Study of solvent interactions in solvolytic reactions of several common pharmaceutical intermediates

MEDI 114

Malcolm J. D'Souza, dsouzama@wesley.edu1, Zoon H. Ryu, zhryu@deu.ac.kr2, Dennis N. Kevill, dkevill@niu.edu3, and Byoung-Chun Park3. (1) Department of Chemistry, Wesley College, 120 N State Street, Dover, DE 19901, (2) Department of Chemistry, Dong-Eui University, Busan, South Korea, (3) Department of Chemistry & Biochemistry, Northern Illinois University, DeKalb, IL 60115
Background: There has been significant interest in the hydrolysis, alcoholysis, and aminolysis processes of acyl halides, as such reactions are useful models for enzymatic mechanisms. A recent study (Tetrahedron Letters, 42, 2001, 7747-7750), proposed a concerted (SN2) process for the methanolysis of paclitaxel-related derivatives having a chloroacetyl substituent on the C2' oxygen. Methods: The effects of solvent variation of the available specific rates of solvolysis of acetyl, chloroacetyl, trimethylacetyl, phenylacetyl, diphenylacetyl, and α-methoxy-α-(trifluoromethyl)phenylacetyl chlorides, are analyzed using the extended Grunwald-Winstein equation utilizing the NT scale based on S-methyldibenzothiophenium ion solvolysis combined with a YCl scale based on 1-adamantyl chloride solvolysis. Conclusions: The results obtained are consistent with our earlier suggestion that acid chlorides of monoesters of carbonic acid and of carboxylic acids tend to solvolyze with competing addition-elimination (with rate-determining addition) and ionization SN1 (assisted by nucleophilic solvation) pathways. [Grant support: NIH grant 2 P20 RR016472-06 from the NCRR]
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007