Advanced Organic Chemistry

Dr. M. J. Wieder

In the Fries rearrangement, aryl esters such as phenyl acetate are converted to acyl phenols such as 2-hydroxyacetophenone by the action of Lewis acids (see below).

Devise an experiment to show whether this rearrangement is intra- or intermolecular in nature. Show what results one would expect in each case.

In the Beckmann rearrangement of benzophenone oxime under acidic conditions to give N-phenylbenzamide (see below), how could one determine whether it is the phenyl group oriented syn or anti to the hydroxyl group that migrates or whether it is possible for either phenyl group to migrate?

In the Curtius rearrangement of benzoyl azide, C₆H₅CON₃ , to phenyl isocyanate, C₆H₅N=C=O, how could one demonstrate that the cyclic compound shown below is not an intermediate in the reaction?

In the Fischer indole synthesis, an example of which is shown below, a phenylhydrazone is converted to an indole by the action of acid.

Outline two experiments, one using isotopic labeling, the other without, to determine which of the two nitrogen atoms of the phenylhydrazone is incorporated in the indole.

Consider the following rearrangement reaction:

a. the rearrangement were intramolecular?

b. the rearrangement were intermolecular?

The Wurtz reaction of (I), in principle, can yield two coupling products, (II) and (III):

X-ray analysis indicates that the coupling product exists in the conformation shown below:

Careful analytical work indicated that only one coupling product was obtained and that the product was chiral. Based on these data, which one of the two possible coupling products, (II) or (III), was in fact obtained. Explain and/or illustrate.

The following mechanism has been proposed to account for the oxidation of NO to NO2:

Use the Steady-State assumption to derive the rate law for the above oxidation reaction.

How would the derived rate law be modified if formation of nitrogen dioxide product is the rate determining step?

Consider the alkaline decomposition of the following pyridinium salt:

Two possible pathways have been proposed to account for the reaction:

Pathway A - Bimolecular Elimination:

Pathway B - Carbanion Intermediate:

Devise a labeling experiment to differentiate between the mechanisms presented above. Show what results would be expected in each case.

The rate of hydrolysis of a-phenylethyl chloride (shown below) in polar media is first order in aryl halide. If the hydrolysis is done using the trideuteromethyl analog, an isotope effect of k_H /k_D = 1.28 is observed. Explain.

In the reaction of aniline with benzoyl chloride to give benzanilide (shown below), the rate determining step is thought to involve attack of the nucleophilic nitrogen atom on the electrophilic carbonyl carbon atom:

 Explain why N,N-dideuterioaniline reacts faster than aniline (k_H /k_D = 0.86).

Explain why 2,6-dideuterioaniline reacts faster than aniline (k_H /k_D = 0.93).

How would the rate of reaction be affected if 2,6-dideuterio-benzoyl chloride were used? Explain.

Rationalize the difference in magnitude of the isotope effect in parts a) and b).

Consider the following reaction:

Two possible pathways to account for product formation are shown below:

Devise an experiment to differentiate between the two pathways. Show what results one would expect in each case.

Compound I, shown below, gives 2,3,3-trimethyl-4-phenyl-1-butene as the sole product of reaction when irradiated with ultraviolet light. Two mechanisms are proposed for your consideration:

Devise a labeling experiment to differentiate between the two proposed pathways. Specify what results would be expected in each case.

Decide whether each of the following is a +R or -R substituent, and justify your choice by drawing resonance structures for benzene rings substituted with these groups:

Predict which substituent in each of the following pairs is a more negative I-group (more electron withdrawing):

In each of the following examples, predict the sign of rho. Explain your answer in each case.

Explain and/or illustrate the following statements:

The rho value correlating the rates of hydrolyses of meta- and para-substituted benzonitriles, X-C₆H₄-CN, is negative for acid- catalyzed hydrolysis but is positive for base-catalyzed hydrolysis.

The order of increasing positive s-values for the following benzene ring-substituents is:

Consider the Pinacol-Pinacolone rearrangement shown below:

Propose an isotopic labeling experiment to differentiate between the two following pathways:

Pathway (I):

Pathway (II):

Cautionary Note: The number of labels and their placement in the reactant molecule need to be carefully considered.