Effects of the hydrophobicity of the reactants oil Diels-Alder reactions in water

To assess the importance of the hydrophobicity of different parts of diene and dienophile on the aqueous acceleration of Diels-Alder reactions, second -order rate constants have been determined for the reactions of cyclopentad iene (1), 2,3-dimethyl-1,3-butadiene(4), and 1,3-cyclohexadiene (6) with N- methyl-, N-ethyl-, N-propyl-, and N-butyhmaleimide (2a-d) in different solv ents. All these reactions are accelerated in water relative to organic solv ents as a result of enhanced hydrogen bonding and enforced hydrophobic inte ractions during the activation process. The beneficial influence of water a s compared to l-propanol on the rate of the Diels-Alder reaction of 4 with 2a-d increases linearly with the length of the alkyl chain of 2. In contras t, for the reaction of both 1 and 6 with 2a-d, no such effect was observed. This difference can be explained by a hydrophobic interaction between the methyl groups of 4 and the N-alkyl group of 2 during the activation process . In the reactions of I and 6, lacking the methyl substituents, this intera ction is not possible and elongation of the alkyl chain from ethyl onward d oes not result in an additional acceleration by water. The enhanced hydroph obicity near the reaction center of dienes 4 and 6 compared to I results in an increased aqueous acceleration of the Diels-Alder reactions of the form er dienes with 2a. These data indicate that an increase in the hydrophobici ty close to the reaction center in the diene has a much more pronounced eff ect on the rate acceleration in water than a comparable increase in hydroph obicity in the dienophile further away from the reaction center. The Gibbs energies of transfer of initial state and activated complex of the Diels-Al der reactions under study have been determined. As expected, for all reacti ons the initial state in water is destabilized compared to that in l-propan ol. This destabilization becomes more pronounced when the nonpolar characte r of diene (close to the reaction center) or dienophile (distant from the r eaction center) is increased. Likewise, an increase in the nonpolar charact er of 2 results in a destabilization of the activated complex. In contrast, addition of methyl or methylene units to the diene is not accompanied by a significant destabilization of the activated complex in water as compared to I-propanol. We conclude that hydrophobic groups near the reaction center seem to lose their hydrophobic character completely in the activated compl ex of the Diels-Alder reaction, whereas more distant groups retain their no npolar character throughout the reaction.