Study on the bromolactonisation of alkenoic acids with (diacetoxyiodo) benzene

Article abstract of DOI:10.3184/030823410X12682297999384

A study on the bromolactonisation of alkenoic acids is reported. When various pent-4-enoic acids reacted with (diacetoxyiodo)benzene (DIB) and lithium bromide in CH₃OH at room temperature, most of the five-membered bromolactones were obtained in good to excellent yields in short times. Some had two diastereoisomers. When but-3-enoic acid and trans-hex-3-enoic acid were treated under the same conditions, only unsaturated lactones were found after workup. When hex-5-enoic acid was subjected to the same conditions, however, the desired six-membered bromolactone was not successfully separated.

Full text of DOI:10.3184/030823410X12682297999384

JOURNAL OF CHEMICAL RESEARCH 2010
MARCH, 167–169
RESEARCH PAPER 167
Study on the bromolactonisation of alkenoic acids with
diacetoxyiodo)benzene
(
Yan He, Zhenping Yang and Jie Yan*
College of Chemical Engineering and Materials Sciences, Zhejiang University ofTechnology, Hangzhou 310032, Zhejiang, P. R. China
A study on the bromolactonisation of alkenoic acids is reported. When various pent-4-enoic acids reacted with
(
diacetoxyiodo)benzene (DIB) and lithium bromide in CH OH at room temperature, most of the five-membered
3
bromolactones were obtained in good to excellent yields in short times. Some had two diastereoisomers. When
but-3-enoic acid and trans-hex-3-enoic acid were treated under the same conditions, only unsaturated lactones
were found after workup. When hex-5-enoic acid was subjected to the same conditions, however, the desired
six-membered bromolactone was not successfully separated.
Keywords: bromolactonisation, alkenoic acids, (diacetoxyiodo)benzene
Lactonisations have been studied extensively, and this type of
transformation serves as an important key reaction in a variety
Recently, Braddock et al. reported a convenient method for the
bromolactonisation of pent-4-enoic acid using the hypervalent
iodine reagent (diacetoxyiodo)benzene (DIB) and lithium
1–3
of syntheses. Among them, halolactonisation and phenyl-
4
–7
23
selenolactonisation are general used methods. Usually, alke-
noic acids are used to construct lactones by halolactonisation,
which involves the electrophilic addition of molecular halo-
gens to the double bond followed by an intramolecular nucleo-
bromide; however, there was only one example. Therefore,
in order to extend the scope and develop a simple, mild and
efficient bromolactonisation, we have investigated the cyclisa-
tion of alkenoic acids with DIB and LiBr, and found that the
reaction was suitable for a series of pent-4-enoic acids, most
of which gave good to excellent yields of 5-(bromomethyl)-
γ-butyrolactones.
8,9
philic cyclisation. Iodolactonisation is the most widespread
applied halolactonisation as molecular iodine is a less toxic
and easy to handle solid. Bromolactonisation has the restric-
tion of molecular bromine is a toxic, difficult to handle, low-
At the beginning, we mixed equal equivalents of pent-
4-enoic acid (1a), DIB (2) and LiBr (3) in THF at room
temperature, and found that after 25 min the reaction was com-
1
0,11
boiling lachrymatory liquid and also a strong oxidant.
To
improve the bromolactonisation, N-bromosuccinimide (NBS)
2
3
in combination with catalysts has been used successfully
pleted as indicated in Braddock et al.’s report. A product of
5-(bromomethyl)-γ-butyrolactone (4a) was obtained in 68%
yield. Then, a series of experiments was performed on the
reaction of pent-4-enoic acid with hypervalent iodine reagents
and bromides in order to determine the optimum reaction con-
ditions. The results are summarised in Table 1. It is shown that
12–16
to replace Br2.
Bis(2,6-disubstitutedpyridine)bromonium
triflates and dibromodiarylselenium (IV) species have been
1
7,18
reported to be efficient sources of positive bromine
and
NaBr and H O2 with selenoxide, arylseleninic acids and
2
1
9–22
organotelluride as catalysts were found to be effective.
Table 1 Optimisation of the bromolactonisation of pent-4-enoic acid
Entry
DIB (equiv reagent)
LiBr (equiv reagent)
Solvent
Time
Yield/%a
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
CH Cl2
16 h
25 min
1 h
54
68
58
22
74
74
49
66
68
47
2
1.0
THF
1.0
1.0
CH CN
3
1.0
1.0
1.0
NaBr (1.0)
KBr (1.0)
NH Br (1.0)
DMF
120 h
20 min
30 min
20 min
40 min
1 h
1.0
CH OH
3
1.0
1.0
CH OH
3
CH OH
3
1.0
CH OH
4
3
PhI=O(1.0)
PhI(OCOCF ) (1.0)
1.0
1.0
CH OH
3
10
CH OH
1 h
3
2
3
1
1
(1.0)
1.0
CH OH
1 h
1 h
34
3
12
(1.0)
1.0
CH OH
67
3
1
1
1
3
4
5
2.0
2.0
1.0
2.0
1.0
2.0
CH OH
1 h
1 h
1 h
69
80
89
3
CH OH
3
CH OH
3
a
Isolated yields.
*
Correspondent. E-mail: jieyan87@zjut.edu.cn

1
68 JOURNAL OF CHEMICAL RESEARCH 2010
the yield of the product depended on solvent and CH OH was
found to be preferred (entries 1–5). LiBr as well as NaBr were
more active in the reaction than the other two bromides (entries
which were then transformed into the unsaturated lactones
during workup procedure by elimination. Efforts for the pre-
paration of the six-membered lactone 6-bromomethyltetrahy-
dropyran-2-one using hex-5-enoic acid were only partially
successful: the H NMR spectrum of the crude product was
indicative of it, but purification was not achieved.
3
5
–8). As a suitable hypervalent iodine reagent, DIB was the
1
most effective one (entries 5, 9–12). When the amount of DIB
was one equivalent and LiBr was two equivalents, the yield
reached the highest, 89% (entries 5, 13–15).
Koser et al. in 1988 reported another lactonisation using the
hypervalent iodine reagent, [hydroxyl((bis(phenyloxy)phosph-
oryl)oxy)iodo]benzene, and they found when 2-methyl-
pent-4-enoic acid (1b) was treated with the hypervalent iodine
reagent, the products were mixture of diastereoisomers, the
Under the optimum reaction conditions, the reaction of
a series of alkenoic acids (1) with DIB (2) and LiBr (3) in
CH OH at room temperature were investigated. Table 2 shows
3
that all the reactions were completed in 2 h. However, the
corresponding products were quite different: when a series
of pent-4-enoic acids was used in the reaction, the desired 5-
2
4
ratios varied from 1.2 to 1.4:1. In our reaction protocol, we
also found when 1b was used, the corresponding products
were mixture of diastereoisomers and the ratio was 40:60,
(bromomethyl)-γ-butyrolactones were obtained, in good to
1
excellent yields (entries 1–4); while 2-cyclopentene-1-acetic
acid (1e) in the reaction gave the corresponding product only
in 43% yield due to the restrictive effect of the ring (entry 5).
On similar treatment of but-3-enoic acid and trans-hex-3-enoic
acids, the reaction only provided the unsaturated lactones,
not the desired bromolactones (entries 6 and 7). It was found
which was determined by examination of the H NMR spectra
of the bromolactones; while 3-methyl-pent-4-enoic acid (1c)
was treated in the reaction, the ratio for the obtained mixture of
diastereoisomers was 56:44.
23
A plausible mechanism is similar to the literature proposal,
which included the electrophilic addition of hypervalent iodine
reagent 1 to the alkene, then an intramolecular nucleophilic
displacement occurred, followed by another nucleophilic
displacement to give the bromolactone.
1
by an H NMR technique that the desired five-membered ring
lactones and four-membered ring lactones were first formed,
In conclusion, we have successfully studied the bromolacto-
nisation of alkenoic acids with (diacetoxyiodo)benzene,
extended the application scope of the simple and efficient
cyclisation and found that the reaction was suitable for a series
of pent-4-enoic acids, most of which gave good to excellent
yields of 5-(bromomethyl)-γ-butyrolactones. Other novel
bromolactonisation reactions, such as using catalytic amounts
of hypervalent iodine (III) reagents for bromolactonisations
are being investigated, and will be reported in due course.
Table 2 The result of the bromolactonisation of alkenoic
acids
Entry Alkenoic acids (1)
Bromolactones (4) Time Yield
/h
/%a
1
1
1
1
1
89
Experimental
IR spectra were recorded on a Thermo-Nicolet 6700 instrument,
1
H NMR spectra were measured on a Bruker AVANCE (500M)
2
3
4
5
6
7
93
87
95
spectrometer, and mass spectra were determined on a Thermo-ITQ
1
100 mass spectrometer. Diacetoxyiodo)benzene and all alkenoic
acids are commercially available.
Bromolactonisation of alkenoic acids; general procedure
The alkenoic acid 1 (0.3 mmol), (diacetoxyiodo)benzene 2 (0.3 mmol)
and lithium bromide 3 (0.6 mmol) were added to CH OH (2 mL). The
3
mixture was stirred at room temperature for 1–2 h (shown in Table 2)
and then separated on a silica gel plate using (3:2 hexane-ethyl
acetate) as eluant to give 4 in good to excellent yields.
23
1
5
-(Bromomethyl)-γ-butyrolactone (4a) : Oil. H NMR (500MHz,
CDCl ): 4.78–4.73 (m, 1H), 3.59–3.52 (m, 2H), 2.69–2.63 (m, 1H),
3
13
2.61–2.54 (m, 1H), 2.49–2.42 (m, 1H), 2.15–2.11(m, 1H). C NMR
(
1
125MHz, CDCl ): 176.1, 77.9, 34.0, 28.3, 26.2. IR (film): ν = 2962,
3
−
1
777, 1168, 1023, 917 cm . MS (EI, m/z, %): 179 (13), 181 (14),
9
9 (100).
25
1
2
-Methyl-5-(bromomethyl)-γ-butyrolactone (4b) : Oil. H NMR
(
500MHz, CDCl ): 4.78–4.73 (3b ) and 4.61–4.55 (3b ) (m, 1H),
3
1
2
0.5 43
3.60–3.57 (3b ) and 3.54–3.50 (3b ) (m, 2H), 2.86–2.81 (3b )
1
2
1
and 2.78–2.71 (3b ) (m, 1H), 2.66–2.60 (3b ) and 2.44–2.38 (3b ) (m,
2
1
2
1
3
3
1
H), 2.13–2.07 (3b ) and 1.75–1.68 (3b ) (m, 1H), 1.31 (d, J = 7.0 Hz,
1 2
13
H), C NMR (125MHz, CDCl ): 179.1, 178.4, 75.9, 75.8, 35.6, 35.5,
3
4.0, 33.8, 33.7, 33.5, 16.1, 15.0. IR (film): ν = 2975, 1775, 1182,
−
1
157, 1016, 927 cm . MS (EI, m/z, %): 193 (100), 195 (93).
26
1
1
2
60
41
3-Methyl-5-(bromomethyl)-γ-butyrolactone (4c) : Oil. H NMR
(
500MHz, CDCl ): 4.72–4.69 (3c ) and 4.30–4.27 (3c ) (m, 1H),
3
1
2
3
.63–3.44 (m, 2H), 2.84–2.50 (m, 2H), 2.34 (dd, J = 17.0, 3.5 Hz, 3c1)
and 2.25 (dd, J = 18.0, 8.0 Hz, 3c ) (1H), 1.23 (d, J = 7.0 Hz, 3c )
2
1
13
and 1.17 (d, J = 7.0 Hz, 3c ) (3H). C NMR (125MHz, CDCl ):
2
3
1
75.6, 175.3, 84.5, 80.9, 37.2, 36.6, 34.1, 34.0, 32.5, 32.3, 28.6,
−1
19.6, 18.3, 13.0. IR (film): ν = 2969, 1781, 1156, 998, 940 cm . MS
EI, m/z, %): 193 (12), 195 (13), 71 (100).
, 2-Dimethyl-5-(bromomethyl)-γ-butyrolactone (4d) : Oil.
(
27
1
2
H
NMR (500MHz, CDCl ): 4.67–4.61 (m, 1H), 3.57 (dd, J = 10.5, 5.0
Hz, 1H), 3.50 (dd, J = 11.0, 6.5 Hz, 1H), 2.28 (dd, J = 13.0, 6.5 Hz,
3
a
Isolated yield.

JOURNAL OF CHEMICAL RESEARCH 2010 169
1
0
3
1
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