2078-54-8

Basic information

• Product Name: Propofol
• Synonyms: RAPINOVET;PROPOFOL;PROPOTOL;2,6-bis(1-methylethyl)-pheno;2,6-Bis(isopropyl)phenol;2,6-diisopropyl-pheno;Diprivan10;Disoprofol
• CAS NO: 2078-54-8
• Molecular Formula: C12H18O
• Molecular Weight: 178.27
• EINECS: 218-206-6
• Product Categories: Heterocyclic Compounds;Intermediates & Fine Chemicals;Pharmaceuticals;GABA/Glycine receptor;GABA;Aromatics;C9 to C20+;Bioactive Small Molecules;Building Blocks;Cell Biology;Chemical Synthesis;DIG-DY;Organic Building Blocks;Oxygen Compounds;Phenols;DIPRIVAN
• Mol File: 2078-54-8.mol
• Article Data: 47

Chemical Properties

• Melting Point: 18 °C(lit.)
• Boiling Point: 256 °C764 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: light yellow liquid
• Density: 0.962 g/mL at 25 °C(lit.)
• Vapor Pressure: 5.6 mm Hg ( 100 °C)
• Refractive Index: n20/D 1.514(lit.)
• Storage Temp.: 0-6°C
• Solubility: Very slightly soluble in water, miscible with hexane and with methanol
• PKA: pKa 11.10(H2O,t =20)(Approximate)
• Water Solubility: Very slightly soluble in water.
• Merck: 14,7834
• BRN: 1866484
• CAS DataBase Reference: Propofol(CAS DataBase Reference)
• NIST Chemistry Reference: Propofol(2078-54-8)
• EPA Substance Registry System: Propofol(2078-54-8)

Safety Data

• Hazard Codes: Xn,T,F
• Statements: 22-36/37/38-20/21/22-39/23/24/25-23/24/25-11
• Safety Statements: 26-36/37/39-37/39-36-45-36/37-16-7
• RIDADR: 2810
• WGK Germany: 3
• RTECS: SL0810000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 2078-54-8(Hazardous Substances Data)

Usage

Uses

Used in Veterinary Medicine:
Propofol is used as an anesthetic for veterinary medicine, providing a safe and effective means of inducing and maintaining anesthesia or sedation in animals.
Used in Human Medicine:
Propofol is used as an anesthetic for the induction and maintenance of anesthesia or sedation in human patients. Its short-acting nature and low side effect profile make it a preferred choice for various medical procedures.
Used in Pharmaceutical Formulations:
2,6-DIPP, the active ingredient for intravenous anesthetic formulations, is also used as an intermediate for polymers. This highlights the versatility of Propofol and its derivatives in the pharmaceutical and chemical industries.

Originator

ICI (United Kingdom)

World Health Organization (WHO)

Propofol, a short acting injectable anaesthetic, was introduced in 1987. In April 1992, the Norwegian Medicines Control Board reported that prolonged use of propofol had been associated with two fatalities in children characterized by metabolic acidosis, liver enlargement, and cerebral oedema. The UK Committee on the Safety of Medicines has received 5 reports of deaths occurring in children who had received propofol while in intensive care.

Biological Functions

Propofol (Diprivan) is rapidly acting, has a short recovery time, and possesses antiemetic properties. A rapid onset of anesthesia (50 seconds) is achieved, and if no other drug is administered, recovery will take place in 4 to 8 minutes.The recovery is attributed to redistribution of the drug and rapid metabolism to glucuronide and sulfate conjugates by the liver and extrahepatic tissues, such as intestine and kidney. Rapid recovery and its antiemetic properties make propofol anesthesia very popular as an induction agent for outpatient anesthesia. Propofol can also be used to supplement inhalational anesthesia in longer procedures. Both continuous infusion of propofol for conscious sedation and with opioids for the maintenance of anesthesia for cardiac surgery are acceptable techniques.

Synthesis Reference(s)

The Journal of Organic Chemistry, 21, p. 712, 1956 DOI: 10.1021/jo01112a621

Biological Activity

Intravenous general anesthetic and hypnotic with a mode of action which includes potentiation of GABA-mediated inhibitory synaptic transmission, direct activation of the GABA A receptor and inhibition of glutamate receptor mediated excitatory synaptic transmission. Also potentiates P2X 4 receptor-mediated currents in P2X 4 -HEK293 cells.

Pharmacology

Propofol is primarily a hypnotic drug with substantial cardiorespiratory depressant actions and with no ability to produce neuromuscular blockade. While propofol lacks analgesic properties, its use permits lower doses of opioids. Likewise, less propofol is required for adequate hypnosis when it is administered with opioids.Thus, it is said that propofol and opioids interact synergistically.

Clinical Use

Generic formulations of propofol may contain sodiummetabisulfite as the antimicrobial agent, and patients allergicto sulfites, especially asthmatic patients, should avoid thisformulation. Aseptic technique must be followed and unusedportions of the drug must be discarded according to the manufacturer’s instructions to prevent microbial contaminationand possible sepsis.

Side effects

The dose of propofol should be reduced in older patients; however, it does have a relatively linear dose– response characteristic, and patients generally can be safely titrated. The pain on injection, especially when small veins are used, can be considerably reduced if lidocaine 20 mg is administered first. Anesthesia induction with propofol causes a significant reduction in blood pressure that is proportional to the severity of cardiovascular disease or the volume status of the patient, or both. However, even in healthy patients a significant reduction in systolic and mean arterial blood pressure occurs. The reduction in pressure appears to be associated with vasodilation and myocardial depression. Although propofol decreases systemic vascular resistance, reflex tachycardia is not observed. This is in contrast to the actions of thiopental. The heart rate stabilization produced by propofol relative to other agents is likely the result of either resetting or inhibiting the baroreflex, thus reducing the tachycardic response to hypotension. Since propofol does not depress the hemodynamic response to laryngoscopy and intubation, its use may permit wide swings in blood pressure at the time of induction of anesthesia. Propofol should be used with utmost caution in patients with cardiac disease.

Safety Profile

Poison by intravenous and intraperitoneal routes. Experimental reproductive effects. Combustible when exposed to heat or flame; can react with oxidizing materials. To fight fire, use foam, CO2, dry chemical. When heated to decomposition it emits acrid smoke and fumes. See also PHENOL

Veterinary Drugs and Treatments

In appropriate patients, propofol may be useful as an induction agent (especially before endotracheal intubation or an inhalant anesthetic), and as an anesthetic for outpatient diagnostic or minor procedures (e.g., laceration repair, radiologic procedures, minor dentistry, minor biopsies, endoscopy, etc.). Propofol is used as a treatment for refractory status epilepticus, as it tends to cause less cardiovascular depression and recoveries can be smoother than with pentobarbital. Propofol may be of particular usefulness for use in Greyhounds and in patients with preexisting cardiac dysrhythmias. At low dosages, propofol is being investigated as an appetite stimulant in dogs. Propofol may be safely used in animals with liver or renal disease and mild to moderate cardiac disease. In dogs, propofol’s labeled indications are: 1) for induction of anesthesia; 2) for maintenance of anesthesia for up to 20 minutes; 3) for induction of general anesthesia where maintenance is provided by inhalant anesthetics.

InChI:InChI=1/C12H18O/c1-8(2)10-6-5-7-11(9(3)4)12(10)13/h5-9,13H,1-4H3

Synthetic route

2,6-diisopropylcyclohexanol (95299-24-4) + platinum (7440-06-4) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
	96.5%

1-tert-butoxycarbonyloxy-2,6-diisopropylbenzene → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With sodium methylate In methanol; dichloromethane at 20℃; for 9h;	96%
With hydrogenchloride In 1,4-dioxane for 3h; Product distribution; Heating; deprotection;	87%

4-hydroxy-3,5-diisopropylbenzoic acid isopropyl ester → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With sodium hydroxide In isopropyl alcohol at 20 - 70℃; for 7h; Inert atmosphere;	94.9%

C14H19N2O2(1+)*O4S(2-) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With formaldehyd; water; sodium hydroxide at 0 - 20℃; for 1h; Reagent/catalyst;	94.7%

2,6-diisopropyl anisole (2944-52-7) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With 1-n-butyl-3-methylimidazolim bromide at 220℃; for 0.666667h; Inert atmosphere; Microwave irradiation;	94%

4-hydroxy-3,5-diisopropylbenzoic acid t-butyl ester → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With sodium hydroxide In tert-butyl alcohol at 20 - 60℃; for 5h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	94%

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
Stage #1: 4-hydroxy-3,5-diisopropylbenzoic acid; sodium hydroxide In ethylene glycol at 140 - 145℃; for 7h; Inert atmosphere; Stage #2: With hydrogenchloride In water; ethylene glycol for 1h; pH=1 - 2;	93.5%
With decarboxylase at 25℃; for 15h; pH=6.5; Enzymatic reaction;	80.3%
With sodium hydroxide In 2-ethoxy-ethanol at 125 - 130℃; Large scale;	74%
Stage #1: 4-hydroxy-3,5-diisopropylbenzoic acid With sodium hydroxide In ethylene glycol at 140 - 145℃; Stage #2: With hydrogenchloride In water; ethylene glycol at 20℃; for 0.5h; pH=1 - 2;	53 g

isopropyl alcohol (67-63-0) + phenol (108-95-2) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With H-β zeolite at 259.84℃; Kinetics; Catalytic behavior; Reagent/catalyst; Temperature;	93%

4-Chloropropofol (91561-75-0) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
Stage #1: 4-Chloropropofol With hydrogen; sodium hydroxide; 5%-palladium/activated carbon In water at 20 - 25℃; under 2250.23 - 3750.38 Torr; Stage #2: With hydrogenchloride In water	90%
Stage #1: 4-Chloropropofol With hydrogen; sodium hydroxide; 5%-palladium/activated carbon In water at 20 - 25℃; under 2250.23 - 3750.38 Torr; Stage #2: With hydrogenchloride In water Product distribution / selectivity;	90%
With nickel; benzene Hydrogenation;

1,3-diisopropyl-2-iodobenzene (163704-47-0) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
Stage #1: 2-iodo-1,3-diisopropylbenzene With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In water; dimethyl sulfoxide at 20 - 100℃; Inert atmosphere; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide at 20℃; Inert atmosphere;	85%
Multi-step reaction with 4 steps 1.1: sodium perborate tetrahydrate / 17 h / 20 - 40 °C 2.1: dichloromethane / 20 °C 3.1: sodium hexamethyldisilazane / pentane; toluene / 0.17 h / 0 - 25 °C / Inert atmosphere; Schlenk technique 3.2: 12 h / 0 - 25 °C / Schlenk technique; Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 3 h / 0 - 25 °C View Scheme

(2,6-diisopropylphenyl) boronic acid (363166-79-4) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With p-benzoquinone; potassium hydroxide In water for 30h; Reflux; Green chemistry;	75%

2,6-diisopropylphenyl tert-butyldimethylsilyl ether (1035347-44-4) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 0 - 25℃; for 3h;	72%

isopropyl alcohol (67-63-0) + phenol (108-95-2) → 2-(1-methylethyl)phenol (88-69-7) + 4-Isopropylphenol (99-89-8) + 5-propylphenol (644-35-9) + 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With supercritical water at 399.84℃; for 1h; Kinetics; Further Variations:; Time;	A 57.9% B 2.4% C 6.9% D 5.9%

2,6-di(prop-1-en-2-yl)phenol → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 2h;	56%

2,6-diisopropylbenzenamine (24544-04-5) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With uranyl nitrate hydrate; water; trifluoroacetic acid for 48h; Irradiation; Inert atmosphere;	48%
Stage #1: 2,6-diisopropylbenzenamine With sulfuric acid; sodium nitrite In water at -5℃; for 0.333333h; Stage #2: In water at 127℃; for 2h; Reagent/catalyst; Temperature;

isopropyl alcohol (67-63-0) + phenol (108-95-2) → 2-(1-methylethyl)phenol (88-69-7) + 4-Isopropylphenol (99-89-8) + 2,6-diisopropylphenol (2078-54-8) + isopropoxybenzene (2741-16-4)

Conditions	Yield
With HMCM-49/MCM-41 composite at 180℃; under 760.051 Torr; for 1h; Flow reactor;	A 41.6% B 13.3% C n/a D n/a

isopropyl alcohol (67-63-0) + phenol (108-95-2) → 2-(1-methylethyl)phenol (88-69-7) + 4-Isopropylphenol (99-89-8) + 2,6-diisopropylphenol (2078-54-8) + 2,4,6-triisopropylphenol (2934-07-8)

Conditions	Yield
With HMCM-49 at 180℃; under 760.051 Torr; for 1h; Flow reactor;	A 35.5% B 9.4% C n/a D n/a

propene (187737-37-7) + aluminium(III) phenoxide (15086-27-8) + phenol (108-95-2) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
at 240℃; under 10297.1 - 25742.8 Torr;
at 240℃; under 10297.1 - 25742.8 Torr; reagiert analog mit Anilin in Gegenwart von Aluminiumanilid bei 330grad/40-55at;
at 240℃; under 10297.1 - 25742.8 Torr; reagiert analog mit N-Methyl-anilin in Gegenwart von Aluminium-<N-methyl-anilid> bei 235grad/49at;

propene (187737-37-7) + phenol (108-95-2) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With aluminium(III) phenoxide at 220 - 240℃;

2-(1-methylethyl)phenol (88-69-7) + 2,4,6-triisopropylphenol (2934-07-8) → 2,4-diisopropylphenol (2934-05-6) + 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
sulfuric acid at 149.9℃; for 268h; Thermodynamic data; Equilibrium constant; Product distribution; other catalyst (AlCl3, AlBr3), temperature, time, ΔHr, ΔSr;

2,4-diisopropylphenol (2934-05-6) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
aluminium trichloride at 149.9℃; for 13h; Thermodynamic data; Equilibrium constant; Product distribution; other catalyst (AlBr3), temperature, time, ΔHr, ΔSr;

4-Isopropylphenol (99-89-8) + isopropyl alcohol (67-63-0) → 2-(1-methylethyl)phenol (88-69-7) + 2,4-diisopropylphenol (2934-05-6) + 2,6-diisopropylphenol (2078-54-8) + 2,4,6-triisopropylphenol (2934-07-8) + 2,5-Diisopropylphenol (35946-91-9)

Conditions	Yield
Houdry HA-100 alumina at 300℃; Product distribution; Mechanism;

isopropyl alcohol (67-63-0) + phenol (108-95-2) → 2-(1-methylethyl)phenol (88-69-7) + 4-Isopropylphenol (99-89-8) + 2,4-diisopropylphenol (2934-05-6) + 2,6-diisopropylphenol (2078-54-8) + 3-isopropylhydroxybenzene (618-45-1) + 2,5-Diisopropylphenol (35946-91-9)

Conditions	Yield
Houdry HA-100 alumina at 350℃; Product distribution; Mechanism; other substrates; other temperatures and concentrations;	A 22.6 % Chromat. B n/a C 9.2 % Chromat. D 6.4 % Chromat. E n/a F 8.1 % Chromat.

propene (187737-37-7) + phenol (108-95-2) → 2,4-diisopropylphenol (2934-05-6) + 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
at 110℃;

4-chloro-phenol (106-48-9) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2SO4 2: Raney nickel; benzene / Hydrogenation View Scheme

methane (34557-54-5) + 2,6-Diisopropylphenyl benzoate (2005-09-6) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With sodium hydroxide In methanol; water

2-(benzyloxy)-1,3-diisopropylbenzene + pyrographite (7440-44-0) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
With acetic acid In ethanol; palladium

2,6-diisopropylphenol (2078-54-8) → 3,3',5,5'-tetraisopropyldiphenoquinone (2178-51-0)

Conditions	Yield
With C24H13Cu2F9N4O7; oxygen In isopropyl alcohol at 90℃; under 760.051 Torr; for 12h;	100%
With Cu2(ophen)2 In methanol at 28℃; for 10h;	100%
With oxygen In chloroform at 49.84℃; under 760.051 Torr; for 24h; Green chemistry; regioselective reaction;	97%

cyclopentadienyl titanium(IV) trichloride (1270-98-0) + 2,6-diisopropylphenol (2078-54-8) → cyclopentadienyl(2,6-di-isopropylphenoxy)titanium dichloride

Conditions	Yield
In dichloromethane room temp.;	100%
With triethylamine In diethyl ether byproducts: HN(C2H5)3Cl; dissolution of Ti-complex in Et2O, addn. of alcohol, stirring for ca. 2 min, dropwise addn. of NEt3, immediate ppt., stirring overnight under Ar; filtn. (in-line glass sinter), washing with Et2O, combining washings with filtrate, removal of solvent in vacuo, recrystn. from n-hexane;	70%

2,6-diisopropylphenol (2078-54-8) + bromoacetic acid methyl ester (96-32-2) → methyl 2-(2,6-diisopropylphenoxy)acetate (1285189-84-5)

Conditions	Yield
With caesium carbonate In acetonitrile for 16h; Reflux;	100%

2,6-diisopropylphenol (2078-54-8) → 4-bromopropofol (2432-03-3)

Conditions	Yield
With bis(trichloromethyl) carbonate; tetrabutylammomium bromide; potassium bromide In water; ethyl acetate at 20℃; for 19h; regioselective reaction;	99%
With bromine; acetic acid at 20℃; for 1h;	98.6%
With bromine In acetic acid at 20℃; for 1h;	94%

2,6-diisopropylphenol (2078-54-8) → 3,3',5,5'-tetraisopropyl-[1,1'-biphenyl]-4,4'-diol (2416-95-7)

Conditions	Yield
Stage #1: 2,6-diisopropylphenol With oxygen In tert-butyl alcohol at 70℃; under 760.051 Torr; for 18h; Green chemistry; Stage #2: With hydrogen In tert-butyl alcohol at 60℃; under 760.051 Torr; for 4h; Green chemistry;	99%
With CuCl(OH)*TMEDA In dichloromethane at 20℃; for 5h;	95%
Stage #1: 2,6-diisopropylphenol In dichloromethane at 20℃; for 5h; Stage #2: With sodium dithionite In ethanol for 0.333333h; Heating;	95%

2,6-diisopropylphenol (2078-54-8) + di-tert-butyl dicarbonate (24424-99-5) → 1-tert-butoxycarbonyloxy-2,6-diisopropylbenzene

Conditions	Yield
With dmap In dichloromethane at 20℃;	99%
With dmap In hexane for 0.5h;	95%
With PNIPAM-bound 4-dialkylaminopyridine-methyl red terpolymer In dichloromethane at 25℃;	93%
With 6,7-dimethoxyisoquinoline In dichloromethane at 20℃; for 10h; Inert atmosphere; chemoselective reaction;	73%
With dmap In tetrahydrofuran at -5 - 20℃; under 760.051 Torr; for 3h;

2,6-diisopropylphenol (2078-54-8) + 1,1'-carbonyldiimidazole (530-62-1) → 2,6-diisopropyl 1H-imidazole-1-carboxylate (127979-33-3)

Conditions	Yield
In dichloromethane for 24h; Heating;	99%
In dichloromethane for 5h; Heating;	97%

2,6-diisopropylphenol (2078-54-8) + titanium tetrachloride (7550-45-0) → bis(2,6-diisopropylphenolato)titanium(IV) dichloride (139416-07-2)

Conditions	Yield
In tetrachloromethane byproducts: HCl; refluxing (3.5 h); evapn. (reduced pressure); elem. anal.;	99%
In hexane at 0 - 20℃; for 16h;	63%
In benzene byproducts: HCl; moisture free atmosphere; stoichiometric amounts; reflux till the evolution of HCl ceased;; removal of the volatiles under reduced pressure;;
In toluene byproducts: HCl; N2, vigorously refluxed for 13 h; cooled, filtered, solvent removed, dried (vac., several h);

tetrahydrofuran (109-99-9) + La2(O-2,6-i-Pr2C6H3)6 + 2,6-diisopropylphenol (2078-54-8) + sodium hydride (7646-69-7) → (THF)La(O-2,6-i-Pr2C6H3)2(μ-O-2,6-i-Pr2C6H3)2Na(THF)2 (172918-17-1)

Conditions	Yield
In tetrahydrofuran; toluene Ar-atmosphere; addn. of La-compd. (in PhMe) to mixt. of diisopropylphenol and NaH (in THF) with stirring, stirring for 72 h at room temp.; filtration (Celite), removal of volatiles (vac.), washing (hexane), extn. into PhMe, filtration (Celite), vol. reduction (vac.), crystn. (-40°C, overnight); elem. anal.;	99%

2,6-diisopropylphenol (2078-54-8) + propargyl bromide (106-96-7) → 1,3-diisopropyl-2-(prop-2-yn-1-yloxy)benzene (1033921-02-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	99%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h;	86%

2,6-diisopropylphenol (2078-54-8) + carbon monoxide (201230-82-2) + buta-1,3-diene (106-99-0) → C21H30O2

Conditions	Yield
With palladium diacetate; triphenylphosphine; benzoic acid In tetrahydrofuran at -40 - 80℃; under 15001.5 Torr; Autoclave; Inert atmosphere;	99%

2,6-diisopropylphenol (2078-54-8) + methyl chloroformate (79-22-1) → C14H20O3

Conditions	Yield
With triethylamine In 1,2-dichloro-ethane at 0 - 5℃; for 2h; Reagent/catalyst; Green chemistry;	98.5%

2,6-diisopropylphenol (2078-54-8) + hexamethylenetetramine (100-97-0) → 3,5-diisopropyl-4-hydroxybenzaldehyde (10537-86-7)

Conditions	Yield
Stage #1: 2,6-diisopropylphenol; hexamethylenetetramine With trifluoroacetic acid at 90℃; for 12h; Inert atmosphere; Stage #2: With hydrogenchloride at 80℃; for 3h; Inert atmosphere;	98%
With acetic acid In water for 2.58333h; Reflux;	97%
With acetic acid In water for 6h; Reflux;	89%

2,6-diisopropylphenol (2078-54-8) → C36H51ClO3Si

Conditions	Yield
With pyridine; tetrachlorosilane In benzene 1.) RT, 12 h, 2.) reflux, 1 h;	98%

phthalic anhydride (85-44-9) + 2,6-diisopropylphenol (2078-54-8) → 3,3-bis-(4-hydroxy-3,5-diisopropylphenyl)-1-(3H)-isobenzofuranone (107303-38-8)

Conditions	Yield
With PPA; zinc(II) chloride at 100℃; for 3h; Product distribution / selectivity;	98%
With Lewis acid at 90℃; for 5h; Product distribution / selectivity;	89%
With methanesulfonic acid at 90℃; for 5h;	89%

2,6-diisopropylphenol (2078-54-8) + V(NC6F5)(CH2SiMe3)3 → V(NC6F5)(CH2SiMe3)2(O-2,6-iPr2C6H3)

Conditions	Yield
In hexane at -30 - 25℃; for 12h; Inert atmosphere;	98%

2,6-diisopropylphenol (2078-54-8) → 2,6-diisopropylcyclohexanol (95299-24-4)

Conditions	Yield
With hydrogen; nickel at 39℃; under 76000 Torr; for 104h;	97%
With hydrogen; nickel at 104℃; under 72960 - 82080 Torr; for 39h;	97%
With hydrogen under 38002.6 Torr;	70%
With nickel at 200℃; under 75021.8 Torr; Hydrogenation;

Methyltrichlorosilane (75-79-6) + 2,6-diisopropylphenol (2078-54-8) → C37H54O3Si

Conditions	Yield
With pyridine In benzene 1.) RT, 12 h, 2.) reflux, 1 h;	97%

2,6-diisopropylphenol (2078-54-8) + 2-methoxy-6-((E)-prop-1-enyl)benzoic acid (143112-20-3) → 2-Methoxy-6-((E)-propenyl)-benzoic acid 2,6-diisopropyl-phenyl ester (438569-39-2)

Conditions	Yield
With trifluoroacetic anhydride In benzene at 20℃; for 24h;	97%

2,6-diisopropylphenol (2078-54-8) + ethyl bromoacetate (105-36-2) → ethyl 2,6-diisopropylphenoxyacetate (145546-92-5)

Conditions	Yield
In water; N,N-dimethyl-formamide	96.1%
With potassium carbonate In N,N-dimethyl-formamide

N-Boc-gabapentin (227626-60-0) + 2,6-diisopropylphenol (2078-54-8) → 2,6-(diisopropyl)phenyl 1-[tert-butoxycarbonylaminomethyl]-1-cyclohexane acetate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In toluene at 90℃; for 14h;	96%

η5-pentamethylcyclopentadienyl(1,2,3,4-tetramethylfulven)ruthenium tetrafluoroborate (111143-98-7, 99898-37-0) + 2,6-diisopropylphenol (2078-54-8) → (2,6-diisopropylphenoxymethyl)nonamethylruthenocene (99898-35-8)

Conditions	Yield
In dichloromethane to soln. of Ru complex in CH2Cl2 added 2,6-diisopropylphenol, stirred overnight at room temp.; evapd., washed with aq. soln. of KOH, dried, recrystd. from hexane; elem. anal.;	96%

tetrahydrofuran (109-99-9) + tris(bis(trimethylsilylamido))cerium(III) (41836-21-9) + 2,6-diisopropylphenol (2078-54-8) → [Ce(2,6-diisopropylphenol(-H))3(tetrahydrofuran)3] (950991-01-2)

Conditions	Yield
In tetrahydrofuran; toluene byproducts: HN(Si(CH3)3)2; under inert atm., Schlenk techniques; soln. of Ce compd. (0.36 mmol) andalcohol (1.1 mmol) stirred for 12 h; concd., crystd. on cooling to -25°C, elem. anal.;	96%

2,6-diisopropylphenol (2078-54-8) → 3,3',5,5'-tetraisopropyldiphenoquinone (2178-51-0) + 3,3',5,5'-tetraisopropyl-[1,1'-biphenyl]-4,4'-diol (2416-95-7) + Acetic acid 4-hydroxy-3,5-diisopropyl-phenyl ester (22944-23-6)

Conditions	Yield
With manganese triacetate In acetic acid at 100℃; for 0.0833333h;	A 95% B 1% C 1%

2,6-diisopropylphenol (2078-54-8) + acetic anhydride (108-24-7) → 2,6-Diisopropylphenyl acetate (28000-66-0)

Conditions	Yield
at 160℃; for 20h;	95%

2,6-diisopropylphenol (2078-54-8) + allyl bromide (106-95-6) → (2,6-diisopropyl)phenyl allyl ether (951-17-7)

Conditions	Yield
With potassium carbonate In acetone for 24h; Heating;	95%

Mo(N(2,6-diisopropylphenyl))(CHtBu)(CH2tBu)2 + 2,6-diisopropylphenol (2078-54-8) → Mo(N-2,6-i-Pr2C6H3)(CH-t-Bu)(CH2-t-Bu)(O-2,6-i-Pr2C6H3)

Conditions	Yield
In dichloromethane under N2 atm. Mo complex and 2,6-diisopropylphenol in pentane was stirred at room temp. for 12 h; solvent was removed in vacuo, residue was dissolved in pentane and stored at -20°C; elem. anal.;	95%
In not given byproducts: C(CH3)4; benzene or toluene, 22°C, up to 24 h;

Upstream product

• 187737-37-7 propene 
• 15086-27-8 aluminium(III) phenoxide 
• 108-95-2 phenol 
• 88-69-7 2-(1-methylethyl)phenol 
• 2934-07-8 2,4,6-triisopropylphenol 
• 99-89-8 4-Isopropylphenol 
• 67-63-0 isopropyl alcohol 
• 2944-52-7 2,6-diisopropyl anisole 
• 363166-79-4 (2,6-diisopropylphenyl) boronic acid 
• 1576-14-3 2,6-Diisopropyl-4-nitrophenol 
• 1035347-44-4 2,6-diisopropylphenyl tert-butyldimethylsilyl ether 
• 951-17-7 (2,6-diisopropyl)phenyl allyl ether 
• 64-17-5 ethanol 
• 90-05-1 2-methoxy-phenol 

Downstream Products

• 55697-99-9 2,6-diisopropyl-4-(1-phenyl-ethyl)-phenol 
• 117864-29-6 [2-(2,6-diisopropyl-phenoxy)-ethyl]-diisopropyl-amine 
• 1485-44-5 [2-(2,6-diisopropyl-phenoxy)-ethyl]-dimethyl-amine 
• 110459-33-1 diethyl-[2-(2,6-diisopropyl-phenoxy)-ethyl]-amine 
• 101778-41-0 1-[2-(2,6-diisopropyl-phenoxy)-ethyl]-pyrrolidine 
• 102703-12-8 1-[3-(2,6-diisopropyl-phenoxy)-2,2-dimethyl-propyl]-piperidine 
• 2944-52-7 2,6-diisopropyl anisole 
• 102707-98-2 1-[2-(2,6-diisopropyl-phenoxy)-ethyl]-piperidine 
• 2432-03-3 4-bromopropofol 
• 1576-14-3 2,6-Diisopropyl-4-nitrophenol 
• 95299-24-4 2,6-diisopropylcyclohexanol 
• 91561-75-0 4-Chloropropofol 
• 100915-72-8 (2,6-diisopropylphenyl)-2-chloroethyl ether 
• 107613-53-6 phosphoric acid tris-(2,6-diisopropyl-phenyl ester) 

Relevant articles and documents

Non-catalytic and selective alkylation of phenol with propan-2-ol in supercritical water

Phenol can be alkylated with propan-2-ol without catalyst in supercritical water at 673 K with mainly ortho substituted alkylphenols being obtained and alkylation reaction rate increasing with increasing water density.

Selective synthesis of propofol (2,6-diisopropylphenol), an intravenous anesthetic drug, by isopropylation of phenol over H-beta and H-mordenite

Propofol (2,6-diisopropylphenol/DIPP) is the world's most widely used intravenous general anesthetic and is typically synthesized by isopropylation of phenol over an acid catalyst. It is highly difficult to stabilize bio-oil containing phenolic compounds. The isopropylation of this phenol (a model compound representing species in bio-oils) is one of the options to stabilize the bio-oil and convert it into valuable products. Probably for the first time, H-beta- and H-mordenite-catalysed vapour phase isopropylation of phenol with isopropyl alcohol (IPA) was studied to selectively synthesize DIPP. The optimization of various operating parameters such as molar ratio (phenol:IPA), weight hourly space velocity (WHSV), reaction temperature and time on stream were performed. H-beta (94% phenol conv. and 56% DIPP sel.) was found to be a potential and more active catalyst than H-mordenite (68% phenol conv. and 43% DIPP sel.) at optimized process parameters. A kinetic model is proposed to probe the intricate reaction kinetics and validated (R2 > 0.98) by the experimental results. H-beta catalyst was observed to be stable for more than 25 h with 94% phenol conversion and 56% selectivity towards DIPP at optimized process parameters. The phenol conversion and DIPP selectivity obtained in the present study are higher than those reported so far. The activation energy obtained for isopropylation of phenol with IPA over H-beta is calculated to be 25.39 kJ mol-1. the Partner Organisations 2014.

Synthesis and catalytic performance of HMCM-49/MCM-41 composite molecular sieve for alkylation of phenol with isopropanol

HMCM-49/MCM-41 composite molecular sieve was synthesized with hydrothermal method. The physicochemical properties of the composite were characterized by using XRD, FT-IR, SEM, N2 isothermal adsorption-desorption and NH3-TPD. Results of different characterizations indicated that the synthesized composite molecular sieve possessed the characteristics of both HMCM-49 and MCM-41. XRD and N2 isothermal adsorption-desorption revealed that it has both micropores and mesopores, a larger surface area than that of HMCM-49, NH3-TPD and pyridine adsorbed FT-IR revealed that the strong acidic sites that caused side reaction in HMCM-49 are deactivated in the composite molecular sieve of HMCM-49/MCM-41. When applied to the alkylation of phenol with isopropanol, the HMCM-49/MCM-41 composite molecular sieve exhibit an enhanced catalytic performance with significant enhancement in p-isopropylphenol and o-isopropylphenol selectivity, which can be ascribed to the composite characteristics of HMCM-49 and MCM-41. This kind of material will has widely industrial application in preparation of alkyl-phenol.

Catalytic performance of Al-MCM-48 molecular sieves for isopropylation of phenol with isopropyl acetate

Al-MCM-48 molecular sieves (Si/Al molar ratios = 25, 50, 75, and 100) were synthesized hydrothermally using cetyltrimethylammonium bromide as the structure directing template. The orderly arrangement of mesopores was evident from the low angle X-ray diffr

A mild and practical method for deprotection of aryl methyl/benzyl/allyl ethers with HPPh2andtBuOK

A general method for the demethylation, debenzylation, and deallylation of aryl ethers using HPPh2andtBuOK is reported. The reaction features mild and metal-free reaction conditions, broad substrate scope, good functional group compatibility, and high chemical selectivity towards aryl ethers over aliphatic structures. Notably, this approach is competent to selectively deprotect the allyl or benzyl group, making it a general and practical method in organic synthesis.

Aryl phenol compound as well as synthesis method and application thereof

The invention discloses a synthesis method of an aryl phenol compound shown as a formula (3). All systems are carried out in an air or nitrogen atmosphere, and visible light is utilized to excite a photosensitizer for catalyzation. In a reaction solvent, ArNR1R2 as shown in a formula (1) and water as shown in a formula (2) are used as reaction raw materials and react under the auxiliary action of acid to obtain the aryl phenol compound as shown in a formula (3). The ArNR1R2 in the formula (1) can be primary amine and tertiary amine, can also be steroid and amino acid derivatives, and can also be drugs or derivatives of propofol, paracetamol, ibuprofen, oxaprozin, indomethacin and the like. The synthesis method has the advantages of cheap and easily available raw materials, simple reaction operation, mild reaction conditions, high reaction yield and good compatibility of substrate functional groups. The fluid reaction not only can realize amplification of basic chemicals, but also can realize amplification of fine chemicals, such as synthesis of drugs propofol and paracetamol. The invention has wide application prospect and use value.

Continuous flow synthesis of propofol

Herein, we report a continuous flow process for the synthesis of 2,6-diisopropylphenol— also known as Propofol—a short-acting intravenous anesthesia, widely used in intensive care medicine to provide sedation and hypnosis. The synthesis is based on a two-step procedure: a double Friedel–Crafts alkylation followed by a decarboxylation step, both under continuous flow.

SIMPLE MANUFACTURING AND PURIFICATION TECHNOLOGY FOR HIGH PURITY PROPOFOL

A process for manufacturing Pure Propofol with a purity of more than 99.90% is disclosed, said process comprising dissolving Crude Propofol in a solvent in which it is soluble to form a solution, treating the solution with aqueous alkali to form an aqueous alkali layer and a solvent layer, separating the aqueous alkali layer from the solvent layer using a phase separation technique, distilling off the solvent from the solvent layer, and distilling a residue of the solvent containing Propofol using steam or boiling water in a presence of dilute alkali and antioxidant like metabisulfite, under normal pressure or mild vacuum.

PROCESS FOR THE PREPARATION OF PROPOFOL

The present provides a simple, convenient and time-efficient process for the preparation of propofol. Particularly, the present invention provides an improved process for the preparation of propofol using a heterocyclic base for the decarboxylation reaction. The present invention provides a time-efficient process for the preparation of propofol with high yield and purity.

Guaiacol demethoxylation catalyzed by Re2O7 in ethanol

Re2O7 is used to convert guaiacol in alcohols at 280–320 °C. In ethanol, guaiacol is deoxygenated and alkylated, and the major products are phenol and alkylphenols (including ethylphenol, diethylphenol, diisopropylphenol, di-tert-butylphenol and 2,6-di-tert-butyl-4-ethylphenol), accounting for 97 mol% of all products after 6 hour reaction at 320 °C. Both catechol and phenol are the intermediates of guaiacol demethoxylation. Among the substituents, ethyl is directly provided by ethanol while isopropyl and tert-butyl are formed by the addition of methyl to ethyl step by step. In addition, Re2O7 has negligible activity for the saturation of benzene ring so it does not cause considerable over-consumption of reductant. The actual catalyst for guaiacol demethoxylation is likely a ReIV?VI species.