J. Org. Chem. 1993,58,4389-4397
4389
Side Arm Effects on Cation Binding, Extraction, and Transport Functions of Oligopyridine-FunctionalizedAza-Crown Ethers Hiroshi Tsukube,.p+ Jun'ichi Uenishi,: Hiromi Higaki3 Ken'ichi Kikkawa,: Takakazu Tanaka,: Shoji Wakabayashi,: and Shigeru Oaet Department of Chemistry, College of Liberal Arts & Science, Okayama University, Okayamn 700, Japan, and Department of Chemistry, Faculty of Science, Okayama University of Science, Ridai-Chou, Okayama 700, Japan Received February 22,1993
A new series of lariat ethers and double-armed crown ethers was prepared in which oligopyridinefunctionalized side arms were attached as secondary donor sites. A novel preparative method of oligopyridine derivativeswas successfully applied to the synthesis of these crown ethers. Introduction of an oligopyridine-functionalizedside arm into the crown ether system, if of the proper chain length and geometrical arrangement, significantly offered three-dimensional complexation with various metal cations suitable for extraction and transport. Liquid-liquid extraction, lac-NMR binding, and liquid membrane transport experiments revealed that the present type of double-armed crown ethers exhibited cation-binding abilities superior to corresponding lariat ethers.
Introduction Lariat ethers, double-armed crown ethers, and related armed macrocycles were designed to enhance the cationbinding ability of common macrocyclic ligands by attachment of cation-ligating side arms and also to offer threedimensional complexation suitable for extraction and transportation.l A8 we and several other research groups have reported, ester, amide, ether, and other oxygen donorfunctionalized side arms have readily been attached to the aza- and diaza-crown ethers.2 These often exhibited different cation-binding properties from those observed with the parent crown ethers via side arm participation. Since their cation-binding behaviors were strongly dependent on the coordination characters of their side arms, introduction of a potential binding site on the side arm is a promising strategy for functionalization of crown ether compounds. Here, we report the synthesis and cation-binding properties of a new series of lariat ethers and doublearmed crown ethers having oligopyridine-functionalized side arms. Although oligopyridine derivatives have potential as specific metal binders,3 incorporation of these moieties into the crown ether system poses many synthetic difficulties, which has kept the examples reported to date to a limited number. We recently developed a general preparation of functionalized 2,2'-bipyridine derivatives by the reaction of 2-(alkylsulfinyl)pyridineswith 2-pyridyllithium reagent^.^ This reaction was successfully t Okayama University. t Okayama University of
employed in the synthesis of various armed aza-crown ethers which contained oligopyridine-functionalizedside arms. We systematically introduced bipyridine, terpyridine, and their derivatives on the side arms of aza- and diaza-18-crown-6rings. The molecular structures of lariat ethers and double-armed crown ethers prepared are summarized in Chart I. They were found to exhibit enhanced binding abilities toward "hard" metal cations, though oligopyridines are potential ligands of "soft" metal cations.5 In particular, double-armed crown ethers had great advantages in extraction and transport processes. A combination of soft oligopyridine and hard crown ring donor groupsoffered unique metal recognition phenomena Side arm effects on the cation binding, extraction, and transport functions of the oligopyridine-armed crown ethers are discussed below. Results and Discussion Synthesis of Oligopyridine-Armed Aza-Crown Ethers. Three kinds of oligopyridine-armedcrown ethers were prepared double-armedcrown ethers, lariat ethers, and their thiaanaloge (seeChart1). Pyridine-armeddiazacrown ether la has been demonstrated to be an effective metal cation binderlcarrier.6 2,2'-Bipyridine and oligopyridine derivatives are known to form coordination complexes with various metal cations, and other armed crown ethers prepared here are also expectedto offer interesting cation recognition via crown ring-side arm c~operation.~ Since the syntheses of unsymmetrical oligopyridine derivatives presented earlier are too long and complicated for scale-up, we developed a new synthetic route which provides ready access to multigram quantities of oligopyridine precursors for synthesisof these armed crown ethers (see Scheme I).
Science. (1) Recent reviews: (a) Gokel,G. W.; Trafton,J.E. In CationBinding by Macrocycles; Marcel Dekker: New York, 1990; p 253. (b) Lindoy, L. F. In The Chemistry of Macrocyclic Ligand Complexes; Cambridge University Press: Cambridge, 1989; p 103. (c) Tsukube, H. In Liquid Membranes: Chemical Applications; CRC Press: Boca Ratan, 1990; p (5) (a) Walba, D. M.; Zheng, Q. Y.; Schilling, K. J. Am. Chem. SOC. 51. (d) Krakowiak, K. E.; Bradehaw, J. S.; Zamecka-Krakowiak,D. J.; 1992,114,6269. (b) Pfeil, A.; Lehn,J. M. J. Chem. Soc., Chem. Commun. Izatt, R. M. Chem. Reo. 1989,89,929. (2) (a)White,B.D.;Mallen,J.;Arnold,K.A.;Fronmek,F.R.;Gandour, 1992,838. (c) Garelli, N.; Vierling, P. J. Org. Chem 1992,67,3046. (d) Chambron,J.-C.;Heitz,V.;Sauvage,J.-P.J. Chem. Soc.,Chem. Commun. R. D.; Gehrig, L. M.; Gokel, G. W. J. Org. Chem. 1989, 54,937. (b) 1992, 1131. Wiclretrom, T.; Dale, J.;Luud, W.; Buoen, S. Anal. Chim. Acta 1988,211, (6) T~ukube,H.; Yamaehita, K.; Iwachido,T.; Zenki, M. J. Org. Chem. 223. (c) Tsukube, H.; Adachi, H.; Morosawa, 5.J. Chem. SOC.,Perkin 1991,56, 268. %M. 1 1989, 89. (7) Several bipyridine-containing crown ethers and cryptan& have (3) (a) Voegtle, F. In Supramolecular Chemistry;John Wiley & Sons: been prepared but rarely employed ae carriem in extractionand transport Chichester. 1991:D 9. (b)Constable, E. C. Adu. Znorg. Chem.Radiochem. experiments. (a) Newkome, G. R.; Kohji, J. K.; Fronczek, F. J. Chem. 1988,30,69. . - . . SOC.,Chem. Commun. 1980,9. (b) Alpha, B.; Lehn, J.-M.; Mathis, G. (4) Uenishi, J.; Tanaka, T.; Wakabayashi, S.; Oae, S.; Tsukube, H. Angew. Chem., Znt. Ed. Engl. 1987,26,286. Tetrahedron Lett. 1990, 31, 4625. ~~
~
~~
0022-32631931195a-43a9$04.0010 Q 1993 American Chemical Society
Tsukube et al.
4390 J. Org. Chem., Vol. 58, No.16,1993 Chart I. Structures of Employed Crown Ethers
R
R
la lb
3c W\A O C H ,
2c
3h
IC 2h Id le
If 1g R
lh
u
4
li 1j
Scheme I. Typical Synthesis of Double-Armed Crown Ether
A
0
C
B
HN
1) , ' H
2 ) CBr4, Ph3P
step
NH
Lo-oJ CH2Br
b
, base w
step
c
D
1g
Our synthetic strategy was to prepare oligopyridine precursors via ipso substitution of 2-(alkylsulfinyl)pyridines by 2-pyridyllithiumsand then react them with azaand diaza-18-crown-6 rings. Typical synthesis of double armed crown ether lg is illustrated in Scheme 1. In step a, 2-pyridyllithium was generated by halogen-metal exchange of 2-bromopyridine B with n-butyllithium in ether or THF at -78 "C and subsequently treated with 2-pyridyl sulfoxide A, giving protected bipyridine C. The THP group was easily removed by the standard procedure (HC1 in MeOH), and the hydroxymethyl group formed waa brominated by carbon tetrabromide with triphenylphosphine to give (bromomethy1)bipyridineD (step b). Finally, double-armed diaza-crown ether l g was prepared by alkylation (step c). We used various (bromomethy1)-
oligopyridines8to prepare a new series of armed crown ethers having oligopyridine-functionalizedside arms (see Experimental Section). Cation Extraction Profile. Cation-binding abilities of the armed aza-crown ethers prepared were assessed by solvent extraction of alkali, alkaline earth, heavy, and transition-metal perchlorates. Nine double-armeddiazacrown ethers la-h and 4, three lariat ethers 2a-h, two thia anaolgs 3c and 3h, and three reference compounds li, 1j, and 21were examined. The extraction percentages, defined aa percent metal cation extracted in the organic phase, were calculated from the concentrations of metal (8) Uenhhi, J.; Tanaka, T.; Niehiwaki, K.; Wakabayaehi, 9.; Oae, S.; Tsukube, H. J. Org. Chem., previous paper in this issue.
Oligopyridine-FunctionalizedAza-Crown Ethers
J. Org. Chem., Vol. 58, No.16,1993 4391 Double Armed Crown Ether-Cation Complex
Ij_
0
1
2
3
Pb2+
f
50 I
1
..o
, 0
1 2 3
0 1 2 3
Number of Pyridine Units on Sidearm
7
0
-1
2
3
ki
1 2 3
-
Figure 1. Side arm effect on cation extraction abilitiesof doublearmed crown ethers (*-) and lariat ethers (+). Number of pyridine unite: 0 (li, 21); 1 (la, 2a); 2 (IC,2 4 ; 3 (lh, 2h). See graph for Pb2+case.
cations in the aqueous phase which were spectroscopically determined. Figure 1 compares side arm effects on the cationextraction abilities of double-armed crown ethers with those of lariat ethers, in which extraction percentages of several metal cations are plotted with the number of pyridine units on the side arms of diaza-crown ethers (la, IC, lh, and li) and aza-crown ethers (2a,2c, 2h, and 2i). Cation-extraction abilities of these crown ethers were apparently dependent on the number of pyridine units on the single arm, and arm functionalization generally enhanced the extraction abilities of parent diaza-18crown-6and aza-18-crown-6. When Ca2+,Ba2+,Ag+,Pb2+, Cu2+, and Zn2+ cations were chosen as guest cations, double-armedcrown ethers exhibited curved plots similar to those observedwith lariat ethers. Typically, bipyridinearmed crown ethers ICand 2c exhibited higher extraction activities for Ba2+and Cu2+cations than monopyridineand terpyridine-armed crown ethers la, lh, 2a, and 2h. As schematically shown in Figure 2, double-armed crown ethers have various kinds of cation-binding modes: only one side arm interacts with guest metal cation (type A); two side arms provide coordination from the same or opposite sides (type B or C); and others. The present observations support the possibility of type A for these metal cations, which may exhibit similar binding profiles to the lariat ether complexation (type D). Since doublearmed crown ethers showed higher extractabilities than lariat ethers, two functionalized side arms of the doublearmed crown ethers may offer a statistical advantage for cooperative binding of these metal cations. For Na+ and K+cations, double-armedcrown ethers provided different side arm effects from those with lariat ethers. This probably suggests that the double-armed crown ethers
Lariat Ether-Cation Complex
Figure 2. Cation binding modes of double-armed crown ether
and lariat ether.
would form the complexes of type B or C. It is noted that when the total number of donor atoms available was 8, both series displayed peak extractability. A similar peak binding property has been reported in the polyetherfunctionalizedlariat ethers by Gokel et al? Aza- and diazacrown rings are directed by the guest cation to envelop and solvate in the geometry most appropriate for the cation. Table I summarizes cation extraction properties of the armed crown ethers employed. This indicates that the oligopyridine-functionalizedside arms are useful as secondary binding sites for various metal cations. Indeed, double-armed crown ethers having bipyridine-functionalized side arms lc-g exhibited higher extraction abilities than simplediaza-crown ethers li and 1j. Their extraction profiles were interestingly dependent on the structures of the bipyridine units introduced, though they were substantially controlled by the ring sizes of the parent diaza18-cr0wn-6.~~Double-armed crown ethers IC and Id extracted Ba2+cation efficiently, while crown ethers If and l g favored Cu2+and Zn2+ions. Bipyridine-armed diaza-crown ether le, which has structural elements the same as but ligand geometry different from IC, was examinedfor comparison. This rarely extracted the alkali and alkaline earth metal cations. Since dipyridylmethyl derivative4 showed greatly different guest selectivityfrom those of pyridine- and bipyridine-armed crown ethers la and IC,geometrical arrangement of pyridine units on the side arm should be seriously considered in the design of an effectivecation binder of this type. Terpyridine-armed diaza-crown ether 1h exhibited lower extraction abilities for Na+,K+,Ca2+,and Ba2+cations than did double-armed crown ether la and for Ba2+and Cu2+cations than did crown ether IC. The terpyridine has more pyridine-nitrogen donor atoms, but they are probably placed at less favorable positions to provide effective coordination of these metal cations trapped in the diaza-18-crown-6ring. The bulky and rigid side arm is sometimes more of a hindrance than an asset. Coordination character and steric effects of the oligopyridine group clearly influenced cooperative binding modes and determined metal selectivity. (9) Schultz, R. A,; White, B. D.; Dishong, D. M.; Arnold, K.A,; Gokel, G. W.J. Org. Chem. 1985, 207,6659. (10) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S. Chem. Reo. 1991, 91, 1721.
Tsukube et al.
4392 J. Org. Chem., Vol. 58, No. 16, 1993
crown la lb
Li+
* 4 4
IC
*
Id le lf 1g lh li 1j 2a 2c 2h
(*)
* * * *
* *
13
* * *
21
Table I. Cation Extraction Properties of Armed Aza-Crown Ethers. extraction percentage ( % ) Na+ K+ Ag+ Mg2+ Ca2+ Ba2+ Pb2+ 6 61 54 99 * 47 59 10 60 99 * (80) * 35 90 * 25 90 * 6 80 * 46 89 * * (76) (83) * (*) (*) (63) 93 (*) (*) * * * 13 76 25 98 * 23 93 * * 10 (80) * 35 95 * * 24 (95) * * 89 * * 4 34 * 3 96 * * 20 41 12 33 92 * * 13 5 21 41 90 * * 38 29 19 20 95 * * 11 49 * * * * 73 15 (*) * * * * * (92) (100) * * * * * (100) (99) * 81 83 84 24 54 100
3c * 3h * 4 a Parentheses indicate that a considerable amount of precipitate was observed. An * indicates a percentage 53%
167
h
E
v
165
t
mixture
1
165
I1-
165
1I
t "b t 88
88
*'
84 85
L
0
1
2
3
0
1
2
3
0
1
2
3
[Metal Cation] / [Crown] (mol/mol)
Figure 3. K+- and Ba2+-inducedchanges in NMR chemical = 12) and crown shifts of amixture (diaza-18-crown-6bipyridine K+ ion. Chemical shift ethers IC and 2c: -0-, Ba2+ion; indicatedwas determined by usingthe peak of the DMF carbonyl carbon (6c 180.00 ppm) as reference.
+-,
Thia-analogs3c and 3h were characterizedby soft donor atoms both on the side arm and parent thia-crown ring.ll Although these efficiently extracted soft Ag+, Pb2+,and Cu2+cations, they rarely bound hard alkali and alkaline earth metal cations. A combination of parent crown structure and cation-ligating side arm should be adjusted to a target metal cation. 13C-NMRBinding Studies. Further information on cation-binding behavior of the armed crown ether was obtained via 13C-NMRspectroscopy in DMF/D20 (4/1) solution. Figure 3 illustrates the K+- and BaZ+-induced changes in the 13C-NMRchemical shifts of selected carbon signals of double-armed crown ether IC and lariat ether (11) Buschmann,H.J.InStereochernicalandStereophysicalBehauior of Macrocycles; Elsevier: New York, 1987; p 103.
cu2+ 6 44 57 20 47 (73) 62 14 14 13
*
26 10 (22) (65) (100) 99
Zn2+ 9 (11) (39) 9 (51) 41 35 86 19 20 12 16 35
* 9 48 68
I
2c, comparing them with those of a mixture of unsubstituted diaza-18-crown-6 and bipyridine (1/2 = mol/mol). Bipyridine-armed diaza-18-crown-6 IC was confirmed to wrap Ba2+ cation very nicely in a three-dimensional fashion. Actually, the addition of Ba(C104)~salt to the crown ether IC solution offered significant changes upon 1:l complexation. Several signals for the carbons on the bipyridine-ring and parent crown-ring shifted greatly, indicating that cooperative action of these two binding sites was involved in encapsulationof the guestBa2+cation. Since some carbon signals broadened at stoichiometries below 1:l (metal/crown),the guest Ba2+cation was thought to be rigidly complexed and to be slowly exchanged. In contrast, the addition of KC104 salt modestly influenced bipyridine-ringsignalsof the crown IC, though continuous and large shifts were observed for signals of crown ring carbons. This may indicate that bipyridine-functionalized side arms loosely interact with K+cation giving a different type of coordination from that observed with the Ba2+ ion. Ba2+and K+ cations have similar ion sizes, but their charge numbers greatly influencedcomplex structures and binding kinetics. In other words, bipyridine-armed diazacrown ether IC distinguished Ba2+cation from K+cation. Figure 3 also indicatesthat bipyridine-armedlariat ether 2c forms 1:lcomplexes with K+and Ba2+cations and that its binding modes are similar. Since aza-18-crown-6ring is more flexible than diaza-18-crown8 ring,the lariat ether 2c can adjust its conformation to the effectivecooperative binding of the bipyridine unit and aza-crown ring. The 13C-NMRspectrum of a mixture of unsubstituted diaza18-crown-6and bipyridine changed in the presence of K+ and Ba2+cations, but only slight changes were observed for bipyridine-ring carbon signals in the presence of both metal cations (see Figure 3). Thus, free bipyridine unit was confirmed to rarely coordinate the metal cation trapped in the diaza-crown ring. Table I1 summarizes the results of 13C-NMRbinding studies for double-armed diaza-crown ethers la and IC, lariat ethers 2a and 2c, and a mixture of diaza-18-crown-6 and bipyridine (1/2 = mol/mol). Bipyridine-armed diazacrown ether IC effectively formed three-dimensional complexes with Ag+, Ba2+,Pb2+,and Zn2+cations, while pyridine-armed crown ether la encapsulated Na+ and K+ cations as well as Ag+, Ba2+,and Zn2+cations. The metal cations, which were accommodated nicely in a threedimensional fashion, were confirmed to be effectively
Oligopyridine-Functionalizedha-Crown Ethers
J. Org. Chem., Vol. 58, No.16, 1993 4393
Table 11. Guest-Induced Changes in WNMR Chemical Shifts of Double-Armed Crown Ethers.
induced chemical shift (ppm) crown
carbonb
mixture
Li+
a
Na+
* *
-0.1 -0.2
K+
* *
Ag+
Ca2+
*
*
Ba2+
*
Pb2+
*
Zn2+
-0.9 -0.8 -0.6 0.7 -0.1 1.0 * la 1.2 0.9 2.6 0.2 0.9 0.1 -0.9 -0.1 -1.9 -1.0 -1.6 -1.2 -0.9 -1.2 -1.7 * IC 0.2 0.2 0.8 0.2 -0.5 0.5 d * -0.8 -1.1 -1.2 -1.1 -0.9 -3.0 d 2a 0.1 1.5 1.1 2.1 0.9 0.6 -0.3 -0.7 -0.5 -2.5 -1.6 -2.8 -2.1 -1.1 -1.2 -3.9 * 2c a 0.3 0.5 1.9 0.7 0.4 0.7 -2.6 b -0.1 -1.6 -1.9 -1.4 -1.4 -1.6 -1.5 -3.5 0 Conditions: crown, 0.025 m o l : guest perchlorate, 0.025 m o l in DMF-D20 (41)0.5 mL. Positive is downfield shift. An * indicates a shift
