Peroxide reagent

Abstract

The present disclosure relates to a peroxide reagent, wherein the peroxide reagent comprises: (a) hydrogen peroxide; and (b) a cyclic ether as disclosed herein. Also disclosed is: a method of preparing a peroxide reagent; use of a peroxide reagent in an oxidation reaction; a method of oxidising a compound; and a complex of: (a) hydrogen peroxide; and (b) a cyclic ether as disclosed herein.

Description

[0001] M&C PG450913W0

[0002] 1

[0003] PEROXIDE REAGENT

[0004] FIELD

[0005] The present invention concerns a peroxide reagent, wherein the peroxide reagent comprises: (a) hydrogen peroxide; and (b) a cyclic ether as disclosed herein. Also disclosed is: a method of preparing a peroxide reagent; use of a peroxide reagent in an oxidation reaction; a method of oxidising a compound; and a complex of: (a) hydrogen peroxide; and (b) a cyclic ether as disclosed herein.

[0006] BACKGROUND

[0007] Peroxides are among the most widely used sources of oxygen and have diverse applications, from consumer goods to industrial processes. Hydrogen peroxide (H2O2), sometimes referred to as simply “peroxide”, is the most widely used source of peroxide, with an annual production volume typically exceeding 4 million tonnes. It is inexpensive, simple to manufacture, and effective across numerous applications including cleaning, bleaching, sterilisation, and oxidation reactions.

[0008] Hydrogen peroxide is particularly attractive as a green oxidant, as the main byproduct from its use is water. In contrast, the use of other common oxidants such as permanganate and chromate salts typically lead to large volumes of toxic inorganic waste. Nonetheless, oxidation reactions are one of the most important classes of chemical reactions, particularly in the functionalisation of organic compounds (see, for example: Targhan et al., A review of the role of hydrogen peroxide in organic transformations, Journal of Industrial and Engineering Chemistry, 2021 , 104, 295).

[0009] Hydrogen peroxide is typically available as an aqueous solution. However, there are some disadvantages concerning the use of aqueous peroxide in the oxidation of organic compounds; in particular, many organic compounds are either not water soluble or are incompatible with water. Even when the compound is not particularly sensitive to water, oxidation reactions of organic compounds using aqueous peroxide are often carried out in a biphasic system. That is, a water-immiscible solvent (traditionally a chlorinated solvent) is used to dissolve the compound, and a phase transfer catalyst is then utilised to facilitate action of the aqueous peroxide on the compound. These multicomponent reaction systems (comprising the organic substrate, peroxide, a phase transfer catalyst, water, an organic solvent, and typically some other additives) often require complex separation and purification procedures to recover the end product, resulting in an overall high-cost and high-waste process. A further challenge with using

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[0011] 2 aqueous peroxide is that the decomposition of concentrated peroxide solutions can form pure dioxygen, potentially resulting in an explosive mixture when combined with the flammable solvents typically utilised in organic chemistry (see, for example: Ten Brink et al., The Baeyer-Villiger Reaction: New Developments toward Greener Procedures, Chemical Reviews, 2004, 104, 4105).

[0012] One approach to take advantage of the desirable qualities of peroxide without the problems introduced by using aqueous conditions is the urea hydrogen peroxide complex, or “UHP”. Whilst the use of UHP in pharmaceutical and dental applications is well established, it receives relatively little application in organic chemistry reactions. This is likely a result of its relatively low reactivity and atom efficiency. Additionally, its use necessarily results in a urea by-product, creating separation and waste challenges. In some cases, UHP is used as a peroxide precursor, i.e., it is added to water or another solvent to release the peroxide. Further information may be found in the literature, for example: Heaney et al., Hydrogen Peroxide-Urea, Encyclopedia of Reagents for Organic Synthesis, 2013.

[0013] An alternative class of peroxide oxidants are organic peracids. Peracids avoid the need for water, but their use in oxidation reactions results in the corresponding carboxylic acid salt as a waste product. Moreover, organic peracids are often expensive and have safety issues (such as shock sensitivity), which limits their commercial application. Further information may be found in the literature, for example: Kaur and Kishore, Peroxy Acids: Role in Organic Synthesis, Synthetic Communications, 2014, 44, 721.

[0014] There is a need in the art for alternative sources of hydrogen peroxide, particularly peroxide sources that are non-aqueous (anhydrous), more affordable, greener, and / or safer than the alternatives known in the art. The present invention addresses one or more of those needs.

[0015] SUMMARY

[0016] The present invention is based on the finding that certain cyclic ethers can be used to form useful peroxide reagents. That is, and without being bound by theory, the present inventors have found that cyclic ethers of a certain structure can form a complex with hydrogen peroxide such that the resultant complex can act as a source of peroxide (and hence a peroxide reagent) in numerous applications. The resultant peroxide reagent is non-aqueous, affordable to produce, green (that is, environmentally friendly: low hazard, low / non-hazardous waste from use, and may be produced from renewable

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[0018] 3 feedstocks), stable, and safe. As described above, these traits pose a significant advantage over other sources of peroxide known in the art.

[0019] Therefore, in a first aspect, there is provided a peroxide reagent, wherein the peroxide reagent comprises:

[0020] (a) hydrogen peroxide; and

[0021] (b) a cyclic ether; wherein the cyclic ether is of formula (I): wherein:

[0022] R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl;

[0023] X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl; and n is 0, 1 , 2, or 3.

[0024] The present inventors have identified a method of preparing the peroxide reagent of the first aspect. The method is affordable, quick, operationally simple, and green, thus contributing to the advantageous properties of the peroxide reagent over other sources of peroxide known in the art.

[0025] Therefore, in a second aspect, there is provided a method of preparing a peroxide reagent of the first aspect, the method comprising contacting:

[0026] (i) hydrogen peroxide; and

[0027] (ii) a cyclic ether as defined in the first aspect of the invention.

[0028] The present inventors have found that the peroxide reagent of the first aspect is an effective source of peroxide in oxidation reactions.

[0029] Therefore, in a third aspect, there is provided the use of a peroxide reagent in a cleaning, bleaching, sterilisation, or oxidation reaction, wherein the peroxide reagent is the peroxide reagent of the first aspect.

[0030] Relatedly, the present inventors have found that the peroxide reagent of the first aspect may be used in a method of oxidising a compound.

[0031] Therefore, in a fourth aspect, there is provided a method of oxidising a compound, comprising:

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[0033] 4

[0034] (a) contacting the compound with the peroxide reagent of the first aspect of the invention.

[0035] As described above, and without being bound by theory, the present inventors believe that cyclic ethers of formula (I) form a complex with hydrogen peroxide. This novel species may form the basis for the peroxide reagent of the first aspect of the invention.

[0036] Therefore, in a fifth aspect, there is provided a complex of:

[0037] (a) hydrogen peroxide; and

[0038] (b) a cyclic ether as defined in the first aspect of the invention.

[0039] The present inventors have also demonstrated that a compound can be oxidised by contacting the compound with a mixture of hydrogen peroxide and a cyclic ether, such as a cyclic ether as defined in the first aspect of the invention. Without being bound by theory, it is thought that a peroxide reagent (e.g. as defined in the first aspect) or a complex (e.g. as defined in the fifth aspect) may form transiently or in situ, enabling oxidation to occur.

[0040] Therefore, in a sixth aspect, there is provided a method of oxidising a compound, comprising:

[0041] (a) contacting the compound with a mixture of (i) hydrogen peroxide and (ii) a cyclic ether as defined in the first aspect of the invention.

[0042] With reference to the peroxide reagent of the first aspect and / or the complex of the second aspect, and without being bound by theory, the inventors believe that a hydrogen bond forms between the oxygen atom of the cyclic ether of formula (I) and a hydrogen atom of hydrogen peroxide.

[0043] In general, cyclic ethers are not water miscible, and hence are not typically expected to form such stable intermolecular interactions with hydrogen peroxide (a hydrophilic compound). This is particularly true with respect to cyclic ethers of formula (I), where the geminal R1 / R2and R3 / R4groups may act to further increase the hydrophobicity of the ether. However, surprisingly, the reagent and / or complex as described herein is stable such that it may be prepared, stored and / or used in a variety of applications.

[0044] Without being bound by theory, the present inventors hypothesise that said geminal groups of the cyclic ether of formula (I) are likely responsible for the observed stabilities, whereby there is a hydrogen bond formed between the oxygen atom of the cyclic ether of formula (I) and a hydrogen atom of hydrogen peroxide; the geminal groups, in the alpha position relative to the oxygen atom, may act to inhibit breakdown

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[0046] 5 of the cyclic ether and peroxide by limiting oxidation of the cyclic ether. As such, surprisingly the present inventors have been able to provide a peroxide reagent that has a stability comparable to conventional peroxide reagents. In particular, when used in excess in an oxidation reaction, the present inventors have observed that an amount of peroxide reagent can remain in the reaction mixture following the completion of the reaction. In other words, surprisingly, the stability of the described peroxide reagent is such that it does not appear to wholly decompose even under elevated temperatures and / or in the presence of a catalyst (in contrast to many conventional sources of hydrogen peroxide, such as those provided in an aqueous solution).

[0047] Further aspects and embodiments of the present invention will be evident from the detailed discussion that follows.

[0048] BRIEF DESCRIPTION OF THE FIGURES

[0049] Figure 1A: IR absorption spectrum of a cyclic ether, TMO (2, 2,5,5- tetramethyloxolane).

[0050] Figure 1 B: IR absorption spectrum of a peroxide reagent, “TMO2” (where the cyclic ether is TMO, the peroxide reagent may be referred to as TMO2). The peroxide reagent is dried and so the broad OH peak cannot be attributed to residual water in the system.

[0051] Figure 1C: IR absorption spectrum of hydrogen peroxide (H2O2, aq.).

[0052] DETAILED DESCRIPTION

[0053] Definitions

[0054] In the discussion that follows, reference is made to a number of terms, which have the meanings provided below, unless a context indicates to the contrary. The nomenclature used herein for defining compounds, in particular the compounds according to the invention, is in general based on the rules of the IUPAC organisation for chemical compounds, specifically the “IUPAC Compendium of Chemical Terminology (Gold Book)”. For the avoidance of doubt, if a rule of the IUPAC organisation is in conflict with a definition provided herein, the definition herein is to prevail. Furthermore, if a compound structure is in conflict with the name provided for the structure, the structure is to prevail.

[0055] The term “comprising” or variants thereof is to be understood herein to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps,

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[0057] 6 but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0058] The term “consisting” or variants thereof is to be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, and the exclusion of any other element, integer or step or group of elements, integers or steps.

[0059] The disclosure also encompasses various deuterated forms of the compounds as described herein. Each available hydrogen atom attached to a carbon atom may be independently replaced with a deuterium atom. A person of ordinary skill in the art will know how to synthesize deuterated forms of the compounds disclosed herein, including those referred to above. For example, deuterated materials, such as alkyl groups may be prepared by conventional techniques (see for example: methyl-d3 -amine available from Aldrich Chemical Co., Milwaukee, Wl, Cat. No.489, 689-2).

[0060] The disclosure also includes isotopically-labelled compounds of the present disclosure, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number most commonly found in nature. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, iodine and chlorine such as3H,11C,14C,18F,123l or125l. Compounds of the present disclosure and pharmaceutically acceptable salts of said compounds that contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of the present disclosure.

[0061] The term “about” herein, when qualifying a number or value, is used to refer to values that lie within ± 5% of the value specified. For example, where a concentration range is defined as from about 0.05% to about 25% w / w, concentrations of 0.0475% and 26.25% w / w are considered to be included.

[0062] The term “alkyl” defines univalent groups derived from alkanes by removal of a hydrogen atom from any carbon atom, wherein the term “alkane” is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n+2, wherein n is an integer >1. Alkyl groups may be Ci-4alkyl groups. Ci-4alkyl refers to any selected from the group consisting of methyl, ethyl, n-propyl, / so-propyl, n-butyl, secbutyl, / so-butyl and tert-butyl.

[0063] The term “alkylene” refers to divalent groups derived from alkyl groups by removal of a hydrogen atom from any carbon atom. Alkylene groups may be Ci-3alkylene groups. Ci-3alkylene refers to any selected from the group consisting of methylene,

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[0065] 7 ethylene, methylmethylene, n-propylene, ethylmethylene, dimethylmethylene, and methylethylene.

[0066] The term “halo” refers to a monovalent halogen radical such as fluoro, chloro, bromo, and iodo.

[0067] The term “haloalkyl” refers to univalent groups derived from alkyl groups wherein one or more hydrogen atoms has been replaced with a halo group. The halo group may be independently selected from fluoro, chloro, bromo, and iodo. Haloalkyl groups may be Ci-4haloalkyl groups. Ci-4haloalkyl refers but is not limited to fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, hexafluoroisopropyl, chloromethyl, 2-chloroethyl, 3-chloropropyl, and 4-chlorobutyl.

[0068] Peroxide reagent

[0069] As described above, in a first aspect, there is provided a peroxide reagent, wherein the peroxide reagent comprises:

[0070] (a) hydrogen peroxide; and

[0071] (b) a cyclic ether; wherein the cyclic ether is of formula (I): wherein:

[0072] R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl;

[0073] X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl; and n is 0, 1 , 2, or 3.

[0074] A peroxide reagent is a chemical reagent that may be used as a source of hydrogen peroxide (“peroxide”, or H2O2). The peroxide reagent of the first aspect of the invention comprises hydrogen peroxide and a cyclic ether of formula (I). In some embodiments, the peroxide reagent consists of, or consists essentially of, hydrogen peroxide and the cyclic ether.

[0075] The peroxide reagent may take any suitable form that allows it to be prepared, stored, and / or used. In some embodiments, the peroxide reagent may take the form of

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[0077] 8 a composition, mixture, solution, or dispersion. In some embodiments, the peroxide reagent is a composition comprising hydrogen peroxide and the cyclic ether. In some embodiments, the peroxide reagent is a mixture of hydrogen peroxide and the cyclic ether. In some embodiments, the peroxide reagent is a solution of hydrogen peroxide in the cyclic ether; that is, the hydrogen peroxide is dissolved in the cyclic ether. In some embodiments, the peroxide reagent is a dispersion of hydrogen peroxide in the cyclic ether. As described above and herein, and without being bound by theory, the peroxide reagent is or may comprise a complex of hydrogen peroxide and the cyclic ether that forms upon contacting the hydrogen peroxide and the cyclic ether. Thus, the peroxide reagent in any of the forms described herein (e.g. a composition, mixture, solution or dispersion) may comprise a complex of hydrogen peroxide and the cyclic ether.

[0078] As stated above, R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl. In some embodiments, R1, R2, R3, and R4are each independently selected from Ci-4alkyl, fluoromethyl, difluoromethyl, trifluoromethyl,

[0079] 2-fluoroethyl, 2,2,2-trifluoroethyl, and perfluoroethyl. In some embodiments, R1, R2, R3, and R4are each independently selected from Ci-4alkyl, fluoromethyl, difluoromethyl, and trifluoromethyl. In some embodiments, R1, R2, R3, and R4are each independently selected from methyl, ethyl, and trifluoromethyl. In more preferred embodiments, R1, R2, R3, and R4are each independently Ci-4alkyl. Typically, R1, R2, R3, and R4are each independently selected from methyl and ethyl. Even more typically R1, R2, R3, and R4are each methyl.

[0080] In some embodiments, R1and R2are the same, for example, R1and R2are methyl. In some embodiments, R3and R4are the same, for example, R3and R4are methyl. Typically, R1, R2, R3, and R4are all the same, for example, R1, R2, R3, and R4are all methyl.

[0081] As described above, X and Y are each independently -CR5R6-, wherein each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl. That is to say, X and Y are each independently a methylene group optionally substituted with one or more groups selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl.

[0082] In some embodiments, each R5and R6is independently selected from H, Ci-4alkyl, fluoro, chloro, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, hexafluoroisopropyl, chloromethyl, 2-chloroethyl,

[0083] 3-chloropropyl, and 4-chlorobutyl. In some embodiments, each R5and R6is independently selected from H, Ci-4alkyl, fluoro, chloro, fluoromethyl, difluoromethyl, and trifluoromethyl. In some embodiments, each R5and R6is independently selected from

[0084] 55651538-1 M&C PG450913W0

[0085] 9

[0086] H, methyl, ethyl, n-propyl, / so-propyl, fluoro, and trifluoromethyl. In some embodiments, each R5and R6is independently selected from H, methyl, ethyl, fluoro, difluoromethyl, trifluoromethyl and perfluoroethyl. In more preferred embodiments, each R5and R6is independently selected from H and Ci-4alkyl, such as methyl, ethyl, n-propyl, / so-propyl, and n-butyl. Typically, each R5and R6is independently selected from H, methyl, and ethyl, more typically H. In some embodiments, each R5and R6is the same; typically, each R5and R6is H.

[0087] In addition to the options described above in formula (I), in additional aspects and embodiments, R1and R3, or R1and R5, together form a Ci-3alkylene bridging group. Thus, the disclosure further extends to a cyclic ether of formula (I): wherein:

[0088] R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl;

[0089] X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl; or R1and R3, or R1and R5, together form a Ci-3alkylene bridging group; and n is 0, 1 , 2, or 3.

[0090] Where R1and R3form a bridging group, it may be depicted structurally by formula (Ila); where R1and R5form a bridging group, and for example, n is 1 , it may be depicted structurally by formula (lib); in both cases, Q represents the Ci-3alkylene bridging group:

[0091] In some embodiments, the cyclic ether is not cineol (or eucalyptol). Where R1and R5form a bridging group, and n is greater than 0, the R5may be that of X or a Y.

[0092] In some embodiments, the Ci-3alkylene bridging group is selected from methylene, ethylene, methylmethylene, n-propylene, ethylmethylene, dimethylmethylene, and methylethylene. Typically, the Ci-3alkylene bridging group is methylene or ethylene.

[0093] 55651538-1 M&C PG450913W0

[0094] 10

[0095] As stated above, n is 0, 1 , 2 or 3. In other words, the cyclic ether may comprise a 4- to 7- membered ring. In some embodiments, n is 1 , 2, or 3. In more preferred embodiments, n is 1 or 2. Typically, n is 1 . For the avoidance of doubt, where n is greater than 1 , each Y is independent; that is, each R5and R6is selected independently.

[0096] In some embodiments, the cyclic ether is a cyclic ethereal solvent. That is to say, the cyclic ether is a compound with an ether functional group comprised within a ring system, and the compound has solvent-like properties, for example: the compound is a liquid at room temperature. The skilled person will be familiar with or will be able to identify compounds that satisfy these criteria.

[0097] In some embodiments, the cyclic ether is selected from formulae (la) to (If):

[0098] The cyclic ether of formula (la) may be referred to as 2,2,5,5-tetramethyltetrahydrofuran (TMTHF), or simply tetramethyloxolane (TMO); formula (lb) as 2,2,6,6-tetramethyltetrahydropyran; formula (Ic) as 2,2,4,4-tetramethyloxetane; formula (Id) as 2,2,7,7-tetramethyloxepane; and the cyclic ethers of formulae (le) and (If) are commonly known as 1 ,8-cineole and 1 ,4-cineole, respectively. In more preferred embodiments, the cyclic ether is selected from formulae (la) to (Id), typically (la) and (lb), more typically (la).

[0099] The cyclic ethers disclosed herein may be obtained commercially or prepared through conventional laboratory synthesis; the skilled person will be familiar with the conventional organic chemistry reactions that may be utilised to synthesise said cyclic ethers. One method of making TMO (formula (la)) is described in WO 2018 / 033635 A1 , the contents of which are incorporated herein by reference. The method is a condensation reaction of a diol in the presence of a p-zeolite catalyst. For the avoidance of doubt, this method, and others also suitable for the synthesis of TMO, may be suitable for many other cyclic ethers of formula (I). The precursor diol for the synthesis of TMO described in WO 2018 / 033635 A 1 may be synthesised from acetone and acetylene, which may be obtained from renewable or sustainable feedstocks. Thus, in some embodiments, the cyclic ether is obtainable from renewable or sustainable feedstocks.

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[0101] 11

[0102] The synthesis of the cyclic ether of formula (lb) is described in Singh et al., Amberlyst- 15-Catalyzed Efficient Cyclization of y- and b-Unsaturated Alcohols: Green Synthesis of Oxygen Heterocycles, Synthetic Communications, 2010, 40, 74, and involves the acid catalysed cyclisation of a linear alcohol comprising an alkene. Specifically, the precursor alcohol for the described synthesis of the cyclic ether of formula (lb) is 2,6-dimethyl-5-hepten-2-ol. This method may be suitable for many other cyclic ethers of formula (I). Additionally, the synthesis of oxetane derivatives such as cyclic ethers of formula (Ic) are described in Mill and Montorsi, The Liquid-Phase Oxidation of 2,4- Dimethylpentane, International Journal of Chemical Kinetics, 1973, V, 119, which may also be applicable to other cyclic ethers of formula (I).

[0103] Where the peroxide reagent comprises a cyclic ether of formula (la), the resultant peroxide reagent is referred to herein as “TMO2”.

[0104] In some embodiments, the cyclic ether is a natural product, or is obtainable from natural sources.

[0105] Cyclic ethers of formulae (le) and (If) are natural products, i.e., they occur in nature, and thus may be obtained from natural sources or produced synthetically. Specifically, 1 ,8-cineole (also known as eucalyptol) and 1 ,4-cineole are components of eucalyptus oil, a distilled oil from the leaf of Eucalyptus, which can be obtained commercially.

[0106] In some embodiments, the concentration of hydrogen peroxide in the peroxide reagent is from about 0.05% to about 25% w / w (percentage by weight, or wt. %, or mass fraction). In some embodiments, the concentration is from about 0.5% to about 10% w / w, typically from about 1 % to about 5% w / w, more typically from about 2% to about 4% w / w, often about 3% w / w.

[0107] The concentration of hydrogen peroxide in the peroxide reagent may be increased through concentrating means, such as through distillation. Therefore, in some embodiments, the concentration of hydrogen peroxide in the peroxide reagent is at least about 1 % w / w, such as at least about 2% w / w, at least about 3% w / w, at least about 4% w / w, at least about 5% w / w, at least about 10% w / w, at least about 15% w / w, at least about 20% w / w, or at least about 25% w / w. In some embodiments, the concentration of hydrogen peroxide in the peroxide reagent is from about 1 % to about 25% w / w, such as from about 2% to about 25% w / w, from about 3% to about 25% w / w, from about 4% to about 25% w / w, from about 5% to about 25% w / w, or from about 10% to about 20% w / w.

[0108] The concentration of hydrogen peroxide in the peroxide reagent may be quantified through some analytical means. This may be performed spectroscopically, or

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[0110] 12 through “wet” methods such as titration. For example, titration may be performed with potassium permanganate (KMnCL) to determine a concentration of hydrogen peroxide in the peroxide reagent.

[0111] In some embodiments, the density of the peroxide reagent is from about 0.5 to about 1.0 g / mL. In some embodiments, the density is from about 0.6 to about 0.9 g / mL, typically from about 0.7 to about 0.8 g / mL, often about 0.75 g / mL. The densities as described herein may be determined under ambient conditions, for example under standard temperature and pressure.

[0112] The peroxide reagent may be characterised through spectroscopic means. For example, the infrared (IR) absorption spectrum of the peroxide reagent can be recorded. The IR spectrum may be obtained through any suitable instrument; the skilled person will be familiar with obtaining such spectra. In some embodiments, the peroxide reagent has an absorbance peak from about 3250 to about 3450 cm-1. This peak is typically due to an O-H stretching vibration, representative of hydrogen peroxide. The peak may be broad and traverse a wide range of wavenumbers. In some embodiments, the peroxide reagent has an IR absorbance peak from about 3300 to about 3400 cm-1, typically from about 3320 to about 3360 cm-1, more typically about 3330 to about 3350 cm-1, often about 3340 cm-1(e.g. about 3342 cm-1). Additionally, the peroxide reagent may have an IR absorption peak due to a C-H stretching vibration, representative of an aliphatic C-H bond of the cyclic ether. Therefore, in some embodiments, the peroxide reagent has an IR absorbance peak at about 3000 cm-1, typically about 2970 cm-1. The C-H stretching peak is typically sharp and not spread over a wide range of wavenumbers.

[0113] As described above, one particularly advantageous feature of the presently disclosed peroxide reagent is that it is anhydrous, i.e., it is substantially free from water. Thus, in some embodiments, the peroxide reagent is anhydrous. The term anhydrous may indicate a water content of <5 wt% water, or <1 wt%, or <0.1 wt%, or <0.01 wt%, or <0.001 wt%. Ideally, the peroxide reagent contains no water. Water content may be represented as wt% or ppm. 5 wt% is equivalent to 50,000 ppm; 1 wt% is 10,000 ppm; 0.1 wt% is 1 ,000 ppm; 0.01 wt% is 100 ppm; 0.001 wt% is 10 ppm.

[0114] As described above, the peroxide reagent may be stable. In some embodiments, the peroxide reagent may be stable for a prolonged period of time when stored at room temperature (e.g. about 20 to about 25 °C), or when stored under refrigerated conditions (e.g. from about 2 to about 8 °C, such as about 4 °C). In some embodiments, the peroxide reagent may be stable for a prolonged period of time even when stored under direct light.

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[0116] 13

[0117] In some embodiments, the peroxide reagent may be stable such that the concentration of hydrogen peroxide remains relatively constant over a period of time. In some embodiments, the concentration of the hydrogen peroxide may be at least about 70%, or at least about 80% of an initial concentration after storage for a period of time. The period of time may be at least 1 week, 2 weeks, 3 weeks or 4 weeks. By way of further example, in some embodiments, the concentration of the hydrogen peroxide may be at least about 80% of an initial concentration after storage at room temperature for a period of 4 weeks.

[0118] As described above, in a fifth aspect, there is provided a complex of:

[0119] (a) hydrogen peroxide; and

[0120] (b) a cyclic ether as defined in the first aspect of the invention.

[0121] For the avoidance of doubt, the embodiments of the first aspect of the invention apply mutatis mutandis to the embodiments of the fifth aspect of the invention. For example, in some embodiments, R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl, typically methyl or ethyl, more typically methyl; X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl, typically H, methyl, and ethyl, more typically H; n is 0, 1 , 2, or 3, typically 1 or 2, more typically 1.

[0122] The term “complex” is used herein to refer to a stable association between two or more molecules through non-covalent intermolecular interactions, such as hydrogen bonding. Without being bound by theory, in some embodiments, the complex comprises a hydrogen bond between the oxygen atom of the cyclic ether and a hydrogen atom of hydrogen peroxide. Accordingly, the complex may comprise hydrogen peroxide complexed to the cyclic ether by way of a hydrogen bond between the oxygen atom of the cyclic ether and a hydrogen atom of hydrogen peroxide.

[0123] Without being bound by theory, the complex of hydrogen peroxide and the cyclic ether may have various stoichiometries. For example, the stoichiometry of the hydrogen peroxide to the cyclic ether may be about 1 :1 , 1 :2, 1 :3, 1.4:, 1 :5, and so on. In other words, the hydrogen peroxide may be complexed to one, two, three, four, or five (and so on) molecules of the cyclic ether. In some embodiments, the stoichiometry of the hydrogen peroxide to the cyclic ether is 1 :1 or 1 :2. It will be appreciated that a given sample of the peroxide reagent or complex may exhibit mixed stoichiometries. For example, in some embodiments, the stoichiometry of the hydrogen peroxide to the cyclic ether is from about 1 :1 to about 1 :2. Alternatively, the stoichiometry of the hydrogen peroxide to the cyclic ether is 2:1. For the avoidance of doubt, these embodiments apply

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[0125] 14 to all aspects of the invention (e.g. the peroxide reagent of the first aspect) mutatis mutandis.

[0126] As stated above, the peroxide reagents described herein may comprise such complexes (which may form spontaneously when hydrogen peroxide and the cyclic ethers are contacted with one another). Without being bound by theory, it is thought that the complex may exist in solution (e.g. dissolved or suspended in a cyclic ether) and that it may be isolated perse.

[0127] The peroxide reagent and / or the complex of hydrogen peroxide and the cyclic ether may be obtainable by the method of the second aspect of the invention, described herein. For the avoidance of doubt, the term “obtainable” includes peroxide reagents and / or complexes obtained by the method of the second aspect, as well as peroxide reagents and / or complexes not obtained by the method of the second aspect but that are identical to those obtained by the method of the second aspect.

[0128] As described above, in a second aspect, there is provided a method of preparing a peroxide reagent of the first aspect, the method comprising contacting:

[0129] (i) hydrogen peroxide; and

[0130] (ii) a cyclic ether as defined in the first aspect of the invention.

[0131] For the avoidance of doubt, the embodiments of the first aspect of the invention apply mutatis mutandis to the second aspect of the invention.

[0132] The term “contacting” is used herein to refer to any one or more of the acts of combining, such as reacting, mixing, stirring, slurrying, blending, dissolving, impregnating, incubating, passing over, flowing over, bubbling, or otherwise, in any order, and for any length of time; the skilled person will recognise that the invention is not limited as such. Nonetheless, in some embodiments, the method comprises mixing and / or reacting the hydrogen peroxide and the cyclic ether. In some embodiments, the contacting involves stirring or some other form of agitation (such as vibration, sonication (e.g. ultrasonication), or centrifugal mixing). Thus, the method may comprise mixing and / or agitating the hydrogen peroxide and the cyclic ether during the contacting step to facilitate the formation of the peroxide reagent. Alternatively, the method may comprise bubbling hydrogen peroxide gas through a cyclic ether to provide the peroxide agent.

[0133] In some embodiments, the contacting occurs in a reaction mixture, such as during an oxidation reaction. That is, in some embodiments, the contacting occurs in situ.

[0134] The contacting of the hydrogen peroxide and the cyclic ether is carried out for a period of time to allow the formation of the peroxide reagent. In some embodiments, the

[0135] 55651538-1 M&C PG450913W0

[0136] 15 contacting is carried out for at least about 5 minutes, at least about 10 minutes, or at least about 15 minutes. In more preferred embodiments, the contacting is carried out for at least about 2 hours, or between about 2 and 48 hours. In some embodiments, the contacting is carried out over an overnight period, or from about 12 to about 18 hours.

[0137] The skilled person will recognise that the hydrogen peroxide of the second aspect may originate from a variety of sources, such as an aqueous solution of hydrogen peroxide of various concentrations, a hydrogen peroxide generator (that is, equipment that produces hydrogen peroxide in situ, often through electrochemical means) ureahydrogen peroxide and so on. That is to say, the invention is not limited to any particular source of hydrogen peroxide.

[0138] By way of example, the inventors have found that the peroxide reagent may be prepared through the use of an aqueous solution of hydrogen peroxide. Therefore, in some embodiments, the method comprises contacting an aqueous solution of hydrogen peroxide with the cyclic ether. In some embodiments, where the method comprises contacting an aqueous solution of hydrogen peroxide with the cyclic ether, the concentration of hydrogen peroxide in the aqueous solution of hydrogen peroxide is from about 10% to about 60% w / v (weight by volume). In some embodiments, the concentration is from about 20% to about 50% w / v. Conventional laboratory grade aqueous solutions of hydrogen peroxide are typically about 30% or about 50% w / v. In some embodiments the concentration is about 30% or about 50% w / v, typically about 30% w / v.

[0139] After the contacting step, there may be one or more separation or purification steps to isolate the peroxide reagent from any by-products, solvents, or excess reagents. In particular, where the method comprises contacting an aqueous solution of hydrogen peroxide with the cyclic ether, the method may further comprise the step of separating an organic phase from an aqueous phase, wherein the separated organic phase comprises the peroxide reagent. An organic phase and an aqueous phase may result from such a contacting step due to the immiscibility of the cyclic ether and the aqueous solution of hydrogen peroxide; the resultant peroxide reagent may then partition into the organic phase, hence it may be isolated through phase separation. Therefore, in some embodiments, the method may further comprise the step of separating an organic phase from an aqueous phase, wherein the separated organic phase comprises the peroxide reagent. The skilled person will be familiar with methods of separating an organic phase from an aqueous phase (such as through the normal operation of a separating funnel, or through a hydrophobic membrane / filter / frit). In some embodiments, the separating step

[0140] 55651538-1 M&C PG450913W0

[0141] 16 is performed with a separating funnel. The method may comprise further separation or purification steps such as chromatography, e.g. column chromatography, thin-layer chromatography, gas chromatography, liquid chromatography (such as HPLC). Additionally, the peroxide reagent may be isolated as a solution or suspension (e.g. in the cyclic ether) or as a ‘neat’ (or ‘pure’) isolate, such as an isolated complex.

[0142] Furthermore following the contacting step, particularly where the method comprises contacting an aqueous solution of hydrogen peroxide with the cyclic ether, there may be some residual (or substantial) quantity of water present in the peroxide reagent. Hence, in some embodiments, the method further comprises the step of drying the peroxide reagent. In some embodiments, where the method further comprises the step of separating an organic phase from an aqueous phase, the method further comprises the step of drying the separated organic phase. Again, the skilled person will be familiar with many suitable methods of drying (an organic phase). For example, an organic phase may be dried with a drying agent such as an anhydrous metal salt (e.g., magnesium sulfate or sodium sulfate) or molecular sieves. Additionally, an organic phase may be dried through a hydrophobic membrane / filter / frit. In some embodiments, the step of drying the separated organic phase comprises the use of a drying agent, such as molecular sieves or a metal sulfate (e.g., magnesium sulfate or sodium sulfate). The skilled person will recognise that the use of a drying agent will typically necessitate a further step of filtering the drying agent from the organic phase.

[0143] Uses

[0144] The peroxide reagent as described herein may find use in a wide variety of applications. In particular, the peroxide reagent can provide an alternative source of hydrogen peroxide and so may find use in any reaction that typically employs the use of hydrogen peroxide. For example, the peroxide reagent may find use in cleaning, bleaching, sterilisation, and oxidation reactions. In some embodiments, the cleaning, bleaching or sterilisation reaction may comprise an oxidation by the peroxide reagent.

[0145] As described above, in a third aspect, there is provided the use of a peroxide reagent in cleaning, bleaching, sterilisation, or oxidation reaction, wherein the peroxide reagent is the peroxide reagent of the first aspect of the invention.

[0146] In some embodiments, the oxidation reaction is an oxidation of a compound and may comprise contacting the compound with the peroxide reagent.

[0147] Thus, as described above, in a fourth aspect, there is provided a method of oxidising a compound, comprising:

[0148] 55651538-1 M&C PG450913W0

[0149] 17

[0150] (a) contacting the compound with the peroxide reagent of the first aspect of the invention.

[0151] Further embodiments related to the uses and methods of oxidising are described in detail below.

[0152] In some embodiments, the oxidation reaction is an oxidation of a compound with an oxidisable group.

[0153] In some embodiments, the oxidation reaction is an oxidation of an organic or an inorganic compound. As used herein, the organic compound is a hydrocarbon-based compound. As used herein, the inorganic compound is a chemical compound lacking any carbon-hydrogen bonds. The inorganic compound may be a complex, that is, a coordination complex consisting of one or more central metal atoms or ions surrounded by bound molecules, ions, or ligands. In some embodiments, the inorganic compound comprises a metal, such as a transition metal, for example one or more selected from cobalt, iron, titanium, vanadium, manganese, and chromium. In some embodiments, the inorganic compound may comprise a non-metallic element, such as phosphorus, sulfur, or the like. An oxidation reaction of an inorganic compound may result in an increase in oxidation state of the one or more metal atoms.

[0154] The organic compound or the inorganic compound may comprise one or more oxidisable groups.

[0155] In particular, with respect to the third aspect of the invention, the organic compound is a hydrocarbon-based compound that comprises one or more oxidisable groups.

[0156] The oxidisable groups may be selected from carbon-based groups (such as alkenes (olefins) (such as long chain alkenes, or styrenes), alkynes, or aromatic rings), oxygen-based groups (such as alcohols (primary, secondary, benzylic, phenolic or otherwise aromatic), aldehydes, ketones, esters (such as lactones), ethers, enols, acetals, and hemiacetals), sulfur-based groups (such as thiols, sulfoxides, and sulfides (thioethers)), nitrogen-based groups (such as amines, imines, enamines, / V- heterocycles, hydrazines, anilines, carbamates, nitriles, and diazonium salts), and phosphor-based groups (such as phosphines).

[0157] In some embodiments, the organic compound comprises one or more oxidisable groups selected from alkenes (such as long chain alkenes, or styrenes), alcohols, aldehydes, ketones (such as cyclic ketones), thiols, amines (such as anilines) and thioethers.

[0158] 55651538-1 M&C PG450913W0

[0159] 18

[0160] In some embodiments, the oxidation reaction may be an oxidative halogenation of a compound, e.g. the oxidative halogenation of an organic compound. In such reactions, the peroxide reagent may be used in combination with a halide salt (e.g. a metal halide) to provide a halogenated product.

[0161] In some embodiments, the oxidation reaction is conducted in the presence of a catalyst. The catalyst may be heterogeneous or homogeneous.

[0162] In some embodiments, the catalyst is a Lewis acid catalyst; that is, the catalyst acts as an electron-pair acceptor to increase the reactivity of a substrate (e.g., the organic compound).

[0163] Suitable Lewis acid catalysts may be based on main group elements such as aluminium, boron, silicon and tin, as well as d-block metals, and the catalysts may comprise salts of these elements / metals. Representative examples include, but are not limited to, oxides, halides, alkoxides, triflates, nitrates, and the like. In some embodiments, the Lewis acid catalyst is selected from molybdenum trioxide (MoOa), isopropoxide salts (such as titanium tetraisopropoxide (Ti( / -PrO)4), boron triisopropoxide (B( / -PrO)3), and aluminium triisopropoxide (AI( / -PrO)3)), aluminium chloride (AICI3), boron trifluoride (BF3), titanium tetrachloride (TiCL), iron trichloride (FeCh), diethylaluminium chloride (Et2AICI), triethylaluminium (EtsAI), titanium dioxide (TiCh), zirconium dioxide (ZrCh), lanthanum triflate (La(OTf)s), ytterbium triflate (Yb(OTf)3), silver nitrate (AgNCh), gold chloride (AuCh), palladium chloride (PdCh), tungsten trioxide (WO3), sodium tungstate dihydrate (Na2O4W*2H2O), lithium tungstate (U2WO4), tungsten dichloride dioxide (WCI2O2), and sodium tungstate (Na2O4W). In some embodiments, the Lewis acid catalyst is selected from molybdenum trioxide (MoOs), and isopropoxide salts (such as titanium tetraisopropoxide (Ti( / -PrO)4), boron triisopropoxide (also known as triisopropyl borate, B( / -PrO)3), and aluminium triisopropoxide (AI( / -PrO)3)), typically molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide.

[0164] The skilled person will be familiar with numerous types of oxidation reactions, from broader classes to more specific named reactions. In some embodiments, the oxidation reaction is selected from: a Baeyer-Villiger reaction; an epoxidation reaction; an oxidation of an imine to an oxaziridine; an oxidation of a thioether to a sulfoxide or sulfone; an oxidation of a sulfoxide to a sulfone; an oxidation of an aldehyde to a carboxylic acid; a hydroxylation of an aromatic ring; an oxidation of an amine to a nitro group (e.g. an oxidation of an aniline to a nitrobenzene compound); an oxidation of an amine to an azoxy group; an oxidative cleavage of an alkene; an oxidative halogenation;

[0165] 55651538-1 M&C PG450913W0

[0166] 19 an oxidation of a lactone to a carboxylic acid (or diacid); an oxidation of an alcohol to an aldehyde; and an oxidation of an alkene to an aldehyde.

[0167] The peroxide reagent as described herein may find use in any reaction that typically uses hydrogen peroxide (or another type of peroxide) as an oxidant. Numerous examples of such oxidation reactions, may be found in the literature, such as C. W. Jones, Applications of Hydrogen Peroxide and Derivatives, Royal Society of Chemistry, 1999, the contents of which are incorporated by reference.

[0168] In some embodiments, the oxidation reaction is a Baeyer-Villiger reaction. A Baeyer-Villiger reaction is an oxidation of a ketone or aldehyde to an ester, or a cyclic ketone to a lactone, typically using peroxides or peracids as the oxidant. In some embodiments where the oxidation reaction is a Baeyer-Villiger reaction, the organic compound comprises a ketone or aldehyde, typically a ketone (for example, the organic compound may be cyclopentanone, cyclohexanone, or levoglucosenone). Additionally, in some embodiments where the oxidation reaction is a Baeyer-Villiger reaction, the reaction is conducted in the presence of a catalyst, typically a Lewis acid catalyst, such as sodium tungstate, molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide, often boron triisopropoxide.

[0169] In some embodiments, the oxidation reaction is an epoxidation reaction. An epoxidation reaction is an oxidation of an alkene to an epoxide, typically using peroxides or peracids as the oxidant. In some embodiments where the oxidation reaction is an epoxidation reaction, the organic compound comprises an alkene. In some embodiments, the organic compound is an alkene and its derivatives, an allyl alcohol and its derivatives, or styrene and its derivatives. Additionally, in some embodiments where the oxidation reaction is an epoxidation reaction, the reaction is conducted in the presence of a catalyst, typically a Lewis acid catalyst, such as sodium tungstate, molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide, often titanium tetraisopropoxide or boron triisopropoxide. In some embodiments, the epoxidation reaction comprises contacting an alkene, such as a C2-24alkene, with the peroxide reagent or with hydrogen peroxide and the cyclic ether. In some embodiments, the reaction is conducted in a biphasic mixture, e.g., in a mixture of aqueous hydrogen peroxide and the cyclic ether. In some embodiments, the alkene is a C^alkene, such as 1 ,2-dodecene. In some embodiments, the reaction is an epoxidation of 1 ,2-dodecene to form 1 ,2-epoxydodecane. In some embodiments, the reaction is heated, e.g. to reflux (which in some cases is about 110 °C such as 112 °C; references to temperature may

[0170] 55651538-1 M&C PG450913W0

[0171] 20 be to internal reaction temperature). In some embodiments, the reaction is as described in Example B.6, such as in Example B.6.1 , B.6.2, or B.6.3.

[0172] In some embodiments, the oxidation reaction is an oxidation of an imine to an oxaziridine. Such oxidation reactions often use a peracid as an oxidant. In some embodiments where the oxidation reaction is an oxidation of an imine to an oxaziridine, the organic compound is a phenylmethanimine. Additionally, in some embodiments, the reaction is conducted in the presence of a catalyst, typically a Lewis acid catalyst, such as sodium tungstate, molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide, often titanium tetraisopropoxide.

[0173] In some embodiments, the oxidation reaction is an oxidation of a thioether to a sulfoxide. Such oxidation reactions may use peroxides or peracids as an oxidant. In some embodiments where the oxidation reaction is an oxidation of a thioether to a sulfoxide, the organic compound is thioxanthone or a derivative. Additionally, in some embodiments, the reaction is conducted in the presence of a catalyst, typically a Lewis acid catalyst, such as sodium tungstate, molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide, often boron triisopropoxide.

[0174] In some embodiments, the oxidation reaction is an oxidation of an aldehyde to a carboxylic acid. Such oxidation reactions often use metal salts as an oxidant. In some embodiments where the oxidation reaction is an oxidation of an aldehyde to a carboxylic acid, the organic compound is benzaldehyde and its derivatives.

[0175] In some embodiments, the oxidation reaction is an oxidation of an amine to a nitro compound, such as an oxidation of an aniline to a nitrobenzene compound. Such oxidation reactions often use metal salts as an oxidant. In some embodiments where the oxidation reaction is an oxidation of an amine to a nitro compound, the organic compound is aniline and its derivatives.

[0176] In some embodiments, the oxidation reaction is an oxidation of an amine to an azoxy compound, such as an oxidation of an aniline to an azoxybenzene compound. Such oxidation reactions often use metal salts as an oxidant. In some embodiments where the oxidation reaction is an oxidation of an amine to an azoxy compound, the organic compound is aniline and its derivatives.

[0177] In some embodiments, the oxidation reaction is conducted at a raised temperature ( / .e., a temperature above room temperature). This may be done for example to increase the rate of reaction and / or increase the solubility of the reagents / substrates. In some embodiments, the reaction is conducted at from about 40 to about 120 °C, or from about 60 to about 120 °C, or from about 80 to about 120 °C,

[0178] 55651538-1 M&C PG450913W0

[0179] 21 typically about 100 to about 120 °C. In more preferred embodiments, the reaction is conducted at about 110 °C.

[0180] In some embodiments, the oxidation reaction is conducted in the peroxide reagent. That is to say, the reaction is carried out neat in the absence of any additional solvent.

[0181] In some embodiments, the oxidation reaction is conducted in a biphasic mixture. A biphasic mixture may form, for example, when an aqueous solution of hydrogen peroxide is contacted with the cyclic ether. That is to say, the peroxide reagent or complex may be formed transiently and / or in situ.

[0182] As described above, a particularly advantageous feature of the present invention is that the peroxide reagent may be anhydrous (or substantially anhydrous). Hence, in some embodiments, the oxidation reaction is carried out under anhydrous (or substantially anhydrous) conditions. Further measures may be implemented to carry out a reaction under anhydrous conditions, such as using dry solvents / reagents, and conducting the reaction under an atmosphere of inert gas such as nitrogen or argon.

[0183] As described above, in a sixth aspect, there is provided a method of oxidising a compound, comprising:

[0184] (a) contacting the compound with a mixture of (i) hydrogen peroxide and (ii) a cyclic ether as defined in any one of claims 1-12.

[0185] For the avoidance of doubt, the embodiments of all aspects of the invention apply mutatis mutandis to the embodiments of the sixth aspect of the invention. For example, in some embodiments, R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl, typically methyl or ethyl, more typically methyl; X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl, typically H, methyl, and ethyl, more typically H; n is 0, 1 , 2, or 3, typically 1 or 2, more typically 1.

[0186] In some embodiments, the hydrogen peroxide and the cyclic ether form a peroxide reagent (e.g. the peroxide reagent of the first aspect) or a complex (e.g. the complex of the fifth aspect). Without being bound by theory, the reagent or complex may form transiently or in situ. Where the hydrogen peroxide and the cyclic ether are immiscible, the peroxide reagent or complex may form only at an interface between the hydrogen peroxide and the cyclic ether. However, the reagent or complex may form preferentially in either the cyclic ether or the hydrogen peroxide, such as the cyclic ether.

[0187] In some embodiments, the method is carried out in a multiphasic system, such as a biphasic system. That is to say, there may be two or more liquid phases, such as

[0188] 55651538-1 M&C PG450913W0

[0189] 22 an organic phase, which may comprise the cyclic ether, and an aqueous phase, which may comprise the hydrogen peroxide. In some embodiments, one of the phases of the multiphasic system is provided by the compound e.g. where the compound is a liquid and the reaction is carried out ‘neat’. In some embodiments, the compound is miscible with, suspended in, or dissolved in, an organic phase.

[0190] In some embodiments, the hydrogen peroxide is an aqueous solution of hydrogen peroxide, optionally wherein the concentration of hydrogen peroxide in the aqueous solution of hydrogen peroxide is from about 10% to about 60% w / v, or from about 20% to about 50% w / v, or about 30% w / v. Where the hydrogen peroxide is an aqueous solution, the method may be carried out in a biphasic system.

[0191] In some embodiments, the cyclic ether is a cyclic ethereal solvent. In some embodiments, the cyclic ether is of formula (la) or (lb), typically formula (la).

[0192] In some embodiments, the method is an epoxidation reaction, such as an epoxidation reaction described above. In particular, in some embodiments, the compound is an alkene and its derivatives, such as a C2-24alkene. Additionally, in some embodiments, the reaction is conducted in the presence of a catalyst, typically a Lewis acid catalyst, such as sodium tungstate, molybdenum trioxide, titanium tetraisopropoxide, and boron triisopropoxide, often titanium tetraisopropoxide or boron triisopropoxide. In some embodiments, the alkene is a C^alkene, such as 1 ,2-dodecene. In some embodiments, the reaction is an epoxidation of 1 ,2-dodecene to form 1 ,2- epoxydodecane. In some embodiments, the reaction is heated, e.g. to reflux (which in some cases is about 110 °C such as 112 °C; references to temperature may be to internal reaction temperature). In some embodiments, the reaction is as described in Example B.6, such as in Example B.6.1 , B.6.2, or B.6.3.

[0193] Examples

[0194] PART A - Preparation and Characterisation of TMO2 (an exemplary peroxide reagent comprising 2,2,5,5-tetramethyltetrahydrofuran (TMTHF), or tetramethyloxolane (TMO) as the cyclic ether and hydrogen peroxide) Preparation of TMO2

[0195] 55651538-1 M&C PG450913W0

[0196] 23

[0197] 30% w / v aqueous TMO

[0198] Scheme 1 : the preparation of TMO2 from hydrogen peroxide and TMO.

[0199] Typical preparation procedure for the preparation of TMOy Distilled TMO (100 mL) and H2O2 (20 mL, 30% w / v aq.) were stirred vigorously overnight. No observable heat change or colour change occurred upon addition of H2O2. The organic phase (comprising TMO2) was separated from the aqueous phase, dried with Na2SO4, and filtered. The presence of peroxide was verified via peroxide strip tests (1001000 mg / L, Supelco, 1.10337.0001). The resultant 3% TMO2 product had no discernible difference in colour or viscosity relative to pure TMO.

[0200] Density of TMOy. The density of TMO2 (-2.4% w / w H2O2) solution was determined by adding 5 mL of TMO2 using a calibrated micropipette to a beaker on a balance. The measurement was repeated nine times, resulting in an average density of 0.74 g / mL at 21 °C.

[0201] Quantification of H2O2 in TMO2: The percentage weight per weight (% w / w) of hydrogen peroxide was determined through titration against freshly prepared KMnO4 solution as follows.

[0202] Typical titration procedure: TMO2 (2.00 g) was washed with purified water (4 mL x 4) and the combined aqueous phase was acidified with potassium hydrogen sulphate (0.5% w / v, 2-3 mL). The titrant, KMnCL (5% w / w, aq.), was added dropwise until the endpoint of the titration (solution colour change from colourless to purple). The results are shown in Table 1.

[0203] Table 1 : titration results for quantification of H2O2 in TMO2.

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[0205] 24

[0206] Characterisation of TMO2: To assess the presence of peroxide in TMO2, an IR spectrum was obtained, and compared to that of pure TMO (Fig. 1A) and 30% w / v aq. hydrogen peroxide (Fig. 1C). The IR spectrum of TMO2 (Fig. 1 B) shows an absorbance at 3342 cm-1, which may be attributed to the -OH stretch of H2O2, and is absent from the IR spectrum of TMO (Fig. 1A) but present in 30% w / v aq. hydrogen peroxide solution (Fig. 1C).

[0207] Stability Profile of TMO2

[0208] To assess the stability of TMO2, a freshly prepared batch was placed in direct light at room temperature. The sample of TMO2 was titrated four times (in triplicate each time) over a period of 20 days. The percentage of hydrogen peroxide in TMO2 decreased over that time from 2.7% to 2.3% w / w, suggesting that the peroxide is quite stable. It was noted that after 12 days, signs of droplets were observed, suggesting some degradation of the hydrogen peroxide to water. In an analogous stability assessment of refrigerated TMO2 (~5 °C), there was no detectable decrease in the concentration of H2O2. The results are shown in Table 2.

[0209] Table 2: titration results for quantification of H2O2 in TMO2 over a period of 20 days.

[0210] N.b., each row is an average of three titrations.

[0211] PART B - Exemplary oxidation reactions using TMO2

[0212] B.1 - Villiger oxidation of levoglucosenone (LGO)

[0213] Scheme 2: oxidation of levoglucosenone with TMO2.

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[0215] TMO2 (27 g, 2.5% H2O2 w / w, -5 equiv.) was added to a flask containing LGO (levoglucosenone, 0.5 g, 3.97 mmol, 1 equiv.) under nitrogen. Triisopropyl borate (0.746 g, 3.97 mmol, 1 equiv.) was added and the mixture was heated at reflux overnight (112 °C internal temperature). The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100-1000 mg / L (Supelco, 1.10337.0001)), which indicated that there was no peroxide remaining. The reaction mixture was dried with Na2SC>4, filtered, and concentrated. The residue was purified by automated flash chromatography using a gradient elution (0-5% MeOH in DCM) to give the product (HBO) as a colourless oil that solidified on standing (341 mg, 75% yield).

[0216] 1H NMR (CDCI3, 600 MHz) 5 7.49 (dd, J = 5, 1.6 Hz, 1 H, 2-CH), 6.18 (dd, J = 5.7, 2.1 Hz, 1 H, 1-CH), 5.16-5.14 (m, 1 H, 3-CH), 3.98 (d, J = 12.2 Hz, 1 H, 4-CHH), 3.77 (d, J = 11.8 Hz, 1 H, 4-CHH), 3.21 (br s, 1 H, -OH);

[0217] IR: 3427 (OH), 2919 (CH), 1731 (C=O), 1412, 1330, 817 cm’1.

[0218] B.2 Oxidation of a thioether to a sulfoxide

[0219] Scheme 3: oxidation of thioxanthone with TMO2.

[0220] TMO2 (-2.3% w / w H2O2, 17.4 g, 5 equiv.) was added to a flask containing thioxanthone (0.500 g, 2.4 mmol, 1 equiv.) under N2. The mixture was heated at 90 °C until the starting material dissolved. Triisopropyl borate (27 pL, 0.12 mmol, 0.05 equiv.) was added and the mixture was heated at reflux (112 °C internal temperature) for 24 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100- 1000 mg / L (Supelco, 1.10337.0001)), which indicated that there was no peroxide remaining. The cooled reaction mixture was diluted with EtOAc and the mixture was dried with Na2SC>4, filtered, and concentrated. The residue was purified by automated flash chromatography using a gradient elution (0-20% EtOAc in cyclohexane) to give 9 / 7- thioxanthen-9-one 10-oxide as a pale yellow solid (0.507 g, 2.2 mmol, 94% yield).

[0221] M.P. 189 °C;

[0222] 1H NMR (CDCh, 600 MHz) 5 8.34 (d, J = 7.9 Hz, 2H, Ar-H), 8.18 (d, J = 7.8 Hz, 2H, Ar- H), 7.88 (t, J = 7.6 Hz, 2H, Ar-H), 7.79 (t, J = 7.7 Hz, 2H, Ar-H);

[0223] IR: 3326, 2934, 1677, 1574, 1437, 1289, 1224, 1162, 1140, 1054, 924 cm’1.

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[0225] 26

[0226] B.3 Oxidation of an aldehyde to a carboxylic acid

[0227] Scheme 4: oxidation of benzaldehyde to benzoic acid.

[0228] TMO2 (~2.5 % w / w H2O2, 32 g, 5 equiv.) was added to a flask containing benzaldehyde (0.500 g, 4.7 mmol, 1 equiv.) under a nitrogen atmosphere. Triisopropyl borate (B( / -OPr)3, 108 pL, 0.47 mmol, 0.1 equiv.) was added and the mixture was heated at reflux for 24 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100-1000 mg / L (Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The reaction mixture was transferred to a separating funnel and the product was extracted into 1 M NaHCCh (x2), and acidified with solid KHSO4, which resulted in a white precipitate. The mixture was transferred back into the separating funnel, extracted into EtOAc (x 2) and washed with water. The organic phase was dried (Na2SO4), filtered and evaporated to give benzoic acid as the sole product (0.432 g, 3.5 mmol, 75% yield); white solid.

[0229] 1H NMR (CDCh, 600 MHz) 5 12.97 (bs, 1 H, -COOH), 7.95-7.94 (m, 2H, Ar-H), 7.64-7.61 (m, 1 H, Ar-H), 7.51-7.49 (m, 2H, Ar-H);

[0230] IR: 3070, 2824, 2551 , 1678 (C=O), 1418, 1287, 929 cm’1.

[0231] B.4 Oxidation of an amine to an azoxy compound

[0232] Scheme 5: oxidation of aniline to azoxybenzene.

[0233] TMO2 (~2.5 % w / w H2O2, 34 g, 5 equiv.) was added to a flask containing aniline (0.485 g, 5.4 mmol, 1 equiv.) under a nitrogen atmosphere. Triisopropyl borate (B( / -PrO)3, 101 pL, 0.54 mmol, 0.1 equiv.) was added and the mixture was heated at reflux for 24 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100-1000 mg / L (Supelco, 1.10337.0001), which indicated a significant amount of

[0234] 55651538-1 M&C PG450913W0

[0235] 27 peroxide remained. The peroxide was quenched by addition of solid sodium bisulfite. The resultant heat spike was control with cooling in a water bath. The mixture was dried by addition of solid sodium sulfate (Na2SO4), filtered and evaporated. The residue was purified by automated flash chromatography using a gradient elution of 0-10% EtOAc in cyclohexane to give (E)-1 ,2-diphenyldiazene-1 -oxide (0.264 g, 1.3 mmol, 51 % yield) as a yellow oil.

[0236] The characterisation data obtained matched that found in the literature (Ke et al., Org. Lett., 2019, 21 , 4008; and Paris et a!., Green Chem., 2018, 20, 382);

[0237] 1H NMR (CDCI3, 600 MHz) 58.35-8.33 (m, 2H, Ar-H), 8.22-8.20 (m, 2H, Ar-H), 7.58-7.55 (m, 1 H, Ar-H), 7.53-7.49 (m, 4H, Ar-H), 7.43-7.40 (m, 1 H, Ar-H);

[0238] 13C NMR 5 148.4, 144.1 , 131.7, 129.7, 128.9, 128.8, 125.6, 122.4;

[0239] IR: 1472, 1436, 760, 680 cm’1.

[0240] B.5 Oxidation of a lactone to a di-carboxylic acid

[0241] Scheme 6: oxidation of caprolactone to 1 ,6-dicarboxylic acid.

[0242] Caprolactone (0.500 g, 5.09 mmol) was added to a 100 mL round-bottom pressure flask containing TMO2 (13.1 mL, 2.5% H2O2 w / w, 1.4 eq.), followed by the addition of 10 mol% B( / -PrO)3 (0.117mL, 0.51 mmol). The mixture was lowered into a preheated oil bath at 120 °C and heated at reflux for 18 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100-1000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The peroxide was quenched until minimal peroxide was detected in the organic layer (by peroxide strip). The organic layer was then filtered and evaporated, affording a crude mixture of colourless oil and white solid. A minimum amount of toluene (2 mL) was added to the crude mixture and left in the freezer overnight, which afforded a white solid in suspension. Then, the mixture was centrifuged at 3600 rpm for 5 minutes at 4 °C, the supernatant removed and the solid washed with fresh toluene. The product was isolated as a white solid (0.148 g, 0.10 mmol, 20% yield).

[0243] IR (ATR): 2949, 2918, 2876, 1683, 920 cm’1.

[0244] 55651538-1 M&C PG450913W0

[0245] 28

[0246] 1H NMR (600 MHz, DMSO-D6) 5 2.19 (m, 4H, CH2); 1.47 (m, 4H, CH2).

[0247] B.6 Epoxidation of an alkene

[0248] Scheme 7: epoxidation of 1 ,2-dodecene to 1 ,2-epoxydodecane.

[0249] The inventors have demonstrated at least three different experimental procedures in which an epoxidation reaction may be performed.

[0250] B.6.1 : (Open system) 1 ,2-Dodecene (0.66 mL, 2.97 mmol) was added to a 100 mL round bottom flask containing TMO2 (7.50 mL, 2.5% H2O2 w / w), followed by the addition of 10mol% B( / -PrO)3 (0.068 mL, 0.30 mmol). The mixture was lowered into a preheated oil bath at 112 °C (internal temperature) and heated at reflux for 18 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100- 1000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The peroxide was quenched by washing with water (2 x 30 mL) until no peroxide was detected in the organic layer (by peroxide strip). The organic layer was dried by addition of solid sodium sulfate (Na2SO4), filtered and evaporated. The residue was purified by automated flash chromatography (12 g column, flow rate: 20 mL / min) using a gradient elution of 0-5% EtOAc in cyclohexane to give 1 ,2-epoxydodecane (0.263 g, 1.42 mmol, 48% yield) as a colourless oil.

[0251] IR: 2924cm-1, 2854cm-1, 1466cm-1.

[0252] 1H NMR (600 MHz, CDCI3) 6 2.92-2.88 (m, 1 H, CH), 2.75 (dd, J = 5.0, 4.0 Hz, 1 H, CH2), 2.46 (dd, J = 5.0, 2.8 Hz, 1 H, CH2), 1 .55 - 1 .49 (m, 2H, CH2), 1 .45 (dd, J = 15.2, 7.8 Hz, 2H, CH2), 1.34 - 1.22 (m, 14H, CH2), 0.88 (t, J = 7.0 Hz, 3H, CH3).

[0253] B.6.2: (Closed pressure system) 1 ,2-Dodecene (0.66 mL, 2.97 mmol) was added to a 100 mL round-bottom pressure flask containing TMO2 (7.50 mL, 2.5% H2O2 w / w), followed by the addition of 5 mol% B( / -PrO)3 (0.034 mL, 0.15 mmol). The mixture was lowered into a preheated oil bath at 112 °C (internal temperature) and heated at reflux for 18 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (100-1000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The peroxide was quenched by washing with water (2 x 30mL) until no peroxide was detected in the organic layer (by peroxide strip). The organic layer was dried by addition of solid sodium sulfate (Na2SO4), filtered and

[0254] 55651538-1 M&C PG450913W0

[0255] 29 evaporated. The residue was purified by automated flash chromatography (12 g column, flow rate: 20 mL / min) using a gradient elution of 0-5% EtOAc in cyclohexane to give 1 ,2- epoxydodecane (0.246 g, 1.33 mmol, 45% yield) as a colourless oil.

[0256] IR(ATR): 2924cm-1, 2854cm-1, 1466cm-1.

[0257] 1H NMR (600 MHz, CDCI3) 5 2.92-2.88 (m, 1 H, CH), 2.75 (dd, J = 5.0, 4.0 Hz, 1 H, CH2), 2.46 (dd, J = 5.0, 2.8 Hz, 1 H, CH2), 1 .55 - 1 .49 (m, 2H, CH2), 1 .45 (dd, J = 15.2, 7.8 Hz, 2H, CH2), 1.34 - 1.22 (m, 14H, CH2), 0.88 (t, J = 7.0 Hz, 3H, CH3).

[0258] B.6.3: (Biphasic reaction) 1 ,2-Dodecene (0.6 6mL, 2.97 mmol) was added to a 100 mL round-bottom flask containing a biphasic mixture of 2,2,5,5-tetramethyltetrahydrofuran (TMO, 7.50 mL, 50.5 mmol) and 30% H2O2in water (1.53 mL, 14.85 mmol), followed by the addition of 5 mol% B( / -PrO)3 (0.034 mL, 0.15 mmol). The mixture was lowered into a preheated oil bath at 112 °C (internal temperature) and heated at reflux for 4 days. Following heating, the reaction mixture was cooled and the presence of peroxide was assessed using peroxide strip tests (100-1000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained in the organic phase (-1000 ppm). The reaction mixture was transferred to separating funnel and peroxide layer isolated (and quenched separately). The peroxide in the organic layer was quenched by washing with water (3 x 30mL) until no peroxide was detected in the organic layer (by peroxide strip). The organic layer was dried by addition of solid sodium sulfate (Na2SC>4), filtered and evaporated. The residue was purified by automated flash chromatography (12 g column, flow rate: 20 mL / min) using a gradient elution of 0-5% EtOAc, over 15mins, in cyclohexane to give 1 ,2-epoxydodecane (0.092 g, 0.50 mmol, 17% yield) as a colourless oil.

[0259] IR (ATR): 2922cm-1, 2853cm-1, 1465cm-1.

[0260] 1H NMR (600 MHz, CDCI3) 6 2.94-2.87 (m, 1 H, CH), 2.74 (m,1 H, CH2), 2.46 (dd, J = 5.1 , 2.8 Hz, 1 H, CH2), 1.50 - 1.37 (m, 2H, CH2), 1.50-1.37 (m, 2H, CH2), 1.34 - 1.22 (m, 14H, CH2), 0.88 (t, J = 7.0 Hz, 3H, CH3).

[0261] B.7 Oxidation of an alcohol to an aldehyde

[0262] Scheme 8: oxidation of benzyl alcohol to benzaldehyde.

[0263] 55651538-1 M&C PG450913W0

[0264] Benzyl alcohol (0.48 mL, 4.62 mmol) was added to a 100 mL round bottom flask containing TMO2 (22.2 g, 16.3 mmol, 2.5% H2O2 w / w), followed by the addition of 10 mol% B( / -PrO)3 (0.11 mL, 0.46 mmol). The mixture was lowered into a preheated oil bath at 112 °C (internal temperature) and heated at reflux for 16 h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (>5000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The reaction mixture was sampled and analysed by GCMS, confirming the formation of benzaldehyde in the crude mixture with a yield of 13%.

[0265] GCMS (El): Retention time = 5.66 min. m / z (%) = 106.1 [M]+(100)

[0266] B.8 Oxidation of an alkene to an aldehyde

[0267] Scheme 9: oxidation of styrene to benzaldehyde.

[0268] Styrene (0.55 mL, 4.80 mmol) was added to a 100 mL round bottom flask containing TMO2 (35.93 g, 26.4 mmol, 2.5% H2O2 w / w), followed by the addition of 10mol% B( / -PrO)3 (0.11 mL, 0.48 mmol). The mixture was lowered into a preheated oil bath at 112 °C (internal temperature) and heated at reflux for 16h. The presence of peroxide was assessed in the cooled reaction mixture using peroxide strip tests (2500-5000 mg / L, Supelco, 1.10337.0001), which indicated a significant amount of peroxide remained. The reaction mixture was sampled and analysed by GCMS, confirming the formation of benzaldehyde in the crude mixture with a yield of 15%.

[0269] GCMS (El): Retention time = 5.67 min. m / z (%) = 106.0 [M]+(100)

[0270] Although the present disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, the descriptions and examples should not be construed as limiting the scope of the disclosure. The disclosures of all patent and scientific literature cited herein are expressly incorporated herein in their entirety by reference.

[0271] 55651538-1

Claims

M&C PG450913W031CLAIMS1. A peroxide reagent, wherein the peroxide reagent comprises:(a) hydrogen peroxide; and(b) a cyclic ether; wherein the cyclic ether is of formula (I):wherein:R1, R2, R3, and R4are each independently selected from Ci-4alkyl and Ci-4haloalkyl;X and Y are each independently -CR5R6-; each R5and R6is independently selected from H, Ci-4alkyl, halo, and Ci-4haloalkyl; and n is 0, 1 , 2 or 3.

2. The peroxide reagent of claim 1 , wherein the cyclic ether is a cyclic ethereal solvent.

3. The peroxide reagent of claim 1 or 2, wherein the peroxide reagent consists of, or consists essentially of: (a) hydrogen peroxide; and (b) the cyclic ether.

4. The peroxide reagent of any one preceding claim, wherein R1, R2, R3, and R4are each independently selected from methyl, ethyl, and trifluoromethyl.

5. The peroxide reagent of any one preceding claim, wherein:(i) R1and R2are the same;(ii) R3and R4are the same; or(iii) R1, R2, R3, and R4are all the same.

6. The peroxide reagent of any one preceding claim, wherein R1, R2, R3, and R4are each selected from Ci-4alkyl, such as methyl.55651538-1M&C PG450913W0327. The peroxide reagent of any one preceding claim, wherein each R5and R6is independently selected from H, methyl, ethyl, fluoro, difluoromethyl, trifluoromethyl, perfluoroethyl.

8. The peroxide reagent of any one preceding claim, wherein each R5and R6is independently selected from H, methyl, and ethyl, optionally wherein each R5and R6is H.

9. The peroxide reagent of any one preceding claim, wherein n is 1 or 2.

10. The peroxide reagent of any one preceding claim, wherein the concentration of hydrogen peroxide in the peroxide reagent is from about 0.05% to about 25% w / w, from about 0.5% to about 10% w / w, or from about 1% to about 5% w / w, or from about 2% to about 4% w / w, or about 3% w / w.

11. The peroxide reagent of any one preceding claim, wherein the cyclic ether is of formula (la) or (lb):

12. The peroxide reagent of any one preceding claim, wherein the cyclic ether is of formula (la).

13. A method of preparing a peroxide reagent as defined in any one preceding claim, the method comprising contacting:(i) hydrogen peroxide; and(ii) a cyclic ether as defined in any one preceding claim.

14. The method of claim 13, wherein the method comprises contacting an aqueous solution of hydrogen peroxide with the cyclic ether, optionally wherein the concentration of hydrogen peroxide in the aqueous solution of hydrogen peroxide is from about 10% to about 60% w / v, or from about 20% to about 50% w / v, or about 30% w / v.55651538-1M&C PG450913W03315. The method of any one of claims 13-14, wherein the contacting is carried out for at least about 5 minutes, at least about 10 minutes or at least about 15 minutes.

16. The method of any one of claims 13-15, wherein, following the contacting step, the method further comprises the step of: separating an organic phase from an aqueous phase, wherein the separated organic phase comprises the peroxide reagent.

17. The method of claim 16, wherein the method further comprises the step of: drying the separated organic phase, such as with a drying agent, for example molecular sieves or a metal sulfate (e.g. sodium sulfate or magnesium sulfate).

18. Use of a peroxide reagent in cleaning, bleaching, sterilisation, or an oxidation reaction (e.g. of a compound), wherein the peroxide reagent is as defined in any one of claims 1-12.

19. The use of claim 18, wherein: the oxidation reaction is conducted in the peroxide reagent, optionally in the absence of any additional solvent; and / or the oxidation reaction is carried out under anhydrous conditions.

20. A method of oxidising a compound, comprising:(a) contacting the compound with a peroxide reagent as defined in any one of claims 1-12.

21. The method of claim 20, wherein the contacting is: carried out in the peroxide reagent, optionally in the absence of any additional solvent; and / or is carried out under anhydrous conditions.

22. The use of any one of claims 18-19, or the method of any one of claims 20-21, wherein the compound is an organic or an inorganic compound.

23. The use of any one of claims 18-19, or 22, or the method of any one of claims 20-22, wherein the oxidation reaction or the oxidising is:55651538-1M&C PG450913W034(a) a Baeyer-Villiger reaction;(b) an epoxidation reaction;(c) an oxidation of an imine to an oxaziridine;(d) an oxidation of a thioether to a sulfoxide;(e) an oxidation of an aldehyde to a carboxylic acid; or(f) an oxidation of an amine to an azoxy compound.

24. The use of any one of claims 22-23, or the method of any one of claims 20-23, further comprising contacting the compound and / or the peroxide reagent with a catalyst, optionally wherein the catalyst is a Lewis acid catalyst, further optionally selected from molybdenum trioxide, titanium tetraisopropoxide, boron triisopropoxide, and sodium tungstate.

25. A complex of:(a) hydrogen peroxide; and(b) a cyclic ether as defined in any one of claims 1-12.

26. A method of oxidising a compound, comprising:(a) contacting the compound with a mixture of (i) hydrogen peroxide and (ii) a cyclic ether as defined in any one of claims 1-12.

27. The method of claim 26, wherein the hydrogen peroxide and the cyclic ether form a peroxide reagent or a complex.

28. The method of claim 26 or 27, wherein the method is carried out in a biphasic system.

29. The method of any one of claims 26-28, wherein the hydrogen peroxide is an aqueous solution of hydrogen peroxide, optionally wherein the concentration of hydrogen peroxide in the aqueous solution of hydrogen peroxide is from about 10% to about 60% w / v, or from about 20% to about 50% w / v, or about 30% w / v.

30. The method of any one of claim 26-29, wherein the cyclic ether is of formula (la).55651538-1M&C PG450913W03531. The method of any one of claims 26-30, wherein the method is an epoxidation reaction, optionally wherein the compound is an alkene.55651538-1

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