General Description

Dicyclohexylamine is a versatile compound with diverse applications in organic synthesis and catalysis. Its synthesis using supported rhodium catalysts enables selective hydrogenation of various functional groups under controlled conditions, making it both environmentally benign and highly efficient. As a reactant, Dicyclohexylamine shows promise in the synthesis of N-nitrosamines, substituted hydrazines, and potentially chiral primary amines. Moreover, it exhibits wide-ranging applications as a ligand or a base in catalysis, contributing to the advancement of synthetic chemistry and enabling the efficient production of chiral compounds with significant industrial importance.

Figure 1. Dicyclohexylamine

Synthesis

Dicyclohexylamine is an important compound used in various industrial applications. Its synthesis can be achieved through the one-step hydrogenation of cyclohexyl nitrite using supported rhodium catalysts. Several catalysts were screened, and it was found that 5% Rh/Al2O3 and 5% Rh/C showed excellent performance in controlling selective hydrogenation. By adjusting the reaction time or temperature, partial and full hydrogenation of various functional groups can be achieved. This method not only allows the hydrogenation of aliphatic C-C, C-N, C-O, and N-O multiple bonds but also successfully hydrogenates C=C double bonds of arenes, which is considered challenging. One notable advantage of this synthesis route is the use of an Al-H2O system that produces hydrogen in situ. This eliminates the need for additional hydrogen sources, making the process more environmentally friendly. Moreover, the high selectivity achieved using the supported rhodium catalysts ensures minimal waste generation, resulting in a highly efficient process. In summary, the synthesis of dicyclohexylamine utilizing supported rhodium catalysts enables selective hydrogenation of various functional groups under controlled conditions. The use of an Al-H2O system and the high selectivity of this method make it both environmentally benign and highly efficient. ¹

Versatile Applications as a Reactant and Catalyst

Reactant

Dicyclohexylamine is a versatile compound used as a reactant in various applications. One important application of Dicyclohexylamine is its use in the synthesis of N-nitrosamines, which are of interest due to their potential pharmaceutical delivery system and regulatory role in physiological functions. In the synthesis of N-nitrosamines, Dicyclohexylamine serves as a reactant by undergoing NO insertion into the N-Li bond of lithium amides. This reaction yields high to almost quantitative yields of N-nitrosamines, which have been found to possess carcinogenic properties. Additionally, the reaction intermediates indicate that this synthetic method can be extended to tandem reactions, broadening its scope. Furthermore, Dicyclohexylamine can be utilized in the preparation of substituted hydrazines. By adding an organolithium reagent to the N=O bond of a hydrazone formed from DCHA, substituted hydrazines can be obtained. These hydrazines may possess a potential chiral carbon, allowing for the production of enantiomerically pure compounds by introducing a chiral auxiliary during the reaction. Moreover, the reduction of the compound with Raney Ni offers the possibility of synthesizing chiral primary amines. This ongoing project aims to expand the applicability of Dicyclohexylamine in the preparation of valuable chiral compounds. In conclusion, Dicyclohexylamine shows promise as a reactant in various synthetic pathways, including the synthesis of N-nitrosamines, substituted hydrazines, and potentially chiral primary amines. Its diverse applications highlight its significance in pharmaceutical research and chemical synthesis. ²

Catalyst

Dicyclohexylamine is a versatile catalyst commonly used in various chemical reactions. It can act as a ligand or a base, depending on the reaction conditions. As a ligand, Dicyclohexylamine forms complexes with transition metals like rhodium, enhancing their catalytic activity. These complexes have been extensively studied for their application in hydrogenation reactions. For example, when combined with Rhodium and the ligand (1R,1′R)-1,1′-(1,2-Ethanediyl)bis[1-[2-(cyclohexyloxy)phenyl]-1-phenylphosphine], Dicyclohexylamine facilitates the enantioselective hydrogenation of α-carboxy, α-aryl amidoethylenes, and activated olefins. This process enables the production of chiral compounds with high optical purity, which find applications in pharmaceutical and fine chemical industries. Moreover, Dicyclohexylamine can also function as a base, facilitating deprotonation reactions and promoting organic transformations. It has been employed in the synthesis of diverse organic compounds, such as (R,R)-1,2-bis[(2-tert-butoxyphenyl)(phenyl)phosphino]ethane ((R,R)-t-Bu-SMS-Phos), a valuable ligand for enantioselective hydrogenations. In summary, Dicyclohexylamine exhibits wide-ranging applications as a catalyst, contributing to the advancement of synthetic chemistry and enabling the efficient production of chiral compounds with significant industrial importance. ³

Reference

1. Xie G, Torok B. Rh-Catalyzed Environmentally Benign Selective Hydrogenation of a Broad Variety of Functional Groups Using Al-Water as a Hydrogen Source. Catalysts, 2022, 12(12): 1578.

2. Vazquez A, Nudelman NS. Complex intermediates in the NO insertion reactions into lithium amides. Journal of Physical Organic Chemistry, 2006, 19(11): 748-751.

3. Stephan M, Mohar B. (R,R)-1,2-Bis[(2-tert-butoxyphenyl)-(phenyl)phosphino]ethane, (R,R)-t-Bu-SMS-Phos. e-EROS Encyclopedia of Reagents for Organic Synthesis, 2014, 1-3.