16150-44-0

Basic information

• Product Name: CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS)
• Synonyms: Sodium Cromoglicate Impurity 2;1,1'-(((2-Hydroxypropane-1,3-diyl);bis(2-hydroxy-6,1-phenylene);diethanone;CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS);1,3-bis(2-acetyl-3-hydroxyphenoxy)-2-propanol;2’,2’’’-(2-hydroxytrimethylenedioxy)bis(6-hydroxy-acetophenon;2’,2’’’-(2-hydroxytrimethylenedioxy)bis(6-hydroxyacetophenone)
• CAS NO: 16150-44-0
• Molecular Formula: C₁₉H₂₀O₇
• Molecular Weight: 360.3579
• EINECS: 240-302-1
• Mol File: 16150-44-0.mol
• Article Data: 4

Chemical Properties

• Melting Point: 168℃ (chloroform hexane )
• Boiling Point: 574.4 °C at 760 mmHg
• Flash Point: 205.3 °C
• Appearance: /
• Density: 1.321±0.06 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: 2-8°C
• PKA: 9.42±0.10(Predicted)
• CAS DataBase Reference: CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS)(CAS DataBase Reference)
• NIST Chemistry Reference: CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS)(16150-44-0)
• EPA Substance Registry System: CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS)(16150-44-0)

Safety Data

• Hazardous Substances Data: 16150-44-0(Hazardous Substances Data)

Usage

General Description

Cromolyn sodium related compound A is a chemical substance with the molecular formula (1,3-bis-(2-acetyl-3-hydroxyphenoxy)-2-propanol) (AS). It is commonly used in the pharmaceutical industry as an active ingredient in medications designed to treat asthma, allergies, and other respiratory conditions. Cromolyn sodium is known for its anti-inflammatory and anti-allergic properties, and it works by stabilizing mast cells to prevent the release of chemicals that cause inflammation in the airways. CROMOLYN SODIUM RELATED COMPOUND A (25 MG) (1,3-BIS-(2-ACETYL-3-HYDROXYPHENOXY)-2-PROPANOL) (AS) is available in the form of 25 mg tablets and is typically administered orally or through inhalation to help manage symptoms associated with asthma and allergies. Additionally, it is considered safe for use when prescribed by a healthcare professional with minimal side effects.

Synthetic route

2,6-dihydroxylacetophenone (699-83-2) + 1-(2-acetyl-3-hydroxyphenoxy)-2,3-epoxypropane (16130-28-2) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
With sodium hydroxide In ethanol for 24h; Heating;	75%

disodium cromoglicate (15826-37-6) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
With sodium hydroxide for 0.333333h; Heating;	59.7%
With potassium hydroxide In water for 2h; Reflux;

2,6-dihydroxylacetophenone (699-83-2) + epichlorohydrin (106-89-8) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
With potassium hydroxide In water; isopropyl alcohol for 48h; Heating;	37%
With potassium hydroxide
With potassium hydroxide In water; isopropyl alcohol for 48h; Heating;

2,6-dihydroxylacetophenone (699-83-2) + 1,3-dibromo-2-hydroxypropane (96-21-9) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
With potassium carbonate

2,6-dihydroxylacetophenone (699-83-2) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 24 percent / KOH / H2O / 48 h / Ambient temperature 2: 75 percent / NaOH / ethanol / 24 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 33 percent / KOH / H2O / 48 h / Ambient temperature 2: 75 percent / KOH / H2O / 2 h / Ambient temperature 3: 75 percent / NaOH / ethanol / 24 h / Heating View Scheme

1-(2-acetyl-3-hydroxyphenoxy)-3-chloro-2-propanol (16130-17-9) → (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / KOH / H2O / 2 h / Ambient temperature 2: 75 percent / NaOH / ethanol / 24 h / Heating View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + 3-methoxy-benzaldehyde (591-31-1) → (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-3-(3-methoxy-phenyl)-acryloyl]-phenoxy}-propoxy)-phenyl]-3-(3-methoxy-phenyl)-propenone (146138-43-4)

Conditions	Yield
With potassium hydroxide In methanol for 48h; Ambient temperature;	84%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + benzaldehyde (100-52-7) → (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-(3-phenyl-acryloyl)]-phenoxy}-propoxy)-phenyl]-3-phenyl-propenone (146138-42-3)

Conditions	Yield
With potassium hydroxide In methanol for 48h; Ambient temperature;	81%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + 4-methoxy-benzaldehyde (123-11-5) → (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-3-(4-methoxy-phenyl)-acryloyl]-phenoxy}-propoxy)-phenyl]-3-(4-methoxy-phenyl)-propenone (146138-44-5)

Conditions	Yield
With potassium hydroxide In methanol for 48h; Ambient temperature;	78%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + ethyl bromoacetate (105-36-2) → 1,3-bis(2-acetyl-3-carbethoxymethoxyphenoxy)-2-propanol (112489-28-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 3h; Ambient temperature;	75%

4-hydroxyphenylacetate (156-38-7) + (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + acetic anhydride (108-24-7) → 2-acetoxy-1,3-bis<3-(4-acetoxyphenyl)-4-methyl-2-oxo-2H-1-benzopyran-5-yloxy>propane (128889-97-4)

Conditions	Yield
With triethylamine for 16h; Heating;	71%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + acetic anhydride (108-24-7) → 1,3-bis(3-acetoxy-2-acetylphenoxy)-2-acetoxypropane (112489-26-6)

Conditions	Yield
With pyridine for 24h; Ambient temperature;	68%

phenylacetic acid (103-82-2) + (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + acetic anhydride (108-24-7) → 2-acetoxy-1,3-bis(4-methyl-3-phenyl-2-oxo-2H-1-benzopyran-5-yloxy)propane (128889-96-3)

Conditions	Yield
With triethylamine for 16h; Heating;	67%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + 4-aminobenzene sulfonic acid (121-57-3) → 4,4'-(2-Hydroxypropan-1,3-diyldioxy)bis[4-(3-acetyl-2-hydroxyphenylazo)benzolsulfonsaeure], Dinatriumsalz

Conditions	Yield
Stage #1: 4-aminobenzene sulfonic acid With hydrogenchloride; sodium nitrite In water cooling; Stage #2: (1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) With sodium hydroxide for 0.166667h;	33%

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + [14C2]-oxalic acid dimethyl ester → 6,6'-bis(2-hydroxy-1,3-propandiyl)bis(oxy)[α-(2-hydroxy)phenyl]bis[1,2-14C2]-2,4-dioxobutanoic acid methyl ester

Conditions	Yield
With sodium methylate In methanol; benzene at 60℃; for 4h; Substitution;

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1,3-bis(2,3-dihydro-4-oxo-2-phenyl-4H-1-benzopyran-5-yloxy)-2-propanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / KOH / methanol / 48 h / Ambient temperature 2: 67 percent / silica gel / CHCl3 / 6 h / 110 °C View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → C35H32O9

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / KOH / methanol / 48 h / Ambient temperature 2: 68 percent / silica gel / CHCl3 / 6 h / 110 °C View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → C35H32O9

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / KOH / methanol / 48 h / Ambient temperature 2: 69 percent / silica gel / CHCl3 / 6 h / 110 °C View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1-[3-(2-{3-[2-(1-Acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-3-hydroxy-phenoxy]-2-hydroxy-propoxy}-6-hydroxy-phenyl)-5-phenyl-4,5-dihydro-pyrazol-1-yl]-ethanone (146138-66-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / KOH / methanol / 48 h / Ambient temperature 2: 86 percent / hydrazine hydrate / Heating View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1,3-bis(2-cinnamoyl-3-ethxoycarbonylmethoxyphenoxy)-2-propanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / KOH / methanol / 48 h / Ambient temperature 2: 90 percent / K2CO3 / dimethylformamide / 20 h View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1-[3-[2-(3-{2-[1-Acetyl-5-(4-methoxy-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-3-hydroxy-phenoxy}-2-hydroxy-propoxy)-6-hydroxy-phenyl]-5-(4-methoxy-phenyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / KOH / methanol / 48 h / Ambient temperature 2: 85 percent / hydrazine hydrate / Heating View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1-[3-[2-(3-{2-[1-Acetyl-5-(3-methoxy-phenyl)-4,5-dihydro-1H-pyrazol-3-yl]-3-hydroxy-phenoxy}-2-hydroxy-propoxy)-6-hydroxy-phenyl]-5-(3-methoxy-phenyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / KOH / methanol / 48 h / Ambient temperature 2: 81 percent / hydrazine hydrate / Heating View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → {3-(3-{3-Ethoxycarbonylmethoxy-2-[(E)-3-(4-methoxy-phenyl)-acryloyl]-phenoxy}-2-hydroxy-propoxy)-2-[(E)-3-(4-methoxy-phenyl)-acryloyl]-phenoxy}-acetic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / KOH / methanol / 48 h / Ambient temperature 2: 90 percent / K2CO3 / dimethylformamide / 20 h View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → {3-(3-{3-Ethoxycarbonylmethoxy-2-[(E)-3-(3-methoxy-phenyl)-acryloyl]-phenoxy}-2-hydroxy-propoxy)-2-[(E)-3-(3-methoxy-phenyl)-acryloyl]-phenoxy}-acetic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / KOH / methanol / 48 h / Ambient temperature 2: 92 percent / K2CO3 / dimethylformamide / 20 h View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → (2-(1-Acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-3-{3-[2-(1-acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-3-ethoxycarbonylmethoxy-phenoxy]-2-hydroxy-propoxy}-phenoxy)-acetic acid ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 81 percent / KOH / methanol / 48 h / Ambient temperature 2: 86 percent / hydrazine hydrate / Heating 3: 82 percent / K2CO3 / dimethylformamide / 20 h View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → 1,3-bis(2-acetyl-3-carbethoxymethoxyphenoxy)-2-acetoxypropane (112489-27-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / K2CO3 / dimethylformamide / 3 h / Ambient temperature 2: 90 percent / pyridine / Ambient temperature View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) → C35H28O7 (128890-01-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 67 percent / Et3N / 16 h / Heating 2: 66 percent / 4percent NaOH / methanol / 4 h View Scheme

(1-{2-[3-(2-acetyl-3-hydroxy-phenoxy)-2-hydroxypropoxy]-6-hydroxy-phenyl}-ethanone) (16150-44-0) + oxalic acid diethyl ester (95-92-1) → ethyl 5-(3-[2-acetyl-3-hydroxyphenoxy]-2-hydroxypropoxy)-4-oxo-4H-1-benzopyran-2-carboxylate (40786-63-8)

Conditions	Yield
With hydrogenchloride; sodium In ethanol; chloroform; water

Upstream product

• 699-83-2 2,6-dihydroxylacetophenone 
• 16130-28-2 1-(2-acetyl-3-hydroxyphenoxy)-2,3-epoxypropane 
• 16130-17-9 1-(2-acetyl-3-hydroxyphenoxy)-3-chloro-2-propanol 
• 15826-37-6 disodium cromoglicate 
• 96-21-9 1,3-dibromo-2-hydroxypropane 
• 106-89-8 epichlorohydrin 

Downstream Products

• 40786-63-8 ethyl 5-(3-[2-acetyl-3-hydroxyphenoxy]-2-hydroxypropoxy)-4-oxo-4H-1-benzopyran-2-carboxylate 
• 128890-01-7 C₃₅H₂₈O₇ 
• 112489-27-7 1,3-bis(2-acetyl-3-carbethoxymethoxyphenoxy)-2-acetoxypropane 
• 146138-66-1 1-[3-(2-{3-[2-(1-Acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-3-hydroxy-phenoxy]-2-hydroxy-propoxy}-6-hydroxy-phenyl)-5-phenyl-4,5-dihydro-pyrazol-1-yl]-ethanone 
• 146138-43-4 (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-3-(3-methoxy-phenyl)-acryloyl]-phenoxy}-propoxy)-phenyl]-3-(3-methoxy-phenyl)-propenone 
• 112489-28-8 1,3-bis(2-acetyl-3-carbethoxymethoxyphenoxy)-2-propanol 
• 146138-44-5 (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-3-(4-methoxy-phenyl)-acryloyl]-phenoxy}-propoxy)-phenyl]-3-(4-methoxy-phenyl)-propenone 
• 146138-42-3 (E)-1-[2-Hydroxy-6-(2-hydroxy-3-{3-hydroxy-2-[(E)-(3-phenyl-acryloyl)]-phenoxy}-propoxy)-phenyl]-3-phenyl-propenone 
• 112489-26-6 1,3-bis(3-acetoxy-2-acetylphenoxy)-2-acetoxypropane 
• 128889-97-4 2-acetoxy-1,3-bis<3-(4-acetoxyphenyl)-4-methyl-2-oxo-2H-1-benzopyran-5-yloxy>propane 
• 128889-96-3 2-acetoxy-1,3-bis(4-methyl-3-phenyl-2-oxo-2H-1-benzopyran-5-yloxy)propane 

Relevant articles and documents

Development of advanced chemometric-assisted spectrophotometric methods for the determination of cromolyn sodium and its alkaline degradation products

Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and its alkaline degradation products (Deg1 and Deg2). Spectrophotometric mean centering ratio spectra method (MCR) and chemometric methods, including principal component regression (PCR) and partial least square (PLS-2) methods, were applied. Peak amplitudes after MCR at 367.8 nm, 373.8 nm and 310.6 nm were used within linear concentration ranges of 2–40 μg mL-1, 5–40 μg mL-1 and 10–100 μg mL-1 for CS, Deg1 and Deg2, respectively. For PCR and PLS-2 models, a calibration set of eighteen mixtures and a validation set of seven mixtures were built for the simultaneous determination of CS, Deg1 and Deg2 in the ranges of 5–13 μg mL-1, 8–16 μg mL-1, and 10–30 μg mL-1, respectively. The authors emphasize the importance of a stability-indicating strategy for the investigation of pharmaceutical products.

Synthesis and antifungal activity of 1,3-bis<2- or 4-(substituted cinnamoyl or 1-acyl-4,5-dihydro-5-substituted phenyl-1H-pyrazol-3-yl)phenoxy-2-propanols and related compounds

Condensation of 1,3-bis(2- or 4-acetylphenoxy or 2-acetyl-3-hydroxyphenoxy)-2-propanol (IIa-c), prepared from 2- or 4-hydroxy- or 2,6-dihydroxyacetophenone (Ia-c) and chloromethyloxirane, with substituted benzaldehydes gives the corresponding 1,3-bis-2-propanols (IIIa-i).Isomerization of the phenols IIIg-i with silica gel in solid phase furnishes the corresponding 1,3-bis(2-aryl-2,3-dihydro-4-oxo-4H-1-benzopyran-5-yloxy)-2-propanols (IVa-c).Condensation of IIIa-i with hydrazine in refluxing formic or acetic acid affords thecorresponding substituted 1,3-bis(2- or 4-(1-acyl-4,5-dihydro-5-substituted phenyl-1H-pyrazol-3-yl)phenoxy>-2-propanols (VIa-r).Alkylation of IIIg-i and VIg,h and VIp with ethylchloroacetate gives the corresponding bisacetic acid esters Va-c and VIIa-c respectively.Some of the tested compounds exhibit in vitro growth inhibitory activity against Curvularia ovoidea and Rhizoctonia solani at concentrations of 25-50 μg/ml.