681-01-6Relevant academic research and scientific papers
A modular, low footprint and scalable flow platform for the expedient α-aminohydroxylation of enolizable ketones
Kassin, Victor-Emmanuel H.,Morodo, Romain,Toupy, Thomas,Jacquemin, Isaline,Van Hecke, Kristof,Robiette, Rapha?l,Monbaliu, Jean-Christophe M.
supporting information, p. 2336 - 2351 (2021/04/07)
The unique reactivity profile of α-chloronitroso derivatives is expressed to its fullest potential through the development of an integrated, modular and scalable continuous flow process for the electrophilic α-aminohydroxylation of various enolizable ketones. Flow conditions contribute to mitigating the high reactivity and toxicity of α-chloronitroso derivatives and provide an efficient, versatile and safe protocol for the α-aminohydroxylation of ketones with a minimal footprint. Fundamental aspects of the α-aminohydroxylation process were computed by DFT and further supported the experimental observations, hence leading to the unprecedented α-chloronitroso-based α-aminohydroxylation of primary, secondary and tertiary substrates. Recycling of the carbon backbone of the α-chloronitroso derivatives provides a high atom economy for the preparation of value-added molecules. This work showcases α-chloronitroso derivatives as economic and efficient vehicles for transferring electrophilic synthons of hydroxylamine toward nucleophilic enolates. A representative range of precursors and analogs of pharmaceutical active ingredients, including WHO essentials and drugs in shortage (such as epinephrine and ketamine), are prepared within minutes according to a fully concatenated process. The process features sequential modules with distinct unit operations including chemical transformations and multiple in-line extractions. The process relies on an upstream chemical Generator that manages the preparation of α-chloronitroso derivatives and that feeds downstream a series of α-aminohydroxylation modules. The setup is amenable to the addition of libraries of compounds for feeding upstream the process of discovery in medicinal chemistry and is transposable to pilot scale. Several layers of in-line analytical procedures are featured to improve process control and safety.
N,N′-Dichloro bis(2,4,6-trichlorophenyl)urea (CC-2): an efficient reagent for the synthesis of α-chloro-nitroso compounds
Gupta,Acharya,Pardasani,Dubey
, p. 767 - 770 (2007/10/03)
A simple, efficient, rapid, and mild method for the synthesis of α-chloro-nitroso compounds is described using bis(2,4,6-trichlorophenyl)urea (CC-2).
A new method for the generation of α-nitrosoolefins from ketooximes and its application to the synthesis of 5,6-dihydro-4H-1,2-oxazine derivatives [1]
Gaonkar,Rai, K. M. Lokanatha
, p. 877 - 881 (2007/10/03)
Reaction of ketooximes containing α-methylene group with chloramine-T followed by treatment with triethylamine leads to the formation of α-nitrosoolefins via α-nitrosochloride, which can react in situ intermolecularly with olefinic compounds to produce 5,
Infrared studies of conformational isomerism in some gem-chloronitrosoalkanes
Evans, K. M.,Ireson, S. J.,McCoustra, M. R. S.,Pfab, J.
, p. 659 - 670 (2007/10/02)
The IR spectra of 2-chloro-2-nitrosopropane, 2-chloro-2-nitrosobutane and 2-chloro-3-methyl-2-nitrosobutane have been studied in the gas phase and solid phase, and in solutions of varying polarity.The spectra reveal clear evidence for the hindered internal rotation of the NO functional group about the C-N bond in a splitting of the N=O stretching band.The spectra can be interpreted as arising from energetically favoured cis conformational isomers, exhibiting the higher of the observed N=O stretching frequencies.In each case, assignment of the lower N=O stretching frequency is uncertain on the basis of experimental evidence.The results of semi-empirical molecular orbital calculations, however, support the assignment of this feature to the gauche conformational isomers.Temperature dependent IR spectroscopy has been employed in the determination of conformational enthalpy differences in both the gas phase and non-polar solution, which are then compared to the results of semi-empirical molecular orbital calculations.
