Catalytic Studies On The Transformation Of Small Organic Amines To Nitrogen-containing Organic Compounds

The nitrogen-containing compounds show important physiological and pharmacological activit ies, and have wide application in the fields of medicine, fungicides, herbicides and insecticides. Generally, primary amines or secondar y amines are used for the synthesis of these compounds via N-H bonds cleavage. However, primary amines or secondary amines are chemica lly unstable, and sensit ive to several functional groups. Compared wit h primary or secondary amines, tertiar y amines are relatively stable, widely present in nature, and easily prepared, so it is important to construct nitrogen-containing compounds from tertiary amines. This paper focuses on the synthesis of propargylamines, amides and N-heterocycle compounds via C-N bond cleavage of tertiary amines. In addit ion, aerobic amination of catechols with primary amines to achieve benzoxazoles was also investigated. The contents and results are summarized as follows:1. A method for the synthesis of propargylamines from terminal alkynes, dichloromethane and tertiary amines using silver catalysts has been developed. In this reaction system, various types of alkynes(aliphatic alkyne, aromatic alkyne), amine(cyclic, chain), methylene halide(chloro, bromo, iodo), are used as substrates for the synthesis of corresponding propargylamine s in 70%-96% yields. Unsymmetrical tertiary amines react readily with phenylacetylene s and dichloromethane to give the corresponding propargylamines via selective C-N bond cleavage. An experiment using CD2Cl2 instead of CH2Cl2 as substrate confirms that the possible mechanism is proposed: methaniminium chloride is formed by the reaction of R1R2R3 N with CH2Cl2, which reacts with silver acetylide to give the corresponding propargylamine.2. The use of tertiary amines for the synthesis of amides has been developed for the first time under Cu/O2 systems. This method successfully combines C-H bond oxygenation, C-C bond activation and C-N bond cleavage in one pot using cheap copper as catalyst and green molecular oxygen as the oxidant. Aliphatic and aromatic tertiary amines are used as substrates for the synthesis of amides via C-N bond activation. Phenylacetonitrile, phenylacetaldehyde, phenylacetic acid and dibenzyl ketone could be amidated by tertiary amine s, giving the expected amides through selective C-C bond activation. In the presence of 18O2, the 18 O labelled product is generated. According to the reported literatures, the possible mechanism is proposed : the tertiary amine is oxidized by oxygen to form secondary amine intermediate; benzoyl compound resulted from the oxidation of aromatic substituted acetonitrile with oxygen in the presence of a copper catalyst; secondary amine intermediate further reacts with benzoyl compound to give the corresponding amide.3. A Ph2P(O)OH-catalyzed aerobic oxidative tertiary amines and ortho-substituted aniline for the synthesis of N-heterocycles has been developed. In addit ion to tertiary amines, secondary and primary amines are also efficient substrates to afford the corresponding N-heterocycles. In which all of the three alkyl groups in tertiary amines can be utilized and transformed into N-heterocycles with high atom efficiency. Based on the reported literatures and the captured N-oxide intermediate, the reaction possibly takes place as shown: in the presence of molecular oxygen, tertiary amine is oxidized to N-oxide, followed the immonium ion wa s produced, which is readily hydrolyzed to produce aldehyde. Finally, N-heterocyclic compound is produced by condensation/oxidative dehydrogenation of in situ aldehydes wit h o-substituted aniline.4. The first copper-catalyzed aerobic oxidative functionalization of C(aryl)-OH bond with primary amines for the synthesis of benzoxazole s have been developed. Under the present reaction system, both electron-rich and electron-deficient group substituted primary amines can be smoothly converted to 2-aryl or 2-alkyl substituted benzoxazoles in 60%-96% yields. Only one kind of benzoxazole was obtained via selectively C-O bond cleavage of catechols, and the structure of 4-3x was unambiguously confirmed by single-crystal. According to the reported literatures and experimental results, a possible reaction mechanism is proposed: oxidation o f catechol catalyzed by copper salt gives the key intermediate ortho-quinone, followed by the reaction of primary amine to produce benzoxazole via dehydration, rearrangement, and cyclization reaction.