JPS60202875A - Alkyl-substituted 14-crown-4-derivative and its use - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R0 is 6-20C alkyl; R1, R2 are H, 1- 8C alkyl). USE:A sensing membrane for lithium ion selective electrode: this compound is used as a neutral carrier to make it possible to measure lithium ion simply and rapidly with high selectivity and high accuracy for hours. PREPARATION:The reaction between 2-substituted-1,3-propane diol compound of formula II and 5-substituted-1,9-tosyloxy-3,7-dioxanonane compound of formula III (where R2 is 1-3C Alkyd; Ts is tosyl), is carried out in dioxane in the presence of sodium hydride and lithium perchlorate to give the compound of formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial Application Field The present invention relates to alkyl-substituted 14-crown-4 derivatives and their uses, particularly to sensitive membranes for lithium ion selective electrodes.

(b) Prior Art In general, an ion-selective electrode is an electrode that supports the concentration of a specific ion in a solution by the membrane potential shown by the membrane electrode, and a typical example thereof is a glass electrode for measurement. By the way, the concentration of lithium ions in living organisms is generally very low, but high concentrations of lithium ions can be found in the blood and urine of patients receiving treatment for special diseases, such as disease III. is important. Conventionally, spectroscopic methods have been used for this measurement. but,
These methods require relatively large equipment and take time to measure, making them unsuitable for use in diagnostic settings.Therefore, it is necessary to develop a simpler method and a smaller device to measure lithium ions more quickly than before. It is strongly requested. Therefore, Li0051-Ag2O3(c)-8i02 (60)
A lithium ion selective electrode using a glass membrane with a composition of There is a need for a simple ion-selective electrode with less carbon interference from existing sodium ions and ammonium ions.

Moreover, among the crown ethers synthesized so far, there are relatively many that have potassium ion and sodium ion selectivity, but there are few that have lithium ion selectivity. This is the ratio of the ion diameter of the lithium ion to the pore diameter of the crown ring (S iZe -fit -CON
This is due to the fact that it is relatively difficult to synthesize a crown ether with a small pore diameter that matches (Jpt) well, and the lithium ion itself is strongly solvated (hydrated).

In general, in monocyclic crown ethers, crown-
Crown-6 (crown ether group with six oxygen atoms represented by 18-crown-6) exhibits selectivity for potassium ions, Crown-5 exhibits selectivity for sodium ions, and Crown-4 exhibits selectivity for lithium ions (n) Pedersen conducted solvent extraction to investigate the complex-forming ability of various crown ethers (C, J, P
edersen, Fed.

Proc., 27.1305 (1968))
, the lithium ion selectivity of the 14-crown-4 derivative is found, but even with the same crown-4, the lithium ion selectivity differs markedly due to differences in the number of members in the crown ring and the basicity of the oxygen atom (LJ , 0lsher
.

J., Jaour-Grodzinski, J.
, Chem, Soc.

Dalton Trans., 1981501). For example, benzo-13-crown-4 represented by formula (A), benzo-12-crown-4 represented by formula (B), dibenzo-14-xilan-4 represented by formula (C), etc. When lithium vicrate is subjected to solvent extraction using the benzocrown-4 derivative, the results shown in Table 1 are obtained.

(Margin below, continued on next page) Hit! 1) As is clear from the table, Pensol 13-Crown-4
shows the greatest lithium ion extraction ability.

This is because the ratio of the pore diameter of benzo-13-crown-4 to the lithium ion diameter is approximately 1, and they match well. On the other hand, in benzo-12-crown-4, the pore diameter is smaller than the lithium ion diameter and the strain in the crown ring is large, so that its lithium ion extraction ability is significantly reduced.

In addition, in the case of dibenzo-14-crown 4, the ratio of the pore diameter to the lithium ion diameter is approximately 0.80 to 0.89, with the pore diameter between the crowns being larger, and the affinity for lithium ions is small, but -13- Inferior to Crown-4.

Recently, dibenzo-14-crown-4 was used as a neutral carrier in PVC membrane ionic electrodes, and its lithium ion selectivity was investigated (U, 0lsher
, J. Am., Chem., Soc.

104, 4006 (1982)). This dibenzo
Logarithm value t of the selectivity coefficient for various ions (M ions) of electrodes using a total of four types of F) VC membranes prepared by changing the plasticizer (solvent) to 14-Crown-4, -
The gate is shown in Figure 1. In the figure, compound (1) is NPOE
(o-nitrophenyl octyl ether) system, (2) is NPOE-KTI) CI PB (potassium tetra(p
-chlorophenyl)borate) system, (3) is DO8 (dioctyl sebacate) system and (4) is DO8-KTp
Compounds using CI PB plasticizers are shown below.

In the figure, the smaller the logarithm value of the selection coefficient 10BK, the less the interference of M ions, but in both cases the value of 1DB)'?aLi exceeds zero,
This is because the electrode using dibenzo-14-crown-4 has the above-mentioned lithium ion selectivity, but has the drawback of large interference by sodium ions. In order to create a practical lithium ion selective electrode, ion selectivity is required that is not interfered with by sodium and potassium ions that often coexist with lithium ions.

(c) Purpose The present invention has been made to solve these problems, and uses an alkyl-substituted 14-crown-4 compound as a neutral carrier to easily and quickly transfer lithium ions with high selectivity and high precision. The main purpose of this invention is to provide a sensitive membrane for a lithium ion selective electrode that can be measured over a long period of time with good reproducibility.

(2>m) Thus, according to the present invention, General formula (■): (In the formula, Ro is an alkyl group having 6 to 20 carbon atoms, and R1 and R2 are each a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. A sensitive membrane for a lithium ion selective electrode is provided, which contains at least one kind of alkyl-substituted 14-crown-4 derivative represented by r as a neutral carrier.

Such alkyl-substituted 14-crown-
The 4 derivatives themselves are a new group of compounds that have not been described in the literature.

According to the present invention, therefore, an alkyl-substituted 14-crown-4 derivative represented by general formula (I) is also provided.

The compound represented by the general formula (I) is, for example, the general formula (Ia): (wherein Ro is an alkyl group having 6 to 20 carbon atoms, and R1 is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms A 2-substituted-1,3-propanediol compound represented by the general formula (Ib): (wherein R2 represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and TS represents a tosyl group. ) 5-substituted-1,9-tosyloxy-3゜7-
A thioxanonan compound can be obtained by reacting in dioxane in the presence of a sodium hydride/lithium perchlorate catalyst.

The sensitive membrane according to the invention can be used as a solid membrane or a liquid membrane. The solid membrane is formed by uniformly dispersing the crown ether compound in a water-insoluble solid organic polymer as a support. The polymer forms a matrix to support the crown ether compound, which is a neutral carrier, in the form of a film, preventing the neutral carrier from eluting into the sample aqueous solution, etc., and allowing the lithium ions in the sample solution to diffuse appropriately into the matrix. Polyvinyl chloride, silicone rubber, polymethyl methacrylate, etc. are usually used.

A sensitive membrane using polyvinyl chloride as a support is usually prepared by dissolving polyvinyl chloride, a plasticizer, and a crown ether compound in a suitable low-boiling organic solvent such as tetrahydrofuran.
For example, it is formed into a film by gradually evaporating the solvent in a Petri dish.

Plasticizers are used to give appropriate flexibility to the resulting sensitive membrane and to prevent crown ether compounds from eluting into the measurement solution, such as dioctyl phthalate,
0-Nitrophenyl octyl etc. are used.

In addition, like a sensitive film using silicone rubber as a support, a crown ether compound, silicone rubber alone, and a silane compound for crosslinking the film are dissolved in an appropriate organic solvent, polymerized into a film, and then molded. It can also be produced by removing the solvent.

The crown ether compound in the solid film is 0.5-20
It is desirable that it is % by weight, preferably 1 to 15 ω% by weight. If the content of the crown ether compound is too small, the response will be poor, and if it is too large, it will be difficult to uniformly disperse it in the polymer and it will be uneconomical. When a plasticizer is used in combination, such as when polyvinyl chloride is used as a support, the amount of plasticizer is suitably 50 to 70% by weight.

In addition, the liquid film is formed by dissolving a crown ether compound in a water-insoluble polar organic solvent. etc. are used. Preferred specific examples include 1-decanol,
Examples include nitrobenzene, chlorobenzene, diphenyl ether, and 1°2-dichloroethane. The content of the crown ether compound in the liquid film is from 0.5 to 20% by weight, preferably from 1 to 10% by weight for the same reason as mentioned above.

The liquid membrane is usually held in a porous support such as ceramics or cellulose. A porous film made of fluororesin is also one of the preferred supports.

Since the crown ether compound represented by the general formula (I) of the present invention has a long-chain alkyl group, Ro in the formula can be stably retained in a solid film or liquid film, and can be used as a neutral for lithium ion selective electrodes. It shows excellent performance as a carrier.

As described above, the sensitive membrane according to the present invention uses a 14-crown-4 compound substituted with one long-chain alkyl group as a neutral carrier, and the crown ether compound is used as a neutral carrier to absorb interfering ions such as sodium ions and potassium ions. Regardless of the presence of This makes it a sensitive membrane for lithium ion selective electrodes of high practical value.

Next, the alkyl substitution 1 represented by the general formula (I) of the present invention
A typical example of a method for producing a 4-crown-4 compound and its physical property values will be shown.

Production Example 1 Alkyl substitution 14 in which Ro is n CnHg and R1 and R2 are hydrogen atoms or methyl groups in general formula (1)
- Various crown-4 derivatives were produced.

10 mmol of 2-methyl-2-dodecyl-1,3-propanediol (2,
58Q) was dissolved, 25 mmol of sodium hydride was added thereto, and after refluxing for 30 minutes, approximately 50 mmol of sodium hydride was added.
Millimole of lithium perchlorate (5 g) was added, and then 11 mmol of 1,9-tosiloxy-3,7-sioxanonan (5.20 g) dissolved in 5011 dioxane was added dropwise with good stirring.

After the dropping was completed, refluxing was continued for 12 hours, and then dioxane was distilled off and concentrated to about 501f. Cool to room temperature, 2
After adding 0.0 xl of water and neutralizing with dilute hydrochloric acid, chloroform extraction was performed and the chloroform layer was concentrated to obtain a waxy substance. After heating and dissolving this in n-hexane, the liquid was cooled to precipitate unreacted glycol, which was recovered and removed, and then concentrated to obtain a pale yellow oil.

This was then subjected to silica gel column chromatography (benzene/methanol, 1-5% methanol),
Ro = n-Ca, LHts, Rt = CHa,
The target product in which R2=H was purified. R.

=n Ctt R25, Rt =H, R2=H compounds were made in exactly the same way except that 2-methyl-2-dodecyl-1,3-propanediol was changed to 2-dodecyl-1,3-propanediol. obtained.

Ro −n −CIZH25, R1=H, R2=CHa
The compound changes 2-methyl-2-dodecyl-1,3-propanediol to 2-dodecyl-1,3-propanediol, and converts 1,9-tosyloxy-3°7-sioxanonan to 5,5-dimethyl- 1,9-tosyloxy-3,7-
It was obtained in exactly the same manner except that thioxanonan was used. Ro=nc12HQ5. Rt=CHa, R2=
The CH3 compound converts 1,9-tosyloxy-3,7-thioxanonan into 5,5-dimethyl-1,9-tosyloxy-
It was obtained in exactly the same manner except that 3,7-thioxanonan was used.

Table 2 shows an example of the physical property values.

Production Example 2 In general formula (1), Ro is ncaHt7, R and R2 are hydrogen atoms or methyl groups, alkyl-substituted 14-
Various Crown-4 derivatives were produced.

Ro = n-08 in exactly the same manner as in Production Example 1 except that 2-methyl-2-dodecyl-1゜3-propanediol was changed to 2-octyl-1,3-propanediol.
Ht+7. The target product in which R□=H and R2=H was purified. Ro -n-C8H17, Rt=CHa, R2=H
The compound was obtained in exactly the same manner except that 2-methyl-2-dodecyl-1,3-propanediol was changed to 2-methyl-2-octyl-1,3-propanediol. R.

=n C8HIT , R1=H, R2=CH3 (7) The compound changes 2-methyl-2-dodecyl-1,3-propanediol to 2-octyl-1,3-propanediol and also converts 1,9- Tosyloxy-3゜7-thioxanonan to 5,5-mesityl-1,9-tosyloxy-3,7-
It was obtained in exactly the same manner except that thioxanonan was used. Ro = n -Ca H + 7',, Rt = CHa
, R2=CHa, 2-methyl-2-dodecyl-1,3-bu[Jpanediol was changed to 2-methyl-2-octyl-1,3-propanediol, and 1,9-tosyloxy-3 It was obtained in exactly the same manner except that 5,5-dimethyl-1,9-tosiloxy-3,7-thioxanonan was used instead of 7-thioxanonan.

Table 3 shows an example of the physical property values.

Table 3 Production Example 3 The procedure was carried out in exactly the same manner as in Production Example 1 except that 2-methyl-2-dodecyl-1°3-propanediol was changed to 2-octadecyl-1°3-propanediol. TR6=n −
C,? The target product with H3q, Rt=H, and R2=H was purified. Ro = n C1g HJ7.

The compound where Rt = CH3, R2 = H is 2-methyl-2
-Dodecyl-1,3-propanediol to 2=methyl-
It was obtained in exactly the same manner except that 2-octadecyl-1,3-propanediol was used. Ro=n-cl
g l-137, Rt = H, R2 = CH3, 2-methyl-2-dodecyl-1゜3-propanediol is changed to 2-octadecyl-1゜3-propanediol, and 1,9-tosyloxy- 3,7-thioxanonan 5
．． It was obtained in exactly the same manner except that 5-dimethyl-1,9-t-kyloxy-3,7-thioxanobune was used.

R.

-n-c,? H37, Rt=CH3, R2=CH
Compound 3 converts 2-methyl-2-dodecyl-1,3-propanediol into 2-methyl-2-octadecyl-1,
Change to 3-propanediol, 1,9-tosyloxy-3
,7-Shioxanobune was changed to 5,5-dimethyl-1,9-tosiloxy-3,7-diAxanonan.

Table 4 shows an example of the physical property values.

Table 4 Production Example 4 R6-n C was produced in exactly the same manner as in Production Example 1 except that 2-methyl-2-dodecyl-1°3-propanediol was changed to 2,2-dioctyl-1°3-propanediol.
8H1? *Rt=nC8H17.

The target product with R2=H was purified.

Table 5 shows an example of its physical properties.

Table 5 Although the present invention will be described with reference to Examples above, the present invention is not limited to these Examples.

(e) Examples Example 1 In general formula (I), Ro -C+t R25, F'1
=CHs, 1% by weight of a crown ether compound which is R2-H, 0.7% by weight of potassium rcumtetrakis(p-chlorophenyl)borate and 70% by weight of 0-nido O phenyl octyl ether as a plasticizer. A polyvinyl chloride membrane was prepared. This sensitive film was cut into a circle with a diameter of 3 mm and attached to the lower part of the Qrion Mode 192 electrode.
Mol N84NOB / sample solution / polyhinyl chloride membrane / 1
Mol Li C (J/Aa CL Aa (7) The activity of lithium ions in the measurement sample solution (αv> and 7
The BNM potential difference (EMF/lit V) was measured and an inspection line was created. An example is shown in FIG.

As a result, the calibration curve showed a Nernst response over a wide range.

Next, various interfering ions M'' (M+ is Cs÷.

Rb', Ni', N84÷, Na' + Ba
2←.

The selectivity coefficient KLIM for Sr2 (meaning 1Ca2' and MO2÷) is determined by the mixed solution method, in which the activity of the interfering ion M4 in the measurement sample solution is kept at a constant αH, and the activity of lithium ions is labored. The potential was measured, and the lithium ion activity αL,+ was calculated until it no longer showed a Nernstian response, and this was divided by αH+.

That is, KL+m=α ÷/α busy.

The selectivity coefficient K LiNa for sodium ions is
1/10 times more than lithium ion, that is,
This shows that the sensitivity is about 145 times higher.

Example 2 Solid films were prepared in the same manner as in Example 1 using various crown ether compounds of the present invention as dichotral carriers, and + and +si were measured.

The logarithmic values of the selection coefficients are shown in Table 6, including Example 1, and the selection coefficients for various interfering ions are shown in Table 6 for each sensitive membrane consisting of compounds NO, 1, 2, 3, and 4 in Table 6. Figure 3 shows numerical values including those of Example 1.

(Margins below, continued on next page) Example 3 1% by weight of the same crown 1-thyl compound as in Example 1, 0% of potassium tetrakis(p-chlorovanyl)borate
．． 711%, 70% by weight of O-nitrophenyl octyl ether and 1% by weight of trioctylphosphine oxide as plasticizers was prepared, and the membrane was cut into circles with a diameter of 3 mm. The activity of lithium ions in the measurement sample solution and the potential difference between the electrodes were measured using the same electrode configuration. As a result, a linear relationship is established over a wide range of lithium ion activities, and L5
It showed KLIN-=-2,7.

(f) Effects As described above, the sensitive membrane of the present invention is a practical and extremely excellent membrane in terms of lithium ion selectivity, response time, and reproducibility.

[Brief explanation of drawings]

Figure 1 shows the logarithm of the selectivity coefficient for various ions (M ions) of electrodes using a total of four types of PVC membranes prepared with various dibenzo-14-4 plasticizers (solvents), 1o5K S:H It is a comparison graph showing. FIG. 2 is a Gunov diagram showing an activity calibration curve when the sensitive membrane of the present invention is used. Figure 3 is a comparison graph showing the difference between Figure 1 and Figure 2.

Claims (1)

[Claims] 1. General formula (■): (In the formula, Ro represents an alkyl group having 6 to 20 carbon atoms, and R1 and R2 each represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. An alkylmi-f-substituted 14-crown-4 derivative represented by 2. General formula (T): (In the formula, Ro represents an alkyl group having 6 to 20 carbon atoms, and R1 and R2 each represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms.) Alkyl@substituted 14 - A sensitive membrane for a lithium ion selective electrode, comprising at least one type of Crown-4M conductor as a neutral carrier. 3. The sensitive membrane according to claim 2, wherein the alkyl-substituted 14-crown-4 derivative is dispersed in a water-insoluble solid organic polymer to form a solid membrane. 4. The sensitive membrane according to claim 3, wherein the water-insoluble solid fabric III polymer comprises polyvinyl chloride, silicone rubber, or polymethacrylic acid ester. 5. The sensitive-6 film according to any one of claims 2 to 4, wherein the alkyl-substituted 14-crown-4 derivative is dissolved in a water-insoluble organic liquid to form a liquid film. 6. The water-insoluble organic liquid is a higher alcohol, a nitro-substituted product or a halogen-substituted product of an aromatic or aliphatic hydrocarbon,
The sensitive membrane according to claim 5, which is an aromatic ether.