2- Amino-3-cyanopyridines, formation

A Thorpe-Ziegler intramolecular cyclization starting with 3-cyanopyridine-2-thione derivatives leads to the formation of 3-amino-2-(organylsulfinyl)thieno[2,3- ]pyridines in high yields <2006RCB529>. 

The reaction products of the treatment of a, 3-unsaturated ketones with malononitrile in most cases are the expected derivatives of 2-amino-3-cyanopyridine. But an alternate direction with the formation of carbocyclic compounds 120 was described [128]. It is clear from structure 120 that two molecules of unsaturated ketone 5 and 1 equiv of malononitrile 107 are involved in the reaction (Scheme 3.37). 

Photocycloaddition of 2-alkoxy-3-cyanopyridines with methylacrylonitrile yields a bicyclic [2+2] cycloadduct intermediate followed by rearrangement to give 368 in 44—55% yield along with 3-acetyl-4-amino-l,5-dicyano-2,5-dimethylcyclohexa-1,3-diene (15-17%). Equimolar quantities of reagents have to be used for the formation of 368... 

In 2014, Odom and coworkers reported a titanium-catalyzed synthesis of 2-amino-3-cyanopyridines (Scheme 3.41) [89]. The reactions were performed in a one-pot manner with two manipulation steps. Firstly, titanium-catalyzed alkyne iminoamination and generation tautomers of 1,3-diimines. Then, 2-amino-3-cyanopyridines were formed in good to modest yields after treatment with base (DBU) and malononitrile. A Dimroth rearrangement mechanism for 2-aminopyridine formation was proposed based on the isolation of a 2-imino-l,2-dihydropyridine intermediate which undergoes rearrangement under the reaction conditions. 

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