1. Principles of Chemical Recognition and Transport in Extractive Separations: Synthesis of Dibenzo-14-Crown-4 Ethers Bearing Fluoroalcohol Lariats Peter V. Bonnesen*, Frederick V. Sloop Jr., Tamara J. Haverlock, and Bruce A. Moyer Chemical Separations Group, Chemical Sciences Division Oak Ridge National Laboratory, Oak Ridge, TN 37831-6119 2003 DOE Separations and Heavy Element Chemistry Contractors’ Meeting Sante Fe, New Mexico April 29, 2003

2. Dibenzo-14-crown-4 forms “sandwich” complex with Na + Crystal structure of (DB14C4) 2 NaClO42CHCl 3 obtained by J. C. Bryan

3. Can we utilize this sandwich formation to extract NaX as an ion-pair? Could lariats with H-bond donor groups appended as shown interact with the anion upon self-assembly of the sandwich?

4. What kinds of lariats with H-bond donor groups should we use?  Presence of electron-withdrawing fluorine atoms increases electropositive character of alcohol proton  Good H-bond donors.  In addition, alcohol oxygen basicity is decreased, reducing tendency for fluorinated alcohols to form H-bond networks with each other. Alcohols with fluorinated side groups are attractive:

5. Initial target compounds To be compared with w/ and w/out and n = 1 or 2 n = 1–3

6. Research Goals  Synthesize target molecules  Perform extraction experiments (with NaX) under conditions that favor sandwich formation, and from extraction behavior, determine whether there is evidence for ion-pairing  Compare extraction behavior with that of controls and determine whether use of lariats gives rise to intermolecular cooperativity then

7. Fluoride-catalyzed addition of CF 3 Si(CH 3 ) 3 to crown-ester Tetrabutylammonium fluoride (TBAF) catalyst as described by Prakash, Olah, and coworkers Angew. Chem. Int. Ed. 1998, 37, 820-821 CsF catalyst as described by Shreeve and coworkers J. Org. Chem. 1999, 64, 2873-2876 A promising approach: Use of CF 3 Si(CH 3 ) 3 (“TMSCF 3 ”) to add a CF 3 group to a carbonyl “crown-ester” precursors readily available

8. TBAF-catalyzed reaction is successful “crown-ester” Isolated yields on alcohol products (from starting ester) are ~35% for both n =1 case (white solid) and n= 2 case (low-melting white solid)

9. When CsF is used as catalyst in 1,2-dimethoxyethane (glyme), there is no reaction No reaction Glyme dried over activated sieves overnight before use. CsF powdered and dried. Other conditions: 10 mol% CsF, glyme, 20 °C, 24 hr: No Reaction 10 mol% CsF, glyme, 48 °C, 4 hr: No Reaction ( Standard reaction conditions as per Shreeve and coworkers, J. Org. Chem. 1999, 64, 2873-2876)

10. Points of Interest The reaction has been reported in the literature for R = alkyl or aryl as proceeding at -78° C (in both toluene and dichloromethane), but that double addition of the -CF 3 group occurs at 0 °C. In our case where R = Dibenzo-14-crown-4 (DB14C4), in toluene we observe no reaction at -78° C but the desired addition of a single -CF 3 group at 0 °C. In dichloromethane we observe no reaction under any conditions. This reaction was probed further using variable temperature NMR.

11. Results of NMR Experiment in Toluene-d 8  About 25% TMSCF 3 hydrolyzes to CF 3 H and TMSOH Remaining 75% of the TMSCF 3 (quartet at 4.0 ppm in 29 Si NMR) still present. No evidence of any other reactions.  Upon warming to 273 K, Crown-ester reacts in 30 min with complete consumption of remaining TMSCF 3. About 70% of the crown-ester was converted with 30% unreacted.  Initial product appears to be as shown with quartet at 98.6 ppm in 13 C NMR (J CF = 31 Hz), and singlet at 15.7 ppm in 29 Si NMR. About half hydrolyzes in tube overnight to give product ketone (carbonyl quartet at 191 ppm with J CF = 34 Hz.) Added 0.1 equiv. TBAF to solution of 1.0 equiv. crown-ester (n = 2) and 1.3 equiv. TMSCF 3 at 233 K

12. 13 C NMR Spectrum 13 C NMR showing ketone and silyl-ether intermediate ketone silyl-ether intermediate ? J CF = 34 Hz J CF = 31 Hz

13. Proposed mechanism for TBAF-catalyzed reaction between carboxylic esters and CF 3 Si(CH 3 ) 3 * *Prakash, Olah and coworkers. Angew. Chem. Int. Ed. 1998, 37, 820-821 How does the nature of the R group affect the rate of addition of TMSCF 3 ? Appears to be much slower when R = DB14C4 than when R = alkyl or aryl

14. Summary  The target Dibenzo-14-crown-4 ethers with fluoroalcohol lariats were successfully synthesized from ester precursors using TMSCF 3 catalyzed by TBAF. However:  The DB14C4 moiety appears to influence (slow) the kinetics of the reaction relative to alkyl or aryl substituents, as the reaction does not proceed in toluene at 194 K (prep-scale) or 233 K (NMR), but proceeds quickly at 273 K, with no detectable evidence of double- addition of the -CF 3 group.  No detectable reaction occurs in dichloromethane at any temperature, both by prep-scale and NMR reactions.

15. Continuing Work  We would like to understand how and why the presence of the crown moiety influences the reactivity of the ester group to TMSCF 3. What accounts for the temperature and solvent effects? What other F - sources can be used?  We will investigate the possibility of using alternate and perhaps more direct synthetic routes to the desired compounds (instead of going through the crown lariat esters). Synthesis: Extraction:  Extraction studies are currently in progress.

16. Office of Science Office of Basic Energy Sciences Oak Ridge National Laboratory is managed and operated by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725. Research Sponsored by Acknowledgments Thanks to Richard A. Sachleben for the supply of starting crown esters.