The tris thiol compound 3.18 was obtained by first converting the tris-bromo compound into the iso-thio-uranium salt followed by hydrolysis of the salt in base medium. Typical solvent used for the first step (making of iso-thio- uranium salt from the bromide) in this type of reaction is ethanol15. But because of the highly activated bridged triphenylamine system, the three bromo-methyl groups in 3.17, are very labile. So the use of protic solvent may induce the hydrolysis of the bromide 3.17 to give back compound 3.16. Even the presence of a trace amount of water in the reaction medium may also promote the hydrolysis of the highly labile bromide in 3.17. So keeping these factors in mind, instead of using protic solvent ethanol, aprotic solvent THF was used for making iso-thio-uranium salt. Then for doing the hydrolysis of the salt, use of a strong base (50% aqueous KOH) has been reported in literature.15 But in our case, it was noticed that the use of KOH lead to decomposition or degradation of the product. So instead of using strong base,
95 an aqueous solution of 2 (M) Na2CO3 has been used for getting the tris-thiol compound 3.18 by doing the hydrolysis of the salt. (Scheme-3.6)
3.2.5. Synthetic approach to Trithia-Bridged Triphenylaminophane (3.10)
Scheme 3.7. Synthetic approach for compound 3.10
Reaction conditions: (i) Cs2CO3, THF, 600 C, 36 h or KOH, THF, r.t 48 h.
The synthetic attempt has been taken for synthesizing the triple clamped trithia-bridged triphenylaminophane (3.10) by performing high dilution coupling reaction between the tri bromo compound 3.17 with the tris-thiol compound 3.18. The choice of base and choice of solvent is very critical factors for doing the high dilution coupling reaction.
Normally in the high dilution coupling reaction15, first the bromide and the thiol are dissolved into benzene and then the benzene solution is dropped into a large amount of ethanol containing small amount of KOH in a very slow rate over a long period of time. The high dilution coupling is done to minimize the possibility of the polymerization.
96 The choice of solvent was very critical for this reaction. Our bridged triphenylamine was highly electron donating so the three bromo-methyl group was very labile. So the use of protic solvent ethanol may lead to hydrolysis or ethanolysis of the compound 3.17. So the use of ethanol was avoided. Instead of ethanol, THF has been used.
Sendhoff et al have reported16 the use of Cs2CO3 as the base for high dilution coupling for the synthesis of triple-decker phane. It’s because of the fact that the cesium ion is bigger in size and hence it’s bonded to the thiolate anion very loosely. So it makes the thiolate anion to be relatively more reactive for the SN2 type attack.
So keeping these facts in mind, the high-dilution coupling is performed in THF solvent using Cs2CO3 as base.
First 0.05 mmol of the 3.17 and 0.05 mmol of the 3.18 were dissolved together into 10 ml of benzene. After degassing the benzene solution, it was added drop wise into a 120 ml solution of THF containing aqueous Cs2CO3. After completion of addition, the solution was heated for 36 h. Then after evaporating all the solvent from the reaction mixture, the yellow crude residue was checked for the presence of the desired cyclophane 3.10. Unfortunately the crude mass and crude NMR does not indicate the formation of even trace amount of desired compound. 3.10.
By changing the base from Cs2CO3 to KOH and repeating the reaction at room temperature, does not lead to any fruitful results.
97 The reason for the failure of the reaction may lies in the nature of the high- dilution coupling reaction and the nature of our central core electron donor bridged triphenylamine system 3.8. Because of the high possibility of the polymerization as the side reaction, normally the high-dilution coupling reaction gives very low yield even for the synthesis of the doubly bridged cyclophane type system. In case of the three sides coupling3,16 the yield is even poorer. So to compensate the low percentage yield of the product, the high- dilution coupling reaction is generally performed by taking large scale of the starting materials. In this project, because of the long and complicated synthetic route, it was beyond our ability to accumulate the starting material 3.17 and 3.18 in very large scale.
At the end of the reaction, we could not isolate even trace amount of either of the un-reacted starting material 3.17 or 3.18. Oxidation of thiol to di-sulfide (S-S) which ultimately leads to polymerization of the thiol 3.18 with itself (this process is facilitated by the electron donating nature of the bridged triphenylamine) and the hydrolysis of the highly labile bromides 3.17 may lead to the total consumption of the two compounds.
3.3. Conclusion
In this section of our work, a synthetic approach has been taken to synthesize a triply clamped cyclophane by connecting two units of bridged triphenylamine moieties with the help of three bridged across them. A detail investigation has been done to optimize the entire synthetic route towards the synthesis of two novel precursors those are needed for doing high-dilution coupling for making the final trithia-bridged triphenylaminophane. Although we were unable to