The dominant use of hexamethylenetetramine is in the production of solid (powder) or liquidphenolic resins and phenolicresin moulding compounds, in which it is added as a hardening component. These products are used as binders, e.g., in brake and clutch linings, abrasives, non-woven textiles, formed parts produced by moulding processes, and fireproof materials.[4]
As themandelic acid salt (methenamine mandelate) or thehippuric acid salt (methenamine hippurate),[13] it is used for the treatment ofurinary tract infections. In an acidic environment, methenamine is believed to act as anantimicrobial by converting toformaldehyde.[13][14] Asystematic review of its use for this purpose in adult women found there was insufficient evidence of benefit and further research was needed.[15] A UK study showed that methenamine is as effective as daily low-dose antibiotics at preventing UTIs among women who experience recurrent UTIs. As methenamine is an antiseptic, it may avoid the issue of antibiotic resistance.[16][17]
Together with1,3,5-trioxane, hexamethylenetetramine is a component ofhexamine fuel tablets used by campers, hobbyists, the military and relief organizations for heating camping food or military rations. It burns smokelessly, has a highenergy density of 30.0megajoules perkilogram (MJ/kg), does not liquify while burning, and leaves no ashes, although its fumes are toxic.[citation needed]
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.[19]
Hexamethylenetetramine or hexamine is also used as afood additive as a preservative (INS number 239). It is approved for usage for this purpose in the EU,[20] where it is listed underE number E239, however it is not approved in the USA, Russia, Australia, or New Zealand.[21]
Hexamethylenetetramine is the base component to produceRDX and, consequently,C-4[4] as well asoctogen (a co-product with RDX), hexamine dinitrate, hexamine diperchlorate,HMTD, andR-salt.
From October 2023, sale of hexamethylenetetramine in the UK is restricted to licensed persons (as a "regulated precursor" under the terms of thePoisons Act 1972).[26]
Hexamethylenetetramine is also used inpyrotechnics to reduce combustion temperatures and decrease the color intensity of various fireworks.[27] Because of its ash-free combustion, hexamethylenetetramine is also utilized in indoor fireworks alongsidemagnesium andlithium salts.[28][29]
Hexamethylenetetramine was first introduced into the medical setting in 1895 as a urinaryantiseptic.[30] It was officially approved by theFDA for medical use in the United States in 1967.[31] However, it was only used in cases of acidic urine, whereas boric acid was used to treat urinary tract infections withalkaline urine.[32] Scientist De Eds found that there was a direct correlation between the acidity of hexamethylenetetramine's environment and the rate of its decomposition.[33] Therefore, its effectiveness as a drug depended greatly on the acidity of the urine rather than the amount of the drug administered.[32] In an alkaline environment, hexamethylenetetramine was found to be almost completely inactive.[32]
Hexamethylenetetramine was also used as a method of treatment for soldiers exposed tophosgene inWorld War I. Subsequent studies have shown that large doses of hexamethylenetetramine provide some protection if taken before phosgene exposure but none if taken afterwards.[34]
Since 1990 the number of European producers has been declining. The French SNPE factory closed in 1990; in 1993, the production of hexamethylenetetramine inLeuna, Germany ceased; in 1996, the Italian facility of Agrolinz closed down; in 2001, the UK producerBorden closed; in 2006, production at Chemko, Slovak Republic, was closed. Remaining producers include INEOS in Germany, Caldic in the Netherlands, andHexion in Italy. In the US,Eli Lilly and Company stopped producing methenamine tablets in 2002.[19] In Australia, Hexamine Tablets for fuel are made by Thales Australia Ltd. In México, Hexamine is produced by Abiya.[citation needed] Many other countries who still produce this include Russia, Saudi Arabia, and China.
^abDreyfors JM, Jones SB, Sayed Y (November 1989). "Hexamethylenetetramine: a review".American Industrial Hygiene Association Journal.50 (11):579–585.doi:10.1080/15298668991375191.PMID2688388.
^abcBlažzević, Nikola; Kolbah, D.; Belin, Branka; Šunjić, Vitomir; Kajfež, Franjo (1979). "Hexamethylenetetramine, A Versatile Reagent in Organic Synthesis".Synthesis.1979 (3). Georg Thieme Verlag KG:161–176.doi:10.1055/s-1979-28602.ISSN0039-7881.
^abcLo TS, Hammer KD, Zegarra M, Cho WC (May 2014). "Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era".Expert Rev Anti Infect Ther.12 (5):549–554.doi:10.1586/14787210.2014.904202.PMID24689705.
^Connolly M, de Berker D (2003). "Management of primary hyperhidrosis: a summary of the different treatment modalities".Am J Clin Dermatol.4 (10):681–697.doi:10.2165/00128071-200304100-00003.PMID14507230.
^Butlerow A (1859)."Ueber einige Derivate des Jodmethylens" [On some derivatives of methylene iodide].Ann. Chem. Pharm. (in German).111 (2):242–252.doi:10.1002/jlac.18591110219. In this article, 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 describes treating formaldehyde with ammonia gas, creating hexamine.
^Kirillov, Alexander M. (2011). "Hexamethylenetetramine: An old new building block for design of coordination polymers".Coordination Chemistry Reviews.255 (15–16). Elsevier BV:1603–1622.doi:10.1016/j.ccr.2011.01.023.ISSN0010-8545.
^abLo TS, Hammer KD, Zegarra M, Cho WC (May 2014). "Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era".Expert Review of Anti-Infective Therapy.12 (5):549–554.doi:10.1586/14787210.2014.904202.PMID24689705.S2CID207199202.
^Blažzević N, Kolbah D, Belin B, Šunjić V, Kajfež F (1979). "Hexamethylenetetramine, A Versatile Reagent in Organic Synthesis".Synthesis.1979 (3):161–176.doi:10.1055/s-1979-28602.S2CID97756228.
^DE patent 3402546, Lohmann, Erwin, "Pyrotechnischer Satz zur Erzeugung von Lichtblitzen", issued 1985-08-01
^US patent 6214139, Hiskey, Michael A.; Chavez, David E. & Naud, Darren L., "Low-smoke pyrotechnic compositions", issued 2001-04-10, assigned to The Regents of the University of California and Los Alamos National Laboratory
^GB patent 2502460, Wraige, John Douglas Michael, "Pyrotechnic composition with spark producing material", issued 2013-11-27
^Hinman F (1913). "An Experimental Study of the Antiseptic Value in the Urine of the Internal Use of Hexamethylenamin".JAMA: The Journal of the American Medical Association.61 (18): 1601.doi:10.1001/jama.1913.04350190019006.
^abcElliot (1913). "On Urinary Antiseptics".British Medical Journal.98:685–686.
^Heathcote RS (1935). "Hexamine as an Urinary Antiseptic: I. Its Rate of Hydrolysis at Different Hydrogen Ion Concentrations. II. Its Antiseptic Power Against Various Bacteria in Urine".British Journal of Urology.7 (1):9–32.doi:10.1111/j.1464-410X.1935.tb11265.x.ISSN0007-1331.
