Chemical Properties
Hexamethylenetetramine 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. It can have heating reaction with strong inorganic acid to generate formaldehyde and ammonium salts. In the presence of zinc powder, it can have reaction with hydrochloric acid to generate the hydrochloride salt of trimethylamine and ammonium chloride. It can also be subject to nitrification and generate RDX. It can also have reaction with nitrous acid to form N'N'-Dinitroso pentamethylene tetramine. It can have reaction with hydrogen peroxide and hydrogen cyanide. It 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, it can react with alcohol. It can also react with organic acid to form salt. It can also react with halides, phenols and amides as well as some natural products such as protein and fiber. It is irritating to the skin and can cause dermatitis. Intravenous-Rats LD50: 1200 mg/kg; Intraperitoneal injection-mice LD50: 512mg/kg.
Figure 1 is the formula of hexamethylenetetramine
Pharmacological effects
It is a therapeutic drug for treating the bacterial urinary tract infections. Hexamethylenetetramine itself has no antibacterial effect. After oral absorption, it 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. It can be used for treating urinary tract infections caused by susceptible strains. When it 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).
Chemical Properties
It is white hygroscopic crystalline powder or shiny colorless rhombic crystals. It is almost odorless with sweet and bitter taste. It is soluble in water and chloroform but less soluble in carbon tetrachloride, acetone, benzene and ether and insoluble in petroleum ether.
The above information is edited by the Chemicalbook of Dai Xiongfeng.
Uses
It can be used as the curing agent for resins and plastics, the vulcanization accelerator of rubber (accelerator H) and textiles shrink-proof agent. It can also be used for making antibacterial drug, explosives and so on. As medicine, after oral administration, it can be decomposed when coming across acidic urine to generate formaldehyde and exerts its antibacterial effect used for treating mild urinary tract infection; it can be externally used for treating ringworm, antiperspirants, and treatment of underarm odor. Its being mixed with caustic soda and sodium phenol can be used as the phosgene absorber of gas masks.
It can be used as a kind of anti-microbial agents.
It can be used as anti-shrinking textile finishing agent, bleaching agents of sodium chlorite and the buffer of waterproofing agents CR.
Hexamethylenetetramine 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. Hexamethylenetetramine is the raw material for organic synthesis and can be used for the production of chloramphenicol in the pharmaceutical industry. Hexamethylenetetramine can be used as the disinfectant of urinary system with itself having no antibacterial effect and being effective in treating gram-negative bacteria. Its 20% solution can be used for the treatment of underarm odor, sweaty feet, tinea and so on. Its being mixed with caustic soda and sodium phenol can be used as the phosgene absorber of gas masks. It can also be used for the manufacture of pesticides. Hexamethylenetetramine can react with fuming nitric acid to obtain highly explosive cyclonite, briefly referred as RDX. Hexamethylenetetramine 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, it 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. It can also be used for the determination of copper, uranium, beryllium, tellurium etc. Moreover, it can be used as gas chromatography fixed solution (maximum usage temperature of 180 ℃ with the solvent being chloroform).
Production method
It 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 hexamethylenetetramine 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.
It is obtained through the reaction between formaldehyde and the calculated amount of ammonia.
Description
Hexamethylenetetramine is a hardener in epoxy resins
of the bisphenol A type and can also be used as an anticorrosive agent. It is a sensitizing agent in ceramics
workers.
Chemical Properties
White or almost white, crystalline powder or colourless crystals.
Uses
Hexamethylenetetramine is a versatile reagent in organic synthesis. It is used in the Duff reaction, the Sommelet reaction, and in the Delepine reaction.
Uses
antibacterial, tuberculostatic
Uses
Used in the treatment of urinary track infection.
Definition
A white crystalline
organic compound made by
condensing methanal with ammonia. It is
used as a fuel for camping stoves, in vulcanizing
rubber, and as a urinary disinfectant.
Hexamine can be nitrated to make the
high explosive cyclonite.
Definition
ChEBI: A polycyclic cage that is adamantane in which the carbon atoms at positions 1, 3, 5 and 7 are replaced by nitrogen atoms.
Preparation
Hexamethylenetetramine (also known as hexamine, hexa or HMT) is prepared
from ammonia and formaldehyde:
Ammonia is passed into formalin at 20-30??C, with agitation. The resulting
solution is evaporated under reduced pressure until most of the water is
removed and the hexamethylenetetramine crystallizes. Yields of about
95% on both ammonia and formaldehyde can be achieved. Hexamethylenetetramine
is a colourless crystalline solid which, on heating, sublimes with
decomposition.
brand name
Uritone (Parke-
Davis); Urotropin (Parke-Davis).
General Description
Odorless white crystalline powder or colorless lustrous crystals. Sublimes in a vacuum at about 505° F with some decomposition. Solutions are strong bases (pH of 0.2 molar aqueous solution is 8.4).
Air & Water Reactions
Highly flammable. Burns readily on contact with a flame with a smokeless flame. Finely powdered dust is significant dust explosion hazard. Water soluble.
Reactivity Profile
Hexamethylenetetramine is hygroscopic. Hexamethylenetetramine is sensitive to exposure to heat. Hexamethylenetetramine is incompatible with oxidizing agents. Hexamethylenetetramine is also incompatible with acids. Hexamethylenetetramine reacts violently with sodium peroxide. Hexamethylenetetramine 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. Hexamethylenetetramine 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 [USCG, 1999].
Hazard
Skin irritant. Flammable, dangerous fire
risk.
Fire Hazard
Special Hazards of Combustion Products: Formaldehyde gas and ammonia may be given off when hot.
Flammability and Explosibility
Highly flammable
Pharmaceutical Applications
Methenamine (hexamine, hexamethylenetetraamine), under
the name Urotropin, was successfully used in cystitis by the
German physician Nicolaier in 1895. It has no intrinsic antibacterial
activity and owes its effect to decomposition in acid conditions
to formaldehyde, which is non-specifically microbicidal,
and ammonia. It 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 methenamine is unsuitable for these infections.
Methenamine 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.
It 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 its 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.
Contact allergens
Hexamethylenetetramine 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. It is an ammonia and formaldehyde releaser sometimes used in topical medicaments and cosmetics
Clinical Use
A venerable drug used for the disinfection of acidic urine, methenamine 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. Methenamine 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.
Carcinogenicity
No significantly increased incidence
of tumors was observed in rats or mice given HMTA
for their lifetimes. Exposures in rats included 400 mg/day for
1 year, 10,000 ppm in drinking water for 2 years in each
of three generations, 10,000 ppm in water for a lifetime
(261), and up to 1000 ppm in the diet for 2 years.
In mice, testing conditions included up to 10,000 ppm in
drinking water for 60 weeks or 50,000 ppm for 30 weeks and
a lifetime holding period, and up to 10,000 ppm in
the diet for 2 years.
Injection of 25–30 g subcutaneously per mouse led to
an increase in subcutaneous sarcomas in two experiments
(418, 419) but not in two other studies. The
relevance of this methodology to the workplace condition is
questionable.
Purification Methods
It is soluble in H2O (67%), CHCl3 (10%), EtOH (8%) and Et2O (0.3%), and a 0.2M solution has a pH of 8.4. Dissolve it in hot absolute EtOH (reflux, Norit), filter using a heated funnel, cool at room temperature first, then in ice. Wash the crystals with cold Et2O, dry them in air or under a vacuum. A further crop can be obtained by adding Et2O to the filtrate. It sublimes above 260o without melting. The picrate has m 179o(dec). [pK2 0 4.85: Reilley & Schmid Anal Chem 30 947 1958, pK2 0 6.30: Pummerer & Hofmann Chem Ber 56 1255 1923.] [Beilstein 26 I 306, 26 II 200, 26 III/IV 1680.]
