94-13-3

Basic information

• Product Name: Propylparaben
• Synonyms: Propyl 4-hydroxybenzoate, 99+% 500GR;Propyl 4-hydroxybenzoate, 99+% 5GR;Propyl 4-hydroxybenzo;Proply p-Hydroxybenzoate;Propyl 4-Hydroxybenzoate, 99.0%(T);Propyl 4-hydroxybenzoate standard solution;4-Hydroxybenzoic acid-propyl ester Solution, 100ppm;Propyl 4-hydroxybenzoate Vetec(TM) reagent grade, 98%
• CAS NO: 94-13-3
• Molecular Formula: C₁₀H₁₂O₃
• Molecular Weight: 180.2
• EINECS: 202-307-7
• Product Categories: API;Other APIs;Cosmetics;Pharmaceutical Raw Materials;Aromatic Esters;Aromatics
• Mol File: 94-13-3.mol

Chemical Properties

• Melting Point: 95-98 °C(lit.)
• Boiling Point: 133°C
• Flash Point: 180°(356°F)
• Appearance: White/Crystalline Powder
• Density: 1.0630
• Vapor Pressure: 0.00093mmHg at 25°C
• Refractive Index: 1.5050
• Storage Temp.: 0-6°C
• Solubility: ethanol: soluble0.1M, clear, colorless
• PKA: pKa 8.4 (Uncertain)
• Water Solubility: <0.1 g/100 mL at 12℃
• Stability: Stable. Incompatible with strong oxidizing agents, strong bases.
• Merck: 14,7866
• BRN: 1103245
• CAS DataBase Reference: Propylparaben(CAS DataBase Reference)
• NIST Chemistry Reference: Propylparaben(94-13-3)
• EPA Substance Registry System: Propylparaben(94-13-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-24/25-36
• WGK Germany: 1
• RTECS: DH2800000
• TSCA: Yes
• Hazardous Substances Data: 94-13-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Propylparaben is used as a preservative and antioxidant in the pharmaceutical industry to prevent the growth of bacteria, mold, and other microorganisms, ensuring the safety and efficacy of medications.
Used in Cosmetics:
Propylparaben is used as an antimicrobial preservative in cosmetics to protect products from microbial contamination and extend their shelf life.
Used in Food Industry:
Propylparaben is used as a preservative in the food industry to prevent spoilage and maintain the quality of food products.
Used as Antimicrobial Preservative:
Propylparaben is one of the most frequently used preservatives against bacteria and mold, providing protection against microbial growth in various products.
Used as Antiseptic and Antimicrobial:
Propylparaben is used as an antiseptic and antimicrobial agent in various applications, including pharmaceuticals, cosmetics, and foods, to prevent infections and maintain product safety.
Used as Pharmaceutic Aid (Antifungal):
Propylparaben is used as a pharmaceutic aid with antifungal properties, helping to prevent fungal contamination in pharmaceutical products.

content analysis

Same with Method 1 in "Butyl p-hydroxybenzoate (07002)". In calculation, per mL of 1 mol/L sodium hydroxide corresponds to 180.2mg of this goods (C10Hl2O8).

Toxicity

Adl? 0-10 mg/kg (FAO/WHO, 2001). LD50? 3.7g/kg (mouse, oral). GRAS? (FDA, § 184.1670, 2000). HACSG? listed in the restricted list.

usage limits

2760--2002 GB (calculate in p-hydroxybenzoic acid; g/kg): fresh fruit and vegetable 0.012; vinegar 0.10; carbonated beverages 0.20; fruit juice (fruit flavor) type beverages, jam (excluding canned), soy sauces 0.25; pastry stuffing 0.5 (the total amount of single use or mixed use with ethyl 4-hydroxybenzoate); egg yolk filling 0.20. Another provision that sodium methylparaben is also equivalent application. FAO/WHO (1984): Jam and jelly, 1000 mg/kg FDA § 184.1670 (2000): 0.1%. EEC(1990, mg/kg): Frozen drinks 160; beet pickled vegetables, salad dressings, 250; fragrance, fruit tarts, purees, concentrated soft drinks, 800; Fruit canned, salted fish, 1000. Japan (calculate in p-hydroxybenzoic acid, g/kg; this product, g): soy sauce 0.25g/L (this product 0.32); vinegarsoysoy 0.1g/L (This product 0.13); soft drinks and syrup 0.1 (this product 0.13); fruit sauce 0.2 (this product 0.26); fruits and vegetables 0.012 (this product 0.015).

Production methods

This product can be derived from the esterification of p-hydroxybenzoic acid and n-propanol. First mix p-hydroxybenzoic acid with propanol and heat to dissolve. Then add sulfuric acid slowly and continue to heat for 8h of refluxion. After cooling, pour them into the 4% sodium carbonate solution for precipitation and crystallization. Filtrate and wash to neutral to obtain the crude product. After further ethanol recrystallization, the finished products are obtained. In the preparation, the cation exchange resin can be used in place of the sulfuric acid catalyst. It can be derived from the esterification of p-hydroxybenzoic acid and n-propanol in the presence of sulfuric acid. Add p-hydroxybenzoic acid and n-propanol in turn to the esterification reactor, and heat to dissolve. Add concentrated sulfuric acid slowly and heat for 8h of refluxion. Pour the reaction solution into 4% sodium carbonate solution before it is cooled. Constantly stir for precipitation and crystallization. Then the crude product can be obtained after centrifugal filtration and washed to neutral. Finally the finished product is acquired after activated carbon decolorization and ethanol recrystallization. The method of preparing ethyl p-hydroxybenzoate can also be used as a reference. HOC6H4COOH + C3H7OH [H2SO4] → HOC6H4COOC3H7 + H2O

Hazards & Safety Information

Category: Toxic substances Toxicity classification :Moderate toxicity Acute Toxicity :Celiac-mouse LD50: 200 mg/kg Flammable hazardous characteristics :Flammable; excrete acrid and pungent smoke from fire Storage and transport characteristics :Stored in the low-temperature, well-ventilated and dry warehouse Fire extinguishing agent :water, carbon dioxide, dry powder, sand

Production Methods

Propylparaben is prepared by the esterification of p-hydroxybenzoic acid with n-propanol.

Preparation

Produced by esterfying p-hydroxybenzoic acid with n-propanol, using an acid catalyst such as sulfuric acid and an excess of propanol. The materials are heated in a glass-lined reactor under reflux. The acid is then neutralized with caustic soda and the product is crystallized by cooling. The crystallized product is centrifuged, washed, dried under vacuum, milled and blended, all in corrosion-resistant equipment to avoid metallic contamination.

Reactivity Profile

Maximum stability of Propylparaben occurs at a pH of 4 to 5. Incompatible with alkalis and iron salts. Also incompatible with strong oxidizing agents and strong acids .

Fire Hazard

Flash point data for Propylparaben are not available; however, Propylparaben is probably combustible.

Flammability and Explosibility

Nonflammable

Pharmaceutical Applications

Propylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations. It may be used alone, in combination with other paraben esters, or with other antimicrobial agents. It is one of the most frequently used preservatives in cosmetics. The parabens are effective over a wide pH range and have a broad spectrum of antimicrobial activity, although they are most effective against yeasts and molds. Owing to the poor solubility of the parabens, the paraben salts, particularly the sodium salt, are frequently used in formulations. This may cause the pH of poorly buffered formulations to become more alkaline. Propylparaben (0.02% w/v) together with methylparaben (0.18% w/v) has been used for the preservation of various parenteral pharmaceutical formulations.

Contact allergens

This substance is one of the parabens family. Parabens are esters formed by p-hydroxybenzoic acid and an alcohol. They are largely used as biocides in cosmetics and toiletries, medicaments, or food. They have synergistic power with other biocides. Parabens can induce allergic contact dermatitis, mainly in chronic dermatitis and wounded skin.

Safety

Propylparaben and other parabens are widely used as antimicrobial preservatives in cosmetics, food products, and oral and topical pharmaceutical formulations. Propylparaben and methylparaben have been used as preservatives in injections and ophthalmic preparations; however, they are now generally regarded as being unsuitable for these types of formulations owing to the irritant potential of the parabens. Systemically, no adverse reactions to parabens have been reported, although they have been associated with hypersensitivity reactions. The WHO has set an estimated acceptable total daily intake for methyl, ethyl, and propyl parabens at up to 10 mg/kg body-weight. LD50 (mouse, IP): 0.2 g/kg LD50 (mouse, oral): 6.33 g/kg LD50 (mouse, SC): 1.65 g/kg

storage

Aqueous propylparaben solutions at pH 3–6 can be sterilized by autoclaving, without decomposition.At pH 3–6, aqueous solutions are stable (less than 10% decomposition) for up to about 4 years at room temperature, while solutions at pH 8 or above are subject to rapid hydrolysis (10% or more after about 60 days at room temperature).

Incompatibilities

The antimicrobial activity of propylparaben is reduced considerably in the presence of nonionic surfactants as a result of micellization. Absorption of propylparaben by plastics has been reported, with the amount absorbed dependent upon the type of plastic and the vehicle. Magnesium aluminum silicate, magnesium trisilicate, yellow iron oxide, and ultramarine blue have also been reported to absorb propylparaben, thereby reducing preservative efficacy. Propylparaben is discolored in the presence of iron and is subject to hydrolysis by weak alkalis and strong acids.

Regulatory Status

Propylparaben and methylparaben are affirmed GRAS direct food substances in the USA at levels up to 0.1%. All esters except the benzyl ester are allowed for injection in Japan. In cosmetics, the EU and Brazil allow use of each paraben at 0.4%, but the total of all parabens may not exceed 0.8%. The upper limit in Japan is 1.0%. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (IM, IV, and SC injections; inhalations; ophthalmic preparations; oral capsules, solutions, suspensions, and tablets; otic, rectal, topical, and vaginal preparations). Included in parenteral and nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

InChI:InChI=1/C10H12O3/c1-2-7-13-10(12)8-3-5-9(11)6-4-8/h3-6,11H,2,7H2,1H3

Synthetic route

n-propyl 4-acetoxybenzoate (27739-13-5) → nipasol (94-13-3)

Conditions	Yield
With sodium; diphenyldisulfane In 1-methyl-pyrrolidin-2-one at 90℃; for 0.5h;	95%
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 3h;	79%

propan-1-ol (71-23-8) + 4-hydroxy-benzoic acid (99-96-7) → nipasol (94-13-3)

Conditions	Yield
With methanesulfonic acid; choline chloride Reflux;	93.4%
With benzimidazole bisulfate ionic liquid Reflux;	93.8%
With NKC-9-type macroporous resin at 98℃; for 3.08333h; Temperature; Microwave irradiation;	89%

n-propyl 4-benzoyloxybenzoate → nipasol (94-13-3)

Conditions	Yield
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 100℃; for 3h;	90%
With sodium; diphenyldisulfane In 1-methyl-pyrrolidin-2-one at 90℃; for 0.5h;	90%
With potassium fluoride; thiophenol In 1-methyl-pyrrolidin-2-one at 100℃; for 1h;	80%

1-(tert-butyldimethylsilyloxy)-2-propane (17348-67-3) + 4-hydroxy-benzaldehyde (123-08-0) → nipasol (94-13-3)

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; Selectfluor In acetonitrile at 20℃; for 7h; Inert atmosphere; Irradiation;	80%

propan-1-ol (71-23-8) + tetrachloromethane (56-23-5) + phenol (108-95-2) → nipasol (94-13-3) + propyl salicylate (607-90-9)

Conditions	Yield
With diiron nonacarbonyl at 130℃; for 6h; Catalytic behavior; Reagent/catalyst; Time; Inert atmosphere; Sealed tube;	A 66% B 34%
With iron(II) bromide at 130℃; for 6h; Reagent/catalyst; Inert atmosphere; Sealed tube;	A 20% B 22%

propan-1-ol (71-23-8) + carbon monoxide (201230-82-2) + phenol (108-95-2) → nipasol (94-13-3)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; oxygen; potassium carbonate; potassium iodide at 100℃; under 6000.6 Torr; for 18h;	50%

carbon dioxide (124-38-9) + tetrapropyl-ammonium; phenolate → nipasol (94-13-3) + 4-hydroxy-benzoic acid (99-96-7)

Conditions	Yield
With potassium carbonate at 125℃; under 37503 Torr; for 2h; Kolbe-Shmitt reaction;	A 3.1 % Chromat. B 30 % Chromat.

Upstream product

• 71-23-8 propan-1-ol 
• 99-96-7 4-hydroxy-benzoic acid 
• 27739-13-5 n-propyl 4-acetoxybenzoate 
• 124-38-9 carbon dioxide 
• 107-21-1 ethylene glycol 
• 9003-39-8 polyvinylpyrrolidone 
• 541-41-3 chloroformic acid ethyl ester 
• 51803-78-2 nimesulide 
• 56-23-5 tetrachloromethane 
• 108-95-2 phenol 
• 201230-82-2 carbon monoxide 
• 17348-67-3 1-(tert-butyldimethylsilyloxy)-2-propane 
• 123-08-0 4-hydroxy-benzaldehyde 

Downstream Products

• 5468-99-5 propyl 4-ethoxybenzoate 
• 68888-15-3 3-chloromethyl-4-hydroxy-benzoic acid propyl ester 
• 70902-91-9 3,5-dibromo-4-hydroxy-benzoic acid propyl ester 
• 34384-48-0 4-hydroxy-3-nitro-benzoic acid propyl ester 
• 758632-87-0 3-amino-4-hydroxy-benzoic acid propyl ester 
• 91842-82-9 4-hydroxy-3,5-diiodo-benzoic acid propyl ester 
• 111222-67-4 4-propoxy-benzoic acid propyl ester 
• 69806-25-3 4-(2-hydroxy-ethoxy)-benzoic acid propyl ester 
• 124103-78-2 4-(Propoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 
• 56220-01-0 4-(2-Isobutyryloxy-butoxy)-benzoic acid propyl ester 
• 108844-32-2 4-hydroxy-3-morpholin-4-ylmethyl-benzoic acid propyl ester 
• 57554-45-7 3-(4-Carbo-propoxy)-phenoxy-1-isopropylamino-2-propanol 
• 70884-50-3 5-Nitro-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid 4-propoxycarbonyl-phenyl ester 
• 70884-76-3 7-Nitro-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid 4-propoxycarbonyl-phenyl ester 

Relevant articles and documents

Method for preparing paraben

The invention discloses a method for preparing paraben. The method comprises the following steps: adding p-hydroxybenzoic acid (Amol), an alcohol (Bmol) and a benzimidazole ionic liquid (Cmol) into adry three-neck flask, slowly heating, carrying out reflux reaction, and carrying out TLC monitoring until reaction is finished; carrying out reduced pressure distillation to remove a solvent, washingresidues with ethyl acetate, carrying out suction filtration, and carrying out spin-drying on an obtained filtrate to obtain paraben. The yield can reach 90% or above; an obtained filter cake is the benzimidazole ionic liquid and can be recycled; the ratio of A to B to C is 1: 5: (0.2-0.5). The method provided by the invention has the advantages that the catalyst can be recycled, green and environment-friendly effects are realized, the cost is reduced, and the method is an efficient method for synthesizing paraben.

Proline ionic liquid and method for catalyzing synthesis of paraben by proline ionic liquid

The invention discloses proline ionic liquid and a method for catalyzing synthesis of paraben by the proline ionic liquid. The preparation method comprises the following steps: adding N-butylbenzimidazole, a solvent and proline into a dry three-neck flask, carrying out reflux reaction until the reaction is complete (monitored by TLC), evaporating to remove the solvent to obtain a faint yellow oilyliquid, namely the proline ionic liquid, adding p-hydroxybenzoic acid, alcohol and a proline ionic liquid into a dry three-necked bottle, heating to reflux reaction, monitoring by TLC until the reaction is finished, evaporating under reduced pressure to remove the solvent, extracting residues with diethyl ether, evaporating the diethyl ether phase to remove the solvent to obtain the methylparabenwith the yield of 88% or above, wherein the remainder is the ionic liquid, and carrying out washing and drying so that the product can be recycled for many times. The method disclosed by the invention is efficient, environment-friendly and safe, the catalyst can be recycled, the cost is reduced, the requirement on equipment is low, and the method is an efficient method for synthesizing paraben.

Single-Step Dual Functionalization: One-Pot Bromination-Cross-Dehydrogenative Esterification of Hydroxy Benzaldehydes with CCl 3 Br - A Comparison with Selectfluor

Bromination of phenolic compounds without directly using molecular bromine possesses much importance. In this article an Ir III /CCl 3 Br-assisted single-step double functionalization of hydroxy benzaldehydes is reported. It involves simultaneous esterification of the aldehyde group and bromination of the aryl ring of phenolic aldehydes in one-pot. The reaction proceeds under mild conditions in the presence of 445 nm blue LED light to obtain highly functionalized bromo hydroxy benzoates in moderate to good yields. In comparison, Selectfluor as an oxidant gives only non-bromo phenolic esters.

A process for preparing Nepal jin zhi method (by machine translation)

The invention discloses a method for preparing Nepal jin zhi method: in a reaction container by adding of formula choline chloride (Amol) and methanesulfonic acid (Bmol), for 80 °C stirring to complete dissolution shall be low altogether [...]; cooling to room temperature, then added to the hydroxy benzoic acid of formula (Cmol) acrylic (Dmol), slow heating, reflux reaction, TLC monitoring until a reaction is finished (1 - 2 h); reaction liquid-cooled to the room temperature, precipitate solid, filtered, cake of a small amount of washing, get [...], a yield of 90% or more; recycling the filtrate to obtain low altogether [...]. Wherein A: B: C: D is 1: (1 - 4): 1: (1.1 - 1.5). The method of the invention short reaction time, efficiency is high, the catalyst can be recycled, environmental protection, and reducing the cost; to reduce the consumption of the stinging; low requirements on equipment, is an efficient method of synthesizing [...]. (by machine translation)

Method for preparing parabens

The invention discloses a method for preparing parabens. The method comprises the following steps: adding an appropriate amount of methanol (A) into a reaction container, sequentially adding a benzothiazole ionic liquid (B) and p-hydroxybenzoic acid (C) while stirring, slowly heating the obtained solution to a reflux temperature, and carrying out TLC monitoring until the reaction ends; and distilling off methanol, washing the obtained reaction product with ethyl acetate, carrying out suction filtration (the filter cake is the benzothiazole ionic liquid), carrying out rotary evaporation on thefiltrate, washing the product with water, carrying out suction filtration, and drying the product to obtain colorless crystals (methylparaben) at a yield of 91% or above. A ratio of A:B:C is 1:4:0.15, and a catalyst has a high activity and a good stability, and can be recycled. Additionally, the method also has a high esterification rate of 87%% or above to other parabens (ethylparaben, propylparaben, isopropylparaben, butylparaben and n-dodecyl 4-hydroxybenzoate), and provides a good method for industrial synthesis of parabens.

Synthesis of Hydroxybenzoic Acids and Their Esters by Reaction of Phenols with Carbon Tetrachloride and Alcohols in the Presence of Iron Catalysts

Alkyl esters of hydroxy-, methoxy-, and ethoxybenzoic and cresotic acids have been synthesized by reaction of phenols, anisole, phenetole, and cresols with carbon tetrachloride and alcohols in the presence of iron catalysts.

Palladium-Catalyzed Aerobic Oxidative Carbonylation of C–H Bonds in Phenols for the Synthesis of p-Hydroxybenzoates

This work reports the synthesis of p-hydroxybenzoates directly from phenols by oxidative carbonylation of phenolic C–H bonds, proceding through oxidative iodination. The developed methodology is efficient and economically attractive because phenols are cheap and easily available starting materials. This one-pot strategy was expediently applied to the synthesis of a variety of p-hydroxybenzoates by utilizing simple primary and secondary alcohols with different phenols under mild reaction conditions. Advantageously, the procedure has no need for co-catalysts, co-solvents or external ligands. The utilization of molecular oxygen as a terminal oxidant for C–H bond oxidation represents an additional benefit.

A method for the preparation method of the hydroxybenzoic acid propyl ester (by machine translation)

This invention discloses a method for the preparation method of the hydroxybenzoic acid propyl ester, comprising the following steps: in the bottle to join the ports of the three-hydroxy benzoic acid, n-propanol and NKC - 9 type macroporous resin, mix, then put into the electromagnetic solder, in microwave oven, stir, reaction, and released timely separated in the water separator; the reaction 2 - 3h off after, pouring the reaction liquid clean three mouth bottle and the excess of steam distillation is propanol, distillation of the residual liquid in the beaker of putting into the clean, cooling crystallization, for 10% of the sodium carbonate solution to the pH value of the washing is 7.0 - 8.0, filtered, the filter cake wash with distilled water, drying, refining to obtain white solid of the product to the hydroxy benzoic acid propyl ester. The invention to NKC - 9 type macroporous resin as catalyst, to hydroxy benzoic acid and propanol as raw materials, the microwave method is adopted for the preparation of hydroxy benzoic acid propyl, excess of the tetrabutylorthotitanate can be reclaimed and reused, to corrode the apparatus, environmental pollution is small, high yield, purity is good, the preparation method is simple, and is suitable for industrial production. (by machine translation)

Trifluoromethanesulfonic acid immobilized on zirconium oxide obtained by the sol-gel method as catalyst in paraben synthesis

The parabens, alkylic esters of p-hydroxybenzoic acid, were synthesized using trifluoromethanesulfonic acid immobilized on zirconium oxide (zirconia) as catalyst. The oxide was obtained by the sol-gel method, using urea as a pore-forming agent. After removing urea by extraction with water, the solid was dried and then calcined at 100, 205, 310 and 425 °C for 24 h. Afterward, it was impregnated with trifluoromethanesulfonic acid in toluene at reflux and leached to remove the weakly adsorbed acid. Mesoporous materials were obtained, whose mean pore diameter increased with the temperature of the thermal treatment of the support, while the specific surface area and the amount of acid bonded to the support decreased. The samples are crystalline from 400 °C and are thermally stable up to 250 °C. The catalysts have strong acidity and the number of acid sites decreased with the acid content in the support. The catalytic activity in the synthesis of propyl paraben, expressed as moles of ester formed at 5 h/mol acid in the catalyst, decreased when samples obtained from supports thermally treated at higher temperature were used. The activity also slightly diminished for the synthesis of different parabens in the order propyl > ethyl > methyl ester.

HPLC analysis of a syrup containing nimesulide and its hydrolytic degradation product

The present paper deals with the evaluation of nimesulide, 2-phenoxy-4-nitroaniline, the main hydrolytic degradation product of nimesulide, of methylparaben and propylparaben, and eventually of 4-hydroxybenzoic acid by HPLC with UV detection at 254 nm in syrup as a pharmaceutical formulation. HPLC analysis was employed on the reversed phase C18 with methanol and 0. 01 M dibasic ammonium phosphate (ρr = 60: 40, pH 4. 0). Validation was performed using standards and a pharmaceutical preparation containing the compounds described above.