JPS6277374A - Bis(monoaza-12-crown-4) derivative and use thereof - Google Patents

Abstract

NEW MATERIAL:The bis(monoaza-12-crown-4) derivative of formula I (A is bivalent organic group). EXAMPLE:The compound of formula II. USE:Sensitive membrane for sodium ion-selective electrode. PREPARATION:The compound of formula V which is one of the compound of formula I can be produced e.g. by (1) reacting (A) a substituted alkanediol corresponding to the bonding part of the crown ring, e.g. the 2-substituted-1,3- propanediol compound of formula III (R1 is R2 are H or 1-20C hydrocarbon group) with (B) p-toluenesulfonyl chloride in pyridine and (2) reacting the resul tant compound of formula IV with a monoaza-12-crown-4-compound in ace tonitrile in the presence of sodium carbonate.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to bis(monoaza-12-crown-4) derivatives and their uses, particularly to sensitive membranes for sodium ion selective electrodes.

(b) Conventional technology In general, an ion-selective "tJJi electrode" is an electrode in which the concentration of a specific ion in a solution is indicated by the membrane potential indicated by the membrane electrode. This is a typical example.

By the way, the sodium ion I IJlt in raw i4-
is closely related to the metabolic reactions of the living body, and the measurement of this ion content in the living body is often used in the diagnosis of various diseases such as hemodialysis, high-grade J1 symptoms, renal disease, and minor disorders. However, conventionally, spectral methods such as flame analysis have been mainly used for this measurement.

However, such spectral measurement requires large equipment and takes time to measure, making it unsuitable for use in the field of diagnosis. There is a strong demand for the development of small-sized devices. For this reason, a method using a glass electrode has recently been proposed, but as is well known, glass electrodes are easily damaged and have a relatively short lifespan. On the other hand, the antibiotics palinomycin and monensin, which are macrocyclic peptides, have stable Kfl with alkali metals.
Utilizing the property of forming a j-form, a liquid film in which these are dissolved in an aromatic organic solvent as a neutral carrier has also been proposed. However, palinomycin shows higher selectivity for potassium ions than for sodium ions, and although monensin forms a complex with sodium ions, it is easily interfered with by coexisting ions such as potassium ions, so both Not used for sensitive membranes for sodium ion selective electrodes.

Generally practical!・Because it is a lithium ion selective bamboo electrode, it has high selectivity for sodium ions without being substantially affected by the interfering effects of potassium ions and ammonium ions that often coexist with sodium ions. It is also necessary that the response time is sufficiently short. As a practical sodium ion selective electrode that satisfies these requirements, Japanese Patent Application Laid-Open No. 58-9285
There is an electrode described in Publication No. 2. The selection 1.1 number KN which indicates the selectivity of this electrode for sodium ions in the presence of potassium ions is 8X10-'', which means that from this electrode 4+1, it is 6125( However, it was still insufficient when the concentration of potassium ions in the object to be measured was high.

(C) Purpose This invention was made to solve and overcome the above-mentioned problems, and it is possible to quickly and efficiently transfer sodium ion Δ into a cylinder. With 1 selection, reproduced with Takakasu Tα f'l yo < al1
Butrium is enough for 1j1! Bamboo
The main purpose is to provide the fi1Φ sensitivity IIr).

2) Structure Thus, according to this invention, general formula (■): (into the formula 2
Bis(monoaz-
12-Crown-4) iAj9 (A sensitive membrane for a sodium ion selective electrode is provided, which is characterized by containing at least one type of wood as a carrier.

Such bis(monoal, /'-12-
Knoun-4) Derivatives are new) jA which are not described in the literature themselves.
It is a group of compounds.

Therefore, according to the present invention, there is also provided a bis('U: noary-12-crown-4) derivative represented by the general formula (J).

” Two self-reflection screws (Monoother 12-Crown-4)
Preferred examples of derivatives include m=general formula (I
Examples include compounds represented by a).

General formula (Ta): In the formula, X and Y have 1 to 5 crosslinked atoms constituting the molecular chain.
A divalent organic group that is, for example? CH21 m=1~
s, -C-0-CI-12-CI-17-+C
H200H20H2-, etc. 1° Here, the number of crosslinking atoms means the number of skeletal atoms forming the main chain of the molecule. Therefore, for example, if X J> and Y are -4-C1]2: m-1
-5, the number of crosslinking atoms is m=1 to 5, and when -C-0-CH2CH2-, it is 4.

R1 and R2 are each a hydrogen atom or a carbon number of 1 to 2
0 hydrocarbon group, n means an integer of 1-3.

Bis(monoaza-1) represented by such general formula (I)
2-Crown-4) derivatives include, for example, (1) a diarynetic alkanedial corresponding to the bonding moiety of the crown ring, for example, the general formula (Ib'') (wherein R1 and [<, represent the general formula <1a
) 2-Kubikae-1, 3-7 expressed by the same symbol as the definition in )
11 Pandiol compound and p-t~luenesulfonyl chloride are reacted in pyridine to form compound (Il]')
Synthesize.

(Tb″)
(A b' ) Can be obtained as compound (1b) by reaction at the bottom right.

■ In addition, R0 and R2 in the general formula (IC") C represent the corresponding UH alkane sulfate, such as a 2-substituted 4%-1,3-propanedicarboxylic acid compound represented by the general formula (Ia> and In1-). Compound (IC') was synthesized by reacting J rubonic acid and dionyl chloride in benzene, and then monoaryl "-1" having a functional group as shown below was synthesized.
In 2-crown-4 compound and benzene, A! Compound (IC) can also be obtained by reacting in the presence of ICN.

■ Furthermore, general 'A: (TI+'') (R1 in the formula
A corresponding hl/i-substituted alkanedicarboxylic acid such as a 2-iff/substituted-1,3-propanedial compound represented by 2 CI 2 COOC7Hs was reacted in methylene chloride to synthesize the compound (Id''), and then reacted with lithium aluminum hydride in a needle as shown below to synthesize the compound (Id'), and further as shown below. , p-t-ruenesulfonyl chloride in pyridine, then monoaza-12
Compound (1d) can also be obtained by reacting the -crown-4 compound with acetonitrile in the presence of sodium carbonate.

(Id') The sensitive membrane according to the invention is used as a solid membrane or a liquid membrane. The solid film is formed by uniformly dispersing the pismonoa IJ' crown ether derivative in a water-insoluble solid organic polymer as a support.

The polymer forms a matrix to support the carrier bismonoaryl crown ether in the form of a film, and prevents the elution of 4-tria into the aqueous sample solution, and also prevents the sodium ions in the aqueous sample solution from becoming 7 Any water-insoluble solid polymer can be used, but typically polyvinyl chloride, polymethyl methacrylate, polyFl#I vinyl, silicone rubber, paraffin, One type or a mixture of two or more types of collodions can be used.

Sensitive membranes using polyvinyl chloride as a support are usually prepared by dissolving polyvinyl chloride, a plasticizer, and a hismonoazacrown ether compound in a suitable low-boiling organic solvent such as tetoxyhydrofuran. Gradually the solvent inside? By emitting A, it is formed in the shape of ii). A plasticizer is used to give the resulting sensitive film an appropriate degree of flexure, and examples include dibutyl phthalate, dioctyl phthalate, and 0-nitrophenyl octyl ether. Either can be used.

In addition, like Sensitive II9, which uses silicone rubber as a support, 11 (J) formed from a bismonoazacrown ether derivative and a silicone rubber monomer is mixed with a silane compound for cross-linking in an appropriate organic solvent. It is also possible to manufacture the product by molding it into a small film shape and using 119 solvent from the molded product.

The amount of the bismonoaza crown ether derivative in the solid film is 0.5 to 20% by weight, preferably 1 to 15% by weight.
It is desirable that If the content of the bismonoaza crown ether derivative is too small, the response will be poor, and if it is too large, it will not only be difficult to disperse it uniformly during hand coalescence, but also cause problems! It's ¥pan. When using a plasticizer in combination with polyvinyl chloride as a support, the appropriate amount of plasticizer in the solid film is 30 to 80% by weight (5+i%).

In particular, 50 to 70 weight u1% is excessive.

The liquid film is formed by dissolving the bismonoazacrown ether derivative in a water-insoluble polar organic solvent.43 Examples of the polar organic solvent include higher alcohols, aromatic or aliphatic hydrocarbons, and Substituted halogens, aromatic ethers, and certain organic phosphorus compounds 'I5' are used. Preferred specific examples include iJ + -decanol,
Nitrobenzene, Kuro "1 Benzen, Bu 1" 1 Hen U -U -UN, Gino Tnill J -Cill, 1,2 -Gichlorethane, Gee N-), Ru 1 Ruff J Nil Small Sphoner 1 -Elephant. Bisshinori 'crown 1-chill X in solution jQ
The content of 79 bodies is 0.5 to 20 weight h1 for the same reason as above.
%, preferably 1 to 10 weight ω%.

The liquid film is usually held in a porous support such as Xeramix or Hirurose and used as an electrode.

A porous film made of a knot resin, for example, a millibore film 1, is also one of the preferred supports.

The sensitive membrane according to the present invention is a constant chain bridge as shown below.
The bis(monoaza-12-crown-4) derivative bonded by the J structure is used after cutting, and the above bismonoaza-crown ether derivative is free from the presence of interfering ions such as potassium ions and ammonium ions. Irrespective of the concentration of Na1~S, a specially and selectively stable 2:1 forceps are formed between the two crown rings at /υ. The object of the present invention is to provide a sodium ion-selective electrode-sensitive membrane that can measure with high selectivity, has a short response time, and has excellent reproducibility, and has high practical value.

(Small) Example A production example of the bis(monoaza-12-crown-4) derivative of the present invention and its physical property values are shown. However, since all of the monoazacrown compounds with functional substituents used as raw materials are already known, a description of their manufacturing method will be omitted.

Note that this invention is not limited to the examples.

[In the general formula (Ia >, R5 is hydrogen, 1- and 2 are dodecyl groups, X=Y=CH2, n=f″C-) A bis(monoaryl-12-crown-4) derivative was synthesized. .

119 Water Ahi 1-21 ~ Lil 100ν! ni, monoaza
12=crown-4IQ (5.7 mmol), carbonate 1-lium 2.650 (2.5X 10-' m(
), and while stirring, blow nitrogen gas through the mixture.
Refluxed. Zoko Hair Se 1~Nitrile 301j! 1.6 g (2.8 mmol) of 2-dodecyl-1,3-propanedi-A-luditosylene dissolved in was added dropwise, and the mixture was reacted for 5 hours under a nitrogen atmosphere. After the reaction is finished, the temperature is returned to room temperature, the acetonide is distilled off, and ionized water is obtained! +
Add 011, 20-3011 glue [] 3 with Roform
Extracted ~4 times. The chloroform layer is 11f in 2011
It was washed 2 to 3 times with 2-ion water, dried with FAM purium, filtered, and the crude q product obtained by distilling off 1 vol of chlorine was purified by G p c. The desired product was obtained.

Table 1 shows the physical properties of this compound.

(Continued in the margin below.) Manufactured j-shield example 2 - In the IKI formula 1a, R1 is a methyl group, R2 is dodecyl 1B, and X=Y--COCH2CH2-.

A bis(monoaza-12-crown-4) derivative in which n=1 was synthesized.

Katsumi Benzene 200 xi, N-Hydroxydiyl Monoother 12-Crown-A 1. ．． 53Q (71
11m0l), A(I CN 1.34(](10
mIIlol) was added and stirred for r'P draft rF+1oe. Dehydrated benzene 30r there! 2-dodecyl-2-methylmalonyl chloride dissolved in 0.97 (+ (3 m
mol> was added dropwise. After completion of the dropwise addition, the temperature was raised to 1α, and the mixture was stirred and refluxed for -1 week. After the reaction is completed, it is filtered and passed through a hyrite column, and then benzene is distilled off and the removed crude product is purified by GP.
It was made viscous by C and the substance was removed.

The physical properties of this compound are shown in Table 2.

(The following is a blank space, continued by Tsugusada.) Negative example 3 In general formula 1a, in ], 1 is aqueous, R2 is a dodecyl group, X=Y-CI+2 0 0H2C1-42-, n=1
A bis(monoaza-12-crown-4) derivative was synthesized.

) Tax water aretoni! ~Lil 100if, Monoaza-12
-Crown-41,05g (G mmol>, sodium carbonate Is 2.!M(+ (2,4X10-2 mo
1), stirred and refluxed 1g2 while bubbling nitrogen gas, 301! 1.73 (2.7 mmol) of 5-dodecyl-3,7-sioxanonan-1,9-diol di-1-sylate dissolved in dehydrated acetodi[lyl] was added dropwise. The crude product obtained by extracting, drying with sodium sulfate, and distilling off chloroform was subjected to a vi purification using GP, C to remove the target substance.

Table 3 shows the physical properties of this compound.

(Continued in the margin on the next page.) Next, examples of the sensitive film for a selective f/L electrode of the present invention will be described. Note that this invention is not limited to the examples.

Example 1 In the general formula (Ta), R1 is a water-based atom, R2 is a dodecyl group, X = Y = CHj, n = 1
10 mg of Bismono Aza Ground M1, which is o
- Nitrov J, = 100 mg of Luokjile Edel and 40 tng of polychloride chloride [Cotran 3'I! 1. Dissolve natural seafood in a veterinary tank and add tetrahydrofuran at room temperature. A sensitive membrane using polyvinyl chloride as a support was prepared. This sensitive membrane was cut into a circle with a diameter of 3 mm and attached to the bottom of the Qrion Model 9'2 electrode.A standard calomel electrode was used as the external reference electrode.
AO・A (IcΩ/IMNaCρ/elf/measurement sample rice solution 1
0.1MNH4NO3/KCρ(saturated)/H(12Cρ
2 ・Measure the activity h1 of sodium ions in the sample solution and the potential difference between the electrodes using a 1-1g electrode configuration, and check ff1
Created FA. Furthermore, this measurement is based on Co
PH=1 using rning pH meter 130 type
The temperature was 0.256±0.1°C.

As a result, as shown in FIG. 1, the test line was linear over the pNa range of 4 to 1, that is, it showed a Nernst response.

Next, the selected it number KN for the interfering ion M' is determined by the mixed solution method (for the experimental method, see GJ, Moody and J, D, R, In other words, the activity of the interfering ion M+ in the measurement sample solution is kept at a constant aK Then, by changing the FfiFil of sodium ions and measuring the inter-electrode occupation, the utilization aN- of 1~lium-A, which no longer shows a Nernst response, is determined, and this is removed with aM0 to obtain methane. Chi KNIIM” =
a Ni”/ayl+.

As a result, the selectivity coefficient K for sodium ions was 1x10-3 as a value of two experiments.

This means that the sensitive membrane is more sensitive to potassium ions than to lithium ions. -31 also indicates that the level of snoring is 1000 times higher. Similarly, KN Engineering NH Gachi1xH1
', and the selectivity 1/I of prI-ium ions relative to ammonium ions is also extremely high.

Practical example 2 God's screw of the present invention (mono ant''-12-crown-4
) A solid film was prepared in the same manner as in Example 1 using Gito A7- as the derivative, and KNO,K was measured. Table 4 shows the logarithm of KNαK obtained by fl′I Song.
Shown below. Here, the value of n is 1.

(Continued in the margin on the next page.) Table 4 Effects As described above, the bis(monoaryl-12-crown-4) derivative of the present invention has excellent response properties and selectivity for sodium ions. Sensitive films for tel-electrodes were evaluated in terms of reproducibility and the like.

[Brief explanation of drawings]

FIG. 1 is a graph illustrating a detection line of a selective electrode using the sensitive membrane of the present invention. 1st r! ! J-log CINC++

Claims (1)

[Claims] 1. General formula (I): ▲There are numerical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A represents a divalent organic group) bis(monoaza-12-crown) -4) Derivatives. 2. General formula (Ia): ▲Mathematical formula, chemical formula, table, etc.▼(Ia) (In the formula, X and Y are each a divalent organic group with 1 to 5 crosslinking atoms constituting the molecular chain. , R_1 and R_2 are each a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms,
The derivative according to claim 1, wherein n is an integer of 1 to 3. 3. General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) At least one of the bis(monoaza-12-crown-4) derivatives represented by (in the formula, A represents a divalent organic group) A sensitive membrane for a sodium ion selective electrode, characterized by containing one type of carrier. 4. General formula (Ia) ▲Mathematical formulas, chemical formulas, tables, etc.▼(Ia) (In the formula, X and Y are each a divalent organic group with 1 to 5 crosslinked atoms constituting the molecular chain, R_1 and R_2 are each a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms,
4. The sensitive film according to claim 3, which contains as a carrier at least one kind of derivative represented by (n means an integer from 1 to 3). 5. The sensitive membrane according to any one of claims 3 to 4, which is formed into a solid membrane by dispersing a bis(monoaza-12-crown-4) derivative in a water-insoluble solid organic polymer. 6. The water-insoluble solid organic polymer is polyvinyl chloride, polymethyl methacrylate, polyvinyl acetate, silicone rubber,
6. The sensitive membrane according to claim 5, comprising at least one of paraffin and collodion. 7. The sensitive membrane according to claim 3 or 4, wherein a bis(monoaza-12-crown-4) derivative is dissolved in a water-insoluble organic liquid to form a liquid film. 8. The sensitive membrane according to claim 7, wherein the water-insoluble organic liquid is a higher alcohol, a nitro-substituted or halogen-substituted aromatic or aliphatic hydrocarbon, an aromatic ether, or an organic phosphoric acid compound.