- Highly Efficient and Selective N-Alkylation of Amines with Alcohols Catalyzed by in Situ Rehydrated Titanium Hydroxide
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Catalytic N-alkylation of amines by alcohols to produce desired amines is an important catalytic reaction in industry. Various noble-metal-based homogeneous and heterogeneous catalysts have been reported for this process. The development of cheap non-noble-metal heterogeneous catalysts for the N-alkylation reaction would be highly desirable. Hereby, we propose the N-alkylation of amines by alcohols over a cheap and efficient heterogeneous catalyst-titanium hydroxide. This catalyst provides a selectivity higher than 90% to secondary amines for functionalized aromatic and aliphatic alcohols and amines with high catalytic activity and stability. Mild Br?nsted acidity formed by the continuous rehydration of Lewis acidity excludes the side reactions and deactivation by adsorbed species. The mechanism of the reaction involves dehydration of alcohols to ethers with subsequent C-O bond cleavage by amine with the formation of secondary amine and recovery of alcohol.
- Khodakov, Andrei Y.,Kusema, Bright T.,Niu, Feng,Ordomsky, Vitaly V.,Wang, Qiyan,Yan, Zhen
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p. 3404 - 3414
(2020/03/23)
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- Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
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Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1-diphenylmethylpiperazine moiety. We present the development of a four-step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1. The incredible bulk: Bulk alcohols are converted continuously into chlorides using HCl in a microflow. A reaction network that consists of four steps and two inline separations leads to the continuous preparation of cinnarizine, cyclizine, and a buclizine derivative with yields of 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1.
- Borukhova, Svetlana,Nol, Timothy,Hessel, Volker
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- Pyrimidine derivatives as IL-8 receptor antagonists
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Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula I In these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, —O—alkyl or —S-alkyl. A representative example is:
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