Table of content :

Download Report

Transcript Table of content :

‫جامعة النجاح الوطنية‬
‫عمل الطالبة ‪:‬‬
‫روند فخري ابو الرب ‪.‬‬
‫إشراف الدكتور ‪:‬‬
‫فؤاد محمود ‪.‬‬
Objectives .
The reaction mechanism .
Application and recent literature .
References .
I make this presentation to achieve the following :
To illustrate this interaction .
To show you the mechanism for this reaction .
Show you the application and the recent literature for
this reaction .
 The
Biginelli reaction is a multiplecomponent chemical reaction that creates
3,4-dihydropyrimidin-2(1H)-ones 4 from
ethyl acetoacetate 1, an aryl aldehyde (such
as benzaldehyde 2), and urea 3. It is named
for the Italian chemist Pietro Biginelli.
 The Biginelli reaction :
This reaction was developed by Pietro Biginelli in
1891. The reaction can be catalyzed by Bronsted
acids and/or by Lewis acids such as boron
trifluoride.Several solid-phase protocols utilizing
different linker combinations have been
Dihydropyrimidinones, the products of the
Biginelli reaction, are widely used in the
pharmaceutical industry as calcium channel
blockers, antihypertensive agents, and alpha-1-aantagonists.
 The
first step in the mechanism is
believed to be the condensation between
the aldehyde and urea, with some
similarities to the Mannich Condensation.
The iminium intermediate generated acts
as an electrophile for the nucleophilic
addition of the ketoester enol, and the
ketone carbonyl of the resulting adduct
undergoes condensation with the urea
NH2 to give the cyclized product.
Application and recent literature:
N-Substituted Ureas and Thioureas in Biginelli
Reaction Promoted by Chlorotrimethylsilane:
Convenient Synthesis of N1-Alkyl-, N1-Aryl-, and
Catalysis of the Biginelli Reaction by Ferric and Nickel
Chloride Hexahydrates. One-Pot Synthesis of 3,4Dihydropyrimidin-2(1H)-ones
Synthetic Manipulation
• So, with the dihydropyrimidine in
hand, whatcan be done?
• Partial of full oxidation (not trivial)
• Reduction of the ring to the
• Alkylation and acylation of the
• Manipulation of the ester at C(5)
• Manipulation of the methyl group at
C(6) (halogenation,nitration, etc.)
• Ring condensing reactions to make
The biological activity is what make
thesepyrimdines such attractive targets
• (A 1930 patent for use of a Biginelli cmpd for
protection of
wool from moths!?!)
• Antiviral activity
• Antibacterial activity
• Antitumor
• Antiinflammatiry)‫(مضاد التهابات‬
• Analgesic (‫(مسكن‬
• Blood palette aggregation inhibitor
• Cardiovascular activity
• Potent calcium channel blockers
. Mechanistic insights have provided rational
modifications to the experiment protocols, allowing
dihydropyrimidines to be synthesized in high yield. The
interesting and diverse biological activity of
dihydropyrimidines has been explored through the
generation of libraries of compounds via microwave,
solid-phase, and fluorous-phase technologies. Most
recently, asymmetric methods have been developed to
give enantioenriched dihydropyrimidines. The frontier
of the Biginelli reaction will continue to be developed as
new asymmetric methods are reported and as the
biological importance of this class of compounds is
explored in greater detail.
S. V. Ryabukhin, A. S. Plaskon, E. N. Ostapchuk, D. M.
Volochnyuk, A. A. Tolmachev, Synthesis, 2007, 417427.
 I. Cepanec, M. Litvić, A. Bartolinčić, M. Lovrić,
Tetrahedron, 2005, 61, 4275-4280.
 J. H. Schauble, E. A. Trauffer, P. P. Deshpande, R. D.
Evans, Synthesis, 2005, 1333-1339.
 H. Hazarkhani, B. , Synthesis, 2004, 1239-1242 .
 .
Thank you very much for your attention
and I hope to be benefited from this