Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Nickel-Catalyzed Deoxycyanation of Activated Phenols via Cyanurate Intermediates with Zn(CN)2: A Route to Aryl Nitriles Majid M. Heravi,*,† Farhad Panahi,*,†,‡ and Nasser Iranpoor‡ †
Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran
‡
S Supporting Information *
ABSTRACT: A novel, and efficient nickel-catalyzed deoxycyanation of phenolic compounds using relatively nontoxic Zn(CN)2 as the cyanide source was developed. The reaction of C−O bond activated phenolic compounds by 2,4,6-trichloro1,3,5-triazine with Zn(CN)2 in the presence of a nickel precatalyst afforded the aromatic nitriles in good to excellent yields.
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cyanating agents, the cyanation of aryl C−O electrophiles has been largely overlooked (Scheme 1).9−12 Noticeably, the aryl C−O electrophiles derived from phenols are more commercially available and more readily accessible than their aryl halides counterparts.13 The direct employment of phenol derivatives (as a chemical feedstock) instead of aryl halides as the aryl C−O electrophile is favorable from both
cyanation reaction toward synthesis of aromatic nitriles plays a key role in organic synthesis because this building block exist in the structure of many natural products,1 pharmaceuticals (Figure 1),2 agricultural chemicals, and advanced materials.3
Scheme 1. Metal-Catalyzed Cyanation of Aryl Halides and Aryl C−O Electrophiles
Figure 1. Chemical structures of some important pharmaceuticals containing an aryl nitrile moiety: (A) rilpivirine, an anti-HIV agent; (B) citalopram, Cipramil (Promonta Lundbeck), a central nervous system (CNS) drug; (c) periciazine, Aolept (Bayer), a antipsychotic agent; (D) RU-58841, a nonsteroidal receptor antagonist.
More importantly, the nitrile group located on the aryl moiety can be readily converted to other important functional groups in organic synthesis, such as aldehyde, carboxylic acid, ketone, esters, amine, amide, etc.4 Conventionally, there are two routes for the synthesis of aryl nitriles: (a) the classical diazotization of anilines followed by the Sandmeyer reaction5 and (b) the Rosenmund−von Braun reaction,6 which suffers from the requirement of a stoichiometric amount of CuCN at temperatures as high as 150 °C to convert aryl iodides to aryl nitriles. Thus, both of these conventional methods require harsh reaction conditions and tedious workup procedures and experience limited substrate scope. Transition-metal-catalyzed cyanation of aryl halides, as another important approach, has made many progress in terms of efficiency and practicality.7,8 Despite much progress in metal-catalyzed cyanation of aryl halides with different © XXXX American Chemical Society
Received: March 27, 2018
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DOI: 10.1021/acs.orglett.8b00974 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of the Reaction Conditionsa
synthetic and environmental points of view.14 In this light, various C−O bond-activating agents have been developed for the preparation of different aryl C−O electrophiles for use in the appropriate organic transformations.13,14 Furthermore, it has been found that nickel species are superior catalysts in the aryl C−O electrophile coupling reactions due to their high capability in oxidative addition, as well as their low price relative to Pd species counterparts.15 It has been reported that 2,4,6-trichloro-1,3,5-triazine (TCT) can effectively activate C−O bonds in phenols in order to be used in nickel-catalyzed coupling reactions.16 Prompted by these reports and our interest in Ni-catalyzed organic transformations,17 in this paper, we disclose that TCT can offer direct conversion of activated phenolic compounds to aromatic nitriles via a Ni-catalyzed process. To the best of our knowledge, this is the first example of the Ni-catalyzed deoxycyanation of phenolic compounds activated by TCT (Scheme 2).
entry 1 2 3 4 5 6 7 8 9 10
Scheme 2. Ni-Catalyzed Deoxycyanation of Phenols Using TCT as C−O Bond-Activating Agent
11 12 13 14 15 16 17 18 19 20 21 22
To find the optimal reaction conditions, p-cresol was selected as a model phenolic compound and initially activated by TCT to provide the corresponding TAT [2,4,6-tris(p-tolyloxy)-1,3,5triazine; 2a], which was then treated with different source of nitriles such as Zn(CN)2, KCN, and TMSCN in the presence of Ni precursor as catalyst under diverse reaction conditions to obtain 4-methylbenzonitrile 3a (Table 1). In the presence of NiCl2 as precatalyst in dioxane at 110 °C, no product was observed (Table 1, entry 1). With addition of PPh3 as ligand in the reaction media, no change in the result was detected (Table 1, entry 2). About 10% of the desired product was detected when dppe was used as ligand along with NiCl2 precatalyst (Table 1, entry 3). Having observed this result, we started screening other ligands. The reaction yield was enhanced to 35% by use of dppf as ligand (Table 1, entry 4). A satisfactory yield of 70% was observed when dcype was used as ligand under the same reaction conditions (Table 1, entry 5). Interestingly, an acceptable yield of 60% (Table 1, entry 6) was obtained when dmg was used as a nonphosphine ligand; however, in the presence of dme the reaction yield was decreased to 25% (Table 1, entry 7). Considering the high yield of product obtained when dcype ligand was used, the other reaction parameters were optimized based on this ligand. Then, different type of Ni sources were examined, and the maximum yield of product (90%) by use of Ni(COD)2 was obtained (Table 1, entries 8−10). No improvement in the reaction yields was observed by increasing of the catalyst loading up to 7.0 mol %, while the reaction yield was decreased when 3.0 mol % of the catalyst was used; thus, 5.0 mol % of catalyst was selected as the optimum catalyst loading (Table 1, entries 11 and 12). Decreasing the amount of ligand to 5.0 mol % (related to 5.0 mol % of Ni source) also decreased the reaction yield to 74% (Table 1, entry 13). Other solvents were also screened, but no superiority was observed in the reaction outcome (Table 1, entries 14−16). By decreasing the reaction temperature to 80
[Ni] (mol %) NiCl2 ·5H2O (5) NiCl2·5H2O (5) NiCl2·5H2O (5) NiCl2·5H2O (5) NiCl2·5H2O (5) NiCl2·5H2O (5) NiCl2·5H2O (5) NiBr2 (5) Ni(COD)2 (5) Ni(PPh3)2(CO)2 (5) Ni(COD)2 (7) Ni(COD)2 (3) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5) Ni(COD)2 (5)
ligand (mol %)
solvent
T (°C)
yieldb (%)
PPh3 (20) dppe (10) dppf (10) dcype (10) dmg (10) dme (10) dcype (10) dcype (10) dcype (10)
dioxane dioxane dioxane dioxane dioxane dioxane dioxane dioxane dioxane dioxane
110 110 110 110 110 110 110 110 110 110
0 0
