Method of converting a nitrile functional group into a hydroxamic functional group by using a peroxocobalt complex at room temperature and normal pressure

Abstract

The method of the present invention for converting a nitrile functional group into a hydroxamic acid functional group can be easily performed at room temperature and under normal pressure by using a peroxocobalt complex. The final hydroxamic acid functional group produced through the intermediate Hydroximatocobalt (III) compound or the derivative comprising the same has been known to be able to inhibit the growth of cancer cells, so that the conversion method of the present invention can be applied to the preparation of a pro-drug for anticancer treatment.

Claims

1. A method of converting a nitrile functional group (CN) into a hydroxamic acid functional group ##STR00024## in the presence of a peroxocobalt complex represented by formula 1 below:
[Co(L)(O.sub.2)].sup.+[Formula 1] wherein, L is ##STR00025## and R.sup.4 and R.sup.5 are independently straight or branched C.sub.1-10 alkyl, substituted or unsubstituted C.sub.3-10 cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl, and wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is a C.sub.3-10 cycloalkyl or C.sub.6-10 aryl, respectively, substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy.

2. The method according to claim 1, wherein the R.sup.4 and R.sup.5 above are independently t-butyl or cyclohexyl.

3. A method of converting a compound comprising a nitrile functional group (CN) represented by formula 2 below into a compound comprising a hydroxamic acid functional group ##STR00026## represented by formula 3 in the presence of a peroxocobalt complex represented by formula 1 below, as shown in reaction formula 1 below: ##STR00027## wherein L is ##STR00028## R.sup.4 and R.sup.5 are independently straight or branched C.sub.1-10 alkyl, substituted or unsubstituted C.sub.3-10, cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl, wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is C.sub.3-10 cycloalkyl or C.sub.6-10 aryl respectively, substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy, R is ##STR00029## an aliphatic hydrocarbon group, or aromatic hydrocarbon group, R.sup.1, R.sup.2 and R.sup.3 are independently OH, straight or branched C.sub.1-10 alkyl, straight or branched C.sub.1-10 alkoxy, substituted or unsubstituted C.sub.3-10 cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl, wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is a C.sub.3-10 cycloalkyl or a C.sub.6-10 aryl, respectively, substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl, straight C.sub.1-5 alkoxy and branched C.sub.1-5 alkoxy.

4. The method according to claim 3, wherein the aliphatic hydrocarbon group is straight C.sub.1-10 alkyl, branched C.sub.1-10 alkyl, substituted C.sub.3-10 cycloalkyl, or unsubstituted C.sub.3-10 cycloalkyl, and wherein the substituted C.sub.3-10 cycloalkyl is a C.sub.3-10 cycloalkyl substituted with one or more substituents, wherein the one or more substituents are halogen, OH, CN, NO.sub.2, straight C.sub.1-5 alkyl, branched C.sub.1-5 alkyl, straight C.sub.1-5 alkoxy, or branched C.sub.1-5 alkoxy; or wherein the aromatic hydrocarbon group is substituted or unsubstituted C.sub.6-10 aryl, and wherein the substituted a C.sub.6-10 aryl is C.sub.6-10 aryl substituted with one or more substituents, wherein the one or more substituents are halogen, OH, CN, NO.sub.2, straight C.sub.1-5 alkyl, branched C.sub.1-5 alkyl, straight C.sub.1-5 alkoxy, or branched C.sub.1-5 alkoxy.

5. The method according to claim 3, wherein the aliphatic hydrocarbon group is straight C.sub.1-5 alkyl, branched C.sub.1-5 alkyl, substituted C.sub.3-8 cycloalkyl, or unsubstituted C.sub.3-8 cycloalkyl, and wherein the substituted C.sub.3-8 cycloalkyl is a C.sub.3-8 cycloalkyl substituted with one or more substituents, wherein the one or more substituents are straight C.sub.1-3 alkyl, branched C.sub.1-3 alkyl, straight C.sub.1-3 alkoxy, or branched C.sub.1-3 alkoxy; or wherein the aromatic hydrocarbon group is substituted or unsubstituted C.sub.6 aryl, and wherein the substituted C.sub.6 aryl is a C.sub.6 aryl substituted with one or more substituents, wherein the one or more substituents are straight C.sub.1-3 alkyl, branched C.sub.1-3 alkyl, straight C.sub.1-3 alkoxy or branched C.sub.1-3 alkoxy.

6. The method according to claim 3, wherein the aliphatic hydrocarbon group is CH.sub.3 or CH.sub.2CH.sub.3; or the aromatic hydrocarbon group is -Ph.

7. The method according to claim 3, wherein the R.sup.1, R.sup.2 and R.sup.3 are independently OH, straight C.sub.1-5 alkyl, or branched C.sub.1-5 alkyl.

8. The method according to claim 3, wherein the R.sup.1 and R.sup.2 are t-butyl; and the R.sup.3 is OH.

9. The method according to claim 3, wherein when the compound comprising the nitrile functional group (CN) of formula 2 is converted into the compound comprising a hydroxamic acid functional group of formula 3 in the presence of the peroxocobalt complex of formula 1, a hydroximato cobalt complex represented by formula 4 below is produced as an intermediate: ##STR00030##

10. A peroxocobalt complex of the formula below:
[Co(L)(O.sub.2)].sup.+ wherein L is ##STR00031## R.sup.4 and R.sup.5 are independently straight C.sub.1-10 alkyl, branched C.sub.1-10 alkyl, substituted C.sub.3-10 cycloalkyl, unsubstituted C.sub.3-10 cycloalkyl, substituted C.sub.6-10 aryl or unsubstituted C.sub.6-10 aryl, wherein the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is a C.sub.3-10 cycloalkyl or a C.sub.6-10 aryl, respectively, substituted with one or more substituents, wherein the one or more substituents are halogen, OH, CN, NO.sub.2, straight C.sub.1-5 alkyl, branched C.sub.1-5 alkyl, straight C.sub.1-5 alkoxy, or branched C.sub.1-5 alkoxy.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The application of the preferred embodiments of the present invention is best understood with reference to the accompanying drawings, wherein:

(2) FIG. 1 is a graph illustrating the electron absorption spectrum of the complex of Example (gray line) and the composite of Preparative Example (dark black line) which is the precursor of the complex of Example 1. The insert on the top right presents the resonance Raman spectrum: 1-.sup.16O (16 mM; top most line); 1-.sup.18O (16 mM; middle line); The difference spectrum between 1-.sup.16O and 1-.sup.18O (bottom line) was obtained by excitation at 355 nm in CH.sub.3CN at 30. 1-.sup.16O and 1-.sup.18O were obtained by the same manner as described in Example 1 by using H.sub.2.sup.16O.sub.2 and H.sub.2.sup.18O.sub.2, respectively.

(3) FIG. 2 is a graph illustrating the ESl-MS spectrum of the complex of Example 1 (1) in CH.sub.3CN at 20. The peak at m/z=443.2 corresponds to [Co.sup.III(TBDAP)(O.sub.2)].sup.+ (1-.sup.16O; calcd. m/z=443.2). The insert on the top right indicates the isotope distribution pattern observed at the peaks of the followings: 1-.sup.16O (lower) is m/z=443.2/1-.sup.18O (upper) is m/z=447.2.

(4) FIG. 3 is a graph illustrating the changes of the UV-vis spectra observed according to the reaction of the complex of Example 1 (2.0 mM) with CH.sub.3CN (3.8 M) in C.sub.6H.sub.6 at 40 in Experimental Example 1. The insert on the top right presents the absorption changes of 790 nm wavelength band due to the generation of [Co(TBDAP)(CH.sub.3C(NO)O] (2).

(5) FIG. 4 shows the ESl-MS spectrum of the solution wherein the complex of Example 1 (2.0 mM) reacted to CH.sub.3CN (3.8 M) in C.sub.6H.sub.6 at 40 in Experimental Example 1. The peak at m/z=484.3 corresponds to [Co.sup.III(TBDAP)(CH.sub.3C(NO)O)].sup.+ (2-.sup.16O) (calculated m/z of 484.2). The insert on the top right indicates the isotope distribution pattern measured with 2-.sup.16O (lower) and 2-.sup.18O (upper) induced from 1-.sup.16O and 1-.sup.18O, respectively.

(6) FIG. 5 is a graph illustrating the changes of the UV-vis spectra observed according to the reaction of the complex of Example 1 (2.0 mM) with CH.sub.3CH.sub.2CN (1.4 M) in CHCl.sub.3 at 40 in Experimental Example 2. The insert on the top right presents the absorption changes of 790 nm wavelength band due to the generation of [Co(TBDAP)(CH.sub.3CH.sub.2C(NO)O] (3).

(7) FIG. 6 shows the ESl-MS spectrum of the solution wherein the complex of Example 1 (2.0 mM) reacted to CH.sub.3CH.sub.2CN (1.4 M) in CHCl.sub.3 at 40 in Experimental Example 2. The peak at m/z=498.3 corresponds to [Co.sup.III(TBDAP)(CH.sub.3CH.sub.2C(NO)O)].sup.+ (calculated m/z of 498.2). The insert on the top right indicates the isotope distribution pattern measured (upper) at the peak of m/z=498.3 and calculated.

(8) FIG. 7 is a graph illustrating the changes of the UV-vis spectra observed according to the reaction of the complex of Example 1 (2.0 mM) with C.sub.6H.sub.5CN (0.98 M) in CHCl.sub.3 at 40 in Experimental Example 3. The insert on the top right presents the absorption chances of 840 nm wavelength band due to the generation of [Co(TBDAP)(C.sub.6H.sub.5C(NO)O] (4).

(9) FIG. 8 shows the ESl-MS spectrum of the solution wherein the complex of Example 1 (2.0 mM) reacted to C.sub.6H.sub.5CN (0.98 M) in CHCl.sub.3 at 40 in Experimental Example 3. The peak at m/z=546.3 corresponds to [Co.sup.III(TBDAP)(C.sub.6H.sub.5C(NO)O].sup.+ (calculated m/z of 546.2). The insert on the top right indicates the isotope distribution pattern measured (upper) at the peak of m/z=546.3 and calculated.

(10) FIG. 9 presents the Hammett plot of log k.sub.obs for .sub.p.sup.+, the Hammett parameter.

(11) FIG. 10 presents the mechanism of nitrile activation according to the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

(12) Hereinafter, the present invention is described in detail.

(13) The present invention provides a method of converting a nitrile functional group (CN) into a hydroxamic acid functional group

(14) ##STR00008##
in the presence of a peroxocobalt complex represented by formula 1 below.
[Co(L)(O.sub.2)].sup.+[Formula 1]

(15) In formula 1,

(16) L is

(17) ##STR00009##

(18) R.sup.4 and R.sup.5 are independently straight or branched C.sub.1-10 alkyl, substituted or unsubstituted C.sub.3-10 cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl,

(19) wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is the C.sub.3-10 cycloalkyl or the C.sub.6-10 aryl substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy.

(20) At this time, the R.sup.4 and R.sup.5 are independently t-butyl or cyclohexyl.

(21) The present invention also provides a method of converting a compound containing a nitrile functional group (CN) represented by formula 2 below into a compound containing a hydroxamic acid functional group

(22) ##STR00010##
represented by formula 3 in the presence of a peroxocobalt complex represented by formula 1 below, as shown in reaction formula 1 below.

(23) ##STR00011##

(24) In reaction formula 1,

(25) L is

(26) ##STR00012##

(27) R.sup.4 and R.sup.5 are independently straight or branched C.sub.1-10 alkyl, substituted or unsubstituted C.sub.3-10 cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl,

(28) wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is the C.sub.3-10 cycloalkyl or the C.sub.6-10 aryl substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy,

(29) R is

(30) ##STR00013##
aliphatic hydrocarbon group, or aromatic hydrocarbon group,

(31) R.sup.1, R.sup.2 and R.sup.3 are independently OH, straight or branched C.sub.1-10 alkyl, straight or branched C.sub.1-10 alkoxy, substituted or unsubstituted C.sub.3-10 cycloalkyl, or substituted or unsubstituted C.sub.6-10 aryl,

(32) wherein, the substituted C.sub.3-10 cycloalkyl or the substituted C.sub.6-10 aryl is the C.sub.3-10 cycloalkyl or the C.sub.6-10 aryl substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy.

(33) In an aspect of the present invention, the aliphatic hydrocarbon group is straight or branched C.sub.1-10 alkyl or substituted or unsubstituted C.sub.3-10 cycloalkyl, and at this time the substituted C.sub.3-10 cycloalkyl is the C.sub.3-10 cycloalkyl substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy; and

(34) the aromatic hydrocarbon group is substituted or unsubstituted C.sub.6-10 aryl, and at this time the substituted C.sub.6-10 aryl is the C.sub.6-10 aryl substituted with one or more substituents selected from the group consisting of halogen, OH, CN, NO.sub.2, straight or branched C.sub.1-5 alkyl and straight or branched C.sub.1-5 alkoxy.

(35) In another aspect of the present invention, the aliphatic hydrocarbon group is straight or branched C.sub.1-5 alkyl or substituted or unsubstituted C.sub.3-8 cycloalkyl, and at this time the substituted C.sub.3-8 cycloalkyl is the C.sub.3-8 cycloalkyl substituted with one or more substituents selected from the group consisting of straight or branched C.sub.1-3 alkyl and straight or branched C.sub.1-3 alkoxy; and

(36) the aromatic hydrocarbon group is substituted or unsubstituted C.sub.6 aryl, and at this time the substituted C.sub.6 aryl is the C.sub.6 aryl substituted with one or more substituents selected from the group consisting of straight or branched C.sub.1-3 alkyl and straight or branched C.sub.1-3 alkoxy.

(37) In another aspect of the present invention, the aliphatic hydrocarbon group is CH.sub.3 or CH.sub.2CH.sub.3; and the aromatic hydrocarbon group is -Ph.

(38) In another aspect of the present invention, the R.sup.1, R.sup.2 and R.sup.3 are independently OH or straight or branched C.sub.1-5 alkyl; the R.sup.1 and R.sup.2 are t-butyl; and the R.sup.3 is OH.

(39) When a compound containing a nitrile functional group (CN) is converted into a compound containing a hydroxamic acid functional group in the presence of a peroxocobalt complex, the complex represented by formula 4 below is produced as an intermediate.

(40) ##STR00014##

(41) In formula 4,

(42) L and R are as defined above.

(43) Hydroximato ligands, the tautomers of hydroxamato analogue, have been used for the treatment of cancer and Alzheimer's disease because they can act as inhibitors of metalloenzymes.

(44) [Relational Expression of Hydroxamato and Hydroximato Tautomer]

(45) ##STR00015##

(46) The hydroximato cobalt complex represented by formula (4) is also referred to as a hydroximatocobalt (III) compound, which can be converted into cobalt (II) in vivo through reduction that can be easily chemically modified, resulting in the release of a hydroxymate functional group, more precisely a hydroxamic acid functional group

(47) ##STR00016##
or a derivative comprising the same.

(48) The released hydroxymate functional group has chelating properties so that it can bind to zinc in the active site of the matrix metalloproteinase over-expressed in cancer cells, indicating that it can inhibit the growth of cancer cells. Therefore, the final product of the activation reaction of nitrile can be used as a pro-drug that is a carrier which can deliver the hydroxymate functional group safely and selectively to cancer cells by taking advantage of the difference of cell potential between normal cells and cancer cells. Marimastat having the structure below is an example of well informed anticancer drugs containing the hydroxamic acid functional group.

(49) [Chemical structure of Marimastat]

(50) ##STR00017##

(51) In a preferred embodiment of the present invention, the present invention provides a method of converting a compound containing a nitrile functional group (CN) represented by formula 2 into a hydroximato cobalt complex represented by formula 4 in the presence of a peroxocobalt complex represented by formula 1, as shown in reaction formula 2.

(52) ##STR00018##

(53) In reaction formula 2,

(54) R and L are as defined above.

(55) The conversion method above can be performed at room temperature under normal pressure to ensure a high yield. At this time, the room temperature can be 050, 040, 030, 025, 1050, 2050, and 2550. The normal pressure herein can be 0.13 atm, 0.12 atm, 0.11.5 atm, 0.11 atm, 0.53 atm, 0.73 atm, 0.93 atm, and 13 atm.

(56) In addition, the present invention provides a peroxocobalt complex represented by formula 1 below.
[Co(L(O.sub.2)].sup.+[Formula 1]

(57) In formula 1,

(58) L is as defined above.

(59) The peroxocobalt complex represented by formula 1 above can be effectively used for the activation of nitrile according to the present invention.

(60) Practical and presently preferred embodiments of the present invention are illustrative as shown in the following Examples.

(61) However, it will be appreciated that those skilled in the art, on consideration of this disclosure, may make modifications and improvements within the spirit and scope of the present invention.

Preparative Example 1: Preparation of [CoII(TBDAP)(NO3)(H2O)](NO3)

(62) ##STR00019##

(63) Co(NO.sub.3).sub.2.6H.sub.2O (0.146 g, 0.50 mmol) and TBDAP(N,N-di-tertbutyl-2,11-diaza[3.3] (2,6)-pyridinophane, 0.176 g, 0.50 mmol) were added to CH.sub.3CN (2.0 mL) and CHCl.sub.3 (2.0 mL), followed by stirring for 12 hours and as a result a pink solution was obtained. Et.sub.2O (40 mL) was added thereto, followed by filtering, washing and drying in vacuo. As a result, the target compound was obtained as a pink powder. Yield: 94% (0.2610 g). Crystallographically appropriate X ray crystals were obtained by diffusing Et.sub.2O slowly in CH.sub.3CN containing the target compound dissolved therein.

(64) ESI-MS in CH.sub.3CN: m/z 205.6 for [Co(TBDAP)].sup.2+, m/z 226.1 for [Co(TBDAP)(CH.sub.3CN)].sup.2+, and m/z 246.7 for [Co(TBDAP)(CH.sub.3CN).sub.2].sup.2+, m/z 473.2 for [Co(TBDAP)(NO.sub.3)]+. Anal. Calcd for C.sub.22H.sub.34CoN.sub.6O.sub.7: C, 47.74; H, 6.19; N, 15.18. Found: C, 47.62; H, 6.194; N, 15.29. Effective magnetic moment eff=3.9 B.M. (measured by 1H NMR Evans method in CH.sub.3CN at 25)

Example 1: Preparation of Peroxocobalt Complex [Co(TBDAP)(O2)] (1)

(65) ##STR00020##

(66) [Co(TBDAP)(NO.sub.3)(H.sub.2O)](NO.sub.3) (0.0277 g, 0.050 mmol) prepared in Preparative Example 1 was treated with H.sub.2O.sub.2 (5.0 eq) in the presence of triethylamine (TEA; 2 eq) dissolved in CH.sub.3CN (1.5 mL) at 40, resulting in the preparation of a green solution. Et.sub.2O (40 mL) was added thereto, followed by filtering, washing and drying in vacuo. As a result, a green powder was obtained. The obtained green powder was dissolved in CHCl.sub.3 at 40. Et.sub.2O was slowly dispersed in the solution obtained at 40 above, and as a result [Co(TBDAP)(O.sub.2)](NO.sub.3)(H.sub.2O).sub.2 (1-NO.sub.3.2H.sub.2O) was obtained as a green crystal. Crystal yield: 72% (0.0157 g).

(67) Crystallographically appropriate X ray crystals of [Co(TBDAP)(O.sub.2)](BPh.sub.4)(1-BPh.sub.4) formed by anion exchange with BPh.sub.4- in 1-NO.sub.3.2H.sub.2O complex were obtained by dispersing Et.sub.2O slowly in CHCl.sub.3 solution of 1 in the presence of NaBPh.sub.4 (0.17 g).

(68) On the other hand, [Co(TBDAP) (.sup.18O.sub.2)].sup.+ (1-.sup.18O.sub.2) can be prepared by treating [Co(TBDAP)(NO.sub.3)(H.sub.2O)](NO.sub.3) (2.0 mM) prepared in Preparative Example 1 with H.sub.2.sup.18O.sub.2 (5.0 eq, 36 L, 95% .sup.18O-enriched, 2.2% H.sub.2.sup.18O.sub.2, dissolved in water) in the presence of triethylamine(TEA; 2 eq) dissolved in CH.sub.3CN (2.0 mL) at 40.

(69) ESI-MS CH.sub.3CN (see FIGS. 1 and 2): m/z 443.2 for [Co(TBDAP)(O.sub.2)].sup.+. Anal. Calcd for C.sub.46H.sub.52BCoN.sub.4O: C, 48.80; H, 6.70; N, 12.93. Found: C, 48.67; H, 6.31; N, 12.91.

Experimental Example 1: Preparation of Hydroximato Cobalt Complex [Co(TBDAP)(CH3C(NO)O] (2)

(70) ##STR00021##

(71) 1-NO.sub.3.2H.sub.2O (0.0234 g, 0.046 mmol) prepared in Example 1 was dissolved in 1.5 mL of CH.sub.3CN. The mixed solution was kept at 25 overnight to induce the color change from green to dark brown. Et.sub.2O was slowly dispersed in the mixed solution and as a result [Co(TBDAP)(CH.sub.3C(NO)O]NO.sub.3.H.sub.2O (2-NO.sub.3.H.sub.2O) complex was obtained as a brown crystal. At this time, the crystal yield was 54% (0.0139 g).

(72) Crystallographically appropriate X ray crystals of 2-BPh.sub.4 formed by anion exchange with BPh.sub.4- in 2-NO.sub.3.H.sub.2O complex were obtained by dispersing Et.sub.2O slowly in CH.sub.3CN solution containing 2 dissolved therein in the presence of NaBPh.sub.4 (0.17 g).

(73) On the other hand, [Co(TBDAP)(CH.sub.3C(N.sup.18O).sup.18O].sup.+ can be prepared by reacting 1-.sup.18O.sub.2 with CH.sub.3CN (2.0 mL) at 25.

(74) ESI-MS CH.sub.3CN (see FIGS. 3 and 4): m/z 484.3 for [Co(TBDAP)(CH.sub.3C(NO)O)].sup.+. FT-IR (ATR): 1523 cm.sup.1 (w, CN). Anal. Calcd for C.sub.24H.sub.37BCoN.sub.6O.sub.6: C, 51.06; H, 6.61; N, 14.89. Found: C, 51.19; H, 6.58; N, 14.79.

(75) As shown in FIG. 3, the absorption band at 974 nm produced by Example 1 (1) disappeared with first-order kinetics. The generated (2) corresponds to electronic absorption bands at .sub.max=450 (=420 M.sup.1 cm.sup.1) and 790 nm (=430 M.sup.1 cm.sup.1), and appeared as an isosbestic point at 960 nm.

(76) As shown in FIG. 4, the ESl-MS spectrum of (2) obtained above showed an important signal at m/z=484.3, which was confirmed to correspond to [Co(TBDAP)(CH3C(NO)O)].sup.+ (2-.sup.16O; calculated m/z of 484.2). .sup.18O-labeling was also performed. The results are shown in the insert of FIG. 4, from which, it was confirmed that the oxygen atom of (2) was induced from the peroxo group of Example 1.

Experimental Example 2: Preparation of Hydroximato Cobalt Complex [Co(TBDAP)(CH3CH2C(NO)O] (3)

(77) ##STR00022##

(78) 1-BPh.sub.4 (0.0172 g, 0.034 mmol) prepared in Example 1 was dissolved in 1.5 mL of CH.sub.3CH.sub.2CN. The mixed solution was kept at 25 overnight to induce the color change from green to dark brown. Et.sub.2O was slowly dispersed in the mixed solution in the presence of NaBPh.sub.4 (0.17 g) and as a result [Co(TBDAP)(CH.sub.3CH.sub.2C(NO)O]BPh.sub.4 (3-BPh.sub.4) complex was obtained as a brown crystal. At this time, the crystal yield was 46% (0.0088 g).

(79) On the other hand, [Co.sup.TTT(TBDAP)(CH.sub.3CH.sub.2C(N.sup.18O).sup.18O].sup.+ can be prepared by reacting 1-.sup.18O.sub.2 with CH.sub.3CH.sub.2CN (2.0 mL) at 25.

(80) ESI-MS CH.sub.3CN (see FIGS. 5 and 6): m/z 498.3 for [Co(TBDAP)(CH.sub.3CH.sub.2C(NO)O].sup.+. FT-IR (ATR): 1523 cm.sup.1 (w, CN). Anal. Calcd. for C.sub.49H.sub.57BCoN.sub.5O.sub.2: C, 71.97; H, 7.03; N, 8.56. Found: C, 71.95; H, 7.23; N, 8.4.

Experimental Example 3: Preparation of Hydroximato Cobalt Complex [Co(TBDAP)(C6H5C(NO)O] (4)

(81) ##STR00023##

(82) 1-BPh.sub.4 (0.0186 g, 0.037 mmol) prepared in Example 1 was dissolved in 1.5 mL of C.sub.6H.sub.5CN. The mixed solution was kept at 25 overnight to induce the color change from green to dark brown. The yield of the obtained [Co(TBDAP)(C.sub.6H.sub.5C(NO)O]BPh.sub.4.H.sub.2O powder was 40% (0.0128 g). Et.sub.2O was slowly dispersed in the mixed solution whose color was changed into dark brown in the presence of NaBPh.sub.4 (0.17 g), during which water molecules were eliminated and as a result [Co(TBDAP)(C.sub.6H.sub.5(NO)O]BPh.sub.4 (4-BPh.sub.4), the crystallographically appropriate X-ray crystal, was obtained.

(83) On the other hand, [Co.sup.III(TBDAP)(C.sub.6H.sub.5 (N.sup.18O).sup.18O].sup.+ can be prepared by reacting 1-.sup.18O.sub.2 with C.sub.6H.sub.5CN (2.0 mL) at 25.

(84) ESI-MS CH3CN (see FIGS. 7 and 8): m/z 546.3 for [Co(TBDAP)(C.sub.6H.sub.5C(NO)O)].sup.+. FT-IR (ATR): 1546 cm.sup.1 (w, CN). Anal. Calcd. for C.sub.53H.sub.59BCoN.sub.5O.sub.3: C, 72.03; H, 6.73; N, 7.92. Found: C, 71.96; H, 6.86; N, 7.91.

Experimental Example 4: Evaluation of Reactivity to Para-Substituted Benzonitrile

(85) To evaluate the reactivity of the peroxocobalt complex [Co(TBDAP)(O.sub.2)] (1) prepared in Example 1 to para-substituted benzonitrile, reaction was induced at 40 by the same manner as described in Experimental Example 2 except that para-substituted benzonitrile was used instead of CH.sub.3CH.sub.2CN. At this time, OMe, Me, H, and Cl were used as para-substituted substituents.

(86) Upon completion of the reaction, k.sub.obs was measured by pseudo-first order fitting of kinetic data. The results are shown in FIG. 9.

(87) FIG. 9 presents the Hammett plot of log k.sub.obs for .sub.p.sup.+, the Hammett parameter.

(88) As shown in FIG. 9, the value was measured as 0.18, and this small value indicated that the reaction did not depend on the flow of electrons into the ring.

(89) Particularly, the Hammett constant presenting the electrostatic property was 0.18, which was close to 0. The Hammet constant is positive when the reaction is nucleophilic, while it is negative when the reaction is electrophilic.

(90) However, the nitrile reaction which shows the Hammet constant of almost 0 undergoes a different transition state from the common nucleophilic reaction of metal-peroxo species. FIG. 10 presents the mechanism of nitrile activation according to the present invention.

(91) The result that the Hammett constant above was close to o and the result of isotope labeling proving that the exchange reaction with external oxygen did not occur suggested that the mechanism was not a progressive transition state stepwise but a simultaneous reaction state.