Issue in Honor of Prof Csaba Szantay ARKIVOC 2008 (iii) 17-24
O O O O Li O O E Cl R i ii Cl R Cl R Cl R R'R'R' R'
34
2
R: H, Cl, MeO R': CH3, Ph, 4-MeOC6H4, 4-F-C6H4, etc. Reaction conditions: (i) butyllithium; (ii) electrophilic reagent;
E:COOH, SO2Cl, CH3, CHO
Scheme 1
The ethylene ketals 1 have been prepared by the traditional method: long refluxing (40 h) of a solution of the ketone, ethylene glycol and para-toluenesulfonic acid (PTSA) in toluene with azeotropic removal of the water.[3–8]
We were seeking a simple and environmentally benign synthesis of benzophenone and acetophenone ethylene ketals. Most of the reported methods that avoided the drawbacks of the traditional protection methods (eg. long reaction times) resulted in procedures having other undesired features (reagents hazardous to the environment, limited scope, etc.).[9]
Some contradictory results have been published on the reaction of acetophenone and benzophenone with ethylene glycol without solvent in a microwave reactor. The irradiation of a mixture of acetophenone, ethylene glycol (~10 equiv.) and PTSA (0.015 equiv.) in a “nonmodified domestic microwave oven” for two minutes has been described to afford the corresponding 1,3-dioxolan-2-yl derivative in 71 % yield.[10] This paper does not discuss the reaction of benzophenones under similar conditions. However, in another study, the mixture of acetophenone or benzophenone and ethylene glycol (2 equiv.) and PTSA (0.1 equiv.) was irradiated in a Prolabo (Synthewave®) oven for 30 minutes (the monitored temperature 120 ºC with a maximum emitted power of 120 W), a low conversion (20 %) was observed with acetophenone, whereas, benzophenone did not react at all.[11] Ketalization of some acetophenones with ethylene glycol has been described in a Teflon cylinder under microwave irradiation in the presence of water in 30-80 % yield, however, the results are not supported by sufficient evidence to be considered reliable.[12]
In this paper we describe a simple and convenient synthesis of acetophenone and benzophenone ethylene ketals by performing the reaction of the starting materials with ethylene glycol in toluene in the presence of PTSA under microwave irradiation and with simultaneous removal of the so formed water. The apparatus used for the irradiations was the same as in the case of the traditional heating (eg. oil bath), except that the reaction flask was placed in the internal space of a microwave instrument (Figure 1).
ISSN 1551-7012 Page 18 ©ARKAT USA, Inc.
