Subject Chemistry
Paper No and Title Paper 14: Organic Chemistry –IV (Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings)
Module No and Title Module 26: Catenanes and Rotaxanes
Module Tag CHE_P14_M26
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
TABLE OF CONTENTS
1. Learning Outcomes 2. Introduction 3. Nomenclature of Catenanes and Rotaxanes 4. Synthesis of Catenanes and Rotaxanes 5. Rotaxanes and Catenanes involving π-π stacking interactions 6. Hydrogen Bonded Catenanes and Rotaxanes 7. Molecular Necklaces 8. Summary
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
1. Learning Outcomes
After studying this module, you shall be able to Basic knowledge of Catenanes and Rotaxanes Preparation of Catenanes and Rotaxanes π-π stacking interactions in Catenanes and rotaxanes Catenanes and Rotaxanes in the form of Molecular Necklaces 2. Introduction
Catenane is a compound consisting of two or more rings that are interlocked mechanically without there being necessarily any chemical interaction between the two. Generally, without breaking a chemical bond, the rings cannot be separated. Rotaxanes consist of a long, fairly linear molecule threaded through a macrocyclic ring, like cotton through the eye of a needle. Same as catenane, rotaxanes also cannot decompose into ring and chain without breaking chemical bonds. Hence, the bulky groups terminated the linear, chain part of the molecule and it is too large to fit through the cyclic fragment. Rotaxanes without such physical barriers, in which the thread can leave the needle, are called pseudorotaxanes. Pseudorotaxanes are necessary precursors for both rotaxanes and catenanes.
3. Nomenclature of Catenanes and Rotaxanes
The nomenclature of catenanes is decided by the number of rings, i.e. how many number of rings are interlocked to each other, e.g. a [2]catenane consists of two interlocked rings (figure 1). Analog ‘ane’ used in end which is similar to alkanes a catenane is mainly consist of organic fragment, it rarely consists of hydrocarbon moieties. The terms [n]catenand and [n]catenate are also used analogously with cryptand and cryptate, for a metal centre which is suitably interlocked in the ring system of a catenane acting as a CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
ligand. The catenand is the free ligand that forms a catenate complex in the presence of metal centre. Rotaxanes can be named in an analogous manner too.
Fig. 1: Nomenclature of catenanes, rotaxanes and pseudorotaxanes
4. Synthesis of Catenanes and Rotaxanes
Typical synthetic procedures consist of the templated self-assembly of a pseudorotaxane (a kind of host-guest complex) using electrostatic or hydrogen bonding forces with metal ion, followed by ring closure (catenanes) or termination at one or both ends with a bulky end group (rotaxanes) (Figure 2).
Fig. 2: Synthesis of catenanes and rotaxanes via host–guest chemistry.
There are two approaches for the catenane synthesis: the statistical approach and the direct synthesis, in which the approaches relying on self-assembly. The statistical approach relies on the small chance that macrocyclisation may occur while a linear precursor is threaded through a macrocyclic component. This type of statistical approach CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
was found in the first synthesis of a [2]catenane in 1960, from cyclisation of the long-
chain diester while threaded through the annulus of a deuterated C34 cycloalkane (Scheme 1). Although the overall yield of the catenation reaction was less than 1% but the existence of the catenane was confidently established.
Scheme 1: The first catenane synthesis via the statistical approach.
For the rotaxane synthesis, the statistical approaches have also been used. Rotaxanes and pseudorotaxanes have been synthesized by refluxing at 120 ˚C, a range of cyclic
hydrocarbons of between 11 and 39 –CH2- groups with a linear triphenylmethyl stoppered components. At the 120 ˚C temperature, larger rings are occasionally able to slide over the end of the triphenylmethyl stoppered groups. On cooling, a low yield (less
than 2%) of rotaxanes was obtained. At room temperature, C29 macrocycle containing rotaxane is stable with respect to slippage back to the constituent components, whereas
macrocycles with chain lengths of C33 and upwards are extremely labile. C28 macrocycle attaches to surface a resin through a covalent bond, reacts with the dumb bell components, provides a total 70 times stable rotaxane that can be cleaved from the resin and purified to result in an overall yield of 6% (Figure 3).
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
Fig. 3: Statistical rotaxane synthesis (a) product from solution and (b) analogue prepared in higher yield (6 %) on a solid support. 5. Rotaxanes and Catenanes involving π-π stacking interactions
A much more directed approach is very much needed due to the low yields obtained in the statistical approach for the synthesis of catenanes and rotaxanes. The clear strategy towards a directed rotaxane and catenane synthesis is to encourage the self-assembly of the reactants before the cyclisation or stoppering reaction that covalently fixes the array together. For the much greater coupling in the desired fashion when they react, the reactants are predominantly coupled in solution as a self-assembled host-guest complex (i.e. relatively large binding constant). Generally, the pre-reaction host-guest complex is a pseudorotaxane and it forms a self-assembled template for the covalent synthesis of the rotaxanes and catenanes (Figure 2). The strong π-stacking interactions occur with the aryl corands and the herbicide paraquat, resulting in solid-state and solution incorporation of the electron-deficient guest within the corand ring. The [2]pseudorotaxane formed due to this insertion of paraquat within the macrocycle. The guest is electron-deficient and the host is the electron rich in the case of paraquat. The stability of pseudorotaxanes increases with increasing chain length. As shown in figure 4, the electron rich podands of
the type ROC6H4OR (R = Me, (a); R = H(OCH2CH2)n, n = 1-4, (b)) are incorporated into
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
a rectangular box made up of two paraquat derivatives (e) to give another [2]pseudorotaxane. Compound (e) is famous as Stoddart’s ‘little blue box’.
Fig. 4: Various type of pseudorotaxanes
Based on the former approach, the higher pseudorotaxanes such as the [3]pseudorotaxane (figure 5) have been constructed rather like threading beads on to a string. The π-stacking and charge-transfer interactions between the aryl rings stabilize the tetracationic cyclophane.
Fig. 5: [3]pseudorotaxane
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
The tetracationic cyclophane is also stablised by the solvation of positive charge on the ‘blue box’ by the crown oxygen atoms, and C-H-O hydrogen bonds from the relatively acidic aryl C-H protons to the crown oxygen atoms. All the complexes which contain this type of binding motifs, show the characteristic orange colour due to charge-transfer interactions.
For the preparation of rotaxane from pseudorotaxane, the most clear protocol is to attach a bulky substituent group to the open end of the threaded molecule. The overall procedure is termed ‘threading’ (Figure 6).
Fig. 6: Synthesis of rotaxanes via self-assembly of electron-rich and electron-poor aryl fragments For example, the preparation of tri-iso-propylsilylated [2]rotaxanes, by the reaction of di- ols and bis(bipyridinium) receptor with tri-iso-propylsilyl trifluoromethanesulfonate (triflate) in the presence of lutidine provide 21% yield of [2]rotaxanes. As shown in figure 7, the same compound can also be prepared by the ‘clipping’ route and afforded 14% yield, using a preformed tri-iso-propylsilylated thread.
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
Fig. 7: Synthesis of a [2]rotaxane via the clipping approach
The final approach to rotaxanes is by slipping, for the passage through the macrocyclic ring upon careful heating/refluxing, by using a terminator group. But at lower temperature, a sufficient amount of energy is required to break through the conformational barrier. An alkene metathesis was used for the synthesis of [3]- and [4]rotaxanes. Porphyrin- derived macrocycle has a very strong affinity for bipyridinium derivatives in dichloroethane. [3]- or [4]rotaxanes developed by the alkene cross coupling reactions between two [2]pseudorotaxane, followed by the Grubb’s catalyst. With this reaction, only 25% yield of [3]rotaxane achieved. For the improvement of yield of [3]rotaxane by the use of excess of macrocycle, resulted in the formation of [4]rotaxane with [3]rotaxanes also. This may be possible due to the thread that binds the two macrocycles before the coupling stage (Figure 8).
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
Fig. 8: Synthesis of [3]- and [4]rotaxanes using alkene cross-coupling.
The manganese (II) complex of the porphyrin-containing macrocycle is a very good catalyst for epoxidation (addition of an oxygen atom to an alkene to give a three- CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
membered C-O-C ring) of alkenes. For such type of oxidation, the iodsylbenzene (PhIO, oxidizing agent) was used. For the addition of oxygen atoms to a threaded polybutadiene substrate, the toroidal complex may act as a processing catalyst analogous to DNA polymerase. The schematic process is shown in figure 9.
Fig. 9: Cartoon representation of the Mn(II) complex of 10.72 acting as a epoxidation processing catalyst. The [4]- and [5]catenane are also prepared by following the clipping route. For the synthesis of [5]catenane, a two-step process involving clipping of the precursors around two molecules to give a [3]catenane. Further clipping of two molecules with [3]catenane, provides the desired [5]catenane. However, due to the conformational mobility of crown ether, the fortuitous scheme ended in failure. This synthetic strategy was modified for the desired product, under atmospheric pressure using the same strategy with the intermediate-sized crown ether providing the intermediate [3]catenane in 3.5% yield. Finally this protocol afforded for a [3]catenane in last step. This is now carried forward to the second stage. Under ultra-high pressure conditions, clipping of other molecule with [3]catenane gave 22% yield of [4]catenane and trace yield of [5]catenane was obtained. For the improved yield of [5]catenane, some other changes have been done and finally achieved by another change of crown ether and the substitution of aryl ring in macrocyclic compound for the 1,5-dioxynapthalene analogue. The strategy is shown in figure 10, which resulted in 5% yield of [5]catenane without using high pressure. The resulting molecule was called as ‘olympiadane’ due to its resemblance to the international Olympic Games symbol. The analogous [4]catenane was also obtained in 31% yield. CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
[5]catenane was characterized by 1H NMR spectroscopy, which shows the highly symmetric property at 60 ˚C temperature due to fast interannular circumrotation of all components. At room temperature, the broad spectrum was obtained, while at 0 ˚C temperature, two signals of small cyclophanes was obtained, which are corresponding to the freezing out of the rotation of these components.
Fig. 10: First synthesis of a [5]catenane
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
6. Hydrogen Bonded Rotaxanes and Catenanes
The formation of catenane is so facile and provides a reasonable yield. Hydrogen bonding gives a clue for the formation of this type of compound. As shown in figure 11, the two rings completely fill one another’s cavity and the complex is held together by amide NH- --O hydrogen bond. Second macrocyclic ring is also included by assembling amide precursor by the same double NH--O=C hydrogen bond and it also causes cyclisation on the included acid chloride.
Fig. 11: Synthesis of an amide-based [2]catenane
The ‘hydrogen bonding’ based formation of interlocked molecules has proved to be very useful and has also been applied to rotaxanes. As shown in figure 12, [3]rotaxane is synthesized by using alkene metathesis under thermodynamic control (which causes the central double bond to break and re-form, it allows the macrocycles to thread by a ‘slipping process’).
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
Fig. 12: Formation of a rotaxane by capping a secondary ammonium guest.
The rotaxanes and pseudorotaxanes are also assembled by the hydrogen bonding of ammonium ions to crown ethers. Some interesting multiple time threaded rotaxane type of compounds are also synthesized by this type approach (Figure 13).
Fig. 13: Crown ether ammonium ion based rotaxane type hydrogen bonded complexes (a) [3]rotaxane, (b) three threads in one ring and (c) two threads linking two rings
7. Molecular Necklaces
Molecular necklaces are also catenanes type compounds, in which a number of macrocycles are looped onto a single central ring like beads onto a string. As shown in CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
figure 14(a), three macrocycles are looped onto a single central ring. As shown in figure 14(b), metallomacrocycle is threaded through three cucurbit[6]uril ‘beads’. This compound can be describe as [4]MN, because there is a total of four different rings in this compound. The larger ring forms the ‘thread’ and this thread is commonly linked using self-assembly of a coordination compound.
Fig. 14: (a) schematic representation of a [4] MN and (b) linking of three cucurbit [6]uril Molecules around a platinum (II) based metallomacrocycle.
We can explain the linkage of cucurbituril in platinum(II)ethylene diamine complex on the basis of molecular necklaces. The square planar platinum(II)ethylene diamine complex, takes advantage of the affinity of cucurbituril for protonated diamine guests as in ligand which links the Pt(II) centres together.
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes
8. Summary
Catenanes are interlocked to each other while rotaxanes are linear molecules which treaded through a macrocyclic ring. The nomenclature assign through the number of rings which are interlocked to each other. The statistical and direct approach have been used for the synthesis of catenanes. The statistical approach have been used for the synthesis of rotaxanes. Catenanes and rotaxanes are synthesized by following the π-π stacking interactions. Hydrogen bonding also play important during the synthesis of Catenanes and rotaxanes.
CHEMISTRY Paper 14: Organic Chemistry –IV(Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings) Module 26: Catenanes and Rotaxanes