Synthesis of alkyl hydroperoxides via alkylation of gem -dihydroperoxides

Article abstract of DOI:10.1021/jo4001564

2-Fold alkylation of 1,1-dihydroperoxides, followed by hydrolysis of the resulting bisperoxyacetals, provides a convenient method for synthesis of primary and secondary alkyl hydroperoxides.

Full text of DOI:10.1021/jo4001564

Note
pubs.acs.org/joc
Synthesis of Alkyl Hydroperoxides via Alkylation of gem-
Dihydroperoxides
ShivaKumar Kyasa, Benjamin W. Puffer, and Patrick H. Dussault*
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States
S
* Supporting Information
ABSTRACT: 2-Fold alkylation of 1,1-dihydroperoxides, followed by hydrolysis of the
resulting bisperoxyacetals, provides a convenient method for synthesis of primary and
secondary alkyl hydroperoxides.
number of methods have been reported for the synthesis
of alkyl hydroperoxides,1 with some of the most widely
derived 1a on the basis of upon previous reports demonstrating
that this DHP more readily undergoes acid hydrolysis
compared with DHPs derived from strain-free ketones; it was
our hope that this increased reactivity would extend to derived
bisperoxyacetals.10 Investigations of conditions for alkylation of
1a are summarized in Table 1. There have been only a few
reports describing alkylation of 1,1-dihydroperoxides.6b,7 The
bisalkylation of 1a with primary iodides was achieved in good
yield using Ag2O;7,11 although the reaction was successful in
several solvents, the best yields were obtained in ethyl acetate.
The corresponding reaction with a primary bromide was
unsuccessful. Attempted alkylation of 1a by a primary iodide in
the presence of cesium hydroxide or cesium carbonate resulted
in decomposition with formation of ketone.7 Silver-promoted
benzylation proceeded in modest yield due to facile Kornblum
fragmentation of the peroxide product.12 No product was
observed upon attempted alkylation in the presence of
potassium tert-butoxide in THF or under phase-transfer
conditions proven effective for alkylation of simple hydro-
peroxides.13 Neither Ag2O nor base was successful in
promoting alkylation with a secondary iodide. In search of
electrophiles that would allow synthesis of secondary peroxides,
we investigated alkyl triflates, which have been successfully
applied to alkylation of alkyl hydroperoxides.2e Alkylation of 1a
with a slight excess (nominally 2.2−3.0 equiv) of primary or
secondary triflates took place rapidly in the presence of
potassium tert-butoxide (entries 10, 11, 14, 15).14 We were
unable to find any method for 2-fold alkylation with a tertiary
electrophile. Ag-promoted alkylation with tert-butyl bromide
furnished a mixture containing mostly recovered starting
material and monoalkylated product; only a trace of the
desired bisperoxyacetal was observed (entry 16). Attempted
alkylation of 1a with tert-butyl bromide in the presence of base
resulted in no reaction or decomposition (entries 17, 18).
A
used based upon displacement of a leaving group by a peroxide
nucleophile.1b,2 Some years ago, we reported a convenient
approach to alkyl hydroperoxides based upon alkylation of 2-
methoxypropyl-2-yl hydroperoxide followed by deprotection of
the resulting monoperoxyacetals.3 Although the method has
seen significant use,4 it is limited by the need to generate and
concentrate a low molecular weight hydroperoxyacetal.5 Our
recent experiences with the synthesis and reactivity of 1,1-
dihydroperoxides (DHPs) led us to hypothesize that these
species might offer useful alternatives as precursors for alkyl
hydroperoxides.6 We were encouraged by a report from Nojima
and co-workers demonstrating alkylations of 1,1-DHPs,7 and by
the demonstrated stability of 1,1-bisperoxyacetals.7,8 We now
report a convenient procedure for synthesis of alkyl hydro-
peroxides via alkylation of 1,1-dihydroperoxides followed by
acidic deprotection of the derived bisperoxyacetals (eq 1). As
initial substrates, we selected cyclododecanone 1,1-dihydroper-
oxide (1a) and 4-tert-butylcyclohexanone dihydroperoxide
(1b), known DHPs possessing sufficient mass to simplify
isolation and mitigate safety concerns.9 Compounds 1a and 1b
were readily prepared via Re2O7-catalyzed condensation of the
corresponding ketone with aqueous hydrogen peroxide (eq
2).6a We chose to initially focus on the cyclododecanone-
Received: January 26, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo4001564 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
yacetal (2a) undergoes exothermic decomposition, but only
upon heating to above 120−125 °C (Figure 1).
The cyclohexanone-derived DHP 1b also underwent Ag-
promoted alkylation with iododecane to generate a good yield
of bisperoxyacetal 4 (eq 3).
Table 1. Alkylation of Dihydroperoxide 1a
Hydrolysis of Bisperoxyacetals. Synthesis of Alkyl
Hydroperoxides. Table 2 illustrates screening of conditions
Table 2. Optimization of Hydrolysis Conditions
a
entry
solvent
acid (equiv)
T (°C)
t (h)
yield (%)
1
2
3
4
5
6
7
8
EtOH
MeOH
MeOH
MeOH
MeOH
THF
1 M aq H2SO4 (6)
H2SO4 (6)
rt
8
1
NR
8
reflux
reflux
rt
50% aq H2SO4 (6)
50% aq H2SO4 (6)
30% aq H2SO4 (6)
camphorsulfonic (2)
50% aq H2SO4 (6)
50% aq H2SO4 (6)
0.16
48
1.5
3
84
19
NR
NR
78
20
rt
rt
THF
55
rt
3
THF
24
a
Isolated yields. Cyclododecanone recovered in comparable yields.
a
A: Ag2O, RBr or RI, EtOAc. B: KOtBu, ROTf, THF. C: CsOH·H2O
(2 equiv), RI (2 equiv) DMF. D: CsCO3 (2 equiv), RI (2 equiv),
DMF. E: KOtBu (2.1 equiv), RI (2equiv), THF. F: 50% KOH (4
equiv), RBr (2 equiv), n-Bu4NBr (10%), cyclohexane, 50 °C. G:
for deprotection of bisperoxyacetal 2a. Little deprotection was
observed upon exposure of 2a to a room temperature ethanolic
solution of dilute aqueous H2SO4 or even upon heating with an
excess of sulfuric acid in methanol. In contrast, refluxing 2a in a
methanolic solution containing 50% aqueous H2SO4 resulted in
rapid deprotection to furnish a high yield of decyl hydro-
peroxide and recovered ketone (entry 3). Application of the
same reagent but at room temperature resulted in only a
b
K2CO3, acetone. H: K2CO3, DMF, 70 °C. NMR-based yield (internal
c
standard). Decomposition of 1a with formation of ketone.
Differential scanning calorimetry/thermal gravimetric anal-
ysis (DSC/TGA) demonstrated that the product bisperox-
Figure 1. Thermal stability of peroxide 2a. Upper curve is percent of original mass; lower curve indicates heat flow.
B
dx.doi.org/10.1021/jo4001564 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
modest yield even after 2 days of reaction (entry 4). A THF
solution of 2a also proved unreactive toward anhydrous acid
(entry 6) but rapidly underwent complete deprotection upon
heating with a slight excess of 50% aqueous H2SO4 (entry 7).
Application of the same conditions at room temperature
resulted in a prolonged reaction time and lower yield (entry 8).
In no case could we detect any ring-expanded lactone. DSC/
TGA analysis of a sample of the purified decyl hydroperoxide
product (3a) revealed a profile for thermal stability very similar
to that described earlier for bisperoxyacetal 2a, with onset of
decomposition occurring well above the temperatures required
for acid hydrolysis; details are provided in Supporting
Information.
Scheme 1. Lack of Stereospecificity in Alkylation with a
Secondary Triflate
derived from bulky alicyclic or strained cyclic frameworks
underwent hydrolysis more rapidly than those based upon a
strain-free backbone.10 Our results demonstrate that these
trends extend to bisperoxyacetals, with 2a undergoing complete
hydrolysis under relatively mild conditions that fail to
completely deprotect cyclohexanone-derived 4. The lack of
ring-expanded products observed during acid hydrolysis
suggests that ionization of the acetal center is greatly favored
relative to C-to-O migration (eq 4). The displacements of
Consistent with our hypothesis regarding the contribution of
ring strain to peroxyacetal hydrolysis,10 bisperoxyacetal 4 could
not be completely hydrolyzed under conditions that had proven
effective for 2a (Table 3).
Table 3. Hydrolysis of Cyclohexanone-Derived
Bisperoxyacetal 4
solvent
T (°C)
t (h)
yield (%)
21
MeOH
THF
reflux
0.25
6
a
50−55
34
a
NMR-based yield.
primary halides are anticipated to proceed through an SN2-type
transition state. In contrast, the displacements of secondary
triflates appear to involve a transition state with significant
cationic character. Although the successful displacement of
highly reactive secondary electrophiles suggests the potential
for extension to tertiary systems, this proved not to be the case
(Table 1, entries 16−18), presumably due to rapid elimination.
In conclusion, we have demonstrated a convenient synthesis
of primary and secondary alkyl hydroperoxides based upon use
of 1,1-dihydroperoxides. The reagents are available in one step
from commercially available ketones, which can be recovered
from the hydrolysis/deprotection step. The ease of generating
1,1-dihydroperoxides and of handling the bisperoxyacetal
intermediates suggests the potential for extension of the
methodology to solid-phase organic synthesis.
The optimized conditions were next applied to deprotection
of bisperoxyacetals 2a−2g (Table 4) to furnish moderate to
good yields of hydroperoxides in highly pure form.
Table 4. Hydrolysis To Form Hydroperoxides
entry
acetal
R
hydroperoxide
yield (%)
78
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
decyl
3a
3b
3c
3d
3e
3f
a
hexyl
49
benzyl
60
62
79
48
63
Note on Safety. Although no safety issues were
encountered in the course of this work, any preparative work
with peroxides should be conducted with an awareness of the
potential for spontaneous and exothermic decomposition
reactions.16
9-decenyl
Ph(CH2)3
2-octyl
2g
2-dodecyl
3g
a
Volatile product.
EXPERIMENTAL SECTION
■
1,1-Dihydroperoxides were prepared using a literature procedure.6a
Alkyl triflates were prepared according to a published procedure and
used without column purification.14 EA = ethyl acetate; Hex = hexane.
NMR spectra were acquired at 400 MHz (1H) or 100 MHz (13C) in
CDCl3 unless noted.
Curious as to the potential for stereospecific displacement of
secondary substrates, we repeated the synthesis of 2-hydro-
peroxyoctane (3f) beginning with the triflate derived from
enantiomerically enriched (R)-(−)-2-octanol (Scheme 1).
Phosphine reduction of the derived hydroperoxide furnished
2-octanol possessing a very low specific rotation, suggesting
that the displacement of secondary triflates proceeds with little
if any stereospecificity.15
Discussion. Our decision to focus on the use of a
cyclododecanone-derived bishydroperoxide was based upon
the report by Terent’ev investigating hydrolysis of analogous
1,1-dihydroperoxides. In that work, the bis-hydroperoxyacetals
General Procedure (Method A): Synthesis of 1,1-Bisperox-
yacetals. To a 0 °C solution of cyclododecanone 1,1-dihydroperoxide
(1 mmol) in ethyl acetate (10 mL) was added freshly prepared Ag2O
(3 mmol) followed by alkyl iodide (2.2 mmol). The reaction was
stirred at room temperature until starting material could no longer be
detected (TLC, 5−30 h).17 The reaction solution was filtered though a
small pad of Celite, and the filtrate was concentrated in vacuo. The
residue was purified by silica chromatography using 1% EA/Hex to
furnish pure samples of the bisperoxyacetal.
C
dx.doi.org/10.1021/jo4001564 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
General Procedure (Method B): Synthesis of Bisperoxyace-
tal from Alkyl Triflates. To a 0 °C solution of 1,1-dihydroperoxide
(0.5 mmol) in dry THF was added KOtBu (2.1 equiv) followed by
alkyl triflate (2.2 equiv/equiv DHP for primary triflates, 3 equiv/equiv
DHP for secondary triflates). The reaction was allowed to stir until
starting material was no longer visible (TLC, 20 min to 1 h) and then
quenched with water (15 mL).17 The combined EA extracts (25 mL ×
2) were dried over Na2SO4 and concentrated on a rotary evaporator.
The crude product was purified by silica chromatography using 1%
diethyl ether and hexane.
4.06 (m, 2H), 1.71−1.58 (m, 7H), 1.48 (m, 5H), 1.36−1.20 (m, 30H),
1.21 (d, J = 6.2 Hz, 6H), 0.90 (t, J = 6.4 Hz, 6H); 13C NMR δ 112.8,
79.6, 79.5, 34.7, 32.1, 31.8, 31.5, 29.4, 27.3, 27.2, 26.2, 26.1, 25.6, 25.5,
25.3, 22.6, 22.4, 22.0, 19.4, 18.8, 14.0; IR (neat) 2927, 2855, 1468,
1055, 989; HRMS (ESI+, TOF) calcd for C28H56NaO4 (M + Na)+
479.4076, found 479.4068.
1,1-Bis(2-dodecyl peroxy) Cyclododecane (2g). Thick color-
1
less liquid, yield 42% (252 mg). Rf (15% EA/Hex) 0.84; H NMR δ
4.23 (m, 2H), 1.71−1.59 (m, 6H), 1.48 (m, 4H), 1.36 (m, 18H), 1.28
(m, 30H), 1.21 (d, J = 6.3 Hz, 6H), 0.90 (t, J = 6.3 Hz, 6H); 13C NMR
δ 112.8, 79.6, 79.5, 34.7, 31.9, 29.8, 29.6, 29.3, 27.3, 26.2, 26.1, 25.7,
25.6, 22.7, 22.3, 22.0, 19.4, 18.86, 18.83, 14.1; IR (neat) 2922, 2851,
1467, 989; HRMS (ESI+, TOF) calcd for C36H72NaO4 (M + Na)+
591.5328, found 591.5319.
4-tert-Butyl-1,1-bis(decylperoxy) Cyclohexane (4). Thick
colorless liquid, yield 89% (866 mg). Rf (10% EA/Hex) 0.71; 1H
NMR δ 4.11 (t, J = 6.7 Hz, 2H), 4.06 (t, J = 6.7 Hz, 2H), 2.29 (bd, J =
12.0 Hz, 2H), 1.69−1.58 (m, 6H), 1.44−1.19 (m, 33H), 0.89 (t, J =
0.89 Hz, 6H), 0.87 (s, 9H); 13C NMR δ 108.9, 75.4, 75.1, 47.5, 32.3,
31.9, 30.6, 29.6, 29.48, 29.47, 29.3, 27.89. 27.83, 27.6, 26.18, 26.16,
23.5, 22.7, 14.1; IR (neat) 2922, 2853, 1466, 1365, 1060; HRMS
(ESI+, TOF) calcd for C30H60NaO4 (M + Na)+ 507.4389, found
507.4384.
General Procedure: Synthesis of Alkyl Hydroperoxides from
1,1-Dihydroperoxides. To a room temperature solution of
bisperoxyacetal (0.3 mmol) in tetrahydrofuran (3 mL) was added
50% aqueous H2SO4 (1.8 mmol, 6 equiv). The reaction was heated at
50−55 °C until starting material could no longer be detected (TLC,
1−3 h).17 The reaction was then allowed to cool to room temperature
and quenched with saturated aqueous Na2CO3 (15 mL). The
combined EA extracts (25 mL × 2) were dried over Na2SO4 and
concentrated. The residue was purified by silica chromatography using
1−3% EA/Hex.
1,1-Dihydroperoxy Cyclododecane (1a). White solid, mp 139−
1
141 °C, yield 78% (909 mg). Rf (20% EA/Hex) 0.54; H NMR δ
(MeOH-d4, 300 MHz) 4.84 (s, 2H), 1.59−1.52 (m, 8H), 1.39 (m,
14H); 13C NMR δ (MeOH-d4, 75 MHz) 113.3, 25.8, 25.7, 21.9, 21.6,
18.9.
4-tert-Butyl 1,1-Dihydroperoxy Cyclohexane (1b). White
solid, mp 78−80 °C, yield 85% (174 mg). Rf (20% EA/Hex) 0.54;
1H NMR δ (300 MHz) 8.95 (bs, 2H), 2.33 (bd, J = 12 Hz, 2H), 1.75
(bd, J = 12 Hz, 2H), 1.48 (dt, J = 13.3, 3.6 Hz, 2H), 1.27 (dq, J = 13.3,
3.6 Hz, 2H), 1.06 (tt, J = 12.0, 2.9 Hz, 1H), 0.88 (s, 9H); 13C NMR δ
111.0, 47.4, 32.3, 29.7, 27.6, 23.4.
1,1-Bis(decylperoxy) Cyclododecane (2a). Thick colorless
liquid, yield 93% (553 mg). Rf (10% EA/Hex) 0.74; 1H NMR δ
4.07 (t, J = 6.8 Hz, 4H), 1.75−1.58 (m, 8H), 1.48 (m, 4H), 1.35−1.27
(m, 42H), 0.88 (t, J = 6.8 Hz, 6H); 13C NMR δ 113.1, 75.0, 31.9, 29.6,
29.5, 29.3, 27.9, 27.0, 26.2, 26.11, 22.7, 22.3, 21.9, 19.4, 14.1; IR (neat)
2922, 2851, 1468, 1054, 989; HRMS (ESI+, TOF) calcd for
C32H64NaO4 (M + Na)+ 535.4702, found 535.4727.
1,1-Bis(hexylperoxy) Cyclododecane (2b). Thick colorless
liquid, yield 79% (317 mg). Rf (10% EA/Hex) 0.65; 1H NMR δ
4.05 (t, J = 6.7 Hz, 4H), 1.67−1.57 (m, 8H), 1.50−1.41 (m, 4H),
1.39−1.27 (m, 26H), 0.88 (t, J = 6.8 Hz, 6H); 13C NMR δ 113.1, 75.0,
31.6, 27.8, 27.0, 26.0, 25.9, 25.7, 22.6, 22.3, 21.9, 19.3, 13.99; IR (neat)
2927, 2852, 1468, 1052, 989; HRMS (ESI+, TOF calcd for
C24H48NaO4 (M + Na)+ 423.3450, found 423.3465.
Decyl Hydroperoxide (3a). CAS no. 4225-91-6. Colorless liquid,
yield 78% (64 mg). Rf (10% EA/Hex) 0.44; 1H NMR, δ 8.23 (s, 1H),
4.03 (t, J = 6.7 Hz, 2H), 1.64 (quintet, J = 6.7 Hz, 2H), 1.37−1.27 (m,
14H), 0.89 (t, J = 6.8 Hz, 3H); 13C NMR δ 76.7, 31.9, 29.5, 29.4, 29.3,
27.5, 25.9, 22.7, 14.1.
Hexyl Hydroperoxide (3b). CAS no. 4312-76-9. Colorless liquid,
1
yield 49% (58 mg). Rf (10% EA/Hex) 0.39; H NMR δ 8.36 (s, 1H),
4.03 (t, J = 6.7 Hz, 2H), 1.64 (quintet, J = 6.8 Hz, 2H), 1.39−1.26 (m,
6H), 0.89 (t, J = 6.9 Hz, 3H); 13C NMR δ 76.7, 31.6, 27.5, 25.5, 22.5,
13.9.
Benzyl Hydroperoxide (3c). CAS no. 3071-34-9. Colorless liquid,
1
yield 60% (75 mg). Rf (10% EA/Hex) 0.22; H NMR δ 8.25 (s, 1H),
7.43−7.39 (m, 5H), 5.02 (s, 2H); 13C NMR δ 135.7, 129.0, 128.6,
79.2.
9-Decenyl Hydroperoxide (3d). CAS no. 123369-53-9. Colorless
1
liquid, yield 62% (107 mg). Rf (10% EA/Hex) 0.37; H NMR δ 8.23
(s, 1H), 5.87−5.77 (m, 1H), 5.03−4.92 (m, 2H), 4.03 (t, J = 6.7 Hz,
2H), 2.07−2.02 (m, 2H). 1.64 (quintet, J = 6.9 Hz, 2H), 1.40−1.25
(m, 10H); 13C NMR δ 139.1, 114.1, 76.7, 33.7, 29.35, 29.34, 29.0,
28.9, 27.5, 25.9.
4-Phenylbutyl Hydroperoxide (3e). CAS no. 99172-63-1.
1
Colorless liquid, yield 79% (133 mg). Rf (10% EA/Hex) 0.30; H
1,1-Bis(benzylperoxy) Cyclododecane: (2c). White solid, yield
NMR δ 8.44 (s, 1H), 7.37−7.33 (m, 2H), 7.27−7.24 (m, 3H), 4.09 (t,
J = 6.1 Hz, 2H), 2.71 (t, J = 7.1 Hz, 2H). 1.80−1.71 (m, 4H); 13C
NMR δ 142.2, 128.48, 128.4, 125.8, 76.9, 35.6, 27.7, 27.2.
1
56% (232 mg). Mp 68−70 °C; Rf (10% EA/Hex) 0.69; H NMR δ
7.41−7.32 (m, 10H), 5.11 (s, 4H), 1.73−1.69 (m, 4H), 1.52−1.42 (m,
4H), 1.35 (m, 14H); 13C NMR δ 136.0, 129.2, 128.3, 128.2, 113.8,
27.1, 26.1, 22.3, 21.9, 19.4; IR (neat) 2927, 2850, 1706, 1469, 1453,
964; HRMS (ESI+, TOF) calcd for C26H36NaO4 (M + Na)+ 435.2511,
found 435.2508.
2-Octyl Hydroperoxide (3f). CAS no. 32956-90-4. Colorless
liquid, yield 48% (105 mg). Rf (10% EA/Hex) 0.37; [α]D −0.5 (c 1.46
g/100 mL, CHCl3;2g 1H NMR δ 7.89 (s, 1H), 4.07 (m, 1H), 1.64 (m,
1H), 1.44−1.28 (m, 9H), 1.23 (d, J = 6.1 Hz, 3H), 0.89 (t, J = 6.9 Hz,
3H); 13C NMR δ 84.7, 34.0, 31.7, 29.3, 25.3, 22.5, 18.1, 14.0.
2-Dodecyl Hydroperoxide (3g). CAS no. 123369-50-6. Colorless
liquid; yield 63% (94 mg). Rf (15% EA/Hex) 0.33; 1H NMR δ 7.81 (s,
1H), 4.12−4.04 (m, 1H), 1.68−1.61 (m, 1H), 1.45−1.27 (m, 17H),
1.24 (d, J = 6.1 Hz, 3H), 0.89 (t, J = 6.9 Hz, 3H); 13C NMR δ 81.7,
34.0, 31.9, 29.69, 29.61, 29.59, 29.55, 29.33, 25.4, 22.6, 18.1, 14.1.
1,1-Bis(9-decenylperoxy) Cyclododecane (2d). Thick colorless
liquid, yield (method B) 80% (122 mg), (method A) 79% (400 mg).
Rf (10% EA/Hex) 0.81; 1H NMR δ 5.81 (m, 2H), 5.02−4.91 (m, 4H),
4.07 (t, J =6.6 Hz, 4H), 2.04 (q, J = 6.8 Hz, 4H), 1.70−1.58 (m, 8H),
1.49−1.31 (m, 38H); 13C NMR δ 139.1, 114.3, 113.1, 75.0, 33.8, 29.4,
29.1, 28.9, 27.9, 27.1, 26.2, 26.1, 22.3, 21.98, 19.4; IR (neat) 3076
(week), 2924, 2852, 1468, 990, 907; HRMS (ESI+, TOF) calcd for
C32H60NaO4 (M + Na)+ 531.4389, found 531.4385.
1,1-Bis(4-phenylbutylperoxy) Cyclododecane (2e). Thick
colorless liquid, yield 68% (340 mg). Rf (10% EA/Hex) 0.82; 1H
NMR δ 7.30 (m, 4H), 7.21 (m, 6H), 4.13 (t, J = 6.0, 4H), 2.67 (t, J =
7.1 Hz, 4H), 1.76−1.69 (m, 12H), 1.51 (m, 4H), 1.39 (m, 14H); 13C
NMR δ 142.3, 128.4, 128.3, 125.7, 113.2, 74.8, 35.7, 28.0, 27.5, 27.1,
26.1, 22.4, 22.0, 19.4; IR (neat) 2927, 2860, 1495, 1469, 1452, 989;
HRMS (ESI+, TOF) calcd for C32H48NaO4 (M + Na)+ 519.3450
found 519.3439.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
1,1-Bis(2-octyl peroxy) Cyclododecane (2f). Thick colorless
liquid, yield 53% (417 mg). Rf (10% EA/Hex) 0.85; 1H NMR δ 4.25−
*E-mail: pdussault1@unl.edu.
D
dx.doi.org/10.1021/jo4001564 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(15) Reported rotation for (R)-2-octanol: [α]D = −6.4 (c 1.02,
CHCl3). Guindon, Y.; Ogilvie, W. W.; Bordeleau, J.; Cui, W. L.;
Durkin, K.; Gorys, V.; Juteau, H.; Lemieux, R.; Liotta, D.; Simoneau,
B.; Yoakim, C. J. Am. Chem. Soc. 2003, 125, 428. However, specific
rotations of up to 7.7−8.2 have been reported; see ref 2f.
(16) For leading references to peroxide safety, see: Medard, L. A.
Accidental Explosions: Types of Explosive Substances; Ellis Horwood
Limited: Chichester, 1989; Vol. 2. Patnaik, P. A. Comprehensive Guide
to the Hazardous Properties of Chemical Substances, 3rd ed.; John Wiley
& Sons: Hoboken, NJ, 2007. Zabicky, J. In The Chemistry of the
Peroxide Group; Rappoport, Z., Ed.; John Wiley & Sons: Chichester,
2006; Vol. 2, pt 2, pp 597−773.
(17) Peroxides are easily detected with a TLC dip based upon N,N′-
dimethyl p-phenylenediamine: Smith, L. L.; Hill, F. L. J. Chromatogr.
1972, 66, 101. Hydroperoxides and dihydroperoxides generate an
immediate pink-red color upon exposure to the dip, while
bisperoxyacetals demonstrate a pink color after heating of the TLC
plate.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Research was conducted with funding from the NSF (CHE-
1057982) in facilities remodeled with support from the NIH
(RR016544). We thank Ms. Sara Basiaga for technical
assistance.
REFERENCES
■
(1) General reviews: (a) Porter, N. A. In Organic Peroxides; Ando, W.,
Ed.; Wiley: Chichester, 1992; pp 101−56. (b) Foglia, T. A.; Silbert, L.
S. J. Am. Oil. Chem. Soc. 1992, 69, 151−4. (c) Sheldon, R. A. In The
Chemistry of Peroxides; Patai, S., Ed.; Wiley: Chichester, New York,
1983; p 161. (d) Scarso, A.; Strukul, G. Sci. Synth. 2008, 38, 9−71.
(2) H2O2, base: (a) Williams, H. R.; Mosher, H. S. J. Am. Chem. Soc.
1954, 76, 2984. (b) Williams, H. R.; Mosher, H. S. J. Am. Chem. Soc.
1954, 76, 2987. (c) Williams, H. R.; Mosher, H. S. J. Am. Chem. Soc.
1954, 76, 3495. H2O2, Ag(I): (d) Cookson, P. G.; Davies, A. G.;
Roberts, B. P. J. Chem. Soc., Chem. Commun. 1976, 1022. H2O2, alkyl
triflates: (e) Salomon, M. F.; Salomon, R. G.; Gleim, R. D. J. Org.
Chem. 1976, 41, 3983. Superoxide: (f) Johnson, R. A.; Nidy, E. G.;
Merritt, M. V. J. Am. Chem. Soc. 1978, 100, 7960. (g) Corey, E. J.;
Nicolaou, K. C.; Shibasaki, M.; Machida, Y.; Shiner, C. S. Tetrahedron
Lett. 1975, 16, 3183.
(3) Dussault, P. H.; Sahli, A. J. Org. Chem. 1992, 57, 1009. For similar
reactions based upon α-silyloxy hydroperoxides, see: Nagata, R.; Saito,
I. Synlett 1990, 291.
(4) (a) Cointeaux, L.; Berrien, J.-F.; Peyrou, V.; Provot, O.; Ciceron,
L.; Danis, M.; Robert, A.; Meunier, B.; Mayrargue, J. Bioorg. Med.
Chem. Lett. 2003, 13, 75. (b) Guerra, F. M.; Zubia, E.; Ortega, M. J.;
Moreno-Dorado, F. J.; Massanet, G. M. Tetrahedron 2010, 66, 157.
(5) Dussault, P. H. Chem. Eng. News 1993, August 9, 2. The hazard
can be partially mitigated by use of higher molecular weight
hydroperoxyacetals at a cost in terms of convenience: Dussault, P.
H.; Zope, U. R.; Westermeyer, T. A. J. Org. Chem. 1994, 59, 8267.
(6) (a) Ghorai, P.; Dussault, P. H. Org. Lett. 2008, 10, 4577.
(b) Ghorai, P.; Dussault, P. H.; Hu, C. Org. Lett. 2008, 10, 2401. (c)
For a review of α-oxygenated hydroperoxides, see: Zmitek, K.; Zupan,
M.; Iskra, J. Org. Biomol. Chem. 2007, 5, 3895.
(7) (a) Kim, H.-S.; Nagai, Y.; Ono, K.; Begum, K.; Wataya, Y.;
Hamada, Y.; Tsuchiya, K.; Masuyama, A.; Nojima, M.; McCullough, J.
K. J. Med. Chem. 2001, 44, 2357−2361. (b) Hamada, Y.; Tokuhara, H.;
Masuyama, A.; Nojima, M.; Kim, H.-S.; Ono, K.; Ogura, N.; Wataya,
Y. J. Med. Chem. 2002, 45, 1374.
(8) Dussault, P. H.; Lee, I. Q.; Lee, H.-J.; Lee, R. J.; Niu, Q. J.;
Schultz, J. A.; Zope, U. R. J. Org. Chem. 2000, 65, 8407.
(9) For a discussion of peroxide safety, including the concept of
active oxygen, see “Safety and Handling of Organic Peroxides Guide”;
spi: The Plastic Industry Trade Association: http://www.
p l a s t i c s i n d u s t r y . o r g / fi l e s / a b o u t / o p p s d /
AS%2D109%20v%208%2006%202012.pdf
(10) Terent’ev, A. O.; Krivykh, O. B.; Krylov, I. B.; Ogibin, Y. N.;
Nikishin, G. I. Russ. J. Gen. Chem. 2010, 80, 1667.
(11) (a) Bloodworth, A. J.; Eggelte, H. J. J. Chem. Soc., Perkin Trans. 1
1981, 3272. (b) Adam, W.; Birke, A.; Cadiz, C.; Diaz, S.; Rodriguez, A.
J. Org. Chem. 1978, 43, 1154.
(12) Kornblum, N.; DeLaMare, H. E. J. Am. Chem. Soc. 1951, 73,
880.
(13) (a) Baj, S.; Siewniak, A. Appl. Catal. A 2010, 385, 208−213 and
references therein. (b) Moulines, J.; Bougeois, M.-J.; Campagnole, M.;
Lamidey, A.-M.; Maillard, B.; Montaudon, E. Synth. Commun. 1990,
20, 349.
(14) Purification of primary and secondary triflates has been
described: Denmark, S. E.; Burk, M. T.; Hoover, A. J. J. Am. Chem.
Soc. 2010, 132, 1232. However, we encountered extensive
decomposition of secondary triflates upon attempted purification.
E
dx.doi.org/10.1021/jo4001564 | J. Org. Chem. XXXX, XXX, XXX−XXX