# Toward Polymeric Room Temperature Acid Generators

## TL;DR

This paper introduces new acid-generating compounds that work at room temperature without needing light, potentially improving biocompatibility.

## Contribution

The novel contribution is the development of polymeric room temperature acid generators based on 4-hydroxybenzyl chloride derivatives.

## Key findings

- 4-hydroxybenzyl chloride derivatives generate hydrochloric acid via hydrolysis at room temperature.
- The acid generation rate can be controlled through substituent effects and polymer incorporation.
- A simple hydrolysis pathway dominates over a potential acid-amplified pathway.

## Abstract

Although a variety of acid‐generating molecules have been developed, the formation of toxic byproducts and the need for light‐activation or temperatures that may be incompatible with physiological conditions leave room for the optimization of biocompatible acid‐generators. Herein, we report 4‐hydroxybenzyl chloride derivatives that generate hydrochloric acid via hydrolysis at the benzylic position at room temperature in the absence of light. Utilizing the acetal protected 4‐hydroxybenzyl chloride scaffold, we access a myriad of compounds that generate acid at different rates.

A series of 4‐chloromethylphenyl acetals have been prepared and studied as thermal acid generators in water. Simple mechanistic studies show that a potential acid amplified pathway involving acetal hydrolysis and quinone methide formation is out‐competed by a simple hydrolysis pathway. The rate of thermal acid generation can be tuned through substituent effects and by incorporating the small molecule into a ROMP polymer.