Preparation method of 2-bromo-4′-methylpropiophenone_Kain Industrial Additive

Background and overview^[1]

2-Bromo-4′-methylpropiophenone can be used as a pharmaceutical synthesis intermediate. For example, 4-methylmethcathinone (4-MMC) is prepared, also known as mephedrone. Other names include drone[1], MCAT[2], whitemagic or meow. Meowmeow. 4-MMC is a synthetic analog of the cathinones found in Alapai tea. The main methods of smoking include swallowing, pumping and injection. 4-MMC was first synthesized in 1929. But until 2003, most countries in the world did not have a clear understanding of 4-MMC. 4-MMC was re-recognized in 2003, when an anonymous chemist named “Kinetic” mentioned on a sharing website that he was trying to synthesize 2-methylmethcathinone and 4-methylmethcathinone. , and described feeling an intense sense of well-being afterwards that no drug could bring about before. At the time, 4-MMC could also be legally sold and purchased on the Internet. It was not until 2008 that law enforcement agencies recognized 4-MMC as a drug. First, in 2008, Israel stated that the trading of 4-MMC was illegal, and later Sweden also stated that 4-MMC was controlled. But before 2010, 4-MMC was particularly popular in most parts of Europe, especially the United Kingdom. In December 2010, the European Union declared 4-MMC illegal; in September of the following year, the United States announced that it would control it. In July 2012, the United States officially added it to the Synthetic Drug Abuse Prevention Act (SDAPA). It has now been proven that it has almost no medicinal value, and every country in the world has included it in the ranks of controlled substances.

Preparation^[1]

2-Bromo-4′-methylpropiophenone is prepared as follows: (1) Under argon protection, add (4g, 30mmol) anhydrous aluminum chloride to the reaction bottle, and then add 20ml of anhydrous dichloromethane , stir to dissolve. After dissolving, add (1.7g, 10mmol) 2-bromopropionyl chloride and continue stirring for 20 minutes. Then add (0.92g, 10mmol) toluene and complete the dropwise addition within 30 minutes. After the dropwise addition is completed, reflux for 2 hours. After the reflux is completed, cool to room temperature. After cooling, pour the solution into 40 ml of ice water, add 20 ml of methylene chloride and 20 ml of 6N hydrochloric acid, shake vigorously and then separate into layers. After layering, the lower methylene chloride phase was left. After washing the methylene chloride phase twice with 1NHCL, it was dried with anhydrous magnesium sulfate, filtered, and rotary evaporated to obtain a transparent oily substance. The transparent substance was placed in a crystallizing dish and ether was added to dissolve it, then petroleum ether was slowly added dropwise until slightly turbid, covered with a piece of paper and left to crystallize in a fume hood to obtain 1.37g of the product 2-bromo-4′-methyl. Transparent crystals of phenylacetone. Yield 60.6% 13CNMR (DMSO) δ: 192.562, 144.674, 134.845, 129.242, 129.025, 41.009, 22.502, 20.963ESIm/z=227 (M+1).