I see 5- and 6-membered ring products as the major products even when 7-membered rings are possible. Why is that 5- and 6-membered rings are more likely to form than 7-membered rings? Is it even true?

My textbook says a 5-membered ring is the major product and the 7-membered ring is the minor product in intra-molecular aldol condensation reaction of 6-oxoheptanal.

Major Product: 1-(cyclopent-1-en-1-yl)propan-2-one
Minor Product: cyclohept-2-ene-1-carbaldehyde and 2-methylcyclopent-1-ene-1-carbaldehyde

This is not the only reaction where I found a 5-membered ring as a major product when a 7-membered ring was possible.

  • 4
    $\begingroup$ Simply because the 5- and 6-membered rings can adopt conformations with less ring strain than 7-membered rings (6-membered rings in particular have the famous chair conformation). That's all there is to it. Look up "ring strain" in any org chem textbook $\endgroup$ – orthocresol Mar 28 '16 at 12:02
  • $\begingroup$ @orthocresol I don't think that's right, at least for saturated systems. $n=6$ rings have minimal ring strain; $n>6$ should also be minimally strained, since they're floppier. I wouldn't think things would be much different for, e.g., the mono-unsaturated system described by OP...? $\endgroup$ – hBy2Py Mar 28 '16 at 12:25
  • 2
    $\begingroup$ @Brian March 7ed pp 199-200 i.imgur.com/tClSmXh.png i.imgur.com/8qLnCqG.png Actually the unsaturation might change things, but the preference for 5- and 6-rings in aldol reactions is definitely thermodynamic. $\endgroup$ – orthocresol Mar 28 '16 at 12:36

There are two factors that need to be considered to answer your question - entropy and enthalpy.

Entropy favors the formation of smaller rings. If we consider a hydrocarbon chain, the number of possible conformations increases dramatically as we go from 3 carbons to, for example, 10 carbons. Only a few of these conformations will be correctly arranged so that the two ends of the chain are close to each other, which is necessary if we are to form a bond. So, entropically speaking, it will be much more probable to form a 3-membered ring than a 10-membered ring. This is shown in the following graph where 3-, 4- and 5-membered ring formation is entropically most favored.

graph of entropy versus ring size

Note that a less negative $\Delta S$ favors the reaction since $\Delta G=\Delta H - T \Delta S$.

Enthalpy comes into play when we consider the strain in the transition state leading to the possible products. Here is a chart showing the relative ring strain as a function of ring size.

strain energy (kcal/mol) vs ring size

As expected, strain is the highest in 3- and 4-membered rings.

If we overlay (add) these entropic and enthalpic effects we would get a graph similar to the one pictured below.

Rate constants vs. Ring Size for the cyclization of malonates

In general, we find that 5-membered ring formation is usually the favored pathway. This web article (J. Am. Chem. Soc. 1984, 106, 1051-1056.) is a nice review of this topic that may be useful for a more in-depth reading on the subject. The above web article is also the source of the above three images.


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.