Acetylsalicylate (5054-56-8) Physical and Chemical Properties
Acetylsalicylate
The deprotonated (anionic) form of acetylsalicylic acid commonly encountered as a salicylate benzoate used in formulation studies, salt chemistry and analytical workflows in pharmaceutical R&D and process development.
| CAS Number | 5054-56-8 |
| Family | Salicylates / carboxylate anions |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP |
Acetylsalicylate is an organic anion derived from acetylsalicylic acid (aspirin) by deprotonation of the carboxyl group; it belongs to the salicylate/benzoate structural class and is formally a 2-acetyloxybenzoate ion. Structurally it is a monoanionic aromatic carboxylate bearing an ortho-acetylated phenolic ester (an acetoxy substituent). The electronic structure is characterized by delocalization of the negative charge across the carboxylate group and conjugation with the aromatic ring, while the acetylated phenolic oxygen is tied in an ester linkage that is less nucleophilic and less basic than a free phenol.
This ion exhibits polar, moderately lipophilic behavior: the carboxylate imparts water solubility and an ability to engage in ionic interactions, while the aromatic and acetyl groups contribute to modest partitioning into nonpolar phases. Key functional-group chemistry is dominated by the carboxylate/acid equilibrium (acid–base behavior) and by ester hydrolysis of the acetyl group under strongly acidic or basic aqueous conditions. As the conjugate base of a widely used pharmaceutical (acetylsalicylic acid), acetylsalicylate is of interest in formulation chemistry, salt/polymorph behavior, analytical methods, and as a reactive intermediate in aqueous and biological media.
Common commercial grades reported for this substance include: EP.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: C9H7O4-
- Molecular weight (computed): \(179.15\,\mathrm{g}\,\mathrm{mol}^{-1}\)
- Exact mass (monoisotopic): \(179.03443370\,\mathrm{Da}\)
Qualitatively, the low molecular weight combined with polar functionality (carboxylate and ester oxygens) means the ion is small enough for facile aqueous mobility and membrane permeation when associated with counterions or in lipophilic formulations.
Charge State and Ion Type
- Formal charge: \(-1\)
Acetylsalicylate is an organic monoanion (carboxylate). In aqueous solution it exists as the deprotonated form of acetylsalicylic acid at pH values above the carboxyl pKa; it forms ion pairs and salts with counterions (e.g., Na+, K+) and can be involved in hydrogen-bonding and ionic interactions with proteins and excipients.
LogP and Polarity
- XLogP3: 1.8
- Topological polar surface area (TPSA): \(66.4\,\text{Å}^2\)
- Hydrogen-bond donors: 0
- Hydrogen-bond acceptors: 4
- Rotatable bond count: 2
The moderate XLogP (1.8) indicates balanced lipophilicity for an aromatic carboxylate ion; the TPSA and acceptor count reflect a molecule capable of polar interactions and limited passive membrane permeability in the anionic form. The absence of hydrogen-bond donors and modest rotatable-bond count are consistent with relatively rigid aromatic ester–carboxylate geometry.
Structural Identifiers (SMILES, InChI)
- SMILES: CC(=O)OC1=CC=CC=C1C(=O)[O-]
- InChI: InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12)/p-1
- InChIKey: BSYNRYMUTXBXSQ-UHFFFAOYSA-M
These canonical structural identifiers correspond to the 2-acetyloxybenzoate connectivity and allow unambiguous representation in cheminformatics workflows.
Acid–Base Behavior
Conjugate Acid and Speciation
The conjugate acid of acetylsalicylate is acetylsalicylic acid (aspirin), obtained by protonation of the carboxylate. Speciation in aqueous media is governed by the carboxylic acid–carboxylate equilibrium: at low pH the protonated, neutral acetylsalicylic acid predominates; at higher pH the acetylsalicylate anion is favored. In biological fluids and typical environmental waters, distribution between these forms depends on pH, ionic strength, and counterion identity.
Acid–Base Equilibria and Qualitative pKa Discussion
The deprotonation/protonation behavior is dominated by the carboxyl group; the ortho-acetoxy substituent exerts an electron-withdrawing resonance/inductive effect that stabilizes the carboxylate anion relative to unsubstituted benzoates, influencing acidity. Intramolecular hydrogen bonding that can be present in salicylates is less available in the deprotonated form. No experimentally established value for this property is available in the current data context.
Chemical Reactivity
Chemical Stability
Acetylsalicylate is chemically stable as a salt or free ion under neutral, dry conditions, but its stability in aqueous media is limited by hydrolysis of the acetyl ester. The aromatic carboxylate is relatively resistant to oxidative degradation under mild conditions, though prolonged exposure to strong oxidants can alter the aromatic ring. Thermal stability is adequate for common handling and formulation steps when moisture is controlled; prolonged heating in aqueous solution accelerates hydrolysis.
Formation and Hydrolysis Pathways
Formation: acetylsalicylate is generated by deprotonation of acetylsalicylic acid (e.g., by base or by formation of a metal salt). Hydrolysis: the acetoxy ester can undergo nucleophilic acyl substitution (ester hydrolysis) to yield salicylate (the corresponding deacetylated salicylate ion) and acetate under acidic or basic conditions; hydrolysis is generally base-catalyzed and can proceed under physiological or strongly basic aqueous conditions. In biological systems, enzymatic esterases rapidly convert acetylsalicylic acid to salicylate; chemical hydrolysis in non-enzymatic settings follows established ester hydrolysis mechanisms.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS number: 5054-56-8
- ChEBI: CHEBI:13719
- DSSTox Substance ID: DTXSID801287465
- Nikkaji Number: J730.352A
- Wikidata: Q27108970
- InChIKey: BSYNRYMUTXBXSQ-UHFFFAOYSA-M
These registry codes are used for unambiguous cataloguing and cross-referencing of the substance in regulatory and inventory systems.
Synonyms and Structural Names
Reported names and synonyms include: - Acetylsalicylate - 2-acetyloxybenzoate - o-Acetoxybenzoate - Benzoic acid, 2-(acetyloxy)-, ion(1-) - A828297
Additional historical or related names reported in association with the structure: - 2-(acetyloxy)benzoate - ACETYLSALICYLIC ACID - 2-Acetoxybenzenecarboxylic acid
Note: some synonyms reflect the parent neutral molecule (acetylsalicylic acid, aspirin) or alternative nomenclature; the presented ion corresponds specifically to the deprotonated carboxylate form.
Industrial and Commercial Applications
Role as Active Ingredient or Intermediate
As the conjugate base of acetylsalicylic acid, acetylsalicylate is directly related to the active pharmaceutical ingredient aspirin. In practical terms, the anionic form is relevant in salt formation, solubility modulation, crystallization/polymorph studies, analytical standards, and formulation science (e.g., in buffered or basic formulations where the carboxylate predominates). It can also appear transiently in biological matrices following absorption and ionization of the parent acid.
Representative Application Contexts
Representative contexts where acetylsalicylate chemistry is relevant include: - Pharmaceutical formulation and quality control for aspirin-containing products (solubility, stability, salt/excipient interactions). - Analytical chemistry and assay development as the anionic species in chromatographic and spectrometric methods. - Preformulation and crystallography studies focusing on salt forms, counterions, and solid-state behavior. - Research into hydrolysis and metabolic transformation pathways (relation to salicylate metabolites).
No concise application summary is available in the current data context; in practice this substance is selected based on its general properties described above.
Safety and Handling Overview
Toxicity and Biological Effects
Pharmacologically, acetylsalicylate is the deprotonated form of a compound that irreversibly acetylates cyclooxygenase enzymes, producing analgesic, antipyretic and antiplatelet effects; platelet inhibition persists for the life of affected platelets. Adverse effects associated with the parent molecule or its salicylate metabolite include gastrointestinal bleeding risk, tinnitus at high exposures, and the potential for Reye's syndrome in pediatric viral illness contexts.
Acute toxicity data reported for related salicylates include: - LD50: \(250\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (oral, mouse) - LD50: \(1010\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (oral, rabbit) - LD50: \(200\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (oral, rat)
Routes of exposure are primarily oral and dermal contact in industrial settings; systemic effects follow absorption and, for the parent ester, rapid hydrolysis to salicylate.
Storage and Handling Considerations
Handle acetylsalicylate using standard laboratory PPE (gloves, eye protection, protective clothing) and engineering controls to minimize dust and aerosol formation. Store in a cool, dry place in tightly closed containers to limit moisture uptake and prevent hydrolysis of the acetyl ester. Avoid exposure to strong acids or bases and to oxidizing agents that can degrade the aromatic ring or ester function. For workplace exposure limits, transport classification, and detailed hazard control measures, users should consult the product-specific Safety Data Sheet (SDS) and applicable local regulations.
