3738-00-9

Basic information

• Product Name: AMBROX DL
• Synonyms: 1-b]furan,dodecahydro-3a,6,6,9a-tetramethyl-Naphtho[2;Dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan;AMBROX DL;DODECAHYDRO-3A,6,6,9A-TETRAMETHYLNAPHTO-(2,1-B)-FURAN;Dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]fur;Ambermor;Tetramethyl perhydronaphthofuran;Naphtho2,1-bfuran, dodecahydro-3a,6,6,9a-tetramethyl-
• CAS NO: 3738-00-9
• Molecular Formula: C₁₆H₂₈O
• Molecular Weight: 236.39
• EINECS: 223-118-6
• Mol File: 3738-00-9.mol

Chemical Properties

• Melting Point: 75-76 °C
• Boiling Point: 273.9 ºC at 760 mmHg
• Flash Point: 104.8 ºC
• Appearance: White crystalline solid
• Density: 0.939 g/cm³
• CAS DataBase Reference: AMBROX DL(CAS DataBase Reference)
• NIST Chemistry Reference: AMBROX DL(3738-00-9)
• EPA Substance Registry System: AMBROX DL(3738-00-9)

Safety Data

• Hazardous Substances Data: 3738-00-9(Hazardous Substances Data)

Usage

Chemical Properties

3a,6,6,9a-Tetramethyldodecahydronaphtho[2,1-b]furan is a crystalline autoxidation product of ambrein with a typical ambergris odor. It is prepared from (?)-sclareol, a diterpene alcohol obtained from extraction of clary sage plants. Oxidative degradation to a lactone (“sclareolide”), hydrogenation of the latter to the corresponding diol, and dehydration yield the title compound.

Occurrence

Reported found in clary sage oil.

Preparation

Racemic sclareolide can be prepared by cyclization of homofarnesic acid in the presence of SnCl4 as a catalyst . Pure diastereomers are obtained by acid cyclization of (E)- and (Z)-4-methyl-6-(2,6,6-trimethylcyclohex-l(2)-enyl)-3- hexen-1-ol, prepared from 2-methyl-4-(2,6,6-trimethylcyclohex-l(2)-enyl)-2- butenal [394]. If the racemic sclareolide mixture is resolved into its enantiomers, the (–)-oxide may also be obtained by a totally synthetic route

Synthesis Reference(s)

Synthesis, p. 216, 1983 DOI: 10.1055/s-1983-30287

Trade name

Compound starting from natural sclareol: Ambermore, Ambermore-DL, Ambermore-EX (Aromor), Ambrox? Super (Firmenich), Ambroxan? (Kao), Ambroxide (Symrise); compound starting from homofarnesic acid derivatives: Ambrox? DL (Firmenich); compound starting from 2-methyl- 4-(2,6,6-trimethylcyclohex-l(2)enyl)-2-butenal: Cetalox? (Firmenich), Cetalor (Aromor).

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

2-((4aSR,8aSR)-2,5,5,8a-tetramethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)ethan-1-ol → (3aRS,5aSR,9aSR,9bRS)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan (3738-00-9)

Conditions	Yield
iron(III) chloride; silica gel In dichloromethane; 1,2-dichloro-ethane at 24℃; for 0.333333h; Product distribution / selectivity;	79%
iron(III) chloride; silica gel In dichloromethane; 1,2-dichloro-ethane at 24℃; for 0.333333h; Product distribution / selectivity;	79%
iron(III) chloride In dichloromethane; 1,2-dichloro-ethane at 10℃; for 3h; Product distribution / selectivity;
scandium tris(trifluoromethanesulfonate) In dichloromethane at 20℃; for 6h; Product distribution / selectivity;
iron(III) chloride In dichloromethane; 1,2-dichloro-ethane at 10℃; for 3h; Product distribution / selectivity;

2-((4aSR,8aSR)-2,5,5,8a-tetramethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)ethan-1-ol → (3aRS,5aSR,9aSR,9bRS)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan (3738-00-9) + (3aSR,5aSR,9aSR,9bRS)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan (3738-00-9)

Conditions	Yield
scandium tris(trifluoromethanesulfonate) In dichloromethane at 20℃; for 6h; Product distribution / selectivity;
methanesulfonic acid In dichloromethane at 0℃; for 0.333333h; Product distribution / selectivity;
iron(III) chloride; silica gel In dichloromethane; 1,2-dichloro-ethane at 20℃; for 0.333333h; Product distribution / selectivity;

Upstream product

• 138152-06-4 (3Z,7E)-4,8,12-Trimethyltrideca-3,7,11-trien-1-ol 
• 459-89-2 (3E,7E)-homofarnesol 
• 173323-70-1 (Z)-β-monocyclohomofarnesylic acid dimethyl amide 
• 173323-69-8 (E)-β-monocyclohomofarnesylic acid dimethyl amide 
• 127-41-3 alpha-ionone 
• 87957-15-1 8-keto-9β-cyanomethyl-(4α,4β),10β-trimethyl-(trans)-decahydronaphthalene 
• 3738-00-9 (+/-)-5β-Ambrox 
• 110202-08-9 (Z)-4-Methyl-6-(2',6',6'-trimethyl-1'-cyclohexenyl)hex-3-en-1-ol 
• 138152-08-6 (3Z,7Z)-4,8,12-Trimethyltrideca-3,7,11-trien-1-ol 
• 133858-87-4 (Z)-4-Methyl-6-(2',6',6'-trimethyl-2'-cyclohexenyl)hex-3-en-1-ol 
• 133859-02-6 (Z)-4-Methyl-6-(2',2'-dimethyl-6'-methylidenecyclohexyl)hex-3-en-1-ol 
• 118672-99-4 3-oxo-5-(2,6,6-trimethyl-cyclohex-2-enyl)-pentanoic acid methyl ester 
• 110202-07-8 (E)-4-Methyl-6-(2',6',6'-trimethyl-1'-cyclohexenyl)hex-3-en-1-ol 
• 138152-07-5 (3E,7Z)-4,8,12-Trimethyltrideca-3,7,11-trien-1-ol 

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 

Relevant articles and documents

Synthesis and Applications of Cyclohexenyl Halides Obtained by a Cationic Carbocyclisation Reaction

The synthesis of cyclic alkenyl halides (mainly fluorides, chlorides and bromides) from alkynol or enyne derivatives by an acid-mediated cationic cyclisation reaction is disclosed. This high-yielding, scalable and technically simple method complements and challenges conventional methodologies. This study includes the development of biomimetic cationic cyclisation reactions of polyenyne derivatives to give interesting halogen-containing polycyclic compounds. The application of this reaction in the key step of the synthesis of two terpenes, namely austrodoral and pallescensin A, and the potent odorant 9-epi-Ambrox demonstrates the potential of the reaction for natural product synthesis.

Diastereoselective Synthesis of (±)-Ambrox by Titanium(III)-Catalyzed Radical Tandem Cyclization

A synthesis of (±)-ambrox, a compound with delicious ambergris-type scent, is presented. The key step is a highly diastereoselective titanocene(III)-catalyzed radical tandem cyclization of a farnesol derivative.

Scalable Synthesis of the Amber Odorant 9-epi-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction

A novel biomimetic nucleophilic bromocyclization reaction is used in the key step of a new and straightforward synthesis of 9-epi-Ambrox, an organic compound of high interest and value in the context of fragrances. This strategic reaction allows access to 9-epi-Ambrox on a gram scale from a dienyne derivative, easily available from geraniol, following a sequence of seven steps (35% global yield) with just one purification process. Both enantiomers of the molecule were obtained by a challenging enzymatic resolution.

Synthesis of five-membered cyclic ethers by reaction of 1,4-diols with dimethyl carbonate

The reaction of 1,4-diols with dimethyl carbonate in the presence of a base led to selective and high-yielding syntheses of related five-membered cyclic ethers. This synthetic pathway has the potential for a wide range of applications. Distinctive cyclic ethers and industrially relevant compounds were synthesized in quantitative yield. The reaction mechanism for the cyclization was investigated. Notably, the chirality of the starting material was maintained. DFT calculations indicated that the formation of five-membered cyclic ethers was energetically the most favorable pathway. Typically, the selectivity exhibited by these systems could be rationalized on the basis of hard-soft acid-base theory. Such principles were applicable as far as computed energy barriers were concerned, but in practice cyclization reactions were shown to be entropically driven. Copyright

Trans-tetrahydrofurans by OH-assisted Ru-catalyzed isomerization of 2-butene-1,4-diols

We herein report a general method for the synthesis of 1,2-annulated trans-tetrahydrofurans by the OH-assisted Ru-catalyzed isomerization of (Z)-2-butene-1,4-diols (using Chaudret's catalyst), followed by reduction of the incipient lactol (using Et3SiH and Amberlyst 15). Alternatively, the lactol can be oxidized to the corresponding lactone (using Ikariya's catalyst). It was shown by labeling experiments that an addition/elimination pathway is (at least to some extent) operative for the isomerization reaction. Only 0.5 mol-% of Chaudret's Ru catalyst is sufficient for the rapid and stereoselective isomerization of enediols of the type shown. This allows ready access to trans-tetrahydrofurans.

PROCESS FOR THE PREPARATION OF TETRANORLABDANE DERIVATIVES

The present invention concerns a process for the preparation of a compound of formula (I), wherein the dotted line is a single bond and n is 1 or the dotted line is a double bond and n is 0, and wherein the relative configuration is as shown, in the form of any one of its diastereoisomers or enantiomers or mixtures thereof.

PROCESS FOR THE PREPARATION OF TETRANORLABDANE DERIVATIVES

The present invention concerns a process for the preparation of a compound of formula (I) wherein the dotted line is a single bond and n is 1 or the dotted line is a double bond and n is 0, and wherein the relative configuration is as shown, in the form of any one of its diastereoisomers or enantiomers or mixtures thereof.

Internal nucleophilic termination in acid-mediated polyene cyclizations part 3. Synthetic access to didehydro and methyl didehydro analogues of (±)-ambrox

Treatment of the unsaturated allenic alcohols (E)-7, (Z)-7, 10, 13, and 19 with an excess of FSO3H in 2-nitropropane at -90° to -30° afforded, in 68-85% yield, diastereoisomer mixtures of racemic tricyclic ethers 14a-d and 20a-d, respectively (Schemes 3 and 5), with high stereoselectivity (see Table and Scheme 6). These stereospecific transformations represent the first reported examples of an acid-mediated polyene cyclization, in which an alkene is the initiating group and an allenic alcohol serves as the internal terminator. In close analogy to our earlier work, a nonsynchronous process is postulated, whereby the stereochemical course of cyclization is directed by the conformational structure of an intermediate cyclohexyl cation (see Schemes 3 and 6). In addition, the organoleptic properties of 14c and 20c, racemic didehydro and methyl didehydro analogues, respectively, of the known odorant Ambrox ((-)-4f), are briefly discussed.

Conversion of Esters and Lactones to Ethers via Thionoesters and Thionolactones Using Reductive Radical Desulfurization

Various thionoesters and thionolactones are readily reduced into the corresponding ethers in high isolated yields by radical desulfuurization with organotin hydrides and Et3B under mild reaction conditions.

Synthesis of d,l-Norlabdane Oxide and Related Odorants: An Intramolecular Radical Approach

A cascade radical approach to d,l-norlabdane oxide and related odorants is reported. Oxidative radical cyclization of polyene 4 with Mn(III) and Cu(II) afforded exclusively bicycle 3, which upon acid treatment gave tricycle 2 possessing the norlabdane oxide skeleton with a modified A-ring system. Tricycle 2 was ultimately converted to d, l-norlabdane oxide 1 and to several new A-ring labdane oxides as potential odorants.