B (zh) 一种含呋喃的有机笼状化合物及其制备方法和应用
Giri et al. Effect of the allylic substituents on ring closing metathesis: the total synthesis of stagonolide B and 4-epi-stagonolide B
Ohba et al. A highly efficient macrolactonization method via ethoxyvinyl ester
Liu et al. Novel C1-symmetric chiral crown ethers bearing rosin acids groups: synthesis and enantiomeric recognition for ammonium salts
Zeng et al. The syntheses and Ag+-selective electrode properties of benzothiazolylthiaalkoxy functionalized calix [4] arenes: an investigation of the structure–selectivity relationship in the ionophore-based ISEs
WO2009088281A2 (fr) Processus de synthèse d'ionophores et molécules obtenues à partir de ceux-ci
Nowik-Zajac et al. Selective transport of Ag+ and Cu2+ across plasticized membranes with calix [4] pyrrole [2] thiophene
JP4588123B2 (ja) クラウンカリックス［４］アレーン、その製造方法及びセシウムを選択抽出するためのその用途
EP2376442B1 (fr) Préparation d'ionophores de phosphate monobasique
Listunov et al. On terminal alkynylcarbinols and derivatization thereof
Ouchi et al. Silver and thallium (I) complexation with dibenzo-16-crown-4
Landais et al. Desymmetrization of Cyclohexa‐1, 4‐dienes− A Straightforward Route to Cyclic and Acyclic Polyhydroxylated Systems
CN116478421B (zh) 基于联萘酚骨架的手性金属框架材料及其制备方法和应用
Raju et al. Regioselective synthesis and antioxidant activity of a novel class of mono and C2-symmetric bis-1, 2, 3-triazole and acridinedione grafted macromolecules
Mandal et al. Ferrocene-histidine conjugates: N-ferrocenoyl-histidyl (imN-ferrocenoyl) methylester: synthesis and structure
Liu et al. Lewis acid induced rearrangement of 2, 3-epoxy amines; characterisation of aziridinium ion intermediates and regiospecific ring opening with nitrogen nucleophiles
Zimmermann et al. Synthesis of enantiomerically and diastereomerically pure 4-hydroxy-1, 2-alkadienyl carbamates and their application in a modified Nazarov cyclization towards chiral cyclopentenones
Kim et al. Metal ion complexation by acyclic polyethers with lipophilic amide, thioamide, and amine end groups
Li et al. The synthesis of novel polysiloxanes with pendant hand-basket type calix [6] crowns and their transporting properties for metal ions in a liquid membrane
Togrul et al. Enantioselective recognition of ammonium perchlorate salts by optically active monoaza‐15‐crown‐5 ethers
Umemiya et al. Synthesis of macrocyclic polyethers via Ru complex-catalyzed metathesis cyclization and their use as the ring component of rotaxanes
Oezluegedik et al. Stereoselective synthesis of highly substituted bicyclic γ-lactones using homoaldol addition of 1-(1-cycloalkenyl) methyl carbamates
Soundararajan et al. Racemic and diastereoselective synthesis of alkyl (1, 3-butadien-2-yl) methanols via a novel homoallenylboration of aldehydes with diisopropyl 2, 3-butadien-1-ylboronate

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09700646

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09700646

Country of ref document: EP

Kind code of ref document: A2