Biginelli Reaction – Lab Report
By: Mark Roberto
Questions 1, 3, and 4 on separate paper.
2) 3,4-dihydropyrimidones are calcium channel blockers. This means that they block calcium ion flow through membrane channels in cells.
Using the Bignelli reaction, acetoacetamide, benzaldehyde, and urea were reacted in a 1:1:1 ratio to synthesize a 3,4-dihydropyrimidinone that will be called “product”. The limiting reagent was determined to be the acetoacetamide, which was 3.936 mM (0.3979g/101.10g/mol). For the urea, 3.996 mM were used (0.2400g/60.06g/mol). For the benzaldehyde, 3.999 mM were used [(0.4062 mL *1.045 g/cm3)/106.12g/mol].
The product has a molecular weight of 231.25 g/mol. Since the mole ratio of limiting reagent to product is 1:1, the theoretical yield is 3.936mM, or 0.9102g. Using this information the percent yield was determined for both the crude product and the final purified product. The percent yield of the crude product was 32.94% (0.2998g*100/0.9102g). The percent yield of the final product was determined to be 16.73% (0.1523g*100/0.9102g).
The percent yield of the reaction was relatively low. This could be due to the fact that not all of the starting material was reacted in the microwave vessel. Another possibility is that some of the product that was dissolved in the hot ethanol did not crystallize. After recrystallizing the product, only about half of the crude product was maintained. This could be due to crystal loss during transfer, or again due to the fact that some product dissolved in the hot ethanol did not recrystallize.
The H1 NMR provides evidence that the desired product was synthesized. It also provides evidence that there were impurities in the final product, most likely from leftover reactants. The peak of 7 hydrogens at 7.25 ppm is due to peaks from the benzylic hydgrogens and also from the two amide hydrogen. The peak at 3.33 ppm is due to the 3 carbon on the methyl group which is shifted downfield due to the proximity to a carbonyl carbon. The last peak from the product is at 2.06 ppm and is due to the two hydrogen on the amine group. The other peaks are probably from leftover acetoacetemide.
The carbon NMR also tells us that the desired product was synthesized. From 127ppm to 153 ppm there are multiple peaks that correspond to the 10 hydrogen that are found in the rings of the molecule. There is also a peak at 168 ppm that corresponds to the carbonyl carbon that is not found in the ring of the molecule. Lastly, there is a peak at 18 ppm which corresponds to the carbon of the methyl group. There are also other peaks in the spectrum that, like the H1 NMR, show that there are impurities in the final product, most likely from left over starting material.
Finally, the LCMS data proves that are compound was made. The LC data shows that the final product is not pure, as there are four peaks relating to the retention time of four different molecules. The MS spectra of the first two LC products (0.387 and 0.616 seconds) both have peaks of 232, which relates to the desired product which has a molecular weight of 231 g/mol (+1 for hydrogen). The other two products from the LCMS are unknown impurities.
In conclusion, the percent yield of this reaction was relatively low due to the difficulty of crystallizing all of the product. Although the NMR and LCMS data shows that the desired product was made, it also shows that there are impurities in the final product, most likely from leftover starting materials that were not completely filtered out.
 “Highly regioselective synthesis of N-3 organophosphorous derivatives of 3,4-dihydropyrimidin-2(1H)-ones and their calcium channel binding studies”
Singh K, Singh K, Trappanese, DM, and Moreland RS
Eur. J Med. Chem. 54: 397-402, 2012.