JPH0510351B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to novel crown ether derivatives, methods for producing them, and ion-selective membrane electrodes containing them. More specifically, the present invention relates to novel crown ether derivatives useful as cation complexing agents, methods for their production, and ion-selective membrane electrodes comprising them. <Prior art and problems to be solved by the invention> The novel crown ether derivatives of the present invention can be used for cationic complex formation under more favorable conditions than the known ethers of the prior art and give better results. Membrane sensors comprising the novel crown ether derivatives of the present invention have a longer lifetime than known membranes when used in ion-selective electrodes, and some analytical property data are also better than known membranes. It is. The invention also relates to ion-selective membrane electrodes comprising the novel crown ether derivatives of the invention, which membranes have a longer lifetime than membranes made from known crown ether compounds, while the membrane electrodes of the invention The performance of is at least comparable to that of known products. The present invention was filed by the same applicant as the present application prior to the filing of the present application, and was filed under No. T/26686 without undergoing substantive examination.
Hungarian patent application published as No.
This is an improvement and development of No. 1999/81 (hereinafter referred to as the "cited specification"). The above “cited specification” includes Swiss patent no.
Valinomycin, disclosed in No. 479870, is described as prior art. Among the main analytical properties of membrane electrodes prepared using valinomycin as active substance, selectivity and potential response are generally good, but for some application areas the Rb ⁺ and Cs ⁺ ion selectivity is unsatisfactory. It's not a thing. The invention protected in the above-mentioned "cited specification" is based on the general formula () [In the formula, Z is a chemical bond, -CH ₂ -, -(CH ₂ ) _{2 to 4}
−, −CH ₂ OCH ₂ −, −CH ₂ SCH ₂ − or other cyclic groups] as ion-selective membrane ligands, high K ⁺ ion selectivity can be obtained, which further interference with alkali metal or alkaline earth metal ions (Na ⁺ , Ca ²⁺ , Mg ²⁺ , Rb ⁺ ,
This was based on the finding that it enables analytical quantification of K ⁺ ion concentration in the presence of Cs ⁺ ).
Electrodes prepared using the active substance have the same main analytical properties (selectivity, potential response) as electrodes prepared using valinomycin, but Rb ⁺ and Cs ⁺
Ion selectivity is better than this. It is known that some compounds belonging to the class of bis-benzo-15-crown-5 derivatives exhibit K ⁺ ion selectivity [Kimura et al.: J. Electroanal.
Chem., 95 , pp. 91-101 (1979)], but the compound disclosed by Kimura et al. has not been widely used in ion-selective electrodes. [Later, Kimura et al. themselves stated that the lifetime of membrane electrodes produced using these compounds was unsatisfactory and that the electrodes lost selectivity after about 200 measurements;
I gave an explanation regarding this. According to our "cited specification", the good ion selectivity of the compounds initiated therein is due to the fact that the nitro group attached to the benzene ring of the benzocrowne ether reduces the complex stability coefficient of the metal ion (this (not advantageous for selectivity per se), but this nitro group, together with the adjacent -NH group, is separated from each other by 2
Intramolecular hydrogen bond (hydrogen bridge) that forces the crown ether rings into a preferred conformation
Due to the fact that the K ⁺ stability increases when using compounds of general formula () to form . In other words, ions larger than K ⁺ ions (Rb ⁺ ,
Cs ⁺ ) cannot enter, and ions smaller than K ⁺ ions (Na ⁺ , Li ⁺ ) escape, creating a K ⁺ ion trap with internal dimensions that only allow complexation of K ⁺ ions. It is formed. On the other hand, this trap forms a "Sandermanch" with potassium ions. Stemming from the foregoing discussion regarding the properties of the crown compounds disclosed in the cited specification, we previously stated that ``selectivity is independent of the quality and length of the chain connecting the crown ether units. ' was what I was thinking. We conducted various experiments in order to examine the scope of the applicable field of the invention of the above-mentioned "cited specification."
As a result, it was found that the above-mentioned good results could be obtained by using this solution for measuring the potassium content of natural water and industrial water. However, when the electrode according to the cited specification is used for repeated or continuous measurements in biological systems, the lifetime of the membrane is not satisfactory, probably due to the slow dissolution of the ligand with insufficient lipophilicity. It has been found. Therefore, the lifespan of the membrane according to the "cited specification" is
It is unsuitable for continuous use in in-vivo measurements, for example for continuous monitoring of the patient's condition during surgery or for permanent automatic measurement systems. The aim of the present invention is to provide new crown compounds which ensure a longer service life for ion-selective membrane electrodes, while retaining at least the original level or preferably improving other advantageous properties. <Means and effects for solving the problems> The present invention provides that the Z group forming the center of symmetry of the symmetrical chain connecting two benzo crown ether moieties is expressed by the general formula

[Formula] [In the formula, R _a and R _b may be the same or different, R _a represents an alkyl group having 1 to 4 carbon atoms, and R _b represents an alkyl group having 1 to 20 carbon atoms. By replacing the general formula Z ¹ with the group corresponding to
It is possible to increase the lifespan while preserving the formed hydrogen bonds as described in the "cited specification", and
Based on the finding that even K ⁺ ion selectivity can be increased (albeit only slightly). The only structural difference between the crown ether derivatives of the present invention and the crown ether derivatives disclosed in the cited specification is the difference between the groups Z and Z ¹ .
However, the effects caused by this structural change are extremely important. We have come to produce the novel compound of the present invention based on the following ideas. It will be clear that hydrogen bond removal is necessary to advantageously increase lipophilicity. However, methylation of the NH moiety of the carbamate group greatly reduces selectivity, and the slope of the calibration curve for electrodes made from this N-methyl derivative is lower than the theoretical value.
Since it is smaller than 59.16 mV/decade, hydrogen bonds cannot be removed. Replacing the group Z by the group Z ¹ at the center of symmetry of the bridge chain (i.e. the 2-position of the propylene group constituting the central part) not only extends the lifetime and somewhat improves the K ⁺ selectivity, but also Additional effects and advantages are brought about: hydrogen bonds are preserved so the slope of the calibration curve is close to the theoretical value; almost no "drift" is observed during the measurement; the reproducibility of the measurements is significantly improved. reduced; sensitivity to agitation is reduced. According to another aspect of the invention, the general formula () [In the formula, Z ¹ is the general formula

A membrane electrode is provided which comprises as an active ingredient a compound of the formula: The compound of the general formula () differs from the compound of the general formula () in that a group Z ¹ is present in place of the group Z at the 2-position of the propylene group. The role played by hydrogen bonds and the Z ¹ group in the advantageous effect achieved is evidenced by the fact that the compounds of general formula (') obtained by removing the nitro group become less selective. . In order to compare the properties of the compounds of the present invention, the general formula () encompassing the general formulas (), (') and () is used. [In the formula, Y represents hydrogen or nitro, R represents hydrogen or methyl, and Z ² represents Z or Z ¹ ]. According to yet another aspect of the present invention, a method for producing a novel compound of general formula () is provided. The substituent R _a bonded to the carbon atom of the group Z ¹ is preferably methyl, ethyl, n-propyl or n-
Butyl, especially methyl, ethyl or n-butyl. R _b is preferably ethyl, n-butyl, n
-represents octyl, n-dodecyl or n-hexadecyl. The chain lengths of substituents R _a and R _b may be the same or different. When the chain lengths of R _a and R _b are the same, they can have the meaning of R _a . The compound of general formula () can be produced either by total synthesis or by nitration of a crown compound of general formula (') which does not contain a nitro group. According to total synthesis, the formula () The crown compound is reacted with a compound of the general formula () HO-CH ₂ -Z ¹ -CH ₂ -OH () in which Z ¹ is as defined above in an aprotic solvent. Nitration is carried out by reacting the crown compound of general formula (') with nitric acid. The total synthesis is preferably carried out with a compound of formula () in a solvent of the chlorinated hydrocarbon or ether type, optionally in the presence of a tertiary amine (e.g. triethylamine) as a catalyst, at a temperature between 0 and 50°C. This can be carried out by reacting the compound of general formula () at a molar ratio of 2:1 (former: latter). The product is isolated by removing the solvent and purified by recrystallization from a suitable solvent (eg ethyl acetate or methyl isobutyl ketone). The nitration of compounds of general formula (') with nitric acid can preferably be carried out in acetic acid or chlorinated hydrocarbons as solvent at temperatures from 30 to 70°C. The product is cooled or filtered;
Alternatively, it can be isolated by pouring on ice followed by extraction with a chlorinated hydrocarbon. The product can be purified by recrystallization from the solvent mixture. The starting materials of formula () for the total synthesis are disclosed in the cited specification. This isocyanate ester is prepared according to the formula () in a high-boiling aromatic solvent according to a method known per se. can be obtained by reacting the amine with phosgene. Compounds of general formula () or mixtures thereof can be used as active components of ion-selective electrodes as follows: a suitable plasticizer, preferably a phthalate ester, such as dipentyl phthalate (DPP ),
Selected compounds using sebacic acid esters, for example dioctyl sebacate (DOS) or o-nitrophenyl-octyl ether (ONPOE) or mixtures thereof, are applied to polyvinyl chloride (PVC) in an amount of 0.1-10% of the weight of the membrane. Formulated in a carrier phase. b. The selected compound is incorporated in an amount of 0.2 to 10% of the weight of the membrane in a suitable polymer having a dielectric constant of 2 to 30, preferably silicone rubber or PVC, polyamide, polyethylene, etc. c. Applying a solution of the selected compound in a suitable solvent, preferably in a plasticizer as described in a above, onto the porous membrane. The membrane prepared as described above is mounted in a suitable electrode and connected to an analytical instrument with a suitable reference electrode. The correlation between battery voltage and logarithmic activity (-loga _K+ = pK) is linear between pK = 1 and 5.0, and is expressed by the so-called modified Nikolsky equation: EME = E _p + S _lpg (a _i + 〓 ^i≠j K ^pot _ij a _j zi/zj) + E _D [where, EME = battery voltage E _p = constant reference potential unique to the same solution E _D = sum of diffusion potentials in the battery a _i , a _j = activity of ion to be measured and activity of interfering ion Z _i , Z _j = number of charges of ion to be measured and number of charges of interfering ion S = so-called Nernst factor, at 25°C
59.16mV/Z _i K ^pot _ij = selectivity factor]. <Examples> The details of the present invention are shown in the following examples, but the scope of protection of the present invention is not limited thereto. Compounds are numbered consecutively. In addition to this serial number, the "internal number" of the novel compound of the present invention and the compound disclosed in the above-mentioned "cited specification" is also shown. This "internal number" consists of the code BME and a two-digit number (Table 1). Table 4 summarizes the electrochemical data for comparison. Groups A, B, and C disclose characteristic data of ion-selective electrodes prepared from compound A of the present invention, compound B disclosed in the cited specification, and control substance C.

[Table] The following reference substances are used: R _V = valinomycin (Philips)
IS 561−K ⁺ in electrode] P _K = Kimura et al.: J.Electroanal.Chem. 95 (1979),
Crown ether derivatives prepared according to pages 91-101. Production of biscrown compound of general formula () a Total synthesis To a solution of 7.08 g (20 mmol) of isocyanate ester of formula () in 60 ml of anhydrous chloroform, 2,
2-diethyl-propane-1,3-diol [Formula ():

[Formula] Add 1.32g (10 mmol). After complete dissolution, 2 drops of triethylamine are added to this solution and the reaction mixture is stirred at room temperature for 2 hours. The solvent is removed under reduced pressure.
The yellow solid residue is triturated with ether. The crystalline product is filtered and dried at room temperature. As a result, 7.73 g (92%) of crude product 2 is obtained (BME-53,
(See Table 1). The product is recrystallized from a mixture of ethyl acetate and ether. As a result, 5.76 g (68.5%) of pure product is obtained. Melting point: 118-119℃. The reaction parameters used in the preparation of other compounds of general formula () are disclosed in Table 2. The physical, analytical and spectroscopic data of the products are listed in Table 3. b Nitration 6.26 g (20 mmol) of N-3,4-(1',4',7',10',13'-pentaoxacyclopentadec-2-ene)-phenyl isocyanate in 60 ml of anhydrous chloroform 2,2-diethyl-propane-1,3-diol [formula ():

[Formula] Add 1.32g (10 mmol). The reaction mixture is stirred at 50°C for 5 hours and cooled to 20°C. A solution of 3 ml of 65% nitric acid (specific weight 1.42) and 10 ml of glacial acetic acid is added dropwise to the reaction mixture. The mixture is stirred for an additional 10 minutes at room temperature and 30 minutes at 65°C. The reaction mixture is cooled, poured onto crushed ice and allowed to separate into two phases. The aqueous layer is extracted four times with 20 ml each of chloroform. The combined organic phases are washed neutral with cold water, dried over magnesium sulphate, filtered and the chloroform solution is evaporated. The residue is purified analogously to method a. Yield: 6.23g (72.5%). Product 2 (BME-53). Compound 1 (BME-44, yield 57
%) and compound 3 (BME-54, yield 61%).

【table】

[Table] Production of potassium ion selective membrane using crown compound of general formula () 1 Polyvinyl chloride (PVC) powder [e.g.
SDP Hochmolecular, Lonza AG., Basel, Switzerland]
30-40 parts by weight, preferably about 34 parts by weight, are dissolved in about 2-3 ml of tetrahydrofuran, 0.1-10 parts by weight, preferably 2 parts by weight of the active ingredient (ionophore), the so-called plasticizer (dielectric constant 2-30).
organic solvent)) and 0 to 5 parts by weight, preferably 0.5 parts by weight of an additive (e.g. sodium tetraphenylborate or potassium p-chloro-tetraphenylborate). Inject this solution into. A glass ring with a height of 10 mm and a diameter of 25 to 35 mm is fixed on a glass plate with a flat surface using a rubber ring.
Afterwards, the prepared mixture is poured onto a glass ring and covered with paper. Tetrahydrofuran evaporates through the paper in 1-2 days at room temperature, leaving an elastic membrane 0.1-0.5 mm thick as a residue at the bottom of the glass ring. This can be easily recovered from the glass plate. 2 about 0.2 to 10 parts by weight of active ingredient, preferably 2.5 parts by weight and dimethylpolysiloxane [e.g.
Siloprene K18000, Farbenfabrik
Bayer)] 80-100 mg, preferably 83 parts by weight, are dissolved in about 2-4 ml of carbon tetrachloride. Add an appropriate amount (preferably 14.5 parts by weight) of crosslinking agent to this solution. T-37 [Batsker Hiemi GmbH
Any cold-curing catalyst suitable for crosslinking can be used, such as (Wacker Chemie GmbH, Milunchen). The mixture is then poured into a glass ring fixed on a glass plate as described in 1 above, and the rest is the same as in 1 above. 3.0 to 10 parts by weight, preferably 2.5 parts by weight, of the active ingredient are finely ground in an agate mortar and mixed with dimethylpolysiloxane [e.g. Siloprene K-1000, Farbenfabrik] until a statistically homogeneous suspension is obtained. - Bayer] Disperse in 80 to 100 mg, preferably 83 parts by weight. The crosslinking agent is added in the amount required for curing (e.g., 1 part by weight dibutyl-Sn-dilaurate and 2 parts by weight hexaethoxysiloxane), after which the mixture is
Apply evenly to the plastic board with a thickness of 0.01 to 1 mm. After curing (which takes no more than a few hours), the elastic board can be recovered from the plastic board. 4. 0.1 to 20 parts by weight of the active ingredient in a water-immiscible solvent (dielectric constant 2 to 30), such as phthalate ester, (dipentyl phthalate), sebacate ester (dioctyl sebacate), o-nitrophenyl-octyl ether and The porous membrane is wetted with the solution thus obtained. 5. A tetrahydrofuran solution containing a plasticizer and an active ingredient prepared according to 1 above, a carbon tetrachloride dimethylpolysiloxane solution containing an active ingredient and a catalyst prepared according to 2 above, or a solution prepared according to 3 above. A dimethylpolysiloxane active ingredient suspension containing a crosslinking agent and/or a catalyst is combined with an electronically conductive substance, preferably metallic silver,
Apply to silver, silver chloride wire, platinum or gold fiber, graphite rod, etc. Electrochemical properties of some selected active substances of general formula () for use as potassium ion-selective membrane electrodes. PVC
A silicone rubber carrier phase membrane is prepared and subsequently applied to a suitable electrode body [e.g. Philips IS
-561 Liquid (Philips IS-561 Liquid) membrane electrode body] to form the following measurement cell: An EME-loga _K+ calibration curve was plotted at 10 ^-1 to ^{10 -6} M KCl using the potential difference data measured with the measurement battery. The selectivity factor of the electrode is determined by the so-called separation solution method (Moody, GJ, Thomas, JDR: Selective Ion-Sensitve Electrodes, Watford, Mellow Publishing). (Merrow Publishing Co. Ltd., UK, 1971)
It was measured using a solution with a concentration of 10 ^-1 M. For easier comparison, the general formula ()
Calibration curve data (FIGS. 1 and 2 and Table 4) and selectivity factors for various ions (FIG. 3 and Table 5) of electrodes containing the compound of the present invention as an active ingredient are calculated using the compound of the present invention. and the corresponding data of electrodes fabricated using the control compound (in Figure 3, "Valinomycin" and "Kimura" are respectively
Compounds in 561-K and Kimura, Maeda, Tamura, Shyouno: J.Electro-anal.Chem., 95 (1979), 91-
Represents a compound listed on page 101. ). Comparing the calibration curves and selectivity data for electrodes made with compounds numbered 1, 2, and 3 by the same membrane and electrode fabrication methods revealed that, contrary to what we previously stated, - Changing the cross-linking chain while retaining the _NO2 and -NH groups significantly increases the K-concentration sensitivity (S~theoretical) and considerably improves the potassium ion selectivity in the presence of sodium ions (-log It was found that K ^pot _k,Na = 3.5). This is particularly important when tracking or measuring the potassium content of biological samples. For flowing solutions, it is most important for use in automatic analyzers that the signal measured by the ion-selective electrode should never be dependent on the flow rate and stirring rate of the sample solution;
Alternatively, theoretical considerations dictate that the dependence must be slight. BME−15,
The dependence of the signal measured by a potassium ion selective electrode prepared using BME-44 and valinomycin ligand on stirring rate is shown in FIG. The values are determined using a laboratory magnetic stirrer in a potassium chloride solution with a concentration of 10 ^-1 mol/ml.
From the data in FIG. 4, the agitation sensitivity of the ion-selective electrode containing BME-44 is much smaller than that of the electrode containing BME-15;
It can be seen that the agitation sensitivity is almost the same as that of the electrode containing valinomycin. Particularly important data from the point of view of highly accurate determination of the K ⁺ content of biological samples are:
For the ion-selective electrode containing the BME-44 ligand, the reproducibility of the potentiometric measurements is ±0.1 mV in the corresponding aqueous potassium chloride solution and serum. The lifetime of an ion-selective electrode is a very important property, and this parameter is determined by taking calibration curves and sensitivity data for the electrode at various times. Between measurements, the electrode is stored in a large volume (300-400 ml) of distilled water. It was found that during one year the potassium concentration sensitivity (S value) of the electrode comprising the compound BME-44 decreases by 1-2 mV/decade, while the selectivity data change only slightly. During this period, the standard deviation of E _p values is only a few mV. Table 6 shows the sensitivity of the ion-selective electrode to potassium ions in serum before storage and after one month of storage. From similar experiments, the compound BME−44
It is clear that the ion-selective electrode prepared from the present invention is suitable for measuring K ⁺ ions in serum for longer periods than 3 months. A comparison of the characteristic data of similarly prepared potassium ion-selective electrodes using various ionophores showed that the parameters were improved in all cases where the benzocrowne ether units were cross-linked by branched chains. I can definitely say that. The following compound is used herein: Compound 1 (BME-44): 2-n-dodecyl-2
-methyl-propylene-1,3-bis-N,
N′-[2″-nitro-4″, 5″-(1, 4, 7,
10,13-pentaoxa-cyclopentadeca-
2-ene)-phenyl]-carbamate; Compound 2 (BME-53): 2,2-diethyl-propylene-1,3-bis-N,N′-[2″-nitro-4″,5″-( 1,4,7,10,13-pentaoxa-cyclopentadec-2-ene)-
phenyl]-carbamate; Compound 3 (BME-54): 2,2-di-n-butyl-propylene-1,3-bis-N,N′-[2″-
Nitro-4″, 5″-(1, 4, 7, 10, 13
-pentaoxa-cyclopentadec-2-ene)-phenyl]-carbamate. The following abbreviations are used in the present invention: ONPOE = o-nitrophenyl-octyl ether NaTPB = sodium tetraphenyl borate SR = silicone rubber DPP = dipentyl phthalate DOS = dioctyl sebacate

[Table] *** Data measured by us.

[Table] *** Data measured by us.

【table】

【table】 [Brief explanation of the drawing]

FIGS. 1 and 2 are graphs showing calibration curve data of a potassium ion-selective membrane electrode containing the compound according to the present invention as an active ingredient, and FIG.
FIG. 4 is a graph showing selectivity data regarding various ions of potassium ion-selective membrane electrodes produced using the compound of the present invention and a control compound;
The figure is a graphical diagram showing the dependence of the signal measured by potassium ion-selective membrane electrodes prepared using compounds of the invention and a reference compound on stirring speed.

Claims (1)

[Claims] 1 General formula () [In the formula, Z ¹ is the general formula [Formula] (wherein, R _a and R _b may be the same or different, R _a represents an alkyl group having 1 to 4 carbon atoms, and R _b represents an alkyl group having 1 to 20 carbon atoms; 2 2,2-diethyl-propylene-1,3-bis-N,N′-[2″-nitro-4″,5″-(1,4
, 7,10,13-pentaoxacyclopentadec-2-ene)-phenyl]-carbamate. 3 2,2-di-n-butyl-propylene-1,
3-bis-N,N′-[2″-nitro-4″,5″-(1
, 4,7,10,13-pentaoxacyclopentadec-2-ene)-phenyl]-carbamate. 4 2-n-dodecyl-2-methyl-propylene-1,3-bis-N,N'-[2''-nitro-4'',
5″-(1,4,7,10,13-pentaoxacyclopentadec-2-ene)-phenyl]
- The crown ether derivative according to claim 1, which is a carbamate. 5 formula () The crown compound and the general formula () HO−CH ₂ −Z ¹ −CH ₂ −OH () [wherein Z ¹ is the general formula [formula] (in the formula, even if R _a and R _b are the same R _a represents an alkyl group having 1 to 4 carbon atoms, and R _b represents an alkyl group having 1 to 20 carbon atoms.
General formula () comprising reacting with a compound of A method for producing a crown ether derivative, wherein Z ¹ is as defined above. 6. Claim 5 comprising reacting said starting materials in the presence of a tertiary amine.
Manufacturing method described in section. 7. The manufacturing method according to claim 6, wherein the tertiary amine is triethylamine. 8. The manufacturing method according to claim 5, which comprises reacting starting materials of formula () and general formula () in a ratio of 2:1 (former:latter) at a temperature of 80 to 50°C. 9 General formula (') [In the formula, Z ¹ is the general formula [Formula] (wherein, R _a and R _b may be the same or different, R _a represents an alkyl group having 1 to 4 carbon atoms, and R _b represents an alkyl group having 1 to 20 carbon atoms) A general formula () comprising reacting a crown compound of 1 to 20 carbon atoms with nitric acid A method for producing a crown ether derivative, wherein Z ¹ is as defined above. 10. Process according to claim 9, comprising reacting the starting materials in acetic acid or chlorinated hydrocarbons at a temperature of 1030 to 70<0>C. 11 General formula () [In the formula, Z ¹ is the general formula [Formula] (wherein, R _a and R _b may be the same or different, R _a represents an alkyl group having 1 to 4 carbon atoms, and R _b represents an alkyl group having 1 to 20 carbon atoms] A potassium ion-selective membrane electrode comprising a crown ether derivative or a mixture thereof as an active ingredient. 12. Comprising as active ingredient 0.2 to 10% by weight of a crown ether derivative of the general formula () or a mixture thereof, bound to a carrier, optionally mixed with plasticizers and further additives. A potassium ion selective membrane electrode according to claim 11. 13. The potassium ion selective membrane electrode according to claim 12, wherein the plasticizer is a phthalate ester. 14. The potassium ion selective membrane electrode according to claim 12, wherein the additive is sodium tetraphenyl borate or potassium p-chlorotetraphenyl borate. 15. The potassium ion-selective membrane electrode according to claim 12, wherein the plasticizer that can be mixed with the carrier is sebacic acid ester or o-nitrophenyl octyl ether. 16 Active ingredient 0.2~10% by weight, plasticizer 55~
75% by weight and a carrier, the plasticizer is a substance with a dielectric constant of 2 to 30, and the carrier is a substance with a dielectric constant of 2 to 30.
The potassium ion selective membrane electrode according to claim 11, which is a silicone rubber or polymer. 17. The potassium ion selective membrane electrode according to claim 16, wherein the polymer is polyvinyl chloride. 18. The method according to any one of claims 11 to 17, wherein the membrane or solution or suspension containing the active ingredient is bonded to a substance having electronic conductivity and/or ionic conductivity or semiconductivity. Potassium ion selective membrane electrode. 19. Potassium ion according to claim 18, wherein the substance having electronic conductivity and/or ionic conductivity or semiconductivity is metallic silver, silver chloride wire, platinum wire, gold fiber, graphite rod, or silica. Selective membrane electrode. 20 2,2-diethyl-[propylene-1,3-bis-N,N'-[2''-nitro-
Any one of claims 11 to 19 comprising 4″,5″-(1,4,7,10,13-pentaoxacyclopentadec-2-ene)-phenyl]-carbamate The potassium ion selective membrane electrode described in . 21 2,2-di-n-butyl- as an active ingredient
Propylene-1,3-bis-N,N'-[2''-nitro-4'',5''-(1,4,7,10,13-
pentaoxacyclopentadec-2-ene)-
The potassium ion-selective membrane electrode according to any one of claims 11 to 19, comprising phenyl]-carbamate. 22 2-n-dodecyl-2-methyl-propylene-1,3-bis-N,N'- as active ingredient
[2″-Nitro-4″, 5″-(1, 4, 7, 10
,13-pentaoxacyclopentadeca-2
The potassium ion selective membrane electrode according to any one of claims 11 to 19, comprising -en)-phenyl]-carbamate.