Characterizing a Tetrahedral Intermediate in an Acvl Transfer Reaction An Undergraduate 'H NMR Demonstration Henry S. Rzepa Imperial College, London. SW7 2AY, UK Ana M. Lobo, M. Matllde Marques, and Sundaresan Prabhakar S e c p 0 de Quimica Organlca Aplicada, F.C.T., New University of Lisbon, Quinta da Torre, 2825 Monte de Caparica, and C.Q.E.. Complexo I, I.S.T., Av. Rovisco Pais, 1096 Lisboa Codex, Portugal Many reactions are thought to involve the formation of transient intermediates that, although not directly detected, have nevertheless been postulated on the basis of indirect evidence such as kinetic measurements, product analysis, isoto~icexchanee. " . etc. The mechanisms of manv ester hvdrolyses, which are examples of a general type of reaction known as nucleo~hilicacvl substitution. were first shown in the early 1950'sA(1)to involve the formation (eq 1) and suhseauent breakdown (ea 2) of a so-called tetrahedral intermediate I, and such a scheme is now generally accepted and well known to all students of organic chemistry.
+ NuH
R-CO-X
I
-
R-C(OH)(Nu)-X R-CO-Nu
(I)
(1)
(11) + HX
(2)
after mixing (A in figure) shows only reactant peaks. The CHz protons appear as a doublet a t 6 3.75 ppm (J 7 Hz), due to coupling with the SH group. No geminal methylene coupling is apparent because of the chemical shift equivalence of the two methylene protons. After 1 day a t 50 "C, or
Despite the common occurrence of such reactions, tetrahedral intermediates formed from precursors such as esters, amides, acyl halides, etc., are rarely detected, since they tend to he relatively high energy species with relatively short lifetimes ( 2 4 ) . I t is only quite recently that procedures and conditions for directly detecting such species have been developed, using methods such as ultraviolet, infrared or NMR spectroscopy ( 2 4 ) . Proof of the "tetrahedral" nature of these intermediates normally comes from spectroscopic evidence that the carbonyl group has been rehybridized (e.g., the '3C chemical shift of a carbonyl carbon has a value between 6 160 and 200, whereas that for the corresponding S D carbon ~ tends to have values between 6 75-120 D . .D ~ ) . M't deicribe here asimple experiment involving thedeterlion bvtH N M H sDectrosroDv uf a stable intermrdiate I (Nu = P ~ C H ~X S ,= CN, R = C H ~ formed ) from nucleophilic attack hv PhCHlSH on CHqCOCN (5) and its characterization as chiral land therefore tetrahedral) species by the observation of diastereotopic behavior' in the "pro-chiral" methylene group close to
