Patent Description:
With the continuous consumption of fossil resources and the increasingly serious environmental pollution, biomass and its derivatives are functionalized, gradually applied to modern organic synthesis and industrial production of bulk and fine chemical through a variety of reaction ways (such as oxidation, reduction and amination), and are expected to become a sustainable substitute for petroleum based chemicals. Where, Achmatowicz rearrangement reaction is an epoxidation reaction which can oxidize furan derivatives (alkyl substituted furans, furfuryl alcohols, alkyl substituted furfuryl alcohols, etc.) to more complex and functional <NUM>-hydroxy-<NUM>H-pyran-<NUM>(<NUM>H)-one that is more complex in structure and has more functionalization, including <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one. These pyrones contain a variety of functional groups and can be further converted, are extremely valuable synthesis intermediates, play a crucial role in synthesis of antibacterial agents, monosaccharides and their analogues, natural products and drugs (<NPL>).

Pyrone is prepared by Achmatowicz rearrangement reaction. The most commonly used oxidants are N-bromosuccinimide (NBS) and me-chloroperoxybenzoic acid (m-CPBA). However, the use of these oxidants will produce quantitative organic byproducts of m-chlorobenzoic acid or succinimide, leading to a reduction in product purity, and therefore it is required to timely column chromatographic separation (<NPL>). Other reported catalytic systems include the combination of acetylacetone vanadium oxide (VO(acac)<NUM>) or tetra(isopropoxy) titanium (Ti(Oi-Pr)<NUM>) and tertbutyl hydroperoxide (TBHP) (<NPL>), potassium bromide (KBr)/potassium peroxymonosulfonate (Oxone) (<NPL>), bromine (Br<NUM>)/methanol (MeOH) (<NPL>), metal complex ([In(COD)Cl]<NUM>)/benzyl alcohol (<NPL>), etc., almost all the synthesis processes involved are homogeneous reactions, and homogeneous catalysts are difficult to separate from liquid reaction products, more attentions are paid to separation problems especially when noble metal complexes are used as catalysts, otherwise it is not economical and pollutes the product, thereby affecting the next step of reaction. In addition, the reaction system usually requires organic solvents, which reduces the "green index" of the reaction. However, the yield of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one obtained by ball milling under solvent-free conditions is not ideal, only <NUM>%-<NUM>% (<NPL>). With the increasing concern to environmental and energy issues in the field of green and sustainable technology, the development of an environmental-friendly, efficient and high-atom-economy synthesis method has become an urgent demand for the preparation of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one.

Falenczyk Carolin, Polloth Benjamin, Hilgers Petra, Konig Burkhard: "Mechanochemically Initiated Achmatowicz Rearrangement" The Achmatowicz rearrangement converts furfuryl alcohols, obtainable from renewable carbohydrates, into <NUM>-hydroxy-<NUM>-pyrane-<NUM>(<NUM>)-ones, which are versatile intermediates for organic synthesis. The first examples of a solvent-free mechanochemical Achmatowicz rearrangement are described here. Furfuryl alcohols were prepared from furfurals using mechamnochemically initiated reductions and Reformatsky reactions. Mechamochemical reaction conditions for the Achmatowicz rearramgement of the obtained furfuryl alcohols were optimized and applied to a series of derivatives, yielding the corresponding rearrangement products in yields of <NUM> to <NUM>%.

<NPL>" Dimethyldioxirane reacts rapidly at room temperature in acetone with a variety of furans, furnishing in high yield products of oxidative ring opening and, with <NUM>-furanmethanol, <NUM>H-pyran-<NUM>(<NUM>H)-one via subsequent ring closure.

<NPL>" Photoxidation of <NUM>-furylcarbinols followed by reduction with triphenyl-phosphine afforded <NUM>-hydroxy-<NUM>-pyran-<NUM>(<NUM>)-one in excellent yield. The method was applied to synthesis of <NUM>-undecyltetrahydro-<NUM>-pyrone, a pheromone of Vespa orientalis.

The main objective of the present application is to provide a method for preparing a biological active molecule <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one by catalytically oxidizing <NUM>,<NUM>-furan dimethanol using titanium silicalite, which is mild in reaction condition, green and economic and efficient, thereby overcoming the defects in the prior art.

In order to realize the objective of the foregoing invention, the technical solution adopted by the present application includes:.

The embodiment of the present application provides a method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through catalytic oxidization, comprising:.

catalytically oxidizing <NUM>,<NUM>-furan dimethanol for <NUM>-<NUM> at <NUM>-<NUM> by using titanium silicalite as a catalyst, hydrogen peroxide as an oxidant and water as a reaction medium so as to obtain <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one.

In some embodiments, the method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through catalytic oxidization comprises: evenly mixing <NUM>,<NUM>-furan dimethanol, titanium silicalite, hydrogen peroxide and water, and stirring the obtained reaction system to react for <NUM>-<NUM> at <NUM>-<NUM>, so as to obtain <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through one-step catalytic oxidization.

In some embodiments, a silica-to-titanium ratio in the titanium silicalite is (<NUM>-<NUM>): <NUM>.

Compared with the prior art, the present application at least has the beneficial effects:.

In order to provide a clearer explanation of the embodiments or technical solutions in the present application, a brief introduction will be given to the accompanying drawings required in the embodiments or description of the prior art. It is evident that the accompanying drawings in the following description are only some of the embodiments recorded in the present application. For ordinary technical personnel in the art, other accompanying drawings can be obtained based on these drawings without any creative effort.

As mentioned above, in view of the drawbacks of the prior art in the synthesis of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one, the inventor of this case, after long-term research and a lot of practice, proposed the technical scheme of the present application, which provides a method for synthesizing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyrano-<NUM>(<NUM>H)-one through efficient catalytic oxidization of <NUM>,<NUM>-furan dimethanol under mild conditions by using the heterogeneous catalyst titanium silicon molecular sieve and cheap and environmentally friendly oxidant (hydrogen peroxide) and directly using clean water as the reaction medium, thereby achieving a cleaner and more economical catalytic process. Compared with the existing reports, the present application has innovativeness and industrial application prospects.

In the present application, the reaction principle for preparing bioactive molecules <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through one-step catalytic oxidization of <NUM>,<NUM>-furan dimethanol may lie in direct epoxidation of a double bond in a furan ring. The reaction formula is as follows:
<CHM>
wherein, I is <NUM>,<NUM>-furan dimethanol, and II is <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one; the reaction temperature is <NUM>-<NUM>, and the reaction time is <NUM>-<NUM>.

The following will provide further explanations and explanations on the technical solution, its implementation process, and principles.

An aspect of the embodiment of the present application provides a method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through catalytic oxidization under mild, green and environmental-friendly and efficient reaction conditions, comprising:.

In some embodiments, the method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through catalytic oxidization comprises: obtaining <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through a one-step catalytic oxidization process by using titanium silicalite as a catalyst, <NUM>,<NUM>-furan dimethanol as a reaction raw material and water as reaction medium in the presence of oxidant hydrogen peroxide under mild conditions (react for <NUM>-<NUM> at <NUM>-<NUM>).

In some more specific embodiments, the method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>-pyran-<NUM>(<NUM>H)-one through catalytic oxidization comprises:.

evenly mixing <NUM>,<NUM>-furan dimethanol, titanium silicalite, hydrogen peroxide and water, stirring the obtained reaction system to react for <NUM>-<NUM> at <NUM>-<NUM>, and performing one-step catalytic oxidization to obtain <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one.

In some preferred embodiments, a silica-to-titanium ratio in the titanium silicalite is (<NUM>-<NUM>): <NUM>, preferably the silica-to-titanium ratio is (<NUM>-<NUM>):<NUM>.

In some preferred embodiments, a mass ratio of the catalyst titanium silicalite to the raw material <NUM>,<NUM>-furan dimethanol is (<NUM>-<NUM>):<NUM>, preferably the mass ratio of the catalyst to the raw material is (<NUM>-<NUM>):<NUM>.

In some preferred embodiments, the reaction raw material <NUM>,<NUM>-furan dimethanol (BHMF) is obtained by reducing <NUM>-hydroxymethylfurfural.

In some preferred embodiments, the mass concentration of <NUM>,<NUM>-furan dimethanol in the mixed reaction system is <NUM>/L-<NUM>/L, preferably <NUM>/L-<NUM>/L. That is to say, in the reaction medium water, the mass concentration of <NUM>,<NUM>-furan dimethanol is <NUM>/L-<NUM>/L, preferably, the concentration of the substrate is <NUM>/L-<NUM>/L.

In some preferred embodiments, the oxidant hydrogen peroxide is a hydrogen peroxide aqueous solution with a mass concentration of <NUM>%-<NUM>%.

In some preferred embodiments, the concentration of the oxidant in the mixed reaction system is <NUM> mol/L-<NUM> mol/L, preferably <NUM> mol/L-<NUM> mol/L. That is to say, in the reaction medium water, the concentration of the oxidant is <NUM> mol/L-<NUM> mol/L, preferably the concentration is <NUM> mol/L-<NUM> mol/L.

In some preferred embodiments, the temperature of the reaction is <NUM>-<NUM>, preferably <NUM>-<NUM>.

In some preferred embodiments, the time of the reaction is <NUM>-<NUM>, preferably <NUM>-<NUM>.

Further, the conversion rate of <NUM>,<NUM>-furan dimethanol in the method is above <NUM>%, and the yield of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one is above <NUM>%.

In conclusion, the method for synthesizing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through one-step efficient catalytic oxidization of <NUM>,<NUM>-furan dimethanol under mild conditions by using heterogeneous catalyst titanium silicalite and inexpensive and an environmental-friendly oxidant (hydrogen peroxide) and directly using water as a reaction medium provided by the present application achieves a cleaner and more economical catalytic process, has low cost, fewer byproducts, a yield of <NUM>%, easily product separation, environmentally friendliness, reused catalyst, has high atom economy and green index, and good industrial application prospects.

In order to make the purpose, technical solution and advantages of the present application clearer, the present invention will be further set forth in conjunction with specific embodiments and accompanying drawings. It should be understood that the specific embodiments described herein are only for explaining the present application, but experimental conditions and set parameters should not be considered as limiting the technical solution of the present application. Furthermore, the scope of protection of the present application is not limited to the following embodiments. In addition, technical features involved in various embodiments of the present application described hereinafter can be mutually combined without conflict.

Unless otherwise stated, raw materials and reagents used in embodiments of the present application are all commercially available.

<NUM>,<NUM>-furan dimethanol (<NUM>, <NUM>/L), titanium silicalite TS-<NUM> (a molar ratio of Si/Ti was <NUM>:<NUM>, <NUM>), H<NUM>O<NUM> (<NUM> wt%, <NUM> mol/L) were added into <NUM> of H<NUM>O and stirred for <NUM> at <NUM>. After cooling, <NUM> of reaction solution was added into a <NUM> volumetric flask so that the total volume was <NUM>, and underwent high performance liquid chromatography determination after passing through a <NUM> microporous filter membrane. The conversion rate of <NUM>,<NUM>-furan dimethanol was <NUM>%, and the yield of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one was <NUM>%. By referring to <FIG>, the product is yellow oil.

The NMR characterization data of the product <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one is as follows: <NUM>-NMR (<NUM>, CDCl<NUM>): δ=<NUM>(d, <NUM>), <NUM>(d, <NUM>), <NUM>(d, <NUM>), <NUM>(d, <NUM>), <NUM>(d, <NUM>), <NUM>(d, <NUM>).

Other process conditions and reaction steps are the same as those in example <NUM>, but different reaction temperatures are used. The results are seen in Table <NUM>.

Other process conditions and reaction steps are the same as those in example <NUM>, but different reaction times are used. The results are seen in Table <NUM>.

Other process conditions and reaction steps are the same as those in example <NUM>, but different catalyst amounts are used, that is, mass ratios of titanium silicalite to <NUM>,<NUM>-furan dimethanol are different. The results are seen in Table <NUM>.

The liquid chromatography-time-of-flight mass spectrometry coupled chromatogram of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one prepared in example <NUM> refers to <FIG>, and a mass spectrum of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one refers to <FIG>.

Other process conditions and reaction steps are the same as those in example <NUM>, but different substrate mass concentrations are used. The results are seen in Table <NUM>.

The UV absorption visible spectrogram of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one prepared in example <NUM> refers to <FIG>.

Other process conditions and reaction steps are the same as those in example <NUM>, but different oxidant hydrogen peroxide concentrations are used. The results are seen in Table <NUM>.

Other process conditions and reaction steps are the same as those in example <NUM>, but titanium silicalite catalysts with different silica-to-titanium ratios are used. The results are seen in Table <NUM>.

By comparing control example disclosed in <NPL> with example <NUM>, the difference was that the oxidant used was m-chloroperoxybenzoic acid. In this control example, when <NUM>,<NUM>-furan dimethanol was completely converted, the yield of <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM> (<NUM>H)-one is not ideal, only <NUM>%-<NUM>%.

<CIT> disclosed a preparation method of a <NUM>-substituted-<NUM>-hydroxy-<NUM>-pyran-<NUM>-one compound, in which an organic solvent was used. Furthermore, cumene hydroperoxide was used as an oxidant, this preparation was carried out in the presence of a triisopropyl oxyvanadate homogeneous catalyst, but the yield was only <NUM>%-<NUM>%.

This control example did not involve conversion of <NUM>,<NUM>-furan dimethanol, and the target product of the present application was not produced.

By virtue of the above technical solution, in the present application, <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one was obtained through a one-step catalytic oxidization process under mild conditions, so as to achieve a cleaner and economic catalysis process. The present application has a yield as high as <NUM>%, is low in cost, less in byproduct and environmental-friendly, and has easily separated product and good industrial application prospects.

Various aspects, embodiments, features and examples of the present application should be deemed as being illustrative in all aspects and are not intended to limit the present application, and the scope of the present application is only defined by claims. Those skilled in the art will understand other embodiments, modifications and uses without departing from the spirit and scope claimed by the present application.

Throughout the present application, when a composition is described as having, comprising, or including specific components, or when a process is described as having, comprising, or including specific process steps, it is expected that the composition taught in the present application will also be substantially composed of or composed of the described components, and the process taught in the present application will also be mainly composed of or composed of the described process steps.

Unless otherwise specifically stated, the use of the terms "include, includes, including" and "have, has or having" should generally be understood as being opened and not limiting.

It should be understood that the order of each step or the order in which specific actions are performed is not very important, as long as the instructions in this application remain operable. In addition, two or more than two steps or actions can be simultaneously performed.

In addition, the inventor of this case also conducted experiments using other raw materials, process operations, and process conditions described in this manual, referring to the aforementioned embodiments <NUM>-<NUM>. They also obtained <NUM>-hydroxy-<NUM>(hydroxymethyl) -<NUM>H-pyran-<NUM>(<NUM>H)-one with high selectivity.

Claim 1:
A method for preparing <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one through catalytic oxidization, comprising:
catalytically oxidizing <NUM>,<NUM>-furan dimethanol for <NUM>-<NUM> at <NUM>-<NUM> by using titanium silicalite as a catalyst, hydrogen peroxide as an oxidant and water as a reaction medium, so as to obtain <NUM>-hydroxy-<NUM>(hydroxymethyl)-<NUM>H-pyran-<NUM>(<NUM>H)-one.