Electrophilic monoiodination of terminal alkenes

Article abstract of DOI:10.1039/c3ob27348b

An excess of elemental iodine in N,N-dimethylacetamide enables effective 3/iodanylium-de-hydronation of terminal alkenes with 3-iodopropene derivatives and hydrogen iodide formation within minutes at room temperature. The optimal molar ratio of iodine to

Full text of DOI:10.1039/c3ob27348b

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Electrophilic monoiodination of terminal alkenes†
Sergiy V. Yemets,a Tatyana E. Shubinab and Pavel A. Krasutsky*a
Cite this: Org. Biomol. Chem., 2013, 11,
2891
An excess of elemental iodine in N,N-dimethylacetamide enables effective 3/iodanylium-de-hydronation
of terminal alkenes with 3-iodopropene derivatives and hydrogen iodide formation within minutes at
room temperature. The optimal molar ratio of iodine to substrate was decreased to 1 : 1 when hydrogen
iodide formed was oxidized on a platinum anode. The electrolytic oxidation recovers iodine as a reagent
and diminishes the hydrogen iodide inhibitory action to accomplish the monoiodination. The proposed
reaction mechanism is based on kinetic measurements and quantum mechanics calculations.
Received 3rd December 2012,
Accepted 20th February 2013
DOI: 10.1039/c3ob27348b
www.rsc.org/obc
molecules by reactions of substitution with various nucleophi-
lic reagents.
Introduction
The potential of iodine in organic synthesis is described in
numerous recent reviews.1–3 The electrophilic addition of
iodine to a double bond particularly is well studied with many
useful variations. The activation of certain unsaturated
carbons with iodine substituents can be considered as a
general concept for synthesis because iodine is an excellent
leaving group for various bond formations.
Results and discussion
The following terminal alkenes were used for this study:
betulin (1), betulonic aldehyde (2), betulinic acid (3), 2,3,3-tri-
methylbut-1-ene (4), methylenecyclohexane (5), α-methyl-
styrene (6) and 2-(1-adamantyl)propene (7) (Table 1, Scheme 1).
The use of elemental iodine in different non-polar (hexane,
benzene, CCl4) and polar solvents (THF, CH2Cl2, CHCl3) did
not give any good results. NMR analyses of reaction mixtures
show, besides starting triterpenes and admixture of iodides,
the presence of products of their transformation. The for-
mation of monoiodinated main products (8–14) was observed
when the reaction was performed in N,N-dimethylacetamide at
room temperature for 1–15 min. Optimization of the iodine to
substrate ratio, reaction time and concentration led to the
monoiodides (8–14) synthesis procedures (Table 1).
It was observed that this monoiodination is not occurring
for non-terminal or conjugated alkenes. Lower yield of 2,3,3-
trimethylbut-1-ene (4) may be explained by a fast consecutive
process of DMA O-alkylation11 with the formed monoiodide.
Discussion of this reaction is outside the scope of this study.
Here we only note that it was necessary to stop the reaction of
monoiodination for this substrate at a lower conversion level
for better isolation of the monoiodide (11). N,N-Dimethylform-
amide also could be used as a medium for similar monoiodi-
nations instead of DMA, but more contaminated products
resulted due to the much faster DMF O-alkylation with the
formed monoiodides.
This study is devoted to the development of a new process
for terminal carbon activation through electrophilic monoiodi-
nation of terminal alkenes. The approach of 3/halogenany-
lium-de-hydronation is principally different from other
terminal alkene monohalogenations – the Wohl–Ziegler reac-
tion4 – which is a radical substitution process at the allylic and
benzylic positions with NBS or NCS and initiators (peroxides,
AIBN or UV light). Use of N-iodosuccinimide (NIS) and elemen-
tal iodine has not been reported in such radical processes
because direct radical iodination is highly endothermic and an
iodine radical itself is not capable of hydrogen abstraction
from C–H bonds.5–7 These factors provide the limited infor-
mation about processes of radical iodination of C–H bonds.8
Iodination of terminal alkenes with I2 or NIS was used to a
lesser extent.9a–c Halogenation of 1,1-disubstituted alkenes
with NCS, NBS and NIS mediated by Yb(OTf)3–TMSCl
suggested that monohalogenation of terminal alkenes pro-
ceeded via a non-free-radical mechanism.10 The goal of this
work is connected with the use of reactive iodoallylic deriva-
tives for synthesis of a broad range of new and useful organic
aUniversity of Minnesota, Natural Resources Research Institute, 5013 Miller Trunk
Highway, Duluth, MN 55811, USA. E-mail: pkrasuts@nrri.umn.edu
bComputer-Chemie-Centrum and Interdisciplinary Center for Molecular Materials,
The allylic radical iodination – the Wohl–Ziegler reaction –
in such polar solvents and reaction conditions (room
temperature) is unlikely and has never been observed. It has
been shown (quantum mechanics calculations, kinetic and
thermodynamic studies discussed below) that charge transfer
University Erlangen-Nuremberg, Nägelsbachstr 25, Germany 91052
†Electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR spectra, kinetic measurement data and optimized geometries for all
species. See DOI: 10.1039/c3ob27348b
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Table 1 Monoiodination of terminal alkenes using molecular iodine in N,N-dimethylacetamidea
Alkene
Product
Yieldb (%)
94
93
75
25
55
75
43
a See Scheme 1 and Experimental for details. b Yield of the pure product calculated on starting materials.
formed exothermically with ΔECTC1 = −8.1 kcal mol−1 and
ΔECTC2 = −2.5 kcal mol−1. ωB97XD/DZVP and MP2/DZVP calcu-
lations show that CTC2 is formed exothermically with ΔECTC2
= −6.8 and −6.5 kcal mol−1 respectively (Fig. 2). CTC2 is a pre-
cursor for synchronous 3/iodanylium-de-hydronation into
three products: N,N-dimethylacetamide, monoiodide (11) and
Scheme 1 Monoiodination of terminal alkenes.
complex CTC112,13a–c (Fig. 1) forms a second charge transfer hydrogen iodide (Scheme 2). The computed activation barrier
complex CTC2 with a terminal alkene substrate. The process of (ΔETS = 28.2 kcal mol−1, PW91PW91/DZVP, up to 45.1 kcal
allylic 3/iodanylynium-de-hydronation takes place within this mol−1, MP2/DZVP) appears high for a room temperature reac-
CTC2 with the formation of monoiodides (8–14) and hydrogen tion. It is obvious that this activation barrier is sufficiently
iodide via transition state TS (Fig. 1, Scheme 2).
decreased under the highly polar experimental conditions.
The total potential energy profile for the 3/iodanylium-de- Inclusion of a DMF solvent effect14 significantly lowers this
hydronation of 2,3,3-trimethylbut-1-ene (4) with iodine in N,N- barrier to ΔE′TS = 12.8 kcal mol−1 and increases exothermicity
dimethylacetamide is described in Fig. 2. PW91PW91/DZVP of CTC1 and CTC2 formation (ΔE′CTC1 = −10.3 kcal mol−1 and
calculations show that both complexes CTC1 and CTC2 are ΔE′CTC2 = −3.3 kcal mol−1). The reaction ends with a slightly
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endothermic (6.9 kcal mol−1, PW91PW91/DZVP or 3.2 kcal
mol−1
, ,
ωB97XD/DZVP) or exothermic (−1.3 kcal mol−1
MP2/DZVP) formation of the DMA⋯(11)⋯HI final cluster (FIN)
(Fig. 1 and 2, Scheme 2). Inclusion of the solvent correction
lowers this value to −9.8 kcal mol−1, thus effectively changing
the reaction to an exothermic one.
The system of CTC1 and an alkene substrate was a starting
point for experimental kinetic measurements, therefore the
determined activation energy EA can be compared to the theo-
retical activation energies EAT and E′AT (Fig. 2). Experimental
kinetic measurements were achieved at 25 °C for a betulin (1)
1
monoiodination process15 by H NMR monitoring. It is shown
that betulin monoiodination in DMA has first order in alkene
substrate (1) and first order in iodine with the following
kinetic equation: r = k[S][I2], where k = (3.99 0.03) × 10−2
l
mol−1 s−1; r is the rate of the reaction, mol l−1 s−1; [S] is the
concentration of substrate (1) and [I2] is the concentration of
iodine, mol l−1. Experimental thermodynamic parameters
have been acquired by 1H NMR monitoring of the mono-
iodination of betulin (1) and a kinetic study at 25–65 °C. The
following data were obtained: EA = 6.7
ΔH‡298 = 6.1 0.4 kcal mol−1, ΔS2‡98 = −44.6 1.4 cal mol−1
K−1, ΔG‡298 = 19.4 0.6 kcal mol−1
0.4 kcal mol−1
,
.
ωB97XD/DZVP and MP2/DZVP calculations gave a higher
value of EAT (38.3 kcal mol−1 and 37.6 kcal mol−1, respectively)
than PW91PW91/DZVP (Fig. 2). PW91PW91/DZVP computed
EAT = 25.7 kcal mol−1 decreases to E′AT = 9.5 kcal mol−1 with
inclusion of the DMF solvent model. This theoretical value
is comparable with the experimental thermodynamic data for
EA = 6.7 kcal mol−1
.
It has been observed that the experimental kinetic para-
meters are quite stable up to nearly 15% of betulin (1) conver-
sion levels. Then the monoiodination process is inhibited
sufficiently due to accumulation of hydrogen iodide in the
reaction media. It is likely that hydrogen iodide hinders the
process of monoiodination by the decomposition of intermedi-
ate complexes and binding iodine with the polyiodides for-
mation. The same inhibition effect occurred when potassium
iodide was added to the reaction media; no reaction was
observed in this case. An excess of iodine was essential to
increase the rate of iodination. Iodine should be used with
more than two-fold excess to the alkene substrate, otherwise
conversion of the substrate and yield of the reaction will be
decreased. We have found a way to oxidize hydrogen iodide
formed on a platinum anode in situ to reduce its inhibiting
role. Iodine that is formed returns back to the process of
monoiodination. Thus the optimal molar ratio of iodine to
alkene was decreased to 1 : 1 (Scheme 3). The presence of urea
allows for buffering the reaction media and accelerates the
process by three times to obtain a pure product. The fact of
acceleration leads to an assumption that urea assists this
transformation in a way that DMA does by forming analogous
CTC1 with iodine to interact with alkene. However, the com-
plete conversion of alkene for a 1 : 1 alkene to iodine molar
ratio cannot be achieved in the presence of urea alone without
use of electrolysis due to the inhibition. The possibility of
Fig. 1 DFT (PW91PW91/DZVP) computed structures of charge transfer com-
plexes (CTC1 and CTC2), transition state (TS) and final cluster (FIN).
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chemo-oxidation for transformation of accumulating hydrogen monohalogenation were formed as a result of electrophilic
iodide to starting iodine with oxygen was also examined. monoiodination and radical bromination with NBS.16
Oxygen was passed into the reaction mixture of betulin and
iodine (1 : 1 molar ratio) in DMA but no significant reduction
of the inhibition was observed. The use of the other oxidative
reagents does not seem to be favorable because this iodination
Conclusion
reaction is very sensitive to the changes in the reaction media.
Therefore the use of anodic oxidation seems to be the most
appropriate way to neutralize the inhibitory action of hydrogen
iodide and to recover iodine in the reaction media.
This work demonstrates that a complex of iodine with N,N-
dimethylacetamide is capable of providing fast and low
temperature electrophilic monoiodination of terminal alkenes
via synchronous 3/iodanylium-de-hydronation.
The principal difference between the studied ionic process
and the radical Wohl–Ziegler reaction is described in
Scheme 4, when two structurally different products of
Experimental
1
NMR spectra (300 MHz H NMR and 75 MHz 13C NMR) were
recorded using a Varian Unity Inova 300. 1H and 13C NMR
Scheme 3 Electrolysis for monoiodination of betulin (1).
Scheme 4 Radical bromination and electrophilic iodination of methylenecyclo-
hexane (5).
Scheme 2 Plausible reaction pathway for 3/iodanylium-de-hydronation of
2,3,3-trimethylbut-1-ene (4).
Fig. 2 The computed profile of potential energy for 3/iodanylium-de-hydronation of 2,3,3-trimethylbut-1-ene (4).
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chemical shifts are referenced to tetramethylsilane as an titled compound as a white powder (2.28 g, 93%), m.p.
internal standard and reported in parts per million (ppm). 110–112 °C. 1H NMR (300 MHz, CDCl3): δ 9.64 (d, 1H), 5.21
N,N-Dimethylacetamide 99+% was purchased from Acros. (s, 1H), 5.02 (s, 1H), 3.95 (dd, 2H), 2.89 (m, 1H), 2.55–2.34
Triterpenoids (1–3) and 2-(1-adamantyl)propene (7) were (m, 2H), 2.23–0.93 (m, 37H). 13C NMR (75 MHz, CDCl3):
obtained using previously developed procedures.17–20 The δ 217.96, 205.93, 151.61, 112.43, 59.34, 54.92, 49.80, 49.53,
other alkenes and reagents were purchased from Aldrich.
47.32, 43.70, 42.61, 40.79, 39.64, 38.66, 36.89, 34.11, 33.66,
32.95, 32.85, 29.06, 28.84, 26.80, 26.62, 21.37, 21.02, 19.60,
15.99, 15.78, 14.20, 10.69. Found: C, 63.60; H, 8.08; I, 22.19.
30-Iodolup-20-en-3β,28-diol (8)
Betulin (1) (4.43 g, 10.00 mmol) was dissolved in N,N-dimethyl- Calc. for C30H45IO2: C, 63.82; H, 8.03; I, 22.48.
acetamide (176 ml) and stirred at 25 °C. Crystalline iodine
(15.23 g, 60.00 mmol) was added to the solution in one
30-Iodo-3β-hydroxylup-20-en-28-oic acid (10)
portion. The reaction mixture was vigorously stirred for 1 min Betulinic acid (3) (4.57 g, 10.00 mmol) was dissolved in N,N-
and poured immediately into a sodium bisulfite (22 g) solution dimethylacetamide (271 ml) and stirred at 25 °C. Crystalline
in water (500 ml). The precipitate was filtered, washed with iodine (15.23 g, 60.00 mmol) was added to the solution in one
cold water (500 ml), then with hot water (60 °C, 500 ml) and portion. The reaction mixture was vigorously stirred for 10 min
dried in a vacuum oven (60 °C, 230 mm Hg), yielding the titled and poured immediately into a sodium bisulfite (22 g) solution
compound as a white powder (5.29 g, 94%), m.p. 163–164 °C. in water (500 ml). The precipitate was filtered, washed with
1H NMR (300 MHz, CDCl3): δ 5.17 (s, 1H), 4.99 (s, 1H), 3.94 cold water (500 ml), then with hot water (60 °C, 500 ml) and
(dd, 2H), 3.81 (d, 1H), 3.33 (d, 1H), 3.19 (dd, 1H), 2.39–2.20 dried in a vacuum oven (60 °C, 230 mm Hg), yielding the titled
(m, 2H), 1.99–0.67 (m, 38H). 13C NMR (75 MHz, CDCl3): compound as a white powder (4.34 g, 75%), m.p. 184–188 °C.
δ 151.96, 112.03, 78.96, 60.34, 55.25, 50.54, 50.33, 47.81, 43.81, 1H NMR (300 MHz, CDCl3): δ 5.19 (s, 1H), 5.00 (s, 1H), 3.95
42.71, 40.94, 38.85, 38.70, 37.21, 37.14, 34.25, 33.76, 33.07, (dd, 2H), 3.19 (dd, 1H), 2.99 (td, 1H), 2.32–0.67 (m, 39H). 13C
29.19, 27.98, 27.37, 26.99, 26.75, 20.92, 18.27, 16.11, 16.02, NMR (75 MHz, CDCl3): δ 179.76, 152.30, 112.21, 78.97, 56.27,
15.36, 14.75, 11.79. 1H NMR (300 MHz, CD3OD): δ 5.18 (s, 1H), 55.30, 51.10, 50.46, 43.35, 42.42, 40.69, 38.85, 38.71, 38.39,
5.00 (s, 1H), 4.01 (dd, 2H), 3.75 (d, 1H), 3.26 (d, 1H), 3.12 (dd, 37.20, 36.85, 34.33, 33.49, 32.01, 29.70, 27.98, 27.38,
1
1H), 2.44–2.21 (m, 2H), 2.00–0.67 (m, 38H). 13C NMR (75 MHz, 26.56, 20.93, 18.27, 16.15, 16.08, 15.35, 14.71, 11.14. H NMR
CD3OD): δ 154.07, 112.35, 79.66, 60.20, 56.82, 51.83, 51.76, (300 MHz, CD3OD): δ 5.19 (s, 1H), 5.00 (s, 1H), 4.01 (dd, 2H),
49.03, 45.29, 43.86, 42.21, 40.08, 39.98, 38.65, 38.31, 35.52, 3.15–3.00 (m, 2H), 2.35–0.69 (m, 39H). 13C NMR (75 MHz,
34.86, 34.21, 30.39, 28.64, 28.17, 28.12, 28.06, 22.11, 19.46, CD3OD): δ 180.03, 154.46, 112.36, 79.68, 57.59, 56.90, 52.14,
16.76, 16.61, 16.16, 15.26, 11.61. Found: C, 63.32; H, 8.74; I, 52.03, 44.80, 43.63, 41.99, 40.12, 39.99, 39.74, 38.37, 37.94,
22.02. Calc. for C30H49IO2: C, 63.37; H, 8.69; I, 22.32.
35.67, 34.71, 33.24, 30.92, 28.65, 28.08, 27.97, 22.23, 19.49,
16.79, 16.73, 16.16, 15.18, 11.31. Found: C, 61.64; H, 8.04;
I, 21.52. Calc. for C30H47IO3: C, 61.85; H, 8.13; I, 21.78.
30-Iodolup-20-en-3β,28-diol (8) (electrolysis)
Betulin (1) (1.00 g, 2.26 mmol) and urea (0.68 g, 11.30 mmol)
were dissolved in N,N-dimethylacetamide (60 ml). The solution
was stirred in an electrolyzer at 25 °C. Crystalline iodine
2-Iodo-2-(tert-butyl)propene (11)
A
fresh 1 M iodine solution in N,N-dimethylacetamide
(0.57 g, 2.26 mmol) was added to the solution and direct (12.00 ml, 12.00 mmol) was added to the stirred 2,3,3-tri-
current (0.05 A, 18.96 V) was immediately applied to electrodes methylbut-1-ene (4), (0.59 g, 6.00 mmol). The mixture was vig-
(platinum cathode and anode plates (2.5 cm × 2.5 cm), 0.5 cm orously stirred at 25 °C for 4 min and poured into a sodium
distance between the plates). Electrolysis was stopped after bisulfite (3.5 g) solution in water (100 ml). The resulting emul-
130 min. The reaction solution was poured into a sodium sion was extracted with pentane (2 × 50 ml). The combined
bisulfite solution (1 g) in water (200 ml). The precipitate was organic phase was washed with water (50 ml), dried over
filtered, washed with cold water (100 ml), then with hot water sodium sulfate, filtered and evaporated in a vacuum, yielding
1
(60 °C, 100 ml) and dried in a vacuum oven (60 °C, 230 mm the titled compound as an orange oil (0.34 g, 25%). H NMR
Hg), yielding the titled compound as a white powder (1.22 g, (300 MHz, CDCl3): δ 5.32 (s, 1H), 5.15 (s, 1H), 4.01 (s, 2H), 1.18
94%).
(s, 1H). 13C NMR (75 MHz, CDCl3): δ 154.46, 115.55, 36.24,
29.89, 4.70. Found: C, 37.48; H, 5.80; I, 56.45. Calc. for C7H13I:
C, 37.52; H, 5.85; I, 56.63.
30-Iodo-3-oxolup-20-en-28-al (9)
Betulonic aldehyde (2) (4.41 g, 10.00 mmol) was dissolved in
N,N-dimethylacetamide (55 ml) and stirred at 25 °C. Crystal-
1-Iodomethylcyclohexene (12)
line iodine (15.23 g, 60.00 mmol) was added to the solution in Methylenecyclohexane (0.24 g, 2.50 mmol) was added to the
one portion. The reaction mixture was vigorously stirred for solution of iodine (2.81 g, 14.99 mmol) in N,N-dimethyl-
10 min and poured immediately into a sodium bisulfite (22 g) acetamide (3 ml). The mixture was vigorously stirred at 25 °C
solution in water (500 ml). The precipitate was filtered, washed for 2 min and poured into a sodium bisulfite (6 g) solution in
with cold water (500 ml), then with hot water (60 °C, 500 ml) water (50 ml). The resulting emulsion was stirred and extracted
and dried in a vacuum oven (60 °C, 230 mm Hg), yielding the with pentane (2 × 50 ml). The combined organic phase was
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washed with water (50 ml), dried over sodium sulfate, filtered dissolved in CDCl3 and analyzed by 1H NMR (500 MHz, Varian
and evaporated in a vacuum, yielding the titled compound as 500 with Auto-Tuner) to determine the content of (8) in the
1
an orange oil (0.31 g, 55%). H NMR (300 MHz, CDCl3): δ 5.95 mixture. This value was used to determine the concentration
(m, 1H), 3.90 (m, 2H), 2.16 (m, 2H), 1.93 (m, 2H), 1.72–1.51 of betulin and iodine at the moment of reaction termination.
(m, 4H). 13C NMR (75 MHz, CDCl3): δ 135.46, 126.58, 27.12, Kinetic data were analyzed by the least squares linear
25.68, 22.42, 21.83, 14.82. Found: C, 37.98; H, 5.14; I, 56.97. regression to find the corresponding functional correlations.
Calc. for C7H11I: C, 37.86; H, 4.99; I, 57.15.
The reaction order, rate constants, activation energy EA,
enthalpy ΔH2‡98, entropy ΔS2‡98 and Gibbs free energy ΔG‡298
were calculated using standard kinetic and thermodynamic
(3-Iodoprop-1-en-2-yl)benzene (13)
A
fresh 1 M iodine solution in N,N-dimethylacetamide equations. See ESI† for detailed kinetic experimental pro-
(12.00 ml, 12.00 mmol) was added to stirred α-methylstyrene cedures and calculations.
(6) (0.71 g, 6.00 mmol). The mixture was vigorously stirred at
25 °C for 15 min and poured into a sodium bisulfite (3.5 g)
solution in water (100 ml). The resulting emulsion was
Computational
Quantum mechanics calculations of the model reaction
extracted with pentane (2 × 50 ml). The combined organic
phase was washed with water (50 ml), dried over sodium
sulfate, filtered and evaporated in a vacuum, yielding the titled
between 2,3,3-trimethylbut-1-ene (4) and iodine in N,N-
dimethylacetamide were performed by using the Gaussian 03
program package.21 Geometries of all structures were fully
optimized at the PW91PW91,22a–c ωB97XD23 and MP224a–c
levels of theory using the DZVP25 basis set. Stationary points
were confirmed to be minima or transition states (TS) by calcu-
lating the normal vibrations within the harmonic approxi-
mation. The reaction pathways along both directions from the
transition structures were followed by the IRC26a,b method. All
computed energies are corrected for zero-point vibrational
energies (ZPVE). Additionally, single-point calculations includ-
ing the solvent model (COSMO, DMF as a model solvent) were
done with the Orca 2.6 program.27
1
compound as an orange oil (1.10 g, 75%). H NMR (300 MHz,
CDCl3): δ 7.47–7.22 (m, 5H), 5.53 (s, 1H), 5.47 (s, 1H), 4.32
(s, 2H). 13C NMR (75 MHz, CDCl3): δ 145.48, 137.80, 128.47,
128.27, 126.05, 115.60, 7.22. Found: C, 44.08; H, 3.86; I, 51.74.
Calc. for C9H9I: C, 44.29; H, 3.72; I, 51.99.
2-(1-Adamantyl)-3-iodopropene (14)
A
fresh 1 M iodine solution in N,N-dimethylacetamide
(24.00 ml, 24.00 mmol) was added to stirred 2-(1-adamantyl)-
propene (7) (1.06 g, 6.00 mmol). The mixture was vigorously
stirred at 25 °C for 5 min and poured into a sodium bisulfite
(7 g) solution in water (100 ml). The resulting emulsion was
extracted with pentane (2 × 50 ml). The combined organic
phase was washed with water (50 ml), dried over sodium
sulfate, filtered and evaporated in a vacuum, yielding the titled
Acknowledgements
1
This work was supported by State special budget of the Univer-
sity of Minnesota Duluth, Natural Resources Research
Institute.
compound as an orange oil (0.79 g, 43%). H NMR (300 MHz,
CDCl3): δ 5.31 (m, 1H), 5.08 (m, 1H), 4.00 (s, 2H), 2.03 (m, 3H),
1.79–1.65 (m, 12H). 13C NMR (75 MHz, CDCl3): δ 154.94,
115.39, 41.55, 38.17, 36.71, 28.55, 3.99. Found: C, 51.89;
H, 6.46; I, 41.84. Calc. for C13H19I: C, 51.67; H, 6.34; I, 41.99.
Notes and references
General procedure for kinetic measurements
The quenching and analyzing technique was used to obtain
reagent concentration/time data. The reaction time intervals
were chosen for a betulin conversion less than 15% when no
inhibition (related to the hydrogen iodide accumulation in the
reaction media) was observed (up to 25–90 s); several sets of
experiments were performed. Betulin (1) and iodine were dis-
solved separately in N,N-dimethylacetamide to form solutions
containing a precisely known concentration of the reagents for
each set of experiments. Determined volumes of the solutions
were mixed (1 : 1, 1 : 1.2 and 1.2 : 1 betulin to iodine molar
ratios) at a specified temperature (25, 35, 45, 55 and 65 °C)
and stirred for a fixed period of time for each experiment.
The mixture was immediately treated with aqueous sodium
bisulfite solution to neutralize iodine and terminate the reac-
tion. The precipitate was filtered, washed with water and dried.
The solid samples from these experiments are mixtures of
30-iodolup-20-en-3β,28-diol (8) and starting betulin. They were
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