High-speed ball milling

Another atom-efficient process that has been studied solvent free is the Baylis-Hillman reaction.This reaction affords useful multifunctional products from an addition reaction between an electrophile (often an aldehyde) and an electron-deficient olefin. Unfortunately, under most conditions it has the significant drawback of a slow rate of reaction. However, this has been overcome through a solvent free approach that uses a high-speed ball mill (HSBM) (Figure 2.9). Previous solvent free studies of this reaction took 3-4 days to achieve completion. In contrast, using an HSBM, the reaction is complete in 30 min. Unfortunately, a chlorinated solvent was chosen for reaction work up clearly, it would be desirable to use a less hazardous VOC here. 

Keywords reduction, ester, high-speed ball milling... 

Fulmer DA, Shearouse WC, Medonza ST, Mack J. Solvent-free Sonogashira coupling reaction via high speed ball milling. Green Chem 2009 11 1821-5. 

Reproduced with permission from Zhu X, Uu J. Chen T, Su W. Mechanically activated synthesis of (Ej-stilbene derivatives by high-speed ball milling. AppI Organomet Chem 2012 26 145-7. Copyright (2012), Wiley. 

Su W, Yu J, Li Z, Jiang Z. Solvent-free cross-dehydrogenative coupling reactions under high speed ball-milling conditions applied to the synthesis of functionahzed tetrahy-droisoquinolines. J Org Chem 2011 76 9144-50. 

Mack et al. carried out A -alkylation reaction in ball mill (8000M SpexCertiprep Mixer Mill, stainless steel) [46], Reaction of 4-bromobenzyl bromide 257 with urea and sodium hydroxide yielding di-(4-bromobenzyl) urea 258 proved that chemical reactions under high-speed ball-milling conditions could be manipulated in order to increase the nucleophilicity of an otherwise weakly nucleophilic substance (Scheme 3.68). Here the hydroxide deprotonates the urea, increasing the nucleophilicity of the nitrogen. Withont NaOH, there was a negligible conversion to a dialkyl urea product. 

Reproduced from Waddell DC, Thiel I, Bunger A, Nkata D, Maloney A, Clark T, et al. Investigating the formation of dialkyl carbonates using high speed ball milling. Green Chem 2011 13 3156-61, with permission from the Royal Society of Chemistry. 

Zhu X, Li Z, Shu Q, Zhou C, Su W. Mechanically activated solid-state synthesis of fla-vones by high-speed ball milling. Synth Commun 2009 39 4199-211. 

Scheme 1.24 The Heck-Mizoroki reaction using the high-speed ball milling (HSBM) technique as described by Su s group [68].

This reaction can proceed in the absence of any added catalyst, either under drastic conditions (393 K, 9 MPa, 24 h) [155] or, by using high speed ball milling (HBSM), at room temperature, under... 

In a recent report using the environmentally friendly high speed ball milling (HSBM) technique, Mack and Shumba described a dramatic increase in reaction rate of the MBH reaction betvv een />-nitrobenzaldehyde 30 and methylacrylate 4 in the presence of DABCO. ° In the event, all reagents were placed in a stainless steel vial and milled with a stainless steel ball-bearing for 30 minutes to afford the MBH adduct 58 in high yield. Previous reports using solvent-free conditions required three to four days and delivered the product in 70-87% yield. 

Scheme 21.31 Model aldol reaction under high-speed ball milling conditions.

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