480-47-7

Basic information

• Product Name: hydrangenol
• Synonyms: hydrangenol;3-(4-Hydroxyphenyl)-8-hydroxy-3,4-dihydro-1H-2-benzopyran-1-one;3-(4-Hydroxyphenyl)-8-hydroxyisochroman-1-one;3,4-Dihydro-8-hydroxy-3-(4-hydroxyphenyl)-1H-2-benzopyran-1-one;Hydrangel
• CAS NO: 480-47-7
• Molecular Formula: C₁₅H₁₂O₄
• Molecular Weight: 256.25
• EINECS: 200-258-5
• Mol File: 480-47-7.mol

Chemical Properties

• Boiling Point: 528.3 °C at 760 mmHg
• Flash Point: 206.4 °C
• Appearance: /
• Density: 1.386 g/cm³
• Vapor Pressure: 8.86E-12mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: 2-8°C
• CAS DataBase Reference: hydrangenol(CAS DataBase Reference)
• NIST Chemistry Reference: hydrangenol(480-47-7)
• EPA Substance Registry System: hydrangenol(480-47-7)

Safety Data

• Hazardous Substances Data: 480-47-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Hydrangenol is used as an anti-allergic agent for its ability to counteract allergic reactions. Its anti-allergic properties make it a potential candidate for the development of medications aimed at treating various allergic conditions.
Used in Allergen Research:
In the field of allergen research, hydrangenol is used to study the mechanisms behind allergic reactions and to develop strategies for mitigating or preventing such responses. Understanding the properties of hydrangenol can contribute to the advancement of allergy treatments and therapies.
Used in Plant Biology:
Hydrangenol's presence in certain plants, such as the hydrangeaceae family, makes it a subject of interest in plant biology. Researchers may study its role in the plant's defense mechanisms or its potential effects on the plant's interactions with other organisms, including pollinators and pathogens.

Contact allergens

Hydrangenol is the allergen of hydrangea (Hydrangea macrophylla Thunb, Hydrangeaceae family).

InChI:InChI=1/C15H12O4/c16-11-6-4-9(5-7-11)13-8-10-2-1-3-12(17)14(10)15(18)19-13/h1-7,13,16-17H,8H2

Synthetic route

(+/-)-3-(4-methoxyphenyl)-8-methoxy-3,4-dihydroisocoumarin (82780-51-6) → hydrangenol (480-47-7)

Conditions	Yield
With boron tribromide In dichloromethane at -78 - 25℃;	94%
With boron tribromide In dichloromethane 1.) -78 deg C , 1 h , 2.) -78 deg C to RT , 12 h;	94%
With boron tribromide In dichloromethane at -78 - 20℃;	88%

3-(4'-benzyloxyphenyl)-8-hydroxy-3,4-dihydro-2-benzopyran-1-one (637774-32-4) → hydrangenol (480-47-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate under 3750.3 Torr;	84%

6-<2-(4-benzyloxyphenyl)ethenyl>salicylic acid → hydrangenol (480-47-7)

Conditions	Yield
With hydrogenchloride In methanol for 4h; Heating;	81%

Hydrangeaic acid (491-79-2, 113428-99-2) → hydrangenol (480-47-7) + (+/-)-hydromacrophyllol B + (+/-)-hydromacrophyllol A

Conditions	Yield
With copper dichloride In acetone for 3h; Heating;	A 75% B 11.2% C 5.1%

Hydrangenol-8-O-glucoside (67600-94-6) → hydrangenol (480-47-7)

Conditions	Yield
With sulfuric acid at 80 - 90℃; for 1h;	73.5%

methyl 2-(tert-butyldimethylsilyloxy)-6-(bromomethyl)-benzoate (1093748-41-4) + p-[(tert-butyldimethylsilyl)oxy]benzaldehyde (120743-99-9) → hydrangenol (480-47-7)

Conditions	Yield
Stage #1: methyl 2-(tert-butyldimethylsilyloxy)-6-(bromomethyl)-benzoate; p-[(tert-butyldimethylsilyl)oxy]benzaldehyde With titanocene(III) chloride In tetrahydrofuran at 20℃; for 17h; Stage #2: With sulfuric acid; water In tetrahydrofuran	51%

Hydrangeaic acid (491-79-2, 113428-99-2) → hydrangenol (480-47-7)

Conditions	Yield
at 180℃;

(Ξ)-8-β-D-glucopyranosyloxy-3-<4-hydroxy-phenyl>-isochroman-1-one → hydrangenol (480-47-7)

Conditions	Yield
With sulfuric acid

1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-ethanol → hydrangenol (480-47-7)

Conditions	Yield
Stage #1: 1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-ethanol With Trimethyl borate; sec.-butyllithium In tetrahydrofuran; hexane; cyclohexane at -78 - 20℃; Stage #2: With dihydrogen peroxide In acetic acid at 20℃; Stage #3: With trifluoroacetic acid In tetrahydrofuran; water Heating; Further stages.;

methyl 2-methyl-6-methoxybenzoate (79383-44-1) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / NBS; AIBN / CCl4 2: 53 percent / Cp2TiCl2 / tetrahydrofuran / 20 °C 3: 88 percent / BBr3 / CH2Cl2 / -78 - 20 °C View Scheme

methyl 2-(bromomethoxy)-6-methoxybenzoate (943595-13-9) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 53 percent / Cp2TiCl2 / tetrahydrofuran / 20 °C 2: 88 percent / BBr3 / CH2Cl2 / -78 - 20 °C View Scheme

p-[(tert-butyldimethylsilyl)oxy]benzaldehyde (120743-99-9) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sBuLi / tetrahydrofuran; cyclohexane; hexane / -78 °C 2.1: sBuLi; B(OMe)3 / tetrahydrofuran; cyclohexane; hexane / -78 - 20 °C 2.2: H2O2 / acetic acid / 20 °C 2.3: TFA / tetrahydrofuran; H2O / Heating View Scheme

4,5-dihydro-4,4-dimethyl-2-(2-methylphenyl)-2-oxazoline (71885-44-4) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sBuLi / tetrahydrofuran; cyclohexane; hexane / -78 °C 2.1: sBuLi; B(OMe)3 / tetrahydrofuran; cyclohexane; hexane / -78 - 20 °C 2.2: H2O2 / acetic acid / 20 °C 2.3: TFA / tetrahydrofuran; H2O / Heating View Scheme

p-benzyloxybenzaldehyde (4397-53-9) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89 percent / sodium ethoxide / ethanol / 24 h / Heating 2: 94 percent / KOH / ethanol / 24 h / Heating 3: 87 percent / trifluoroacetic acid / 1,2-dichloro-ethane; H2O / 5 h / Heating 4: 84 percent / H2 / Pd/C / ethyl acetate / 3750.3 Torr View Scheme
Multi-step reaction with 5 steps 1: 68.2 percent / 10percent aq. NaOH / 14 h / Ambient temperature 2: 78 percent / dimethylformamide / 4 h / 80 °C 3: 1.) NaH, 2.) BuLi, 3.) Bf3*OEt2, 4.) KF 4: 90 percent / 10percent KOH / ethanol / 3 h / Heating 5: 81 percent / conc. HCl / methanol / 4 h / Heating View Scheme

(3-acetyloxy-2-ethoxycarbonylbenzyl)-triphenylphosphonium bromide (118842-88-9) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89 percent / sodium ethoxide / ethanol / 24 h / Heating 2: 94 percent / KOH / ethanol / 24 h / Heating 3: 87 percent / trifluoroacetic acid / 1,2-dichloro-ethane; H2O / 5 h / Heating 4: 84 percent / H2 / Pd/C / ethyl acetate / 3750.3 Torr View Scheme

2-(4'-benzyloxyphenyl)-1-(3-hydroxy-2-ethoxycarbonylphenyl)ethene (148324-47-4) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / trifluoroacetic acid / 1,2-dichloro-ethane; H2O / 5 h / Heating 2: 84 percent / H2 / Pd/C / ethyl acetate / 3750.3 Torr View Scheme

2-(4'-benzyloxyphenyl)-1-(3-hydroxy-2-ethoxycarbonylphenyl)ethene (148324-45-2) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / KOH / ethanol / 24 h / Heating 2: 87 percent / trifluoroacetic acid / 1,2-dichloro-ethane; H2O / 5 h / Heating 3: 84 percent / H2 / Pd/C / ethyl acetate / 3750.3 Torr View Scheme

3-(4-methoxyphenyl)-7-methoxy-2-benzopyran-1(1H)-one (36640-12-7) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 2: 78 percent / BBr3 View Scheme

m-methoxyphenylacetic acid (1798-09-0) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 5: 78 percent / BBr3 View Scheme
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 5: 78 percent / BBr3 View Scheme
Multi-step reaction with 6 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 90 percent / 95percent phosphoric acid / 0.25 h / Heating 5: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 6: 78 percent / BBr3 View Scheme
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 64 percent / sodium borohydride, 10percent NaOH 5: 78 percent / BBr3 View Scheme

methoxybenzene (100-66-3) + 2-chloro-decalin → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 5: 78 percent / BBr3 View Scheme
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 5: 78 percent / BBr3 View Scheme
Multi-step reaction with 6 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 90 percent / 95percent phosphoric acid / 0.25 h / Heating 5: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 6: 78 percent / BBr3 View Scheme
Multi-step reaction with 5 steps 1: 78.5 percent / polyphosphoric acid / 1.5 h / 70 - 75 °C 2: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 3: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 4: 64 percent / sodium borohydride, 10percent NaOH 5: 78 percent / BBr3 View Scheme

1′-(3-methoxyphenyl)-2′-(4′′-methoxyphenyl)ethan-2′-one (98540-26-2) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 2: 1.) 1.6M butyllithium / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 3: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 4: 78 percent / BBr3 View Scheme
Multi-step reaction with 4 steps 1: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 2: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 3: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 4: 78 percent / BBr3 View Scheme
Multi-step reaction with 5 steps 1: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 2: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 3: 90 percent / 95percent phosphoric acid / 0.25 h / Heating 4: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 5: 78 percent / BBr3 View Scheme
Multi-step reaction with 4 steps 1: 1.) trimethyl orthoformate, methanol, p-toluenesulphonic acid, 2.) p-toluenesulphonic acid / 1.) heating, 15 min, 2.) benzene, heating 2: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 3: 64 percent / sodium borohydride, 10percent NaOH 4: 78 percent / BBr3 View Scheme

3',4-dimethoxydeoxybenzoin ethylene acetal (117970-24-8) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) 1.6M butyllithium / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 2: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 3: 78 percent / BBr3 View Scheme
Multi-step reaction with 3 steps 1: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 2: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 3: 78 percent / BBr3 View Scheme
Multi-step reaction with 4 steps 1: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 2: 90 percent / 95percent phosphoric acid / 0.25 h / Heating 3: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 4: 78 percent / BBr3 View Scheme
Multi-step reaction with 3 steps 1: 1.) 1.6M butyllithium, 2.) CO2 / 1.) toluene, hexane, 24 h, 0 deg C, 2.) toluene, hexane, -20 deg C up to r.t. 2: 64 percent / sodium borohydride, 10percent NaOH 3: 78 percent / BBr3 View Scheme

3',4-dimethoxydeoxybenzoin-2'-carboxylic acid (117970-26-0) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / 95percent phosphoric acid / 0.25 h / Heating 2: 60 percent / H2 / 10percent Pt/C / tetrahydrofuran 3: 78 percent / BBr3 View Scheme
Multi-step reaction with 2 steps 1: 64 percent / sodium borohydride, 10percent NaOH 2: 78 percent / BBr3 View Scheme

5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-ol (66947-61-3) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 96 percent / lithium 2,2,6,6-tetramethylpiperidide / tetrahydrofuran / Ambient temperature 2: 77 percent / PCC / CH2Cl2 / 12 h / Ambient temperature 3: 83 percent / BBr3 / CH2Cl2 / 3 h / Ambient temperature View Scheme

4-methoxy-benzaldehyde (123-11-5) + homopyrocatechol(?) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 96 percent / lithium 2,2,6,6-tetramethylpiperidide / tetrahydrofuran / Ambient temperature 2: 77 percent / PCC / CH2Cl2 / 12 h / Ambient temperature 3: 83 percent / BBr3 / CH2Cl2 / 3 h / Ambient temperature View Scheme

3-(4'-Methoxyphenyl)-1-hydroxy-8-methoxyisochroman (157251-01-9) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / PCC / CH2Cl2 / 12 h / Ambient temperature 2: 83 percent / BBr3 / CH2Cl2 / 3 h / Ambient temperature View Scheme

1-(4-benzyloxyphenyl)but-1-en-3-one (75676-91-4) → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 78 percent / dimethylformamide / 4 h / 80 °C 2: 1.) NaH, 2.) BuLi, 3.) Bf3*OEt2, 4.) KF 3: 90 percent / 10percent KOH / ethanol / 3 h / Heating 4: 81 percent / conc. HCl / methanol / 4 h / Heating View Scheme

1-(4-benzyloxyphenyl)-5-dimethylamino-1,4-pentadien-3-one → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaH, 2.) BuLi, 3.) Bf3*OEt2, 4.) KF 2: 90 percent / 10percent KOH / ethanol / 3 h / Heating 3: 81 percent / conc. HCl / methanol / 4 h / Heating View Scheme

ethyl 6-<2-(4-benzyloxyphenyl)ethenyl>salicylate → hydrangenol (480-47-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / 10percent KOH / ethanol / 3 h / Heating 2: 81 percent / conc. HCl / methanol / 4 h / Heating View Scheme

hydrangenol (480-47-7) → Hydrangeaic acid (491-79-2, 113428-99-2)

Conditions	Yield
With potassium hydroxide In methanol for 1.5h; Heating;	100%
With sodium hydrogencarbonate In methanol

hydrangenol (480-47-7) → lunularic acid (23255-59-6)

Conditions	Yield
With sodium tetrahydroborate; palladium dichloride In methanol for 1h; Ambient temperature;	99.6%

hydrangenol (480-47-7) → dl-3,4-dihydro-8-hydroxy-3-(p-hydroxyphenyl)isocarbostyryl (80394-91-8)

Conditions	Yield
With ammonia In ethanol at 100℃; for 17h; autoclave;	64%

hydrangenol (480-47-7) → 2-hydroxy-6-methylbenzoic acid (567-61-3) + 4-hydroxy-benzoic acid (99-96-7)

Conditions	Yield
Bei der Kalischmelze;

hydrangenol (480-47-7) + tert-butyldimethylsilyl chloride (18162-48-6) → 8-(tert-Butyl-dimethyl-silanyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-isochroman-1-one (183619-44-5)

Conditions	Yield
With 1H-imidazole
With 1H-imidazole In N,N-dimethyl-formamide at 25℃; for 4h;	240 mg

hydrangenol (480-47-7) + sodium amalgam + aqueous-alcoholic natrium carbonate → lunularic acid (23255-59-6)

Conditions	Yield

ethanol (64-17-5) + hydrangenol (480-47-7) + sodium → lunularic acid (23255-59-6)

Conditions	Yield

hydrangenol (480-47-7) + alkaline solution → Hydrangeaic acid (491-79-2, 113428-99-2)

Conditions	Yield

hydrangenol (480-47-7) + aq. barium hydroxide solution → Hydrangeaic acid (491-79-2, 113428-99-2)

Conditions	Yield

hydrangenol (480-47-7) + natrium carbonate solution → Hydrangeaic acid (491-79-2, 113428-99-2)

Conditions	Yield

hydrangenol (480-47-7) → 3'-Deoxythunberginol A (80458-94-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 240 mg / imidazole / dimethylformamide / 4 h / 25 °C 2: 89.9 percent / DDQ / benzene / 5 h / Heating 3: 100 percent / n-Bu4NF / tetrahydrofuran / 0.08 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1: imidazole 2: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone 3: n-Bu4NF View Scheme

Upstream product

• 491-79-2 Hydrangeaic acid 
• 66947-61-3 5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-ol 
• 1093748-41-4 methyl 2-(tert-butyldimethylsilyloxy)-6-(bromomethyl)-benzoate 
• 120743-99-9 p-[(tert-butyldimethylsilyl)oxy]benzaldehyde 
• 123-11-5 4-methoxy-benzaldehyde 
• 82780-49-2 2-[2-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-6-methoxy-N,N-dimethyl-benzamide 
• 82780-48-1 N,N-Dimethyl-2-methoxy-6-methylbenzamide 
• 7291-34-1 2-methoxy-N,N-dimethylbenzamide 
• 75676-91-4 1-(4-benzyloxyphenyl)but-1-en-3-one 
• 157251-01-9 3-(4'-Methoxyphenyl)-1-hydroxy-8-methoxyisochroman 
• 117970-26-0 3',4-dimethoxydeoxybenzoin-2'-carboxylic acid 
• 117970-24-8 3',4-dimethoxydeoxybenzoin ethylene acetal 
• 98540-26-2 1′-(3-methoxyphenyl)-2′-(4′′-methoxyphenyl)ethan-2′-one 
• 100-66-3 methoxybenzene 

Downstream Products

• 567-61-3 2-hydroxy-6-methylbenzoic acid 
• 99-96-7 4-hydroxy-benzoic acid 
• 23255-59-6 lunularic acid 
• 491-79-2 Hydrangeaic acid 
• 157598-00-0 (+/-)-hydromacrophyllol A 
• 157598-00-0 (+/-)-hydromacrophyllol B 
• 183619-48-9 8-(tert-Butyl-dimethyl-silanyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-isochromen-1-one 
• 80458-94-2 3'-Deoxythunberginol A 
• 80394-91-8 dl-3,4-dihydro-8-hydroxy-3-(p-hydroxyphenyl)isocarbostyryl 
• 183619-44-5 8-(tert-Butyl-dimethyl-silanyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-isochroman-1-one 

Relevant articles and documents

Titanocene(III) chloride mediated radical-induced synthesis of 3,4-dihydroisocoumarins: synthesis of (±)-hydrangenol, (±)-phyllodulcin, (±)-macrophyllol and (±)-thunberginol G

A radical-promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp2TiCl) as the radical initiator. The total synthesis of four naturally occurring dihydrocoumarins hydrangenol, phyllodulcin, macrophyllol and thunberginol G has been accomplished using the radical technology. Cp2TiCl was prepared in situ from commercially available titanocene dichloride (Cp2TiCl2) and Zn-dust in THF under argon.

Radical-mediated synthesis of 3,4-dihydroisocoumarins: total synthesis of hydrangenol

A radically promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp2TiCl) as the radical initiator. The total synthesis of (±)-hydrangenol has been completed using this radical technology. Cp2TiCl was prepared in situ from commercially available titanocene dichloride (Cp2TiCl2) and Zn-dust in THF under argon.

Synthesis of 3-substituted 8-hydroxy-3,4-dihydroisocoumarins via successive lateral and ortho-lithiations of 4,4-dimethyl-2-(o-tolyl)oxazoline

Sequential treatment of 4,4-dimethyl-2-(o-tolyl)oxazoline in THF with sec-BuLi, aromatic or aliphatic aldehydes, sec-BuLi, B(OMe)3, and H2O2 produced the laterally alkylated and ortho-hydroxylated oxazolines in one-pot. Treatment of these products with TFA in aqueous THF provided 3-substituted 8-hydroxy-3,4-dihydroisocoumarins in 44-75% overall yields. This procedure allowed the short synthesis of (±)-hydrangenol and (±)-phyllodulcin, naturally occurring 3,4-dihydroisocoumarins of pharmacological interest. A more economical synthesis of (±)-phyllodulcin via the trianion intermediate is also described.

Efficient syntheses of (+/-)-hydrangenol, (+/-)-phyllodulcin and (+/-)-macrophyllol

In this paper we report on a efficient and flexible synthetic route towards the total syntheses of the dihydrocoumarine derivatives hydrangenol (1), phyllodulcin (1a) and macrophyllol (6b). The syntheses started with a readily available phosphonium salt 2 and suitable modified benzaldehydes 3/3a/3b resulting in 46 to 61 percent overall yields in three to four-steps sequences. The racemic products could be separated by chiral HPLC. The evidence of the (R)-enantiomer for sweetness could be demonstrated for 1a.

Development of bioactive functions in Hydrangeae Dulcis Folium. VI. Syntheses of thunberginols A and F and their 3'-deoxy-derivatives using regiospecific lactonization of stilbene carboxylic acid: Structures and inhibitory activity on histamine release of hydramacrophyllols A and B

Lactonization reaction of 2-carboxystilbene mediated by copper(II) chloride proceeded regiospecifically to give the five-membered lactone, while the bromolactonizations using N-bromosuccinimide and anodic oxidation were found to furnish the six-membered lactone. Using these regiospecific lactonization reactions as a key step, antiallergic and antimicrobial isocoumarins and the benzylidenephthalides thunberginols A and F and their 3'-deoxyanalogs were synthesized from phyllodulcin and hydrangenol. Two phthalides called hydramacrophyllols A and B were isolated from Hydrangeae Dulcis Folium and their stereostructures were determined on the basis of physicochemical and chemical evidence, which included the syntheses of hydramacrophyllols A and B from hydrangenol by the application of the lactonization method using copper(II) chloride. In addition, hydramacrophyllols A and B were found to exhibit an inhibitory effect on the histamine release from rat peritoneal exudate cells induced by antigen- antibody reaction.

Reaction of Benzocyclobutenoxides with Aldehydes: Synthesis of Peshawarine and Other 3,4-Dihydroisocoumarins

Deprotonation of benzocyclobutenols 6 in presence of aromatic aldehydes affords benzopyranols 7 in high yield.In the key step of this process, an o-tolualdehyde anion generated by the known ring-opening of benzocyclobutenoxides adds to the aldehyde to give 7 which is easily oxidized to 3-substituted 3,4-dihydroisocoumarins 8 including intermediates in some natural product syntheses.For example, reaction of 6-methoxybenzocyclobutenol (1) with LTMP and p-anisaldehyde gave in 96percent yield to benzopyranol 16, which subsequently was converted to (+/-)-hydrangenol (17).Similar treatment of 1 with LDA and isovanillin benzyl ether afforded the benzopyranol 19 (87percent yield) which already has been converted to (+/-)-phyllodulcin (21).Finally, reaction of 5,6-(methylenedioxy)benzocyclobutenol (10) with LTMP and the aldehyde 26 (from treatment of hydrastinine with ClCO2Me) followed by methanolysis produced the acetal 28 in 96percent yield.The overall yield was 65percent for the five-step synthesis of the alkaloid (+/-)-peshawawine (24) from 10 and 26.Extension of the process to aliphatic aldehydes was illustrated by the preparation of 32 from benzocyclobutenol and isobutyraldehyde in 69percent overall yield after oxidation with PCC.

SYNTHESES OF DIHYDROISOCOUMARINS, (+/-)-HYDRANGENOL AND (+/-)-PHYLLODULCIN, UTILIZING AN ANNELATION REACTION OF ENAMINONES WITH ETHYL ACETOACETATE. STUDIES ON THE β-CARBONYL COMPOUNDS CONNECTED WITH THE β-POLYKETIDES XIII

Naturally occurring dihydroisocoumarins, (+/-)-hydrangenol (1) and (+/-)-phyllodulcin (2) were synthesized from the enaminones (3) and (4) by the annelation reactions with ethyl acetoacetate (5).

A HIGHLY EFFICIENT PREPARATION OF LUNULARIC ACID AND SOME BIOLOGICAL ACTIVITIES OF STILBENE AND DIHYDROSTILBENE DERIVATIVES

Lunularic acid, an acid possessing dormancy inducing, antifungal, thromboxane synthetase and hyaluronidase inhibitory and plant growth inhibitory activities, was obtained quantitatively from hydrangenol by reduction using sodium borohydride-palladium chloride.Some stilbene and dihydrostilbene derivatives prepared from hydrangenol and its glucoside also showed plant growth inhibitory, hyaluronidase inhibitory and piscicidal activities.Key Word Index - Lunularic acid; dihydrostilbenes; stilbenes; hydrangenol; dihydroisocoumarin; sodium borohydide-palladium chloride reduction; dormancy; plant growth inhibitory activity; piscicidal activity; hyaluronidase inhibitory activity.

TOTAL SYNTHESIS OF (+/-)-HYDRANGENOL

The title compound 8 has been synthesized in five steps and in about 33percent overall yield from 3-methoxyphenylacetic acid, 1.Acid 1 was condensed with anisole in polyphosphoric acid to give 3',4-dimethoxydeoxybenzoin, 2, which was converted to the ethylene acetal 3.The latter was metallated with buthyllithium and carbonated giving crude 3',4-dimethoxydeoxybenzoin-2'-carboxylic acid, 4, from which 3,4-dihydro-8-methoxy-3-(4'-methoxyphenyl)isocoumarin, 7, was obtained either by reduction with sodium borohydride and dehydration, or dehydration to 8-methoxy-3-(4'-methoxyphenyl)isocoumarin, 6, and catalytic hydrogenation.Finally, demethylation of 6 to 8 was performed with boron tribromide.

Ortho-Lithiated Tertiary Benzamides. Chain Extension via o-Toluamide Anion and General Synthesis of Isocoumarins Including Hydrangenol and Phyllodulcin

Lithiation of N,N-diethyl-2-methylbenzamide (2a) followed by condensation with aromatic aldehydes and basic hydrolysis leads to 3-aryl-3,4-dihydroisocoumarins 4 in modest overall yields.Adoption of this methodology to N,N-dimethyl-2-methyl-6-methoxybenzamide (7b) provides isocoumarins 9a and 9b which by selective demethylation procedures yields hydrangenol (10a) and phyllodulcin (10c), naturally occurring isocoumarins of pharmacological interest.A one-pot, abbreviated procedure for the preparation of both 9a and 9b starting with N,N-Dimethyl-2-methoxybenzamide (6c) is also described.