Attention:

We are currently upgrading the certain systems that support this website.  You may experience some functionality loss, though we expect the site to be fully functional by 9:00PM CT (US), February 24th.

We apologize for any inconvenience and appreciate your patience during this improvement process.Please note that you still have telephone and email access to our local offices. We apologize for any inconvenience.

Biginelli Reaction

Aldrich ChemFiles 2006, 6.7, 9.

Aldrich ChemFiles 2006, 6.7, 9.

The Biginelli Reaction (Scheme 3) is an acid catalyzed, threecomponent reaction between an aldehyde, b-ketoester, and urea that produces tetrahydropyrimidones, which have potential pharmaceutical applications.

Scheme 3

This reaction was first reported in 1893 and has increased interest because of the final products close structural relationship to the clinically important dihydropyrimidines.1 These compounds are known to show biological activities such as antiviral, antitumor, antibacterial, anti-inflammatory, and more recently, antihypertensive agents.2

The mechanism for this reaction is believed to first be the condensation between the aldehyde and the urea. This produces an iminium intermediate that is the electrophile for the nucleophilic addition of the ketoester enol. The ketone carbonyl that is formed then goes under a condensation reaction with the NH2 of the urea. This gives the cyclized final product.

back to top Back to Top

Materials

     

References

  1. Kappe, C.O. J. Org. Chem. 1997, 62, 7201–7204.
  2. Rafiee, E.; Jafari, Hadi. Bioorg. Med. Chem. Lett. 2006, 16, 2463–2466.

back to top Back to Top

Related Links