Hexamethylenetetramine, also known as methenamine, hexamine, or urotropin, is a
heterocyclic organic compound with the formula (CH
2)
6N
4. This white
crystal
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macro ...
line compound is highly soluble in water and polar organic solvents. It has a cage-like structure similar to
adamantane
Adamantane is an organic compound with a formula C10H16 or, more descriptively, (CH)4(CH2)6. Adamantane molecules can be described as the fusion of three cyclohexane rings. The molecule is both rigid and virtually stress-free. Adamantane is the ...
. It is useful in the synthesis of other organic compounds, including plastics, pharmaceuticals, and rubber additives. It
sublimes in vacuum at 280 °C.
Synthesis, structure, reactivity
Hexamethylenetetramine was discovered by
Aleksandr Butlerov in 1859.
[ In this article, Butlerov discovered formaldehyde, which he called "dioxymethylen" (methylene dioxide) ]age 247
Age or AGE may refer to:
Time and its effects
* Age, the amount of time someone or something has been alive or has existed
** East Asian age reckoning, an Asian system of marking age starting at 1
* Ageing or aging, the process of becoming older ...
because his empirical formula for it was incorrect (C4H4O4). On pages 249–250, he describes treating formaldehyde with ammonia gas, creating hexamine.
It is prepared industrially by combining
formaldehyde
Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
and
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
:
:
The reaction can be conducted in gas phase and in solution.
The molecule has a
tetrahedral
In geometry, a tetrahedron (plural: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular faces, six straight edges, and four vertex corners. The tetrahedron is the simplest of all the ...
cage-like structure, similar to
adamantane
Adamantane is an organic compound with a formula C10H16 or, more descriptively, (CH)4(CH2)6. Adamantane molecules can be described as the fusion of three cyclohexane rings. The molecule is both rigid and virtually stress-free. Adamantane is the ...
. Four vertices are occupied by
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, which are linked by
methylene group
In organic chemistry, a methylene group is any part of a molecule that consists of two hydrogen atoms bound to a carbon atom, which is connected to the remainder of the molecule by two single bonds. The group may be represented as , where th ...
s. Although the molecular shape defines a cage, no void space is available at the interior for binding other atoms or molecules, unlike
crown ethers or larger
cryptand structures.
The molecule behaves like an amine base, undergoing protonation and ''N''-
alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
(e.g.
quaternium-15
Quaternium-15 (systematic name: hexamethylenetetramine chloroallyl chloride) is a quaternary ammonium salt that has been used as a surfactant and preservative. It acts as an antimicrobial agent because it slowly releases formaldehyde, which is ...
).
Applications
The dominant use of hexamethylenetetramine is in the production of powdery or liquid preparations of
phenolic resin
Phenol formaldehyde resins (PF) or phenolic resins (also infrequently called phenoplasts) are synthetic polymers obtained by the reaction of phenol or substituted phenol with formaldehyde. Used as the basis for Bakelite, PFs were the first commerc ...
s and phenolic
resin
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on nat ...
moulding compounds, where it is added as a hardening component. These products are used as binders, e.g. in brake and clutch linings, abrasive products, non-woven textiles, formed parts produced by moulding processes, and fireproof materials.
Medical uses
As the mandelic acid
Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. T ...
salt (methenamine mandelate) or the hippuric acid
Hippuric acid ( Gr. ''hippos'', horse, ''ouron'', urine) is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenolic ...
salt (methenamine hippurate), it is used for the treatment of urinary tract infection. In an acidic environment, methenamine is believed to act as an antimicrobial
An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...
by converting to formaldehyde
Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
. A systematic review
A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
of its use for this purpose in adult women found there was insufficient evidence of benefit and further research is needed.
Methenamine acts as an over-the-counter antiperspirant
A deodorant is a substance applied to the body to prevent or mask body odor due to bacterial breakdown of perspiration or vaginal secretions, for example in the armpits, groin, or feet. A subclass of deodorants, called antiperspirants, preven ...
due to the astringent
An astringent (sometimes called adstringent) is a chemical that shrinks or constricts body tissues. The word derives from the Latin ''adstringere'', which means "to bind fast". Calamine lotion, witch hazel, and yerba mansa, a Californian pla ...
property of formaldehyde.
Histological stains
Methenamine silver stains are used for staining
Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in th ...
in histology
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures v ...
, including the following types:
*Grocott's methenamine silver stain
In pathology, the Grocott-Gomori's (or Gömöri) methenamine silver stain, abbreviated GMS, is a popular staining method in histology. The stain was originally named after György Gömöri, the Hungarian physician who developed the stain.
It is ...
, used widely as a screen for fungal organism
In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells ( cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fu ...
s.
*Jones' stain
Jones' stain, also Jones stain, is a methenamine silver-Periodic acid-Schiff stain used in pathology. It is also referred to as methenamine PAS which is commonly abbreviated MPAS.
It stains for basement membrane and is widely used in the invest ...
, a methenamine silver- Periodic acid-Schiff that stains for basement membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium an ...
, availing to view the "spiked" Glomerular basement membrane
The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular basement membrane, and the filtration slits between the podocytes perform the filtration function of ...
associated with membranous glomerulonephritis.
Solid fuel
Together with 1,3,5-trioxane
1,3,5-Trioxane, sometimes also called trioxane or trioxin, is a chemical compound with molecular formula CHO. It is a white, highly water-soluble solid with a chloroform-like odor. It is a stable cyclic trimer of formaldehyde, and one of the t ...
, hexamethylenetetramine is a component of hexamine fuel tablets used by campers, hobbyists, the military and relief organizations for heating camping food or military rations. It burns smokelessly, has a high energy density
In physics, energy density is the amount of energy stored in a given system or region of space per unit volume. It is sometimes confused with energy per unit mass which is properly called specific energy or .
Often only the ''useful'' or extrac ...
of 30.0 megajoules per kilogram
The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
(MJ/kg), does not liquify while burning, and leaves no ashes, although its fumes are toxic.
Standardized 0.149 g tablets of methenamine (hexamine) are used by fire-protection laboratories as a clean and reproducible fire source to test the flammability of carpets and rugs.
Food additive
Hexamethylene tetramine or hexamine is also used as a food additive
Food additives are substances added to food to preserve Taste, flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), sal ...
as a preservative ( INS number 239). It is approved for usage for this purpose in the EU, where it is listed under E number
E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
E239, however it is not approved in the USA, Russia, Australia, or New Zealand.
Reagent in organic chemistry
Hexamethylenetetramine is a versatile reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
in organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
. It is used in the Duff reaction The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. It is named after James Cooper Duff, who was a chemist at the Coll ...
(formylation of arenes), the Sommelet reaction (converting benzyl halides to aldehydes), and in the Delepine reaction (synthesis of amines from alkyl halides).
Explosives
Hexamethylenetetramine is the base component to produce RDX and, consequently, C-4[ as well as Octogen, hexamine dinitrate, hexamine diperchlorate and ]HMTD
Hexamethylene triperoxide diamine (HMTD) is a high explosive organic compound. HMTD is an organic peroxide, a heterocyclic compound with a cage-like structure. It is a primary explosive. It has been considered as an initiating explosive for bl ...
.
Historical uses
Hexamethylenetetramine was first introduced into the medical setting in 1895 as a urinary antiseptic
An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
. However, it was only used in cases of acidic urine, whereas boric acid was used to treat urinary tract infections with alkaline
In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a basic, ionic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a ...
urine. Scientist De Eds found that there was a direct correlation between the acidity of hexamethylenetetramine's environment and the rate of its decomposition. Therefore, its effectiveness as a drug depended greatly on the acidity of the urine rather than the amount of the drug administered. In an alkaline environment, hexamethylenetetramine was found to be almost completely inactive.
Hexamethylenetetramine was also used as a method of treatment for soldiers exposed to phosgene
Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, esp ...
in World War I
World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
. Subsequent studies have shown that large doses of hexamethylenetetramine provide some protection if taken before phosgene exposure but none if taken afterwards.
Producers
Since 1990 the number of European producers has been declining. The French SNPE factory closed in 1990; in 1993, the production of hexamethylenetetramine in Leuna
Leuna is a town in Saxony-Anhalt, eastern Germany, south of Merseburg and Halle, on the river Saale.
The town is known for the '' Leunawerke'', at 13 km2 one of the biggest chemical industrial complexes in Germany, where a very wide ra ...
, Germany ceased; in 1996, the Italian facility of Agrolinz closed down; in 2001, the UK producer Borden closed; in 2006, production at Chemko, Slovak Republic, was closed. Remaining producers include INEOS in Germany, Caldic in the Netherlands, and Hexion
Hexion Inc. or Hexion (previously Momentive Specialty Chemicals) is a chemical company based in Columbus, Ohio. It produces thermoset resins and related technologies and specialty products.
Hexion is organized into two divisions: the Epoxy, Phen ...
in Italy. In the US, Eli Lilly and Company
Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
stopped producing methenamine tablets in 2002.[Alan H. Schoen (2004)]
''Re: Equialence of methenamine Tablets Standard for Flammability of Carpets and Rugs''
. U.S. Consumer product Safety Commission, Washington, DC, July 29, 2004. Many other countries who still produce this include Russia, Saudi Arabia, China and Australia. In Australia, Hexamine Tablets for fuel are made by Thales Australia Ltd. In México, Hexamine is produced by Abiya.
References
{{Authority control
Nitrogen heterocycles
Preservatives
Antibiotics
Fuels
Reagents for organic chemistry
Corrosion inhibitors
Heterocyclic compounds with 3 rings
Adamantane-like molecules
E-number additives