CS247158B2

CS247158B2 - Method of complex forming ring ethers production

Info

Publication number: CS247158B2
Application number: CS559082A
Authority: CS
Inventors: Laszlo Toeke; Bela Agai; Istvan Bitter; Ernoe Pungor; Klara Szepesvary; Ernoe Lindner; Maria Horvath; Jenoe Havas
Original assignee: Magyar Tudomanyos Akademia
Priority date: 1982-07-22
Filing date: 1982-07-22
Publication date: 1986-12-18

Abstract

Způsob výroby komplexotvorných kruhových etherů obecného vzorce I, ve kterém R, η, X, Y a Z mají definovaný význam, vyznačující se tím, že se isokyanát obecného vzorce II, ve kterém Y a n mají výše uvedený definovaný význam, nechá reagovat se sloučeninou obecného vzorce III, ve kterém R, X a Z mají výše uvedené definovaný význam, v prostředí organického aprotického rozpouštědla při teplotě v rozmezí 0 až 50 °C při molárním poměru sloučenin obecných vzorců II a III 2:1, popřípadě v přítomnosti 0,1 až 0,5 molárních % terciárního aminu, s výhodou triethylaminu, jakožto katalyzátoru, načež se vzniklý produkt obecného vzorce I izoluje.Method of making complexing agents ring ethers of the formula I, wherein R, η, X, Y and Z are defined meaning that the isocyanate is of formula II in which Y and n are as defined above, is reacted with a compound of the general formula of formula III wherein R, X and Z are as defined above defined meaning, in the environment an organic aprotic solvent at at a temperature in the range of 0 to 50 ° C at molar the ratio of compounds of formulas II and III 2: 1, optionally in the presence of 0.1 to 0.5 mole% tertiary amine, preferably triethylamine as a catalyst, followed by the product of general formula I isolates.

Description

247158

The present invention relates to a process for the preparation of novel ring ethers capable of forming cationic complex compounds, which ring ethers can be used to form ion selective membrane electrodes.

The use of ring ethers is widespread due to their ability to form complexes with different cations. The extent of complex formation (the stability constant of a complex) depends on the cation, apart from the geometric properties of the circular ether, such as the number of heteroatoms, also on the solvent.

The stoichiometry of the formed complex is influenced by the diameter ratio of the circular ether of the cation diameter. All of the above factors rely on the use of circular ethers as the active component of ion-selective membrane electrodes. Various substances have been used in the last 17 years, such as inorganic compounds, various ion exchange compounds, electrically charged or uncharged complexing agents, as ion selective electrodes for measuring various anions (halides, pseudohalogens, nitrates, etc.) as well as various cations (alkaline ions) metals, alkaline earth metal ions and heavy metal ions, etc.) (Karl Camman, Das Arbeiten mit ionenselektivenElektroden, Springen, Berlin, Heidelberg, New York, 1977: Peter L. Bailey, Analysis with ηοη-Selective Electrodes, Heyden Publishing , London, New York, Rheine, 1976).

The individual electrodes have different active components, mechanical and dynamic properties, and various types. selectivity factors, which latter factors are the most important parameters in terms of use. In the most important field of application in practice, ie in the field of biochemical use, those electrodes that are suitable for controlling ionic post-cellular metabolism in the body are particularly important. Of particular interest in measuring probes suitable for the measurement of biologically important are electrodes suitable for measuring cations from the group of sodium, potassium, calcium and magnesium. In life processes, measurement of potassium ions is particularly important. This explains the large number of research papers on the creation of potassium-selective electrodes, their properties, and the optimization of their preparation.

The best potassium-selective electrode used so far is the ion selective electrode having valinomycin as active ingredient (Swiss Patent No. 479,870).

For biological use, the most preferred property of this electrode is its sodium ion selectivity factor: it is about 3 x 10 The valinomycin potassium electrode has been found to have greater or equal selectivity for large-volume alkaline metal ions (Rb +, Cs +). ) than K + ions, ie this electrode measures these ions better or with almost the same selectivity as potassium (1. AR Pioda, V. Stankova and W. Simon, Anal. Letters, 2 (1969) p. 665).

Since, in nature, alkali metal ions often coexist, such a selectivity factor may be disadvantageous in the case of potassium electrodes prepared for non-biochemical purposes. The above drawbacks can be eliminated without a noticeable reduction in the selectivity to other ions when the bis-ring compounds are used as the ion selective substance, the two rings of which are linked together via an aliphatic chain.

Kimura et al. (K. Kimura, T. Muedn, ii. Tai: i & T. Shono: J. Elektroanal.

Chem. 95 (1979) ctr. 91-101, K. 1'tmur.i, li. T.iiniira, T. shono ·. Hulí. Chem. Soc. Japan, 53, 3, 4, 7, 5, pp. 547-548 (1980) have described two such group compounds and their electroanalytics. These compounds have a common structural member: two benzo-15-ring-5 units, linked to dicarboxylic acids via oxygen or nitrogen atoms.

The practical applicability of these compounds cannot be assessed, since the electroanalytical evaluation of these compounds is not mentioned above; in the articles only the ion selectivity data, alkali metal, is contained.

It has now been found that some bis-ring compounds meet the requirement for selectivity with alkali metal and alkaline earth metal ions. These compounds contain the nitro groups attached to the aromatic ring of the bis-ring ether structural unit, and the chain linking the ring ether unit is linked to the aromatic ring via the urethane and the aromatic ring respectively. urea group.

The nitro groups form a hydrogen bond with an NH unit of the urethane chain. urea groups. Both of these circular ether units occupy the optimum steric position required to form a complex with only potassium ion, thereby producing a large potassium selectivity.

It is surprising that this selectivity does not depend on the nature of the chain linking the two ring ether units (number of heteroatoms and their type) and on its length.

Many of the novel compounds produced by the process of the present invention are suitable for forming potassium ion selective electrodes. The electrodes made from these novel compounds have the same potassium ion sensitivity sensitivity as the valinomycin-based potassium concentration of the potassium electrodes, with their selectivity factor for the alkali metal bulk ionization being more favorable (0.1 to 0.01) than the electrode selectivity factor. basivalinomycin, whose selectivity factor is between 4.6 and 0.5, but the selectivity factor for alkaline earth ions is the same as for valinomycin-based electrodes (KK)

The novel compounds of the present invention can be represented by the formula (I)

NR x CH n -Z CH 2 X Ύ o O'''Or NR 0, (i) wherein R is hydrogen or C 1 -C 4 alkyl, n is 1 or 2, X is oxygen, sulfur or -NH, Y is hydrogen or nitro, and Z is a bond, - (CH 2). -CH, -O-CH-CH-O-CH3 - or a group of formula (2) 247158

(1), (2) or CH 0 -O-CH, - w

The process according to the invention for the preparation of the compounds of the formula I is characterized in that the isocyanate of the general formula II (II) where

Y is as defined above and reacts with a compound of formula III

RX - CH2 - Z - CH2 --XR (III) (wherein R, X and Z are as defined above) in an organic aprotic solvent environment. The reaction may be carried out at a temperature in the range of 0 to 50 ° C in an environment of chlorinated hydrocarbons, ethers, optionally in the presence of tertiary amines such as triethylamine, in a molar amount of 0.1 to 0.5% as catalyst.

The compounds of formulas II and III are used in a molar ratio of 2: 1. The product is isolated by filtration or evaporation of the solvent followed by recrystallization from a suitable solvent such as ethyl acetate or methyl isobutyl ketone.

The isocyanates of the formula II used as starting material in the process of the invention have not been described in the technical literature to date. Compounds of formula (II) may be prepared by known procedures for reacting a compound of formula (IV)

. Y nh2 i <(IV), i-247158 in Y Y n ni.i? with the phosphogenia at the high temperature boiling point aromatic solvent. Some of the novel compounds prepared by the process of the invention and their mixtures are used as active components of ion-selective electrodes as follows: a) the selected compound or compounds are incorporated into the polyvinyl chloride carrier phase in an amount of 0.2 to 3% by use of a suitable plasticizer such as phthalic acid esters, sebacic esters or o-nitrophenyloctyl ether. b) The selected compound or compounds are incorporated into a silicone rubber or other polymer such as polyamide, polyvinyl chloride, polyethylene whose dielectric constant is in the range of 2 to 30. c) The selected compound or compounds are deposited on a porous membrane, dissolved in a veneer. a suitable solvent, preferably in the plasticizers mentioned in paragraph a).

Membranes prepared as described above are placed in a suitable electrode and connected to a suitable reference electrode to form an analytical instrument. Examples

Preparation of the isocyanates of formula (II) 0.1 moles of the amino compound of formula (IV) are dissolved in 500 ml of chlorobenzene and the resulting solution is added to 150 ml of chlorobenzene saturated with phosgene at room temperature with stirring. The reaction mixture was then slowly heated to boiling.

When hydrogen chloride gas escapes, the phosgene feed is interrupted and excess phosgene is blown off by boiling nitrogen and argon gas (for about 1.5 to 2 hours). The chlorobenzene was then distilled off under reduced pressure and the residue was purified as shown in Table I. The following compounds were prepared as described above: (IIa) 2-nitro-4,5- (1 ', 4', 7 ', 10', 13 '). pentacyclopentadec-2'-en) phenyl isocyanate, (IIb) 3,4- (1 ', 4', 7 ', 10', 13'-pentaoxacyclopentadec-2'-en) phenyl isocyanate, (lc) 3,4 - ( 1 ', 4', 7 ', 10', 13 ', 16'-hexaoxacyclooctadec-2'-en) phenyl isocyanate.

Table I

Compound of formula (II) Data from the preparation of 4'-isocyanatobenzo-m-ring-n and its physical and spectroscopic data

Method Temperature Analysis (%) IR spectrum Mole production melting empirical calculated- (cm -1) J spherical ° C formula teno zeno N = C = 0 mass-molecular weight mass MX (%) crystallization 116 C15H18N2 ° 8 C 50 , 85 51,19 H 5,12 4,81 2 270 - Benzene benzene mixture 354 N 7,91 7,81 247158 Table 1 Example (II) S. η Y Production method 'Melting point ° C Analysis (%) nale - zene IR spectrum Molecular formula molecular weight calculated, -1, (cm) N = C = O spherical mass MX (%) 2 b 1 H vacuum 38 C15H19NO6 C 58.24 57.89 distillation H 6 , 19 6.59 2 300 309 a) 309.30 N 4.53 4.34 (35) 3 c 2 H vacuum b) C17K23NO7 C 57.78 57.93 distillation H 6.56 6.71 2 290 353 353 , 36 N 3.96 3.89 (3.7) a) Melting point: 150 to 152 ° C / 13.3 Pa b) Melting point:. 168-180 ° C / 13.3 Pa Yield: a: 94%; b: 70%; c: 74%

Preparation of the two-ring compounds of formula (I)

A solution of 0.2 mol of isocyanate (formula IIa, b, c) in 500 ml of anhydrous dioxane or anhydrous chloroform is stirred at room temperature for 1 to 2 hours with 0.1 mol of suitable glycol (6.2 g of ethylene glycol, 10.6 g of diethylene glycol, 12.2 g of thioethylene glycol, 19.8 g of 2,2'-bis-hydroxyethylpyrocatechin, 12.8 g of 2,5-dihydroxymethylfuran, 13.9 g of 2,6-dihydroxymethylpyridine) or 0.1 mol of alpha, oinega-polymethylenediamine (6.0 g of ethylenediamine, 7.4 g of 1,3-propylenediamine, 11.6 g of 1,6-hexamethylenediamine). Using hydroxyl-containing compounds, 0.005 mol of triethylamine catalyst is used.

Isolation a) If the resulting product is precipitated, it is filtered off, washed with dioxane or chlocoform and recrystallized from the solvent shown in Table II. b) If the product does not precipitate, then the solvent is distilled off under reduced pressure and the residue is recrystallized from the solvent shown in Table II. The following compounds were prepared as above: (Ia: ethylene-1,2-bis-N- (2'-nitro-4 ', 5' - {1 ", 4", 7 ", 10", 13 ") -pentaoxacyclopentadec-2 "-en) phenyl] carbamate (1b): ethylene-1,2-bis-N- (3 ', 4' - (1", 4 ", 7", 10 ", 13", 16 "-hexaoxacyclooctadec-2" -en) -phenyl] -carbamate (1c): diethyl ether-2,2'-bis-N- (2-nitro-4 ", 5" - {1 "', 4") ','',10'',13''-pentaoxacyclopenta-dec-2''- en) phenyl / carbamate (1d): diethyl ether-2,2'-bis-N- (3 ", 4") - (1 ", 4"', 7 "', 10"'/ 13 "' - pentaoxacyclopentadec-2" -en) -phenyl / carbamate (1e): diethyl ether-2,2 * -bis-Ni 3 ", 4 "- (L"', 4 "*, 7"', 10 "*, 13", 16 "'- hexaoxacyclooctadec - 2"' -en-phenyl) carbamate. (1f): diethylsulfide-2, 2 '-bis-N- (2 "-nitro-4", 5 "- (1", 4 "', 7", 10 ", 13" pentaoxacyclo-pentadec-2 '' -en) -phenyl / carbamate 7 247158 (Ig): diethylsul - 2,2 -bi sN- / 1 ", -I" - (I ", 4"', 7 "', 1011 ', 13"''-pentaoxacyclopentadec-2)"'- (en) -phenyl] -carbamate (l): diethylsulfide-2,2 * -bis-N- / 3", 4 "- (1", 4 "', 7"', 10 "', 13 "', 16"' - hexaoxacyclooctadec - 2 "'-en) - phenyl / carbamate t (li): (1,2-phenylenedioxy) -dio th ~ L-2 ', 2 "-bis-N- (3", 4 "' - (1"",4"") , 7 "", 10 "", 13 "" -pentaoxy- 'cyclopentadec-2 "" -en) -phenyl] -carbamate (1J): (1,2-phenylendioxy) -diethyl-2 * , 2 "~ bis-N- (3"', 4 "'" (l '' *, 4 "'', 7"",10," l, l3 "", 16 "1 '- hexaoxacyclooctadec-2 "" -en) -phenyl] -carbamate (lk): (1,2-phenylendioxy) -diethyl-2 ', 2 "-bis-N- / 2" - nitro-4 "", 5 "' - (1 "", 4 "", 7 "", 10 "", 13 "-petnoxoxyclopentadec-2" - en) -phenyl / carbamate (II): 2,5-bis- (2'-nitro-4) 5 '- (1 ", 4", 7 ", 10", 13 "-pentaoxacyclopentadec-2" -en) -phenylcarbamoyloxymethyl / furan. Yield: 60-85%

Characteristic data for the above compounds (melting point, solvent for recrystallization, IR spectrum, 1 H-NMR spectrum, analysis) are shown in Tables II to IV.

Table II (I) Melting point where X is oxygen analysis, IR spectrum of carbamates of general formula (I) Example (I) n YZ Temperature Empirical Analysis <%) IR (KBr) No melting ° C formula calculated cm 1 molecular ^ NC-0 weight 0 2.1. a 1 no2 - 170-172 C32H42N4 ° 18 c 49.87 49.54 H 5.49 5.94 3 320 1 735 a) 770.67 N 7.27 6.96 2.2. b 2 H - 130-132 C36H52N2 ° 16 C 56.23 56.16 H 6.82 7.11 3 270 1 690 b) 768.79 N 3.64 3.45 2.3. c 1 N ° 2 -CH 2 OCH 2 - 98 C34H46N4 ° 19 C 50.12 50.27 H 5.69 5.58 3,320 1,735 a) 814.72 N 6.88 6.72 2.4 d 1H-ch2och2-84 C34H48N2 ° 15 C 56.35 56.33 H 6.68 7.07 3 260 1,715 b) 727.72 N 3.87 3.95 1,690 2.5 e 2 H -CH 2 OCH 2 '64 C38H56N2 ° 17 C 56.14 56.04 H 6.94 7.33 3 280 1.715 b) 812.84 N 3.45 3.44 1,690 2.6. f 1 NO2 -CH2SCH2 · 100 C34H46N4 ° 18 Ξ C 49.16 48.92 H 5.58 5.64 3,320 1,740 a) 830.70 N 6.75 6.15 247158

continuation of Table II

Example (I) η Y

Temperature Empirical Analysis (%). ,. on there C formula calculated molecular weight IR (KBr) -1 cm found

in NM in 'NC-0h0 2.7. g 1 H -ch2sch2 - 135 C34H48N2 ° 14S c 5 5.3.3 55.28 H 6.53 6.96 b) 740.70 N 3.78 3.77 2.8. h 2 H -ch2sch2 87 C38H56N2 ° 16S C 55.06 54.56 H 6.81 7.30 b) 728.82 N 3.38 3.16 3,280 1,7151,690 3,270 1,715 1,690 Recrystallization: a) from ethyl acetate b) from methyl isobutyl ketone

Table III

The carbamates of formula I wherein X is oxygen data for delta NMR spectra (ppm) (CDCl 3, ^) Example (I) m / n O-CH-, (ring) 2.1. and 15/5 / 7,67 / s, 2H 8,10 (s, 2H Ar-H-6 / Ar-H-3 / 3,6-4,4 / m, 32H /, 4, 45 ( s, 4H CO-CH% 2 ^ 2.2 b 18/6 H - 6.77 / s, 4H Ar-H-5.6 / 3.5-4.2 / m, 40H / 4, 37 / s 4H CO-CH 3, 6.98 / s, 2H Ar-H-3/0 2.3 c L5 / 5 nu 9 -CH 2 OCH 2 - 7.58 / s, 2H Ar-H-3 / 3.6-4.5 / m, 40H / 8.05 / s, 2H Ar-H-6 / 2.4 d 15/5 H -CH 2 GCH 2 - 6.7 6 / s, 4H Ar-H-5.6 / 2.2-4, 5 / m, 40H / c) 7.13 / s, 2H Ar-H-3 / 2.5 e 18/6 H -CH2OCH ^ - 6.82 / s, 411 Ar-H-5.6 / 3.5 -4.5 / m, 48H / 7, 10 / 3.211,, Ar-H-3 / 3.5-4.6 / m, a1 2 2.6 f 15/5 n ° 2 -CH2SC »2-7, 61 (s, 2H, AR-H-3), 90 (t, 4H-S-CH2) d) 8.05 / s, 2ΪΙ-Ar-Hb / 4, 36 / t, CO-CH112 and ) 2.7. g 15/5 H -CH 2 CH 2 -, 75 / s, 4 µl Ar-H, 5.6 / 3.5-4.5 / m and 2, 83 / t, 4H S-CH, / 4, 33/1 , CO-CH-, M 2 O a) 2.8. li 18/6 11 -CH ^ SCIl ^ - 6, 8G! s, 4II Ar-H-5,6 / 3,6-4,5 / mb 2, 88 / t, 4H s-ch 2 / 7.22 / s, 2H Ar-H-3/4, 38 / t , CC l-CH, / b) a) d)

gross unit 3 (· II binding constant b) gross unit 44 H in all cases d - 6 liz c) The CH 2 group of the chain is indicated by the formation of a multiplet at 3.34 and 4.31 ppm 2.9. (i) melting point: 148 - 1A (1 H, N, calculated: C :ť,,, znamená znamená stands for 1 hydrogen group of formula found: C r>, 4 22 'J'' ( (1) IKI b, 8) (3) IR spectrum: (KBr) Ϊ 0 -i μ) NC / 1690 cmý NH 0 NMR spectrum δ (ppm) 660 MHz, CDCl ^, TMS 3.5-4.6 O-CH 2 (m, 40H) 6.76 Ar-H-5.6 (s, 4H) 6.93 Ar-H (s, 4H) 7.12 Ar-H-3 (s, 2H) 9 247,158 n means 2 2.10. (Ij) melting point: 109 ° C (methyl isobutyl ketone) Y is hydrogen Z is a group of formula (3)

H, 6.38; N, 3.10; Found: C, 58.37; IR spectrum: NN 1 685 cm -1 NH 3 250 cm -1 1 NMR spectrum d elta (ppm i) (60 1 MHz, CDCl 3, TMS): 3.4-4.6 o-ch 2 (m, 48H) 6 76 Ar-H-5.6 (s, 4H) 6.92 Ar'-H (s, 4H) 7.14 Ar-H-3 (s, 2H) 2.11. (Ik) Melting point: 11 8-119 ° C n stands for 1 Y stands for NO 2 Z stands for group of formula Analysis for Η4θΗNO 50n4u20 (906.8) calculated: C 52, 98 H 5, 56 N 6.18% found: C 52, 87 H 5, 24 N 6.55%. IR spectrum (KBr)

In NC 1 735 cm -1 ýNH '3 300 cm 2.12. d1) melting point: 190 DEG-192 DEG C. (from the toluene / benzene mixture n = 1 Y = N @ 2 z = Analysis: For C36H44N4O19 (836.7) calculated: C 51.67 H 5.26 N 6.69 % found: C 52.39 H 5.95 N 6.67% IR spectrum (KBr) V NC 0 0 10 730 cm 1 ν> 350 3,350 NMR spectrum ppm (60 MHz, CDCl 3, TMS) 3.60 4.40 o-ch 2 (m, 32H) ring 5,10-ch 2 - (furan) (s, 4H)

Claims

247158 10 6.39 -CH = (furan) (s, 2H) 7.28 Ar-H-3 (s, 2H) 7.60 NH <2> H 8.05 Ar-H-6 (s, 2H). Table IV and IR spectrum data for ureas of formula Ia-d Melting point analysis Example z Melting point (° C) Empirical formula molecular weight Analysis (%) No. (I) Y calculated found 2.13. P N ° 2 -CH 2 - 235 C 33 H 46 N 6 ° 16 C 50.64 50.31 H 5.92 6.23 782.73 N 10.74 10.38 2.14. q H - <ch2) 4- 183 C33H48N4 ° 12 C 57.21 56.64 H 6.89 7.27 692.66 N 8.09 7.67 2.15. r n ° 2 - (ch2) 4- 230 C36H52N6 ° 16 C 52.42 52.50 H 6.36 6.44 824.80 N 10.19 9.70 2.16. s H - <ch2) 4- 183 C36H54N4 ° 12 C 58.84 58.69 H 7.41 7.68 734.80 N 7.63 7.39 2.17. t N02 - <ch2, ock2) 2 153 C36H52N6 ° 18 C 50.46 50.31 H 6.12 6.26 856.83 N 9.81 9.74 "Η ýNH ýH-C 3 370 1 700 3 280 1 620 1 660 Wide 3 370 1 690 3 280 1 630 1 680 Wide 3 380 3 300 1 690 SUBJECT OF THE INVENTION Process for the production of complexing ring ethers of the general formula I

wherein R is hydrogen or C 1 -C 4 alkyl, is 1 or 2 11 247158 X is oxygen, sulfur or -NH, Y is hydrogen or nitro, and Z is chemical bond, -CH 2 -, - (CH) -CH 9 -O-CH-CH-O-CH 9 - or a group of Formula 2

2 CH 3 CH 3 CH 2 CH 2 -, N V 'O (2) or CH 2 O 2 CH 2 characterized in that the isocyanate of the general formula (II) is ~ OO 0. / ° (li). wherein Y is as defined above, reacted with a compound of formula III (III) wherein R, X and Z are as defined above, in an organic aprotic solvent at a temperature ranging from 2: 1 to the compounds of formulas II and III optionally in the presence of a% tertiary amine, preferably triethylamine, as the catalyst, of the formula (I). up to 50 ° C at a molar-0.1 to 0.5 molar; the product formed