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Hexamethylene tetramine is a hardener in epoxy resins of the bisphenol A type and can also be used as an anticorrosive agent.
Hexamethylene tetramine is a sensitizing agent in ceramics workers.
A polycyclic cage that is adamantane in which the carbon atoms at positions 1, 3, 5 and 7 are replaced by nitrogen atoms.
CAS: 100-97-0
MF: C6H12N4
MW: 140.19
EINECS: 202-905-8
Hexamethylene tetramine, also known as methenamine, hexamine, or urotropin, is a heterocyclic organic compound with the formula (CH2)6N4.
This white crystalline compound is highly soluble in water and polar organic solvents.
Hexamethylene tetramine has a cage-like structure similar to adamantane.
Hexamethylene tetramine is useful in the synthesis of other organic compounds, including plastics, pharmaceuticals, and rubber additives.
Hexamethylene tetramine sublimes in vacuum at 280 °C.
A white crystalline organic compound made by condensing methanal with ammonia.
Hexamethylene tetramine is used as a fuel for camping stoves, in vulcanizing rubber, and as a urinary disinfectant.
Hexamethylene tetramine can be nitrated to make the high explosive cyclonite.
Hexamethylene tetramine is a water soluble, heterocyclic organic compound with a cage-like structure resembling adamantane.
Hexamethylene tetramine is commonly used in treating urinary tract infection.
C6H12N4 – Hexamethylene tetramine – is an odorless, white, crystalline compound also known as “solid fuel.”
As Hexamethylene tetramine burns easily, it is popular among campers, hobbyists, and the military for heating camping food or military rations.
Also known as urotropin, Hexamethylene tetramine is used in various fields, ranging from the production of phenol-formaldehyde resins to pyrotechnics.
Hexamethylene tetramine is also used in medicine as an antiseptic.
Hexamethylene tetramine Chemical Properties
Melting point: 280 °C (subl.) (lit.)
Boiling point: 246.7°C (rough estimate)
Density: 1.33
Vapor density: 4.9 (vs air)
Vapor pressure: <0.01 mm Hg ( 20 °C)
Refractive index: 1.4260 (estimate)
Fp: 482 °F
Storage temp.: Store below +30°C.
Solubility: H2O: 1 M at 20 °C, clear, colorless
Form: Solid
pka: 5.1(at 25℃)
Color: white
Odor: Odorless
PH: 7-10 (100g/l, H2O, 20℃)
Water Solubility: 895 g/L (20 ºC)
Sensitive: Hygroscopic
Merck: 14,5966
Sublimation: 263-295 ºC
BRN: 2018
Stability: Stable. Incompatible with strong acids, strong oxidizing agents.
LogP: -2.18--2 at 20℃
CAS DataBase Reference: 100-97-0(CAS DataBase Reference)
NIST Chemistry Reference: Hexamethylene tetramine(100-97-0)
EPA Substance Registry System: Hexamethylene tetramine (100-97-0)
Hexamethylene tetraminee has an adamantane structure with high degree of symmetry and the characteristics of tertiary amines.
Each of the four nitrogen atoms has a pair of unshared electron with being able to form coordination compound with many kinds of inorganic compounds.
Hexamethylene tetramine can have heating reaction with strong inorganic acid to generate formaldehyde and ammonium salts.
In the presence of zinc powder, Hexamethylene tetramine can have reaction with hydrochloric acid to generate the hydrochloride salt of trimethylamine and ammonium chloride.
Hexamethylene tetramine can also be subject to nitrification and generate RDX.
Hexamethylene tetramine can also have reaction with nitrous acid to form N'N'-Dinitroso pentamethylene tetramine.
Hexamethylene tetramine can have reaction with hydrogen peroxide and hydrogen cyanide.
Hexamethylene tetramine can also have reaction with sulfur and sulfur compounds or react with the alkali metal salts, alkaline earth metal, and rare earth metal salts to form a complex.
In acidic medium, Hexamethylene tetramine can react with alcohol.
Hexamethylene tetramine can also react with organic acid to form salt.
Hexamethylene tetramine can also react with halides, phenols and amides as well as some natural products such as protein and fiber.
Hexamethylene tetramine is irritating to the skin and can cause dermatitis.
Intravenous-Rats LD50: 1200 mg/kg; Intraperitoneal injection-mice LD50: 512mg/kg.
Hexamethylene tetramine is white hygroscopic crystalline powder or shiny colorless rhombic crystals.
Hexamethylene tetramine is almost odorless with sweet and bitter taste.
Hexamethylene tetramine is soluble in water and chloroform but less soluble in carbon tetrachloride, acetone, benzene and ether and insoluble in petroleum ether.
Synthesis, structure, reactivity
Hexamethylene tetramine was discovered by Aleksandr Butlerov in 1859.
Hexamethylene tetramine is prepared industrially by combining formaldehyde and ammonia:
The reaction can be conducted in gas phase and in solution.
The molecule has a tetrahedral cage-like structure, similar to adamantane.
Four vertices are occupied by nitrogen atoms, which are linked by 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 (e.g. quaternium-15).
Applications
The dominant use of Hexamethylene tetramine is in the production of powdery or liquid preparations of phenolic resins and phenolic resin moulding compounds, where Hexamethylene tetramine 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.
Uses
Hexamethylene tetramine can be used as the curing agent for resins and plastics, the vulcanization accelerator of rubber (accelerator H) and textiles shrink-proof agent.
Hexamethylene tetramine can also be used for making antibacterial drug, explosives and so on.
As medicine, after oral administration, Hexamethylene tetramine can be decomposed when coming across acidic urine to generate formaldehyde and exerts its antibacterial effect used for treating mild urinary tract infection; Hexamethylene tetramine can be externally used for treating ringworm, antiperspirants, and treatment of underarm odor.
Hexamethylene tetramine's being mixed with caustic soda and sodium phenol can be used as the phosgene absorber of gas masks.
Hexamethylene tetramine can be used as a kind of anti-microbial agents.
Hexamethylene tetramine can be used as anti-shrinking textile finishing agent, bleaching agents of sodium chlorite and the buffer of waterproofing agents CR.
Hexamethylene tetramine is mainly used as the curing agent of plastic and resin, the catalyst and foaming agent of aminoplast, rubber vulcanization accelerator (accelerator H), and the shrink-proof agents of textiles.
Hexamethylene tetramine is the raw material for organic synthesis and can be used for the production of chloramphenicol in the pharmaceutical industry.
Hexamethylene tetramine can be used as the disinfectant of urinary system with itself having no antibacterial effect and being effective in treating gram-negative bacteria.
Hexamethylene tetramine's 20% solution can be used for the treatment of underarm odor, sweaty feet, tinea and so on.
Hexamethylene tetramine's being mixed with caustic soda and sodium phenol can be used as the phosgene absorber of gas masks.
Hexamethylene tetramine can also be used for the manufacture of pesticides.
Hexamethylene tetramine can react with fuming nitric acid to obtain highly explosive cyclonite, briefly referred as RDX.
Hexamethylene tetramine can be used as the reagent and chromatography reagents for determination of bismuth, indium, manganese, cobalt, thorium, platinum, producing magnesium, lithium, copper, uranium, beryllium, tellurium, bromide, and iodide.
In the liver function tests, Hexamethylene tetramine can be used for formulating thymol turbidity, test and measurement of object such as bismuth, iron, manganese, cobalt, thorium, platinum and magnesium as well as the determination and identification of lithium, iron cyanide, iron bromide and iodide.
Hexamethylene tetramine can also be used for the determination of copper, uranium, beryllium, tellurium etc.
Moreover, Hexamethylene tetramine can be used as gas chromatography fixed solution (maximum usage temperature of 180 ℃ with the solvent being chloroform).
Hexamethylene tetramine used in the treatment of urinary track infection.
Hexamethylene tetramine is a versatile reagent in organic synthesis.
Hexamethylene tetramine is used in the Duff reaction, the Sommelet reaction, and in the Delepine reaction.
Hexamethylene tetramine is used as a formylation agent in the synthesis and as a precipitating agent.
Hexamethylene tetramine is also used in the production of phenolic resins and its moulding compounds, which finds application as binders in fire proof materials, brake and clutch linings.
Hexamethylene tetramine is involved in the preparation of 5-tert-butyl-2-hydroxy-isophthalaldehyde.
Hexamethylene tetramine is useful for the treatment of urinary tract infection.
Further, Hexamethylene tetramine is used in the Duff reaction, Sommelet reaction and in the Delepine reaction.
Medical uses
As the mandelic acid salt (methenamine mandelate) or the hippuric acid salt (methenamine hippurate), Hexamethylene tetramine is used for the treatment of urinary tract infection.
In an acidic environment, Hexamethylene tetramine is believed to act as an antimicrobial by converting to formaldehyde.
A systematic review of Hexamethylene tetramine's use for this purpose in adult women found there was insufficient evidence of benefit and further research is needed.
A UK study showed that Hexamethylene tetramine is as effective as daily low-dose antibiotics at preventing UTIs among women who experience recurrent UTIs.
As methenamine is an antiseptic, Hexamethylene tetramine may avoid the issue of antibiotic resistance.
Hexamethylene tetramine acts as an over-the-counter antiperspirant due to the astringent property of formaldehyde.
A venerable drug used for the disinfection of acidic urine, Hexamethylene tetramine is a low-molecular-weight polymer of ammonia and formaldehyde that reverts to its components under mildly acidic conditions.
Formaldehyde is the active antimicrobial component.
Hexamethylene tetramine is used for recurrent urinary tract infections.
The drug is available in various dosage forms as well as various salts, including the hippurate and mandelate.
Solid fuel
Together with 1,3,5-trioxane, hexamethylene tetramine is a component of hexamine fuel tablets used by campers, hobbyists, the military and relief organizations for heating camping food or military rations.
Hexamethylene tetramine burns smokelessly, has a high energy density of 30.0 megajoules per kilogram (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 as a preservative (INS number 239).
Hexamethylene tetramine is approved for usage for this purpose in the EU, where it is listed under E number E239, however Hexamethylene tetramine is not approved in the USA, Russia, Australia, or New Zealand.
Historical uses
Hexamethylene tetramine was first introduced into the medical setting in 1895 as a urinary antiseptic.
However, Hexamethylene tetramine was only used in cases of acidic urine, whereas boric acid was used to treat urinary tract infections with alkaline urine.
Scientist De Eds found that there was a direct correlation between the acidity of hexamethylene tetramine's environment and the rate of its decomposition.
Therefore, Hexamethylene tetramine's effectiveness as a drug depended greatly on the acidity of the urine rather than the amount of the drug administered.
In an alkaline environment, hexamethylene tetramine was found to be almost completely inactive.
Hexamethylene tetramine was also used as a method of treatment for soldiers exposed to phosgene in World War I. Subsequent studies have shown that large doses of hexamethylene tetramine provide some protection if taken before phosgene exposure but none if taken afterwards.
Pharmaceutical Applications
Methenamine (hexamine, hexamethylene tetraamine), under the name Urotropin, was successfully used in cystitis by the German physician Nicolaier in 1895.
Hexamethylene tetramine has no intrinsic antibacterial activity and owes its effect to decomposition in acid conditions to formaldehyde, which is non-specifically microbicidal, and ammonia.
Hexamethylene tetramine is often used in the form of organic acid salts, methenamine hippurate and methenamine mandelate, which have been claimed (unconvincingly) to keep the urinary pH low.
Mandelic acid has some antibacterial activity in its own right and is sometimes given alone as a urinary antiseptic, usually as the calcium or ammonium salt.
Infection with urea-splitting organisms such as Proteus spp. causes the urine to become alkaline and Hexamethylene tetramine is unsuitable for these infections.
Hexamethylene tetramine is absorbed from the gut and mainly excreted unchanged in the urine, achieving concentrations of around 2–60 mg/L, sufficient to inhibit most bacteria and yeasts. Higher concentrations are achieved by the hippurate salt.
Hexamethylene tetramine is given in enteric-coated tablets to prevent the liberation of formaldehyde by gastric acid.
There is little breakdown in the blood and no systemic effect or toxicity.
Some patients complain of gastrointestinal upset or frequent and burning micturition.
Attempts to control these side effects with alkali will abolish the antibacterial effect of the drug.
Contact dermatitis and anterior uveitis have occasionally been encountered.
Prolonged administration or high dosage may produce proteinuria, hematuria and bladder changes. Methenamine should not be given to patients with acidosis, gout or hepatic insufficiency.
There have been fears about the potential carcinogenicity of formaldehyde.
Methenamine and Hexamethylene tetramine's salts are unsuitable for the treatment of acute urinary tract infection.
Their main use, now largely supplanted by other agents, has been in the long-term prophylaxis of recurrent cystitis.
Pharmacological effects
Hexamethylene tetramine is a therapeutic drug for treating the bacterial urinary tract infections.
Hexamethylene tetramine itself has no antibacterial effect.
After oral absorption, Hexamethylene tetramine can be secreted out by renal with being broken down into ammonia and formaldehyde in acidic urine with the later one being able to effectively inhibit the G-bacteria, especially having a strong antibacterial effect on Escherichia coli, Enterobacter aerogenes and Pseudomonas aeruginosa.
Hexamethylene tetramine can be used for treating urinary tract infections caused by susceptible strains.
When Hexamethylene tetramine is subject to oral administration, the patients should also take vitamin C or ammonium chloride at the same time in order to acidify the urine (pH≤5.5).
Production method
Hexamethylene tetramine can be made from the condensation reaction of formaldehyde and ammonia.
Place the formaldehyde solution in a reactor, put through the ammonia with condensation reaction being carried out in alkaline solution and the reaction temperature being maintained at 50-70 ℃; the material liquid was cooled and fed into the film vacuum evaporator and subject to evaporation at 60-80 ℃ to make its concentration be increased from 24% to 38%-42%.
Then the reaction mixture was filtered and subjected to vacuum evaporation and crystallization, filtration drying to derive the hexamethylene tetramine product.
Put the formaldehyde (37% aqueous solution) and excess amount of ammonia for 3 h at 38 ℃.
After completion of reaction, the reaction mixture was further subject to clarification, filtration, membrane evaporation (pressure 9.806~9.866 kPa) for twice with concentrated liquid subjecting cooling and crystallization, filtration, and drying at 150 ℃ to obtain the products.
Hexamethylene tetramine is obtained through the reaction between formaldehyde and the calculated amount of ammonia.
Reactivity Profile
Hexamethylene tetramine is hygroscopic.
Hexamethylene tetramine is sensitive to exposure to heat.
Hexamethylene tetramine is incompatible with oxidizing agents.
Hexamethylene tetramine is also incompatible with acids.
Hexamethylene tetramine reacts violently with sodium peroxide.
Hexamethylene tetramine reacts explosively with 1-bromopentaborane(9) at temperatures above 194° F.
The complex with iodine deflagrates at 280° F.
The 1:1 addition complex with iodoform has exploded at 352° F.
Hexamethylene tetramine is corrosive to some metals, such as aluminum and zinc.
Special Hazards of Combustion Products: Formaldehyde gas and ammonia may be given off when hot.
Contact allergens
Hexamethylene tetramine is used in the foundry, tire and rubber, and phenol formaldehyde resins industries and in other applications such as a hardener in epoxy resins Bisphenol A type and as an anticorrosive agent.
Hexamethylene tetramine is an ammonia and formaldehyde releaser sometimes used in topical medicaments and cosmetics.
Synonyms
methenamine
Hexamethylenetetramine
100-97-0
Hexamine
Urotropine
Aminoform
Urotropin
Hexamethylenamine
Hexamethylene tetramine
1,3,5,7-Tetraazaadamantane
HMTA
Methenamin
Uritone
Hexamethylenetetraamine
Formamine
Aminoformaldehyde
Ammonioformaldehyde
Ammoform
Antihydral
Cystamin
Cystogen
Duirexol
Hexaform
Hexaloids
Metramine
Resotropin
Uratrine
Urodeine
Xametrin
Formin
Heterin
Hexasan
Uramin
Preparation AF
Hexamethyleneamine
Hexilmethylenamine
Hexa-Flo-Pulver
Ekagom H
methenaminum
Aceto HMT
Herax UTS
Hexamethylentetramin
Metenamina
Hexaminum
Formin (heterocycle)
Nocceler H
Sanceler H
Hexamine (heterocycle)
Vulkacit H 30
Hexamethylentetraminum
1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane
Hexamethylentetramine
Hexasan (VAN)
S 4 (heterocycle)
Hexamethylenetetraminum
Uro-phosphate
1,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane
Esametilentetramina
Metenamine
Methamin
Vesaloin
Hexa (vulcanization accelerator)
1,3,5,7-Tetraazatricyclo (3.3.1.1(3,7))decane
HMT
Hexamine (JAN)
Hexamine (TN)
1,3,5,7-Tetraazatricyclo(3.3.1.13,7)decane
Hexamethylenetetramine (aliphatic)
Methenamine (USP/INN)
NSC-26346
J50OIX95QV
1,3,5,7-Tetraazatricyclo(3.3.1.1(sup 37))decane
CHEBI:6824
H.M.T.
INS NO.239
INS-239
1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane
Formin (the heterocyclic compound)
NSC26346
Silver Methenamine
MFCD00006895
NSC-403347
1,3,5,7-Tetraazatricyclo(3.3.1.1(sup 3,7))decane
NCGC00094719-04
E239
HEXAMINE [JAN]
Hexamine Silver
E-239
Methenamine Silver
1,3,5,7-Tetraazatricyclo[3.3.1.1(3,7)]decane
1,3,5,7-tetraazatricyclo[3.3.1.1^{3,7}]decane
Caswell No. 482
Methenamine [USAN:INN]
Sanceler HT
Metenamina [INN-Spanish]
Methenaminum [INN-Latin]
Heksa K
Hexamine Superfine
Nocceler H-PO
Sanceler HT-PO
Hexa B
1,3,5,7-Tetraazatricyclo(3.3.1.13,7)decane hydroiodide
CAS-100-97-0
Esametilentetramina [Italian]
Hexamethylentetramin [German]
SMR000857139
Cohedur H 30
CCRIS 2297
HSDB 563
hexamethylene-tetramine
NSC403347
Rhenogran HEXA 80
Thixon 715B
1,3,5,7-Tetraazotricyclo[3.3.1.13,7]decane
SR-05000002024
Methenamine [USP:INN]
1,3,5,7-Tetraazatricyclo[3.3.1.1{3,7}]decane
EINECS 202-905-8
NSC 26346
UN1328
UNII-J50OIX95QV
1,3,5,7-Tetraazatricyclo[3.3.1.1(sup 3,7)]decane
EPA Pesticide Chemical Code 045501
NSC 403347
Hexamethylamine
Naphthamine
Urisol
Carin
EL 10 (corrosion inhibitor)
AI3-09611
HEXAMETHYLENETETRAMINE, ACS
EL 10
Prestwick_79
Vulkacit H30
1,3,5,7-Tetraazatricyclo[3.3.1.13,7 ]decane
Grasselerator 102
Cystex (Salt/Mix)
hexam-ethylenetetraamine
hexamethylene tetraamine
Spectrum_000991
METHENAMINE [MI]
Spectrum2_000827
Spectrum3_001730
Spectrum4_000872
Spectrum5_001603
Methenamine (Mandelamine)
METHENAMINE [INN]
Formaldehyde-ammonia 6:4
[16]-Adamazane, INN
component of Uro-Phosphate
METHENAMINE [HSDB]
METHENAMINE [INCI]
Uro-phosphate (Salt/Mix)
1,5,7-Tetraazaadamantane
EC 202-905-8
Hexamethylentetramin(german)
METHENAMINE [VANDF]
Hexamethylenetetramine, 8CI
METHENAMINE [MART.]
1,3,5,7-tetraazatricyclo[3.3.1.1?,?]decane
SCHEMBL33785
BSPBio_003380
Hexamethylenetetramine, tech.
KBioGR_001563
KBioSS_001471
METHENAMINE [USP-RS]
METHENAMINE [WHO-DD]
Hexamethylenetetramine [UN1328] [Flammable solid]
MLS001332361
MLS001332362
MLS002207085
DivK1c_000322
SPECTRUM1500394
SPBio_000753
Hexamethylenetetramine, BioXtra
CHEMBL1201270
DTXSID6020692
GTPL10913
HMS501A04
KBio1_000322
KBio2_001471
KBio2_004039
KBio2_00660
KBio3_002600
NINDS_000322
HMS1920L13
HMS2091D08
HMS2233B09
HMS3371O15
HMS3652A05
HMS3715D17
METHENAMINE [EP MONOGRAPH]
Pharmakon1600-01500394
METHENAMINE [USP MONOGRAPH]
HY-B0514
STR00289
Tox21_113455
Tox21_201606
Tox21_300502
CCG-40289
Hexamethylenetetramine, LR, >=99%
NSC757101
s3139
STL197471
ZINC86040406
AKOS000120003
AKOS005169648
Tox21_113455_1
Urotropine 100 microg/mL in Methanol
DB06799
NSC-757101
IDI1_000322
NCGC00094719-01
NCGC00094719-02
NCGC00094719-03
NCGC00094719-05
NCGC00094719-06
NCGC00094719-08
NCGC00254463-01
NCGC00259155-01
SBI-0051439.P003
FT-0627024
FT-0669190
H0093
Hexamethylenetetramine, ReagentPlus(R), 99%
SW199604-2
EN300-16855
1,5,7-Tetraazatricyclo[3.3.1.13,7]decane
D00393
Hexamethylenetetramine, ACS reagent, >=99.0%
Q71969
AB00052038_08
AB00052038_09
1,3,5,7-tetraaza-tricyclo[3.3.1.13,7]decane
1,3,5,7-tetraazatricyclo-[3.3.1.13,7]decane
1,3,5,7-tetraazatricyclo[3,3,1,13,7]decane
1,3,5,7-tetraazatricyclo[3.3.1.1,3,7]decane
1,5:3,7-Dimethano-1,3,5,7-tetraazacyclooctane
AE-641/00560026
WLN: T66 B6 A B-C 1B I BN DN FN HNTJ
Hexamethylenetetramine [UN1328] [Flammable solid]
Hexamethylenetetramine, analytical reference material
Hexamethylenetetramine, p.a., ACS reagent, 99.0%
Hexamethylenetetramine, SAJ first grade, >=98.5%
J-000293
J-521456
SR-05000002024-1
SR-05000002024-3
1,3,5,7-tetraaza-tricyclo[3.3.1.1*3,7*]decane
1,3,5,7-Tetraazatricyclo-[3.3.1.1(3,7)]decane
BRD-K30114692-001-10-0
Hexamethylenetetramine, JIS special grade, >=99.0%
F2173-0429
Z362014242
Methenamine, European Pharmacopoeia (EP) Reference Standard
1,3,5,7-TETRAAZATRICYCLO(3.3.1.1 SUP(3,7))DECANE
Methenamine, United States Pharmacopeia (USP) Reference Standard
Hexamethylenetetramine, anhydrous, free-flowing, Redi-Dri(TM), ACS reagent, >=99.0%
