Method for preparing 8-hydroxy julolidine and derivative thereof

Abstract

The invention discloses a method for preparing 8-hydroxy julolidine and a derivative thereof. The method comprises the following steps of: (1) solving 3-aminophenol compound and X(CH2)3Y in an organic solvent S1, adding alkali B1, performing intramolecular reaction, reacting until the 3-aminophenol compound fully converts into an intermediate, and processing after finishing the reaction to obtain an intermediate; and (2) adding the intermediate obtained in the step (1) and alkali B2 into an organic solvent S2, performing intramolecular reaction, and processing until finishing the reaction to obtain the objective product. The method for preparing the 8-hydroxy julolidine and the derivative thereof is simple in steps; by strictly controlling the reaction stages, occurrence of disubstituted side reaction and oxidation side reaction is reduced, and productivity ratio of the objective product is improved; and high-poisonous and high-polluted substrate or reagent is avoided in the whole reaction process, which is suitable for industrialization.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of 8-hydroxyjulolidine and derivatives thereof. Background technique [0002] Coumarins are commonly used as laser dyes and fluorescent probes for bioassays because they exhibit good characteristics of wavelength tunability, high quantum yield, high absorption coefficient, and small overlap in absorption and emission spectra. According to reports in U.S. patent documents US3873940, US3932415, US4005092, US4471041, US4736032, US4794184, and US6433176, the nitrogen ring of coumarin compounds greatly hinders the mobility of amino groups, thereby reducing the energy consumption caused by the rotation of non-cyclic amino groups. Coumarin also greatly increases the dipole moment of the excited state, leading to a high quantum yield. [0003] 8-Hydroxyjulolidine and its derivatives are important precursors for the synthesis of coumarin. The s...

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Problems solved by technology

The above-mentioned preparation method has several disadvantages: first, large-scale production of 8-hydroxyjulolidine or 8,10-dihydroxyjulolidine needs to add a large excess of 1-bromo-3-chloropropane, which will make the production relatively high cost

Secondly, strong corrosive acids such as hydrochloric acid, hydroiodic acid, and boron tribromide are required, which are harmful to the environment

The 3rd, above-mentioned method owing to need two additional steps, first utilizes poisonous dimethyl sulfate reagent to protect hydroxyl group, removes methyl group after cyclization reaction again, and makes total yield lower, reduces the greenness property of this method greatly. atom economy

But said method has serious 1,3-disubstituted propane side reaction (intermolecular side reaction) in actual operation, and the productive rate of product is very low (<5%), and the structure of the by product of generation is shown in the following formula :

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