Hexamethylenetetramine is a heterocyclic organic compound with the formula (CH
2)
6N
4. This white
crystalA crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
line compound is highly soluble in water and polar organic solvents. It has a cage-like structure similar to
adamantaneAdamantane is a colorless, crystalline chemical compound with a camphor-like odor. With a formula C10H16, it is a cycloalkane and also the simplest diamondoid. Adamantane molecules consist of three cyclohexane rings arranged in the "armchair" configuration. It is unique in that it is both rigid...
. It is useful in the synthesis of other chemical compounds, e.g. plastics, pharmaceuticals, rubber additives. It sublimes in a vacuum at 280 °C.
The compound was discovered by
Aleksandr ButlerovAleksandr Mikhailovich Butlerov was a Russian chemist, one of the principal creators of the theory of chemical structure , the first to incorporate double bonds into structural formulas, the discoverer of hexamine , and the discoverer of the formose reaction.The...
in 1859.
Synthesis, structure, reactivity
Hexamethylenetetramine is prepared by the
reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
of
formaldehydeFormaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
and
ammoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. The reaction can be conducted in gas-phase and in solution.
The molecule has a symmetric
tetrahedralIn geometry, a tetrahedron is a polyhedron composed of four triangular faces, three of which meet at each vertex. A regular tetrahedron is one in which the four triangles are regular, or "equilateral", and is one of the Platonic solids...
cage-like structure, similar to
adamantaneAdamantane is a colorless, crystalline chemical compound with a camphor-like odor. With a formula C10H16, it is a cycloalkane and also the simplest diamondoid. Adamantane molecules consist of three cyclohexane rings arranged in the "armchair" configuration. It is unique in that it is both rigid...
, whose four "corners" are
nitrogenNitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atoms and "edges" are methylene groups. Although the molecular shape defines a cage, no void space is available at the interior for binding other atoms or molecules, unlike
crown etherCrown ethers are cyclic chemical compounds that consist of a ring containing several ether groups. The most common crown ethers are oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., -CH2CH2O-. Important members of this series are the tetramer , the pentamer , and the hexamer...
s or larger
cryptandCryptands are a family of synthetic bi- and polycyclic multidentate ligands for a variety of cations. The Nobel Prize for Chemistry in 1987 was given to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen for their efforts in discovering and determining uses of cryptands and crown ethers,...
structures.
The molecule behaves like an amine base, undergoing protonation and
N-
alkylationAlkylation 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 . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
.
Applications
The main use of hexamethylenetetramine is in the production of powdery or liquid preparations of phenolic resins and phenolic
resinResin in the most specific use of the term is a hydrocarbon secretion of many plants, particularly coniferous trees. Resins are valued for their chemical properties and associated uses, such as the production of varnishes, adhesives, and food glazing agents; as an important source of raw materials...
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.
Historic medical uses
As urotropine, it was widely used in combination with other antibiotics between 1965 and 1990 to combat urinary unfections until proved for its harmful side effects.
Histological stains
Methenamine silver stains are used for staining in
histologyHistology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
, including the following types:
- Grocott's methenamine silver stain, used widely as a screen for fungal organisms.
- 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....
, a methenamine silver-Periodic acid-SchiffPeriodic acid-Schiff is a staining method used to detect glycogen and other polysaccharides in tissues. The reaction of periodic acid oxidizes the diol functional groups in glucose and other sugars, creating aldehydes that react with the Schiff reagent to give a purple-magenta color...
that stains for basement membraneThe basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
, availing to view the "spiked" Glomerular basement membraneThe glomerular basement membrane is the basal laminal portion of the glomerulus. The Glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that...
associated with membranous glomerulonephritisMembranous glomerulonephritis is a slowly progressive disease of the kidney affecting mostly patients between ages of 30 and 50 years, usually Caucasian.It is one of the more common forms of nephrotic syndrome.-Terminology:...
.
Solid fuel
Together with
1,3,5-trioxane1,3,5-Trioxane, sometimes also called trioxin, is a chemical compound with molecular formula C3H6O3. It is a stable cyclic trimer of formaldehyde, and one of the two trioxane isomers; its molecular backbone consists of a six membered ring with three carbon atoms alternating with three oxygen...
, hexamethylenetetramine is a component of
hexamine fuel tabletA hexamine fuel tablet is a form of solid fuel in tablet form. The tablets burn smokelessly, have a high energy density, do not liquify while burning and leave no ashes. Invented in Murrhardt, Germany, in 1936, the main component is hexamine .A number of alternative names are in use, including heat...
s used by campers, hobbyists, the military and relief organizations for heating camping food or military rations. It burns smokelessly, has a high energy density (30.0 MJ/kg), does not liquify while burning, and leaves no ashes.
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.
The explosives
RDXRDX, an initialism for Research Department Explosive, is an explosive nitroamine widely used in military and industrial applications. It was developed as an explosive which was more powerful than TNT, and it saw wide use in WWII. RDX is also known as cyclonite, hexogen , and T4...
,
HMXHMX, also called octogen, is a powerful and relatively insensitive nitroamine high explosive, chemically related to RDX. Like RDX, the name has been variously listed as High Melting eXplosive, Her Majesty's eXplosive, High-velocity Military eXplosive, or High-Molecular-weight rdX.The molecular...
, and
HMTDHexamethylene triperoxide diamine is ahigh explosive organic compound, first synthesised in 1885 by Legler. The theorised structure lent itself well to acting as an initiating, or primary explosive...
can be derived from hexamethylenetetramine.
Food additive
Hexamethylene tetramine or Hexamine is also used as a
food additiveFood additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...
as a preservative (INS number 239). It is approved for usage for this purpose in the EU, where it is listed under
E numberE numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...
E239, however it is not approved in the USA or Australia and New Zealand.
Reagent in organic chemistry
Hexamethylenetetramine is a versatile
reagentA reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
in
organic synthesisOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
. It is used in the
Duff reactionThe 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...
(formylation of arenes), the
Sommelet reactionThe Sommelet reaction is an organic reaction in which a benzyl halide is converted to an aldehyde by action of hexamine and water..The reaction is formally an oxidation of the carbon...
(converting benzyl halides to aldehydes), and in the
Delepine reactionThe Delépine reaction is the organic synthesis of primary amines by reaction of a benzyl or alkyl halides with hexamethylenetetramine followed by acid hydrolysis of the quaternary ammonium salt...
(synthesis of amines from alkyl halides).
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
LeunaLeuna is a town in the Saalekreis, Saxony-Anhalt, eastern Germany, south of Merseburg and Halle. It is known for the Leunawerke , at 13 km2 one of the biggest chemical industrial complexes in Germany, where a very wide range of chemicals and plastics is produced...
, Germany ceased; in 1996, the Italian facility of Agrolinz closed down; in 2001, the UK producer
BordenBorden, Inc., was an American producer of food and beverage products, consumer products, and industrial products. At one time, the company was the largest U.S. producer of dairy and pasta products. Its food division, Borden Foods, was based in Columbus, Ohio, and focused primarily on pasta and...
closed; in 2006, production at Chemko, Slovak Republic, was closed. Remaining producers include INEOS in Germany, Caldic in the Netherlands, and Hexion in Italy. In the US,
Eli Lilly and CompanyEli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
stopped producing methenamine tablets in 2002.