The Use of Anhydrous CeCl 3 as a Recyclable and Selective Catalyst for the Acetalization of Aldehydes and Ketones

Um método eficiente, limpo, quimiosseletivo e sem a utilização de solventes para a síntese de dimetil acetais de aldeídos e cetonas foi desenvolvido usando ortoformiato de trimetila e CeCl 3 anidro como catalisador. O método é geral e, sob condições reacionais brandas, fornece compostos carbonílicos protegidos em bons rendimentos, incluindo aril e alquil cetonas e aldeídos. O catalisador pode ser reutilizado diretamente, três vezes, sem perda significativa da atividade.


Results and Discussion
Initially, we chose benzaldehyde 1a (2.0 mmol) and trimethyl orthoformate (2.2 mmol) as standard starting materials to establish the best conditions for the reaction under solvent-free media.We examined the temperature, amount of anhydrous CeCl 3 25 and the reaction time (Table 1).
It was found that using 10 mol% of dry CeCl 3 the acetal 2a was obtained in 83% yield after stirring at room temperature for 6 h (Table 1, entry 1).The reaction time was reduced to 1 h when the mixture was stirred at 0 °C, affording the same result (Table 1, entry 2).By stirring at lower temperatures, such as -20 and -78 °C, the product was obtained only in modest yields (entries 3 and 4).The effect of the amount of the catalyst was also evaluated.When 5 mol% of CeCl 3 was used, 2a was obtained in excellent yield (95%) after stirring at 0 °C for 1 h (Table 1, entry 5).The use of lower amounts of CeCl 3 did not presented satisfactory results (entries 6 and 7).We also tested the effect of the solvent in the reaction, such as CH 3 CN, CH 3 NO 2 and CH 3 OH (entries 8-11).When CH 3 OH (2 mL) was used, 2a was obtained in 75% yield after stirring for 6 h at room temperature (entry 10) and in 65% yield after 5 h at 0 °C (entry 11).The lower yields observed in these cases are probably due to the reduction of the catalytic activity of CeCl 3 in view of a competition between the heteroatom of the solvent and the carbonyl group of the aldehyde for the cerium metal centre. 3ince the best conditions were established, the protocol was extended to other aromatic and aliphatic aldehydes and ketones (Table 2).
The dimethyl acetals 2 were obtained in good to excellent yields under solvent-free conditions after stirring at 0 °C for 1-4 h in all but three tested examples.In the case of solid p-chlorobenzaldehyde (entry 4) and the less reactive ketones acetophenone and heptan-2-one (entries 11 and 12), it was necessary the use of methanol (2 mL) as solvent under reflux.Besides, a longer reaction time (8-10 h) was required to obtain satisfactory yields from ketones.The chemoselectivity of the reaction was also investigated.Thus, when an equimolar mixture of benzaldehyde 1a, cyclohexanone 1h and trimethylorthoformate was subjected to acetalization reaction in presence of CeCl 3 , only the acetal of benzaldehyde 2a was isolated after stirring for 4 h, while the cyclohexanone was completely recovered, along with a small amount of 1a.This result shows the high selectivity of our method.In addition, citral 1g, which is a mixture of trans-and cis-3,7-dimethylocta-2,6-dienal (Z:E = 40:60), was selectively converted to the respective dimethyl acetal in 78% yield after 4 h without any isomerization of the double bonds (Z:E = 40:60; entry 7).To extend the scope of CeCl 3 -catalyzed acetalization of carbonyl compounds we sought to explore the use of triethyl orthoformate for the synthesis of diethyl acetals, under the same conditions employed to methyl acetals.In this way, the reaction was performed with benzaldehyde and cyclohexanone, and the corresponding diethyl acetals were obtained in 93 and 86% isolated yield, respectively.
It was observed that the CeCl 3 can be successfully reused up to 2 times without any treatment, with good results.Thus, for example, after the completion of the acetalization of benzaldehyde 1a (in 10.0 mmol scale), the crude product 2a was simply separated by decantation from the insoluble catalyst and a small amount of CeCl 3 (0.05 mmol; 0.5 mol % each time) was added each time before repeating the reaction.Under these conditions, 2a was obtained with similar yield (2 runs, 93 and 94% yield

Conclusions
In summary, anhydrous CeCl 3 has proved to be an effective, robust and recyclable catalyst for the acetalization of aryl and alkyl carbonyl compounds.The method is simple, clean and general and the catalyst can be reused directly for 2 times without loss of activity.For almost all the examples studied, this new, green methodology eliminates completely the necessity of using organic solvents in the reaction.b Yields of pure products isolated.c The reaction was carried out in the presence of methanol (2 mL) under reflux.d Z:E = 40:60.