Direct bromination and iodination of non-activated alkanes by hypohalite reagents

Article abstract of DOI:10.1055/s-2005-865322

The direct functionalisation of alkanes through bromination and iodination has been successfully achieved. The combination of stoichiometric mixtures of elemental halogen and sodium alkoxides leads to the formation of alkyl hypobromites and hypoiodites as reagents. The halogenation occurs without external photostimulation under thermal reaction conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865322

PAPER
1473
Direct Bromination and Iodination of Non-Activated Alkanes by Hypohalite
Reagents
D
irec
t
Brominatio
a
n
and Iodi
ú
nation of
N
o
l
n-Activated A
M
lkanes by Hypohalite
oReagents ntoro, Thomas Wirth*
Cardiff School of Chemistry, Cardiff University, Cardiff, CF10 3AT, UK
Fax +44(29)20876968; E-mail: wirth@cf.ac.uk
Received 14 February 2005
Dedicated to Bernd Giese on the occasion of his 65th birthday
kanes.11 The photolysis and thermolysis of alkyl hy-
pochlorites, derived from alcohols with hypochlorous
acid, has been extensively used for the preparation of d-
chlorohydrins, tetrahydrofuranes12 and spiro ethers.13
Abstract: The direct functionalisation of alkanes through bromina-
tion and iodination has been successfully achieved. The combina-
tion of stoichiometric mixtures of elemental halogen and sodium
alkoxides leads to the formation of alkyl hypobromites and hy-
poiodites as reagents. The halogenation occurs without external
photostimulation under thermal reaction conditions.
tert-Butyl hypobromite has been successfully prepared by
reaction of t-BuOH with hypobromous acid in trichloro-
fluoromethane and used for the radical bromination of
alkanes and alkenes such as cyclohexene to give 3-bro-
mocyclohexene, a reaction which occurs photochemically
in a few minutes at room temperature.14
Key words: alkanes, halogenation, hypobromites, hypoiodites
There are various methods known for the functionalisa-
tion and manipulation of non-activated C–H bonds, but
many of them are still lacking the desired control and se-
lectivity. Highly reactive reagents are necessary to per-
form such transformations, such as carbenes,1
superacids,2 free radicals,3 or transition metals.4 The
strong reaction conditions required by these reagents
might be incompatible with other functional groups and
also skeletal rearrangements can occur.
The unstable tert-butyl hypoiodite has only been generat-
ed in situ from reaction of mercury iodide and tert-butyl
hypochlorite but found to be a promising iodinating re-
agent for the functionalisation of alkanes15 and cubane
skeletons16 when irradiated in Freon-113 as inert solvent.
One of the first applications of organic hypoiodites was in
steroid chemistry. Barton17 used tert-butyl hypoiodite,
prepared from tert-butyl hypochlorite or from potassium
tert-butoxide and iodine, as a reagent to prepare steroid
hypoiodites from the corresponding alcohols. These were
used as intermediates in a photochemical intramolecular
hydrogen abstraction, followed by iodination and subse-
quent ring closure of the 1,5-iodoalcohols to tetrahydro-
furans or spiroketals.18 Other hypoiodites can also be
prepared from heavy metal salts [Pb(OAc)4, Hg(OAc)2,
AgOAc, HgO] in combination with iodine to generate I2O
that leads to hypoiodite formation in situ.19
The halogenation of alkanes is particularly interesting.
Hydrocarbons are cheap and abundant starting materials,
which are used for the direct synthesis of haloalkanes be-
ing valuable and useful building blocks in synthesis.
The iodination of alkanes, unlike bromination and chlori-
nation, is thermodynamically forbidden,5 with an overall
positive enthalpy of 20–30 kcal/mol. Recently, new meth-
odologies have been established for such transformations.
For example, the discovery of the first ionic iodination of
alkanes by superelectrophilic tetrahalomethane–alumini-
um triiodide complexes at –20 °C,6 the first application of
the Suárez reagent, a combination of iodine and (diacet-
oxyiodo)benzene, for a carbon-hydrogen bond activation
in the synthesis of monoiodoalkanes or 1-acetoxy-2-io-
docycloalkanes,7 and the radical monoiodination of al-
kanes by mixtures of tetraiodomethane or iodoform with
powdered NaOH at room temperature.8
We have recently reported the in situ generation of tert-
butyl hypoiodite for an efficient iodination of various al-
kanes.20 We now describe an expansion of these studies
towards bromination and discuss the observed selectivi-
ties in more detail (Scheme 1). We reported the formation
of iodocyclohexane by iodination of cyclohexane with io-
dine and sodium tert-butoxide, which implied the genera-
tion of the corresponding hypoiodite intermediate.
Alkyl hypohalites are positive halogen carrier reagents
which have found extensive application for the activation
of alkanes and other non-activated C–H bonds. tert-Butyl
hypochlorite is a stable compound in the dark and easily
prepared by reaction of t-BuOH with chlorine in aqueous
NaOH.9 It has promising chlorinating properties for non-
activated allylic10 and benzylic positions and for al-
Other alkoxides seem to be less efficient in the iodination
which apparently only proceeds with tertiary alkoxides.
We show that the addition of small amounts of bromine
(20 mol%) can improve reproducibility and yields. These
Hal
RONa, Hal2
1 Hal = I
2 Hal = Br
SYNTHESIS 2005, No. 9, pp 1473–1478
Advanced online publication: 19.04.2005
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x
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x
x
.2
0
0
5
DOI: 10.1055/s-2005-865322; Art ID: C00505SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Iodination and bromination of cyclohexane

1474
R. Montoro, T. Wirth
PAPER
results are shown in Table 1, where the yield of iodocy- with the values described in the literature for halogen and
clohexane 1 could be improved from 84% to 94% (entry alkoxyl radicals.
4). Although 20 mol% bromine are present, bromocyclo-
hexane 2 is not isolated at all in this reaction and no traces
could be found by GC analysis. A possible conversion of
initially formed 2 to 1 under the reaction conditions is not
taking place: After the addition of small amounts of 2 (0.2
equiv) to the reaction the crude product was found to be a
mixture of 1 and 2.
To establish the relative reactivities of the tert-butyl hypo-
halites towards primary and secondary hydrogen abstrac-
tion, we investigated the reaction with pentane in detail. A
reaction at one of the primary hydrogen atoms will lead to
1-halopentane (3a), whereas an abstraction of a secondary
hydrogen will lead to 2-halopentane (3b) or 3-halopen-
tane (3c) (Scheme 3). A comparison to ratios obtained in
However, the addition of only 0.1 equivalents of an alco- other radical reactions as described in literature is possible
hol to the iodination with iodine and sodium tert-butox- and these references are included in Table 2.
ide, completely stops the iodination process. Only if
additional bromine is present, the iodination takes place.
In the presence of 0.2 equivalents of alcohol (MeOH,
EtOH, t-BuOH) and 0.2 equivalents of bromine the reac-
various
reaction
conditions
Hal
Hal
tion yields only 1 in up to 65%.
Hal
3a
3b
3c
Table 1 Iodination and Bromination of Cyclohexane
Scheme 3 Halogenation of pentane
Entry RONa
Hal2: I2
Hal2: I2
Hal2: Br2
+ 0.2 equiv Br2
1, yield (%) 1, yield (%)
In Table 2 the results of the halogenation of pentane are
compared with some reactions described in literature. The
identification of the reactive radicals operating in these re-
actions is complicated because other reactive species
might be involved as shown in Scheme 4.
2, yield (%)
1
2
3
4
5
–
0
0
–
0
86
21
MeONa
EtONa
1
1
60
I
tert-BuONa
EtMe2CONa
84
70
94
72
100
50
t-BuO
I
I
t-BuO
Ot-Bu
4
Conditions: Addition of 1 equiv of alkoxide to a 0.1 M solution of 1
equiv Hal2 in cyclohexane, then stirring at 40 °C for 15 h.
–I
–I
The radical bromination of cyclohexane is known.5 Upon
addition of primary alkoxides a decreased yield of bro-
mocyclohexane 2 was observed in the bromination of cy-
clohexane. The primary alkyl hypobromites formed are
obviously less efficient for hydrogen abstraction (Table 1,
entries 2 and 3) than bromine itself (Table 1, entry 1).
Only with tert-butyl hypobromite an even higher yield
than with elemental bromine was observed (Table 1, entry
4).
t-BuO
I
t-BuO
Ot-Bu
5
Scheme 4 Radicals derived from tert-butyl hypoiodite
The analysis of the reactivities towards the abstraction of
primary and secondary hydrogen atoms suggests that the
formation of tert-butyl hypoiodite using tert-butyl hy-
pochlorite and mercury iodide (Table 2, entry 10) which
can involve dimerisation to molecules such as 4. The re-
active species might be radical 5 showing comparable
selectivities than the radical derived from (dichloro-
iodo)benzene (Table 2, entry 3). On the basis of this selec-
tivity observed for the tert-butoxyl radical derived from
tert-butyl hypoiodite, the existence of hypervalent species
of type 4 and radicals 5 was postulated. The unimolecular
decomposition of the tert-butyl radical into acetone and a
methyl radical is known but does not compete with the
fast abstraction of hydrogen atoms from alkanes.25 The se-
lectivities found in reactions described in Table 2, entries
2, 8, 11 and 13 involve tert-butoxyl radicals and are com-
parable. The radical obtained from the alkoxide of 2-me-
thyl-2-butanol shows similar reactivities to the tert-
butoxyl radical (Table 2, entries 12 and 14) whereas in the
reaction with only bromine the selectivity (1:19) might in-
The reaction proceeds in the absence of external photo-
stimulation under thermal conditions. Bromination and
iodination of toluene occur at the side chain and not on the
aromatic nucleus, which is indicative of the radical nature
of the process.
As shown in Scheme 2, the tert-butoxyl radical is formed
by homolysis of the corresponding tert-butyl hypohalite.
It has been identified as the free radical chain carrier and
hydrogen abstracting species by comparing its relative re-
activities with primary and secondary hydrogen atoms
Hal2
+
t-BuONa
t-BuO
t-BuOHal
t-BuO + Hal
Alkyl-Hal
t-BuOHal
Alkane
[ Alkyl ]
Scheme 2 Generation of tert-butoxyl radicals as hydrogen abstrac-
ting species for alkanes
Synthesis 2005, No. 9, 1473–1478 © Thieme Stuttgart · New York

PAPER
Direct Bromination and Iodination of Non-Activated Alkanes by Hypohalite Reagents
1475
Table 2 Halogenation of Pentane
Entry
Reagents/Temp
Ratio
Relative reactivities
Yield (%)
Reference
3a:3b:3c
Primary:Secondary hydrogen atoms
1
2
Cl2, 40 °C
1:4
21
22
23
t-BuOCl, 40 °C
PhICl2, 40 °C
Br2, 40 °C
1:8
3
1:21
1:240
1:220
1:53
1:242
1:9
4
1:189:51
85
5
Br2, 80 °C
24
6
Br2, MeONa
1:41:12
1:190:52
1:6:4
53
53
61
80
71
61
37
94
50
7
Br2, EtONa
8
Br2, t-BuONa
Br2, EtMe2CONa
t-BuOCl, HgI2
I2, t-BuONa
9
1:11.7:7.9
1:19
1:29
1:8
a
10
11
12
13
14
12
1:5:3
I2, EtMe2CONa
I2, Br2, t-BuONa
I2, Br2, EtMe2CONa
1:8.2:3.1
1:6.7:2.7
1:3:1
1:11.3
1:9.4
1:4
a Ratio based on the reaction with n-butane (1-iodobutane:2-iodobutane = 1:29).
Table 3 Yields of Reaction of Alkanes with Alkyl Hypobromites
Entry
1
Substrate
Products
Yield (%)
(Hal = Br)
Yield
(Hal = I)
61
94
(3a:3b:3c =
1:10.4:3.7)
(3a:3b:3c =
1:6.7:2.7)
Hal
Hal
3b
Hal
3c
3a
2
3
80
90
(6a:6b:6c =
1:11.8:7.8)
(6a:6b:6c =
1:5:4)
Hal
6a
Hal
Hal
6c
6b
59
70
(7a:7b:7c:7d =
1:10.1:6.5:3.5)
(7a:7b:7c:7d =
1:8.7:5.9:2.4)
Hal
Hal
7a
7b
Hal
Hal
7c
7d
4
5
Quant.
Quant.
65
94
8
Hal
9
Hal
6
7
60
84
40
10
Hal
Quant.
Hal
11
dicate an involvement of a hypervalent radical of type 5 or The regioselectivity in the iodination of linear alkanes
some free bromine reacting independently with pentane.
with stoichiometric mixtures of iodine and sodium tert-
butoxide implies the in situ formation of alkoxide radi-
cals, which act as the hydrogen abstracting species and as
Synthesis 2005, No. 9, 1473–1478 © Thieme Stuttgart · New York

1476
R. Montoro, T. Wirth
PAPER
spectra available and are not included. All reagents were purchased
as ACS grade and used without any further purification.
the radical chain carrier species of the halogenation. The
formation of alkyl hypoiodites from such reagent mix-
tures is supported by the fact that similar regioselectivities GC analysis was performed on a Varian 3900 GC apparatus using a
Varian Factor FOUR Capillary Column VF-1ms 15 m × 0.25 mm
ID DF = 0.25. The retention times indicated with each compound
are referring to the temperature programme used for the analysis
(from 50 °C to 150 °C with 3 °C/min). tR (1-Bromopentane) = 6.24
min, tR (2-bromopentane) = 4.48 min, tR (3-bromopentane) = 4.62
min, tR (1-iodopentane) = 8.85 min, tR (2-iodopentane) = 6.30 min,
tR (3-iodopentane) = 6.74 min, tR (1-bromohexane) = 8.49 min, tR
(2-bromohexane) = 6.92 min, tR (3-bromohexane) = 7.10 min, tR (1-
iodohexane) = 11.11 min, tR (2-iodohexane) = 8.74 min, tR (3-io-
dohexane) = 9.30 min, tR (1-bromoheptane) = 9.96 min, tR (2-bro-
moheptane) = 8.11 min, tR (3-bromoheptane) = 8.04 min, tR (4-
bromoheptane) = 7.71 min, tR (1-iodoheptane) = 17.58 min, tR (2-
have been reported for the chlorination of linear alkanes
by tert-butyl hypochlorite as chlorinating reagent.21
The regioselectivities for the hydrogen abstraction in the
reaction of alkanes with alkyl hypobromites generated
from stoichiometric mixtures of bromine and tertiary
alkoxides as shown in Tables 2 and 3 are similar to regio-
selectivities reported for alkoxy radicals and different
from the selectivities reported for bromine radicals
(Table 2, entries 4 and 5). Therefore, the mechanism in-
volves the homolysis of alkyl hypohalites, but seems to be
restricted to tertiary alkyl derivatives. There is no trace of iodoheptane) = 12.71 min, tR (3-iodoheptane) = 12.21 min, tR (4-io-
doheptane) = 10.17 min, tR (bromocylopentane) = 4.65 min, tR (io-
docyclopentane) = 10.90 min, tR (bromocyclohexane) = 12.46, tR
(iodocyclohexane) = 22.99, tR (bromocycloheptane) = 19.16 min, tR
(iodocycloheptane) = 25.39 min, tR (benzyl bromide) = 19.30 min,
iodoalkanes when primary alkoxides are used for hy-
poiodite formation, and bromoalkanes are also formed in
lower yields when primary alkoxides are used. This indi-
cates a thermodynamically unfavorable formation, ho-
tR (benzyl iodide) = 20.58 min.
molysis or halogenation of alkanes with primary alkyl
hypohalites.
Iodocyclohexane; Typical Procedure
Iodine (635 mg, 2.5 mmol) and Br2 (80 mg, 25.6 mL, 0.5 mmol)
were dissolved in cyclohexane (20 mL, 185 mmol) and t-BuONa
(288 mg, 3 mmol) was added. The suspension was stirred at 40 °C
for 15 h. The mixture was washed with 1% aq Na2S2O3 (30 mL) and
dried over MgSO4. The solvent was removed under reduced pres-
As mentioned above, a remarkable effect on reproducibil-
ity and yields was observed in the iodination of alkanes
when sub-stoichiometric amounts of bromine were added
to the reaction. The presence of bromine seems to improve
the radical initiation step because of the more favorable sure and the residue distilled to yield iodocyclohexane 9 (Hal = I) in
94% yield (493 mg) as a light yellow liquid.
energetic balance of the formation and homolysis of tert-
butyl hypobromite than of tert-butyl hypoiodite. Mixed
1-Bromopentane (3a; Hal = Br)
hypervalent species of type 4 might be involved as well.
1H NMR (400 MHz, CDCl3): d = 0.95 (m, 3 H, CH3, H-5), 1.30–
As a hydrogen abstracting species, the tert-butoxyl radical
was found to exhibit modest selectivities. A general com-
parison for alkanes showed a selectivity of approximately
1:14:40 for primary–secondary–tertiary hydrogen atoms.
This selectivity roughly reflects the strength of the corre-
sponding C–H bonds, although only for substrates with
hydrogen–carbon bond dissociation energies of larger
than ca. 92 kcal/mol normal reactivity trends are ob-
served. Interestingly, benzylic C–H bonds with about 10
kcal/mol difference in bond strength to aliphatic C–H
bonds are comparable in reactivity. A recent analysis of
data on the hydrogen abstraction with tert-butoxyl radi-
cals from hydrocarbons indicates that most of these reac-
tions in solution at room temperature are entropy-
controlled.26 One of the few examples of the solvent po-
1.50 (m, CH2, 4 H), 1.85 (m, 2 H, CH2, H-2), 3.40 (m, 2 H,
CH2Br).28
13C NMR (100 MHz, CDCl3): d = 13.9 (C-5), 22.0 (C-4), 30.5 (C-
3), 32.7 (C-2), 33.7 (C-1).29
2-Bromopentane (3b; Hal = Br)30
1H NMR (400 MHz, CDCl3): d = 0.98 (t, 3 H, J = 7.2 Hz, CH3, H-
5), 1.44 (m, 2 H, CH2), 1.66 (d, J = 6.6 Hz, 3 H, CH3), 1.75 (m, 2 H,
CH2), 4.06 (m, 1 H, CHBr).
13C NMR (100 MHz, CDCl3): d = 13.4 (C-5), 21.0 (C-4), 26.4 (C-
3), 43.2 (C-1), 51.6 (C-2).
3-Bromopentane (3c; Hal = Br)
1H NMR (400 MHz, CDCl3): d = 1.02 (t, J = 7.3 Hz, 6 H, CH3), 1.81
(m, 4 H, CH2), 3.86 (m, 1 H, CHBr).31
13C NMR (100 MHz, CDCl3): d = 12.1 (C-3), 31.8 (C-2), 61.0 (C-
larity having a significant effect on the rate of radical re- 1).32
actions is the increase of the relative rate b-C–C vs. C–H
1-Iodopentane 3a (Hal = I)33
abstraction in more polar solvents.27
1H NMR (400 MHz, CDCl3): d = 0.88 (m, 3 H, CH3, H-5), 1.34 (m,
2 H, CH2, H-4), 1.43 (m, 2 H, CH2, H-3), 1.81 (m, 2 H, CH2), 3.12
(t, J = 7.06 Hz, 2 H, CH2I).
In conclusion, we have developed a metal-free process for
the direct iodination and bromination of alkanes using
tert-butyl hypohalites as cheap and efficient reagents. The
procedures described here are very simple and can be per-
formed without prior purification of the solvents.
13C NMR (100 MHz, CDCl3): d = 6.4 (C-1), 14.1 (C-5), 21.6 (C-4),
32.6 (C-3), 33.5 (C-2).
2-Iodopentane (3b; Hal = I)32
1H NMR (400 MHz, CDCl3): d = 0.95 (t, J = 7.2 Hz, 3 H, CH3), 1.32
(m, 2 H, CH2, H-4), 1.75 (m, 2 H, CH2, H-3), 1.86 (d, J = 7.8 Hz, 3
H, CH3, H-1), 4.14 (m, 1 H, CHI).
1H NMR and 13C NMR spectra were recorded on Bruker DPX ma-
chines; CDCl3 was used as solvent and as internal reference (d =
7.26/77.0) in all the spectra; coupling constants J are given in Hz.
The NMR spectra for 3- and 4-bromoheptane and 2-, 3- and 4-io-
doheptane could not be unambiguously assigned from the NMR
13C NMR (100 MHz, CDCl3): d = 13.1 (C-5), 22.9 (C-4), 28.9 (C-
1), 30.4 (C-2), 44.9 (C-3).
Synthesis 2005, No. 9, 1473–1478 © Thieme Stuttgart · New York

PAPER
Direct Bromination and Iodination of Non-Activated Alkanes by Hypohalite Reagents
1477
3-Iodopentane (3c; Hal = I)31,34
1-Iodoheptane (7a; Hal = I)36
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 7.2 Hz, 6 H, CH3), 1.80
1H NMR (500 MHz, CDCl3): d = 0.91 (t, J = 6.9 Hz, 3 H, CH3, H-
(m, 4 H, CH2), 4.01 (m, 1 H, CHI).
7), 1.33 (m, 6 H, CH2), 1.39 (m, 2 H), 1.84 (m, 2 H, H-2), 3.21 (t,
J = 7.1 Hz, 2 H, CH2I).
13C NMR (125 MHz, CDCl3): d = 7.4, 14.1, 22.6, 28.3, 30.5, 31.6,
33.6.
13C NMR (100 MHz, CDCl3): d = 14.1 (C-3), 44.7 (C-1), 44.7 (C-2).
1-Bromohexane (6a; Hal = Br)
1H NMR (400 MHz, CDCl3): d = 0.89 (m, 3 H, CH3, H-6), 1.30 (m,
4 H, CH2, H-4, H-5), 1.41 (m, 2 H, CH2, H-3), 1.82 (m, 2 H, CH2,
H-2), 3.34 (t, J = 6.9 Hz, 2 H, CH2I).
Bromocyclopentane (8; Hal = Br)
1H NMR (300 MHz, CDCl3): d = 1.60 (s, 2 H), 1.81 (s, 2 H), 2.05
(s, 4 H, H-2), 4.41 (m, 1 H, CHBr).
13C NMR (100 MHz, CDCl3): d = 14.1 (C-6), 22.6 (C-5), 27.8 (C-
3), 30.9 (C-4), 32.8 (C-2), 33.7 (C-1).
13C NMR (75 MHz, CDCl3): 23.2 (C-3), 37.8 (C-2), 53.8 (C-1).
2-Bromohexane (6b; Hal = Br)
Iodocyclopentane (8; Hal = I)31,37
1H NMR (400 MHz, CDCl3): d = 0.93 (m, 3 H, CH3, H-6), 1.35 (m,
2 H, CH2, H-5), 1.37 (m, 1 H, CH2, H-4), 1.50 (m, 1 H, CH2, H-4),
1.70 (d, J = 6.9 Hz, 3 H, CH3, H-1), 1.78 (m, 2 H, CH2, H-3), 4.08
(m, 1 H, CHBr, H-2).
1H NMR (400 MHz, CDCl3): d = 1.57 (m, 2 H, CH2), 1.76 (m, 2 H,
CH2), 1.99 (m, 4 H, CH2), 4.29 (m, 1 H, CHI).
13C NMR (100 MHz, CDCl3): d = 23.9 (C-3), 28.7 (C-1), 39.8 (C-2).
13C NMR (100 MHz, CDCl3): d = 14.0 (C-6), 22.1 (C-5), 26.4 (C-
Bromocyclohexane (9; Hal = Br)31,37
1), 29.9 (C-4), 40.8 (C-3), 51.9 (C-2).32
1H NMR (400 MHz, CDCl3): d = 1.32 (s, 3 H), 1.60 (s, 1 H), 1.75
(s, 4 H), 2.15 (s, 2 H), 4.16 (m, 1 H, CHBr).
3-Bromohexane (6c; Hal = Br)
13C NMR (100 MHz, CDCl3): d = 25.1 (C-4), 25.9 (C-3), 37.5 (C-
1H NMR (400 MHz, CDCl3): d = 0.88 (m, 3 H, CH3, H-6), 0.99 (m,
3 H, CH3, H-1), 1.30 (m, 2 H, CH2, H-5), 1.74 (m, 4 H, CH2, H-2,
H-4), 3.95 (m, 1 H, CHBr, H-3).
2), 53.6 (C-1).
Iodocyclohexane (9; Hal = I)31
13C NMR (100 MHz, CDCl3): d = 12.1 (C-1), 13.5 (C-6), 20.8 (C-
1H NMR (400 MHz, CDCl3): d = 1.34 (m, 3 H), 1.60 (m, 3 H), 1.91
(m, 2 H, CH2), 2.11 (m, 2 H, CH2), 4.28 (m, 1 H, CHI).
5), 32.2 (C-2), 40.8 (C-4), 60.4 (C-3).32
13C NMR (100 MHz, CDCl3): d = 25.2 (C-4), 27.3 (C-3), 35.5 (C-
1-Iodohexane (6a; Hal = I)35
1), 39.6 (C-2).
1H NMR (400 MHz, CDCl3): d = 0.88 (m, 3 H, CH3), 1.29 (m, 6 H,
CH2, H-3–H-5), 1.82 (m, 2 H, CH2, H-2), 3.18 (t, J = 7.1 Hz, 2 H,
CH2I).
Bromocycloheptane (10; Hal = Br)
1H NMR (400 MHz, CDCl3): d = 1.45 (m, 2 H, H-3), 1.52 (m, 4 H,
H-4), 1.70 (m, 2 H, H-3), 2.15 (m, 2 H, H-2), 2.45 (m, 2 H, H-2),
4.25 (m, 1 H, CHBr).
13C NMR (100 MHz, CDCl3): d = 7.1 (C-1), 14.0 (C-6), 22.5 (C-5),
30.2 (C-3), 30.7 (C-4), 33.6 (C-2).
13C NMR (100 MHz, CDCl3): d = 26.4 (C-4), 28.9 (C-3), 41.2 (C-
2-Iodohexane (6b; Hal = I)32
2), 58.0 (C-1).
1H NMR (400 MHz, CDCl3): d = 0.89 (m, 3 H, CH3, H-6), 1.25 (s,
2 H, CH2, H-5), 1.39 (m, 1 H, CH2), 1.49 (m, 1 H, CH2), 1.79 (s,
CH2, 2 H, H-3), 1.85 (d, J = 6.8 Hz, 3 H, H-1), 4.15 (m, 1 H, CHBr,
H-2).
Iodocycloheptane (10; Hal = I)38
1H NMR (400 MHz, CDCl3): d = 1.55 (s, 8 H), 2.25 (m, 4 H), 4.42
(m, 1 H, CHI).
13C NMR (100 MHz, CDCl3): d = 13.9 (C-6), 21.9 (C-5), 28.9 (C-
1), 30.2 (C-2), 31.9 (C-4), 42.7 (C-3).
13C NMR (100 MHz, CDCl3): d = 27.0 (C-2), 27.4 (C-3), 36.3 (C-
1), 42.0 (C-4).
3-Iodohexane 6c (Hal = I)32
Benzyl Bromide (11; Hal = Br)36
1H NMR (400 MHz, CDCl3): d = 0.85 (m, 3 H, CH3, H-6), 0.98 (t,
J = 7.2 Hz, 3 H, CH3, H-1), 1.30 (s, 2 H, CH2, H-5), 1.81 (s, 4 H,
CH2, H-2, H-4), 4.05 (m, 1 H, CHBr, H-3).
1H NMR (500 MHz, CDCl3): d = 4.37 (s, 2 H, CH2Br), 7.14–7.28
(m, 5 H, Ar-H).
13C NMR (125 MHz, CDCl3): d = 33.7, 128.5, 128.9, 129.9, 137.9.
13C NMR (100 MHz, CDCl3): d = 13.2 (C-6), 14.1 (C-1), 22.8 (C-
6), 33.8 (C-2), 41.7 (C-3), 42.4 (C-4).
Benzyl Iodide (11; Hal = I)39
1H NMR (400 MHz, CDCl3): d = 4.39 (s, 2 H, CH2I), 7.15–7.31 (m,
5 H, Ar-H).
1-Bromoheptane (7a; Hal = Br)
1H NMR (400 MHz, CDCl3): d = 0.81 (t, J = 6.4 Hz, 3 H, CH3, H-
7), 1.24 (m, 6 H, CH2, H-4–H-6), 1.34 (m, 2 H, CH2, H-3), 1.78 (m,
2 H, CH2, H-2), 3.34 (t, J = 7.5 Hz, 2 H, CH2Br, H-1).
13C NMR (100 MHz, CDCl3): d = 5.8 (CH2I), 127.7, 128.5, 128.6,
139.5.
13C NMR (100 MHz, CDCl3): d = 14.1 (C-7), 22.7 (C-6), 28.2 (C-
5), 28.5 (C-4), 31.7 (C-3), 33.0 (C-2), 33.8 (C-1).
Acknowledgment
Funding was provided by the School of Chemistry, Cardiff Univer-
sity and by EPSRC grant no. GR/S25456 (NMR).
2-Bromoheptane (7b; Hal = Br)
1H NMR (500 MHz, CDCl3): d = 0.84 (m, 3 H, CH3, H-7), 1.25 (m,
4 H, CH2), 1.35 (m, 1 H), 1.45 (m, 1 H), 2.06 (d, J = 6.6 Hz, 3 H,
CH3, H-1), 2.20 (m, 2 H), 4.09 (m, 1 H, CHBr, H-2).
Synthesis 2005, No. 9, 1473–1478 © Thieme Stuttgart · New York

1478
R. Montoro, T. Wirth
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