54528-00-6Relevant articles and documents
Kinetic characterization of a transient reaction by degeneration of the precursor mechanism: Application to the synthesis of 3,4-diazabicyclo[4.3.0]non- 2-ene
Delalu,Berthet,Metz,Elkhatib
, p. 327 - 338 (2006)
The rate of the oxidation of N-amino-3-azabicyclo[3.3.0]octane by chloramine has been studied by GC and HPLC between pH 10.5 and 13.5. The second-order reaction exhibits specific acid catalysis. The formation of N,N′-azo-3-azabicyclo(3.3.0)octane or 3,4-diazabicyclo(4.3.0)non-2-ene is pH, concentration, and temperature dependent. In alkaline media, the exclusive formation of 3,4-diazabicyclo[4.3,0]non-2-ene is observed. Kinetic studies show that the oxidation of N-amino-3-azabicyclo[3.3.0]octane by chloramine is a multi-step process with the initial formation of a diazene-type intermediate, which is converted by hydroxide ions into 3,4-diazabicyclo[4.3.0]non-2-ene. Because it was not possible to follow the rate of change of the intermediate concentration, to determine the kinetics of 3,4diazabicyclo[4.3.0]non-2-ene formation, a procedure based on the degeneration of the precursor process was adopted. An appropriate mathematical treatment allowed a quantitative interpretation of all the phenomena observed over the given pH interval. The activation parameters were determined.
Kinetics of the Autocatalytic Oxidation of N-Amino-3-Azabicyclooctane by Chloramine in Aqueous Medium
Khatib, M. El,Marchand, A.,Counioux, J. J.,Delalu, H.
, p. 757 - 768 (1995)
The kinetics of the degradation of N-amino-3-azabicyclooctane by chloramine has been studied by GC and HPLC in stoichiometric conditions in a solution buffered with NaOH/KH2PO4 and Na2B4O7*10H2O between pH = 10.5 and 13.5.The second-order reaction exhibits specific acid catalysis which indicates competitive oxidation between the haloamine and the neutral and ionic forms of the bicyclic hydrazine.The enthalpy and entropy of activation were determined at pH 12.89.In a nonbuffered solution, the interaction is autocatalyzed due to acidification of the mixture by the ammonium ions.In basic medium, the reaction forms an endocyclic hydrazone.A mathematical treatment based on an implicit equation allows a quantitative interpretation of all the phenomena observed over the above pH interval.This takes both the acid/base dissociation equilibria and the alkaline hydrolysis of the chloro-derivative into account.
Synthesis and NMR investigation of 3,4-diazabicyclo[4.3.0]non-2-ene and N,N'-azo-3-azabicyclo[3.3.0]octane. X-ray crystal structure analysis of a new tetrazene derivative
Delalu,Elkhatib,Peyrot,Fenet,Mentzen
, p. 681 - 686 (1999)
3,4-Diazabicyclo[4.3.0]non-2-ene and N,N'-azo-3-azabicyclo[3.3.0]octane are the main products of the oxidation of N-amino-3-azabicyclo[3.3.0]octane by chloramine. These new compounds have been isolated and characterized. A structural study has been performed with the goal of establishing the cis- trans configuration at the bicyclic junction. Multinuclear proton decoupling carried out on the endocyclic hydrazone has allowed the determination of the coupling constant of the bridgehead hydrogens. A low temperature conformational study shows splitting of the 13C signal of the carbon atom located α with respect to the ammonia nitrogen. This result, consistent with a cis structure, was confirmed by a nmr analysis conducted on the solid tetrazene derivative. The X-ray data collection on a single crystal of the tetrazene has permitted us to determine the crystallographic properties of this compound. Data processing by direct methods reveals that the geometry of the molecule presents a cis configuration for the bicyclic bridge link and a trans one for the azo group, confirming thus the main results obtained by nmr studies.
Formation of 3,4-Diazabicyclonon-2-ene and N,N'-Azo-3-azabicyclooctane by Oxidation of an Alicyclic Hydrazine. Influence of pH on the Diazene Rearrangement
Delalu, H.,El Khatib, M.,Marchand, A.
, p. 1113 - 1120 (1994)
3,4-Diazabicyclonon-2-ene and N,N'-azo-3-azabicyclooctane are the main products of the oxidation of N-amino-3-azabicyclooctane by chloramine.The reaction leads to the transient formation of a saturated bicyclic aminonitrene (diazene).At pH > 13, the diazene undergoes an intramolecular rearrangement to afford a hydrazone.At pH non-2-ene; N,N'-Azo-3-azabicyclooctane; Diazene; Hydrazine; NMR.
Preparation method of gliclazide side chain and preparation method of gliclazide
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Paragraph 0063-0069; 0071; 0072; 0076-0079; 0084-0087, (2017/07/04)
The invention relates to a preparation method of N-amino-3-azabicyalo [3.3.0] octane serving as a gliclazide side chain. The gliclazide side chain is obtained by carrying out one-step hydrogenation reduction on N-cyclopentyl amine imide through a transition metal atom-modified ruthenium-carbon catalyst. The activity of the modified ruthenium-carbon catalyst used in the method is obviously higher than that of an existing commercial ruthenium-carbon catalyst, so that the imide hydrogenation reaction which is hard to realize in the N-cyclopentyl amine imide can be carried out successfully. The preparation method of the gliclazide side chain is safe, efficient, high in yield and simple for posttreatment; the catalyst can be cyclically used indiscriminately, so that the production cost is substantially reduced, and green synthesis is basically realized; no waste water and no waste slag are produced; and the preparation method is particularly suitable for large-scale industrial production. The invention further relates to a production method of gliclazide, which has the advantages of short synthesis path, high yield, low preparation cost and the like.
Preparation method of gliclazide in green synthesis technology
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Paragraph 0017, (2017/08/29)
The present invention provides a gliclazide green synthesis process which is simple in process, safe and environmentally-friendly, and convenient to actually operate, N-amino-1, 2-cyclohexane dicarboximide is used as a raw material, the gliclazide green synthesis process mainly includes the following steps: N-amino-3-azabicyalo[3, 3, 0] octane is prepared by high pressure hydrogenation of the N-amino-1, 2-cyclohexane dicarboximide, the N-amino-3-azabicyalo[3, 3, 0] octane is reacted with phosgene in high pressure conditions to prepare N-(hexahydrocyclopentadiene[c] pyrrole-2(1H)-yl)-amino chloride, and finally gliclazide prepared by condensation reaction of the N-(hexahydrocyclopentadiene[c] pyrrole-2(1H)-yl)-amino chloride and para toluene sulfonamide.
New method for preparing gliclazide intermediate
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Paragraph 0008; 0021-0024; 0036; 0038; 0041; 0043; 0046-0063, (2017/06/02)
The invention discloses a new method for preparing a gliclazide intermediate, and particularly relates to a preparation method for a blood sugar lowering medicine gliclazide intermediate 2-amino octahydrocyclopenta[c]pyrrole. The method sequentially includes the following steps that octahydrocyclopenta[c]pyrrole is adopted as a raw material, and the product is obtained sequentially through nitrosation and a reduction reaction. Conditions of a brand-new reduction reaction are provided, the raw material for use is wide and sufficient in source, the price is low, the reaction condition is mild, the process is simple, all steps of the reaction are conventional operation, and the production cost is reduced.
Halogenation and amination dual properties of haloamines in Raschig environment: a chlorine transfer reaction between chloramine and 3-azabicyclo[3,3,0] octane
Elkhatib,Marchand,Peyrot,Counioux,Delalu
, p. 89 - 98 (2007/10/03)
The chlorine transfer reaction between 3-azabicyclo[3,3,0]octane 'AZA' and chloramine was studied over pH 8-13 in order to follow both the amination and halogenation properties of NH2Cl. The results show the existence of two competitive reactions which lead to the simultaneous formation of N-amino- and N-chloro- 3-azabicyclo[3,3,0]octane by bimolecular kinetics. The halogenation reaction is reversible and the chlorine derivative obtained, which is thermolabile and unstable in the pure state, was identified by electrospray mass spectrometry. These phenomena were quantified by a reaction between neutral species according to an apparent SN2-type mechanism for the amination process and a ionic mechanism involving a reaction between chloramine and protonated amine for the halogenation process. Amination occurs only in strongly basic solutions (pH ≥ 13) while chlorination occurs at lower pH's (pH ≤ 8). At intermediate pH's, a mixture of these two compounds is obtained. The relative proportions of the products are a function of intrinsic rate constants, pH and pKa of the reactants. The rate constants and thermodynamic activation parameters are the following: k1 = 45.5 × 10-3 M-1 s-1; ΔH10* = 59.8 kJ mol-1; ΔS10* = -86.5 J mol-1 K-1 for amination; k2 = 114 × 10-3 M-1 s-1; ΔH20* = 63.9 kJ mol-1; and ΔS20* = -48.3 J K-1 for chlorination. The ability of an interaction corresponding to a specific (NH3Cl+/RR′NH) or general (NH2Cl/RR′NH) acid catalysis has been also discussed.
Cinetique de formation du (N-amino-aza-3-bicyclooctane) par action de NH2Cl et NHCl- sur l'aza-3-bicyclooctane en solution alcaline concentree
Delalu, H.,Marchand, A.
, p. 1413 - 1426 (2007/10/02)
In this paper is described a new synthesis of the N-amino-aza-3-bicyclooctane from NH2Cl and aza-3-bicyclooctane.The kinetics is investigated in terms of concentrations (2*10-4-10-2 mol*l-1), pH between 11 and 14.42 (3 mol*l-1 NaOH) and temperature in the range 298-325.5 K.The overall reaction, first order in both reagents is the result of two competing steps: the first being pH independent, the second accelerated by increasing pH.The results can be interpreted by considering a dissociation of NH2Cl in a rapid equilibrium and the elementaries reactions SN2 between the amine and the ionic and molecular form of the chloro-compound.The rate bimolecular constant is modelized as a function of hydrogen ions activity.The enthalpy and entropy of activation of the molecular process are established at 298 K .In dilute solution, the yield of the reaction reaches 90percent for the following conditions (/ = 15; pH = 13.5; T = 298 K).
