| Identification | More | [Name]
Isoquinoline | [CAS]
119-65-3 | [Synonyms]
2-AZANAPHTHALENE
2-BENZAZINE
BENZO(C)PYRIDINE
FEMA 2978
ISOCHINOLIN
ISOQUINOLINE
LEUCOLINE
2-Benzanine
Benzopyridine
beta-Quinoline
ISOQUINOLINE 99.9%
ISOQUINOLIN
ISOQUINOLINE, TECH., 90-92%
ISOQUINOLINE 97+%
Isoquinoline (6CI,8CI,9CI)
ISOQINOLINE
gliquidone intermediate
Isochinoline
Isoquinoline ,98%
3,4-Benzopyridine | [EINECS(EC#)]
204-341-8 | [Molecular Formula]
C9H7N | [MDL Number]
MFCD00006898 | [Molecular Weight]
129.16 | [MOL File]
119-65-3.mol |
| Chemical Properties | Back Directory | [Appearance]
LIGHT BROWN LOW MELTLING SOLID | [Melting point ]
26-28 °C (lit.) | [Boiling point ]
242-243 °C (lit.) | [density ]
1.099 g/mL at 25 °C(lit.)
| [vapor pressure ]
5Pa at 20℃ | [FEMA ]
2978 | [refractive index ]
n20/D 1.623(lit.)
| [Fp ]
225 °F
| [storage temp. ]
2-8°C
| [solubility ]
5g/l | [form ]
Low Melting Solid | [pka]
5.42(at 20℃) | [color ]
Light brown | [Odor]
at 0.10 % in triacetin. sweet balsam herbal benzaldehyde anise | [PH]
7.5 (5g/l, H2O, 20℃) | [Odor Type]
balsamic | [Water Solubility ]
practically insoluble | [Detection Methods]
GC,NMR | [JECFA Number]
1303 | [Merck ]
14,5222 | [BRN ]
107549 | [Dielectric constant]
10.7（20℃） | [InChIKey]
AWJUIBRHMBBTKR-UHFFFAOYSA-N | [LogP]
2.08 | [Uses]
Manufacture of pharmaceuticals (such as nicotinic acid), dyes, insecticides, rubber accelerators,
and in organic synthesis. | [Dissociation constant]
5.19 at 25℃ | [CAS DataBase Reference]
119-65-3(CAS DataBase Reference) | [NIST Chemistry Reference]
Isoquinoline(119-65-3) | [Storage Precautions]
Heat sensitive | [EPA Substance Registry System]
119-65-3(EPA Substance) |
| Safety Data | Back Directory | [Hazard Codes ]
T | [Risk Statements ]
R22:Harmful if swallowed.
R24:Toxic in contact with skin.
R38:Irritating to the skin. | [Safety Statements ]
S36/37:Wear suitable protective clothing and gloves .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection . | [RIDADR ]
UN 2811 6.1/PG 3
| [WGK Germany ]
2
| [RTECS ]
NW6825000
| [TSCA ]
Yes | [HazardClass ]
6.1 | [PackingGroup ]
II | [HS Code ]
29334900 | [Toxicity]
LD50 orally in rats: 360 mg/kg (Smyth) |
| Hazard Information | Back Directory | [Hazard]
Toxic by ingestion. | [Description]
Isoquinoline has an odor reminiscent of benzaldehyde and anise.
Isoquinoline may be obtained from coal tar (238 - 250°C boiling
fraction); it is isolated as the sulfate or as is by repeated freezing. | [Chemical Properties]
Isoquinoline is a colorless hygroscopic liquid at temperatures above its melting point with a heavy sweet balsamic, herbaceous odor. Impure samples can appear brownish, as is typical for nitrogen heterocycles. Isoquinoline is a slightly stronger base than quinoline (pKa=5.14) and has a larger dipole of 2.60D. | [Occurrence]
Reported found in milk and dried bonito; also occurs in coal tar, where it is formed during the dry distillation
of coal | [Definition]
ChEBI: An ortho-fused heteroarene that is a benzopyridine in which the N atom not directly attached to the benzene ring. | [Preparation]
Bischler-Napieralski synthesis is used to synthesize isoquinolines. β-phenylethylamine is acylated, and then cyclodehydrated using phosphoryl chloride, phosphorus pentoxide or other Lewis acids to yield dihydroisoquinoline, which can be aromatized by dehydrogenation with palladium, for example in the synthesis of papaverine, a pharmacologically active isoquinoline alkaloid.
Pictet-Spengler synthesis is another method of preparing isoquinolines. β-phenylethylamine reacts with an aldehyde to produce an imine, which undergoes acid-catalysed cyclization, resulting in the synthesis of the tetrahydroisoquinoline system. Again, tetrahydroisoquinoline can be aromatized by palladium dehydrogenation to produce an isoquinoline system. | [Production Methods]
High-temperature coal tar contains an average of 0.2% isoquinoline. It is separated by distillation from the lower-boiling quinoline and the higherboiling 2-methylquinoline of the quinoline base mixture. Further refining is based on the fact that isoquinoline, in contrast to quinoline and 2-methylquinoline, cannot be hydrated but can be crystallized at low temperature.
Isoquinoline can by synthesized, for example, via the Bischler–Napieralski reaction by cyclodehydration of N-acyl derivatives of b-phenylethylamine with Lewis acids and subsequent dehydrogenation. | [Synthesis Reference(s)]
The Journal of Organic Chemistry, 29, p. 2240, 1964 DOI: 10.1021/jo01031a031
Synthesis, p. 288, 1974 | [General Description]
The intensity of fluorescence peak of isoquinoline increases with increasing pressure in polymethylmethacrylate and in polyisobutylene polymeric media. | [Health Hazard]
The toxic properties of this compound aresimilar to those of quinoline. It is moderatelytoxic in rats and rabbits by oral routeand skin absorption. The oral LD50 value inrats is 360 mg/kg. The irritation effects onskin and eyes in rabbits were moderate tosevere. Carcinogenicity due to isoquinolinein animals or humans is not known. The histidinereversion–Ames test for mutagenicitywas inconclusive. | [Fire Hazard]
Noncombustible liquid (solid). | [Chemical Reactivity]
Isoquinoline is aromatic with a resonance energy of 143 kJ/ mol and is considered to be a resonance hybrid of the following contributing structures. Structures I, II, and II, which are of lower energy, are the major contributors to the resonance hybrid. Additional charged structures IV-VIII are also possible, but there is disruption of the π system of both rings in these structures.
1. Reaction with bases: Strong bases like Grignard reagent and organolithium tend to react like nucleophiles with isoquinoline. There are examples where isoquinoline has been converted into Grignard reagent by treatment with (iPr)2NMgCl, which has been shown to add to the variety of iodobenzenes.
2. Reaction with acids: Isoquinoline being basic reacts with acids to form salts. Protonation usually takes place under strong acidic conditions at position 5. When isoquinoline is exposed to strong acidic conditions, reduction of the benzene ring takes place. | [Pharmaceutical Applications]
Medicinal Uses of Isoquinoline
Isoquinoline is important because this nucleus is present in a large number of alkaloids like berberine and papavarine, and is also a useful template for medicinal chemistry. Papaverine, an opium alkaloid, finds use as a muscle relaxant and a vasodilator. Antihypertensive drugs like debrisoquine, quinalapril, and quinalaprilat all contain an isoquinoline nucleus. Quinisocaine or dimethisoquin is a topical anesthetic, which finds use as an antipruritic. Hexadecamethylenedisoquinolium dichloride, which is used as a topical antiseptic, is prepared by Nalkylation of isoquinoline with an appropriate allkyl halide. | [Synthesis]
Isoquinoline is synthesized by isolation from coal tar. It represents 10% of the total Quinoline fraction.
| [Solubility in organics]
Miscible with alcohol and oils
| [storage]
Store at -20°C | [Purification Methods]
Dry isoquinoline with Linde type 5A molecular sieves or Na2SO4 and fractionally distil at reduced pressure. Alternatively, it can be refluxed with, and distilled from, BaO. It is also purified by fractional crystallisation from the melt and distilled from zinc dust. It forms a phosphate (m 135o) and a picrate (m 223o), which are purified by crystallisation, and the free base can be recovered and distilled. [Packer et al. J Am Chem Soc 80 905 1958.] The procedure for purification via the picrate comprises the addition of quinoline to picric acid dissolved in the minimum volume of 95% EtOH to yield yellow crystals which are washed with EtOH and air dried before recrystallising from acetonitrile. The crystals are dissolved in dimethyl sulfoxide (previously dried over 4A molecular sieves) and passed through a basic alumina column, on which picric acid is adsorbed. The free base in the effluent is extracted with n-pentane and distilled under vacuum. Traces of solvent from small quantities are removed by vapour phase chromatography. The hydrochloride crystallises from EtOH with m 193o. [Mooman & Anton J Phys Chem 80 2243 1976, Beilstein 20 II 236, 20 III/IV 3410, 20/7 V 333.] |
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