499-44-5

Basic information

• Product Name: Hinokitiol
• Synonyms: HINOKITIOL;BETA-THUJAPLICIN;BETA-THUJAPLICINE;B-THUJAPLICIN;2-HYDROXY-4-ISOPROPYLCYCLOHEPTA-2,4,6-TRIEN-1-ONE;2-HYDROXY-4-ISOPROPYL-2,4,6-CYCLOHEPTATRIEN-1-ONE;2-HYDROXY-4-ISOPROPYL-2,4,6-CYCLOHEPTATRIENE;2-hydroxy-4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one
• CAS NO: 499-44-5
• Molecular Formula: C₁₀H₁₂O₂
• Molecular Weight: 164.2
• EINECS: 207-880-7
• Product Categories: Tropolones;Tropolones & Azulenes
• Mol File: 499-44-5.mol
• Article Data: 16

Chemical Properties

• Melting Point: 50-52 °C(lit.)
• Boiling Point: 140 °C10 mm Hg(lit.)
• Flash Point: 128.1 °C
• Appearance: /
• Density: 1.0041 (rough estimate)
• Vapor Pressure: 8.98E-05mmHg at 25°C
• Refractive Index: 1.5190 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 25 mg/ml).
• PKA: 7.06±0.30(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 4 months.
• Merck: 14,9390
• CAS DataBase Reference: Hinokitiol(CAS DataBase Reference)
• NIST Chemistry Reference: Hinokitiol(499-44-5)
• EPA Substance Registry System: Hinokitiol(499-44-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: GU4200000
• Hazardous Substances Data: 499-44-5(Hazardous Substances Data)

Usage

Chemical Properties

Hinokitiol is a tropolone derivative containing an unsaturated seven-membered carbon ring. It is a monoterpenoid – cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. It is a enol and a cyclic ketone. It derives from a hydride of a cyclohepta-1,3,5-triene. Thujaplicins are soluble in organic solvents and aqueous buffers.Hinokitiol provides acetone on vigorous oxidation and gives the saturated monocyclic diol upon catalytic hydrogenation.It is stable to alkali and acids, forming salts or remaining unchanged, but does not convert to catechol derivatives. Hinokitiol, as other thujaplicins and tropolones, reversibly binds metal ions. It forms complex salts with metal ions.

benefits

Hinokitiol (β-thujaplicin) is a naturally occurring antioxidant, found in the heartwood of certain plants. It acts as a metal chelator and, also, enhances the activity of superoxide dismutase (Huang et al., 2015). It was found to be very protective in the assay. It has not been previously studied as a HC protectant. In addition to its antioxidant properties, hinokitiol has been shown to reduce inflammation via suppression of NFκB, and metalloproteinases, and to activate caspase 3. The former activities could contribute to its protective effect.Hinokitiol is a superpower ingredient that has anti-inflammatory, antioxidant, antibacterial, anti-fungal and anti-melanogenic properties. Best of all, hinokitiol is as gentle as it is powerful. Hinokitiol’s properties allow it to target the inflammatory redness and blemishes seen in rosacea and acne. Hinokitiol is effective against P. acnes bacteria, and there is no known acquired resistance to it, unlike other prescription antibiotics.

Safety

The safety of hinokitiol has been tested in rats and no carcinogenic effect to rats was found.In 2006, hinokitiol was categorized under the Domestic substances list (DSL) in Canada as non-persistent, non-bioaccumulative and non-toxic to aquatic organisms.

Description

Hinokitiol (β-thujaplicin) is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. It is a tropolone derivative and one of the thujaplicins.Hinokitiol is used in oral and skin care products,and is a food additive used in Japan.

Uses

Different sources of media describe the Uses of 499-44-5 differently. You can refer to the following data:
1. Antibacterial additive in foods, cosmetics, eye drops and toothpaste.
2. Hinokitiol is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. It is a tropolone derivative and one of the thujaplicins. Hinokitiol has inhibitory effects on Chlamydia trachomatis and may be clinically useful as a topical drug.

Definition

ChEBI: A monoterpenoid that is cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. Isolated from Thuja plicata and Chamaecyparis obtusa, it exhibits antimicrobial activities.

Anticancer Research

Studied in xenograft tumors such lung adenocarcinoma cell, EGFR-TKI-resistantlines PC9-IR and H1975 in which the growth inhibition was observed, a novel antitumormechanism was hypothesized. In summary, the hinokitiol can induce DNAdamage and autophagy (Rodrigues et al. 2015).

References

1) Ido et al (1999) Induction of apoptosis by hinokitiol, a potent iron chelator, in teratocarcinoma F9 cells is mediated through the activation of caspase-3; Cell Prolif., 32 63 2) Suzuki et al. (2000) Hinokitiol, a selective inhibitor of the platelet-type isozyme of arachidonate 12-lipoxygenase; Biochem. Biophys. Res. Commun., 275 885 3) Morita et al. (2007) The mechanism of the bactericidal activity of hinokitiol; Biocontrol Sci., 12 101 4) Liu and Yamauchi (2006) Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines; Biochem. Biophys. Res. Commun., 351 26 5) Lee et al. (2010) Hinokitiol activates the hypoxia-inducible factor (HIF) pathway through inhibition of HIF hydroxylases; Biochem. Biophys. Res. Commun., 396 370

InChI:InChI=1/C10H12O2/c1-7(2)8-4-3-5-9(11)10(12)6-8/h3-7H,1-2H3,(H,11,12)

Synthetic route

2-amino-6-isopropyl-cycloheptatrienone (55076-49-8) → hinokitiol (499-44-5)

Conditions	Yield
With potassium hydroxide	100%

β-dolabrin (4570-11-0) → hinokitiol (499-44-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol at 22℃; under 760 Torr; for 6.5h;	98%
With hydrogen; palladium on activated charcoal In ethanol	98%

isopropanol boric acid (52732-22-6) + 2-hydroxy-4-chloro-2,4,6-cycloheptatrien-1-one (698-48-6) → hinokitiol (499-44-5)

Conditions	Yield
With potassium phosphate In tetrahydrofuran at 100℃; for 2h;	97.5%

(5S)-6-isopropyl-3-cycloheptene-1,2-dione (310905-95-4) → hinokitiol (499-44-5)

Conditions	Yield
Stage #1: (5S)-6-isopropyl-3-cycloheptene-1,2-dione With pyrrolidone hydrotribromide In tetrahydrofuran at 20℃; for 1h; Bromination; Stage #2: With lithium carbonate; lithium bromide In N,N-dimethyl-formamide for 2h; Aromatisation; Heating;	71%

4-bromo-2-hydroxycycklohepta-2,4,6-trien-1-one (698-47-5) + isopropenyltrimethylstannane (3043-46-7) → hinokitiol (499-44-5)

Conditions	Yield
Stage #1: 4-bromo-2-hydroxycycklohepta-2,4,6-trien-1-one; isopropenyltrimethylstannane With bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane for 1h; Reflux; Stage #2: With 5%-palladium/activated carbon; hydrogen In ethanol at 20℃; under 760.051 Torr; for 24h;	53%

4-isopropyl-cycloheptanone (13656-84-3) → hinokitiol (499-44-5)

Conditions	Yield
With selenium(IV) oxide; ethanol Erwaermen des Reaktionsprodukts mit N-Brom-succinimid in CHCl3;

4-isopropyl-cycloheptanone (13656-84-3) → hinokitiol (499-44-5) + 3-bromo-5-isopropyl-tropolone (2891-67-0)

Conditions	Yield
With selenium(IV) oxide; ethanol Behandeln des Reaktionsprodukts mit Brom in Essigsaeure und Erhitzen des hierbei erhaltenen Reaktionsprodukts mit Wasserdampf;

3-isopropylcycloheptanone (108168-72-5) → hinokitiol (499-44-5)

Conditions	Yield
With selenium(IV) oxide; ethanol Erwaermen des Reaktionsprodukts mit N-Brom-succinimid in CHCl3;
Multi-step reaction with 2 steps 1: selenium dioxide / ethanol; H2O / 2 h / 90 °C 2: 1.) phenyltrimethylammonium tribromide 2.) LiCl, Li2CO3 / 1.) THF, RT, 1.75 h, 2.) DMF, 120 deg C, 45 min View Scheme

(1S,5R)-7,7-Dichloro-1-isopropyl-bicyclo[3.2.0]hept-2-en-6-one → hinokitiol (499-44-5)

Conditions	Yield
With potassium acetate

(1R,5S)-7,7-Dichloro-3-isopropyl-bicyclo[3.2.0]hept-2-en-6-one → hinokitiol (499-44-5)

Conditions	Yield
With potassium acetate

2-hydroxy-6-isopropyl-2,4,6-cycloheptatrien-1-one (499-44-5) → (Z)-Cyclooctene (931-88-4, 931-87-3) + hinokitiol (499-44-5)

Conditions	Yield
In decalin at 180℃; for 4h;	A 95 % Spectr. B n/a

2-hydroxy-6-isopropyl-2,4,6-cycloheptatrien-1-one (499-44-5) → hinokitiol (499-44-5) + cyclopentene (142-29-0)

Conditions	Yield
In decalin at 180℃; for 3h;	A n/a B 95 % Spectr.

4-isopropylcycloheptane-1,2-dione (108168-73-6) → hinokitiol (499-44-5)

Conditions	Yield
With C6H5N(1+); lithium chloride Yield given. Multistep reaction;
With phenyltrimethylammonium tribromide; lithium carbonate; lithium chloride 1.) THF, RT, 1.75 h, 2.) DMF, 120 deg C, 45 min; Yield given. Multistep reaction;

2-chloro-6-isopropyl-cycloheptatrienone (66967-15-5) → hinokitiol (499-44-5)

Conditions	Yield
With phosphoric acid; acetic acid

2-chloro-5-isopropyltropone (66967-10-0) → hinokitiol (499-44-5)

Conditions	Yield
With phosphoric acid; acetic acid Heating;

/PBWLC126-1000/ → hinokitiol (499-44-5)

Conditions	Yield
oxidation;

(R)-3-(1-methylethyl)-6-oxoheptanal dimethylacetal (105897-85-6) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions

Yield

Multi-step reaction with 7 steps 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -15 - 0 °C 1.2: tetrahydrofuran; hexane / 2 h / -78 - 20 °C 2.1: TiCl4 / CH2Cl2 / 0.17 h / -78 °C 3.1: 63 percent / p-TsOH; 4 Angstroem molecular sieves / benzene / 1 h / Heating 4.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -15 - 0 °C 4.2: tetrahydrofuran; hexane / 0.5 h / -15 - 20 °C 5.1: MCPBA / hexane / 4 h / 20 °C 5.2: 0.8 g / Et3N*3HF / CH2Cl2 / 2 h / 20 °C 6.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 7.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 7.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

(5R)-5-isopropyl-2-cyclohepten-1-one (310905-92-1) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions

Yield

Multi-step reaction with 4 steps 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -15 - 0 °C 1.2: tetrahydrofuran; hexane / 0.5 h / -15 - 20 °C 2.1: MCPBA / hexane / 4 h / 20 °C 2.2: 0.8 g / Et3N*3HF / CH2Cl2 / 2 h / 20 °C 3.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 4.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 4.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

(5S)-7-hydroxy-5-isopropyl-2-cyclohepten-1-one (310905-94-3) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 2.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 2.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

(5R)-5-isopropyl-3-methoxycycloheptanone (310905-91-0) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 63 percent / p-TsOH; 4 Angstroem molecular sieves / benzene / 1 h / Heating 2.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -15 - 0 °C 2.2: tetrahydrofuran; hexane / 0.5 h / -15 - 20 °C 3.1: MCPBA / hexane / 4 h / 20 °C 3.2: 0.8 g / Et3N*3HF / CH2Cl2 / 2 h / 20 °C 4.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 5.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 5.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

((S)-4-Isopropyl-cyclohepta-1,6-dienyloxy)-trimethyl-silane (310905-93-2) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: MCPBA / hexane / 4 h / 20 °C 1.2: 0.8 g / Et3N*3HF / CH2Cl2 / 2 h / 20 °C 2.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 3.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 3.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

[(R)-4-(2,2-Dimethoxy-ethyl)-5-methyl-1-methylene-hexyloxy]-trimethyl-silane (310905-90-9) → hinokitiol (499-44-5) + 2-bromoprop-2-enyl halide

Conditions

Yield

Multi-step reaction with 6 steps 1.1: TiCl4 / CH2Cl2 / 0.17 h / -78 °C 2.1: 63 percent / p-TsOH; 4 Angstroem molecular sieves / benzene / 1 h / Heating 3.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 0.5 h / -15 - 0 °C 3.2: tetrahydrofuran; hexane / 0.5 h / -15 - 20 °C 4.1: MCPBA / hexane / 4 h / 20 °C 4.2: 0.8 g / Et3N*3HF / CH2Cl2 / 2 h / 20 °C 5.1: 88 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 20 °C 6.1: pyrrolidone hydrotribromide / tetrahydrofuran / 1 h / 20 °C 6.2: 71 percent / LiBr; Li2CO3 / dimethylformamide / 2 h / Heating View Scheme

4-bromo-2-hydroxycycklohepta-2,4,6-trien-1-one (698-47-5) → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 54 percent / dichlorobis(triphenylphosphine)palladium(II) / dioxane / 1.3 h / Heating 2: 98 percent / hydrogen / 5percent Pd/C / ethanol View Scheme
Multi-step reaction with 2 steps 1: 54 percent / dichlorobis(triphenylphosphine)palladium(II) / dioxane / 1.33 h / Heating 2: 98 percent / H2 / 5percent Pd/C / ethanol / 6.5 h / 22 °C / 760 Torr View Scheme

3-Methoxycyclohepta-1,3,5-triene (1714-40-5) → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et4NOTs / dimethylformamide / electroreduction 2: 1.) pyridinium bromide perbromide 2.) LiCl/LiCO3 / 2.) DMF 3: 100 percent / NH2NH2 4: 100 percent / KOH View Scheme
Multi-step reaction with 5 steps 1: Et4NOTs / dimethylformamide / electroreduction 2: 87 percent / aq. H2SO4 / tetrahydrofuran 3: 82 percent / 30percent H2O2/NaOH 4: 72 percent / aq. HCl 5: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme

1-methoxycyclohepta-1,3,5-triene (1728-32-1) → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 4 steps 2: 1.) pyridinium bromide perbromide 2.) LiCl/LiCO3 / 2.) DMF 3: 100 percent / NH2NH2 4: 100 percent / KOH View Scheme
Multi-step reaction with 5 steps 2: 87 percent / aq. H2SO4 / tetrahydrofuran 3: 82 percent / 30percent H2O2/NaOH 4: 72 percent / aq. HCl 5: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme
Multi-step reaction with 4 steps 1: Et4NOTs / dimethylformamide / electroreduction 2: 1.) pyridinium bromide perbromide 2.) LiCl/LiCO3 / 2.) DMF 3: 100 percent / NH2NH2 4: 100 percent / KOH View Scheme
Multi-step reaction with 5 steps 1: Et4NOTs / dimethylformamide / electroreduction 2: 87 percent / aq. H2SO4 / tetrahydrofuran 3: 82 percent / 30percent H2O2/NaOH 4: 72 percent / aq. HCl 5: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme

β-isopropyltropolone (35193-01-2) → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / NH2NH2 2: 100 percent / KOH View Scheme

6-Isopropyl-cyclohept-3-enone → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 82 percent / 30percent H2O2/NaOH 2: 72 percent / aq. HCl 3: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme

1-methoxy-6-isopropyl-1,3-cycloheptadiene (133826-10-5) → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) pyridinium bromide perbromide 2.) LiCl/LiCO3 / 2.) DMF 2: 100 percent / NH2NH2 3: 100 percent / KOH View Scheme
Multi-step reaction with 4 steps 1: 87 percent / aq. H2SO4 / tetrahydrofuran 2: 82 percent / 30percent H2O2/NaOH 3: 72 percent / aq. HCl 4: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme

4-Isopropyl-8-oxa-bicyclo[5.1.0]octan-2-one → hinokitiol (499-44-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 72 percent / aq. HCl 2: 1.) C6H5N(1+) 2.) LiCl/LiCO3 View Scheme

hinokitiol (499-44-5) → 2-hydroxy-7-iodo-4-isopropyltropone (32659-57-7)

Conditions	Yield
With sulfuric acid; iodine; potassium carbonate In chloroform	100%
With iodine; potassium carbonate In diethyl ether for 24h; Ambient temperature;	100%
With iodine	70%

piperazine (110-85-0) + formaldehyd (50-00-0) + hinokitiol (499-44-5) → 1,4-bis(6-hydroxy-4-isopropyl-7-oxo-1,3,5-cycloheptatrienylmethyl)piperazine (1211884-65-9)

Conditions	Yield
Stage #1: piperazine; formaldehyd; hinokitiol With acetic acid In methanol at 60℃; Mannich reaction; Stage #2: With sodium hydrogencarbonate In methanol; water	100%

formaldehyd (50-00-0) + 4-ethoxycarbonylpiperazine (120-43-4) + hinokitiol (499-44-5) → 4-(6-hydroxy-4-isopropyl-7-oxo-1,3,5-cycloheptatrienylmethyl)-1-piperazinecarboxylic acid ethyl ester (1211884-44-4)

Conditions	Yield
Stage #1: formaldehyd; 4-ethoxycarbonylpiperazine; hinokitiol With acetic acid In methanol at 60℃; Mannich reaction; Stage #2: With sodium hydrogencarbonate In methanol; water	99%

formaldehyd (50-00-0) + hinokitiol (499-44-5) + (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(piperazin-1-yl)methanone (122003-27-4) → 1-[N-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-ylcarbonyl)]-4-(6-hydroxy-4-isopropyl-7-oxo-1,3,5-cycloheptatrienylmethyl)piperazine (1211884-55-7)

Conditions	Yield
Stage #1: formaldehyd; hinokitiol; (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(piperazin-1-yl)methanone With acetic acid In methanol at 60℃; Mannich reaction; Stage #2: With sodium hydrogencarbonate In methanol; water	99%

hinokitiol (499-44-5) + methyl iodide (74-88-4) → 4-isopropyltropolone methyl ether (18448-52-7)

Conditions	Yield
With perhydrodibenzo-18-crown-6; potassium carbonate In acetonitrile for 10h; Heating;	96.4%

hinokitiol (499-44-5) + trifluoroborane diethyl ether (109-63-7) → difluoro(3-isopropyl-7-oxo-1,3,5-cycloheptatrienyloxy)borane (2248-50-2)

Conditions	Yield
In not given react. hinokitiol and boron trifluoride etherate; product recrystd. from chloroform-benzene (4:7);	96%

hinokitiol (499-44-5) + p-toluenesulfonyl chloride (98-59-9) → 4-(1-methylethyl)-2-[[(4-methylphenyl)sulfonyl]oxy]-2,4,6-cycloheptatrien-1-one (69141-46-4)

Conditions	Yield
In pyridine	96%

hinokitiol (499-44-5) + OsHCl(CO)(P(p-tolyl)3)3 → C53H54O3OsP2

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene for 2.5h; Reflux; Inert atmosphere;	95%

indium chloride + hinokitiol (499-44-5) → trans-{tris(4-iso-propyl-2-hydroxy-2,4,6-cycloheptatrien-1-onato-O,O')-indium(III)} (154727-99-8, 16973-43-6)

Conditions	Yield
In ethanol refluxed; 1 h; left to stand for 48 h;; pptd. from H2O; crystd. after 48 h; washed with EtOH/H2O; dried over CaCl2; elem. anal.;;	91%

hydridocarbonylchlorotris(triphenylphosphine)osmium(II) (16971-31-6, 36007-23-5) + hinokitiol (499-44-5) → C47H42O3OsP2

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene for 5.5h; Reflux; Inert atmosphere;	91%

morpholine (110-91-8) + formaldehyd (50-00-0) + hinokitiol (499-44-5) → 4-(4-isopropyl-6-hydroxy-7-oxo-1,3,5-cycloheptatrienylmethyl)morpholine

Conditions	Yield
With acetic acid In methanol at 60℃; Mannich reaction;	88%

(carbonyl)(chloro)(hydrido)tris(triphenylphosphine)ruthenium(II) (157072-60-1, 61521-25-3, 166941-05-5, 16971-33-8) + hinokitiol (499-44-5) → C47H42O3P2Ru

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene for 2.5h; Reflux; Inert atmosphere;	88%

Iron(III) nitrate nonahydrate + hinokitiol (499-44-5) → tris(4-isopropyltropolonato)iron(III) (31396-80-2)

Conditions	Yield
In methanol; ethanol to soln. of iron salt in MeOH was added to soln. of hinokitiol in MeOH, stirred for 1 h at room temp.; filtered, washed with EtOH, Et2O, dried in vac. for 2 h;	87.6%
In ethanol at 20℃; for 2h;	86.7%

copper(ll) sulfate pentahydrate + hinokitiol (499-44-5) → [Cu(II)(4-isopropyltropolone)2] C20H22CuO4, monoclinic, P21/N (14076-63-2, 685836-60-6)

Conditions	Yield
In ethanol; water to soln. of ligand in 1:1 mixt. EtOH and water (20 ml) was added CuSO4, soln. was refluxed for 2 h; soln. was passed through folded filter paper, filtrate was evapd. slowlyat room temp., after few days crystals were grown, ppt. collected, wash ed with H2O, dried in vac.; elem. anal.;	76.5%

hinokitiol (499-44-5) + 3,4,5-Trimethoxybenzoyl chloride (4521-61-3) → 3,4,5-trimethoxy-benzoic acid 3-isopropyl-7-oxo-cyclohepta-1,3,5-trienyl ester

Conditions	Yield
With pyridine In dichloromethane for 12h; Heating;	76%

hinokitiol (499-44-5) + titanium tetrachloride (7550-45-0) → [Ti(hinokitiol)2Cl2] (1106674-51-4)

Conditions	Yield
In methanol; diethyl ether to soln. of TiCl4 in ether was added soln. of hinokitiol in ether, stirred for 2 h at room temp.; filtered, washed with ether, dried in vac. for 2 h;	74.1%

4-methoxybenzaldehyde diethylacetal (2403-58-9) + hinokitiol (499-44-5) → 3-(α-ethoxy-4-methoxybenzyl)-6-isopropyltropolone (92832-11-6)

Conditions	Yield
In toluene for 20h; Heating;	72%

6-hydroxy-2,5,7,8-tetramethyl-N-(2-piperazinoethyl)-2-chromanecarboxamide (313988-88-4) + formaldehyd (50-00-0) + hinokitiol (499-44-5) → 1-[N-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-ylcarbonyl)ethylamino]-4-(6-hydroxy-4-isopropyl-7-oxo-1,3,5-cycloheptatrienylmethyl)piperazine (1211884-59-1)

Conditions	Yield
Stage #1: 6-hydroxy-2,5,7,8-tetramethyl-N-(2-piperazinoethyl)-2-chromanecarboxamide; formaldehyd; hinokitiol With acetic acid In methanol at 60℃; Mannich reaction; Stage #2: With sodium hydrogencarbonate In methanol; water	71%

tris(triphenylphosphine)ruthenium(II) chloride (15529-49-4, 41756-81-4) + hinokitiol (499-44-5) → C56H52O4P2Ru

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol for 1.5h; Inert atmosphere; Reflux;	71%

copper(ll) sulfate pentahydrate + hinokitiol (499-44-5) → [Cu(II)(4-isopropyltropolone)2]

Conditions	Yield
In ethanol; water to soln. of ligand in 1:1 mixt. EtOH and water (30 ml) was added CuSO4, soln. was refluxed for 2 h; soln. was passed through folded filter paper, filtrate was evapd. slowlyat room temp., after few days crystals were grown, ppt. collected, wash ed with H2O, dried in vac.; elem. anal.;	70.7%

1-ethoxyisochromane (75802-22-1) + hinokitiol (499-44-5) → 3-(1-isochromanyl)-6-isopropyltropolone (87864-22-0)

Conditions	Yield
at 150 - 160℃; for 6h;	66%
heating;

hinokitiol (499-44-5) + 4-methoxy-benzoyl chloride (100-07-2) → 4-methoxy-benzoic acid 3-isopropyl-7-oxo-cyclohepta-1,3,5-trienyl ester

Conditions	Yield
With pyridine In dichloromethane for 12h; Heating;	65%

hinokitiol (499-44-5) + antimony(III) bromide (7789-61-9) → [Sb(III)(hinokitiol)2Br]

Conditions	Yield
In methanol; benzene to soln. of SbBr3 in C6H6 was added soln. of hinokitiol in MeOH, stirredfor 2 h; filtered, evapd. in vac. at 30°C, dissolved in EtOH, filtered, filtrate slow evapd. at room temp., filtered, washed with cold EtOH, driedin vac. for 2 h;	62.5%

tin(II) chloride dihdyrate (10025-69-1) + hinokitiol (499-44-5) → Sn(hinokitiol)2 (58528-20-4)

Conditions	Yield
In ethanol; water a soln. of hydroxyketone in ethanol was added a stirred soln. of Sn-compound in water under N2, the soln. was stirred for 1.5 h; filtered, ppt. was dried under vac.; elem. anal.;	56%

1,1-diethoxy-but-2-ene (10602-34-3) + hinokitiol (499-44-5) → 3-isopropyl-6-(1-ethoxy-2-butenyl)tropolone (92397-04-1)

Conditions	Yield
at 160℃; for 5h;	55%

formaldehyd (50-00-0) + hinokitiol (499-44-5) + 1-(3,4-dimethoxybenzoyl)piperazine → 7-[4-(3-(3,4-dimethoxybenzoyl)piperazin-1-yl)methyl]-2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one

Conditions	Yield
With acetic acid In methanol at 60℃;	55%

Upstream product

• 13656-84-3 4-isopropyl-cycloheptanone 
• 108168-72-5 3-isopropylcycloheptanone 
• 310905-95-4 (5S)-6-isopropyl-3-cycloheptene-1,2-dione 
• 1728-32-1 1-methoxycyclohepta-1,3,5-triene 
• 35193-01-2 β-isopropyltropolone 
• 698-47-5 4-bromo-2-hydroxycycklohepta-2,4,6-trien-1-one 
• 3043-46-7 isopropenyltrimethylstannane 
• 110-83-8 cyclohexene 
• 2415-79-4 7,7-dibromonorcarane 
• 55076-44-3 1-isopropyl-8-oxa-bicyclo[3.2.1]oct-6-en-3-one 
• 55076-46-5 3-Isopropylcyclohepta-2,6-dienon 
• 10599-59-4 2-isopropylfuran 
• 35071-52-4 7,7-dichloro-3-isopropylbicyclo[3.2.0]hept-2-ene-6-one 
• 542-92-7 cyclopenta-1,3-diene 

Downstream Products

• 69141-47-5 6-(1-methylethyl)-2-[[(4-methylphenyl)sulfonyl]oxy]-2,4,6-cycloheptatrien-1-one 
• 69141-46-4 4-(1-methylethyl)-2-[[(4-methylphenyl)sulfonyl]oxy]-2,4,6-cycloheptatrien-1-one 
• 92832-17-2 α,α-bis(2-hydroxy-6-isopropyltropon-3-yl)-4-methoxytoluene 
• 92832-11-6 3-(α-ethoxy-4-methoxybenzyl)-6-isopropyltropolone 
• 101403-51-4 C₂₈H₃₀O₅ 
• 931-88-4 cis-Cyclooctene 
• 142-29-0 cyclopentene 
• 87864-24-2 α,α-bis(2-hydroxy-6-isopropyl-1-oxocyclohepta-2,4,6-trien-3-yl)toluene 
• 87864-23-1 3-(α-ethoxybenzyl)-6-isopropyltropolone 
• 101403-50-3 C₂₇H₂₈O₄ 
• 92397-07-4 α,α-bis(7-hydroxy-5-isopropyltropon-2-yl)-2-methoxytoluene 
• 92832-15-0 α,α-bis(2-hydroxy-6-isopropyl-tropon-3yl)-4-chlorotoluene 
• 92397-08-5 α,α-bis(7-hydroxy-5-isopropyltropon-2-yl)-3-methoxytoluene 
• 101403-63-8 C₃₀H₃₄O₇ 

Relevant articles and documents

Preparation method of beta-thujaplicine

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of beta-thujaplicine. The preparation method comprises the steps that tri-n-propylamine, glacial acetic acid and water serve as reaction reagents, and a ring enlargement reaction occurs by 7,7-dichloro-3-isopropylbicycle[3.2.0]heptyl-2-ene-6-one (the compound structure is shown in formula 2).

A high-purity chinese juniper methyl alcohol of preparation method (by machine translation)

The invention discloses a method for preparing high-purity chinese juniper methyl alcohol, cyclopentadiene activated reagent after activation with isopropyl bromine instead should be containing various isomers of the isopropyl cyclopentadiene, then in the isomer conversion catalyst under the action of the isomerization reaction to obtain 1 - isopropyl cyclopentadiene; 1 - isopropyl cyclopentadiene and [...] react 1 - isopropyl cyclopentadiene and 4, 4 - [...] 5 - one; 1 - isopropyl cyclopentadiene and 4, 4 - [...] 5 - ketone with triethylamine heating reflux generating ring enlargement reaction to obtain the target product chinese juniper methyl alcohol. The invention raw materials used are cheap and easily obtained, and the step A through the isomer of a hydrocarbon conversion catalyst in use significantly reduces the by-product 2 - isopropyl cyclopentadiene and 5 - isopropyl cyclopentadiene generation, improves the yield of products, and Ru (Ac)3 - ZSM - 5 can be repeatedly used for four times still maintains good catalytic activity; step B by adjusting reaction solution in glacial acetic acid, effectively prevent the emergence of the diketone by-product. (by machine translation)