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Isoquinoline is an individual chemical specimen - a heterocyclic aromatic organic compound - as well as the name of a family of many thousands of natural plant alkaloids, any one of which might be referred to as "an isoquinoline". It is a structural isomer of quinoline. Isoquinoline and quinoline are , 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. 1-Benzylisoquinoline is the structural backbone in many naturally occurring alkaloids such as papaverine. The isoquinoline ring in these natural compound derives from the aromatic amino acid tyrosine.Gilchrist, T.L. (1997). Heterocyclic Chemistry (3rd ed.). Essex, UK: Addison Wesley Longman.Harris, J.; Pope, W.J. " isoQuinoline and the isoQuinoline-Reds" Journal of the Chemical Society (1922) volume 121, pp. 1029–1033.Katritsky, A.R.; Pozharskii, A.F. (2000). Handbook of Heterocyclic Chemistry (2nd ed.). Oxford, UK: Elsevier.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.Nagatsu, T. "Isoquinoline neurotoxins in the brain and Parkinson's disease" Neuroscience Research (1997) volume 29, pp. 99–111.O'Neil, Maryadele J. (Ed.). (2001). The Merck Index (13th ed.). Whitehouse Station, NJ: Merck.
Being an analog of pyridine, isoquinoline is a weak base, with a p Ka of 5.14. It protonates to form salts upon treatment with , such as HCl. It forms with , such as BF3.
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 react to form isoquinoline. Alternatively, benzylamine and a glyoxal acetal can be used, to produce the same result using the Schlittler-Müller modification.
Several other methods are useful for the preparation of various isoquinoline derivatives.
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.
The Pictet–Gams reaction and the Pictet–Spengler reaction are both variations on the Bischler–Napieralski reaction. A Pictet–Gams reaction works similarly to the Bischler–Napieralski reaction; the only difference being that an additional hydroxy group in the reactant provides a site for dehydration under the same reaction conditions as the cyclization to give the isoquinoline rather than requiring a separate reaction to convert a dihydroisoquinoline intermediate.
In a Pictet–Spengler reaction, a condensation of a β-phenylethylamine and an aldehyde forms an imine, which undergoes a cyclization to form a tetrahydroisoquinoline instead of the dihydroisoquinoline. In enzymology, the (S)-norcoclaurine synthase () is an enzyme that catalysis a biological Pictect-Spengler synthesis:
Intramolecular aza Wittig reactions also afford isoquinolines.
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