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Azelaic acid (AzA), or nonanedioic acid, is an organic compound with the formula HOOC(CH2)7COOH.
This saturated dicarboxylic acid exists as a white powder.
Azelaic acid (AzA) is found in wheat, rye, and barley.
CAS: 123-99-9
MF: C9H16O4
MW: 188.22
EINECS: 204-669-1
Synonyms
azelaicacid,technicalgrade;Azelainic acid;Emerox 1110;Emerox 1144;emerox1110;emerox1144;Emery's L-110;ninandioic acid
Azelaic acid (AzA) is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of several hair and skin conditioners.
In medicine, topical formulations of Azelaic acid (AzA) are used in the treatment of acne vulgaris, where they exert antimicrobial and keratolytic effects that reduce clogged hair follicles and inflammation.
In plants, Azelaic acid (AzA) functions as a mobile signaling molecule that primes systemic acquired resistance against pathogens by inducing the accumulation of salicylic acid.
Azelaic acid (AzA) also inhibits tyrosinase.
Azelaic acid (AzA) is a topical antiacne agent which exerts its therapeutic action through a myriad of antimicrobial, antiproliferative and cytostatic effects.
In vitro, Azelaic acid (AzA) hasbeen shown to inhibit DNA polymerases in several tumor cell lines.
Azelaic acid (AzA) is a naturally occurring saturated binary carboxylic acid containing nine carbon atoms, which is an important medium and long chain dibasic acid.
Azelaic acid (AzA) has been used in cosmetics for a long time.
Azelaic acid (AzA) has the function of inhibiting excessive secretion of oil, removing acne and freckles, and whitening skin, and it is very safe.
Azelaic acid (AzA) Chemical Properties
Melting point: 98 °C
Boiling point: 286 °C100 mm Hg(lit.)
Density: 1,029 g/cm3
Vapor density: 6.5 (vs air)
Vapor pressure: <1 mm Hg ( 20 °C)
Refractive index: 1.4303
Fp: 215 °C
Storage temp.: Store below +30°C.
Solubility: 2.4g/l
Form: Slightly Crystalline Powder or Flakes
pka: 4.53, 5.33(at 25℃)
Color: White to slightly yellow
PH: 3.5 (1g/l, H2O)
Water Solubility: 2.4 g/L (20 ºC)
Merck: 14,905
BRN: 1101094
Stability: Stable. Combustible. Incompatible with bases, strong oxidizing agents. Readily biodegrades in soil and water with >70% DOC reduction after 28 days.
InChIKey: BDJRBEYXGGNYIS-UHFFFAOYSA-N
LogP: 1.57 at 25℃
CAS DataBase Reference: 123-99-9(CAS DataBase Reference)
NIST Chemistry Reference: Azelaic acid (AzA) (123-99-9)
EPA Substance Registry System: Azelaic acid (AzA) (123-99-9)
Azelaic acid (AzA) is an organic compound with the formula (CH2)7(CO2H)2.
This saturated dicarboxylic acid exists as a white powder.
Azelaic acid (AzA) is found in wheat, rye, and barley.
Azelaic acid (AzA) is a component of a number of hair and skin conditioners.
Azelaic acid (AzA) is the best known dicarboxylic acid.
Azelaic acid (AzA)'s name stems from the action of nitric acid (azote, nitrogen, or azotic, nitric) oxidation of oleic or elaidic acid.
Azelaic acid (AzA) was detected among products of rancid fats.
Azelaic acid (AzA)'s origin explains for its presence in poorly preserved samples of linseed oil and in specimens of ointment removed from Egyptian tombs 5000 years old.
Azelaic acid (AzA) was prepared by oxidation of oleic acid with potassium permanganate, but now by oxidative cleavage of oleic acid with chromic acid or by ozonolysis.
Azelaic acid (AzA) is used, as simple esters or branched-chain esters) in the manufacture of plasticizers (for vinyl chloride resins, rubber), lubricants and greases.
Azelaic acid (AzA) is now used in cosmetics (treatment of acne).
Azelaic acid (AzA) displays bacteriostatic and bactericidal properties against a variety of aerobic and anaerobic micro-organisms present on acne-bearing skin.
Azelaic acid (AzA) was identified as a molecule that accumulated at elevated levels in some parts of plants and was shown to be able to enhance the resistance of plants to infections.
Azelaic acid (AzA) is a naturally occurring dicarboxylic acid produced by the yeast Malassezia furfur.
Azelaic acid (AzA) inhibits tyrosinase, a rate-limiting enzyme in the synthesis of the pigment melanin.
Azelaic acid (AzA) may explain why diminution of melanin pigmentation occurs in the skin of some patients with pityriasis versicolor, a disease caused by M. furfur.
Azelaic acid (AzA) is bacteriostatic against a number of species thought to participate in the pathogenesis of acne, including Propionibacterium acnes.
The drug may also reduce microcomedo formation by promoting normalization of epidermal keratinocytes.
Azelaic acid (AzA) is an alpha,omega-dicarboxylic acid that is heptane substituted at positions 1 and 7 by carboxy groups.
Azelaic acid (AzA) has a role as an antibacterial agent, an antineoplastic agent, a dermatologic drug and a plant metabolite.
Azelaic acid (AzA) is a dicarboxylic fatty acid and an alpha,omega-dicarboxylic acid.
Azelaic acid (AzA) is a conjugate acid of an azelaate(2-) and an azelaate.
Azelaic acid (AzA) is used as a therapeutic agent in dermatology.
In plants, Azelaic acid (AzA) serves as a "distress flare" involved in defense responses after infection.
Azelaic acid (AzA) serves as a signal that induces the accumulation of salicylic acid, an important component of a plant's defensive response.
Uses
Azelaic acid (AzA) is used in lacquers, alkyd resins, plasticizers, adhesives, polyamides, urethane elastomers, and organic syntheses.
Azelaic acid (AzA) is also used in treating of acne.
Azelaic acid (AzA), also known as azalea acid, is a white to slightly yellow powder.
Azelaic acid (AzA) is a medium-long chain dibasic acid.
In recent years, with the rapid development of the organic synthetic chemical industry, the demand for medium and long chain dibasic acids is increasing.
The medium and long chain dibasic acids and their derivatives have a wide range of industrial applications and a broad product market.
Polymers and related materials
Esters of this dicarboxylic acid find applications in lubrication and plasticizers.
In lubricant industries, Azelaic acid (AzA) is used as a thickening agent in lithium complex grease.
With hexamethylenediamine, Azelaic acid (AzA) forms Nylon-6,9, which finds specialized uses as a plastic.
Medical
In 2023, Azelaic acid (AzA) was the 309th most commonly prescribed medication in the United States, with more than 200,000 prescriptions.
Azelaic acid (AzA) is used to treat mild to moderate acne, both comedonal acne and inflammatory acne.
Azelaic acid (AzA) belongs to a class of chemicals called dicarboxylic acids.
Azelaic acid (AzA) works by killing acne bacteria that infect skin pores.
Azelaic acid (AzA) also decreases the production of keratin, which is a natural substance that promotes the growth of acne bacteria.
Azelaic acid (AzA) is also used as a topical gel treatment for rosacea, due to its ability to reduce inflammation.
Azelaic acid (AzA) clears the bumps and swelling caused by rosacea.
In topical pharmaceutical preparations and scientific research Azelaic acid (AzA) is typically used in concentrations between 15% and 20% but some research demonstrates that in certain vehicle formulations, the pharmaceutical effects of 10% Azelaic acid (AzA) have the potential to be fully comparable to that of some 20% creams.
Acne treatment
Azelaic acid (AzA) is effective for mild to moderate acne when applied topically at a 15%-20% concentration.
In patients with moderate acne, twice daily application over 3 months of 20% Azelaic acid (AzA)significantly reduced the number of comedones, papules, and pustules; at this strength, it's considered to be as effective as benzoyl peroxide 5%, tretinoin 0.05%, erythromycin 2%, and oral tetracycline at 500 mg-1000 mg.
In a comparative review of effects of topical Azelaic acid (AzA), Salicylic acid, Nicotinamide, Sulfur, Zinc, and alpha-hydroxy acid, Azelaic acid (AzA) had more high-quality evidence of effectiveness than the rest.
Results can be expected after 4 weeks of twice-daily treatment.
The effectiveness of long-term use is unclear, but Azelaic acid (AzA)'s been recommended that AzA be used for at least 6 months continuously for maintenance.
Whitening agent
Azelaic acid (AzA) is used for the treatment of skin pigmentation, including melasma and postinflammatory hyperpigmentation, particularly in those with darker skin types.
Azelaic acid (AzA) has been recommended as an alternative to hydroquinone.
As a tyrosinase inhibitor, azelaic acid reduces synthesis of melanin.
According to one report in 1988, Azelaic acid (AzA) in combination with zinc sulfate in vitro was found to be a potent (90% inhibition) 5α-reductase inhibitor, similar to the hair loss drugs finasteride and dutasteride.
In vitro research during mid-1980s evaluating azelaic acid's depigmenting (whitening) capability concluded it is effective (cytotoxic to melanocytes) at only high concentrations.
A 1996 review claimed 20% Azelaic acid (AzA)is as potent as 4% hydroquinone after a period of application of three months without the latter's adverse effects and even more effective if applied along with tretinoin for the same period of time.
Biological function
Plants biology
In plants, Azelaic acid (AzA) functions as an endogenous signaling molecule that plays a central role in systemic defense responses after infection.
Azelaic acid (AzA) acts as a "distress flare," produced primarily in response to biotic stress such as pathogen attack, and is transported from infected tissues to distant parts of the plant.
There, Azelaic acid (AzA) primes systemic acquired resistance (SAR) against a broad spectrum of pathogens by inducing the accumulation of salicylic acid, a key component of the plant's immune response.
Mechanistically, Azelaic acid (AzA) works in concert with other mobile signals, including glycerol-3-phosphate and specific lipid transfer proteins, to orchestrate a systemic defense network that enhances disease resistance and enables rapid defensive responses to subsequent infections.
Human Biology
Azelaic acid (AzA) treats acne through a multifaceted mechanism that includes antibacterial, anti-keratinizing, and anti-inflammatory activities, as well as direct effects on skin microflora.
Azelaic acid (AzA) exerts bacteriostatic action against Propionibacterium acnes and Staphylococcus epidermidis by disrupting microbial cellular metabolism and membrane pH balance, resulting in reduced bacterial proliferation without promoting resistance.
In keratinocytes, azelaic acid inhibits DNA, RNA, and protein synthesis, thus normalizing follicular keratinization, which helps prevent the formation of comedones—clogged hair follicles that can develop into acne lesions and are considered a hallmark of the disease.
Additionally, Azelaic acid (AzA)'s anti-inflammatory properties decrease the production of reactive oxygen species and pro-inflammatory cytokines, collectively reducing both visible inflammation and the severity of acne lesions.
Production
Azelaic acid (AzA) is industrially produced by the ozonolysis of oleic acid.
The side product is nonanoic acid.
Azelaic acid (AzA) is produced naturally by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin.
The bacterial degradation of nonanoic acid gives azelaic acid.
Production Methods
Azelaic acid (AzA) is industrially produced by the ozonolysis of oleic acid.
The side product is nonanoic acid.
Azelaic acid (AzA) is produced naturally by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin.
The bacterial degradation of nonanoic acid gives azelaic acid.
Manufacturing Process
Two step oxidation of tall oil fatty acid using peroxyformic acid and nitric acid/sodium metavanadate were used to produce azelaic acid.
Step 1 (derivatization of the double bond):
A hydroxy acyloxy derivative of tall oil fatty acid (TOFA) was prepared by mixing 200 g of TOFA (63% oleic acid, 31% linoleic acid) with 500 mL of formic acid.
The resulting mixture was vigorously stirred by magnetic action.
Hydrogen peroxide solution, 180 mL of 35% by weight, was added in aliquots to the mixture throughout the course of the reaction.
A third of the total amount of peroxide solution was added at once to initiate the reaction.
The peroxyformic acid in this case was prepared in situ.
The start of the reaction was signalled by heat evolution and a dramatic color change, from pale yellow to deep rust red.
The exothermicity of the reaction required external cooling to control the temperature.
The reaction was maintained at 40°C to minimize oxygen loss through the decomposition of the peroxide.
As required, the temperature of the reaction was maintained with an external heating source.
A total reaction time of 5 to 6 hours was necessary for complete reaction.
The end of the reaction was indicated by a color change, the reaction mixture changed from rust red back to yellow.
One last aliquot of peroxide solution was added at the end of the reaction period to provide a peroxide atmosphere during the reaction work-up.
TOFA as a substrate produced a mixture of mono- and dihydroxy formoxystearic acid from the oleic and linoleic acid components, respectively.
The final product was obtained in essentially 100% yield by removing the unreacted formic acid and hydrogen peroxide as well as water.
Azelaic acid (AzA) was obtained as a viscous, syrupy yellow oil that upon gas chromatographic analysis of the methyl esters of the reaction mixture gave no evidence of unreacted substrate.
Step 2 (oxidation of derivative obtained from step 1):
A 2 L three neck flask fitted with an air condenser attached to a gas scrubbing apparatus was filled with 500 mL of concentrated nitric acid (70% by weight).
The acid was stirred by magnetic action and 1 g of sodium metavanadate was added to Azelaic acid (AzA).
The resulting mixture was heated slowly to 40°-50°C.
At this point a small amount of product as obtained from Step 1 was added to the acid-catalyst mixture.
Heating was continued until a sharp temperature increase accompanied by evolution of NOx gases was observed.
The reaction temperature was self-sustained with the addition of aliquots of the hydroxy formoxy ester mixture obtained from Step 1. (External cooling may be required throughout the substrate addition period to keep the temperature within 65°-70°C).
At the end of the addition period the reaction temperature was maintained for an additional 1.5 to 2 hours, for a total reaction time of 3 hours.
The final products were obtained by quenching the reaction by adding excess water and extracting the organic layer with purified diethyl ether.
he ether extract was dried over anhydrous sodium sulfate overnight before its removal with a roto-vap apparatus.
Addition of petroleum ether (boiling range 35°- 60°C) to the product mixture caused precipitation of the diacid component.
Vacuum filtration was used to remove the solid diacids from the liquid monoacid mixture.
The latter was obtained by removing the excess petroleum ether from the resulting filtrate.
Quantitative analysis by gas chromatography of the methyl esters showed that the products to be 96% yield of diacid (66% azelaic, 30% suberic).
