18683-91-5

Basic information

• Product Name: Ambroxol
• Synonyms: 4-((2-amino-3,5-dibromobenzyl)amino)-(e)-cyclohexano;5-dibromophenyl)methyl)amino)-4-(((2-amino-trans-cyclohexano;Cyclohexanol, 4-((2-amino-3,5-dibromobenzyl)amino)- (E)-;Cyclohexanol, 4-[[(2-amino-3,5-dibromophenyl)methyl]amino]-, trans-;n-(2-amino-3,4-dibromociclohexil)-trans-4-aminociclohexanol;n-(2-amino-3,4-dibromocyclohexyl)-trans-4-aminocyclohexanol;N-(trans-4-Hidroxiciclohexil)-(2-amino-3,5-dibromobencil)amina;N-(trans-4-Hydroxycyclohexyl)-(2-amino-3,5-dibromobenzyl)-amine
• CAS NO: 18683-91-5
• Molecular Formula: C₁₃H₁₈Br₂N₂O
• Molecular Weight: 378.1
• EINECS: 242-500-3
• Product Categories: API
• Mol File: 18683-91-5.mol

Chemical Properties

• Melting Point: 233-234 C
• Boiling Point: 468.647 °C at 760 mmHg
• Flash Point: 237.23 °C
• Appearance: /
• Density: 1.5863 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6220 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Soluble in Water.
• PKA: 15.12±0.40(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Ambroxol(CAS DataBase Reference)
• NIST Chemistry Reference: Ambroxol(18683-91-5)
• EPA Substance Registry System: Ambroxol(18683-91-5)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 36-26
• WGK Germany: 3
• RTECS: GV8423000
• Hazardous Substances Data: 18683-91-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ambroxol is used as an expectorant for promoting the removal of mucus from the respiratory tract, facilitating easier breathing and reducing coughing. Its bronchosecretolytic properties make it a valuable component in the treatment of respiratory conditions.
Used in Antioxidant Applications:
Ambroxol is used as an antioxidant for its ability to block the generation of reactive oxygen species, which can cause cellular damage and contribute to various diseases. Its radical scavenging activity helps protect cells from oxidative stress and supports overall health.
Used in Inflammatory Conditions:
Ambroxol is used as an anti-inflammatory agent for its capacity to inhibit doxorubicin-induced lipid peroxidation and the release of inflammatory mediators from human leukocytes and mast cells. This makes it a potential therapeutic option for managing inflammation-related disorders.

Originator

Mucosolvan,Thomae,W. Germany,1980

Manufacturing Process

6.5 g of N-(trans-p-hydroxycyclohexyl)-(2-aminobenzyl)-amine were dissolved in a mixture of 80 cc of glacial acetic acid and 20 cc of water, and then 9.6 g of bromine were added dropwise at room temperature while stirring the solution. After all of the bromine had been added, the reaction mixture was stirred for two hours more and was then concentrated in a water aspirator vacuum. The residue was taken up in 2 N ammonia, the solution was extracted several times with chloroform, and the organic extract solutions were combined and evaporated. The residue, raw N-(trans-phydroxycyclohexyl)-( 2-amino-3,5-dibromobenzyl)-amine, was purified with chloroform and ethyl acetate over silica gel in a chromatographic column, the purified product was dissolved in a mixture of ethanol and ether, and the solution was acidified with concentrated hydrochloric acid. The precipitate formed thereby was collected and recrystallized from ethanol and ether, yielding N-(trans-p-hydroxycyclohexyl)-(2-amino-3,5-dibromobenzyl)-amine hydrochloride, MP 233-234.5°C (decomposition).

Therapeutic Function

Expectorant

References

1) Teramoto et al. (1999), Effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary diseases; Pharmacology, 59 135 2) Nowak et al. (1995), Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice; Free Radic. Biol. Med., 19 659 3) Gibbs et al. (1999), Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells; Inflamm. Res., 48 86

InChI:InChI=1/C13H18Br2N2O/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10/h5-6,10-11,17-18H,1-4,7,16H2/t10-,11-

Upstream product

• 96039-76-8 trans-4-chloro-2-cyclohexen-1-yl acetate 
• 23828-92-4 ambroxol hydrochloride 
• 95-53-4 o-toluidine 
• 27489-62-9 trans-4-hydroxycyclohexylamine 
• 50739-76-9 (2-amino-3,5-dibromophenyl)methanol 
• 50910-55-9 3,5-dibromo-2-amino benzaldehyde 
• 861787-48-6 3,5-dibromo-2-nitro-benzaldehyde 
• 552-89-6 2-nitro-benzaldehyde 

Downstream Products

• 301669-90-9 4-[(2-tert-butoxycarbonylamino-3,5-dibromophenyl)methylamino]trans cyclohexanol 
• 1241045-90-8 (2R,3R,4S,5S,6S)-2-(4-(2-amino-3,5-dibromobenzylamino)-cyclohexyloxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 1445719-53-8 4-(2-amino-3,5-dibromobenzylamino)cyclohexanone 
• 96989-76-3 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid trans-4-[[(2-amino-3,5-dibromophenyl)methyl]amino]cyclohexanol 
• 23828-92-4 ambroxol hydrochloride 

Related news

Ambroxol (cas 18683-91-5) as a pharmacological chaperone for mutant glucocerebrosidase09/30/2019

Gaucher disease (GD) is characterized by accumulation of glucosylceramide in lysosomes due to mutations in the GBA1 gene encoding the lysosomal hydrolase β-glucocerebrosidase (GCase). The disease has a broad spectrum of phenotypes, which were divided into three different Types; Type 1 GD is not...detailed

Original articleThe chaperone activity and toxicity of Ambroxol (cas 18683-91-5) on Gaucher cells and normal mice09/29/2019

Gaucher disease (GD), caused by a defect of acid β-glucosidase (β-Glu), is one of the most common sphingolipidoses. Recently, ambroxol, an FDA-approved drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified as a chemical chaperone for GD. In the...detailed

Original ArticleCiprofloxacin plus erythromycin or Ambroxol (cas 18683-91-5) ameliorates endotracheal tube-associated Pseudomonas aeruginosa biofilms in a rat model09/28/2019

Background and objectivePseudomonas aeruginosa is a multi-drug resistant bacterium, with its biofilm-growing mucoid (alginate-producing) strains being particularly resistant. As atomized drug administration is a common practice in pediatric patients, we compared the effect of inhalational therap...detailed

Inhalation of Ambroxol (cas 18683-91-5) inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway10/01/2019

Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying wo...detailed

Time-shifted co-administration of sub-analgesic doses of Ambroxol (cas 18683-91-5) and pregabalin attenuates oxaliplatin-induced cold allodynia in mice09/26/2019

BackgroundOxaliplatin-induced cold allodynia is a frequent complication appearing in patients treated with this anti-tumor drug. Since, there are no clear algorithms to overcome this painful condition effectively, it is important to establish novel strategies for its treatment.detailed

Short CommunicationEffect of Ambroxol (cas 18683-91-5) chaperone therapy on Glucosylsphingosine (Lyso-Gb1) levels in two Canadian patients with type 3 Gaucher disease09/24/2019

Type 3 Gaucher disease (GD3) is characterized by progressive neurological features in addition to the typical systemic manifestations. Enzyme replacement therapy (ERT), the main stay treatment for Gaucher disease (GD), is not efficacious for the neurological manifestations. Ambroxol, in combinat...detailed

Protective effects of Ambroxol (cas 18683-91-5) in psoriasis like skin inflammation: Exploration of possible mechanisms09/10/2019

The purpose of this study was to investigate the protective effects of ambroxol in psoriasis-like skin inflammation both in vitro and in vivo and delineate the molecular mechanism of ambroxol. Our data demonstrated that ambroxol has an imperative role in inhibiting the lipopolysaccharide (LPS) s...detailed

Relevant articles and documents

Preparation method of ambroxol hydrochloride

The invention discloses a preparation method of ambroxol hydrochloride, which comprises the steps of 1) reacting (A) o-aminodibromobenzaldehyde (I) with (E)-p-aminocyclohexanol (II) to obtain Schiff base; 2) reducing a carbon-nitrogen double bond C = N by (E)-4-[(2-amino-3, 5-dibromobenzylidene) amino] cyclohexanol to obtain ambroxol; and 3) salifying to obtain the finished product ambroxol hydrochloride (compound 1). The route is simple, the product is obtained through condensation, reduction and salification, aldehyde and amido react to generate Schiff base, and the reaction yield is relatively high; and in the reduction reaction of ambroxol, a sodium borohydride zinc chloride complexing system is adopted, the catalytic effect is better, and the production cost is further reduced. The method has the advantages of simple process, low safety and environmental protection risk, easily available raw materials, simple equipment requirements, very little generated wastewater, and easy treatment of three wastes to reach the standard.

Ambroxol hydrochloride synthesis method

The invention discloses an ambroxol hydrochloride synthesis method, which comprises: in a first-step bromination reaction, adding water to o-methylaniline, cooling, adding a hydrobromic acid solutionin a dropwise manner, carrying out a reaction, controlling the temperature at 30-60 DEG C, adding bromine, hydrogen peroxide and a sodium hydroxide solution in a dropwise manner, carrying out a reaction, and filtering to obtain 2,4-dibromo-6-(bromomethyl)aniline; and in a second-step amination reaction, sequentially adding DMF, potassium carbonate and trans cyclohexanolamine to the prepared 2,4-dibromo-6-(bromomethyl)aniline, heating to a temperature of 90-110 DEG C, carrying out thermal insulation for 2-6 h, adding toluene, carrying out stirring crystallization, and filtering to obtain ambroxol. The invention provides a new ambroxol hydrochloride synthesis process, wherein the reaction conditions are artfully controlled at the benzene ring section, the halogens at the ring and the side chain are respectively replaced with bromine for replacing chlorine, and the bromination is sequentially performed and is completed in one step, such that the selectivity of the linking reaction betweenthe benzene ring and the cyclohexyl ring is good, and the yield is high.

Preparation method and application of 2-amino-3,5-bibromobenzyl intermediate compound

The invention provides a preparation method of a 2-amino-3,5-bibromobenzyl intermediate compound and further discloses an application of the 2-amino-3,5-bibromobenzyl intermediate compound in preparation of bromhexine and ambroxol. A cheap and available raw material 2-amino-3,5-dibromobenzaldehyde is adopted, 2-amino-3,5-dibromobenzyl alcohol is obtained through reduction, and the reaction condition is milder; N'N-carbonyldiimidazole is used for activating hydroxyl of 2-amino-3,5-dibromobenzyl alcohol to produce active ester, and the active ester is subjected to a condensation reaction with N-methylcyclohexylamine and trans-p-aminocyclohexanol to produce corresponding products respectively. The preparation method has the advantages that the reproducibility is good, the process is simple, the product purity is high and potential gene poison impurities can be avoided, and the medication safety of the 2-amino-3,5-bibromobenzyl intermediate compound can be further improved.

Ambroxol hydrochloride synthetic method

The invention belongs to the field of pharmaceutical synthesis and particularly discloses a synthesis method of ambroxol hydrochloride. The synthesis method comprises the steps of brominating o-nitrobenzaldehyde serving as a starting raw material to obtain 2-nitro-3, 5-dibromobenzaldehyde; reacting the obtained 2-nitro-3, 5-dibromobenzaldehyde and trans-4-aminocyclohexanol; and then, reducing and salifying hydrochloride to finally prepare ambroxol hydrochloride. The synthesis method disclosed by the invention is low in raw material cost, simple in operation, safe and environment-friendly, capable of simplifying the production process and increasing the yield and purity of products and suitable for industrial production.

Synthesis, structural characterization and Hirshfeld analysis studies of three novel co-crystals of trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol with hydroxyl benzoic acids

Combination of active pharmaceutical ingredients, trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol (AMB) and some organic acids, e.g., p-hydroxybenzoic acid (PHBA), m-hydroxybenzoic acid (MHBA), and 3,4-dihydroxy benzoic acid (DHBA), yield three novel co-crystals characterized by X-ray single-crystal, Fluorescence spectroscopy and thermal analysis (DSC and TGA), which included co-crystal 1 with 2:2: 1 stoichiometry of AMB, PHBA and H2O, co-crystal 2 with 1:1 stoichiometry of AMB and MHBA, and co-crystal 3 with 1:1:1 stoichiometry of AMB, DHBA and CH3OH. Constituents of the co-crystalline phase were also investigated in terms of Hirshfeld surfaces. In the crystal lattice, a three-dimensional hydrogen-bonded network is observed, including formation of a two-dimensional molecular scaffolding motif. Hirshfeld surfaces and fingerprint plots of three co-crystals show that structures are stabilized by H?H, N-H?O, H?Br and C?H intermolecular interactions. Besides, the studies of the solubility showed that this co-crystal strategy could promote the solubility of AMB and follow the order: co-crystal 1 co-crystal 2 co-crystal 3.

Synthesis of chiral and achiral analogues of ambroxol via palladium-catalysed reactions

Chiral cis- and trans-4-aminocyclohex-2-enols and achiral 4-aminocyclohexanols, which all are analogues of ambroxol, are prepared via stereoselective allylic substitution of cyclohex-2-ene-1,4-diol derivatives or 1-acetoxy-4-chlorocyclohex-2-ene. The chiral target molecules are obtained in enantiomerically pure form by employing a previously described enantiodivergent synthesis of cis- and trans-4-aminocyclohex-2-enols. It has been found that bis(amine) nucleophiles 7a and 7b react only at the benzylic amino group under the conditions employed.

Effervescent systems using reaction doping agents

The effervescent tablet contains an effervescent system composed of carrier crystals of at least one solid, edible, organic acid, at least one component which forms gas by reacting with the acid with salt formation and at least one salt formed from the acid and the gas-forming component. A first layer of a different acid and a second layer of a (preferably acidic) salt of at least one of the two acids are applied to the carrier crystals. Of the total amount of the acid(s) used and of the gas-forming components, 10 to 40, in particular 10 to 20, percent by weight are in the form of the salts, preferably in the form of acidic salts. Carrier crystals are, in particular, citric acid, malic acid, tartartic acid, monosodium citrate and/or ascorbic acid. The first layer may contain gluconic acid delta-lactone and is preferably covered with citric acid, malic acid and/or tartaric acid. This is covered with a layer of a monosalt formed by reaction of part of the total amount of the gas-forming component with at least one of the acids used.