Editing Intramolecular reaction (section)

== Relative rates ==
In intramolecular [[organic reaction]]s, two reaction sites are contained within a single molecule. This configuration elevates the effective [[concentration]] of the reacting partners resulting in high [[reaction rate]]s.  Many intramolecular reactions are observed where the [[intermolecular]] version does not take place.

Intramolecular reactions, especially ones leading to the formation of 5- and 6-membered rings, are rapid compared to an analogous intermolecular process. This is largely a consequence of the reduced entropic cost for reaching the transition state of ring formation and the absence of significant strain associated with formation of rings of these sizes. For the formation of different ring sizes via cyclization of substrates of varying tether length, the order of reaction rates (rate constants ''k<sub>n</sub>'' for the formation of an ''n''-membered ring) is usually ''k''<sub>5</sub> > ''k''<sub>6</sub> > ''k''<sub>3</sub> > ''k''<sub>7</sub> > ''k''<sub>4</sub> as shown below for a series of ω-bromoalkylamines. This somewhat complicated rate trend reflects the interplay of these entropic and strain factors:
[[File:SN2intramolecular.png|center|frameless|320x320px]]
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
|+Relative rate constants for cyclization
(''n'' = 5 set to ''k''<sub>rel</sub> = 100)
|-
|+
!''n'' 
!''k''<sub>rel</sub>
!''n''
!''k''<sub>rel</sub>
!''n''
!''k''<sub>rel</sub>
|-
|3
|0.1
|6
|1.7
|12
|0.00001
|-
|4
|0.002
|7
|0.03
|14
|0.0003
|-
|5
|100
|10
|0.00000001
|15
|0.0003
|}
For the '''<nowiki/>'small rings'<nowiki/>''' (''3- and 4- membered''), the slow rates is a consequence of [[Ring strain|angle strain]] experienced at the transition state. Although three-membered rings are more strained, formation of aziridine is faster than formation of azetidine due to the proximity of the leaving group and nucleophile in the former, which increases the probability that they would meet in a reactive conformation. The same reasoning holds for the '''<nowiki/>'unstrained rings'<nowiki/>''' (''5-, 6-, and 7-membered''). The formation of '''<nowiki/>'medium-sized rings'<nowiki/>''' (''8- to 13-membered'') is particularly disfavorable due to a combination of an increasingly unfavorable entropic cost and the additional presence of [[transannular strain]] arising from steric interactions across the ring. Finally, for '''<nowiki/>'large rings'''' (''14-membered or higher''), the rate constants level off, as the distance between the leaving group and nucleophile is now so large the reaction is now effectively intermolecular.<ref>{{Cite book|title=Introduction to Organic Chemistry|last1=Streitwieser|first1=Andrew|last2=Heathcock|first2=Clayton H.|last3=Kosower|first3=Edward M.|publisher=Medtech (Scientific International, reprint of 1998 revised 4th edition, Macmillan)|year=2017|isbn=9789385998898|location=New Delhi|pages=198}}</ref><ref>{{Cite book|url=https://archive.org/details/organicchemistry00clay_0/page/454|title=Organic chemistry|date=2001|publisher=Oxford University Press|author=Jonathan Clayden|isbn=0198503474|location=Oxford|pages=454]|oclc=43338068}}</ref> 

Although the details may change somewhat, the general trends hold for a variety of intramolecular reactions, including radical-mediated and (in some cases) transition metal-catalyzed processes.