阅读说明：本技术 O-(二烷基次膦酰基)酮肟的合成方法 (Synthesis method of O- (dialkyl phosphinic group) ketoxime ) 是由 曾庆乐 李怒涛 于 2019-10-23 设计创作，主要内容包括：O-(二烷基次膦酰基)酮肟在药物和有机合成有着重要用途。本申请开发出一种新的酮肟与二烷基膦氧化物的氧化偶联方法。过氧化氢用作绿色氧化剂,分子碘用作非金属催化剂,该反应具有较高的原子经济性,且副产物仅是水。另外,该反应避免了贝克曼重排反应的发生,并且以高收率获得了26种O-(二烷基次膦酰基)酮肟目标产物。(O- (dialkylphosphinic) ketoximes have important applications in pharmaceutical and organic synthesis. The present application develops a novel process for the oxidative coupling of ketoximes with dialkylphosphine oxides. Hydrogen peroxide is used as a green oxidant and molecular iodine is used as a non-metallic catalyst, the reaction has high atom economy, and the byproduct is only water. In addition, the reaction avoids the occurrence of Beckmann rearrangement and provides 26O- (dialkylphosphinic group) ketoxime target products in high yield.)

1. A method for synthesizing O- (dialkyl phosphinic group) ketoxime is characterized by comprising the following steps: in the presence of an oxidant hydrogen peroxide, acetonitrile is used as a solvent, and the iodine simple substance catalyzes ketoxime and dialkyl phosphine oxide to carry out oxidative coupling to synthesize O- (dialkyl phosphinic group) ketoxime in one step.

2. The process for synthesizing an O- (dialkylphosphinic) ketoxime according to claim 1, wherein the ketoxime comprises 1-indanone oxime, 5-fluoro-1-indanone oxime, 5-chloro-1-indanone oxime, 6-bromo-1-indanone oxime, 5-methoxy-1-indanone oxime, 4-methoxy-1-indanone oxime, acetophenone oxime, 3-methylacetophenone oxime, 3-methoxyacetophenone oxime, 4-fluoroacetophenone oxime, 2-fluoroacetophenone oxime, 4-trifluoromethylacetophenone oxime, 3-methyl-2-butanone oxime, cyclopentanone oxime, 3-acetylthiophene oxime and 2-acetylfuran oxime.

3. The method for synthesizing an O- (dialkylphosphinic acid oxime according to claim 1 wherein the dialkylphosphine oxide is selected from the group consisting of diphenylphosphine oxide, bis (3-fluorophenyl) phosphine oxide, bis (4-chlorophenyl) phosphine oxide, bis (4-methoxyphenyl) phosphine oxide, bis (3-methoxyphenyl) phosphine oxide, bis (2-methoxyphenyl) phosphine oxide, bis (4-methylphenyl) phosphine oxide, bis (3, 5-dimethylphenyl) phosphine oxide, dithienylphosphine oxide and dicyclopentylphosphine oxide.

Technical Field

The patent relates to the research field of organic synthesis, drug synthesis and organic chemical industry, in particular to a synthesis method for synthesizing O- (dialkyl phosphinic group) ketoxime compounds by one step through oxidative coupling of ketoxime and dialkyl phosphine oxide compounds.

Background

In recent years, more and more oxime functional groups have been used for biologically active compounds and drugs, such as fungicides, spasmolytics, anticonvulsants and antivirals (Kleeman A, Engel J, Kutscher B, Reichert D (1999)Pharmaceutical substances3rd edn. Thieme, Stuttgart). In addition, oxime derivatives play an important role in organic reactions, and some of them can participate in organic reactions as highly reactive precursors. Depending on their different activity manifestations, they can be used as protecting groups for 1, 3-dipoles, electrophiles, nucleophiles and carbonyl compounds, etc. (Sandler SR, Karo W (1989) Organic functional group preparation).Academic PressSan Diego). In the field of pesticides, certain derivatives with fluorescent oximes are useful for the detection of pesticides and other organophosphates (Walton, i., Davis, m., Munro, l., Catalano, v. j., Cragg, p. j., Huggins, m. t.,&Wallace, K. J. (2012).Organic Letters, 14(11), 2686-2689). Therefore, the incorporation of reactive heteroatoms into oxime chains has become an increasingly interesting research focus for scientists, and in particular the introduction of phosphorus atoms has considerable application potential. Among the various phosphorus-containing organic compounds, the phosphorus-containing organic compounds,phosphonates are a key component of polymer science and of biologically active compounds (west, r.t., Chambers, r.j., Green, m.d.,&Murphy, W. R. (1994).Bioorganic & Medicinal Chemistry Letters, 4(16), 2005–2010)。

the construction of N-O-P bonds from oximes and organophosphorus reagents has also attracted considerable attention from chemists. In the early 1978, Hudson was directly substituted with oximes and chlorodialkylphosphine oxides to form O- (dialkylphosphinic) ketoximes (Hudson, r.f.,&Woodcock, R. C. (1978).Justus Liebigs Annalen Der Chemie, 1978(1), 176-187). In 1981, Harger used diphenylhydroxylamine and acetone, acetone oxime and chlorodiphenylphosphine oxide, respectively. The same product was used to replace O- (dialkylphosphinic) ketoxime (harder, m.j.p. (1981).Journal of the Chemical SocietyPerkin Transactions 1, 3284); in 1987, Socloff used chloronitroso compound and diphenyl phosphine oxide to produce the corresponding dialkyl phosphine oxide ester (Sokolov, V.B., Ivanov, A.N., Epishina, T.A.,&Martynov, I. V. (1987).Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 36(11), 2401-2402). In 1990, Socloff, in turn, obtained the corresponding dialkyl phos-phate by an allen reaction with a nitroso-chlorine compound and a more active trimethyl phosphate diphenyl phosphate (Sokolov, V.B., Ivanov, A.N., Epishina, T.A., Goreva, T.V.,&Martynov, I. V. (1990).Bulletin of the Academy of Sciences of the USSR Division of Chemical Science39(2), 413-414); in 2007, oxime phosphates were synthesized by Wu by Atherton-Todd reaction with oxime and diethyl phosphite (Wu, S. M.; Zhang, X.H. (2007).Journal of Chemical Research, 2007(3), 146-147). In 2015, Hashemi used an oxime and a trialkyl phosphite to produce decyl phosphite under the action of azodiisopropyl dicarboxylate (Hashemi, s.a.,&Khalili, G.(2015).Monatshefte Für Chemie - Chemical Monthly, 146(6), 965–968)。

although there are many reports on the synthesis of O- (dialkylphosphinic) ketoximes, most of these methods use halogen-substituted substancesFor example, chlorodiphenylphosphine oxide, chloronitroso compounds, etc. Is not environmentally friendly and increases the raw material cost. Many other reactions use toxic chlorinated alkanes, such as dichloroethane, carbon tetrachloride, etc. (Zhu, j. -l., Wu, s. -t.,&Shie, J.-Y. (2014).The Journal of Organic Chemistry, 79(8),3623-3633). In the other part of the reaction, which must be at-78, an organic precursor with a higher activity is used^oC, which clearly greatly increases the difficulty of the reaction (Russell, g. a., Ros, f., Hershberger, j.,&Tashtoush, H. (1982).The Journal of Organic Chemistry, 47(8), 1480–1483)。

to the best of our knowledge, no literature reports are found which are the same as the present application.

Disclosure of Invention

The invention provides a method for synthesizing O- (dialkyl phosphinic group) ketoxime.

The synthesis method of the O- (dialkyl phosphinic group) ketoxime disclosed by the invention is completed in one step, namely in the presence of an oxidant, iodine simple substance catalyzes the ketoxime and dialkyl phosphine oxygen compound to carry out oxidative coupling reaction to synthesize the O- (dialkyl phosphinic group) ketoxime in one step.

The present invention is illustrated in more detail by the following examples, which are not to be construed as limiting the scope of the invention.

Detailed Description