WO2017037296A1

WO2017037296A1 - Stable adducts of 2-iodoxybenzoic acid

Info

Publication number: WO2017037296A1
Application number: PCT/EP2016/070883
Authority: WO
Inventors: Simone Mantegazza; Gabriele Razzetti; Emanuele Attolino; Chiara Vladiskovic
Original assignee: Dipharma Francis SRL
Current assignee: Dipharma Francis SRL
Priority date: 2015-09-03
Filing date: 2016-09-05
Publication date: 2017-03-09
Anticipated expiration: 2018-03-03
Also published as: ITUB20153373A1

Abstract

The present invention relates to novel adducts of 2-iodoxybenzoic acid, known as IBX, a novel process for the preparation thereof, and their use in alcohol oxidation reactions.

Description

STABLE ADDUCTS OF 2-IODOXYBENZOIC ACID

PRIOR ART

2-Iodoxybenzoic acid o

discovered in 1893 by C. Hartmann and V. Meyer, is a known oxidizing agent, based on pentavalent iodine and is the precursor of the well-known Dess- Martin periodinane (DMP) of formula (II), described for the first time in J. Org. Chem. 1983, 48, 4155-4156.

Both reagents allow a rapid, chemoselective conversion of primary and secondary alcohols to aldehydes and ketones, respectively, and are also used in the oxidation of diols.

The different solubility of the two compounds of formulas (I) and (II) has previously limited the use of the two reagents to DMP of formula (II), which is more soluble in common organic solvents and can be used in dichloromethane or other common inert solvents. Frigerio and Santagostino demonstrated in Tetrahedron Lett. 1994, 35, 8019 that IBX is soluble in dimethylsulfoxide up to a concentration of 1.5 M, and the resulting solution can be used as such or mixed with THF to oxidize alcohols and diols. Moreover, More and Finney demonstrated in Org. Lett. 2002, 4, 3001 that IBX can also be used for oxidations in acetone, ethyl acetate or other common solvents at temperatures ranging between 55 and 80°C.

Comparative studies of the reactivity of IBX of formula (I) and DMP of formula (II) are reported by Frigerio and Santagostino in J. Org. Chem. 1996, 61, 9272. A review of the synthesis applications of IBX was published in Tetrahedron 2010, 66, 7659.

IBX of formula (I) can be prepared by oxidizing 2-iodobenzoic acid with potassium bromate in aqueous sulfuric acid as described by Greenbaum in Am. J. Pharm. 1936, 108, 17, also used by Dess and Martin in J. Org. Chem. 1983, 48, 4155-4156, or by the safer and more reproducible procedure described by Frigerio and Santagostino in J. Org. Chem. 1999, 64, 4537, which uses potassium peroxymonosulfate (Oxone®) as oxidant in water at 70°C.

Although said compounds have been widely used for years for laboratory synthesis, their use on an industrial scale was basically limited for safety reasons. Plumb and Harper reported already in 1990 in Chem. Eng. News 1990, Jul. 16, 3 that IBX is a shock-sensitive compound and was found to be explosive at 194°C, whereas DMP resulted to be not shock-sensitive, but breaks down violently at 130°C. However, in the same article, the authors state that DMP breaks down to give a species that exhibits the reactivity and danger of IBX, when treated with water.

It was also found in our laboratories that the breakdown of DMP occurs rapidly, even in presence of only humidity in the air, leading to the formation of IBX. This condition strongly limits the safe use of said oxidizing agents on an industrial scale.

US 2,566,592 claimed formulations containing calcium or ammonium salts of IBX stabilised by the presence of sorbitol, while more recently, US 6,462,227 disclosed a method of preparing a stabilised formulation of IBX (SIBX) obtained by mixing IBX with aliphatic or aromatic carboxylic acids. In both cases, the formulation benefits from a stabilising effect derived by physical mixing. However, this is difficult to control at an industrial stage and subject to a possible lack of standardisation of the produced samples at molecular level.

Finally, a communication published in Mendeleev Commun. 2012, 22, 129 described the preparation and use of a novel salt of IBX with pyridine (PIBX), which was found not to be shock-sensitive. The use of 2,6-dimethylpyridine instead of pyridine did not lead to the formation of the PIBX analogue.

Our laboratories tested the preparation and isolation of PIBX as reported in the publication. However, it was found that this compound can only be prepared by using pyridine as solvent. Moreover, in an attempt to purify the PIBX with a solvent it was observed both by NMR and X PD analysis that the PIBX after washing with solvent contains a lower pyridine content, thus comprises free IBX. For example, PIBX suspended in an organic solvent, for example in 10 volumes of acetone and stirred overnight, once filtered off resulted to have a pyridine content diminished by about 50%, thus providing a solid with about 50% of free IBX.

In the case of large-scale preparations, this behaviour would present a further safety risk when handling the such obtained solid. There is consequently a need for novel adducts of IBX, which have the characteristics of being heat- stable while maintaining the oxidizing power of IBX, which do not contain IBX in the solid state, and which maintains the composition during common industrial manufacturing processes.

SUMMARY OF THE INVENTION

The invention provides a class of stable adducts with IBX having a defined stoichiometry, which are safer than IBX and PIBX, and a synthesis method for obtaining them, which can be developed on an industrial scale, allowing their synthesis with high reproducibility.

The inventors of the present invention have surprisingly found that adducts of IBX with a compound of formula (III), as defined herein, are more soluble than IBX in both organic and aqueous solvent; they are able to oxidize alcohols like IBX, and, no less importantly, have exhibited improved safety characteristics enabling them to be used on an industrial scale. The improved safety properties have been demonstrated by DSC (figures 3-6), wherein the compounds of the present invention exhibited considerably lower decomposition energies than IBX or PIBX. Furthermore, the NMR and XRPD analyses of the herein disclosed compounds demonstrate the precise 1 : 1 stoichiometry of the adducts and the absence of free IBX, even after a thorough washing with a solvent or maintaining in suspension in a solvent for long periods.

BRIEF DESCRIPTION OF FIGURES AND METHODS OF

ANALYSIS

The adducts of IBX with a compound of formula (III) were characterised by nuclear magnetic resonance (NMR) spectrometer, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).

The ^lH and ¹³C NMR spectra were acquired with a Varian Mercury 300 spectrometer at 300 MHz (proton) and 75 MHz (C I 3 carbon).

The X-ray diffraction (XRPD) spectra were collected with a Bruker D8 Advance diffractometer. The detector used was a LynxEye PSD detector. The radiation used was Cu Ka filtered with nickel. The X-ray powder diffraction (XRPD) spectra were collected in the 2Θ range from 3° to 40° with a step size of 0.02°.

The DSC patterns were acquired with a Mettler-Toledo DSC 822e differential scanning calorimeter, at the following operating conditions: aluminium capsules, range 30-300°C at the rate of 10°C/min, with nitrogen as purge gas (80 ml/min).

Figure 1 : XRPD spectrum of the adduct of IBX with nicotinamide wherein the most intense peaks (expressed in ° in 2Θ) are: 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ± 0.1 °.

Figure 2: XRPD spectrum of the adduct of IBX with quinoline, wherein the most intense peaks (expressed in ° in 2Θ) are: 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ± 0.1 °.

Figure 3: DSC analysis of the adduct of IBX with nicotinamide.

Figure 4: DSC analysis of the adduct of IBX with quinoline.

Figure 5: DSC analysis of IBX.

Figure 6: DSC analysis of the adduct of IBX with pyridine.

DETAILED DESCRIPTION OF THE INVENTION

Object of the invention is an adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1

wherein each of Rl , R2, R3, R4 and R5, which are the same or different, is H, halogen, NO₂, CN, an optionally substituted Ci-C₆ alkyl or aryl group, an ORa or COORa group wherein Ra is H, or an optionally substituted Ci-C₆ alkyl or aryl group, a CON(RbRc) group, wherein Rb and Rc, which are the same or different, are H, or an optionally substituted Ci-C₆ alkyl or aryl group, or Rb and Rc, taken together with the nitrogen to which they are bound, form a heterocycle; or 1 to 4 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form a C₃-C₄ alkyl chain, or form an aromatic or a heteroaromatic ring; provided that one of R1 -R5, being as defined above, is not H, and that one or two of R1-R5 are not methyl when the remainder of R1 -R5 are hydrogen.

A Ci-C₆ alkyl group, which can be straight or branched, is typically a Ci-C₄ alkyl group, optionally substituted by one to three substituents independently selected from halogen, cyano, nitro and phenyl, optionally substituted by one to three substituents independently selected from halogen, and Ci-C₄ alkyl.

An aryl group is typically phenyl or naphthyl, preferably phenyl optionally substituted by one to three substituents independently selected from halogen, and Ci-C₄ alkyl.

A halogen is preferably fluorine, chlorine bromine or iodine, being in particular fluorine or chlorine.

In case of the CON(RbRc) group, when Rb and Rc, taken together with the nitrogen to which they are bound, form a heterocycle, said heterocycle is preferably a saturated heterocycle, such as pyrrolidine, piperidine, piperazine or morpholine, or an unsaturated heterocycle, such as imidazole.

When 1 to 4 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form a C₃-C₄ alkyl chain or an aromatic or a heteroaromatic ring, the compound of formula (III) thus formed preferably consists of 2 or 3 condensed rings, and is optionally substituted by 1 to 4 substituents selected independently from halogen, NO₂ and CN, an optionally substituted Ci-C₆ alkyl or aryl group, an ORa or COORa group, wherein Ra is H or an optionally substituted Ci-C₆ alkyl or aryl group, and a CON(RdRe) group, wherein Rd and Re, which are the same or different, are H or an optionally substituted Ci-C₆ alkyl or aryl group.

The aromatic ring is, for example, phenyl or naphthyl, preferably phenyl. The heteroaromatic ring, which can preferably contain 1 to 3 heteroatoms selected independently from oxygen, nitrogen and sulfur is, for example, benzofuran, benzoimidazole, indazole, quinoline, benzothiazole or quinazoline, preferably quinoline.

In a preferred embodiment, each of Rl , R2, R3, R4 and R5, which are the same or different, is H, an optionally substituted aryl group, a CON(RbRc) group, wherein Rb and Rc, which are the same or different, are H or a C1-C6 alkyl group; or 1 to 2 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form an aromatic or a heteroaromatic ring.

More preferably, in said adduct, in a compound of formula (III), Rl is H; R2 is H or CONH2; R3 is H or phenyl; R4 is H or CONH2, and R5 is H; or one of Rl and R2 or R4 and R5, taken together, form a phenyl, naphthalene or quinoline ring, or R2 and R3 or R3 and R4, taken together, form a phenyl ring.

Preferred examples of specific compounds of formula (III) are nicotinamide, quinoline, benzo[(g)]quinoline, benzo[h]quinoline, acridine, 9-phenylacridine, phenanthridine and phenanthroline, in particular nicotinamide and quinoline.

Examples of an adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 , which are representative of the invention, are:

- adduct of IBX with nicotinamide, preferably in crystalline form, in particular in a crystalline form having an XRPD spectrum wherein the most intense peaks (expressed in ° in 2Θ) fall at 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ± 0.1 °; and

- adduct of IBX with quinoline, preferably in crystalline form, in particular in a crystalline form having an XRPD spectrum wherein the most intense peaks (expressed in ° in 2Θ) fall at 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ± 0.1 °.

An adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be prepared, for example, by a process comprising mixing IBX of formula (I) with a compound of formula (III), optionally in a solvent.

A compound of formula (III) can be used in a stoichiometric quantity or in excess relative to the amount of IBX of formula (I), preferably over-stoichiometric, for example in a quantity ranging between about 1.0 and 5 equivalents. According to a preferred aspect of the invention, a compound of formula (III) is used in a quantity comprised between about 1.0 and 2.0 equivalents relative to IBX of formula (I).

A compound of formula (III) can be added to pure IBX of formula (I) or dissolved in a solvent.

A solvent used to form the adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be a polar aprotic solvent, such as dimethylformamide, dimethylsulfoxide or acetonitrile; an ethereal solvent, such as diethyl ether, methyl tert-butyl ether or tetrahydrofuran; a ketone, such as methyl ethyl ketone, methyl isobutyl ketone or acetone; an apolar aprotic solvent, such as hexane, heptane, toluene or xylene; a polar protic solvent, such as a C1-C5 tertiary alkanol, for example tertbutanol, or a Ci-C₄ alkyl carboxylic acid as defined above, or water; or a mixture of two or more, typically two or three, of said solvents.

The mixture of IBX of formula (I) and a compound of formula (III) in a solvent, as defined above, can be optionally prepared at a temperature ranging between about - 10°C and the reflux temperature of the solvent, preferably between about 0 and 40°C, more preferably between about 10 and 35°C.

The adduct of IBX of formula (I) with a compound of formula (III) can be recovered from the reaction mixture by isolating it as a solid by filtration or centrifugation, as well known to the skilled person. There is no necessity to wash the solid with water.

The obtained solid can be washed with a solvent as defined above and stove-dried, optionally under vacuum, to obtain a solid, typically in crystalline form.

As reported above, IBX of formula (I) is a known compound and can be prepared, for example, as described in J. Org. Chem. 1983, 48, 4155-4156.

The compound of formula (III) is a known compound with a pyridine core moiety, which is commercially available or can be prepared by well-known methods (Heterocyclic Chemistry / John A. Joule, Keith Mills. - 5th ed. John Wiley & Sons, Ltd., 2010).

It has been surprisingly found that the formation of an adduct of IBX of formula (I) with a compound of formula (III) proceeds with high yields and purity if water is present in the solvent used for the preparation. Thus according to a preferred aspect of the invention, an adduct between IBX of formula (I) and a compound of formula (III) in the ratio of 1 : 1 can be prepared by mixing IBX of formula (I) with a compound of formula (III) in a solvent containing water.

The adducts of IBX of formula (I) with a compound of formula (III) in solid crystalline form obtained by the method previously described were analysed and characterised. ^lH NMR analysis demonstrated a precise 1 : 1 stoichiometry of the adducts, but the chemical shifts proved identical to those of the starting compounds of formulas (I) and (III). X PD analysis (Figures 1 and 2) confirmed the formation of novel adducts with a well-defined crystalline structure and the absence of free IBX, even in traces.

Even when the adduct of IBX of formula (I) with a compound of formula (III) has been thoroughly washed with a solvent or maintained in suspension in a solvent for long periods, the NMR and XRPD analyses of the solid filtrate demonstrate the precise 1 : 1 stoichiometry of the adducts and the absence of free IBX. For example, the adducts of IBX of formula (I) with nicotinamide and quinoline of formula (III) exhibited improved safety characteristics on DSC analysis (figures 3 and 4), and the decomposition energy was much lower than that of IBX (figure 5) or that of the adduct of IBX of formula (I) with pyridine (figure 6). In specific, the decomposition energy of IBX resulted to be 1 163.8 Jg^"1 (figure 5), for the adduct of IBX of formula (I) with pyridine (figure 6) 847.5 Jg^"1, while the decomposition energy with 724.3 Jg^"1 (figure 3) and 584.1 Jg^"1 (figure 4) was considerably lower for the adducts IBX of formula (I) with nicotinamide and quinoline, respectively.

The two adducts of IBX of formula (I) with nicotinamide and quinoline of formula (III) exhibited higher solubility in both organic and aqueous solvent than IBX of formula (I).

An adduct of IBX of formula (I) with a compound of formula (III) forming the subject of the invention demonstrated to be able to oxidize alcohols such as IBX of formula (I).

Comparative examples of use of adducts of IBX of formula (I) with nicotinamide and quinoline of formula (III) in three different solvents (dichloromethane, tetrahydrofuran and dimethylsulfoxide) in the oxidation reaction of cyclohexanol to cyclohexanone are shown in the Table.

The oxidations were carried out at a temperature of 25 °C using a single adduct equivalent per mole of cyclohexanol, which is different to the procedures usually reported in the literature, wherein at least 3 equivalents of IBX are used. Table: Oxidation of cyclohexanol to cyclohexanone.

As demonstrated by the experimental data reported in the Table, the oxidation reaction resulted to be highly chemoselective in all three solvents, and reaction was faster in the more polar solvents.

For example, 95% conversion of cyclohexanol to cyclohexanone was observed in DMSO after 17 hours' reaction time, and isolated cyclohexanone was obtained with a yield exceeding 90%.

A further subject of the present invention is therefore the use of an adduct of IBX of formula (I) with a compound of formula (III) as oxidant in the oxidation reactions of primary and secondary alcohols.

The following examples further illustrate the invention.

Example 1 - Preparation of the IBX-nicotinamide adduct

Nicotinamide (4.80 g, 39.3 mmol) is added to a suspension of IBX (10.0 g, 35.7 mmol) in methyl isobutyl ketone (50 ml) and water (25 ml) at 25°C, and the mixture is stirred vigorously for 24 hours. The solid is then filtered off, washed with water (10 ml), then with methyl isobutyl ketone (3 x 10 ml), and the product is dried at 30-35°C at low pressure providing 9.8 g of the IBX- nicotinamide adduct (yield 68%). Ή-NMR (300 MHz, DMSO-d₆) δ: 9,00 (d, 1H); 8,68 (dd, 1H); 8,25-7,90 (m, 5H); 7,83 (t, 1H); 7,56 (s, 1H); 7,45 (dd, 1H). ¹³C-NM (75 MHz, DMSO-d₆) δ: 167,2; 166,1 ; 151 ,3; 148,1 ; 146,2; 135,0; 133,0; 132,6; 130,9; 129,7; 129,3; 124,6; 123, 1. The adduct of IBX with nicotinamide presents an XRPD spectrum, wherein the most intense peaks (expressed in ° in 2Θ) are 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ± 0.1 °, as illustrated in Figure 1 ; and a DSC pattern as shown in Figure 3.

Example 2 - Preparation of the IBX-quinoline adduct

Quinoline (10.0 g, 77.7 mmol) is added to a suspension of IBX (14.5 g, 51.8 mmol) in acetone (60 ml) and water (10 ml), and is stirred vigorously for 24 hours. The formed solid is filtered off, washed with acetone (4 x 10 ml), the product is dried at 30-35°C at low pressure providing 18.1 g of the IBX- quinoline adduct with a yield of 87%. Ή-NMR (300 MHz, DMSO-d₆) δ: 8,90 (dd, 1H); 8,36 (d, 1H); 8, 15 (d, 1H); 8, 10-7,90 (m, 4H); 7,83 (t, 1H); 7,75 (t, 1H); 7,60 (t, 1H), 7,52 (dd, 1H). ¹³C-NMR (75 MHz, DMSO-d₆) δ: 167,6; 150,4; 147,4; 146,7; 136,4; 133,4; 133,0; 131 ,5; 130,2; 129,7; 128,7; 128,1 ; 128,0; 126,7; 125,0; 121 ,5. The adduct of IBX with quinoline presents an XRPD spectrum wherein the most intense peaks (expressed in ° in 2Θ) fall at 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ± 0.1°, as illustrated in Figure 2; and a DSC pattern as shown in Figure 4.

Example 3 - Oxidation of cyclohexanol with the adducts

General procedure:

The adduct of IBX of formula (I) with a compound of formula (III) (see Table; 5.2 mmol) is added to a solution of cyclohexanol (0.5 g, 5.0 mmol) in 20 ml of solvent (see Table), and the mixture is stirred at room temperature. The reaction is monitored with GC-MS analysis.

Claims

1. An adduct between IBX of formula (I) and a compound of formula (III) in a ratio of 1 : 1

wherein each of Rl , R2, R3, R4 and R5, being the same or different, is H, halogen, NO2, CN, an optionally substituted C1-C6 alkyl or aryl group, an ORa or COORa group wherein Ra is H or an optionally substituted C1-C6 alkyl or aryl group, a CON(RbRc) group, wherein Rb and Rc, being the same or different, are H or an optionally substituted C1-C6 alkyl or aryl group, or Rb and Rc, taken with the nitrogen to which they are bound, form a heterocycle; or 1 to 4 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form a C3-C4 alkyl chain, or form an aromatic or a heteroaromatic ring; provided that one of R1-R5, being as defined above, is not H, and that one or two of R1-R5 is not methyl, when the remaining R1-R5 are H.

2. An adduct according to claim 1 ,

wherein in a compound of formula (III) each of Rl , R2, R3, R4 and R5, being the same or different, is H, an optionally substituted aryl group, a CON(RbRc) group, wherein Rb and Rc, being the same or different, are H or a C1-C6 alkyl group; or 1 to 2 of Rl and R2; R2 and R3; R3 and R4; and R4 and R5, taken together, form an aromatic or a heteroaromatic ring.

3. An adduct according to claim 1 ,

wherein in a compound of formula (III) Rl is H; R2 is H or CONH2; R3 is H or phenyl; R4 is H or CONH2, and R5 is H; or one of Rl and R2 or R4 and R5, taken together, form a phenyl, a naphthalene or a quinoline ring, or one of R2 and R3 or R3 and R4, taken together, form a phenyl ring.

4. An adduct according to claim 1 , wherein a compound of formula (III) is selected from nicotinamide, quinoline, benzo[g]quinoline, benzo[h] quinoline, acridine, 9-phenylacridine, phenanthridine and phenanthroline.

5. An adduct according to claim 1 , wherein a compound of formula (III) is selected from nicotinamide or quinoline.

6. An adduct according to claim 1 , selected from an adduct of IBX with nicotinamide or quinoline.

7. An adduct according to claim 6, wherein the adduct of IBX with nicotinamide or quinoline is in crystalline form.

8. An adduct of IBX with nicotinamide according to claim 6 having an XRPD spectrum, wherein the most intense peaks (expressed in ° in 2Θ) fall at 8.25, 1 1.65, 12.59, 13.45, 13.87, 14.34, 16.49, 16.88, 17.48, 20.16, 20.30, 22.15, 23.39, 24.50, 26.10 and 28.84 ± 0.1 °.

9. An adduct of IBX with quinoline according to claim 6 having an XRPD spectrum, wherein the most intense peaks (expressed in ° in 2Θ) fall at 9.68, 10.78, 1 1.02, 12.1 1 , 14.17, 15.96, 17.1 1 , 17.67, 18.40, 18.78, 19.43, 19.81 , 23.08, 25.28, 26.04 and 27.42 ± 0.1 °.

10. Process for the preparation of an adduct between IBX of formula (I) and a compound of formula (III), as defined in claim 1 , comprising mixing IBX of formula (I) with a compound of formula (III), optionally in a solvent.

1 1. Process according to claim 10, wherein a compound of formula (III) is used in a stoichiometric amount or in excess to the moles of IBX of formula (I), preferably over stoichiometric, typically in an amount comprised between about 1.0 and 5 equivalents, preferably in an amount comprised between about 1.0 and 2.0 equivalents to IBX of formula (I).

12. Process according to claims 10 or 1 1 , wherein the solvent is selected from dimethylformamide, dimethylsulfoxide or acetonitrile; an ethereal solvent, preferably diethylether, methyl tertbutyl ether or tetrahydrofuran; a ketone, preferably methyl ethyl ketone, methyl isobutyl ketone or acetone; an apolar aprotic solvent, preferably hexane, heptane, toluene or xylene; a protic polar solvent, typically a tertiary C1-C5 alkanol, preferably tert-butanol or a C1-C4 alkyl carboxylic acid, preferably acetic acid, or water; or a mixture of two or more, preferably from one to three, of said solvents with water.

13. Process according to claims 10 to 12, wherein the solvent contains water.

14. Process according to claims 10 to 13, wherein a compound of formula (III) is added to IBX of formula (I), pure or dissolved in a solvent, and the mixture is prepared at a temperature between about -10°C and the reflux temperature of the solvent, preferably between about 0 and 40°C, more preferably between about 10 and 35°C.

15. A process for oxidizing primary and secondary alcohols comprising using an IBX adduct of formula (I) with a compound of formula (III), as defined in claim 1 , as oxidizing agent.