Tetrazoles are a class of

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic ...

organic

heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, an ...

, consisting of a 5-member ring of four

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

atoms and one

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...

atom. The name tetrazole also refers to the parent compound with formula CH₂N₄, of which three isomers can be formulated.

Structure and bonding

Three isomers of the parent tetrazole exist, differing in the position of the double bonds: 1''H''-, 2''H''-, and 5''H''-tetrazole. The 1''H''- and 2''H''- isomers are

tautomer Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hy ...

s, with the equilibrium lying on the side of 1''H''-tetrazole in the solid phase. In the gas phase, 2''H''-tetrazole dominates. These isomers can be regarded as

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

, with 6 π-electrons, while the 5''H''-isomer is nonaromatic. Tetrazole_Tautomerism_V

Synthesis

1''H''-Tetrazole was first prepared by the reaction of anhydrous

hydrazoic acid Hydrazoic acid, also known as hydrogen azide or azoimide, This also contains a detailed description of the contemporaneous production process. is a compound with the chemical formula . It is a colorless, volatile, and explosive liquid at room tem ...

and

hydrogen cyanide Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on a ...

under pressure. Treatment of organic nitriles with sodium azide in the presence of

iodine Iodine is a chemical element with the Symbol (chemistry), symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , ...

or silica-supported

sodium bisulfate Sodium bisulfate, also known as sodium hydrogen sulfate, is the sodium salt of the bisulfate anion, with the molecular formula NaHSO4. Sodium bisulfate is an acid salt formed by partial neutralization of sulfuric acid by an equivalent of sodium ...

as a heterogeneous

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

enables an advantageous synthesis of 5-substituted 1''H''-tetrazoles. Another method is the deamination of 5-aminotetrazole, which can be commercially obtained or prepared in turn from

aminoguanidine Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug. Pimagedine functions as an inhibitor of diamine oxidase and nitric oxide synthase. It a ...

. :

2-Aryl-''2H''-tetrazoles are synthesized by a +2

cycloaddition In organic chemistry, a cycloaddition is a chemical reaction in which "two or more unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity" ...

reaction between an aryl diazonium and trimethylsilyldiazomethane.

Uses

There are several pharmaceutical agents which are tetrazoles. Tetrazoles can act as bioisosteres for

carboxylate group In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...

s 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 The MTT assay is a colorimetric assay for assessing cell metabolic activity. NAD(P)H-dependent cellular oxidoreductase enzymes may, under defined conditions, reflect the number of viable cells present. These enzymes are capable of reducing the t ...

to quantify the respiratory activity of live cells

culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups ...

, 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 with high energy have been investigated as high performance

explosives An explosive (or explosive material) is a reactive substance that contains a great amount of potential energy that can produce an explosion if released suddenly, usually accompanied by the production of light, heat, sound, and pressure. An expl ...

as a replacement for TNT and also for use in high performance solid rocket propellant formulations. These include the

azidotetrazolate Azidotetrazolate (CN7−) is an anion which forms a highly explosive series of salts. The ion is made by removing a proton from 5-azido-1H-tetrazole. The molecular structure contains a five-membered ring with four nitrogen atoms, and an azido side ...

salts of nitrogen bases. 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 generator A gas generator is a device for generating gas. A gas generator may create gas by a chemical reaction or from a solid or liquid source, when storing a pressurized gas is undesirable or impractical. The term often refers to a device that uses a ...

s in

automobile A car or automobile is a motor vehicle with wheels. Most definitions of ''cars'' say that they run primarily on roads, seat one to eight people, have four wheels, and mainly transport people instead of goods. The year 1886 is regarded ...

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, all of which are desirable properties. The delocalization energy in tetrazole is 209 kJ/mol. 1''H''-Tetrazole and 5-(benzylthio)-1''H''-tetrazole (BTT) are widely used as acidic activators of the coupling reaction in

oligonucleotide synthesis Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure ( sequence). The technique is extremely useful in current laboratory practice because it provides a rapid and inexpe ...

Related heterocycles

Triazole A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within ...

s, analogs with three nitrogen atoms *

Pentazole Pentazole is an aromatic molecule consisting of a five-membered ring with all nitrogen atoms, one of which is bonded to a hydrogen atom. It has the molecular formula . Although strictly speaking a homocyclic, inorganic compound, pentazole ha ...

, the analog with five nitrogen atoms (strictly speaking, an inorganic homocycle, not a heterocycle) * Oxatetrazole * Thiatetrazole

References

{{reflist Simple aromatic rings Nitrogen heterocycles Azoles