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The role of water in this mono-acylation reaction is unknown at this time. One hypothesis is that diamines form clusters through intermolecular hydrogen bonding in organic solvents like those formed by BuLi in hexane. This cluster formation lowers the reactivity of the diamine toward acylating agents. Compared to diamine, the mono-acylated product is associated with the clusters to a lesser degree and is therefore more reactive. As a result, di-acylated product is favored over mono-acylated product in organic media. In the presence of water, the clusters may be broken by hydrogen bonding between the diamine and water, and the reactivity of diamine is increased. This would lead to a 50% theoretical yield of mono-acylated product.
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The role of water in this mono-acylation reaction is unknown at this time. One hypothesis is that diamines form clusters through intermolecular hydrogen bonding in organic solvents like those formed by BuLi in hexane. This cluster formation lowers the reactivity of the diamine toward acylating agents. Compared to diamine, the mono-acylated product is associated with the clusters to a lesser degree and is therefore more reactive. As a result, di-acylated product is favored over mono-acylated product in organic media. In the presence of water, the clusters may be broken by hydrogen bonding between the diamine and water, and the reactivity of diamine is increased. This would lead to a 50% theoretical yield of mono-acylated product. The higher than 50% yield may be attributed to the reduced reactivity of the second amino group in mono-acylated diamine caused by the electron-withdrawing amide group, lower solubility of mono-acylated diamine than diamine in the reaction media and the solid state of the mono-acylated product and the liquid state of diamine at the reaction temperature.
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