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Synthesis 2008(1): 39-44  
DOI: 10.1055/s-2007-1000825
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Convenient Synthesis of Trifluoroacetamide Derivatives of Diaza[32]cyclophanes and Triaza[33]cyclophanes

Hideki Okamoto*a, Hiroyuki Takemurab, Kyosuke Satakea
a Division of Chemistry and Biochemistry, The Graduate School of Natural Science and Technology, Okayama University, Tsushima-Naka 3-1-1, Okayama 700-7530, Japan
e-Mail: hokamoto@cc.okayama-u.ac.jp;
b Department of Chemistry and Biological Science, Japan Women’s University, Tokyo 112-8681, Japan
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Publication History

Received 22 August 2007
Publication Date:
07 December 2007 (online)

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Abstract

The diaza[32]cyclophane skeleton has been constructed by the bis-N-alkylation of 1,4-bis[(4-nitrophenylsulfonylamino)methyl]benzene with 1,4-bis(halomethyl)benzene in the presence of sodium hydride. The 4-nitrophenylsulfonyl (Ns) amides in the bridge chains of the cyclophane were effectively deprotected by sodium ethanethiolate and the resulting free amine moieties were reprotected as the trifluoroacetamide under mild conditions to afford 3,7-bis(trifluoroacetyl)-3,7-diaza-1,5(1,4)-dibenzenacyclooctaphane in 26% overall yield. This Ns-amide method has also been applied for the preparation of a higher homologue, the trifluoro­acetamide derivative of triaza[33]cyclophane, 3,5,7-tris(trifluoroacetyl)-3,7,10-triaza-1,5(1,3,5)-dibenzenabicyclo[3.3.3]undeca­-phane, in 18% overall yield. Thus, the present procedure provides a convenient synthetic route to azacyclophane derivatives possessing trifluoroacetamide groups in the bridge chains.

Key words

cyclophanes - sulfonamides - amides - chromophores - amines

6

Shinmyozu et al. has reported that, according to the method shown in Scheme [1] , path a, (R = COCF3), the diaza[32]cyclophane 11 was prepared and isolated as its
N-methyl derivative in 0.5% overall yield after removal of the trifluoroacetyl groups followed by methylation on the bridge nitrogen atoms.5 Our own examination according to their method [Scheme [1] , path a (R = COCF3)] resulted in a 3% yield of diazacyclophane 11.

13

In the originally reported Ns-amide strategy, PhSH-K2CO3 or HSCH2CO2H-LiOH mixtures were used as the typical deprotection reagents of Ns group, and aprotic solvents, e.g. MeCN or DMF, were used.12 In the present study, EtSNa was used for the deprotection of the cyclophanes 9 and 14 because this reagent is commercially available as a convenient thiolate source. Additionally, the bridge Ns amide parts are sterically hindered, we considered that primary alkyl thiolate would serve as an effective deprotection agent in the present case. As for the solvent employed in this work, the solubility of the Ns-protected cyclophanes 9 and 14 in the originally reported solvents was poor, thus, we selected DMSO in which Ns amides 9 and 14 were slightly soluble and the deprotection proceeded successfully.