Heterocyclic compounds containing the CF3 group are interesting targets of advanced researches to ge — Organic Chemistry Chemistry Question
Small heterocycles
Heterocyclic compounds containing the CF3 group are interesting targets of advanced researches to generate biologically active compounds. It is quite difficult to bring the trifluoromethyl group into saturated heterocyclic structures, especially heterocycles containing nitrogen. However, these heterocycles bearing CF3 groups have several promising applications. Therefore, studies of such compounds have been carried out by many chemists.
Trifluoroacetaldehyde (A) was treated with ethanol and then refluxed with benzylamine in toluene to afford compound B (C9H8NF3). The reaction of compound B with ethyl diazoacetate in diethyl ether with boron trifluoride etherate (BF3.Et2O) as a catalyst at -78 oC for 4 hours provided compound C (C13H14NO2F3). The reduction of compound C by LiAlH4 in THF at room temperature for 2 hours formed compound D. Then, D reacts with hydrogen in the presence of Pd(OH)2 as a catalyst in CH2Cl2 at room temperature for 60 hours to obtain E (C4H6NOF3). Compound E was then allowed to react with 2 equivalents of tosyl chloride (TsCl) in dicloethane with Et3N and an amount of 4-dimethylaminopyridine (DMAP) as catalyst. The reaction was carried out at room temperature for 2 hours, then 3 hours of reflux, to furnish compound F. F reacted with 1.2 equivalents of phenol in the presence of K2CO3 in DMF to form compound G (C17H16NSO3F3).
A derivative of G can be synthesized according to the following diagram:
[VISUAL]
Note:
BnNH2 = benzylamine, C6H5CH2NH2;
Bn = Benzyl, C6H5CH2-,
THF = tetrahydrofuran
LiHMDS = Lithium bis(trimethylsilyl)amide,
Et = C2H5-;
Equi = equimolarity
Complete schemes of syntheses from B to L.
Model Answer
Scheme 1:
[VISUAL]
Scheme 2:
[VISUAL]
(Reagents, conditions, and intermediates featured in the solution include: AcOH, NaBH4, EtOH, THF, SOCl2, LiHMDS, CH2Cl2, and compounds/structures NH, NH, F3C, Bn, Bn, OH, Cl, Bn, F3C, NH, CF3, Bn, N, L, IH (C13H14NO2F3))
Write reaction mechanisms from B to C.
Model Answer
Reaction mechanism for the transformation from B to C:
[VISUAL]
Write reaction mechanisms from F to G.
Model Answer
Reaction mechanism for the transformation from F to G:
[VISUAL]
(Structures/fragments featured in the solution mechanism: OTs, N, Ts, F3C -O-Ph, N -, Ts, F3C OPh)