Gabriel-Colman

GABRIEL COLMAN Rearrangement Synthesis of isoquinolines by rearrangement ol phthahmides. 

The Gabriel-Colman rearrangement entails reaction of the enolate of a maleimidyl acetate (2) to provide isoquinoline 1,4-diol 3. ... 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

The Gabriel-Colman reaction can be used to prepare isoquinoline-1,4-diols regioselectively by the use of unsymmetrically substituted phthalimides. Reaction of phthalimide 32 with sodium ethoxide in ethanol provides a 1 7 mixture of 33 34. It was rationalized that attack at carbon b is preferred because of its greater steric accessibility and diminished electron density compared to carbon a. In spite of the reasonable regioselectivity observed m this reaction, the Gabriel-Colman reaction has not been substantially investigated in the preparation of non-symmetrically substituted isoquinolines. 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

The mechanism of this variant of the Gabriel-Colman reaction has been investigated. Treatment of saccharine derivatives 45-48 with 1-2 equivalents of sodium alkoxide at room temperature provides esters 49-52 in good yields treatment of 45-48 with sodium alkoxide at reflux provides the expected benzothiazines 53-56. Increased concentration leads to higher yields. 

Pflum, D. A. Gabriel-Colman Rearrangement In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hohoken, NJ, 2005, 416—422. (Review). 

Pyracen 3-Methyl-3-(2-nitro-ethenyl)-2-oxo-tetrahydro-E1S/1, 1176/E21a, 1111 (Lacton + R2N —CH = N02) Pyridin 2-Ethoxycarbonyl-3-hydroxy-6-oxo-l,4,5,6-tetra-hydro- E15/2, 1250 (Gabriel-Colman-Umlager.)... 

Isoquinolin 6(bzw. 7)-Chlor-3-ethoxycarbonyl-4-hydroxy-1 -oxo-l, 2,4a,5,8,8a-hexahydro-E15/2, 1250 (Gabriel-Colman-Umiager.)... 

Gabriel-Colman rearrangement. Formation of isoquinoline derivatives by the action of sodium ethoxide on phthalimidoacetic esters. 

Diphenylpteridine can be prepared by the Gabriel-Isay (Gabriel-Colman) reaction34,35 using pyrimidine-4,5-diamine (4) and benzil (2), but if the dicarbonyl compound used in this reaction is unsyinmetrical, then two regioisomeric products 5 and 6 are possible. 

Table 1. Use of Glyoxal in the Gabriel Colman Pteridine Synthesis ...

Further examples of the Gabriel-Colman synthesis of pteridines using formyl ketones are given in Table 2. 

Table2. The Gabriel-Colman Synthesis Using Formyl Ketones3...

The original Gabriel-Colman pteridine synthesis7 used 6-methylpyrimidine-4,5-diamine and benzil to yield 4-methyl-6,7-diphenylpteridine (see Section 7.3.1.1.1.). This type of reaction generally gives good yields of the required pteridine, and is exemplified by the synthesis of 6,7-dimethylpteridine (l).49... 

Table 5. The Gabriel-Colman Reaction with Diketones2...

Some other examples of the use of a-oxo esters, or their equivalents, are given in Table 6. Table 6. Gabriel-Colman Synthesis Using Oxo Esters ... 

GABRIEL - COLMAN Rearrangement Synthesis of tsoqumolines by rearrangement ot phthahmides. 

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