| HS Code | 291039 |
| Product Name | Potassium Phenylacetate |
| Chemical Formula | C8H7KO2 |
| Molecular Weight | 174.24 g/mol |
| Cas Number | 13005-36-2 |
| Einecs Number | 235-845-6 |
| Synonyms | Potassium phenylacetate; Benzeneacetic acid potassium salt; Potassium 2-phenylacetate |
| Appearance | White to off-white crystalline powder |
| Odor | Slight characteristic odor |
| Assay | ≥98.0% |
| Solubility | Soluble in water; slightly soluble in ethanol |
| Ph | 8.0-9.0 (1% aqueous solution) |
| Melting Point | >300 °C (decomposes) |
| Storage Conditions | Store in a cool, dry, well-ventilated area away from moisture and oxidizers |
| Usage | Pharmaceutical intermediate; organic synthesis; flavor and fragrance intermediate |
| Packaging | 25 kg net fiber drum or as requested |
| Hs Code | 2916340000 |
As an accredited Potassium Phenylacetate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Potassium Phenylacetate is supplied in 100 g amber glass bottles with chemical-resistant caps, sealed for laboratory use. |
| Container Loading (20′ FCL) | Potassium Phenylacetate is loaded in a 20′ FCL container, properly packaged, labeled, and secured for safe ocean transport. |
| Shipping | Potassium Phenylacetate is generally shipped as a non-hazardous solid in tightly sealed, labeled containers. Store in a cool, dry, well-ventilated area away from moisture, acids, oxidizers, and sunlight. Use appropriate PPE. Verify current DOT, IATA, and IMDG rules; unless listed, transport as non-regulated cargo. |
| Storage | Store Potassium Phenylacetate in a cool, dry, well-ventilated area away from direct sunlight and heat. Keep containers tightly closed and protected from moisture. Segregate from strong oxidizing agents, acids, and incompatible materials. Use appropriate secondary containment. Maintain good housekeeping; avoid dust generation. Keep away from food, drink, and animal feed. Follow local regulations and SDS. |
| Shelf Life | Stable about two years when stored cool, dry, tightly sealed, and protected from moisture and light; verify supplier expiry date. |
During production-scale penicillin G potassium fermentation, potassium phenylacetate (CAS 13005-36-2) is introduced as a side-chain precursor. The phenylacetate ion controls acylation of the β-lactam thiazolidine intermediate to benzylpenicillin. The compound is prepared as a 15–20% w/v aqueous feed solution and delivered into stirred-tank bioreactors of 50–150 m³ equipped with Rushton or Lightnin A315 impellers. The precursor feed line is sterilized with saturated steam at 121–125 °C for 30 min or through 0.22 µm tangential-flow filtration. Addition begins after late logarithmic growth, typically 40–60 h post-inoculation. Residual phenylacetate is maintained at 0.5–1.2 g/L using online HPLC or in-situ Raman monitoring. Dissolved oxygen is held above 30% of air saturation at airflow rates of 0.8–1.5 vvm and backpressure of 0.05–0.15 MPa. pH is controlled at 6.2–6.8 with ammonia gas or sulfuric acid, and temperature is maintained at 25–27 °C through internal coils supplied with 12–15 °C water.
The effective formulation addition ratio is a residual concentration rather than a fixed mass percentage. In a typical production campaign, total potassium phenylacetate consumption ranges from 20–30 kg per 1,000 kg benzylpenicillin potassium isolated, equivalent to 2.0–3.0% w/w of final API mass. Overfeeding above 1.8 g/L residual phenylacetate produces respiratory uncoupling, foam generation, and reduced penicillin titre. Underfeeding below 0.3 g/L shifts product distribution toward 6-aminopenicillanic acid and other phenylacetate-deficient intermediates. Downstream isolation involves chilling the broth to 4–8 °C, clarification by disc-stack separators, solvent extraction with butyl acetate at pH 2.0–2.5 in countercurrent Podbielniak extractors, and back-extraction into aqueous potassium acetate before crystallization from ethanol. Compliance is governed by ICH Q7 Section 18 for fermentation-derived APIs, 21 CFR Part 210 and 21 CFR Part 211 for penicillin-containing drug products, and current EU GMP Part II. Dedicated penicillin suites with negative air pressure and separate waste inactivation are mandatory. Terminal product types include benzylpenicillin potassium sterile crystalline API, benzylpenicillin procaine suspension intermediates, and lyophilized combination vials.
The synthesis route from potassium phenylacetate to 2-chlorophenylacetic acid is positioned as a pharmaceutical intermediate stage for thienopyridine antiplatelet APIs. The potassium salt is first acidified with 31–35% hydrochloric acid at 10–20 °C to precipitate phenylacetic acid. The isolated phenylacetic acid is dried to ≤0.5% moisture and then molten at 80–95 °C in a glass-lined chlorination reactor. Chlorine is sparged into the melt in the presence of ferric chloride on silica or iodine at 0.1–0.3% w/w. The chlorine feed is controlled at 0.6–0.9 mol per hour per mole phenylacetic acid to maintain jacket temperature between 85–100 °C and to avoid runaway chlorination. After 1.05–1.10 mol Cl₂ per mole phenylacetic acid has been absorbed, the reaction mass is quenched with water and extracted into toluene at 60–70 °C. The ortho isomer is isolated by recrystallization from mixed hexane-ethyl acetate at 0–5 °C, yielding 2-chlorophenylacetic acid with HPLC purity above 99.0% and para-isomer content below 0.15%.
Compliance for this intermediate is structured around ICH Q7 when the material is declared as an API starting material, ISO 9001:2015 for non-GMP early steps, and REACH (EC) No 1907/2006 for EU market access. Residual solvent limits follow ICH Q3C, with toluene below 890 mg/kg and hexane below 290 mg/kg in the dried product. The potassium phenylacetate input ratio in this route is 1.28–1.33 kg per 1.0 kg 2-chlorophenylacetic acid isolated after recrystallization, accounting for chlorination regioisomer losses and mechanical hold-up. Terminal finished products include 2-chlorophenylacetic acid, clopidogrel bisulfate API, and methyl 2-chlorophenylacetate process intermediates. Published data for this specific configuration is limited; the molar ratios are derived from standard electrophilic chlorination practice and require site-specific qualification.
Esterification throughput is governed by the solubility of inorganic potassium salts and the boiling point of the polar aprotic solvent. Potassium phenylacetate is suspended in dimethylformamide or dimethyl sulfoxide at 15–25% w/v before alkylating agent addition. The reaction vessel is a 2,000–5,000 L glass-lined or stainless steel reactor with a pressure rating of 0.6 MPa for methyl chloride service. Alkyl halide is added over 3–6 h at 60–95 °C; the liberated potassium halide precipitates and is removed by Nutsche filtration or centrifugation. Molar ratio of alkylating agent to potassium phenylacetate is kept at 1.05–1.15:1. Conversion above 97% is achieved before solvent recovery by vacuum distillation at 2–5 kPa and 70–85 °C. The downstream production process for benzyl phenylacetate requires slower addition of benzyl chloride to suppress dibenzyl ether formation at higher temperatures.
Compliance for fragrance ester intermediates centers on the current edition of the IFRA Code of Practice for final fragrance formulation safety and 21 CFR 172.515 for food-grade methyl and ethyl phenylacetate where applicable. The final product types include methyl phenylacetate used in honey and cocoa flavor compositions, ethyl phenylacetate used in rose and fruit fragrance bases, and benzyl phenylacetate used in jasmine reconstructions. Residual alkylating agent is controlled below 50 mg/kg by vacuum stripping and aqueous bicarbonate washing. The potassium phenylacetate input ratio is 1.00 mol per 1.00 mol ester product, with the 5–15% excess alkylating agent removed downstream.
| Ester | Alkylating agent | Solvent | Temperature (°C) | Molar ratio alkylating agent:potassium phenylacetate | End-use segment |
|---|---|---|---|---|---|
| Methyl phenylacetate | Methyl chloride | DMF | 60–75 | 1.10:1 | Honey/cocoa flavor |
| Ethyl phenylacetate | Ethyl bromide | DMSO | 70–85 | 1.12:1 | Rose/fruit fragrance |
| Benzyl phenylacetate | Benzyl chloride | DMF | 85–95 | 1.08:1 | Jasmine/floral fragrance |
Potassium phenylacetate, as a non-sodium auxin source, is used in research and commercial plant micropropagation when media sodium must be minimized in salt-sensitive woody species and orchid mericlones. The phenylacetic acid anion exhibits weak auxin activity compared with indole-3-butyric acid, but the potassium counterion avoids the sodium load of sodium phenylacetate. The addition ratio in Murashige and Skoog basal medium is 0.1–5.0 mg/L, with 1.0–3.0 mg/L for callus induction and 0.2–0.8 mg/L for adventitious root initiation. Media are prepared with 3% w/v sucrose and 0.7% w/v agar, autoclaved at 121 °C for 15 min, and potassium phenylacetate is added as a filter-sterilized stock solution through 0.22 µm polyethersulfone membrane after cooling to 50–55 °C.
Growth room environmental conditions are controlled at 25±2 °C, 16 h photoperiod, and 40–60 µmol m−2 s−1 photosynthetic photon flux density from white LED lamps. Vessels are polypropylene or glass jars with PTFE membrane lids for gas exchange and microbial exclusion. Compliance in this sector is governed by ISO/IEC 17025:2017 for analytical support and phytosanitary certification under ISPM 15 for any wood packaging of shipped plantlets; pharmaceutical GMP does not apply. Terminal finished product types include indexed ornamental mericlones, acclimatized plug plants, and containerized forestry seedlings. Published data for this specific configuration is limited; cultivar-level optimization of phenylacetate concentration is required.
Acid chloride formation from potassium phenylacetate is a two-stage sequence used to supply low-molecular-weight pharmaceutical intermediates. In the first stage, phenylacetic acid is liberated by hydrochloric acid and dried to ≤0.3% water. In the second stage, thionyl chloride is charged at 1.1–1.3 mol per 1.0 mol phenylacetic acid in dichloromethane or toluene at 50–65 °C. The reactor is a 1,000–3,000 L glass-lined vessel with a scrubbing system for hydrogen chloride and sulfur dioxide using 10–15% aqueous sodium hydroxide. Amidation follows with anhydrous ammonia at 0–5 °C for phenylacetamide or with urea at 60–75 °C for phenylacetylurea; the amine-to-acid chloride molar ratio is 1.0–1.1:1. Crude phenylacetamide is recrystallized from toluene-ethanol to yield material with melting point 156–158 °C and purity above 99.0%.
Compliance for this class of intermediates is framed by ICH Q7 where the material is designated as an API starting material, ICH Q3C for residual dichloromethane and toluene, and ICH Q3A for impurity reporting. EU REACH registration under (EC) No 1907/2006 is mandatory for product placed on the EU market above 1 t/a. The potassium phenylacetate input ratio is approximately 1.18–1.25 kg per 1.0 kg phenylacetyl chloride isolated, with losses attributed to acidification moisture and distillation hold-up. Terminal finished products include phenacemide anticonvulsant API, phenylacetamide chemical intermediate, and substituted phenylacetamides used in early-stage drug discovery. The amidation step is run under nitrogen to avoid moisture ingress and acyl chloride hydrolysis.
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Potassium phenylacetate, the potassium salt of phenylacetic acid, is supplied under CAS 13005-36-2 with molecular formula C8H7KO2 and formula weight 174.24 g/mol. Two commercial grades are commonly specified: a technical grade with assay not less than 98.0% on the dried basis and a pharmaceutical intermediate grade with assay not less than 99.0%, water content not more than 0.5% by Karl Fischer titration, and residual phenylacetic acid not more than 0.5%. The material is a white to off-white crystalline powder with a bulk density that is not standardized across suppliers and therefore should be confirmed by tapped density measurement according to USP chapter <616> when volumetric feeders or automated dispensing systems are used. The free acid, phenylacetic acid, has a pKa of 4.31 at 25 °C, remains substantially undissociated in neutral water, and requires pH adjustment to dissolve; the potassium salt instead dissolves directly and produces a mildly alkaline solution. This solubility and ionization difference is the principal technical reason for selecting the potassium salt in aqueous reaction, fermentation, and separation operations.
Quality-control identification of the salt is normally performed by Fourier-transform infrared spectrophotometry. The carboxylate anion displays asymmetric and symmetric stretching bands near 1560 cm-1 and 1380 cm-1; the absence of the free acid carbonyl band near 1698 cm-1 confirms complete neutralization. Assay by ion chromatography with conductivity detection allows simultaneous determination of the potassium and phenylacetate ions, while reversed-phase HPLC with UV detection at 254 nm is used for phenylacetic acid and related aromatic impurities after acidification of the injection solution. A robust impurity method uses an octadecylsilane column, 25 mM sodium phosphate buffer adjusted to pH 3.0, and an acetonitrile gradient from 10% to 70% over 20 min; method validation should include forced degradation of the free acid to confirm separation of benzaldehyde and phenylacetaldehyde oxidation products.
For pharmaceutical intermediate applications, residual solvent control follows ICH Q3C and USP chapter <467>. When toluene is used as a recrystallization solvent, its concentration is controlled below 890 ppm, consistent with the ICH Q3C Class 2 limit; methanol is controlled below 3000 ppm. Water content is determined by Karl Fischer titration according to USP chapter <921> and limited to 0.5% for the pharmaceutical intermediate grade because water above this value accelerates particle agglomeration, reduces stoichiometric accuracy in subsequent syntheses, and contributes to acid chloride hydrolysis when the material is converted to phenylacetyl chloride. Elemental impurities are assessed by ICP-MS according to USP chapter <233> and ICH Q3D; the acceptance criteria depend on the intended finished dosage form and daily dose, but typical certificates include individual limits for lead, cadmium, arsenic, and mercury. For use in aqueous fermentation feeds, a bioburden specification of not more than 100 CFU/g and the absence of Escherichia coli and Salmonella in 10 g is often applied using USP chapters <61> and <62>. A pharmaceutical intermediate supplier should provide a certificate of analysis that includes identification by infrared spectrophotometry, loss on drying, residue on ignition, assay by ion chromatography, residual solvent results, and the elemental impurity profile.
Because the potassium salt enters solution without a transient pH depression, it is substituted for the free acid in aqueous precursor feeds for benzylpenicillin fermentation. In a conventional 30 L stirred-tank bioreactor equipped with two Rushton impellers and a sterilizable pH electrode, the precursor feed is prepared at 150–300 g/L phenylacetate equivalent, adjusted to pH 7.0–7.8 with potassium hydroxide, and delivered by a peristaltic or diaphragm metering pump under pH-stat control. Reported penicillin fermentation studies indicate that phenylacetic acid is inhibitory above strain-dependent thresholds; residual phenylacetic acid is therefore maintained below approximately 1.0 g/L in the broth by coupling precursor addition to pH and offline HPLC measurements. The potassium salt allows precursor delivery without generating free acid droplets or local acidification around the feed port, reducing the risk of precipitate fouling on probes and baffles. A practical limitation is that potassium accumulates in the broth and may influence clarified broth conductivity; downstream ion-exchange or activated carbon treatment may be required if the potassium concentration exceeds the target range for waste discharge. At scale-up from a 30 L to a 2000 L bioreactor, the feed pump must be recalibrated against the actual phenylacetate concentration because solution density and viscosity differ from water; a mass-flow controller on the feed line is preferred over volumetric dosing when the feed concentration exceeds 250 g/L.
Published differential scanning calorimetry data for dry potassium phenylacetate is limited; unlike the free acid, which melts at 76–77 °C, the potassium salt does not exhibit a sharp melting endotherm and is processed as a solid without melting operations. Thermal gravimetric analysis of the material after vacuum drying commonly shows initial mass loss from adsorbed water between 40 °C and 80 °C, followed by decomposition with carbon dioxide evolution at temperatures above 200 °C. Drying is therefore performed in an agitated vacuum dryer with jacket temperature not exceeding 60 °C and vacuum below 10 kPa; drying cycles last 4–6 h depending on batch size and residual water target. Maintaining the jacket temperature within ±5 °C of the 60 °C setpoint is critical because temperatures above 65 °C cause discoloration and partial fusion, while temperatures below 50 °C extend drying times and may prevent the water content from falling below 0.5% within a single shift. The dried material is hygroscopic and cakes when exposed to relative humidity above 60% for more than 2 h; if a caked batch is discharged from a conical dryer without a lump breaker, downstream milling in a pin mill with a 0.8 mm screen under dry nitrogen is required to restore a flowable particle size distribution. A target D50 of 150–250 µm is common for free-flowing powder, while a D90 below 500 µm prevents bridging in hoppers and rotary valves. Batches stored in paper-lined fiber drums without sealed plastic liners should be re-tested for water content before use in water-sensitive chemistry.
In non-aqueous alkylation chemistry, the counterion influences the nucleophilicity of the phenylacetate anion through ion pairing in dipolar aprotic solvents. In dimethylformamide or dimethyl sulfoxide, potassium phenylacetate generally exhibits faster alkylation with benzyl chloride or methyl iodide than the sodium salt, consistent with looser ion pairing for the larger potassium cation; however, solvent-specific kinetic data for this exact reagent pair is limited. The free acid is preferred when the reaction requires conversion to phenylacetyl chloride or esterification under acid catalysis; the potassium salt can be converted to the free acid by acidification and extraction with methyl tert-butyl ether, and the resulting organic phase must be washed with water until the potassium content falls below 100 ppm if the free acid is destined for a water-sensitive chlorination step. Conversion of the potassium salt to phenylacetyl chloride is a two-stage operation that begins with acidification to the free acid in water/toluene, separation of the organic phase, and azeotropic drying before treatment with thionyl chloride or oxalyl chloride. Residual water in the free acid above 0.5% causes acid chloride hydrolysis and lowers the yield of subsequent amidation with 6-aminopenicillanic acid; at pilot scale above 20 kg, a wiped-film evaporator is sometimes used to remove final traces of water before chlorination.
Aqueous solutions of potassium phenylacetate at 100 g/L are mildly alkaline; actual pH values depend on residual free acid and dissolved carbon dioxide, but the solution should be protected from prolonged exposure to air because carbon dioxide absorption lowers pH and can lead to slight free acid formation. In open feed tanks, nitrogen blanketing and a 0.2 µm cartridge vent filter are used for hold times exceeding 24 h to prevent both pH drift and microbial growth. The solution is not a strong buffer; when the downstream reaction requires a controlled pH, buffering should be achieved with phosphate or bicarbonate rather than relying on the phenylacetate anion alone. This is particularly relevant in enzymatic coupling where the pH optimum for penicillin acylase is between 6.0 and 7.5; uncontrolled pH excursions above 8.5 reduce enzyme activity and shift the equilibrium toward phenylacetate rather than the coupled product.
Selection between potassium and sodium phenylacetate should be made on the basis of millimoles of cation contributed per gram of phenylacetate equivalent, not on a weight-to-weight basis. Sodium phenylacetate contains 14.5% sodium by mass and delivers 6.32 mmol of sodium per gram; potassium phenylacetate contains 22.4% potassium by mass and delivers 5.74 mmol of potassium per gram. In renal or cardiac-compromised process streams where potassium load is restricted, the sodium salt is preferable, provided the sodium load is acceptable. In sodium-restricted fermentation batches where potassium accumulation is already managed by ion-exchange or discharge permits, the potassium salt avoids adding sodium to the spent broth. The free acid remains the preferred phenylacetate source for solvent-based extractions and distillations because it does not introduce an alkali-metal counterion that must be removed from the organic phase. The sodium salt is more frequently referenced in parenteral formulation literature than the potassium salt; published clinical data for potassium phenylacetate itself in urea cycle disorder management is limited, and electrolyte replacement decisions should be made under pharmaceutical development protocols rather than by simple substitution.
| Parameter | Phenylacetic acid | Sodium phenylacetate | Potassium phenylacetate |
|---|---|---|---|
| CAS number | 103-82-2 | 114-70-5 | 13005-36-2 |
| Molecular formula | C8H8O2 | C8H7NaO2 | C8H7KO2 |
| Formula weight (g/mol) | 136.15 | 158.13 | 174.24 |
| Cation content (% by mass) | — | 14.5 | 22.4 |
| Cation delivery (mmol/g) | — | 6.32 | 5.74 |
| Water solubility | Sparingly soluble, approximately 16.6 g/L at 20 °C | Freely soluble | Freely soluble |
| Typical role | Solvent extraction, esterification, chlorination | Aqueous precursor feed, parenteral formulation reference | Aqueous precursor feed where sodium is limited, non-aqueous alkylation |
Ammonium phenylacetate is another water-soluble phenylacetate salt, but it introduces ammonia, which can interfere with pH control and downstream amine monitoring. Potassium phenylacetate avoids volatile amine contamination and is therefore preferred when the phenylacetate anion must be delivered without nitrogen-containing counterions. Calcium and magnesium phenylacetate salts are less commonly specified; published data for their solubility and thermal behavior is limited, and they are not direct substitutes without reformulation because divalent cations alter ionic strength and precipitation equilibria.
In storage, potassium phenylacetate should be kept in a tightly closed container under dry conditions at controlled room temperature 15–25 °C. Contact with strong mineral acids liberates phenylacetic acid, which has limited water solubility and can precipitate in transfer lines, pumps, or static mixers; if acidification is required, it should be performed in a vessel with sufficient agitation and a bottom drain designed for slurry removal. The salt is incompatible with strong oxidizers, and mixing with concentrated nitric acid or peroxides may generate carbon dioxide and heat. For waste treatment, aqueous streams containing potassium phenylacetate are best neutralized and biologically treated; discharge permits should account for the potassium load and residual total organic carbon. Material safety data sheets for the technical and pharmaceutical intermediate grades should be reviewed before pilot-plant trials because airborne dust from milling operations can form combustible dust clouds when suspended above the minimum explosible concentration. A documented quality system such as ICH Q7 is expected for pharmaceutical intermediate manufacture, and analytical laboratories should operate under an ISO 17025 quality management system for certificate of analysis data used in regulatory submissions.
