Direct Synthesis of N,N-Dimethylated and β-Methyl N,N-Dimethylated Amines from Nitriles Using Methanol: Experimental and Computational Studies

Paul, Bhaskar; Shee, Sujan; Panja, Dibyajyoti; Chakrabarti, Kaushik; Kundu, Sabuj

doi:10.1021/acscatal.8b00021

Cited by 56 publications

(40 citation statements)

References 45 publications

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“…In recent years, various homogeneous and heterogeneous catalytic methods have emerged in the borrowing hydrogen field. For homogeneous applications, different transition metal catalysts based on iridium, copper, nickel, iron, cobalt, manganese, rhodium and ruthenium have been employed. Especially the ruthenium‐based systems have been widely and successfully applied to a large variety of amines and nitriles…”

Section: Introductionmentioning

confidence: 99%

Ruthenium Catalyzed N‐Alkylation of Cyclic Amines with Primary Alcohols

2020

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A robust alcohol amination protocol using common saturated amines and primary alcohols as starting materials is described. The reactions are catalyzed by combination of dichloro(p-cymene)ruthenium(II) dimer precatalyst with triphenylphosphine ligand, with the excess alcohol substrate or toluene [a] Dr.amines. An important secondary goal was to minimize the waste produced in the purification of the products, i.e., simple removal of catalyst complex and purification of products without the need of chromatographic separation. Here, we describe a robust triphenylphosphine ligated dichloro(p-cymene)ruthenium(II) dimer catalyzed methodology for alkylation of cyclic amines with primary alcohols, while simultaneously minimizing the necessary purification operations. Results and DiscussionThe N-alkylation of morpholine with 1-butanol, illustrated in Scheme 2, was selected as a model reaction, based on the good availability of the reactants. This allowed the reactions to be performed at close to one gram scale in the preliminary screening, carried out in stainless steel reactors at elevated pressure and temperature. Scheme 2. N-Alkylation of morpholine with 1-butanol using dichloro(p-cymene)ruthenium(II) dimer precatalyst in combination with phosphine ligands.Based on prior art, [16][17][18]20] a selection of phosphine ligands illustrated in Figure 2 were tested. Results from the ligand screening are summarized in Table 1. As expected, the bidentate ligands DPPF, DPPB and DPEphos in combination with dichloro(p-cymene)ruthenium(II) dimer provided good results even at 0.13 mol-% catalyst loading within 21 hours (Table 1, Entries 4, 15 and 17). Tridentate Triphos ligand provided acceptable results in the same reaction setting (Table 1, Entry 21). Also, a number of monodentate ligands, cataCXium®PCy, triphenylphosphine (Ph 3 P) and methoxy derivatized triphenylphosphines were investigated. All monodentate ligands resulted in relatively poor GC-based yields for N-butyl morpholine, or in no reaction at all. In cases of bidentate ligands, having excess of ligand to ruthenium center (above 1:1 ratio) had minimal to no benefits with respect to the overall yield of N-butyl Figure 2. Ligands used in the reaction screening.

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Section: Introductionmentioning

confidence: 99%

Ruthenium Catalyzed N‐Alkylation of Cyclic Amines with Primary Alcohols

2020

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“…The 16‐electron complex 9 is presumably the catalytically active species. A similar 16‐electron NNN–Ru species was shown to be active for methanol dehydrogenation by Kundu and co‐workers . Very recently, Yu and Li have also proposed the release of phosphine and generation of CNP–Ru(II) species as the first step in the dehydrogenation of benzyl alcohol .…”

Section: Resultsmentioning

confidence: 77%

N–Alkylation of Amines Catalyzed by a Ruthenium–Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

et al. 2019

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We report the use of ruthenium–NNN‐pincer complexes of the type (R2NNN)RuCl2(PPh3) (R = tBu, iPr, Cy and Ph) for the catalytic N‐alkylation of primary amines under solvent‐free conditions. For the first time, the base that is required to promote these reactions is generated in situ from the alcohol by the use of sodium. The resulting sodium alkoxide regenerates the alcohol substrate while acting as the water scavenger thus mitigating the need of an additional base. Among the catalysts screened, (tBu2NNN)RuCl2(PPh3) (0.02 mol‐%) gives very high turnovers and good yields at 140 °C. The (tBu2NNN)RuCl2(PPh3) catalyzed N‐alkylation tolerates a variety of amine and alcohol substrates. While excellent turnover (29000) was obtained for the (tBu2NNN)RuCl2(PPh3) (0.002 mol‐%) catalyzed alkylation of aniline with cyclohexyl methanol, the turnovers obtained in the corresponding catalytic methylation of p‐anisidine was also very high (12000). The (tBu2NNN)RuCl2(PPh3) catalyzed reactions have also been accomplished under open‐vessel conditions resulting in a net dehydrogenative coupling reaction. This protocol has been used to transform benzene‐1,2‐diamines to benzimidazoles with high productivity (12000 turnovers). DFT studies indicate that while β‐hydride elimination is rate‐determining (RDTS: 24.31 kcal/mol) for the alcohol dehydrogenation segment which is endothermic, insertion of the imine is rate‐determining (RDTS: 11.26 kcal/mol) for its hydrogenation that is exothermic.

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“…When phenothiazine reacted with acrylonitrile and N , N ‐dimethyl acrylamide under base catalysis, the corresponding aza‐Michael adducts 9 and 11 were obtained in good yields. Notably, compounds 9 and 11 can be formally transformed directly to commercial drug molecule promazine ( 12 ), used for the treatment of schizophrenia (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

Thiyagarajan

Krishnakumar

Gunanathan

2020

Chemistry An Asian Journal

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Designed transition metal complexes predominantly catalyze Michael addition reactions. Inorganic and organic base‐catalyzed Michael addition reactions have been reported. However, known base‐catalyzed reactions suffer from the requirement of solvents, additives, high pressure and also side‐reactions. Herein, we demonstrate a mild and environmentally friendly strategy of readily available KOtBu‐catalyzed Michael addition reactions. This simple inorganic base efficiently catalyzes the Michael addition of underexplored acrylonitriles, esters and amides with (oxa‐, aza‐, and thia‐) heteroatom nucleophiles. This catalytic process proceeds under solvent‐free conditions and at room temperature. Notably, this protocol offers an easy operational procedure, broad substrate scope with excellent selectivity, reaction scalability and excellent TON (>9900). Preliminary mechanistic studies revealed that the reaction follows an ionic mechanism. Formal synthesis of promazine is demonstrated using this catalytic protocol.

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Direct Synthesis of N,N-Dimethylated and β-Methyl N,N-Dimethylated Amines from Nitriles Using Methanol: Experimental and Computational Studies

Cited by 56 publications

References 45 publications

Ruthenium Catalyzed N‐Alkylation of Cyclic Amines with Primary Alcohols

Ruthenium Catalyzed N‐Alkylation of Cyclic Amines with Primary Alcohols

N–Alkylation of Amines Catalyzed by a Ruthenium–Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

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