Multi-halothane five-member cyclic nitrone derivative and preparation method thereof

Abstract

The invention discloses a multi-halothane five-member cyclic nitrone derivative indicated in the formula (II), i.e. 4-multi-halothane-2,4-di-substituted pyrroline-N-oxide derivative and a preparation method thereof. The preparation method comprises the following steps of dissolving fluorine-containing conjugated enyne, hydroxylamine hydrochloride and alkali into organic solvent to be adequately reacted at the temperature of 0 DEG C to room temperature, removing the solvent, and obtaining fluorine-containing alkynyl group hydroxy amine compound of the formula (I) through the column chromatography; then dissolving the fluorine-containing alkynyl group hydroxy amine compound into the organic solvent to be cyclized in the presence of silver catalyst and under the room temperature condition, removing the solvent, and obtaining 4-multi-halothane-2,4-di-substituted pyrroline-N-oxide derivative through the column chromatography. Raw materials are easy to obtain, the yield is high, the reaction condition is moderate, and simplicity in operation is realized. The invention also provides a fluorine-containing alkynyl-containing group hydroxyl amine compound of the formula (I) and a preparation method thereof. The 2,4-di-substituted multi-halothane-containing cyclic nitrone compound skeleton has an important significance on the substituted fluorine-containing cyclic nitrone compound and the synthesis of the derived heterocyclic compound.

Description

technical field [0001] The invention relates to a preparation method of a five-membered cyclic nitrone derivative containing a polyfluoroalkyl group, in particular to a preparation method of a 4-polyfluoroalkyl-2,4-disubstituted pyrroline-N-oxide derivative The method belongs to the technical field of chemical substances and their preparation. Background technique [0002] Nitrones are an important class of intermediates in organic synthesis, which have attracted the attention of many scientists in recent years. Nitrones have been successfully used to construct molecular skeletons of natural products and biologically active compounds, stable nitroxyl radicals, and some special-purpose spin trapping agents; cycloaddition reactions involving nitrones and organometallic reagents Alkylation reactions have shown broad application prospects (E.Breuer, H.G.Aurich, A.Nielsen, Nitrones, Nitronates and nitrogenates, John Wiley and Sons, New Jersey, 1989., K.B.G.Torsell, Nitrile oxid...

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Problems solved by technology

The synthetic method of nitrone mainly contains following 4 kinds: (1) N, the oxidation method of N-disubstituted hydroxylamine, though this kind of reaction condition is milder, but, the reaction time is all relatively long, often accompanied by side reactions. The conversion rate is low, and the product yield is low; (2) the reaction of oxime and halogenated hydrocarbon, what adopt this kind of synthetic method to obtain is often the mixture of nitrone and oxime ether, not only yield is lower, and separation is more difficult; (3 ) The rearrangement method of oxa-acine, adopting this method can obtain nitrone, but also generate by-products such as amides simultaneously; Commonly used method, but this reaction is a reversible reaction, under different conditions, the yield and the quality of gained nitrone are different, and the product is easy to decompose and polymerize (J.Chem.S oc, 1959, 2094., J.Am. Chem S oc, 1962, 84, 1197., Org Synth, 1991, 70: 265., Collection Czech Chem Commun, 1951, 16, 258., J Org Chem, 1995, 60, 1741)

After years of development, although the synthesis methods of nitrones have been mutually supplemented and improved, there are no reports in the literature on the synthesis of polyfluoroalkyl nitrone compounds.

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