Method for performing Mitsunobu reaction between alcoholic hydroxyl group donor and active hydrogen donor

1 . A method for performing Mitsunobu reaction between an alcoholic hydroxyl group donor and an active hydrogen donor, which specifically comprises the following steps:

performing reaction of the alcoholic hydroxyl group donor, the active hydrogen donor, a trihydrocarbylphosphine reagent and an azodicarboxylate reagent in the presence of an organic solvent to obtain the product of dehydration condensation of the alcoholic hydroxyl group donor and the active hydrogen donor;

wherein, the organic solvent is a C 8-16 linear or branched alkane;

wherein the alcoholic hydroxyl group donor is selected from the group consisting of 4′-propyl-[1,1′-bis(cyclohexane)]-4-yl)methanol, 4-(4-ethyl-2-fluorophenyl)cyclohexanol, 4-(2′,3′-difluoro-4′-methyl-[1,1′-biphenyl]-4-yl)cyclohexanol, and 4-(3-fluoro-4-isopropylphenyl)cyclohexanol; and

wherein the active hydrogen donor is selected from the group consisting of 4-ethoxy-2,3-difluorophenol, 4-(4-propylcyclohexyl)aniline, and 4-propylbenzoic acid.

2 . The method according to claim 1 , wherein the organic solvent is selected from the group consisting of isomeric decane, isomeric dodecane, normal dodecane, and isomeric pentadecane.

3 . The method according to claim 2 , wherein, the organic solvent is isomeric dodecane.

4 . The method according to claim 1 , wherein, the trihydrocarbylphosphine reagent is selected from the group consisting of triphenylphosphine, tributylphosphine, and trimethylphosphine.

5 . The method according to claim 1 , wherein, the azodicarboxylate reagent is selected from the group consisting of diethyl azodicarboxylate, diisopropyl azodicarboxylate, bis-2-methoxyethyl azodicarboxylate, and bis(4-chlorobenzyl) azodicarboxylate.

6 . The method according to claim 1 , wherein, a molar ratio of the alcoholic hydroxyl group donor and the active hydrogen donor is 1:1-1.2;

optionally, the molar ratio of the alcoholic hydroxyl group donor and the trihydrocarbylphosphine reagent is 1:1.05-1.3;

optionally, the molar ratio of the alcoholic hydroxyl group donor and the azodicarboxylate reagent is 1:1.05-1.3.

7 . The method according to claim 1 , wherein, a reaction temperature is 30-120° C. and reaction duration is 1-12 h.

8 . The method according to claim 1 , wherein, material addition sequence of the reaction is as follows: dropping the azodicarboxylate slowly into an organic solvent containing an alcoholic hydroxyl group donor, an active hydrogen donor, and a trihydrocarbylphosphine reagent, or, mixing the azodicarboxylate and the trihydrocarbylphosphine reagent first, and then adding the alcoholic hydroxyl group donor and the active hydrogen donor into the mixed liquid;

optionally, temperature during the dropping process is controlled at 30-120° C.

9 . The method according to claim 1 , wherein, the reaction is carried out under inert gas protection;

optionally, adding an organic base in the reaction;

optionally, using ultrasound or microwave during the reaction process.

10 . The method according to claim 1 , comprising:

performing reaction of the alcoholic hydroxyl group donor, the active hydrogen donor, the trihydrocarbylphosphine reagent and the azodicarboxylate reagent in the presence of an organic solvent at 30-120° C. for 1-12 h to obtain the product of dehydration condensation of the alcoholic hydroxyl group donor and the active hydrogen donor;

wherein

a molar ratio of the alcoholic hydroxyl group donor and the active hydrogen donor is 1:1-1.2, and a molar ratio of the alcoholic hydroxyl group donor and the trihydrocarbylphosphine reagent is 1:1.05-1.3; a molar ratio of the alcoholic hydroxyl group donor and the azodicarboxylate reagent is 1:1.05-1.3.