Solvent-Free Synthesis of Diazocine

Widukind Moormann; Daniel Langbehn; Rainer Herges

doi:10.1055/s-0036-1590685

Synthesis, Table of Contents

Synthesis 2017; 49(15): 3471-3475
DOI: 10.1055/s-0036-1590685

paper

Solvent-Free Synthesis of Diazocine

Widukind Moormann

Otto Diels Institute for Organic Chemistry, University of Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany Email: rherges@oc.uni-kiel.de

,

Daniel Langbehn

Otto Diels Institute for Organic Chemistry, University of Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany Email: rherges@oc.uni-kiel.de

,

Rainer Herges*

Otto Diels Institute for Organic Chemistry, University of Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany Email: rherges@oc.uni-kiel.de

› Author Affiliations

Abstract

All articles of this category

Dedicated to Professor Herbert Mayr on the occasion of his 70^th birthday

Abstract

A convenient two-step synthesis of diazocine starting from 2-nitrotoluene is described. The first step, the oxidative dimerization of 2-nitrotoluene, is improved to 95% yield. The second step, the reductive azo cyclization, is performed as a solvent-free reaction with lead powder in a ball mill (51% yield). As a reference, the previously described azo cyclization with Zn/Ba(OH)₂ is investigated in detail. The results explain why in previous experiments the yields are low and extremely dependent on the reaction conditions. In view of potential applications in photopharmacology, we checked the stability under reducing conditions. Diazocine does not react with glutathione, indicating intracellular stability.

Key words

bridged azobenzene - diazocine - reductive azo-cyclization - solvent-free synthesis - oxidative C–C coupling - lead - azoxy - hydrazine - glutathione

Full Text

References

References
1 Duval H. Bull. Soc. Chim. Fr. 1910; 7: 727
2 Siewertsen R. Neumann H. Buchheim-Stehn B. Herges R. Näther C. Renth F. Temps F. J. Am. Chem. Soc. 2009; 131: 15594
3 Siewertsen R. Schönborn JB. Hartke B. Renth F. Temps F. Phys. Chem. Chem. Phys. 2011; 13: 1054
4 Lerch MM. Hansen MJ. van Dam GM. Szymanski W. Feringa BL. Angew. Chem. Int. Ed. 2016; 55: 10978
5 Broichhagen J. Frank JA. Trauner D. Acc. Chem. Res. 2015; 48: 1947
6 Samanta S. Qin C. Lough AJ. Woolley GA. Angew. Chem. Int. Ed. 2012; 51: 6452
7 Eljabu F. Dhruval J. Yan H. Bioorg. Med. Chem. Lett. 2015; 25: 5594
8 Chauduri NK. Ball TJ. J. Labelled Compd. Radiopharm. 1980; 18: 1189
9 Paudler WW. Zeiler AG. J. Org. Chem. 1969; 43: 3237
10 Joshi DK. Mitchell MJ. Bruce D. Lough AJ. Yan H. Tetrahedron 2012; 68: 8760
11 Tellkamp T. Shen J. Okamoto Y. Herges R. Eur. J. Org. Chem. 2014; 25: 5456
12 Deo C. Bogliotti N. Métivier R. Retailleau P. Xie J. Chem. Eur. J. 2016; 22: 9092
13 Tauer E. Machinek R. Liebigs Ann. Chem. 1996; 1213
14 Fan Q. Wang T. Dai J. Kuttner J. Hilt G. Gottfried JM. Zhu J. ACS Nano 2017; 11: 5070
15 Bielawski CW. Benitez D. Grubbs RH. Science 2002; 297: 2041
16 Tanaka K. Toda F. Chem. Rev. 2000; 100: 1025
17 Wada S. Urano M. Suzuki H. J. Org. Chem. 2002; 67: 8254
18 Mori H. Mori Y. Sugie S. Yoshimi N. Takahashi M. Hiroaki N.-i. Yamazaki H. Toyoshi K. Williams GM. Cancer Res. 1986; 46: 1654
19 Neish WJ. P. Davies HM. Reeve PM. Biochem. Pharm. 1964; 13: 1291
20 Krämer R. Dissertation. Bergischen Universität Wuppertal; Germany: 2016