The cyano group in the synthesis of heterocycles

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The cyano group in the synthesis of heterocycles

The polarity of the CN bond of the cyano group (also called nitrile) means that this reagent can react with nucleophiles and electrophiles, giving rise to heterocycles with one or several heteroatoms in the ring.

Thus, it is very common to observe the participation of the nitrile group in intramolecular cyclizations, when the same molecule has an electrophilic or nucleophilic end. Propose a synthesis plan, from simple materials, to the following molecules:

MOb: 75

MOb: 76

MOb 75 . Retrosynthetic analysis . the MOb , presents in one of the heterocycles, the guanidine structure and in the other heterocycle there is a saturated structure, which can be transformed to a lactam. The disconnection with the latter begins and then continues to be disconnected by the guanidine structure, obtaining a lactam hydroxynitrile precursor, which can produce a dilactam structure, which is disconnected by the N-CO bond, to form a 1.5 molecule. -diCO, which disconnected leads to simple materials for synthesis.

Synthesis : the condensation The aldol type of the starting materials leads to a 1,5-diCO compound, which with NH3 forms the first dilactam cycle capable of combining with guanidine to form the second heterocycle. The CN group is very important in the second cycle.

Finally, the reduction of the C=O groups leads to the MOb 75.

MOb 76. Retrosynthetic analysis . The CN bond of amines is taken into account, for the first disconnection, of the mob 76, then continue with the simultaneous disconnection of an H and a Br.

The planned synthesis operations lead to a precursor molecule with two CN groups, which are disconnected into a dihalide, and two moles of HCN. Synthesis. Diethyl malonate as starting material serves for the preparation of the required dihalide, which is combined with HCN.