TETRAZOLE

Tetrazole provides a compact nitrogen-rich framework that is especially useful for constructing complex molecules with tailored chemical and coordination properties.
Tetrazole's derivatives are widely employed in medicinal chemistry, ligand design, functional materials, and the preparation of specialized heterocyclic intermediates.
Tetrazole is an important nitrogen-rich building block used in pharmaceutical chemistry, coordination chemistry, energetic-material research, and specialty organic synthesis.

CAS Number: 288-94-8
EC Number: 206-023-4
Molecular Formula: CH2N4
Molecular Weight: 70.05 g/mol

Synonyms: 1H-Tetrazole, 288-94-8, Tetraazacyclopentadiene, 1,2,3,4-tetrazole, D34J7PAT68, NSC 36712, NSC-36712, DTXSID5075280, CHEBI:33193, RefChem:79967, DTXCID9037876, 206-023-4, Tetrazole, 2H-Tetrazole, 27988-97-2, 1-H-Tetrazole, 100043-29-6, MFCD00005247, 1H-Tetrazole (~0.3M in Acetonitrile), CH2N4, 1tetrazole, racemic tetrazole, 1H-tetrazol, 2H-Tetrazole; 1H-TZ; 2,3,4-Triazapyrrole; NSC 36712; Tetraazacyclopentadiene, 1H-Tetraazole #, NSC36712, EINECS 206-023-4, SCHEMBL230, SCHEMBL877, SCHEMBL6606, UNII-D34J7PAT68, SCHEMBL13639, SCHEMBL29478, SCHEMBL30779, 1H-1,2,3,4-tetrazol, 2H-1,2,3,4-tetrazole, SCHEMBL348638, SCHEMBL435092, 2,3,4-TRIAZAPYRROLE, orb1220038, orb1298862, CHEMBL2148103, alpha-1H-1,2,3,4-tetrazole, CHEBI:33194, CS-D1473, AC-784, STK366101, AKOS003615496, AKOS015955446, 1H-Tetrazole, 0.45M in acetonitrile, FT64687, 1H-Tetrazole (0.45M in Acetonitrile), BP-14127, BP-30175, DB-000385, NS00042246, T8520, 1H-Tetrazole - ~0.45M solution in acetonitrile, Q58826308, Q58826418, F8889-0313, Tetrazole solution, reagent grade, 3 wt % in acetonitrile, InChI=1/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5, 288-95-9

A tetrazole is a synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom.
The name tetrazole also refers to the parent compound - a whitish crystalline powder with the formula CH2N4, of which three isomers exist.

Tetrazole is used in oligonucleotide synthesis, pharmaceutical-intermediate production, heterocyclic synthesis and coordination-chemistry research.

Tetrazole is a five-membered aromatic heterocyclic compound containing one carbon atom and four nitrogen atoms in its ring.
Tetrazole is an important nitrogen-rich building block used in pharmaceutical chemistry, coordination chemistry, energetic-material research, and specialty organic synthesis.
The tetrazole ring is particularly valued as a functional-group substitute in medicinal chemistry and as a versatile platform for preparing salts, ligands, and substituted heterocyclic derivatives.

Tetrazole is a class of synthetic organic heterocyclic compound containing a 5-member ring of four nitrogen atoms and one carbon atom.
Tetrazole appears as an odorless white to light-yellow crystalline powder.

Tetrazole has several pharmaceutical applications.
Tetrazole can act as a bioisotere for the carboxylate group, angiotensin II receptor blockers such as losartan and candesartan as well as dimethyl thiazolyl diphenyl tetrazolium bromide (MTT), which can be used in MTT assay for quantifying the respiratory activity of liver cells.

Tetrazole can also be used in DNA assays.
In addition, Tetrazole derivatives have also been used in explosives such as TNT or high performance solid rocket propellant formulations.
Tetrazole can be synthesized through the reaction between anhydrous hydrazoic acid and hydrogen cyanide under pressure.

Tetrazole is an odorless white to light-yellow crystalline powder.
Tetrazole is a tetrazole tautomer where the proton is located on the 1st position.

Tetrazole is a tetrazole and a one-carbon compound.
Tetrazole is a tautomer of a 2H-tetrazole and a 5H-tetrazole.

Tetrazole is defined as a five-membered heterocycle that contains four nitrogen atoms and one carbon atom at the 5-position, characterized by delocalized 6π electrons over the ring structure.

Uses of Tetrazole:
Tetrazole is a catalyst for phosphoramidite synthesis.
Tetrazole is also used as an intermediate for the drug cilostazol.

Cilostazol is an antiplatelet drug and a vasodilator.
Tetrazole derivatives are used as antibiotics and optically active tetrazole-containing antifungal preparations of azole type was reported.

Tetrazole is used as a bioisostere for the carboxylate group.
Tetrazole is also used as coupling reagent for preparation of polynucleotides.

There are several pharmaceutical agents which are tetrazoles, including several cephalosporin-class antibiotics.
Tetrazoles can act as bioisosteres for carboxylate groups because they have similar pKa and are deprotonated at physiological pH.

Angiotensin II receptor blockers — such as losartan and candesartan, often are tetrazoles.
A well-known tetrazole is dimethyl thiazolyl diphenyl tetrazolium bromide (MTT).

This tetrazole is used in the MTT assay to quantify the respiratory activity of live cells culture, although it generally kills the cells in the process.
Some tetrazoles can also be used in DNA assays.
Studies suggest VT-1161 and VT-1129 are a potential potent antifungal drugs as they disturbs fungal enzymatic function but not human enzymes.

Some tetrazole derivatives have been investigated as high performance explosives (e.g azidotetrazole) and also for use in high performance solid rocket propellant formulations.

Other tetrazoles are used for their explosive or combustive properties, such as tetrazole itself and 5-aminotetrazole, which are sometimes used as a component of gas generators in automobile airbags.
Tetrazole based energetic materials produce high-temperature, non-toxic reaction products such as water and nitrogen gas and have a high burn rate and relative stability,[20] all of which are desirable properties.
The delocalization energy in tetrazole is 209 kJ/mol.

Tetrazole and 5-(benzylthio)-1H-tetrazole (BTT) are widely used as acidic activators of the coupling reaction in oligonucleotide synthesis.

C,N substituted tetrazoles can undergo controlled thermal decomposition to form highly reactive nitrilimines.
These can in turn undergo a variety of 1,3-dipolar cycloaddition reactions.

Structure and Bonding of Tetrazole:
Three isomers of the parent tetrazole exist, differing in the position of the double bonds: 1H-, 2H-, and 5H-tetrazole.
The 1H- and 2H- isomers are tautomers, with the equilibrium lying on the side of Tetrazole in the solid phase.

In the gas phase, 2H-tetrazole dominates.
These isomers can be regarded as aromatic, with 6 π-electrons, while the 5H-isomer is nonaromatic.

Phosphorus analogs do not have the same electronic nature, with 1H-tetraphosphole having a more pyramidal geometry of the phosphorus at position 1.
Instead, Tetrazole is the anionic tetraphospholides that are aromatic.

Strongly inductively electron-withdrawing functional groups attached to a tetrazole may stabilize a tautomeric ring-opening equilibrium with an azidoimine form.

Synthesis of Tetrazole:
Tetrazole was first prepared by the reaction of anhydrous hydrazoic acid and hydrogen cyanide under pressure.
A Pinner reaction of organic nitriles with sodium azide in the presence of a buffered strong acid (e.g. triethylammonium chloride) synthesizes 5-substituted Tetrazoles cleanly.
Another method is the deamination of 5-aminotetrazole, which can be commercially obtained or prepared in turn from aminoguanidine.

2-Aryl-2H-tetrazoles are synthesized by a [3+2] cycloaddition reaction between an aryl diazonium and trimethylsilyldiazomethane.

Stability and Reactivity of Tetrazole:

Chemical stability:
Tetrazole is stable under recommended storage conditions but is sensitive to heat and may present an explosion risk when subjected to shock or friction.

Conditions to avoid:
Avoid heat, sparks, open flames, grinding, impact, friction, and contact with incompatible materials.

Incompatible materials:
Avoid strong oxidizing agents and other highly reactive substances.

Handling and Storage of Tetrazole:

Safe handling:
Handle carefully in a well-ventilated area and avoid dust formation, shock, friction, and unnecessary contact.

Storage conditions:
Keep tightly closed in a cool, dry place, preferably refrigerated at 0–10°C and under inert gas.

First Aid Measures of Tetrazole:

Inhalation:
Move the affected person to fresh air and seek medical attention if symptoms occur.

Skin contact:
Wash thoroughly with plenty of water and remove contaminated clothing.

Eye contact:
Rinse cautiously with water for several minutes and seek medical attention if irritation persists.

Ingestion:
Rinse the mouth and obtain medical advice.

Firefighting Measures of Tetrazole:

Suitable extinguishing media:
Use appropriate extinguishing media while considering the potential explosion risk.

Protective equipment:
Firefighters should wear full protective equipment and self-contained breathing apparatus.

Accidental Release Measures of Tetrazole:

Personal precautions:
Keep away from ignition sources, avoid shock and friction, and ensure adequate ventilation.

Cleanup methods:
Carefully collect spilled material without generating dust or applying mechanical impact and place it in a suitable container.

Exposure Controls/Personal Protective of Tetrazole:

Engineering controls:
Use suitable local exhaust ventilation where dust may be generated.

Eye protection:
Wear safety goggles or suitable eye protection.

Hand protection:
Wear protective chemical-resistant gloves.

Skin protection:
Wear suitable protective clothing.

Respiratory protection:
Use appropriate particulate respiratory protection when ventilation is insufficient.

Identifiers of Tetrazole:
Chemical Name: 1H-Tetrazole
CAS No.: 288-94-8
Molecular Formula: CH₂N₄
Molecular Weight: 70.05 g/mol
Purity: ≥98.0%
EINECS No.: 206-023-4

CAS Number: 288-94-8
3D model (JSmol): Interactive image
ChEBI: CHEBI:33193
ChemSpider: 60842
ECHA InfoCard: 100.005.477
PubChem CID: 67519
UNII: D34J7PAT68
CompTox Dashboard (EPA): DTXSID5075280
InChI: InChI=1S/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)
Key: KJUGUADJHNHALS-UHFFFAOYSA-N
InChI: InChI=1/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)
Key: KJUGUADJHNHALS-UHFFFAOYAI
InChI: InChI=1S/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)
Key: KJUGUADJHNHALS-UHFFFAOYSA-N
SMILES: [nH]1nnnc1

CAS No.: 288-94-8
Chemical Name: Tetrazole
CBNumber: CB4230898
Molecular Formula: CH2N4
Molecular Weight: 70.05
MDL Number: MFCD00005247

Properties of Tetrazole:
Molecular Weight: 70.05 g/mol
XLogP3-AA: -0.5
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 3
Rotatable Bond Count: 0
Exact Mass: 70.027946081 Da
Monoisotopic Mass: 70.027946081 Da
Topological Polar Surface Area: 54.5 Ų
Heavy Atom Count: 5
Complexity: 26.8
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

Chemical Formula: CH2N4
Molar Mass: 70.05 g/mol
Density: 1.477 g/mL
Melting Point: 157 to 158 °C (315 to 316 °F; 430 to 431 K)
Boiling Point: 220 ± 23 °C (428 ± 41 °F; 493 ± 23 K)
Acidity (pKa): 4.90

Melting Point: 156-158°C
Boiling Point: 220℃
Density: 0.798 g/mL at 20 °C
Refractive Index: n20/D 1.348
RTECS: UW7370000
Flash Point: 5 °C
Storage Temperature: Room temperature.
Solubility: DMSO, Methanol
Form: Liquid
pKa: 4.9(at 25℃)
Color: Cream to orange
Water Solubility: Soluble
Decomposition: 220°C
BRN: 105799
Stability: Stable at RT
InChI: 1S/CH2N4/c1-2-4-5-3-1/h1H,(H,2,3,4,5)
InChIKey: KJUGUADJHNHALS-UHFFFAOYSA-N
SMILES: c1nnn[nH]1
CAS DataBase Reference: 288-94-8(CAS DataBase Reference)
FDA UNII: D34J7PAT68
NIST Chemistry Reference: 1H-Tetrazole(288-94-8)
EPA Substance Registry System: 1H-Tetrazole (288-94-8)
UNSPSC Code: 12352100
NACRES: NA.21