To design the synthesis route of 2-fluoro-5-(trifluoromethoxy)benzaldehyde, we can adopt the following steps:
1.Choose the right starting material: Choose a simple benzene derivative as the starting material, such as benzene or other benzene derivatives that already contain the desired functional groups.
2.Introduction of fluorine atoms: The introduction of fluorine atoms on the benzene ring can be achieved by a variety of methods, such as direct fluorination of the benzene ring using a fluorinating agent such as N-fluorosulfonamide. For 2-position fluorination, targeted introduction of fluorine atoms using directed metallization strategies (e.g., with lithium reagents) can be considered.
3.Introduction of trifluoromethoxy groups: Trifluoromethoxy groups (-OCF) are usually introduced by reaction with trifluoromethol or its derivatives. This step may require targeted introduction of functional groups at the 5-bit, such as using a protection base strategy.
4.Construct aldehyde group: Benzaldehyde structure can be constructed by various methods. If the starting substance is benzoic acid or its derivatives, rosenmund reduction can be used to convert the acid chloride to aldehyde. If the starting substance is benzene, it can first be introduced by Friedel-Crafts acylation and then converted to aldehydes.
Based on the above ideas, a possible synthetic route is as follows:
Starting substance selection: 2-fluorinated benzoic acid was chosen as the starting substance, as this can simplify the introduction of fluorine atoms.
Step 1: Trifluoromethoxy group is introduced at the 5-position of the benzene ring using trifluoromethanol and a related catalyst (e.g., ALCL) by the Friedel-Crafts reaction.
Step 2: 2-fluoro-5-(trifluoromethoxy)benzoic acid is converted into the corresponding aldehyde by an acid chloride intermediate. This can be done by first converting the acid to acyl chloride (using e.g. SOCL) and then reducing it using rosenmund to obtain aldehydes.