123-99-9 Usage
Description
Azelaic acid is a topical antiacne agent which exerts its therapeutic action through a
myriad of antimicrobial, antiproliferative and cytostatic effects. In vitro, azelaic acid hasbeen shown to inhibit DNA polymerases in several tumor cell lines.
Chemical Properties
Different sources of media describe the Chemical Properties of 123-99-9 differently. You can refer to the following data:
1. Azelaic acid is an organic compound with the formula (CH2)7(CO2H)2. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a component of a number of hair and skin conditioners.
2. white to cream solid
3. Nonanedioic acid is the best known dicarboxylic acid. Its name stems from the action of nitric acid (azote, nitrogen, or azotic, nitric) oxidation of oleic or elaidic acid. It was detected among products of rancid fats. Its 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 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 is used, as simple esters or branched-chain esters) in the manufacture of plasticizers (for vinyl chloride resins, rubber), lubricants and greases. Azelaic acid is now used in cosmetics (treatment of acne). It displays bacteriostatic and bactericidal properties against a variety of aerobic and anaerobic micro-organisms present on acne-bearing skin. Azelaic acid 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.
Originator
Schering AG (W. Germany)
Uses
Different sources of media describe the Uses of 123-99-9 differently. You can refer to the following data:
1. antiacne, antiproliferative agent
2. antifungal, binds to membrane sterols
3. Azelaic acid is used in lacquers, alkyd resins, plasticizers,
adhesives, polyamides, urethane elastomers, and organic
syntheses. Azelaic acid is also used in treating of
acne.
Application
Different sources of media describe the Application of 123-99-9 differently. You can refer to the following data:
1. Azelaic acid, also known as azalea acid, is a white to slightly yellow powder. Azelaic acid is a medium-long chain dibasic acid[1]. 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.
2. Polymers and related materials Esters of this dicarboxylic acid find applications in lubrication and plasticizers. With hexamethylenediamine azelaic acid forms Nylon - 6,9, which finds specialized uses as a plastic. Medical Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne . It belongs to a class of medication called dicarboxylic acids. It works by killing acne bacteria that infect skin pores. It also decreases the production of keratin, which is a natural substance that promotes the growth of acne bacteria Azelaic acid is also used as a topical gel treatment for rosacea, due to its ability to reduce inflammation . It clears the bumps and swelling caused by Rosacea. Azelaic acid has been used for treatment of skin pigmentation including melasma and post inflammatory hyper pigmentation , particularly in those with darker skin types. It has been recommended as an alternative to hydroquinone (HQ). As a tyrosinase inhibitor, azelaic acid reduces synthesis of melanin. Brand names AzClear Action ( 20 % lotion, Ego Pharmaceuticals), Azelex (20% cream, Allergan), White Action cream (20 % cream ,2 % glycolic acid), SynCare), Finacea (15 % gel, Intendis/Berlex Laboratories, subsidiaries of Bayer AG), Finevin (20 % cream, Intendis / Berlex Laboratories), Skinoren (20 % cream or 15% gel, Intendis), Melazepam, Strata Dermatologics, 2oz, Mixed Dicarboxylic Acids 20 % Azelaic Acid Cream.,and Azaclear (azelaic acid and niacinamide, Epikinetics LLC). .
Indications
Azelaic acid (Azelex) is a naturally occurring dicarboxylic
acid produced by the yeast Malassezia furfur.
Azelaic acid inhibits tyrosinase, a rate-limiting enzyme
in the synthesis of the pigment melanin. This 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 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.
Production Methods
Azelaic acid is industrially produced by the ozonolysis of oleic acid. The side product is nonanoic acid. It 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.
Preparation
Azelaic acid is made by the ozonolysis of oleic 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. It 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 it. 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. The 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).
Brand name
Azelex (Allergan); Finacea (Intendis);Skinoren.
Therapeutic Function
Antiacne, Depigmentor
Synthesis Reference(s)
Journal of the American Chemical Society, 77, p. 4846, 1955 DOI: 10.1021/ja01623a048Organic Syntheses, Coll. Vol. 2, p. 53, 1943
General Description
Azelaic acid is used as a therapeutic agent in dermatology.
Biochem/physiol Actions
Azelaic acid is a potent inhibitor of 5α-reductase activity. It is a reversible competitive inhibitor of thioredoxin reductase in human melanoma cells.
Biotechnological Applications
In plants, azelaic acid serves as a "distress flare" involved in defense responses after infection. It serves as a signal that induces the accumulation of salicylic acid, an important component of a plant's defensive response.
Mechanism of action
Naturally occurring dicarboxylic acid that is bacteriostatic
to Propionibacterium acnes. It also decreases conversion of testosterone
to 5{pi}ga-dihydrotestosterone (DHT) and alters keratinization of the microcomedone.
It may also be beneficial in the treatment of melasma. The
mechanism of action is not fully understood. Deoxyribonucleic acid (DNA)
synthesis is reduced, and mitochondrial cellular energy products are inhibited
in melanocytes.
Clinical Use
Azelaic acid is used for the treatment of mild to
moderate acne, particularly in cases characterized by
marked inflammation-associated hyperpigmentation.
Safety Profile
Low toxicity by ingestion. A skinand eye irritant. Closely related to glutaric acid and adipicacid. Combustible when exposed to heat or flame; canreact with oxidizing materials.
Purification Methods
Recrystallise it from H2O(charcoal) or thiophene-free *benzene. The acid can be dried by azeotropic distillation with toluene, the residual toluene solution is then cooled and filtered, and the precipitate is dried in a vacuum oven. It has been purified by zone refining or by sublimation onto a cold finger at 10-3torr. It distils above 360o with partial formation of the anhydride. The dimethyl ester has m –3.9o and b 140o/8mm. [Hill & McEwen Org Synth Coll Vol II 53 1943, Beilstein 2 IV 2055.]
Check Digit Verification of cas no
The CAS Registry Mumber 123-99-9 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 3 respectively; the second part has 2 digits, 9 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 123-99:
(5*1)+(4*2)+(3*3)+(2*9)+(1*9)=49
49 % 10 = 9
So 123-99-9 is a valid CAS Registry Number.
InChI:InChI=1/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)/p-2
123-99-9Relevant articles and documents
Lapworth,Mottram
, p. 1987 (1925)
γ-hydroxyalkenals are oxidatively cleaved through Michael addition of acylperoxy radicals and fragmentation of intermediate β-hydroxyperesters
Balamraju, Yuvaraju N.,Sun, Mingjiang,Salomon, Robert G.
, p. 11522 - 11528 (2004)
Oxidative cleavage of arachidonate (C20) and linoleate (C 18) phospholipids generates truncated C8 or C12 γ-hydroxyalkenal phospholipids as well as C5 or C9 carboxyalkanoate phospholipids,
Preparation, characterization, and theoretical studies of azelaic acid derived from oleic acid by use of a novel ozonolysis method
Kadhum, Abdul Amir H.,Wasmi, Bilal A.,Mohamad, Abu Bakar,Al-Amiery, Ahmed A.,Takriff, Mohd S.
, p. 659 - 668 (2012)
Environmentally friendly manufacture of organic compounds has been intensively reexamined in recent years. Many excellent methods have been devised to produce organic compounds from renewable resources. Azelaic acid has been produced by ozonolysis of oleic acid. The reaction was performed in a Bach bubbling reactor, with fine bubbles, at high temperature (150 °C) without utilizing any catalyst or any solvent. Yield of the reaction was 20% after 2 h. Production of azelaic acid was confirmed by use of FT-IR and 1H NMR spectroscopic data and high-performance liquid chromatography of both synthesized and reference azelaic acid. A theoretical study was performed to obtain quantum chemical data for azelaic acid and to optimize the molecule's geometry. Springer Science+Business Media B.V. 2011.
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Acker,Anderson
, p. 1162 (1959)
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Thermoplastic polyester amides derived from oleic acid
Zuo, Jiaqing,Li, Shaojun,Bouzidi, Laziz,Narine, Suresh S.
, p. 4503 - 4516 (2011)
Three lipid-based Polyester Amides (PEAs) with varying ratios of ester and amide linkages were synthesized. Oleic acid was used as the starting material to produce the intermediates, characterized by MS and NMR, used for polymerization. PEAs were characterized by FTIR and GPC. The PEAs were constrained to have similar number average molecular weights, in the 2 × 104 range, thereby enabling comparison of their physical properties from a structural perspective. The thermal behavior of the polymers was assessed by DSC, DMA and TGA. Thermal degradation was not affected by ester/amide ratios, but Tg increased non-linearly with decreasing ester/amide ratios and correlated with hydrogen-bond density and repeating unit chain length. Crystallinity was studied by XRD and DSC. Degree of crystallization and multiple melting behavior as a function of cooling kinetics were explained well by hydrogen-bond density, repeating unit chain length and density of ester moieties. Mechanical properties were investigated by DMA and Tensile Analysis, with a non-linear increase of storage and tensile moduli recorded as a function of decreasing ester/amide ratios. The findings suggest how approaches to the synthesis of lipid-based PEAs can be targeted to the delivery of specific physical properties.
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Nunn,Smedley-Maclean
, p. 2744 (1935)
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Scalable, sustainable and catalyst-free continuous flow ozonolysis of fatty acids
Atapalkar, Ranjit S.,Athawale, Paresh R.,Srinivasa Reddy,Kulkarni, Amol A.
supporting information, p. 2391 - 2396 (2021/04/07)
A simple and efficient catalyst-free protocol for continuous flow synthesis of azelaic acid is developed from the renewable feedstock oleic acid. An ozone and oxygen mixture was used as the reagent for oxidative cleavage of double bond without using any metal catalyst or terminal oxidant. The target product was scaled up to more than 100 g with 86% yield in a white powder form. Complete recycling and reuse of the solvent were established making it a green method. The approach is significantly energy efficient and also has a very small chemical footprint. The methodology has been successfully tested with four fatty acids making it a versatile platform that gives value addition from renewable resources.
METHOD FOR MANUFACTURING PELARGONIC ACID AND AZELAIC ACID
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Paragraph 0055-0083, (2021/07/27)
The present invention relates to a method for producing pelargonic acid and azelaic acid, and more specifically, provides a method for producing pelargonic acid and azelaic acid, which comprises the following steps of: a) reacting an unsaturated carboxylic acid compound under a tungstic acid catalyst to obtain an intermediate product comprising vicinal diol; and b) reacting the intermediate product under a transition metal hydroxide catalyst to obtain the pelargonic acid and azelaic acid. The production method is capable of producing the pelargonic acid and azelaic acid in a high yield from the unsaturated carboxylic acid compound.
Process for preparing azelaic acid
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Paragraph 0105-0108, (2021/02/19)
A process for preparing azelaic acid is disclosed. In particular, the process for preparing azelaic acid is an ozone free process. The process for preparing azelaic acid comprises a step of decarboxylation of tetra-carboxylic acid in the presence of a organic sulfonic acid.
