Synthesis Of Naphthoquinonefuran Derivatives

Naphthoquinofuran and its derivatives have an oxygen-containing heterocyclic fused ring structure with a large number of unique biological activities.These compounds are widely used in pharmacology,pesticides,organic composite materials and other fields.Efficient,fast and low-cost synthesis of naphthoquinofurans is a hot topic discussed by organic synthesis workers in recent years.Alkynyl bromide is a very important class of organic synthetic materials.It is widely used in the synthesis of various heterocyclic compounds.Its significance in the preparation of pharmaceutical intermediates,nanomaterials and pesticides is undoubted.Therefore,it is of great significance to explore the new organic synthesis process of naphthoquinofuran compounds with high step-atomic economy using alkynyl bromide as a substrate.In this paper,2-hydroxynaphthoquinone and alkynyl bromide are used as raw materials,and the corresponding polysubstituted naphthoquinofuran derivatives are formed under the action of bases and additives,and expensive transition metal catalysts and organic ligands are avoided in this process.The paper carefully explored the effects of control conditions such as bases,solvent,additives,temperature,time on the yield,and obtained the optimized conditions.In the solvent N,N-dimethylacetamide(DMA),tetrabutylammonium bromide(2 equiv)was added as an additive,and CH;ONa(3 equiv)was used as a base.The reaction was performed at 120℃ for 24 hours,2-hydroxynaphthoquinone and alkynyl bromide can react to form 2-phenylnaphthalene[2,3-b]furan-4,9-dione with a yield of 65%.Under the standard reaction conditions,the thesis made a further study on the generality and limitations of the reaction.The types and positions of the substituents on the alkynyl bromide and 2-hydroxynaphthoquinone aromatic rings were changed in turn.Correspondingly,24 kinds of polysubstituted naphthoquinofuran derivative products are obtained,and the effects of electronic effects and steric effects of different substituents on the yield are analyzed in detail.Experimental data show that this method has a wide scope of substrates:(1)For the alkynyl bromide substrate,the electron-withdrawing group or the electron-donating group has a great influence on the reaction yield.The yield of the electron-donating group can generally reach more than 75%,while the yield of the electron-withdrawing group is only 55%.(2)The introduction of substituent groups at the ortho,meta.and para positions of alkynyl bromide substrates does not significantly affect the reaction yield.The para position is greater than the meta position,and the meta position is greater than the ortho position.It means that the less steric hindrance,the higher the yield;(3)For 2-hydroxynaphthoquinone substrates,the substituents on the aromatic ring have little effect on the yield regardless of the electronic effect or steric hindrance effect,and may be too far away from the reaction position.On the basis of the above results,a plausible reaction pathway for the one-pot tandem synthesis of naphthofuroquinone derivatives was proposed.A sodium methoxide-promoted deprotonation of 2-hydroxynaphthoquinones produced sodium enolate,which was then brominated at the 3-position of 2-hydroxynaphthoquinones to form the intermediate using the alkynylbromide as the source of Br+.A nucleophilic attack by the produced arylacetylide gave the alkynated intermediate,which was transformed into 3-alkynated hydroxynaphthoquinone through a keto-enol tautomeric process.A sodium methoxide-promoted deprotonation and subsequent intramolecular nucleophilic addition of enolate anion to conjugated ynone furnished the cyclized product.In this paper,a synthetic method of polysubstituted naphthoquinonefuran derivatives with mild conditions,convenient operation,good tolerance of substituents and wide scope was reported,which provided a novel route for the synthesis of naphthoquinonefuran derivatives.