Ag+Ion-selective lariat ethers: high pressure syntheses and cation recognition properties

摘要

J. CHEM. SOC. PERKIN TRANS. I 1995 Ag Ion-selective lariat ethers: high pressure syntheses and cation + recognition properties Kiyoshi Matsumoto,*9" Masao Hashimoto," Mitsuo Toda " and Hiroshi Tsukube *9b a Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-01,JapanDepartment of Chemistry, College of Liberal Arts and Science, Okayama University, Okayama 700, Japan A new series of lariat ethers have been prepared by a high pressure S,Ar reaction, in which various heteroaromatics are directly connected to the nitrogens of 12-, 15- and 18-membered aza-crown ethers. Liquid membrane transport studies demonstrated that lariat ethers having thiazole, oxazole, pyrazine and pyridazine rings on their sidearms exhibited excellent Ag + ion selectivity.3CNMR binding experiments revealed that these lariat ethers selectively formed encapsulated Ag' complexes in a different fashion from that of double armed crown ethers. Cooperative action between the heteroaromatic sidearm and the aza-crown ring afforded unique cation recognition. Lariat ethers and double armed crown ethers have been recognized as potential cation-binders and are characterized by a parent crown ring with cation-ligating sidearms. They offer three dimensional complexation suitable for selective recog- nition and a modification of the cation binding ability of the parent crown ethers.' Although a variety of armed crown ethers have been reported, their syntheses have mostly been based upon common organic reactions and therefore variations in molecular structures have been limited.3 Thus, new synthetic methodology is desirable to develop new cation-selective binders of this type.We have recently prepared a novel type of double armed crown ether, with heteroaromatic substituents -H la 2a 3a -cN]S lb 2b 3b lc 2c 3c on their sidearms, by means of a high pressure S,Ar They selectively coordinated Ag ions by the cooperative + binding of two types of nitrogen atoms and mediated its selective transport. Highly selective reagents for Ag+ ions are of commercial interest, because Ag ions occur in nature together + with Pb" and other metal cations. Furthermore, some stable Ag' complexes have been reported to have potential in cancer radioimmunotherapy. We have applied the high pressure S,Ar reaction to the synthesis of a new series of lariat ethers,6 since there are methods available for the synthesis of the parent aza-12-crown- and aza-l8-cro~n-6~,~4,7+8aza-15-cr0wn-5,~,~ which are neither difficult experimentally nor involve high dilution. They exhibited excellent Ag+ ion selectivity in binding and transport processes. Based upon extraction and 13C NMR binding experiments, it has been proved that the'new lariat ethers recognize Ag' ions in a different fashion from that of double armed crown ether^.^ Although high pressure techniques have recently been employed as a facile and useful methodology in various synthetic reactions, few examples have been reported in the field of host-guest chemistry.'' The present study describes a further synthetic application of this technique for the synthesis of metal-selective lariat ethers.Results and discussion High pressure functionalization of aza-crown ethers High pressure (0.8 GPa) S,Ar reactions of unsubstituted aza- crowns la, 2a and 3a with halogenoheteroaromatics gave a variety of new lariat ethers in practical yields [eqn. (l)]. The yields were generally higher than those of the corresponding double armed crown ethers reported bef~re.~ In particular, medium-sized crown ethers 2b-2g and 3b-3g were almost quantitatively obtained by the one-step reaction. In contrast, rea~tion.~ Id 2d 3d 0 le 2e 3e If 2f 3f I€! 2g 3g lh 2h 3h li 21 31 Structures of the lariat ethers and related aza-crown ethers similar reactions in a sealed tube only gave very low yields of the products.Thus, the high pressure reaction is useful for the synthesis of lariat ethers having heteroaromatic substituents on their sidearms. Since our high pressure functionalization requires neither a high-dilution technique nor other laborious J. CHEM. SOC. PERKIN TRANS. 1 1995 +procedures, it should have wide application in the synthesis of different. Ag ions coordinate with crown-nitrogen/heteroaro-various functionalized materials. matics (Type A) or heteroaromatic/heteroaromatic (Type B) in Double armed crown ethers with two similar heteroaromatics the double armed crown ether complexes. Such cooperative Fig.1 binding of the crown nitrogen and heteroaromatics on the on their sidearms form two types of Ag' complexe~.~ shows the ligand topology of our new lariat ethers along with sidearm are restricted by steric factors in the lariat ether those of double armed crown ethers. Both have a parent crown complex. Since an N-substituted mono-aza crown ring is more ring with functionalized sidearms for Agf ion binding, but their flexible and effective at surrounding the Agf ion than the donor arrangement and ligand topology are apparently N,N'-disubstituted diaza-crown ring, the present lariat ethers are expected to form an encapsulated Ag' complex of Type C. Ag Ion-selective transport across a liquid membrane+ We examined three kinds of aza-crown ethers as synthetic carriers using a CH2C1, liquid membrane system: the aza-crown ethers directly connected to heteroaromatics lblg, 2b 2g and 3b3g, the aza-crown ethers having flexible pyridyl- TypeA Type methyl sidearms lh, 2h and 3hand the simple aza-crown ethers li, 2i9 and 3i.9Table 1 summarizes their initial transport rates for Li', Na', K', Ag+, Pb2+, Cu2+ and Cd2+ ions, along with those measured for the related double armed crown ethers 4b, 5b, 6b and 5h.4 The aza-crown ethers lblf, 2b2f and 3b3f possessing heteroaromatics on their sidearms selectively transported Ag ' ions, whereas they hardly carried any of the Lif, Na', K', Type c Pb2+, Cu2' and Cd2+ ions (Table 1).In contrast, lariat ethers Fig. 1 Cation binding modes of lariat ethers and double armed crown lh, 2h and 3h with flexible pyridylmethyl sidearms effectively ethers transported Lif, Na+, K', Pb2+ and Cu2+ cations.Since the Table 1 Transport properties of new lariat ethers' Transport rate/lO mol h-' Ether Li + Na + K+ Ag + Pb2+ cu2+ Cd2+ lb 0.3 0.3 0.3 1.9 0.3 0.3 0.3 2b 0.3 0.3 0.3 1.4 0.3 0.3 0.3 3b 0.3 0.3 0.3 2.5 0.3 0.3 0.3 lc 0.3 0.3 0.3 1.5 0.3 0.3 0.3 2c 0.3 0.3 0.3 0.4 0.3 0.3 0.3 3c 0.3 0.3 0.3 1.6 0.3 0.3 0.3 Id 0.3 0.3 0.3 I .9 0.3 0.3 0.3 2d 0.3 0.3 0.3 1.n 0.3 i0.3 0.3 3d 0.3 0.3 0.3 2.2 0.3 0.3 0.3 le 0.3 0.3 0.3 0.4 0.3 0.3 0.3 2e 0.3 0.3 0.3 I .3 0.3 0.3 0.3 3e 0.3 0.3 0.3 1.5 0.3 0.3 0.3 If 0.3 0.3 0.3 0.3 0.3 0.3 0.3 2f 0.3 0.3 0.3 0.3 0.3 0.3 0.3 3f 0.3 0.3 0.3 1.3 0.3 0.3 0.3 Ig 2g 3glhb 0.3 0.3 0.3 0.7 0.3 0.3 0.3 0.9 0.3 0.3 0.3 0.4 0.3 0.3 0.4 0.9 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 2h 4.4 4.0 2.8 0.3 0.6 0.3 0.6 3h 1.7 8.3 8.9 0.3 2.3 1.8 c lib 0.3 0.3 0.3 9.2 0.3 0.3 0.3 2i 0.3 0.9 0.4 2.8 0.3 0.3 0.3 3i 0.3 1.8 9.4 2.2 2.5 0.3 c 4b 0.3 0.3 0.3 7.9 0.3 0.3 c 5b I, 0.3 0.3 0.3 4.9 0.3 0.3 C 6b 0.3 0.3 0.3 5.1 0.3 0.3 C 5h 5.0 10.5 7.9 0.3 1.6 2.2 c 4b 5b 6b 5h 'Conditions: Aq 1: guest perchlorate (0.5 mmo1)-H,O (5 cm3).Membrane: ether (0.0372 mmo1)-CH,Cl, (12 cm3).Aq 2: H,O (5 cm3). Cited from literat~re.~'.'~'Not determined. .I.CHEM. SOC. PERKIN TRANS. I 1995 Table 2 Competitive cation extraction properties of lariat ethersa Extraction percentage' (%) Ether Na+ Kf Ag' PbZf cu2+ Cd2+ 2b 0 0 35 I 0 I 2h I 0 99 0 0 2 2i I 0 96 15 9 0 3b 0 0 43 0 0 I 3h 0 0 96 24 6 I 3i' 0 11 99 48 76 0 '' Cotidrtron.\ ether (0.2 mmol)-CH,C1, (5 cm3); NaCIO, (0.05 mmol), KCIO, (0.05 mmol), AgClO, (0.05 mmol), Pb(CIO,), (0.05 mmol), Cu(CI0, Iz (0.05 mmpl), Cd(CIO,), (0.05 mmo1)-H,O (5 cm3), stirred for 2 h. '1 -[M extracted in CH,Cl,]/[M+ initially added in HzO]j x 1'00. ' Precipitate appeared and a considerable amount of metal species was removed from the aqueous phase. N-benzyl crown ethers li, 2i and 3i exhibited high carrier activities for Na+, K+, Ag+ and Pb2+ cations, the direct junction of a heteroaromatic unit with the nitrogen atom of crown ring is responsible for the remarkably high Ag+ ion selectivity.The present type of lariat ethers showed a different effect of size of parent crown ring on Ag+ ion transport rates from double armed crown ethers. Lariat ethers 3b3g with aza- 18-crown-6 rings transported Ag' ions faster than aza-15- crown-5 and am-12-crown-4 derivatives lb-lg and 2b2g. If an Ag ion is nicely accommodated in the crown ring, then the lariat ether may form a stable Ag+ complex of Type C (see Fig. l), although the formation of a 2 :2 complex cannot be ruled out. Thus, the cation selectivity of this lariat ether is apparently controlled by the 'ion-cavity size concept' established in crown ether chemistry2' and can be modified easily.In contrast, double armed crown ether 4b with a 15-membered ring was a better carrier than diaza- 18-crown-6 5b and diaza-2 I-crown-7 6b., They formed complexes of Types A and B. Competitive cation transport experiments were carried out using a mixture of KCIO,, AgClO,, Pb(ClO,j, and Cu(CIO,), (0.1 rnol m 3, each) as the Aq. 1 phase. When lariat ether 3b with a thiazole sidearm was employed as the carrier, Ag' ions were selectively and effectively transported; transport rates were determined to be 8.4 x 10 mol h-' for Ag+, 0.9 x lop6 rnol h-' for Pb2+ and ~0.3x rnol h for K+ and Cu2+ cations. The transport rate of the Ag+ ion was greatly enhanced probably because of the presence of an excess of perchlorate ions.On the other hand, the transport properties of aza-crown ether 3i were quite different when four kinds of cations were present. The transport rates were much less: 1.0 x lop6 rnol h ' for Ag+, 0.5 x 10 'mol h-' for Pb2+ and 0.3 x lop6rnol h-' for K+ and Cu2 ions. These results clearly indicate that the present lariat ethers can be used as selective carriers in a competitive transport system. Ag Ion-selective extraction + We performed liquid-liquid extraction experiments using a mixture of NaCIO,, KCIO,, AgCIO,, Pb(C10,)2, Cu(ClO,), and Cd(ClO,j,. The extraction percentage was estimated on the basis of the partition of the metal perchlorate between CH2C12 and the aqueous solution.Typical results of the competitive extractions are summarized in Table 2. Table 2 shows that lariat ethers 2b and 3b with thiazole sidearms predominantly extracted Ag ions from among the + metal cations examined. Their extraction results mirror those of the transport experiments (see Table 1). They selectively bound Ag + ions, efficiently solubilized them into the CH2C12 membrane and rapidly transported them. The extraction selectivity of Ag+ ions over Pb2+ and other metal cations was also found with crown ethers 2h, 2i, 3h and 3i, but their Ag+ ion selectivities were lower than those of lariat ethers 2b and 3b. Direct attachment of the thiazole ring to the aza-crown ring decreased extraction efficiency,? but remarkably enhanced the Ag ion selectivity.Thus, selectivity enhancement for Ag + + ions has been achieved by high pressure functionalization of aza-crown ethers, although several sulfur-containing macro- cycles have recently been reported to be Ag ion-selective+ ligands. Ag Ion-selective changes in '3CNMR spectra+ The cation binding behaviour of the new lariat ethers was examined by 13C NMR spectroscopy in DMF-D,O (4: 1). DMF-D20 was chosen as the solvent system partly because of solubility problems and partly to compare the results with those previously obtained with double armed diaza-crown ethers.," Fig. 2 illustrates Ag+- and Pb2+-induced changes in I3C NMR chemical shifts of selected carbons of lariat ethers 2b and 3b and a mixture of aza-18-crown-6 and thiazole.The addition of AgCIO, to a solution of the 15-membered lariat ether 2b caused significant and continuous spectral changes, whereas the addition of Pb(CIO,), offered no spectral change [Fig. 2(a)]. This indicates that the lariat ether 2bdiscriminates well between Ag+ and Pb2+ ions even in a homogeneous solution, although they have similar metal characteristics and ion sizes. Sig- nificant shifts were observed in the signals for the carbons of the crown ring (-N-CH,-) and the heteroaromatic substituents (-C=N-) upon addition ofAg+ to a DMF-D,O (4 : 1 ) solution of 2b, supporting the formation of an encapsulated Ag complex.+ Indeed, based upon the X-ray analyses of binuclear silver complexes with diaza- IS-crown-6 5b and diaza- 15-crown-5 4b with thiazole sidearms, each silver ion is basically coordinated by the two nitrogen atoms of the thiazole and the crown ring ~xygens.f*~'In contrast, the 18-membered lariat ether 3b showed different complexing behaviour.Fig. 2(b)indicates that its Pb2+ complex structure is very different from that of its Ag+ complex; the Pb2' complex has circular coordination in the same way as simple crown ethers, while Ag' ions are wrapped in a three dimensional fashion. Even though the electron density of the crown ring-nitrogen atom was decreased by the introduction of a thiazole group, the aza- 18-crown-6 ring was still effective at binding Pb2 + ions. Such Pb2 binding was not observed for the double armed crown ethers 4b, 5b and 6b.Disubstituted diaza-crown rings probably have a more rigid structure than single armed crown ethers and therefore were ineffective at binding Pb2+ ions. Inspection of Fig. 2(c) suggests that the parent aza-18-crown-6 formed sandwich-type 2: 1 complexes with Ag+ and Pb2+ cations, while thiazole itself interacted with Ag+ cations non-stoichiometrically. These results clearly indicate that the combination of a heteroaromatic-functionalized sidearm and an N-substituted monoaza-crown ring was responsible for the selective binding of Ag+ ions in a three dimensional complex. Table 3 summarizes the results of 13C NMR binding experiments for K+ and Cd2+ cations as well as for Ag+ and Pb2+ cations.Lariat ethers 3i interacted strongly with various metal cations except for Cd2+ as deduced from the induced changes in I3C NMR chemical shifts. In contrast, 2b and 3b hardly bound K+ and Cd2+ cations at all, whereas they selectively formed three dimensional complexes with Ag ions.+ Although the unsubstituted aza- 18-crown-6 and thiazole together interacted with various metal cations, the intramolecu- lar association of these two functional moieties gave a unique cation recognition ability. The thiazole substituent acts as an electron-withdrawing group and reduces the electron-density on the nitrogen atom of the aza-crown ring. $ Unfortunately, all our attempts to obtain crystals of 2b.Ag and 3b.Ag complexes were unsuccessful. J.CHEM. soc. PERKIN TRANS. 1 1995 174 carbon b 173 I 01234 53( -*Ic 1 52 carbon aI 151 uu 01234 01234 01234 53 51 carbon a carbon52r52 1 I_-.51 47 I -. . -L . _Id 01234 01234 Guest/ether (moVmol) Fig. 2 Ag': 0;Pb2+:e.Carbons as indicated by a and b in Table 3. Table 3 Guest-induced changes in 13C NMR chemical shifts of lariat ethers" Induced chemical shift (ppm) Ether Carbon K+ Ag+ PbZ+ Cd2+ * * *2b a 0.6* * *b 1.7 3b a * 1.o 0.9 * * *b 0.1 2.1 3a + thiazoleb a 0.4 1.5 -0.4' -0.7* *Cb 1.8 0.5 3i a 1.3 1.4 -1.9 -0.1* b --7.9 -6.8 -4.9 w 2bot Sb 3a + thiazole FO3y-JL"0 31 ~ a Conditions: ether (0.025 mmol), guest perchlorate (0.025 mmol) in DMF-D,O (4: 1) (0.5 cm3).Positive values refer to downfield shifts. 0.025 mmol of thiazole was added. 'Turbid. * f0.I ppm. In conclusion, high pressure functionalization of the parent crown ethers la, 2a and 3b allowed one-step synthesis of the Ag+- and Pb2+-induced changes in 13CNMR chemical shifts of lariat ethers 2b (a)and 3b (b)and a mixture of crown 3a and thiazole (c). new lariat ethers Ibg, 2b-g and 3b-g. These lariat ethers showed modified coordination character of the parent crown ethers, and enhanced Ag ion selectivity. Further applications + of the high pressure technique may offer new host molecules having novel binding sites and unique functions. Experimental General Melting points were taken on a Yanagimoto micro melting point apparatus and are uncorrected.'H NMR spectra were measured on a Hitachi R40 (90 MHz) or a JEOL JNM-EX270 (270 MHz) instrument. 13CNMR spectra were recorded on a JEOL JNM-FX90Q, a JNM-EX270 or a JNM-ALPHA500 spectrometer operating at 22.49 MHz, 67.80 Hz and 125.65 Hz, respectively. Chemical shifts are expressed in parts per million downfield from internal tetramethylsilane. J Values are given in Hz. Preparative medium-pressure liquid chromatography was carried out using a column (25 x 310 mm) prepacked with silica gel (Lobar, LiChroprep Si60, Merck). Crown ethers la,2a, 3a,li and 2i were prepared according to the methods reported in the Crown ethers 3h and 3i were also synthesized by the methods described in the literat~re.~.'~All new compounds had the correct elemental compositions as determined by microanalysis. The preparation and selected spectroscopic data for the compounds lh and 2h are given below.10-(2-Pyridylmethyl)-1,4,7-trioxa-10-azacyclododecane 1h. A solution of mono-aza crown la (177 mg, 1 mmol), 2-picolyl chloride hydrochloride (246 mg, 1.5 mmol), and triethylamine (1.O g, 10 mmol) in ethanol (20 cm3) was refluxed for 20 h. The mixture was diluted with water and extracted with dichlorometh- ane (50 cm3 x 3). The combined organic extracts were dried over anhydrous MgSO,. After evaporation of the dichlorometh- ane, the residue was subjected to column chromatography on alumina using hexane and hexane-ethyl acetate as eluent in a J. CHEM. SOC. PERKIN TRANS.I 1995 gradient fashion to give the title compound lh as a pale yellow oil (149 mg, 48%) (Found: C, 63.2; H, 8.1; N, 10.5. C,,H,,O,N, requires C, 63.14; H, 8.33; N, 10.52%); &(CDCI,) 2.79 (4 H, t, J5.0), 3.54-3.76 (12 H, s + m), 3.80 (2 H,s),6.96-7.15(1H,m),7.52-7.64(2H,m)and8.368.48(1H, m); Gc(CDC1,) 55.1, 62.5, 70.1, 70.5, 71.3, 121.6, 123.0, 136.1, 148.7 and 160.2. 13-(2-Pyridylmethyl)-1,4,7,1O-tetraoxa-l3-azacyclopentade-cane 2h. Prepared by the method described above, as a pale yellow oil (68%) (Found: C, 61.8; H, 8.7; N, 8.8. C16H2604N2 requires C, 61.91; H, 8.44; N, 9.03%); S,(CDCl,) 2.79 (4 H, t, J 5.8), 3.13-3.47 (16 H, s + m), 3.50 (2 H, s), 6.62-7.37 (3 H, m) and 8.02-8.18 (1 H, m);G,(CDCl,) 54.9, 62.5, 70.0, 70.3, 70.7, 71.1, 121.8, 123.0, 136.3, 148.4and 160.4.Functionalization of monoaza-crown ethers General procedure. A mixture of unsubstituted aza-crown ether la, 2a or 3a (1 mmol), heteroaromatic chloride (1.5 mmol) and triethylamine (3 mmol) was diluted with tetrahydrofuran (THF) in a polytetrafluoroethylene tube (4 cm3), which was compressed to 0.8 GPa (8 kbar) and heated and kept at 100 "C for several days. The high pressure instrument employed has been described elsewhere. 'After cooling and depressuriz- ation, the triethylamine and THF were evaporated under reduced pressure. Benzene (ca. 50 cm3)was added to the residue and the quaternary salt was removed by filtration. The filtrate was then subjected to chromatography on silica gel (Wakogel C-200 or C-loo), using hexane, hexane-ethyl acetate and ethyl acetate as eluent in a gradient fashion.Reaction time (days), yield (%), melting point ("C), microanalytical data, and selected spectroscopic data for the new compounds are as follows. l0-(Thiazol-2-yl)-l,4,7-trioxa-lO-azacyclododecane 1b. 4 Days (64%), mp 30-32 "C (Found: C, 51.3; H, 7.2; N, 10.7. C,,H,,O,N,S requires C, 51.14; H, 7.02; N, 10.84%); SH(CDC1,) 3.60 (8 H, s), 3.63-3.95 (8 H, m), 6.37 (1 H, d, J 3.8) and 7.04 (1 H, d. J3.8);Gc(CDC1,) 53.9, 69.5, 70.0, 71.4, 105.9, 139.5 and 171.4. 1O-(Benzothiazol-2-yl)-1,4,7-trioxa-lO-azacyclododecanelc. 6 Days (44%), mp 77-79 "C (Found: C, 58.4; H, 6.5; N, 9.1. C,sH200,N,S requires C, 58.42; H, 6.54; N, 9.08%); SH(CDCl,) 3.54 (8 H,s), 3.60-4.00 (8 H, m) and 6.85-7.60 (4 H, m);G,(CDCl,) 53.6, 69.6, 70.9, 114.9, 128.2, 145.7 and 158.2.1O-(Benzoxazol-2-yl)-1,4,7-trioxa-lO-azacyclododecaneId. 6 Days (5773, mp 105-107 "C (Found: C, 61.6; H, 7.0; N, 9.6. C, 5H2004NZrequires C, 61.63; H, 6.90; N, 9.58%); G,(CDCl,) 3.58 (8 H, s), 3.63-3.95 (8 H, m) and 6.68-7.33 (4 H, m); G,(CDCl,) 50.7, 69.8, 70.1, 71.2, 108.7, 116.1, 120.2, 123.8, 143.6, 149.0 and 162.7. 1O-(bChloropyridazin-3-yl)-l,4,7-trioxa-lO-azacyclodode-cane le. 4 Days (62%), mp 89-92 "C (Found: C, 50.3; H, 6.3; N, 14.7. C,,H,,O,N,CI requires C, 50.09; H, 6.31; N, 14.60%); &(CDCl,) 3.52 (8 H, s), 3.57-3.75 (4 H, m),3.80-3.97 (4 H, m) and 7.03 (2 H, s); G,(CDCl,) 52.0, 69.4,69.7, 71.2, 116.2, 128.2, 146.0 and 158.7.1O-(Pyrimidin-2-yl)-1,4,7-trioxa-l0-azacyclododecane 1f. 5 Days (74%), mp 35-36 "C (Found: C, 57.1; H, 7.7; N, 16.5. C,,H,,O,N, requires C, 56.90; H, 7.56; N, 16.59%); dH(CDC1,) 3.56 (8 H, s), 3.84 (8 H, s), 6.40 (1 H, t, J4.8) and 8.22(2H,d,J4.8);Gc(CDC1,)49.6, 69.9,70.2,71.5, 109.4,157.3 and 161.9. 10-(5-Trifluoromethyl-2-pyridy1)-1,4,7-trioxa-1O-azacyclodo-decane lg. 4 Days (58%), mp 70-72 "C (Found: C, 52.4; H, 6.1; N, 8.7. C,,H,,O,N,F, requires C, 52.50; H, 5.98; N, 8.75%); G"(CDC1,) 3.55-3.95, 3.58 (16 H, m + s), 6.64 (1 H, d, J9.1), 7.50 (I H, dd, J 2.6, 9.1) and 8.26 (1 H, br s); G,(CDCl,) 51.2, 69.8,71.6,106.1, 114.3(Jc,33), 125.0(Jc,270), 133.8,145.4and 160.3. 250 1 13-(Thiazol-2-yll,4,7,1O-tetraoxa-l3-azacyclopentadecane 2b.5 Days (9979, oil (Found: C, 51.5; H, 7.3; N, 9.3. C,,H,,0,N2S requires C, 51.64; H, 7.33; N, 9.26%); G,(CDCl,) 3.58 (4 H, s), 3.60 (8 H, s), 3.63-3.88 (8 H, m), 6.37 (1 H, d, J3.6) and 7.04(1 H, d, J3.6);dc(CDC13) 53.9, 68.8, 70.3, 70.4, 71.2, 105.9, 139.6 and 170.8. 13-(Benzothiazo1-2-yl)-1,4,7,10-tetraoxa-13-azacyclopentade-cane 2c. 4 Days (99%), mp 77-79 "C (Found: C, 57.8; H, 7.0; N, 7.9. C,,H,,O,N,S requires C, 57.93; H, 6.86; N, 7.95%); GH(CDCl,) 3.55 (4 H, s), 3.58 (8 H, s), 3.70-3.88 (8 H, m) and 6.81-7.54(4H,m);Gc(CDCl,) 53.6,68.9,70.3,70.4,71.2,118.9, 120.5, 120.9, 125.7, 130.9, 153.2and 167.8. 13-(Benzoxazol-2-yl)-1,4,7,l0-tetraoxa-l3-azacyclopentade-cane 2d. 4 Days (99%), mp 80-82 "C (Found: C, 60.7; H, 7.1; N, 8.2.C,,H,,O,N, requires C, 60.70; H, 7.19; N, 8.33%); d,(CDCl,) 3.55 (4 H, s), 3.62 (8 H, s), 3.75 (8 H, m)and 6.73- 7.32 (4 H, m); Gc(CDC1,) 51.0, 69.3, 70.2, 70.4, 71.1, 108.6, 116.0, 120.1, 123.8, 143.6, 149.0 and 162.3. 13-(6-Chloropyridazin-3-yl)-1,4,7,1O-tetraoxa-l3-azacyclo-pentadecane 2e. 4 Days (96%), mp 74-76 "C (Found: C, 50.5; H, 6.6; N, 12.8. C,,H,,O,N,C1 requires C, 50.68; H, 6.68; N, 12.66%);GH(CDC1,) 3.53 (4 H, s), 3.58 (8 H, s), 3.75 (8 H, br s), 6.85(1 H,d,J9.6)and7.09(1 H,d,J9.6);Sc(CDC1,)51.6,69.1, 70.1, 70.3, 71.1, 114.8, 128.3, 145.8 and 158.0. 13-(Pyrimidin-2-yl)-1,4,7,lO-tetraoxa-l3-azacyclopentade-cane 2f. 4 Days (87%), mp 57-59 "C (Found: C, 56.7; H, 7.9; N, 13.9. C14H2304N3 requires C, 56.55; H, 7.80; N, 14.13%); d~(cDC1,) 3.63 (4 H, s), 3.67 (8 H, s), 3.70 (8 H, s), 6.38 (1 H, t, J 4.9) and 8.22 (2 H, d, J 4.9); d,(CDCl,) 50.3, 69.4, 70.3, 109.4, 157.5 and 161.6.13-(5-Trifluoromethyl-2-pyridyl)-1,4,7,1O-tetraoxa-l3-azacy-clopentadecane 2g. 4 Days (8873, mp 4749 "C (Found: C, 52.8; H, 6.2; N, 7.6. C,,H,,O,N,F, requires C, 52.74; H, 6.36; N, 7.69%); G,(CDCl,) 3.60 (4 H, s), 3.68 (8 H, s), 3.77 (8 H, m), 6.5 1 (1 H, d, J 8.0), 7.50 (1 H, dd, J 2.5, 8.0) and 8.28 (1 H, br s); G,(CDCl,) 51.2,70.3,70.4,71.3, 114.3 (JCF 33), 125.0 (JCF 270), 133.9, 145.7 and 159.6. 16-(Thiazol-2-yl)-l,4,7,10,13-pentaoxa-1bazacyclooctade-cane 3b. 4 Days (92%), oil (Found: C, 52.1; H, 7.8; N, 8.1. C,,H,,O,N,S requires C, 52.00; H, 7.56; N, 8.09%); G,(CDCl,) 3.65 (16 H, s), 3.77 (8 H, s), 6.38 (1 H, d, J 5.0) and 7.05 (1 H, d, J5.0);G,(CDC13) 52.3,68.7,70.5,70.6,70.8,105.7, 139.5 and 170.7.16-(Benzothiazol-2-yl)-1,4,7,10,13-pentaoxa-l6-azacycloocta-decane 3c. 4 Days (99%), oil (Found: C, 57.3; H, 7.2; N, 6.9. C,,H,,O,N,S requires C, 57.55; H, 7.12; N, 7.07%); d,(CDCl,) 3.53 (16 H, s), 3.72 (8 H, s) and 6.80-7.53 (4 H, m); Gc(CDCl3) 52.3, 69.1, 70.8, 71.0, 118.8, 120.5, 120.9, 125.8, 130.9, 153.2 and 167.9. 16-(Benzoxazol-2-yl)-1,4,7,10,13-pentaoxa-l6-azacycloocta-decane 3d.4 Days (96%), mp 53-54 "C (Found: C, 59.7; H, 7.6; N, 7.2. C19Hz806N, requires C, 59.99; H, 7.42; N, 7.36%); G,(CDCl,) 3.60 (16 H, s), 3.75 (8 H, m) and 6.72-7.33 (4 H, m); GC(CDC1,) 69.5, 70.7, 70.9, 108.6, 116.0, 120.1, 123.8, 143.6, 149.0 and 162.4.16-(6-Chloropyridazin-3-y1)-1,4,7,10,13-pentaoxa-l6-azacy-clooctadecane 3e. 4 Days (89%), oil (Found: C, 51.1 ;H, 6.9; N, 11.4. Cl,H,60,N,Cl requires C, 51.13; H, 6.97; N, 11.18%); dH(CDC13) 3.58 (16 H, s), 3.74(8 H, m), 6.87 (1 H, d, J9.8) and 7.06 (1 H, d, J 9.8); Gc(CDCl,) 50.3, 69.3, 70.9, 114.9, 128.2, 145.7 and 158.2. lb(Pyrimidin-2-y1)- 1,4,7,10,13-pentaoxa- 16-azac yclooctade-cane 3f. 4 Days (9779, oil (Found: C, 56.2; H, 8.2; N, 12.3. Cl6H2,0,N3 requires C, 56.29; H, 7.97; N, 12.31%);SH(CDC1,) 3.58-3.94 (16 H, s + m), 6.34 (1 H, t, J4.6) and 8.17 (2 H, d, J 4.6); dc(CDC13) 48.7, 69.4, 70.7, 70.8, 71.0, 109.3, 157.5 and 161.6. 16-(5-Trifluoromethyl-2-pyridyl)-l,4,7,10,13-pentaoxa-l6- 2502 azacyclooctadecane 3g.4 Days (92%), oil (Found: C, 52.7; H, 6.6; N, 6.9. C,,H,,0,N2F3 requires C, 52.94; H, 6.66; N, 6.86%); G,(CDC13) 3.63 (1 6 H, s), 3.70-3.84 (8 H, m), 6.58 (1 H, d,J9.0),7.52(1 H,dd,J2.8,9.0)and8.28(1H,brs);G,(CDC13) 50.0, 69.3, 70.9, 105.2, 114.2 (JcF 33), 125.1 (JCF270), 134.0, 145.8 and 159.8. Extraction experiment Competitive extraction experiments were carried out as follows. A methylene chloride solution of the crown ether (0.015 mmol, 1.5 cm3) was added to an aqueous solution of metal perchlorates (0.01 5 mmol, 1.5 cm3 of each), After the mixture had been stirred for 2 h, the aqueous phase was separated. The concentrations of metal cations were determined by atomic absorption or flame spectroscopic methods (performed at Exlan Technical Center Co., Okayama). Transport experiments Transport experiments were performed at room temperature (ca.20 "C) in a U-tube glass cell (2.0 cm i.d.).2a The carrier, dissolved in methylene chloride, was placed in the base of the U- tube, and two aqueous phases were placed in the tube arms, floating on the organic membrane phase. The membrane phase was constantly (50 rpm) stirred with a magnetic stirrer (MS magnetic stirrer). The transport rates indicated in Table 2 were calculated from the initial rates of appearance of co-transported C104- anion into the Aq. 2 phase, which was determined by a ClO, -ion-selective electrode (Orion EA940 Autochemistry System). The amount of each metal cation transported was also determined by atomic absorption or flame spectroscopic method (Shimadzu AA-630- 12 Atomic Absorption/Flame Emission Spectrophotometer), and was nearly equal to that of the co-transported anion.It was confirmed that all guest salts were hardly transported at all in the absence of a carrier (transport rate 0.3 x mol h-'). Acknowledgements This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan (No. 06242210 to K. M. and No. 04804037 to H. T.) and from the Salt Science Research Foundation (No. 9312 to H. T.). The authors are also grateful to the Ministry of Education, Science, and Culture, Japan for purchasing the high-field NMR instruments (JEOL JNM-ALPHA500 and JNM-EX270) from the special fund (to K.M. as a representative in 1992). References 1 Recent reviews: (a)G. W. Gokel and J. E. 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