Catalytic Reductive Alkylation of Amines in Batch and Microflow Conditions Using a Silicon-Wafer-Based Palladium Nanocatalyst

Abstract

We describe the development of the catalytic reductive alkylation of amines with aldehydes under the atmospheric pressure of H 2 using a brush-like silicon-nanostructure-supported palladium nanoparticle composite (SiNS–Pd) as a silicon-wafer-based reusable heterogeneous catalyst. The present reaction of primary and secondary amines with various aliphatic and aromatic aldehydes in the presence of the catalyst (0.02–0.05 mol % Pd) gave the corresponding secondary and tertiary amines including Lomerizine and Aticaprant in a 68% quantitative yield without overalkylation. We also designed and fabricated a flow device equipped with SiNS–Pd for microflow reactions, which was applied to the gas–liquid–solid triphasic reaction system (i.e., H 2 gas, a substrate solution, and a solid catalyst). A multigram-scale reaction of aniline and benzaldehyde was demonstrated to obtain N -benzylaniline (ca. 4 g/day), in which the internal volume of the flow channel was 43 μL, the residence time was approximately 1 s, and the turnover number (TON) reached 4.0 × 10 4 in a continuous 24 h run (1.7 × 10 3 h –1 ; 0.50 s –1 ).

Efficient preparation of (S)‐2‐(3,5‐dimethylphenyl)pyrrolidine via a recycle process of resolution

“…Subsequently, different solvents were tested to improve the efficiency of resolution and the ratio of EtOH over water showed the significant effects in resolving efficiency and the optimal solvent was 95% EtOH, affording the (S)-1-D-tartaric acid in 36.7% yield with 99.06% chiral purity after two times of recrystallizations (entry 5). The direction of the specific rotation of freebase from this salt (α = À33.8[c = 1.08, MeOH]) was the same as that reported in the literature [7] (α = À30.5[c = 1.01, MeOH]), so the absolution configuration of (S)-1 was confirmed.…”

“…( S )‐2‐(3,5‐dimethylphenyl)pyrrolidine(( S )‐ 1 ) was a key chiral fragment in the synthesis of aticaprant, and the methods to synthesize ( S )‐ 1 mainly involved the asymmetric reduction of imine 4 under the catalysis of the chiral small molecule [5] or chiral metal [6]. Besides, it was also reported that ( S )‐ 1 could be obtained through the asymmetric induced synthesis, which was carried out with ( R )‐tert‐butylsulfonamide as chiral auxiliary and the starting materials were derived from Weinreb amide and Grignard reagent [7]. However, these methods suffered some deficiencies such as the requirement for costly catalysts, extreme reaction conditions (−78°C), and low reaction yield.…”

Preparation of core–shell catalyst for the tandem reaction of amino compounds with aldehydes

“…Furthermore, compared with other catalyst ( Table 1 , entry 10), it is found that the initial reactant can be converted into the target product only under relatively harsh conditions (60 °C, 18 h, 160 mg catalyst). 64 In summary, the prepared catalyst enables the reaction of aniline and benzaldehyde to generate the target product under very mild conditions.…”

“… a Reaction conditions: 25 °C, atmospheric pressure, 5 mg catalyst, 0.5 mmol benzaldehyde, 1 mmol aniline, 3 mL solvent, H 2 balloon, reaction time: 1 h. b 1 mmol benzaldehyde. c 1 mmol aniline, 1.2 mmol benzaldehyde, 2 mL 2-propanol, 160 mg SiNS–Pd catalyst, 1.0 MPa H 2 , 60 °C, reaction time: 18 h. 64 …”

Diverse Supports for Immobilization of Catalysts in Continuous Flow Reactors

“…The intimate and direct contact of the binary reagents leads to enhanced mass transfer and facilitating reactions (Figure 9a). Yamada and coworkers [90] developed a brush-like silicon-nanostructure-supported palladium nanoparticle composite (SiNSÀ Pd, length ca. 500 nm, width ca.…”