Editing Nucleophile (section)

== Properties ==
In general, in a group across the periodic table, the more basic the ion (the higher the pK<sub>a</sub> of the conjugate acid) the more reactive it is as a nucleophile. Within a series of nucleophiles with the same attacking element (e.g. oxygen), the order of nucleophilicity will follow basicity. Sulfur is in general a better nucleophile than oxygen.{{cn|date=March 2024}}

=== Nucleophilicity ===
Many schemes attempting to quantify relative nucleophilic strength have been devised. The following [[empirical]] data have been obtained by measuring [[reaction rate]]s for many reactions involving many nucleophiles and electrophiles. Nucleophiles displaying the so-called [[alpha effect]] are usually omitted in this type of treatment.{{cn|date=March 2024}}

==== Swain–Scott equation ====
The first such attempt is found in the Swain–Scott equation<ref>{{Cite journal |last=Swain |first=C. Gardner |last2=Scott |first2=Carleton B. |date=January 1953 |title=Quantitative Correlation of Relative Rates. Comparison of Hydroxide Ion with Other Nucleophilic Reagents toward Alkyl Halides, Esters, Epoxides and Acyl Halides 1 |url=https://pubs.acs.org/doi/abs/10.1021/ja01097a041 |journal=Journal of the American Chemical Society |language=en |volume=75 |issue=1 |pages=141–147 |doi=10.1021/ja01097a041 |issn=0002-7863|url-access=subscription }}</ref><ref>{{cite book |doi=10.1351/goldbook.S06201 |doi-access=free |chapter=Swain–Scott equation |title=The IUPAC Compendium of Chemical Terminology |year=2014 }}</ref> derived in 1953:
:<math>\log_{10}\left(\frac{k}{k_0}\right) = sn</math>

This [[free-energy relationship]] relates the [[pseudo first order reaction|pseudo first order]] [[reaction rate constant]] (in water at 25&nbsp;°C), ''k'', of a reaction, normalized to the reaction rate, ''k''<sub>0</sub>, of a standard reaction with water as the nucleophile, to a nucleophilic constant ''n'' for a given nucleophile and a substrate constant ''s'' that depends on the sensitivity of a substrate to nucleophilic attack (defined as 1 for [[methyl bromide]]).

This treatment results in the following values for typical nucleophilic anions: [[acetate]] 2.7, [[chloride]] 3.0, [[azide]] 4.0, [[hydroxide]] 4.2, [[aniline]] 4.5, [[iodide]] 5.0, and [[thiosulfate]] 6.4. Typical substrate constants are 0.66 for [[tosylate|ethyl tosylate]], 0.77 for [[lactone|β-propiolactone]], 1.00 for [[epoxide|2,3-epoxypropanol]], 0.87 for [[benzyl chloride]], and 1.43 for [[benzoyl chloride]].

The equation predicts that, in a [[nucleophilic displacement]] on [[benzyl chloride]], the [[azide]] anion reacts 3000 times faster than water.

==== Ritchie equation ====
The Ritchie equation, derived in 1972, is another free-energy relationship:<ref>{{cite book |doi=10.1351/goldbook.R05402 |doi-access=free |chapter=Ritchie equation |title=The IUPAC Compendium of Chemical Terminology |year=2014 }}</ref><ref>{{Cite journal |last=Ritchie |first=Calvin D. |date=1972-10-01 |title=Nucleophilic reactivities toward cations |url=https://pubs.acs.org/doi/abs/10.1021/ar50058a005 |journal=Accounts of Chemical Research |language=en |volume=5 |issue=10 |pages=348–354 |doi=10.1021/ar50058a005 |issn=0001-4842|url-access=subscription }}</ref><ref>{{Cite journal |last=Ritchie |first=Calvin D. |date=March 1975 |title=Cation-anion combination reactions. XIII. Correlation of the reactions of nucleophiles with esters |url=https://pubs.acs.org/doi/abs/10.1021/ja00838a035 |journal=Journal of the American Chemical Society |language=en |volume=97 |issue=5 |pages=1170–1179 |doi=10.1021/ja00838a035 |issn=0002-7863|url-access=subscription }}</ref>
:<math>\log_{10}\left(\frac{k}{k_0}\right) = N^+</math>

where ''N''<sup>+</sup> is the nucleophile dependent parameter and ''k''<sub>0</sub> the [[reaction rate constant]] for water. In this equation, a substrate-dependent parameter like ''s'' in the Swain–Scott equation is absent. The equation states that two nucleophiles react with the same relative reactivity regardless of the nature of the electrophile, which is in violation of the [[reactivity–selectivity principle]]. For this reason, this equation is also called the ''constant selectivity relationship''.

In the original publication the data were obtained by reactions of selected nucleophiles with selected electrophilic [[carbocation]]s such as [[tropylium]] or [[diazonium]] cations:
:[[File:RichieEquationDiazonium.png|400px|Ritchie equation diazonium ion reactions]]

or (not displayed) ions based on [[malachite green]]. Many other reaction types have since been described.

Typical Ritchie '''N<sup>+</sup>''' values (in [[methanol]]) are: 0.5 for [[methanol]], 5.9 for the [[cyanide]] anion, 7.5 for the [[methoxide]] anion, 8.5 for the [[azide]] anion, and 10.7 for the [[thiophenol]] anion. The values for the relative cation reactivities are −0.4 for the malachite green cation, +2.6 for the [[benzenediazonium cation]], and +4.5 for the [[tropylium cation]].

==== Mayr–Patz equation ====
In the Mayr–Patz equation (1994):<ref>{{cite journal | doi = 10.1002/anie.199409381| title = Scales of Nucleophilicity and Electrophilicity: A System for Ordering Polar Organic and Organometallic Reactions| journal = Angewandte Chemie International Edition in English| volume = 33| issue = 9| pages = 938| year = 1994| last1 = Mayr| first1 = Herbert| last2 = Patz| first2 = Matthias}}</ref>
:<math>\log(k) = s(N + E)</math>

The [[rate law|second order]] [[reaction rate constant]] ''k'' at 20&nbsp;°C for a reaction is related to a nucleophilicity parameter ''N'', an electrophilicity parameter ''E'', and a nucleophile-dependent slope parameter ''s''. The constant ''s'' is defined as 1 with [[2-methyl-1-pentene]] as the nucleophile.

Many of the constants have been derived from reaction of so-called [[benzhydrylium ion]]s as the [[electrophile]]s:<ref>{{cite journal | doi = 10.1021/ja010890y| pmid = 11572670| title = Reference Scales for the Characterization of Cationic Electrophiles and Neutral Nucleophiles | journal = Journal of the American Chemical Society| volume = 123| issue = 39| pages = 9500–12| year = 2001| last1 = Mayr| first1 = Herbert| last2 = Bug| first2 = Thorsten| last3 = Gotta| first3 = Matthias F| last4 = Hering| first4 = Nicole| last5 = Irrgang| first5 = Bernhard| last6 = Janker| first6 = Brigitte| last7 = Kempf| first7 = Bernhard| last8 = Loos| first8 = Robert| last9 = Ofial| first9 = Armin R| last10 = Remennikov| first10 = Grigoriy| last11 = Schimmel| first11 = Holger| s2cid = 8392147}}</ref>
:[[File:Benzhydryliumion.png|150px|benzhydrylium ions used in the determination of Mayr–Patz equation]]

and a diverse collection of π-nucleophiles:
:[[File:MayrNucleophiles.png|300px|Nucleophiles used in the determination of Mayr–Patz equation, X = tetrafluoroborate anion]].

Typical E values are +6.2 for R = [[chlorine]], +5.90 for R = [[hydrogen]], 0 for R = [[methoxy]] and −7.02 for R = [[dimethylamine]].

Typical N values with s in parentheses are −4.47 (1.32) for [[electrophilic aromatic substitution]] to [[toluene]] (1), −0.41 (1.12) for [[electrophilic addition]] to 1-phenyl-2-propene (2), and 0.96 (1) for addition to 2-methyl-1-pentene (3), −0.13 (1.21) for reaction with triphenylallylsilane (4), 3.61 (1.11) for reaction with [[2-methylfuran]] (5), +7.48 (0.89) for reaction with isobutenyltributylstannane (6) and +13.36 (0.81) for reaction with the [[enamine]] 7.<ref>An internet database for reactivity parameters maintained by the Mayr group is available at http://www.cup.uni-muenchen.de/oc/mayr/</ref>

The range of organic reactions also include [[SN2 reaction]]s:<ref name=Mayr2006>{{cite journal | doi = 10.1002/anie.200600542| pmid = 16646102| title = Towards a General Scale of Nucleophilicity?| journal = Angewandte Chemie International Edition| volume = 45| issue = 23| pages = 3869–74| year = 2006| last1 = Phan| first1 = Thanh Binh| last2 = Breugst| first2 = Martin| last3 = Mayr| first3 = Herbert| citeseerx = 10.1.1.617.3287}}</ref>
:[[File:Mayr2006.png|400px|Mayr equation also includes SN2 reactions]]

With E = −9.15 for the ''S-methyldibenzothiophenium ion'', typical nucleophile values N (s) are 15.63 (0.64) for [[piperidine]], 10.49 (0.68) for [[methoxide]], and 5.20 (0.89) for water. In short, nucleophilicities towards sp<sub>2</sub> or sp<sub>3</sub> centers follow the same pattern.

==== Unified equation ====
In an effort to unify the above described equations the Mayr equation is rewritten as:<ref name=Mayr2006 />
:''<math>\log(k) = s_Es_N(N + E)</math>''

with s<sub>E</sub> the electrophile-dependent slope parameter and s<sub>N</sub> the nucleophile-dependent slope parameter. This equation can be rewritten in several ways:
* with s<sub>E</sub> = 1 for carbocations this equation is equal to the original Mayr–Patz equation of 1994,
* with s<sub>N</sub> = 0.6 for most n nucleophiles the equation becomes
::<math>\log(k) = 0.6s_EN + 0.6s_EE</math>
:''or the original Scott–Swain equation written as:''
::<math>\log(k) = \log(k_0) + s_EN</math>
* with s<sub>E</sub> = 1 for carbocations and s<sub>N</sub> = 0.6 the equation becomes:
::<math>\log(k) = 0.6N + 0.6E</math>
:or the original Ritchie equation written as:
::<math>\log(k) - \log(k_0) = N^+</math>