(You can find figures and such in the actual presentation; I haven't supplied you with a link to this presentation, but all you have to do is click "Open" on the toolbar in Netscape Composer, go to web_docs/Chemistry/Calendar/Chem4089/formal_oral/derek2_presentation, then double-click on the "index" icon, then click "Preview" on the toolbar (you'll need to save a local file . . . just delete it later) and you can view the whole presentation.)

Scope 

• Nitrile oxides are useful in syntheses of oxazoles (five membered rings with an adjacent N and O) and related materials.
• To better exploit nitrile oxides in the manufacture of these compounds, which are difficult to manufacture by any other route, the stereoselectivity of nitrile oxides, the effect of temperature on this stereoselectivity, and an understanding of the electronic demands of the reaction is necessary.

Research Goals

• Quantity effect of different p-substituents on face selectivity during reaction using Hammett plot studies.
• Determine sensitivity of reaction rates to temperature and express differences in activation parameters to explain face selectivity of reaction.
• Look at how HOMO and LUMO energies of the dipolarophiles vary with the substituents.

Effect of different p-substituents on face selectivity

• Hammett plots were used to describe the sensitivity of the reaction to varying p-substituents on benzonitrile oxide.
• Hammett plots are graphs of log(k_x/k_H) against s, which equals log(K_x/K_H).
• In these values for the rate of the reaction versus the equilibrium constant of each reaction, k_x and K_x are the rate constant and equilibrium constant for the reaction under investigation when one substituent is varied from a hydrogen to electron-withdrawing and electron-releasing substituents. The values k_H and K_H are the rate and equilibrium constants for a reference reaction in which the substituent whose character is varied over the course of several reactions is a hydrogen.
• The values of s come from a reference reaction, in which the value of s is calculated for each changing substituent (X). The values of s are then set, and whenever the reaction under investigation is run, the substituent used in that particular instance dictates the value of s to use in the domain of the Hammett plot. The determined logarithm of the rate of the observed reaction relative to that of the reference reaction dictates the range of the Hammett plot.
• If one is lucky, the Hammett plot will come out to be a straight line (indicating there is a linear relationship between the free energies of reaction).
• The slope of the line (r) reveals the severity of the change in rate of reaction with respect to changing substituents. If different substituents change the rate of one set of reactions drastically, the slope will be larger than a set of reactions in which the electronics of the molecules involved do not factor into the reaction as much. The rise (log(k_x/k_H)) is larger in one reaction, while the run (log(K_x/K_H) is constant
• The researchers reacted eight nitrile oxides of varying electronic character with two different adamantanes, 5-fluoro-2-methyleneadamantane and 5-fluoroadamantane-2-thione, only to find r values of 0.0 and 0.12, respectively. In both cases, yield data were clearly centered around certain values as well.
• These low values of r indicate the reaction is not too sensitive to the electronics of the functionalities involved, and reinforce the notion that 1,3-dipolar cycloaddition reactions of nitrile oxides proceed by a concerted mechanism.

• The most cut-and-dry example of the effect temperature changes can have on the face selectivity of reactions between nitrile oxides and certain adamantanes is that at sufficiently high temperatures the reaction between benzonitrile oxide and 5-chloro-adamantane-2-thione could be made to favor one isomer less (yield E:yield Z = 58:42) than at 0^oC (yield E:yield Z = 65:35).
• Hence, it was demonstrated that higher temperatures had the ability to alter the face selectivity of the reaction.
• At the same time, the researchers wanted to express some thermodynamic parameters of activation which had never been calculated before.
• Plotting ln(E/Z) for a reaction in which the E product was favored (where E/Z is the ratio between yield of E product and yield of Z product) against 1000/T (ln(Z/E) was done to find the Y values for a reaction in which the Z product was favored), the slope was used to solve the following equation and determine the different in enthalpy and different in entropy of activation.

• The domain of the function (x) is 1000/T; the slope of the function (m) is the value of (DH_anti - DH_syn)/R. Ergo, divide by 1000 and multiply by the universal gas constant and the differences in activation enthalpies is found (not the activation enthalpies for attack by the nitrile oxide on either face of the adamantane).
• Take the actual value in the range of the function (y), subtract off the contribution from the mx term, and you are left with b—which equals the difference in activation entropies divided by the universal gas constant. Multiply this value by R and, voila, the difference in entropies of activation is found.
• The differences in enthalpy and entropy for one reaction (benzonitrile oxide and 5-chloro-adamantane-2-thione) studied was found to be tiny. The differences were more pronounced in the reaction between benzonitrile oxide and 5-chloro-2-methyleneadamantane, but still fairly small. In both instances attack on the syn face had lower activation enthalpies, and it was found that face selectivity could be reversed at higher temperatures (as mentioned above).

• HOMO/LUMO interactions are explained using purely computational methods. So, all these researchers had to do was plug a bunch of numbers into a computer, let the computer do the calculations, see which energy levels from the nitrile oxides and the adamantanes were closest to each other, and, bingo!
• It was found the LUMO’s of the nitrile oxides and the HOMO’s of the adamantanes overlapped during the cycloadditions.
• What the researchers found was that adamantan-2-ones were precluded from cycloaddition reactions due to the large gap between their HOMO’s and the nitrile oxides’ LUMO’s.
• Further, the gap increases (i.e., reaction less favorable) from imine to thione, from thione to alkene, and from alkene to ketone (which did not actually react at all).

• Small differences in r indicate the electronic demands of this reaction are negligible--variations in electrostatic properties from reaction to reaction had little impact on the speed and extent of reaction.
• This same datum supports the theory of a concerted mechanism in 1,3-dipolar cycloadditions involving nitrile oxides.
• Electrostatic effects are not of great importance in adamantane systems--they appreciable enhance neither the reactivity or sluggishness of species relative to their inherent reactivity.
• Reactions of this type appear dependent upon the LUMO of the dipole and the HOMO of the dipolarophile, with the energy gap increasing from imine to thione to alkene to ketone derivatives of adamantane.
• The bearing of temperature on the face selectivity of the reaction has been determined, and it is detectable.
• For the first time, thermodynamic activation parameters of this type of reaction have been determined.