Hexamethylenetetramine

Hexamethylenetetramine
IUPAC name 1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane
Other names Hexamine; Methenamine; Urotropine; 1,3,5,7- tetraazaadamantane, Formin, Aminoform
Identifiers
CAS number	100-97-0 Y
PubChem	4101
ChemSpider	3959 Y
UNII	J50OIX95QV Y
EC number	202-905-8
KEGG	D00393 Y
MeSH	Methenamine
ChEBI	CHEBI:6824 Y
ChEMBL	CHEMBL1201270 N
Jmol-3D images	Image 1
SMILES C1N2CN3CN1CN(C2)C3
InChI InChI=1S/C6H12N4/c1-7-2-9-4-8(1)5-10(3-7)6-9/h1-6H2 Y Key: VKYKSIONXSXAKP-UHFFFAOYSA-N Y InChI=1/C6H12N4/c1-7-2-9-4-8(1)5-10(3-7)6-9/h1-6H2 Key: VKYKSIONXSXAKP-UHFFFAOYAW
Properties
Molecular formula	C6H12N4
Molar mass	140.186 g/mol
Density	1.33 g/cm³ (at 20 °C)
Boiling point	280 °C (sublimes)
Solubility in water	85.3 g/100 mL
Hazards
Main hazards	Highly flammable, harmful
Autoignition temperature	410 °C (770 °F)
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Hexamethylenetetramine is a heterocyclic organic compound with the formula (CH₂)₆N₄. This white crystalline compound is highly soluble in water and polar organic solvents. It has a cage-like structure similar to adamantane. 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 Butlerov in 1859.^[1][2][3]

Synthesis, structure, reactivity

Hexamethylenetetramine is prepared by the reaction of formaldehyde and ammonia.^[4] The reaction can be conducted in gas-phase and in solution.

The molecule has a symmetric tetrahedral cage-like structure, similar to adamantane, whose four "corners" are nitrogen 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 ethers or larger cryptand structures.

The molecule behaves like an amine base, undergoing protonation and N-alkylation.

Applications

The main use of hexamethylenetetramine is in the production of powdery or liquid preparations of phenolic resins and phenolic resin 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.^[4]

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.^{[citation needed]}

Histological stains

Methenamine silver stains are used for staining in histology, including the following types:

• Grocott's methenamine silver stain, used widely as a screen for fungal organisms.
• Jones' stain, a methenamine silver-Periodic acid-Schiff that stains for basement membrane, availing to view the "spiked" Glomerular basement membrane associated with membranous glomerulonephritis.

Solid fuel

Together with 1,3,5-trioxane, 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 (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.^[5]

The explosives RDX, HMX, and HMTD can be derived from hexamethylenetetramine.

Food additive

Hexamethylene tetramine or Hexamine is also used as a food additive as a preservative (INS number 239). It is approved for usage for this purpose in the EU,^[6] where it is listed under E number E239, however it is not approved in the USA or Australia and New Zealand.^[7]

Reagent in organic chemistry

Hexamethylenetetramine is a versatile reagent in organic synthesis. It is used in the Duff reaction (formylation of arenes),^[8] the Sommelet reaction (converting benzyl halides to aldehydes),^[9] and in the Delepine reaction (synthesis of amines from alkyl halides).^[10]

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, 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 in Italy. In the US, Eli Lilly and Company stopped producing methenamine tablets in 2002.^[5]

References

1. ^ A. Butlerow (1859) "Ueber einige Derivate des Jodmethylens" (On some derivatives of methylene iodide), Annalen der Chemie und Pharmacie, vol . 111, pages 242 - 252. In this paper, Butlerov discovered formaldehyde, which he called "Dioxymethylen" (methylene dioxide) [page 247] because his empirical formula for it was incorrect (C₄H₄O₄). On pages 249-250, he reacted formaldehyde with ammonia gas, creating hexamine.
2. ^ See also: A. Butlerow (1860) "Ueber ein neues Methylenderivat" (On a new methylene derivative), Annalen der Chemie und Pharmacie, vol. 115, no. 3, pages 322-327.
3. ^ http://library.istu.edu/hoe/books/ruschem.pdf
4. ^ ^{a b} Karsten Eller, Erhard Henkes, Roland Rossbacher, Hartmut Höke "Amines, Aliphatic" in Ullmann's Encyclopedia of Industrial Chemistry, 2005 Wiley-VCH Verlag, Weinheim. doi:10.1002/14356007.a02_001
5. ^ ^{a b} 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.
6. ^ UK Food Standards Agency: "Current EU approved additives and their E Numbers". http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist. Retrieved 2011-10-27. 
7. ^ Australia New Zealand Food Standards Code"Standard 1.2.4 - Labelling of ingredients". http://www.comlaw.gov.au/Details/F2011C00827. Retrieved 2011-10-27. 
8. ^ A. T. Bottini, Vasu Dev, and Jane Klinck (1963), "Syringic Aldehyde", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV4P0866 ; Coll. Vol. 4: 866 
9. ^ Kenneth B. Wiberg (1963), "2-Thiophenaldehyde", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV3P0811 ; Coll. Vol. 3: 811 
10. ^ A. T. Bottini, Vasu Dev, and Jane Klinck (1963), "2-Bromoallylamine", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV5P0121 ; Coll. Vol. 5: 121