FIELD OF INVENTION

The present invention concerns the synthesis of binucleating macrocyclic ligands that may be used to form complexes that have utility as bleach and/or oxidation catalysts. BACKGROUND OF THE INVENTION

Manganese complexes containing the ligands Me ₃ TACN (1,4,7- trimethyl-1, , 7-triazacyclononane) and Me-DTNE (1,2-bis- (4, 7-dimethyl~1, 4, 7-triazacyclonon-l-yl ) -ethane) are of interest for different bleaching of cellulosic and other substrates .

The reaction with 1, 4-ditosyl-l, 4, 7-triazacyclonone with 2 equivalents of ditosyl-ethyleneglycol in DMF yielded Ts ₄ -DTNE is also disclosed in Inorg. Chem. 1985, 24, 1230; Inorg.

Chem. 1996, 35, 1974-1979; Inorg. Chem. 1998, 37(5), 3705- 3713; Inorg. Chem. 2005, 44 (2), 401-409; and J. Chem. Soc, Dalton Trans. 1994, 457-464. Ts -DTNE has also been obtained using 0, 0' N, ' -tetratosyl- N, ' -bis (2-hydroxyethyl) ethylenediamine and ethylenediamine (Synthesis 2001, 2381-2383; Inorg. Chem. 2007, 46(1), 238- 250; Green Chem. 2007, 9, 996-1007). Synthesis of 1, 2-bis (1, , 7-triazacyclonon-l-yl) -ethane (DTNE) from methine-1, 4 , 7-triazacyclononane and dibromoethane or diiodoethane has been disclosed in J.Chem.Soc, Chem Commun 1987, 886; J.Am. Chem. Soc. 1998, 120, 13104-13120 _/ Inorg.

Chem. 1993, 32, 4300-4305; Inorg. Chem. 1997, 36, 3125-3132; Chem. Lett. 2000, 416-417; J.Chem.Soc, Dalton Trans. 2000, 3034-3040.

Synthesis of Me ₄ -DTNE from DTNE using formaldehyde and formic acid can be found in J.Am. Chem. Soc. 1998, 120, 13104-13120; Inorg. Chem. 1993, 32(20), 4300-4305; Chem. Lett. 2000, 416- 7.

Using the known methods, the binucleating triazacyclononane ligand can be obtained in a reasonable yield. However, as the purity level is insufficient to obtain the dinuclear manganese complex ( [Mn ^IV Mn ^Ii:i (μ-Ο) ₂ (μ-OAc) (Me ₄ -DTNE) ] ²⁺ ) in high yield, an additional purification step, such as vacuum destination is needed. Although this gives then a high purity material, the yield loss is quite substantial.

Therefore there is still a need to be able to synthesise manganese complexes using Me ₄ -DTNE that has been obtained in a more simple synthetic procedure, with preferably without needing to distil Me ₄ -DTNE prior complexation .

SUMMARY OF THE INVENTION

Reaction of 1, 4-di (arylsulfonate) -1, 4, 7-triazacyclonane with dihaloethane in a solvent, optionally, in the presence of water, and a base yields 1, 2-bis- (4, 7-diarylsulfonate-1, 4, 7- triazacyclonon-l-yl) -ethane in high yield. Removing the arylsulfonate protecting groups and then reacting further with formaldehyde and formic acid in one-pot reaction yields e ₄ -DTNE (1, 2-bis- (4, 7-dimethyl-l, 4, 7-triazacyclonon-l-yl ) - ethane) . Surprisingly, when acetonitrile/water is employed as a solvent in the step to form Ts ₄ -DTNE, the purity level of Me ₄ -DTNE is high enough to allow complexation to form the manganese complex, ( [Μη ^ιν Μη ^ι:α (μ-Ο) ₂ (μ-OAc) ( e ₄ -DTNE) ] ²⁺ ) , without the need to distil the Me ₄ -DTNE ligand prior the complexation step.

In one aspect the present invention provides a method of producing a compound of formula (C) , the method comprising the following step:

(a) reacti

with a bridging element of the form ZCH ₂ CH ₂ Z, wherein P is an arylsulfonate protecting group and Z is a halogen selected from: Cl; Br; and, I.

In chemistry one-pot synthesis/reaction is a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one reactor. This is much desired by chemists because avoiding a lengthy separation process and purification of the intermediate chemical compound would save time and resources while increasing chemical yield.

In another aspect the present invention provides a one-pot method for the preparation of 1, 2-bis- ( 4 , 7-dimethyl-l, 4 , 7 , - triazacyclonon-l-yl) -ethane (Me-DTNE) the method comprising deprotecting a compound of formula (C) :

with an acidic medium and to form 1, 2-bis (1, 4, 7- triazacyclonon-l-yl) -ethane and subsequently adding

formaldehyde and formic acid to the reaction medium, wherein P is an arylsulfonate .

DETAILED DESCRIPTION OF THE INVENTION A method for obtaining Me ₄ DTNE is provided. A preferred synthetic scheme for obtaining e ₄ DTNE is

outlined below.

Br Base, solvent

Ts ₂ TACN.TsOH + Br Ts ₄ DTNE cone. H2S04

Ts ₄ DTNE Me ₄ DTNE

HCHO, HCOOH

1, 4-di (arylsulfonate) -1, 4, 7-triazacyclonane reacts with 1,2- dihaloethane in a solvent and a base, wherein the water level in the solvent is between 0 and 90%. The 1,2- dihaloethane is preferably selected from 1 , 2-dibromoethane , 1, 2-diodoethane and 1, 2-dichloroethane, with 1,2- dibromoethane being most preferred. Different solvents can be employed, such as acetonitrile, dimethylformamide (dmf) , xylene, toluene, dioxane, 1-butanol, 2-butanol, t-butanol, 1-propanol, and 2-propanol. The solvent may contain

additional water. The water content of the solvent may be between 0 and 90%.

The base used for the coupling of 1 , 4-di (arylsulfonate) - 1, 4, 7-triazacyclonane with dihaloethane should not be too strong; the base used for the coupling reaction is

preferably sodium carbonate.

It is preferred that a tosyl group is used as protecting group for the secondary amines of the 1 , 4 , 7-triazacyclonane moiety. The tosyl group (abbreviated Ts or Tos) is CH ₃ C ₆ H ₄ S0 ₂ . This group is usually derived from the compound 4-toluene sulfonyl chloride, CH ₃ C ₆ H ₄ S0 ₂ C1, which forms esters and amides of toluene sulphonic acid. The para orientation illustrated (p-toluenesulfonyl) is most common, and by convention tosyl refers to the p-toluenesulfonyl group. Tosylate refers to the anion of p-toluenesulfonic acid (CH ₃ C ₆ H ₄ SO ₃ ^"" ) . Whilst the tosyl group is the preferred protecting group other

arylsulfonyl groups (ArS0 ₂ ) will function to provide the advantages of the present invention. Preferably the

arylsulfonyl employed is a benzenesulfonate .

Preferred solvents are acetonitrile, 1-butanol, 2-butanol, t-butanol, and dimethylformamide (dmf) . These solvent are preferably used with additional water, preferably between 10 and 90%. Most preferably, acetonitrile/H ₂ 0 is used, as 1,2- bis (4, 7-arylsulfonate-1, 4, 7-triazacyclonon-l-yl) -ethane obtained is of higher purity than using other solvents. This allows the formation of the Me ₄ -DTNE ligand of higher purity and therefore the ligand does not need to be distilled prior using for the complexation step with manganese.

The protecting groups of 1 , 2-bis ( 4 , 7-arylsulfonate-1 , 4 , 7- triazacyclonon-l-yl) -ethane are removed by treatment with an acid to yield 1 , 2-bis ( 1 , 4 , 7-triazacyclonon-l-yl) -ethane . The preferred acid used for deprotection is concentrated

sulphuric acid. After deprotection the solution containing the deprotected ligand is neutralised to pH 5 to 9,

preferably pH 6 to 8.

The 1, 2-bis (1, , 7-triazacyclonon-l-yl) -ethane is preferably methylated by reaction with formaldehyde and subsequent reduction. In this regard, reaction with formaldehyde and formic acid (Eschweiler-Clarke methylation) are the

preferred reagents to effect methylation. This reductive W 201

- 7 - amination step will not produce quaternary ammonium salts, but instead will stop at the tertiary amine stage. For the aforementioned reason the Eschweiler-Clarke methylation is preferred over other methylation procedures.

Whilst the Eschweiler-Clarke methylation step is preferred other methylation reactions may be used. Methylation of secondary amines is well known in the art. Some examples of references are Ber. 1905, 38, 880; J. Am. Chem. Soc, 1933, 55, 4571; J. Org. Chem. 1972, 37(10), 1673-1674; J. Chem.

Soc, Perkin Trans 1, 1994, (1), 1-2; Synth. Commun., 2002, 32(3), 457-465; Synth. Commun., 1989, 19(20), 3561-3571; Synth. Commun., 2006, 36(23), 3609-3615; EP0553954A2;

US5105013; J. of the Indian Chemical Society 1967, 44(5), 430-435; J. of the Indian Chemical Society 1970, 8(8), 725- 727.

Reductive metylation in general applying formaldehyde and a reducing agent like cyanoborohydride, formic acid, molecular hydrogen and a catalyst (Nickel, Palladium on coal, etc.) can be employed. Also direct methylation with methyl-X (X = CI, Br, I) .

Catalytic conversions for preparing tertiary amines from secondary and primary amines using hydrogen gas and

formaldehyde can be for example found in US 4,757,144.

After the methylation is reaction is complete, increasing the pH to preferably higher than 12, more preferably higher than 13, the Me ₄ -DTNE ligand can be extracted using a C5-C8 hydrocarbon as solvent. The C5-C8 is preferably selected from pentane, hexane, heptane, octane, cyclopentane,

cyclohexane, cycloheptane , cyclooctane, toluene, xylene and combinations thereof. Most preferred solvents are hexane or heptane. When not using acetonitrile to synthesise 1,2-bis- (4, 7-arylsulfonate-1, 4, 7-triazacyclonon-l-yl ) -ethane, the ligand obtained is best vacuum distilled before further complexing with manganese salts. Alternatively, the ligand may be purified by precipitating as HC1 salt, after which the free Me ₄ -DTNE ligand was obtained by addition of

concentrated NaOH solution, as exemplified in J. Am. Chem. Soc . 1998, 120, 13104-13120.

The following examples will more fully illustrate the embodiments of this invention.

EXPERIMENTAL

1. Preparation of Ts ₄ -DTNE using acetonitrile as aprotic solvent (Ts ₄ -DTNE = 1 , 2-bis ( 4 , 7-ditosyl-l , 4 , 7- triazacyclonon-l-yl) -ethane)

The mixture of the protonated tosylate salt of 1,4-ditosyl- 1, 4, 7-triazacyclonone (Ts ₂ TACN . TsOH -3.0 g, 5 mmol) and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 20 mL acetonitrile was stirred under reflux for 5 min. Then 1, 2-dibromoethane (0. 3 mL, 5 mmol) was added and the resulting mixture was refluxed overnight (TLC showed the completion of the reaction,

CH ₂ Cl ₂ /methanol (97:3)). Then the solvent was evaporated and to the residue 50 mL water was added and the resulting mixture was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 1.84 g (84%) with 84% purity. ^X H NMR (400 MHz, CDC1 ₃ ) :

1.42 (s, [ArCH3, 12H] ) , 2.73 (s, [bridging N-CH2, 4H] ) , 2.93 (s, 8H) , 3.19 (s, 8H) , 3.46 (s, 8H) , 7.30 (d, J = 7.4 Hz, 8H), 7.65 (d, J = 7.4 Hz, 8H) . ESI-MS (ES+) : m/z 901 (M + H) ⁺

2. Preparation of Ts ₄ -DTNE in acetonitrile/water

The mixture of Ts ₂ TACN-TsOH (3.0 g, 5 mmol) in 25 mL

acetonitrile and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 10 mL water was stirred at 100 °C for 5 min. Then 1 , 2-dibromoethane (0. 3 mL, 5 mmol) was added and the resulting mixture was refluxed overnight (TLC showed the completion of the reaction,

CH ₂ Cl ₂ /methanol (97:3)). After being cooled to room

temperature, the mixture was poured into 50 mL water and was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 1.6 g (72%) with 93.3% purity.

3. Preparation of Me ₄ -DTNE using TS ₄ -DTNE prepared in

acetonitrile/H ₂ 0 (Me -DTNE = 1, 2-bis- (4, 7-dimethyl- I _f 4 , 7-triazacyclonon-l-yl) -ethane)

TS4-DTNE (93.3% purity) (25 g, 26 mmol) and 96% sulphuric acid (59.2 mL, composed of 56.8 mL concentrated H ₂ S0 ₄ (98%) plus 2.4 mL water) were stirred at 110°C (oil bath) in a 1 L 3-necked flask overnight. The reactants were cooled to 50 °C, then water (71 mL) and NaOH solution (108 g NaOH in 200 mL water) was added dropwise under ice-bath with stirring until Ph = 6~7 then formaldehyde (25.3 g(37%)) and formic acid (99%) (28.7 g) were added successively with stirring, the mixture was stirred at 90-100 °C (110 °C oil bath) overnight, then cooled to room temperature, the contents were made strongly alkaline by adding NaOH (32 g in 60 mL water) until H 14 while maintaining the temperature at 30 °C, the brown slurry was stirred efficiently with hexane (20Q mL) then filtered over celite. After separating the phase, the filter cake was washed with hexane (4x200 mL) which was

subsequently used to extract the aqueous, then the aqueous was extracted with hexane (4x500 mL) , the combined hexane layer was evaporated to get the crude product 7.4 g (84%) as yellow oil with purity 85%. Similar results were obtained when heptane was used as the extraction solvent.

¾ N R (400 MHz, CDCI ₃ ) : 2.3 (s, 12H, -CH3) , 2.6 (m, 28H, -N- CH2) . ESI-MS (ES+) : m/z 341 (M + H) ⁺ .

4. Preparation of Ts ₄ -DTNE in butanol/water

The mixture of Ts ₂ TACN'TsOH (3.0 g, 5 mmol) and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 10 mL water and 1.7 mL butanol was stirred at

115 °C for 5min. Then 1 , 2-dibromoethane ( 0.43 mL, 5 mmol) was added and the resulting mixture was refluxed for 3 hrs (TLC showed the completion of the reaction, CH ₂ Cl ₂ /methanol

( 97 : 3) ) . After being cooled to room temperature, the mixture was poured into 50 mL water and was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 2.06 g (94%) with 75% purity.

5. Preparation of Me ₄ -DTNE using Ts ₄ -DTNE prepared in

butanol/water.

TS4-DTNE (52 g (77% purity), 44.5 mmol) and 96% sulphuric acid (130.6 mL, composed of 125.6 mL concentrated H ₂ S0 ₄ (98%) plus 5ml water) were stirred at 110°C (bath) in a 1L 3-necked flask until TLC showed the detosylation to be completed

(about 22hrs) . The reactants were cooled to 50°C, then water (121 mL) and NaOH solution (4.63 mol, 185 g NaOH in 230 itiL water) was added dropwise under ice-bath with stirring until PH=6~7, then formaldehyde (0.693 mol, 56.6 g(37%)) and formic acid (1.626 mol, 64 g) were added successively with stirring, the mixture was stirred at 90°C (110°C oil bath) overnight , then cooled to room temperature, the contents were made strongly alkaline by adding NaOH (56 g in 68 mL water) while maintaining the temperature at 30°C, the brown slurry was stirred efficiently with hexane (300 mL) then filtered over celite. After separating the phase, the filter cake was washed with hexane (6x200 mL) which was

subsequently used to extract the aqueous solution, then the aqueous solution was extracted with hexane (4x500 mL) , the combined hexane was evaporated to get the crude product

13.53g as an yellow oil which was redistilled under reduced pressure to afford the product 8.3 g (55%) at 136~138°C/lmbar as a pale yellow liquid with purity 93%.

6. Preparation of Ts ₄ -DTNE in DM

The mixture of Ts ₂ TACN-TsOH (3.0 g, 5 mmol) and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 12 mL DMF was stirred at 110 °C for 5min. Then 1, 2-dibromoethane (0.43 mL, 5 mmol) was added and the

resulting mixture was refluxed for 3 hrs (TLC showed the completion of the reaction, CH ₂ Cl ₂ /methanol (97:3)). After being cooled to room temperature, the mixture was poured into 200 mL water and was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 1.8 g (82%) with 66% purity. W

7. Preparation of Ts ₄ -DTNE in DMF/H ₂ 0

The mixture of Ts ₂ TACN-TsOH (3.0 g, 5 mmol) in 24 mL DMF and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 10 mL water was stirred at 110 °C for 5min. Then 1, 2-dibromoethane (0.43 mL, 5 mmol) was added and the resulting mixture was refluxed for 4 hrs (TLC showed the completion of the reaction, CH ₂ Cl ₂ /methanol ( 97 : 3) ) . After being cooled to room temperature, the mixture was poured into 200 mL water and was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the

product 1.76 g (80%) with 42% purity.

8. Preparation of Ts ₄ -DTNE in toluene

The mixture of Ts ₂ TACN-TsOH (3.0 g, 5 mmol) and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 20 mL toluene was stirred at 125 °C for 5min .

Then 1, 2-dibromoethane (0.43 mL, 5 mmol) was added and the resulting mixture was refluxed for 6 hrs (TLC showed the completion of the reaction, CH ₂ Cl ₂ /methanol (97:3)). Then the solvent was evaporated and to the residue 50 mL water was added and the resulting mixture was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 1.9 g (83%) with 56% purity.

9. Preparation of Ts ₄ -DTNE in acetone

The mixture of Ts ₂ TACN-TsOH (3.0 g, 5 mmol) and Na ₂ C0 ₃ (2.12 g, 20 mmol) in 20 mL acetone was stirred at 85 °C for 5min. Then 1, 2-dibromoethane (0. 3 mL, 5 mmol) was added and the

resulting mixture was refluxed for 3 hrs (TLC showed the completion of the reaction, CH ₂ Cl ₂ /methanol (97:3)). Then the solvent was evaporated and to the residue 50 mL water was added and the resulting mixture was filtered. The solid was washed with water (4x50 mL) , dried under vacuum to afford the product 1.95 g (89%) with 66% purity.

10 . General procedure for the preparation of

[Mn ₂ (p-O) 2 (p-CH ₃ COO) (Me ₄ -DTNE) ] Cl ₂

Under N ₂ , to Me ₄ -DTNE in EtOH/H ₂ 0 (2 : 1, v/v) , solid mixture of MnCl ₂ ^» 4H ₂ 0 and sodium acetate were added. The mixture was stirred for 30 min at 58 °C. After another stirring for 10 min cooled 'in an ice/water bath, the freshly prepared mixture of 1 M of H ₂ 0 ₂ in water and 1.5 M of NaOH was added dropwise over 5 min. The mixture turned immediately dark green-brown. The mixture was stirred for 20 min in an ice water bath and then for 20 min at room temperature. 1 M of acetic acid was added. After stirring for another 20 min, the mixture was filtered to remove the brown solid and the filtering bed was washed with ethanol . Then the green filtrate was evaporated (the water bath temperature < 45 °C) . The residual dark green oil was co-evaporated with ethanol and ethyl acetate to facilitate the removal of most of the remaining water. Dark green oils were taken up in ethanol, and the insoluble white salts separated by filtration were washed with ethanol. After removing all ethanol, the dark green oil was obtained again. The small amount of ethanol was added and stirred for 2 min. Then the large amount of ethyl acetate was added. The green solid was precipitated immediately. After 3 hours at -20 °C, the suspension was filtered off, with obtaining a green solid, which was washed with ethyl acetate, n-hexane, and dried under vacuum at 45 °C for 5 hrs to afford dark green powder as [ (Mn ₂ (μ-Ο) ₂ (μ- OAc) ( e ₄ -DTNE) ]C1 ₂ ^» H ₂ 0. 10.1 Preparation of [Mn ₂ (p-O) ₂ (p-CH ₃ COO) (Me ₄ -DTNE) ] Cl ₂ from the distilled Me ₄ -DTNE in the BuOH/H ₂ 0 route

Me ₄ -DTNE (89.3% purity with 1.3% Me ₃ -TACN) (765 mg,2 mmol); EtOH/H ₂ 0 (2:1, v/v) : 20 mL; MnCl ₂ H ₂ 0 (840 mg, 4.2 mmol);

NaAc(82 mg, 1 mmol); 1 M of H ₂ 0 ₂ in water (5 mL, 5 mmol); 1.5 M of NaOH (2.5 mL, 3.75 mmol); 1 M of HAc (1.25 mL, 1.25 mmol). 1.2 g of green powder as [ (Mn ₂ (μ-O) ₂ (μ-OAc) (Me ₄ - DTNE) ] C1 ₂ 'H ₂ 0.

UV-Vis purity of 91.1%, the yield of 86.8% (The yield (%) = the weight of the compound (g) ^χ the purity of the compound (%)/the calcd. weight of the compound (g) ) . UV-Vis spectrum of a purified sample: (ε : mol ^~1 -L-cm ^"1 , in water, Mw: 630) : 271 nm (13332), 554 nm (317), 639 nm (327).

UPLC analysis confirmed 1.53 % of the free [H ₂ (Me ₄ -DTNE) ] Cl ₂ , 0.7 % of the free [H (Me ₃ -TACN) ] CI, and 0.08% of [(Μη ₂ (μ- 0) ₃ ( e ₃ -TACN) ] Cl ₂ .

Total chloride amount was 11.17 %.

Water analysis (Karl-Fischer method) : Anal, calcd. for

[ (Mn ₂ (μ-0) 2 (μ-OAc) (Me ₄ -DTNE) ] C1 ₂ ^» H ₂ 0: 2.86%; Found: 1.14%.

10.2 Preparation of [Mn ₂ (μ-Ο) ₂ (p-CH ₃ COO) (Me ₄ -DTNE) ] Cl ₂ from the undistilled Me ₄ DTNE in the BuOH/H ₂ Q route

Me ₄ -DTNE (70.5% purity with 22.8% Me ₃ -TACN) (1.93 g, 4 mmol); EtOH/H ₂ 0 (2:1, v/v): 40 mL; MnCl ₂ '4H ₂ 0 (2.22 g, 11.2 mmol); NaAc(166 mg, 2 mmol); 1 M of H ₂ 0 ₂ in water (15 mL, 15 mmol) ; 1.5 M of NaOH (7.5 mL, 11.25 mmol); 1 M of HAc (2.5 mL, 2.5 mmol). 2.93 g of green powder as [ (Mn ₂ (μ-Ο) ₂ (μ-OAc) (Me ₄ - DTNE) ]C1 ₂ ^« H ₂ 0. UV-Vis purity of 84.6%, the yield of 75.5%. ( The yield (%) = the weight of the compound (g) * the purity of the

compound (%)/(the calcd. weight of the compound (g) + the calcd. weight of [ (Mn ₂ (μ-Ο) ₃ (Me ₃ -TACN) ] Cl ₂ (g) ) ) .

UPLC analysis confirmed 6.96 % of the free [H ₂ (Me ₄ -DTNE) ] Cl ₂ , 3.2 % of the free [H (Me ₃ -TACN) ] CI, and 4.3% of [(Μη ₂ (μ- 0) 3 (Me ₃ -TACN) ] Cl ₂ .

Total chloride amount was 10.35 %.

Water analysis (Karl-Fischer method): Anal, calcd. for

[ (Mn ₂ (μ-0) ₂ (μ-OAc) ( e ₄ -DTNE) ]C1 ₂ »H ₂ 0: 2.86%; Found: 1.07%.

10.3 Preparation of [Mn ₂ (p-O) ₂ (p-CH ₃ COO) (Me ₄ -DTNE) ] Cl ₂ from the undistilled Me ₄ DTNE in the CH ₃ CN/H ₂ Q route Me ₄ -DTNE (84% purity with 5.2% Me ₃ -TACN) : (1.62 g, 4 mmol);

EtOH/H ₂ 0 (2:1, v/v) : 40 mL; MnCl ₂ «4H ₂ 0 (1.78 g, 9 mmol);

NaAc(166 mg, 2 mmol); 1 of H ₂ 0 ₂ in water (9 mL, 9 mmol);

1.5 M of NaOH (4.5 mL, 6.75 mmol); 1 M of HAc (2.5 mL, 2.5 mmol). 2.6 g of green powder as [ (Mn ₂ (μ-O) ₂ (μ-OAc) (Me ₄ - DTNE) ] C1 ₂ ^» H ₂ 0.

UV-Vis purity of 84.8%, the yield of 88.7% (The yield (%) = the weight the compound (g) the purity of the compound

(%)/the calcd. weight of the compound (g) ) .

UPLC analysis confirmed 7.2 % of the free [H ₂ (Me ₄ -DTNE) ] Cl ₂ , 2.56 % of the free [H (Me ₃ -TACN) ] CI, and 0.14 % of [(Μη ₂ (μ- 0) ₃ (Me ₃ -TACN) ]C1 ₂ .

Total chloride amount was 10.91 %.

Water analysis (Karl-Fischer method): Anal, calcd. for

[ (Mn ₂ (μ-0) 2 (μ-OAc) (Me ₄ -DTNE) ]C1 ₂ ^« H ₂ 0: 2.86%; Found: 1.35%. Using acetonitrile/H ₂ 0 as solvent for the formation of Ts ₄ - DTNE has advantages as the purity Me ₄ -DTNE product is much higher than when using other solvents. This leads to

formation of Me ₄ -DTNE ligand that does not need to be further purified to make the dinuclear manganese complex. The method using butanol/water leads to a need to be distilled the Me ₄ - DTNE ligand to obtain high-purity material, leading to significant losses in yields (experiment 4). A yield

improvement of the ligand about 20% can be thus achieved (experiment 3 vs experiment 5) .