There are herein disclosed a process for continuously and stably synthesizing a ketazine from hydrogen peroxide, ammonia and methyl ethyl ketone in the presence of a working solution containing a catalyst, said process comprising a step of removing sec-butyl alcohol by distillation from methyl ethyl ketone which is reused by circulation, and a process for preparing a hydrazine hydrate which comprises the step of hydrolyzing this ketazine.

According to the present invention, while unreacted ketone is circulated, the accumulation of impurities in the circulated ketone can be prevented to maintain the yield of the ketazine and the yield of the hydrazine hydrate at a high level for a long period of time.

Die Erfindung betrifft ein verbessertes Verfahren zur Herstellung von substituierten Phenylhydrazonen ausgehend von Anilin-Derivaten und 1,3-Dicarbonylverbindungen, das dadurch gekennzeichnet ist, daß die Umsetzung des Diazonium-Salzes mit der 1,3-Dicarbonylverbindung in einem mit Wasser nicht mischbaren Lösungsmittel stattfindet sowie die Verwendung der so hergestellten Verbindungen zur Herstellung von Indolen.

La présente invention concerne un procédé de synthèse d'azines à partir d'eau oxygénée, d'ammoniac et d'un réactif portant un groupe carbonyle caractérisé en ce qu'on met en contact ce réactif avec un amide d'acide faible et le sel d'ammonium correspondant à cet acide puis qu'on sépare l'azine obtenue.

L'invention concerne aussi des procédés dans lesquels la réaction se fait en présence de tout mélange contenant un amide puis on récupère l'azine et le reste du milieu réactionnel est traité pour régénérer l'amide.

A compound represented by Chemical Formula 1 according to the present invention can coordinate with metal ions to form a bidirectional or multidirectional metal-organic hybrid structure. Thus, the present invention can synthesize various ligands using amine-aldehyde condensation, and synthesize metal-organic materials using the same.

It relates to a preparation process of 2'-(benzyloxy)-3'-nitro-1,1'-biphenyl-3-carboxylic acid or a salt thereof comprising reacting 2-(benzyloxy)-1-bromo-3-nitrobenzene with a either 3-carboxyphenylboronic acid or a salt thereof or a (C₁-C₄)-alkyl ester thereof in the presence of Pd(OAc)₂, tricyclohexylphosphine, a base, an appropriate solvent, and at an appropriate temperature; if appropriate, submitting the compound thus obtained to a hydrolysis reaction; and isolating the compound thus obtained in form of a salt of compound of formula (VI) or in form of the free acid by adding an acid. It also comprises the further preparation to eltrombopag or its salts from the new intermediate thus obtained by subsequent reduction of the nitro group and deprotection of the phenol, conversion of the amine intermediate obtained in a diazonium derivative, and either (1) subsequent reaction with ethyl acetoacetate and with (3,4-dimethylphenyl)hydrazine or a salt thereof, occurring the pyrazole ring formation by intermolecular cyclization, or (2) introduction of the pyrazole ring by reaction with 1-(3,4-dimethylphenyl)-3-methyl-3-pyrazolin-5-one.

The purpose of the invention is to provide a resin, which has a high refractive index, excellent heat resistance and moldability, and high transparency, and is useful as a material for configuring optical devices, etc. The invention provides a resin comprising acyl hydrazone bonds and having a number average molecular weight of 500 - 500,000, wherein the acyl hydrazone bond equivalent is 100 - 4000.

The present invention provides a method represented by Scheme 1: wherein

X

represents I, Br, Cl, alkylsulfonate, or arylsulfonate;

Z

represents optionally substituted aryl, heteroaryl or alkenyl;

catalyst

comprises a copper atom or ion, and a ligand;

base

represents a Bronsted base; and

R

represents optionally substituted alkyl, cycloalkyl, aralkyl, heteroaralkyl, alkenylalkyl, or alkynylalkyl.

The present invention provides a method represented by Scheme 1: wherein

X represents I, Br, Cl, alkylsulfonate, or arylsulfonate;

Z represents optionally substituted aryl, heteroaryl or alkenyl;

L represents hydrogen or a negative charge;

catalyst comprises a copper atom or ion, and a ligand;

base represents a Bronsted base;

R represents H, optionally substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl;

R' represents independently for each occurrence H, alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl, formyl, acyl, -CO₂R", -C(O)N(R)₂, sulfonyl, -P(O)(OR")₂, -CN, or -NO₂;

R" represents independently for each occurrence optionally substituted alkyl, cycloalkyl, aralkyl, aryl, or heteroaryl; and

C (R')₂(R) taken together may represent nitrile.

A process for preparing a ketazine compound of the formula (1) from a ketone compound of the formula (2), ammonia and an oxidizing agent, wherein a solution containing the ketone compound of the formula (2) and ammonia is brought into contact with an aqueous solution of the oxidizing agent in a tubular reactor having a flow channel width of 2 to 10000 µm wherein R¹ and R² are the same or different and are each a C_1-6 alkyl group, or R¹ and R² are combined with each other into a straight-chain C_2-7 alkylene group wherein R¹ and R² are the same as above.

A process comprising allowing a peroxide compound represented by following Formula (2): wherein R^a, R^b, R^c and R^d are the same or different and are each a hydrogen atom or a hydrocarbon group, and wherein R^a and R^b, R^c and R^d may be combined to form a ring together with the adjacent carbon atom, respectively, to react with ammonia and water to yield an azine compound represented by following Formula (3): wherein R^a, R^b, R^c and R^d have the same meanings as defined above, or oxime compounds represented by following Formulae (4a) and/or (4b): wherein R^a, R^b, R^c and R^d have the same meanings as defined above, in the presence of a nitrogen-containing cyclic compound constitutively having a skeleton represented by following Formula (A) in its ring: wherein X is one of an oxygen atom and an -OR group, and wherein R is one of a hydrogen atom and a hydroxyl-protecting group. This process can produce an oxime compound or an azine compound useful as a material for oxime compounds from low-cost materials by easy and simple procedures.