OXADIAZOLE

Oxadiazole is an important nitrogen- and oxygen-containing heterocyclic structure valued for its stability, compact aromatic framework, and ability to support a wide variety of chemical substitutions in advanced synthesis.
Oxadiazole's derivatives are extensively explored in pharmaceuticals, crop-protection chemistry, functional materials, fluorescent systems, and electronic applications where controlled molecular architecture and electronic performance are required.
The broad adaptability of the oxadiazole ring makes it a useful platform for designing high-value intermediates, specialized research compounds, and next-generation organic materials across multiple industrial and scientific fields.

CAS Number: 288-99-3
EC Number: 873-098-3
Molecular Formula: C2H2N2O
Molecular Weight: 70.05 g/mol

Synonyms: 11120-54-0, DTXSID00436582, RefChem:168776, CHEBI:46685, DTXCID20387406, Oxadiazole, Oxadiazoles, 1,2,3-oxadiazole, oxadiazol, racemic oxadiazole, SCHEMBL3006, SCHEMBL7612, SCHEMBL25166, SCHEMBL216935, SCHEMBL5149931, WCPAKWJPBJAGKN-UHFFFAOYSA-N

Oxadiazoles are a class of heterocyclic aromatic chemical compounds of the azole family with the molecular formula C2H2N2O.

There are four isomers of oxadiazole:
1,2,4-Oxadiazole, 1,2,5-oxadiazole, and 1,3,4-oxadiazole are all known and appear in a variety of pharmaceutical drugs including raltegravir, butalamine, fasiplon, oxolamine, and pleconaril.
The 1,2,3-isomer is unstable and ring-opens to form the diazoketone tautomer; however, it does exist within the unusual sydnone motif.

In 2018, a compound called bis(1,2,4-oxadiazole)bis(methylene) dinitrate which might have 1.5 times the power of TNT was developed at the United States Army Research Laboratory (ARL) working with the Los Alamos National Laboratory.

Oxadiazole is a five-membered aromatic heterocyclic compound containing one oxygen atom, two nitrogen atoms, and two carbon atoms in its ring.
The parent oxadiazole has the molecular formula C2H2N2O and molecular weight 70.05 g/mol.
Oxadiazoles occur as four positional isomers: 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole (furazan), and 1,3,4-oxadiazole.

Oxadiazole derivatives are widely used as heterocyclic building blocks in pharmaceutical, agrochemical, and specialty organic synthesis.
Their aromatic ring can provide structural rigidity and useful electronic properties, making substituted oxadiazoles valuable intermediates in the development of biologically active compounds and functional materials.

Oxadiazole is defined as a five-membered aromatic heterocyclic compound belonging to the azole family, with the molecular formula C2H2N2O, characterized by the presence of two carbons, two adjacent nitrogens, and one oxygen atom.
Oxadiazole has four isomers and is found in various pharmaceutical drugs.

1,3,4-Oxadiazole is a nitrogen and oxygen containing heterocycle, and one of the four isomers of oxadiazole.
Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.

Oxadiazole is a heterocyclic ring with 5 members that has 1 oxygen atom, 2 nitrogen atoms, 2 double bonds, and 2 carbons.
In furan, they are created by placing two methylene groups (=CH) for two nitrogen (-N=) atoms.

The aromaticity was reduced by the substitution of these groups.
There were four different isomer of oxadiazole that were identified: 1,3,4-oxadiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, and 1,2,4-oxadiazole.

Because of their vast array of chemical and biological characteristics, 1,2,4-oxadiazoles and 1,3,4-oxadiazoles are One of them that scientists are more familiar with oxadiazole and have studied more extensively.
The 1,3,4-oxadiazole has grown in importance as a synthon.

Non-steroidal anti-inflammatory drugs, like diclofenac (DCF), is generally prescribed to reduce pain.
Through cyclooxygenase (COX) inhibition, prostaglandin synthesis can be inhibited.

Important adverse effects include cardiovascular, gastrointestinal, liver and renal damage are displayed.
Diclofenac's center contains a carboxylic group (COOH), which harm gastrointestinal Tract.

By employing the retro-synthetic method, which reduces gastrointestinal side effects while increasing chemical and biological activity, the hydroxyl (OH) component of COOH was replaced with new functional groups i.e methyl, methoxy, CH2NH2, NH2, NHCOCH3, NHCONH2, Chlorine, CF3.

1,2,5-Oxadiazole is a five-membered, heteroaromatic, planar heterocycle comprised of one oxygen atom with two vicinal nitrogen atoms (N-O-N) and two carbon atoms at the 3- and 4-positions of the ring.
Oxadiazole is a π-excessive heterocycle also referred to by its trivial name furazan and corresponding 2-N-oxide as furoxan.

The ionization energy of oxadiazole is 11.79 eV and the dipole moment is 3.38 D greater than isoxazole.
The π electron density of the nitrogen atom is greater than the oxygen and carbon atoms as depicted in the following scheme.

Derivatives:
1,3,4-Oxadiazole itself is not commonly used in organic chemistry, but many of its derivatives are important.
For example, raltegravir is an HIV drug which contains an 1,3,4-oxadiazole ring.
Other pharmaceutical drugs containing the 1,3,4-oxadiazole ring include fenadiazole, zibotentan, and tiodazosin.

1,3,4-Oxadiazole derivatives can be synthesized in a variety of ways.
One pathway is from oxidation of tetrazoles in the presence of aldehydes.

Similarly, the reaction of tetrazoles with acyl chlorides provides oxadiazoles.
Both methods involve the release of N2.

Applications of Oxadiazole:
1,2,5-Oxadiazole derivatives are found to be potent inhibitors of indoleamine 2,3-dioxygenase and are useful for the treatment of cancer and other disorders.
They are also useful as a new class of SENP2 inhibitors and can be used for the development of novel therapeutic agents for various diseases targeting SENPs.

1,2,5-Oxadiazole-2-oxides are used as a source of NO in biological studies.
4-Amino-1,2,5-oxadiazole-2-oxide-3-carboxylic acid and azo derivatives have been studied for their vasodilating properties.

Oxadiazole and its derivatives are widely used as important heterocyclic building blocks in pharmaceutical, agrochemical, and specialty chemical synthesis.
They are frequently incorporated into the design of biologically active molecules because the oxadiazole ring can serve as a stable linker or bioisosteric replacement for functional groups such as esters and amides.

Oxadiazole derivatives are investigated and used in the development of compounds with antimicrobial, antifungal, anti-inflammatory, antiviral, anticancer, and enzyme-inhibitory activities.
In agrochemical research, substituted oxadiazoles are utilized as intermediates in the preparation of herbicides, fungicides, insecticides, and other crop-protection compounds.

The oxadiazole ring is also valuable in materials science, where certain derivatives are employed in organic light-emitting diodes, charge-transport materials, fluorescent compounds, and other optoelectronic applications.
Their electron-deficient aromatic structure makes many oxadiazole derivatives suitable for use in electron-transporting and electron-accepting materials.

In synthetic organic chemistry, oxadiazoles are used as versatile intermediates for producing more complex nitrogen- and oxygen-containing heterocyclic compounds.
They are also applied in research involving polymers, dyes, sensors, coordination compounds, and functional organic materials where controlled electronic and structural properties are required.

Synthesis of Oxadiazole:
Oxadiazole derivatives can be synthesized through several established cyclization methods, with the selected route depending on the desired oxadiazole isomer and substituent pattern.
One of the most common approaches to 1,3,4-oxadiazoles involves the cyclodehydration of diacylhydrazines, which can be prepared by reacting hydrazides with carboxylic acids, acid chlorides, or related acylating agents.
Dehydrating reagents such as phosphorus oxychloride, thionyl chloride, phosphorus pentoxide, or other suitable cyclization agents may then promote ring closure to form the oxadiazole nucleus.

Another widely used route involves the oxidative cyclization of acylhydrazones or related hydrazide derivatives.
In this method, an appropriately substituted hydrazide is first condensed with an aldehyde or ketone to form a hydrazone intermediate, followed by oxidation and intramolecular ring formation to generate the corresponding oxadiazole derivative.
The reaction conditions can be adjusted to introduce different aromatic, heteroaromatic, or aliphatic substituents onto the oxadiazole ring.

1,2,4-Oxadiazoles are commonly prepared through reactions involving amidoximes and activated carboxylic acid derivatives.
Amidoximes can be acylated with acid chlorides, esters, anhydrides, or activated carboxylic acids, producing O-acylated intermediates that undergo thermal or reagent-assisted cyclodehydration to yield the 1,2,4-oxadiazole structure.
This route is particularly useful because a wide variety of substituents can be incorporated through the choice of amidoxime and acylating component.

Modern synthetic methods may also employ microwave-assisted cyclization, transition-metal-mediated reactions, one-pot procedures, or environmentally improved catalytic systems to reduce reaction times and improve product yields.
After cyclization, the resulting oxadiazole derivative is generally isolated by extraction, crystallization, or chromatographic purification, depending on the reaction scale and required product purity.

Stability and Reactivity of Oxadiazole:

Chemical stability:
Oxadiazole is generally stable under normal ambient temperatures and recommended storage conditions.

Reactivity:
No significant reactivity is expected during normal handling and use under controlled conditions.

Conditions to avoid:
Avoid excessive heat, open flames, sparks, prolonged exposure to moisture, and contact with incompatible substances.

Incompatible materials:
Avoid strong oxidizing agents, strong acids, strong bases, and highly reactive reducing agents.

Hazardous decomposition products:
Thermal decomposition or combustion may produce carbon monoxide, carbon dioxide, and nitrogen oxides.

Handling and Storage of Oxadiazole:

Safe handling:
Handle in a well-ventilated area and avoid unnecessary inhalation, ingestion, and contact with the skin and eyes.

Storage conditions:
Keep the container tightly closed in a cool, dry, and well-ventilated location away from heat, ignition sources, and incompatible materials.

First Aid Measures of Oxadiazole:

Inhalation:
Move the affected person to fresh air and obtain medical attention if discomfort or symptoms develop.

Skin contact:
Remove contaminated clothing and wash the affected area thoroughly with soap and water.

Eye contact:
Rinse cautiously with clean water for several minutes, removing contact lenses when easy to do, and seek medical advice if irritation persists.

Ingestion:
Rinse the mouth with water and obtain medical advice if adverse effects occur.

Firefighting Measures of Oxadiazole:

Suitable extinguishing media:
Use water spray, dry chemical, carbon dioxide, or suitable foam according to surrounding fire conditions.

Protective equipment:
Firefighters should wear appropriate protective clothing and self-contained breathing apparatus where necessary.

Fire-related decomposition:
Combustion may generate carbon oxides, nitrogen oxides, and irritating organic fumes.

Accidental Release Measures of Oxadiazole:

Personal precautions:
Ensure adequate ventilation, avoid generating dust or vapors, and use suitable personal protective equipment during cleanup.

Cleanup methods:
Collect spilled material carefully using appropriate non-sparking tools and place it in a suitable closed container for disposal.

Environmental precautions:
Prevent unnecessary release into drains, surface water, and soil.

Exposure Controls/Personal Protective of Oxadiazole:

Engineering controls:
Provide adequate general or local exhaust ventilation, particularly where dust or vapor formation may occur.

Eye protection:
Use suitable chemical safety glasses or protective goggles.

Hand protection:
Wear chemically resistant protective gloves appropriate for the conditions of use.

Skin protection:
Wear suitable laboratory or industrial protective clothing to minimize direct contact.

Respiratory protection:
Use suitable respiratory protection when ventilation is insufficient or when airborne concentrations cannot be adequately controlled.

Hygiene measures:
Wash hands thoroughly after handling and before eating, drinking, or leaving the work area.

Identifiers of Oxadiazole:
CAS Number: 288-99-3
ChemSpider: 87937
PubChem CID: 97428
UNII: 20O2F20OUR
CompTox Dashboard (EPA): DTXSID10182987
InChI: InChI=1S/C2H2N2O/c1-3-4-2-5-1/h1-2H
Key: FKASFBLJDCHBNZ-UHFFFAOYSA-N
SMILES: C1=NN=CO1

CAS Number: 288-99-3
EC Number: 873-098-3
Molecular Formula: C2H2N2O
Molecular Weight: 70.05 g/mol

Compound ChEMBL ID: CHEMBL314737
Name: OXADIAZOLE
Max Phase: Preclinical Learn more
Molecular Formula: C8H12N4O
Molecular Weight: 180.21
Molecule Type: Small molecule

Properties of Oxadiazole:
Chemical Formula: C2H2N2O
Molar Mass: 70.051 g·mol−1

Molecular Weight: 70.05 g/mol
XLogP3-AA: -0.2
Hydrogen Bond Donor Count: 0
Hydrogen Bond Acceptor Count: 3
Rotatable Bond Count: 0
Exact Mass: 70.016712692 Da
Monoisotopic Mass: 70.016712692 Da
Topological Polar Surface Area: 38.9 Ų
Heavy Atom Count: 5
Complexity: 30.8
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Names of Oxadiazole:

Preferred IUPAC name:
1,3,4-Oxadiazole