A new approach to the synthesis of vicinal iodoperoxyalkanes by the reaction of alkenes with iodine and hydroperoxides

Article abstract of DOI:10.1055/s-2007-990776

A convenient procedure was developed for the synthesis of vicinal iodoperoxyalkanes by the reaction of alkenes with iodine and hydroperoxides. The best results were achieved with the use of excess iodine. The replacement of one iodine atom by hydroperoxid

Full text of DOI:10.1055/s-2007-990776

PAPER
2979
A New Approach to the Synthesis of Vicinal Iodoperoxyalkanes by the
Reaction of Alkenes with Iodine and Hydroperoxides
S
A
ynthesis of
V
icin
l
al Iodo
e xn es ander O. Terent’ev,* Igor B. Krylov, Dmitry A. Borisov, Gennady I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., Moscow 119991, Russian Federation
Fax +7(495)1355328; E-mail: terentev@ioc.ac.ru
Received 24 April 2007; revised 12 July 2007
which is easy to replace, these compounds are valuable re-
Abstract: A convenient procedure was developed for the synthesis
agents in preparative nucleophilic substitution reactions
occurring with retention of the peroxide fragment. This
excess iodine. The replacement of one iodine atom by hydroperox- may find use in the synthesis of biologically active com-
ides in vicinal diiodoalkanes was discovered. A suggestion was pounds.
of vicinal iodoperoxyalkanes by the reaction of alkenes with iodine
and hydroperoxides. The best results were achieved with the use of
made about the reaction mechanism.
The proposed method for the synthesis of iodoperoxyal-
kanes is based on the reaction of alkenes with iodine and
hydroperoxides (Scheme 1). The reactions were complet-
Key words: iodination, peroxidation, hydrogen peroxide, tert-bu-
tyl hydroperoxide, iodoperoxyalkanes
ed in 3 hours (with hydrogen peroxide), 5 hours (with tert-
butyl hydroperoxide), and 72 hours (with tetrahydropyra-
In recent years, organic peroxides and methods for their
synthesis have attracted considerable interest, particular-
ly, after the discovery of antimalarial activity of com-
nyl hydroperoxide) at room temperature by mixing alk-
enes 1–7, excess iodine, and hydroperoxide in diethyl
ether or dichloromethane. Iodoperoxyalkanes 8–22 were
synthesized in yields of up to 70%. Iodohydroxyalkanes
1
pounds belonging to this class, tetraoxanes and ozonides,
showing stronger activity. The presence of the peroxide
fragment in artemisinin, which is used for the treatment of
2
3–29 were obtained as by-products.
2
malaria, is of importance. A series of more recent studies
I
R''
I
R''
2
I , ROOH
in this field were concerned with a search for simple ana-
logues of artemisinin.3
R'
R''
R'
OOR
R'
OH
Natural peroxides, such as plakinic acid E and its structur-
1–7
8–22
23–29
al analogues isolated from Plakortis sp., have cytotoxic
1
2
3
4
5
6
7
8
,
,
,
,
,
,
,
–
8
,
15
, 15', 19, 23 R' = H, R'' = n-Bu;
4
9,
24 R' = H, R'' = n-C
5
H
11
;
17
;
activity against some types of tumor cells, which has at-
10
11
12
13
14
,
,
,
,
,
25 R' = H, R'' = n-C
26 R' = H, R'' = n-C
16
17
18
8
H
5
tracted attention to the chemistry of 1,2-dioxolanes. In in-
8
H
16COOMe;
dustry, organic peroxides are still of importance as radical
polymerization initiators and oxidizing agents.6 The
above-mentioned practical aspects of the use of peroxides
stimulated the development of new methods for their syn-
thesis.
,
,
,
20,
21,
22,
27 R', R'' = - C
28 R', R'' = - C
29 R', R'' = - C
3
H
4
H
6
H
6
-;
-;
12
-
8
14 R = t-Bu; 15–18 R = H; 19–22 R =
O
Scheme 1 Synthesis of iodoperoxyalkanes
In this study, we performed a simple synthesis of perox-
ides containing iodine and the peroxy group in the vicinal Tables 1 and 2 present the influence of the reagent ratio
position. Earlier, iodoperoxyalkanes had been prepared on the selectivity of iodoperoxidation of alkanes, as exem-
by peroxymercuration of alkenes followed by iodination,7 plified by the reaction of cyclohexene (6) with an I -tert-
2
and by the reaction of alkenes with 1,3-diiodo-5,5-di- butyl hydroperoxide system. The most interesting result
8
methylhydantoin and hydrogen peroxide. Cyclic iodop- obtained in a series of experiments is that an increase in
eroxides, which are of interest for the design of new the excess amount of iodine leads to an increase, though
antimalarial drugs, were synthesized primarily by in- only slight, in the yield of 1-(tert-butylperoxy)-2-iodocy-
tramolecular cyclization of hydroperoxyalkenes with the clohexane (13) and a decrease in the amount of 2-iodocy-
use of bis(collidine)iodine hexafluorophosphate,9 clohexanol (28) by a factor of more than 2.5 (Table 1),
9
c,10
NIS,
potassium hydride (or tert-butoxide) or pyridine whereas vicinal diiodoalkane is produced in trace
10c,11
and iodine
and, with worse results, with the use of amounts.
2
1
only iodine. Related vicinal iodomonoperoxyacetals
were synthesized by the reaction of enol esters with NIS
and t-BuOOH.13 Since iodoperoxides contain iodine,
An increase in the amount of t-BuOOH from 1.2 to 5
moles per mole of alkene allows an increase in the selec-
tivity of the synthesis (the 13:28 ratio increases from 1.24
to 2.9, see Table 2).
SYNTHESIS 2007, No. 19, pp 2979–2986
x
x.
x
x
.
2
0
0
7
The chromatographic monitoring of the conversion of cy-
clohexene during the course of the reaction was inefficient
Advanced online publication: 11.09.2007
DOI: 10.1055/s-2007-990776; Art ID: P05007SS
Georg Thieme Verlag Stuttgart · New York
©

2
980
A. O. Terent’ev et al.
PAPER
Table 1 Influence of the Amount of I on the Yield of 13 and 28a
because of the volatility of this compound and the pres-
ence of peroxides and iodine in the tested samples.
2
t
OO Bu
OH
tBuOOH, I2
Et2O
Vicinal tert-butylperoxyiodoalkanes 8–14 (Table 3, en-
tries 1–7) and hydroperoxyiodoalkanes 15–18 (entries 8–
11) were synthesized from alkenes using the above-men-
tioned reagent ratios. 2-Hydroperoxytetrahydropyran is
characterized by lower reactivity compared to hydrogen
peroxide and tert-butyl hydroperoxide. Hence, the reac-
tion time required for the preparation of vicinal tetrahy-
dropyranylperoxyiodoalkanes 19–22 (entries 12–15) was
increased to 72 hours (Table 3).
I
I
6
13
28
Moles of I per mole of 6
0.5
0.7
61
22
1
2
2
Yield (%) of 13b
54
31
65
18
70
12
Yield (%) of 28b
Yield ratio 13:28
1.74
2.77
3.61
5.83
Peroxides 8–14 and 19–22 can be easily isolated in pure
state by column chromatography. The isolation of hydro-
peroxides 15–18 in the reaction with iodine (0.7 mol per
mole of alkene) and t-BuOOH (4 mol per mole of alkene)
presented difficulties, and these compounds were ob-
tained as mixtures with substantial amounts of iodoal-
kanols 23 and 27–29. Iodohydroperoxides 15–18 and the
a
Reaction conditions: A 50% t-BuOOH solution (2.63 g, 14.6 mmol)
in Et O, I (0.48–1.86 g, 1.88–7.32 mmol), and 6 (0.3 g, 3.66 mmol)
2
2
were successively added to Et O (5 mL). The homogeneous mixture
2
was kept at 20–25 °C for 5 h.
b
Yield based on the isolated product.
corresponding iodoalkanols 23 and 27–29 differ in R by
f
Table 2 Influence of the Amount of t-BuOOH on the Molar Ratio
of 13 and 28 (cf. Table 1)
only 0.03–0.08. The characteristic signals of the hydrogen
a
1
atoms in the H NMR spectra for CHOOH are shifted
downfield by more than 0.2 ppm compared to CHOH,
which allowed us to determine the yields of 15–18 from
the H NMR spectroscopic data. Iodohydroperoxides 15–
Moles of t-BuOOH per mole of 6
Molar ratio 13:28b
1.2
2.5
4
5
1
1.24
2.13
2.8
2.9
1
8 were isolated in individual state by column chromatog-
a
Reaction conditions: A 50% t-BuOOH solution (0.79–3.29 g, 4.39–
8.3 mmol) in Et O, I (0.65 g, 2.56 mmol), and 6 (0.3 g, 3.66 mmol)
raphy after the reaction with excess iodine (4 mol per
mole of alkene). Under these conditions, the formation of
iodoalkanols was substantially suppressed. The drawback
of this method for the synthesis of iodoperoxides is that it
is difficult to remove the large excess of unconsumed io-
dine.
1
2
2
were successively added to Et O (5 mL). The homogeneous mixture
2
was kept at 20–25 °C for 5 h.
b 1
H NMR spectroscopic data.
Table 3 a Vicinal tert-Butylperoxyiodoalkanes 8–14, Hydroperoxyiodoalkanes 15–18, and Tetrahydropyranylperoxyiodoalkanes 19–22
Prepared
Entry
Alkene
Iodoperoxide
Yield (%)
57
t
OO Bu
1
Hex-1-ene (1)
I
8
9
1
t
OO Bu
2
3
Hept-1-ene (2)
Dec-1-ene (3)
( )2
52
61
I
t
OO Bu
( )5
I
0
t
O
OO Bu
4
5
Methyl undec-10-enoate (4)
Cyclopentene (5)
( )8
53
68
Me
I
1
1
t
OO Bu
I
1
2
Synthesis 2007, No. 19, 2979–2986 © Thieme Stuttgart · New York

PAPER
Synthesis of Vicinal Iodoperoxyalkanes
2981
Table 3 a Vicinal tert-Butylperoxyiodoalkanes 8–14, Hydroperoxyiodoalkanes 15–18, and Tetrahydropyranylperoxyiodoalkanes 19–22
Prepared (continued)
Entry
6
Alkene
Iodoperoxide
Yield (%)
61
t
OO Bu
Cyclohexene (6)
I
1
3
4
t
OO Bu
7
Cyclooctene (7)
Hex-1-ene (1)
67
I
1
OOH
I
62, 63c
b
8
9
I
OOH
1
1
1
5 + 15¢
OOH
59, 61c
61, 62c
43, 51c
b
Cyclopentene (5)
Cyclohexene (6)
Cyclooctene (7)
I
6
7
OOH
b
1
1
0
1
I
OOH
b
I
1
8
I
O
O
O
1
2
Hex-1-ene (1)
O
31
1
2
2
9
I
O
O
1
1
3
4
Cyclopentene (5)
Cyclohexene (6)
47
51
O
0
I
O
O
1
I
O
O
1
5
Cyclooctene (7)
O
37
2
2
a
General reaction conditions: 0.7 mol of I per mole of alkene, 4 mol of hydroperoxide per mole of alkene; reaction time: 5 h (8–14), 3 h (15–
2
1
8), and 72 h (19–22); temperature: 20–25 °C. Yield based on isolated product, exept where otherwise specified.
Yield from H NMR spectroscopic data.
b
1
c
4
mol of I per mole of alkene; yield based on the isolated product.
2
The reaction of hydrogen peroxide with hex-1-ene pro- of the mixtures presents difficulties because of similar Rf
duced a mixture of regioisomers of iodoperoxides 15 and and the tendency of iodoperoxides to undergo decomposi-
1
5¢ (entry 8).
tion.
2
-Tetrahydropyranylperoxy-1-iodoalkanes were isolated The reactions of all hydroperoxides afforded also vicinal
1
3
as mixtures of diastereomers. The C NMR spectra of iodoalkanols as by-products in yields from ~10 to 40%. In
these mixtures show double sets of signals. The separation most cases, these by-products were not isolated and were
Synthesis 2007, No. 19, 2979–2986 © Thieme Stuttgart · New York

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A. O. Terent’ev et al.
PAPER
H2O
+
–
I2
δ
δ
I
I
A
X
tBuOOH
t
OO Bu
I
I2
B
+
HI
I
tBuOOH
OH
I
I
I2
+
–
H2O
δ
δ
I
I3
Y
H2O
tBuOOH
Scheme 2 Proposed mechanism of formation of iodoperoxyalkanes and iodoalkanols.
t
identified in mixtures with iodoperoxyalkanes based on
I
OO Bu
1
3
1
the characteristic signals in the C and H NMR spectra
and by TLC comparison with iodoalkanols, which were
3
3
0
1
I
8
I
1
4
prepared according to known procedures. In the synthe-
ses of iodoperoxides 12,13,20, and 21, the yields of io-
doalkanols 27 and 28 were 28, 26, 17, and 15%,
respectively, based on the isolated products. In the synthe-
sis of iodoperoxide 11, iodoalkanol 26 was isolated in
tBuOOH, I2
t
I
OO Bu
Et2O
I
I
13
3
3% yield. Virtually the same result was obtained in the
Scheme 3 Synthesis of iodoperoxyalkanes from diiodoalkanes.
synthesis of 13 in dichloromethane.
We propose the following mechanism of formation of io-
doperoxyalkanes and iodoalkanols (Scheme 2). Appar-
ently, iodoperoxyalkane is formed by two pathways, A
and B. The pathway A corresponds to the classical scheme
of the successive addition of electrophilic iodine and nu-
cleophilic hydroperoxide to the double bond.
Table 4 Synthesis of Vicinal tert-Butylperoxyiodoalkanes from
Vicinal Diiodoalkanesa
Iodoperoxide
Moles of I per mole of diiodoalkane 30 or 31
2
without I2
traces
15
0.1
29
41
0.5
67
70
Yield (%) of 8c
The pathway B is an original hypothesis of the present
study. It is based on experimental data, according to
which an increase in the amount of iodine (a nucleophile
competing with tert-butyl hydroperoxide) leads to an in-
crease in the yield of 1-(tert-butylperoxy)-2-iodocyclo-
hexane (13), whereas the expected 1,2-diiodocyclohexane
Yield (%) of 13b,c
a
Reaction conditions: A 50% t-BuOOH solution (3.6 g, 20 mmol) in
Et O, I (0.13 or 0.64 g, 0.5 or 2.5 mmol), and diiodoalkane (5 mmol)
2
2
were successively added to Et O (5 mL). The mixture was kept at 20–
2
2
5 °C for 2 h.
(
31) is formed in trace amounts (Table 1). Apparently, io-
b
The formation of 13 in the reaction in the absence of I is apparently
2
doperoxide is formed by the pathway B as a result of the attributed to the fact that we failed to prepare 1,2-diiodocyclohexane
previously unknown process. Initially, the reaction pro- (31) not contaminated with I
; compound 31 partially decomposes in
2
the course of isolation with elimination of I .
duces 1,2-diiodocyclohexane (31) (diiodides are known to
2
c
1
5
Yield based on the isolated product.
be in equilibrium with iodine and alkene ), which is
transformed under the action of iodine into intermediate Y
containing a partially positive charge on the carbon atoms.
The latter reacts with hydroperoxide.
Attempts to replace iodine by the tert-butylperoxy group
in structurally similar halogen-containing compounds,
such as iodocyclohexane, 2-iodocyclohexanol (28), and
To confirm this hypothesis, authentic 1,2-diiodohexane
(
30) and 1,2-diiodocyclohexane (31) were introduced into
1
,2-dibromocyclohexane, in the presence of iodine (0.5
the reaction with tert-butyl hydroperoxide. The reactions
were carried out in the absence and in the presence of io-
dine (Scheme 3, Table 4).
mol per mole of halide) failed. Hence, the above-de-
scribed reaction is characteristic of vicinal diiodo deriva-
tives.
It can be seen that iodine actively catalyzes the replace-
ment of one iodine atom in diiodoalkanes by tert-butyl hy-
droperoxide. In the absence of iodine, the reaction
virtually does not proceed. In the presence of 0.5 mol of I2
per mole of alkene, iodoperoxides 8 and 13 were obtained
We failed to perform iodoperoxidation of allyl propionate
by tert-butyl hydroperoxide; instead, we obtained a diiod-
ination product of the double bond. Iodine was also not re-
placed by tert-butyl hydroperoxide in the separately
prepared diiodination product of allyl propionate. Appar-
ently, this is associated with the ability of the carbonyl ox-
in 67 and 70% yield, respectively.
Synthesis 2007, No. 19, 2979–2986 © Thieme Stuttgart · New York

PAPER
Synthesis of Vicinal Iodoperoxyalkanes
2983
1
9
ygen atom to compensate the partially positive charge in 1,2-Dibromocyclohexane
1
H NMR (250.13 MHz, CDCl ): d = 1.42–1.59 (m, 2 H, CH ), 1.63–
intermediates X and Y through the cyclic transition state.
3
2
1
.97 (m, 4 H, CH ), 2.36–2.55 (m, 2 H, CH ), 4.39–4.52 (m, 2 H,
2
2
Iodoalkanols are, apparently, generated as a result of the
CHI).
addition of water to intermediates X and Y. In turn, water
2
1
is formed upon oxidation of HI with t-BuOOH 1,2-Diiodohexane (30)
1
H NMR (250.13 MHz, CDCl ): d = 0.93 (t, J = 7.1 Hz, 3 H, CH ),
(
Scheme 2). Iodoalkanols are not formed by reduction of
3
3
1
4
.20–2.01 (m, 6 H, CH ), 3.67 (dd, J = 9.85, 3.94 Hz, 1 H, CH I),
2
2
iodoperoxides under the reaction conditions (under the ac-
tion of iodine) or in the course of their isolation, which
was confirmed by the corresponding experiments with the
separately prepared iodoperoxide, which remained un-
consumed. It cannot be completely ruled out that a small
amount of iodoalkanol is generated due to the presence of
residual water in hydroperoxide solutions.
.05 (dd, J = 9.85, 11.81 Hz, 1 H, CH I), 4.27–4.38 (m, 1 H, CHI).
2
1
3
C NMR (62.9 MHz, CDCl ): d = 13.8, 13.9 (CH I, CH ), 21.7
CH CH ), 30.9 (CH CH CH ), 33.3 (CHI), 38.7 (CH CHI).
2 3 2 2 3 2
3
2
3
(
,2-Diiodocyclohexane (31)22
H NMR (250.13 MHz, CDCl ): d = 1.30–2.39 (m, 8 H, CH ), 4.95–
1
1
3
2
5
.07 (m, 2 H, CHI).
We performed an experiment on the determination of the
competitive influence of tert-butyl hydroperoxide and
water in iodoperoxidation of cyclohexene. In a t-BuOOH/
1
-tert-Butylperoxy-2-iodoalkanes 8–14; General Procedures
A 50% t-BuOOH solution (1.2–5 mol per mole of alkene) in Et O,
I2 (0.5–2 mol per mole of alkene), and the appropriate alkene (0.3 g)
were successively added to Et O (5 mL). The homogeneous mixture
2
H O/I /alkene system (the molar ratio was 8:2:0.7:1), io-
2
2
2
doperoxide 13 and iodoalkanol 28 were obtained in a ratio was kept at 20–25 °C for 5 h. Then hexane (40 mL) was added, and
1
of 1.05 ( H NMR spectroscopic data). The results of the the mixture was successively washed with H
O (2 × 10 mL) and aq
2
1
0% KI (7 × 10 mL) until the mixture became slightly colored, and
experiment allow a conclusion that tert-butyl hydroperox-
ide, which is traditionally considered as a stronger nucleo-
phile than water, is less reactive than the latter in the
process under consideration.
again with H O (2 × 10 mL). Then the mixture was dried (MgSO )
2
4
and filtered. The filtrate was concentrated in vacuum (~10 mm Hg)
at a temperature not higher than 30 °C. Peroxides 8–14 were isolat-
ed in individual state by silica gel chromatography using hexane–
EtOAc (30:1) as eluent. The iodohydroxyalkane by-products were
isolated by silica gel chromatography using hexane–EtOAc (5:1) as
eluent.
Iodoperoxides were isolated according to an original pro-
cedure based on removal of an iodine residue through the
formation of the KI·I complex by washing the reaction
mixture with a KI solution. In this case, a standard proce-
dure for removal of iodine with Na S O is unsuitable be-
cause it leads to reduction of iodoperoxides to
iodoalkanols.
2
The synthesis of 13 was carried out using CH Cl (5 mL) and a 30%
2
2
t-BuOOH solution in CH Cl .
2
2
2
2
5
Iodoperoxidation of allyl propionate was carried out analogously; t-
BuOOH (4 mol per mole of allyl propionate) and I (0.7 mol per
mole of allyl propionate) were used, the reaction time was 5 h. 2,3-
2
To summarize, we have developed a simple procedure for Diiodopropyl propionate was isolated.
the synthesis of vicinal iodoperoxides by the reaction of
The formation of iodoalkanols by reduction of iodoperoxides with
I2 under the reaction conditions or during isolation was determined
alkenes with iodine and hydroperoxides, which enables
the preparation of the target compounds in yields of up to by adding authentic 1-tert-butylperoxy-2-iodocyclohexane (0.3 g)
7
0%. The reaction of vicinal diiodides with hydroperox- instead of the alkene to the reaction mixture or by isolating 1-tert-
butylperoxy-2-iodocyclohexane by working up its solution (0.3 g)
ides was discovered. In the presence of iodine, only one
iodine atom is replaced by the peroxy group to form vici-
nal iodoperoxides. A mechanism has been suggested for
this reaction.
in Et O (10 mL) according to the procedure used for the isolation of
peroxides 8–14.
2
-(tert-Butylperoxy)-1-iodohexane (8)23
2
Slightly yellow oil; R = 0.34 (TLC, hexane–EtOAc, 20:1).
f
1
NMR spectra were recorded on Bruker AC-200 (200.13 MHz for
H NMR (300.13 MHz, CDCl ): d = 0.88 (t, J = 7 Hz, 3 H, CH ),
3
3
1
13
1
H, 50.32 MHz for C), Bruker WM-250 (250.13 MHz for H, 62.9
1.14–1.71 (m, 15 H, CH ), 3.27 (dd, J = 10, 6.6 Hz, 1 H, CH I), 3.43
(dd, J = 10, 3.4 Hz, 1 H, CH I), 3.69–3.78 (m, 1 H, CH).
2
2
1
3
1
MHz for C), and Bruker AM-300 (300.13 MHz for H, 75.4 MHz
2
for 13C) spectrometers in CDCl . Analytical TLC: Silufol UV-254,
3
13
C NMR (62.9 MHz, CDCl ): d = 9.1 (CH I), 13.9 (CH CH ), 26.5
3
2
3
2
Silpearl as the sorbent, starch as the binder. Chromatography was
performed on silica gel (63–200 mesh, Merck). Alkenes, allyl pro-
pionate, Na S O , 70% aq t-BuOOH, and KI were purchased from
(
CH C), 22.5, 27.5, 32.1 (CH ), 80.1 (CO), 81.8 (CHO).
3
2
2
2
5
2
-(tert-Butylperoxy)-1-iodoheptane (9)
Acros. THF, hexane, Et O, EtOAc, I , and 37% aq H O (all of re-
2
2
2
2
Slightly yellow oil; R = 0.41 (TLC, hexane–EtOAc, 20:1).
f
agent grade) were used without additional purification. Solutions of
1
H NMR (300.13 MHz, CDCl ): d = 0.88 (t, J = 7 Hz, 3 H, CH ),
t-BuOOH in Et O and CH Cl and a solution of H O in Et O were
3
3
2
2
2
2
2
2
1
.18–1.69 (m, 17 H, CH ), 3.28 (dd, J = 10, 6.6 Hz, 1 H, CH I), 3.43
prepared by extraction of the corresponding peroxides from their
2
2
1
6
(dd, J = 10, 3.5 Hz, 1 H, CH I), 3.69–3.81 (m, 1 H, CH).
13
aqueous solutions followed by drying over MgSO . The concen-
2
4
1
7
tration of peroxides was determined by titration. Iodocyclohex-
C NMR (62.9 MHz, CDCl ): d = 9.0 (CH I), 13.9 (CH CH ), 26.6
3
2
3
2
18
19
ane,
1,2-dibromocyclohexane,
tetrahydro-2H-pyran-2-yl
(
CH C), 22.5, 25.0, 31.7, 32.5 (CH ), 80.1 (CO), 81.9 (CHO).
3
2
hydroperoxide,20 and diiodoalkanes 30 and 31 were prepared ac-
21
22
Anal. Calcd for C H IO : C, 42.05; H, 7.38; I, 40.39. Found: C,
4
1
1
23
2
cording to known procedures.
2.12; H, 7.77; I, 40.65.
Iodocyclohexane18
1
2-(tert-Butylperoxy)-1-iododecane (10)
H NMR (250.13 MHz, CDCl ): d = 1.26–2.25 (m, 10 H, CH ),
3
2
Slightly yellow oil; R = 0.54 (TLC, hexane–EtOAc, 20:1).
f
4
.30–4.44 (m, 1 H, CHI).
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PAPER
1
H NMR (300.13 MHz, CDCl ): d = 0.87 (t, J = 7 Hz, 3 H, CH ),
Anal. Calcd for C H I O : C, 19.59; H, 2.74; I, 68.98. Found: C,
19.39; H, 2.47; I, 68.71.
3
3
6
10 2
2
1
.14–1.69 (m, 23 H, CH ), 3.30 (dd, J = 10, 6.6 Hz, 1 H, CH I), 3.45
2
2
(
1
dd, J = 10, 3.5 Hz, 1 H, CH I), 3.69–3.81 (m, 1 H, CH).
2
2-Iodohexan-1-ol (23)14a
Rf = 0.5 (TLC, hexane–EtOAc, 4:1).
3
C NMR (62.9 MHz, CDCl ): d = 9.2 (CH I), 14.1 (CH CH ), 26.5
3
2
3
2
(
8
CH C), 22.6, 25.4, 29.2, 29.4, 29.5, 31.8, 32.5 (CH ), 80.3 (CO),
3
2
1
1.9 (CHO).
H NMR (250.13 MHz, CDCl ): d = 0.82–0.95 (t, J = 7 Hz, 3 H,
3
3
CH ), 1.22–1.64 (m, 6 H, CH ), 2.12–2.27 (br s, 1 H, OH), 3.20 (dd,
2
Anal. Calcd for C H IO : C, 47.20; H, 8.20; I, 35.62. Found: C,
4
14
29
2
J = 9.8, 6.7 Hz, 1 H, CH I), 3.37 (dd, J = 9.8, 3.3 Hz, 1 H, CH I),
2
2
7.33; H, 8.09; I, 35.17.
3
.42–3.54 (m, 1 H, CHO).
1
3
Methyl 10-(tert-Butylperoxy)-11-iodoundecanoate (11)
C NMR (62.9 MHz, CDCl ): d = 13.9 (CH ), 16.5, 22.5, 27.7, 36.2
3 3
Slightly yellow oil; R = 0.74 (TLC, hexane–EtOAc, 5:1).
(CH , CH I), 70.9 (CHO).
f
2
2
1
H NMR (250.13 MHz, CDCl ): d = 1.15–1.65 (m, 23 H, CH ,
3
2
24
Methyl 10-Hydroxy-11-iodoundecanoate (26)
CH ), 2.27 (m, J = 7.5 Hz, 2 H, CH CO Me), 3.28 (dd, J = 9.9, 6.6
Hz, 1 H, CH I), 3.43 (dd, J = 9.9, 3.3 Hz, 1 H, CH I), 3.63 (s, 3 H,
OCH ), 3.67–3.77 (m, 1 H, CHO).
1
3
2
2
24
White crystals; mp 40.5–42 °C (Lit. mp 43–44 °C); R = 0.25
f
2
2
(
TLC, hexane–EtOAc, 5:1).
3
1H NMR (250.13 MHz, CDCl
): d = 1.24–1.66 (m, 14 H, CH
m, J = 7.2 Hz, 2 H, CH CO Me), 1.87–1.99 (br s, 1 H, OH), 3.21
dd, J = 10.1, 6.7 Hz, 1 H, CH I), 3.43 (dd, J = 10.1, 3.3 Hz, 1 H,
CH I), 3.44–3.54 (m, 1 H, CHO), 3.65 (s, 3 H, OCH ).
), 2.29
2
3
3
C NMR (62.9 MHz, CDCl ): d = 9.2 (CH I), 26.5 (CH C), 24.9,
3
2
3
(
(
2
2
2
8
5.3, 29.0, 29.1, 29.3, 32.4, 34.9 (CH ), 51.4 (OCH ), 80.3 (CO),
2
3
2
1.9 (CHO), 174.2 (CO Me).
2
2
3
Anal. Calcd for C H IO : C, 46.38; H, 7.54; I, 30.63. Found: C,
4
16
31
4
13
C NMR (62.9 MHz, CDCl ): d = 16.6 (CH I), 24.9, 25.6 (CH ),
3
2
2
5.98; H, 7.36; I, 30.81.
2
1
9.1–29.3 (4 CH ), 34.0, 36.6 (CH ), 51.4 (OCH ), 71.0 (CHOH),
2 2 3
74.2 (CO Me).
2
2
-(tert-Butylperoxy)-1-iodocyclopentane (12)
Slightly yellow oil; R = 0.31 (TLC, hexane).
Anal. Calcd for C H IO : C, 42.12; H, 6.77; I, 37.08. Found: C,
12 23 3
f
1
42.37; H, 7.02; I, 37.28.
H NMR (250.13 MHz, CDCl ): d = 1.20 (s, 9 H, CH ), 1.45–2.24
3
3
(
1
m, 6 H, CH ), 4.55–4.60 (m, 1 H, CHO), 4.73–4.78 (m, 1 H, CHI).
2
-Iodocyclopentanol (27)14a
H NMR (250.13 MHz, CDCl ): d = 1.44–1.62 (m, 1 H, CH ), 1.69–
2
3
C NMR (62.9 MHz, CDCl ): d = 26.4 (CH ), 22.6, 27.5, 31.4, 35.8
2
1
3
3
3
2
(
CH , CHI), 80.2 (CO), 92.7 (CHO).
1.86 (m, 2 H, CH ), 1.92–2.16 (m, 2 H, CH ), 2.22–2.41 (m, 1 H,
2 2
CH ), 2.67–2.80 (s, 1 H, OH), 3.95–4.06 (m, 1 H, CHOH), 4.34–
Anal. Calcd for C H IO : C, 38.04; H, 6.03; I, 44.66. Found: C,
2
9
17
2
4
.48 (m, 1 H, CHI).
3
8.44; H, 6.32; I, 44.42.
1
3
C NMR (62.9 MHz, CDCl ): d = 22.0, 31.0, 34.1 (CH ), 35.6
3
2
2
-(tert-Butylperoxy)-1-iodocyclohexane (13)
(
CHI), 82.0 (CHOH).
Slightly yellow oil; R = 0.33 (TLC, hexane).
f
1
4a
1
2-Iodocyclohexanol (28)
H NMR (250.13 MHz, CDCl ): d = 1.25 (s, 9 H, CH ), 1.30–2.39
3
3
1
H NMR (250.13 MHz, CDCl ): d = 1.28–2.51 (m, 8 H, CH ), 2.55–
.70 (s, 1 H, OH), 3.53–3.67 (m, 1 H, CHOH), 3.92–4.06 (m, 1 H,
(
m, 8 H, CH ), 3.94–4.04 (m, 1 H, CHO), 4.21–4.32 (m, 1 H, CHI).
3
2
2
2
1
3
C NMR (62.9 MHz, CDCl ): d = 26.5 (CH ), 22.6, 25.9, 29.1,
3
3
CHI).
3
0.7, 36.0 (CH , CHI), 80.4 (CO), 84.4 (CHO).
2
1
3
C NMR (62.9 MHz, CDCl ): d = 24.2, 27.7, 33.6, 38.4 (CH ), 42.8
3
2
Anal. Calcd for C H IO : C, 40.28; H, 6.42; I, 42.56. Found: C,
10
19
2
(
CHI), 75.6 (CHOH).
4
0.32; H, 6.80; I, 42.88.
2
-Iodocyclooctanol (29)14b
1
-(tert-Butylperoxy)-2-iodocyclooctane (14)
1
H NMR (250.13 MHz, CDCl ): d = 1.25–2.33 (m, 13 H, CH , OH),
4
3
2
Slightly yellow oil; R = 0.39 (TLC, hexane).
f
.00–4.14 (m, 1 H, CHOH), 4.41–4.51 (m, 1 H, CHI).
1
H NMR (250.13 MHz, CDCl ): d = 1.15–2.21 (m, 21 H, CH ,
13
3
2
C NMR (62.9 MHz, CDCl ): d = 25.4, 25.9, 26.9, 32.4, 34.3, 42.0
2
3
CH ), 4.19–4.33 (m, 2 H, CHO, CHI).
3
(
CH ), 50.2 (CHI), 78.2 (CHOH).
1
3
C NMR (62.9 MHz, CDCl ): d = 26.7 (CH ), 25.1, 25.6, 26.4,
3
3
2
6.9, 30.1, 32.4, 35.4 (CH , CHI), 80.0 (CO), 89.4 (CHO).
1-Hydroperoxy-2-iodoalkanes 15–18 and Terahydro-2H-pyran
Derivatives 19–22; General Procedure
I2 (0.7 or 4 mol per mole of alkene) was dissolved in a 5–6% ethe-
real solution of H O or tetrahydro-2H-pyran-2-yl hydroperoxide (4
mol per mole of alkene) and the appropriate alkene (0.3 g) was add-
ed at 20–25 °C. The homogeneous mixture was allowed to stand for
3
2
+
+
MS (EI, 70 eV): m/z (%) = 326 ([M] , 1), 237 ([M – t-BuOO] , 63),
1
+
+
+
27 ([I] , 17), 109 ([M – t-BuOO – HI] , 61), 73 ([t-BuO] , 69), 57
+
2
2
(
[t-Bu – H] , 100).
Anal. Calcd for C H IO : C, 44.18; H, 7.11; I, 38.90. Found: C,
4
12
23
2
4.78; H, 7.35; I, 38.54.
h (15–18) or 72 h (for 19–22). Hexane (40 mL for 19–22) or Et O
2
(
70 mL for 15–18) was added, and the mixture was successively
2
,3-Diiodopropyl Propionate
washed with H O (2 × 10 mL) and aq 10% KI (7 × 10 mL) until the
2
Slightly red oil.
mixture became slightly colored, and again with H O (2 × 10 mL).
2
1
H NMR (250.13 MHz, CDCl ): d = 1.13 (t, J = 7.8 Hz, 3 H, CH ),
Then the mixture was dried (MgSO ) and filtered. The filtrate was
4
3
3
2
.36 (q, J = 7.8 Hz, 2 H, CH ), 3.69 (dd, J = 10.5, 10.4 Hz, 1 H,
concentrated under vacuum (~10 mm Hg) at a temperature not high-
er than 30 °C. Peroxides were isolated by silica gel chromatography
using hexane–EtOAc (5:1) (15–18) or hexane–EtOAc (30:1) (19–
2
CH I), 3.86 (dd, J = 10.5, 3.9 Hz, 1 H, CH I), 4.28–4.46 (m, 3 H,
CHI, CH2).
2
2
2
2) as eluent.
1
3
C NMR (62.9 MHz, CDCl ): d = 8.2, 9.0 (CH I, CH ), 24.8, 27.3
3
2
3
(
CH CH , CHI), 67.9 (CH O), 173.2 (C=O).
2 3 2
Synthesis 2007, No. 19, 2979–2986 © Thieme Stuttgart · New York

PAPER
Synthesis of Vicinal Iodoperoxyalkanes
2985
Mixture of 1-Hydroperoxy-2-iodohexane (15) and 2-Hydroper-
Anal. Calcd for C H IO : C, 38.48; H, 5.49; I, 40.66. Found: C,
38.70; H, 5.68; I, 40.82.
1
0
17
3
oxy-1-iodohexane (15¢)
Slightly yellow oil; R = 0.54–0.56 (TLC, hexane–EtOAc, 4:1).
f
1
2-[(2-Iodocyclohexyl)peroxy]tetrahydro-2H-pyran (21)
Slightly yellow oil; R = 0.28 (TLC, hexane–Et O, 20:1).
H NMR (250.13 MHz, CDCl ): d = 0.83–1.1 (m, 3 H, CH ), 1.17–
3
3
f
2
1
.69 (m, 6 H, CH ), 3.40–4.30 (m, 3 H, CH I, CHI, CH OO,
2
2
2
1
CHOO), 7.90–8.00 (br s, 1 H, OOH).
1
H NMR (250.13 MHz, CDCl ): d = 1.18–2.37 (m, 14 H, CH ),
3
2
3
3.54–3.67 (m, 1 H, CH
2
O), 3.92–4.04 (m, 1 H, CH
2
O), 4.10–4.22,
C NMR (62.9 MHz, CDCl ): d = 8.5 (CH I), 13.9 (CH ), 20.0,
3
2
3
4
.32–4.45 (m, 2 H, CHI, CHO), 5.16–5.21 (m, 1 H, OCHO).
2
2.4, 27.5, 31.5, 31.7, 35.7, 41.5 (CH , CHI), 83.4, 81.7 (COO).
2
1
3
C NMR (62.9 MHz, CDCl ): d = 19.7, 19.9, 22.5, 22.6, 25.0, 25.1,
3
Anal. Calcd for C H IO : C, 29.53; H, 5.37; I, 51.99. Found: C,
2
6
13
2
2
5.3, 25.4, 27.9, 28.6, 28.7, 30.67, 30.73, 35.5 (CH , CI), 62.6, 62.8
2
9.93; H, 5.65; I, 51.62.
(
CH O), 85.2, 85.4 (CHO), 101.0, 101.4 (OCHO).
2
(
E)-1-Hydroperoxy-2-iodocyclopentane (16)
2
-[(2-Iodocyclooctyl)peroxy]tetrahydro-2H-pyran (22)
Slightly yellow oil; R = 0.42 (TLC, hexane–EtOAc, 4:1).
f
Slightly yellow oil; R = 0.32 (TLC, hexane–Et O, 20:1).
f
2
1
H NMR (250.13 MHz, CDCl ): d = 1.25–2.27 (m, 6 H, CH ), 4.56–
3
2
1
H NMR (200.13 MHz, CDCl ): d = 1.14–2.29 (m, 18 H, CH ),
3
2
4
.64, 4.82–4.89 (m, 2 H, CH), 8.05–9.45 (br s, 1 H, OOH).
3
.54–4.44 (m, 4 H, CH O, CHI, CHO), 5.20–5.29 (m, 1 H, OCHO).
2
1
3
C NMR (62.9 MHz, CDCl ): d = 22.7, 27.7, 29.6, 35.9 (CH ,
3
2
13
C NMR (50.32 MHz, CDCl ): d = 19.81, 19.87, 25.0, 25.1, 25.5,
3
CHI), 95.0 (CHO).
2
5.6, 27.0, 27.1, 27.8, 28.0, 29.3, 29.6, 30.9, 31.0, 32.0, 32.2, 35.8,
Anal. Calcd for C H IO : C, 26.34; H, 3.98; I, 55.65. Found: C,
2
5
9
2
35.9 (CH ), 62.6, 62.8 (CH O), 91.0, 91.5 (CHO), 100.4, 101.6
2
2
6.69; H, 4.22; I, 55.31.
(OCHO).
Anal. Calcd for C H IO : C, 44.08; H, 6.54; I, 35.83. Found: C,
1
3
23
3
(
E)-1-Hydroperoxy-2-iodocyclohexane (17)
4
4.37; H, 6.31; I, 35.97.
Slightly yellow oil; R = 0.46 (TLC, hexane–EtOAc, 4:1).
f
1
H NMR (250.13 MHz, CDCl ): d = 1.05–2.45 (m, 8 H, CH ), 3.85–
3
2
1-tert-Butylperoxy-2-iodoalkanes 8 and 13 from Diiodoalkanes
0 and 31
A 50% t-BuOOH solution (3.6 g, 20 mmol; 4 mol per mole of di-
iodoalkane) in Et O, I (0.13 or 0.64 g; 0.5 or 2.5 mmol; 0.1 or 0.5
3
1
.98, 4.21–4.33 (m, 2 H, CH), 8.90–9.40 (br s, 1 H, OOH).
3
3
C NMR (62.9 MHz, CDCl ): d = 22.7, 25.8, 28.6, 30.7, 36.2 (CH ,
3
2
CHI), 86.3 (CHO).
2
2
mol per mole of diiodoalkane), and 1,2-diiodoalkane (5 mmol) were
+
+
MS (EI, 70 eV): m/z (%) = 242 ([M] , 3), 224 ([M – H O] , 8), 127
(
2
successively added to Et O (5 mL). The mixture was allowed to
+
+
2
[I] , 10), 115 ([M – I] , 13), 41 (100).
stand at 20–25 °C for 2 h. The isolation was performed analogously
Anal. Calcd for C H IO : C, 29.77; H, 4.58; I, 52.43. Found: C,
to the preparation of 8–14.
6
11
2
3
0.19; H, 4.87; I, 52.63.
The reactions of tert-butyl hydroperoxide with iodocyclohexane, 2-
iodocyclohexanol, and 1,2-dibromocyclohexane were carried out
(
E)-1-Hydroperoxy-2-iodocyclooctane (18)
analogously using I in an amount of 0.5 mol per mole of halide.
2
Slightly yellow oil; R = 0.5 (TLC, hexane–EtOAc, 5:1).
f
1
H NMR (250.13 MHz, CDCl ): d = 1.15–2.48 (m, 12 H, CH ),
Determination of the Competitive Influence of t-BuOOH and
H O on Iodoperoxidation of Cyclohexene
2
3
2
4
.22–4.48 (m, 2 H, CH), 8.20–8.65 (br s, 1 H, OOH).
1
3
A 50% t-BuOOH solution (5.27 g, 29.3 mmol, 8 mol per mole of cy-
C NMR (62.9 MHz, CDCl ): d = 25.1, 25.4, 26.8, 26.9, 30.6, 32.5,
3
clohexene) in Et O, H O (0.13 g, 7.32 mmol, 2 mol per mole of cy-
2
2
3
5.9 (CH , CHI), 92.1 (CHO).
2
clohexene), I2 (0.65 g, 2.56 mmol, 0.7 mol per mole of
cyclohexene), and cyclohexene (0.3 g, 3.66 mmol) were successive-
Anal. Calcd for C H IO : C, 35.57; H, 5.60; I, 46.98. Found: C,
3
8
15
2
5.82; H, 5.65; I, 46.52.
ly added to Et O (10 mL). The mixture was allowed to stand at 20–
2
2
5 °C for 5 h. Iodoperoxide 13 and iodoalkanol 28 were isolated
2
-{[1-(Iodomethyl)pentyl]peroxy}tetrahydro-2H-pyran (19)
analogously to 8–14.
Slightly yellow oil; R = 0.45 (TLC, hexane–EtOAc, 10:1).
f
1
H NMR (200.13 MHz, CDCl ): d = 0.79–0.95 (m, 3 H, CH ), 1.14–
3
3
Acknowledgment
1
5
.79 (m, 12 H, CH ), 3.26–4.03 (m, 4 H, CH O, CH I, CHO), 5.10–
2
2
2
.18 (m, 1 H, OCHO).
This work is supported by the Program for Support of Leading Sci-
entific Schools of the Russian Federation (Grant NSh 5022.2006.3),
the Grant of President of Russian Federation (No. MK-
3515.2007.3) and the Russian Science Support Foundation.
1
3
C NMR (50.32 MHz, CDCl ): d = 9.3, 8.3 (CH I), 13.7, 13.8
3 2
3
2
(
2
1
CH CH ), 19.68, 19.74, 22.0, 22.4, 25.0, 26.1, 27.3, 27.5, 27.7,
7.8, 31.7, 31.9 (CH ), 62.5, 62.6 (CH O), 82.6, 82.7 (CHO), 100.5,
2 2
01.7 (OCHO).
Anal. Calcd for C H IO : C, 40.26; H, 6.45; I, 38.67. Found: C,
11
21
3
References
4
0.32; H, 6.28; I, 38.91.
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f
2
1
H NMR (300.13 MHz, CDCl ): d = 1.45–2.30 (m, 12 H, CH ),
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2
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3
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3
2
9
7.6, 27.8, 27.9, 30.9, 31.3, 35.8 (CH , CI), 62.3, 62.8 (CH O), 92.7,
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2
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Synthesis 2007, No. 19, 2979–2986 © Thieme Stuttgart · New York

2
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