View source for Grignard reagent

{{Short description|Organometallic compounds used in organic synthesis}}
[[File:Methylmagnesium-chloride-THF-3D-balls.png|thumb|right|Usually Grignard reagents are written as R-Mg-X, but in fact the magnesium(II) centre is tetrahedral when dissolved in [[Lewis basic]] solvents, as shown here for the bis-adduct of methylmagnesium chloride and THF.]]

'''Grignard reagents''' or '''Grignard compounds''' are  [[chemical compound]]s with the general formula {{chem2|R\sMg\sX}}, where X is a [[halogen]] and R is an organic [[functional group|group]], normally an [[alkyl]] or [[aryl]].  Two typical examples are [[methylmagnesium chloride]] {{chem2|Cl\sMg\sCH3}} and [[phenylmagnesium bromide]] {{chem2|(C6H5)\sMg\sBr}}. They are a subclass of the [[organomagnesium compound]]s.

Grignard compounds are popular reagents in [[organic synthesis]] for creating new [[carbon–carbon bond]]s. For example, when reacted with another halogenated compound {{chem2|R'\sX'}} in the presence of a suitable [[catalysis|catalyst]], it typically yield {{chem2|R\sR'}} and the magnesium halide {{chem2|MgXX'}} as a byproduct; and the latter is insoluble in the solvents normally used.

Grignard reagents are rarely isolated as solids.  Instead, they are normally handled as solutions in solvents such as [[diethyl ether]] or [[tetrahydrofuran]] using [[air-free technique]]s. Grignard reagents are [[coordination complex|complex]] with the magnesium atom bonded to two [[ether]] [[ligand]]s as well as the halide and organyl ligands.

The discovery of the [[Grignard reaction]] in 1900 was recognized with the Nobel Prize awarded to [[Victor Grignard]] in 1912.

==Synthesis==

=== From Mg metal===
Traditionally Grignard reagents are prepared by treating an organic halide (normally organobromine) with magnesium metal. [[Ether]]s are required to stabilize the [[organomagnesium compound]].  Water and air, which rapidly destroy the reagent by [[protonolysis]] or oxidation, are excluded.<ref>{{cite journal| doi = 10.1021/ja01331a065 | title = The Oxidation of Grignard Reagents | year = 1933 | last1 = Goebel | first1 = M. T. | last2 = Marvel | first2 = C. S. | journal = Journal of the American Chemical Society | volume = 55 | issue = 4 | pages = 1693–1696| bibcode = 1933JAChS..55.1693G }}</ref>  Although the reagents still need to be dry, ultrasound can allow Grignard reagents to form in wet solvents by activating the magnesium such that it consumes the water.<ref>{{cite journal| doi = 10.1021/ed076p1427 | title = Grignard Reactions in "Wet" Ether | year = 1999 | last1 = Smith | first1 = David H. | journal = Journal of Chemical Education | volume = 76 | pages = 1427 | issue = 10|bibcode = 1999JChEd..76.1427S }}</ref>

As is common for reactions involving solids and solution, the formation of Grignard reagents is often subject to an [[induction period]]. During this stage, the passivating oxide on the magnesium is removed.  After this induction period, the reactions can be highly [[exothermic]]. This exothermicity must be considered when a reaction is scaled-up from laboratory to production plant.<ref>{{cite book| title = Handbook of Grignard reagents |editor1=Gary S. Silverman |editor2=Philip E. Rakita | author = Philip E. Rakita | chapter = 5. Safe Handling Practices of Industrial Scale Grignard Ragents | pages = 79–88 | chapter-url = https://books.google.com/books?id=82CaxfY-uNkC&pg=PA80 | chapter-format = [[Google Books]] excerpt | year = 1996 | isbn = 0-8247-9545-8 | publisher = [[CRC Press]]}}</ref>
Most organohalides will work, but [[carbon-fluorine bond]]s are generally unreactive, except with specially activated magnesium (through [[Rieke metal]]s).

==== Magnesium ====
Typically the reaction to form Grignard reagents involves the use of magnesium ribbon.  All magnesium is coated with a  [[Passivation (chemistry)|passivating]]  layer of [[magnesium oxide]], which inhibits reactions with the organic halide. Many methods have been developed to weaken this [[Passivation (chemistry)|passivating]] layer, thereby exposing highly reactive magnesium to the organic halide.  Mechanical methods include crushing of the Mg pieces in situ, rapid stirring, and [[sonication]].<ref>{{cite journal|last=Smith|first=David H.|title=Grignard Reactions in "Wet" Ether|journal=Journal of Chemical Education|year=1999|volume=76|issue=10|pages=1427|doi=10.1021/ed076p1427|bibcode = 1999JChEd..76.1427S }}</ref>  [[Iodine]], [[methyl iodide]], and [[1,2-dibromoethane]] are common activating agents.  The use of 1,2-dibromoethane is advantageous as its action can be monitored by the observation of bubbles of [[ethylene]].  Furthermore, the side-products are innocuous:
:{{chem2|Mg  +  BrC2H4Br ->  C2H4  +  MgBr2}}
The amount of Mg consumed by these activating agents is usually insignificant. A small amount of [[mercuric chloride]] will [[amalgam (chemistry)|amalgamate]] the surface of the metal, enhancing its reactivity.  Addition of preformed Grignard reagent is often used as the initiator.

Specially activated magnesium, such as [[Rieke metals|Rieke magnesium]], circumvents this problem.<ref name=Science>{{cite journal| author=Rieke, R. D.|title=Preparation of Organometallic Compounds from Highly Reactive Metal Powders|journal= [[Science (journal)|Science]]|year= 1989|volume= 246| pages= 1260–1264|doi=10.1126/science.246.4935.1260| pmid=17832221| issue=4935|bibcode = 1989Sci...246.1260R |s2cid=92794 }}</ref> The oxide layer can also be broken up using ultrasound, using a stirring rod to scratch the oxidized layer off,<ref>{{cite book|author1=Clayden, Jonathan|author2=Greeves, Nick|title=Organic chemistry|year=2005|publisher=Oxford Univ. Press|location=Oxford|isbn=978-0-19-850346-0|pages=[https://archive.org/details/organicchemistry00clay_0/page/212 212]|url-access=registration|url=https://archive.org/details/organicchemistry00clay_0/page/212}}</ref> or by adding a few drops of iodine or [[1,2-Diiodoethane]]. Another option is to use sublimed magnesium or [[magnesium anthracene]].<ref>{{cite book|author1 = Wakefield, Basil J. | title=Organomagnesium Methods in Organic Chemistry | year=1995 | publisher=Academic Press | isbn=0080538177 | pages=21–25}}</ref>

"Rieke magnesium" is prepared by a [[redox|reduction]] of an [[anhydrous]] [[magnesium chloride]] with a [[potassium]]:
:{{chem2|MgCl2 + 2 K -> Mg + 2 KCl}}

====Mechanism====
In terms of mechanism, the reaction proceeds through [[single electron transfer]]:<ref>Garst, J. F.; Ungvary, F. "Mechanism of Grignard reagent formation". In ''Grignard Reagents''; Richey, R. S., Ed.; John Wiley & Sons: New York, 2000; pp 185–275. {{ISBN|0-471-99908-3}}.</ref><ref>''Advanced Organic chemistry Part B: Reactions and Synthesis'' F.A. Carey, R.J. Sundberg 2nd Ed. 1983. Page 435</ref><ref>Garst, J.F.; Soriaga, M.P. "Grignard reagent Formation", Coord. Chem. Rev. '''2004''', 248, 623 - 652. doi:10.1016/j.ccr.2004.02.018.</ref>

<math chem="" display="block">\begin{align}
 \ce{R-X {}+ Mg} &\longrightarrow  \ce{[R-X^\bullet]^- {}+ [Mg^\bullet]+} \\
 \ce{[R-X^\bullet]-} &\longrightarrow \ce{R^\bullet {}+ X-} \\
 \ce{R^\bullet {}+ [Mg^\bullet]+} &\longrightarrow \ce{R-Mg+} \\
 \ce{R-Mg+ {}+ X-} &\longrightarrow \ce{R-MgX}
\end{align} 
</math>

===Mg transfer reaction (halogen–Mg exchange)===
An alternative preparation of Grignard reagents involves transfer of Mg from a preformed Grignard reagent to an organic halide.  Other organomagnesium reagents are used as well.<ref>{{cite journal |doi=10.15227/orgsyn.089.0460|first1=Juan D.|last1=Arredondo|first2=Hongmei|last2=Li|first3=Jaume|last3=Balsells|
title=Preparation of t-Butyl-3-Bromo-5-Formylbenzoate Through Selective Metal-Halogen Exchange Reactions|journal=Organic Syntheses|year=2012|volume=89|page=460|doi-access=free}}</ref> This method offers the advantage that the Mg transfer tolerates many functional groups.  An illustrative reaction involves [[isopropylmagnesium chloride]] and aryl bromide or iodides:<ref name=":0">{{cite journal | last1 = Knochel | first1 = P. | last2 = Dohle | first2 = W. | last3 = Gommermann | first3 = N. | last4 = Kneisel | first4 = F. F. | last5 = Kopp | first5 = F. | last6 = Korn | first6 = T. | last7 = Sapountzis | first7 = I. | last8 = Vu | first8 = V. A. | year = 2003 | title = Highly Functionalized Organomagnesium Reagents Prepared through Halogen–Metal Exchange | journal = Angewandte Chemie International Edition | volume = 42 | issue = 36| pages = 4302–4320 | doi = 10.1002/anie.200300579 | pmid=14502700}}</ref>
:{{chem2|''i''\-PrMgCl  +  ArBr   ->  ''i''\-PrCl  +  ArMgBr}}

===From alkylzinc compounds (reductive [[transmetalation]])===
A further method to synthesize Grignard reagents involves reaction of Mg with an [[organozinc compound]].  This method has been used to make [[adamantane]]-based Grignard reagents, which are, due to C-C coupling side reactions, difficult to make by the conventional method from the alkyl halide and Mg. The reductive [[transmetalation]] achieves:<ref>{{cite journal | last1 = Armstrong | first1 = D. | last2 = Taullaj | first2 = F. | last3 = Singh | first3 = K. | last4 = Mirabi | first4 = B. | last5 = Lough | first5 = A. J. | last6 = Fekl | first6 = U. | year = 2017 | title = Adamantyl Metal Complexes: New Routes to Adamantyl Anions and New Transmetallations | journal = Dalton Transactions | volume = 46 | issue = 19| pages = 6212–6217 | doi = 10.1039/C7DT00428A | pmid = 28443859 }}</ref> 
:AdZnBr + Mg  →  AdMgBr  +  Zn

==Testing Grignard reagents ==
Because Grignard reagents are so sensitive to moisture and oxygen, many methods have been developed to test the quality of a batch.  Typical tests involve titrations with weighable, anhydrous protic reagents, e.g. [[menthol]] in the presence of a color-indicator.  The interaction of the Grignard reagent with [[phenanthroline]] or 2,2'-biquinoline causes a color change.<ref>{{cite journal | last1 = Krasovskiy | first1 = Arkady | last2 = Knochel | first2 = Paul | year = 2006| title = Convenient Titration Method for Organometallic Zinc, Harshal ady Magnesium, and Lanthanide Reagents | journal = Synthesis | volume = 2006 | issue = 5| pages = 890–891 | doi = 10.1055/s-2006-926345}}</ref>

==Reactions of Grignard reagents==
{{Use mdy dates|date=January 2019}}
{{Reactionbox|Name=Grignard reagent reactions|Type=Coupling reaction|NamedAfter=[[Victor Grignard]]|Section3={{Reactionbox Identifiers
   | OrganicChemistryNamed = 
   | RSC_ontology_id = 
 }}|Reaction={{Reactionbox Reaction
   | Reactant1 =  Carbon [[electrophile]]s
   | Reactant2 = R-MgX
   | Reagent1= (H<sub>3</sub>O<sup>+</sup>)
   | Product1 = Coupling Product
}}|BoxWidth=25%}}

=== As nucleophiles ===
Grignard reagents react with a variety of [[carbonyl]] derivatives.<ref>{{OrgSynth | title = Butyric acid, α-methyl- | author = Henry Gilman and R. H. Kirby | collvol = 1 | collvolpages = 361 | year = 1941 | prep = cv1p0361}}</ref>
[[File:Grignard with carbonyl.png|center|600px|Reactions of Grignard reagents with carbonyls]]

The most common application of Grignard reagents is the alkylation of aldehydes and ketones, i.e. ''the'' [[Grignard reaction]]:<ref name="Haugan1997">{{cite journal|last1=Haugan|first1=Jarle André|year=1997|title=Total Synthesis of C31-Methyl Ketone Apocarotenoids 2: The First Total Synthesis of (3''R'')-Triophaxanthin|journal=Acta Chemica Scandinavica|volume=51|pages=1096–1103|url=http://actachemscand.dk/pdf/acta_vol_51_p1096-1103.pdf|access-date=2009-11-26|doi=10.3891/acta.chem.scand.51-1096|last2=Songe|first2=Pål|last3=Rømming|first3=Christian|last4=Rise|first4=Frode|last5=Hartshorn|first5=Michael P.|last6=Merchán|first6=Manuela|last7=Robinson|first7=Ward T.|last8=Roos|first8=Björn O.|last9=Vallance|first9=Claire|last10=Wood|first10=Bryan R.|doi-access=free}}</ref>
[[File:GrignardReactionVinylation.png|400px|center|Reaction of {{chem2|CH3C(\dO)CH(OCH3)2}} with {{chem2|H2C\dCHMgBr}}]]
Note that the [[acetal]] functional group (a protected carbonyl) does not react.

Such reactions usually involve an aqueous acidic workup, though this step is rarely shown in reaction schemes.  In cases where the Grignard reagent is adding to an aldehyde or a [[prochiral]] ketone, the [[Asymmetric induction|Felkin-Anh model or Cram's Rule]] can usually predict which stereoisomer will be formed.  With easily deprotonated 1,3-[[diketone]]s and related acidic substrates, the Grignard reagent RMgX functions merely as a base, giving the [[enolate]] anion and liberating the alkane RH.

Grignard reagents also react with many "carbonyl-like" compounds and other electrophiles:
[[File:Grignard with others.png|center|500px|Reactions of Grignard reagents with various electrophiles]]

Grignard reagents are [[nucleophile]]s in [[nucleophilic aliphatic substitution]]s for instance with [[alkyl halide]]s in a key step in industrial [[Naproxen]] production:
[[File:Naproxen synthesis.png|center|550px|Naproxen synthesis]]

In the [[Bruylants reaction]], a nitrile can be replaced by the Grignard nucleophile, rather than the Grignard attacking the nitrile to form an imino structure.<ref>{{cite journal|doi=10.1021/ol0059908 |title=Synthesis of α-Substituted Allylic Amines via a Modified Bruylants Reaction |date=2000 |last1=Agami |first1=Claude |last2=Couty |first2=François |last3=Evano |first3=Gwilherm |journal=Organic Letters |volume=2 |issue=14 |pages=2085–2088 |pmid=10891236 }}</ref>

===Reactions as a base===
Grignard reagents serve as a base for non-protic substrates (this scheme does not show workup conditions, which typically includes water).  Grignard reagents are basic and react with alcohols, phenols, etc. to give [[alkoxide]]s (ROMgBr). The phenoxide derivative is susceptible to formylation by [[paraformaldehyde]] to give [[salicylaldehyde]].<ref>{{Cite journal | doi = 10.1021/ed083p290| title = A Multistep Synthesis for an Advanced Undergraduate Organic Chemistry Laboratory| journal = Journal of Chemical Education| volume = 83| issue = 2| pages = 290| year = 2006| last1 = Peters | first1 = D. G. | last2 = Ji | first2 = C. | bibcode = 2006JChEd..83..290P}}</ref>

===Alkylation of metals and metalloids===
Like [[organolithium compound]]s, Grignard reagents are useful for forming carbon–heteroatom bonds.

<math chem title="Reactions of Grignard reagents with non carbon electrophiles" display=block>
\begin{matrix}
\ce{R4B-}\\
{\color{White}\scriptstyle\ce{Et2O.BF3\ or\ NaBF4}}\Bigg\uparrow\scriptstyle\ce{Et2O.BF3\ or\ NaBF4}\\
\ce{Ph2PR <-[\ce{Ph2PCl}] RMgX ->[\ce{Bu3SnCl}] Bu3SnR}\\
{\color{White}\scriptstyle\ce{B(OMe)3}}\Bigg\downarrow\scriptstyle\ce{B(OMe)3}\\
\ce{RB(OMe)2}
\end{matrix}
</math>
Grignard reagents react with many metal-based electrophiles.  For example, they undergo [[transmetallation]] with [[cadmium chloride]] (CdCl<sub>2</sub>) to give [[Organocadmium compound|dialkylcadmium]]:<ref>{{cite book|title=Chemistry Part II Textbook for class XII|year=2010|isbn=978-81-7450-716-7|pages=355|volume=2|chapter=Unit 12 Aldehydes, Ketones and Carboxylic Acids|publisher=National Council of Educational Research and Training|location=India|chapter-url=http://ncertbooks.prashanthellina.com/class_12.Chemistry.ChemistryII/Unit%2012.pdf|access-date=2019-03-09|archive-date=2018-09-20|archive-url=https://web.archive.org/web/20180920172337/http://ncertbooks.prashanthellina.com/class_12.Chemistry.ChemistryII/Unit%2012.pdf|url-status=dead}}</ref>
:{{chem2|2 RMgX + CdCl2 -> R2Cd + 2 Mg(X)Cl}}

=== Schlenk equilibrium===
Most Grignard reactions are conducted in ethereal solvents, especially [[diethyl ether]] and [[Tetrahydrofuran|THF]]. Grignard reagents react with [[1,4-Dioxane|1,4-dioxane]] to give the diorganomagnesium compounds and insoluble coordination polymer {{chem2|MgX2(dioxane)2}} and  (R = organic group, X = halide):
:{{chem2|2 RMgX  +  dioxane  <->  R2Mg  +  MgX2(dioxane)2}}
This reaction exploits the [[Schlenk equilibrium]], driving it toward the right.

===Precursors to magnesiates===
Grignard reagents react with organolithium compounds to give [[ate complex]]es (Bu = butyl):<ref>{{cite journal |doi=10.15227/orgsyn.089.0460|title=Preparation of t-Butyl-3-Bromo-5-Formylbenzoate Through Selective Metal-Halogen Exchange Reactions|journal=Organic Syntheses|year=2012|volume=89|page=460|first1=Juan D. |last1=Arredondo|first2=Hongmei|last2=Li|first3=Jaume|last3=Balsells
|doi-access=free}}</ref>
:{{chem2|BuMgBr  + 3 BuLi  ->  LiMgBu3  +  BuBr}}

===Coupling with organic halides===
Grignard reagents do ''not'' typically react with organic halides, in contrast with their high reactivity with other main group halides.  In the presence of metal catalysts, however, Grignard reagents participate in C-C [[coupling reaction]]s. For example, nonylmagnesium bromide reacts with methyl ''p''-chlorobenzoate to give ''p''-nonylbenzoic acid, in the presence of [[Tris(acetylacetonato)iron(III)]] (Fe(acac)<sub>3</sub>), after workup with [[Sodium hydroxide|NaOH]] to [[Hydrolysis|hydrolyze]] the [[ester]], shown as follows. Without the Fe(acac)<sub>3</sub>, the Grignard reagent would attack the [[ester]] [[functional group|group]] over the [[aryl halide]].<ref>{{OrgSynth | title = 4-Nonylbenzoic Acid | author = A. Fürstner, A. Leitner, G. Seidel | year = 2004 | volume = 81 | pages = 33–42 | prep = v81p0033}}</ref>

[[File:4nonylbenzoicacidSynthesis.svg|center|4-nonylbenzoicacid synthesis using a grignard reagent]]

For the coupling of aryl halides with aryl Grignard reagents, [[nickel chloride]] in [[tetrahydrofuran]] (THF) is also a good catalyst. Additionally, an effective catalyst for the couplings of alkyl halides is the [[Gilman reagent|Gilman catalyst]] [[lithium tetrachlorocuprate]] ({{chem2|Li2CuCl4}}), prepared by mixing [[lithium chloride]] (LiCl) and [[copper(II) chloride]] ({{chem2|CuCl2}}) in THF. The [[Kumada-Corriu coupling]] gives access to [substituted] [[styrene]]s.

===Oxidation===
Treatment of a Grignard reagent with oxygen gives the magnesium organoperoxide. Hydrolysis of this material yields [[hydroperoxide]]s or alcohol.  These reactions involve [[radical (chemistry)|radical]] intermediates.

<math chem title="Grignard oxygen oxidation pathways" display=block>
\begin{array}{lcrll}
\ce{{R-MgX} + O2 ->}\ {\color{Red}\ce{{R^\bullet} + [O2^\bullet]-}} + \ce{MgX+ ->} & \ce{R-O-O-MgX} & {\color{Gray}+\ \ce{H3O+}} & \ce{-> {R-O-O-H}} &{\color{Gray}+\ \ce{{HO-MgX} + H+}}\\
& \Bigg\downarrow \ce{R-MgX} \\
& \ce{R-O-MgX} & {\color{Gray}+\ \ce{H3O+}} &\ce{-> {R-O-H}} &{\color{Gray}+\ \ce{{HO-MgX} + H+}}\\
\end{array}
</math>

The simple oxidation of Grignard reagents to give alcohols is of little practical importance as yields are generally poor. In contrast, two-step sequence via a borane (''vide supra'') that is subsequently oxidized to the alcohol with hydrogen peroxide is of synthetic utility.

The synthetic utility of Grignard oxidations can be increased by a reaction of Grignard reagents with oxygen in presence of an [[alkene]] to an ethylene extended [[Alcohol (chemistry)|alcohol]].<ref>{{cite journal| title = Air-Assisted Addition of Grignard Reagents to Olefins. A Simple Protocol for a Three-Component Coupling Process Yielding Alcohols |author1=Youhei Nobe |author2=Kyohei Arayama |author3=Hirokazu Urabe | journal = [[J. Am. Chem. Soc.]] | volume = 127 | issue = 51 | pages = 18006–18007 | doi = 10.1021/ja055732b | year = 2005 | pmid = 16366543|bibcode=2005JAChS.12718006N }}</ref>  This modification requires [[aryl]] or [[Vinyl group|vinyl]] Grignards. Adding just the Grignard and the alkene does not result in a reaction demonstrating that the presence of oxygen is essential. The only drawback is the requirement of at least two equivalents of Grignard although this can partly be circumvented by the use of a dual Grignard system with a cheap reducing Grignard such as n-butylmagnesium bromide.

[[File:Grignard oxidation example.png|center|400px|Grignard oxygen oxidation example]]

===Elimination===
In the [[Boord olefin synthesis]], the addition of magnesium to certain β-haloethers results in an [[elimination reaction]] to the alkene. This reaction can limit the utility of Grignard reactions.

[[File:BoordReactionOverview.png|300px|center|Boord olefin synthesis, X = Br, I, M = Mg, Zn]]

==Industrial use==
An example of the Grignard reaction is a key step in the (non-stereoselective) industrial production of [[Tamoxifen]]<ref>{{cite book
 | title = Grignard Reagents: New Developments
 | author=Richey, Herman Glenn |publisher=Wiley|year= 2000|isbn=0471999083
}}</ref> (currently used for the treatment of [[estrogen receptor]] positive [[breast cancer]] in women):<ref name="Jordan_1993">{{cite journal
 |author=Jordan VC
 |title=Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer
 |journal= Br J Pharmacol
 |volume= 110
 |issue= 2
 |pages= 507–17
 |year= 1993
 |pmid= 8242225
 |pmc=2175926
 |doi=10.1111/j.1476-5381.1993.tb13840.x}}</ref>

[[File:TamoxifenSynthesisGrignard.svg|400px|center|Tamoxifen production]]

==See also==
*[[Dibutylmagnesium]]
*[[Hauser base]]

==Gallery==
<gallery mode="packed">
Grignard reaction experiment 01.jpg|Magnesium turnings are placed in a flask.
Grignard reaction experiment 02.jpg|Tetrahydrofuran and a small piece of iodine are added.
Grignard reaction experiment 03.jpg|A solution of alkyl bromide is added while heating.
Grignard reaction experiment 04.jpg|After completion of the addition, the mixture is heated for a while.
Grignard reaction experiment 05.jpg|Formation of the Grignard reagent is complete. A small amount of magnesium still remains in the flask.
Grignard reaction experiment 06.jpg|The Grignard reagent thus prepared is cooled to {{nowrap|0°C}} before the addition of the carbonyl compound. The solution becomes cloudy as the Grignard reagent precipitates out.
Grignard reaction experiment 07.jpg|A solution of carbonyl compound is added to the Grignard reagent.
Grignard reaction experiment 08.jpg|The solution is warmed to room temperature. At this point the reaction is complete.
</gallery>

==References==
<references />

==Further reading==
* {{cite book |editor1-last=Rakita |editor1-first=Philip E. |editor2-last=Silverman |editor2-first=Gary S. |title=Handbook of Grignard Reagents |publisher=Marcel Dekker |location=New York, N.Y |year=1996 |isbn=0-8247-9545-8}}
*Mary McHale, "Grignard Reaction," Connexions, http://cnx.org/content/m15245/1.2/. 2007.
*''Grignard knowledge: Alkyl coupling chemistry with inexpensive transition metals'' by Larry J. Westrum, Fine Chemistry  November/December 2002, pp.&nbsp;10–13 [https://web.archive.org/web/20161010125746/http://www.bouldersci.com/wp-content/uploads/2011/02/Grignard_Knowledge.pdf]

==Specialized literature==
*{{Cite journal| doi = 10.1021/ja00521a034| title = Mechanism of formation of Grignard reagents. Kinetics of reaction of alkyl halides in diethyl ether with magnesium| year = 1980| last1 = Rogers | first1 = H. R.| last2 = Hill | first2 = C. L.| last3 = Fujiwara | first3 = Y.| last4 = Rogers | first4 = R. J.| last5 = Mitchell | first5 = H. L.| last6 = Whitesides | first6 = G. M.| journal = Journal of the American Chemical Society| volume = 102| issue = 1| pages = 217 | bibcode = 1980JAChS.102..217R}}
*{{cite journal | last1 = De Boer | first1 = H.J.R. | last2 = Akkerman | first2 = O.S | last3 = Bickelhaupt | first3 = F. | year = 1988 | title = Carbanions as intermediates in the synthesis of Grignard Reagents | journal = Angew. Chem. Int. Ed. | volume = 27 | issue = 5 | pages = 687–89 | doi=10.1002/anie.198806871}}
*{{cite journal | last1 = Van Klink | first1 = G.P.M. | last2 = de Boer | first2 = H.J.R | last3 = Schat | first3 = G. | last4 = Akkerman | first4 = O.S. | last5 = Bickelhaupt | first5 = F. | last6 = Spek | first6 = A. | year = 2002 | title = Carbanions as Intermediates in the Formation of Grignard Reagents | journal = Organometallics | volume = 21 | issue = 10 | pages = 2119–35 | doi=10.1021/om011083a| hdl = 1874/14334 | s2cid = 94556915 | hdl-access = free }}
*{{cite journal | last1 = Shao | first1 = Y. | last2 = Liu | first2 = Z. | last3 = Huang | first3 = P. | last4 = Liu | first4 = B. | year = 2018 | title = A unified model of Grignard reagent formation | journal = Physical Chemistry Chemical Physics | volume = 20 | issue = 16 | pages = 11100–08 | doi=10.1039/c8cp01031e| pmid = 29620768 | bibcode = 2018PCCP...2011100S }}

{{organometallics}}
{{Organic reactions}}
{{Authority control}}

[[Category:Organometallic chemistry]]
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Carbon-heteroatom bond forming reactions]]
[[Category:Reagents for organic chemistry]]
[[Category:Magnesium]]
[[Category:Chemical tests]]
[[Category:Organomagnesium compounds]]