Simonis chromone synthesis

Simonis Chromone Synthesis Timothy T. Curran 8.7.1 Description... 

The Simonis chromone synthesis is the reaction of a phenol la-c with a P-keto ester 2 using an appropriate acid promoter to generate a chromone or benzo-y-pyrone 3 (also called a benzo-l,4-pyrone). While compound 3 is actually a chromenone, for this article, whether the double bond is present or not, the system will be characterized as a chromone. The condensation is related to the Pechmann-Duisberg reaction, which yields coumarins from the condensation of a phenol with a P-keto ester and like its relative, the reaction conditions require the loss of water from the ketone moiety and alcohol from the ester moiety. 

Simonis continued to prove the correct structural assignment by degradation and began exploring the scope and limitation of the reaction As more co-workers joined in the exploration, many were convinced that Simonis did not make the chromone, but actually made the coumarin and that the structure was merely misassigned. While descriptions of early work solely on the Simonis chromone synthesis are lacking, reviews on the synthesis of coumarins (the Pechmann reaction) typically include an overview on the Simonis chromone synthesis " ... 

The Simonis chromone synthesis and the Pechmann-Duisberg reaction can be considered as O-analogs of the Conrad-Limpach and Knorr reactions for the preparation of quinolines from the corresponding aniline. ... 

A more recent report on the use of PPE to promote cyclization of a P-naphthol has appeared. The reagent allowed product formation in excellent yield at room temperature. Such results were a great improvement to the reaction conditions and yield typically obtained in the Simonis chromone synthesis. 2,6-Dihydroxy-naphthol 35 gave chromone 36 in 98% yield. 

The Simonis chromone synthesis has also been applied to phenol-like systems. The reaction of 40b (in equilibrium with 40a) with 6 and P2O5 provided a mixture of the Pechmann and Simonis products 41 and 42 when anhydride 40a,b was substituted (R = Me). When the material was unsubstituted (R = H) only 43 was isolated. The authors suggested that the formation of the 1,4-pyran was followed by rearrangement to the more stable product. While the yields were low, entry was established into these highly oxidized bis-pyranyl systems. 

The Simonis chromone synthesis was reported as a key reaction in the preparation of the natural product visnagin 48, a component found in fruits. Badawi and Fayez reported the conversion of 44 and 46 using heat in diphenyl ether in satisfactory yield. The aldehydic product 47 was derived from phloroglucin aldehyde 45 via similar thermal reaction conditions and was subsequently converted into visnagin 48. Note that the cyclization occurred under thermal conditions with no acid catalysis. 

While the chromone moiety is found in several natural products, the Simonis chromone synthesis has not been exclusively used to prepare chromones. Other methods exist that are oftentimes more easily utilized, run under more mild conditions, or provide higher yields. For example, the Kostanecki-Robinson reaction has found application in this arena. However, alternative reaction types are not without their own issues therefore, the Simonis chromone synthesis remains a tool for the synthetic chemist. 

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