2-bromo-4 -methylacetophenone

From the diverse examples on Hantzsch syntheses reported, the reaction of 2-bromo-4 -methylacetophenone and l-acetyl-2-thiourea was exemplarily chosen to be represented here [10]. 

GlaxoSmithKline Pharmaceuticals in Harlow, UK, performed the Hantzsch synthesis of 2-bromo-4 -methylacetophenone and l-acetyl-2-thiourea in NMP (N-methyl-2-pyrrolidone) using a microchip reador under EOF conditions [10] (for EOF see [11]) [10] This is claimed to be the first example of a heated organic reaction performed on a glass chip reactor under electroosmotic flow control, whereas only room temperature reactions were made earlier. In a wider scope, the Hantzsch synthesis is a further example to evaluate the potential of microfluidic systems for high-throughput... 

Bromo-4-methylacetophenone from aluminum chloride catalyzed bromination of 4-methylacetophe-none, 40, 9... 

The most reactive position is the one that is para to bromine. The predicted product is therefore 4-bromo-3-methylacetophenone. Indeed, this is what is observed experimentally. 

Lithium aluminium hydride (LAH) (6.45 g, 170 mmol) and one magnetic stirrer bar were added into a 250-mL round-bottomed flask, which was then closed with a septum and dried under vacuum followed by filling with nitrogen. One part of dry ether (50 mL) was first injected into the stirred LAH. The mixture of 3-bromo-4-methylacetophenone (38 g, 180 mmol) in dry ether (50 mL) was injected into the flask dropwise. Stirring was continued after the completion of addition of 3-bromo-4-methylacetophenone until no more gas was generated. 

Recalling that alkyl gronps attached to the benzene ring by CH2 may be prepared by redaction of the appropriate ketone, we may rednce 3-bromo-4-methylacetophenone, as prepared in part (g), by the Clemmensen on Wolff-Kishner procedure to give 2-bromo-4-ethyltoluene. 

It is interesting to point out that the combination of cyclopropane and cyclobutane chemistry has allowed the synthesis of all three regioisomers of cuparenone possessing a cyclopentanone bearing two quartemary centers in the vicinal position from p-methylacetophenone and a-selenoalkyllithiums (Scheme 98). It can be noted than a-Lithiocyclopropyl sulfides or a-lithiocyclopropyl selenides are particularly suitable when a nonalkylated cyclopropane ring is needed whereas a-lithio-a-bromo cyclopropanes are the reagents of choice for the introduction of the... 

Preparation by reaction of bromine (1 mol) with 5-bromo-2-hydroxy-3-methylacetophenone (1 mol) in acetic acid on a water bath for 20 min (47%) [4466]. 

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