Isoquinoline: Difference between revisions

| Watchedfields = changed

| verifiedrevid = 387430391

| Name = Isoquinoline

| ImageFile = Isoquinoline_chemical_structure.png

| ImageSize = 300px

| ImageName = Chemical structure of Isoquinoline

| IUPACName = Isoquinoline

| OtherNames = benzo[c]pyridine, 2-benzanine

| Section1 = {{Chembox Identifiers

| CASNo_Ref = {{cascite}}

| CASNo = 119-65-3

| EINECS = 204-341-8

| SMILES = C1(C=NC=C2)=C2C=CC=C1

| PubChem = 8405

| ChemSpiderID = 8098

| InChI = 1/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H

| InChIKey = AWJUIBRHMBBTKR-UHFFFAOYAX

| StdInChI = 1S/C9H7N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-7H

| StdInChIKey = AWJUIBRHMBBTKR-UHFFFAOYSA-N

}}

| Section2 = {{Chembox Properties

| Formula = C₉H₇N

| MolarMass = 129.16 g/mol

| Appearance = yellowish oily liquid, hygroscopic<br />platelets when solid

| Density = 1.099 g/cm³

| MeltingPt = 26 - 28 °C

| BoilingPtC = 242

| pKa=5.14<ref>Brown, H.C., et al., in Baude, E.A. and Nachod, F.C., ''Determination of Organic Structures by Physical Methods'', Academic Press, New York, 1955.</ref>

'''Isoquinoline''' is a [[heterocyclic]] [[aromatic]] [[organic compound]]. It is a [[structural isomer]] of [[quinoline]]. Isoquinoline and quinoline are [[benzopyridine]]s, which are composed of a [[benzene]] ring fused to a [[pyridine]] ring. In a broader sense, the term isoquinoline is used to make reference to isoquinoline [[derivatization|derivatives]]. [[1-Benzylisoquinoline]] is the structural backbone in naturally occurring [[alkaloids]] including [[papaverine]] and [[morphine]]. The isoquinoline ring in these natural compound derives from the aromatic [[amino acid]] [[tyrosine]] <ref>Gilchrist, T.L. (1997). ''Heterocyclic Chemistry'' (3rd ed.). Essex, UK: Addison Wesley Longman.</ref><ref>Harris, J.; Pope, W.J. "''iso''Quinoline and the ''iso''Quinoline-Reds" Journal of the Chemical Society (1922) volume 121, pp. 1029-1033.</ref><ref>Katritsky, A.R.; Pozharskii, A.F. (2000). ''Handbook of Heterocyclic Chemistry'' (2nd ed.). Oxford, UK: Elsevier.</ref><ref>Katritsky, A.R.; Rees, C.W.; Scriven, E.F. (Eds.). (1996). ''Comprehensive Heterocyclic Chemistry II: A Review of the Literature 1982-1995'' (Vol. 5). Tarrytown, NY: Elsevier.</ref><ref>Nagatsu, T. "Isoquinoline neurotoxins in the brain and Parkinson's disease" Neuroscience Research (1997) volume 29, pp. 99-111.</ref><ref>O'Neil, Maryadele J. (Ed.). (2001). ''The Merck Index'' (13th ed.). Whitehouse Station, NJ: Merck.</ref>.

Isoquinoline is a colorless [[hygroscopic]] liquid at room temperature with a penetrating, [[unpleasant odor]]. Impure samples can appear brownish, as is typical for nitrogen heterocycles. It crystallizes platelets that have a low [[solubility]] in [[water]] but dissolve well in [[ethanol]], [[acetone]], [[diethyl ether]], [[carbon disulfide]], and other common [[organic solvent]]s. It is also soluble in dilute [[acid]]s as the protonated derivative.

Being an [[analog (chemistry)|analog]] of [[pyridine]], isoquinoline is a weak [[base (chemistry)|base]], with a [[pKb|pK_b]] of 8.6. It protonates to form [[salts]] upon treatment with [[strong acid]]s, such as HCl. It forms [[adduct]]s with [[Lewis acid]]s, such as BF₃.

Isoquinoline was first isolated from [[coal tar]] in 1885 by Hoogewerf and van Dorp. They isolated it by fractional crystallization of the acid sulfate. Weissgerber developed a more rapid route in 1914 by selective extraction of coal tar, exploiting the fact that isoquinoline is more basic than quinoline. Isoquinoline can then be isolated from the mixture by fractional crystallization of the acid sulfate.

Although isoquinoline derivatives can be synthesized by several methods, relatively few direct methods deliver the unsubstituted isoquinoline. The '''Pomeranz-Fritsch reaction''' provides an efficient method for the preparation of isoquinoline. This reaction uses a [[benzaldehyde]] and aminoacetoaldehyde diethyl acetal, which in an [[acid]] [[Solvent|medium]] react to form isoquinoline. Alternatively, [[benzylamine]] and a [[glyoxal]] [[acetal]] can be used, to produce the same result.

[[File:Pomeranz-Fritsch einfach.svg|Pomeranz-Fritsch reaction|700px]]

In the [[Bischler-Napieralski reaction]] an β-[[phenylethylamine]] is acylated and cyclodehydrated by a Lewis acid, such as [[phosphoryl chloride]] or [[phosphorus pentoxide]]. The resulting 1-substituted-3,4-dihydroisoquinoline can then be dehydrogenated using palladium. The following Bischler-Napieralski reaction produces papaverine.

[[File:Papaverine bn.gif|800px]]

The '''Pictet-Gams synthesis''' and the [[Pictet-Spengler reaction]] are both variations on the Bischler-Napieralski reaction. The differences are as follows. The Pictet-Gams reaction avoids the final [[dehydrogenation]] step of the Bischler-Napieralski reaction by constructing a β-[[phenylethylamine]] with a hydroxy group in the [[side chain]]. This reaction results in a 1-alkyl-isoquinoline.

[[File:Pictet-Gams reaction.svg|400px|Pictet-Gams reaction]]

The [[Pictet-Spengler reaction]] combines a β-[[phenylethylamine]] and an [[aldehyde]] in an [[acid]] [[Solvent|medium]], which cyclizes the imine in a reaction of the Mannich type. This produces the [[tetrahydroisoquinoline]] instead of the [[dihydroisoquinoline]].

Isoquinolines find many applications, including (but not limited to):

*anesthetics; [[dimethisoquin]] is one example (shown below).

[[File:Quinisocaine.svg|200x200px]]

*antihypertension agents, such as [[quinapril]], [[quinapirilat]], and [[debrisoquine]] (all derived from 1,2,3,4-tetrahydroisoquinoline).

*antifungal agents, such as 2,2'Hexadecamethylenediisoquinolinium dichloride, which is also used as a topical antiseptic. This derivative, shown below, is prepared by N-alkylation of isoquinoline with the appropriate dihalide.

[[File:Antifungal ex.gif]]

*disinfectants, like N-laurylisoquinolinium bromide (shown below), which is prepared by simple N-alkylation of isoquinoline.

[[File:N-laurylisoquin.gif]]

*vasodilators, a well-known example, [[papaverine]], shown below.

[[File:Papaverin - Papaverine.svg|250px|Papaverine]]

'''Bisbenzylisoquinolinium''' compounds are compounds similar in structure to [[tubocurarine]]. They have two isoquinolinium structures, linked by a [[carbon]] chain, containing two [[ester]] linkages.

==Isoquinolines and the human body==

[[Parkinson's disease]], a slowly progressing movement disorder, is thought to be caused by certain [[neurotoxins]]. A neurotoxin called [[MPTP]] (1[N]-methyl-4-phenyl-1,2,3,6-[[tetrahydropyridine]]), the precursor to MPP+, was found and linked to Parkinson's disease in the 1980s. The active neurotoxins destroy [[dopaminergic neuron]]s, leading to parkinsonism and Parkinson's disease. Several [[tetrahydroisoquinoline]] derivatives have been found to have the same neurochemical properties as MPTP. These derivatives may act as neurotoxin precursors to active neurotoxins.

Isoquinolines are used in the manufacture of [[dyes]], [[paints]], [[insecticides]] and [[antifungal]]s. It is also used as a [[solvent]] for the [[Liquid-liquid extraction|extraction]] of [[resins]] and [[terpenes]], and as a [[corrosion]] inhibitor.

* [[Quinoline]], an analog with the nitrogen atom in position 1.

* [[Pyridine]], an analog without the fused [[benzene]] ring.

* [[Naphthalene]], an analog without the nitrogen atom.

* [[Simple aromatic ring]]s

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