Aldehydes, acetal formation from with oxygen

In the presence of acid, hemiacetals can undergo an elimination reaction, losing the oxygen atom that once belonged to the parent aldehyde s carbonyl group. These oxonium ions are powerful electrophiles, and react rapidly with a second molecule of alcohol to from new stable compounds, called acetals. Scheme 7.72 shows the mechanism of acetal formation from a hemiacetal. 

In contrast to oxidation in water, it has been found that 1-alkenes are directly oxidized with molecular oxygen in anhydrous, aprotic solvents, when a catalyst system of PdCl2(MeCN)2 and CuCl is used together with HMPA. In the absence of HMPA, no reaction takes place(100]. In the oxidation of 1-decene, the Oj uptake correlates with the amount of 2-decanone formed, and up to 0.5 mol of O2 is consumed for the production of 1 mol of the ketone. This result shows that both O atoms of molecular oxygen are incorporated into the product, and a bimetallic Pd(II) hydroperoxide coupled with a Cu salt is involved in oxidation of this type, and that the well known redox catalysis of PdXi and CuX is not always operalive[10 ]. The oxidation under anhydrous conditions is unique in terms of the regioselective formation of aldehyde 59 from X-allyl-A -methylbenzamide (58), whereas the use of aqueous DME results in the predominant formation of the methyl ketone 60. Similar results are obtained with allylic acetates and allylic carbonates[102]. The complete reversal of the regioselectivity in PdCli-catalyzed oxidation of alkenes is remarkable. 

The starting material for the tricyclic NSAID meseclazone (69-5) consists, appropriately, of chlorosalicylic acid (69-1), which has NSAID activity in its own right. Reaction of the acid with hydroxylamine gives the hydroxamic acid (69-2). Treatment of that product with the diethyl acetal from 4-chlorobutyraldehyde (69-3) gives the derivative (69-4), which is in effect a carbinolamine derivative of the aldehyde. Exposure to a mild base results in the formation of the final ring by displacement of the terminal side chain chlorine by the hydroxylamine oxygen [71]. It is not at all unlikely that the product, meseclazone (69-5), is actually converted back to the salicylate (69-1) in vivo. 

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