2-(Acetyloxy)benzoesäure Chemische Eigenschaften,Einsatz,Produktion Methoden
ERSCHEINUNGSBILD
FARBLOSE BIS WEISSE KRISTALLE ODER WEISSES KRISTALLINES PULVER MIT CHARAKTERISTISCHEM GERUCH.
PHYSIKALISCHE GEFAHREN
Staubexplosion der pulverisierten oder granulierten Substanz in Gemischen mit Luft möglich.
CHEMISCHE GEFAHREN
Schwache Säure in wässriger Lösung.
ARBEITSPLATZGRENZWERTE
TLV: 5 mg/m?(als TWA) (ACGIH 2005).
MAK nicht festgelegt (DFG 2005).
AUFNAHMEWEGE
Aufnahme in den Körper durch Inhalation und durch Verschlucken.
INHALATIONSGEFAHREN
Verdampfung bei 20°C vernachlässigbar; eine gesundheitsschädliche Partikelkonzentration in der Luft kann jedoch beim Dispergieren schnell erreicht werden, vor allem als Pulver.
WIRKUNGEN BEI KURZZEITEXPOSITION
WIRKUNGEN BEI KURZZEITEXPOSITION: Die Substanz reizt die Augen, die Haut und die Atemwege. Möglich sind Auswirkungen auf Blut und Zentralnervensystem, wenn große Mengen verschluckt werden.
WIRKUNGEN NACH WIEDERHOLTER ODER LANGZEITEXPOSITION
Tierversuche zeigen, dass die Substanz möglicherweise fruchtbarkeitsschädigend oder entwicklungsschädigend wirken kann.
LECKAGE
Verschüttetes Material in Behältern sammeln; falls erforderlich durch Anfeuchten Staubentwicklung verhindern. Reste sorgfältig sammeln. An sicheren Ort bringen. Persönliche Schutzausrüstung: Atemschutzgerät, P2-Filter für schädliche Partikel.
R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
Aussehen Eigenschaften
C9H8O4; 2-Acetoxy-benzoesäure. Farbloses, kristallines Pulver, fast geruchlos.
Gefahren für Mensch und Umwelt
Gesundheitsschädlich beim Verschlucken.
Zu vermeidende Stoffe sind Oxidationsmittel.
LD
50 (oral, Ratte) 1000 mg/kg.
Zeigte bei hohen Dosen im Tierversuch fortpflanzungsstörende Wirkung und kann das Kind im Mutterleib schädigen.
Reizt die Schleimhäute und die oberen Atemwege.
Schutzmaßnahmen und Verhaltensregeln
Schutzhandschuhe als kurzzeitiger Staubschutz.
Verhalten im Gefahrfall
Trocken aufnehmen. Der Entsorgung zuführen. Nachreinigen.
Kohlendioxid, Wasser, Schaum, Pulver.
Brennbar. Im Brandfall Entstehung gefährlicher Dämpfe möglich.
Erste Hilfe
Nach Hautkontakt: Mit reichlich Wasser abwaschen.
Nach Augenkontakt: Mit reichlich Wasser bei geöffnetem Lidspalt mindestens 10 Minuten ausspülen. Augenarzt hinzuziehen.
Nach Einatmen: Frischluft.
Nach Verschlucken: Viel Wasser trinken lassen, Erbrechen auslösen, Arzt hinzuziehen.
Ersthelfer: siehe gesonderten Anschlag
Sachgerechte Entsorgung
Als feste Laborchemikalienabfälle oder gelöst in z. B. Aceton in halogenfreie Lösemittelabfälle.
Beschreibung
Acetylsalicylic acid is a white crystalline powder commonly known by its common name as aspirin or ASA. Aspirin is the most widely used medication in the world.
Chemische Eigenschaften
Acetylsalicylic acid is a white crystalline solid with a slightly bitter taste. It is odorless but hydrolyzes in moist air to give an acetic acid odor
Physikalische Eigenschaften
Acetylsalicylic acid, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C , and a boiling point of 140 °C .
Synthesis The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group (R-OH → R-OCOCH
3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction.
Polymorphism Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs are receiving regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005 , and fine structural details were given by Bond et al. .
History
The use of Acetylsalicylic acid goes back thousands of years, and there are numerous accounts of the medicinal properties of plants from the Salix (willow) and Myrtaceae (Myrtle) families. Writings from ancient civilizations indicate the use of willow bark in Mesopotamia and myrtle leaves in Egypt as medicines existing several thousand years b.c.e. Hippocrates (460–377 b.c.e. ) and the ancient Greeks used powdered willow bark and leaves to reduce fever (antipyretic) and as a pain reliever (analgesic). Willow and oil of wintergreen was used as medications by native Americans.
The chemical responsible for the medicinal properties in willow and oil of wintergreen are forms of salicylates, a general name to describe compounds containing the general structure of salicylic acid. Willows (genus Salix) contain salicin and oil of wintergreen contains methyl salicylate. Although the use of willow bark and oil of wintergreen as an accepted antipyretic and analgesic has occurred for at least 2,000 years, by the 19th century medicines were starting to be synthesized in chemical laboratories.
Verwenden
Acetylsalicylic acid is the prototypical analgesic used in the treatment of mild to moderate pain. Acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Acetylsalicylic acid also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Along with sodium salicylate (sc-3520), aspirin has been shown to block the long terminal repeat from the human immunodeficiency virus and the Ig κ enhancer from NFκB dependent transcription.
Indications
Acetylsalicylic acid is available as capsules, tablets, enteric-coated
tablets (Ecotrin), timed-release tablets (ZORprin),
buffered tablets (Ascriptin, Bufferin), and as rectal suppositories.
Sodium salicylate is available generically.
Other salicylates include choline salicylate (Arthropan),
choline magnesium trisalicylate (Trilisate), and magnesium
salicylate (Momentum).
Definition
ChEBI: A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with moA cyclooxygenase inhibitor activity.
Weltgesundheitsorganisation (WHO)
Acetylsalicylic acid, a nonsteroidal anti-inflammatory, analgesic and
antipyretic agent, was introduced into medicine in 1899 and has since been widely
available in over-the-counter preparations. Recent studies carried out in the USA
have shown an association between acetylsalicylic acid consumption in children and
the development of Reye's syndrome (a rare condition characterized by a
combination of encephalopathy and liver disorder and usually preceded by an acute
viral illness, such as influenza, diarrhoea, or chickenpox). Many drug regulatory
authorities have acted to caution against the use of the drug in children and young
adults with febrile conditions. Even within this group the risk of exposure is remote
and has been estimated to be of the order of 1.5 per million. This warning also
concerns products containing other salicylates. The new indication of acetylsalicylic
acid - prophylaxis of myocardial infarction due to its antithrombotic effect - requires
loneterm use and may lead to serious adverse reactions, including cerebral
haemorrhage. Acetylsalicylic acid retains a valuable place in medicine and remains in
the WHO Model List of Essential Drugs.
Biologische Funktion
Acetylsalicylic acid is one of the most important NSAIDs because
it decreases pain at predominantly peripheral
sites with little cortical interaction and thus has few
CNS effects. The prototypical COX-2 inhibitors are
celecoxib (Celebrex) and its chemical cousin, rofecoxib
(Vioxx). In addition to a role in inflammatory processes,COX-2 seems to play a role in colon cancer and
Alzheimer’s disease, providing potential additional uses
for COX-2-selective drugs.
Acquired resistance
Acetylsalicylic acid is rapidly absorbed in the stomach and quickly degraded by plasma cholinesterases
(half-life, 15–20 min). A once-daily dose of 160 mg of aspirin, which is much lower than dosages
needed for its anti-inflammatory/analgesic actions, is sufficient to completely inactivate platelet
COX-1 irreversibly. Higher doses of aspirin only contribute to its side effects, especially
internal bleeding and upper gastrointestinal irritations.
Allgemeine Beschreibung
Acetylsalicylic acid (Aspro, Empirin), was introducedinto medicine by Dreser in 1899.Acetylsalicylic acid occurs as white crystals or as a white crystallinepowder and must be kept under dry conditions. It is not advisableto keep Acetylsalicylic acid products in the kitchen or bathroomcabinets, because Acetylsalicylic acid is slowly decomposed into aceticand salicylic acids in the presence of heat and moisture.Several proprietaries (e.g., Bufferin) use compounds such as sodium bicarbonate, aluminum glycinate, sodium citrate,aluminum hydroxide, or magnesium trisilicate to counteractAcetylsalicylic acid’s acidic property. One of the better antacids is dihydroxyaluminumaminoacetate. Acetylsalicylic acid is unusually effectivewhen prescribed with calcium glutamate. The more stable,nonirritant calcium acetylsalicylate is formed, and theglutamate portion (glutamic acid) maintains a pH of 3.5 to5. Practically all salts of Acetylsalicylic acid, except those of aluminumand calcium, are unstable for pharmaceutical use. Thesesalts appear to have fewer undesirable side effects and induceanalgesia faster than Acetylsalicylic acid. A timed release preparationof Acetylsalicylic acid is available. It does not appear to offer anyadvantages over Acetylsalicylic acid, except for bedtime dosage.
Air & Water Reaktionen
Slowly hydrolyzes in moist air. Has been involved in dust cloud explosions. Water insoluble. Solution in water is acid to methyl red indicator.
Reaktivität anzeigen
The active ingredient in common aspirin. Incompatible with oxidizers and strong acids. Also incompatible with strong bases. May react with water or nucleophiles (e.g. amines and hydroxy groups). May also react with acetanilide, amidopyrine, phenazone, hexamine, iron salts, phenobarbitone sodium, quinine salts, potassium and sodium iodides, alkali hydroxides, carbonates, stearates and paracetanol.
Hazard
An allergen; may cause local bleeding espe-
cially of the gums; 10-g dose may be fatal. May
cause excessive biosynthesis of prostaglandins.
Dust dispersed in air is serious explosion risk. Skin
and eye irritant.
Brandgefahr
Acetylsalicylic acid is combustible.
Pharmakologie
Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is poorly soluble in the acidic conditions of the stomach, which can delay absorption of high doses for eight to 24 hours. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed rapidly there, which in turn allows more of the salicylate to dissolve. Owing to the issue of solubility, however, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.
Nebenwirkungen
ContraindicationsAcetylsalicylic acid should not be taken by people who are allergic to ibuprofen or naproxen , or who have salicylate intolerance[70][71] or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID - precipitated bronchospasm.
GastrointestinalAcetylsalicylic acid use has been shown to increase the risk of gastrointestinal bleeding . Although some enteric-coated formulations of Acetylsalicylic acid are advertised as being "gentle to the stomach", in one study, enteric coating did not seem to reduce this risk. Combining Acetylsalicylic acid with other NSAIDs has also been shown to further increase this risk.
Central effectsLarge doses of salicylate, a metabolite of Acetylsalicylic acid, have been proposed to cause tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.
Reye syndrome Reye syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given Acetylsalicylic acid for a fever or other illnesses or infections.
Sicherheitsprofil
Poison by ingestion, intraperitoneal, and possibly other routes. Human systemic effects by ingestion: acute pulmonary edema, body temperature increase, changes in kidney tubules, coma, constipation, dehydration, hematuria, hepatitis, nausea or vomiting, respiratory stimulation, somnolence, tinnitus, decreased urine volume. Implicated in aplastic anemia. A 10 gram dose to an adult may be fatal. A human teratogen. Human reproductive effects by ingestion and possibly other routes: menstrual cycle changes, parturition, various effects on newborn including Apgar score, developmental abnormalities of the cardlovascular and respiratory systems. Experimental animal reproductive effects. Human mutation data reported. An allergen; skin contact, inhalation, or ingestion can cause asthma, sneezing, irritation of eyes and nose, hves, and eczema. Combustible when exposed to heat or flame. When heated to decomposition it emits acrid smoke and fumes.
mögliche Exposition
Used as an over-the counter and proprietary pharmaceutical and veterinary drug. Those engagedin manufacture of aspirin or, more likely, in its consumption in widespread use as an analgesic, antipyretic, and antiinflammatory agent
Environmental Fate
The toxicity of Acetylsalicylic acid is multifactorial. Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain occur as a result of both local gastric irritation and stimulation of the medullary chemoreceptor trigger zone. Salicylates directly stimulate the respiratory drive in the brain stem, leading to hyperventilation and respiratory alkalosis. Anion gap metabolic acidosis occurs from a buildup of organic acids as well as the uncoupling of oxidative phosphorylation, which results in an imbalance in ATP consumption and production, resulting in a net buildup of hydrogen ions. Therefore, Acetylsalicylic acid often causes a mixed acid–base status. Furthermore, the uncoupling of oxidative phosphorylation results in failure to produce ATP despite increased oxygen utilization, which leads to heat production and hyperthermia. Acetylsalicylic acid interferes with glucose metabolism and gluconeogenesis, and can cause profound decreases in cerebrospinal fluid glucose concentrations despite normal blood glucose concentrations.
Versand/Shipping
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required
läuterung methode
Crystallise aspirin twice from toluene, wash it with cyclohexane and dry it at 60o under vacuum for several hours [Davis & Hetzer J Res Nat Bur Stand 60 569 1958]. It has been recrystallised from isopropanol and from diethyl ether/pet ether (b 40-60o). It crystallises from EtOH (m 143-144o), *C6H6 (m 143o), hexane (m 115o and 128o), octane (m 121o), and has m 110o after sublimation. It has pK2 6 3.69(H2O), 4.15(20% aqueous EtOH), 4.47(30% aqueous EtOH) and 4.94(40% aqueous EtOH). It is an analgesic. [Beilstein 10 H 67, 10 II 41, 10 III 102, 10 IV 138.]
Inkompatibilitäten
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, carbonates, moisture. Dust dispersed in air is explosive
Waste disposal
May be flushed to sewer with large volumes of water.
2-(Acetyloxy)benzoesäure Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
