I am having a problem with double bond/E and Z isomers. I have two compounds that are different isomers at a single double bond, one the E isomer the other the Z isomer, but the InstantJChem software is labeling them duplicates of each other. How do I fix this short of turning off the duplicate structure flag (although that should not be an issue since they are different compounds)? Thanks.
Benjamin E Blass
Could you attach or send us the two E/Z isomers that should be recognized different?
Here is the requested file. Thanks.
Benjamin E Blass
Thanks for the note. It seems that you are correct, the tautomer duplicate checking is turned on in my data table. The question now becomes how do I turn it off. As to the software assuming that double bonds isomerize and are tautomers of each other, I am not sure that this is not a good assumption for the software to be making. The majority of double bonds are stable as drawn and are not subject to tautomerization. Thanks.
Benjamin E Blass
In Instant JChem it is not possible to change the tautomer duplicate filtering option once the structure table has been created (we have not implemented this yet), though it is possible with the jcman tool. See here for more info:
The main thing you need to do this is to determine the JDBC URL of the database. If you don't know this (and for local databases you probably don't) then right click on the schema node in the projects window, choose the 'Schema settings' option and look at the appropriate properties.
Once you have these you can connect as described here:
As to the software assuming that double bonds isomerize and are tautomers of each other, I am not sure that this is not a good assumption for the software to be making. The majority of double bonds are stable as drawn and are not subject to tautomerization.
Unfortunately, in this tautomer duplication algorithm we cannot do a detailed energetic evaluation of stable tautomers.This is just a quick way to warn about any theoretically possible tautomer transformation. I agree that your molecule is a stable tautomer, but in extreme conditions there may exist other tautomers as well. JChem also recognizes these minor forms as tautomers. (Even if they are non-existent at standard conditions.)
Thank you for your response regarding the double bond issue. At this point, I would recommend that ChemAxon revaluate the definitions that you are using for tautomers, as the isomers that we are discussing are not tautomers of each other, they are diasteromers (that is to say they are distinct compounds). Tautomers are defined as a specific kind of structural isomer that are readily interconverted through a rapid equilibrium. The full definition, which can be found in text books such as McMurry's Organic Chemistry, specifically exclude alkenes from this definition. Amides exist in tautomeric form, as do ketones, esters and other compounds capable of enolization, but this is not the case with simple alkenes such as the ones we have been discussing. Under the proper chemical conditions (temperature induced or reagent based conditions), one can iterconvert one alkene into another through isomerization of the double bond, but this is a true chemical conversion, not a tautomerization. This is different from enolization of a ketone/enol equilibrium. This equilibrium is a tautomerization as there is an equilibirum at all conditions between the enolic form and the keto form, even if it may be shifted heavily towards one side of the equilibrium. 1,3-diketones are another examlpe of tautomerization. In this case the equilibrium between the keto and enol tautomers is dependent on the solvent used. In methanol, the enol form predominates, where in ethyl acetate, the keto form predominates.
Alkenes on the other hand, do not undergo these kind of tautomerizations. They exist as distinct diasteromers and do not readily interconverted through a rapid equilibrium, as is required by the definition of tautomers. Thanks.
Benjamin E Blass
Thanks for the detailed explanation. I think that we are aware of all these concepts.
The "only" issue is that our method used in the tautomerization detection is overly theoretical and it cannot predict whether a possible "tautomerism-looking transformation" is likely to take place or not. We do have methods that are capable of predicting that, but we will need to think about how to use them efficiently in the database environment. (When handling large collections, the performance is key.)
Another problem is how to handle cases when a minor (unstable) "tautomer" comes into the database that always interconverts into a stable form but never backwards. (For example: CC=C(O)O or by iupac name: prop-1-ene-1,1-diol.)
We will work on solving these issues and come up with a revised tautomer identification algorithm in the future.