Amide formation

Hello.





I tried to use reactor for a simple amide formation. I want ammonia, a primary or secondary amine react with an acid.





Now I tried to put this reaction in one SMARTS and tried the following:





[#1:4][N:1]([#1,CX4,c:2])[#1,CX4,c:3].[#8:8][C:6]([#1,CX4,c:5])=[O:7]>>[#1,CX4,c:2][N:1]([#1,CX4,c:3])[C:6]([#1,CX4,c:5])=[O:7]





Well, it works perfectly for a secondary amine with an acid. But the reaction with a primary amine produces the correct result followed by the following thrown exception:





Exception in thread "main" java.lang.NullPointerException


at chemaxon.reaction.ReactionPerformer.fragment(ReactionPerformer.java:1020)


at chemaxon.reaction.ReactionPerformer.reactHit(ReactionPerformer.java:715)


at chemaxon.reaction.ReactionPerformer.reactOne(ReactionPerformer.java:541)


at chemaxon.reaction.ReactionPerformer.react(ReactionPerformer.java:514)


at chemaxon.reaction.Reactor.reactMain(Reactor.java:1159)


at chemaxon.reaction.Reactor.react(Reactor.java:1075)


at chemaxon.reaction.Reactor.processReaction(Reactor.java:1442)


at chemaxon.reaction.Reactor.run(Reactor.java:1586)


at chemaxon.reaction.Reactor.main(Reactor.java:1813)





Now, the reaction with ammonia is not working at all. I just get the exception mentioned above.


The trouble is obviously in my way to describe a amine, but without specifying if it is a primary or secondary amine (or even ammonia).





At the moment I really have no clue how to solve this...





Thanks a lot in advance,





tobias

Seems working perfectly:

Code:

$ react -r '[#1:4][N:1]([#1,CX4,c:2])[#1,CX4,c:3].[#8:8][C:6]([#1,CX4,c:5])=[O: 7]>>[#1,CX4,c:2][N:1]([#1,CX4,c:3])[C:6]([#1,CX4,c:5])=[O:7]' 'NC' 'CC(=O)O' CNC(C)=O

Code:

$ react -r '[#1:4][N:1]([#1,CX4,c:2])[#1,CX4,c:3].[#8:8][C:6]([#1,CX4,c:5])=[O: 7]>>[#1,CX4,c:2][N:1]([#1,CX4,c:3])[C:6]([#1,CX4,c:5])=[O:7]' 'CNC' 'CC(=O)O' CN(C)C(C)=O

Code:

$ react -r '[#1:4][N:1]([#1,CX4,c:2])[#1,CX4,c:3].[#8:8][C:6]([#1,CX4,c:5])=[O: 7]>>[#1,CX4,c:2][N:1]([#1,CX4,c:3])[C:6]([#1,CX4,c:5])=[O:7]' 'N' 'CC(=O)O' CC(N)=O

Which JChem version do you use?

I tried that:

Code:

$ react -r '[#1:4][N:1]([#1,CX4,c:2])[#1,CX4,c:3].[#8:8][C:6]([#1,CX4,c:5])=[O: 7]>>[#1,CX4,c:2][N:1]([#1,CX4,c:3])[C:6]([#1,CX4,c:5])=[O:7]' 'NC' 'CC(=O)O' CNC(C)=O

Still got the exception with JChem v3.0.11...


I upgraded now to JChem v3.1.1 and it works now... I was in the believe that I had the newest JChem version...





Thanks a lot and sorry for bothering you with such a detail,





tobias

I am sorry about that bug in the earlier version, but I am glad, that a simple update has solved the problem. Just do bother us again if you land in troubles with Reactor or have questions!

Hello once again...





Now the same problem occured again....





I tried to split an amine by using:





[N:1](-[#1,CX4,c:2])(-[#1,CX4,c:3])[C:4](-[#1,CX4,c:5])(-[#1,CX4,c:6])-[#1,CX4,c:7]>>[N:1](-[#1,CX4,c:2])(-[#1,CX4,c:3])[#1:8].[#1,CX4,c:5]-[#6:4](-[#1,CX4,c:6])(-[#1,CX4,c:7])-[#1:9]





This gives me for the following CNCC the following exception:





Exception in thread "main" java.lang.NullPointerException


at chemaxon.reaction.ReactionPerformer.fragment(ReactionPerformer.java:1310)


at chemaxon.reaction.ReactionPerformer.reactHit(ReactionPerformer.java:754)


at chemaxon.reaction.ReactionPerformer.reactOne(ReactionPerformer.java:651)


at chemaxon.reaction.ReactionPerformer.reactBase(ReactionPerformer.java:625)


at chemaxon.reaction.ReactionPerformer.react(ReactionPerformer.java:585)


at chemaxon.reaction.Reactor.reactMain(Reactor.java:1249)


at chemaxon.reaction.Reactor.react(Reactor.java:1184)


at chemaxon.reaction.Reactor.processReaction(Reactor.java:1614)


at chemaxon.reaction.Reactor.run(Reactor.java:1777)


at chemaxon.reaction.Reactor.main(Reactor.java:2023)





I am using JChem 3.1.1...





I really do not know what is wrong...





Thanks a lot in advance,





tobias

This is a bug in Reactor related to the implicit H handling mechanism. I have fixed this and the correction will be availabel in the next JChem release. In the meantime, as a workaround you can use the equivalent reaction SMARTS r1.smarts:





[N:1](-[#1,CX4,c:2])(-[#1,CX4,c:3])[C:4](-[#1,CX4,c:5])(-[#1,CX4,c:6])-[#1,CX4,c:7]>>[N:1](-[#1,CX4,c:2])(-[#1,CX4,c:3])[#1A:8].[#6:4](-[#1,CX4,c:5])(-[#1,CX4,c:6])(-[#1,CX4,c:7])[#1A:9]





which produces the two possible splits:

Code:

react -r r1.smarts "CNCC" CCN C CN CC react -r r1.smarts -t reaction "CNCC" CCNC>>CCN.C CCNC>>CN.CC

Thanks for the report.