Arsenic and lead (beudantite) contamination of agricultural rice soils in the Guandu Plain of northern Taiwan

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Substituent eﬀects in the binding of bis(4-ﬂuorobenzyl)ammonium

ions by dianilino[24]crown-8

Sheng-Hsien Chiu,

*

_{Kang-Shyang Liao and Jen-Kuan Su}

Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, ROC Received 8 July 2003; revised 12 September 2003; accepted 16 October 2003

Abstract—A series of para-substituted dianilino[24]crown-8 (DA24C8) macrocycles were synthesized and their ability to form host– guest complexes with bis(4-ﬂuorobenzyl)ammonium ions (DFAþ_{) were investigated. Although these crown ethers contain weakly}

hydrogen bonding aniline motifs, they do bind DFAþ_{in CDCl}

3/CD3NO2solution, presumably in a pseudorotaxane-like manner. A

plot of the values of the relative binding strengths (log½KaðRÞ=KaðHÞ) versus the Hammett substituent constants rþof the groups at

the para-position of the aniline units suggests that a linear free energy correlation exists for this self-assembly process. The strength of the binding between the crown ether and the thread-like ion can be ﬁne-tuned over a narrow range by judicious choice of the substituting groups.

The binding between dibenzo[24]crown-8 (DB24C8) and

various dibenzylammonium ions (DBAþ_{) has been}

in-vestigated extensively for almost a decade.1 _The

favor-able [Nþ_{–H O] and [N}þ_{–C–H O] hydrogen bonding} interactions between the ammonium ion and the ether motifs of the macrocycle result in the interpenetration of

the DBAþ_{ion into the cavity of the DB24C8 macroring}

to form a 1:1 pseudorotaxane2 _{complex. To date, the}

geometry of this inclusion complex and the strong

noncovalent interactions between DB24C8 and DBAþ

units have led to eﬃcient syntheses of many interlocked molecular compounds, such as catenanes and

rotax-anes.3 _{DB24C8 cannot be substituted simply in a}

sym-metrical manner, however, and this feature is one that complicates stereochemical matters when it comes to building intricate interlocked molecules from mono- or

bifunctional DB24C8 macrocycles.4 _{To overcome this}

problem, other symmetrical crown ethers, such as

bis-m-phenylene-[26]crown-8 (BMP26C8)5 _and

dipyrido[24]-crown-8 (DP24C8),6_{have been synthesized and}

investi-gated as alternative host molecules (Fig. 1).

An additional issue to address in preparing molecular

shuttles and molecular switches7 _{based on these species}

is that the strong binding interactions between the components can results in high activation energies and

corresponding slow rates of switching,8_{which could be}

drawbacks for their eventual use in high-speed devices. Using components that bind less strongly would over-come this problem, albeit at the expense of low yields for their molecular assembly. Thus, in making high-speed, symmetrical, machine-like molecules it would be useful to be able to adjust the strength of the hydrogen bonding interactions after assembly of the interlocked

N O O O N O O O N O O O N O O O O O O O O O O O O O O O O O O O DB24C8 BMP26C8 DP24C8 DA24C8 N H₂ + PF₆ _ DBA PF. 6

Figure 1. Some crown ethers that bind to the thread-like DBAþ_ion. Keywords: crown ethers; pseudorotaxanes; linear free energy

correla-tion.

* Corresponding author. Tel.: 23690152x150; fax: +886-2-24980963; e-mail:shchiu@ntu.edu.tw

Tetrahedron Letters 45 (2004) 213–216

Tetrahedron

Letters

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molecules. From this point of view, using the crown

ether dianilino[24]crown-8 (DA24C8)9 _{and its D}

2h -sym-metrical substituted derivatives in the synthesis of interlocked molecules may be a solution to these prob-lems. The binding behavior between DA24C8 and

DBAþ _{has not been reported so far, but we expected}

that it would be reasonably strong because of the pres-ence of six aliphatic ether oxygen atoms and two aniline nitrogen atoms (cf. DB24C8, which has four aliphatic (strong) and four aromatic (weak) ether oxygen atoms) in the crown ether that are capable of accepting hydrogen bonds. Although we expected the aniline nitrogen atoms to be quite weak hydrogen bond accep-tors, because their lone pairs of electrons are positioned perpendicular to the mean plane of the macrocycle rather than within it,10_{their basicity can be increased by} positioning electron-donating groups at their

para-positions,11 _{which would enhance the strength of}

bind-ing between the crown ether and DBAþ _{ions. Thus, a}

crown ether with strongly electron-donating groups could be used in the synthesis of an interlocked mole-cule, which is then modiﬁed with electron-withdrawing groups that decrease the energy barrier for translation of the macrocyclic ring. As a ﬁrst steptoward such con-trollable molecular devices, in this paper we report the syntheses of a series of para-substituted DA24C8 mac-rocycles and investigate their binding to

bis(4-ﬂuoro-benzyl)ammonium hexaﬂuorophosphate (DFAÆPF6).

Scheme 1 depicts the route we used to synthesize the substituted DA24C8 macrocycles 6a–d. Reactions of excess p-substituted anilines 1a–d with the bistosylate 2 aﬀorded diamines 3a–d. The diamines 3a–d were then

reacted with tetraethyleneglycoyl dichloride12 _{in dry}

toluene under conditions of high dilution to give the macrocyclic lactams 5a–d, which were subsequently reduced smoothly by borane in THF into the corre-sponding substituted DA24C8 macrocycles 6a–d. The overall yields of these synthetic procedures, from ani-lines 1a–d to crown ethers 6a–d, are between 18% and 33%. Crown ether 6e was synthesized in 78% yield from

crown ether 6d by a palladium-catalyzed amination.13

When a1_{H NMR spectrum was obtained from a}

solu-tion (20 mM) of both the crown ether 6a and

dibenzyl-ammonium hexaﬂuorophosphate (DBAÆPF6) in CD3CN

at 298 K, we observed no signiﬁcant movement of any of

the signals in the spectrum relative to the spectra of the individual components. This result suggests that the degree of binding between crown ether 6a and

thread-like ion DBAþ _{is negligible in CD}

3CN at 298 K. To

enhance the hydrogen bonding strength, we changed the

solvent to a 2:1 mixture of CDCl3 and CD3NO214 and

replaced DBAÆPF6 with the more-soluble DFAÆPF6.

Thus, when DFAÆPF6 and the crown ether 6a were

mixed together (20 mM) in CDCl3/CD3NO2 (2:1), we

observed the appearance of additional broad signals in

the 1_{H NMR spectrum recorded at 298 K. To monitor}

the complexation more conveniently, we cooled the solution to 223 K. At this temperature, more than half of the components in the solution were complexed (Fig. 2).

Upon complexation, the signal of the methylene protons

of DFAÆPF6 that are adjacent to the NH2þ unit is

shifted downﬁeld by 0.49 ppm, relative to its signal when uncomplexed, to 4.46 ppm. The broad signal at 3.25– 3.60 ppm, which represents the resonances of the ethyl-ene protons of the crown ether 6a, is split upon complexation into four signals at 3.16, 3.41, 3.50 and

N O O O N O O O R R NH O O O NH R R NH₂ R OTs O O O OTs + O O O O O Cl Cl O O BH₃-THF N O O O N O O O R R OMe H Br R N O 6b 6c 6d 6e Crown Ether 2 1a-d 3a-d 5a-d 4 CH3 6a 6d morpholine 6e Pd(OAc)2/P(t-Bu)3 / t-BuONa Scheme 1. Syntheses of the DA24C8 derivatives.

Figure 2. Partial1_{H NMR spectrum [400 MHz, CDCl3/CD3NO2}_(2:1), 223 K] of an equimolar mixture (20 mM) of 6a and DFAÆPF6, which demonstrates that uncomplexed (uc) and complexed (c) species equil-ibrate with one another slowly on this NMR spectroscopy timescale.

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3.56 ppm, respectively. In the mixture, the signals of the aromatic protons of 6a exist in two distinct groups: sharp complexed and broad uncomplexed signals. These signals are consistent with the notion that 6a and

DFAÆPF6 form a pseudorotaxane-like complex in

CDCl3/CD3NO2, with possible [Nþ–H O] and [Nþ– H N] hydrogen bonding interactions. The fast-atom bombardment (FAB) mass spectrum recorded on an

equimolar mixture of 6a and DFAÆPF6reveals a peak at

m=z765 corresponding to the 1:1 complex having lost its

PF6 ion.

We could not accurately determine the association

constant for this assembly by 1_{H NMR spectroscopy}

using the single-point method15 _{at either 223 or 298 K}

because of diﬃculty in integrating the broad and, in some cases, overlapping signals; instead, the binding

constant was elucidated at 298 K using19_{F NMR}

spec-troscopy.4b _{As expected, a solution (20 mM) of a}

mix-ture of the salt DFAÆPF6and the crown ether 6a gave an

19_{F NMR spectrum at 298 K having sharp and}

distin-guishable signals (Fig. 3). The signals appearing at )112.94 and )111.23 ppm were assigned to the

uncom-plexed and comuncom-plexed DFAþ _{ions, respectively, based}

on a literature precedent.4b;16 _{By integration of these}

signals, the association constant for pseudorotaxane

formation between DFAÆPF6 and 6a was calculated to

be 15 M1 _{at 298 K. We used this method to determine}

the association constants for the complexes formed

be-tween DFAÆPF6 and the other substituted DA24C8

crown ethers;17_{Table 1 lists the values of the association} constants and their derived free energies of association. We note that among these crown ethers, it is macrocycle 6e, which bears the most-strongly electron-donating substituents (morpholine units) on its aniline rings, that

binds most strongly to DFAÆPF6; the crown ether with

the most-electron-withdrawing bromine substituents (6d) is the weakest binder. The values of DH° and DS° of each complexation process were obtained from the intercept and slope, respectively, of the straight line in the plot of DG° versus T , which was obtained from the variable-temperature NMR spectroscopy experiments.

The negative values of DH° and DS° in each case suggest

that these complexation events are enthalpy-driven processes. A linear free energy correlation has been reported in the supramolecular complexation between DB24C8 and variety of meta- and para-substituted

DBAþ _ions.15b_{The electronic nature of the substituents}

on the DBAþ _{unit aﬀects the NH}þ

2 centers ability to donate a hydrogen bond and the ability to form p–p stacking interactions between the substituted benzyl unit and the catechol ring of the DB24C8 macrocycle. From Table 1, it is clear that the strength of the binding

between DA24C8 derivatives and DFAþ _{ions is related}

to the electronic nature of the substituents on the aniline units of the macrocycles. To examine whether a linear free energy correlation exists in this case or not, the

relative association constants (log½KaðRÞ=KaðHÞ) for

pseudorotaxane formation between the

ﬂuoro-substi-tuted salt DFAÆPF6 and the substituted crown ethers

were plotted against the substituent constant (rþ_).18 _A straight line is the result (Fig. 4), which suggests that a linear free energy correlation does exist for this supra-molecular complexation event. The slope of the straight line, which corresponds to the value of for the

com-plexation process, is ca. )0.28. The linear tendency

implies that the binding strength between DFAþ _and

other substituted DA24C8 macrocycles may be closely

estimated simply by knowing the value of rþ _{of the}

substitutents.

The negative value of q suggests that the

ﬂuoro-substi-tuted salt DFAÆPF6favors complexation with DA24C8

macrocycles bearing strongly electron-donating

Figure 3. Partial variable-temperature 19_{F NMR spectra [376 MHz,} CDCl3/CD3NO2 (2:1)] of an equimolar mixture (20 mM) of 6a and DFAÆPF6.

Table 1. Stability constantsa_{(Ka) and derived thermodynamic data for the complexation of substituted DA24C8 macrocycles and DFAÆPF6} Crown ether Ka(M1₎a _{DG° (kcal mol}1₎b _{DH° (kcal mol}1₎c _{DS° (cal mol}1_K1₎c

6a 15 1.60 )4.7 ± 0.7 )10.7 ± 2.8 6b 11 1.42 )4.3 ± 0.5 )10.3 ± 2.0 6c 16 1.64 )6.3 ± 0.8 )15.5 ± 2.8 6d 8 1.23 )4.0 ± 0.4 )9.2 ± 1.7 6e 30d _2.02 _{)8.8 ± 1.1} _{)22.7 ± 4.0} a

Stability constants (Ka) were obtained as outlined in Ref. 15 based on the19_{F NMR spectra in CDCl3/CD3NO2}_{(2:1) at 298 K (error 6 15%).} b

The free energy of complexation (DG°) was calculated from each value of Kausing the equationDG° ¼ RT ln Ka. c

The values of DH° and DS° were obtained from the intercept and slope of the straight line in the plot of DG° versus T using the relationship DG° ¼ DH ° T DS°.

d_{The samples were prepared by dissolving freshly prepared 6e in the degassed deuterated solvent: they were then kept in the dark to minimize any} possible photooxidation.

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substitutents. The small value of q implies that it is possible to modify the binding aﬃnity between the crown ether and the thread-like ion over a reasonable range by controlling the electronic properties of the substitutents on the aniline ring, but that the magnitude of this change in the association constant is not dra-matic. Since a simple oxidation reaction can readily convert the electron-donating methyl groups of macro-cycle 6a into more-electron-withdrawing formyl groups, and that an amination reaction can translate the mac-rocycle 6d into a fourfold stronger binder (6e), it seems reasonable to expect that judicious choice of the sub-stituent on the crown ether, coupled with a suitable post-assembly modiﬁcation, would allow the prepara-tion of speed-controllable machine-like molecules. We have synthesized a series of DA24C8 derivatives and

demonstrated that their aﬃnity for binding with DFAþ

ions can be ﬁne-tuned by judicious choice of substitu-ents. We are now trying to assemble this recognition system into a [2]rotaxane through dynamic imine for-mation.19

Acknowledgements

We thank the National Science Council for ﬁnancial support (NSC 91-2113-M-002-055).

References and Notes

1. (a) Cantrill, S. J.; Pease, A. R.; Stoddart, J. F. J. Chem. Soc., Dalton Trans. 2000, 3715–3734; (b) Cliﬀord, T.; Abushamleh, A.; Busch, D. H. Proc. Natl. Acad. Sci. USA 2002, 99, 4830–4836; (c) Gibson, H. W.; Yamaguchi, N.; Jones, J. W. J. Am. Chem. Soc. 2003, 125, 3522– 3533.

2. Asakawa, M.; Ashton, P. R.; Balzani, V.; Boyd, S. E.; Credi, A.; Mattersteig, G.; Menzer, S.; Montalti, M.; Raymo, F. M.; Ruﬃlli, C.; Stoddart, J. F.; Venturi, M.; Williams, D. J. Eur. J. Org. Chem. 1999, 985–994. 3. Molecular Catenanes, Rotaxanes and Knots; Sauvage,

J.-P., Dietrich-Buchecker, C., Eds.; VCH-Wiley: Wein-heim, 1999.

4. (a) Ashton, P. R.; Baxter, I.; Cantrill, S. J.; Fyfe, M. C. T.; Glink, P. T.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 37, 1294–1297; (b) Cantrill, S. J.; Youn, G. J.; Stoddart, J. F.; Williams, D. J. J. Org. Chem. 2001, 66, 6857–6872.

5. (a) Bryant, W. S.; Guzei, I. A.; Rheingold, A. L.; Merola, J. S.; Gibson, H. W. J. Org. Chem. 1998, 63, 7634–7639; (b) Cantrill, S. J.; Fulton, D. A.; Heiss, A. M.; Pease, A. R.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 2000, 6, 2274–2287.

6. Chang, T.; Heiss, A. M.; Cantrill, S. J.; Fyfe, M. C. T.; Pease, A. R.; Rowan, S. J.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 2947–2950.

7. Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2000, 39, 3348–3391.

8. Cao, J.; Fyfe, M. C. T.; Stoddart, J. F. J. Org. Chem. 2000, 65, 1937–1946.

9. Ghorbanian, S.; Mehta, L. K.; Parrick, J.; Robson, C. H. Tetrahedron 1999, 55, 14467–14478.

10. There are [N–H N] hydrogen bonding interactions in the solid-state structure of a [2]rotaxane comprised of a DBAþ _{ion and a crown ether containing an aniline-like}

unit. See: Glink, P. T.; Oliva, A. I.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 2001, 40, 1870–1875.

11. (a) Summerhays, K. D.; Pollack, S. K.; Taft, R. W.; Hehre, W. J. J. Am. Chem. Soc. 1977, 99, 4585–4587; (b) The Chemistry of the Amino Group; Patai, S., Ed.; VCH-Wiley: London, 1968.

12. Lehn, J.-M. U.S. Patent 888,877, 1975; Chem. Abstr. 1976, 85, 160192x.

13. (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805–818; (b) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046–2067.

14. The binding constant between DB24C8 and DBAþ _is

400 M1 _{in CD}

3CN, but it is much higher in CDCl3

27,000 M1_{; see: Ashton, P. R.; Campbell, P. J.; Chrystal,}

E. J. T.; Glink, P. T.; Menzer, S.; Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1865–1869, and in CD3NO2(8000 M1).

15. (a) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 709–728; (b) Ashton, P. R.; Fyfe, M. C. T.; Hicking-bottom, S. K.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. J. Chem. Soc., Perkin Trans. 2 1998, 2117– 2124.

16. 19_{F NMR spectra were recorded on a Varian Unity Plus}

(376 MHz) spectrometer and are referenced to C6F6

()163.0 ppm) present as a CH2Cl2 solution in an internal

capillary tube.

17. The values of Ka for the binding of DFAÆPF6 and 6d in

CDCl3/CD3NO2 (2:1) were determined at 273, 263, 253,

243, and 233 K from the recorded19_{F NMR spectra using}

a single-point method (see, i.e. Ref. 4b). Extrapolation of the vant Hoﬀ plot obtained using these data gives a value for Ka at 298 K of about 8 M1.

18. Since the electron density of the para-substituents of the aniline ring can interact both inductively and mesomer-ically to the aniline N-atom (see, Ref. 11b)––the hydrogen bonding interacting site––the substitution constant rþ

was applied instead of r values. See: (a) Okamoto, Y.; Brown, H. C. J. Org. Chem. 1957, 22, 485–494; (b) Brown, H. C.; Okamoto, Y. J. Am. Chem. Soc. 1958, 80, 4979– 4987.

19. Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2002, 41, 899–952. 0.5 -0.5 -1.0 -1.5 0.5 -0.5 log[K_a(R)/K_a(H)]

σ

+ O N OMe _CH 3 H Br = -0.28 ρ

Figure 4. Hammett correlation between log½KaðRÞ=KaðHÞ and rþ _in CDCl3/CD3NO2(2:1) at 298 K. The slope of the straight line obtained corresponds to the supramolecular reaction constant (q).