Reactions of hydrogen peroxide with acetylacetone and 2- acetylcyclopentanone

Russian Chemical Bulletin, International Edition, Vol. 62, No. 10, pp. 2171—2190, October, 2013

2171

Reactions of hydrogen peroxide with acetylacetone and 2ꢀacetylcyclopentanone

V. L. Novikov and O. P. Shestak

G. B. Elyakov Pacific Institute of Bioorganic Chemistry, FarꢀEastern Branch of the Russian Academy of Sciences,

159 prosp. 100 let Vladivostoku, 690022 Vladivostok, Russian Federation.

Fax: +7 (423) 231 4050. Eꢀmail: shestak@piboc.dvo.ru

A reaction of acetylacetone with equimolar amount of concentrated aqueous H₂O₂in both

organic solvents (Bu^tOH, AcOH) and water at various temperatures gave the corresponding

3,5ꢀdihydroxyꢀ1,2ꢀdioxolanes with different configuration of stereogenic centers. In the presꢀ

ence of an excess of H₂O₂, 3,5ꢀdihydroxyꢀ1,2ꢀdioxolanes were converted to a mixture of

5ꢀhydroperoxyꢀ3ꢀhydroxyꢀ1,2ꢀdioxolanes and further to a mixture of dimeric 1,2ꢀdioxolanꢀ3ꢀ

ylperoxides. All the peroxides formed exist in solutions as equilibrium mixtures with the starting

reagents. A prolonged reflux of solutions of 3,5ꢀdihydroxyꢀ1,2ꢀdioxolanes in Bu^tOH in the

presence of a large excess of H₂O₂led to the skeletal rearrangements of the substrates to

a mixture of propionic acid and hydroxyacetone, which underwent further oxidative transforꢀ

mations. Unlike acetylacetone, 2ꢀacetylcyclopentanone reacted with H₂O₂in aqueous phase

or in solutions in Bu^tOH under thermodynamic or kinetic control with the formation of the

corresponding 5ꢀhydroperoxyꢀ3ꢀhydroxyꢀ1,2ꢀdioxolanes, rather than 3,5ꢀdihydroxyꢀ1,2ꢀdiꢀ

oxolanes. Thermodynamically controlled process in solution in AcOH gave a mixture of all four

possible hydroperoxyhydroxyꢀ1,2ꢀdioxolanes. These cyclic peroxides in solutions in Bu^tOH or

AcOH readily converted to a mixture of AcOH, glutaric, ꢀmethyladipic, and ꢀhydroxyꢀꢀ

methyladipic acids. An active ꢀhydroxylation of the substrate was observed upon reflux of

a solution of 2ꢀacetylcyclopentanone and H₂O₂in AcOH.

Key words: ꢀdiketones, acetylacetone, 2ꢀacetylcyclopentanone, hydrogen peroxide, therꢀ

mal oxidation, hydroxyꢀ and hydroperoxyꢀ1,2ꢀdioxolanes, di(1,2ꢀdioxolanꢀ3ꢀyl)peroxides, skelꢀ

etal rearrangement of 1,2ꢀdioxolanes.

Hydrogen peroxide and its complexes with various reꢀ

agents are widely used for the oxidative transformations of

ꢀdicarbonyl compounds, in the course of which the startꢀ

ing compound skeleton can be either retained or disinteꢀ

grated. One of the directions of oxidative transformation

proceeding without skeleton destruction is an ꢀhydroxyꢀ

lation of ꢀdicarbonyl compounds, leading to the preparaꢀ

tion of synthetically important products. ꢀHydroxyꢀꢀ

dicarbonyl group is a common structural unit of many

natural compounds and pharmaceutical agents.^1,22ꢀAlkylꢀ

substituted cyclohexaneꢀ1,3ꢀdiones readily undergo a diꢀ

rect ꢀhydroxylation upon treatment with a 30% solution

of H₂O₂in alkaline medium.³Cyclohexaneꢀ1,3ꢀdiones

unsubstituted at position 2, for example, dimedone, under

these conditions are converted to dimeric 1,3ꢀdiketones

containing a hydroxy group at position 2 of one of the

fragments.⁴It was also reported⁵an ꢀhydroxylation of

pentacyclic ꢀketoester upon treatment with a 85% soluꢀ

tion of H₂O₂in the presence of Bu^tOK. The presence of

such complexed agents as MeReO₃/H₂O₂(see Ref. 6) and

FeCl₃•6H₂O/H₂O₂(see Ref. 7) facilitates a direct ꢀhyꢀ

droxylation of ꢀdicarbonyl compounds, which proceeds

under mild conditions in high yields.

Depending on the ratio of reagents, the latter system

facilitates oxidative chlorination. Oxidative ꢀhalogenaꢀ

tion of ꢀdicarbonyl compounds can be also effected

with such systems of reagents as I₂/H₂O/H₂O₂,⁸

V₂O₅/H₂O₂/NH₄Br,⁹H₂O₂/KBr,¹⁰H₂O₂/HBr,¹¹and

TiCl₄(TiBr₄)/H₂O₂.¹²

An important direction of oxidative transformation of

ꢀdicarbonyl compounds upon treatment with hydrogen

peroxide is their conversion into cyclic peroxides. In the

last 20 years, such cyclic peroxides as tetroxanes, trioxanes,

and ozonides, became the objects of persistent interest

because of high antimalarial, antiproliferative, antimicoꢀ

bacterial, antifungal, and antitumor activity exhibiting by

various representatives of the indicated classes of comꢀ

pounds. To a considerable extent, this interest is also

caused by the fact that cyclic peroxides are widely met in

the nature and are produced by both plants (for example,

the well known antimalaria compound artemizinin¹³) and

animals (for example, the sponge metabolites diacarperꢀ

oxide and sigmosceptrellin B).¹⁴A rather broad review of

synthetic approaches to cyclic peroxides and the results of

analysis of their biological activity is given in the works.^15—18

The studies of reactivity of cyclic peroxides¹⁹and mechaꢀ

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2171—2190, October, 2013.

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

nisms of their biological effects, including theoretical studꢀ

ies,²⁰are still an actual problem.

diyl)dicyclopentanecarboxylic acid was first reported more

than 70 years ago.³²Later, it was shown that many aliꢀ

phatic 1,3ꢀdiketones, 2ꢀacylcyclanones, and cyclic 1,3ꢀdiꢀ

ketones undergo oxidative transformations with the skeleꢀ

ton disintegration upon treatment with H₂O₂. There are

described examples of oxidative transformations of aliꢀ

phatic ꢀdiketones in neutral,^24,25acidic,²⁵and alkaline²⁹

media, 2ꢀacylcyclanones with the ring size of from 5 to 13 carꢀ

bon atoms and various nature of acyl substituent (CHO,

COAlk, COAr, COOAlk, COOH) in neutral,^{25,26,30,31,33,34}

acidic,^30,31and alkaline^{4,26,29,30,34}media, as well as of

cyclohexaneꢀ1,3ꢀdiones in neutral²⁶and alkaline^4,26,29meꢀ

dia. The mechanisms of the oxidative transformations of

various 1,3ꢀdicarbonyl compounds upon treatment with

H₂O₂are studied slightly.

During our recent studies³⁵of the reactions of thermal

and photochemical oxidation of 2ꢀacetylcyclopentanone

with molecular oxygen, a question arose on a possibility of

ꢀhydroxylation of this ꢀdiketone in neutral or weakly

acidic medium upon treatment with hydrogen peroxide

formed in situ. There are no literature data on a possibility

of ꢀhydroxylation of ꢀdiketones under such conditions.

The purpose of the present work is to thoroughly study

thermal oxidation of acetylacetone and 2ꢀacetylcyclopenꢀ

tanone with a 30% hydrogen peroxide under various conꢀ

ditions in neutral and acidic media for analysis of the

mechanisms of the formation and further transformations

of the corresponding 3,5ꢀdialkylꢀ3,5ꢀdihydroxyꢀ1,2ꢀdiꢀ

oxolanes and to ascertain a possibility of ꢀhydroxylation

of ꢀdiketones mentioned upon treatment with H₂O₂unꢀ

der these conditions.

Recently, it was shown that the bridged 1,2,4,5ꢀtetroxꢀ

anes are readily formed from aliphatic 1,3ꢀdiketones and

some 2ꢀacylcyclanones (for example, from 2ꢀacetylcycloꢀ

hexanone) by their reaction with an excess of a 37% H₂O₂

in the presence of a large amount of a strong acid (H₂SO₄,

HClO₄, HBF₄or BF₃, phosphomolybdic, phosphotungꢀ

stic) at room or at reduced temperature.^{15—18,21,22}At eleꢀ

vated temperatures (80—120 C) in the mixture of H₂O₂,

an alcohol, and a strong acid, the intermediately formed

1,2,4,5ꢀtetroxanes are converted into the corresponding

carboxylic esters through a sequence of the acidꢀcatalyzed

rearrangements.²³Skeletal rearrangements were also freꢀ

quently observed earlier in the case of simpler cyclic perꢀ

oxides, viz., 3,5ꢀdialkylꢀ3,5ꢀdihydroxyꢀ1,2ꢀdioxolanes,

formed, as it was first suggested in the works,^24,25from

1,3ꢀdiketones by their reaction with hydrogen peroxide.

Establishing structure of the reaction products is compliꢀ

cated by the fact that the reaction of ꢀdicarbonyl comꢀ

pound with the equimolar amount of H₂O₂can lead to

two products with different configuration of stereogenic

centers, whereas in the presence of an excess of H₂O₂the

initially formed compounds can give more complicated

oxidation products, whose structure considerably depends

on the amount of hydrogen peroxide used. Thus, in Refs 25

and 26 the structures of the reaction products of acetylacꢀ

etone with H₂O₂were not established, whereas in the

work²⁷the conclusions about their structures were made

based only on the results of elemental analysis and in part

on the IR spectroscopic data. The structure of 1,2ꢀdiꢀ

oxolane obtained by the reaction of acetylacetone with

1

1 mole of H₂O₂, was established using only the H NMR

Results and Discussion

spectroscopic data.^28,29However, a low quality of the specꢀ

tra measured on spectrometers with operating frequency

of 60 MHz and some specific properties of the solvents

used in the spectra recording give the base for doubts in

the correctness of interpretation of these spectral data.

Under certain conditions (an organic solvent, elevated

temperature, the presence of an acid or a base), the initialꢀ

ly formed 3,5ꢀdialkylꢀ3,5ꢀdihydroxyꢀ1,2ꢀdioxolanes can

undergo skeletal rearrangements. In these cases, the oxiꢀ

dative transformations of ꢀdicarbonyl compounds upon

treatment with H₂O₂lead to the disintegration of the subꢀ

strate skeleton. Such transformations include a simultaꢀ

neous proceeding of the processes conventionally called

oxidative rearrangements and oxidative cleavages.^{24,25,29—31}

The products of these reactions are various monoꢀ and

dicarboxylic acids. The rearrangement and cleavage proꢀ

cesses of 1,2ꢀdioxolanes can proceed not only in acidic or

alkaline media, but also in neutral medium, probably, in

the presence of traces of acids.

Reactions with a 30% H₂O₂were studied in solutions

in both organic solvents and aqueous phase. Carrying out

the reactions in neutral Bu^tOH allowed us to observe the

dynamics of the oxidative conversions of these substrates.

Principal transformations of acetylacetone are given in

Scheme 1.

Under conditions described in the work²⁵(reflux of

a solution of reagents in Bu^tOH at the molar ratio 1 : H₂O₂=

= 1 : 1.25), acetylacetone 1 slowly reacted with the oxiꢀ

dant (Table 1), giving in the first step a tautomeric mixꢀ

ture of the openꢀchain hydroxyperoxide 2a with cyclic

peroxides 2b,c, the equilibrium in which was virtually comꢀ

pletely shifted to the right. Even after 16 h, the conversion

of the substrate did not exceed 90%. The yield of the mixꢀ

ture of poorly separable cyclic cisꢀ and transꢀperoxides (2b

and 2c, respectively) under these conditions reached 81%

(see Scheme 1). An increase in the reaction time to 22 h

led to the decrease in the yield of cyclic peroxides 2b,c

caused by their conversion into the cyclic hydroperoxyꢀ

peroxides 4a and 4b. The oxidation proceeded much faster

when the molar ratio of reactants was increased to 1 : 2.2.

Contraction of one of the rings in the tricyclic diꢀ

spiro[4.1.5.2]tetradecaneꢀ6,8ꢀdione upon treatment with

H₂O₂in solution in AcOH leading to 1,1´ꢀ(ethaneꢀ1,2ꢀ

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2173

Scheme 1

R = H (5a,b), OH (8a,b)

Already after reflux of the solution for 15 min, the converꢀ

sion of the substrate reached 58%, and the yield of the

mixture 2b,c was 68%. When the mixture was heated for

30 min, the yield of cyclic peroxides 2b,c gradually deꢀ

creased, whereas the yield of a mixture of poorly separable

cyclic hydroperoxyperoxides 4a,b increased. After reflux

for 5 h, the yield of the mixture 4a,b reached the maximum

(49%), after which a reverse process of gradual conversion

of hydroperoxyperoxides 4a,b into cyclic peroxides 2b,c

was observed. After 10 h, the yield of the mixture 2b,c was

52%, whereas that of the mixture 4a,b was only 21%.

The reaction progress of the oxidation of substrate 1

with hydrogen peroxide was monitored by ¹H NMR

spectroscopy of the aliquot samples of mixtures of

products.

A prolonged (51 h) reflux of a solution of acetylaceꢀ

tone and a 6ꢀfold excess of H₂O₂in Bu^tOH led to a comꢀ

plete conversion of the substrate into a complicated mixꢀ

ture of products, among which we identified acetic and

lactic (10) acids, Oꢀacyl derivative of lactic acid 11, the

product of cycloacylation of the latter 12, 3ꢀacetoxyꢀ3ꢀ

methylbutyric acid (13), ethylene glycol diꢀtertꢀbutyl ether

(14), and acetonylacetone (15).

In solution in AcOH, hydrogen peroxide oxidized

acetylacetone even at ~20 C (see Table 1). After 24 h at

the molar ratio substrate : H₂O₂= 1 : 1.25, the conversion

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

reached 51%. The yield of hydroperoxyperoxides 4a,b

(41%) exceeded the yield of peroxides 2b,c (30%). After

240 h, peroxides 2b,c were absent in the mixture of oxidaꢀ

tion products, whereas hydroperoxyperoxides 4a,b began

their transformation to dimeric peroxides 5a,b. After 576 h,

compounds 5a,b became the major reaction products, but

cyclic peroxides 2b,c were already found among them

formed in the process of the reverse conversion of comꢀ

pounds 5a,b and 4a,b.

An increase in the molar ratio substrate : H₂O₂to 1 : 2.2

(AcOH, 22 C) led to a considerable increase in the rate of

the reaction (see Table 1).

Unlike in solutions in Bu^tOH, the reaction of acetylꢀ

acetone with H₂O₂in water proceeded very fast and was

difficult to control. The results of our studies showed that

the conclusions made by the authors of the works^27—29

related to the formation of different oxidation products

of substrate 1 in aqueous phase have much proved to

be wrong.

Table 1. Conditions of thermal oxidation of acetylacetone (1)

with a 30% hydrogen peroxide in organic solvents and yields of

the products*

Thus, the reaction of substrate 1 with H₂O₂under conꢀ

ditions of the work²⁷(the molar ratio 1 and 30% H₂O₂was

1 : 1, ~20 C) already after 10 min led to a complete conꢀ

version of substrate 1 into a poorly separable mixture of

peroxides 2b,c containing considerable amount of a mixꢀ

ture of peroxides 4a,b (27% out of all the reaction prodꢀ

ucts, Table 2). Similar result was obtained in the reaction

of substrate 1 with 50% H₂O₂under conditions of the

work²⁸(the molar ratio 1 : H₂O₂= 1 : 1, 0 C, 4.5 h).

The ¹H NMR spectroscopic data (500 MHz, acetoneꢀd₆)

showed that the reaction of substrate 1 with a 30% H₂O₂

at the molar ratio 1 : 1 carried out under kinetic control

(–15 C, 20 h) led to the exclusive formation of transꢀ

peroxide 2c. If the reaction of substrate 1 with a 30% H₂O₂

is carried out with the molar ratio 1 : 3 under kinetic conꢀ

trol (–15 C, 120 h), the reaction product is a mixture of

transꢀ and cisꢀperoxides 2c and 2b (96 and 4%, respectively).

At the same time, carrying out this reaction at reduced

temperature under conditions described in the work²⁹(the

molar ratio 1 : 75% H₂O₂= 1 : 1, –10 C, 30 min) gave

a mixture of cisꢀ and transꢀperoxides 2b and 2c in the

ratio 1 : 5.7 (¹H NMR spectroscopic data (300 MHz,

acetoneꢀd₆)).

Contrary to the results obtained in the works,^27,28an

increase in the amount of H₂O₂to 2 mol (30% H₂O₂,

40 C, 0.5 h (see Ref. 27) or 50% H₂O₂, 0 C, 20 min, then

20 C, 96 h (see Ref. 28)) did not lead to the formation of

the mixture of peroxides 4a,b. Their percentage in this

case increases to 33% of the total weight of oxidation

products, but a mixture of peroxides 2b,c still is a predomꢀ

inant product (see Table 2). Peroxides 4a,b began to preꢀ

dominate in the mixture of reaction products at the molar

ratio of reagents 1 : 3 (30% H₂O₂, 50 C, 0.5 h).²⁷Conꢀ

trary to the results obtained in the work,²⁷di(hydroꢀ

peroxy)peroxide 7 under these conditions is formed in low

yield (~6%). An increase in the molar ratio of reagents to

1 : Н₂О₂

(mol.)

Solvent

T/C

/h Conversion

Products

(yield)

of substrate

%

1 : 1.25

Bu^tOH

83

3.5

7

16

22

46

75

90

95

2b,c (72)

2b,c (79)

2b,c (81)

2b,c (70),

4a,b (10)

2b,c (68),

4a,b (3)

1 : 2.2

Bu^tOH

83

0.25

58

63

85

90

95

85

0.5

1

2b,c (78),

4a,b (6)

2b,c (72),

4a,b (11)

2b,c (51),

4a,b (35)

2b,c (30),

4a,b (49)

2b,c (52),

4a,b (21),

10 (2)

2b,c (30),

4a,b (41)

4a,b (58),

5a,b (18)

2b,c (8),

4a,b (14),

5a,b (33)

2b,c (12),

4a,b (50),

5a,b (12)

4a,b (52),

5a,b (21)

4a,b (54),

5a,b (18)

3

5

10

1 : 1.25

AcOH

22

24

240

576

51

90

85

1 : 2.2

AcOH

22

24

94

1 : 2.2

AcOH

22

48

100

92

240

* Here and in Tables 2 and 5 are given yields of isolated comꢀ

pounds calculated on the reacted substrate.

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2175

Table 2. Conditions of thermal oxidation of acetylacetone (1)

with hydrogen peroxide in aqueous solution and yields of the

products

Even under kinetic control, the reaction of substrate 1

with a 30% H₂O₂in the presence of traces of conc. H₂SO₄

(the molar ratio of reagents 1 : 1, –15 C, 120 h) leads to

a predominant formation of dimeric peroxides 8a,b (see

Table 2). Lactic acid (10) was formed only in a trace

amount under these conditions.

It was reported earlier^27,28that a shortꢀtime heating

a solution of peroxides 4a,b in AcOH gave tetroxane 9. We

showed that keeping a solution of peroxides 4a,b in AcOH

at 75—80 C for 10—15 min led to compound 9, whereas

the conversion of the substrate did not exceed 5%. An

increase in the reaction time to 3.5 h results in the formaꢀ

tion of a complicated mixture of products, among which

acids 10 and 11 and acetonylacetone (15) predominate.

Besides compounds already indicated, di(hydroperoxy)ꢀ

peroxide 7 was also detected. The conversion of the subꢀ

strate was not complete and reached only ~75%.

The facts described above show that in each of the

cases studied with any molar ratio of acetylacetone and

hydrogen peroxide irrespective of the concentration of the

latter (30, 50, or 75%), the formation of a rather comꢀ

plicated mixture of reaction products was observed (see

Table 2). The only exception was the lowꢀtemperature

reaction of substrate 1 with a 30% H₂O₂with the molar

ratio 1 : 1.

This observation, as well as a tendency of some perꢀ

oxides to the formation of crystal hydrates and an unusual

behavior of compounds under consideration depending on

the nature of solvents used for their purification and specꢀ

troscopic studies make it difficult to prepare peroxides

given in Scheme 1 in the individual state and to characterꢀ

ize them. These circumstances also explain large discrepꢀ

ancies in the melting point values even for the most simple

cyclic peroxides 2b,c described in the works.^27—29

The structure of the major oxidation products of subꢀ

strate 1, i.e., compounds 2b,c, 4a,b, 5a,b, 7, 8a,b, and 9,

as well as that of the products of oxidative transformations

of peroxides 2b,c, i.e., compounds 10—15, was established

based on IR spectroscopic and ¹H and ¹³C NMR spectroꢀ

scopic data (Tables 3 and 4).

Conꢀ

1 : H₂O₂T/C

/h Conversion Products

tent of

(mol.)

of substrate

(yield)

Н₂О₂(%)

%

30

50

1 : 1

22

0

0.17

4.5

100

2b,c (71),

4a,b (25)

2b,c (73),

4a,b (21)

2c (98)

2b,c (98)

2b,c (65),

4a,b (31)

2b,c (63),

4a,b (30)

2b,c (22),

4a,b (67),

5a,b (5),

7 (6)

30

75

30

1 : 1

1 : 2

–15

–10

40

20

0.5

100

50

30

1 : 2

1 : 3

0

20

50

0.33

96

0.5

100

30

1 : 4

40

1

100

2b,c (24),

4a,b (70),

7 (2)

30

1 : 3

1 : 2

–15 120

100

2b,c (97)

4a (10),

8a,b (24),

10 (10),

12 (4),

30, traces

H₂SO₄

20

4

1.5

24

15 (20)

30, traces

H₂SO₄

1 : 1

–15 120

100

4a,b (12),

8a,b (22),

10 (0.5)

1 : 4 (30% H₂O₂, 40 C, 1 h) results in the increase in the

percentage of peroxides 4a,b in the mixture of reaction

products to 72%, whereas that of peroxide 7 decreases to 2%.

To sum up, carrying out the reactions of substrate 1

with H₂O₂with the molar ratios of reactants from 1 : 3 to

1 : 4 (30% H₂O₂, 40—50 C, 0.5—1 h) under thermoꢀ

dynamic control leads to a predominant formation of

a mixture of peroxides 4a,b, rather than peroxide 7 as it

was stated in the works.^27,28

Acid catalysis (conc. H₂SO₄) of the reaction of acetylꢀ

acetone with H₂O₂leads to very complicated mixtures of

products, in which dimeric peroxides of the type 8 preꢀ

dominate. Thus, the reaction of substrate 1 with a 30%

H₂O₂in the presence of traces of conc. H₂SO₄(the molar

ratio of reagents 1 : 2, 20 C, 1.5 h, then 4 C, 24 h) gives

a complicated mixture of products, in which dimeric perꢀ

oxides 8a,b compose more than a half of the total amount.

Under these conditions, the formation of the primary oxiꢀ

dation products 2b,c is accompanied by their active oxidaꢀ

tive transformation to the products of the nonꢀperoxide

nature, which is confirmed by the isolation of considerꢀ

able amounts of compounds 10, 12, and 15.

The splitting of signals for the protons of the CH₂units

in the ¹H NMR spectra of cyclic peroxides is an indicative

feature, allowing one to firmly assign these compounds to

cisꢀ or transꢀperoxides.

Chemical shift for the proton of the methylene group

located in ꢀregion of the fiveꢀmembered ring of the molꢀ

ecule of cisꢀperoxide 2b (see Scheme 1) is strongly affectꢀ

ed by two ꢀoriented Me groups, whereas two ꢀoriented

OH groups primarily affect chemical shift for the proton

located in ꢀregion. This is the reason that chemical shifts

for the CH₂protons considerably differ ( = 0.20 ppm)

in the ¹H NMR spectrum (CDCl₃) of cisꢀperoxide 2b (see

Table 3). At the same time, in transꢀperoxide 2c these

protons are placed symmetrically with respect to the OH

and Me groups (see Scheme 1) and due to the magnetic

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

Table 3. ¹H NMR spectroscopic data (500.13 MHz) for monomeric and dimeric peroxides^a

Compound

Solvent

 (J/Hz)

С(3)—Ме,

С(5)—Ме

Н_(4),

Н_(4)

С(3)—ОН,

С(5)—ОН

С(3)—ООН

С(5)—ООН

2 Н(6), 2 Н(7),

2 Н(8) (m, 6 Н)

cisꢀ2b

CDCl₃

1.60 (s, 6 H)

2.53 (d, 1 Н,

J = 12.6);

2.73 (d, 1 Н,

J = 12.6)

2.56 (d, 1 Н,

J = 12.6);

2.61 (d, 1 Н,

J = 12.6)

4.20 (br.s, 1 Н)

7.69 (br.s, 1 Н)

2.88 (br.s, 1 Н)

3.56 (br.s, 1 Н)

—

Acetoneꢀd₆

1.51 (s, 6 H)

—

transꢀ2с

cisꢀ4а

CDCl₃

Acetoneꢀd₆

CDCl₃

1.62 (s, 6 H)

1.51 (s, 6 H)

1.56 (s, 3 H)

1.63 (s, 3 H)

1.48 (s, 3 H)

1.59 (s, 3 H)

1.58 (s, 3 H)

1.67 (s, 3 H)

1.55 (s, 3 H)

1.60 (s, 3 H)

1.58 (s, 6 H)^b

1.65 (s, 6 H)^b

1.57 (s, 6 H)^b

1.72 (s, 6 H)^b

1.59 (s, 6 H)

2.73 (s, 2 H);

4.38 (br.s, 1 Н);

7.25 (br.s, 1 Н)

2.85 (br.s, 1 Н);

5.28 (br.s, 1 Н)

4.04 (br.s, 1 Н)

—

2.67 (s, 2 H)

2.66 (d, 1 Н,

J = 14.0);

2.81 (d, 1 Н,

J = 14.0)

2.58 (d, 1 Н,

J = 14.0);

2.66 (d, 1 Н,

J = 14.0)

2.65 (d, 1 Н,

J = 15.0);

2.72 (d, 1 Н,

J = 15.0)

2.66 (d, 1 Н,

J = 15.0);

2.70 (d, 1 Н,

J = 15.0)

2.69 (d, 2 Н,

J = 14.0)^b;

2.94 (d, 2 Н,

J = 14.0)^b

2.62 (d, 2 Н,

J = 14.0)^b;

2.71 (d, 2 Н,

J = 14.0)^b

8.84 (br.s, 1 Н)

Acetoneꢀd₆

CDCl₃

2.92 (br.s, 1 Н)

4.35 (br.s, 1 Н)

5.29 (br.s, 1 Н)

4.50 (br.s, 2 Н)^b

4.74 (br.s, 2 Н)^b

10.78 (br.s, 1 Н)

—

transꢀ4b

8.32 (br.s, 1 Н)

Acetoneꢀd₆

CDCl₃

10.94 (br.s, 1 Н)

cisꢀ5а

—

transꢀ5b

transꢀ7

CDCl₃

Acetoneꢀd₆

CDCl₃

2.69 (s, 2 H)

—

8.44 (br.s,

2 Н, С(3)OOH,

С(5)ООН)

1.54 (s, 6 H)

2.64 (s, 2 H)

11.29 (br.s,

—

2 Н, С(3)OOH,

С(5)ООН)

8.82 (br.s, 2 H)^b

—

cisꢀ8а

1.59 (s, 6 H)^b

1.66 (s, 6 H)^b

2.67 (d, 2 Н,

J = 10.3)^b;

2.96 (d, 2 Н,

J = 10.3)^b;

2.65 (d, 2 Н,

J = 13.0)^b;

2.77 (d, 2 Н,

J = 13.0)^b

2.99 (dd, 1 Н,

J = 2.8, J = 8.8)

2.93 (dd, 1 Н,

J = 3.4, J = 9.3)

—

transꢀ8b

synꢀcisꢀ36a

CDCl₃

1.62 (s, 6 H);^b

1.69 (s, 6 H)^b

—

8.32 (br.s, 2 H)^b

CDCl₃

1.54 (s, 3 H)

1.47 (s, 3 H)

4.36 (br.s, 1 Н)

5.07 (br.s, 1 Н)

8.56 (br.s, 1 Н)

10.64 (br.s, 1 Н)

1.65—2.50

1.60—2.45

Acetoneꢀd₆

(to be continued)

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2177

Table 3 (continued)

Compound

Solvent

 (J/Hz)

С(3)—Ме,

С(5)—Ме

Н_(4),

Н_(4)

С(3)—ОН,

С(5)—ОН

С(3)—ООН

С(5)—ООН

2 Н(6), 2 Н(7),

2 Н(8) (m, 6 Н)

antiꢀcisꢀ36b

synꢀcisꢀ36c

antiꢀcisꢀ36d

CDCl₃

Acetoneꢀd₆

CDCl₃

1.50 (s, 3 H)

1.42 (s, 3 H)

1.65 (s, 3 H)

1.57 (s, 3 H)

1.55 (s, 3 H)

1.46 (s, 3 H)

2.96 (t, 1 Н,

J = 8.8)

4.41 (br.s, 1 Н)

4.13 (br.s, 1 Н)

4.51 (br.s, 1 Н)

5.12 (br.s, 1 Н)

4.54 (br.s, 1 Н)

5.05 (br.s, 1 Н)

7.99 (br.s, 1 Н)

10.03 (br.s, 1 Н)

8.37 (br.s, 1 Н)

10.65 (br.s, 1 Н)

8.42 (br.s, 1 Н)

10.13 (br.s, 1 Н)

1.65—2.50

1.60—2.45

1.60—2.55

1.60—2.45

1.65—2.50

1.60—2.45

2.86 (dd, 1 Н,

J = 6.9, J = 9.3)

3.12 (dd, 1 Н,

J = 2.3, J = 8.8)

3.09 (dd, 1 Н,

J = 2.3, J = 8.3)

2.90 (dd, 1 Н,

J = 6.4, J = 9.3)

2.84 (t, 1 Н,

Acetoneꢀd₆

CDCl₃

Acetoneꢀd₆

J = 8.6)

^aNumbering of C atoms and the corresponding H atoms is given in the compound formulas in Schemes 1 and 3.

^bThe signals for the corresponding protons of the other ring of this compound have the same chemical shifts.

equivalency are found in the ¹H NMR spectrum as a sinꢀ

glet with intensity of 2 H.

2b,c exhibits only very weak signals for the protons of the

Me group of hydroperoxide 2a ( 1.75 (s, 3 H, C(4)Me)

and 2.28 (s, 3 H, COMe)). Their total integral intensity

does not exceed 1.5% from the total integral intensity of

the signals for the Me groups of peroxides 2b and 2c. The

signals for the protons of the CH₂group of hydroperꢀ

oxide 2a in the H NMR spectrum cannot be found beꢀ

cause of the overlap with the signals for the protons of the

CH₂groups of peroxides 2b and 2c. Similar pattern was

Peroxides 2b,c are the ring forms of hydroperoxide 2a

resulted from the attack by one molecule of H₂O₂on the

diketo or the enol form of substrate 1 (see Scheme 1). As it

was indicated above, the tautomeric equilibrium between

the chain form 2a and the ring forms 2b,c is virtually

completely shifted to the side of the ring forms. The

¹H NMR spectrum (CDCl₃) of a mixture of peroxides

1

Table 4. ¹³C NMR spectroscopic data (125.75 MHz) for monomeric and dimeric peroxides^a

Compound

Solvent



С(3)

C(4)

С(5)

С(6)

C(7)

C(8)

C(9)

cisꢀ2b

CDCl₃

Acetoneꢀd₆

CDCl₃

Acetoneꢀd₆

CDCl₃

Acetoneꢀd₆

CDCl₃

Acetoneꢀd₆

CDCl₃

Acetoneꢀd₆

CDCl₃

105.5

106.0

106.2

107.0

106.2

106.9

106.5

107.0

112.9^b

112.8^b

113.2

113.6

112.6^b

112.8^b

107.9

108.4

118.1

119.1

55.2

57.2

58.5

60.6

54.0

56.7

54.8

57.0

54.8^b

55.6^b

51.7

53.5

52.4^b

52.9^b

69.2

66.6

68.1

67.4

105.5

106.0

106.2

107.0

112.9

113.8

113.4

114.5

106.3^b

106.9^b

113.2

113.6

112.5^b

119.8

119.1

114.9

113.6

22.5

23.8

23.2

23.8

19.6

19.5

18.6

20.1

22.7^b

23.0^b

17.7

19.0

18.4^b

18.0^b

37.4

39.7

35.9

37.0

22.5

23.8

23.2

23.8

22.7

23.8

22.9

23.9

19.9^b

19.4^b

17.7

19.0

18.7^b

28.1

26.9

27.3

25.1

—

transꢀ2с

cisꢀ4а

transꢀ4b

cisꢀ5а

transꢀ5b

transꢀ7

cisꢀ8а

transꢀ8b

synꢀcisꢀ36a

antiꢀcisꢀ36b

synꢀcisꢀ36c

antiꢀcisꢀ36d

—

Acetoneꢀd₆

CDCl₃

27.7

28.9

28.0

30.3

24.9

24.1

18.8

15.2

CDCl₃

^aNumbering of C atoms in compounds is given in Schemes 1 and 3.

^bThe signals for the corresponding C atoms of the other ring of this compound have the same chemical shifts.

2178

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

also observed in the ¹H NMR spectra recorded in solution

in acetoneꢀd₆( 1.64 (s, 3 H, C(4)Me) and 2.24 (s, 3 H,

COMe)).

weak band (C=O) in the region 1716 cm^–1, which beꢀ

comes stronger in solution in CCl₄. Computer modeling

of the spatial structure of cyclic peroxides 2b and 2c showed

that in cisꢀperoxide 2b there is an intramolecular hydroꢀ

gen bond between the proton of one of the OH groups

and the oxygen atom of the other OH group, and the

distance between these oxygen atoms is 2.78 Å (the band

(OH) in the region of 3512 cm^–1of the IR spectrum

(CHCl₃)), whereas in transꢀperoxide 2c, this bond involves

one of the oxygen atoms of the peroxy group (the band

(OH) in the region of 3537 cm^–1of the IR spectrum),

and the distance between these oxygen atoms is 2.85 Å.

From this it follows that in solution in CHCl₃, cisꢀperoxꢀ

ide 2b is energetically slightly more favorable than transꢀ

peroxide 2c.

The presence of the ringꢀchain tautomerism in soluꢀ

tions of compound 2 in different organic solvents is conꢀ

firmed by the fact that the ratio of cisꢀ and transꢀperoxides

2b and 2c strongly depends on the nature of the solvent.

1

The H NMR spectroscopic data (300 MHz) in solution

in CDCl₃show that the ratio is 1.67 : 1, in acetoneꢀd₆it is

1 : 2.85, whereas in CD₃OD it is 1 : 4.7. The authors of the

works^28,29failed to correctly assign signals for the protons

of the Me and CH₂groups in the ¹H NMR spectra of cisꢀ

and transꢀperoxides 2b,c, which resulted in the erroneous

conclusion that in solutions in CDCl₃and CD₃OD, the

ratio 2b : 2c is the same and equal to 2 : 3,²⁸whereas in

solutions in acetoneꢀd₆and CD₃OD it is 1 : 5.7.²⁹Moreꢀ

over, the authors of the work²⁹assigned the signals for the

protons of the Me group of the enol ( 2.02 (s)) and the

diketo forms ( 2.20 (s)) of acetylacetone in solution in

CD₃OD to the protons of the CH₂groups of peroxides

2b,c. This confusion occurred because of the unusual specꢀ

tral pattern observed in solutions of peroxides 2b,c in

An interesting question is a possibility of a reliable

characterization of the 2b,c type cyclic peroxides by IR

spectroscopy. It is known that the (O—O) characteristic

bands in the IR spectra of aliphatic peroxides are observed

in the region 810—890 cm^–1and, as a rule, have small

intensity.^36,37In this region of the IR spectrum (MeCN)

of transꢀperoxide 2c, there are recorded two bands at

812 (intensity 0.14) and 864 cm^–1(0.33), whereas in the

IR spectrum (MeCN) of cisꢀperoxide 2b, three bands at

820 (0.20), 848 (0.29), and 883 (0.13) cm^–1. A theoretical

IR spectrum of transꢀperoxide 2c obtained on the B3LYP/

6ꢀ311++(2d,2p) level using a correction coefficient

1/1.023 contains three bands in this region: at 835 (0.60),

856 (0.10), and 874 cm^–1(0.01), with 81% of (O—O)

belonging to the band at 874 cm^–1with the intensity close

1

CD₃OD. According to the H NMR spectroscopic data

(300 MHz), a solution of 2b,c in CD₃OD contains 48% of

a mixture of the enol (82.5%) and the diketo forms (17.5%)

of acetylacetone. At the same time, in solution of 2b,c in

acetoneꢀd₆the signals for the two forms of acetylacetone

virtually were not found, whereas in solution in CDCl₃the

content of the enol (50%) and the diketo forms (50%) of

acetylacetone is 17%. These facts indicate that in soluꢀ

tions in CDCl₃and, especially, CD₃OD, the tautomeric

to zero and only 14% belong to the band at 856 cm^–1

.



equilibrium 2b,c

2a is shifted to the side of the nonꢀ

A theoretical IR spectrum of cisꢀperoxide 2b also contains

three bands in this region: at 834 (0.50), 844 (0.17), and

878 cm^ꢀ1(0.29), with 53% of (O—O) belonging to the

band at 878 cm^–1and 43% to the band at 844 cm^–1. The

patterns observed in the experimental IR spectra do not fit

with the theoretical predictions and, therefore, IR specꢀ

troscopy cannot be used for a reliable confirmation of the

presence of a cyclic peroxy group in the structure of comꢀ

pounds under consideration.



cyclic form 2a, whereas the latter dissociates to the startꢀ

ing reactant 1 and H₂O₂, after which the reaction reverts

toward formation of peroxides 2b,c. This conclusion can

be confirmed by consideration of the ¹H NMR spectra of

transꢀperoxide 2c obtained under kinetic control (–15 C).

The ¹H NMR spectroscopic data (300 MHz, acetoneꢀd₆)

of this compound do not show the presence of even traces

of cisꢀperoxide 2b and acetylacetone (1). However, upon

dissolution in CDCl₃, peroxide 2c converts to a mixture of

compounds containing 80% of a mixture of cisꢀ and transꢀ

peroxides 2b,c (the ratio 1.56 : 1), 17% of a mixture of the

enol and the keto forms of acetylacetone 1 (the ratio

2.33 : 1), and 3% of a mixture of cisꢀ and transꢀperoxides

4a,b (the ratio 1 : 4).

An approach used above for the assignment of comꢀ

pounds 2b and 2c to, respectively, cisꢀ and transꢀperoxides

was also used for establishing structure of cyclic monoꢀ

meric peroxides 4a and 4b and dimeric peroxides 5a and

1

5b (see Scheme 1). The H NMR spectra of cisꢀperoxide

4a in solution in both CDCl₃and acetoneꢀd₆show that

the difference in chemical shifts for the protons of the

CH₂group is ~2 times larger than that in the spectra of

transꢀperoxide 4b (see Table 3). The J_gemvalues for the

protons of the CH₂group in the ¹H NMR spectra of perꢀ

oxides 4a and 4b (14.0 and 14.7 Hz, respectively) unamꢀ

biguously evidence in favor of the cyclic structure of these

compounds, since in the spectra of the openꢀchain comꢀ

pounds such J_gemvalues, as a rule, are not observed. The

presence of the hydroperoxide group in the structure of

This is yet another evidence that it is quite difficult to

establish structure of cyclic peroxides, which have a tenꢀ

dency to various transformations, even when the modern

methods of the NMR spectroscopy are used.¹⁵

The presence of a small amount of the chain form 2a in

solutions of compound 2 in CDCl₃is also confirmed by

1

the presence in its H NMR spectrum of a very weak

signal for the proton of the hydroperoxy group ( 7.84 (s))

and the presence in its IR spectrum (CHCl₃) of a very

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2179

compounds 4a and 4b is confirmed by the presence of the

singlets for the protons of the OOH group in the ¹H NMR

spectra of peroxides 4a and 4b (respectively,  8.84 and

8.32 in the spectra recorded in solutions in CDCl₃, and

 10.78 and 10.94 in the spectra recorded in solutions in

acetoneꢀd₆).

According to the ¹H NMR spectroscopic data (CDCl₃),

the content of transꢀperoxide 4b in a poorly separable

mixture of peroxides 4a,b is 4.5 times higher than that of

cisꢀ peroxide 4a. The spectrum exhibits very weak signals

for the protons of the Me groups of the intermediate 2a

and weak signals for the protons of the Me groups of the

enol (30%) and the diketo forms (70%) of acetylacetone 1,

a total integral intensity of which does not exceed 2% of

the intensity for the signals of the Me groups of perꢀ

oxides 4a,b.

Conversely, cisꢀperoxide 4a considerably (96.5%) preꢀ

dominates in solution in acetoneꢀd₆, whereas the content

of transꢀperoxide 4b does not exceed 3.5%. The authors of

the work²⁸were wrong in drawing a conclusion that hyꢀ

droperoxide 4 exists in the transꢀform b in solution in

acetoneꢀd₆. As it has been already noted earlier for the

¹H NMR spectrum (acetoneꢀd₆) of peroxides 2b,c, the

spectrum of peroxides 4a,b exhibits very weak signals for

the protons of the Me group of the intermediate 2a, but no

signals for the protons of the Me group of acetylacetone

are virtually seen.

In the ¹H NMR spectrum (CDCl₃) of peroxide 5a with

a cisoid arrangement of the peroxide bridge at positions 3,

3´ and the OH groups at positions 5, 5´, the difference in

the chemical shifts for the protons of the CH₂groups is

equal to 0.25 ppm, whereas in the spectrum of peroxide 5b

with a transoid arrangement of these groups, it is equal to

0.09 ppm, that is in good agreement with the specific

features indicated earlier for the ¹H NMR spectra of comꢀ

pounds 2b,c and 4a,b.

A direction of the oxidation of peroxides 4a,b in soluꢀ

tion in Bu^tOH leading to the formation of carbocation 6

and its conversion into peroxide 7 is not virtually effected

(see Scheme 1).

Cyclic peroxides 2b,c are stable compounds and in

a dry state can be stored under ambient conditions in air

without decomposition for up to 2 months. Hydroperꢀ

oxides 4a,b are less stable on storage. The presence of the

peroxide groups in the structure of all the cyclic peroxides

isolated was confirmed by the positive results of the tests

with the system of reagents KI—AcOH—H₂O.

The most of the oxidation processes shown in Scheme 1

require acid catalysis. They can be initiated by traces of

mineral acids present in the commercial hydrogen perꢀ

oxide, then decomposition of cyclic peroxides leads to the

accumulation of organic acids in the reaction mixture

(Scheme 2).

The isolation of products 10—15 of the oxidative transꢀ

formations of peroxides 2b,c in solution in Bu^tOH gives us

a base to state that these processes proceed in two direcꢀ

tions. The first of them, the soꢀcalled oxidative rearrangeꢀ

ment, involves migration of the C(4)—C(5) bond of the

peroxides to the Me group at atom C(3), which results in

the formation of propionic (16) and acetic acids (see

Scheme 2). Acid 16 undergoes radical oxidation upon

treatment with hydroxyl radical generated in the thermal

decomposition of H₂O₂. Further, lactic acid (10) is parꢀ

tially acylated through the ionic or radical mechanism,

giving rise to Oꢀacyl derivative 11.^41,42The selfꢀacylation

of two molecules of acid 10 leads to the formation of cyclic

diester 12.^43,44The second direction, the soꢀcalled oxidaꢀ

tive cleavage, involves the migration of the C(4)—C(5)

bond to O(2) atom, resulting in the formation of acetic

acid and epoxyalcohol 17. The latter readily rearranges to

hydroxyacetone (18). The tendency of epoxyalcohols of

the type 17 to the rearrangements to ꢀhydroxyketones

was noted earlier.^5,6,29,45Under the reaction conditions,

hydroxyacetone (18) can be further oxidized to pyruvic

(ꢀoxopropionic) acid or decomposed upon treatment with

H₂O₂to acetic aldehyde (23) and formaldehyde (24). The

presence of the latter was confirmed by the presence in the

¹H NMR spectrum (CDCl₃) of a mixture of the rearꢀ

rangement products of peroxides 2b,c of the signal for the

proton of the CHO group at  8.02 and the signal for the C

atom of this group at  162.4 in the ¹³C NMR spectrum.

Both aldehydes can be oxidized to the corresponding acids.

In further reactions leading to the formation of more

complicated oxidation products, a key role is apparently

played by peroxides 4a,b.

It is known that the H₂O₂molecule adds to the CO

group of ketones, giving initially ꢀhydroxyhydroperꢀ

oxides, which further form bis(1ꢀhydroxyalkyl)peroxides

and more complicated peroxides through the further reacꢀ

tions with the carbonyl compound.³⁸The equilibrium mixꢀ

ture can contain linear and cyclic dimers, trimers, and

tetramers, which can bear or not free hydroxyꢀ and hydroꢀ

peroxy groups.³⁹For example, cyclohexanone mainly gives

a mixture of dimeric ,´ꢀdihydroxyꢀ, ꢀhydroperoxyꢀ´ꢀ

hydroxyꢀ, and ,´ꢀdi(hydroperoxy)peroxides, as well as

more complicated products.⁴⁰The formation of ꢀhyꢀ

droxyꢀ´ꢀhydroperoxyꢀ and ,´ꢀdi(hydroperoxy)dicycloꢀ

hexylperoxides from the molecule of the initially formed

,´ꢀdihydroxydicyclohexylperoxide indicates that the folꢀ

lowing processes take place: a protonation of the OH

groups of the latter, a sequential elimination of one or two

water molecules, and an attack by the molecule of oxidant

on the carbocations formed.

In our case, the role of oxidant can be played by perꢀ

oxides 4a,b. Their reaction with carbocations 3a,b is

a predominant direction of the reaction in solution in

Bu^tOH, which results in the formation of a poorly separꢀ

able mixture of dimeric peroxides 5a and 5b. The ¹H NMR

spectroscopy (CDCl₃) shows that transoid dimer 5b predoꢀ

minates in the mixture (the ratio 5b : 5a is 2 : 1).

2180

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

Scheme 2

Small amounts of acids mentioned above are alꢀ

ways detected in the mixtures of oxidation products. Thus,

weak signals of AcOH ( 2.09 (s, 3 H)), MeCOCOOH

( 2.35 (s, 3 H)), and MeCH₂COOH ( 1.15 (t, 3 H, Me,

J = 7.6 Hz) and 2.38 (q, 2 H, CH₂, J = 7.6 Hz)) are

(27) and hydroxyl radicals, whereas recombination of radꢀ

icals 27 gives ꢀdiketone 15.⁴⁶Homolysis of the MeCO—

CH₂OH bond in the intermediate 18 generates acetyl (28)

and hydroxymethyl (29) radicals. Recombination of two

radicals 29 gives ethylene glycol (30). The formation of

ethylene glycol by the recombination of radicals 29 generꢀ

ated through the homolysis of the H—C bond in methanol

was recently reported in the work.⁴⁷Etherification of

ethylene glycol (30) with Bu^tOH by ionic or radical mechꢀ

anism leads to the formation of ethylene glycol diꢀtertꢀ

butyl ether (14).^47,48

1

persistently present in the H NMR spectra (CDCl₃) of

these mixtures.

Under reaction conditions, the H—C bond of formic

acid (25) can undergo homolytic cleavage, giving carbꢀ

oxyl radical (26). The processes of radical disintegration

of the intermediate 18 and Bu^tOH (the solvent used to

carry out the reaction) lead to the formation of several

reaction products. Thus, homolysis of the CH₂—OH bond

in the intermediate 18 leads to the formation of acetonyl

Finally, homolysis of the H—C bond in Bu^tOH generꢀ

ates radical 31, recombination of which with radical 26

leads to the formation of ꢀhydroxyacid 32. Esterification

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2181

of the latter with acetic acid by ionic or radical mechaꢀ

nism should give Oꢀacyl derivative 13.⁴⁹

out the reaction under conditions of the work²⁵(the molar

ratio 33 : H₂O₂= 1 : 1.25, Bu^tOH, reflux, 16 h) showed

that when the conversion of the substrate reached 89%,

ꢀmethyladipic acid (37) was not the only reaction prodꢀ

uct, as it was reported earlier²⁵(Scheme 4). The second

major product of this reaction, glutaric acid (43), was

formed in solutions in Bu^tOH in the equal or slightly largꢀ

er amount than acid 37 (see Table 5), the third product

was acetic acid.

It is obvious that these acids are formed because of the

low stability of cyclic peroxides of the type 35 (see Scheme 3)

readily undergoing various skeletal rearrangements. The

reaction of diketone 33 with H₂O₂undoubtedly proceeds

through the formation of the intermediates 34a and 34b,

however, unlike in the reaction of diketone 1 with H₂O₂,

for which the formation of the intermediate 2a was detectꢀ

ed experimentally, such a detection of the intermediates

34a,b appears to be impossible because of a complicated

spectral pattern in the region of the signals for H(2) and

Me groups of these compounds.

The structure of the products 10—15 allows us to draw

a conclusion that the acidꢀcatalyzed rearrangements of

peroxides 2b,c follow the mechanisms different from the

mechanisms of a classic Baeyer—Villiger rearrangement,

since the latter in our case would lead to acetonyl acetate

(acetoxyacetone) and methyl acetoacetate as the reaction

products.

1

The H NMR spectrum (CDCl₃) of the mixture of

oxidation products of acetylacetone with H₂O₂in solution

in Bu^tOH exhibits weak signals for the protons of the Me

group and characteristic CH₂group of acetoxyacetone⁵⁰

( 2.21 (s, 6 H, 2 Me) and 4.66 (s, 2 H, CH₂)), but its

presence among reaction products is most likely results

from the Oꢀacylation of the intermediately formed hyꢀ

droxyacetone (18).

No products of ꢀhydroxylation of acetylacetone, i.e.

its oxidation with hydrogen peroxide at position 3, were

detected in neither of the cases studied.

Unlike acetylacetone (1), 2ꢀacetylcyclopentanone (33)

appeared to be much more active with respect to 30%

H₂O₂in solutions in organic solvents (Scheme 3).

In solution in Bu^tOH with the molar ratio substraꢀ

te : H₂O₂equal to 1 : 1.25, diketone 33 was oxidized at

~20 C for 5 days more than by half (Table 5). Carrying

In contrast to 3,5ꢀdihydroxyperoxides 2b,c, peroxides

of the type 35 are extremely readily converted to the correꢀ

sponding hydroperoxyhydroxyperoxides of the type 36, and

our attempts to detect the formation of compounds of the

type 35 from diketone 33 and H₂O₂in solution in Bu^tOH

at ~20 C or in aqueous phase at reduced temperature

Scheme 3

R¹= OH, R²= H (36a,b); R¹= H, R²= OH (36c,d)

2182

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

Scheme 4

failed. At the same time, peroxides of the type 36 appeared

to be more stable and were isolated in the individual state

(see Tables 3—5).

 10.64 and 10.23 for solutions in acetoneꢀd₆, as well as by

the presence in their ¹³C NMR spectra (acetoneꢀd₆) of the

signals in the region  119.7 and 119.1, which indicate the

presence in the structure of carbon atoms simultaneously

bonded to the peroxy group of the fiveꢀmembered ring and

the hydroperoxy group. Analysis of the ¹³C NMR spectroꢀ

scopic data for compounds with similar structure^51—53

showed that such carbon atoms, as a rule, resonate in the

region  111—122 of the spectrum. The location of

the OOH groups in the structures of compounds 36a,b

at atom C(5) unambiguously follows from the compariꢀ

son of their ¹³C NMR spectra with the spectra of similar

hydroperoxides 4a,b (see Table 4). As compared to the

OH group, the hydroperoxy group has much stronger

deshielding effect on the carbon atom nucleus, to which

Thus, the reaction of diketone 33 with H₂O₂in soluꢀ

tion in Bu^tOH (the molar ratio 33 : H₂O₂= 1 : 1.25, 22 C,

1 h) gave a mixture of peroxides 36a and 36b. The same

mixture of peroxides 36a and 36b was formed under kinetic

control (the molar ratio 33 : H₂O₂= 1 : 1.25, –15 C,

1

72 h). The H NMR spectroscopic data showed that the

ratio 36a : 36b changed from 1.85 : 1 in solution in CDCl₃

to 5.5 : 1 in solution in acetoneꢀd₆.

The fact that compounds 36a and 36b are hydroperꢀ

1

oxides was confirmed by the presence in their H NMR

spectra of the signals for the OOH groups, respectively, in

the region  8.39 and 8.60 for solutions in CDCl₃and

Table 5. Conditions of thermal oxidation of 2ꢀacetylcyclopentanone (33) with a 30% hydrogen peroxide in organic solvents and yields

of the products

1 : Н₂О₂

Solvent

T/C

/h

Conversion of substrate

Products (yield)

(mol.)

%

1 : 1.25

1 : 2.2

1 : 1.25

1 : 2.5

Bu^tOH

—

22

–15

22

83

22

1

72

24

120

384

16

10

24

240

17

3

8

80

21

52

78

89

100

72

100

90

100

36a,b (42), 37 (3)

36a,b (67), 37 (7)

43 (42), 37 (38), 49 (9), 46 (4)

43 (40), 37 (40), 49 (4), 46 (3), 51 (2), 52 (2)

43 (59), 37 (22), 49 (6), 46 (4), 51 (4)

43 (45), 37 (39), 46 (4), 51 (4)

43 (44), 37 (44), 46 (2), 51 (2), 52 (2)

43 (59), 37 (28), 49 (2), 46 (2)

Bu^tOH

AcOH

43 (67), 37 (30), 38 (2), 59 (0.5)

20

118

37 (32), 43 (26), 36c,d (22), 36a,b (17), 38 (3)

43 (62), 37 (18), 59 (6), 46 (4), 41 (3), 56 (2), 51 (1), 52 (1)

43 (60), 37 (14), 41 (11), 59 (9), 46 (2), 51 (2), 56 (1), 52 (1)

1 : 1.25

6

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2183

1

the OOH group is directly bonded, and, at the same time,

a considerable shielding effect on the carbon atom nucleꢀ

us of the Me group bonded to this carbon atom. The

¹³C chemical shifts of the signals for the Me groups of

hydroperoxides 36a and 36b in their spectra (acetoneꢀd₆,

 24.9 and 24.1, respectively) indicate that ꢀpositions

to the Me groups are occupied by the OH, rather than

OOH groups.

Assignment of stereochemistry for the fused rings in

compounds 36a,b is a separate problem. Bicyclo[3.3.0]ꢀ

octane systems are known to exist in both cisꢀ and transꢀ

form.⁵⁴transꢀIsomer is more strained than cisꢀisomer. Its

enthalpy is 6.0 kcal mol^–1higher than that of cisꢀisomer.

At the same time, their 2(3)ꢀoxa analogs form transꢀisoꢀ

mers much easier than their carbocyclic counterparts.

From this it follows that peroxides 36a,b can principally

exist as eight structures with different configuration of

stereogenic centers C(3), C(4), and C(5). Stereochemisꢀ

try of stereogenic centers C(4) and C(5) cannot be deterꢀ

mined based only on the ¹H and ¹³C NMR spectral data of

peroxides 36a,b.

exceed 7%. The H NMR spectroscopic data (500 MHz)

showed that the mixture in solution in CDCl₃contained

diketone 33 (23%, the ratio of the enol and the diketo

form was 3 : 2), acids 37 (31%), 38 (2%), 43 (28%), and

AcOH (12%), peroxides 36a (1%) and 36b (3%), whereas

in solution in acetoneꢀd₆(¹H NMR spectroscopic data) it

contained a mixture of diketone 33 (20%, the ratio of the

enol and the diketo form was 1 : 1.8), acids 37 (33%), 38

(2%), 43 (27%), and AcOH (11%), peroxides 36a (1%)

and 36b (6%).

Similar transformations also took place when peroxides

36a,b were stored in solutions at ~20 C for 15 days. In the

case of the solution of the mixture 36a,b in CDCl₃a comꢀ

plete conversion of peroxides to a mixture of diketone 33

and the acids mentioned above was observed, whereas

an incomplete conversion was observed in the case of

1

the solution in acetoneꢀd₆. The H NMR spectroscopy

(500 MHz) showed that the mixture contained diketone

33 (40%, the ratio of the enol and the diketo form was

1 : 2), acids 37 (16%), 38 (2%), 43 (7%), and AcOH

(14%), peroxides 36a (19% ) and 36b (2%).

To solve this problem, we carried out quantum chemiꢀ

cal calculations of enthalpy (H) for all the theoretically

possible steric structures of compounds 36a—d on the

B3LYP/6ꢀ311G(d) level. These calculations showed that

the H values of all the structures with transꢀfusion of the

rings are 11.6—16.4 kcal mol^–1higher than in the case of

the corresponding structures with cisꢀfusion. From this it

follows that hydroperoxides 36a,b have the synꢀcisꢀ and

antiꢀcisꢀconfiguration of stereogenic centers C(3), C(4),

and C(5). Besides, according to the calculations, comꢀ

pound 36a with the synꢀcisꢀconfiguration of stereogenic

centers (see Scheme 3) is energetically slightly more faꢀ

vorable than compound 36b with the antiꢀcisꢀconfiguraꢀ

tion of these centers (H = 0.67 kcal mol^–1).

The reaction of 1,3ꢀdiketone 33 with a 30% H₂O₂in

solution in AcOH (the molar ratio 33 : H₂O₂= 1 : 2.5,

20 C, 17 h) led to the formation of a complicated mixture

of products, in which acids 37 and 43 (>50%) and a mixꢀ

ture of hydroperoxides 36a—d were the major compoꢀ

nents. The content of hydroperoxides 36c,d with the OOH

group at atom C(3) was ~1.3 times higher than that of

hydroperoxides 36a,b with the OOH group at atom C(5)

(see Table 5). The structure of synꢀcisꢀperoxide 36c and

antiꢀcisꢀperoxide 36d was confirmed by ¹H and ¹³C NMR

spectroscopy (see Tables 3 and 4).

The main pathways for the formation of products of

the acidꢀcatalyzed rearrangements of peroxides of the type

35 are given in Schemes 4 and 5. Protonation of atom

O(1) of peroxides 35 results either in the oxidative rearꢀ

rangement involving migration of the C(4)—C(5) bond to

the Me group at atom C(3) and giving ꢀmethyladipic

acid (37) or the oxidative cleavage involving migration of

the C(4)—C(5) bond to atom O(2), that leads to the formaꢀ

Unlike hydroperoxides 4a,b, bicyclic hydroperoxides

36a,b appeared to be less stable on storage even at reduced

(4 C) temperature without exposure to light. After 48 days,

a dry mixture of peroxides 36a,b converted to a mixture of

products, in which a total content of peroxides did not

Scheme 5

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

Scheme 6

tion of glutaric acid (43) through the chain of conversions

given in Scheme 4. Isolation of acid 37 from the products

of oxidation of 1,3ꢀdiketone 33 with hydrogen peroxide in

neutral medium was reported earlier in the work;²⁵siꢀ

multaneous isolation of acids 37 (yield 41%), 43 (15%),

and 2ꢀmethylglutaric acid (11%) in the oxidation of

the substrate with H₂O₂in acidic medium was described

in the work.³⁰Since it is difficult to explain formation of

2ꢀmethylglutaric acid during reaction under consideration,

we reproduced the experiment under conditions described

in the work³⁰(the molar ratio diketone 33 and 30%

H₂O₂= 1 : 2.5, AcOH, 20 C, 17 h). We already discussed

above results of this experiment. Among reaction prodꢀ

ucts, besides predominant acids 37 and 43, we found

a small amount of ꢀhydroxyacid 38 formed, probably,

through the radical oxidation of acid 37 with hydrogen

peroxide. No other acids were found among the reaction

product (see Table 5).

Rearrangements of peroxides 35 protonated at atom

O(2) can take several pathways. Migration of the Me group

to atom C(4) with a simultaneous migration of the

C(4)—C(5) bond to atom O(1) leads to acid 37 (see

Scheme 4). Migration of the C(3)—C(4) bond to atom

C(6) with a simultaneous migration of the C(5)—C(6)

bond to atom O(1) should promote the formation of the

ring contraction product, viz., cyclobutanecarboxylic acid

(44), which is not actually observed (see Scheme 5). Fiꢀ

nally, migration of the C(3)—C(4) bond to atom O(1)

should lead to the formation of epoxyalcohol 45, easily

rearrangable to 2ꢀhydroxycyclopentanone (46).⁵⁵The

latter was in fact found among the reaction products.

ꢀHydroxyketone 46 under the reaction conditions can

undergo oxidation to ꢀdiketone 47 upon treatment with

O₂liberated upon thermal decomposition of H₂O₂. Earliꢀ

er, it was reported²⁵that reactions of 1,3ꢀdiketones with

H₂O₂upon heating in solution in Bu^tOH were accompaꢀ

nied by the liberation of a considerable amount of oxygen.

Oxidative cleavage of 1,2ꢀdiketone 47 upon treatment with

H₂O₂leads to the formation of acid 43.

Skeletal rearrangement of the dioxetane intermediate

42 can give not only glutaric acid (43), as it is shown in

Scheme 4, but also glutaric anhydride (49) (Scheme 6),

one of the minor products of the oxidation of the subꢀ

strate. Acid 37 exhibited a slight tendency to the reaction

with the H₂O₂molecule with the formation of ꢀhydroꢀ

peroxy acid 50 and propionic acid (16) (see Scheme 6).

Acid 50 under the reaction conditions underwent

conversion to ꢀbutyrolactone (51), which further was

partially converted to aceburic acid (52) by the reaction

with AcOH.⁵⁶

AcOH at ~20 C led to the appearance among reaction

products of a trace amount of 2ꢀhydroxyꢀ1,3ꢀdiketone 59,

the product of ꢀhydroxylation of the substrate. The proꢀ

cess of its formation was more efficient upon reflux of the

solution of reactants in AcOH (see Table 5). The set of the

oxidation products formed in this case was virtually the

same (excluding acid 37) as that obtained by us earlier in

the oxidation of substrate 33 with atmospheric oxygen.³⁵

Carrying out the reaction of substrate 33 with H₂O₂in

solution in AcOH upon reflux leads to the active formaꢀ

tion of reactive 5,6ꢀdioxoheptanoic acid (41). The latter

can react with H₂O₂to give acid 43 (see Scheme 4) and

anhydride 49 (see Scheme 6), as well as with peroxy acids

(for example, with peroxyacetic acid), that leads through

the intermediates 53 and 54 (Scheme 7) to a whole numꢀ

ber of oxidation products: glutaric acid (43), glutaric anꢀ

hydride (49), pyruvic acid (55), ꢀbutyrolactone (51), and

aceburic acid (52) (see Table 5).

A possible formation of peroxy acids (for example, perꢀ

oxyacetic acid) under these conditions is probably responꢀ

sible for the appearance of ꢀacetoxycyclopentanone (56)

among the reaction products (Scheme 8), which is formed

through the oxidation of substrate 33a by the Baeyer—

Villiger reaction. However, an alternative pathway of

its formation through the ionic or radical acylation of alꢀ

cohol 46 cannot be excluded. The presence under these

conditions of peroxy acids in the reaction medium proꢀ

vides a possibility for the formation of ꢀhydroxyꢀ1,3ꢀ

diketone 59 by the oxidation of substrate 33a not only with

oxygen,³⁵but also with a peroxy acid (a sequence of reacꢀ

tions 33a  57  58  59, see Scheme 8).

Oxidation of substrate 33 with H₂O₂in solutions in

acetic acid proceeded much more faster than in the case of

Bu^tOH, with glutaric acid (43) being a predominant reacꢀ

tion product. A prolonged standing (10 days) of a solution

of substrate 33 and H₂O₂(the molar ratio = 1 : 1.25) in

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2185

Scheme 7

Scheme 8

i. MeCOOOH.

Our studies showed that in solution in Bu^tOH, acetylꢀ

acetone reacts with hydrogen peroxide upon heating with

the formation of poorly separable mixtures of monomeric

cyclic cisꢀ and transꢀperoxides 2b,c and cisꢀ and transꢀ

hydroperoxyperoxides 4a,b, whereas in solution in acetic

acid at room temperature it gives, besides the mixtures of

compounds 2b,c and 4a,b, also a mixture of dimeric cyclic

cisꢀ and transꢀperoxides 5a,b, in which the monomeric

units are bound by a peroxide bridge.

When a large excess of H₂O₂and a prolonged reflux of

solutions in Bu^tOH are used, cyclic peroxides 2b,c activeꢀ

ly undergo acidꢀcatalyzed skeletal rearrangements, leadꢀ

ing to the formation of acetic, propionic, and pyruvic acꢀ

ids, as well as hydroxyacetone. Under these conditions,

propionic acid is involved into further conversions to

2ꢀacetoxypropionic acid and 3,6ꢀdimethylꢀ1,4ꢀdioxaneꢀ2,5ꢀ

dione, whereas hydroxyacetone is converted to hexaneꢀ

2,5ꢀdione, 3ꢀacetoxyꢀ3ꢀmethylbutyric acid, and ethylene

glycol diꢀtertꢀbutyl ether.

The reaction in aqueous phase under kinetic control

(–15 C) with the molar ratio acetylacetone and 30% H₂O₂

equal to 1 : 1 leads to the formation of the only oxidation

product, transꢀperoxide 2c, whereas in all the other cases

studied the product was a complicated mixture of peroxides,

which in solutions in organic solvents exist in the state of

equilibrium, which can be readily shifted to the side of the

starting reactants. Peroxides 2b,c and 4a,b are especially

inclined to this in solutions in CDCl₃and CD₃OD.

No formation of ꢀhydroxylation products of acetylꢀ

acetone was observed in its reaction with hydrogen peroxide.

Unlike acetylacetone, 2ꢀacetylcyclopentanone (33)

reacts with hydrogen peroxide in solution in tertꢀbutyl alꢀ

cohol even at ~20 C, but cyclic peroxides of the type 35

formed in this case were found to be low stable and readily

underwent acidꢀcatalyzed skeletal rearrangements with the

formation of acetic, glutaric, and ꢀmethyladipic acids as

predominant products.

The primary oxidation products of substrate 33, i.e.,

1,3ꢀperoxyꢀ1,3ꢀdiols, were not detected experimentally

because of their easy conversion to the corresponding

1ꢀhydroperoxyꢀ1,3ꢀperoxyꢀ3ꢀols, which were formed even

under kinetic control at –15 C. The minor products of

the skeletal rearrangements of cyclic peroxides are glutarꢀ

ic anhydride, 2ꢀhydroxycyclopentanone, ꢀbutyrolactone,

and ꢀacetoxybutyric (aceburic), and 2ꢀhydroxyꢀ2ꢀmethꢀ

yladipic acids. A prolonged (10 days) standing of a soluꢀ

tion of substrate 33 and H₂O₂in AcOH at ~20 C leads to

the appearance of a trace amount of 2ꢀacetylꢀ2ꢀhydroxyꢀ

cyclopentanone among reaction products, that , most likeꢀ

ly, results from the oxidation of the substrate not with

hydrogen peroxide, but with molecular oxygen liberated

upon a slow decomposition of hydrogen peroxide or even

with the molecule of peroxyacetic acid formed under these

conditions. It is known⁵⁷that a slow formation of peroxy

acids by the reaction of carboxylic acid with H₂O₂can

take place under fairly mild conditions.

Reflux of a solution of diketone 33 and H₂O₂in AcOH

leads to the active formation of 2ꢀacetylꢀ2ꢀhydroxycycloꢀ

pentanone, the product of ꢀhydroxylation of the subꢀ

strate. Under these conditions, simultaneously three agents

2186

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

Elution with the mixture of hexane—acetone (5 : 1) gave

a mixture of 3R(S),5S(R)ꢀ3,5ꢀdihydroxyꢀ3,5ꢀdimethylꢀ1,2ꢀdiꢀ

oxolane (2b) and 3R(S),5R(S)ꢀ3,5ꢀdihydroxyꢀ3,5ꢀdimethylꢀ1,2ꢀ

dioxolane (2c) (0.59 g, 52%) as colorless crystals, m.p. 72—74 C

(cf. Ref. 27: m.p. 52 C; cf. Ref. 28: m.p. 57—61C; cf. Ref. 29:

m.p. 82—84 C). A single crystallization from CHCl₃gave colꢀ

orless crystals, m.p. 81—84 C. IR of a mixture of peroxides 2b

and 2c, _max/cm^–1: 3680 (H₂O), 3584 (OH), 3537 (OH), 3512

(OH), 1618, 1603, 1438, 1420, 1383, 1361, 1305, 1285, 1241,

1227, 1190, 1173, 1129, 1079, 1047. MS of a mixture of peroxꢀ

ides 2b and 2c (EI, 70 eV), m/z (I_rel(%)): 153 [M + 1]⁺+ H₂O (5),

152 [M]⁺+ H₂O (37), 136 [M]⁺(4), 135 [M – 1]⁺(35), 109 (2),

107 (4), 100 (4), 92 (4), 85 (5), 77 (7), 60 (4), 46 (5), 45 (100),

44 (22), 36 (17), 32 (85). Found (%): C, 39.64; H, 8.01.

C₅H₁₀O₄•H₂O. Calculated (%): C, 39.47; H, 7.95. The ¹H and

¹³C NMR spectra are given in Tables 3 and 4, respectively.

Elution with the mixture of hexane—acetone (3 : 1) gave

a mixture of 3S(R),5R(S)ꢀ5ꢀhydroperoxyꢀ3ꢀhydroxyꢀ1,2ꢀdioxolane

(4a) and 3R(S),5R(S)ꢀ5ꢀhydroperoxyꢀ3ꢀhydroxyꢀ1,2ꢀdioxolane

(4b) (0.27 g, 21%) as colorless crystals, m.p. 107—110 C

(cf. Ref. 27: m.p. 110—112 C; cf. Ref. 28: m.p. 105 C). A single

crystallization from CHCl₃gave colorless crystals, m.p.

109—112 C. IR spectrum of the mixture of compounds 4a and

4b, _max/cm^–1: 3587 (OH), 3584 (OH), 3520 (OH), 3511 (OH),

3440 (OH), 3312 (OH), 3059, 3002, 2946, 2935, 2857, 1602,

1451, 1438, 1381, 1360, 1352, 1324, 1310, 1303, 1241, 1184,

1179, 1171, 1128, 1081, 1079. Found (%): C, 35.88; H, 7.24.

C₅H₁₀O₅•H₂O. Calculated (%): C, 35.72; H, 7.19. The ¹H and

¹³C NMR spectra are given in Tables 3 and 4, respectively.

Thermal oxidation of acetylacetone (1) with hydrogen perꢀ

oxide in solution in acetic acid. A solution of diketone 1 (1.00 g,

0.01 mol) and 30% H₂O₂(2.50 g, 0.022 mol) in AcOH (10 mL)

was stirred for 48 h at ~20 C. The solvent and the unreacted

H₂O₂were evaporated at reduced pressure, the residue was subꢀ

jected to chromatography on a column with SiO₂. Elution with

the mixture of hexane—acetone (3 : 1) gave a mixture of hydroꢀ

peroxides 4a,b (0.78 g, 52%), identical to those described above.

Elution with the mixture of hexane—acetone (2 : 1) gave

act as oxidants: hydrogen peroxide, molecular oxygen and,

apparently, peroxyacetic acid, that expectedly leads to the

formation of a complicated mixture of products, in which

glutaric acid predominates. The most probable pathway

for the formation of ꢀhydroxyꢀ1,3ꢀdiketone 59 is the reacꢀ

tion of substrate 33 with the molecule of peroxyacetic

acid. ꢀHydroxylation of 1,3ꢀdicarbonyl compounds upon

treatment with peroxy acids was reported earlier in a numꢀ

ber of works.^45,58,59

The results obtained allow us to draw a conclusion that

hydrogen peroxide does not promote ꢀhydroxylation of

enolizable 1,3ꢀdicarbonyl compounds under mild condiꢀ

tions in solutions in organic solvents of nonꢀacidic nature

and even in weak organic acids.

Experimental

Melting points were determined on a Boetius heating stage

and were not corrected. IR spectra were recorded on a Bruker

Vector 22 spectrophotometer in solution in CHCl₃. ¹H and

¹³C NMR spectra were recorded on Bruker Avance DPXꢀ300

(¹H, 300.13 MHz; ¹³C, 75.47 MHz) and Bruker Avance DRXꢀ500

spectrometers (¹H, 500.13 MHz; ¹³C, 125.75 MHz) in solutions

in CDCl₃, acetoneꢀd₆, and CD₃OD, using Me₄Si as an internal

standard. Mass spectra (EI) were obtained on an AMD 604 S

instrument (8 kW) with direct injection at ionization energies 15

and 70 eV. Elemental analysis was performed on a Flash EA1112

C,H,Nꢀanalyzer. Reaction progress and individuality of comꢀ

pounds obtained were monitored by TLC on Silufol UV 254

plate in the systems benzene—acetone (from 15 : 1 to 2 : 1). Inꢀ

dividual compounds were isolated from mixtures of reaction

products on columns with SiO₂(Alfa Aesar, 70—230 m), elutꢀ

ing with mixture of hexane with acetone.

Reagents were distilled before use: acetylacetone (b.p.

20

139—141 C at atmospheric pressure, [n]_D1.4517), 2ꢀacetylꢀ

cyclopentanone (b.p. 88—90 C at 15 Torr, [n]_D²⁰1.4900) (both

Lancaster, Great Britain), tertꢀbutyl alcohol (b.p. 82—83 C at

atmospheric pressure, [n]_D²⁰1.3869), and acetic acid (b.p. 118 C

at atmospheric pressure, [n]_D²⁰1.3723), as well as concentrated

(30%) aqueous solution of hydrogen peroxide.

a

mixture of 3R(S),3´R(S),5S(R),5´S(R)ꢀ5,5´ꢀdihydroxyꢀ

3,3´,5,5´ꢀtetramethyldi(1,2ꢀdioxolanꢀ3ꢀyl)peroxide (5a) and

3R(S),3´R(S),5R(S),5´R(S)ꢀ5,5´ꢀdihydroxyꢀ3,3´,5,5´ꢀtetraꢀ

methyldi(1,2ꢀdioxolanꢀ3ꢀyl)peroxide (5b) (0.28 g, 21%) as a colꢀ

orless dense oil. IR of a mixture of peroxides 5a and 5b,

Quantum chemical calculations were performed using the

GAUSSIAN 03 software.⁶⁰



_max/cm^–1: 3584 (OH), 3520 (OH), 3440 (OH), 3057, 3001,

Thermal oxidation of acetylacetone (1) with hydrogen perꢀ

oxide in solution in tertꢀbutyl alcohol. A solution of diketone 1

(1.00 g, 0.01 mol) and 30% H₂O₂(2.50 g, 0.022 mol) in Bu^tOH

(10 mL) was refluxed for 10 h. The solvent and the unreacted

H₂O₂were evaporated at reduced pressure, the residue was subꢀ

jected to chromatography on a column with SiO₂. Elution with

the mixture of hexane—acetone (25 : 1) gave the starting diꢀ

2945, 2933, 2855, 1602, 1451, 1438, 1381, 1360, 1303, 1241,

1179, 1126, 1079. Found (%): C, 45.28; H, 6.89. C₁₀H₁₈O₈.

Calculated (%): C, 45.11; H, 6.81. ¹H and ¹³C NMR spectra are

given in Tables 3 and 4, respectively.

Thermal oxidation of acetylacetone (1) with hydrogen perꢀ

oxide in aqueous solution. A mixture of diketone 1 (1.00 g,

0.01 mol) and 30% H₂O₂(3.75 g, 0.033 mol) was heated for

10 min at 50 C until a clear solution was obtained and kept for

0.5 h at ~20 C. Water and the unreacted H₂O₂were evaporated

at reduced pressure, the residue was subjected to chromatography

on a column with SiO₂.

Elution with the mixture of hexane—acetone (5 : 1) gave

a mixture (1.5 : 1) of cisꢀ and transꢀperoxides 2b and 2c (0.25 g,

22%), identical to those described above.

Elution with the mixture of hexane—acetone (4 : 1) gave

3R(S),5R(S)ꢀ3,5ꢀdi(hydroperoxy)ꢀ3,5ꢀdimethylꢀ1,2ꢀdioxolane

(7) (0.099 g, 6%) as a colorless dense oil. IR, _max/cm^–1: 3391

ketone 1 (0.15 g, 15%) as a colorless light liquid. IR, _max/cm^–1

:

3380—2200 (OH), 1729 (C=O), 1707 (C=O), 1618 (C=O,

C=C), 1601 (C=O, C=C), 1522, 1458, 1421, 1361, 1300, 1241,

1212, 1173. ¹H NMR (CDCl₃),  of diketo form 1a: 2.22 (s, 6 H,

2 COMe); 3.57 (s, 2 H, CH₂). ¹³C NMR (CDCl₃),  of diketo

form 1a: 30.8 (C(1), C(5)); 58.6 (C(3)); 201.9 (C(2), C(4)).

¹H NMR (CDCl₃),  of enol form 1b: 2.03 (s, 6 H, 2 Me); 5.48

(s, 1 H, H(3)); 15.43 (br.s, 1 H, OH). ¹³C NMR (CDCl₃),

 of enol form 1b: 24.8 (C(1), C(5)); 100.4 (C(3)); 191.1

(C(2), (C(4)).

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2187

(OH), 3057, 2921, 2860, 1602, 1441, 1431, 1374, 1362, 1349,

1317, 1307, 1301, 1229, 1176, 1172, 1118, 1074, 1067. The ¹H

and ¹³C NMR spectra are given in Tables 3 and 4, respectively.

Elution with the mixture of hexane—acetone (3 : 1) gave

a mixture (1 : 8) of cisꢀ and transꢀperoxides 4a and 4b (0.86 g,

67%), identical to those described above.

Elution with the mixture of hexane—acetone (2 : 1) gave

a mixture (1 : 1) of cisꢀ and transꢀperoxides 5a and 5b (0.067 g,

5%), identical to those described above.

Thermal oxidation of acetylacetone (1) with hydrogen perꢀ

oxide in aqueous solution catalyzed by a mineral acid. A mixture

of diketone 1 (1.00 g, 0.01 mol) and 30% H₂O₂(2.50 g, 0.022 mol)

containing conc. H₂SO₄(0.010 g) was kept for 1.5 h at ~20 C

and another 24 h at 4 C. Sodium hydrogen carbonate (0.018 g))

was added to the mixture, water and the unreacted H₂O₂were

evaporated at reduced pressure, the residue was subjected to

chromatography on a column with SiO₂.

CH₂). ¹³C NMR (75.5 MHz, CDCl₃), : 11.0 (C(8), C(9)); 50.9

(C(7)); 110.2 (C(1), C(4)). ¹³C NMR (75.5 MHz, acetoneꢀd₆),

: 11.4 (C(8), C(9)); 51.9 (C(7)); 109.9 (C(1), C(4)).

Thermal oxidation of acetylacetone (1) with an excess of hyꢀ

drogen peroxide in solution in tertꢀbutyl alcohol upon reflux.

A solution of diketone 1 (2.00 g, 0.02 mol) and 30% H₂O₂(2.50 g,

0.022 mol) in Bu^tOH (25 mL) was refluxed for 15 h, followed by

addition of 30% H₂O₂(2.50 g, 0.022 mol) and reflux for another

15 h. Then, another portion of 30% H₂O₂(2.50 g, 0.022 mol)

was added, and the mixture was refluxed for 21 h. The solvent

and the unreacted H₂O₂were evaporated at reduced pressure,

the residue was subjected to chromatography on a column with

SiO₂. Elution with the mixture of hexane—acetone (25 : 1) gave

1,2ꢀdiꢀtertꢀbutoxyethane (ethylene glycol diꢀtertꢀbutyl ether) (14)

(0.28 g, 16%) as a colorless clear liquid, [n]_D²⁰1.4162. ¹H NMR

(CDCl₃), : 1.23 (s, 18 H, 6 Me); 3.44 (s, 4 H, 2 CH₂). ¹³C NMR

(CDCl₃), : 26.0 (Me); 71.3 (CH₂); 76.6 (C—O).

Elution with the mixture of hexane—acetone (20 : 1) gave

hexaneꢀ2,5ꢀdione (15) (0.47 g, 20%) as a colorless clear liquid,

[n]_D²⁰1.4258. IR, _max/cm^–1: 1717 (C=O). ¹H NMR (CDCl₃),

: 2.21 (s, 6 H, 2 Me); 2.74 (s, 4 H, 2 CH₂). ¹³C NMR (CDCl₃),

: 29.8 (Me); 37.0 (CH₂); 207.4 (C=O).

Elution with the mixture of hexane—acetone (15 : 1) gave

3,6ꢀdimethylꢀ1,4ꢀdioxaneꢀ2,5ꢀdione (12) (0.057 g, 4%) as colorꢀ

less crystals, m.p. 124—126 C (cf. Ref. 43: m.p. 126—127 C;

cf. Ref. 44: m.p. 89—90 C). IR, _max/cm^–1: 1765 (C=O), 1247,

1109. ¹H NMR (CDCl₃), : 1.58 (d, 6 H, 2 Me, J = 7.1 Hz); 5.26

(q, 2 H, H(3), H(6), J = 7.1 Hz). ¹³C NMR (CDCl₃), : 20.7

(Me); 67.9 (CH); 160.2 (C=O). Found (%): C, 40.19; H, 6.81.

C₄H₈O₄. Calculated (%): C, 40.00; H, 6.71.

Elution with the mixture of hexane—acetone (20 : 1) gave

hexaneꢀ2,5ꢀdione (15) (0.14 g, 6%), identical to that described

above.

Elution with the mixture of hexane—acetone (15 : 1) gave

3,6ꢀdimethylꢀ1,4ꢀdioxaneꢀ2,5ꢀdione (12) (0.022 g, 2%), identiꢀ

cal to that described above.

Elution with the mixture of hexane—acetone (8 : 1) gave

3ꢀacetoxyꢀ3ꢀmethylbutanoic acid (13) (0.42 g, 24%) as a dense

oil. IR, _max/cm^–1: 3430—2400 (COOH), 3115, 3016, 2983,

2940, 1728 (C=O), 1714 (C=O), 1472, 1443, 1413, 1371, 1254,

1176, 1131, 1021. ¹H NMR (CDCl₃), : 1.55 (s, 6 H, 2 Me); 1.99

(s, 3 H, OCOMe); 2.94 (s, 2 H, CH₂); 9.63 (br.s, 1 H, COOH).

¹³C NMR (CDCl₃), : 22.2 (OCOMe); 26.6 (Me); 43.8 (CH₂);

175.9 (COOH). MS (EI, 70 eV), m/z (I_rel(%)): 161 [M + 1]⁺(1),

Elution with the mixture of hexane—acetone (4 : 1) gave

2ꢀhydroxypropionic (lactic) acid (10) (0.18 g, 10%) as a colorless

109 (3), 103 (13), 101 [M⁺

– CH₂COOH] (16), 100

clear liquid, [n]_D1.4265. IR, _max/cm^–1: 3598 (OH), 3552

[M⁺– AcOH] (41), 85 (27), 83 (7), 82 (13), 72 (8), 61 (10),

59 (53), 57 (6), 55 (9), 45 (3), 44 (4), 43 (100).

20

(OH), 3515 (OH), 3470—2220 (COOH), 1747 (C=O), 1718

(C=O), 1458, 1379, 1265, 1192, 1128, 1091, 1039. ¹H NMR

(CDCl₃), : 1.47 (d, 3 H, Me, J = 7.1 Hz); 4.35 (q, 1 H, H(2),

J = 7.1 Hz); 6.30 (br.s, 1 H, OH); 9.06 (br.s, 1 H, COOH).

¹³C NMR (CDCl₃), : 20.5 (Me); 66.9 (CH); 180.0 (COOH).

Elution with the mixture of hexane—acetone (3 : 1) gave cisꢀ

peroxide 4a (0.13 g, 10%), identical to that described above.

Elution with the mixture of hexane—acetone (2 : 1) gave

a mixture (1.5 : 1) of 3R(S),3´R(S),5S(R),5´S(R)ꢀ5,5´ꢀdi(hydroꢀ

peroxy)ꢀ3,3´ꢀdimethyldi(1,2ꢀdioxolanꢀ3ꢀyl)peroxide (8a) and

3R(S),3´R(S),5R(S),5´R(S)ꢀ5,5´ꢀdi(hydroperoxy)ꢀ3,3´ꢀdimethꢀ

yldi(1,2ꢀdioxolanꢀ3ꢀyl)peroxide (8b) (0.71 g, 24%) as a dense oil.

IR of a mixture of peroxides 8a and 8b, _max/cm^–1: 3306 (OH),

3054, 2999, 2948, 2932, 2847, 1602, 1450, 1431, 1379, 1350,

1325, 1308, 1240, 1183, 1170, 1126, 1082. Found (%): C, 40.39;

H, 6.02. C₁₀H₁₈O₁₀. Calculated (%): C, 40.27; H, 6.08. The ¹H

and ¹³C NMR spectra are given in Tables 3 and 4, respectively.

Cyclodehydration of a mixture of peroxides 4a,b upon treatꢀ

ment with acetic acid. A solution of the mixture of peroxides 4a,b

(0.15 g, 0.01 mol) in AcOH (2 mL) was kept for 15 min at

75—80 C. The solvent was evaporated at reduced pressure, the

residue was subjected to chromatography on a column with SiO₂.

Elution with the mixture of hexane—acetone (15 : 1) gave

1,4ꢀdimethylꢀ2,3,5,6ꢀtetraoxabicyclo[2.2.1]heptane (9) (0.007 g,

5%) as colorless crystals, m.p. 122—124 C (cf. Ref. 27: m.p.

123 C; cf. Ref. 28: m.p. 125—126 C). ¹H NMR (300 MHz,

CDCl₃), : 1.67 (s, 6 H, 2 Me); 2.74 (s, 2 H, CH₂). ¹H NMR

(300 MHz, acetoneꢀd₆), : 1.60 (s, 6 H, 2 Me); 2.70 (s, 2 H,

Elution with the mixture of hexane—acetone (6 : 1) gave

2ꢀacetoxypropionic acid (11) (0.13 g, 5%) as colorless crystals,

m.p. 55—58 C (cf. Ref. 41: m.p. 57—60 C). IR, _max/cm^–1

:

3420—2380 (COOH), 1726 (C=O), 1711 (C=O). ¹H NMR

(CDCl₃), : 1.53 (d, 3 H, Me, J = 7.1 Hz); 2.14 (s, 3 H, OCOMe);

5.11 (q, 1 H, H(2), J = 7.1 Hz); 9.70 (br.s, 1 H, COOH).

¹³C NMR (CDCl₃), : 20.9 (Me); 22.7 (OCOMe); 68.4 (C(2));

170.8 (OCOMe); 176.3 (COOH).

Elution with the mixture of hexane—acetone (4 : 1) gave

2ꢀhydroxypropionic (lactic) acid (10) (0.70 g, 39%), identical to

that described above.

Thermal oxidation of 2ꢀacetylcyclopentanone (33) with hyꢀ

drogen peroxide in solution in tertꢀbutyl alcohol at ~20 C.

A solution of diketone 33 (1.26 g, 0.01 mol) and 30% H₂O₂(1.42 g,

12.5 mmol) in Bu^tOH (10 mL) was stirred for 120 h at ~20 C.

The solvent and the unreacted H₂O₂were evaporated at reduced

pressure. A residue obtained was dissolved in chloroform (50 mL),

the acids were extracted with a saturated aq. NaHCO₃(3×20 mL),

then the organic phase was washed with brine (3×15 mL) and

dried with anhydrous Na₂SO₄. The solvent was evaporated, the

residue was subjected to chromatography on a column with SiO₂.

Elution with the mixture of hexane—acetone (35 : 1) gave the

starting diketone 33 (0.60 g, 48%) as a colorless light liquid. IR,



_max/cm^–1: 3530—2400 (OH), 1744 (C=O), 1709 (C=O), 1660

(C=O), 1610 (C=O, C=C), 1588 (C=O, C=C), 1451, 1405,

1387, 1360, 1285, 1239, 1197, 1180, 1139, 1121. ¹H NMR

(CDCl₃),  of enol form 33b (33c): 1.91 (quint, 2 H, 2 H(4),

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

Novikov and Shestak

J = 7.1 Hz); 1.99 (s, 3 H, C(6)Me); 2.41 (t, 2 H, 2 H(5),

J = 7.1 Hz); 2.55 (t, 2 H, 2 H(3), J = 7.1 Hz); 13.50 (br.s, 1 H,

OH). ¹³C NMR (CDCl₃),  of enol form 33b (33c): 20.1 (C(4));

20.6 (C(7)); 25.7 (C(3)); 36.8 (C(5)); 109.7 (C(2)); 175.7 (C(6));

204.9 (C(1)). ¹H NMR (CDCl₃),  of diketo form 33a: 1.87

(m, 1 H, H(4)); 2.06 (m, 2 H, H(3), H(4)); 2.25 (m, 1 H, H(5));

2.29 (m, 1 H, H(5)); 2.32 (s, 3 H, COMe); 2.42 (m, 1 H, H(3));

3.39 (dd, 1 H, H(2), J = 5.7 Hz, J = 8.1 Hz). ¹³C NMR (CDCl₃),

 of diketo form 33a: 20.5 (C(4)); 25.0 (C(3)); 30.0 (C(7)); 38.6

(C(5)); 62.6 (C(2)); 202.3 (C(6)); 212.7 (C(1)).

2 COOH). ¹³C NMR (CDCl₃), : 20.1 (C(3)); 33.3 (C(2), C(4));

178.7 (C(1), C(5)).

Thermal oxidation of 2ꢀacetylcyclopentanone (33) with aqueꢀ

ous solution of hydrogen peroxide at reduced temperature. A soluꢀ

tion of diketone 33 (1.26 g, 0.01 mol) in a 30% H₂O₂(1.42 g,

12.5 mmol) was kept for 72 h at –15 C. Water was evaporated at

reduced pressure at the temperature of 45 C, the residue was

subjected to chromatography on a column with SiO₂. Elution

with the mixture of hexane—acetone (35 : 1) gave the starting

diketone 33 (0.252 g, 20%).

Elution with the mixture of hexane—acetone (20 : 1) gave

glutaric anhydride (49) (0.023 g, 4%) as colorless crystals, m.p.

51—54 C. IR, _max/cm^–1: 1748 (C=O), 1715 (C=O), 1602,

1451, 1415, 1290, 1240, 1132. ¹H NMR (CDCl₃), : 2.02 (quint,

2 H, 2 H(4), J = 6.8 Hz); 2.75 (t, 4 H, 2 H(3), 2 H(5), J = 6.8 Hz).

¹³C NMR (CDCl₃), : 16.7 (C(4)); 30.3 (C(3), C(5));

166.8 (C(2), C(6)).

Elution with the mixture of hexane—acetone (6 : 1) gave

a mixture (1.8 : 1) of 3S(R),4R(S),5R(S)ꢀ5ꢀhydroperoxyꢀ3ꢀ

hydroxyꢀ3ꢀmethylꢀ1,2ꢀdioxabicyclo[3.3.0]octane (36a) and

3R(S),4R(S),5R(S)ꢀ5ꢀhydroperoxyꢀ3ꢀhydroxyꢀ3ꢀmethylꢀ1,2ꢀ

dioxabicyclo[3.3.0]octane (36b) (0.943 g, 67%) as a dense colorꢀ

less oil. IR, _max/cm^–1: 3586 (OH), 3518 (OH), 3431 (OH),

3309 (OH), 3152, 3103, 3087, 3062, 3043, 3008, 2948, 2932,

2856, 1602, 1454, 1439, 1386, 1357, 1350, 1326, 1308, 1302,

1240, 1181, 1176, 1173, 1130, 1084, 1077. Found (%): C, 47.83;

H, 6.76. C₇H₁₂O₅. Calculated (%): C, 47.73; H, 6.87. The ¹H

and ¹³C NMR spectra of compounds 36a and 36b are given in

Tables 3 and 4, respectively.

Elution with the mixture of hexane—acetone (15 : 1) gave

20

ꢀbutyrolactone (51) (0.011 g, 2%) as a colorless liquid, [n]_D

1.4351. IR, _max/cm^–1: 1772 (C=O). ¹H NMR (CDCl₃), : 2.23

(m, 2 H, 2 H(4)); 2.45 (m, 2 H, 2 H(3)); 4.35 (t, 2 H, 2 H(5),

J = 7.1 Hz). ¹³C NMR (CDCl₃), : 22.2 (C(4)); 27.8 (C(3)); 68.5

(C(5)); 177.8 (C(2)).

Elution with the mixture of hexane—acetone (4 : 1) gave

ꢀmethyladipic acid (37) (0.09 g, 7%), identical to that deꢀ

scribed above.

Elution with the mixture of hexane—acetone (7 : 1) gave

2ꢀhydroxycyclopentanone (46) (0.016 g, 3%) as a colorless dense

oil (cf. Ref. 55: dense oil). IR, _max/cm^–1: 3526 (OH), 3471

Thermal oxidation of 2ꢀacetylcyclopentanone (33) with hyꢀ

drogen peroxide in solution in acetic acid at ~20 C. A solution of

diketone 33 (1.26 g, 0.01 mol) and 30% H₂O₂(1.42 g, 12.5 mmol)

in AcOH (10 mL) was stirred for 240 h at ~20 C. The solvent

and the unreacted H₂O₂were evaporated at reduced pressure,

the residue was subjected to chromatography on a column with

SiO₂. Elution with the mixture of hexane—acetone (8 : 1) gave

2ꢀacetylꢀ2ꢀhydroxycyclopentanone (59) (0.007 g, 0.5%) as a colꢀ

orless dense oil (cf. Ref. 1: yellow oil; cf. Ref. 2: white solid

compound, m.p. 58—59 C). IR, _max/cm^–1: 3511 (OH), 1753

(C=O), 1711 (C=O), 1402, 1360, 1227, 1157, 1092, 1048.

¹H NMR (CDCl₃), : 1.94—2.05 (m, 1 H, H(3)); 2.06—2.20

(m, 2 H, 2 H(4)); 2.23 (s, 3 H, COMe); 2.40—2.50 (m, 3 H,

H(3), 2 H(5)); 3.93 (br.s, 1 H, OH). ¹³C NMR (CDCl₃), : 18.4

(C(4)); 25.7 (C(7)); 34.7 (C(3)); 36.0 (C(5)); 86.3 (C(2)); 207.2

(C(6)); 215.2 (C(1)). MS (EI, 70 eV), m/z (I_rel(%)): 142 [M]⁺

(7), 125 (5), 124 (2), 115 (16), 114 (22), 100 (39), 99 (28), 88 (10),

87 (34), 86 (100), 85 (25), 83 (10), 74 (10), 73 (37), 71 (44),

70 (13), 69 (12), 60 (76), 58 (45), 57 (23), 55 (88), 46 (39), 45 (13),

44 (94), 43 (47), 42 (34), 40 (18), 32 (53), 31 (30). Found (%):

C, 59.83; H, 8.16. C₅H₈O₂. Calculated (%): C, 59.98; H, 8.05.

Elution with the mixture of hexane—acetone (4 : 1) gave

ꢀmethyladipic acid (37) (0.48 g, 30%), identical to that deꢀ

scribed above.

1

(OH), 1751 (C=O). H NMR (CDCl₃), : 1.61—1.93 (m, 2 H,

H(3), H(4)); 1.98—2.54 (m, 4 H, H(3), H(4), 2 H(5)); 2.99 (br.s,

1 H, OH); 4.21 (dd, 1 H, H(2), J = 3.7 Hz, J = 7.8 Hz). ¹³C NMR

(CDCl₃), : 16.3 (C(4)); 30.3 (C(3)); 34.0 (C(5)); 71.7 (C(2));

211.8 (C(1)).

Aqueous soda solution (60 mL) left after the washing the

organic extract was acidified with a 2 M solution of hydrochloric

acid to pH 1.0, and the reaction products were extracted with

chloroform (5×10 mL). The combined organic extracts were

washed with brine (4×5 mL) and dried with anhydrous Na₂SO₄.

The solvent was evaporated, the crude product was subjected to

chromatography on a column with SiO₂.

Elution with the mixture of hexane—acetone (5 : 1) gave

4ꢀacetoxybutyric (aceburic) acid (52) (0.017 g, 2%) as a colorless

dense oil (cf. Ref. 56: a colorless oil). IR, _max/cm^–1: 3400—2600

(COOH), 1728 (C=O), 1717 (C=O), 1710 (C=O). ¹H NMR

(CDCl₃), : 1.99 (m, 2 H, 2 H(3), J = 6.3 Hz, J = 7.2 Hz); 2.06

(s, 3 H, OAc); 2.47 (t, 2 H, 2 H(2), J = 7.2 Hz); 4.13 (t, 2 H,

2 H(4), J = 6.3 Hz). ¹³C NMR (CDCl₃), : 21.2 (C(6)); 24.1

(C(3)); 30.8 (C(2)); 63.6 (C(4)); 171.1 (C(5)); 179.0 (C(1)).

Elution with the mixture of hexane—acetone (4 : 1) gave

2ꢀmethylhexaneꢀ1,6ꢀdioic (ꢀmethyladipic) acid (37) (0.335 g,

40%) as colorless plates, m.p. 56—58 C (hexane—benzene)

(cf. Ref. 35: m.p. 57—58 C). IR, _max/cm^–1: 3420—2395 (COOH),

Elution with the mixture of hexane—acetone (2 : 1) gave

glutaric acid (43) (0.884 g, 67%), identical to that described above.

A solution of diketone 33 (1.26 g, 0.01 mol) and 30% H₂O₂

(2.84 g, 0.025 mol) in AcOH (10 mL) was stirred for 17 h at

~20 C. The solvent and the unreacted H₂O₂were evaporated at

reduced pressure and 40—45 C, the residue was subjected to

chromatography on a column with SiO₂. Elution with the mixꢀ

ture of hexane—acetone (30 : 1) gave the starting diketone 33

(0.126 g, 10%).

1

1723 (C=O), 1714 (C=O). H NMR (CDCl₃), : 1.20 (d, 3 H,

C(2)Me, J = 7.0 Hz); 1.51 (m, 2 H, 2 H(3)); 1.69 (m, 2 H,

2 H(4)); 2.37 (t, 2 H, 2 H(5), J = 7.2 Hz); 2.48 (m, 1 H, H(2));

10.21 (br.s, 2 H, 2 COOH). ¹³C NMR (CDCl₃), : 16.9 (C(2)Me);

22.6 (C(4)); 32.8 (C(3)); 34.0 (C(5)); 39.3 (C(2)); 179.6 (C(6));

182.8 (C(1)).

Elution with the mixture of hexane—acetone (2 : 1) gave

glutaric acid (43) (0.276 g, 40%) as colorless crystals, m.p.

97—98 C. IR, _max/cm^–1: 3400—2370 (COOH), 1715 (C=O).

¹H NMR (CDCl₃), : 2.01 (quint, 2 H, 2 H(3), J = 6.7 Hz);

2.46 (t, 4 H, 2 H(2), 2 H(4), J = 6.7 Hz); 10.30 (br.s, 2 H,

Elution with the mixture of hexane—acetone (6 : 1) gave

a mixture of hydroperoxides 36a,b (0.269 g, 17%), identical to

those described above.

Thermal oxidation of 1,3ꢀdiketones by H₂O₂

Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013

2189

Elution with the mixture of hexane—acetone (5 : 1) gave

a mixture (3 : 1) of 3S(R),4S(R),5R(S)ꢀ3ꢀhydroperoxyꢀ5ꢀhyꢀ

droxyꢀ3ꢀmethylꢀ1,2ꢀdioxabicyclo[3.3.0]octane (36c) and

3R(S),4S(R),5R(S)ꢀ3ꢀhydroperoxyꢀ5ꢀhydroxyꢀ3ꢀmethylꢀ1,2ꢀ

dioxabicyclo[3.3.0]octane (36d) (0.348 g, 22%) as a dense colorꢀ

less oil. IR, _max/cm^–1: 3591 (OH), 3513 (OH), 3437 (OH),

3306 (OH), 3149, 3106, 3092, 3071, 3050, 3011, 2944, 2935,

2850, 1600, 1458, 1442, 1390, 1352, 1347, 1329, 1303, 1299,

1245, 1177, 1174, 1134, 1086, 1072. Found (%): C, 47.81;

H, 6.76. C₇H₁₂O₅. Calculated (%): C, 47.73; H, 6.87.

Elution with the mixture of hexane—acetone (6 : 1) gave

5,6ꢀdioxoheptanoic acid (41) (0.047 g, 3%) as a pale yellow dense

oil. IR, _max/cm^–1: 3400—2400 (COOH), 1745 (C=O), 1714

(C=O), 1417, 1358, 1239, 1133, 1046. ¹H NMR (CDCl₃),

: 1.94 (quint, 2 H, 2 H(3), J = 7.2 Hz); 2.34 (s, 3 H, COMe); 2.43

(t, 2 H, 2 H(2), J = 7.2 Hz); 2.85 (t, 2 H, 2 H(4), J = 7.2 Hz);

9.82 (br.s, 1 H, COOH). ¹³C NMR (CDCl₃), : 18.3 (C(3)); 24.0

(C(7)); 33.0 (C(2)); 35.1 (C(4)); 178.9 (C(1)); 197.6 (C(6));

198.6 (C(5)). MS (EI, 70 eV), m/z (I_rel(%)): 158 [M]⁺(1), 141

(2), 140 (1), 116 (3), 115 (43), 114 (4), 112 (2), 101 (2), 100 (3),

98 (2), 97 (5), 87 (37), 86 (14), 85 (7), 73 (6), 69 (5), 60 (8),

58 (4), 55 (24), 46 (29), 45 (3), 44 (100), 43 (13), 42 (17), 32 (5),

31 (7). Found (%): C, 53.24; H, 6.35. C₇H₁₀O₄. Calculated (%):

C, 53.16; H, 6.37.

Elution with the mixture of hexane—acetone (5 : 1) gave

4ꢀacetoxybutyric acid (52) (0.015 g, 1%), identical to that deꢀ

scribed above.

Elution with the mixture of hexane—acetone (4 : 1) gave

ꢀmethyladipic acid (37) (0.288 g, 18%), identical to that deꢀ

scribed above.

Elution with the mixture of hexane—acetone (4 : 1) gave

ꢀmethyladipic acid (37) (0.46 g, 32%), identical to that described

above.

Elution with the mixture of hexane—acetone (3 : 1) gave

2ꢀhydroxyꢀ2ꢀmethylhexaneꢀ1,6ꢀdioic acid (38) (0.047 g, 3%) as

a colorless dense oil. IR, _max/cm^–1: 3591 (OH), 3571 (OH),

3520 (OH), 3439—2231 (COOH), 1745 (C=O), 1713 (C=O).

¹H NMR (CDCl₃), : 1.47 (s, 3 H, C(2)Me); 1.72 (m, 2 H,

2 H(4)); 1.76 (m, 1 H, H(3)); 2.38 (t, 2 H, 2 H(5), J = 7.2 Hz);

2.48 (m, 1 H, H(3)); 10.18 (br.s, 2 H, 2 COOH). ¹³C NMR

(CDCl₃), : 22.5 (C(4)); 26.3 (C(2)Me); 34.1 (C(5)); 39.3 (C(3));

73.0 (C(2)); 179.5 (C(6)); 182.5 (C(1)). Found (%): C, 47.81;

H, 6.69. C₇H₁₂O₅. Calculated (%): C, 47.73; H, 6.87.

Elution with the mixture of hexane—acetone (2 : 1)

gave glutaric acid (43) (0.818 g, 62%), identical to that described

above.

Elution with the mixture of hexane—acetone (2 : 1) gave

glutaric acid (43) (0.31 g, 26%), identical to that described above.

Thermal oxidation of 2ꢀacetylcyclopentanone (33) with hyꢀ

drogen peroxide in solution in acetic acid with heating. A solution

of diketone 33 (1.26 g, 0.01 mol) and 30% H₂O₂(1.42 g,

12.5 mmol) in AcOH (10 mL) was refluxed for 3 h. The solvent

and the unreacted H₂O₂were evaporated at reduced pressure.

The residue was dissolved in chloroform (50 mL), the acids were

extracted with a saturated aq. NaHCO₃(3×20 mL), then the

organic phase was washed with brine (3×15 mL) and dried with

anhydrous Na₂SO₄. The solvent was evaporated, the residue was

subjected to chromatography on a column with SiO₂. Elution

with the mixture of hexane—acetone (15 : 1) gave ꢀbutyrolacꢀ

tone (51) (0.009 g, 1%), identical to that described above.

Elution with the mixture of hexane—acetone (10 : 1) gave

2ꢀacetoxycyclopentanone (56) (0.028 g, 2%) as a colorless oil

(cf. Ref. 55: dense oil). IR, _max/cm^–1: 1756 (C=O), 1718 (C=O),

1405, 1356, 1232, 1209, 1158, 1092, 1049. ¹H NMR (CDCl₃),

: 1.87—2.13 (m, 2 H, 2 H(4)); 2.14 (s, 3 H, OAc); 2.09—2.19

(m, 2 H, 2 H(5)); 2.16—2.27 (m, 2 H, 2 H(3)); 5.05 (m, 1 H,

H(2), J = 8.1 Hz, J = 4.1 Hz, J = 3.8 Hz, J = 2.2 Hz). ¹³C NMR

(CDCl₃), : 17.2 (C(4)); 20.9 (C(7)); 28.5 (C(3)); 34.4 (C(5));

75.8 (C(2)); 170.4 (C(6)); 215.0 (C(1)). MSS (EI, 70 eV), m/z

(I_rel(%)): 142 [M]⁺(10), 100 (100), 99 (85), 98 (21), 83 (6),

82 (17), 73 (6), 72 (16), 71 (34), 60 (14), 55 (18), 44 (39).

Elution with the mixture of hexane—acetone (8 : 1) gave

2ꢀacetylꢀ2ꢀhydroxycyclopentanone (59) (0.085 g, 6%), identical

to that described above.

The authors are grateful to Dr. V. P. Glazunov for his

help in carrying out quantum chemical calculations of the

peroxide molecules.

This work was financially supported by the Russian

Academy of Sciences (Grant of the FarꢀEastern, the Sibeꢀ

rian, and the Ural Branches of RAS No. 12ꢀIIꢀSUꢀ05ꢀ006,

Grants of the FarꢀEastern Branch of RAS Nos 12ꢀIIIꢀAꢀ

05ꢀ056 and 12ꢀIIIꢀAꢀ05ꢀ062).

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in revised form July 31, 2013

Article Doi

Reactions of hydrogen peroxide with acetylacetone and 2- acetylcyclopentanone

DOI: 10.1007/s11172-013-0316-6

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