Ammonium iodide-promoted cyclization of aryl-substituted carboxylic acids

Article abstract of DOI:10.1080/00397911.2013.864773

An efficient procedure was developed for direct preparation of aryl-substituted lactones from corresponding aryl carboxylic acids, which was promoted by ammonium iodide. In this protocol, aryl carboxylic acids were treated with ammonium iodide, potassium bromide, and oxidant Oxone in a mixture of acetonitrile and 2,2,2-trifluoroethanol (6:4) at room temperature for 12 h, resulting in corresponding aryl lactones in moderate to good yields.

Full text of DOI:10.1080/00397911.2013.864773

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Ammonium Iodide–Promoted Cyclization
of Aryl-Substituted Carboxylic Acids
Bijun Zhang a , Liuquan Han a , Tingting Li a , Jie Yan a & Zhenping
Yang a
a College of Chemical Engineering and Materials Sciences , Zhejiang
University of Technology , Hangzhou , China
Accepted author version posted online: 10 Feb 2014.Published
online: 14 May 2014.
To cite this article: Bijun Zhang , Liuquan Han , Tingting Li , Jie Yan & Zhenping Yang (2014)
Ammonium Iodide–Promoted Cyclization of Aryl-Substituted Carboxylic Acids, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:11, 1608-1613, DOI: 10.1080/00397911.2013.864773
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Synthetic Communications1, 44: 1608–1613, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.864773
AMMONIUM IODIDE–PROMOTED CYCLIZATION OF
ARYL-SUBSTITUTED CARBOXYLIC ACIDS
Bijun Zhang, Liuquan Han, Tingting Li, Jie Yan, and
Zhenping Yang
College of Chemical Engineering and Materials Sciences, Zhejiang University
of Technology, Hangzhou, China
GRAPHICAL ABSTRACT
Abstract An efficient procedure was developed for direct preparation of aryl-substituted
lactones from corresponding aryl carboxylic acids, which was promoted by ammonium
iodide. In this protocol, aryl carboxylic acids were treated with ammonium iodide,
potassium bromide, and oxidant Oxone in
a mixture of acetonitrile and 2,2,2-
trifluoroethanol (6:4) at room temperature for 12 h, resulting in corresponding aryl
lactones in moderate to good yields.
Keywords Ammonium iodide; benzylic cyclization; lactone
INTRODUCTION
Lactones are important and ubiquitous building blocks in organic synthesis,
material science, medicine, polymer areas, and natural product chemistry.[1] Because
some aryl-substituted lactones have significant biological behaviors, such as anti-
biotic and cytotoxic properties,[2] the methods for their preparation have been of
increasing importance. The direct oxidative cyclization of aryl carboxylic acids is a
convenient and attractive route for synthesis of the corresponding lactones.[3] How-
ever, the use of expensive, unstable, or toxic metal oxidants and the need for higher
reaction temperatures in these procedures have limited the oxidative cyclization.[4]
Because of low toxicity, ready availability, easy handling, and reactivity similar
to that of heavy-metal reagents or anodic oxidation, hypervalent iodine compounds
have found broad application in organic chemistry and are frequently used in
synthesis.[5] In 2007, Kita and coauthors reported a new and metal-free oxidative
cyclization for direct formation of aryl lactones from aryl carboxylic acids, in which
Received October 6, 2013.
Address correspondence to Zhenping Yang, College of Chemical Engineering and Materials
Sciences, Zhejiang University of Technology, Hangzhou 310032, China. E-mail: zengpyang@163.com
1608

AMMONIUM IODIDE PROMOTED CYCLIZATION
1609
a stoichiometric hypervalent iodine reagent 4-methoxyphenyliodine(III) diacetate
was used as oxidant, and a benzyl radical mechanism formed via sp3 C-H abstraction
was hypothesized.[6] In recent years, the catalytic utilization of hypervalent iodine
reagents is increasing in importance, with growing interest in the development of
environmentally benign synthetic transformations.[7] To develop a novel catalytic
cyclization of aryl carboxylic acids, we have investigated the possibility of using a
catalytic amount of iodobenzene in place of the stoichiometric hypervalent iodine
reagent and successfully obtained the desired aryl lactones. During this research,
we found that inorganic iodides, especially ammonium iodide, when used in place
of iodobenzene can also promote this cyclization, resulting in similar results. Here
we report a novel cyclization for direct preparation of aryl lactones from aryl
carboxylic acids promoted by inorganic ammonium iodide, which is more environ-
mentally benign, and to our knowledge this processes has not been reported before.
DISCUSSION AND RESULTS
First, 4-phenylbutanoic acid was treated with 0.3 equiv. of ammonium iodide
(NH4I), 1.0 equiv. of potassium bromide (KBr), and 1.5 equiv. of potassium hydro-
gen persulfate (Oxone) in organic solvents at room temperature for 12 h. Generally,
the reaction proceeded smoothly and the desired product of c-phenyl-c-lactone was
afforded (Table 1).
It was found from Table 1 that when the reaction was carried out in an organic
solvent or water, poor yields were usually obtained (entries 1–9). As the reaction was
stirred in a mixture of solvents, the yield was increased, and the mixture of acetonitrile
(MeCN) and 2,2,2-trifluoroethanol (CF3CH2OH) (6:4) was suitable for the reaction
(entries 10–14). Compared with other inorganic iodides, NH4I was the best choice;
however, in the absence of it, a rather poor yield of 29% was observed (entries 11,
15–18). The suitable reaction time was 12 h (entries 11, 19, and 20). Other oxidants,
such meta-chloroperbenzoic acid (mCPBA) and K2S2O6 usually led to poor yields
(entries 21 and 22). The amount of oxidant Oxone was checked, and 1.5 equiv. was
the most effective for the reaction (entries 11, 23–27). It was also obvious that the
yield was affected by the amounts of KBr and NH4I: When the amount of KBr
was decreased to 0.8 equiv. and the amount of NH4I was increased to 0.5 equiv.,
the best yield of 69% was provided (entries 28–33).
With the optimal conditions in hand, and to check the generality and applica-
bility of this method, a series of aryl carboxylic acids were investigated with 0.5
equiv. of NH4I, 1.5 equiv. of Oxone and 0.8 equiv. of KBr in a mixture of MeCN
and CF3CH2OH (6:4) at room temperature for 12 h. The results are summarized
(Table 2).
As shown in Table 2, this reaction was compatible with some substrates and
gave the corresponding five-membered and six-membered aryl lactones in moderate
to good yields (entries 1–4). In the treatment of 3-phenylpropanoic acid (1e) and
6-phenylhexanoic acid (1f), the desired product 2e was not observed due to the insta-
bility of four-membered ring lactones (entry 5); although another seven-membered
ring product 2f was separated, the yield was only 26% (entry 6). Therefore, the
NH4I-promoted cyclization was suitable for preparation of five-membered and
six-membered aryl lactones, especially with respect of c-aryl-c-lactones. Under the

1610
B. ZHANG ET AL.
Table 1. Optimization of the NH4I-promoted cyclization of 4-phenylbutanoic acid
Oxidant
(1.5 equiv)
NH4I
(equiv)
KBr
(equiv)
Time
(h)
Yield
(%)a
Entry
Solvent
1
2
CH2Cl2
THF
Oxone
Oxone
Oxone
0.3
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.8
1.5
2.0
0.8
0.8
0.8
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
21
19
43
30
21
28
28
26
39
52
54
39
42
43
44
44
39
29
45
56
23
39
39
34
37
26
43
55
45
47
59
69
62
0.3
0.3
3
MeCN
MeOH
4
Oxone
Oxone
0.3
0.3
5
EtOH
EtOAc
6
Oxone
Oxone
0.3
0.3
7
DMF
H2O
CF3CH2OH
8
Oxone
Oxone
0.3
0.3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
MeCN–CF3CH2OH (5:5)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (8:2)
MeCN–CF3CH2OH (9:1)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (6:4)
Oxone
Oxone
0.3
0.3
Oxone
Oxone
0.3
0.3
Oxone
Oxone
0.3
KI (0.3)
NaI (0.3)
TBAI (0.3)
0
Oxone
Oxone
Oxone
Oxone
Oxone
0.3
0.3
24
12
12
12
12
12
12
12
12
12
12
12
12
12
mCPBA (1.5)
K2S2O6 (1.5)
Oxone (2.0)
Oxone (2.5)
Oxone (3.0)
Oxone (4.0)
Oxone (1.0)
Oxone
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
Oxone
Oxone
0.3
0.3
Oxone
Oxone
Oxone
0.4
0.5
0.6
aYield of isolated 2a.
same reaction conditions, some short-branched chains of benzoic acids were exam-
ined, and corresponding two phthalides and two benzopyran-3-ones were afforded
with somewhat poor yields compared with the aryl lactones (entries 7–10).
A plausible mechanism for the present reaction is shown in Scheme 1. NH4I is
first oxidized by Oxone to the active hypoiodous acid, which is transformed into the
active molecular IBr by treatment with KBr. IBr then is split into the active key

AMMONIUM IODIDE PROMOTED CYCLIZATION
1611
Table 2. Results of NH4I-promoted cyclization of aryl carboxylic acids
Entry
1
Carboxylic acid 1
Lactone 2
Yield (%)a
69
64
56
58
0
2
3
4
5
6
7
8
9
2 e
26
58
52
48
41
10
aYield of isolated 2.
bromine species, following a benzyl radical formation via sp3 C-H abstraction.
Finally, the intramolecular cyclization takes place to provide the corresponding aryl
lactones. To identify it, the commercially available molecular IBr was used to react
with 4-pentenoic acid, and the desired product of c-phenyl-c-lactone was afforded in
42%. It was also found that when ethyl benzene was used in place with 4-pentenoic
acid, the a-bromoethyl benzene was obtained in good yield, which supports the
benzyl radical process.

1612
B. ZHANG ET AL.
Scheme 1. Possible mechanism for the cyclization of aryl carboxylic acids promoted by NH4I.
CONCLUSION
In summary, we have developed an efficient method for direct preparation of
aryl-substituted lactones from corresponding aryl carboxylic acids promoted by
ammonium iodide, which is a more environmentally benign procedure. It has some
advantages such as mild reaction conditions, simple procedure, and moderate to
good yields.
EXPERIMENTAL
Melting points were measured with an XT-4 melting-point apparatus and were
uncorrected. Infrared (IR) spectra were recorded on a Thermo-Nicolet 6700 instrument,
1H NMR and 13C NMR spectra were measured on a Bruker Avance I (500-MHz)
spectrometer, and mass spectra were determined on Thermo-ITQ 1100 mass spec-
trometer. Carboxylic acids, Oxone, NH4I, and KBr were commercially available.
Typical Procedure for the NH4I-Promoted Cyclization of
Carboxylic Acids
Carboxylic acid 1 (0.5 mmol), NH4I (0.25 mmol), KBr (0.4 mmol), and Oxone
(0.75 mmol) were added to a mixture of MeCN and CF3CH2OH (6:4) (5.0 mL).
The resulting mixture was stirred at room temperature for 12 h and then solvents were
removed under reduced pressure. Water (10 mL), saturated aqueous Na2S2O3 (4 mL),
and saturated aqueous Na2CO3 (4 mL) were added to the residue and the mixture was
stirred for another 5 min. The mixture was extracted with CH2Cl2 (3 Â 10 mL), and
the combined organic layer was washed with brine, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The residue was purified by pre-
parative thin-layer chromatography (TLC) on silica gel using hexane–AcOEt (3:1)
as eluant to give the pure product of aryl lactone 2.
FUNDING
Financial support from the Natural Science Foundation of China (Project
21072176) is greatly appreciated.

AMMONIUM IODIDE PROMOTED CYCLIZATION
1613
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
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