GB1588870A - Peroxides and hydroperoxides - Google Patents

Description

(54) PEROXIDES AND HYDROPEROXIDES (71) We, INTEROX CHEMICALS LIMITED of Hanover House, 14 Hanover Square, London, W.l., a British company, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to the production of organic peroxides and hydroperoxides, and to novel organic peroxides and hydroperoxides.

A known method for preparing alkyl peroxides or hydroperoxides involves the nucleophilic substitution of a peroxide reagent at a carbon centre, according to the equation RAOOH + RBX' o R*OORB + HX' wherein RA represents H or alkyl, R6 represents alkyl, and X' represents OH, OSO2OH, OSO2Oalkyl, or OSO2Me. When R6 is a primary or secondary alkyl group, RBX' is usually a sulphate or a methanesulphonate and the reaction is usually carried out under basic conditions, but the peroxides formed are sensitive to base-catalysed decomposition so that yields are generally poor, particularly when RB is a secondary alkyl group. When R1 is a tertiary alkyl group, the reaction is normally carried out in the presence of concentrated sulphuric acid, and RsX' is an alcohol or an alkyl hydrogen sulphate. There is a tendency for the alcohol to be dehydrated and rearrangement of the hydroperoxide compound can occur, so that, for example, Et2(n-Pr)COOC(n-Pr)Et2 cannot be obtained by this route.

The present invention provides a process for preparing a compound which contains in the molecule a group of the formula (I) or (II).

COOH (I).

COOC COOC (II) which comprises reacting a compound which contains in the molecule a group of the formula (III), C-X (III) wherein X represents a chlorine, bromine, or iodine atom, with hydrogen peroxide and a silver salt other than AgX.

For convenience, the compound containing in the molecule a group of formula (III) will be referred to hereinafter as the "organic starting material", and the compound containing a group of formula (I) or (II) will be referred to as the "organic product". The organic product will be referred to as a hydroperoxide if it contains a group of formula (I) and as a peroxide if it contains a group of formula (it).

The reactions involved in the process according to the invention may be represented as -C-X + H > O2 + AgY -, -COOH + HY + AgX / (I) (111) (1) and 2 -C-X + H2O2+ 2AgY -COOC- + 2HY + 2AgX (2) (III) (11) where Y + X for any particular conversion performed.

We believe that reaction (2) occurs via the formation of an intermediate hydroperoxide in situ according to reaction (1) and that the hydroperoxide then reacts with further organic starting material. However, we do not intend to limit the scope of the present invention by this explanation of reaction (2).

Y in these equations may represent a fractional species where the silver sali is a salt of a dibasic or polybasic acid.

The reactions (1) and (2) take place with the combination of silver salt with the halogen from the organic starting material to form an insoluble silver halide. The reactive silver salt is more soluble than the silver halide formed, and preferably should have a rather high solubility in a liquid phase containing the organic starting material.

Side reactions such as CX + AgY - C + Y + AgX (3) and

are less likely to occur if Y is a rather poor nucleophile.

Preferably, the silver salt of a strong acid is employed, e.g. salts of appropriately substituted organic acids, such as fluoro or chloro substituted organic acids. Particularly preferably the salt is of an acid at least as strong as difluoroacetic acid. Especially preferred salts are silver trifluoroacetate, silver nitrate, silver tetrafluoroborate, and silver trifluoromethanesulphonate. In various experiments we have found that silver nitrate and silver trifluoroacetate when used in diethyl ether give roughly similar yields, by-products being formed predominantly by reaction (3), i.e. by substitution. Silver trifluoroacetate reacts more quickly than silver nitrate, however, possibly because it is more soluble in diethyl ether than is silver nitrate. Silver tetrafluoroborate has been found to give a reasonable yield, but by-products were formed predominantly by reaction (4), i.e.

by elimination. The route by which by-products are formed affects the way in which, and the ease with which, the product can be purified.

A combination of a reactive silver salt with a less reactive silver compound (e.g. Ag2O) may be used. Thus, net reactions (1) and (2) can be achieved, even for a not very reactive compound AgY, if there is present a certain amount of a reactive silver in salt AgY' (especially a silver salt which is more soluble in a liquid phase containing the organic starting material). The catalytic effect of the AgY' can be described formally by the scheme -C-X+ H202 + AgY H (III) COOH + HY' + AgX (1) (6, AgY + HY' o AgY' + HY (7; (6) + (7) = (1) and similarly for reaction (2).

It will be readily appreciated that if a single organic starting material containing in the molecule a single group of formula (III) is used, the corresponding hydroperoxide and/or the corresponding peroxide may be produced depending on the amounts of the reactants used, in particular on the ratio of moles of H202 to moles of (Ill). If a mixture of two different organic starting materials is used (these compounds not differing only in X), then of course one or more of two hydroperoxides and three peroxides may result; and so on.

An interesting case is where the organic starting material contains a plurality of halide groups in the molecule. Thus, for example, alkylene dihalides, e.g. 1,4diiodobutane, can be reacted with hydrogen peroxide to generate in situ a compound containing a halide and a hydroperoxide group which can further react intra- or inter-molecularly to form polymeric or cyclic peroxides. In general, the probability of cyclic peroxides being formed is greatest where the number of atoms in the ring to be formed is 5, 6, or 7.

The organic starting material usually contains from 1 to 25 carbon atoms, often from 1 to 12.

Conveniently, groups of formula (Ill) can be provided by any available alkyl halide or a mixture of such alkyl halides. Thus, suitable alkyl halides are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl halides including all isomers thereof. The alkyl halides can contain more than 10 carbon atoms if desired. It will be apparent that the alkyl moiety can be a straight chain or branched, and in secondary and tertiary alkyl moieties the chains extending from the carbon atom that is substituted by X can be the same or different as in, e.g. s- butyl, isopropyl, 1-ethyl-I -methylbutyl, 1,1 -dimethylisobutyl, and 1,1 -dipropylbutyl moieties.

In general, there are two trends apparent in the rate of reaction of alkyl halides with the hydrogen peroxide and the reactive silver salt. First, an alkyl iodide reacts faster than the corresponding alkyl bromide and much faster than the corresponding alkyl chloride. Secondly, and superimposed upon the first trend is the trend that, for any given halide, the tertiary alkyl halide reacts fastest, the secondary alkyl halide has an intermediate rate of reaction, and the primary alkyl halide is the least reactive. Thus, for butyl halides there are nine rates of reaction ranging from t-butyl iodide (which is the fastest) through s-butyl-iodide, t-butyl bromide, and the others to n-butyl chloride (which is the slowest). The relative rates of reaction are generally such that it is often preferable to employ the bromide or iodide instead of the chloride when it is desired to obtain a secondary or tertiary alkyl hydroperoxide or peroxide, and the iodide in preference to the others when seeking to obtain a primary alkyl hydroperoxide or peroxide. The benefit of selecting the more reactive reactants can be taken by using shorter reaction times to obtain the same throughput, or, where desired, using a lower reaction temperature.

Other suitable organic starting materials are aralkyl halides, that is to say compounds in which X is a substituent of an aliphatic carbon which is linked directly or through aliphatic carbon atoms to an aryl group, e.g. phenyl or naphthyl as in l-iodo-2-phenylethane or l-bromo-l.phenylethane.

Further suitable organic starting materials are cyclic compounds, for example cycloalkyl halides and cycloalkylene dihalides. Thus inter alia cyclohexyl halides, optionally substituted by one or more further alkyl groups such as a methyl or a tbutyl group, may be used.

The reaction is conveniently carried out in solution. The solvent should be substantially inert towards the hydrogen peroxide, and is preferably a good solvent for the hydrogen peroxide as well as for the organic starting material. Such a solvent is preferably free of hydroxyl groups, and acid or ester groups. The solvent is also, preferably, free of halide groups, for such a solvent could react instead of or in addition to the organic starting material, depending upon the relationship between the solvent and the selected organic starting material. Thus, where the organic starting material is, for example, a tertiary iodide, a primary alkyl chloride may be employed as solvent since the rate of reaction of a tertiary alkyl iodide is many times faster than that of a primary alkyl chloride. We prefer to use an ether as solvent, for example diethyl ether. It will be recognised that excess of an alkyl halide RX could be employed as solvent since the majority of such compounds are liquid at or around 0 C.

The hydrogen peroxide is usually employed as a concentrated aqueous solution; the greater is the concentration of this solution, the smaller is the amount of water which is present to compete with the hydrogen peroxide. The concentration by weight is preferably at least 30%, and more preferably at least 60%, hydrogen peroxide. Although in theory up to 100% hydrogen peroxide could be employed, in practice satisfactory results can be achieved when the hydrogen peroxide content is not more than 90%, conveniently in the range of 65% to 85%, all percentages being by weight.

Preferably, the hydrogen peroxide and the silver salt are present in excess so as to render the presence of reacted organic starting material in the resultant solution less likely. Also, by using a substantial excess of hydrogen peroxide, for example at least three times the theoretical stoichiometric amount, and by adding the organic starting material in small amounts to the hydrogen peroxide, rather than vice versa, the further reaction of the hydroperoxide formed with further organic starting material to form organic product containing groups of formula (II) can be reduced in extent. It should be noted that the organic starting material containing groups of formula (I) thus formed can be subsequently reacted with a different compound containing groups of formula (lit) to form an asymmetrical compound containing groups of formula (II).

A convenient temperature at which to carry out the reaction is from -10 to 10"C. It will be recognised that lower temperatures than this can be employed, at a penalty of decreased reaction rates which can be acceptable, e.g. for alkyl iodides and possibly alkyl bromides, but in general are not acceptable for the primary and secondary alkyl chlorides. In general the reaction is exothermic, so that continuous cooling of the reaction vessel is desirable. At temperatures in the range of -10 to 10 C, the reaction generally takes no more than a few seconds in the case of alkyl iodides or bromides when silver trifluoroacetate is used, but much longer for chlorides and increasingly longer as the temperature is lowered. Often one or two reactants are introduced progressively into the third, generally the organic starting material and silver salt into a solution of hydrogen peroxide, so that the overall reaction period selected within the range of I minute to 10 hours. The appropriate reaction period can be easily determined by experiment. It will be recognised that where the reaction period is short, e.g. less than 10 minutes, the process is particularly suitable to be carried out continuously.

The silver halide formed when the silver salt reacts with the other reactants is substantially insoluble, and can therefore be separated from a solution containing the organic product by standard apparatus for separating solids from liquids, e.g.

filters and centrifuges. It will be recognised that because silver is an expensive material, it is preferably recycled to the original silver salt, for example by reaction with aqueous sodium hydroxide to form silver oxide which can then be furhter reacted, if desired, with a strong acid to form the silver salt of that acid.

The solution containing the reaction product can be distilled, with the normal precautions required for handling an organic hydroperoxide or peroxide, to remove impurities such as hydrogen peroxide or the acid of the silver salt. Solutions of di(tertiary alkyl) peroxides can be treated with sodium hyroxide, and the solutions of other dialkyl peroxides and of alkyl hydroperoxides with sodium bicarbonate. Certain tertiary alkyl peroxides can be conveniently crystallised from a non-aqueous organic solvent, e.g. methanol, including bis(tripropylmethyl) peroxide and peroxides having a similar or slightly greater molecular weight.

Otherwise, purification of tertiary alkyl peroxides can generally be effected by passage of the solution through a chromatographic column containing alumina.

It will be recognised that the process according to this invention enables certain peroxides to be made which hitherto have not been made. In these peroxides, each alkyl moiety contains at least 8 carbon atoms in a tertiary alkyl group, each of the three chains radiating from the peroxide-substituted carbon atom containing at least 2 carbon atoms. Such peroxides include bis(diethyl(n-propyl)-methyl) peroxide, bis(tripropylmethyl) peroxide and analogous symmetrical or asymmetrical compounds in which the ethyl or propyl groups have been replaced by butyl, pentyl, or hexyl groups.

One feature of the reactions (1) and (2) above is that they often display a substantial degree of stereospecificity, with inversion of configuration at the carbon atom in group (III) in the manner expected for an 5N2 reaction. Therefore, they can be used for the production of organic products in a desired stereoisomeric form. Of course, the degree of stereospecificity achieved will depend on the usual factors which determine whether a reaction follows an SNI or 5N2 mechanism (see, for example, E S Gould, Mechanism and Structure in Organic Chemistry, Holt, Rinehart, and Winston (New York 1959)).

It has been already mentioned that it is possible to prepare compounds containing a group of formula (III) by a two-step procedure in which an organic product containing a group of formula (II) is prepared in accordance with the invention (reaction (I) above) in a first step and this organic product is reacted with a compound containing a group of formula (III) in a second step. Such a procedure is especially advantageous for the production of asymmetrical organic peroxides, where the use of reaction (2) according to the invention could result in a mixture of two symmetrical peroxides with the desired asymmetrical peroxide. We have found that the second step of such a procedure can be performed in a rather similar manner to the process of the invention; that is to say, a compound which contains in the molecule a group of the formula (II) can be prepared by reacting a compound which contains in the molecule a group of the formula (III), wherein X represents a chlorine, bromine, or iodine atom, with a compound containing in the molecule a group of the formula (I) and a silver salt. The reaction involved may be represented as -COOH + -C-X + AgY -* -COOC- + NY + / / / \ AgX (5) (I) (III) (II) For reaction (5), we choose the compound containing a group of the formula (III) and the silver salt in the same way as when we perform reactions (I) and (2).

The conditions in which we perform the reaction are also chosen in the same way, with the exception that rather different solvents are generally preferred, because of the generally higher solubility, compared with hydrogen peroxide, of compounds containing groups of formula (I) in less polar solvents. Thus, while an ether may be used as a solvent in reaction (5), we have found liquid hydrocarbons to be suitable, for example liquid alkanes such as pentane, hexane, heptane, or octane, arenes such as benzene, and alkyl-substituted arenes such as toluene and xylene.

Having described the invention in general terms, we shall describe specific embodiments by way of example only. Examples 1 to 11 illustrate the process of the invention. Examples 12 to 21 illustrate the performance of reaction (5) and thereby the manner in which products of reaction (1) may be used.

Examples 1--6 In Examples 1 to 6 alkyl hydroperoxides were prepared by dissolving the appropriate alkyl halide and up to 50% excess of aqueous hydrogen peroxide (85% by weight) over the theoretical amount in reaction (I) in diethyl ether, and the solutions were cooled to about 0 to 50C by contact with an ice bath. Small portions of particulate silver trifluoroacetate were then added to the solution with constant agitation, until a slight excess over the theoretical amount had been added.

Generally, reaction occurred almost instantaneously, as evidenced by change in the colour of the solid phase to yellow. The solution was then allowed to warm to room temperature, the silver halide formed in the reaction was filtered off, the trifluoroacetic acid and the excess hydrogen peroxide were removed by treatment with aqueous sodium bicarbonate and crude hydroperoxide was separated by solvent removal. The reagents used, products obtained and yields are summarised in Table I.

TABLE 1

Example Peroxide Reagents Yield (%) I n-C6H1OOH n-C6Hl31+H202 38 2 BuSOOH BuSBr+H,O, 42 3 Me2EtCOOH Me2EtCBr+H2O2 39 4 Me2PriCOOH Me2PriCBr+H2O2 40 5 Me2ButCOOH Me2BuBr+H2O2 45 6 PrOOH Pr3CBr+H2O2 60 Example 7.

In this Example, a similar method to that employed in Examples 1 to 6 was employed, employing as reagents I,l-dimethylpropyl bromide, hydrogen peroxide, and silver trifluoroacetate in a mole ratio of 2:1:2.1. Bis(l,l-dimethylpropyl) peroxide was isolated from the solution in a 30% yield. It will be noted that the molar ratio of bromide to hydrogen peroxide used was the stoichiometric ratio for reaction (2).

Example 8.

This Example illustrates the use of silver nitrate as AgY in reaction (I) above.

Powdered silver nitrate (1.80 g, 10.6 mmol) was added to a stirred solution of 2bromooctane (1.94 g, 10 mmol) and 84% hydrogen peroxide (1.64 g, 10 mmol) in diethy! ether. The mixture was stirred at room temperature for 48 hours, and then the silver bromide formed was filtered off. The filtrate was washed with aqueous sodium hydrogen carbonate and dried with MgSO4, and the solvent was removed on a rotary evaporator, leaving 1.60 g (65%) of crude 2-octyl hydroperoxide with a purity of 60% (by iodimetric titration). The i.r. and n.m.r. spectra showed the impurity to be 2-octyl nitrate.

Examples 9-11 In these Examples, an optically active bromide was converted to a hydroperoxide. The relation between optical rotation of the bromides used and that of the corresponding alcohols of the same configuration is known. Further, we know, from experiments in which the hydroperoxides are reduced (with retention of configuration), how the rotations of the hydroperoxides and the corresponding alcohols compare for the same configuration.

In Examples 9 and 10 the conversion was effected by the procedure of Examples 1 to 6, and in Example 11 by the procedure of Example 8.

The results are summarised in Table 2.

TABLE 2

Reaction occurs with inversion of configuration x & optical w Reaction and comparisons with alcohol (aD in brackets) purity of: * * H2O2 * * PhCHMe llliCHMe > PhCHMe PhCHMe 9 1 1 AgO2CCF3 | g 1 1.55/6.05 OH Br OOH OH =26% (-6.050) (-22.550) (+4.900) (+1.550) * * H2O2 * * C6H1HMe C H13CHMe C,,lll13CHMe C6H1HMe I I AgO2CCF3 I 10 OH Br OOH OH (-3.900) (-21.080! (+2.590) (+3.900) 100% * * H2O2 * * C6H13CHMe = C6H^3CHMe C H~CHMe C,,lI13CHMe - C6Ht3CHMe I AgNO I 11 OH Br OOH OH (6.600) (-35.640) (+4.390) (+6.620) 100% Examples 1221 In Examples 12 to 21 a similar procedure was adopted to that used in Examples I to 6, except that an alkyl hydroperoxide was used instead of hydrogen peroxide; that the reaction was carried out in pentane instead of diethyl ether; and that product solutions containing di(tertiary alkyl) peroxides were treated with aqueous sodium hydroxide, while solutions containing other alkyl peroxides were treated with aqueous sodium bicarbonate. The dialkyl peroxides produced were purified by distillation or by passage through a chromatographic column containing basic alumina except for Example 16, in which purification was recrystallisation from methanol. The results are summarised in Table 3. The products were characterised by elemental analyses, i.r. and 'H and 13C n.m.r. spectroscopy, and mass spectrometry.

TABLE 3

Example Peroxide Reagents Yield (%) 12 BunOOBut Bunl+ButOOH 50 13 #-C6H13OOn-C6H13 n-C6H13I+n-C6H13OOH 40 14 BuSOOBUt BuSBr+ButOOH 38 15 Bu OOBus BusBr+BusOOH 27 16 ButOOBut Butr+ButOOH 48 17 Me2EtCOOCEtMe2 Me2EtCBr+Me2EtCOOH 93 18 Me2EtCOOBut Me2EtCBr+ButOOH 66 19 Me2PriCOOCPriMe2 Me2PriCBr+Me2PriCOOH 60 20 Me2ButCOQCButMe2 Me2ButCBr+Me2BUtCOOH 58 21 Prn3COOCPrn Pr3nCBr+Pr3nflC3OOH 54 WHAT WE CLAIM IS: 1. A process for preparing a compound which contains in the molecule a group of the formula (I) or (II), COOH (I) -COOC- (11) which comprises reacting a compound which contains in the molecule a group of the formula (III), - C-X (III) wherein X represents a chlorine, bromine, or iodine atom, with hydrogen peroxide and a silver salt other than AgX.

2. A process as claimed in claim 1, wherein the silver salt is silver trifluoroacetate.

3. A process as claimed in claim or claim 2, which is performed in an ether as a solvent.

4. A process as claimed in claim 3, wherein the ether is diethyl ether.

5. A process as claimed in any one of claims I to 4, wherein the temperature of reaction is in the range from -10 C to 10 C.

6. A process as claimed in any one of claims 1 to 5, wherein the compound which contains in the molecule a group of the formula (III) is an alkyl halide having not more than 10 carbon atoms in the molecule.

7. A process as claimed in claim 6, wherein the starting material comprises n-C3Hl31, BusBr, Me2EtCBr, MezPrlCBr, Me2ButCBr, or Pr3CBr.

8. A process as claimed in any one of claims 1 to 6, wherein the compound which contains in the molecule a group of the formula (III) contains in the molecule two such groups, and the compound prepared contains in the molecule a group of the

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (24)

**WARNING** start of CLMS field may overlap end of DESC **. TABLE 3 Example Peroxide Reagents Yield (%) 12 BunOOBut Bunl+ButOOH 50 13 #-C6H13OOn-C6H13 n-C6H13I+n-C6H13OOH 40 14 BuSOOBUt BuSBr+ButOOH 38 15 Bu OOBus BusBr+BusOOH 27 16 ButOOBut Butr+ButOOH 48 17 Me2EtCOOCEtMe2 Me2EtCBr+Me2EtCOOH 93 18 Me2EtCOOBut Me2EtCBr+ButOOH 66 19 Me2PriCOOCPriMe2 Me2PriCBr+Me2PriCOOH 60 20 Me2ButCOQCButMe2 Me2ButCBr+Me2BUtCOOH 58 21 Prn3COOCPrn Pr3nCBr+Pr3nflC3OOH 54 WHAT WE CLAIM IS:

1. A process for preparing a compound which contains in the molecule a group of the formula (I) or (II), COOH (I) -COOC- (11) which comprises reacting a compound which contains in the molecule a group of the formula (III), - C-X (III) wherein X represents a chlorine, bromine, or iodine atom, with hydrogen peroxide and a silver salt other than AgX.

2. A process as claimed in claim 1, wherein the silver salt is silver trifluoroacetate.

3. A process as claimed in claim or claim 2, which is performed in an ether as a solvent.

4. A process as claimed in claim 3, wherein the ether is diethyl ether.

5. A process as claimed in any one of claims I to 4, wherein the temperature of reaction is in the range from -10 C to 10 C.

6. A process as claimed in any one of claims 1 to 5, wherein the compound which contains in the molecule a group of the formula (III) is an alkyl halide having not more than 10 carbon atoms in the molecule.

7. A process as claimed in claim 6, wherein the starting material comprises n-C3Hl31, BusBr, Me2EtCBr, MezPrlCBr, Me2ButCBr, or Pr3CBr.

8. A process as claimed in any one of claims 1 to 6, wherein the compound which contains in the molecule a group of the formula (III) contains in the molecule two such groups, and the compound prepared contains in the molecule a group of the

formula (II) within a group of the formula (it), (V), or (Vl).

9. A process as claimed in any one of claims I to 8, wherein the carbon atom in formula (III) is asymmetric, and the compound containing the group of formula (III) is not usedln ttie tbrm of a racemic mixture.

10. A process as claimed in any one of claims 1 to 9, wherein the compound which contains in the molecule a group of the formula (III) is 2-bromooctane.

I 1. A process as claimed in any one of claims I to 9, wherein the compound which contains in the molecule a group of the formula (III) is l-phenylethyl bromide.

12. A process as claimed in claim 1, wherein the silver salt is silver nitrate, silver tetrafluoroborate, or silver trifluoromethanesulphonate.

13. A process as claimed in claim 12, which has the feature specified in any one of, or each of any two or more of, claims 3 to 8.

14. A process as claimed in claim 12, which has the feature specified in any one of, or each of any two or more of, claims 3 to 11.

15. A process as claimed in claim I performed substantially as described in any one of Examples I to 6 herein.

16. A process as claimed in claim 1, performed substantially as described in Example 7 herein.

17. A process as claimed in claim 1, performed substantially as described in Example 8 herein.

18. A process as claimed in claim 1, performed substantially as described in either of Examples 9 or 10 herein.

19. A process as claimed in claim 1, performed substantially as described in Example 11 herein.

20. A compound which contains in the molecule a group of the formula (I) or (II) given in claim 1, whenever prepared by a process as claimed in any one of claims 1 to 19.

21. A compound of the general formula

wherein each of the substituents R, which may be the same or different, represents an alkyl group of at least two carbon atoms, and each moiety

contains at least 8 carbon atoms.

22. Me2PrlCOOCMe2Pr'

23. Me2Bu'COOCMe2But

24. Pr3nCOOCPr3n