Synthesis of 4-tert-butylperoxy-4-methylpentan-2-one and 3-tert-butylperoxy-3-methylbutanoic acid

Article abstract of DOI:10.1134/S1070428013090042

Alkylation of tert-butyl hydroperoxide with 1,3-diols gave the corresponding hydroxy-containing ditertiary peroxides which were oxidized with pyridinium chlorochromate to carbonyl-containing peroxides. 3-tert-Butylperoxy- 3-methylbutanal was oxidized with

Full text of DOI:10.1134/S1070428013090042

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 9, pp. 1270–1272. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.B. Vostres, R.I. Fleichuk, S.A. Voronov, O.I. Gevus’, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 9,
pp. 1287–1289.
Synthesis of 4-tert-Butylperoxy-4-methylpentan-2-one
and 3-tert-Butylperoxy-3-methylbutanoic Acid
V. B. Vostres, R. I. Fleichuk, S. A. Voronov, and O. I. Gevus’
“Lviv Polytechnic” National University, ul. S. Bandery 12, Lviv, 79013 Ukraine
e-mail: fleychuk@polynet.lviv.ua
Received April 2, 2012
Abstract—Alkylation of tert-butyl hydroperoxide with 1,3-diols gave the corresponding hydroxy-containing
ditertiary peroxides which were oxidized with pyridinium chlorochromate to carbonyl-containing peroxides.
3-tert-Butylperoxy-3-methylbutanal was oxidized with oxygen at room temperature to obtain 3-tert-butyl-
peroxy-3-methylbutanoic acid.
DOI: 10.1134/S1070428013090042
Ditertiary peroxides containing a carbonyl or
carboxy group attract interest as peroxy synthons and
initiators of radical reactions for the synthesis of oligo-
mers with terminal functional groups. 4-tert-Butyl-
peroxy-4-methylpentan-2-one (IIIb) and 3-tert-butyl-
peroxy-3-methylbutanoic acid (IV) are among the
simplest representatives of such compounds. There-
fore, much attention was given to their synthesis.
Peroxy ketone IIIb was prepared by reaction of tert-
butyl hydroperoxide with diacetone alcohol [1–5] or
mesityl oxide [3, 6] in 70% sulfuric acid. Unsuccessful
attempts were made to obtain compound IIIb by
alkylation of tert-butyl hydroperoxide with mesityl
oxide in the presence of alkali [7] or via peroxy-
mercuration followed by protodemercuration [8]. The
physical constants of peroxy ketone IIIb given in [1–6,
9–11] were considerably different, and this fact was
previously noted in [2, 10]. The experimental molec-
ular refraction of IIIb also differed from the calculated
incomplete or no spectral data were given at all.
Peroxy acid IV was prepared in a satisfactory yield by
oxidation of peroxy ketone IIIb with sodium hypo-
bromite [3, 12].
Our attempts to synthesize pure peroxy ketone IIIb
following all the above procedures were unsuccessful,
though the properties of the product obtained in each
case were consistent with those given in the literature.
In all cases, a complex mixture of peroxy-containing
compounds was formed, and we failed to isolate pure
ketone IIIb therefrom. Presumably, the reason is that
tert-butyl hydroperoxide reacted simultaneously with
the hydroxy and carbonyl groups of diacetone alcohol.
Therefore, we have proposed an alternative method
for the synthesis of peroxides IIIb and IV by oxidation
of peroxy alcohols IIa and IIb (Scheme 1). Initial
peroxides IIa and IIb were prepared by alkylation of
tert-butyl hydroperoxide with 1,3-diols Ia and Ib in
the presence of 56% perchloric acid. The subsequent
oxidation of IIa and IIb with pyridinium chloro-
1
value, while the given H NMR and IR data were
Scheme 1.
HO
HO
O
t-BuOOH, H+
Me
Me
OH
Me
Me
Me
Me
PCC
–H2O
R
R
OOBu-t
R
OOBu-t
Ia, Ib
IIa, IIb
IIIa, IIIb
Me
Me
t-BuOO
O
H
Me
Me
Me
Me
O2
H2NC(O)NHNH2
N
NH2
CHO
N
t-BuOO
OH
t-BuOO
O
IV
IIIa
V
R = H (a), Me (b).
1270

SYNTHESIS OF 4-tert-BUTYLPEROXY-4-METHYLPENTAN-2-ONE
1271
(68%). The properties of the product were consistent
with those reported in [22].
chromate afforded almost pure carbonyl-containing
peroxides IIIa and IIIb which contained a small im-
purity of unreacted initial hydroxy peroxides IIa and
IIb. Compound IIIb was additionally purified via
transformation into semicarbazone and subsequent
regeneration of the carbonyl group by treatment with
pyruvic acid [13]. Aldehyde IIIa was readily oxidized
to acid IV with oxygen at room temperature.
4-tert-Butylperoxy-4-methylpentan-2-ol (IIb) was
synthesized in a similar way from 5.90 g (50 mmol) of
diol Ib and 9.38 g (100 mmol) of 96% tert-butyl
hydroperoxide using 17.8 g (100 mmol) of 56% per-
chloric acid (reaction time 7 h). Yield 5.08 g (53%),
bp 84°C (11mm), d420 = 0.9023, nD20 = 1.4254. IR spec-
trum (film), ν, cm–1: 3448 (OH), 1240 (C–OH), 1125
1
EXPERIMENTAL
(C–O), 864 (O–O). H NMR spectrum, δ, ppm: 1.18 d
(3H, CH3CH), 1.27 s (9H, t-Bu), 1.31 s (6H, CH3),
1.72 m and 2.12 m (2H, CH2), 3.15 s (1H, OH), 4.05 m
(1H, CH3CH). Found, %: C 62.58; H 11.72.
MRD 53.97. C10H22O3. Calculated, %: C 63.12;
H 11.65. MRD 53.90.
The purity of the products was checked by GLC on
a Buck Scientific-910C chromatograph equipped with
a flame ionization detector (15-m×0.53-mm Restek
capillary column, stationary phase MXT-5, film thick-
ness 1.5 μm; carrier gas helium). The IR spectra were
recorded on a Specord M80 spectrometer from thin
films (liquid samples) or from solutions in carbon
tetrachloride (c = 0.05 M, layer thickness 0.998 mm)
or mulls in mineral oil (crystalline samples). The
1H NMR spectra were measured on Bruker 150
(300 MHz; IIa, IIb, IV; CDCl3) and Avance DRX-500
(500 MHz; IIIa, CDCl3; IIIb, DMSO-d6) spectrom-
eters. The 13C NMR spectrum of IIIb was obtained on
a Bruker Avance DRX-500 instrument from a solution
in DMSO-d6. Analytical thin-layer chromatography
was performed on Silica gel 60 F254 plates (Merck).
The elemental compositions of peroxides were deter-
mined using a setup described in [14]. The molecular
refractions MRD were calculated from the atomic
refractions tabulated in [15]. The molecular refraction
of peroxy group was taken from [16]. All solvents and
tert-butyl hydroperoxide were purified as described in
[17]. Pyridinium chlorochromate was prepared accord-
ing to [18]. 3-Methylbutan-1,3-diol (Ia) was com-
mercial product (Fluka); its physical constants coin-
cided with those given in [19]. 2-Methylpentane-2,4-
diol was prepared as described in [20]; its properties
were consistent with published data [21].
3-tert-Butylperoxy-3-methylbutan-1-ol (IIa).
A mixture of 5.20 g (50 mmol) of diol Ia and 9.4 g
(100 mmol) of 96% tert-butyl hydroperoxide was
cooled to 12–14°C, 17.8 g (100 mmol) of 56% HClO4
was added dropwise under stirring, and the mixture
was stirred for 14 h at that temperature, saturated with
ammonium sulfate, and extracted with hexane (3×
10 ml). The combined extracts were treated in succes-
sion with 5% aqueous sodium hydroxide and a saturat-
ed solution of ammonium sulfate. The solvent was dis-
tilled off, and the residue was distilled under reduced
pressure through a 15-cm Vigreaux column. A fraction
with bp 62–64°C (0.5 mm) was collected. Yield 5.99 g
4-tret-Butylperoxy-4-methylpentan-2-one (IIIb).
A solution of 3.50 g (18.39 mmol) of hydroxy peroxide
IIb in 5 ml of methylene chloride was added in one
portion at 20–25°C to a suspension of 6.50 g
(30.15 mmol) of pyridinium chlorochromate and
0.44 g (5.36 mmol) of sodium acetate in 37 ml of
methylene chloride, and the mixture was kept for 3 h.
The mixture was then diluted with 37 ml of diethyl
ether, and the black precipitate was separated by
decanting and washed with diethyl ether. The com-
bined organic phases were evaporated, the residue was
dissolved in diethyl ether, the solution was passed
through a short column charged with MgSO4, and the
eluate was evaporated. Yield 2.96 g (86%).
Compound IIIb, 2.96 g (15.7 mmol), was added to
a solution of 3.12 g (28.0 mmol) of semicarbazide hy-
drochloride and 3.80 g (46.4 mmol) of sodium acetate
in 20 ml of water, 10 ml of ethanol was then added,
and the mixture was stirred until fine white crystals
separated. The mixture was kept for 48 h at room tem-
perature, and the precipitate was filtered off, thor-
oughly washed with water, and dried at room tempera-
ture. Yield of 4-tret-butylperoxy-4-methylpentan-2-one
semicarbazone 2.80 g (77%), mp 150°C (decomp.);
published data [11]: mp 149–150°C. A 2.28-g (9.86-
mmol) portion of the isolated semicarbazone was dis-
solved in a mixture of 1.26 g (14.3 mmol) of pyruvic
acid, 1.20 g (14.6 mmol) of sodium acetate, 1.25 g of
water, and 48 ml of acetic acid, and the mixture was
kept for 4 days at room temperature. The mixture was
then treated with 60 ml of chloroform and 120 ml of
water, the organic phase was separated, and the
aqueous phase was extracted with chloroform. The
extracts were combined with the organic phase,
washed with water, a solution of sodium hydrogen
carbonate, and a saturated solution of sodium chloride,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 9 2013

VOSTRES et al.
1272
2. Rakhimov, A.I., Kalmykova, G.A., and Mudraya, L.M.,
and dried over MgSO4, and the solvent was removed.
Yield of IIIb 1.38 g (74%), Rf –0.48 (ethyl acetate–
hexane, 1:10; N,N-dimethyl-p-phenylenediamine as
developer). The product was additionally purified by
vacuum distillation at a residual pressure of 2 mm.
bp 75°C (11 mm), d420 = 0.9030, nD20 = 1.4185. IR spec-
trum (film), ν, cm–1: 2976, 2936, 2876 (CH), 1712
(C=O), 1472 (CH2), 872 (O–O). 1H NMR spectrum, δ,
ppm: 1.20 s (9H, t-Bu), 1.22 s (6H, CH3), 2.62 s (2H,
Zh. Org. Khim., 1978, vol. 14, p. 1337.
3. Barter, I.J., Eddy, C.O., and Stevens, H.C., US Patent
no. 3642755, 1972; Chem. Abstr., 1972, no. 141543k.
4. Samoilov, V.M., Funktsional’nye organicheskie soedi-
neniya i polimery (Functional Organic Compounds and
Polymers), Khardin, A.P., Ed., Volgograd, 1975, p. 10.
5. Shreibert, A.I. and Samoilov, V.M., USSR Inventor’s
Certificate no. 430093, 1974; Byull. Izobret., 1974,
no. 20.
13
CH2), 2.13 s (3H, CH3). C NMR spectrum, δC, ppm:
6. Chang, Y.G. and Bailey, P.S., US Patent no. 3842129,
25.65 [C(CH3)2], 26.38 [C(CH3)3], 31.77 (CH3CO),
53.90 (CH2), 76.25 (C4), 76.29 [C(CH3)3], 211.10
(C=O). Found, %: C 63.40; H 10.84. MRD 52.60.
C10H20O3. Calculated, %: C 63.80; H 10.71.
MRD 52.38.
1974; Ref. Zh., Khim., 1975, no. 18N62P.
7. Yang, N.C. and Finnegan, R.A., J. Am. Chem. Soc.,
1958, vol. 80, p. 5845.
8. Bloodworth, A.J. and Bunce, R.J., J. Chem. Soc., Perkin
Trans. 1, 1972, p. 2787.
3-tert-Butylperoxy-3-methylbutanoic acid (IV)
was synthesized through 3-tert-butylperoxy-3-methyl-
butanal (IIIa). Peroxide IIa, 2.26 g (12.8 mmol), was
added in one portion under stirring at 20–25°C to
a suspension of 4.15 g (19.3 mmol) of pyridinium
chlorochromate and 0.31 g (3.8 mmol) of sodium
acetate in 17 ml of methylene chloride, and the mixture
was stirred for 2 h and treated as described above for
compound IIIb. We isolated 1.85 g (83%) of com-
pound IIIa which was identified as semicarbazone V
with mp 115–116°C (from ethanol). IR spectrum
(KBr), ν, cm–1: 3176, 3472 (N–H), 1688 (C=O), 1592
9. Yuvchenko, A.P., Dikusar, E.A., Zvereva, T.D., and
Murashko, V.L., Russ. J. Org. Chem., 2003, vol. 39,
p. 164.
10. Rakhimov, A.I., Khimiya i tekhnologiya organicheskikh
perekisnykh soedinenii (Chemistry and Technology of
Organic Peroxy Compounds), Moscow: Khimiya, 1979,
p. 210.
11. Ol’dekop, Yu.A. and Churkina, L.A., Vestsі Akad.
Navuk BSSR, Ser. Khіm. Navuk, 1976, no. 3, p. 84.
12. Ol’dekop, Yu.A. and Churkina, L.A., Vestsі Akad.
Navuk BSSR, Ser. Khіm. Navuk, 1974, no. 4, p. 70.
1
13. Hershberg, E.B., J. Org. Chem., 1948, vol. 13, p. 542.
(C=N), 872 (O–O). H NMR spectrum, δ, ppm: 1.15 s
14. Hazenberg, W.M., Microchim. Acta, 1958, vol. 46,
[9H, C(CH3)3], 1.15 s [6H, C(CH3)2], 2.38 d (2H, CH2,
J = 5.9 Hz), 7.19 d (1H, CH=N, J = 5.4 Hz). Found, %:
C 51.90; H 9.17; N 17.98. C10H21O3N3. Calculated, %:
C 51.93; H 9.15; N 18.17.
p. 709.
15. Ioffe, B.V., Refraktometricheskie metody khimii
(Refractometric Methods in Chemistry), Leningrad:
Khimiya, 1974, p. 335.
The residue obtained after removal of the solvent
was kept for two weeks in an oxygen atmosphere at
room temperature and normal pressure. The resulting
suspension was applied onto a sheet of paper. After
complete imbibition of the liquid phase we isolated
0.56 g (23%) of peroxide IV as hexagonal plates. The
product was additionally purified by double sublima-
tion under reduced pressure. mp 38–39°C. IR spectrum
(KBr), ν, cm–1: 2800–3200 (OH), 1712 (C=O), 872
16. Milas, N.A., Surgenor, D.M., and Perry, L.H., J. Am.
Chem. Soc., 1946, vol. 68, p. 1617.
17. Armarego, W.L.F. and Chai, C.L.L., Purification of
Laboratory Chemicals, Amsterdam: Butterworth-
Heinemann, 2003, 5th ed.
18. Corey, E.G. and Suggs, J.W., Tetrahedron Lett., 1975,
vol. 16, p. 2647.
19. Beilsteins Handbuch der organischen Chemie, Berlin:
1
Springer, 1936, 4th ed., vol. 1, p. 2549.
(O–O). H NMR spectrum, δ, ppm: 1.26 s (9H, t-Bu),
20. Gren’, A.I., Kuznetsov, V.V., Vil’chinskaya, N.I., and
Stepanov, D.E., Reaktivy i osobo chistye veshchestva
(Chemical Reagents and Ultrapure Substances),
Moscow: NIITEKhIM, 1978, vol. 6, p. 24.
1.33 s [6H, C(CH3)2], 2.71 s (2H, CH2), 7.26 s (1H,
COOH). Found, %: C 56.63; H 9.63. C9H18O4. Cal-
culated, %: C 56.82; H 9.54.
21. Lide, D.R., CRC Handbook of Chemistry and Physics,
REFERENCES
Boca Raton: CRC, 2004.
22. Fleichuk, R.I., Gevus’, O.I., and Voronov, S.A., Russ. J.
Org. Chem., 2003, vol. 39, p. 1799.
1. Akimova, G.S. and Grinblat, M.P., Zh. Org. Khim.,
1971, vol. 7, p. 2279.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 9 2013