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.
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).
Reactivity Profile
HEXAMETHYLENETETRAMINE(100-97-0) is hygroscopic. HEXAMETHYLENETETRAMINE(100-97-0) is sensitive to exposure to heat. This chemical is incompatible with oxidizing agents. HEXAMETHYLENETETRAMINE(100-97-0) is also incompatible with acids. HEXAMETHYLENETETRAMINE(100-97-0) reacts violently with sodium peroxide. HEXAMETHYLENETETRAMINE(100-97-0) 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(100-97-0) 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].
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.
Hazard
Skin irritant. Flammable, dangerous fire
risk.
Fire Hazard
Special Hazards of Combustion Products: Formaldehyde gas and ammonia may be given off when hot.
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.
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).
Flammability and Explosibility
Highlyflammable
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.
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.]
