Synthesis and thermal reactivity of a novel bis-salicylaldimino enediyne and its Cu(II) and Ni(II) complexes

Article abstract of DOI:10.1016/S0040-4039(00)01233-8

A novel bis-salicylaldimino enediyne 1, along with its Ni(II) and Cu(II) complexes 6 and 7, respectively, were prepared. Differential Scanning Calorimetric studies revealed an elevation of the onset temperature for Bergman cyclization upon complexation. (

Full text of DOI:10.1016/S0040-4039(00)01233-8

Tetrahedron Letters 41 (2000) 7231±7234
Synthesis and thermal reactivity of a novel bis-salicylaldimino
enediyne and its Cu(II) and Ni(II) complexes
Amit Basak* and Kakali Rani Rudra
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
Received 17 July 2000; accepted 21 July 2000
Abstract
A novel bis-salicylaldimino enediyne 1, along with its Ni(II) and Cu(II) complexes 6 and 7, respectively,
were prepared. Di€erential Scanning Calorimetric studies revealed an elevation of the onset temperature
for Bergman cyclization upon complexation. # 2000 Published by Elsevier Science Ltd.
Harnessing the DNA-damaging activity of enediynes through rational design has been an
active area of research in recent years.1 An important criteria for a successful design is the
incorporation of attachments (functionalities) to the enediyne framework which may act as
devices to modulate the kinetics of the Bergman cyclization (BC).2 One approach towards that
end is to synthesize enediynes with side-chains capable of ligating to metal ions. Complexation, in
most cases,3 leads to a lowering of the activation barrier for BC. Only in cases of crown ether
containing enediynes, did complexation4 to alkali metal ions such as Na+ or K+ cause an
elevation of onset temperature for BC, compared to that for the free ligands. In this
communication, we provide an interesting example of a bis-salicylaldimino enediyne 1 which
upon complexation to transition metal ions like nickel(II) or copper(II) undergoes BC at a
temperature much higher than the parent ligand.
The synthesis of 1 is shown in Scheme 1. First of all, the enediyne diol 2 was prepared from 1,2-
dibromobenzene and propargyl alcohol (2 equiv.) via a double Pd(0)-mediated Sonogashira
coupling.5 Conversion to the dimesylate 3 followed by displacement with sodium azide furnished
the diazide 4. Reduction of both azide groups with PPh3 and water gave the diamine 5 which was
isolated pure by column chromatography (Si-gel, 50% MeOH CH2Cl2). The bis-salicylaldehyde
imine 1 was obtained as an orange-yellow viscous oil by re¯uxing a solution of the diamine 5 and
salicylaldehyde (1:2 molar ratio) in ethanol, followed by chromatography of the residual oil
obtained after evaporation (Si-gel, hexane:EtOAc 7:1). The combined yield over the ®nal two
steps was 60%. The Ni2+ and Cu2+ complexes (6 and 7) were prepared as brown and green solids,
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01233-8

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Scheme 1. Spectral data for 1: ꢀH (CDCl3, 300 MHz) 8.74 (2H, s, NCHˆ), 7.50 (2H, m, Ar-H), 7.30±7.23 (6H, m, Ar-H),
6.93 (2H, d, J=8.3 Hz, H-30), 6.83 (2H, t, J=7.6 Hz, H-50), 4.71 (4H, s, NCH2); Mass (FAB) m/z 393 (MH+), 289, 273,
244
respectively, by re¯uxing the solution of 1 and nickel(II) perchlorate or copper(II) acetate in
methanol. The formation of the complex was also shown by the appearance of a strong emission
band at 318 nm for the Ni complex in methanol (Fig. 1) when the excitation was carried out at
268 nm. The free ligand at a similar concentration failed to show any strong emission band.
Figure 1. Fluorescence spectra at 319 nm with excitation at 268 nm; A for free ligand and B for Ni complex
The onset temperatures for BC of 1 and its complexes 6/7 were recorded by Di€erential
Scanning Calorimetry (DSC).4 For the starting enediyne 1, cyclization started at ꢀ137ꢁC (Fig. 2).
This high onset temperature was expected because of its acyclic nature. Interestingly, both the
Ni2+ and the Cu2+ complexes 6 and 7 showed an elꢁevation of the onset temperature of BC. For
the Ni2+ complex 6, the cyclization started at ꢀ225 C, (Fig. 3) whereas for the Cu2+ complex 7,
the onset temperature was found to be ꢀ215ꢁC (Fig. 4). The incorporation of metal ions to form
the complex is probably forcing the acetylenic carbons to move away from each other,6 thus

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Figure 2. DSC of enediyne 1
Figure 3. DSC of Ni complex
Figure 4. DSC of Cu complex
raising the activation barrier for BC. However, until we get a crystal structure for the complex,
the exact reason for the elevation of cyclization temperature cannot be de®nitely established.
In conclusion we have provided the ®rst example of a novel bis-salen type enediyne. The
substantial elevation of the onset temperature for BC upon metal ion complexation is an
interesting feature of the enediyne. E€orts are currently underway to study the DNA cleavage
activity of various metal complexes of 1 under oxidative conditions.6

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Acknowledgements
The author (A.B.) thanks CSIR, New Delhi for ®nancial assistance.
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