Trimethylorthoformate water

The most common ketals are dioxolane and dioxane these form more readily and have fewer problems with enol ether contamination. Sometimes, however, they can be difficult to hydrolyze, particularly when the molecule contains sensitive functional groups. The reaction is acid catalyzed, with some of the more common acids being para-toluenesulfonic, pyridinium para-toluenesulfonic, and eamphorsulfonie. The eluninated water can be removed either with an azeotroping solvent (such as toluene or benzene) or by the addition of a dehydrating agent such as trimethylorthoformate. 

These authors investigated the preparation of solid-supported precursors of N-acyliminium ion and, after attempting to translate the Katritzky s procedure [392] onto solid phase, with very poor results mainly due to the technical difficulty in performing azeotropic removal of water from a solid-phase reaction, they switched to N-(a-aLkoxyaIkyl)amide. Thus, 4-hydroxybenzamide (527) was supported on Merrifield resin, and was then, after optimization, treated with 11 different aldehydes in the presence of trimethylorthoformate (TMOF) and TFA in THF at 30 °C for 12 h (511) (Scheme 106). 

The formation of dimethyl acetals is relatively easy. In most cases, the reaction of an aldehyde with an acid in the presence of a water scavenger such as trimethylorthoac-etate or trimethylorthoformate will give the acetal in excellent yield. 

The most common method to prepare a ketal is to treat the carbonyl compound with ethylene glycol and an acid at reflux with a solvent that will azeotrope water using a Dean-Stark trap. For substrates that can not tolerate high temperatures, a dehydrating agent such as trimethylorthoformate is often used to scavenge the water. 

Virtually aU the water can be removed from methanol by adding an ortho ester, trimethylorthoformate (TMOF) and a small amount of sulfuric acid to catalyze the reaction [25, 26]. 

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