Pictet-Gams synthesis

A recent paper on the Pictet-Gams synthesis of isoquinolines (Scheme 44) describes the use of oxazoline intermediates for an improved method of preparing the starting materials. or/ o-Halogenated A -alkyl-A -acyl-benzylamines (67) can be cyclized to dihydroisoquinolones (68) by their reaction with KNH2 in liquid ammonia or with LiNPr 2 in THF under thermal... 

Hydroxy-substituted A -(2-arylethy)amides 51 lead to isoquinolines 48 under Bischler-Napieralski conditions. In this case, dehydrogenation is not required Pictet-Gams synthesis), because H2O elimination occurs at the dihydroisoquinoline step. The starting materials 51 are available e.g. from aryl-4,5-dihydrooxazoles (e.g. 57). 

This reaction is related to the Bradsher Pyridinium Salt Synthesis, Pictet-Gams Synthesis, Pictet-Spengler Reaction, and Skraup Reaction. 

Other references related to the Pictet-Gams synthesis are cited in the literature. ... 

The educt 64 for the Pictet-Gams synthesis is prepared from the oxazohne 63 (accessible from methyl isocyanide by application of the SchOllkope methodology (cf p. 173)). 

Parham cycloalkylation 343 Patemo-Btichi reaction 46 von Pechmann synthesis (coumarin) 322 Pellizari synthesis (1,2,4-triazole) 270 Perkin rearrangement 82 Pfitzinger synthesis (quinoline) 398 Pictet-Gams synthesis (isoquinoline) 414 Pictet-Spengler synthesis (isoquinoline) 415 Piloty-Robinson synthesis (pyrrole) 119 Pinner synthesis (pyrimidine) 467 Plancher rearrangement 128 Polonovski reaction 545 Pomeranz-Fritsch synthesis (isoquinoline) 415 Prileschajew reaction 23 Prins reaction 452 Pummerer rearrangement 26, 457... 

The Pictet and Gams synthesis of oxyberberine also proved on reinvestigation to be illusory, but several syntheses of this substance... 

Holsworth, D. D. Pictet—Gams Isoquinoline Synthesis In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hohoken, NJ, 2005, 457—465. (Review). 

Alternatively, a P-methoxy-P-phenylethylamine can be used to circumvent the oxidation step after the conventional Bischler-Naperialski cyclization. Here, when treated with the phosphorus reagent the amide (R = OMe) undergoes both cyclization and the elimination of methanol to give the isoquinoline (R = H) directly. This is known as the Pictet-Gams modification of the Bischler-Napieralski synthesis. 

The Pictet-Gams modification of the Bischler-Napieralski synthesis has also been reviewed (5loR(6)74, 81HC(38-l)l6i). As shown in equation (32), the additional unsaturation is achieved by elimination of ROH before the cyclization. The commonest examples use j8-hydroxy or /3-methoxy substituents on the phenethylamide. Papaverine (107) is an example of an isoquinoline obtained from both precursors (09CB2943, 27AP(265)l). The precursors can be made from 5-aryloxazolines by reaction with an acid chloride and... 

This method [Eq. (10)] was first used in 1930 by Kondo and Tanaka60 for the preparation of 4-hydroxy-5-methoxytetrahydroisoquinoline from j8-hydroxy-j8-(o-methoxyphenyl)ethylamine and methylal (mixed in aqueous HC1). Such ethanolamine derivatives are frequently used in the Bischler-Napieralski synthesis of isoquinolines61 as the Pictet-Gams modification. In this case, the reaction proceeds with dehydration to yield completely aromatic isoquinolines directly. Preparations of the ethanolamines have been reviewed.62... 

Pictet-Gams isoquinoline synthesis. Formation of isoquinolines by cychzation of acylated aminomethyl phenyl carbinols or their ethers with phosphorus pentoxide in toluene or xylene. 

Papaverine is an alkaloid from opium it is a smooth-muscle relaxant and thus useful as a coronary vasodilator - the synthesis illustrates the Pictet-Gams variation of the Bischler-Napieralski sequence. 

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