72-48-0

Basic information

• Product Name: 1,2-Dihydroxy-9,10-anthracenedione
• Synonyms: 10-Anthracenedione,1,2-dihydroxy-9;9,10-Anthracenedione, 1,2-dihydroxy-;9,10-Anthracenedione,1,2-dihydroxy-;Ailzarin(c.1.No.5800);Aliazrin;Alizarin B;Alizarin,CI 58000;Alizarina
• CAS NO: 72-48-0
• Molecular Formula: C₁₄H₈O₄
• Molecular Weight: 240.213
• EINECS: 200-782-5
• Product Categories: Intermediates of Dyes and Pigments;Anthraquinones, Hydroquinones and Quinones;Anthraquinones;Hydroxyanthraquinones;Inhibitors;Anthraquinone;Miscellaneous
• Mol File: 72-48-0.mol

Chemical Properties

• Melting Point: 287 °C
• Boiling Point: 430 °C
• Flash Point: 430°C subl.
• Appearance: Orange to orange-brown/Fine Powder
• Density: 1.06 g/mL at 20 °C
• Vapor Pressure: 5.34E-08mmHg at 25°C
• Refractive Index: 1.5190 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Solubility Virtually insoluble in water; moderately soluble in e
• PKA: 6.77(at 25℃)
• Water Solubility: Soluble in hexane and chloroform. Slightly soluble in water.
• Stability: Stable. Incompatible with strong oxidizing agents, strong bases.
• Merck: 14,251
• BRN: 1914037
• CAS DataBase Reference: 1,2-Dihydroxy-9,10-anthracenedione(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2-Dihydroxy-9,10-anthracenedione(72-48-0)
• EPA Substance Registry System: 1,2-Dihydroxy-9,10-anthracenedione(72-48-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/38-36/37/38
• Safety Statements: 26-36-24/25-22
• WGK Germany: 3
• RTECS: YO8300000
• TSCA: Yes
• Hazardous Substances Data: 72-48-0(Hazardous Substances Data)

Usage

Uses

1. Used in Antimutagenesis:
Alizarin is used as an antimutagen, which helps in preventing genetic mutations and protecting cells from damage.
2. Used in Textile Industry:
Alizarin is widely used as a prominent red dye for textile fabrics. It is known for its excellent colorfastness properties, making it a preferred choice for dyeing wool fabrics.
3. Used in Biochemical Assays:
Alizarin red is used in biochemical assays to determine the presence of calcific deposition by cells of the osteogenic lineage through colorimetry.
4. Used in Pharmaceutical Industry:
Alizarin derivatives have been evaluated as new inhibitors of the HIV-1 reverse transcriptase associated DNA polymerase and RNase H. It has also shown to inhibit proliferation, tumor growth, and suppress tumorigenesis in human osteosarcoma and breast cancer cell lines.
5. Used in Pigment Manufacturing:
Alizarin has a major application in the manufacture of madder lake pigments, commonly known as Rose madder and Alizarin crimson.
6. Used in Medical Research:
Alizarin is involved in studies of bone growth, osteoporosis, bone marrow, and calcium deposits in the vascular system. It is also used as a stain in calcite and aragonite to identify calcium carbonate and in synovial fluid to assess basic calcium phosphate crystals.
7. Used in Colorimetric Measurements:
Alizarin is used in colorimetric measurements for the quantification of amine extraction by model food simulants from epoxy polymer.
8. Used as an Organic Pigment:
Due to its color properties, Alizarin is used as an organic pigment in various applications.

History

In ancient times, alizarin was the preferred red dye. Cloth dyed with it has been found in Egyptian tombs dating 6000 years ago. The dye is found in the madder plant, a member of the Rubiaceae family. In 1944 about 35 species of this plant were known, but the use of more sophisticated analytical methods led to the detection of many more species; by 1984 the number had increased to 50. Alizarin is a mordant dye forming various colored coordination complexes with different metallic salts.

Preparation

(a) 2 – Bromoanthraquinone and Potassium hydroxide heating; (b) 9,10-Dioxo-9,10-dihydroanthracene-2-sulfonic acid (Sodium) and Sodium hydroxide and Sodium nitrate and Sodium chlorate heating; (C) Anthracene-9,10-dione?and Sodium hydroxide and Sodium chlorate and Sodium nitrate heating (GP 186526); (d) in the presence of Sodium nitrite and Sodium hydroxide and Anthracene-9,10-dione?and Sodium nitrate heating (GP 241806245 987); (e) in the Oxidant and Sodium sulfite and the presence of lime, anthracene in a nitrocellulose derivatives and Sodium hydroxide heating (GP 292247); (f) 2 – Anthraquinonesulfonic acid in the presence of air, with the Sodium hydroxide Etanol wetting treatment (GP 287270); (g) 2-Chloroanthracene-9,10-dione Sodium chlorate in the presence of alkali fusion for (USP 1744815); (h) 2-Methylanthracene-9,10-dione in the presence of Oxidant, with Sodium hydroxide treatment (BP 293328).

Biological Activity

alizarin is an anthraquinone dye for detecting the presence of calcium salts [1].alizarin belongs to the anthraquinone group. it is a chelator for calcium and is commonly used to stain the calcifying or calcio-receptive zone of the collagenous matrix where calcium salts are being deposited. on the other hand, the alizarin complexone is used for bone staining in vivo to study bone remodeling [1].alizarin is proved to have anti-tumor efficacy. it suppresses the cell growth of the prostate cancer, breast cancer and osteosarcoma cell lines in vitro. among these, the osteosarcoma cells appear to be most sensitive. the ic50 values of alizarin against three osteosarcoma cell lines saos-2, mg-63 and u-2 os are 27.5, 29 and 69.9μg/ml, respectively. alizarin inhibits the cell growth through cell proliferation blockade rather than induction of apoptosis. it inhibits the phosphorylation of erk. in addition, alizarin is also found to induce s-phase arrest as well as a decrease of the g0/g1 and g2/m phases [1].

Standard

Ironing Fastness

Alkali

Acid

ISO

3-4

Purification Methods

Alizarin crystallises from glacial acetic acid or 95% EtOH. It can also be sublimed at 110o/2mm. It is an indicator with max at 452nm (pH 5.8) and 520nm (pH 7.2). [Beilstein 8 IV 3256.]

references

[1] fotia c, avnet s, granchi d, baldini n. the natural compound alizarin as an osteotropic drug for the treatment of bone tumors. j orthop res. 2012 sep;30(9):1486-92.

InChI:InChI=1/C14H8O4/c15-10-6-5-9-11(14(10)18)13(17)8-4-2-1-3-7(8)12(9)16/h1-6,15,18H

Synthetic route

benzene-1,2-diol (120-80-9) + Phthaloyl dichloride (88-95-9) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With aluminium trichloride In nitrobenzene at 80℃; for 0.25h;	60%
With aluminium trichloride; C6H4NO2 at 165℃; for 4h; Fridel-Crafts acylation;

phthalic anhydride (85-44-9) + benzene-1,2-diol (120-80-9) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With aluminium trichloride; sodium chloride at 165℃; for 4h; Fridel-Crafts acylation;	55%
Stage #1: phthalic anhydride; benzene-1,2-diol With aluminum (III) chloride; sodium chloride at 110 - 165℃; for 4h; Friedel Crafts Acylation; Stage #2: With hydrogenchloride In water at 0 - 100℃; for 0.75h; Heating / reflux;	55%
Stage #1: phthalic anhydride; benzene-1,2-diol With aluminum (III) chloride; sodium chloride at 110 - 165℃; for 4h; Friedel-Crafts Acylation; Stage #2: With hydrogenchloride In water at 20 - 100℃; for 0.75h;	36%

1-nitroanthraquinone (82-34-8) → 1-hydroxyanthraquinone (129-43-1) + 1,4-dihydroxy-9,10-anthracenedione (81-64-1) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium hydroxide; Cumene hydroperoxide In dimethyl sulfoxide at 15 - 25℃; for 10h;	A 55% B 13% C 32%
With Cumene hydroperoxide; potassium tert-butylate In N,N,N,N,N,N-hexamethylphosphoric triamide at 15 - 20℃; for 3h;	A 45% B 8% C 35%

2-aminoanthraquinone (117-79-3) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 6,15-dihydroanthrazine-5,9,14,18-tetrone (81-77-6) + 16-hydroxy-8,17-dihydrodinaphtho<2,3-a:2',3'-i>phenazine-5,10,15,18-tetrone (16135-99-2)

Conditions	Yield
With potassium hydroxide; potassium chlorate In various solvent(s) at 168 - 172℃; for 2h;	A n/a B 48% C n/a
With potassium hydroxide; potassium chlorate In 2-ethoxy-ethanol at 168 - 172℃; for 2h; Product distribution; further solvents and oxidants;

tetrachloromethane (56-23-5) + 2,3-dichloro-anthraquinone (84-45-7) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
beim Schmelzen;

phthalic anhydride (85-44-9) + benzo-1,4-dioxane (493-09-4) → hystazarin (483-35-2) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With aluminium trichloride; sodium chloride at 130 - 140℃;
With aluminium trichloride; sodium chloride at 170 - 180℃;

phthalic anhydride (85-44-9) + benzo-1,4-dioxane (493-09-4) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With aluminium trichloride; sodium chloride at 130 - 140℃;
With aluminium trichloride; sodium chloride at 170 - 180℃;

phthalic anhydride (85-44-9) + 2-monochlorophenol (95-57-8) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sulfuric acid; boric acid at 240 - 255℃;

phthalic anhydride (85-44-9) + benzene-1,2-diol (120-80-9) → hystazarin (483-35-2) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With Japanese acid earth
With sulfuric acid at 180 - 200℃;
With aluminium trichloride; sulfuric acid; sodium chloride 1.) reflux, 2 h, 2.) reflux, 3 h; Multistep reaction. Title compound not separated from byproducts;

phthalic anhydride (85-44-9) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

2-(3,4-dimethoxybenzoyl)benzoic acid (51439-85-1) → hystazarin (483-35-2) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sulfuric acid at 100℃; Verseifen den Hystazarindimethylaether mit konz.Schwefelsaeure auf 200-205grad;

3,4-dimethoxyphthalic anhydride (1567-56-2) + benzene (71-43-2) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With aluminium trichloride Erwaermen des Reaktionsprodukts mit konz.Schwefelsaeure auf 100grad,und nachfolgend verseifen mit Jodwasserstoffsaeure;

ethanol (64-17-5) + 1,2-dihydroxy-3-hydroxyazo-anthraquinone → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

1-methyl-4-nitrosobenzene (623-11-0) + 2-hydroxy-2,4a-dihydro-anthraquinone → 2-hydroxy-9,10-anthraquinone (605-32-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
at 215℃; und Leiten von Luft durch die Reaktionsloesung;

2-hydroxy-9,10-anthraquinone (605-32-3) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium carbonate durch Schmelzen;
Multi-step reaction with 2 steps 1: aqueous ammonia / 150 °C 2: NaNO2; concentrated sulfuric acid / 190 °C View Scheme

1-nitroanthraquinone (82-34-8) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium carbonate durch Schmelzen;

1-hydroxyanthraquinone (129-43-1) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium carbonate durch Schmelzen;

9-nitroanthrone (6313-44-6) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sodium hydroxide; methyllithium; nitric acid; calcium carbonate at 200℃; Reagens 4: Na2SO3;

2-chloro-1-hydroxy-anthraquinone (35582-88-8) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
bei der Kalischmelze;

2-chloroanthracene-9,10-dione (131-09-9) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sodium chlorate; sodium hydroxide technische Darstellung durch Schmelzen;

2-bromoanthracene-9,10-dione (572-83-8) → 2-hydroxy-9,10-anthraquinone (605-32-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium hydroxide

2-bromoanthracene-9,10-dione (572-83-8) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium hydroxide
With sodium hydroxide

1,3-dichloroanthraquinone (602-73-3) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium hydroxide bei Schmelzen;
With sodium hydroxide bei Schmelzen;
in der Kalischmelze;

anthragallol (602-64-2) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sodium amalgam

2-phenylaminoanthraquinone (36339-31-8) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1-Hydroxy-2-phenylaminoanthraquinone (68637-85-4)

Conditions	Yield
With potassium hydroxide; potassium acetate; potassium nitrate weiteres Reagens: H2O;

2,3-dichloro-anthraquinone (84-45-7) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With sodium hydroxide
durch Kalischmelze;
With potassium hydroxide

2-sulfo-anthraquinone (84-48-0) → 2-hydroxy-9,10-anthraquinone (605-32-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With potassium hydroxide

2-sulfo-anthraquinone (84-48-0) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

Conditions	Yield
With alkali anschliessendes Oxydation des gebildeten 2-Oxy-anthrachinons mit Luft;
With potassium chlorate anschliessendes Oxydation des gebildeten 2-Oxy-anthrachinons mit Luft;

Alizarin S (83-61-4) → 1,2-dihydroxy-9,10-anthracenedione (72-48-0)

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + propynoic acid ethyl ester (623-47-2) → ethyl 6,11-dihydro-6,11-dioxoanthra[1,2-d][1,3]-dioxole-2-acetate (1312024-63-7)

Conditions	Yield
With triphenylphosphine In toluene for 24h; Reflux;	97%

Cyclohexyl isocyanide (931-53-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) + acetylenedicarboxylic acid diethyl ester (762-21-0) → diethyl 2-(cyclohexylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	97%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1,1,3,3-tetramethylbutane isonitrile (14542-93-9) + dimethyl acetylenedicarboxylate (762-42-5) → dimethyl 2-(2,4,4-trimethylpentan-2-ylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	96%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + benzoyl chloride (98-88-4) → 1,2-dibenzoyloxy-9,10-anthraquinone (6375-18-4)

Conditions	Yield
for 0.5h; Heating;	95%
With pyridine
at 190℃;

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + dimethyl acetylenedicarboxylate (762-42-5) → methyl 6,11-dihydro-12-hydroxy-2,6,11-trioxo-2H-naphtho[2,3-g]chromene-4-carboxylate (1312024-60-4)

Conditions	Yield
With triphenylphosphine In toluene for 24h; Reflux;	95%

Cyclohexyl isocyanide (931-53-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) + dimethyl acetylenedicarboxylate (762-42-5) → dimethyl 2-(cyclohexylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	95%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1,1,3,3-tetramethylbutane isonitrile (14542-93-9) + acetylenedicarboxylic acid diethyl ester (762-21-0) → diethyl 2-(2,4,4-trimethylpentan-2-ylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	95%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + acetylenedicarboxylic acid diethyl ester (762-21-0) → ethyl 6,11-dihydro-12-hydroxy-2,6,11-trioxo-2H-naphtho[2,3-g]chromene-4-carboxylate (1312024-61-5)

Conditions	Yield
With triphenylphosphine In toluene for 24h; Reflux;	94%

potassium tetrachloropalladate(II) (10025-98-6) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → [C6H4(CO)2C6H2O(OH)]2Pd (757898-87-6, 74091-57-9)

Conditions	Yield
With potassium hydroxide In water alizarin dissolved in boiling water with equimolar amount of KOH, K2PdCl4 added, pptd., suspn. standed overnight, cooled; ppt. filtered, washed (dilute HCl soln., water, acetone, ether), dried (air) elem. anal.;	93%
In N,N-dimethyl-formamide byproducts: KCl; mixed, suspn. stirred at 90°C, cooled, KCl filtered off; solv. removed (vac.), washed (ether), elem. anal., IR;	83%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1-Bromooctadecane (112-89-0) → 1,2-bis[octadecyloxy]anthraquinone (912278-50-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide; water	93%
Stage #1: 1,2-dihydroxy-9,10-anthracenedione With potassium carbonate In ISOPROPYLAMIDE at 80℃; for 1h; Stage #2: 1-Bromooctadecane In ISOPROPYLAMIDE for 7h;	93%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + ethyl chloromethyl ether (3188-13-4) → 2-(ethoxymethoxy)-1-hydroxyanthracene-9,10-dione

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;	93%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + N-methyl-N-tert-butyldimethylsilyl-1,1,1-trifluoroacetamide (77377-52-7) → 1,2-bis(tert-butyldimethylsiloxy)-9,10-anthracenedione

Conditions	Yield
With tert-butyldimethylsilyl chloride In acetonitrile at 70℃; for 0.25h; silylation;	92%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + (2,4-dinitro-phenyl)-hydrazine (119-26-6) → 10-[(2,4-dinitro-phenyl)-hydrazono]-1,2-dihydroxy-10H-anthracen-9-one

Conditions	Yield
With sulfuric acid In methanol for 48h; Heating;	92%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + (2,4-dinitro-phenyl)-hydrazine (119-26-6) → 10-[(2,4-dinitrophenyl)hydrazono]-1,2-dihydroxy-10H-anthracen-9-one

Conditions	Yield
With sulfuric acid In ethanol at 60℃; for 2h; Product distribution / selectivity;	92%
With sulfuric acid In methanol at 50℃; for 48h; Product distribution / selectivity; Heating / reflux;	92%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + methyl iodide (74-88-4) → 1-hydroxy-2-methoxyanthraquinone (6003-11-8)

Conditions	Yield
With lithium carbonate In N,N-dimethyl-formamide at 60℃; for 24h;	90%
With sodium hydroxide In N,N-dimethyl-formamide at 60℃; for 24h;	28%
With potassium carbonate
With water; barium(II) oxide In N,N-dimethyl-formamide
With sodium hydroxide In N,N-dimethyl-formamide

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 5-methyl-o-tolyl isocyanide (71119-75-0) + acetylenedicarboxylic acid diethyl ester (762-21-0) → diethyl 2-(2,6-dimethylphenylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	90%

tetrahydrofuran (109-99-9) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → C36H28O10Si

Conditions	Yield
With tetrachlorosilane at 75℃; for 20h; Inert atmosphere; Schlenk technique;	90%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 5-methyl-o-tolyl isocyanide (71119-75-0) + dimethyl acetylenedicarboxylate (762-42-5) → dimethyl 2-(2,6-dimethylphenylamino)-6,11-dihydro-12-hydroxy-6,11-dioxo-4H-naphtho[2,3-g]chromene-3,4-dicarboxylate

Conditions	Yield
In toluene for 24h; Reflux;	88%

dichloro(2-anilinopyridyl-kappa.N,C)gold (198711-19-2) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → [Au(alizarin)(2-anilinopyridyl)]

Conditions	Yield
With trimethylamine In methanol for 0.333333h; Reflux;	87%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + di(n-butyl)tin oxide (818-08-6) → [(Bu2Sn)3O(1,2-dihydroxyanthraquinone(-2H))2]

Conditions	Yield
In methanol refluxing alizarin and Bu2SnO in MeOH for 3 h; elem. anal.;	86%

cisplatin (15663-27-1) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → C14H12N2O4Pt

Conditions	Yield
Stage #1: cisplatin With silver nitrate In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; Stage #2: 1,2-dihydroxy-9,10-anthracenedione With sodium hydroxide In water; N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere;	85%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1-dodecylbromide (143-15-7) → 1,2-bis(dodecycloxy)anthracene-9,10-dione

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 12h; Heating;	84%
With potassium carbonate In dimethyl sulfoxide; butanone for 15h; Reflux;	42%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + di(n-butyl)tin oxide (818-08-6) + dimethyl sulfoxide (67-68-5) → [Bu2Sn(1,2-dihydroxyanthraquinone(-2H))(dmso)]2 (1202356-51-1)

Conditions	Yield
In chloroform; dimethyl sulfoxide refluxing alizarin and Bu2SnO in DMSO/CHCl3 for 6 h; slow evapn. of CHCl3; elem. anal.;	83%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + bromoacetic acid (79-08-3) → 1-hydroxyanthracene-9,10-dione-2-yl 2-bromoacetate (1610041-41-2)

Conditions	Yield
Stage #1: bromoacetic acid With dmap In dimethyl sulfoxide at 20℃; for 0.0833333h; Stage #2: With dicyclohexyl-carbodiimide In dimethyl sulfoxide for 0.166667h; Stage #3: 1,2-dihydroxy-9,10-anthracenedione In dimethyl sulfoxide for 4h;	82%

trifluoromethylsulfonic anhydride (358-23-6) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → 1,2-bis[(trifluoromethylsulfonyl)oxy]anthraquinone (1234556-16-1)

Conditions	Yield
Stage #1: 1,2-dihydroxy-9,10-anthracenedione With pyridine In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at -78 - 20℃; for 14h; Inert atmosphere;	81%
With pyridine In dichloromethane at -78 - 20℃; for 14h; Inert atmosphere;	81%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 2-Bromopropionic acid (598-72-1) → 1-hydroxyanthracene-9,10-dione-2-yl 2-bromopropionate (1610041-42-3)

Conditions	Yield
Stage #1: 2-Bromopropionic acid With dmap In dimethyl sulfoxide at 20℃; for 0.0833333h; Stage #2: With dicyclohexyl-carbodiimide In dimethyl sulfoxide for 0.166667h; Stage #3: 1,2-dihydroxy-9,10-anthracenedione In dimethyl sulfoxide for 4h;	80%

dodecacarbonyl-triangulo-triruthenium (15243-33-1) + tributylphosphine (998-40-3) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1,2-bis-(diphenylphosphino)ethane (1663-45-2) → Ru(CO)(dppe)(PBu3)(AL-2H)

Conditions	Yield
In toluene soln. of Ru-complex, dppe, and ligand in toluene was heated at reflux under Ar for 4 h, PBu3 was added, refluxed for 6 h; evapd. to dryness, recrystd. from CH2Cl2/MeOH; elem. anal.;	79%

1,2-dihydroxy-9,10-anthracenedione (72-48-0) + 1-bromoacetone (598-31-2) → 1-hydroxy-2-acetonyloxyanthraquinone (1204905-36-1)

Conditions	Yield
With potassium carbonate In acetone Reflux;	79%

(CH3CO2CH2CH2)2SnCl2 (10175-01-6) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → (CH3OCOCH2CH2)2Sn(C14H6O4) (114048-37-2)

Conditions	Yield
With ammonia In methanol byproducts: NH4Cl; heated on a water bath, ammonia soln. was added; filtered, refluxed for 1 h, recrystd. from chloroform/methanol; elem. anal.;	78%

1-methyl-piperazine (109-01-3) + formaldehyd (50-00-0) + 1,2-dihydroxy-9,10-anthracenedione (72-48-0) → C20H20N2O4

Conditions	Yield
Stage #1: 1-methyl-piperazine; formaldehyd With hydrogenchloride In ethanol at 80℃; for 2h; Stage #2: 1,2-dihydroxy-9,10-anthracenedione In ethanol at 80℃; for 10.5h; Inert atmosphere;	78%

Upstream product

• 56-23-5 tetrachloromethane 
• 84-45-7 2,3-dichloro-anthraquinone 
• 85-44-9 phthalic anhydride 
• 493-09-4 benzo-1,4-dioxane 
• 95-57-8 2-monochlorophenol 
• 120-80-9 benzene-1,2-diol 
• 51439-85-1 2-(3,4-dimethoxybenzoyl)benzoic acid 
• 1567-56-2 3,4-dimethoxyphthalic anhydride 
• 71-43-2 benzene 
• 64-17-5 ethanol 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 605-32-3 2-hydroxy-9,10-anthraquinone 
• 82-34-8 1-nitroanthraquinone 
• 129-43-1 1-hydroxyanthraquinone 

Downstream Products

• 6003-11-8 1-hydroxy-2-methoxyanthraquinone 
• 6003-12-9 alizarin dimethyl ether 
• 108-95-2 phenol 
• 605-32-3 2-hydroxy-9,10-anthraquinone 
• 81-54-9 1,2,4-trihydroxy-9,10-anthraquinone 
• 81-61-8 1,2,5,8-tetrahydroxy-anthraquinone 
• 120-12-7 anthracene 
• 568-93-4 3-nitroalizarin 
• 2243-71-2 4-nitroalizarin 
• 61169-36-6 1,2,4,5,6,8-hexahydroxy-9,10-anthraquinone 
• 83-61-4 Alizarin S 
• 96652-08-3 3,4-dihydroxy-9,10-dioxo-9,10-dihydro-anthracene-1-sulfonic acid 
• 577-95-7 1,2-dihydroxyanthracene 
• 88-99-3 benzene-1,2-dicarboxylic acid 

Relevant articles and documents

Evaluation of a series of 9,10-anthraquinones as antiplasmodial agents

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. Objective: The present study aimed to investigate the structural requirements of 9,10-anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 μM, and when C-6 was substituted with a methyl group, 1,3-dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02μM, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 A and 3.02 A, respectively. Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin.

COLLAGEN MATRIX WITH LOCALLY CONTROLLED INTRAFIBRILLAR AND EXTRAFIBRILLAR MINERAL CONTENT AND METHODS OF PRODUCING

A mineralized collagen matrix with an intrafibrillar and/or extrafibrillar gradient of mineralization for insertion replacement is disclosed. The intrafibrillar mineralization of the collagen matrix is formed by the addition of fetuin to the simulated body fluid. The gradient of intrafibrillar mineralization may stiffen the collagen matrix and simulate a natural insertion for improved cell infiltration and regeneration.

Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety

A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca2+ and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.

Total synthesis, cytotoxic effects of damnacanthal, nordamnacanthal and related anthraquinone analogues

Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC 50 = 5.70 ± 0.21 and 8.50 ± 1.18 μg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC 50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC 50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.

An anthraquinone scaffold for putative, two-face bim BH3 α-helix mimic

Bim BH3 peptide features an α-helix with hotspot residues on multiple faces. Compound 5 (6-bromo-2,3-dihydroxyanthracene-9,10-dione), which adopts a rigid-plan amphipathic conformation, was designed and evaluated as a scaffold to mimic two faces of Bim α-helix. It reproduced the functionalities of both D67 and I65 on two opposing helical sides. Moreover, it maintained the two-faced binding mode during further evolution. A putative BH3 α-helix mimic and nanomolar Bcl-2/Mcl-1 dual inhibitor, 6, was obtained based on the structure of 5.

Synthesis and activity of substituted anthraquinones against a human filarial parasite, Brugia malayi

Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel anthraquinones A-S and their antifilrarial activity. Anthraquinones A-S were synthesized by a single-step Friedel-Crafts acylation reaction between phthalic anhydrides and substituted benzenes. The antifilarial properties of these synthetic anthraquinones were tested against microfilaria as well as adult male and female worms of B. malayi. The most active anthraquinone was K, which showed 100% mortality within 1, 5, and 3 days, respectively, against microfilaria and adult male and female worms at 5 ppm concentration. Albendazole, an oral drug currently used to treat parasitic infections, was used as a positive control. Methylated products of anthraquinones did not affect the microfilaria. Histological examination of treated adult female parasites showed most of the anthraquinones caused marked effects on intrauterine embryos.

Novel anthraquinones and process for the preparation and method of use thereof

A process for the preparation of hydroxyl substituted anthraquinones is described. The process couples a phthalic anhydride (substituted or unsubstituted) to benzene ring moiety substituted with at least two hydroxyl groups. Remaining hydroxy groups were converted to methoxy groups in some anthraquinones. The compounds are particularly useful for the treatment of parasitic diseases. Also, a method of treating or preventing malaria, filariasis schistosomiasis and other parasitic diseases using anthraquinones.

Pathway of anthracene modification under simulated solar radiation

Exposure of polycyclic aromatic hydrocarbons (PAHs) to sunlight results in rapid structural photomodification generally via oxidation reactions. These PAH modification products are in many cases more toxic than their parent compounds. In this study, anthracene (ANT), a rapidly photooxidized PAH, was irradiated with simulated solar radiation (SSR, 100 μmol m-2 s- 1) in aqueous solution to examine the photomodification pathway. The photoproducts formed were identified by HPLC. The ANT product profile after 9 h in SSR was very complex, with more than 20 compounds detected. The photoproducts formed were anthraquinones, benzoic acids, benzaldehydes and phenols showing the process to be oxidative in nature. Some of the anthraquinones were themselves subject to photooxidation, and were thus intermediates in the product pathway. The kinetics of ANT photooxidation revealed a pseudo first-order reaction with a half-life of 2 h under the SSR source used. The kinetics of product formation allowed deduction of a probable photomodification pathway. This study indicates that PAH photooxidation products are likely to exist as complex, dynamically changing mixtures in PAH contaminated aquatic environments.

Different synthetic routes towards efficient organogelators: 2,3-substituted anthracenes

Three synthetic approaches towards 2,3-substituted anthracenes are reported and discussed in terms of selectivity and viability. This allowed us to introduce a variety of substituents as sidearms. Promising results have been found using a tandem Diels-Alder aromatization reaction using 2,2,3-dimethoxybuladiene 9 as a key intermediate. However, for multigram preparations the Friedel-Crafts approach is preferred.

1H and 13C NMR studies of some anthraquinones and anthracenetetrones

1H and 13C NMR chemical shifts are reported and assigned for 1,4,9,10- and 2,3,9,10-anthracenetetrone. In addition, NMR data are given for 2,3-dihydroxy-9, 10-anthraquinone, 2,3-dimethoxy-9,10-anthraquinone and 1-hydroxy-2-acetoxy-9,10-anthraquinone, encountered during the preparation of the anthracenetetrones.