J. Phys. Chem. 1986, 90, 6571-6576
6571
Sodium Ion Complexation by Ionizable Crown Ethers in Methanol-Water Solvents. A Thermodynamic and Kinetic Evaluation of Side-Arm Interaction Raymond J. Adamic, Barry A. Lloyd, Edward M. Eyring,* Department of Chemistry, University of Utah, Salt Lake City, Utah 841 12
Sergio Petrucci, Department of Chemistry, Polytechnic University, Farmingdale, New York 11735
Richard A. Bartsch, Michael J. Pugia, Brian E. Knudsen, Yung Liu, and Dhimant H. Desai Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409 (Received: June 12, 1986; In Final Form: August 4, 1986)
The stability constants, log K , (ionized ligand) and log K2 (free acid), for Na' complexation by four monoionizable crown acid (l), ethers with a common sym-dibenzo-16-crown-5 polyether ring framework, sym-dibenzo-16-crown-5-oxyacetic sym-dibenzo-16-crown-5-oxypropanoicacid (2), sym-dibenzo-16-crown-5-propanesulfonicacid (3), and sym-dibenzo-16crown-5-oxymethyl phosphonic acid monoethyl ester (4), have been determined in 80% (w/w) methanol-water by calorimetric titration. Acid dissociation constants, pK,, have also been determined for these compounds in the same solvents by potentiometric titration. Similar constants have also been measured for 2,6-dimethylenebenzoicacid-18-crown-5 (5) and its methyl ester analogue 6. Furthermore, log K,, log K2, and pK, values were determined for 1, 5, and 6 in 99% (w/w) methanol-water. Increasing the length of the acidic side arm has a destabilizing effect upon the complexes formed with log K ,for 5 > 1 > 2 > 3 in 80% (w/w) methanol-water. The highest stability is achieved when the negative charge density of the side arm is located near the cavity space to be occupied by the sodium ion. Solvation effects are evident in the magnitude of the stability constants obtained in 5 and 6. For 5 in 99% (w/w) methanol-water, Naf is apparently competing with an intramolecular hydrogen bond for the cavity space of the crown ether. With crown phosphonic acid monoalkyl ester 4, Na' is more selectively complexed relative to K+ than with crown carboxylic acid 1. The kinetics of complexation of the crown carboxylate from 1 with Na+ in 99% (w/w) methanol-water were examined with the electric field-jump technique. The rate of formation is nearly diffusion controlled and indicates significant interaction between the side arm and Na' prior to desolvation by the polyester ring. An additional relaxation, but of opposite amplitude, was also observed.
Introduction Ionizable crown ethers are macrocyclic compounds consisting of a polyether cavity and a proton ionizable group and are capable of complexing cations with varying degrees of stability. Stability constants of alkali metal ion complexed by the crown carboxylic acid (1) in 80% (w/w) acid sym-dibenzo-16-crown-5-oxyacetic methanol-water1 have recently been determined. It was reported that the increased stability of the complexes when 1 was completely ionized in comparison to the protonated or free acid form can be attributed to participation of the carboxylic acid side arm in the complexation process. However, the exact role of the metal-side arm interaction in terms of the thermodynamic and kinetic properties of the system is not firmly established. Additional ionizable crown ethers with a common sym-dibenzo-16-crown-5 cavity with different ionizable side arms have been synthesized. Structural variations such as changes in the position, length, and type of side-arm substituent might be expected to produce changes in complex stability and selectivity. Information obtained from thermodynamic and kinetic studies is needed to evaluate the influence of ionizable side-arm interaction. Therefore, we have undertaken a systematic investigation of N a + complexation by several ionizable crowns in methanol-water solvents. Complexation thermodynamics may be studied by potentiometric and calorimetric titrations of the ionizable crowns. In addition to 1 the following ionizable crown analogues that have a common sym-dibenzo- 16-crown-5 ring have now been investiacid (2), similar gated: 3-(sym-dibenzo-l6-crown-5-oxy)propanoic to 1 but with the side arm lengthened by one methylene group, 3-(sym-dibenzo- 16-crown-5-oxy)propanesulfonicacid (3), with two additional methylene groups in the side arm as compared to 1 and a strongly acidic end group, and sym-dibenzo-16-crown-~ 5-oxymethylphosphonicacid monoethyl (4), with a (1) Adamic, R. J.; Chem. 1985, 89, 3152.
E. M.; petrucci,
s.; Bartsch, R. A. J . phys.
0022-3654/86/2090-6571$01.50/0
CHART I 0
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I1
Hfi°CH2C-oH
a: LOJ 1
u
0 H~OCH~CH~CH~SO~H
ao to3 3
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(", L
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2 acidic end group but with nearly the same side-arm length as 1. Both 3 and 4 are unusual in that they allow for complexation by the anionic form to occur in acidic solution whereas neutral or basic solutions are required for 1 and 2. In addition, stability 0 1986 American Chemical Society
6572
The Journal of Physical Chemistry, Vol. 90, No. 24, 1986
constants for an acid crown wherein the side arm is positioned inside the cavity, 2,6-dimethylenebenzoic acid- 18-crown-5 ( 9 , and its methyl ester analogue 6, are reported. Acid dissociation constants (pK,s) were determined for crown compounds 1-5 in 80% (w/w) methanol-water. Stability constants were also determined for all six crown compounds in 80% (w/w) methanolwater and for 1, 5 , and 6 , in 99% (u/w) methanol-water. Kinetically, complexation of alkali metal cations by crown ethers is very fast. approaching the diffusion-controlled limit of 108-1O9 dm3 mol-l s-' as was reported2 for the complexation of various group I (1)24cations by 18-crown-6 in water. A stepwise substitution of solvent molecules surrounding the ion, rather than a concerted process, can account for the high rates ~ b t a i n e d . ~ Therefore, one might expect a negatively charged crown ether to have a cation complexation rate as high or possibly even higher than that observed for the nonionizable crown ether species. Particularly this would be the case if the side-arm anion significantly participates in the complexation process since there would exist, besides the diffusion of two oppositely charged species toward one another, the possibility of solvent labilization by the anionic side arm. Nearly diffusion-controlled rates of formation for the complexation of Naf by the negatively charged antibiotics nigericin and monensin have been found. A rate of formation greater than 2 X 1O'O dm3 mol-' s-' was reported4 for nigericin in methanol while a value of 1.1 X 1O9 dm3 mol-' s-l was recently recordeds for monensin in ethanol. Both antibiotics are acyclic molecules with rather complicated structures and undergo large conformational changes to complex the metal ion. On the other hand, the ionizable crowns are simpler structures with &ell-defined cavities that undergo relatively small changes in conformation upon complexation with metal ions. Thus, interpretation of the kinetics of complexation for the acid crowns should better be directed toward the evaluation of side-arm participation. In this paper, a kinetic study of Naf complexation by carboxylic acid crown 1 in 99% ( w / w ) methanol-water is reported. An electric field jump (E-jump) relaxation apparatus6 with spectrophotometric monitoring of the reaction course was used in conjunction with the metal ion indicator, murexide. The 99% (w/w) methanolwater solution was chosen for two reasons: (1) the high methanol concentration ensures a large stability constant for sodium murexide and thus a large amplitude change; (2) trace amounts of water become less of a factor in the kinetic measurements.
Experimental Section Materials. Crown carboxylic acid 1 was prepared by the published procedure7 and recrystallized from ethanol/water. Calcd for C21H2408:C , 62.38; H, 5.94. Found: C, 62.61; H , 6.08. Compounds 5 and 6 were synthesized by the published procedures.* Crown carboxylic acid 5 was purified by interaction of an aqueous solution of 5 with CHzClzand drying of MgSO,. After removal of the solvent in vacuo the residue was recrystallized first from methylene chloride/pentane and then from acetonitrile. Calcd for C17H2407: C, 60.00; H, 7.10. Found: C, 60.14; H, 7.03. Crown carboxylic acid 2 was prepared by a new procedure. Under nitrogen, potassium tert-butoxide (6.28 g, 56.0 mmol) was added very slowly to a cooled and stirred solution of symhydroxydibenzo-l 6-crown-59 (20.0 g, 57.7 mmol) in ethyl acrylate (190 mL) at such a rate that the temperature did not exceed 5 (2) Liesegang, G.W.; Farrow, M. M.; Vazquez. F. A,; Purdie, N.; Eying, E. M. J . Am. Chem. Soc. 1977, 99, 3240. (3) Diebler, H.; Eigen, M.; Ilgenfritz, G.; Maass, G.; Winkler, R. Pure Appl. Chem. 1969, 20, 93. (4) Chock. P. B.; Eggers, F.: Eigen, M.; Winkler, R. Biophys. Chem. 1977. 6, 239. ( 5 ) Cox, B. G.; van Trugon. Ng.; Rzeszotarska, J.; Schneider, H . J . Am. Chem. Soc. 1984, 106, 5965. (6) Bernasconi, C. F. Relaxation Kinetics: Academic: New York, 1976; p 232. (7) Bartsch, R. A.; Heo, G.S.; Kang, S . I.; Liu. Y.; Strzelbicki, J. J . Org. Chem. 1982, 47, 457. (8) Newcomb, M.; Cram, D. J. J . Am. Chem. Soc. 1975, 97. 1257. (9) Heo, G. S . ; Bartsch. R. A.: Schlobohm. L. L.; Lee, J. G. J . Org. Chem. 1981. 44. 3 5 7 4 .
Adamic et al. OC. The reaction mixture was stirred for 9 h at room temperature and quenched with 15% HCI. The mixture was washed with several portions of petroleum ether to remove most of the excess ethyl acrylate. The residue was extracted with CH2C12and the CH2CI2layer was washed with water (6 X 100 mL), dried over MgSO,, and evaporated in vacuo. The residue was eluted through a short silica gel column with Et,O as eluent to remove polymeric materials. After evaporation of the Et,O in vacuo, the resultant thick, yellow oil (44 g) was added to 450 mL of dioxane/lO% HCI ( 2 : l ) and the solution was refluxed for 48 h. The dioxane was removed in vacuo and, after cooling, the aqueous solution was decanted. A CH2C12extract of the residue was washed with water (6 X 200 mL), dried over MgSO,, and evaporated to vacuo to give 38 g of yellow oil. This crude material was purified by eluting five successive silica gel columns with MeOH-CH2C12 (1:20 (v/v)) as eluent to yield I .90 g (7.9%) of solid with mp 1 13-1 16 OC (lit7 mp 116-1 19 "C): I R (KBr pellet, cm-l) 3600-2350 ( C 0 2 H ) , 1715 (CEO), 1250 (CO): ' H N M R (CDCI,) 6 2.65-2.88 (t, 2 H), 3.75-4.50 (m, 15 H), 6.95 (s, 8 H), 8.95 (br s, I H). Calcd for C2,H2,0,: C, 63.16; H, 6.22. Found: C ? 63.41; H , 6.53. Crown sulfonic acid 3 was prepared via its sodium salt by the following procedure. After removal of the protecting mineral oil by washing sodium hydride (1.52 g, 32 mmol, 50% dispersion) with pentane 3 times under nitrogen, the dry solid was slowly added to a stirred solution of sym-hydroxydibenzo- I 6-crown-59 in THF (70 mL). After 30 min, a solution of 1,3-propane sultone (4.23 g, 34.7 mmol, Aldrich) in T H F (10 mL) was added dropwise. Almost immediately formation of a precipitate was observed. After 2.5 h, an additional 20 mL of THF was added to thin the suspension followed by stirring for 3 h. The solid was filtered and dried to give 14.0 g (quantitative yield) of sodium 3 - ( s j ~ - d i benzo- 16-crown-5-oxy)propanesulfonateas a light tan solid with mp 90 OC: I R (deposit, cm-') 1355. 1180 (SO,Na), I240 (CO); ' H N M R ( D 2 0 ) 6 1.8 (br m, 2 H), 2.7 (br m, 2 H), 3.2-4.2 (br m, 15 H), 4.5 (br s, 2 H, H20), 6.3-7.0 (br s, 8 H). Anal. Calcd for Cz2Hz,S0,Na.H20: C. 51.97: H, 5.71. Found: C. 51.98: H, 6.05. Dry HCI gas was passed through a cloudy solution of this sodium sulfonate (10.0 g, 20.4 mmol) in CH2C12(80 mL). The clear solution was decanted from the precipitated NaCl and additional HCI gas was administered until no further precipitation of NaCl was observed. After filtration the solution was evaporated in vacuo to give a white solid that was dried under vacuum to provide 8.5 g (80%) of compound 3 with mp 60-70 OC: IR (deposit, cm-l) 3400-2500 (SO,H), 1240 (CO); IH NMR (CDCI,) 6 1.7-2.35 (m, 2 H), 2.8-3.2 (br m, 2 H), 3.5-4.6 (m, 15 H), 6.86 (s, 8 H). Calcd for C2,H2,09.2H20: C, 52.38: H , 6.35; S, 6.35. Found: C, 52.59; H , 6.16; S, 5.95. Crown phosphonic acid monoethyl ester 4 was synthesized as follows. Sodium hydride (2.0 g, 49.5 mmol, 50% dispersion in mineral oil) was washed with pentane (3 times) under nitrogen to remove the mineral oil. T o the dry powder was added 150 mL of T H F and the suspension was stirred for 15 min. A solution of sym-hydroxydibenzo-16-crown-59 (10.0 g, 24.7 mmol) in T H F (50 mL) was added dropwise and the mixture was stirred for 1 h. A solution of monoethyl iodomethylphosphonic acidlo in T H F (50 mL) was added over 20 min followed by stirring a t room temperature for 5 h and reflux for 24 h. The reaction mixture was evaporated in vacuo and water (50 mL) was added followed by acidification to pH I with I Iv HCI. The mixture was extracted with CH2CI2(3 X 100 mL), dried (MgS04), and evaporated in vacuo. The residue was purified by column chromatography on silica gel with CHzC12and EtOH:Et,O ( 1 : l ) as eluents. Evaporation of the EtOH:Et20 eluent gave 10.22 g (88.4%) of the title compound as an extremely hygroscopic white crystalline solid with mp 48-52 OC: IR (deposit, cm-l) 3600, 2275, 1650 (PO,HR), 1240 (CO); ' H N M R (CDCl3) 6 1.30 (t, 3 H), 3.5-4.4 (m, 17 H), 6.90 (s, 8 H), 8.3 (br s, 1 H). Calcd for C22H2909P.1.5H20: C, 53.37: H, 6.37: P, 6.26. Found: C, 53.63; H, 6.14; P. 5.89. ( I O ) Ford-Moore, A H ; Williams, J H J Am Chem. Soc 1947, 49. I465
Complexation by Ionizable Crown Ethers
The Journal of Physical Chemistry, Vol. 90, No. 24, 1986 6513
TABLE I: Thermodynamic Acid Dissociation Constants, pK, and pK,,',' for Complexation of Na+ by Ionizable Crown Ethers 1-5 in 80%(w/w) Methanol-Water and 1 and 5 in 99%(w/w) Methanol-Water ~
compd
PKa (water)
1 2
(4.59)b (4.89)b
3 4 5
(4.80)*
80% CHjOH-HzO
99% CH30H-HZ0
PK, 5.90 6.72 -2.68 3.57 7.76
f 0.09c3d f 0.Ov f 0.ov f 0.06'qd
PK,'
PK,
4.93 f 0.18d*c
5.64
* 0.12'
8.27 f 0.18c
PK,' 7.06 f 0.06'
10.32 f 0.04e
7.39 f 0.16'
K,' = [NaCR][H+]/[NaHCR+]. bReference 9. cReference 1. dAverage of three titrations with uncertainty expressed as mean deviation. eAverageof 10-1 3 values with uncertainty expressed as mean deviation. /Average of two titrations with uncertainty expressed as mean deviation. g Approximate value. Reference 8. Reference 19.
The salts, NaC1, NaI, and NaC104, were dried under vacuum prior to weighing. All weighing operations involving acid crown 3 were carried out in a drybox due to the extremely hygroscopic nature of this compound. N a O H was purified to remove water and carbonates by the method of Kelly and Snyder," with all operations carried out in a drybox. Ammonium purpurate (murexide) was used as received and dried under vacuum. Methanol, absolute acetone free, was used as received as well as HPLC-grade water. The pH buffers for standardization of 80% and 99% methanol-water solutions were prepared as noted in ref 1. Dilute solutions of n-(Bu),NOH, n-(Et),NOH, and HC1 in 80% and 99% methanol-water were also prepared for adjustment of pH. Potentiometry. pH measurements and potentiometric titrations were carried out by procedures described in ref 1, with the following exceptions: A Sargent-Welch miniature combination pH electrode (catalogue no. S-30070-10) was used for the 80% methanol-water solvent and a Beckman pH combination electrode (catalogue no. 39520) for 99% methanol-water. The dissociation constants were corrected to their thermodynamic values with the Debye-Huckel relationship - A ~ ~J 2I , ~
1% Y i =
1
+ BaI,1/2
where A and B equal 1.265 and 0.446 for 80% methanol-water and 1.822 and 0.502 for 99% methanol-water.I2 The values of a in the two solvents were taken as 5 and 4 A, respectively. I , is the ionic strength at the midpoint of the titration. Spectrophotometry. The stability constant of sodium murexide in 99% methanol-water was determined by spectrophotometric titration of murexide with sodium perchlorate at 25.0 f 0.1 OC using a Cary 17D spectrophotometer. Thermometric Titration Calorimetry and Kinetic Relaxation Spectrometry. The thermometric titration of the acid crowns and the analysis of the data were carried out by the methods given in ref 1. NaCl was used as titrant in 80% methanol-water solutions and N a I for the 99% methanol-water titrations. The p H was measured before and after each experiment. Kinetic relaxation data were obtained with an E-jump apparatus that has been previously described.I3 Experiments were conducted at 25.0 f 0.1 OC and four to seven traces were recorded and averaged to obtain the relaxation time. Microliter pipets were used to dispense salt, base, and standardized ionizable crown ether solutions. The stock solution of murexide (
