50-50-0

Basic information

• Product Name: Estradiol benzoate
• Synonyms: (17beta)-Estra-1,3,5(10)-triene-3,17-diol 3-benzoate;1,3,5(10)-Estratriene-3,17-diol-3-benzoate;1,3,5(10)-Oestratriene-3,17-beta-diol 3-benzoate;1,3,5(10)-oestratriene-3,17-beta-diol3-benzoate;17beta-Estradiol monobenzoate;17-beta-estradiolmonobenzoate;17-beta-Oestradiol 3-benzoate;17-beta-oestradiol3-benzoate
• CAS NO: 50-50-0
• Molecular Formula: C₂₅H₂₈O₃
• Molecular Weight: 376.49
• EINECS: 200-043-7
• Product Categories: Hormone;Biochemistry;Hydroxysteroids;Steroids;API;progestogen estrogen;ACCUTANE;Hormone Drugs
• Mol File: 50-50-0.mol
• Article Data: 9

Chemical Properties

• Melting Point: 191-198 °C(lit.)
• Boiling Point: 465.03°C (rough estimate)
• Flash Point: 212 °C
• Appearance: /
• Density: 1.0493 (rough estimate)
• Vapor Pressure: 4.08E-12mmHg at 25°C
• Refractive Index: 1.5460 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in acetone, slightly soluble in methanol.
• PKA: 15.06±0.40(Predicted)
• Water Solubility: 0.4mg/L(25 oC)
• Merck: 3703
• BRN: 3107526
• CAS DataBase Reference: Estradiol benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Estradiol benzoate(50-50-0)
• EPA Substance Registry System: Estradiol benzoate(50-50-0)

Safety Data

• Hazard Codes: T
• Statements: 60-61-40
• Safety Statements: 53-22-36/37/39-45
• WGK Germany: 3
• RTECS: KG4050000
• F: 8
• Hazardous Substances Data: 50-50-0(Hazardous Substances Data)

Usage

Chemical Properties

White solid

Uses

Different sources of media describe the Uses of 50-50-0 differently. You can refer to the following data:
1. antiacne, antineoplastic
2. Estradiol is the major estrogen secreted by the premenopausal ovary. Estradiol benzoate is an estradiol analog which contains a benzyl ester at the C-3 position. Estradiol benzoate is useful in the tr eatment of lesions produced by diminution of bodily production of estrogens.
3. Estradiol is the major estrogen secreted by the premenopausal ovary. Estradiol benzoate is an estradiol analog which contains a benzyl ester at the C-3 position. Estradiol benzoate is useful in the treatment of lesions produced by diminution of bodily production of estrogens.

Definition

ChEBI: A benzoate ester resulting from the formal condensation of benzoic acid with the phenolic hydroxy group of 17beta-estradiol.

Clinical Use

Estradiol is a semisynthetic estrogen compound. Its effects will mimic that of estrogen in animals. The most common use in small animals has been to terminate pregnancy. Estradiol benzoate also has been used to terminate pregnancy (5-10 mg/kg divided into two or three SQ injections). Estradiol cypionate formulation had high efficacy (95%), but it had serious adverse effects and is not recommended. Estradiol cypionate is longer acting and more potent than other estrogen formulations. Estradiol valerate injection (20 mg/mL) is also available for human medicine to treat hypoestrogenism.

Safety Profile

Confirmed carcinogen with experimental carcinogenic, tumorigenic, and teratogenic data. Human reproductive effects by intramuscular route: menstrual cycle changes and disorders. Experimental reproductive effects. Mutation data reported. A steroid. When heated to decomposition it emits acrid smoke and irritating fumes. See also ESTRADIOL.

InChI:InChI=1/C25H28O3/c1-25-14-13-20-19-10-8-18(28-24(27)16-5-3-2-4-6-16)15-17(19)7-9-21(20)22(25)11-12-23(25)26/h2-6,8,10,15,20-23,26H,7,9,11-14H2,1H3/t20-,21-,22+,23+,25+/m1/s1

Synthetic route

dibenzoyl disulfide (644-32-6) + estradiol (50-28-2) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 1h;	92%

(8R,9S,13S,14S,17S)-17-[(4-methoxybenzyl)oxy]-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl benzoate → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
Stage #1: (8R,9S,13S,14S,17S)-17-[(4-methoxybenzyl)oxy]-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl benzoate With sodium hydrogencarbonate; bis-[(trifluoroacetoxy)iodo]benzene; meso-2,5-bis(methoxycarbonyl)-2,5-dimethylpyrrolidine-1-oxyl In dichloromethane at 20℃; for 2h; Stage #2: With water In dichloromethane chemoselective reaction;	91%

estrone 3-benzoate (2393-53-5) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
With potassium borohydride; Aliquat 336 In water at 20℃; for 6.5h;	85%

estradiol (50-28-2) + benzoyl triflate (36967-85-8) → estra-1,3,5(10)-triene-3,17β-diol dibenzoate (4147-13-1) + Estradiol 3-benzoate (50-50-0)

Conditions	Yield
In dichloromethane at -78℃; for 2.5h;	A 72% B 12%
In dichloromethane at -78℃; for 1h;	A 72% B 12%

estrone 3-benzoate (2393-53-5) → estradiol (50-28-2) + Estradiol 3-benzoate (50-50-0)

Conditions	Yield
With 1,4-dioxane; methanol; sodium tetrahydroborate
With potassium borohydride In ethanol at 20℃; for 4h;

estradiol (50-28-2) + benzoyl chloride (98-88-4) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
With alkaline solution
Stage #1: estradiol With tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In dichloromethane; water Stage #2: benzoyl chloride In dichloromethane; water at 22℃; for 2h; Reagent/catalyst;
With triethylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;

3-benzoyloxy-estratrien-(1.3.5(10))-one-(17) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
With ethanol; nickel-chromium catalyst at 120℃; Hydrogenation.unter Druck;

3-benzoyloxy-estratrien-(1.3.5(10))-one-(17) → Estradiol 3-benzoate (50-50-0) + 3-benzoyloxy-estratrien-(1.3.5(10))-ol-(17α)

Conditions	Yield
With aluminum isopropoxide; isopropyl alcohol

benzoyl chloride (98-88-4) + O5-benzoyl-O1,O2-isopropyliden-β-D-arabinofuranose → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66 percent / 1) 0 deg C, 2) 20 h, room temperature 2: 12 percent / CH2Cl2 / 2.5 h / -78 °C View Scheme

Estrone (53-16-7) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol; nickel catalyst / 120 °C / 14710.2 Torr / Hydrogenation 2: aqueous alkaline solution View Scheme
Multi-step reaction with 2 steps 1: ethanol; sodium 2: aqueous alkaline solution View Scheme

1-dehydrotestosterone (846-48-0) → Estradiol 3-benzoate (50-50-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 9.10-dihydro-phenanthrene / 370 - 390 °C 2: aqueous alkaline solution View Scheme

2-oxocyclopentane-1-carboxylic acid (50882-16-1) + Estradiol 3-benzoate (50-50-0) → 3-Benzoyloxy-17-(5-oxocyclopentylcarbonyloxy)-Δ1,3,5-estratriene (134512-87-1)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 3.5h;	99%

Nonafluorobutanesulfonyl fluoride (375-72-4) + Estradiol 3-benzoate (50-50-0) → C29H27F9O5S

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 0℃; for 0.25h;	96%

Estradiol 3-benzoate (50-50-0) + 4-nitro-benzoic acid (62-23-7) → 4-Nitro-benzoic acid (8R,9S,13S,14S,17R)-3-benzoyloxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl ester

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In toluene at 80℃; for 1.5h;	95%
With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 25 - 100℃; for 1h; Mitsunobu Displacement; diastereoselective reaction;

nicotinic anhydride (16837-38-0) + Estradiol 3-benzoate (50-50-0) → 3-<(phenylcarbonyl)oxy>-17β-<(3-pyridinylcarbonyl)oxy>estra-1,3,5(10)-triene (4263-55-2)

Conditions	Yield
With dmap In pyridine for 120h; Ambient temperature;	94%
dmap In pyridine	3.01 g (94%)
dmap In pyridine	3.01 g (94%)

Estradiol 3-benzoate (50-50-0) + [bromo(difluoro)methyl](trimethyl)silane (115262-01-6) → (8R,9S,13S,14S,17S)-17-(Difluoromethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl benzoate

Conditions	Yield
With potassium acetate In dichloromethane; water at 20℃; for 10h; Reagent/catalyst;	86%

Estradiol 3-benzoate (50-50-0) + acetic anhydride (108-24-7) → benzoate of 17β-acetylestradiol (4954-17-0)

Conditions	Yield
With pyridine; dmap In dichloromethane at 0℃; for 24h;	86%

Estradiol 3-benzoate (50-50-0) + 3,4,6-tri-O-benzyl-D-galactal (80040-79-5) → 17-O-(2-deoxy-3,4,6-tri-O-benzyl-α-D-galactopyranosyl)estradiol benzoate

Conditions	Yield
With bromopropionitrile; tetrabutylammonium trifluoromethylsulfonate at 20℃; Electrochemical reaction;	82%

Estradiol 3-benzoate (50-50-0) + trichloroacetonitrile (545-06-2) → C27H28Cl3NO3

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 12h;	81%

Estradiol 3-benzoate (50-50-0) + (trifluoromethyl)trimethylsilane (81290-20-2) → (8R,9S,13S,14S,17S)-13-methyl-17-(trifluoromethoxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl benzoate

Conditions	Yield
With potassium fluoride; 2-fluoropyridine; silver trifluoromethanesulfonate; Selectfluor In ethyl acetate at 20℃; for 12h; Glovebox; Inert atmosphere;	80%

Estradiol 3-benzoate (50-50-0) + 2,3-bis(tert-butoxycarbonyl amino)propanoic acid (104010-92-6) → Estra-1,3,5(10)-trien-3,17β-diyl 3-benzoat 17β-(2,3-diamino-N,N'-diBOC-propionat)

Conditions	Yield
With 1,1'-carbonyldiimidazole In chloroform	65%

Estradiol 3-benzoate (50-50-0) + (2S,3S,4S,5R,6R)-2-(methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate) (201789-50-6) → (2S,3S,4S,5R,6R)-6-((8R,9S,13S,14S,17S)-3-Benzoyloxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yloxy)-3,4,5-tris-(2,2-dimethyl-propionyloxy)-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; 4 A molecular sieve In 1,2-dichloro-ethane at 0 - 20℃; for 1.5h;	65%

Estradiol 3-benzoate (50-50-0) + (2S,3S,4S,5R,6R)-2-(methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2-methylpropanoate) (150607-96-8) → 3-O-benzoyl,17-O-isobutyrylestra-3,17β-diol

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; 4 A molecular sieve In 1,2-dichloro-ethane at 0 - 20℃; for 1.5h;	60%

glutaric anhydride, (108-55-4) + Estradiol 3-benzoate (50-50-0) → 4-(3-benzoyloxy-1,3,5(10)-estratrien-17β-yloxycarbonyl)butyric acid (194995-13-6)

Conditions	Yield
With pyridine; triethylamine at 80℃; for 24h;	58.1%

Estradiol 3-benzoate (50-50-0) + p-methoxybenzyl chloride (824-94-2) → (8R,9S,13S,14S,17S)-17-[(4-methoxybenzyl)oxy]-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl benzoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; sodium iodide at 140℃; for 20h;	55%

Estradiol 3-benzoate (50-50-0) + (2S,3S,4S,5R,6R)-2-(methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2-methylpropanoate) (150607-96-8) → (2S,3S,4S,5R,6R)-6-((8R,9S,13S,14S,17S)-3-Benzoyloxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yloxy)-3,4,5-tris-isobutyryloxy-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; 4 A molecular sieve In 1,2-dichloro-ethane at 0 - 20℃; for 1.5h;	29%

Estradiol 3-benzoate (50-50-0) + (2S,3S,4S,5R,6R)-2-(methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate) (201789-50-6) → 3-O-benzoyl,17-O-pivaloylestra-3,17β-diol

Conditions	Yield
With boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 20℃; for 1.5h;	19%

Estradiol 3-benzoate (50-50-0) + methyl salicylate (119-36-8) → 3-hydroxy-estra-1,3,5(10)-trien-17β-ylsalicylate (161088-53-5)

Conditions	Yield
Stage #1: Estradiol 3-benzoate; methyl salicylate With sodium at 110℃; Stage #2: In toluene at 200℃; for 0.5h; Microwave irradiation;	18.4%

Estradiol 3-benzoate (50-50-0) + methyl salicylate (119-36-8) → 3-hydroxy-estra-1,3,5(10)-trien-17β-ylsalicylate (161088-53-5) + estra-1,3,5(10)-triene-3,17β-diyl 3-benzoate 17-salicylate

Conditions	Yield
With sodium In toluene for 5.5h; Reflux;	A 10.8% B 17.5%

Estradiol 3-benzoate (50-50-0) + α-hepta-O-acetylmaltosyl bromide (4753-07-5, 5160-10-1, 14206-57-6, 14227-66-8, 14257-35-3, 67650-37-7, 68682-05-3, 69308-57-2, 69349-74-2, 70223-96-0, 70223-97-1, 71276-38-5, 85248-99-3, 118493-15-5, 120575-76-0, 42385-75-1) → 3-benzoyloxy-17β-[O2,O3,O6-triacetyl-O4-(tetra-O-acetyl-α-D-glucopyranosyl)-β-D-glucopyranosyloxy]-estra-1,3,5(10)-triene (6107-79-5)

Conditions	Yield
With silver carbonate; benzene

Estradiol 3-benzoate (50-50-0) + mercaptoacetic acid (68-11-1) → 3-benzoyloxy-17β-mercaptoacetoxy-estra-1,3,5(10)-triene (120035-97-4)

Estradiol 3-benzoate (50-50-0) + n-valeryl chloride (638-29-9) → 3-benzoyloxy-17β-valeryloxy-estra-1,3,5(10)-triene (63042-21-7)

Conditions	Yield
With pyridine

Estradiol 3-benzoate (50-50-0) + 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester (21085-72-3) → O2,O3,O4-triacetyl-O1-(3-benzoyloxy-estra-1,3,5,(10)-trien-17β-yl)-β-D-glucopyranuronic acid methyl ester

Conditions	Yield
With silver carbonate; benzene

3-ethoxyandrosta-3,5-dien-17-one (972-46-3) + Estradiol 3-benzoate (50-50-0) → C44H52O4

Conditions	Yield
With pyridinium p-toluenesulfonate In benzene Heating;
With pyridine; toluene-4-sulfonic acid

Upstream product

• 2393-53-5 estrone 3-benzoate 
• 644-32-6 dibenzoyl disulfide 
• 50-28-2 estradiol 
• 846-48-0 1-dehydrotestosterone 
• 53-16-7 Estrone 
• 98-88-4 benzoyl chloride 
• 36967-85-8 benzoyl triflate 

Downstream Products

• 4263-55-2 3-<(phenylcarbonyl)oxy>-17β-<(3-pyridinylcarbonyl)oxy>estra-1,3,5(10)-triene 
• 41623-06-7 Benzoic acid (8R,9S,13S,14S,17S)-17-(1-ethoxy-1-methyl-ethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl ester 

Relevant articles and documents

Application of in Situ FTIR for the Preparation of 17-α-Estradiol via Mitsunobu Reaction

An efficient synthesis of 17-α-estradiol 1 is described. Utilization of in situ IR allowed for an online monitoring of the key Mitsunobu reaction and development of a safe and reliable synthesis of 17-α-estradiol 1 in 78% overall yield over three steps. Benzoylation of 17-β-estradiol 2 is conducted at high regioselectivity under phase-transfer catalysis (PTC) conditions, followed by a Mitsunobu reaction to invert the chiral center at C-17 and provide intermediate 5, containing the core structure of 17-α-estradiol 1. Finally, the desired active pharmaceutical ingredient (API) is prepared by saponification of the remaining esters.

HYALURONAN CONJUGATES AND USES THEREOF

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Diacyl Disulfide: A Reagent for Chemoselective Acylation of Phenols Enabled by 4-(N,N-Dimethylamino)pyridine Catalysis

A general and excellent acylation reagent, diacyl disulfide, was uncovered for efficient ester formation enabled by DMAP (4-(N,N-dimethylamino)pyridine) catalysis. This protocol offered a promising synthetic platform on site-selective acylation of phenolic and primary aliphatic hydroxyl groups, which greatly expanded the realm of protecting group chemistry. The importance of the reagent was also reflected by its excellent moisture tolerance, high efficiency, and potential in synthetic chemistry and biologically meaningful natural product modification.