Tetrazoles are a class of 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, and ...

, 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 In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...

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 hydr ...

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 an ...

under pressure. Treatment of organic

nitriles In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

with sodium azide in the presence of

iodine Iodine is a chemical element with the 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 , and boils to a vi ...

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 act ...

. :

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 hydrocarbon, unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of th ...

reaction between an aryl

diazonium Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide. General properti ...

and

trimethylsilyldiazomethane Trimethylsilyldiazomethane is the organosilicon compound with the formula (CH3)3SiCHN2. It is classified as a diazo compound. Trimethylsilyldiazomethane is a commercially available reagent used in organic chemistry as a methylating agent and as ...

Uses

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

bioisostere In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound. In drug design, the purpose of exchanging one bi ...

s for carboxylate groups because they have similar pKa and are deprotonated at physiological pH.

Angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrena ...

II receptor blockers — such as

losartan Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin II receptor antagonist, angiotensin receptor blocker (ARB) family of medication, and is consider ...

and

candesartan Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. The metabolism for the drug is unique as it is a cascading prodrug. Can ...

, 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.Tyl ...

, 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 The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics * Brzozowski derivative in the theory of formal languages * Formal derivative, an ...

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 Trinitrotoluene (), more commonly known as TNT, more specifically 2,4,6-trinitrotoluene, and by its preferred IUPAC name 2-methyl-1,3,5-trinitrobenzene, is a chemical compound with the formula C6H2(NO2)3CH3. TNT is occasionally used as a reagen ...

and also for use in high performance

solid rocket propellant Rocket propellant is the reaction mass of a rocket. This reaction mass is ejected at the highest achievable velocity from a rocket engine to produce thrust. The energy required can either come from the propellants themselves, as with a chemical ...

formulations. These include the azidotetrazolate 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 Wheel, wheels. Most definitions of ''cars'' say that they run primarily on roads, Car seat, seat one to eight people, have four wheels, and mainly transport private transport#Personal transport, pe ...

airbags An airbag is a vehicle occupant-restraint system using a bag designed to inflate extremely quickly, then quickly deflate during a collision. It consists of the airbag cushion, a flexible fabric bag, an inflation module, and an impact sensor. T ...

. 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 inexpens ...

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 t ...

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 has ...

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

Oxatetrazole 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 ...

Thiatetrazole 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, and ...

References

{{reflist Simple aromatic rings Nitrogen heterocycles Azoles