Regioselectivity of Radical Addition of Thiols to 1-Alkenes

Article abstract of DOI:10.1002/ejoc.201701692

The addition of dodecanethiol (1) to 1-alkenes H₂C=CHR that have substituents R = Hex, (CH₂)₈COOMe, Ph, Bn, cHex, CH₂cHex, tBu (2a–2g) with different steric effects was studied. Some few percent of branched Mark

Full text of DOI:10.1002/ejoc.201701692

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Title: Regioselectivity of Radical Addition of Thiols to 1-Alkenes
Authors: Ursula Biermann and Jürgen O. Metzger
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
Regioselectivity of Radical Addition of Thiols to 1-Alkenes
Ursula Biermann[a] and Jürgen O. Metzger*[a,b]
Abstract
The addition of dodecanethiol (1) to 1-alkenes H2C=CHR having substituents R =
Hex, (CH2)8COOMe, Ph, Bn, cHex, CH2cHex, tBu (2a-g) with different steric effect
was studied. Some few percent of the branched Markownikow addition product 4 was
formed in all cases with the exemption of styrene (2c) in addition to the linear anti-
Markownikow product 3 as main product. The regioselectivities correlate well with the
Taft steric parameter ES of the R-substituent at the alkene. This gives evidence that
the regioselective outcome of the radical addition of thiols to 1-alkenes is mainly
steered by the steric effect of the R-substituent as it is well known for the addition of
alkyl radicals to alkenes. In the case of thiol addition, however, the regioselectivity is
strongly enhanced by the much faster fragmentation of the intermediate
Markownikow than of the anti-Markownikow adduct radical.
[a] Institute of Chemistry, University of Oldenburg
26111 Oldenburg, Germany
juergen.metzger@uni-oldenburg.de
http://www.metzger.chemie.uni-oldenburg.de/
[b] abiosus e.V.
Bloherfelder Str. 239
26129 Oldenburg, Germany
http://www.abiosus.org
Supporting information for this article is given via a link at the end of the document.
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
Introduction
The radical addition of thiols to alkenes is a long-known reaction and has been
studied and applied intensively since more than hundred years.[1] The addition is
initiated photochemically or thermally with and without radical initiators.[1, 2, 3] It is
thoroughly used for the synthesis of low molecular [2] as well as polymeric
thioethers,[3, 4 , 5] and is often named thiol-ene click reaction.[5a] There is a large
number of review articles on most aspects of the radical chemistry of thiols including
addition reactions.[6, 7] It is well-known that the addition to 1-alkenes occurs with high
selectivity as anti-Markownikow orientation. The most recent review by Dénès et al.
has been assessing that the thiyl radical adds to the less substituted end of the C=C
bond to form a carbon centered radical via a reversible process. This regioselectivity
was rationalized in terms of the heat of formation or by the enhanced stability of the
intermediate carbon-centered radical.[7] The given references [8, 9] appeared some
years before Giese´s seminal paper demonstrating the importance of steric effects on
the addition of carbon radicals to alkenes.[10] Only some very few papers have been
reporting on the detection of both regioisomers,[11, 12, 13, 14] also in polymeric thioether
synthesis.[15] Cadogan and Sadler found a ratio of methyl thioglycollate addition to
C(1) and C(2) of 1-octene and 1-heptene of about 98:2 at room temperature.[12] They
attributed this selectivity to the greater stability of the secondary in comparison to the
primary adduct radical. However, the small predominance of the attack at C(2) of 2-
octene was rationalized with a greater steric effect of the pentyl substituent at C(3)
than the methyl substituent at C(2). Oswald and Naegele reported on the UV-initiated
addition of methanethiol, ethanethiol, benzenethiol at 16°C and thiolacetic acid at
room temperature to diallyl maleate giving 2 – 5 % of the branched Markownikow
beside the linear anti-Markownikow addition products. The regioselectivity was
explained on the basis of the relative stability of the intermediate radicals involved.[11]
Brace studied the radical addition of 2-(perfluorohexyl) ethanethiol to 1-hexene and
observed 2.3 % of the branched Markownikow product.[14] Morgan et al. polymerized
1,4-butanediol-di-N-allyl carbamate with ethylene glycol di--mercaptopropionate and
observed extremely minor formation of the Markownikow product (<10%) by 1H-
NMR spectroscopy.[15] Both latter papers didn´t give any explanation of this
regioselective outcome. Finally, Crich stated that the addition of thiyl radicals to
alkenes is much less susceptible to steric hindrance in the alkene than are the
corresponding reactions of alkyl radicals, though no respective examples were
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
given.[16] Most remarkably, there are no systematic investigations on this most
important topic. We are reporting herein our studies on the radical addition of
dodecanethiol (1) to 1-alkenes 2a-g giving unambiguous evidence of the importance
of steric effects on the regioselective outcome.
Results and Discussion
We studied the addition of thiol 1 to 1-alkenes 2 with alkyl groups R having different
steric effects as given in Table 1 and measured by GC the ratio of the regioisomeric
addition products 3 and 4. In the case of alkene 2d a further addition product 5d was
observed. We performed the reaction without any solvent and initiator added, taking
advantage of the molecule assisted homolysis (MAH) of thiol and alkene.[17, 18] This
radical chain initiation gives often cleaner, though slower reactions than other more
often used initiations, because of the fact that only both substrates without any
additional reagent are present in the reaction mixture and because of the very low
steady state concentration of the chain carrying radical. For comparison, some
examples were initiated with AIBN as well. The reaction temperature was mostly
80°C with some variation to obtain information on the temperature dependence of the
regioselectivity. Alkenes 2e and 2g were also reacted at room temperature. The
reaction time was about some hours to some days. The major isomers 3 were
unambiguously identified by 1H-NMR, 13C-NMR and GC-MS, and the minor isomers 4
by GC-MS. All isomers 4 show the same characteristic -scission of the molecular
ion in EI-MS giving fragment peak m/z 229 (Scheme S1). The results are compiled in
Table 1.
The generally accepted mechanism of the thiol radical chain addition reaction [2, 7] is
given in Scheme 1, here initiated by MAH and assuming the competitive addition of
the thiyl radical to C(1) and C(2) of alkene 2. Because the addition of thiyl radicals
with the rate constants ka,I > ka,II is reversible, the ratio of the products 3 and 4 is not
only influenced by the ratio of the addition rate constants ka,I and ka,II, as can be
assumed for carbon radicals at moderate temperature,[10] but also by the
fragmentation rate constants kf,I << kf,II of the adduct radicals I and II and by their
trapping reaction having the rate constants k3 < k4, respectively (Eq. 1, Scheme 1).[12]
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European Journal of Organic Chemistry
Table 1. Results of the addition of thiol 1 to 1-alkenes 2 to give the regioisomeric
thioethers 3 and 4.a
Entry
2
R
ES
T [°C] [3]:[4]b
S=log([3]:[4])
1c
2c
3c
4c
5c
6
7
8
9
10
11
12
13
14
a
a
a
b
b
c
-0.4
70
80
90
63
80
80
80
80
60
80
r. t.
80
80
r. t.
97.9:2.1 1,67
97.8:2.2 1.65
97.7:2.3 1.63
98.4:1.6 1.82
98.1:1.9 1.71
(CH2)5Me
(CH2)8COOMe -0.4d
Ph
100:1
-
d e
d e,f
d e,f
e
Bn
-0.38
96.9:2.8 1.54
96.2:3.5 1.4
97.0:2.8 1.54
98.1:1.9 1.71
98.9:1.1 1.95
98.6:1.4 1.85
97.8:2.2 1.64
99.4:0.6 2.21
cHex
-0.79
-0.98
-1.54
e
f
CH2cHex
tBu
f e
g
a [1]:[2] = 1.5:1, neat; b determined by GC; c [1]:[2a, b] = 1:1, neat; d Es was assumed
to be the same as of R=(CH2)5Me; e 0.3 % (entry 7,8) and 0.2 % (entry 9) of isomer
5d was formed (see Scheme 2); f AIBN was added.
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European Journal of Organic Chemistry
Scheme 1. Radical chain addition of thiol 1 to 1-alkenes 2 initiated by molecule
assisted homolysis (MAH) [17,18] giving regioselectively addition products 3 and 4. The
rate constants of addition ka,I and ka,II, fragmentation kf,I and kf,II and hydrogen
abstraction k3 and k4 assumed for the estimation of the regioselectivity of the addition
of dodecanethiol 1 onto 1-octene 2a using Eq.(1) are given.
All alkenes 2 showed preferential addition to the terminal carbon atom as expected,
but also some addition to C-2 of the double bond with the exemption of styrene (2c)
(Table 1, entry 6). We were not able to detect any addition product 4c beside 3c. The
difference of the stability of the benzylic radical Ic and the primary radical IIc is about
65 kJ/mol.[19, 20] Thus with kf,Ic << kf,IIc , non-detectable amounts of product 4c may be
formed (Scheme 1). The observation of addition product 5d that is formed via a
secondary adduct radical (Scheme 2) having in comparison to the benzylic adduct
radical a lower difference of stability of 53 kJ/mol gives evidence for this explanation.
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
The ratio of [3a]:[4a]=97.8:2.2 (Table 1, entry 1) is almost the same as given by
Cadogan for the addition of thioglycollate to alkene 2a,[12] by Brace for the addition of
2-(perfluorohexyl) ethanethiol to 1-hexene,[14] and similar to the additions of various
thiols as reported by Oswald and Naegele.[11] This gives evidence that the polar as
well as steric effect of R´ of the thiyl radical (Scheme1) has only minor influence on
the regioselective outcome.
The selectivity increased slightly with decreasing temperature, for example 2a (entry
1-3), 2b (entry 4,5) and 2e (entry 10,11), also with AIBN as initiator (entry 8,9). This
slight temperature dependence is characteristic for systems showing reversibility of
the radical addition, because of some compensation of the temperature effect of the
involved rate constants of addition, -fragmentation and hydrogen transfer (Eq. 1)
and was reported also for radical alkane additions to alkenes at elevated
temperature.[21, 22] It may be mentioned that the selectivity was found to be somewhat
lower using AIBN as initiator in comparison to the MAH initiation (entries 7 and 8, 12
and 13).
Fortunately, the relevant absolute rate constants of the thiol radical chain addition
reaction are known from literature and allow to estimate the regioselectivity of the
addition of a primary alkane thiol i.e. 1 to alkene 2a at room temperature.
Chatgialialoglu et al. reported on the addition rate constant as ka = 2.0 x 105 M-1 s-1 of
2-hydroxyethanethiyl radical (HOC2H4S.) to an internal (E)-configured double bond of
monounsaturated fatty compounds as well as on the fragmentation rate constant of
the adduct radical as kf = 1.6 x 108 s-1.[23] McPhee et al. determined the addition rate
constant of t-BuS. to 1-octene as ka = 1.9 x 106 M-1 s-1.[24] The reported kinetic data
allowed Chatgialialoglu et al.[23] to calculate the rate constant of the reverse
fragmentation reaction as kf = 3.4 x 105 using the trapping rate constant of a
secondary alkyl radical as kSH = 1 x 107 M-1 s-1. Eventually, Troche et al. measured
the trapping rate constant of a primary alkyl radical by octadecanethiol as kSH = 1.9 x
107.[25] Insertion of these rate constants as compiled in Scheme 1 with [R´SH] = 2.5
mol.L-1 in Eq. 1 gives a ratio [3a]:[4a] = 97.4:2.6, in good agreement with the results
given in Table 1. Interestingly, the ratio of the addition of alkanethiyl radical R´S. to
C(1) and C(2) amounts to ka,I:kA,II = 90.5:9.5. Thus, the reason for the high selectivity
of the addition of thiols to 1-alkenes is the fact that the moderate selectivity of the
addition of thiyl radicals to 1-alkenes is strongly enhanced by the fragmentation of the
adduct radicals I and II with kf,I<<kf,II.
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Most importantly, the regioselectivities correlate with Taft Es parameters of
substituent R of alkene 2 [26] (Figure 1) giving clear evidence that the regioselectivity
of the radical addition of thiols to 1-alkenes is mainly controlled by the steric effect of
substituent R because of an unsymmetrical transition state of the thiyl radical addition
as was shown by Giese for alkyl radicals.[10] Northrup et al. expected, as a first
approximation, that thiyl radicals will follow similar trends as carbon-centered
radicals. [27]
The slope of the correlation line is = -0.80. This value can be compared with the
addition of the cyclohexyl radical to alkenes at room temperature (= -1.19)[10] and at
400°C (= -0.84).[21] This gives evidence that the steric effect of substituent R on the
thiyl radical addition is in the order of magnitude of the addition of the cyclohexyl
radical.
2,5
2
S=log ([3]:[4])
1,5
1
y = ‐0,7962x + 1,1546
0,5
R² = 0,945
0
-2
-1
0
1
2
ES
Figure 1. Correlation between the selectivity S = log ([3]:[4]) of the addition of thiol 1
to 1-alkenes 2a-f at 80°C and 2g at r.t. (see Table 1) and Taft ES parameters
including R=H (Es +1.24).
It is known that thiyl radicals can abstract hydrogen from bisallylic C-H bonds,[28] and
especially form allylic C-H bonds of allyl ethers,[29] -amines and -thioethers, giving an
allylic radical, which by retransfer of hydrogen from thiol would result in isomerization
of 1- to 2-alkene.[30] Addition of the thiyl radical to C(2) of the 2-alkene, though much
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
slower than to C(1) of the 1-alkene, could be another way to the minor regioisomer 4,
though also addition to C(3) giving a further isomer 5 should be observed (Scheme
2). Cadogan didn´t observe any addition to C(3) in the studied reaction of 1-octene
and thioglycolic acid and concluded thereof that allylic hydrogen abstraction by thiyl
radicals does not occur in the studied reaction.[12] We could confirm this result. We
could not observe any third addition product beside the main product 3 and the minor
isomer 4 with the exemption of alkene 2d having allylic-benzylic C-H bonds. 0.3 % of
isomer 5d was formed at 80°C after 3 days reaction time (Table 1, entry 15),
increasing to 0.6% after 6 days and 1.6 % after 8 days reaction time (see
Experimental). 0.3 % and 0.2 % of isomer 5d was formed at 80°C and 60°C,
respectively, using AIBN as initiator after 100 min. reaction time (entry 8, 9). These
results give clear evidence of the double bond isomerization followed by thiol
addition. The observation of the formation of isomer 5d via a secondary adduct
radical seems to be remarkable because in the case of styrene 2c via a primary
adduct radical no respective isomer 4c could be detected.
Scheme 2: Abstraction of an allylic-benzylic hydrogen giving an allylic-benzylic
radical and in addition to products 3d and 4d the regioisomeric product 5d via
propenyl benzene.
Conclusions
In conclusion, we could show unambiguously that the radical addition of thiyl radicals
to 1-alkenes is mainly steered by the steric effect of substituent R at the alkene.
However, the regiochemical outcome of the thiol addition is strongly enhanced by the
much faster fragmentation of the intermediate Markownikow adduct radical II in
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
comparison to the anti-Markownikow adduct radical I giving with high selectivity the
major product by addition to C(1), and the minor product to C(2). This result is of
utmost importance considering the wide applications of this reaction in synthesis and
especially in macromolecular synthesis.
Experimental section
1. Materials and methods
1.1 General information
Dodecanethiol (1), 1-octene (2a), allyl benzene (2d), vinylcyclohexane (2e),
allylcyclohexane (2f) were purchased from Sigma-Aldrich, Germany, and 3,3-dimethyl-
1-butene (2g) (min. 96 %) from TCI Deutschland GmbH and used as received. Styrene
(2c), Sigma-Aldrich, Germany, was freshly distilled. Methyl 10-undecenoate (2b) was
obtained from elf atochem, France, and was dried over molecular sieve.
Analytical equipment: Analytical GC was performed on a Carlo Erba GC series 4160
with a FID detector and fused silica capillary column DB1, 29 m, 0.25 mm. 1H and 13C
NMR spectra were recorded in CDCl3 on a Bruker AM 300 or Bruker DRX 500
spectrometer at 300 K using residual non-deuterated solvent (1H NMR) or CDCl3 (13C
NMR) as internal standards. GC/MS (EI) using Thermo DSQII with GC Focus, fused
silica capillary column DB5, 25m x 0.25 mm
All reactions were performed under nitrogen using standard Schlenk techniques.
1.2 General Procedure of addition of thiol 1 to alkenes 2
1.5 eq. of 1 was stirred in a 2-necked round-bottomed flask under nitrogen. 1 eq. of
alkene 2 was added. The mixture was reacted for the time and at the temperature
given. The reaction was followed by GC. Non-reacted 1 and 2 was removed and
product 3 with 4 obtained by Kugelrohr distillation.
1.2.1 Dodecyl(octyl)sulfane (3a) and dodecyl(octan-2-yl)sulfane (4a): 0.56 g (5
mmol) of 1-Octene (2a) was reacted with 1.03 g (5 mmol) of thiol 1 at 90°C, 6 h.
Kugelrohr distillation (125°C, 5x10-3 mbar) yielded 0.92 g (58 %) of product. [3a]:[4a]=
97.7:2.3,
During the complete reaction time [3a]:[4a]=97.7:2.3. The reaction was performed
analogously at 80°C: [3a]:[4a]=97.8:2.2, and at 70°C: [3a]:[4a]=97.9:2.1.
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1
3a: H NMR (500.1 MHz, CDCl3): δ = 2.50 (t, J = 7.7 Hz, 4 H, SCH2), 1.54 (m, 4 H,
SCH2CH2), 1.35 (m, 4 H, SCH2CH2CH2), 1.22 (m, 24 H, CH2), 0.84 (2 x t, J = 7.2 Hz,
6 H, CH3). 13C NMR (125.7 MHz, CDCl3): δ = 32.2, 31.9, 31.8, 29.7-29.0, 22.7, 22.6,
2 x 14.1 ppm. EI-MS (70 eV): m/z (%): 314 (3) [M+], 201 (26), 145 (68), 111 (12), 97
(30), 83 (42), 69 (100). 4a: EI-MS (70 eV): m/z (%): 314 (3) [M+], 229 (34), 201 (40),
145 (25), 112 (30), 97 (16), 83 (44), 69 (100).
1.2.2 Methyl 11-(dodecylthio)-undecanoate (3b) and methyl 10-(dodecylthio)-
undecanoate (4b): 1.98 g (10 mmol) of 2b was reacted with 2.02 g (10 mmol) of thiol
1 at 80°C, 24 h. Non-reacted substrates were removed by Kugelrohr distillation (75°C,
6x10-3 mbar), 3.3 g of residue, [3b]:[4b]=98.1:1.9. Recrystallisation from ethanol
yielded 2.71 g (68 %) of pure 3b. The reaction was performed analogously at 63°C
giving [3b]:[4b]=98.4:1.6. M. p. 46-47°C; 1H NMR (500.1 MHz, CDCl3): δ = 3.65 (s, 3
H, OCH3), 2.51 (t, J = 7.7 Hz, 4 H, SCH2), 2.32 (t, J = 7.5 Hz, 2 H, COCH2), 1.60 (m,
bs, 6 H, SCH2CH2 and COCH2CH2), 1.38 (m, 4 H, SCH2CH2CH2), 1.35-1.26 (m, 28 H,
13
CH2), 0.90 (t, J = 7.2 Hz, 3 H, CH3). C NMR (125.7 MHz, CDCl3): δ = 174.2, 51.4,
34.0, 32.1, 31.9, 29.7-28.9, 24.9, 22.6, 14.1 ppm. EI-MS (70 eV): m/z (%): 400 (0.5)
[M+], 231 (2), 201 (38), 199 (36), 87 (38), 74 (40), 69 (100). 4b: EI-MS (70 eV): m/z
(%): 400 (0.5) [M+], 231 (4), 229 (8), 201 (16), 199 (10), 97 (26), 83 (46), 74 (24), 100
(53).
1.2.3 Dodecyl(2-phenylethyl)sulfane (3c): 1.04 g (10 mmol) of 2c was reacted with
3.03 g (15 mmol) thiol 1 at 80°C, 4.5 h. Kugelrohr distillation (170°C, 1x10-3 mbar).
1
Isolated yield of 3c 2,4 g (80 %). H NMR (500.1 MHz, CDCl3): δ = 7.28 (m, 2 H, H-
Ph), 7.20 (m, 3 H, H-Ph), 2.88 (dd, J = 7.6, 9.0 Hz, 2 H, CH2-Ph), 2.76 (dd, J = 7.6, 9.0
Hz, 2 H, CH2CH2-Ph), 2.52 (t, J = 7.7 Hz, 2 H, SCH2),1.58 (m, 2 H, SCH2CH2), 1.37
(m, 2 H, SCH2CH2CH2), 1.36-1.20 (m, 16 H, CH2), 0.88 (t, J = 7.2 Hz, 3 H, CH3). 13C
NMR (125.7 MHz, CDCl3): δ = 140.7, 128.4, 128.3, 126.2, 36.5, 33.7, 32.4, 31.8, 29.7-
28.5, 22.6, 14.0 ppm. EI-MS (70 eV): m/z (%): 306 (2) [M+], 215 (24), 201 (4), 151 (1),
138 (4), 105 (52), 104 (100).
1.2.4 Dodecyl(3-phenylpropyl)sulfane (3d), Dodecyl(2-phenylpropyl)sulfane (4d)
and Dodecyl(1-phenylpropyl)sulfane (4d): a) 1.18 g (10 mmol) of 2d was reacted
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European Journal of Organic Chemistry
with 3.03 g (15 mmol) thiol 1 at 80°C, 8d. The reaction was followed by GC. Yield 80
% (GC), [3d]:[4d]:[5d]=96.9:2.8:0.3 (t=3d); 96.7:2.7:0.6 (t=6d); 95.3:3.1:1.6 (t=8d).
b) 0.59 g (5 mmol) of 2d, 1.52 g (7.5 mmol) of thiol 1 and 100 mg AIBN was reacted at
80°C, 100 min. Kugelrohr distillation yielded 1.5 g (94 %) product, [3d]:[4d]:[5d]=
96.2:3.5:0.3.
The
reaction
was
performed
analogously
at
60°C.
[3d]:[4d]:[5d]=97.0:2.8:0.2.
3d: 1H NMR (500.1 MHz, CDCl3): δ = 7.32 (m, 2 H, H-Ph), 7.24 (m, 3 H, H-Ph), 2.77 (t,
J = 7.6 Hz, 2 H, CH2-Ph), 2.56 (t, J = 7.5, 7.4 Hz, 4 H, SCH2),1.95 (tt, J = 7.6, 7.7 Hz,
2 H, CH2CH2C), 1.62 (m, 2 H, SCH2CH2), 1.41 (m, 2 H, SCH2CH2CH2), 1.38-1.25 (m,
16 H, CH2), 0.94 (t, J = 7.0 Hz, 3 H, CH3). 13C NMR (125.7 MHz, CDCl3): δ = 141.6,
129.2, 128.5, 128.3, 125.9, 34.9, 34.8, 32.1, 31.9, 31.5, 31.4, 31.0-29.0, 22.7, 14.1
ppm. EI-MS (70 eV): m/z (%): 320 (1) [M+], 229 (0.5), 201 (0.5), 118 (100), 117 (35),
91 (24). 4d: EI-MS (70 eV): m/z (%): 320 (0.5) [M+], 229 (46), 207 (26), 201 (0.5), 117
(16), 91 (100). 5d: EI-MS (70 eV): m/z (%): 320 (2) [M+], 207 (60), 201 (10), 118 (100),
117 (40), 117 (16), 91 (54).
1.2.5 2-(Cyclohexylethyl)(dodecyl)sulfane (3e) and 1-(Cyclohexylethyl) (dodecyl)
sulfane (4e): a) 1.37 mL (1.1 g, 10 mmol) of 2e was reacted with 3.03 g (15 mmol) of
1 at 80°C for 3 h. Kugelrohr distillation yielded 2.87 g (92 %) of product, [3e]:[4e]=
98.2:1.8.
b) The reaction was also performed at r.t. After 24 h of reaction time 2e was completely
converted. [3e]:[4e]=98.9:1.1
1
3e: H NMR (500.1 MHz, CDCl3): δ = 2.51 (m, 4 H, SCH2), 1.74 (m, 5 H, CH and
cCHCH2 ), 1.60 (dt, J = 8.1, 7.3, Hz, 2 H, SCH2CH2CH), 1.51 (m, 2 H, SCH2CH2), 1.38
(m, 2 H, SCH2CH2CH2), 1.28 (m, 22 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3). 13C NMR
(125.7 MHz, CDCl3): δ = 37.3, 37.0, 33.1, 32.1, 31.9, 29.7-28.5, 26.6, 26.2, 22.7, 14.1
ppm. EI-MS (70 eV): m/z (%): 312 (1) [M+], 201 (4), 143 (16), 110 (46), 96 (16), 81
(100). 4e: EI-MS (70 eV): m/z (%): 312 (1) [M+], 229 (16), 201 (6), 143 (6), 110 (56),
69 (100).
1.2.6 3-(Cyclohexylpropyl)(dodecyl)sulfane (3f) and 2-(Cyclohexylpropyl)
(dodecyl)sulfane (4f): a) 1,24 g (10 mmol) of 2f was reacted with 3.03 g (15 mmol) of
1 at 80°C for 22 h and followed by GC. Kugelrohr distillation (170-180°C, 3x10-3 mbar)
yielded 2.25 g (70% ) of product. During the complete reaction time [3f]:[4f]= 98.2:1.8.
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10.1002/ejoc.201701692
European Journal of Organic Chemistry
b) The reaction was also performed in the presence of 100 mg of AIBN. [3f]:[4f]=
97.8:2.2.
3f: 1H NMR (500.1 MHz, CDCl3): δ = 2.52 (t, J = 7.6 Hz, 4 H, SCH2), 1.71 (m, 4 H,
cCHCH2), 1.62 (m, 5 H, CH and SCH2CH2CH), 1.42 (m, 2 H, SCH2CH2CH2), 1.28 (m,
13
24 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3). C NMR (125.7 MHz, CDCl3): δ = 37.4,
36.7, 33.3, 32.5, 32.2, 31.9, 29.6-29.3, 27.1, 26.7, 26.3, 22.7, 14.1 ppm. EI-MS (70
eV): m/z (%): 326 (1) [M+], 201 (8), 157 (100), 123 (10), 81 (74). 4f: EI-MS (70 eV):
m/z (%): 326 (1) [M+], 229 (2), 201 (2), 157 (6), 124 (100), 82 (96).
1.2.7 (3,3-dimethylbutyl)(dodecyl)sulfane (3g) and (3,3-dimethylbutan-2-
yl)(dodecyl)sulfane (4g): 1.29 mL (0.84 g, 10 mmol) of 2g was reacted 14 d with
3.03 g (15 mmol) thiol 1 at r.t. Non-reacted substrates were removed by Kugelrohr
distillation. Yield: n.d.; [3g]:[4g]= 99.4:0.6.
3g: 1H NMR (300.1 MHz, CDCl3): δ = 2.49 (m, 4 H, SCH2), 1.61 (tt, J = 7.5, 6.7 Hz, 2
H, SCH2CH2), 1.50 (m, 2 H, CH2C), 1.32-1.23 (m, 18 H, CH2), 0.92 (s, 9 H, C(CH3)3),
0.88 (t, J = 7.0 Hz, 3 H, CH3). 13C NMR (75.5 MHz, CDCl3): δ = 44.1, 32.1, 31.9, 30.7,
29.7-29.0, 27.6, 22.7, 14.1 ppm. EI-MS (70 eV): m/z (%): 286 (12) [M+], 229 (100), 215
(16), 201 (82). 4g: EI-MS (70 eV): m/z (%): 286 (1) [M+], 229 (100), 201 (4).
Acknowledgements
We thank Stefanie Möller for skillful technical assistance and abiosus e.V., Oldenburg,
Germany for financial support.
Keywords: Radical reactions • Regioselectivity • Steric hindrance• Substituent effect
• Molecule Assisted Homolysis
Table of Contents
Steric effect
Ursula Biermann, Jürgen O. Metzger*
Regioselectivity of Radical Addition of Thiols to 1-Alkenes
4
2
0
-2
0
2
ES
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European Journal of Organic Chemistry
The regioselectivities of the radical addition of thiol 1 to 1-alkenes 2 correlate with
Taft Es parameters of substituent R of 2 giving clear evidence that it is mainly
controlled by the steric effect of substituent R because of an unsymmetrical transition
state of the thiyl radical addition as is well known for alkyl radicals.
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European Journal of Organic Chemistry
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