[Messi]

So I was thinking:

We have ΔG=ΔH-TΔS and I want to undergo a cyclization reaction in order to create a medium-sized ring let's say.

In order to create medium sized rings, the ΔH term is always positive because of ring strain, while the ΔS term is obviously negative because I am decreasing entropy by making a ring (bonds become rigid; loss of entropy). So, based on this, ΔG would be a positive number. So how is it possible for me to get a reaction if ΔG is positive. Changing temperature would have no effect on making ΔG negative.

I hope my question makes sense. Could someone explain to me if my thinking is "wrong" or if I am missing something very fundamental .

Thanks!

[Altered State]

We have ΔG=ΔH-TΔS and I want to undergo a cyclization reaction in order to create a medium-sized ring let's say.
Changing temperature would have no effect on making ΔG negative.

If we have ΔS > 0, if you decrease the temperature, your TΔS component will be smaller. If you are able to diminish T so ΔH is higher than TΔS, you will have negative free Gibbs energy.
But the truth is that we won't get ΔG negative by that way, this is going to be a procces which is spontaneous in reverse so it wouldn't go.
That may be one of the reasons we don't get cyclocompounds that large, as far as I know.

Maybe in so energical conditions? (High pressure and temperature, or using a catalyist..)
I cannot really tell, specially if you are not more specific about what are you talking about... I know there are things you can do to make some nonspontaneous procces to be so, but for some other ones, there is nothing you can do, it is against nature.

[Corribus]

@Messi

Be careful with generalizations like this.  The enthalpy change of ring formation is not the entire enthalpy change of the reaction.  There are other things going on that contribute to the overall enthalpy change.  Likewise, while entropy may decrease due to ring closure, it may be increasing in other areas.  If a gas would be generated from the ring closure, for example, that would obviously counteract any loss in entropy due to the ring closure. You have to consider the entirety of each reaction - even stuff going on secondary to the reaction, like solvent reorganization - to understand the thermodynamical driving force.  You have to consider each reaction individually

Also, keep in mind that thermodynamics is only part of the equation.  It's a refrain I sing a lot but kinetics, though related to thermodynamics, also includes other factors which have nothing to do with enthalpy and entropy.

Just some stuff to chew on.

[Messi]

Well, I am just confused by this:

When you create a ring... enthalpy increases due to strain (far from ideal bond angles, eclipses conformations with in ring, repulsive interactions within ring). So ΔH is + most of the time.

Now, when you look at entropy, by creating a ring you are decreasing entropy. Bonds cannot rotate as easily which is clearly an example of entropy decreasing. So ΔS is - most of the time.

Now if ΔG=ΔH-TΔS and ΔH is + and ΔS is -, ΔG will always be positive. If ΔG is positive, how is it we can create rings then! This is what I don't understand!

[Altered State]

Well, I am just confused by this:

When you create a ring... enthalpy increases due to strain (far from ideal bond angles, eclipses conformations with in ring, repulsive interactions within ring). So ΔH is + most of the time.

Now, when you look at entropy, by creating a ring you are decreasing entropy. Bonds cannot rotate as easily which is clearly an example of entropy decreasing. So ΔS is - most of the time.

Now if ΔG=ΔH-TΔS and ΔH is + and ΔS is -, ΔG will always be positive. If ΔG is positive, how is it we can create rings then! This is what I don't understand!

You ought to read again Corribus' post, there is the key.
You can't just consider only the factors you have mentioned, there are more things to take into account.

[Messi]

You ought to read again Corribus' post, there is the key.
You can't just consider only the factors you have mentioned, there are more things to take into account.

Well, I am reading this article: http://pubs.acs.org/doi/pdf/10.1021/ar00064a001

Take a look at it, it seems to say ΔH is always positive from my impression.

I also found the picture below that shows lactone formation. ΔG is positive so how is lactone formation occuring!

[Corribus]

In the spirit of full disclosure, I am not an expert on ring closure reactions.  However I do know quite a bit about thermodynamics.  And a key part of thermodynamics is dynamics.  That is, change.  Which means that delta this and delta that only have relevance with respect to the entire process involved.

I have not read the article you linked to (can't access it from home), so can't comment.  The figure also doens't mean a whole lot taken out of context.  Is that theoretical data or empirical data?  Based only what is provided in your post, my impression is that these may be thermodynamical values ONLY for the lactone rings themselves, and do not include other parameters like those I mentioned above.  A lot of these "delta whatever of formation" values are determined as enthalpy or entropy with respect to formation from basic standard state starting products (carbon, hydrogen gas, oxygen gas) etc. Taken by themselves, then, they don't mean a whole lot because substances are rarely formed simply by just combining pure elements in their standard states.  They're formed by reactions with other complex substances, so heats of formation (and so forth) only have meaning with compared to other heats of formation.  And even those kinds of comparisons ignore important solvent events and so forth.

Thermodynamics is only really useful to analyze processes, not static entities.  When considering whether formation of a lactone (any lactone) is a favorable process, you have to ask what they're being formed from.  Sure, a lactone may have a lot of ring strain and may be a high energy molecule.  But it may be perfectly favorable to form one from an even higher energy, less favorable starting material.  In other words, while in some processes formation of a 4 member lactone ring may be quite unfavorable, in others it may be favorable.  It all depends on the point of origin. 

So to say something like "delta G for lactone formation is ALWAYS positive" is an overgeneralization and to ask a question "how can they exist" doesn't mean a whole lot of sense in light of what we know to be fact.  The point of fact, obviously, is that lactones DO exist, and since we know thermodynamics is a pretty solid body of scientific laws, doesn't it make sense to conclude that delta G for lactone formation can't always be positive?  In other words, the empirical evidence suggests the premise of your argument is wrong, not the argument itself.

[Messi]

I have not read the article you linked to (can't access it from home), so can't comment.  The figure also doens't mean a whole lot taken out of context.  Is that theoretical data or empirical data?  Based only what is provided in your post, my impression is that these may be thermodynamical values ONLY for the lactone rings themselves, and do not include other parameters like those I mentioned above.

This is theoretical data for lactone rings ONLY, yes.

The point of fact, obviously, is that lactones DO exist, and since we know thermodynamics is a pretty solid body of scientific laws, doesn't it make sense to conclude that delta G for lactone formation can't always be positive?  In other words, the empirical evidence suggests the premise of your argument is wrong, not the argument itself.

Of course this is true. But, really understanding WHY things are happening I think is important. We know something is happening, but why!

[Corribus]

Of course this is true. But, really understanding WHY things are happening I think is important. We know something is happening, but why!

Absolutely it is important.  My point is that you trying to understand something but you are only using half the information required.