EUR. J. org. Chem.: one pot synthesis of benzoquinonyl diazo [3,3] cyclo

The first synthesis of cyclotubo has been reported more than a century ago Since then, due to its unique structure and performance, it has aroused great interest in many fields, especially the face-to-face interaction of non planar aromatic system due to its unstable structure The specific structural characteristics of cyclotubo are used in molecular structure, asymmetric synthesis, material science, photochemistry and other fields Staub et al Designed various schemes to synthesize [2.2] and [3.3] rings containing quinone and hydroquinone to study their properties as charge transfer complexes The synthesis method includes several steps, such as ring contraction reaction by gas phase pyrolysis, and the two products with different structures are not selective Interestingly, nitrogen bridging rings are rarely studied in depth Although the C-N bond is shorter than the C-C bond, this structure may show stronger interaction between two aromatic cores, but sulfur bridged ring is more common In the process of studying nanoscale hydrogel particles, a new method for direct synthesis of nitrogen bridged [3.3] p-xylene quinone (4) has been discovered Initially, the team intended to construct a linear amine linked quinone (3) by alkylamination of dimethylquinone (1) with bis (bromomethyl) However, during the reaction, the team observed for the first time the formation of this (4) pair of cyclopods The authors say their team has been interested in new molecular structures for supramolecular sensing The existence of cyclo - Tubo structure was confirmed by crystal structure measurement Because of the strong torsion in cyclo - Tubo system, the quinone part is bent out of plane The maximum torsion of the carbon atom carrying carbonyl group is 11 ° in the plane and 6 ° in the bridge The team was able to prepare the raw material for cyclophosphate synthesis, 2,5-Bis (bromomethyl) - 3,6-dimethyl-1,4-quinone (1), by four steps Furthermore, all steps are easy to perform and scalable In the last step of the oxidation reaction, it is found that the by-product of chlorine atom replacing bromine atom will appear in water treatment Finally, pure water was used to solve the problem The author also experimented with the next reaction of the perchloride, but as expected, the reaction was slower because of the lower reactivity of the chlorine derivatives The synthesis route of compound 1 (source: EUR J org Chem.) started to optimize the synthesis conditions after the first detection of cyclofan products In the optimization study, the easily obtained propylamine (9) was used as the raw material In addition, they also established a simple chromatographic scheme to purify cyclo - 10 First, the team studied different solvents, reaction time and temperature They observed the optimum yield of dichloromethane as a solvent at room temperature Under these conditions, the longest reaction time was 3 days It is speculated that due to the slow reaction, the selectivity (compared with the oligomeric by-products) of the products required for synthesis is increased After that, they studied the effects of various bases Only specific bases can be used to synthesize cyclo - Tubo The best results were obtained by using potassium carbonate, and 24% of the products were produced In addition, instead of adding alkali, we used ten times the amount of amine to react In this case, no product is found After that, the reaction was carried out under microwave conditions, but it did not produce the desired product Generally, the favorable reaction conditions for the construction of macrocycles are high temperature and high dilution conditions As the boiling point of propylamine (9) is 49-50 ℃, it is not suitable for high temperature reaction In order to clarify this parameter, we used benzylamine (11, boiling point 184-187 ℃), and the reaction at 83 ℃ or higher did not improve the yield The best results were obtained in dichloromethane at room temperature Using the optimized reaction conditions, the research team synthesized 11 kinds of cyclotubo The advantage of using acetonitrile is the obvious acceleration of the reaction Pseudo ortho form (source: EUR J org Chem.) by using optically active raw materials, the formation of two non enantiomeric products was observed Two diastereomers can be separated and characterized by using valinol (29) as the raw material The orientation of quinones in the core of the distorted naphthenic structure of the two co formers can be distinguished by 180 ° In the further study, the scheme was applied to bis (bromomethyl) quinone as the starting material of cyclo - Tubo synthesis No enantiomers were found by NMR and MS Due to the high space demand of methyl group and the electrostatic repulsion of carbonyl group, the pseudo ortho form (4) was formed In summary, 2,5-dimethyl-p-benzoquinone (5) was used as raw material to synthesize 2,5-di (bromomethyl) - 3,6-dimethyl-1,4-benzoquinone (compound 1) by a four step reaction The yield was 93%, 89%, 67% and 93% respectively In the process of the formation of linear products, the author 's research team started to study the direction of cyclophosphamide, screened the optimal conditions, and finally synthesized 11 new nitrogen bridged quinone containing cyclophosphamide, and studied and discussed the mechanism and properties Paper link: http://onlinelibrary.willey.com/doi/10.1002/ejoc.201701124/full