Editing Free-radical addition

{{Short description|Organic addition reaction which involves free radicals}}
{{Use dmy dates|date=December 2023}}

In [[organic chemistry]], '''free-radical addition''' is an [[addition reaction]] which involves [[free radical]]s.  These reactions can happen due to the free radicals having an unpaired electron in their valence shell, making them highly reactive. <ref>{{Cite web |last=McMurry |first=John |last2=Emeritus |first2=Professor |date=2023-09-20 |title=6.6 Radical Reactions - Organic Chemistry {{!}} OpenStax |url=https://openstax.org/books/organic-chemistry/pages/6-6-radical-reactions |access-date=2024-10-07 |website=openstax.org |language=English}}</ref> Radical additions are known for a variety of unsaturated substrates, both olefinic or aromatic and with or without heteroatoms.

Free-radical reactions depend on one or more relatively weak [[Chemical bond|bonds]] in a reagent.  Under reaction conditions (typically heat or light), some weak bonds [[homolysis (chemistry)|homolyse]] into radicals, which then induce further decomposition in their compatriots before recombination.  Different mechanisms typically apply to reagents without such a weak bond.

== Mechanism and regiochemistry ==
[[File:Peroxide_Free-radical-addition.png|thumb|619x619px|{{Visible anchor|Radical hydrobromination}} of an alkene]]
The basic steps in any free-radical process (the radical chain [[Reaction mechanism|mechanism]]) divide into:<ref name=Wade />
* [[radical initiator|Radical initiation]]: A radical is created from a non-radical precursor.
* [[Chain propagation]]: A radical reacts with a non-radical to produce a new radical species
* [[Chain termination]]: Two radicals react with each other to create a non-radical species

In a free-radical addition, there are two chain propagation steps.  In one, the adding radical attaches to a [[Multiple bond|multiply-bonded]] precursor to give a radical with lesser bond order.  In the other, the newly-formed radical product abstracts another substituent from the adding reagent to regenerate the adding radical.<ref name="March" />{{Rp|pages=743–744}}

In general, the adding radical attacks the alkene at the [[Steric effects|most sterically accessible]] (typically, least substituted) carbon; the radical then stabilizes on the [[Markovnikov's rule|more substituted]] carbon.<ref name="March" />{{Rp|pages=188,751}}  The result is typically anti-[[Markovnikov's rule|Markovnikov]] addition, a phenomenon [[Morris Kharasch]] called the "peroxide effect".<ref name="Kharasch" /> Reaction is slower with alkynes than alkenes.<ref name="March" />{{Rp|page=750}}

In [[Free-radical addition#Radical hydrobromination|the paradigmatic example]], [[hydrogen bromide]] radicalyzes to monatomic bromine.  These bromine atoms add to an alkene at the most accessible site, to give a bromoalkyl radical, with the radical on the more substituted carbon.  That radical then abstracts a hydrogen atom from another HBr molecule to regenerate the monatomic bromine and continue the reaction.<ref name="March" />{{Rp|page=758}}

== Compounds that add radically ==
{{See also|Hydrohalogenation}}
Radical addition of [[hydrogen bromide]] is a valuable synthetic technique for anti-Markovnikov carbon substitution,{{Citation needed|date=November 2023}}<!-- Some possible citation sources: 
* E. Jolles (ed.): Bromine and its Compounds, Academic Press, New York 1966.
* S. Patai (ed.): The Chemistry of the Carbon–Halogen Bond, part 1 & 2, J. Wiley & Sons, New York 1973.
* A. Roedig et al. in E. Müller (ed.): Houben-Weyl Methoden der Organische Chemie, vol. v/4, George Thieme, Stuttgart 1960, pp. 13–516, 679–775.
* W.K.R. Musgrave, vol. 1 A, p. 478; W.J. Feast, W.K.R. Musgrave, vol. 3 A, p. 241, both in S. Coffey (ed.): Rodds Chemistry of Carbon Compounds, 2nd ed., Elsevier, Amsterdam 1964, 1971, respectively.
* W.J. Feast, vol. 1 AB, p. 31; vol. 3A, p. 141, in M.F. Ansell (ed.): Rodds Chemistry of Carbon Compounds, 2nd ed. supplement, Elsevier, Amsterdam 1975, 1983, respectively.
* R.D. Chambers, S.R. James in D. Barton, W.D. Ollis (eds.): Comprehensive Organic Chemistry, vol. 1, Pergamon, Oxford 1979, p. 493.
* J. Hoyle in S. Patai (ed.): The Chemistry of Halides, Pseudo-halides and Azides, part 1, J. Wiley & Sons, New York 1995, p. 222. DOI: 10.1002/9780470682531.pat0013. --> but free-radical addition does not occur with the other hydrohalic acids.  Radical formation from HF, HCl, or HI is extremely [[endothermic]] and chemically disfavored.<ref name="March" />{{Rp|pages=692–694}}  Hydrogen bromide is incredibly selective as a reagent,<ref name="March" />{{Rp|pages=687–688}} and does not produce detectable quantities of polymeric byproducts.<ref name="OrgRxn" />{{Rp|page=156–157}}

The behavior of hydrogen bromide generalizes in two separate directions.  Halogenated compounds with a relatively stable radical can dissociate from the halogen.  Thus, for example, [[Sulfonyl halide|sulfonyl]], [[Sulfenyl halide|sulfenyl]], and other sulfur halides can add radically to give respectively β{{nbh}}halo sulfones, sulfoxides, or sulfides<!--thiiranes?-->.<ref name="OrgRxn" />{{Rp|pages=200,204,206}}

Separately, unsubsituted compounds with a relative stable radical can dissociate from hydrogen.  In general, these reactions risk polymerized byproducts (see {{Slink||Side reactions}}).  For example, in the [[thiol-ene reaction]], [[thiol]]s,<ref name="OrgRxn" />{{Rp|pages=165–166}} [[disulfide]]s,<ref name="OrgRxn" />{{Rp|pages=207}} and [[hydrogen sulfide]]<ref name="OrgRxn" />{{Rp|page=191}} add across a double bond.  But if the unsaturated substrate polymerizes easily, they catalyze polymerization instead.<ref name="OrgRxn" />{{Rp|pages=171–172}}  In thermal [[Silanes|silane]] additions, telomerization usually proceeds to about 6 units.<ref name="OrgRxn" />{{Rp|page=211}}

In the case of silicon, germanium, or phosphorus, the energetics are unfavorable unless the heavy atom bears a pendant hydrogen.<ref name="OrgRxn" />{{Rp|pages=209,217–219}}  Other electronegative substituents on silicon appear to reduce the barrier.<ref name="OrgRxn" />{{Rp|pages=213,217–224}}

Although nitrogen oxides naturally radicalize, careful control of the radical species is difficult.  [[Dinitrogen tetroxide]] adds to give a mixture: a [[Vicinal (chemistry)|vicinal]] dinitro compound, but also a [[Nitro compound|nitro substituent]] adjacent to a [[nitrite ester]].<ref name="OrgRxn" />{{Rp|page=225}}

== To aryl radicals ==
{{See also|Radical substitution}}
Although aromatic [[Resonance (chemistry)|resonance]] stabilizes [[aryl radical]]s, bonds between arenes and their substituents are (in)famously strong.  Radical reactions with arenes typically present [[Retrosynthetic analysis|retrosynthetically]] as instances of [[nucleophilic aromatic substitution]],{{Citation needed|date=November 2023}} because generating the aryl radical requires a strong (radical) leaving group.<ref name="March" />{{Rp|pages=686–687}}  One example is the [[Meerwein arylation]].

== Side reactions ==
A radical addition which leaves an [[Alkene|unsaturated]] product can undergo [[radical cyclization]] between the two propagation steps.<ref name="March" />{{Rp|page=744}}  In general, radical additions can also start [[radical polymerization]] processes.<ref name="OrgRxn" />{{Rp|pages=171–172}}

==With stable inorganic radicals==
[[File:Self_terminating_radical_cylization,_updated.png|alt=A self-terminating radical cyclization reaction scheme|thumb|600x600px|{{vanchor|Self-terminating oxidative radical cyclization}}]]
In '''self-terminating oxidative radical cyclization''', [[Inorganic compound|inorganic]] radicals oxidize [[alkyne]]s to [[ketone]]s through an [[Intramolecular reaction|intramolecular]] [[radical cyclization]].  This reaction is not catalytic, and requires the oxidized radical source in [[stoichiometry|stoichiometric]] amounts.  In effect, the radical species is [[synthon|synthetically equivalent]] to [[monatomic oxygen]].<ref name="SelfTerm" />

In [[#Self-terminating oxidative radical cyclization|the paradigmatic example]], a [[nitrate]] radical (from [[photolysis]] of [[ammonium cerium(IV) nitrate|ceric ammonium nitrate]]) adds to an [[alkyne]] to generate a very reactive [[Vinyl ester|vinyl nitrate ester]] radical.  The vinyl radical [[hydrogen atom transfer|abstracts an intramolecular hydrogen atom]] 5 atoms away before [[Baldwin's rules|5-''exo''-trig ring-closure]].  The resulting [[alkyl nitrate]] radical can then [[Fragmentation (chemistry)|fragment]] to a [[ketone]] and the stable radical [[nitrogen dioxide]].<ref name="SelfTerm" />

[[Sulfate]] (from [[ammonium persulfate]]) and [[hydroxyl]] radicals show similar reactivity.<ref name="SelfTerm" />

==See also==
The other radical reactions: 
* [[radical substitution]] 
* [[radical polymerization]]
* [[free-radical halogenation]]
{{Clear}}

==References==
<references>
<ref name=SelfTerm>Dreessen, Tim; Jargstorff, Christian; Lietzau, Lars; Plath, Christian; Stademann, Arne; and Wille, Uta (2004).  "[http://www.mdpi.org/molecules/papers/90600480.pdf Self-Terminating, Oxidative Radical Cyclizations]".  [[Molecules (journal)|''Molecules'']], issue&nbsp;9, pp.&nbsp;480–497.</ref>  
<ref name=Kharasch>{{cite journal |last1=Kharasch |first1=M. S. |last2=Mayo |first2=Frank R. |year=1933 |title=The Peroxide Effect in the Addition of Reagents to Unsaturated Compounds. I. The Addition of Hydrogen Bromide to Allyl Bromide |journal=Journal of the American Chemical Society |volume=55 |issue=6 |pages=2468–2496 |doi=10.1021/ja01333a041}}</ref>
<ref name=March>{{March4th}}</ref>
<ref name=OrgRxn>{{Cite book |last=Stacey |first=F.&nbsp;W. |title=Organic Reactions |title-link=Organic Reactions |last2=Harris |first2=((J.&nbsp;F., Jr.)) |date=2004-04-30 |publisher=Wiley |isbn=978-0-471-26418-7 |editor-last=Denmark |editor-first=Scott E. |edition=1 |language=en |chapter=Formation of carbon-hetero atom bonds by free-radical chain additions to carbon-carbon multiple bonds |doi=10.1002/0471264180.or013.04}}</ref>
<ref name=Wade>L.G. Wade's Organic Chemistry 5th Ed. (p 319) – Mechanism supplements original.</ref>
</references>

{{Reaction mechanisms}}

{{DEFAULTSORT:Free Radical Addition}}
[[Category:Addition reactions]]
[[Category:Free radical reactions]]
[[Category:Reaction mechanisms]]