Selective carbonyl protection using ethylene glycol

Question

Can anyone explain to me which position is more favourable to form ketal i.e aldehyde or ketone Also which reducing agent also reduce this ketal. And how thioketal formed from thioethyleneglycol different from ketal

Answer 1

Aldehydes are generally more reactive than ketones. According to my copy of "Protective Groups in Organic Synthesis" by Greene & Wuts (John Wiley & Sons, 1991) aldehydes form dimethyl acetals preferentially to ketones, for example in MeOH with dry HCl for 2 mins followed by 12 mins reflux (p178, quoting Cameron et al, J. Chem. Soc., 3864 (1953)).

Acetals are generally resistant to reducing conditions, particularly hydride-based reagents. The only conditions where they are reactive are conditions where they are first hydrolysed by the aq. acid present to reform the carbonyl group which is then reduced e.g. Clemmensen

Thioketals are produced by reaction of carbonyl compounds with thiols under similar acidic conditions to ketals mechanism here. They are different from ketals in that they are resistant hydrolysis by aq. acid and in the case of thioacetals of aldehydes the proton on the carbon bearing the two sulfurs is activated to deprotonation (see Corey-Seebach reaction here.)