Synthesis of 2,3-Dihydro-pyrrolopyridinones

Recently, Bischoff et al. has described the synthesis of 2,3-Dihydropyrrolopyridinone by a tandem aminomethylation-Cyclization using in situ generated formimine and an ortho-lithiated pyridinecarboxamide, depending on the reaction conditions it is also possible to continue the cascade reaction with a bis alkylation of the pyrrolidinone ring.

Org. Lett.; (Letter); 2006; 8(25); 5889-5892.

3-arylquinoline

Side reactions in organic chemistry can be considered as a failure in a target oriented synthesis, but it can be a valuable source a inspiration for the design of new methodologies.
In 2004, Baldwin and coll. tried to synthesize the 5,5',6,6'-tetrahydroxy-3,3'-biindolyl, a potent antioxidant, he proposed as key step a bis-cyclization of the two 2-aminoaryl substituents on the furan (as 1,4-dialdheyde precursor).


Cyclization was attempted with para-toluenesulfonic acid in benzene, and lead to the formation of a 3-arylquinoline in poor 25% yield along with the starting material.


Finally, the 3,3'-biindole has been synthesized by a palladium catalyzed homocoupling reaction from the corresponding 3-iodoindole.

For the mechanism of the quinoline formation and other informations see:

Tetrahedron 60 (2004) 3695–3712

SYNTHESIS OF 3,4-disubstitutedpyrrole-2,5-dicarboxylate

The post of today is an elegant synthesis of tetrasubstituted pyrrole from a pyridazine ring, this synthesis has been described by Dale Boger et al. and require only zinc metal (9-20 equiv. and previously activated(1)) and acetic acid (0.09M), this transformation is performed in about 24h at room temperature with moderate to good yields (42-70%).


(1) Fieser, L. F.; Fieser, M. "Reagents for Organic Synthesis"; Wiley: New York, 1967; Vol. 1, p.
1276.

For more information about the procedure and the synthesis of pyridazine see:
Organic Syntheses, Coll. Vol. 9, p.335 (1998); Vol. 70, p.79 (1992).

SYNTHESIS OF 3-HydroxyCinchoninic acid

The synthesis of the 3-hydroxycinchoninic acid has been performed with the reaction a commercially available isatin in presence of chloropyruvic acid (previously synthesized from pyruvic acid and sulfuryl chloride in 95-98% Yield.) in a aqueous potassium hydroxyde solution. After the workup the 3-hydroxycinchoninic acid is isolated as a yellow solid(60-71%).

For more information:

Organic Syntheses, Coll. Vol. 5, p.635 (1973); Vol. 40, p.54 (1960).

James Cason and James D. Willett.

SYNTHESIS OF 2,3-PYRAZINEDICARBOXYLIC ACID

I will start this blog with a quite old but very interesting synthesis of pyrazine dicarboxylic acid.

This synthesis starts with the formation of quinoxaline, by the reaction of glyoxal and o-phenylendiamine in water with a 85-90% yield(1). Then the benzene fused ring is cleaved with a hot aqueous potassium permanganate solution (2), the mixture is cooled at room temperature and acidified with a 36% hydrochloric acid (3). The crude material is filtered off and recristallized in acetone to give the 2,3-pyrazinedicarboxylic acid with a 75-77% yield.

Interestingly, this synthesis can be applied to quinolines, isoquinolines and naphtalenes to provide the corresponding dicarboxylic derivatives.


For more information:

2,3-PYRAZINEDICARBOXYLIC ACID

Organic Syntheses, Coll. Vol. 4, p.824 (1963); Vol. 30, p.86 (1950).

Reuben G. Jones and Keith C. McLaughlin.

Welcome to my Blog Dedicated to Heterocyclic Chemistry.

You will find here different ways to synthesize and to functionalize heterocyclic rings, mainly 6-membered rings but not only.

I will try to keep this blog update ASAP.

ENJOY.