:Cyanation

Typically, alkyl nitriles are formed via S_N1 or S_N2-type cyanation with alkyl electrophiles. Illustrative is the synthesis of benzyl cyanide by the reaction of benzyl chloride and sodium cyanide.{{cite journal|last1=Adams|first1=Roger|last2=Thal|first2=A. F.|title=Benzyl cyanide|journal=Organic Syntheses|date=1922|volume=2|page=9|doi=10.15227/orgsyn.002.0009}} In some cases cuprous cyanide is used instead of sodium cyanide.{{cite journal|journal=Org. Synth.| title = Allyl Cyanide | author1 = J. V. Supniewski | author2 = P. L. Salzberg| volume= 8 | page = 4|year=1928|

doi= 10.15227/orgsyn.008.0004}}

Cyanation of ketones or aldehydes yields the corresponding cyanohydrins, which can be done directly with the cyanide ion (the cyanohydrin reaction) or by using bisulfite, followed by displacement of sulfite:{{Cite journal|last=Mowry|first=David T.|date=1948|title=The Preparation of Nitriles.|url=https://pubs.acs.org/doi/abs/10.1021/cr60132a001|journal=Chemical Reviews|language=en|volume=42|issue=2|pages=189–283|doi=10.1021/cr60132a001|pmid=18914000 |issn=0009-2665}}{{cite journal| author = Corson, B. B.| author2 = Dodge, R. A.| author3 = Harris, S. A.| author4 = Yeaw, J. S. |journal=Org. Synth.| title = Mandelic Acid | volume= 6 | page = 58| year = 1926| doi=10.15227/orgsyn.006.0058}}

Image:Cyanation of aldehyde with bisulfate.svg

A related reaction is hydrocyanation, which installs the elements of H-CN.

Cyanation of arenes offers access to benzoic acid derivatives, as well as the utility of aryl nitriles themselves in as fine chemicals:

File:Cyanation starburst.png

A variety of mechanistically distinct pathways are known to cyanate arenes:

While the classical Rosenmund Von-Braun reaction utilizes stoichiometric copper(I) cyanide as a cyanation source,{{Cite web|url=https://chemistry.stackexchange.com/questions/63892/will-cyanide-substitute-bromine-in-bromobenzene|title=cyanide substitution of bromobenzene|last=Warzecha|first=Klaus-Dieter}} newer variants have been developed that are catalytic in copper:{{Cite journal|last=Wu|first=Jeff|date=2002|title=Catalytic Rosenmund–von Braun reaction in halide-based ionic liquids|journal=Tetrahedron Letters|volume=43|issue=3 |pages=387–389|doi=10.1016/s0040-4039(01)02168-2}}

File:Cat rosenmund.png

In addition, palladium-catalyzed cyanations of aryl halides have been extensively explored. Generally, KCN or its less toxic surrogate Zn(CN)₂ are used as nucleophilic cyanide sources. To further diminish toxicity concerns, potassium ferricyanide has also been used as a cyanide source. Catalytic cycles are believed to proceed through a standard Pd (0/II) pathway with reductive elimination forging the key C-C bond. Deactivation of Pd(II) with excess cyanide is a common problem.{{Cite journal|last=Cohen|first=Daniel|date=2015|title=Mild Palladium-Catalyzed Cyanation of (Hetero)aryl Halides and Triflates in Aqueous Media|journal=Organic Letters|volume=17|issue=2 |pages=202–205|doi=10.1021/ol5032359 |pmid=25555140 |pmc=4301087|doi-access=free}} Palladium catalysis conditions for aryl iodides, bromides, and even chlorides have been developed:{{Cite journal|last=Jin|first=Fuqiang|date=2000|title=Palladium-catalyzed cyanation reactions of aryl chlorides|journal=Tetrahedron Letters|volume=41|issue=18 |pages=3271–3273|doi=10.1016/s0040-4039(00)00384-1}}

File:Pd cyanation.png

Nickel-catalyzed cyanations avoid the use of precious metals, and can take advantage of benzyl cyanide or acetonitrile as a cyanide source, via reductive C-C bond cleavage:{{Cite journal|last=Ueda|first=Yohei|date=2019|title=Nickel-catalyzed cyanation of aryl halides and triflates using acetonitrile via C–CN bond cleavage assisted by 1,4-bis(trimethylsilyl)-2,3,5,6-tetramethyl-1,4-dihydropyrazine|journal=Chemical Science|volume=10|issue=4 |pages=994–999|doi=10.1039/c8sc04437f|pmid=30774893 |pmc=6349056 |doi-access=free}}

File:Nickel cyanation.png

Sandmeyer cyanation is a means of converting aniline derivatives to benzonitriles.{{cite journal|title=o-Tolunitrile and p-Tolunitrile|author=H. T. Clarke|author2=R. R. Read|journal=Org. Synth.|year=1925|volume=4|page=69|doi=10.15227/orgsyn.004.0069}} The cyanation is generally postulated to be two-electron, while with radical mediators in absence of metals, the reaction is likely radical.{{Cite journal|last=Barbero|first=Margherita|date=2016|title=Copper-free Sandmeyer cyanation of arenediazonium o-benzenedisulfonimides|journal=Organic & Biomolecular Chemistry|volume=14|issue=4 |pages=1437–1441|doi=10.1039/c5ob02321a|pmid=26676962 |hdl=2318/1554335|hdl-access=free}}

Metalated arenes can be cyanated with electrophilic cyanide sources, including cyanamides, cyanates, dimethylmalononitrile, or ethyl (ethoxymethylene)cyanoacetate. These methods can proceed with or without transition metal mediation:{{Cite journal|last=Reeves|first=Jonathan|date=2015|title=Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis|journal=Journal of the American Chemical Society|volume=137|issue=29 |pages=9481–9488|doi=10.1021/jacs.5b06136|pmid=26151426 }}

File:Electrophilic cyanation.png

Radical approaches to arene C-H cyanation are known. Photoredox mediators (metallic or organic) are most common:{{cite journal|title=Carbon-Carbon Bond Forming Reactions via Photogenerated Intermediates

|last1=Ravelli|first1=Davide|last2=Protti|first2=Stefano|last3=Fagnoni|first3=Maurizio

|journal=Chemical Reviews|year=2016|volume=116|issue=17 |pages=9850–9913|doi=10.1021/acs.chemrev.5b00662|pmid=27070820 }}{{Cite book|title=C-H Bond Activation in Organic Synthesis|last=Li|first=Jie Jack|publisher=CRC Press, Taylor & Francis Group|year=2015}}

File:Photo cyanation.png

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Category:Chemical reactions