Names | |||
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Preferred IUPAC name 1,3,5,7-Tetraazaadamantane | |||
Other names
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Identifiers | |||
3D model (JSmol) | |||
2018 | |||
ChEBI | |||
ChEMBL | |||
ChemSpider | |||
DrugBank | |||
ECHA InfoCard | 100.002.642 | ||
EC Number |
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E number | E239 (preservatives) | ||
26964 | |||
KEGG | |||
MeSH | Methenamine | ||
PubChem CID | |||
RTECS number |
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UNII | |||
UN number | 1328 | ||
CompTox Dashboard (EPA) | |||
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Properties | |||
C6H12N4 | |||
Molar mass | 140.186 g/mol | ||
Appearance | White crystalline solid | ||
Odor | Fishy, ammonia like | ||
Density | 1.33 g/cm3 (at 20 °C) | ||
Melting point | 280 °C (536 °F; 553 K) (sublimes) | ||
85.3 g/100 mL | |||
Solubility | Soluble in chloroform, methanol, ethanol, acetone, benzene, xylene, ether | ||
Solubility in chloroform | 13.4 g/100 g (20 °C) | ||
Solubility in methanol | 7.25 g/100 g (20 °C) | ||
Solubility in ethanol | 2.89 g/100 g (20 °C) | ||
Solubility in acetone | 0.65 g/100 g (20 °C) | ||
Solubility in benzene | 0.23 g/100 g (20 °C) | ||
Acidity (pKa) | 4.89 [1] | ||
Pharmacology | |||
J01XX05 ( WHO ) | |||
Hazards | |||
Occupational safety and health (OHS/OSH): | |||
Main hazards | Highly combustible, harmful | ||
GHS labelling: | |||
Warning | |||
H228, H317 | |||
P210, P240, P241, P261, P272, P280, P302+P352, P321, P333+P313, P363, P370+P378, P501 | |||
NFPA 704 (fire diamond) | |||
Flash point | 250 °C (482 °F; 523 K) | ||
410 °C (770 °F; 683 K) | |||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Hexamethylenetetramine, also known as methenamine, hexamine, or its trade name Urotropin, 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 organic compounds, including plastics, pharmaceuticals, and rubber additives. It sublimes in vacuum at 280 °C.
Hexamethylenetetramine was discovered by Aleksandr Butlerov in 1859. [2] [3] It is prepared industrially by combining formaldehyde and ammonia: [4]
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,[ citation needed ] unlike crown ethers or larger cryptand structures.
The molecule behaves like an amine base, undergoing protonation and N-alkylation (e.g. alkylation with chloroallyl chloride gives quaternium-15).
The dominant use of hexamethylenetetramine is in the production of solid (powder) or liquid phenolic resins and phenolic resin 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 the mandelic acid salt (methenamine mandelate) or the hippuric acid salt (methenamine hippurate), [5] it is used for the treatment of urinary tract infections. In an acidic environment, methenamine is believed to act as an antimicrobial by converting to formaldehyde. [5] [6] A systematic review of its use for this purpose in adult women found there was insufficient evidence of benefit and further research was needed. [7] 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. [8] [9]
Methenamine acts as an over-the-counter antiperspirant due to the astringent property of formaldehyde. [10] Specifically, methenamine is used to minimize perspiration in the sockets of prosthetic devices. [11]
Methenamine silver stains are used for staining in histology, including the following types:
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 of 30.0 megajoules per kilogram (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. [12]
Hexamethylenetetramine 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, [13] where it is listed under E number E239, however it is not approved in the USA, Russia, Australia, or New Zealand. [14]
Hexamethylenetetramine is a versatile reagent in organic synthesis. [15] It is used in the Duff reaction (formylation of arenes), [16] the Sommelet reaction (converting benzyl halides to aldehydes), [17] and in the Delepine reaction (synthesis of amines from alkyl halides). [18]
Hexamethylenetetramine is the base component to produce RDX and, consequently, C-4 [4] as well as octogen (a co-product with RDX), hexamine dinitrate, hexamine diperchlorate and HMTD.
Hexamethylenetetramine is also used in pyrotechnics to reduce combustion temperatures and decrease the color intensity of various fireworks. [19] Because of its ash-free combustion, hexamethylenetetramine is also utilized in indoor fireworks alongside magnesium and lithium salts. [20] [21]
Hexamethylenetetramine was first introduced into the medical setting in 1895 as a urinary antiseptic. [22] It was officially approved by the FDA for medical use in the United States in 1967. [23] However, it was only used in cases of acidic urine, whereas boric acid was used to treat urinary tract infections with alkaline urine. [24] Scientist De Eds found that there was a direct correlation between the acidity of hexamethylenetetramine's environment and the rate of its decomposition. [25] Therefore, its effectiveness as a drug depended greatly on the acidity of the urine rather than the amount of the drug administered. [24] In an alkaline environment, hexamethylenetetramine was found to be almost completely inactive. [24]
Hexamethylenetetramine 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 hexamethylenetetramine provide some protection if taken before phosgene exposure but none if taken afterwards. [26]
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. [12] 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.
A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyelonephritis). Symptoms from a lower urinary tract infection include suprapubic pain, painful urination (dysuria), frequency and urgency of urination despite having an empty bladder. Symptoms of a kidney infection, on the other hand, are more systemic and include fever or flank pain usually in addition to the symptoms of a lower UTI. Rarely, the urine may appear bloody. Symptoms may be vague or non-specific at the extremities of age.
Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. As a medication, it is mainly used to treat methemoglobinemia by chemically reducing the ferric iron in hemoglobin to ferrous iron. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. It has previously been used for treating cyanide poisoning and urinary tract infections, but this use is no longer recommended.
In organic chemistry, an imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base. An alternative name is chlorhydrate, which comes from French. An archaic alternative name is muriate, derived from hydrochloric acid's ancient name: muriatic acid.
In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.
Triphosgene (bis(trichloromethyl) carbonate (BTC) is a chemical compound with the formula OC(OCCl3)2. It is used as a solid substitute for phosgene, which is a gas and diphosgene, which is a liquid. Triphosgene is stable up to 200 °C. Triphosgene is used in a variety of halogenation reactions.
Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure.
In organic chemistry, the Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl functional group by formaldehyde and a primary or secondary amine or ammonia. The final product is a β-amino-carbonyl compound also known as a Mannich base. Reactions between aldimines and α-methylene carbonyls are also considered Mannich reactions because these imines form between amines and aldehydes. The reaction is named after Carl Mannich.
The Duff reaction or hexamine aromatic formylation is a formylation reaction used in organic chemistry for the synthesis of benzaldehydes with hexamine as the formyl carbon source. The method is generally inefficient. The reaction is named after James Cooper Duff.
1,3,5-Trioxane, sometimes also called trioxane or trioxin, is a chemical compound with molecular formula C3H6O3. It is a white, highly water-soluble solid with a chloroform-like odor. It is a stable cyclic trimer of formaldehyde, and one of the three trioxane isomers; its molecular backbone consists of a six-membered ring with three carbon atoms alternating with three oxygen atoms.
Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic mixture is known as paramandelic acid.
Methacrylic acid, abbreviated MAA, is an organic compound with the formula CH2=C(CH3)CO2H. This colorless, viscous liquid is a carboxylic acid with an acrid unpleasant odor. It is soluble in warm water and miscible with most organic solvents. Methacrylic acid is produced industrially on a large scale as a precursor to its esters, especially methyl methacrylate (MMA), and to poly(methyl methacrylate) (PMMA).
Pivalic acid is a carboxylic acid with a molecular formula of (CH3)3CCO2H. This colourless, odiferous organic compound is solid at room temperature. Two abbreviations for pivalic acid are t-BuC(O)OH and PivOH. The pivalyl or pivaloyl group is abbreviated t-BuC(O).
Benzyl cyanide (abbreviated BnCN) is an organic compound with the chemical formula C6H5CH2CN. This colorless oily aromatic liquid is an important precursor to numerous compounds in organic chemistry. It is also an important pheromone in certain species.
Propionaldehyde or propanal is the organic compound with the formula CH3CH2CHO. It is the 3-carbon aldehyde. It is a colourless, flammable liquid with a pungent and fruity odour. It is produced on a large scale industrially.
1-Tetralone is a bicyclic aromatic hydrocarbon and a ketone. In terms of its structure, it can also be regarded as benzo-fused cyclohexanone. It is a colorless oil with a faint odor. It is used as starting material for agricultural and pharmaceutical agents. The carbon skeleton of 1-tetralone is found in natural products such as Aristelegone A (4,7-dimethyl-6-methoxy-1-tetralone) from the family of Aristolochiaceae used in traditional Chinese medicine.
Propionyl chloride (also propanoyl chloride) is the organic compound with the formula CH3CH2C(O)Cl. It is the acyl chloride derivative of propionic acid. It undergoes the characteristic reactions of acyl chlorides. It is a colorless, corrosive, volatile liquid.
2-Quinolone is an organic compound related structurally to quinoline. It is the majority tautomer in equilibrium with 2-quinolinol. The compound can be classified as a cyclic amide, and as such is used as an isostere for peptides and other pharmaceutically inspired targets. The 4-methyl-2-quinolone can be prepared by dehydration of acetoacetanilide.
Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene.
Hydroxymethylation is a chemical reaction that installs the CH2OH group. The transformation can be implemented in many ways and applies to both industrial and biochemical processes.