[624-75-9] · C2H2IN · Iodoacetonitrile · (MW 166.95)
Alternate Name: iodomethyl cyanide.
Physical Data: bp 182-184 °C/720 mmHg, 75 °C/10 mmHg; d 2.307 g cm-3.
Solubility: insol hexane; slightly sol H2O; sol benzene, alcohol, acetone, ether, CH2Cl2.
Form Supplied in: yellow to amber liquid; commercially available.
Handling, Storage, and Precautions: lachrymator; avoid inhalation of vapors; flammable (toxic fumes); possible mutagen; refrigerate. Handle in a fume hood.
Iodoacetonitrile is commonly used for the alkylation (cyanomethylation) of a wide variety of nucleophiles (eq 1), including ketone enolates,1 ester enolates,2 amines,3,4 thiols,5 phosphines,6 enolic hydroxyls,7 enol-TMS intermediates,8 borates,9 thioamides,10 arene p-complexes,11 and miscellaneous nitrogen heterocycles.12,13 The value of the resulting alkylation products often lies in their versatility with respect to further synthetic transformations, either straightforward reactions such as conversion to amides, amines, or acids, or more substrate-specific reactions including rearrangements,14 ring expansion,12 conversion to formaldehyde iminium intermediates,3 or conversion to novel heterocycles.13
In a Reformatsky-type reaction, aldehydes (not ketones) react with ICH2CN in the presence of freshly prepared metallic Nickel (eq 2)15 to give b-hydroxy nitriles. Yields are good due to the low basicity of the cyanomethylnickel halides, and the selectivity for aldehydes in the presence of ketones may prove useful in complex substrates.
a,b-Unsaturated nitriles are available in good yield by the reaction of ICH2CN with carbonyl compounds mediated by tri-n-butylstibine, under mild and essentially neutral conditions (eq 3).16
The reaction of ICH2CN with thioamides provides a racemization-free route to b-keto nitriles through the intermediacy of an a-cyanoenamine (eq 4).17 When primary thioamides are alkylated with ICH2CN, a substituted thiazole is the predominant product (eq 5).18
Radical addition of ICH2CN to alkyl-substituted alkynes leads to g-iodo-b,g-unsaturated nitriles, which are good precursors for radical translocation reactions (eq 6).19
g-Keto-nitriles (useful in the synthesis of heterocycles) and b,g-unsaturated nitriles with controlled geometry and substitution pattern are synthesized by treating alkynyltrialkylborates with ICH2CN followed by oxidation or protonolysis (eq 7).20
Gordon L. Bundy
The Upjohn Company, Kalamazoo, MI, USA