Scale-up of organic reactions in ball mills: process intensification with regard to energy efficiency and economy of scale

Abstract

The scale-up of the Knoevenagel-condensation between vanillin and barbituric acid carried out in planetary ball mills is investigated from an engineering perspective. Generally, the reaction proceeded in the solid state without intermediate melting and afforded selectively only one product. The reaction has been used as a model to analyze the influence and relationship of different parameters related to operation in planetary ball mills. From the viewpoint of technological parameters the milling ball diameter, dMB, the filling degree with respect to the milling balls' packing, ΦMB,packing, and the filling degree of the substrates with respect to the void volume of the milling balls' packing, ΦGS, have been investigated at different reaction scales. It was found that milling balls with small dMB lead to higher yields within shorter reaction time, treaction, or lower rotation frequency, rpm. Thus, the lower limit is set considering the technology which is available for the separation of the milling balls from the product after the reaction. Regarding ΦMB,packing, results indicate that the optimal value is roughly 50% of the total milling beakers' volume, VB,total, independent of the reaction scale or reaction conditions. Thus, 30% of VB,total are taken by the milling balls. Increase of the initial batch sizes changes ΦGS significantly. However, within the investigated parameter range no negative influence on the yield was observed. Up to 50% of VB,total can be taken over by the substrates in addition to 30% for the total milling ball volume. Scale-up factors of 15 and 11 were realized considering the amount of substrates and the reactor volume, respectively. Beside technological parameters, variables which influence the process itself, treaction and rpm, were investigated also. Variation of those allowed to fine-tune the reaction conditions in order to maximize the yield and minimize the energy intensity.

Effect of Reaction Parameters on the Synthesis of 5-Arylidene Barbituric Acid Derivatives in Ball Mills

“…As can be seen in Table 2, with increasing beaker volume, t 97% decreases significantly with a constant Φ MB and grinding stock filling degree Φ GS , which is defined as the ratio of the bulk volume of the substrates and V MV . 5 While no quantitative yields could be achieved in an 80 mL beaker after 1 h, full conversion was achieved after 30 and 18 min in 250 and 500 mL beakers, respectively. Thus, V MV is not the only parameter of importance, d MV and h MV also influence yield.…”

Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free

“…8,9 We therefore chose this as the first organic reaction to be studied by twin screw extrusion, and subsequently extended it to include the reaction of barbituric acid with two other aldehydes, veratraldehyde and 5-bromovanillin (Scheme 1). Comparison between the three aldehydes provides insight as to whether reactant melting points (Table 1) are important factors in this type of synthesis (i.e.…”

“…12 In particular, several successful mechanochemical condensation reactions have been reported, including the Knoevenagel condensation and Aldol reaction. 8,9 , 17 , 10 Other examples of organic reactions performed mechanochemically include the Wittig reaction, Diels-Alder, click and Suzuki reactions, some of which usually require quite stringent conditions in their conventional solution-based synthesis such as the use of dry solvents and inert atmospheres. However, there are several examples where ball milling has been done successfully without such rigorous conditions.…”

“…[1][2][3][4][5] Avoiding toxic solvents not only decreases potential hazards, but can also reduce the overall cost of a process. 5 A variety of materials and compounds have been prepared mechanochemically including metal alloys, 6 metal organic frameworks (MOFs), 7 and organic compounds from reactions such as the Knoevenagel condensation [8][9][10] and Wittig reaction, 11 amongst others. 12 However, two main drawbacks of mechanochemical synthesis are the general lack of both temperature control and scalability.…”

CHAPTER 2. Carbon–Carbon Bond Forming by Ball Milling

“…Although there are some example for performing Knoevenagel condensations in ball mills, the influence of process parameters, like rotation frequency, milling ball diameter or milling ball filling degree on the outcome of 40,41 The results showed that milling balls with smaller diameter led to higher yields in shorter reaction times. A medium milling ball filling degree was also beneficial due to optimal energy entry.…”