1,5-Benzodiazepine Educational Synthesis – Conclusion

Good afternoon, everyone!

After nearly eight weeks of literature research and experimenting in the lab, I have finalized my initial procedure for the synthesis of 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine using ortho-Phenlenediamine, an excess of acetone, and sulfamic acid catalyst.  I made several alterations to the skeletal procedure by Fletcher given to me by Prof. Lashley, including an increase in reaction time (from 30 minutes to 60 minutes), an increase in catalyst (from 10% molar to 20% molar), the use of reagent-grade acetone (instead of solvent-grade), the use of magnesium sulfate drying agent (instead of sodium sulfate drying agent), the use of a drying column to eliminate atmospheric water from entering the system, and limiting the extraction solvent to 30 mL of DCM (instead of 50 mL).  With these changes, the reaction yields more pure product, in a timely fashion.

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1,5-Benzodiazepine Educational Synthesis – Update #3

Good afternoon, everybody!

I have successfully obtained a clear H1-NMR for my 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine synthesis, and narrowed down my procedure to a consistent yield of reasonably pure product!  I have found the melting point for this NMR-verified product to be consistently within the range of 95 – 98 °C using the Mel-Temp device, instead of 121 – 124 °C, which is the experimental range found by BIONET-Key Organics on ChemSpider; upon further researching on the same ChemSpider page, however, I have found theoretical confirmation from EPISuite of a melting point around 99 °C, which is much closer to mine.  There still exists the possibility of atmospheric contaminants within my product, messing with the melting point, but such is science.

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1,5-Benzodiazepine Educational Synthesis – Update #2

Good morning, everybody!

I am very excited (and relieved) to announce that I have made progress with my procedure!  By allowing my reaction to stir for twice as long (60 minutes as opposed to 30 minutes), it finally formed half of the expected imine product!  I say half, because upon examination of the resulting H1-NMR spectrum, it appears to be missing a peak suggesting the completion of the ring structure.  (I managed to retrieve around 0.30 grams of dried product, post-Rotovap and pre-filtration.  Hooray!)

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1,5-Benzodiazepine Educational Synthesis – Update #1

Hello everybody,

I have made some progress with regards to my improvement upon the educational drug synthesis of a 1,5-Benzodiazepine, a structural precursor to benzodiazepine psychoactive drugs such as Valium and Xanax.  After discovering that my sulfamic acid catalyst was several years out of date (oops), I am now working with a fresh batch.  The sulfamic acid acts as an electron acceptor in the condensation reaction between ortho-Phenlenediamine and an excess of acetone, altogether known as an imine formation, which produces a structure containing stable carbon-nitrogen double bonds.  Without the sulfamic acid catalyst working to remove the water that is produced as a byproduct, the reaction proceeds at an agonizingly slow pace — definitely not completely under 30 minutes of stirring, which is why my yield has been almost nonexistent, up until now.

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Abstract: Educational Drug Synthesis for Improvement of Organic Chemistry II Lab Curriculum

In the current curriculum for the Organic Chemistry II Lab, there is limited opportunity for undergraduates aiming for future medical and pharmaceutical careers to gain actual, hands-on experience with medicinal chemistry.   In order to rectify this, our small team of independently working undergraduates will be continuing our improvement of various drug synthesis procedures, for use in the Organic Chemistry II Lab handbook next semester onward.  My own procedure will allow students to synthesize compounds of 1,5-benzodiazepine, a safe precursor to important psychoactive drugs such as Diazepam (Valium) and Alprazolam (Xanax); not only is the procedure inexpensive and straightforward, but will also allow students to review almost all of the important laboratory techniques and set-ups taught throughout the semester, while engaging in medicinal chemistry through a relevant drug synthesis.  Being a Neuroscience major interested in pharmaceuticals myself, I will definitely include supplementary information on the pharmacokinetics/pharmacodynamics of sedative psychoactive drugs in the introduction to my chapter.  Overall, the aim of my research is the enrichment of the Organic Chemistry II Lab experience, as well as the engagement of all students in the importance of medicinal chemistry.