Editing Cahn–Ingold–Prelog priority rules (section)

{{short description|Naming convention for stereoisomers of molecules}}
{{more citations needed|date=February 2016}}
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[[Image:CIP priority diagram.png|class=skin-invert-image|thumb|320px|right|An example of the prioritisation of structure within the CIP system. Priority is assigned according to the substitution of elements with higher atomic numbers, or other attached groups. In red is the substituent which determines the final priority.]]

In [[organic chemistry]], the '''Cahn–Ingold–Prelog''' ('''CIP''') '''sequence rules''' (also the '''CIP priority convention'''; named after [[Robert Sidney Cahn]], [[Christopher Kelk Ingold]], and [[Vladimir Prelog]]) are a standard process to completely and unequivocally [[Chemical nomenclature|name]] a [[stereoisomer]] of a molecule.<ref>{{cite book|last1=March|first1=Jerry|last2=Michael B.|first2=Smith|title=March's advanced organic chemistry : reactions, mechanisms, and structure|date=2007|publisher=Wiley-Interscience|location=Hoboken, NJ|isbn=978-0-471-72091-1|pages=155–162|edition=6.}}</ref><ref name = IUPAC>{{cite book|first1 = L.C| last1 = Cross| first2 = W.| last2 = Klyne| title = Rules for the Nomenclature of Organic Chemistry: Section E: Stereochemistry (Recommendations 1974)| date =1974|url= http://www.iupac.org/publications/pac/1976/pdf/4501x0011.pdf|isbn =  978-0-08-021019-3| archive-url=https://web.archive.org/web/20160407110019/http://www.iupac.org/publications/pac/1976/pdf/4501x0011.pdf|archive-date = 2016-04-07}}</ref>{{rp|26}} The purpose of the CIP system is to assign an [[Absolute configuration#By absolute configuration: R- and S-|''R'' or ''S'' descriptor]] to each [[stereocenter]] and an [[E-Z notation|''E'' or ''Z'' descriptor]] to each [[double bond]] so that the configuration of the entire molecule can be specified uniquely by including the descriptors in its systematic name. A molecule may contain any number of stereocenters and any number of double bonds, and each usually gives rise to two possible isomers. A molecule with an integer {{mvar|n}} describing the number of stereocenters will usually have {{math|2{{sup|''n''}}}} [[stereoisomer]]s, and {{math|2{{sup|''n''−1}}}} [[diastereomer]]s each having an associated pair of [[enantiomer]]s.<ref name=ClaydenOC12>{{cite book | author = Clayden, Jonathan  | author2 = Greeves, Nick  | author3 = Warren, Stuart | name-list-style = amp | year = 2012 | title = Organic Chemistry | edition = 2nd | pages = 316f | location = Oxford, UK | publisher = Oxford University Press | url = https://books.google.com/books?isbn=0199270295 | access-date = 2 February 2016 | isbn =  978-0199270293 }}</ref><ref name = usually/> The CIP sequence rules contribute to the precise naming of every stereoisomer of every [[organic compound|organic]] molecule with all atoms of [[Coordination number|ligancy]] of fewer than 4 (but including ligancy of 6 as well, this term referring to the "number of neighboring atoms" bonded to a center).<ref name = IUPAC/>{{rp|26f}}<ref name = usually>The "usually" has its basis in the fact that molecules with chiral centers nevertheless may have mirror planes of symmetry, e.g. [[meso compound]]s, that make some of the stereoisomers "degenerate" (identical), so that this mathematical expression overestimates the number. See Clayden, op. cit., p. 317.</ref>

The key article setting out the CIP sequence rules was published in 1966,<ref>{{Cite journal | author = Cahn, R.S. | author-link = Robert Sidney Cahn | author2 = Ingold, C.K. | author2-link = Christopher Kelk Ingold | author3 = Prelog, V. | author3-link = Vladimir Prelog  | title = Specification of Molecular Chirality | journal = [[Angewandte Chemie International Edition]]  | volume = 5 | issue = 4 | pages = 385–415 | year = 1966 | doi = 10.1002/anie.196603851}}</ref> and was followed by further refinements,<ref>{{cite journal | author = Prelog, V. | author-link = Vladimir Prelog | author2 = Helmchen, G. | author2-link = Günter Helmchen | name-list-style = amp | title = Basic Principles of the CIP-System and Proposals for a Revision | journal = [[Angewandte Chemie International Edition]] | volume = 21 | issue = 8 | pages = 567–58  | year = 1982 | doi = 10.1002/anie.198205671}}</ref> before it was incorporated into the rules of the [[IUPAC|International Union of Pure and Applied Chemistry]] (IUPAC), the official body that defines [[IUPAC nomenclature|organic nomenclature]], in 1974.<ref name = IUPAC/>{{rp|26ff}} The rules have since been revised, most recently in 2013,<ref name=IUPAC2013>{{BlueBook2013|rec=9}}</ref> as part of the IUPAC book [[Nomenclature of Organic Chemistry]]. The IUPAC presentation of the rules constitute the official, formal standard for their use, and it notes that "the method has been developed to cover all compounds with ligancy up to 4... and… [extended to the case of] ligancy 6… [as well as] for all configurations and conformations of such compounds."<ref name = IUPAC/>{{rp|26ff}} Nevertheless, though the IUPAC documentation presents a thorough introduction, it includes the caution that "it is essential to study the original papers, especially the 1966 paper, before using the sequence rule for other than fairly simple cases."<ref name = IUPAC/>{{rp|26f}}

A recent paper argues for changes to some of the rules (sequence rules 1b and 2) to address certain molecules for which the correct descriptors were unclear.<ref>{{cite journal |last1=Hanson |first1=Robert M. |last2=Mayfield |first2=John |last3=Vainio |first3=Mikko |last4=Yerin |first4=Andrey |last5=Redkin |first5=Dmitry Vladimirovich |last6=Musacchio |first6=Sophia |title=Algorithmic Analysis of Cahn-Ingold-Prelog Rules of Stereochemistry: Proposals for Revised Rules and a Guide for Machine Implementation |journal=Journal of Chemical Information and Modeling |volume=58 |issue=9 |pages=1755–1765 |date=30 July 2018 |doi=10.1021/acs.jcim.8b00324|pmid=30059222 |s2cid=51876996 |url=https://chemrxiv.org/engage/chemrxiv/article-details/60c73e14337d6ca46ae26282 |url-access=subscription }}</ref> However, a different problem remains: in rare cases, two different stereoisomers of the same molecule can have the same CIP descriptors, so the CIP system may not be able to unambiguously name a stereoisomer, and other systems may be preferable.<ref>{{cite conference |url = https://www.slideshare.net/NextMoveSoftware/cinf-17-comparing-cahningoldprelog-rule-implementations-the-need-for-an-open-cip |access-date = 2020-07-22 |title = Comparing CIP implementations: The need for an open CIP |last1 = Mayfield |first1 = John |last2 = Lowe |first2 = Daniel |last3 = Sayle |first3 = Roger |year = 2017 |conference = Abstracts of papers of the American Chemical Society |volume = 254 }} [https://tpa.acs.org/abstract/acsnm254-2751688/comparing-cip-implementations-the-need-for-an-open-cip Abstract on publisher web site]{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}[[File:Lock-gray-alt-2.svg|9px|link=|alt=Free registration required|Free registration required]]</ref>{{rp|at=27}}