Cation Effects on Solvents, Ligands, and Nucleophiles - American

30 Cation Effects on Solvents, Ligands, and Nucleophiles

Downloaded by MICHIGAN STATE UNIV on February 18, 2015 | http://pubs.acs.org Publication Date: July 1, 1987 | doi: 10.1021/ba-1987-0215.ch030

Effect of Side Arms on Cation Binding by Macrocycles G. W. Gokel, L. Echegoyen, Κ. A. Arnold, T. P. Cleary, V. J. Gatto, D. A. Gustowski, C. Hanlon, A. Kaifer, M. Kim, S. R. Miller, C. Minganti, M. Ouchi, C. R. Morgan, I. Posey, R. A. Schultz, T. Takahashi, A. M. Viscariello, B. D. White, and H. Yoo Department of Chemistry, University of Miami, Coral Gables, FL 33124 Macrocyclic polyether compounds having one (lariat ethers) or two (bibracchial lariat ethers, BiBLEs) donor-group-bearing side arms exhibit Na+-, K+-, NH4+-, and Ca -binding affinities and selec tivities different from those of the unsubstituted macrocycles. Mac rocycles utilizing a nitrogen atom as the point of attachment (pivot atom) show generally higher flexibility and binding strength than compounds having the sidearm(s) attached at a carbon (carbon pivot). The moreflexibleand less polar compounds favor K over the more charge-dense cations irrespective of hole size. The cation bind ing involves both the macroring and the side arms. This fact is demonstrated for solutions as well as the solid state. Ν-pivot BiBLEs can be prepared by a very convenient single-step cyclization or by a two-step approach that is more conventional but that affords high yields of product. Both lariat ethers and BiBLEs can be electrochemically "switched" to alter the cation-binding affinities and strengths. 2+

+

V^ROWN ETHERS AND THEIR RELATIVES have proved so interesting to the chemical community in part because of their ability to complex and stabilize various cations. In the process, these compounds may alter the properties of associated anions. Nowhere has this anion effect been more exploited than in phase-transfer catalysis (1-3). The two classes of macrocyclic polydentate cation binders that have been known the longest and have been most studied are the crown ethers developed by Pedersen (4) and the cryptands invented by Lehn (5, 6). Not 0065-2393/87/0215-0443$07.00/0 © 1987 American Chemical Society In Nucleophilicity; Harris, J., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

NUCLEOPHILICITY


444

long after their introduction, efforts were made to incorporate these mac rocycles into polymeric matrices of one sort or another. This work had several goals. First, incorporation in the polymer matrix possibly would enhance catalyst stability. Second, unusual selectivities might be realized from the polymer that were not observed in the monomers. Third, improvement in recoverability and thus the economics of using these relatively expensive compounds was anticipated. One method for attaching macrocycles to polymers is to use a molecular tether such as a hydrocarbon or polyethylene glycol chain. A hydrocarbon chain attached to the macrocycle should function largely in a mechanical sense to connect backbone and ring. A polyethylene glycol chain could serve as a mechanical link but also "cooperate" with the macroring in cation binding. Also, possibly a side arm containing donor groups could dominate the cation binding and render useless the crown ether. Two types of mo lecular tethers and two possible methods for attaching them to crown ethers are as follows:

When the tether is attached to the macroring at carbon, the molecule is said to have a carbon pivot atom. When the side arm is attached as illustrated at the right, the pivot atom is nitrogen. Because the molecular models of these compounds resemble lassos and because the combination of side arm and macroring donors can permit a cation to be "roped and tied", we have called such macrocycles "lariat ethers". Classes of Lariat Ethers Because crown ethers and cryptands are composed most commonly of re peating - C H C H 0 - or related units that differ by the number of carbons or the identity of heteroatoms, we can predict that side arms are likely to be attached either at carbon or at nitrogen. Sulfur and oxygen are usually divalent and therefore unavailable to serve as pivot atoms. To be effective, the side arms themselves must have embedded Lewis basic donor groups that can augment the macrorings cation-binding ability. Our own studies have thus far focused only on carbon- and nitrogen-pivot molecules and on compounds having only one or two arms. This focus was done so that detailed and systematic information about the cation-binding strengths and selec2

2

In Nucleophilicity; Harris, J., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1987.

Effect of Side Arms on Cation Binding by Macrocycles 445

30. GOKEL ET AL.

tivities could be developed. Such a systematic survey should permit an understanding of cation binding in general, and this understanding, in turn, should permit an understanding of anion chemistry. Single-Armed, Carbon-Pivot Lariat Ethers Our survey of sidearm-bearing materials began with the readily accessible 15-membered ring, carbon-pivot systems. Glycerol, H O C H - C H O H - C H O H , was chosen as the basic pivot unit because it is both inexpensive and versatile. The glycerol unit was incorporated into the macrorings by using one of the primary and the secondary hydroxyl groups. The remaining hydroxyl group was used to attach the tether. Practically, attachment was accomplished by the reaction of epichlorohydrin with either an alcohol or a phenol as the nucleophile. The glycidyl ethers were then hydrolyzed to yield the R - 0 - C H - C H O H - C H O H derivatives required for cyclization. The diols were cyclized in the standard way [NaH, tetrahydrofuran (THF)] with tetraethylene glycol ditosylate or tetraethylene glycol dimesylate (7).


2

2

2

C1-CH -CH—CH 2

2

2

+ ( A r ) R - O H -+ ( A r ) R - 0 - C H - C ^ H — C H 2

Ο ,

2

->

Ο TsOCH (CH OCH ) CH OTs

v

2

(Ar)R-0-CH -CHOH-CH OH 2

2

2

2

n

2

N a H , T H F , reflux

OCH,

I, ortho II, para Early results with these systems were encouraging. A comparison of 2(I) and 4-(methoxyphenoxy)methyl (II) ( C H - 0 - C H - 0 - C H - ) derivatives of 15-crown-5 (111) with the latter compound proved instructive. Liotta (8) reported that the cyclization yield for 15-crown-5 was 29%. We found that when the methoxy group was para and too remote to interact with a ringbound cation, the cyclization yield was 30%. When the methoxy group was ortho, the cyclization yield more than doubled (ca. 70%). Two-phase extrac tion constant studies (9) also proved encouraging. The method involves extraction of sodium picrate from water into a nonpolar solvent like chlo roform or dichloromethane. The picrate anion is highly colored and its 3

6

4

2


446

NUCLEOPHILICITY

crown-cation-facilitated extraction into the nonpolar solvent from water can be measured with considerable accuracy. 15-Crown-5 extracts about 7% of the available sodium picrate into chloroform. Para isomer II extracts about 6% and ortho isomer I extracts about 18% of the available N a . At an early stage in the work, we felt two reservations about using the extraction technique for determining cation-binding information. First, the extraction "constant" values depend on a variety of factors such as ionic strength in the salt-containing aqueous solution, temperature, the particular solvent pair chosen, the solvent volumes, the ratio of metal cation to picrate anions, and so on. Although useful information can be obtained by using this technique, all of the many variables must remain constant for data to be comparable. Our second reservation about this method was our feeling that the best binding information available was equilibrium stability constant (K or log K ) values determined by Ν M R , calorimetry, conductivity, and other methods. Tables of these values in a variety of solvents are now readily available (10). When we compared the homogeneous sodium cation binding strengths of I—III to the values obtained by the two-phase method, quite different results were obtained. In 90% aqueous methanol solution, the N a binding constants (log K ) were, for 15-crown-5 (III), 2.97; for para (II), 2.56; and for ortho (I), 2.97. In other words, the sidearm did not enhance binding at all and diminished it when the donor group was inappropriately placed on the sidearm. Although we prepared a variety of carbon-pivot macrocycles, the cationbinding strengths of these molecules was never impressive. At first, we attributed this finding to "sidedness", that is, the sidearm must always be over the same face of the macroring. In collaboration with Okahara (11, 12), we prepared a number of macrocycles having a geminal methyl group at the pivot atom. The binding strengths for these quaternary-methyl lariats were substantially higher than when the methyl group was absent. We believe that this is due to a conformational effect that disfavors the best binding conforma tion of the ring. We therefore turned our attention to the nitrogen-pivot species, which have the advantage of rapid nitrogen inversion to enhance overall molecular flexibility.


+

s

s

+

s

Single-Armed, Nitrogen-Pivot Lariat Ethers The monoaza crown ethers can be conveniently prepared from N,N-diethanolamine. Sidearms are incorporated as electrophiles rather than as nucleophiles in the carbon-pivot series. Alkylation is generally accomplished in acetonitrile solution using N a C 0 as the base. The sidearm-bearing precursor fragment, R - N ( C H C H O H ) is then cyclized. In this case, two ethyleneoxy units are incorporated from the precursor. Reaction of R - N ( C H C H O H ) with triethylene glycol ditosylate affords the 15-mem2

2

2

2

2

3

2

2



30. GOKEL ET AL.

bered ring system, and reaction with tetraethylene glycol ditosylate affords monoaza-18-crown-6 derivatives.

R-X + HN(CH CH OH) -> R-N(CH CH OH) ζ 2

2

2

2

2

2

-Ο

+ TsOCH (CH OCH ) N C H C H O C H C H O C H side chain is ideally placed to hydrogen bond the apical N H hydrogen. The binding constant data (open circles and squares) shown in Figure 1 corroborate this appraisal. Another interesting observation emerges from the ammonium cation binding data (19). Presumably, all four Ν H bonds are associated with an oxygen when optimal binding occurs. In methanol solution, peak binding occurs at 4.8 log units or 1.2 "binding" units per hydrogen bond. The 15membered rings exhibit more modest binding and presumably never coordi nate more than three Ν H groups at a time. Surely, that peak binding occurs for the 15-membered ring systems in methanol solution at 3.6 log units is no coincidence. 4

+

+

2 +

+

4

2

2

2

2

3

+

4




30. GOKEL ET AL.

Figure 2. (a) Framework drawing of N-(2-methoxyethyl)monoaza-18-crown-6 complexed by KI. Framework drawing (b) and molecular structure (c) of the complex between K+ and CH OCH CH OCH CH OCH CH N(CH CH 0) , the so-called "calabash" complex. 3

2

2

2

2

2

2

2


2

3

NUCLEOPHILICITY

452 Bibracchial Lariat Ethers,

BiBLEs


Clearly a single arm augments the cation binding of monoaza lariat ethers. Will two arms increase or diminish cation binding strength and by how much? Will two-armed compounds exhibit similar or altered cation-binding selectivity? Will a higher level of cation involvement afford enhanced nu cleophilicity of associated anions even though the lariat ethers and B i B L E s are "dynamic" cation binders? To answer these questions, we have con structed a series of Ν,Ν'-disubstituted diaza-15-crown-5 and -18-crown-6 compounds. When two arms are present, we use the Latin bracchium for arm and refer to the compounds as bibracchial lariat ethers, B i B L E s . Synthesis of

Diaza-BiBLEs

4,13-Diaza-18-crown-6 derivatives (24-42) can be prepared by using a unique, single-step reaction of primary amines with triethylene glycol diiodide (42):

/ R-NH + I 2

V Ο

\ / Ο

\

Na C0 CH CN 2

3

3

I —

\ R-N

N-R Ο

Ο

The synthesis of the 15-membered rings is accomplished by a more conventional, two-step approach: R-NH + Cl-CO-CH -0-CH -CO-Cl — (R-NH-CO-CH -) — R - N H - C H - C H - 0 - C H - C H - N H - R + ICH (CH OCH ) CH I — 2

2

2

2

2

2

2

2

2

R-N

2

2

2

2

2

N-R Ο

Ο W

Although the latter method appears both more cumbersome and less imaginative when applied to the 18-membered ring systems, it has the advantages of high yield and ease of operation. Using this approach, we have been able to obtain both 15- (43-47) and 18-membered ring systems in yields of approximately 70% overall. Using this synthetic approach, we have been able to compile the cation-binding data shown in Table III. Several conclusions can be made from the data tabulated in Table III. First, more polar donor groups in the side arms afford selectivity for the more charge-dense cations. This trend is clear from the binding constants for compounds XIa,b and XVIa,b. Second, there is a temptation to invoke a


30. GOKEL ET AL.

Effect of Side Arms on Cation Binding by Macrocycles 453 2 +

Table III.

Na+, K+, and C a Binding for 15- and 18-Membered Ring Bibracchial Lariat Ethers Stability Constant (log K in Methanol at 25 °C s

15-Membered Rings (a) 18-Membered Rings (b)


Compd No. VI VII VIII IX X XI XII XIII XIV XV XVI XVII a

+

Na

Sidearm H n-butyl n-hexyl n-nonyl CH C H CH CH OH CH CH OCH CH -2-furyl CH C H -2-OCH CH C H -2-OH CH COOCH CH CH COOH 2

6

Cation Effects on Solvents, Ligands, and Nucleophiles - American

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