A Theoretical Study on the Mechanism of Methylation of N‐methylaniline with CO₂ and Silyl Hydrides

Abstract

The mechanism of methylation of N‐methylaniline with CO2 and the phenylsilane (PhSiH3) was studied using density functional theory (DFT) at the M05‐2X(THF, SMD)/6‐311++G**//M05‐2X/6‐31G* level. The calculations show that the three‐component reaction takes place from the reduction of CO2 with PhSiH3, forming the formoxysilane (FOS) species. This hydrosilylation step requires the highest activation free energy barrier (41.6 kcal/mol), and thus can be regarded as the rate‐determining step (RDS) for the entire reaction. Once the FOS species is formed, its subsequent formylation with the amine to formamide (FA) species and the two successive reductions of the FA species to the desired methylamine (MA) product are easy to proceed. Furthermore, our calculations show that 1,3‐diphenyldisiloxan‐1‐ol (PhSiH2OSiHOHPh) is together formed with the product MA. The Si–H bond activity in PhSiH2OSiHOHPh is higher than that in reactant PhSiH3 and intermediate phenylsilanol (PhSiH2OH). Thus, there exists a product catalysis as the activation free energy barrier for the FOS species formation is lowered to 36.9 kcal/mol when this species is used as a reducing agent.

Pivotal Role of the Basic Character of Organic and Salt Catalysts in C−N Bond Forming Reactions of Amines with CO2

“…However, experimental and computational evidence supports only two, and both proceed by a formoxysilane intermediate (Scheme ). In addition, DFT calculations indicate that in the absence of a catalyst, formoxysilane formation is the rate‐determining step . The same nucleophilic activation of the hydrosilane by anion of a salt, base–CO 2 adducts and carbamate salts have been proposed as the mode‐operandi of N‐methylation catalysts .…”

“…In contrast, the reaction with hydroboranes is less well understood and the involvement of formoxyboranes remains rather speculative . In all cases, the CO 2 reduction stage is regarded as rate determining and is the focus of catalyst development …”

Pivotal Role of the Basic Character of Organic and Salt Catalysts in C−N Bond Forming Reactions of Amines with CO2

“…[22,23] Pathway 1i si dentical to the N-formylation reaction pathway followed by direct reduction of the formamide to Nmethylamine.D FT calculations indicate that it is energetically favored in the absence of ac atalyst due to unfavorable formoxysilane reduction to silylacetal along pathway 2. [25,42] Experimentally,C s 2 CO 3 [47] and [TBA]F [19] catalysts were shown to reduce N,N-methylformanilide to N,N-dimethylaniline in the presence of phenylsilane.H owever,e xtended reaction times and excess phenylsilane are required. In comparison, reduction of N,N-methylformanilide was not observed with DBU, [27] TMG, [20] K 2 WO 4 , [48] CsCOOH, [55] or glycine betaine [40] catalysts nor catalyst-free in DMF [58] under the N-methylation reaction conditions.DFT calculations with TBD indicate that formoxysilane reduction to silylacetal is facile in polar aprotic solvents,w here the [TBDH]-[RR'NCOO] catalyst reduces the energy barrier below the barrier of formoxysilane aminolysis,a tl east for most amines.…”

“…[21][22][23][24] In all cases,t he CO 2 reduction stage is regarded as rate determining and is the focus of catalyst development. [25] Catalysts for the N-formylation reaction can be divided into six groups ( Figure 2). Thef irst group is composed of organic superbases.T he reaction has been optimized with Scheme 2.…”

“…Pathway 1 is identical to the N‐formylation reaction pathway followed by direct reduction of the formamide to N‐methylamine. DFT calculations indicate that it is energetically favored in the absence of a catalyst due to unfavorable formoxysilane reduction to silylacetal along pathway 2 . Experimentally, Cs 2 CO 3 and [TBA]F catalysts were shown to reduce N,N‐methylformanilide to N,N‐dimethylaniline in the presence of phenylsilane.…”