6790-58-5

Basic information

• Product Name: Ambroxane
• Synonyms: [3aR-(3aalpha,5abeta,9aalpha,9bbeta)]-dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan;Amberoxan;Ambropur;(-)-AMBROXIDE 99+%;Naphtho2,1-bfuran, dodecahydro-3a,6,6,9a-tetramethyl-, (3aR,5aS,9aS,9bR)-;(3aR,5aS,9aS,9bR)-Dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan;Ambroxane;()-Ambroxide,1,5,5,9-Tetramethyl-13-oxatricyclo[8.3.0.04,9]tridecane
• CAS NO: 6790-58-5
• Molecular Formula: C16H28O
• Molecular Weight: 236.39
• EINECS: 229-861-2
• Product Categories: Flavors & Fragrances;Flavors and Fragrances
• Mol File: 6790-58-5.mol
• Article Data: 62

Chemical Properties

• Melting Point: 74-76 °C(lit.)
• Boiling Point: 273.9 °C at 760 mmHg
• Flash Point: 104.8 °C
• Appearance: /
• Density: 0.939
• Vapor Pressure: 0.00934mmHg at 25°C
• Refractive Index: 1.48
• Storage Temp.: Sealed in dry,Room Temperature
• Water Solubility: 1.88mg/L at 20℃
• CAS DataBase Reference: Ambroxane(CAS DataBase Reference)
• NIST Chemistry Reference: Ambroxane(6790-58-5)
• EPA Substance Registry System: Ambroxane(6790-58-5)

Safety Data

• WGK Germany: 1
• Hazardous Substances Data: 6790-58-5(Hazardous Substances Data)

Usage

Description

Ambroxan is a synthetic spice with the special aroma of natural ambergris, and it is recognized as one of the best substitutes for natural ambergris. It is one of the most critical trace components of natural ambergris tincture. Natural ambergris is a precious animal spice. It is a kind of stone in the stomach of sperm whale. It is vomited or excreted on the sea surface by the whale, and it emits a special fragrance in the air for a long time.

Uses

(-)-Ambroxide can be used:To prepare (+)-sclareolide through C-H oxidation strategy.As a substrate in C(sp3)-H alkylation/arylation studies of ethers.As a substrate in the study of ethereal hydrocarbon hydroperoxidation using singlet O2.

Definition

ChEBI: Ambroxan is a diterpenoid derived from sclareol that is responsible for the odour of ambergris (a solid, waxy, flammable substance produced in the digestive system of sperm whales). It is an organic heterotricyclic compound and a diterpenoid.

Preparation

Ambroxene naturally occurring autoxidation or photooxide of the triterpenoid secreted by sperm whales.Industrially, High acacia acid was prepared from nerolidol. After acid internal esterification, the racemic Ambroxene was obtained.Ambroxide is synthesized from sclareol, a component of the essential oil of clary sage. Sclareol is oxidatively degraded to a lactone, which is hydrogenated to the corresponding diol. The resulting compound is dehydrated to form ambroxide.

Application

Ambroxan has a strong, characteristic ambergris aroma. Used in high-grade perfumes and cosmetic essences, because it is non-irritating to the human body and non-allergic to animals, it is very suitable for fragrances for skin, hair and fabrics. Often used in soaps, talcum powders, creams and shampoos for perfuming and fixing fragrance.

General Description

Ambroxide is a terpenoid, which has vast applications in the perfume industry due to its fixative property and odor. Ambergris, which was originally sourced from sperm whale, has been substituted by synthetic ambroxides.

Flammability and Explosibility

Notclassified

Side effects

The most common side effects associated with Ambroxane use include those which are observed among patients developing allergic reactions. These include pruritus, hives, and swelling in the face, lips, tongue, or throat. It is important to immediately seek medical attention upon the development of dangerous adverse allergic reactions like difficulty in breathing, shortness of breath, convulsions, and mood changes.

Synthesis

Perillyl alcohol is used as raw material to synthesize nordrone ether, which is oxidized by KMnO4 in two steps (Switzerland uses ozone oxidation, Russia uses sodium chromate oxidation). That is (1) alkaline oxidation; (2) weak acid oxidation. The oxide is obtained, and then the oxide is soaped, dehydrated and lactonized to obtain ambroxolide. lactones are reduced to ambroxol with lithium aluminum hydride in ether (or with borane in tetrahydrofuran). D-camphor-β-sulfonic acid is used as a cyclizing agent to cyclize diols to obtain ambrox (foreign cyclizing agents include sulfuric acid, p-toluenesulfonic acid and β-naphthalenesulfonic acid, etc.).

InChI:InChI=1/C16H28O/c1-14(2)8-5-9-15(3)12(14)6-10-16(4)13(15)7-11-17-16/h12-13H,5-11H2,1-4H3

Synthetic route

(3aR)-(+)-sclareolide (564-20-5, 1216-84-8, 30450-17-0, 58976-28-6, 64090-92-2, 67844-42-2, 79768-41-5, 79768-42-6, 86688-27-9, 86688-28-0, 95406-08-9, 98719-44-9, 98719-46-1, 131831-65-7, 140851-80-5) → (1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) + (-)-ambroxide (6790-58-5)

Conditions	Yield
With RuCl2(2-(diphenylphosphino)-N-(thiophen-2-ylmethyl)ethanamine)PPh3; hydrogen In toluene at 100℃; under 37503.8 Torr; for 16h; Catalytic behavior; Reagent/catalyst; Temperature; Solvent; Inert atmosphere; Autoclave;	A 99.5% B n/a
With RuCl2(2-(diphenylphosphino)-N-(2-(methylthio)ethyl)ethanamine)PPh3; hydrogen; sodium methylate In toluene at 100℃; for 16h; Catalytic behavior; Autoclave;	A 67% B 12%

biscyclohomofarnesane-8α,12-diol (320756-17-0) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With ammonium cerium(IV) nitrate In acetonitrile at 20℃; for 11h;	98%

(8α-Methyl)-iresan-8β,11-diol (10207-83-7, 38419-75-9, 41747-05-1, 55881-96-4, 64090-93-3, 86023-44-1, 86023-45-2, 100679-84-3, 105087-83-0, 106035-74-9, 106091-98-9, 106091-99-0, 122566-14-7, 131831-64-6, 131831-66-8, 131831-67-9, 131831-74-8) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With ammonium cerium(IV) nitrate In acetonitrile at 20℃; for 10h;	97%

(1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With n-butyllithium; p-toluenesulfonyl chloride In tetrahydrofuran; hexane at 0 - 20℃;	96%
With sodium hydride; p-toluenesulfonyl chloride In dichloromethane at 25℃;	94%
With zinc(II) chloride In 1,2-dichloro-ethane for 3h;	92%

Δ2(3)-ambrox (1038482-07-3) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With 10% Pd/C; hydrogen In ethyl acetate at 20℃; for 12h;	96%
With palladium 10% on activated carbon; hydrogen In methanol under 760.051 Torr;	92%

aqueous sodium sulfate + (1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With hydrogenchloride In water; toluene	95%

<1R-(1α,2β,4aβ,8aα)>-decahydro-1-(2-chloroethyl)-2,5,5,8a-tetramethyl-2-naphthalenol acetate (121067-50-3) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With potassium hydroxide In water; isopropyl alcohol	92%

(3aS,5aS,9aS,9bR)-3a,6,6,9a-Tetramethyl-decahydro-naphtho[2,1-b]furan-4-one (116163-57-6) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With potassium hydroxide; hydrazine	90%

(3aR)-(+)-sclareolide (564-20-5, 1216-84-8, 30450-17-0, 58976-28-6, 64090-92-2, 67844-42-2, 79768-41-5, 79768-42-6, 86688-27-9, 86688-28-0, 95406-08-9, 98719-44-9, 98719-46-1, 131831-65-7, 140851-80-5) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With sodium tetrahydroborate; zinc(II) iodide In tetrahydrofuran for 1h; Heating;	85%
Multi-step reaction with 2 steps 1: 95 percent / potassium borohydride / ethanol / 10 h / Heating 2: 92 percent / bromotrichloromethane; triphenylphosphine; NaHCO3 / CH2Cl2 / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 97 percent / LiAlH4 / tetrahydrofuran / 3 h / 20 °C 2: 96 percent / n-BuLi; TsCl / hexane; tetrahydrofuran / 0 - 20 °C View Scheme

<1R-(1α,2β,4aβ,8aα)>-1-decahydro-1-(2-iodoethyl)-2,5,5,8a-tetramethyl-2-naphthalenol acetate (121067-46-7) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With potassium hydroxide In water; isopropyl alcohol for 18h; Heating;	81%

2-((1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6, 7,8,8a-octahydronaphthalen-1-yl)ethan-1-ol (31207-73-5) → 2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethanol (31222-15-8) + (-)-ambroxide (6790-58-5)

Conditions	Yield
With toluene-4-sulfonic acid In nitromethane for 18h; Ambient temperature;	A n/a B 80%

2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethanol (31222-15-8) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With iron(III) chloride In 1,2-dichloro-ethane at 25℃; Reagent/catalyst; enantioselective reaction;	77%
Acidic conditions;

13,14,15,16-tetranor-8βH-labdane-8,12-diol (41747-05-1) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With toluene-4-sulfonic acid In nitromethane at 80℃; for 0.5h;	76%
With toluene-4-sulfonic acid In nitromethane at 40℃; for 0.0833333h;	45%

8α,12-epoxy-13,14,15,16-tetranorlabdan-19-al (152185-80-3) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With potassium hydroxide; hydrazine hydrate In various solvent(s) for 1h; Heating;	71%
With potassium hydroxide; hydrazine hydrate In various solvent(s) for 1h; Heating;	71%

(1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyldecahydronaphthalen-2-yl acetate (38419-76-0) → (1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) + (-)-ambroxide (6790-58-5)

Conditions	Yield
With sodium methylate; carbonic acid dimethyl ester In tetrahydrofuran; methanol at 65℃; for 2h;	A 4% B 67%

<1S-(1α,2β,3β,4β,4aβ,8aα)> decahydro-3-hydroxyl-2,5,5,8a-tetramethylnaphthalene-1-ethanol (158577-90-3) → (-)-ambroxide (6790-58-5) + 8β,12-epoxy-13,14,15,16-tetranorlabdane (68365-88-8)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 80℃; for 2h;	A 48% B 10%

(1R,2R,4aS,8aS)-1-(3-Hydroperoxy-3-methyl-pent-4-enyl)-2,5,5,8a-tetramethyl-decahydro-naphthalen-2-ol (105735-95-3, 105735-96-4) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With copper diacetate; iron(II) sulfate In methanol at 50℃; for 3h;	33%
With copper diacetate; iron(II) sulfate In methanol at 50℃; for 3h; Product distribution; other amounts of reagents;
Multi-step reaction with 4 steps 1: triphenylphosphine / diethyl ether / 24 h / 20 °C 2: 83 percent / H2 / 5percent Pd/C / ethanol / 760 Torr / Ambient temperature 3: 1.) aq. NaOCl / 1.) AcOH, CCl4, 0 deg C, 3h, 2.) 30-35 deg C, 3h 4: 80percent NaH / tetrahydrofuran / 3 h / Heating View Scheme

sclareol (515-03-7) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With dihydrogen peroxide In water at 70℃; for 4h;	20%
Multi-step reaction with 2 steps 1.1: potassium permanganate; acetic anhydride / acetone / 2 h / 0 °C 1.2: 97 percent / lithium aluminum hydride / tetrahydrofuran / 2 h / 20 °C 2.1: 92 percent / bromotrichloromethane; triphenylphosphine; NaHCO3 / CH2Cl2 / 6 h / Heating View Scheme
Multi-step reaction with 6 steps 1.1: peracetic acid; NaOAc / ethyl acetate / 192 h / 20 °C 2.1: 1 N aq. NaOH / 2-methyl-propan-2-ol / 20 °C 2.2: H2SO4 / ethyl acetate / 2 h / 0 - 20 °C 3.1: 97 percent / NaIO4 / tetrahydrofuran; H2O / 16 h / 20 °C 4.1: 95 percent / peracetic acid / 50 - 55 °C 5.1: 97 percent / LiAlH4 / tetrahydrofuran / 3 h / 20 °C 6.1: 96 percent / n-BuLi; TsCl / hexane; tetrahydrofuran / 0 - 20 °C View Scheme

C20H39N2O3P (113327-33-6) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With lithium In various solvent(s) Yield given;

(1R,2R,4aS,8aS)-1-(2-Chloro-ethyl)-2,5,5,8a-tetramethyl-decahydro-naphthalen-2-ol (113105-33-2) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran for 3h; Heating; Yield given;

Toluene-4-sulfonic acid 2-((1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydro-naphthalen-1-yl)-ethyl ester → (-)-ambroxide (6790-58-5)

Conditions	Yield
for 1h; Ambient temperature; Yield given;

(4aS,6aR,11aR,11bS)-4,4,6a,11b-Tetramethyl-dodecahydro-7,9-dioxa-cyclohepta[a]naphthalene (38419-77-1) → (-)-ambroxide (6790-58-5)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane

(4aS)-1t-<2-hydroxy-ethyl>-2t,5,5,8a-tetramethyl-(4ar,8at)-decahydro-<2c>naphthol → (-)-ambroxide (6790-58-5)

(4aS)-1t(?)-<2-hydroxy-ethyl>-2c(?),5,5,8a-tetramethyl-(4ar,8at-decahydro-<2t?>naphthol → (-)-ambroxide (6790-58-5) + 8β,12-epoxy-13,14,15,16-tetranorlabdane (68365-88-8)

Conditions	Yield
With naphthalene-2-sulfonate Erhitzen unter vermindertem Druck;

(1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) → 2-((1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6, 7,8,8a-octahydronaphthalen-1-yl)ethan-1-ol (31207-73-5) + 2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethanol (31222-15-8) + (-)-ambroxide (6790-58-5)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane for 0.5h; Heating; Title compound not separated from byproducts;	A 7.2 % Chromat. B 16.8 % Chromat. C 67.4 % Chromat.
With toluene-4-sulfonic acid In dichloromethane at 20℃; for 1h; Title compound not separated from byproducts;	A 7.6 % Chromat. B 16.8 % Chromat. C 65.2 % Chromat.

(1R,2R,4aS,8aS)-1-(2-hydroxyethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (38419-75-9) → 2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalen-1-yl]ethanol (31222-15-8) + (-)-ambroxide (6790-58-5) + 8β,12-epoxy-13,14,15,16-tetranorlabdane (68365-88-8)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane for 30h; Heating; Title compound not separated from byproducts;	A 11.2 % Chromat. B 29.6 % Chromat. C 59.1 % Chromat.

(E,E)-homofarnesyl triethylsilyl ether (425681-11-4) → (+)-ambrox (ent-1) + (-)-ambroxide (6790-58-5)

Conditions	Yield
Stage #1: (E,E)-homofarnesyl triethylsilyl ether With (R)-2-(o-fluorobenzyloxy)-2'-methoxy-1,1'-binaphthyl*SnCl4 In toluene at -78℃; for 72h; Stage #2: With 1H-imidazole; triethylsilyl chloride In N,N-dimethyl-formamide at 20℃; for 5h; Stage #3: With TFA*SnCl4 In toluene at -78℃; for 24h; Further stages. Title compound not separated from byproducts.;

(4aS)-1t(?)-<2-hydroxy-ethyl>-2c(?),5,5,8a-tetramethyl-(4ar,8at)-decahydro-<2t?>naphthol → (-)-ambroxide (6790-58-5) + 8β,12-epoxy-13,14,15,16-tetranorlabdane (68365-88-8)

Conditions	Yield
With naphthalene-2-sulfonate Erhitzen unter vermindertem Druck;

8-hydroxy-15,16-dinor-labdan-13-one (16736-51-9) → (-)-ambroxide (6790-58-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / sodium chromate; acetic anhydride; glacial acetic acid / benzene / 4 h / 70 °C 2: 95 percent / potassium borohydride / ethanol / 10 h / Heating 3: 92 percent / bromotrichloromethane; triphenylphosphine; NaHCO3 / CH2Cl2 / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 83 percent / sodium chromate; acetic anhydride; glacial acetic acid / benzene / 4 h / 70 °C 2: 85 percent / zinc iodide; sodium borohydride / tetrahydrofuran / 1 h / Heating View Scheme

Farnesal (502-67-0) → (-)-ambroxide (6790-58-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 96 percent / PhLi / tetrahydrofuran; cyclohexane; diethyl ether / 1 h / 20 °C 2.1: tetrahydrofuran / 24 h / 20 °C 3.1: H2O2; NaOH / tetrahydrofuran 4.1: 100 percent / imidazole / dimethylformamide / 20 °C 5.1: (R)-2-(o-fluorobenzyloxy)-2'-methoxy-1,1'-binaphthyl*SnCl4 / toluene / 72 h / -78 °C 5.2: ClSiEt3; imidazole / dimethylformamide / 5 h / 20 °C 5.3: TFA*SnCl4 / various solvent(s); toluene / 24 h / -78 °C View Scheme

2-((trifluoromethyl)thio)isoindoline-1,3-dione (719-98-2) + (-)-ambroxide (6790-58-5) → (3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyl-2-((trifluoromethyl)thio)dodecahydronaphtho[2,1-b]furan

Conditions	Yield
With sodium benzoate; [Ir(2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine)2(4,4'-di-tert-butyl-2,2'-bipyridine)](PF6) In acetonitrile at 20℃; for 2h; Inert atmosphere; Irradiation; regioselective reaction;	95%

(-)-ambroxide (6790-58-5) → (3aR)-(+)-sclareolide (564-20-5, 1216-84-8, 30450-17-0, 58976-28-6, 64090-92-2, 67844-42-2, 79768-41-5, 79768-42-6, 86688-27-9, 86688-28-0, 95406-08-9, 98719-44-9, 98719-46-1, 131831-65-7, 140851-80-5)

Conditions	Yield
With dipotassium hydrogenphosphate; C17H18ClFeN6O6(2-); 3-chloro-benzenecarboperoxoic acid In water; acetonitrile at 20℃;	90%
With (R,R)-Fe(PDP); dihydrogen peroxide; acetic acid regioselective reaction;	80%
With 2,6-dichloropyridine N-oxide; dichloro(5,10,15,20-tetramesitylporphyrinato)ruthenium(IV) In 1,2-dichloro-ethane at 40℃; for 24h; Reagent/catalyst; Inert atmosphere; regioselective reaction;	80%

P-toluenesulfonyl cyanide (19158-51-1) + (-)-ambroxide (6790-58-5) → ambroxide-12-carbonitrile (1338695-87-6)

Conditions	Yield
With benzophenone In acetonitrile at 20℃; for 2h; Inert atmosphere; UV-irradiation; stereoselective reaction;	89%
With benzophenone In acetonitrile at 20℃; for 2h; Inert atmosphere; UV-irradiation; chemoselective reaction;	89%

1,1-bis(phenylsulfonyl)ethylene (39082-53-6) + (-)-ambroxide (6790-58-5) → C30H40O5S2

Conditions	Yield
With [Ir(dF(CF3)ppy)2(5,5'dCF3bpy)]PF6; dibutylphosphoric acid tetrabutylammonium salt In dichloromethane at 20℃; for 24h; Glovebox; Inert atmosphere; Irradiation;	88%
With 2-chloroanthracene-9,10-dione In dichloromethane at 20℃; for 4h; Irradiation; Optical yield = 48 %de; diastereoselective reaction;

(-)-ambroxide (6790-58-5) → C16H27N3O

Conditions	Yield
With 4-toluenesulfonyl azide; 4-Benzoylpyridine In benzene at 20℃; for 3h; UV-irradiation; Inert atmosphere; chemoselective reaction;	77%

(prop-2-ene-1,2-diyldisulfonyl)dibenzene (2525-55-5) + (-)-ambroxide (6790-58-5) → C25H36O3S

Conditions	Yield
With pentacene-5,7,12,14-tetraone; potassium carbonate In dichloromethane at 20℃; for 24h; Inert atmosphere; Irradiation;	74%

(-)-ambroxide (6790-58-5) → (1S,6S)-2-(2-bromoethyl)-1,3,7,7-tetramethylbicyclo[4.4.0]dec-2-ene (308255-94-9)

Conditions	Yield
With boron trifluoride diethyl etherate; tetraethylammonium bromide In dichloromethane at 20℃; Ring cleavage;	72%

(4-methoxy)benzenesulfonylmethanal O-benzyl oxime + (-)-ambroxide (6790-58-5) → C24H35NO2

Conditions	Yield
With 4-Benzoylpyridine In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; UV-irradiation;	70%

(-)-ambroxide (6790-58-5) → (4aS,8aS)-5-(2-iodoethyl)-1,1,4a,6-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalene (308255-96-1)

Conditions	Yield
With aluminium trichloride; sodium iodide In dichloromethane; acetonitrile at 20℃; Ring cleavage;	69%

4-methoxycarbonylphenyl bromide (619-42-1) + (-)-ambroxide (6790-58-5) → methyl 4-((2R,3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)benzoate + methyl 4-((2S,3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)benzoate

Conditions	Yield
With bis(acetylacetonate)nickel(II); 5,5'-dimethyl-2,2'-bipyridine; (4-methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone; sodium carbonate In benzene at 20℃; for 96h; Schlenk technique; diastereoselective reaction;	A 69% B n/a
With bis(acetylacetonate)nickel(II); 5,5'-dimethyl-2,2'-bipyridine; (4-methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone; sodium hydrogencarbonate In benzene at 20℃; for 96h; Schlenk technique; Inert atmosphere; Irradiation; Overall yield = 69 %; Overall yield = 76.7 mg; diastereoselective reaction;	A n/a B n/a

Benzylidenemalononitrile (2700-22-3) + (-)-ambroxide (6790-58-5) → 2-(phenyl((3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)methyl)malononitrile

Conditions	Yield
With eosin In tert-butyl alcohol at 0 - 60℃; for 48h; Sealed tube; Inert atmosphere; Irradiation;	68%

(-)-ambroxide (6790-58-5) → C16H28O3 (1217488-90-8)

Conditions	Yield
With Botrytis cynerea for 72h; Microbiological reaction; chemoselective reaction;	60%

(-)-ambroxide (6790-58-5) → (1R,2R,4aS,8aS)-(2-hydroxy-2,5,5,8a-tetramethylperhydronaphthyl)acetic acid (13456-36-5) + (3aR)-(+)-sclareolide (564-20-5, 1216-84-8, 30450-17-0, 58976-28-6, 64090-92-2, 67844-42-2, 79768-41-5, 79768-42-6, 86688-27-9, 86688-28-0, 95406-08-9, 98719-44-9, 98719-46-1, 131831-65-7, 140851-80-5)

Conditions	Yield
With [((S,S)-N,N′-bis(2-pyridylmethyl)-(S,S)-2,2′-bipyrrolidine)FeII(OTf)2]; dihydrogen peroxide; acetic acid In water; acetonitrile at 0 - 20℃; Catalytic behavior; Inert atmosphere; regiospecific reaction;	A 29% B 54%

isoquinoline (119-65-3) + (-)-ambroxide (6790-58-5) → 1-((3aR,5aS,9aS,9bR)-3 a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)isoquinoline

Conditions	Yield
With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; diastereoselective reaction;	53%

Upstream product

• 121067-50-3 <1R-(1α,2β,4aβ,8aα)>-decahydro-1-(2-chloroethyl)-2,5,5,8a-tetramethyl-2-naphthalenol acetate 
• 121067-46-7 <1R-(1α,2β,4aβ,8aα)>-1-decahydro-1-(2-iodoethyl)-2,5,5,8a-tetramethyl-2-naphthalenol acetate 
• 31207-73-5 2-((1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6, 7,8,8a-octahydronaphthalen-1-yl)ethan-1-ol 
• 196805-72-8 2,3,4,4a,5,6,7,8-octahydro-2β,3α-dihydroxy-4aβ,8,8-trimethylnaphthalene 
• 196805-70-6 2,3,4,4a,5,6,7,8-octahydro-2β,3β-dihydroxy-4aβ,8,8-trimethylnaphthalene 
• 106035-70-5 2-((1'R,4'aS,8'aS)-5',5',8'a-Trimethyl-octahydro-spiro[[1,3]dioxolane-2,2'-naphthalen]-1'-yl)-ethanol 
• 196805-77-3 2-((1'S,4'aS,8'aS)-5',5',8'a-Trimethyl-octahydro-spiro[[1,3]dioxolane-2,2'-naphthalen]-1'-yl)-ethanol 
• 196805-86-4 (1R,2S,4aS,8aS)-1-(2-Benzyloxy-ethyl)-2,5,5,8a-tetramethyl-decahydro-naphthalen-2-ol 
• 196805-79-5 (1S,4aS,8aS)-1-(2-Benzyloxy-ethyl)-5,5,8a-trimethyl-octahydro-naphthalen-2-one 
• 196805-85-3 (1R,4aS,8aS)-1-(2-Benzyloxy-ethyl)-5,5,8a-trimethyl-octahydro-naphthalen-2-one 
• 196805-83-1 ((1'R,4'aS,8'aS)-5',5',8'a-Trimethyl-octahydro-spiro[[1,3]dioxolane-2,2'-naphthalen]-1'-yl)-acetic acid ethyl ester 
• 196805-76-2 ((1'S,4'aS,8'aS)-5',5',8'a-Trimethyl-octahydro-spiro[[1,3]dioxolane-2,2'-naphthalen]-1'-yl)-acetic acid ethyl ester 
• 1616-86-0 cis-abienol 
• 74483-92-4 (+)-3-oxo-sclareolide 

Downstream Products

• 3738-00-9 (3aRS,5aSR,9aRS,9bSR)-dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan 
• 3738-00-9 (-)-norlabdane 
• 122566-19-2 <3aR-(3aα,4α,6aα,10aS^*)> dodecahydro-3a,4,7,7-tetramethyl-2H-naphtho<8a,1-b>furan 
• 29064-99-1 2-oxosclareolide 
• 292643-80-2 (+)-1-oxo-sclareolide 
• 1422446-22-7 C₁₆H₂₆O₃ 
• 74483-92-4 (+)-3-oxo-sclareolide 
• 13456-36-5 (1R,2R,4aS,8aS)-(2-hydroxy-2,5,5,8a-tetramethylperhydronaphthyl)acetic acid 
• 564-20-5 (3aR)-(+)-sclareolide 

Relevant articles and documents

Preparation of two diastereoisomeric decalin synthons and (-)-ambrox

Two diastereoisomeric decalins, (2S,4aS,5S,6R)- and (2S,4aS,5R,6R)-5-(2- hydroxyethyl)-1,1,4a,6-tetramethyldecalin-2,6-diol (5 and 6) were prepared from the degradation products of oleanolic acid. Starting from 6, (-)-ambrox (4) was synthesized.

Manganese-Catalyzed Hydrogenation of Sclareolide to Ambradiol

The hydrogenation of (+)-Sclareolide to (?)-ambradiol catalyzed by a manganese pincer complex is reported. The hydrogenation reaction is performed with an air- and moisture-stable manganese catalyst and proceeds under relatively mild reaction conditions at low manganese and base loadings. A range of other esters could be successfully hydrogenated leading to the corresponding alcohols in good to quantitative yields using this easy-to-make catalyst. A scale-up experiment was performed leading to 99.3 % of the isolated yield of (?)-Ambradiol.

A SOLID FORM OF (-)-AMBROX FORMED BY A BIOVERVERSION OF HOMOFARNESOL IN THE PRESENCE OF A BIOCATALYST

A solid form of (-)-Ambrox formed by a bioconversion process.

A drop of the fragrant ether perfuming preparation method

The invention discloses a preparation method for ambrox and relates to the technical field of daily use chemicals. According to the preparation method disclosed by the invention, by taking cheap and easily available ferric trichloride as a catalyst, high quality ambrox is prepared by cyclodehydrating ambradiol in an organic solvent. In the reaction, ferric trichloride is taken as the catalyst, so that the reaction temperature is low and the reaction time is short. The method disclosed by the invention further has the advantages of being clean and environmental-friendly, low in cost of product, convenient in post-treatment, more suitable for industrial production and the like.