Synthesis of   Benzofurans and Benzothiophenes

(By the method of disconnections)

1. Synthesis of Benzofurans

Benzofuran, usually called coumarone,   It is a colorless liquid, which is isolated from coal tar and is much more stable to chemical attack than furan.

The most classic syntheses for the preparation of benzofurans will be mentioned and developed:

to. From the coumarin

b. From an internal Claisen condensation reaction

c.        Starting   of a Claisen rearrangement

Propose a synthesis design, for the following benzofurans:

MOb 127, Retrosynthetic analysis. The disengagement strategy, in the MOb 127, is directed towards an intermediate, which is a derivative of coumarin, which in turn is prepared by reaction of   aldol type condensation between ethyl acetate and a derivative of benzaldehyde

Synthesis. The intermediate 2-hydroxy-5-methylbenzaldehyde is prepared from benzene. The coumarin derivative that is formed is halogenated, hydrolyzed in a KOH sol and subsequently heated with CaO, to decarboxylate and thus form the   MOb 127.

MOb 128. Retrosynthetic analysis. the MOb 128 is functionalized with the addition of a –COOEt group, which later allows disconnecting via the C=C link. The intermediate dicarbonyl compound is formed by the reaction of a bromoester with a ketone derivative of phenol.

Synthesis. Claisen condensation is used to form the intermediates that are cyclized and decarboxylated with final heating to form the   MOb 128.

2.       Synthesis of benzothiophenes

Benzothiophene is the most important sulfur-containing impurity of technical naphthalene, so benzothiophene itself has little commercial value, but some of its derivatives in the form of indigo dye have great value.

The synthetic methods of benzothiophene are similar to those used for benzofuran, but the following methods can be mentioned.

to.       From suitable benzothioderivatives:

b.       Through a Diels-Alder reaction

c.       By displacement of ortho groups to a cyano group (leading to 3-amino compounds) or aldehyde on a benzene ring by a suitable sulfur nucleophile and subsequent cyclization.

Propose a feasible synthesis plan for the following molecules:

MOb 129 . Retrosynthetic analysis.

Synthesis

MOb 130 . Retrosynthetic analysis.

Synthesis.{mosimage}