933-88-0

Basic information

• Product Name: o-Toluoyl chloride
• Synonyms: o-Toluoyl chloride, 2-(Chlorocarbonyl)toluene;o-Toluoyl chloride, 99% 5GR;o-Toluoyl chlori;o-Toluoyl chloride 99%;2-methyl-benzoylchlorid;o-Toluic acid chloride;2-TOLUOYL CHLORIDE;2-METHYLBENZOYL CHLORIDE
• CAS NO: 933-88-0
• Molecular Formula: C₈H₇ClO
• Molecular Weight: 154.59
• EINECS: 213-273-8
• Product Categories: Tolvaptan intermediate;ACIDHALIDE
• Mol File: 933-88-0.mol
• Article Data: 110

Chemical Properties

• Melting Point: 159.5-160.9 °C(Solv: ligroine (8032-32-4); dichloromethane (75-09-2))
• Boiling Point: 88-90 °C12 mm Hg(lit.)
• Flash Point: 170 °F
• Appearance: Clear pale yellow to yellow to faintly pink/Liquid
• Density: 1.185 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.5549(lit.)
• Storage Temp.: Room Temperature, Under Inert Atmosphere
• Water Solubility: Reacts with water.
• Sensitive: Moisture Sensitive
• BRN: 507933
• CAS DataBase Reference: o-Toluoyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: o-Toluoyl chloride(933-88-0)
• EPA Substance Registry System: o-Toluoyl chloride(933-88-0)

Safety Data

• Hazard Codes: C
• Statements: 34-36/37
• Safety Statements: 23-26-27-36/37/39-45-24/25
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• F: 10-19-21
• TSCA: Yes
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 933-88-0(Hazardous Substances Data)

Usage

Chemical Properties

clear pale yellow to yellow to faintly pink liquid

Uses

O-Toluoyl Chloride is used in the synthesis if quinolinone compounds as SARS CoV 3CLpro inhibitors. Also used in the synthesis of benzooxaboroles as orally active anti-inflammatory agents.

General Description

Flash vacuum pyrolysis of o-toluoyl chloride at 780°C and 0.5 mmHg yields benzocyclobutenone.

InChI:InChI=1/C8H7ClO/c1-6-4-2-3-5-7(6)8(9)10/h2-5H,1H3

Synthetic route

ortho-methylbenzoic acid (118-90-1) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With oxalyl dichloride In benzene at 20℃; for 14h;	100%
With thionyl chloride Reflux;	100%
With thionyl chloride; N,N-dimethyl-formamide at 90℃; for 3h; Concentration; Reagent/catalyst; Temperature;	99.7%

ortho-methylphenyl iodide (615-37-2) + carbon monoxide (201230-82-2) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With bis(tri-t-butylphosphine)palladium(0); benzyltriphenylphosphonium chloride In toluene at 110℃; under 38002.6 Torr; for 24h; Glovebox; Autoclave; Inert atmosphere;	93%

2-methyl-benzyl alcohol (89-95-2) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With o-chlorobenzoyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 12h;	70%

ortho-methylphenyl iodide (615-37-2) + 4-nitro-benzoyl chloride (122-04-3) → p-nitrobenzene iodide (636-98-6) + ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With (Xantphos)Pd(4-C6H4NO2)(I) In benzene at 90℃; for 20h; Sealed tube; Inert atmosphere;	A n/a B 68%

o-xylene (95-47-6) → ortho-toluoyl chloride (933-88-0) + Phthaloyl dichloride (88-95-9)

Conditions	Yield
Stage #1: o-xylene With ruthenium(II) chloride; C88H48Cl8Fe2N8O; oxygen at 185℃; under 10501.1 Torr; Stage #2: With thionyl chloride Reagent/catalyst; Temperature; Pressure;	A 63.1% B 10.1%
Stage #1: o-xylene With ruthenium(II) chloride; C88H48Cl8Fe2N8O; oxygen at 185℃; under 10501.1 Torr; Stage #2: With thionyl chloride Reagent/catalyst; Temperature; Pressure;	A 24.1% B 38.7%

2-methylbenzoic anhydride (607-86-3) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate

ortho-tolylmagnesium bromide (932-31-0) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether / Einleiten von Kohlendioxid 2: thionyl chloride View Scheme

o-tolylmagnesium iodide → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether / Einleiten von Kohlendioxid 2: thionyl chloride View Scheme

ortho-methylbenzoic acid (118-90-1) + oxalyl dichloride (79-37-8) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
In dichloromethane

ortho-methylbenzoic acid (118-90-1) + 2-(4,5-Dihydro-1,3-oxazol-2-yl)aniline (3416-93-1) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide

2-methylphenyl aldehyde (529-20-4) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
With tert.-butylhydroperoxide; N-chloro-succinimide; tris(2,2'-bipyridyl)ruthenium dichloride In acetonitrile at 20℃; for 24h; Sealed tube; Irradiation;

2-Methyl-benzoic acid methyl ester (89-71-4) → ortho-toluoyl chloride (933-88-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol / 60 °C / pH 3 / Schlenk technique; Inert atmosphere 2: oxalyl dichloride / N,N-dimethyl-formamide; dichloromethane / 17 h / 0 - 20 °C / Schlenk technique; Inert atmosphere View Scheme

ortho-methylphenyl iodide (615-37-2) + terephthaloyl chloride (100-20-9) → ortho-toluoyl chloride (933-88-0) + 4-iodobenzoic acid chloride (1711-02-0)

Conditions	Yield
With (Xantphos)Pd(4-C6H4NO2)(I) In benzene at 110℃; for 20h; Sealed tube; Inert atmosphere;	A 53 %Spectr. B n/a

1,3-Benzothiazole (95-16-9) + trimethylsilyl cyanide (7677-24-9) + ortho-toluoyl chloride (933-88-0) → 2-Cyano-3-o-toluoyl-2,3-dihydrobenzothiazole

Conditions	Yield
With aluminium trichloride In dichloromethane	100%

2-Amino-2-methyl-1-propanol (124-68-5) + ortho-toluoyl chloride (933-88-0) → N-(1-hydroxy-2-methylpropan-2-yl)-2-methylbenzamide (95217-40-6)

Conditions	Yield
In dichloromethane at 0℃; for 0.5h;	100%
With triethylamine In dichloromethane at 0℃;
With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere;

ortho-toluoyl chloride (933-88-0) + dimethyl amine (124-40-3) → N,N,2-trimethylbenzamide (6639-19-6)

Conditions	Yield
	100%
In water; toluene
In diethyl ether at 20℃; for 16h;

ortho-toluoyl chloride (933-88-0) + aniline (62-53-3) → 2-methyl-N-phenylbenzamide (7055-03-0)

Conditions	Yield
In diethyl ether Ambient temperature;	100%
With pyridine; dmap at 0 - 20℃;	99%
With triethylamine In dichloromethane at 0 - 20℃;	96%

1-bromo-5,6,7,8-tetrahydronaphthalen-2-ol (32337-86-3) + ortho-toluoyl chloride (933-88-0) → 2-benzyloxy-1-bromo-5,6,7,8-tetrahydronaphthalene (142626-67-3)

Conditions	Yield
With triethylamine In dichloromethane for 1h;	100%
With triethylamine In dichloromethane

ortho-toluoyl chloride (933-88-0) + L-proline (147-85-3) → N-(2-methylbenzoyl)-L-proline

Conditions	Yield
With sodium hydroxide for 0.5h;	100%
With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃;	0.77 g

ortho-toluoyl chloride (933-88-0) + 1-(4-aminobenzoyl)-9-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137983-89-2) → 9-chloro-1-[4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137978-31-5)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1.5h; Acylation;	100%

ortho-toluoyl chloride (933-88-0) + 1-(4-aminobenzoyl)-8-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137984-96-4) → 8-chloro-1-[4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137977-41-4)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1.5h; Acylation;	100%

ortho-toluoyl chloride (933-88-0) + 1-(4-aminobenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137984-95-3) → 7-chloro-1-[4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137977-35-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1.5h; Acylation;	100%

ortho-toluoyl chloride (933-88-0) + 1-(4-amino-2-methoxybenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137976-75-1) → 7-chloro-1-[2-methoxy-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137974-15-3)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1.5h; Acylation;	100%

2,6-bis-([4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-pyridine (863491-46-7) + ortho-toluoyl chloride (933-88-0) → 2,6-bis-(1-(2-methyl-benzoyl)-[4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-pyridine

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃;	100%
With dmap In dichloromethane at 20℃; for 12h;	100%

ortho-toluoyl chloride (933-88-0) + 2-Methylaziridine (75-55-8, 41927-28-0, 76612-76-5, 76612-77-6, 205537-16-2) → 1-(2-methylbenzoyl)-2-methylaziridine (21384-42-9)

Conditions	Yield
With sodium hydroxide In diethyl ether at 0℃;	100%
With sodium hydroxide In diethyl ether; water at 0℃; Schotten-Baumann reaction;

3-methylbenzyl alcohol (587-03-1) + ortho-toluoyl chloride (933-88-0) → 3-methylbenzyl 2'-methylbenzoate (1070881-26-3)

Conditions	Yield
With pyridine at 0℃; for 1.5h;	100%

ortho-toluoyl chloride (933-88-0) + N-butylamine (109-73-9) → N-(n-butyl)-2-methylbenzamide

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 2.5h; Inert atmosphere;	100%
With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	86%

ortho-toluoyl chloride (933-88-0) + (2S)-N-phenylpyrrolidine-2-carboxamide (25746-83-2, 64030-43-9, 104261-87-2) → (S)-N-(2-methylbenzoyl)proline anilide (1415831-64-9)

Conditions	Yield
With triethylamine In Dichlorofluoromethane at 20℃; Inert atmosphere;	100%

ortho-toluoyl chloride (933-88-0) + Cyclopentamine (1003-03-8) → N-cyclopentyl-2-methylbenzamide (123862-57-7)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 14h; Inert atmosphere;	100%
With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	94%

4-trifluoromethylphenylamine (455-14-1) + ortho-toluoyl chloride (933-88-0) → 2-methyl-N-(4-(trifluoromethyl)phenyl)benzamide

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 3h;	100%

N-aminopyridin-1-ium iodide (6295-87-0) + ortho-toluoyl chloride (933-88-0) → 1-(2-methyl-benzoylamino)-pyridinium betaine (36048-80-3)

Conditions	Yield
With sodium hydroxide at 25℃; for 24h;	99.9%

4-methoxy-aniline (104-94-9) + ortho-toluoyl chloride (933-88-0) → α-(p-anisidino)-o-tolualdehyde (55814-36-3)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 1h;	99%
With sodium hydroxide for 0.25h;	55%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 6h;

ortho-toluoyl chloride (933-88-0) + 1-(4-amino-2-chlorobenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137978-00-8) → 7-chloro-1-[2-chloro-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (137973-86-5)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1.5h; Acylation;	99%

2-Chloroethanesulfonyl chloride (1622-32-8) + 4-fluoro-2-phenethylamine (1583-88-6) + ortho-toluoyl chloride (933-88-0) + 4-(4-((p-methylbenzylamino)methyl)-3-methoxyphenoxy)butyryl AM resin → N-[2-(4-fluoro-phenyl)-ethyl]-2-methyl-N-[2-(4-methyl-benzylsulfamoyl)-ethyl]-benzamide

Conditions	Yield
Multistep reaction;	99%

(1R,2S)-norephedrine (492-41-1) + ortho-toluoyl chloride (933-88-0) → (1R,2S)-2-o-toluamide-1-phenylpropanol (696659-64-0)

Conditions	Yield
With potassium hydroxide In dichloromethane; water at 0 - 20℃; for 2.5h;	99%

L-Phenylalaninol (3182-95-4) + ortho-toluoyl chloride (933-88-0) → (2S)-2-o-toluamide-3-phenylpropanol (497954-01-5)

Conditions	Yield
With potassium hydroxide In dichloromethane at 0 - 20℃;	99%
With triethylamine In tetrahydrofuran for 1h;

ortho-toluoyl chloride (933-88-0) + phenylacetylene (536-74-3) + l → (5-phenyl-2H-1,2,3-triazol-4-yl)(o-tolyl)methanone (1171248-95-5)

Conditions	Yield
Stage #1: ortho-toluoyl chloride; phenylacetylene; l With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 1h; Sonogashira coupling; Inert atmosphere; Ultrasonic; Stage #2: With sodium azide In dimethyl sulfoxide at 20℃; for 1h;	99%

ortho-toluoyl chloride (933-88-0) + 3,5-Dichloroaniline (626-43-7) → 1-(3,5-dichlorophenyl)-3-(o-tolyl)urea (97146-53-7)

Conditions	Yield
Stage #1: ortho-toluoyl chloride With pyridine; trimethylsilylazide In N,N-dimethyl-formamide at 20℃; Curtius rearrangement; Microflow reaction; Inert atmosphere; Stage #2: 3,5-Dichloroaniline With acetic acid In N,N-dimethyl-formamide at 110℃; Microflow reaction; Inert atmosphere;	99%

ortho-toluoyl chloride (933-88-0) + benzyl alcohol (100-51-6) → N-benzyloxycarbonyl-2-methylaniline (108714-89-2)

Conditions	Yield
Stage #1: ortho-toluoyl chloride With pyridine; trimethylsilylazide In N,N-dimethyl-formamide at 20℃; Curtius rearrangement; Microflow reaction; Inert atmosphere; Stage #2: benzyl alcohol With acetic acid In N,N-dimethyl-formamide at 110℃; Microflow reaction; Inert atmosphere;	99%

1-(hydroxyethyl)-2-(methylamino)-1,2,3,6,7,12b-hexahydroindolo[2,3-a]quinolizin-4(12H)-one + ortho-toluoyl chloride (933-88-0) → N-(3-(1-hydroxyethyl)-4-oxo-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-N-2-dimethylbenzamide

Conditions	Yield
With triethylamine In dichloromethane for 0.75h; Inert atmosphere;	99%

ortho-toluoyl chloride (933-88-0) + Propargylamine (2450-71-7) → 2-methyl-N-(prop-2-yn-1-yl)benzamide (1090993-70-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 4h;	99%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 3.25h; Inert atmosphere;	82%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 5.25h; Inert atmosphere;
With dmap; triethylamine In dichloromethane at 0 - 20℃;
With dmap; triethylamine In dichloromethane at 0 - 20℃;

m-Anisidine (536-90-3) + ortho-toluoyl chloride (933-88-0) → 2-methyl-N-(3-methoxyphenyl)-benzamide (55814-35-2)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 18h; Inert atmosphere;	99%
With triethylamine In dichloromethane at 0 - 20℃;	90%

Upstream product

• 118-90-1 ortho-methylbenzoic acid 
• 607-86-3 2-methylbenzoic anhydride 
• 932-31-0 ortho-tolylmagnesium bromide 
• 79-37-8 oxalyl dichloride 
• 68-12-2 N,N-dimethyl-formamide 
• 3416-93-1 2-(4,5-Dihydro-1,3-oxazol-2-yl)aniline 
• 89-95-2 2-methyl-benzyl alcohol 
• 615-37-2 ortho-methylphenyl iodide 
• 122-04-3 4-nitro-benzoyl chloride 
• 100-20-9 terephthaloyl chloride 
• 95-47-6 o-xylene 
• 89-71-4 2-Methyl-benzoic acid methyl ester 
• 529-20-4 2-methylphenyl aldehyde 
• 201230-82-2 carbon monoxide 

Downstream Products

• 4209-23-8 2-chloro-1-(o-tolyl)ethan-1-one 
• 6933-35-3 (2-methylphenyl)-(thiophen-2-yl)methanone 
• 51725-82-7 ethyl (2-methylbenzoyl)acetate 
• 577-16-2 2-Methylacetophenone 
• 41204-59-5 (4-methoxyphenyl)(2-methylphenyl)methanone 
• 52980-94-6 5-chloro-2-hydroxy-2'-methylbenzophenone 
• 59410-21-8 bis(2-methylbenzoyl) sulfide 
• 79674-08-1 di-o-toluoyl-disulfane 
• 1018-97-9 2,2'-dimethylbenzophenone 
• 172375-97-2 3,4-Dimethoxyphenyl 2-methylphenyl ketone 
• 68723-25-1 (2-methylphenyl)-1-naphthylmethanone 
• 85296-08-8 biphenyl-4-yl-(2-methylphenyl)methanone 
• 149083-01-2 2,5-dichloro-2'-methyl-benzophenone 
• 20002-30-6 2,3',4'-trimethyl-benzophenone 

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