500-49-2

Usage

Uses

Used in Pharmaceutical Industry:
5-Propyl-1,3-benzenediol is used as an intermediate for the preparation of Cannabigerovarin (C175140), a compound that stimulates thermosensitive transient receptor potential (TRP) channels of vanilloid type-4 (TRPV4). This stimulation leads to an increase in intracellular calcium ion concentration ([Ca2+]i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC50 0.9-6.4 μM). 5-Propyl-1,3-benzenediol has potential applications in the development of drugs targeting TRPV4 channels, which are involved in various physiological processes and diseases.

Synthesis

In a 100 mL round bottom flask, open to the atmosphere was added the crude product Benzene, 1,3-dimethoxy-5-propyl (0.736 g, 4.08 mmol, 1.0 equiv.) and a 1:1 mixture of glacial acetic acid (20 mL, 349.7 mmol, 17.4 M) and hydrobromic acid (48% in H2O, 20 mL, 368.3 mmol, 18.4 M). The reaction mixture was refluxed at 125 °C for 3 hours while stirring, or until the starting material was consumed via TLC analysis. At this point, the reaction was allowed to cool to room temperature and quenched by the addition of DI H2O. The biphasic solution was added to a separatory funnel, wherein the organic portion was extracted Et2O (ca. 3x 20 mL). The organic layers were then combined, neutralized with a concentrated sodium bicarbonate solution (ca. 30 mL), washed with a saturated brine solution (ca. 50 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford the final product without 5-Propyl-1,3-benzenediol (0.609 g, 99% yield) as a pale yellow oil.

Solubility in organics

5-Propyl-1,3-benzenediol is soluble in N,N-dimethylformamide, soluble in methanol, slightly soluble in glacial acetic acid, very slightly soluble in chloroform, almost insoluble in water.

InChI:InChI=1/C9H12O2/c1-2-3-7-4-8(10)6-9(11)5-7/h4-6,10-11H,2-3H2,1H3

Synthetic route

1,3-dimethoxy-5-propylbenzene (41395-10-2) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With hydrogen bromide; acetic acid In water at 125℃; for 3h; Inert atmosphere;	99%
With hydrogen iodide; acetic anhydride for 1h; Heating;	90%
With hydrogen bromide; acetic acid for 3h; Heating;	70%

2-hydroxy-4-methoxy-6-propylbenzoic acid (6245-56-3) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With hydrogen iodide

divaricatic acid (491-62-3) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With potassium hydroxide
With hydrogen iodide
Multi-step reaction with 2 steps 1: natrium carbonate 2: hydriodic acid View Scheme
Multi-step reaction with 2 steps 1: natrium carbonate 2: alkalies View Scheme
Multi-step reaction with 2 steps 1: alkali 2: hydriodic acid View Scheme

2,4-dihydroxy-6-propylbenzoic acid (4707-50-0) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With water
With alkalies

2-Bromo-3-hydroxy-5-propyl-cyclohex-2-enone (70336-33-3) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With acetic acid

2,4-dihydroxy-6-propylbenzoic acid ethyl ester (21855-51-6) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With sodium hydroxide In water Heating;

3-allylresorcinol (142039-78-9) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
With triphenyl phosphite; hydrogen In chloroform at 25℃; Rate constant; Mechanism;

1,3-dimethoxy-5-propylbenzene (41395-10-2) + hydrogen iodide (10034-85-2) → 5-propyl-1,3-benzenediol (500-49-2)

divaricatic acid (491-62-3) + alkali → 5-propyl-1,3-benzenediol (500-49-2) + carbon dioxide (124-38-9) + 2-hydroxy-4-methoxy-6-propylbenzoic acid (6245-56-3)

2-hydroxy-4-methoxy-6-propylbenzoic acid (6245-56-3) + hydrogen iodide (10034-85-2) → 5-propyl-1,3-benzenediol (500-49-2) + carbon dioxide (124-38-9) + methyl iodide (74-88-4)

divaricatic acid (491-62-3) + hydrogen iodide (10034-85-2) → 5-propyl-1,3-benzenediol (500-49-2) + carbon dioxide (124-38-9) + methyl iodide (74-88-4)

2,4-dihydroxy-6-propylbenzoic acid (4707-50-0) + water (7732-18-5) → 5-propyl-1,3-benzenediol (500-49-2)

2,4-dihydroxy-6-propylbenzoic acid (4707-50-0) + alkali → 5-propyl-1,3-benzenediol (500-49-2)

2-hydroxy-4-(2-hydroxy-4-methoxy-6-pentyl-benzoyloxy)-6-propyl-benzoic acid (491-57-6) + aqueous KOH-solution → 5-propyl-1,3-benzenediol (500-49-2) + 2-hydroxy-4-methoxy-6-pentylbenzoic acid (52189-68-1)

3,5-dimethoxybenzyl alcohol (705-76-0) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: Et3N / tetrahydrofuran / 1 h / 0 - 20 °C 2: 62 percent / Li, naphthalene / tetrahydrofuran / 2 h / -30 - 0 °C 3: 69 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C 4: 60 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 5: 70 percent / 45percent HBr, glacial AcOH / 3 h / Heating View Scheme

1-(3,5-dimethoxyphenyl)propan-2-ol (79859-93-1) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 69 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C 2: 60 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 3: 70 percent / 45percent HBr, glacial AcOH / 3 h / Heating View Scheme

3,5-dimethoxybenzyl trimethylsilyl ether (185249-83-6) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 62 percent / Li, naphthalene / tetrahydrofuran / 2 h / -30 - 0 °C 2: 69 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C 3: 60 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 4: 70 percent / 45percent HBr, glacial AcOH / 3 h / Heating View Scheme

Methanesulfonic acid 2-(3,5-dimethoxy-phenyl)-1-methyl-ethyl ester (185249-88-1) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 2: 70 percent / 45percent HBr, glacial AcOH / 3 h / Heating View Scheme

3,5-dimethoxybenzaldehdye (7311-34-4) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 2: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 3: NaI, ClSiMe3 / acetonitrile / 36 h / Heating View Scheme
Multi-step reaction with 3 steps 1: diethyl ether / 1 h / 0 °C 2: hydrogen; palladium 10% on activated carbon; sulfuric acid / ethanol / 4 h / 3040.2 Torr 3: boron tribromide / dichloromethane / 2 h / -15 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: 5%-palladium/activated carbon; hydrogen / ethyl acetate / 2 h 3.1: acetic acid; hydrogen bromide / water / 3 h / 125 °C / Inert atmosphere View Scheme

1-(3,5-dimethoxy-phenyl)-propan-1-ol (203912-55-4) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 2: NaI, ClSiMe3 / acetonitrile / 36 h / Heating View Scheme
Multi-step reaction with 2 steps 1: hydrogen; palladium 10% on activated carbon; sulfuric acid / ethanol / 4 h / 3040.2 Torr 2: boron tribromide / dichloromethane / 2 h / -15 - 20 °C / Inert atmosphere View Scheme

3,5-dimethoxybenzoic acid (1132-21-4) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: 89 percent / (COCl)2 / benzene / 2 h, room t., 1 h, reflux 2: 70 percent / NaOAc, H2 / 10percent Pd-C / 2427.2 Torr / 1h, then 60 degC, overnight 3: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 4: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 5: NaI, ClSiMe3 / acetonitrile / 36 h / Heating View Scheme
Multi-step reaction with 8 steps 4: 28.8 g / fluoroboric acid, sodium nitrite / H2O 5: 7.6 g / warming, distillation 6: 1.) lithium / 1.) ether, 2 h 7: Cu-quinoline 8: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 7 steps 4: 28.8 g / fluoroboric acid, sodium nitrite / H2O 5: 7.6 g / warming, distillation 6: 63.5 percent / lithium chips / diethyl ether / 0.5 h 7: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 85 percent / diethyl ether / 1.) from -78 deg C to 0 deg C , 1.5 h, 2.) RT, 18 h 2: 1.) H2N4*H2O, 2.) KOH / 1.) EtOH, reflux, 6 h, 2.) 230 deg C, 0.5 h 3: 90 percent / Ac2O, HI / 1 h / Heating View Scheme
Multi-step reaction with 6 steps 1: thionyl chloride; N,N-dimethyl-formamide / toluene / 6 h / 100 °C 2: triethylamine / dichloromethane / 0 °C 3: 2-methyltetrahydrofuran / 5 h / 0 °C 4: hydrazine hydrate / ethanol / 6 h / Reflux 5: potassium hydroxide / 0.5 h / 230 °C 6: pyridine hydrochloride / 4 h / 200 °C View Scheme

3,5-dimethoxybenzoyl chloride (17213-57-9) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 percent / NaOAc, H2 / 10percent Pd-C / 2427.2 Torr / 1h, then 60 degC, overnight 2: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 3: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 4: NaI, ClSiMe3 / acetonitrile / 36 h / Heating View Scheme
Multi-step reaction with 7 steps 3: 28.8 g / fluoroboric acid, sodium nitrite / H2O 4: 7.6 g / warming, distillation 5: 1.) lithium / 1.) ether, 2 h 6: Cu-quinoline 7: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 6 steps 3: 28.8 g / fluoroboric acid, sodium nitrite / H2O 4: 7.6 g / warming, distillation 5: 63.5 percent / lithium chips / diethyl ether / 0.5 h 6: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 5 steps 1: triethylamine / dichloromethane / 0 °C 2: 2-methyltetrahydrofuran / 5 h / 0 °C 3: hydrazine hydrate / ethanol / 6 h / Reflux 4: potassium hydroxide / 0.5 h / 230 °C 5: pyridine hydrochloride / 4 h / 200 °C View Scheme

ethyl 3,5-dimethoxybenzoate (17275-82-0) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 12 steps 1: 78 percent / hydrazine hydrate / 2 h / Heating 2: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 3: 93 percent / toluene / 2.5 h / Heating 4: 8.7 g / sodium hydroxide (20percent) / 60 °C 8: 28.8 g / fluoroboric acid, sodium nitrite / H2O 9: 7.6 g / warming, distillation 10: 1.) lithium / 1.) ether, 2 h 11: Cu-quinoline 12: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 11 steps 1: 78 percent / hydrazine hydrate / 2 h / Heating 2: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 3: 93 percent / toluene / 2.5 h / Heating 4: 8.7 g / sodium hydroxide (20percent) / 60 °C 8: 28.8 g / fluoroboric acid, sodium nitrite / H2O 9: 7.6 g / warming, distillation 10: 63.5 percent / lithium chips / diethyl ether / 0.5 h 11: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

3,5-Dihydroxybenzoic acid (99-10-5) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 9 steps 1: 84 percent / sodium hydroxide / heating 5: 28.8 g / fluoroboric acid, sodium nitrite / H2O 6: 7.6 g / warming, distillation 7: 1.) lithium / 1.) ether, 2 h 8: Cu-quinoline 9: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 8 steps 1: 84 percent / sodium hydroxide / heating 5: 28.8 g / fluoroboric acid, sodium nitrite / H2O 6: 7.6 g / warming, distillation 7: 63.5 percent / lithium chips / diethyl ether / 0.5 h 8: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

3,5-dimethoxybenzamide (17213-58-0) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 6 steps 2: 28.8 g / fluoroboric acid, sodium nitrite / H2O 3: 7.6 g / warming, distillation 4: 1.) lithium / 1.) ether, 2 h 5: Cu-quinoline 6: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 5 steps 2: 28.8 g / fluoroboric acid, sodium nitrite / H2O 3: 7.6 g / warming, distillation 4: 63.5 percent / lithium chips / diethyl ether / 0.5 h 5: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

2,4-dimethoxy-6-propylbenzoic acid (52189-64-7) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Cu-quinoline 2: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

azido(3,5-dimethoxyphenyl)methanone (75996-26-8) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 10 steps 1: 93 percent / toluene / 2.5 h / Heating 2: 8.7 g / sodium hydroxide (20percent) / 60 °C 6: 28.8 g / fluoroboric acid, sodium nitrite / H2O 7: 7.6 g / warming, distillation 8: 1.) lithium / 1.) ether, 2 h 9: Cu-quinoline 10: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 9 steps 1: 93 percent / toluene / 2.5 h / Heating 2: 8.7 g / sodium hydroxide (20percent) / 60 °C 6: 28.8 g / fluoroboric acid, sodium nitrite / H2O 7: 7.6 g / warming, distillation 8: 63.5 percent / lithium chips / diethyl ether / 0.5 h 9: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

3,5-dimethoxy-benzoic acid hydrazide (51707-38-1) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 11 steps 1: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 2: 93 percent / toluene / 2.5 h / Heating 3: 8.7 g / sodium hydroxide (20percent) / 60 °C 7: 28.8 g / fluoroboric acid, sodium nitrite / H2O 8: 7.6 g / warming, distillation 9: 1.) lithium / 1.) ether, 2 h 10: Cu-quinoline 11: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 10 steps 1: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 2: 93 percent / toluene / 2.5 h / Heating 3: 8.7 g / sodium hydroxide (20percent) / 60 °C 7: 28.8 g / fluoroboric acid, sodium nitrite / H2O 8: 7.6 g / warming, distillation 9: 63.5 percent / lithium chips / diethyl ether / 0.5 h 10: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

3,5-dimethoxyfluorobenzene (52189-63-6) → 5-propyl-1,3-benzenediol (500-49-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) lithium / 1.) ether, 2 h 2: Cu-quinoline 3: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: 63.5 percent / lithium chips / diethyl ether / 0.5 h 2: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C View Scheme

5-propyl-1,3-benzenediol (500-49-2) → 4,6-dibromo-5-propylbenzene-1,3-diol

Conditions	Yield
Stage #1: 5-propyl-1,3-benzenediol With bromine In dichloromethane at -50℃; for 0.5h; Stage #2: With sodium thiosulfate In dichloromethane; water at 0℃; Temperature;	82%

C18H8F2N4O10 (937720-91-7) + 5-propyl-1,3-benzenediol (500-49-2) → C27H18N4O12 (937720-92-8)

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 8h;	69%

diethyl 2-acetylglutarate (1501-06-0) + 5-propyl-1,3-benzenediol (500-49-2) → 3-(5-hydroxy-4-methyl-2-oxo-7-propyl-2H-chromen-3-yl)-propionic acid ethyl ester (468095-79-6)

Conditions	Yield
With trichlorophosphate	61%

5-propyl-1,3-benzenediol (500-49-2) + 4-benzyloxy-2-hydroxy-6-pentylbenzoic acid (53530-19-1) → 4-Benzyloxy-2-hydroxy-6-pentyl-benzoic acid 3-hydroxy-5-propyl-phenyl ester

Conditions	Yield
With dicyclohexyl-carbodiimide In toluene for 47h; Ambient temperature;	58%

5-propyl-1,3-benzenediol (500-49-2) + (+)-cis-piperityl acetate → cannabidivarin (24274-48-4) + C19H26O2

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane for 0.116667h; Flow reactor;	A 56% B 30%

5-propyl-1,3-benzenediol (500-49-2) + 2-hydroxy-4-methoxy-6-propylbenzoic acid (6245-56-3) → 3'-hydroxy-5'-propylphenyl 2-hydroxy-4-methoxy-6-propylbenzoate + depsidellin D

Conditions	Yield
With dicyclohexyl-carbodiimide In toluene for 120h; Ambient temperature;	A 38% B 13%

5-propyl-1,3-benzenediol (500-49-2) + (-)-trans-Isopiperitenol (74410-00-7) → 2-((1S,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)-5-propylbenzene-1,3-diol + C29H40O2 + C19H26O2

Conditions	Yield
With aluminum oxide; boron trifluoride diethyl etherate In dichloromethane for 0.00277778h; Inert atmosphere; Reflux;	A 37% B 12% C 18%

5-propyl-1,3-benzenediol (500-49-2) + (S)-cis-Verbenol (18881-04-4) → Propyl-delta(8)-tetrahydrocannabiol (31262-38-1)

Conditions	Yield
With trifluorormethanesulfonic acid In dichloromethane at 0 - 20℃; for 3h;	20%

hydrogen cyanide (74-90-8) + 5-propyl-1,3-benzenediol (500-49-2) → 2,4-dihydroxy-6-propylbenzaldehyde (37455-87-1)

Conditions	Yield
With diethyl ether durch Erhitzen des Reaktionsprodukts mit Wasser;

5-propyl-1,3-benzenediol (500-49-2) → 2,4,6-tribromo-5-propyl-resorcinol

Conditions	Yield
With bromine; acetic acid

5-propyl-1,3-benzenediol (500-49-2) + acetic anhydride (108-24-7) → 1,3-diacetoxy-5-propyl-benzene

Conditions	Yield
With sodium acetate at 85℃;
With pyridine Acetylation;

5-propyl-1,3-benzenediol (500-49-2) + ethyl 4-methyl-2-cyclohexanone-1-carboxylate (13537-82-1) → 1-hydroxy-9-methyl-3-propyl-7,8,9,10-tetrahydro-benzo[c]chromen-6-one (41516-21-6)

Conditions	Yield
With trichlorophosphate; benzene

5-propyl-1,3-benzenediol (500-49-2) + (+-)-pulegone → (R)-6,6,9-trimethyl-3-propyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-1-ol

Conditions	Yield
With trichlorophosphate; benzene

5-propyl-1,3-benzenediol (500-49-2) + zinc cyanide → 2,4-dihydroxy-6-propylbenzaldehyde (37455-87-1)

Conditions	Yield
With hydrogenchloride; diethyl ether durch Erhitzen des Reaktionsprodukts mit Wasser;

5-propyl-1,3-benzenediol (500-49-2) + pulegone (89-82-7) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) + benzene (71-43-2) → (+)(R)-1-hydroxy-6.6.9-trimethyl-3-propyl-7.8.9.10-tetrahydro-6H-benzochromene

5-propyl-1,3-benzenediol (500-49-2) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) + benzene (71-43-2) + 2-oxo-4-methyl-cyclohexane-carboxylic acid-(1)-ethyl ester → 1-hydroxy-9-methyl-3-propyl-7,8,9,10-tetrahydro-benzo[c]chromen-6-one (41516-21-6)

hydrogenchloride (7647-01-0) + diethyl ether (60-29-7) + 5-propyl-1,3-benzenediol (500-49-2) + zinc cyanide → 2,4-dihydroxy-6-propylbenzaldehyde (37455-87-1)

Conditions	Yield
Kochen des Reaktionsprodukts mit Wasser;

Upstream product

• 41395-10-2 1,3-dimethoxy-5-propylbenzene 
• 6245-56-3 2-hydroxy-4-methoxy-6-propylbenzoic acid 
• 491-62-3 divaricatic acid 
• 4707-50-0 2,4-dihydroxy-6-propylbenzoic acid 
• 70336-33-3 2-Bromo-3-hydroxy-5-propyl-cyclohex-2-enone 
• 21855-51-6 2,4-dihydroxy-6-propylbenzoic acid ethyl ester 
• 142039-78-9 3-allylresorcinol 
• 10034-85-2 hydrogen iodide 
• 7732-18-5 water 
• 491-57-6 2-hydroxy-4-(2-hydroxy-4-methoxy-6-pentyl-benzoyloxy)-6-propyl-benzoic acid 
• 705-76-0 3,5-dimethoxybenzyl alcohol 
• 79859-93-1 1-(3,5-dimethoxyphenyl)propan-2-ol 
• 185249-83-6 3,5-dimethoxybenzyl trimethylsilyl ether 
• 185249-88-1 Methanesulfonic acid 2-(3,5-dimethoxy-phenyl)-1-methyl-ethyl ester 

Downstream Products

• 37455-87-1 2,4-dihydroxy-6-propylbenzaldehyde 
• 31262-38-1 3-norpentyl-3-propyl-Δ⁸-tetrahydrocannabinol 
• 31262-37-0 tetrahydrocannabivarin 
• 55824-11-8 CBGV 
• 64924-07-8 6-carboxylic acid-2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-propyl-benzene-1,3-diol 
• 28172-17-0 (6aS,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol 
• 24274-48-4 cannabidivarin 
• 41408-19-9 2-methyl-2-(4-methylpent-3-enyl)-7-propyl-5-chromenol 
• 33745-21-0 cannabivarin 

Relevant academic research and scientific papers

A Novel and Practical Continuous Flow Chemical Synthesis of Cannabidiol (CBD) and its CBDV and CBDB Analogues

Cannabidiol is one of the main non-psychoactive cannabinoids present in Cannabis sativa and, in the last decade, it is gaining great interest among the scientific community for its pharmaceutical, nutraceutical, and cosmetic applications. Herein, we report the first continuous flow chemical synthesis of cannabidiol (CBD) and its analogues cannabidivarin (CBDV) and cannabidibutol (CBDB). This approach permits to synthesize products in very good yields (55–59 %), limiting the formation of psychoactive and illegal cannabinoids such as tetrahydrocannabinol (THC).

Using (+)-carvone to access novel derivatives of (+)-ent-cannabidiol: The first asymmetric syntheses of (+)-ent-CBDP and (+)-ent-CBDV

(?)-Cannabidiol [(?)-CBD] has recently gained prominence as a treatment for neuro-inflammation and other neurodegenerative disorders; interest is also developing in its synthetic enantiomer, (+)-CBD, which has a higher affinity to CB1/CB2 receptors than the natural stereoisomer. We have developed an inexpensive, stereoselective route to access ent-CBD derivatives using (+)-carvone as a starting material. In addition to (+)-CBD, we report the first syntheses of (+)-cannabidivarin, (+)-cannabidiphorol as well as C-6/C-8 homologues.

Cannabidiol derivative as well as preparation method and medical application thereof

The invention relates to a cannabidiol derivative and application thereof in medicine, in particular to a pyrimidine derivative as shown in a general formula (I), or a stereoisomer, a solvate, a metabolite, a prodrug, a pharmaceutically acceptable salt or a co-crystal thereof, and definition of each substituent in the general formula (I) is the same as that in the specification.

A Revised Modular Approach to (–)-trans-Δ8-THC and Derivatives Through Late-Stage Suzuki–Miyaura Cross-Coupling Reactions

A revised modular approach to various synthetic (–)-trans-Δ8-THC derivatives through late-stage Suzuki–Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp2- and sp3-hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki–Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature.

BIOENZYMATIC SYNTHESIS OF THC-v, CBV AND CBN AND THEIR USE AS THERAPEUTIC AGENTS

The present invention provides methods for producing cannabinoids. More specifically, the invention is directed to the bio-enzymatic synthesis of THC-v, CBV and CBN by contacting a compound according to Formula I with a cannabinoid synthase enzyme. Also described is a system for producing these pharmaceutically important cannabinoids and the use of such cannabinoids as therapeutic agents.

PROCESS FOR THE PRODUCTION OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL

The present disclosure relates to the preparation of a cannabidiol compound or a derivative thereof. The cannabidiol compound or derivatives thereof can be prepared by an acid-catalyzed reaction of a suitably selected and substituted di-halo-olivetol or derivative thereof with a suitably selected and substituted cyclic alkene to produce a dihalo-cannabidiol compound or derivative thereof. The dihalo-cannabidiol compound or derivative thereof can be produced in high yield, high stereospecificity, or both. It can then be converted under reducing conditions to a cannabidiol compound or derivatives thereof.

APPARATUS AND METHODS FOR THE SIMULTANEOUS PRODUCTION OF CANNABINOID COMPOUNDS

The present invention provides an apparatus and methods for simultaneously producing different compounds in various ratios under set conditions.

BIOSYNTHESIS OF CANNABINOIDS

The present invention provides methods for producing cannabinoids and cannabinoid analogs as well as a system for producing these compounds. The inventive method is directed to contacting a compound according to Formula I or Formula II with a cannabinoid synthase. Also described is a system for producing cannabinoids and cannabinoid analogs by contacting a THCA synthase with a cannabinoid precursor and modifying at least one property of the reaction mixture to influence the quantity formed of a first cannabinoid relative to the quantity formed of a second cannabinoid.

Simple synthesis of 5-substituted resorcinols: A revisited family of interesting bioactive molecules

The reaction of 3,5-dimethoxybenzyl trimethylsilyl ether (3) with different aldehydes (n-PrCHO, n-C11H23CHO, MeCHO, PhCHO) in the presence of lithium powder and a catalytic amount of naphthalene (4 mol %) gave, after hydrolysis, the expected alcohols 4 in moderate yields. The dehydroxylation of these compounds through the corresponding mesylates 5 or directly from benzylic derivatives by catalytic hydrogenation, afforded compounds 6, which are finally demethylated to yield 5-alkyl-3,5-dihydroxyresorcinols, such as olivetol (7a), grevillol (7b), 1,3-dihydroxy-5-propylbenzene (7c), or dihydropinosilvine (7d). Dehydration of alcohol derivatives 4 followed by demethylation led to hydroxylated stilbene-type structures, such as pinosilvine (9d), resveratrol (9e), or piceatannol (9f), which in some cases can be hydrogenated to give saturated molecules such as combretastanin B-4 tetramethyl ether (6f) or chrysotobibenzyl (6g). Finally, when the naphthalene-catalyzed lithiation of compound 3 was performed in the presence of other electrophiles [Me3SiCl, t-BuCHO, CH3(CH2)4CHO, 4-Me3SiOC6H4CHO, (CH2)5CO, PhN = C = O, PhN = CHPh], the expected reaction products 12 were isolated, after hydrolysis.

Substrate selective catalysis by rhodium metallohosts

A novel supramolecular catalyst functioning according to the principles of enzymatic catalysis is described. It consists of a basket-shaped molecule to which a catalytically active Rh(I) complex is attached. The catalyst selectively hydrogenates and isomerizes allyl-substituted dihydroxyarene substrates that are bound in its cavity. The reactivity of this supramolecular catalyst and its affinity for several substrates is compared with that of the corresponding catalyst without a binding site. Features known from enzymatic catalysis, e.g. Michaelis-Menten kinetics and rate enhancement by cooperative binding, are described and discussed.