An Effective One-pot Synthesis of Aldehydes from Acid Chlorides

Abstract

The establishment of a simple, general and practical method to get aldehydes from acid chlorides is one of the most important and highly desirable objectives in organic synthesis, and a number of reducing agents for this purpose have been reported. It has been reported that several reducing agents for partial reduction of acid chlorides, such as Li(t-BuO)3AlH, NaBH4-DMF, [(PPh3)2CuBH3CN]2, (PPh3)2CuBH4, and sodium diethyldihydroaluminate (SDDA)-piperidine, can be used. Among these, the SDDApiperidine system with acid chlorides is usually considered to be the method of choice. However, the yields of aldehydes from various acid chlorides are moderate to good (61-93%) and this method has a great problem in that the use of SDDA is not commercially feasible now. We have recently reported that lithium diisobutyl-t-butoxyaluminum hydride (LDBBA), sodium diisobutyl-t-butoxyaluminum hydride (SDBBA), and potassium diisobutyl-t-butoxyaluminum hydride (PDBBA), the t-butoxy ‘ate’ complexes of DIBAH, are new effective partial reducing agents which can convert various esters to aldehydes in very good yields. With these results in hand, we anticipated that treatment of several acid chlorides with metal diisobuyl-t-butoxyaluminum hydrides (LDBBA, SDBBA and PDBBA) would be effective in developing an efficient method for partial reduction of acid chlorides. However, we could not get the corresponding aldehydes by these reducing agents only, but alcohols. Next, we tried the similar reactions of benzoyl chloride with the reducing agents and secondary amines such as morpholine for obtaining benzaldehyde from benzoyl chloride. Among these, we could find the best results with PDBBA at room temperature (Table 1). Also, as shown in Table 2, we examined partial reduction of benzoyl chloride to benzaldehyde with PDBBA in the presence of various secondary amines such as diethylamine, dicyclohexylamine, piperidine, pyrrolidine, pyrrole and indole. However, we could not find better results than those with morpholine. Finally, we applied PDBBA in the pre-