Method for synthesizing 1-azabicyclo[2, 2, 1]heptane and derivatives thereof

Abstract

The invention relates to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing 1-azabicyclo[2, 2, 1]pyridine and derivatives thereof. A hydroxyl group in 4-(1-hydroxymethyl)piperidine derivatives reacts with p-toluenesulfonyl chloride (TsCl) to be converted into an OTs group which is easy to leave, a tert-butyloxycarbonyl (-boc) protecting group on an N atom is removed under an acidic condition, a nucleophilic substitution ring closing reaction is performed under an alkaline condition, and extraction, solvent removal and concentration are carried out on a final reaction mixture to obtain the pure product 1-azabicyclo[2, 2, 1]heptane and derivatives thereof. The 1-azabicyclo[2, 2, 1]heptane and the derivatives thereof are obtained through three-step synthesis by reacting the 4-(1-hydroxymethyl)piperidine derivative with cheap and easily available common chemical reagents, and the method is discovered for the first time. The N-boc-4-(1-hydroxymethyl)piperidine used in the method is a cheap and easily available raw material, the synthesis method is simple, few in synthesis steps and easy to separate, and a large amount of target products can be synthesized.

Description

technical field [0001] The invention belongs to the technical field of organic chemical synthesis, and relates to the synthesis of 100-gram level 1-azabicyclo[2,2,1]heptane and derivatives thereof. Background technique [0002] 1-Azabicyclo[2,2,1]heptane is a compound with one carbon less than quinuclidine, which has an approximately spherical or spherical structure with quinuclidine, triethylenediamine (DBACO) and its derivatives , they easily produce disordered to ordered structural phase transition from high temperature to low temperature, and are often used to design phase change molecular ferroelectric materials. As reported for 1-azabicyclo[2,2,1]heptane perrhenate and periodate, due to the disordered orientation of the 1-azabicyclo[2,2,1]heptane cation , resulting in multiaxial ferroelectricity, and in thin-film devices, showing low coercive-field operating voltages (Harada, J.; Kawamura, Y.; Takahashi, Y.; Uemura, Y.; Hasegawa, T. ; Taniguchi, H.; Maruyama, K. J. ...

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Problems solved by technology

[0003] Quinucidine and some of its derivatives and DBACO compounds are already commercial products, however, 1-azabicyclo[2,2,1]heptane and its derivatives cannot be purchased directly from the market, and so far There is no suitable method for large-scale synthesis of 1-azabicyclo[2,2,1]heptane and its derivatives

Although there are a few literature or patent reports on the synthesis of 1-azabicyclo[2,2,1]heptane, some methods require high temperature (Guan Shiyou, Chen Xiaojun, Zhao Zhen, Wang Lixia, Zhao Chunhua, Lin Fangqin, Ren Dayong, invented Patent application (patent number: CN 102584816 A), 2012-07-18), or some methods cannot achieve a large number of synthesis (Clemo, G. R.; Prelog, V. J. Chem. Soc., 1938, 400.)

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