66504-05-0

Upstream product

• 14062-24-9 4-chloro-benzeneacetic acid, ethyl ester 
• 56695-75-1 (1R,2S)-1-(4-Chloro-phenyl)-cyclopropane-1,2-dicarboxylic acid 
• 56695-75-1 (1S,2R)-(-)-1-(4-chlorophenyl)-1,2-cyclopropanedicarboxylic acid 
• 17559-40-9 (1S,2R)-1-(4-Chloro-phenyl)-cyclopropane-1,2-dicarboxylic acid diethyl ester 
• 5445-25-0 ethyl 2-bromo-2-(4-chlorophenyl)acetate 
• 148261-93-2 (1S,2R)-1-phenyl-1,2-cyclopropanedicarboxylic anhydride 
• 56815-97-5 1-(p-Chlorphenyl)-cis-cyclopropandicarbonsaeureimid 

Downstream Products

• 90821-76-4 (1S,5R)-1-phenyl-3-azabicyclo<3.1.0>hexane 

Relevant academic research and scientific papers

Chiroptical Properties of 1,2-Cyclopropanedicarboxylic Anhydrides and Imides. The Cyclopropane Ring Contribution to the Cotton Effect

Several optically active 1,2-cyclopropanedicarboxylic anhydrides and imides were prepared and their chiroptical spectra studied.Despite the strained bicyclicc skeleton of these compounds, their CD spectra show an unusual solvent dependence.This phenomenon can be explained in terms of the cyclopropane ring contribution to the Cotton effect.A deviation of the skeleton and the anhydride or imide group from the local Cs symmetry, shown by MNDO calculations, causes formation of an inherently chiral chromophore constituted by the three-membered ring and neighboring carbonyls.This kind of chromophore is responsible for the observed strong Cotton effects.

1-Aryl-3-azabicyclohexanes, a New Series of Nonnarcotic Analgesic Agents

A series of 1-aryl-3-azabicyclohexanes was synthesized by hydride reduction of 1-arylcyclopropanedicarboximides.Hydroxyphenyl analogues 20, 22, and 24 were prepared by EtSNa-DMF ether cleavage of the corresponding methoxyphenyl analogues 2m, 2n, and 23, respectively, with the secondary amines 20 and 22 going through the N-formyl intermediates 19 and 21.The p-ethoxy analogue 26 was obtained by O-ethylation of 19, followed by base hydrolysis of the amide 25.The greatest analgesic potency in mouse writhing and rat paw-pain assays was observed for para-substituted compounds.Bicifadine, 1-(4-methylphenyl)-3-azabicyclohexane (2b), was the most potent member of the series and is presently undergoing clinical trials in man.Analgesic activity of 2b is limited to the (+) enantiomer 2v, which has the 1R,5S absolute configuration as determined by single-crystal X-ray analysis.The N-methyl analogue (27d) of 2b showed significant analgesic potency, whereas the N-allyl (27a), N-(cyclopropylmethyl) (27b), and N-(n-hexyl) (27c) analogues were inactive.Bicifadine (2b) showed a nonnarcotic profile different from analogous azabicycloalkane and 3-phenylpyrrolidine analgesics.