The Biginelli reaction is a multiple-component

Multi-component reaction

In chemistry, a multi-component reaction , sometimes referred to as a "Multi-component Assembly Process" , is a chemical reaction where three or more compounds react to form a single product...

 chemical reaction

Chemical reaction

A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

 that creates 3,4-dihydropyrimidin-2(1H)-ones 4 from ethyl acetoacetate

Ethyl acetoacetate

The organic compound ethyl acetoacetate is the ethyl ester of acetoacetic acid. It is mainly used as a chemical intermediate in the production of a wide variety of compounds, such as amino acids, analgesics, antibiotics, antimalarial agents, antipyrine and aminopyrine, and vitamin B1; as well as...

 1, an aryl aldehyde

Aldehyde

An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

 (such as benzaldehyde

Benzaldehyde

Benzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...

 2), and urea

Urea

Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

 3. It is named for the Italian chemist Pietro Biginelli

Pietro Biginelli

Pietro Biginelli was an Italian chemist, who have discovered a three-component reaction between urea, acetoacetic ester and aldehydes...

.
This reaction was developed by Pietro Biginelli

Pietro Biginelli

Pietro Biginelli was an Italian chemist, who have discovered a three-component reaction between urea, acetoacetic ester and aldehydes...

 in 1891. The reaction can be catalyzed by Brønsted acids and/or by Lewis acid

Lewis acid

]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

s such as boron trifluoride

Boron trifluoride

Boron trifluoride is the chemical compound with the formula BF3. This pungent colourless toxic gas forms white fumes in moist air. It is a useful Lewis acid and a versatile building block for other boron compounds.-Structure and bonding:...

. Several solid-phase

Solid-phase synthesis

In chemistry, solid-phase synthesis is a method in which molecules are bound on a bead and synthesized step-by-step in a reactant solution; compared with normal synthesis in a liquid state, it is easier to remove excess reactant or byproduct from the product. In this method, building blocks are...

 protocols utilizing different linker combinations have been published.

Dihydropyrimidinones, the products of the Biginelli reaction, are widely used in the pharmaceutical industry as calcium channel

Calcium channel

A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...

 blockers, antihypertensive agents

Antihypertensive

The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

, and alpha-1-a-antagonists.
The reaction mechanism of the Biginelli reaction is a series of bimolecular reactions leading to the desired dihydropyrimidinone.

According to a mechanism proposed by Sweet in 1973 the aldol condensation

Aldol condensation

An aldol condensation is an organic reaction in which an enol or an enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone, followed by a dehydration to give a conjugated enone....

 of ethylacetoacetate 1 and the aryl aldehyde is the rate-limiting step leading to the carbenium ion 2.