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Methylphenidate:Treatment of ADHD Drugs

Release time:2019-10-09 17:32:52

    Methylphenidate, also known as Ritalin, is a drug that is effective in treating children with attention deficit hyperactivity disorder. Since the 1990s, the demand for this drug has risen sharply, with more than 2.4 billion doses consumed worldwide each year in 2013. Methylphenidate mainly has the following four structures:




Figure 1: Four isomers of methylphenidate
Professor Jean-Christophe M. Monbaliu studied the feasibility of synthesizing this compound on a microchannel reactor. His research was published on Reaction Chemistry & Engineering on November 24, 2016. The following is a summary of this article.
1. Analyze the synthesis method as shown in Figure 2 below

Figure 2: Inverse analysis of synthesis
2. Comparison of traditional methods and improved continuous flow synthesis methods
 
The following is an example of how the compound 3b can be synthesized into a compound 5b by a continuous flow process using an intramolecular reaction as an example.
3. Synthesis of β-lactam compound 5b
The schematic diagram of the continuous flow reaction is shown in Figure 3:

圖三:連續流合成5b示意圖
Even with a continuous flow process, it can be achieved by heating or a certain wavelength of illumination. The authors conducted experiments on these two methods, and the results are shown in Table 1:

Table 1: Experimental conditions and results for the synthesis of 5b on a microchannel reactor
We can see from the results that 99% conversion rate is obtained in 5 minutes under heating, and the effect is obvious.
4. Alcoholysis reaction
The alcoholysis of β-lactam (5b) is then combined to optimize the reaction. The reaction equations and schematics are as follows:


Figure 4: Equation of the alcoholysis reaction and schematic diagram of the reactor
The optimization results are shown in Table 2:
Table 2: Experimental conditions and results of alcoholysis reaction on a microchannel reactor
It can be seen from the above table that by optimizing the concentration of hydrochloric acid, the ratio of solvent, the reaction temperature and the residence time, the reaction conversion rate can reach more than 99%.

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