97095-89-1Relevant academic research and scientific papers
Oxidation-Reduction Condensation of Diazaphosphites for Carbon-Heteroatom Bond Formation Based on Mitsunobu Mechanism
Huang, Hai,Kang, Jun Yong
, p. 544 - 547 (2017/02/10)
An efficient oxidation-reduction condensation reaction of diazaphosphites with various nonacidic pronucleophiles in the presence of DIAD as a weak oxidant has been developed for carbon-heteroatom bond formation. This mild process affords structurally diverse tertiary amines, secondary amines, esters, ethers, and thioethers in moderate to excellent yields. The selective synthesis of secondary amines from primary amines has been achieved. Importantly, a practical application to the synthesis of antiparkinsonian agent piribedil has been demonstrated.
Mitsunobu Reaction Using Basic Amines as Pronucleophiles
Huang, Hai,Kang, Jun Yong
, p. 6604 - 6614 (2017/07/15)
A novel protocol for extending the scope of the Mitsunobu reaction to include amine nucleophiles to form C-N bonds through the utilization of N-heterocyclic phosphine-butane (NHP-butane) has been developed. Both aliphatic alcohols and benzyl alcohols are suitable substrates for C-N bond construction. Various acidic nucleophiles such as benzoic acids, phenols, thiophenol, and secondary sulfonamide also provide the desired products of esters, ethers, thioether, and tertiary sulfonamide with 43-93% yields. Importantly, C-N bond-containing pharmaceuticals, Piribedil and Cinnarizine, have been synthesized in one step from the commercial amines under this Mitsunobu reaction system.
Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
Borukhova, Svetlana,Nol, Timothy,Hessel, Volker
, p. 67 - 74 (2016/01/16)
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.
Synthesis and crystal structures of N,N′-disubstituted piperazines
Safko, Jason P.,Pike, Robert D.
, p. 981 - 987 (2012/10/30)
The structure of 1,4-diphenylpiperazine (1) was determined; it crystallized in the orthorhombic space group Pbca, a = 8.6980(7), b = 8.4287(7), c = 17.6359(15), V = 1292.94(19), Z = 4. Three novel N,N′-disubstituted piperazines were synthesized via reduct
