The Synthesis Of Benzoxanthenes,4,4'-arylidene-bis(3-methyl-pyrazolones) And Chiral Oxazoline Derivatives

(1) Benzoxanthene compounds have many applications. They have manybiological and pharmaceutical effects, such as analgesics, anti-inflammatory drugs,antibacterial drugs, anti-viral activity and the fluorescent material.Because of the value of the benzoxanthene compounds, the researchersdeveloped many synthetic methods, including Sr(OTf)₂, phase transfer catalysttetrabutylammonium bromide, NaHSO₄/SiO₂, InCl₃and P₂O₅, I2, toluenesulfonicacid, molecular sieves, Cu/SiO₂, proline trifluoromethane sulfonate, cericammonium nitrate (CAN) and camphor sulfonic acid (CSA). These methods havetheir own advantages, but as a coin has two sides, also have some drawbacks, suchas long reaction time (5-7hours), toxic organic solvents, toxic metal catalysts,corrosive catalyst, and expensive catalyst.Clearly, these methods are not in line with the concept of "green chemistry", itis necessary to develop new synthetic method. We developed a new syntheticmethod using [NSPTEA][HSO₄] and ZrOCl₂8H₂O as catalyst for the synthesis ofbenzoxanthene compoundsCompared to the reported synthetic methods, our newly developed method hasthe following significant advantages:a) High yield,74%-87%.b) The reaction time is significantly shortened, only requires10-30min.c) The reaction does not require solvents.d)[NSPTEA][HSO₄] can be reused.e)[NSPTEA][HSO₄], and ZrOCl₂8H₂O are not corrosive or toxic at all.f) The preparation of [NSPTEA][HSO₄] is very simple. And the rawmaterials are cheap and easy to get.g) ZrOCl₂8H₂O costs lower.h)[NSPTEA][HSO₄] and ZrOCl₂8H₂O are water stable. (2) Pyrrole ring is the core structure of biologically active compounds, andtherefore arise widespread concern in the pharmaceutical industry. And it hasbecome one of the synthetic target molecules. Moreover, derivatives of4,4'-arylidene-bis (3-methyl-pyrazolones) can be used as fungicides, pesticides,insecticides, dyes, and different metal ion chelators and extraction reagents.However, the overall reaction yields and time are unsatisfying and lengthy. Sothere is still need to develop a new and convenient method for the synthesis of4,4'-arylidene-bis(3-methyl-pyrazolones).Our group developed a multi-component one-pot method, starting directly fromaldehydes, ethyl acetoacetate and hydrazine hydrate, for the synthesis of4,4'-arylidene-bis (3-methyl-pyrazolones) compounds. The advantages of our methodare:1) more simple procedure,2) high yields,3) shorter reaction time,4) avoid theuse of organic solvents which is harmful to environment.(3) Oxazolines are important class of heterocyclic compounds with a wide rangeof pharmaceutical and biological activities. In addition, these compounds have alsovarious synthetic uses in modern day chemistry which play an important role inasymmetric synthesis. Numerous methods have been developed for the preparationof2-substituted oxazolines. However, these methods have some shortcomings,including drastic thermal conditions (160–220℃), long reaction times (12–18h),modest yields, expensive coupling reagents.We have developed a new, simple and mild synthesis of optically active2-(N,N-dialkyl)oxazolines by only two or three steps from cheap tetraalkyl ureas andα-amino acids with good overall yields. These new2-(N, N-dialkyl)oxazolines maybe potential chiral auxiliaries or ligands, and are being investigated in our laboratoryfor further application.