Knoevenagel aminopropyl silica

Figure 4.20 Solvent effects in the Knoevenagel reaction using (a) aminopropyl silica and (b) aminopropyl HMS catalysts...

Scheme 3 Deactivation mechanism of aminopropyl-grafted silicas in the Knoevenagel reaction...

Having elucidated the optimum conditions for the Knoevenagel reaction in a flow reactor, a range of other reactions using different activated methylene derivatives and aldehydes (Table 14.3) was conducted. In all cases excellent product purities and yields were obtained. The reaction of benzaldehyde and ethyl cyanoacetate was also performed using 3-(dimethylamino)propyl-functionalized silica gel, 3-aminopropyl-functionalised silica gel, 3-(l,3,4,6,7,8-hexahydro-2H-pyrimidojl, 2-l]pyrimidino)propyl-functionalized silica gel and polymer-supported diazabicyclo[2.2.2]octane, whereby excellent conversions were obtained (> 99.0%) in all cases [37]. 

The majority of work on organically modified solids as solid bases has been carried out on the simple 3-aminopropyl-derivatised silica. This material is established as an efficient catalyst for the Knoevenagel reaction.136-138 There are several interesting features about this application. One of these is the solvent, a... 

Besides this early example another application was reported in 1988 by Ven-turello and coworkers [10]. They disclosed the use of aminopropyl-function-alized silica gel as a suitable catalyst in Knoevenagel condensations under continuous flow conditions (Scheme 4). Good yields were obtained when aromatic aldehydes, cyclohexanone, and acetophenone were condensed with ethyl acetoacetate, ethyl cyanoacetate or malononitrile [11,12]. The concept was based on a conventional column reactor which was equipped with a vertical double-jacket thermostat. The catalyst was introduced into the column while the reactants were placed on the top of the column. Toluene was passed through the column and the products were conveniently obtained by evaporation of the solvent. 

The use of supported organocatalysts in flow chemistry is not new. A pioneering work using an organic base catalyst was reported by Venturello. Knoevenagel condensations of aromatic aldehydes, cyclohexanone, and acetophenone with acetoa-cetate, cyanoacetate, or malonate were catalyzed by aminopropyl-functionalized silica gel (56), which was packed in a gravity-fed column, under continuous-flow conditions (Scheme 7.40) [149]. A flowcell microreactor, whose wall surfaces were coated with aminopropylsilica, was utilized in Knoevenagel and Michael reactions [150]. 

Aminopropylated functionalized hexagonal mesoporous silicas (HMS) and SBA-15 materials with different amino-loadings (5-30 wt. % NH ) were synthesized by Pineda et al. (2013). These play important role as catalyst in the microwave-assisted Knoevenagel condensation of cyclohexanone and ethyl cyanoacetate as well as in the Michael reaction between 2-cyclohexen-l-one and nitromethane. The low loaded HMS-5%NH2 and higher loaded SBA-15-20% NH were found to give the best activities in the reactions. High activities and selectivities to the condensation product could be achieved in short times of microwave irradiation for both these base-catalyzed processes. 

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