The Pellizzari reaction was discovered in 1911 by Guido Pellizzari, and is the

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...

of an

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

and a

hydrazide Hydrazides in organic chemistry are a class of organic compounds with the formula RNHNH2 where R is acyl (R'CO-), sulfonyl (R'SO2-), or phosphoryl (R'2P(O)-). Unlike hydrazine and alkylhydrazines, hydrazides are nonbasic owing to the inductive infl ...

to form a

1,2,4-triazole 1,2,4-Triazole (as ligand in coordination compounds, Htrz abbreviation is sometimes used) is one of a pair of isomeric chemical compounds with molecular formula CHN, called triazoles, which have a five-membered ring of two carbon atoms and three n ...

. The product is similar to that of the Einhorn-Brunner reaction, but the mechanism itself is not

regioselective In chemistry, regioselectivity is the preference of chemical bonding or breaking in one direction over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base ...

. :

Mechanism

The mechanism begins by the nitrogen in the hydrazide attacking the

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

carbon on the amide to form compound 3. The negatively charged oxygen then abstracts two hydrogens from neighboring nitrogens in order for a molecule of water to be released to form compound 5. The nitrogen then performs an intramoleculer attack on the carbonyl group to form the five-membered ring of compound 6. After another proton migration from the nitrogens to the oxygen, another water molecule is released to form the 1,2,4-triazole 8. : Pellizzari-Reaktion Mechanismus-v4

Uses

The synthesis of the 1,2,4-triazole has a wide range of biological functions. 1,2,4-triazoles have

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

, antifungal,

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

and

hypoglycemic Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

properties. 3-benzylsulfanyl derivates of the triazole also show slight to moderate antimycobacterial activity, but are considered moderately toxic.

Problems and variations

The Pellizzari reaction is limited in the number of substituents that can be on the ring, so other methods have been developed to incorporate three elements of diversity. Liquid-phase synthesis of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles by PEG support has given moderate yields with excellent purity. In practice, the Pellizzari reaction requires high temperatures, long reaction times, and has an overall low yield. However, adding microwave irradiation shortens the reaction time and increases its yield.

Related reactions

* Einhorn-Brunner reaction

References

{{Reflist Condensation reactions Heterocycle forming reactions Name reactions