A kind of nitration method of aryl phenols or aryl ether derivatives

Abstract

The present invention relates to a kind of nitration method of aryl phenols or aryl ether derivatives. In the acetonitrile solution, stirring at room temperature, while monitoring the degree of reaction by TLC dot plate, after the substrate is completely consumed, then remove the solvent with a rotary evaporator, and purify the mixture by silica gel column to obtain the nitroalkene derivative . At the same time, by controlling the nitrate equivalent, the substrate-selective mono-nitration or double-nitration can be realized. Compared with the prior art, the nitration method of the present invention avoids the use of strong acid substances, has mild reaction conditions, high yield, and wide application range of substrates, and the reactivity does not appear to be significantly attenuated after the amplification reaction, still obtains excellent yield, and has obvious advantages. industrial application value.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a nitration method of aryl phenols or aryl ether derivatives. Background technique [0002] Nitro-substituted aromatic compounds are a kind of very important intermediates, which have a wide range of application values ​​in the fields of medical treatment, pesticides, dyes, and explosives. The traditional nitration reaction uses concentrated sulfuric acid and nitric acid mixed acid as the nitration reagent. This method is mature in technology and low in cost, but has low atomic utilization rate, serious environmental pollution, and many by-products, and the reaction is violent, which has a huge potential safety hazard. [0003] In recent years, many chemists have been working on the optimization of the nitration of aromatic hydrocarbons. In addition to using nitric acid and concentrated sulfuric acid, trifluoromethanesulfonic acid or acetic anhydride as nitrating reagents (Coon,...

AI Technical Summary

Problems solved by technology

The common nitration process involving transition metal catalysis is the most common C-H nitration strategy with Rh and Pd as catalysts, while transition metals such as Zr, Ce, Bi and Fe achieve the target substrate at high temperature through the corresponding nitrate of super chemical equivalent. Nitration (Xie, F.; Qi, Z.; Li, X.Angew.Chem., Int.Ed.2013,52,11862-11866.Fors,B.P.; Buchwald,S.L.J.Am.Chem.Soc.2009,131 , 12898-12899. Selvam, J.J.P.; Suresh, V.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 2507-2509. Wasinska, M.; Korczewska, A.; -150.), these methods either use expensive transition metal catalysis, or the substrate is severely restricted, and require aryl halides or other aromatic hydrocarbons with directing groups; and the reaction conditions require high temperatures (such as 130 ° C), which is potentially safe At the same time, most of these new methods are nitration reactions of free radical processes, and the reactions are uncontrollable when enlarged, with many by-products and a serious decline in yield, which also limits its industrial application

In 2019, Maruoka developed an electrophilic nitration of phenol using trivalent iodine as a catalyst at room temperature and using relatively expensive aluminum nitrate, but the corresponding nitrated products could only be obtained in a low yield (Kevin, A.J.O.; Maruoka, K.; Org. Lett. 2019, 21, 1315-1319.)

Although the method has relatively mild conditions and high product yield, its substrates are severely limited, and the acetyl nitrate needs to be prepared with fuming nitric acid, and the preparation process of the ionic functional liquid is cumbersome.

Chinese patent (CN108530242A) "A direct nitration method for electron-rich aromatics" uses tert-butyl nitrite to nitrate phenyl ethers at room temperature. The method has mild reaction conditions and does not require a catalyst, but the product yield is low

This method is simple to operate and the conditions are mild, but it uses sodium nitrite and hydrogen peroxide system. When scaled up, the mixture of peroxide and nitration products has the risk of explosion, and the atom economy is low, which does not conform to the concept of green chemistry.

Chinese patent (CN107033005A) "A Nitrification Method for Aromatic Compounds" improves the production process and uses a high-gravity reactor to avoid side reactions caused by excessive local concentrations and improves nitrification efficiency. However, it still uses a mixed acid system. The equipment is corrosive and the reaction temperature is high

[0005] To sum up, in the existing nitration technology solutions, the classic mixed acid nitration system has safety risks, and the reaction is violent and uncontrollable; the newly developed C-H nitration technology requires guiding groups and noble metal catalysis, and its amplification reaction has many by-products ; and the direct nitrification of substrates by transition metal nitrates generally requires a high temperature environment, and most transition metal nitrates are relatively expensive (Zr(NO 3 ) 4 , Bi(NO 3 ) 3 etc.), which is not conducive to actual production, and the nitration process developed by Maruoka has disadvantages such as high raw material cost and low yield

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