Acetonitrile as a Cyanating Reagent: Cu-Catalyzed Cyanation of Arenes

Abstract

A novel approach to the Cu-catalyzed cyanation of simple arenes using acetonitrile as an attractive cyano source has been documented. The C-H functionalization of arenes without directing groups involves a sequential iodination/cyanation to give the desired aromatic nitriles in good yields. A highly efficient Cu/TEMPO system for acetonitrile C-CN bond cleavage has been discovered. TEMPO is used as a cheap oxidant and enables the reaction to be catalytic in copper. Moreover, TEMPOCH2CN 6 has been identified as the active cyanating agent and shows high reactivity for forming the -CN moiety.

Photocatalyzed Cyanodifluoromethylation of Alkenes

“…An examination of the substituent effects in aryl alkenes showed that neither electron-withdrawing nor -donating groups had an obvious impact on the yields.A variety of functional groups were tolerated, such as ether, ester,k etone,c hloride,b romide,i odide,b oronic acid ester, and amide groups.The compatibility of this reaction with the reactive functional groups,i ncluding bromide (4-14, 4-15, 4-24), iodide (4-16), and boronic acid ester (4-12), allowed further CÀCc oupling transformations.T he HCF 2 /CN-containing estrone derivatives were synthesized by this cyanodifluoromethylation conversion, further demonstrating the synthetic utility of this method (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). An examination of the substituent effects in aryl alkenes showed that neither electron-withdrawing nor -donating groups had an obvious impact on the yields.A variety of functional groups were tolerated, such as ether, ester,k etone,c hloride,b romide,i odide,b oronic acid ester, and amide groups.The compatibility of this reaction with the reactive functional groups,i ncluding bromide (4-14, 4-15, 4-24), iodide (4-16), and boronic acid ester (4-12), allowed further CÀCc oupling transformations.T he HCF 2 /CN-containing estrone derivatives were synthesized by this cyanodifluoromethylation conversion, further demonstrating the synthetic utility of this method (4)(5)(6)(7)(8)…”

“…Because ac opper source is usually required in cyanotrifluoromethylation of alkenes, [13] various Cu complexes were examined (entries 1-4) and CuI was found to be as uperior choice (entry 1). Other nitrogen sources for the nitrile group were screened (entries [15][16][17][18][19], and ammonia (NH 3 )w as also an efficient source (entry 15). A7 8% yield was obtained when 3equivalents of NaNH 2 (entry 9) were used.…”

“…It has been reported that the generation of cyanide anion (CN À )can be detected by aCN À indicator,sodium picrate, [15] and therefore this method was adopted to identify the sources of the CN À anion (for experimental details see the Supporting Information). No CN À anion was detected in the absence of Ph 3 P + CF 2 CO 2 À ( Table 2, entries 1and 2) or NaNH 2 (entry 3), but the anion was formed when both Ph 3 P + CF 2 CO 2 À and NaNH 2 were present (entry 4), indicating that Ph 3 P + CF 2 CO 2 À and NaNH 2 are the carbon source and the nitrogen source of the CN À anion, respectively.Furthermore,the CN À anion can Scheme 1.…”

New trends and applications in cyanation isotope chemistry

“…They obtained yields from 41% to 88%, and the reaction showed good functional group tolerance . Finally, there are further cyanation sources, eg, acetonitrile, or (ethoxy‐methylene)cyanoacetate, mentioned in the recent 12 C‐carbon literature; however, these provide less benefit for isotope science due to the necessity to produce the cyanation reagent first from 14 C‐KCN and their needing a stoichiometric excess which is unfavorable for labelling applications.…”

An Insight into Nitromethane as an Organic Nitrile Alternative Source towards the Synthesis of Aryl Nitriles

“…Requirement of elevated temperatures (150–250 °C) being another shortcoming of those processes. One of the practical solutions that has emerged to reduce the risk of hazardous metal cyanides, is to employ, either non‐metallic cyanide sources, such as aryl(cyano)‐iodonium triflates, acetone cyanohydrin, malononitrile, AIBN, benzyl cyanide, acetonitrile, butyronitrile, ethyl (ethoxymethylene)cyanoacetate, etc., or sources which can generate CN – group in situ (indirect sources). Recent examples of such “indirect sources” are nitromethane, the combination of NH 4 I‐DMF, NH 4 HCO 3 ‐DMSO or NH 4 HCO 3 ‐DMF, DMF and t BuNC…”