Acylation of secondary amines and nitrogen heterocycles

I have a (hopefully) quick question regarding Reactor. Is it possible to have a single reaction which will handle the addition of both a secondary amine (like piperidine) and an aromatic amine (like pyrazole) with a carboxylic acid ?

One simple solution is this reaction scheme in SMIRKS:





"[#7X3:1][H:2].[H][O:4][C:3]=O>>[#7:1][C:3]=O"





The mapping here follows the Reactor format (each atom having changing bond is mapped). You can try it from the command line this way:





react -r "[#7X3:1][H:2].[H][O:4][C:3]=O>>[#7:1][C:3]=O" "C1CCCCN1" "CC(O)=O"





react -r "[#7X3:1][H:2].[H][O:4][C:3]=O>>[#7:1][C:3]=O" "c1cc[nH]n1" "CC(O)=O"





You can certainly improve the scheme further (ie. excluding amide nitrogens) by using recursive SMARTS expressions (available from JChem version 2.3, check the beta release here http://www.chemaxon.com/restricted/jtest/) or by adding REACTIVITY rules to the reaction in mrv or rdf formats.

Is there a way to define a reaction using MarvinSketch which will work for both aromatic and aliphatic amines? Our application is being used by chemists who have no interest in writing SMIRKS.

Certainly there is. The image of the reaction was created with MarvinSketch. The connection count (X3) can be set with the X+ button located in the More window. You can then save the reaction in RXN, RDF or MRV formats. Testing with the react tool is similar to the SMARTS version:





react -r amidation.rxn pyrazole.mol acetic_acid.mol





If you do not like the connection count property, you can define the amines in an other way. For example, attaching two carbons with single-or-aromatic query bonds to the nitrogen on the left side of the scheme.


I attached these two rxn file versions of the reaction.