861892-40-2

Basic information

• Product Name: (4R)-1-METHYL-4-(1-METHYLETHENYL)-2-CYCLOHEXEN-1-OL
• Synonyms: (4R)-1-METHYL-4-(1-METHYLETHENYL)-2-CYCLOHEXEN-1-OL;(4R)-1-METHYL-4-(1-METHYLVINYL)CYCLOHEX-2-ENE-1-OL;(4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-enol;(4R)-1-methyl-4-prop-1-en-2-ylcyclohex-2-en-1-ol
• CAS NO: 861892-40-2
• Molecular Formula: C₁₀H₁₆O
• Molecular Weight: 152.23
• Mol File: 861892-40-2.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 216.9±40.0 °C(Predicted)
• Appearance: /
• Density: 0.947±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.66±0.40(Predicted)
• CAS DataBase Reference: (4R)-1-METHYL-4-(1-METHYLETHENYL)-2-CYCLOHEXEN-1-OL(CAS DataBase Reference)
• NIST Chemistry Reference: (4R)-1-METHYL-4-(1-METHYLETHENYL)-2-CYCLOHEXEN-1-OL(861892-40-2)
• EPA Substance Registry System: (4R)-1-METHYL-4-(1-METHYLETHENYL)-2-CYCLOHEXEN-1-OL(861892-40-2)

Safety Data

• Hazardous Substances Data: 861892-40-2(Hazardous Substances Data)

Usage

Uses

(4R)-1-Methyl-4-isopropenylcyclohex-2-en-1-ol is a chemical reagent used in the synthesis of Δ8-THC cannabinoid analogs with activity against CB receptors.

Synthetic route

(4R)-limonene 1,2-epoxide (1195-92-2) → (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2)

Conditions	Yield
Stage #1: (4R)-limonene 1,2-epoxide With sodium tetrahydroborate; diphenyl diselenide In ethanol for 2h; Heating; Stage #2: With dihydrogen peroxide In tetrahydrofuran for 2h; Heating;	52%
Stage #1: (4R)-limonene 1,2-epoxide With sodium tetrahydroborate; ethanol; diphenyl diselenide at 0℃; Reflux; Inert atmosphere; Stage #2: With dihydrogen peroxide In tetrahydrofuran; water at 0℃; Reflux;	52%
Stage #1: (4R)-limonene 1,2-epoxide With sodium tetrahydroborate; diphenyl diselenide at 0℃; Stage #2: With dihydrogen peroxide at 0℃; Further stages.;	28%

D-limonene (5989-27-5) → (2S,4S)-carveol (7632-16-8) + (+)-trans-carveol (2102-58-1) + (R)-Perillyl alcohol (57717-97-2) + (5S)-2-methylene-5-(prop-1-en-2-yl)cyclohexanol (216655-62-8) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2)

Conditions	Yield
Stage #1: D-limonene With C48H42N2O4S5 In acetonitrile for 0.5h; Irradiation; Stage #2: With sodium tetrahydroborate In ethanol at 0℃; Darkness; Stage #3: With water In ethanol

D-limonene (5989-27-5) → 5-Isopropenyl-2-methyl-cyclohex-2-enol (99-48-9) + (5R)-2-methylene-5-(1-methylethenyl)-1-cyclohexanol (216655-61-7) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2)

Conditions	Yield
Stage #1: D-limonene With sodium molybdate dihydrate; dihydrogen peroxide; sodium hydroxide In methanol; water for 0.583333h; pH=10; Heating; Stage #2: With sodium sulfite In methanol; water at 60℃; for 3h; Reagent/catalyst;

carbon dioxide (124-38-9) + cis-(R)-limonene oxide (4680-24-4) → L-carveol (308363-12-4) + (R)-dihydrocarvone (116499-64-0) + 1-methyl-4-(1-methylethenyl)-1,2-cyclohexanediol (185329-56-0) + (5R)-2-methylene-5-(1-methylethenyl)-1-cyclohexanol (216655-61-7) + C11H16O3 + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2)

Conditions	Yield
With tetrabutylammomium bromide; 3C25H54N(1+)*O24PW4(3-) In neat (no solvent) at 140℃; for 24h; Reagent/catalyst; High pressure; Autoclave;

carbon dioxide (124-38-9) + (1S,2R,4R)-limonene-1,2-epoxide (6909-30-4) → L-carveol (308363-12-4) + 1-methyl-4-(1-methylethenyl)-1,2-cyclohexanediol (185329-56-0) + (5R)-2-methylene-5-(1-methylethenyl)-1-cyclohexanol (216655-61-7) + (R)-(+)-limonene carbonate + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2)

Conditions	Yield
With tetrabutylammomium bromide; 3C25H54N(1+)*O24PW4(3-) In neat (no solvent) at 140℃; for 24h; Reagent/catalyst; High pressure; Autoclave;

2-(3,5-dihydroxyphenyl)-2-methylhexane (22930-09-2) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → (6aR,10aR)-6,6,9-trimethyl-3-(2-methylhexan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol (22663-41-8)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 20 - 80℃; for 7h; Dean-Stark;	85.5%
With toluene-4-sulfonic acid In benzene for 12h; Reflux;

(4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) + 5-(1-hexylcyclopentyl)resorcinol (487578-68-7) → 5-(1-Hexyl-cyclopentyl)-2-((1R,6R)-6-isopropenyl-3-methyl-cyclohex-2-enyl)-benzene-1,3-diol (1025965-31-4)

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 10 - 20℃; for 1h;	85%

5-(1-adamantanyl)resorcinol (60526-91-2) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → AM411

Conditions	Yield
With toluene-4-sulfonic acid In chloroform at 65℃; for 6h;	84%

methyl 2,4-dihydroxy-6-pentylbenzoate (58016-28-7) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → methyl (1'R,2'R)-2,6-dihydroxy-5'-methyl-4-pentyl-2'-(prop-1 -en-2- yl)-1',2',3',4'-tetrahydro-[1,1'-biphenyl]-3-carboxylate (55658-71-4)

Conditions	Yield
Stage #1: methyl 2,6-dihydroxy-6-pentylbenzoate; (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol With boron trifluoride diethyl etherate In chlorobenzene at 22℃; Stage #2: With sodium hydrogencarbonate In chlorobenzene at 20℃; for 0.333333h;	70%
With boron trifluoride diethyl etherate In chlorobenzene at 20℃; for 1h; Reagent/catalyst; Temperature; Solvent;	70%
Stage #1: methyl 2,6-dihydroxy-6-pentylbenzoate; (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol With boron trifluoride diethyl etherate In chlorobenzene at 22℃; Flow reactor; Stage #2: With sodium hydrogencarbonate In chlorobenzene at 22℃; for 0.333333h;
With boron trifluoride diethyl etherate In chlorobenzene at 20℃; for 1h; Solvent;

5-(8-bromo-2-methyloctan-2-yl)benzene-1,3-diol (160512-71-0) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → (-)-7′-bromo-1',1'-dimethylheptyl-Δ8-tetrahydrocannabinol

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 4h; Reflux;	65%

5-(2,5,5-trimethyl-1,3-dioxan-2-yl) benzene-1,3-diol + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → 1-((2'R)-2,6-dihydroxy-5'-methyl-2'-(prop-1-en-2-yl)-1',2',3',4'-tetrahydro-[1,1'-biphenyl]-4-yl)ethan-1-one

Conditions	Yield
With boron trifluoride diethyl etherate; magnesium sulfate In dichloromethane at -10 - 0℃; for 3h; Inert atmosphere;	62%

5-(2-methyl-1,3-dithiolan-2-yl)benzene-1,3-diol + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → (2'R)-5'-methyl-4-(2-methyl-1,3-dithiolan-2-yl)-2'-(prop-1-en-2-yl)-1',2',3',4'-tetrahydro-[1,1'-biphenyl]-2,6-diol

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 20℃; for 1h; Inert atmosphere;	58.5%

5-(2-adamantyl)methylresorcinol (861892-38-8) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → AM757

Conditions	Yield
With toluene-4-sulfonic acid In chloroform at 65℃; for 6h;	57%

4-(3,5-dihydroxyphenyl)-1-bromobutane (1260669-57-5) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → 5-(4-bromobutyl)-4-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol (1260669-54-2) + 5-(4-bromobutyl)-4-[(1S,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol (1305300-52-0) + 5-(4-bromobutyl)-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol (1260669-38-2)

Conditions	Yield
With boron trifluoride diethyl etherate; magnesium sulfate In dichloromethane at -40℃; for 1h; Inert atmosphere;	A 50% B 33% C 17%

(4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) + Olivetol (500-66-3) → Δ8-tetrahydrocannabinol

Conditions	Yield
With toluene-4-sulfonic acid In water; benzene for 2h; Reflux;	49%

5-(2-adamantanyl)resorcinol (861892-36-6) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → AM744

Conditions	Yield
With toluene-4-sulfonic acid In chloroform at 65℃; for 6h;	48.5%

1-(3,5-dihydroxyphenyl)cyclobutanecarboxylic acid (1314744-72-3) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → 1-[(6aR,10aR)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-3-yl]cyclobutanecarboxylic acid (1510836-51-7)

Conditions	Yield
With toluene-4-sulfonic acid In chloroform for 6h; Inert atmosphere; Reflux;	45%

5-(1-adamantyl)methylresorcinol (861892-39-9) + (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) → AM 729

Conditions	Yield
With toluene-4-sulfonic acid In chloroform at 65℃; for 6h;	43.4%

(4R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-2-en-1-ol (861892-40-2) + 5-[2-hexyl-1,3-dithian-2-yl]resorcinol (579444-48-7) → 5-(2-Hexyl-[1,3]dithian-2-yl)-2-((1R,6R)-6-isopropenyl-3-methyl-cyclohex-2-enyl)-benzene-1,3-diol (1027023-77-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 10 - 20℃; for 1h;	43%

Upstream product

• 5989-27-5 D-limonene 
• 124-38-9 carbon dioxide 
• 6909-30-4 (1S,2R,4R)-limonene-1,2-epoxide 
• 4680-24-4 cis-(R)-limonene oxide 
• 1195-92-2 (4R)-limonene 1,2-epoxide 

Downstream Products

• 22663-41-8 (6aR,10aR)-6,6,9-trimethyl-3-(2-methylhexan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol 
• 1260669-54-2 5-(4-bromobutyl)-4-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol 
• 1305300-52-0 5-(4-bromobutyl)-4-[(1S,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol 
• 1260669-38-2 5-(4-bromobutyl)-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-1,3-benzenediol 
• 13956-30-4 (-)-5'-methyl-4-pentyl-2'-(prop-1-en-2-yl)-1',2',3',4'-tetrahydro-[1,1'-biphenyl]-2,6-diol 
• 24274-48-4 cannabidivarin 
• 31262-37-0 tetrahydrocannabivarin 
• 55658-71-4 methyl (1'R,2'R)-2,6-dihydroxy-5'-methyl-4-pentyl-2'-(prop-1 -en-2- yl)-1',2',3',4'-tetrahydro-[1,1'-biphenyl]-3-carboxylate 
• 13956-29-1 CBD 

Relevant articles and documents

PROCESS FOR THE SYNTHESIS OF CANNABIDIOL AND INTERMEDIATES THEREOF

The present invention relates to process for the preparation of cannabidiol (A) from the coupling of (D) and (E) through the intermediates (C) and (D) starting from compound (B). The invention further relates to the novel compounds (B), (C), (D) and (E) and reagents used in this process. More specifically, this invention provides the manufacturing of Cannabidiol (A) in milligram to gram or kilogram scale.

Method for continuously preparing cannabidiol intermediate through green photooxidation

The invention relates to a novel method for synthesizing cannabidiol (-)-Cannabidiol (CBD, formula I), aiming at solving the defects in the prior art. The production process is characterized by comprising the following steps that: (R)-(+)-Limonene (compound I-a) is adopted as an initial raw material; the initial raw material and a photocatalyst are subjected to an oxidation reaction under illumination,and then a reduction reaction is performed; and a pure key intermediate I-e is obtained through purification. The reaction formula involved in the steps is shown in the specification. The reaction and purification are simple; The method of the invention has the advantages of simple and easy-to-implement technical route, wide raw material source range, mild conditions, low production cost, high yield and environment-friendly performance, and provides a more effective synthesis method for industrial production.

OXIDATION OF LIMONENE

The invention discloses a process for the oxidation of limonene, comprising the reaction of limonene with hydrogen peroxide in the presence of a catalyst containing atoms and/or ions of at least one metal, selected from the group consisting of molybdenum, tungsten, scandium, vanadium, titanium, lanthanum, zirconium, praseodymium, neodymium, samarium, europium, terbium, dysprosium, erbium or ytterbium, characterised in that the molecular weight of the catalyst is less than 2,000 g/mol and that the reaction is performed at a pH value of more than 7.5.