62882-02-4

Basic information

• Product Name: Isoquinoline, 6-chloro- (6CI,9CI)
• Synonyms: Isoquinoline, 6-chloro- (6CI,9CI);6-CHLOROISOQUINOLINE;6-chloro-Isoquinoline, (6CI,9CI);Isoquinoline, 6-chloro-
• CAS NO: 62882-02-4
• Molecular Formula: C₉H₆ClN
• Molecular Weight: 163.6
• EINECS: -0
• Product Categories: ISOQUINOLINE
• Mol File: 62882-02-4.mol
• Article Data: 6

Chemical Properties

• Melting Point: 39-40 °C
• Boiling Point: 289.5 °C at 760 mmHg
• Flash Point: 156.4 °C
• Appearance: /
• Density: 1.27 g/cm³
• Vapor Pressure: 0.00382mmHg at 25°C
• Refractive Index: 1.652
• Storage Temp.: 2-8°C
• PKA: 4.83±0.10(Predicted)
• CAS DataBase Reference: Isoquinoline, 6-chloro- (6CI,9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Isoquinoline, 6-chloro- (6CI,9CI)(62882-02-4)
• EPA Substance Registry System: Isoquinoline, 6-chloro- (6CI,9CI)(62882-02-4)

Safety Data

• Hazardous Substances Data: 62882-02-4(Hazardous Substances Data)

Usage

General Description

Isoquinoline, 6-chloro- (6CI,9CI) is a chemical compound with the molecular formula C9H6ClN. It is a derivative of isoquinoline and is classified as a chloro-organic compound. Isoquinoline, 6-chloro- is commonly used in organic synthesis and pharmaceutical research due to its potential therapeutic properties. It may also have applications in the development of new drugs and agrochemicals. Additionally, this chemical may have uses in the production of dyes, pigments, and other industrial chemicals. Isoquinoline, 6-chloro- is an important compound with potential applications across a variety of industries.

InChI:InChI=1/C9H6ClN/c10-9-2-1-8-6-11-4-3-7(8)5-9/h1-6H

Synthetic route

6-chloro-1H-indene (3970-52-3) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
Stage #1: 6-chloro-1H-indene With ozone In methanol; dichloromethane at -78℃; ozonolysis; Stage #2: With dimethylsulfide; sodium hydrogencarbonate In methanol; dichloromethane for 6h; Reduction; Stage #3: With ammonium hydroxide In methanol; dichloromethane for 15h; Cyclization; Further stages.;	64%
Multi-step reaction with 2 steps 1.1: ozone; oxygen / methanol; dichloromethane / 0.5 h / -78 - -65 °C / Inert atmosphere 1.2: 16 h / 20 °C / Inert atmosphere 2.1: ammonium hydroxide / dichloromethane; methanol / 24 h / 20 °C View Scheme

2-acetyl-3-(4-chlorophenyl)isoxazol-5(2H)-one (267877-39-4) → 4-Cyanochlorobenzene (623-03-0) + 6-chloroisoquinoline (62882-02-4) + 4-(4-chlorophenyl)-2-methyloxazole (79965-68-7) + p-chlorobenzyl cyanide (140-53-4)

Conditions	Yield
at 750℃; Rearrangement; Further byproducts given;	A 22% B 8% C 10% D 17%

(4-chloro-benzylidenamino)-acetaldehyde diethylacetal (101263-60-9) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
With sulfuric acid; phosphorus pentoxide at 150℃;

[1-(4-Chloro-phenyl)-meth-(Z)-ylidene]-(2,2-dimethoxy-ethyl)-amine (54879-73-1) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
With sulfuric acid at 140 - 150℃; for 0.5h;

4-chlorobenzaldehyde (104-88-1) + KOH-solution → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / benzene / Heating 2: concd. H2SO4 / 0.5 h / 140 - 150 °C View Scheme

4-chlorobenzaldehyde (104-88-1) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: concentrated sulfuric acid; phosphorus (V)-oxide / 150 °C View Scheme

5-chloro-2,3-dihydro-1H-inden-1-ol (33781-38-3, 147592-14-1) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 1.5 h / 120 °C / Dean-Stark 2.1: ozone; oxygen / methanol; dichloromethane / 0.5 h / -78 - -65 °C / Inert atmosphere 2.2: 16 h / 20 °C / Inert atmosphere 3.1: ammonium hydroxide / dichloromethane; methanol / 24 h / 20 °C View Scheme

C9H7ClO2 → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
With ammonium hydroxide In methanol; dichloromethane at 20℃; for 24h;	2.74 g

5-chloro-1-indanone (42348-86-7) → 6-chloroisoquinoline (62882-02-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / methanol / 1.5 h / 20 °C / Inert atmosphere 2.1: toluene-4-sulfonic acid / toluene / 1.5 h / 120 °C / Dean-Stark 3.1: ozone; oxygen / methanol; dichloromethane / 0.5 h / -78 - -65 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere 4.1: ammonium hydroxide / dichloromethane; methanol / 24 h / 20 °C View Scheme

6-chloroisoquinoline (62882-02-4) + 1-chloro-2-(chloromethyl)benzene (611-19-8) → 2-(2-chlorobenzyl)-isoquinolinium chloride

Conditions	Yield
In acetonitrile at 20℃;	97%

6-chloroisoquinoline (62882-02-4) → 6-chloroisoquinoline 2-oxide

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h;	96%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h;	96%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 24h;
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 6h;	3.4 g

6-chloroisoquinoline (62882-02-4) + cyclohexane (110-82-7) → 6-chloro-1-cyclohexylisoquinoline

Conditions	Yield
With dipotassium peroxodisulfate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; trifluoroacetic acid In acetonitrile at 20℃; for 16h; Irradiation; Inert atmosphere;	93%

diazoacetic acid ethyl ester (623-73-4) + 6-chloroisoquinoline (62882-02-4) + diethyl dicarbonate (1609-47-8) → ethyl (R)-6-chloro-1-(1-diazo-2-ethoxy-2-oxoethyl)isoquinoline-2(1H)-carboxylate

Conditions	Yield
With (R)-6,6’-bis((4-(tert-butyl)-2-methylphenyl))-1,1'-spirobiindane-7,7'-diyl phosphate In toluene at -20℃; for 88h; Inert atmosphere; Molecular sieve; enantioselective reaction;	92%

tetrahydrofuran (109-99-9) + 6-chloroisoquinoline (62882-02-4) → 6-chloro-1-(tetrahydrofuran-2-yl)isoquinoline

Conditions	Yield
With ammonium persulfate; 1-hydroxy-pyrrolidine-2,5-dione In water at 40℃; for 24h; Green chemistry;	90%
With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation;	83%
With C24H42N3(1+)*ClO4(1-); lithium perchlorate; acetic acid; trifluoroacetic acid In acetonitrile at 20℃; for 36h; Irradiation; Electrochemical reaction; Inert atmosphere;	81%

6-chloroisoquinoline (62882-02-4) + potassium (1-benzyloxy-3-phenylpropyl)trifluoroboranuide (1402010-11-0, 1402085-44-2, 1402085-52-2) → 6-(1-(benzyloxy)-3-phenylpropyl)isoquinoline (1402010-77-8)

Conditions	Yield
With cesiumhydroxide monohydrate; cyclopentyl methyl ether; [2′-(amino-κN)[1,1′-biphenyl]-2-yl-κC][butylbis(tricyclo-[3.3.1.13,7]dec-1-yl)phosphine]chloropalladium at 105℃; for 24h; Suzuki-Miyaura Coupling; Sealed tube;	88%

6-chloroisoquinoline (62882-02-4) → 6-chloro-5-nitroisoquinoline

Conditions	Yield
With sodium nitrate; sulfuric acid at 0℃; for 2h;	88%

6-chloroisoquinoline (62882-02-4) + phenyltrifluorosilane (368-47-8) → 6-phenylisoquinoline (70125-61-0)

Conditions	Yield
Stage #1: phenyltrifluorosilane With tetrabutyl ammonium fluoride; palladium diacetate; XPhos In tert-butyl alcohol at 20℃; for 0.0833333h; Hiyama cross-coupling reaction; Inert atmosphere; Sealed vial; Stage #2: 6-chloroisoquinoline In tert-butyl alcohol at 100℃; Hiyama cross-coupling reaction; Inert atmosphere; Sealed vial;	85%

6-chloroisoquinoline (62882-02-4) + diethyl dicarbonate (1609-47-8) + dimethyl diazomethylphosphonate (27491-70-9, 28447-24-7, 25411-73-8) → ethyl (R)-6-chloro-1-(diazo(dimethoxyphosphoryl)methyl)isoquinoline-2(1H)-carboxylate

Conditions	Yield
With (R)-6,6’-bis(3',4',5'-trifluoro-2,6-dimethyl[1,1'-biphenyl]-4-yl)-1,1'-spirobiindane-7,7'-diyl phosphate In toluene at -30℃; for 90h; Inert atmosphere; Molecular sieve; enantioselective reaction;	83%

6-chloroisoquinoline (62882-02-4) + tris-iso-propylsilyl acetylene (89343-06-6) + Allyl chloroformate (2937-50-0) → C24H32ClNO2Si

Conditions	Yield
Stage #1: tris-iso-propylsilyl acetylene With isopropylmagnesium bromide In tetrahydrofuran; 2-methyltetrahydrofuran for 1h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; 2-methyltetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #3: 6-chloroisoquinoline; Allyl chloroformate Further stages;	82%

6-chloroisoquinoline (62882-02-4) + 3,5,5-Trimethylcyclohex-2-en-1-one (78-59-1) → 2-(isoquinolin-6-yl)-3,5,5-trimethylcyclohex-2-en-1-one

Conditions	Yield
With palladium diacetate; 2-(2-(di-tert-butylphosphanyl)phenyl)-1-methyl-1H-indole; lithium tert-butoxide In 1,4-dioxane at 100℃; for 18h; Schlenk technique; Inert atmosphere;	80%

6-chloroisoquinoline (62882-02-4) + 4-methoxy-phenol (150-76-5) → 6-(4-methoxyphenoxy)isoquinoline

Conditions	Yield
With potassium phosphate; copper(l) iodide; N1-benzyl-N2-(5-methyl-[1,1'-biphenyl]-2-yl)oxalamide In dimethyl sulfoxide at 120℃; for 24h; Inert atmosphere;	79%

6-chloroisoquinoline (62882-02-4) + 1,3-dioxoisoindolin-2-yl cyclohexanecarboxylate → 6-chloro-1-cyclohexylisoquinoline

Conditions	Yield
With tetrakis(acetonitrile)copper(I)tetrafluoroborate; 2.9-dimethyl-1,10-phenanthroline; zinc trifluoromethanesulfonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In N,N-dimethyl acetamide for 24h; Inert atmosphere; Irradiation;	78%

potassium cyanate (590-28-3) + 6-chloroisoquinoline (62882-02-4) + butan-1-ol (71-36-3) → butyl isoquinolin-6-ylcarbamate

Conditions	Yield
With potassium phosphate; copper(l) iodide; 2-((2-methylnaphthalen-1-yl)amino)-2-oxoacetic acid at 120℃; for 48h; Schlenk technique; Inert atmosphere; Sealed tube;	75%

6-chloroisoquinoline (62882-02-4) + 1-phenylcyclopropan-1-ol (29526-96-3) → 3-(6-chloroisoquinolin-1-yl)-1-phenylpropan-1-one

Conditions	Yield
With dipotassium peroxodisulfate In water; dimethyl sulfoxide at 70℃; for 12h; Inert atmosphere;	74%

6-chloroisoquinoline (62882-02-4) + methyl iodide (74-88-4) → 6-chloro-2-methylisoquinolin-2-ium iodide

Conditions	Yield
In acetonitrile at 80℃; for 16h;	73%
In acetonitrile for 12h; Reflux;
In 1,4-dioxane Reflux;

6-chloroisoquinoline (62882-02-4) + 3-methoxybenzenetrifluorosilane (50625-29-1) → 6-(3-methoxybenzene)isoquinoline (1337563-02-6)

Conditions	Yield
Stage #1: 3-methoxybenzenetrifluorosilane With tetrabutyl ammonium fluoride; palladium diacetate; XPhos In tert-butyl alcohol at 20℃; for 0.0833333h; Hiyama cross-coupling reaction; Inert atmosphere; Sealed vial; Stage #2: 6-chloroisoquinoline In tert-butyl alcohol at 100℃; Hiyama cross-coupling reaction; Inert atmosphere; Sealed vial;	71%

6-chloroisoquinoline (62882-02-4) + toluene (108-88-3) → 2-benzyl-6-chloroisoquinoline-1,3,4(2H)-trione

Conditions	Yield
With tert.-butylhydroperoxide; iodine In water at 110℃; for 24h; Sealed tube;	67%

6-chloroisoquinoline (62882-02-4) + (trifluoromethyl)trimethylsilane (81290-20-2) → 6-chloro-1-(trifluoromethyl)isoquinoline

Conditions	Yield
With potassium fluoride; bis-[(trifluoroacetoxy)iodo]benzene In 1-methyl-pyrrolidin-2-one at 0℃; for 24h; Glovebox; Inert atmosphere; Sealed tube; regioselective reaction;	64%

2-methyltetrahydrofuran (96-47-9) + 6-chloroisoquinoline (62882-02-4) → 6-chloro-1-(5-methyltetrahydrofuran-2-yl)isoquinoline

Conditions	Yield
With C24H42N3(1+)*ClO4(1-); lithium perchlorate; acetic acid; trifluoroacetic acid In acetonitrile at 20℃; for 36h; Irradiation; Electrochemical reaction; Inert atmosphere; regioselective reaction;	62%

6-chloroisoquinoline (62882-02-4) + tert-butyldimethylsilane (29681-57-0) → C15H20ClNSi

Conditions	Yield
With sodium persulfate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate In dimethyl sulfoxide; 1,2-dichloro-ethane at 30℃; for 24h; Irradiation; regioselective reaction;	61%

6-chloroisoquinoline (62882-02-4) + 1,1,1-trifluoro-2-chloroethane (75-88-7) → 6-(2,2,2-trifluoroethyl)isoquinoline

Conditions	Yield
With 4,4'-di-tert-butyl-2,2'-bipyridine; magnesium chloride; nickel dibromide; zinc In N,N-dimethyl acetamide at 80℃; for 12h; Inert atmosphere; Schlenk technique;	55%

6-chloroisoquinoline (62882-02-4) + 1-iodocyclohexane (626-62-0) → 6-chloro-1-cyclohexylisoquinoline

Conditions	Yield
With tert-butyl peroxyacetate; [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; trifluoroacetic acid In acetonitrile at 20℃; for 24h; Inert atmosphere; Sealed tube; Irradiation;	54%

6-chloroisoquinoline (62882-02-4) + tert-butyl (Z)-(1-(((chloro(phenyl)methylene)amino)oxy)-1-oxo-3-phenylpropan-2-yl)carbamate → tert-butyl (1-(6-chloroisoquinolin-1-yl)-2-phenylethyl)carbamate

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate In acetonitrile at 20℃; for 12h; Minisci Aromatic Substitution; Inert atmosphere; Irradiation;	53%

6-chloroisoquinoline (62882-02-4) + 1H-indol-7-yl acetate (5526-13-6) + dimethylamino sulfonyl chloride (13360-57-1) → C21H20ClN3O4S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In toluene at 50℃; for 1h; Inert atmosphere;	48%

6-chloroisoquinoline (62882-02-4) + 1H-indol-7-yl acetate (5526-13-6) + 2-cyanoethyl(methyl)sulfamoyl chloride (209971-18-6) → C23H21ClN4O4S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In toluene at 45℃; for 1h; Inert atmosphere;	46%

6-chloroisoquinoline (62882-02-4) + [Ru(bda)(DMSO)2] (1357927-37-7) → C30H18Cl2N4O4Ru

Conditions	Yield
In methanol at 80℃; for 8h; Inert atmosphere;	42%

6-chloroisoquinoline (62882-02-4) + (-)-ambroxide (6790-58-5) → 6-chloro-1-((3aR,5aS,9aS,9bR)-3 a,6,6,9 a-tetramethyldodecahydronaphtho[2,1-b]furan-2-yl)isoquinoline

Conditions	Yield
With ethanol; bis-[(trifluoroacetoxy)iodo]benzene In dimethyl sulfoxide; 1,2-dichloro-ethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Irradiation; diastereoselective reaction;	31%

6-chloroisoquinoline (62882-02-4) + p-toluenesulfonyl chloride (98-59-9) → (6-chloroisoquinolin-2-ium-2-yl)(tosyl)amide

Conditions	Yield
Stage #1: 6-chloroisoquinoline With O-(2,4-dinitrophenyl)hydroxylamine In acetonitrile at 20℃; for 24h; Inert atmosphere; Stage #2: p-toluenesulfonyl chloride With potassium carbonate In tetrahydrofuran; water at 20℃; for 12h; Inert atmosphere;	26%

Upstream product

• 3970-52-3 6-chloro-1H-indene 
• 42348-86-7 5-chloro-1-indanone 
• 33781-38-3 5-chloro-2,3-dihydro-1H-inden-1-ol 
• 104-88-1 4-chlorobenzaldehyde 
• 267877-39-4 2-acetyl-3-(4-chlorophenyl)isoxazol-5(2H)-one 
• 54879-73-1 [1-(4-Chloro-phenyl)-meth-(Z)-ylidene]-(2,2-dimethoxy-ethyl)-amine 
• 101263-60-9 (4-chloro-benzylidenamino)-acetaldehyde diethylacetal 

Downstream Products

• 70125-61-0 6-phenylisoquinoline 
• 131002-09-0 6-chloroisoquinolin-1(2Η)-one 
• 630421-73-7 1,6-dichloroisoquinoline 
• 1337563-02-6 6-(3-methoxybenzene)isoquinoline 
• 33537-99-4 6‐chloro‐1,2,3,4‐tetrahydroisoquinoline 

Relevant articles and documents

Synthesis of Indole-Dihydroisoquinoline Sulfonyl Ureas via Three-Component Reactions

Isoquinolines activated with sulfamoyl chlorides were reacted with indoles in a 3-component reaction to generate a library of dihydroisoquinoline derivatives. Using a differential protecting group strategy, products could be further derivatised. Synthesis of isoquinoline starting materials using several different methods is also described.

High-temperature rearrangements of 2-acylisoxazol-5(2H)-ones and related oxazoles

2-Acyl-3-arylisoxazol-5(2H)-ones give 2-alkyl(aryl)-4-aryloxazoles in good yields at 540°C under flash vacuum pyrolysis conditions, but at higher temperatures the expected oxazoles are accompanied by increasing amounts of isomeric 2,5-disubstituted oxazoles, as well as anilides and decomposition products of the 2,4-disubstituted oxazole. The rearrangement mechanisms have been studied by the use of 13C labelled substrates and p-substituted 3-arylisoxazolones. The 2,5-disubstituted oxazoles are considered to arise from 1H-azirines, and the anilides from the nitrone ketene isomer of the acylisoxazolone.

New N-aryl and N-heteroarylamide and urea derivatives as inhibitors of acyl coenzyme A: cholesterol acyl transferase

Compounds of the formula the pharmaceutically acceptable salts thereof, wherein Q and R1 are as defined below, and novel carboxylic acid and acid halide intermediates used in the synthesis of such compounds. The compounds of formula I are inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) and are useful as hypolipidemic and antiatherosclerosis agents.