Reduction of Carboxylic Acids and Carboxylic Esters
The reduction of carboxylic acids and carboxylic acid esters is an important class of reactions in organic chemistry with a wide range of applications. Carboxylic acid esters are generally easier to reduce to primary alcohols, and commonly used methods are lithium aluminum hydride, sodium borohydride, lithium borohydride, etc. Carboxylic acids, on the other hand, are less reactive than carboxylic acid esters. Carboxylic acid, on the other hand, has much lower activity than carboxylic acid ester and is a more difficult substance to reduce, so lithium aluminum hydride is commonly used as a reducing agent. However, lithium aluminum hydride as a reducing agent, the selectivity is poor, easy to reduce the bottom species other functional groups. Borane reduction is also an important method to reduce carboxylic acids, which has good reducing effect for fatty acids and most aromatic acids, but the reaction speed is slow or even non-reactive for some aromatic acids. Recently, the research on the reduction of carboxylic acids and carboxylic esters has had a rapid development, and new methods of reduction are constantly being discovered. In this paper, a brief overview of some reduction systems of carboxylic acids and carboxylic acid esters is given in conjunction with the reduction of various carboxylic acids and carboxylic acid esters carried out in
our laboratory in recent months.
Reduction of carboxylic acid esters
Carboxylic acid esters are generally easier to reduce to primary alcohols, and the commonly used methods are lithium aluminium hydride, sodium borohydride, lithium borohydride and so on, and Na-EtOH system can also be used, but the latter is only widely used in industry at present, and has been seldom used in the laboratory.
Aluminum lithium hydride reduction of carboxylic acid esters into alcohols
Lithium aluminum hydride is a common reagent for reducing carboxylic acid esters. However, this reagent can reduce a variety of functional groups, so the selectivity is poor. However, the reducing ability of lithium aluminum hydride can be reduced by lowering the reaction temperature, adding anhydrous AlCl3, and replacing the hydrogen atom of lithium aluminum hydride with an alkyl or alkoxy group to achieve selective reduction. In our experiments we encountered a heterocycle for reduction as follows. Reduction with NaBH4, LiBH4, the raw material is quickly reacted, but the heterocyclic ring is also reduced at the same time, reduce the temperature is not reacted. We tried to hydrolyze the ester to acid and then reduce it with BH3-Me2S, but it did not react even after refluxing for a long time. Later, we tried to use LiAlH4 to reduce the ester at -20 degrees Celsius, and achieved better results, the heterocyclic ring and nitro group were retained, and only the ester group was reduced.
Reduction of carboxylic acid esters to alcohols by sodium borohydride
NaBH4 reduction of carboxylic acid esters is a commonly used method, because the reaction is simple and safe, the requirements for anhydrous conditions are not very demanding, and the reaction can be completed in a few hours with highly active substrates. However, due to the sodium borohydride is not strong enough to reduce, some of the less active substrates can only be partially reacted overnight at room temperature, and then it needs to be heated and refluxed.
Reduction of carboxylic acid esters to alcohols by NaBH4/I2, NaBH4/AlCl3, NaBH4/ZnCl2 systems
The reduction of esters by NaBH4 alone is poor, but the addition of iodine or Lewis acids such as AlCl3, ZnCl2, BF3 can greatly improve the reduction ability of NaBH4, and even some less reactive esters can be reduced successfully. Bhaskar et al. found that, if I2 was added to a tetrahydrofuran solution of sodium borohydride at 0°C, and then carboxylic esters were added after the reaction for 2.5 h, the esters could be easily reduced. Bhaskar et al. found that if I2 was added to sodium borohydride in tetrahydrofuran solution at 0°C for 2.5 h and then carboxylic acid was added, the ester could be easily reduced to alcohol in 85-98 % yield. By adding Ph3P to the reaction system to capture the BH3, the researchers noted that the real reducing agent in the reaction in this order was the borane: NaBH4/IH4/IH4/IH4/IH4/IH4/IH4/IH4/IH4/IH4/IH4/IH4.
In addition, the NaBH4/I2 system successfully reduced amides and nitriles.
