Question

I am performing an esterfication reaction between an activated phosphonic acid (chloride) and a series of alcohols. Until now, I was not able to make the reaction work with prenol, while isoprenol is working fine. I am wondering, what could be the reason for such different chemical behaviour and reactivity? I tried different solvents like THF, DCM and acetonitrile and also bases like pyridine, NaH as well as DBU and DMAP, but until now, me only observed the isoprenol adduct. Isoprenol is working with absolute standard conditions. Is there anything you can recommend I haven't tried? Would you expect such different reactivity just by the positioning of the double bond?

Answer 1

The different reactivity of prenol and isoprenol in the esterification reaction can be attributed to the positioning of the double bond. Isoprenol has a terminal double bond, which allows for easier access of the reactants to the reactive sites, resulting in the formation of the isoprenol adduct. On the other hand, prenol has an internal double bond, which hinders the access of the reactants to the reactive sites, leading to low reactivity and the absence of the prenol adduct.

Step-by-step explanation:

The different reactivity of prenol and isoprenol in the esterification reaction can be attributed to the positioning of the double bond. Isoprenol has a terminal double bond, which allows for easier access of the alcohol and phosphonic acid to the reactive sites, resulting in the formation of the isoprenol adduct. On the other hand, prenol has an internal double bond, which hinders the access of the reactants to the reactive sites, leading to low reactivity and the absence of the prenol adduct.

It seems like you have tried different solvents and bases, but none of them have resulted in the formation of the prenol adduct. To further enhance the reactivity, you can consider using a more reactive alcohol, such as allyl alcohol or benzyl alcohol, which have been shown to react effectively in esterification reactions. Additionally, you can try using different catalysts, such as acidic ionic liquids or Lewis acid catalysts, which can promote the esterification reaction and improve the yield of the prenol adduct.

Overall, the presence and positioning of the double bond in alcohols play a crucial role in determining their reactivity in esterification reactions. By selecting alcohols with more accessible double bonds and using appropriate catalysts, you can increase the chances of obtaining the desired ester product.