Preparation and Properties of Quinoline

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Preparation and Properties of Isoquinoline Isoquinoline • Isoquinoline consists of a benzene ring fused to the β- and ϒ-positions of a pyridine ring. • Occurs in coal-tar and bone oil • Isoquinoline is also found as part of the total structure of a number of alkaloids e.g., papaverine and morphine. • Isoquinoline is one of the very few heterocyclic compounds in which numbering of the ring atoms does not start on the hetero atom. Preparation Methods (1) From Cinnamaldehyde: This involves condensation of cinnamaldehyde with hydroxylamine to form the corresponding oxime. The oxime is then heated with phosphorus pentoxide to yield Isoquinoline. It is believed that the oxime first undergoes rearrangement which is then followed by ring closure. (2) By Bischler-Napieralski Synthesis: In this reaction, 2-phenylethylamine is first treated with formyl chloride in the presence of a base to form N.formyl- 2-phenylethylamine. This amide is next heated with phosphorous pentoxide in pyridine to give 3,4-dihydroisoquinoline which on oxidation (dehydrogenation) with palladium or selenium yields isoquinoline. Physical properties of Isoquinoline • Isoquinoline is a colorless solid • (mp 26°C; bp 243°C) • Smell like that of benzaldehyde (Almond like). • It is sparingly soluble in water, and is soluble in many organic solvents. • It turns yellow on normal storage. Chemical properties of Isoquinoline Isoquinoline resembles quinoline in most of its chemical properties. 1. Basic Character: • Isoquinoline is a stronger base than quinoline. It forms stable salts with acids. 2. Electrophilic Substitution Like quinoline, it undergoes electrophilic substitution at C-5 and C-8. 3. Nucleophilic Substitution Isoquinoline undergoes nucleophilic substitution at C-1 or C-3 if C-1 is occupied. 4. Reduction Mild Reduction: Mild reduction of isoquinoline with tin and hydrochloric acid yields 1,2,3,4-tetrahydroisoquinoIine Catalytic Reduction: Reduction with hydrogen and platinum catalyst produces decahydroisoquinoline 5. Oxidation: Oxidation with peracetic acid gives the N-oxide. It is also oxidized by alkaline potassium permanganate to give pyridine-3,4-dicarboxylic acid (Cinchomeronic acid)..

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A New Synthesis of 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline
A NEW SYNTHESIS OF 1-BENZYL-1,2,3,4-TETRAHYDROISOQUINOLINE By L. W. DEADY,*N, H. PIRZADA,*R. D. TOPSOM,"and J. M. BOBBITT~ [Manuscript received 5 March 19731 Abstract The synthesis of N-(2-bromoethy1)-N-(1,2-diphenylethy1)ammoniumbromide and its aluminium chloride catalysed decomposition to 1-benzyl-1,2,3,4-tetrahydro- isoquinoline is described. We have recently reported convenient preparations of tetrahydroquinolinesl (m = 0, n = 3) and tetrahydroisoquinolines2 (m = 1, n = 2) by the cyclization of compounds of type (1). 1-Benzyl-1,2,3,4-tetrahydroisoquinolineis the parent compound of an impor- tant class of alkaloids3 and methods of synthesis of this system are of considerable interest. Normally, the system has been prepared by ring closure between C 1 of the incipient isoquinoline and the aromatic ring, the so-called Bischler-Napieralski rea~tion,~although several new methods have been described and ~ummarized.~In theory, the ring system can be prepared by closure of C4 (as an aldehyde or blocked aldehyde) to the aromatic ring by a variation of the Pomeranz-Fritsch synthe~is,~,~ but there are several difficulties with intramolecular ring closures6 and only one successful synthesis has been reported.' In any case, such a synthesis results in oxygenation at C4 or some type of unsaturation in the isoquinoline ring. In this paper, we report a synthesis which is an extension of our previous work2 and which gives the tetrahydroisoquinoline ring directly in reasonable yield. Deoxybenzoin was used as the starting material in the synthesis of the required intermediate (2). Though the synthesis of (2) involved three steps it was experi- * Organic Chemistry Department, La Trobe University, Bundoora, Vic.
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