The present invention relates to novel open-cage fullerenes having a 17-membered opening and a method for preparing the same. BACKGROUND OF THE INVENTION

Fullerenes have attracted a significant interest over the last 30 years, e.g. as materials useful in, e.g., lubricants. Technologies have been developed to introduce ions, metals, and even molecules into the confined subnano space inside a fullerene. Some of the initial methods included the preparation of fullerenes from carbon having metals included therein, ion- implantation of metals and ions into empty fullerenes, and high-pressure and high- temperature treatment to introduce e.g. rare gases into fullerenes.

More recent methodologies involve preparation of open-cage fullerenes which allows for introduction of atoms and smaller molecules into the cavity of the fullerene via an orifice and for subsequent closure of the cage. Murata et al. (Murata, Y., Murata, M. and Komatsu, K. "Synthesis, Structure, and Properties of Novel Open-Cage Fullerenes Having Heteroatom(s) on the Rim of the Orifice", Chem. Eur. J. 2003, 9, Vol. 7, page 1600-1609) disclose the preparation of a series of open-cage C ₆₀ fullerene derivatives with a 10-, 12-, or 13-membered-ring orifice containing heteroatom(s) on the rim. The derivatives were prepared from an aza-open-cage fullerene derivative. The C ₆₀ fullerene derivative with a sulphur-containing 13-membered-ring orifice could be used for encapsulating small molecules like hydrogen (H ₂ ), deuterium (D ₂ ), deuterium hydride (HD), water (H ₂ 0), nitrogen (N ₂ ), nitric oxide (NO), carbon monoxide (CO) and the like (see JP 2005/289755 A2; Murata, Y., Murata, M. and Komatsu, K. "100% Encapsulation of a

Hydrogen Molecule into an Open-Cage Fullerene Derivative and Gas-Phase Generation of H ₂ @C ₆₀ ", J. Am. Chem. Soc. 2003, 125, 7152-7153, and Kurotobi, K. and Murata, Y. "A Single Molecule of Water Encapsulated in Fullerene C ₆₀ ", Science, Vol. 333, 613-616). The corresponding C ₆ o fullerene derivative with a selenium-containing 13-membered-ring orifice provides a slightly larger opening (see Chuang, S., Murata, Y., Murata, M., Mori, S., Maeda, S., Tanabe, F., and Komatsu, K. "Fine tuning of the orifice size of an open-cage fullerene by placing selenium in the rim: insertion/release of molecular hydrogen", 2007, Chem. Comm., 12, 1278-80). WO 2010/119063 A2 (Bucky'O'Zun ApS) discloses various uses of O ₂ @C ₆₀ and O ₃ @C ₆₀ , e.g. as an efficient UV-absorbing material. The publication further discloses a method for preparing 0 ₂ @C ₆ o via the C ₆₀ fullerene derivative having a sulphur-containing 13-membered- ring orifice (cf. above). The method involves the subsequent conversion of the entrapped dioxygen to ozone by ion implantation.

As it has been shown in above literature, the conditions for introducing molecules into the cavity of open-cage fullerenes need to be rather vigorous with respect to pressure, temperature and time because of the limited size of the orifice even in case of the 13- membered-ring orifice reported in the literature. Needless to say that for introduction of oxygen (0 ₂ ) as well as ozone (0 ₃ ), which are relatively large molecules, it is envisaged that fullerenes with even larger orifices which can be closed under mild conditions may provide for an easier introduction of such molecules into the cavity for the preparation of e.g. 0 ₂ @C ₆ o and O ₃ @C ₆₀ .

In view of the above, it is an object of embodiments of the invention to provide alternative and/or improved open-cage fullerenes.

SUMMARY OF THE INVENTION

It has been found by the present inventor(s) that a novel open-cage fullerene having a sulphur-containing 17-membered opening was obtained by applying an elemental sulphur (i.e., S ₈ ) in the presence of a catalytic amount of polyamine to a specified open-cage fullerene having a 16-membered opening. The effective mean diameter of the opening of the novel open-cage fullerene is larger than any known open-cage fullerenes, therefore larger guest molecules can more easily be encapsulated into the open-cage fullerenes.

So, in a first aspect the present invention relates to a novel open-cage fullerene having a sulphur-containing 17-membered opening of the general formula Xn@3: wherein X is selected from the group consisting of H ₂ 0, N ₂ , H ₂ , 0 ₂ and 0 ₃ , and n is from 0 to 1; and 3 is represented by the following general formula 3:

wherein, each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl and an optionally substituted Ci _-8 -alkyl. "Xn@3" means an open-cage fullerene 3 encapsulated with molecule Xn.

A second aspect of the present invention relates to a method for the preparation of an open- cage fullerene having a sulphur-containing 17-membered opening of the general formula 3.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 shows the *H NM R (300 M Hz, CDCI ₃ ) spectrum for the derivative 3/H ₂ 0@3. Figure 2 shows the ¹³ C NM R spectra (75 MHz, CDCI ₃ ) spectrum for the derivative 3/H ₂ 0@3.

Figure 3 shows the APCI-FTICR MS (negative mode) mass spectrum for the derivative

3/H ₂ 0@3.

Figure 4 shows the VT *H NMR (600 MHz, toluene-tfg) spectrum for the derivative H ₂ 0@3.

Figure 5 illustrates the results of a computer simulation showing the barrier to insertion of H ₂ 0 into compound 3 and into compounds 2, 4 and 5 (comparative examples) .

Figure 6 illustrates the results of a computer simulation involving the compounds 2 and 3.

Figure 7 illustrates the thermodynamic parameters for the equilibrium : 3 + H ₂ 0 < > H ₂ 0@3. DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an open-cage fullerene having a sulphur-containing 17- membered opening of the general formula : Xn@3 wherein X is selected from the group consisting of H ₂ 0, N ₂ , H ₂ , 0 ₂ and 0 ₃ , and n is from 0 to 1 ; and 3 is represented by the general formula 3 :

wherein each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl, and an optionally substituted Ci _-8 -alkyl.

The fullerene in the general formula 3 of the present invention is preferably selected from the group consisting of C ₆ o-fullerene, C ₇ o-fullerene, C ₇₆ -fullerene, C ₇ 8-fullerene, C ₈₂ -fullerene, C ₈₄ - fullerene and C ₁₂₀ -fullerene.

A preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is a water encapsulating open-cage fullerene of the general formula Xn@3 wherein X= H ₂ 0 and n = l (designated as H ₂ 0@3) .

Another preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is a nitrogen encapsulating open-cage fullerene of the general formula Xn@3 wherein X= N ₂ and n= l (designated as N ₂ @3) . Another preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is a hydrogen encapsulating open- cage fullerene of the general formula Xn@3 wherein X= H ₂ and n = l (designated as H ₂ @3) .

Another preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is an oxygen encapsulating open-cage fullerene of the general formula Xn@3 wherein X=0 ₂ and n = l (designated as 0 ₂ @3) . Another preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is an ozone encapsulating open-cage fullerene of the general formula Xn@3 wherein X=0 ₃ and n = l (designated as 0 ₃ @3).

Another preferable embodiment of the open-cage fullerene having a sulphur-containing 17- membered opening according to the present invention is an open-cage fullerene having a sulphur-containing 17-membered free of any encapsulated molecule which is designated as general formula Xn@3 wherein n = 0. This encapsulation-free 3 can be a starting material for the encapsulation of other molecule than H ₂ 0 such as N ₂ , H ₂ , 0 ₂ or 0 ₃ , or other small molecules, as will be illustrated in detail in the preparation sections. As to the substituents R, R may be selected from a wide variety of organic groups consisting of an optionally substituted heteroaryl, an optionally substituted aryl and an optionally substituted Ci- ₈ -alkyl. Among them, an optionally substituted heteroaryl is preferable, and a substituted nitrogen-containing heteroaryl, such as substituted 3-pyridyl, e.g. 2-tert-butyl-3- pyridyl, is more preferable. As a substitute group, any one selected from the groups consisting of Ci- ₈ -alkyl, C ₂ - ₈ -alkenyl, C ₂ - ₈ -alkynyl, aryl, heteroaryl (nitrogen-containing, oxygen-containing, sulphur containing, etc.) may be acceptable.

The term "Ci- ₈ -alkyl" is intended to encompass straight-chain, branched and cyclic saturated hydrocarbon groups having 1 to 8 carbon atoms. Similarly, the term "C ₂ - ₈ -alkenyl" is intended to encompass straight-chain, branched and cyclic hydrocarbon groups having 1 to 8 carbon atoms and including one unsaturated double bond. Likewise, the term "C ₂ _ ₈ -alkynyl" is intended to encompass straight-chain, branched and cyclic hydrocarbon groups having 1 to 8 carbon atoms and including one unsaturated triple bond.

The term "aryl" is intended to encompass cyclic hydrocarbon moieties having at least one aromatic ring or ring system. Examples are phenyl, naphthyl, etc. Likewise, the term

"heteroaryl" is intended to encompass cyclic hydrocarbon moieties including at least one heteroatom (nitrogen-containing, oxygen-containing, sulphur-containing, etc.), and including at least one aromatic ring or ring system.

The term "optionally substituted" is intended to mean that the moiety in question may or may not be substituted, e.g. with Ci_ ₈ -alkyl, C ₂ - ₈ -alkenyl, C ₂ - ₈ -alkynyl, aryl, or heteroaryl. Then, the synthetic method of the present invention is described in detail as follows:

Scheme 1 illustrates the overall synthetic scheme for the preparation of the open-cage fullerenes having a sulphur-containing 17-membered opening (Scheme 1 illustrates the specific reaction conditions disclosed in Example 2) . The synthesis process comprises two reactions in one pot. The first step is a dehydration reaction of a starting open-cage fullerene having a 16-membered opening (compound 1) resulting in a formation of a hypothetical intermediate compound 2, which is then followed by the insertion reaction of elemental sulphur, resulting in a formation of the object product 3. Of course, the scope of the present invention is not limited by the presence or absence of the hypothetical intermediate compound 2.

Hence, the invention provides a method for the preparation of an open-cage fullerene having a sulphur-containing 17-membered opening of the general formula (H ₂ 0) _n @3, wherein n is from 0 to 1, and 3 is :

wherein each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl, and an optionally substituted alkyl;

said method comprising the step of reacting an elemental sulphur with an open-cage fullerene having a 16-membered opening of the following general formula 1:

wherein R is the same as defined above, in the presence of a catalytic amount of a polyamine.

In the reaction, the amount of elemental sulphur (S ₈ ) to the starting open-cage fullerene having a 16-membered opening of the formula 1 is generally 1 equivalent or more, e.g. 1-2 equivalents, preferably approx. 1 equivalent.

The choice of polyamine is not to be limited to any specific polyamine, but preferably may be selected from polyamines like TDAE (tetrakis(dimethylamino)ethylene), PDA (Ν,Ν,Ν',Ν'- tetramethyl-l,4-phenylene diamine), DBU (diazabicycloundecene) and DMAP (Ν,Ν-dimethyl- 4-aminopyridine), or even combinations thereof. Among them, TDAE is the currently preferred. The polyamine is typically used in a catalytic amount. The "catalytic amount" means less than 1 equivalent relative to the starting compound 1. A higher amount of the polyamine, i.e. 1 equivalent or more relative to the compound 1 tends to lower the yield of the reaction. A preferable amount of the polyamine may be less than 0.8 equivalent, for example in the range of 0.6 to 0.05, more preferable in the range of 0.4 to 0.1, for example approx. 0.2 equivalent, relative to the compound 1.

The reaction is usually carried out in the presence of a solvent. As a solvent, a non-protic polar solvent is preferable for conducting the reaction homogeneously. In order to be able to utilize a high reaction temperature, chlorinated benzene such as 1,2-dichlorobenzene or mono-chlorobenzene is suitable. There is no specific limitation in the reaction temperature, but usually the reaction is carried out in the range of 50°C to 250°C, preferably in the range of 100°C to 200°C, for example approx. 180°C. The appropriate reaction time is variable depending on the reaction

temperature or the concentration of the substrates, but usually in the range of 0.5 to 24 hours, preferably in the range of 1.0 to 10 hours, for example approx. 2 hours. In Scheme 1, the produced open-cage fullerene encapsulates a water molecule within its cavity, since the water molecule produced by the dehydration step of the starting compound 1 is expected to be simultaneously encapsulated into the cavity of the product 3. Therefore, in this embodiment, the product is a H ₂ 0-encapsulated open-cage fullerene designated as H ₂ 0@3. This encapsulated H ₂ 0 can be eliminated irreversibly by heating or evacuating, as will be described in detail in the following sections, resulting in the formation of a water-free open-cage fullerene 3. It is also envisaged that it may be possible to effectively remove the water in process by suitable means.

Hence, the invention also provides a method for the preparation of an open-cage fullerene having a sulphur-containing 17-membered opening and free of encapsulation of the following general formula 3 :

wherein each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl, and an optionally substituted alkyl,

said method comprising a step of dehydrating a compound the of the general formula H ₂ 0@3 in vacuum and/or at a temperature of from 50°C to 250°C to form the open-cage fullerene of the general formula 3.

It is envisaged that such an open-cage fullerene will be suitable for introducing molecules like N ₂ , H ₂ , 0 ₂ and even 0 ₃ .

Hence, the invention also provides a method for the preparation of an open-cage fullerene having a sulphur-containing 17-membered opening represented by any one of the general formulae N ₂ @3, H ₂ @3, 0 ₂ @3, or 0 ₃ @3, wherein 3 is:

wherein each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl, and an optionally substituted Ci-8-alkyl;

said method comprising a step of encapsulating, using a gas phase technology, a molecule selected from N ₂ , H ₂ , 0 ₂ , or 0 ₃ into an open-cage fullerene of the general formula 3 to form the open-cage fullerene represented by one of the general formulae N ₂ @3, H ₂ @3, 0 ₂ @3, or 0 ₃ @3. The "gas phase technology" used herein is reacting reagents in gas phase resulting in the formation of, for example, H ₂ @3 in a gaseous phase. The details of the gas phase technology are described in Michihisa Murata, " 100% Encapsulation of Hydrogen Molecule into an Open-cage Fullerene Derivative and Gas-Phase Generation of H2@3", Institute for Chemical Research, Kyoto University, 2006, http://repository. kuNb. kyoto- u.as.j p/dspace/bitstream/2433/64942/l/D_M urata_Michihisa . pdf (refer to page 6, lines 19- 23 in WO2010/119063) .

An alternative route for preparing 0 ₃ @3 may be that of first preparing 0 ₂ @3, and then converting 0 ₂ to 0 ₃ by means of an oxygen ion by using an ion bombardment technology. The "ion bombardment technology" used herein is a method wherein a third oxygen atom is introduced into the fullerene structure by bombarding a sample of the fullerenes with oxygen ions using, for example, a beam machine (refer to page 7, lines 1-3 in WO 2010/119063) .

Hence, the invention further provides a method for the preparation of an open-cage fullerene having a sulphur-containing 17-membered opening of the general formula 0 ₃ @3, wherein 3 is :

wherein each R is the same or different and is selected from the group consisting of an optionally substituted heteroaryl, an optionally substituted aryl, and an optionally substituted Ci-s-alkyl;

said method comprising a step of reacting a compound of the general formula 0 ₂ @3, wherein 3 is as above, with an oxygen ion by using an ion bombardment technology to form the open-cage fullerene of the general formula 0 ₃ @3. EXAMPLES

Example 1 - Preparation of an open-cage fullerene having a 16-membered opening.

The starting material for the preparation of compound 3 is an open-cage fullerene having a 16-membered opening of the formula 1 which can be prepared by a known method such as described, for example, in K. Kurotobi, Y. M urata, Science 2011, 333, 613, the reaction schemes of which are illustrated as Scheme 2 below.

K. Kurotobi, Y. Murata, Science 2011 , 333, 613.

Scheme 2 Example 2 - Preparation of the open-cage fullerene having a 17-membered opening

(3/H ₂ 0@3)

A suspension of compound 1 ( 101 mg, 0.090 mmol) and elemental sulfur (25 mg, 0.098 mmol as S8) in 1,2-dichlorobenzene (ODCB) (5 mL) was heated at 180 °C for 10 min to give a dark brown solution. To this was added tetrakis(dimethylamino)ethylene (3.7 pL, 0.016 mmol) at 180 °C and stirred under reflux for 1 h. Then the resulting dark red-brown solution was cooled to room temperature and was subjected to flash chromatography on silica gel eluted with toluene/ethyl acetate (50 : 1) . The resulting red-brown solution was evaporated to give cage-opened fullerene derivative 3/H ₂ 0@3 (48 mg, 0.042 mmol, 47%) as a brown powder.

The *H NMR (300 M Hz, CDCI ₃ ) and ¹³ C NMR spectra (75 MHz, CDCI ₃ ) for the derivative

3/H ₂ 0@3 are shown in Figure 1 and Figure 2, respectively. The APCI-FTICR MS (negative mode) for the derivative 3/H ₂ 0@3 is shown in Figure 3. The VT *H NMR (600 MHz, toluene- d ₈ ) for the derivative H ₂ 0@3 at different temperatures is shown in Figure 4.

Example 3 - Calculation of activation barriers for dinitrogen insertion

The open-cage fullerene having a sulphur-containing 17-membered opening according to the present invention is characterized in its substantially larger opening diameter, which can be determined kinetically by using a probe molecule such as N ₂ . A larger opening diameter is specifically advantageous for encapsulating a molecule in mild conditions (such as, lower temperature or lower pressure) . The kinetic parameters can be also determined by a computer simulation as well as a physical experimentation . The evaluation of the diameter of the opening is conducted by comparing the difference of the activation energy (delta E) of the diffusion of the small molecule through the opening. The diameter of the opening does not necessarily proportional to the member of the atoms composing the opening since the opening has not a planer structure. The computer simulation can be carried out according to the method described in Y. Murata et. al. JACS, 2003, 124, 7152-7153. In order to examine the feasibility of insertion of small molecules through the opening (or orifice) of the open- cage fullerene, theoretical calculations using "hybrid density functional theory (B3LYP/6- 31G//B3LYP/3-21G)" are conducted . A lower energy barrier (lower delta E) calculated means a larger opening diameter of the open-cage fullerene.

The results of the computer simulation are shown in Figure 5. The simulation shows that the barrier to insertion as well as the energy of encapsulation is lower in case of the novel 17- membered opening (compound 3) than for the comparative examples, cf. compounds 2, 4 and 5. Results of a similar simulation involving the compounds 2 and 3 are shown in Figure 6. The compound 4 (the members composing the opening (or orifice) are 21) is considered to have the largest opening known ever, and the insertion barrier to the compound 4 was calculated to be +7.0. On the other hand, the insertion barrier to the compound 3 of the present invention was calculated to be +6.8, the lowest value among the four compounds 2- 4 (Figs. 5 and 6). Therefore, the opening diameter of the compound 3 is estimated to be the largest among the four compounds.

Figure 7 illustrates the thermodynamic parameters for the equilibrium : 3 + H ₂ 0 < > H ₂ 0@3.