STUDYING THE STEREOCHEMISTRY OF NAPROXEN USING ROTATIONALLY RESOLVED

STUDYING THE STEREOCHEMISTRY OF NAPROXEN USING ROTATIONALLY RESOLVED ELECTRONIC SPECTROSCOPY Justin Young, Leonardo Alvarez-Valtierra and David W. Pratt. University of Pittsburgh Science(2006), vol. 323, pg. 237(4) http: //www. novelcs. com/Chirality. html http: //www. mcescher. com/

An Example R-naproxen S-naproxen

Diastereomers? S-naproxen R-naproxen Alvarez-Valtierra, L. (2008) University of Pittsburgh. School of Arts and Science

Low Resolution Spectrum IB IR Wavenumbers Chem. Phys. Lett. (2003), 375, pg 634

Experimental Setup To Beam Machine (BM)

Red Conformer of S-Naproxen 30586. 06 cm-1 30584. 35 cm-1 0. 08 cm-1

Red Conformer of R-Naproxen 30584. 35 cm-1 30585. 98 cm-1 0. 08 cm-1

Right Vs. Left S-Naproxen R-Naproxen 0. 08 cm-1

Red Conformer Inertial Parameters S-Naproxen (Red) R-Naproxen (Red) A” (MHz) 1241. 59 (6) 1241. 56 (5) B” (MHz) 214. 70 (3) 214. 73 (3) C” (MHz) 202. 15 (3) 202. 16 (3) ∆I” (amu Ǻ 2) -260. 8 (4) -260. 7 (4) A’ (MHz) 1217. 62 (5) 1217. 59 (5) B’ (MHz) 215. 49 (3) 215. 50 (3) C’ (MHz) 202. 44 (2) 202. 46 (2) ∆I” (amu Ǻ 2) -263. 8 (4) -263. 9 (4) a/b/c-character 8. 3/87. 6/4. 2 7. 8/88. 7/3. 5 Band origin (cm-1) 30585. 2 OMC (MHz) 2. 91 2. 88 Temp (K) 3. 0 S 0 S 1

R-Naproxen Blue Conformer R-Naproxen 30686. 50 cm-1 30687. 96 cm-1 0. 08 cm-1

S-Naproxen Blue Conformer S-Naproxen 30686. 50 cm-1 30687. 96 cm-1 0. 08 cm-1

Right Vs. Left R-Naproxen S-Naproxen 0. 08 cm 1 0. 08 cm-1

Blue Conformer Inertial Parameters S-Naproxen (Blue) R-Naproxen (Blue) A” (MHz) 1315. 80 (6) 1315. 71 (7) B” (MHz) 205. 36 (3) 205. 30 (3) C” (MHz) 196. 10 (3) 196. 07 (3) ∆I” (amu A 2) -267. 9 (5) -267. 9(5) A’ (MHz) 1304. 20 (5) 1304. 10 (7) B’ (MHz) 204. 90 (3) 204. 87 (4) C’ (MHz) 195. 46 (3) 195. 45 (3) ∆I” (amu Ǻ 2) -268. 4 (5) -268. 9 (6) a/b/c-character 5. 6/84. 7/0. 7 Band origin (cm-1) 30687. 2 OMC (MHz) 3. 32 3. 91 Temp (K) 3. 0 S 0 S 1

Possible R-Conformations R-Naproxen IV MP 2 / 6 -31 G** R-Naproxen II R-Naproxen V R-Naproxen III R-Naproxen VI

Conformation Determination Experimental Red Blue Theory I II IV V VI A” 1241. 5 1315. 7 1314. 9 1240. 6 1447. 6 1254. 8 1274. 0 1226. 7 B” 214. 7 205. 3 205. 7 215. 7 198. 1 214. 2 213. 6 C” 202. 2 196. 07 195. 7 202. 1 191. 4 200. 6 197. 2 199. 7 MP 2 / 6 -31 G** R-naproxen II R-naproxen I

Experimental vs. Theoretical Results (MP 2 / 6 -31 G**) S-Naproxen (Naproxen I) R-Naproxen (Naproxen I) S-Naproxen (Naproxen II) R-Naproxen (Naproxen II) A” (MHz) 1315. 0 1314. 9 1240. 5 1240. 6 B” (MHz) 205. 7 215. 7 C” (MHz) 195. 7 202. 1 ∆I” (amu A 2) -258. 8 -249. 7 Experimental Results S-Naproxen (Blue) R-Naproxen (Blue) S-Naproxen (Red) A” (MHz) 1315. 80 (6) 1315. 71 (7) 1241. 59 (6) 1241. 56 (5) B” (MHz) 205. 36 (3) 205. 30 (3) 214. 73 (3) C” (MHz) 196. 10 (3) 196. 07 (3) 202. 15 (3) 202. 16 (3) ∆I” (amu Ǻ 2) -267. 9 (5) -267. 9(5) -260. 8 (4) -260. 7 (4) S 0 MP 2 / 6 -31 G**

Lowest Energy Conformations S-naproxen II S-naproxen I MP 2 / 6 -31 G** R-naproxen II R-naproxen I Chem. Phys. Lett. (2003), 375, pg 634

c c b b a a S-naproxen II R-naproxen II c c a a b S-naproxen I b R-naproxen I

Summary • Rotationally resolved electronic spectra of R- and S-naproxen were obtained. • For each enantiomer two conformations were assigned. • As expected the conformations R and Snaproxen have matching spectra and inertial parameters

Future work Chiral axis Chiral center Diastereomers

Acknowledgments • Leonardo Alvarez, Ryan Bird, Casey Clements, Adam Fleisher, Philip Morgan and Jessica Thomas • Professor David W. Pratt for his encouragement and continuing support • Funding by the National Science Foundation (CHE-0615755)